136 results on '"Lima WG"'
Search Results
2. Cardiomyopathy prognosis after benznidazole treatment in chronic canine Chagas' disease.
- Author
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Santos FM, Lima WG, Gravel AS, Martins TA, Talvani A, Torres RM, and Bahia MT
- Published
- 2012
3. Biodistribution and Tumor Targeted Accumulation of Anti-CEA-loaded Iron Nanoparticles.
- Author
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Correa TS, Lima WG, do Couto Campos AB, Galdino AS, de Oliveira Lima EC, Cardoso VN, Fernandes SOA, and Campos-da-Paz M
- Subjects
- Animals, Tissue Distribution, Mice, Female, Cell Line, Tumor, Carcinoembryonic Antigen metabolism, Technetium chemistry, Mice, Inbred BALB C
- Abstract
Introduction: Active targeting of tumors by nanomaterials favors early diagnosis and the reduction of harsh side effects of chemotherapeuticals., Methods: We synthesized magnetic nanoparticles (64 nm; -40 mV) suspended in a magnetic fluid (MF) and decorated them with anti-carcinoembryonic antigen (MFCEA; 144 nm; -39 mV). MF and MFCEA nanoparticles were successfully radiolabeled with technetium-99m (
99m Tc) and intravenously injected in CEA-positive 4T1 tumor-bearing mice to perform biodistribution studies. Both99m Tc-MF and99m Tc-MFCEA had marked uptake by the liver and spleen, and the renal uptake of99m Tc-MFCEA was higher than that observed for99m Tc-MF at 20h. At 1 and 5 hours, the urinary excretion was higher for99m Tc-MF than for99m Tc-MFCEA., Results: These data suggest that anti-CEA decoration might be responsible for a delay in renal clearance. Regarding the tumor,99m Tc-MFCEA showed tumor uptake nearly two times higher than that observed for99m Tc-MFCEA. Similarly, the target-nontarget ratio was higher with99m Tc-MFCEA when compared to the group that received the99m Tc-MF., Conclusion: These data validated the ability of active tumor targeting by the as-developed anti- CEA loaded nanoparticles and are very promising results for the future development of a nanodevice for the management of breast cancer and other types of CEA-positive tumors., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)- Published
- 2025
- Full Text
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4. Diversity of Colletotrichum Species Causing Anthracnose in Chayote in Brazil, with a Description of Two New Species in the C. magnum Complex.
- Author
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Vieira WADS, Costa CAD, Veloso JS, Lima WG, Correia KC, Michereff SJ, Pinho DB, Câmara MPS, and Reis A
- Abstract
Anthracnose caused by Colletotrichum species is the most important disease of chayote ( Sicyos edulis ) in Brazil. The etiology of chayote anthracnose has been assigned to the species C. orbiculare , an important plant pathogenic fungus also reported as the causal agent of anthracnose in other cucurbits worldwide. However, there is no recent survey of the Colletotrichum species causing anthracnose in chayote in Brazil. In this study, Colletotrichum isolates associated with anthracnose on the fruit and leaves of chayote, from various producing regions in Brazil, were collected and identified. Haplotype analysis based on sequences of the β-tubulin genomic region ( TUB2 ) of 44 Colletotrichum isolates was carried out as a first measure of genetic diversity. A subset of 22 isolates were sequenced using the partial sequences of actin ( ACT ), glyceraldehyde-3-phosphate dehydrogenase ( GAPDH ), and the rDNA ITS (ITS) region. Maximum likelihood analysis was performed using the concatenated sequences. The multilocus sequence analysis revealed four previously described species, Colletotrichum chrysophilum , C. menezesiae , C. plurivorum , and C. karsti, and two novel species, named C. cucurbitacearum and C. sicyi . All species were able to induce typical symptoms of anthracnose in chayote fruits but varied in their aggressiveness. The species C. menezesiae and C. sicyi were the most aggressive, while C. plurivorum was the least aggressive. The species C. orbiculare was not found to cause chayote anthracnose in Brazil.
- Published
- 2024
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5. Piperine as an Herbal Alternative for the Prevention of Drug-Induced Liver Damage Caused by Paracetamol.
- Author
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Coelho AM, Queiroz IF, Perucci LO, Menezes TP, Lima WG, Talvani A, and Costa DC
- Abstract
Background/Objective: Hepatic drug intoxication is becoming increasingly common with the increasing use of chronic medications. Piperine has emerged as a promising alternative for protecting the liver against drug-induced injury. We evaluated the prophylactic effects of piperine in C57BL/6 mice with an acute liver injury induced by a paracetamol (APAP) overdose. Methods: Piperine was administered at a dose of 20 mg/kg (P20) or 40 mg/kg (P40) for eight consecutive days before the animals were exposed to a hepatotoxic dose of paracetamol (500 mg/kg). The animals were euthanized 3 h after the paracetamol overdose. Results: The prophylactic treatment with piperine (P20 and P40) maintained the levels of alanine aminotransferase (ALT) and the biomarkers of oxidative damage (TBARS and carbonylated proteins), which were statistically similar to those for the control group. The extent of hepatocyte necrosis and TNF-α (tumor necrosis factor-alpha) levels were lower than those in the group exposed to liver injury (APAP group). Piperine modulated the gene expression of CYP2E1 (cytochrome P4502E1) and the inflammasome pathway (NLRP3, CASP-1, IL-1β, and IL-18), which play a crucial role in the inflammatory response. In the P40 group, the degree of hepatic hyperemia was similar to that in the control group, as was the increase in metalloproteinase 9 (MMP-9) activity. Conclusion: Piperine has demonstrated beneficial and promising effects for the prevention of liver injury resulting from paracetamol-induced drug intoxication.
- Published
- 2024
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6. Ocimum basilicum L. (basil) presents pro-apoptotic activity in an Ehrlich's experimental tumor murine model.
- Author
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Sant'Ana PGDS, Lima WG, Lopes GFM, Oliveira SE, Costa GAFD, Lima LARDS, Ferreira EE, Santos ICD, Damázio LCM, Ribeiro RIMA, and Pinto FCH
- Subjects
- Animals, Mice, Male, Immunohistochemistry, Proto-Oncogene Proteins c-bcl-2 analysis, Reproducibility of Results, Carcinoma, Ehrlich Tumor drug therapy, Carcinoma, Ehrlich Tumor pathology, Plant Extracts pharmacology, Plant Extracts therapeutic use, Apoptosis drug effects, Ocimum basilicum chemistry, Disease Models, Animal
- Abstract
Purpose: This study aimed to evaluate the therapeutic effect of an ethanol extract of Ocimum basilicum L. (EEOb) aerial parts against Ehrlich's experimental tumor (EET) in mice., Methods: Swiss mice were divided into two groups (control and treated; n = 6). On day 21, all mice were inoculated subcutaneously with 2 × 106 (0.05 mL) EET cells in the left paw for solid tumor development. This study lasted 28 days. Treatment began 24 hours after inoculation with EET. Measurements of dorsoplantar thickness were used to assess tumor growth. The paw pad was collected for histopathological analysis and stained using the argyrophilic nucleolar organizing regions (AgNOR) technique and immunohistochemistry for proliferating cell nuclear antigen, Bcl-2 and Bax., Results: The treatment of animals with EEOb at 100 mg/kg intraperitoneally was able to reduce the growth (Control = 3.7 ± 0.1 mm vs. EEOb = 5.7 ± 0.2 mm) and the number of AgNORs of solid Ehrlich tumor. The antitumor effect of EEOb was associated with the induction of apoptosis of tumoral cell, as suggested by the reduction of the content of Bcl-2 induced by extract., Conclusions: The study demonstrated that daily administration of EEOb is able to reduce the growth of EET by induce apoptosis of tumoral cells.
- Published
- 2024
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7. The Synthetic Peptide LyeTx I mn∆K, Derived from Lycosa erythrognatha Spider Toxin, Is Active against Methicillin-Resistant Staphylococcus aureus (MRSA) In Vitro and In Vivo.
- Author
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Vieira APGC, de Souza AN, Lima WG, Brito JCM, Simião DC, Gonçalves LVR, Cordeiro LPB, de Oliveira Scoaris D, Fernandes SOA, Resende JM, Bechinger B, Verly RM, and de Lima ME
- Abstract
The urgent global health challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) infections demands effective solutions. Antimicrobial peptides (AMPs) represent promising tools of research of new antibacterial agents and LyeTx I mn∆K, a short synthetic peptide based on the Lycosa erythrognatha spider venom, is a good representative. This study focused on analyzing the antimicrobial activities of LyeTx I mn∆K, including minimum inhibitory and bactericidal concentrations, synergy and resensitization assays, lysis activity, the effect on biofilm, and the bacterial death curve in MRSA. Additionally, its characterization was conducted through isothermal titration calorimetry, dynamic light scattering, calcein release, and finally, efficacy in a mice wound model. The peptide demonstrates remarkable efficacy against planktonic cells (MIC 8-16 µM) and biofilms (>30% of inhibition) of MRSA, and outperforms vancomycin in terms of rapid bactericidal action and anti-biofilm effects. The mechanism involves significant membrane damage. Interactions with bacterial model membranes, including those with lysylphosphatidylglycerol (LysylPOPG) modifications, highlight the versatility and selectivity of this compound. Also, the peptide has the ability to sensitize resistant bacteria to conventional antibiotics, showing potential for combinatory therapy. Furthermore, using an in vivo model, this study showed that a formulated gel containing the peptide proved superior to vancomycin in treating MRSA-induced wounds in mice. Together, the results highlight LyeTx I mnΔK as a promising prototype for the development of effective therapeutic strategies against superficial MRSA infections.
- Published
- 2024
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8. LoRa Technology Propagation Models for IoT Network Planning in the Amazon Regions.
- Author
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Lima WG, Lopes AVR, Cardoso CMM, Araújo JPL, Neto MCA, Tostes MEL, Nascimento AA, Rodriguez M, and Barros FJB
- Abstract
Designing and deploying telecommunications and broadcasting networks in the challenging terrain of the Amazon region pose significant obstacles due to its unique morphological characteristics. Within low-power wide-area networks (LPWANs), this research study introduces a comprehensive approach to modeling large-scale propagation loss channels specific to the LoRaWAN protocol operating at 915 MHz. The objective of this study is to facilitate the planning of Internet of Things (IoT) networks in riverside communities while accounting for the mobility of end nodes. We conducted extensive measurement campaigns along the banks of Universidade Federal do Pará, capturing received signal strength indication (RSSI), signal-to-noise ratio (SNR), and geolocated point data across various spreading factors. We fitted the empirical close-in (CI) and floating intercept (FI) propagation models for uplink path loss prediction and compared them with the Okumura-Hata model. We also present a new model for path loss with dense vegetation. Furthermore, we calculated received packet rate statistics between communication links to assess channel quality for the LoRa physical layer (PHY). Remarkably, both CI and FI models exhibited similar behaviors, with the newly proposed model demonstrating enhanced accuracy in estimating radio loss within densely vegetated scenarios, boasting lower root mean square error (RMSE) values than the Okumura-Hata model, particularly for spreading factor 9 (SF9). The radius coverage threshold, accounting for node mobility, was 945 m. This comprehensive analysis contributes valuable insights for the effective deployment and optimization of LoRa-based IoT networks in the intricate environmental conditions of the Amazon region.
- Published
- 2024
- Full Text
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9. Jelleine, a Family of Peptides Isolated from the Royal Jelly of the Honey Bees ( Apis mellifera ), as a Promising Prototype for New Medicines: A Narrative Review.
- Author
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Lima WG, Brito JCM, Verly RM, and Lima ME
- Subjects
- Humans, Bees, Animals, Fatty Acids pharmacology, Larva, Peptides pharmacology, Honey
- Abstract
The jelleine family is a group of four peptides (jelleines I-IV) originally isolated from the royal jelly of honey bee ( Apis mellifera ), but later detected in some honey samples. These oligopeptides are composed of 8-9 amino acid residues, positively charged (+2 to +3 at pH 7.2), including 38-50% of hydrophobic residues and a carboxamide C -terminus. Jelleines, generated by processing of the C -terminal region of major royal jelly proteins 1 (MRJP-1), play an important biological role in royal jelly conservation as well as in protecting bee larvae from potential pathogens. Therefore, these molecules present numerous benefits for human health, including therapeutic purposes as shown in preclinical studies. In this review, we aimed to evaluate the biological effects of jelleines in addition to characterising their toxicities and stabilities. Jelleines I-III have promising antimicrobial activity and low toxicity (LD
50 > 1000 mg/Kg). However, jelleine-IV has not shown relevant biological potential. Jelleine-I, but not the other analogues, also has antiparasitic, healing, and pro-coagulant activities in addition to indirectly modulating tumor cell growth and controlling the inflammatory process. Although it is sensitive to hydrolysis by proteases, the addition of halogens increases the chemical stability of these molecules. Thus, these results suggest that jelleines, especially jelleine-I, are a potential target for the development of new, effective and safe therapeutic molecules for clinical use.- Published
- 2024
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10. High-fat diet increases mortality and intensifies immunometabolic changes in septic mice.
- Author
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Gomes SV, Dias BV, Júnior PAM, Pereira RR, de Souza DMS, Breguez GS, de Lima WG, Magalhães CLB, Cangussú SD, Talvani A, Queiroz KB, Calsavara AJC, and Costa DC
- Subjects
- Female, Mice, Animals, Interleukin-17, Interleukin-6, Tumor Necrosis Factor-alpha metabolism, Diet, High-Fat adverse effects, Mice, Inbred C57BL, Interleukin-10, Sepsis metabolism
- Abstract
Immunometabolic changes in the liver and white adipose tissue caused by high-fat (HF) diet intake may worse metabolic adaptation and protection against pathogens in sepsis. We investigate the effect of chronic HF diet (15 weeks) on mortality and immunometabolic responses in female mice after sepsis induced by cecum ligation and perforation (CLP). At week 14, animals were divided into four groups: sham C diet, sepsis C diet (C-Sp), sham HF diet (HF-Sh) and sepsis HF diet (HF-Sp). The surviving animals were euthanized on the 7th day. The HF diet decreased survival rate (58.3% vs. 76.2% C-Sp group), increased serum cytokine storm (IL-6 [1.41 ×; vs. HF-Sh], IL-1β [1.37 ×; vs. C-Sp], TNF [1.34 ×; vs. C-Sp and 1.72 ×; vs. HF-Sh], IL-17 [1.44 ×; vs. HF-Sh], IL-10 [1.55 ×; vs. C-Sp and 1.41 ×; HF-Sh]), white adipose tissue inflammation (IL-6 [8.7 ×; vs. C-Sp and 2.4 ×; vs. HF-Sh], TNF [5 ×; vs. C-Sp and 1.7 ×; vs. HF-Sh], IL-17 [1.7 ×; vs. C-Sp], IL-10 [7.4 ×; vs. C-Sp and 1.3 ×; vs. HF-Sh]), and modulated lipid metabolism in septic mice. In the HF-Sp group liver's, we observed hepatomegaly, hydropic degeneration, necrosis, an increase in oxidative stress (reduction of CAT activity [-81.7%; vs. HF-Sh]; increase MDA levels [82.8%; vs. HF-Sh], and hepatic IL-6 [1.9 ×; vs. HF-Sh], and TNF [1.3 × %; vs. HF-Sh]) production. Furthermore, we found a decrease in the total number of inflammatory, mononuclear cells, and in the regenerative processes, and binucleated hepatocytes in a HF-Sp group livers. Our results suggested that the organism under metabolic stress of a HF diet during sepsis may worsen the inflammatory landscape and hepatocellular injury and may harm the liver regenerative process., (Copyright © 2023 Elsevier Inc. All rights reserved.)
- Published
- 2023
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11. Temporal analysis of paracetamol-induced hepatotoxicity.
- Author
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Coelho AM, Queiroz IF, Lima WG, Talvani A, Perucci LO, Oliveira de Souza M, and Costa DC
- Subjects
- Mice, Animals, Thiobarbituric Acid Reactive Substances metabolism, Mice, Inbred C57BL, Liver, Acetaminophen toxicity, Chemical and Drug Induced Liver Injury pathology
- Abstract
Paracetamol-induced hepatotoxicity (APAP) causes severe damage that may be irreversible. Understanding the evolution of liver injury caused by overdose of the drug is important to assist in the treatment. In the present study, we evaluated the acute intoxication by APAP (500 mg/kg) in periods of 3 and 12 hours in C57BL/6 mice through biochemical, histological, inflammatory parameters, and the redox status. The results showed that in the 3-hour period there was an increase in creatinine dosage and lipid peroxidation (TBARS) compared to the control group. In the period of 12 hours after APAP intoxication all parameters evaluated were altered; there was an increase of ALT, AST, and necrosis, besides the increase of redox status biomarkers as carbonylated protein, TBARS, and MMP-9. We also observed activation of the inflammasome pathway as well as a reduction in the regenerative capacity of hepatocytes with a decrease in binucleated liver cells. In cytochrome gene expression, the mRNA level increased in CYP2E1 isoenzyme and reduced CYP1A2 expression. This study indicated that early treatment is necessary to mitigate APAP-induced acute liver injury, and alternative therapies capable of controlling the progression of intoxication in the liver are needed.
- Published
- 2023
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12. Oropouche virus infection induces ROS production and oxidative stress in liver and spleen of mice.
- Author
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da Silva Menegatto MB, Ferraz AC, Lima RLS, Almeida LT, de Brito RCF, Reis AB, Carneiro CM, de Lima WG, de Mello Silva B, de Magalhães JC, and Magalhães CLB
- Subjects
- Orthobunyavirus, Reactive Oxygen Species, Oxidative Stress, Animals, Liver pathology, Mice, Spleen pathology, Bunyaviridae Infections
- Abstract
Oropouche virus (OROV) is the aetiological agent of Oropouche fever, the symptoms of which are common to most arboviruses, such as fever, headache, malaise, nausea and vomiting. More than half a million people have been infected with OROV since its isolation in 1955. Although Oropouche fever is classified as a neglected and emerging disease, to date, there are no antiviral drugs or vaccines available against the infection and little is known about its pathogenicity. Therefore, it is essential to elucidate the possible mechanisms involved in its pathogenesis. Since oxidative stress plays a pivotal role in the progression of various viral diseases, in this study, redox homeostasis in the target organs of OROV infection was evaluated using an animal model. Infected BALB/c mice exhibited reduced weight gain, splenomegaly, leukopenia, thrombocytopenia, anaemia, development of anti-OROV neutralizing antibodies, increased liver transaminases, and serum levels of pro-inflammatory cytokines tumour necrosis factor (TNF-α) and interferon-γ (IFN-γ). The OROV genome and infectious particles were detected in the liver and spleen of infected animals, with liver inflammation and an increase in the number and total area of lymphoid nodules in the spleen. In relation to redox homeostasis in the liver and spleen, infection led to an increase in reactive oxygen species (ROS) levels, increased oxidative stress biomarkers malondialdehyde (MDA) and carbonyl protein, and decreased activity of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT). Taken together, these results help elucidate some important aspects of OROV infection that may contribute to the pathogenesis of Oropouche.
- Published
- 2023
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13. Therapeutic Prospection of Animal Venoms-Derived Antimicrobial Peptides against Infections by Multidrug-Resistant Acinetobacter baumannii : A Systematic Review of Pre-Clinical Studies.
- Author
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Lima WG and de Lima ME
- Subjects
- Animals, Antimicrobial Peptides, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents chemistry, Drug Resistance, Multiple, Bacterial, Microbial Sensitivity Tests, Acinetobacter baumannii, Acinetobacter Infections drug therapy, Acinetobacter Infections microbiology, Arthropod Venoms pharmacology
- Abstract
Infections caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) have become a public health emergency. Due to the small therapeutic arsenal available to treat these infections, health agencies have highlighted the importance of developing new antimicrobials against MDR-Ab. In this context, antimicrobial peptides (AMPs) stand out, and animal venoms are a rich source of these compounds. Here, we aimed to summarize the current knowledge on the use of animal venom-derived AMPs in the treatment of MDR-Ab infections in vivo. A systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The eight studies included in this review identified the antibacterial activity of eleven different AMPs against MDR-Ab. Most of the studied AMPs originated from arthropod venoms. In addition, all AMPs are positively charged and rich in lysine residues. In vivo assays showed that the use of these compounds reduces MDR-Ab-induced lethality and bacterial load in invasive (bacteremia and pneumonia) and superficial (wounds) infection models. Moreover, animal venom-derived AMPs have pleiotropic effects, such as pro-healing, anti-inflammatory, and antioxidant activities, that help treat infections. Animal venom-derived AMPs are a potential source of prototype molecules for the development of new therapeutic agents against MDR-Ab.
- Published
- 2023
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14. Antifungal activity of a shortened analogue of the natural peptide LyeTx I isolated from the venom of the spider Lycosa erythrognatha .
- Author
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Cardoso BG, de Lima WG, Fernandes SOA, de Lima ME, and Cardoso VN
- Subjects
- Candida, Candida albicans, Peptides pharmacology, Microbial Sensitivity Tests, Biofilms, Antifungal Agents pharmacology, Venoms
- Abstract
The increase in the incidence of fungal infections associated with the limited therapeutic arsenal available and the increasing rate of resistance of pathogenic fungi reinforce the need for research of new antifungal agents. Thus, this study aims to evaluate the antifungal activity of the peptide LyeTx I mnΔK, a shortened analogue of the natural peptide LyeTx I derived from spider venom, against Candida species. LyeTx I mnΔK showed potent activity against Candida spp. with minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) between 4 and 32 µM. The peptide also completely inhibited the yeast-to-hypha transition (at 2 µM) and broke mature biofilms (67% reduction at 32 µM) of C. albicans . In addition, LyeTx I mnΔK did not induce resistance in C. albicans during 21 days of exposure. Therefore, the LyeTx I mnΔK is a promising prototype for the development of new antifungal agents.
- Published
- 2023
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15. Anti-Mayaro virus activity of a hydroethanolic extract from Fridericia chica (Bonpl.) L. G. Lohmann leaves.
- Author
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Lopes GFM, Lima WG, Santos FRS, Nunes DAF, Passos MJF, Fernandes SOA, de Magalhães JC, Dos Santos LL, and Ferreira JMS
- Subjects
- Animals, Antiviral Agents pharmacology, Bromides pharmacology, Chlorocebus aethiops, Mammals, Plant Extracts pharmacology, Vero Cells, Alphavirus, Bignoniaceae
- Abstract
Ethnopharmacological Relevance: Mayaro fever is a neglected tropical disease. The region of the most significant circulation of the Mayaro virus (MAYV) is the Amazon rainforest, situated in remote areas that are difficult to access and where medicine is scarce. Thus, the regional population uses plants as an alternative for the treatment of various diseases. Fridericia chica is an endemic plant of tropical regions used in traditional medicine to treat fever, malaise, inflammation, and infectious diseases such as hepatitis B. However, its antiviral activity is poorly understood., Aim of the Study: This study aimed to investigate the anti-MAYV activity of the hydroethanolic extract of the leaves of Fridericia chica (HEFc) in mammalian cells and its possible mechanism of action., Materials and Methods: The antiviral activity of HEFc was studied using Vero cell lines against MAYV. The cytotoxicity and antiviral activity of the extract were evaluated by the 3-(4, 5- dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay. The overall antiviral activity was confirmed by the plaque forming units (PFU) method. Then, the effects of HEFc on MAYV multiplication kinetics, virus adsorption, penetration, and post-penetration, and its virucidal activity were determined in Vero cells using standard experimental procedures., Results: HEFc exerted a effect against viral infection in Vero cells at a non-cytotoxic concentration, and no virion was detected in the supernatant in a dose-dependent and selective manner. HEFc inhibited MAYV in the early and late stages of the viral multiplication cycle. The extract showed significant virucidal activity at low concentrations and did not affect adsorption or viral internalization stages. In addition, HEFc reduced virions at all post-infection times investigated., Conclusions: HEFc has good antiviral activity against MAYV, acting directly on the viral particles. This plant extract possesses an excellent and promising potential for developing effective herbal antiviral drugs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)
- Published
- 2022
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16. Hatchery tanks induce intense reduction in microbiota diversity associated with gills and guts of two endemic species of the São Francisco River.
- Author
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Damasceno MRA, Lemes CGC, Braga LSSB, Tizioto PC, Montenegro H, Paduan M, Pereira JG, Cordeiro IF, Rocha LCM, da Silva SA, Sanchez AB, Lima WG, Yazbeck GM, Moreira LM, and Garcia CCM
- Abstract
The São Francisco River (SFR), one of the main Brazilian rivers, has suffered cumulative anthropogenic impacts, leading to ever-decreasing fish stocks and environmental, economic, and social consequences. Rhinelepis aspera and Prochilodus argenteus are medium-sized, bottom-feeding, and rheophilic fishes from the SFR that suffer from these actions. Both species are targeted for spawning and restocking operations due to their relevance in artisanal fisheries, commercial activities, and conservation concerns. Using high-throughput sequencing of the 16S rRNA gene, we characterized the microbiome present in the gills and guts of these species recruited from an impacted SFR region and hatchery tanks (HT). Our results showed that bacterial diversity from the gill and gut at the genera level in both fish species from HT is 87% smaller than in species from the SFR. Furthermore, only 15 and 29% of bacterial genera are shared between gills and guts in R . aspera and P. argenteus from SFR, respectively, showing an intimate relationship between functional differences in organs. In both species from SFR, pathogenic, xenobiont-degrading, and cyanotoxin-producer bacterial genera were found, indicating the critical pollution scenario in which the river finds itself. This study allowed us to conclude that the conditions imposed on fish in the HT act as important modulators of microbial diversity in the analyzed tissues. It also raises questions regarding the effects of these conditions on hatchery spawn fish and their suitability for restocking activities, aggravated by the narrow genetic diversity associated with such freshwater systems., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Damasceno, Lemes, Braga, Tizioto, Montenegro, Paduan, Pereira, Cordeiro, Rocha, da Silva, Sanchez, Lima, Yazbeck, Moreira and Garcia.)
- Published
- 2022
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17. Antibacterial, anti-biofilm, and anti-adhesive activities of melittin, a honeybee venom-derived peptide, against quinolone-resistant uropathogenic Escherichia coli (UPEC).
- Author
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Lima WG, Batista Filho FL, Lima IP, Simião DC, Brito JCM, da Cruz Nizer WS, Cardoso VN, and Fernandes SOA
- Subjects
- Humans, Melitten pharmacology, Adhesives, Biofilms, Anti-Bacterial Agents pharmacology, Microbial Sensitivity Tests, Uropathogenic Escherichia coli, Quinolones pharmacology, Bee Venoms pharmacology, Urinary Tract Infections drug therapy, Urinary Tract Infections microbiology
- Abstract
Here, we demonstrated the in vitro and in vivo antibacterial and anti-biofilm activities of melittin, a peptide derived from honeybee venom, against uropathogenic Escherichia coli (UPEC) resistant to quinolones. The minimum inhibitory concentration (MIC) of melittin varied from 0.5 to 8 μM. The bactericidal effect was considered rapid and potent (ranging from 3.0 to 6.0 h after incubation) against a quinolone-resistant and Extended Spectrum Beta-lactamase (ESBL)-producing UPEC strain. Prior exposure to melittin did not reduce the MIC of the quinolones tested, but it decreased the MIC of ceftizoxime by 8-fold due to its ability to form pores in the membrane. Furthermore, melittin disrupted mature biofilms (39.58% at 32 μM) and inhibited the adhesion of this uropathogen to the surfaces of urethral catheter. These results show that melittin is a promising molecule that can be incorporated into invasive urethral medical devices to prevent urinary infections caused by multidrug-resistant UPECs.
- Published
- 2022
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18. Netzahualcoyonol from Salacia multiflora (Lam.) DC. (Celastraceae) roots as a bioactive compound against gram-positive pathogens.
- Author
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da Cruz Nizer WS, Ferraz AC, Moraes TFS, Lima WG, Dos Santos JP, Duarte LP, Magalhães CLB, Vieira-Filho SA, and de Magalhães JC
- Subjects
- Microbial Sensitivity Tests, Staphylococcus aureus, Gram-Positive Bacteria, Anti-Bacterial Agents pharmacology, Salacia, Celastraceae
- Abstract
The expression of virulence factors, such as biofilm formation, in association with the acquisition of resistance to multiple drugs, has evidenced the need for new and effective antimicrobial agents against Staphylococcus aureus . The evaluation of the pharmacological properties of plant-derived compounds is a promising alternative to the development of new antimicrobials. In this study, we aimed to evaluate the antibacterial, antibiofilm, and the synergistic and cytotoxic effects of netzahualcoyonol isolated from Salacia multiflora (Lam.) DC. roots. Netzahualcoyonol presented bacteriostatic (1.56-25.0 µg/mL) and bactericidal (25.0-400.0 µg/mL) effects against Gram-positive bacteria, disrupted the biofilm of S. aureus, and presented a synergistic effect after its combination with β-lactams and aminoglycosides. The low cytotoxicity of netzahualcoyonol (Selectivity Index (SI) for S. aureus (2.56), S. saprophyticus (20.56), and Bacillus subtilis (1.28)) suggests a good security profile. Taken together, these results show that netzahualcoyonol is promising for the development of a new effective antibacterial agent.
- Published
- 2022
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19. Study of the influence of fecal material on the prognosis of intra-abdominal candidiasis using a murine model of technetium-99 m ( 99 m Tc)-Candida albicans.
- Author
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Lima WG, Campos ABDC, Brito JCM, Cardoso VN, and Fernandes SOA
- Subjects
- Animals, Antifungal Agents metabolism, Disease Models, Animal, Mice, Technetium, Tissue Distribution, Candida albicans metabolism, Candidiasis diagnostic imaging, Candidiasis drug therapy
- Abstract
Intra-abdominal candidiasis (IAC) occurs due to the direct inoculation of Candida into the sterile peritoneal cavity or leakage of the gastrointestinal tract. An important difference between the two forms of the disease is the presence of fecal material, which is exclusive to the latter condition. However, the influence of fecal material on the prognosis of IAC is still poorly understood. Furthermore, methodologies that use the quantification of fungal load by culture methods have low sensitivity, as they do not adequately show the precocity of the infectious process. Here, we developed a new method to evaluate the aspects of the pathophysiology of IAC, mainly the influence of fecal material on the prognosis of infection, by using C. albicans radiolabeled with technetium-99 m (
99 m Tc). C. albicans was successfully radiolabeled with99 m Tc (18.5 MBq) using dihydrate stannous chloride (100 µM) as a reducing agent. This binding was stable for 72 h. Viability, yeast-to-hyphae transition, morphology, and antifungal susceptibility were not altered by radiolabeling C. albicans with99 m Tc. The biomass and the fungal load of99 m Tc-C. albicans biofilms were reduced compared to the C. albicans non-radiolabeled after 72 h and 48 h of incubation, respectively. In the IAC model, the fungal load in the biodistribution of99 m Tc-C. albicans and culture assays was higher in animals receiving fungal inoculum without fecal material, suggesting that the presence of this component reduces the invasiveness of the pathogen., (Copyright © 2022 Elsevier GmbH. All rights reserved.)- Published
- 2022
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20. Trypanosoma cruzi infection increases atherosclerotic lesion in ApoE-deficient mice.
- Author
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Figueiredo VP, Silva MC, Souza DMS, Coelho Junior D, Lopes LR, Azevedo MA, Menezes APJ, de Lima WG, Peluzio MDCG, and Talvani A
- Subjects
- Animals, Chylomicrons, Endothelial Cells pathology, Mice, Mice, Inbred C57BL, Mice, Knockout, Apolipoproteins E deficiency, Apolipoproteins E genetics, Atherosclerosis complications, Atherosclerosis pathology, Chagas Disease complications, Trypanosoma cruzi
- Abstract
Apolipoprotein E (ApoE) is the major ligand for the transporting and removal of chylomicrons and lipoproteins by the liver. Since the creation of the ApoE-knockout mice, it is well established that ApoE deficiency results in spontaneous atherosclerosis in aged animals. Atherosclerosis is also observed in animals infected with Trypanosoma cruzi, a protozoan that elicits a systemic inflammatory response in mammalian hosts, culminating in damage to cardiac, neuronal, and endothelial cells. Pro-atherogenic effects related to the experimental infection with T. cruzi may be induced by inflammatory components affecting the vascular wall. Herein, we evaluated whether infection with different strains of T. cruzi worsened the atherogenic lesions observed in aged ApoE
-/- mice. After four weeks of infection with Berenice-78 (Be-78) or Colombian (Col) strains of the parasite, mice presented increased CCL2 and CCL5 production and high migration of inflammatory cells to cardiac tissue. Although the infection with either strain did not affect the survival rate, only the infection with Col strain caused abundant parasite growth in blood and heart and increased aortic root lesions in ApoE-/- mice. Our findings show, for the first time that ApoE exerts a protective anti-atherosclerotic role in the aortic root of mice in the acute phase of experimental infection with the Col strain of T. cruzi. Further studies should target ApoE and nutritional interventions to modulate susceptibility to cardiovascular disabilities after T. cruzi infection, minimizing the risk of death in both experimental animals and humans., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)- Published
- 2022
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21. Animal venoms as a source of antiviral peptides active against arboviruses: a systematic review.
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Lima WG, Maia CQ, de Carvalho TS, Leite GO, Brito JCM, Godói IPD, de Lima ME, and Ferreira JMS
- Subjects
- Animals, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Peptides pharmacology, Venoms pharmacology, Venoms therapeutic use, Yellow fever virus, Arboviruses, Chikungunya Fever, Chikungunya virus, Dengue drug therapy, West Nile virus, Zika Virus, Zika Virus Infection
- Abstract
Arthropod-borne viruses (arboviruses), such as Zika virus (ZIKV), chikungunya virus (CHIKV), dengue virus (DENV), yellow fever virus (YFV), and West Nile virus (WNV), are pathogens of global importance. Therefore, there has been an increasing need for new drugs for the treatment of these viral infections. In this context, antimicrobial peptides (AMPs) obtained from animal venoms stand out as promising compounds because they exhibit strong antiviral activity against emerging arboviral pathogens. Thus, we systematically searched and critically analyzed in vitro and in vivo studies that evaluated the anti-arbovirus effect of peptide derivatives from toxins produced by vertebrates and invertebrates. Thirteen studies that evaluated the antiviral action of 10 peptides against arboviruses were included in this review. The peptides were derived from the venom of scorpions, spiders, wasps, snakes, sea snails, and frogs and were tested against DENV, ZIKV, YFV, WNV, and CHIKV. Despite the high structural variety of the peptides included in this study, their antiviral activity appears to be associated with the presence of positive charges, an excess of basic amino acids (mainly lysine), and a high isoelectric point (above 8). These peptides use different antiviral mechanisms, the most common of which is the inhibition of viral replication, release, entry, or fusion. Moreover, peptides with virucidal and cytoprotective (pre-treatment) effects were also identified. In conclusion, animal-venom-derived peptides stand out as a promising alternative in the search and development of prototype antivirals against arboviruses., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)
- Published
- 2022
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22. Piperine as Therapeutic Agent in Paracetamol-Induced Hepatotoxicity in Mice.
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Coelho AM, Queiroz IF, Perucci LO, Souza MO, Lima WG, Talvani A, and Costa DC
- Abstract
High doses of paracetamol (APAP) can cause irreversible liver damage. Piperine (P) inhibits cytochrome P450, which is involved in the metabolism of various xenobiotics, including paracetamol. We evaluated the hepatoprotective effects of piperine with or without N-acetylcysteine (NAC) in APAP-induced hepatotoxicity. The mice were treated with two doses of piperine (P20 or P40) and/or NAC at 2 h after administration of APAP. The NAC+P20 and NAC+P40 groups showed a reduced area of necrosis, MMP-9 activity, and Casp-1 expression. Furthermore, the NAC+P20 group was the only treatment that reduced alanine aminotransferase (ALT) and increased the levels of sulfhydryl groups (-SH). In the NAC+P40 group, NLRP-3 expression was reduced. Aspartate aminotransferase (AST), thiobarbituric acid-reactive substances (TBARS), and IL-1β expression decreased in the NAC, NAC+P20, and NAC+P40 groups compared to the APAP group. The liver necrosis area, TNF levels, carbonylated protein, and IL-18 expression decreased in the P40, NAC, NAC+P20, and NAC+P40 groups compared to the APAP group. The cytokine IL-6 was reduced in all treatments. Piperine can be used in combination with NAC to treat APAP-induced hepatotoxicity., Competing Interests: The authors declare that there are no conflicts of interest.
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- 2022
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23. A 3-alkylpyridine-bearing alkaloid exhibits potent antimicrobial activity against methicillin-resistant Staphylococcus aureus (MRSA) with no detectable resistance.
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Herrera KMS, Lopes GFM, Oliveira ME, Sousa JF, Lima WG, Silva FK, Brito JCM, Gomes AJPS, Viana GHR, Soares AC, and Ferreira JMS
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- Anti-Bacterial Agents chemistry, Anti-Bacterial Agents pharmacology, Biofilms, Humans, Microbial Sensitivity Tests, Staphylococcus, Vancomycin pharmacology, Vancomycin therapeutic use, Alkaloids pharmacology, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections drug therapy
- Abstract
Staphylococcus aureus is a Gram-positive bacterium responsible for a wide variety of infectious diseases, and its methicillin-resistant isolates pose a serious worldwide public health risk. New drugs are urgently needed for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Here, we evaluated the antibacterial activity of five 3-alkyl-pyridinic analogs against MRSA and, of these compounds, compound 6 showed promising antibacterial activity against Staphylococcus with minimum inhibitory concentration (MIC) ranging from 0.98 to 3.9 μgmL
- ¹ . In addition, it exhibited a rapid bactericidal action, with complete elimination of MRSA after 6 h of incubation at 15.6 μgmL- ¹ . Compound 6 had the ability to damage the bacterial membrane and induce cell lysis and, due to its action on the membrane, showed low resistance induction potential in vitro. In the combination study, compound 6 revealed an additive effect (FICI = 1) with vancomycin and ofloxacin and ciprofloxacin (FICI = 0.75) against MRSA, reducing the effective concentration of this antibiotic two-fold. The anti-staphylococcal activity of compound 6 was stable in the presence of different concentrations of NaCl (50, 200, and 400 µM), trypsin ( 1:500, 1:250) and under a variety of pH values (4, 5, 6, and 8); however, its binding to plasmatic proteins (i.e., albumin) was substantial. The previous exposure of MRSA to the compound was able to reduce the formation of bacterial biofilm and reduce the biomass of mature biofilms. Compound 6 showed low selectivity in vitro for MRSA USA 300 when compared to eukaryotic cells (epithelial, fibroblast, and red blood cells)., (Copyright © 2022 Elsevier GmbH. All rights reserved.)- Published
- 2022
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24. Antifungal effect of hydroethanolic extract of Fridericia chica (Bonpl.) L. G. Lohmann leaves and its therapeutic use in a vulvovaginal candidosis model.
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Lima WG, Araújo MGF, Brito JCM, Castilho RO, Cardoso VN, and Fernandes SOA
- Subjects
- Animals, Candida, Candida albicans, Female, Humans, Plant Extracts pharmacology, Plant Extracts therapeutic use, Antifungal Agents pharmacology, Antifungal Agents therapeutic use, Candidiasis, Vulvovaginal drug therapy, Candidiasis, Vulvovaginal microbiology
- Abstract
Vulvovaginal candidosis (VVC) is one of the most frequent causes of gynecological consultations. Therefore, the development of new antifungal therapies against VVC is relevant. In this context, the leaves of Fridericia chica (Bonpl.) L. G. Lohmann are considered a therapeutic alternative since they are traditionally used in VVC therapy. However, no scientific evidence has supported this use against fungal vaginal infections. Then, we aimed to characterize the antifungal effect of a hydroethanolic extract of F. chica leaves (HEFc) and evaluate the therapeutic potential of this extract in a VVC model. HEFc inhibited the growth of C. albicans (256-1,204 µg/mL) and C. krusei (512 µg/mL) in vitro. HEFc inhibited yeast-to-hypha transition in C. albicans and has a low ability to induce resistance in this species. Intravaginal use of the HEFc at 50 mg/mL causes mycological cure in animals with VVC after 6 days of treatment, similar to the effect observed for the commercial antifungal nystatin. These results support the traditional use of F. chica leaves as a topical therapeutic option to treat VVC., (Copyright © 2022 SFMM. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2022
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25. Effect of honey and propolis, compared to acyclovir, against Herpes Simplex Virus (HSV)-induced lesions: A systematic review and meta-analysis.
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Rocha MP, Amorim JM, Lima WG, Brito JCM, and da Cruz Nizer WS
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- Acyclovir pharmacology, Antiviral Agents pharmacology, Herpes Simplex drug therapy, Herpes Simplex virology, Humans, Honey, Propolis pharmacology, Simplexvirus drug effects
- Abstract
Ethnopharmacological Relevance: Apitherapy is a branch of traditional medicine that uses bee products to manage numerous diseases. In this context, the antiherpetic effect of these bee products has been demonstrated in some studies with some controversial results., Aim of the Study: Thus, we conducted a systematic review and meta-analysis to compare the effectiveness of honey and propolis with acyclovir, the reference drug, in the treatment of cold sores and genital herpes., Materials and Methods: The selection of eligible studies was conducted through the search in Pubmed/MEDLINE, Scopus, Cochrane Library, LILACS, and Electronic Scientific Library., Results: The search yielded 147 articles, of which nine were considered eligible for analysis. The analysis of these studies showed that the healing property of propolis is superior to that obtained for acyclovir (95% CI: 2.70 to 8.25; p = 0.0001). Furthermore, honey also presented a better healing effect than acyclovir against Herpes simplex virus-induced wounds (95% CI: 3.58 to -0.19; p = 0.03), inducing complete re-epithelization of herpetic lesions after 8 days, while for acyclovir, the healing time average was 9 days. It also provoked a similar reduction of pain caused by herpetic compared to acyclovir (95% CI: 2.27 to -0.42; p = 0.18)., Conclusions: Overall, these results confirm the use of honey and propolis as potent antiherpetic agents., (Copyright © 2021 Elsevier B.V. All rights reserved.)
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- 2022
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26. NS2B-NS3 protease inhibitors as promising compounds in the development of antivirals against Zika virus: A systematic review.
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Nunes DAF, Santos FRDS, da Fonseca STD, de Lima WG, Nizer WSDC, Ferreira JMS, and de Magalhães JC
- Subjects
- Animals, Antiviral Agents chemistry, Humans, Molecular Targeted Therapy, Protease Inhibitors chemistry, Viral Nonstructural Proteins metabolism, Virus Replication drug effects, Zika Virus enzymology, Zika Virus Infection virology, Antiviral Agents pharmacology, Protease Inhibitors pharmacology, Viral Nonstructural Proteins antagonists & inhibitors, Zika Virus drug effects, Zika Virus Infection drug therapy
- Abstract
Zika virus (ZIKV) infections are associated with severe neurological complications and are a global public health concern. There are no approved vaccines or antiviral drugs to inhibit ZIKV replication. NS2B-NS3 protease (NS2B-NS3 pro), which is essential for viral replication, is a promising molecular target for anti-ZIKV drugs. We conducted a systematic review to identify compounds with promising effects against ZIKV; we discussed their pharmacodynamic and pharmacophoric characteristics. The online search, performed using the PubMed/MEDLINE and SCOPUS databases, yielded 56 articles; seven relevant studies that reported nine promising compounds with inhibitory activity against ZIKV NS2B-NS3 pro were selected. Of these, five (niclosamide, nitazoxanide, bromocriptine, temoporfin, and novobiocin) are currently available on the market and have been tested for off-label use against ZIKV. The 50% inhibitory concentration values of these compounds for the inhibition of NS2B-NS3 pro ranged at 0.38-21.6 µM; most compounds exhibited noncompetitive inhibition (66%). All compounds that could inhibit the NS2B-NS3 pro complex showed potent in vitro anti-ZIKV activity with a 50% effective concentration ranging 0.024-50 µM. The 50% cytotoxic concentration of the compounds assayed using A549, Vero, and WRL-69 cell lines ranged at 0.6-1388.02 µM and the selectivity index was 3.07-1698. This review summarizes the most promising antiviral agents against ZIKV that have inhibitory activity against viral proteases., (© 2021 Wiley Periodicals LLC.)
- Published
- 2022
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27. Antifungal activity of a novel 3-Alkylpyridine analog derived from Marine sponge alkaloids.
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Andrade JT, Lima WG, Barbosa CS, Gonçalves AMMN, Silva MKP, Morais FB, Palumbo JMC, Viana GHR, and Ferreira JMS
- Subjects
- Animals, Antifungal Agents pharmacology, Candida, Microbial Sensitivity Tests, Alkaloids pharmacology, Porifera
- Abstract
Candida spp. is considered an important cause of healthcare-associated infections worldwide. Currently, the emergence and spread of resistant Candida isolates are being increasingly reported, making the development of new agents urgently needed. In this study, we showed the in vitro anti-Candida activity of seven synthetic 3-alkylpyridine alkaloid analogs. Among them, alkaloid 1 presented a potent antifungal effect, which was independent of its capacity of binding with the fungal membrane ergosterol or cell wall. Analog 1 showed fungistatic and fungicidal effects against C. albicans (MIC 7.8 μg/mL and MFC 62.5 μg/mL), C. glabrata, C. krusei (MIC and MFC 31.2 μg/mL), and C. tropicalis (MIC 31.2 μg/mL and MFC 125 μg/mL). The time kill-curve study showed that compound 1 has a potent fungicidal effect in vitro, eliminating C. albicans cells. Furthermore, an in vitro synergistic effect with ketoconazole was observed for compound 1. This compound also eliminated the yeast-to-hypha transition. However, it showed high cytotoxicity against mammalian cells. Taken together, these findings support the use of compound 1 as a prototype to develop new anti-Candida agents, but molecular modifications should be done to minimize the high cytotoxicity obtained.
- Published
- 2021
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28. Aerobic exercise training prevents impairment in renal parameters and in body composition of rats fed a high sucrose diet.
- Author
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de Souza JA, Pinto ABG, de Oliveira EC, Coelho DB, Totou NL, de Lima WG, and Becker LK
- Subjects
- Animals, Body Composition, Creatinine, Diet, Exercise, Glomerular Filtration Rate, Kidney physiology, Sucrose
- Abstract
Objective: This study aimed to evaluate the effect of swimming training (T) on the renal system and body composition parameters in young animals treated with a high sucrose diet (SUD) during 12 weeks., Results: The SUD impaired the physical performance, increased the body adiposity index (BAI), Lee index (LI) and retroperitoneal adipose tissue (RAT) weight, plasma creatinine and number renal cells nuclei, decreased urinary volume and urinary creatinine excretion besides creatinine clearance. The T reversed the increased the BAI, LI, RAT weight, plasma and urinary creatinine, creatinine clearance and number renal cells nuclei in addition to promoting decrease in urinary protein excretion. This study found that eight weeks of swimming physical training protected renal function and restored normal glomerular filtration rate (GFR) values. Swimming training also contributed to prevention of the onset of a renal inflammatory process and caused a decrease in the risk of development of obesity promoted by SUD decreasing the body composition parameters (BAI, LI, and RAT weight)., (© 2021. The Author(s).)
- Published
- 2021
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29. Jaboticaba ( Myrciaria cauliflora ) Peel Supplementation Prevents Hepatic Steatosis Through Hypolipidemic Effects and Cholesterol Metabolism Modulation in Diet-Induced Nonalcoholic Fatty Liver Disease Rat Model.
- Author
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Lage NN, Carvalho MMF, Guerra JFDC, Lopes JMM, Pereira RR, Rabelo ACS, Arruda VM, Pereira MFA, Layosa MA, Noratto GD, Lima WG, Silva ME, and Pedrosa ML
- Subjects
- Animals, Anthocyanins, Cholesterol, Diet, High-Fat adverse effects, Dietary Supplements, Liver, Rats, Tandem Mass Spectrometry, Non-alcoholic Fatty Liver Disease drug therapy, Non-alcoholic Fatty Liver Disease prevention & control
- Abstract
Jaboticaba ( Myrciaria cauliflora ), a Brazilian fruit, is a good source of dietary fiber and phenolic compounds, which are concentrated mainly in the peel. These compounds have been considered promising in prevention and treatment of hypercholesterolemia and hepatic steatosis. In this study, we investigated the effects of 4% jaboticaba peel powder (JPP) supplementation on cholesterol metabolism and hepatic steatosis in livers of rats fed a high-fat (HF) diet. The rats were fed a standard AIN-93M (control) diet or an HF diet containing 32% lard and 1% cholesterol, both with and without 4% JPP. The M. cauliflora peel composition revealed a low-lipid high-fiber content and phenolic compounds. The phenolic compounds in JPP, tentatively identified by high-performance liquid chromatography and mass spectrometry (HPLC-MS/MS) analysis, were confirmed to contain phenolic acids, flavonoids, and anthocyanins. Moreover, JPP presented significant antioxidant activity in vitro and was not cytotoxic to HepG2 cells, as determined by the lactate dehydrogenase (LDH) assay. After 6 weeks of treatment, our results showed that JPP supplementation increased lipid excretion in feces, reduced serum levels of total cholesterol and nonhigh-density lipoprotein cholesterol, decreased serum aspartate aminotransferase (AST) activity, and attenuated hepatic steatosis severity in rats fed the HF diet. Furthermore, JPP treatment downregulated expression of ACAT-1 , LXR-α , CYP7A1 , and ABCG5 genes. Therefore, jaboticaba peel may represent a viable dietary strategy to prevent nonalcoholic fatty liver disease as the JPP treatment alleviated hepatic steatosis through improvement of serum lipid profiles and modulation of mRNA expression of genes involved in cholesterol metabolism.
- Published
- 2021
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30. Effectiveness of supplementation with quercetin-type flavonols for treatment of viral lower respiratory tract infections: Systematic review and meta-analysis of preclinical studies.
- Author
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Brito JCM, Lima WG, Cordeiro LPB, and da Cruz Nizer WS
- Subjects
- Animals, Dietary Supplements, Humans, Flavonols therapeutic use, Quercetin therapeutic use, Respiratory Tract Infections drug therapy, Respiratory Tract Infections virology, Virus Diseases drug therapy
- Abstract
Viral infections of the lower respiratory tract are considered a public health problem. They affect millions of people worldwide, causing thousands of deaths, and are treated with expensive medicines, such as antivirals or palliative measures. In this study, we conducted a systematic review to describe the use of quercetin-type flavonols against lower respiratory tract viruses and discussed the preclinical impact of this approach on different signs and clinical mechanisms of infection. The systematic review was performed in PubMed/MEDLINE, Scopus, Scielo, and Biblioteca Virtual de Saúde (BVS). After the database search, 11 relevant studies were identified as eligible. The analysis of these studies showed evidence of antiviral activity of quercetin-type flavonols with significantly reduced mortality rate (M-H = 0.19, 95% CI: 0.05 to 0.65, p-value = 0.008) of infected animals and a reduction in the average viral load (IV = -1.93, 95% CI: -3.54 to -0.31, p-value = 0.02). Additionally, quercetin and its derivatives reduced the amount of proinflammatory cytokines, chemokines, reactive oxygen species, mucus production, and airway resistance in animals infected with a respiratory virus. Overall, supplementation with quercetin-type flavonols is a promising strategy for treating viral-induced lower respiratory tract infections., (© 2021 John Wiley & Sons Ltd.)
- Published
- 2021
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31. Effects of physical exercise combined with captopril or losartan on left ventricular hypertrophy of hypertensive rats.
- Author
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Tomaz de Castro QJ, Araujo CM, Watai PY, de Castro E Silva SS, de Lima WG, Becker LK, Locatelli J, Guimarães HN, and Grabe-Guimarães A
- Subjects
- Animals, Antihypertensive Agents pharmacology, Antihypertensive Agents therapeutic use, Blood Pressure drug effects, Captopril pharmacology, Matrix Metalloproteinase 2 pharmacology, Rats, Rats, Inbred SHR, Hypertension drug therapy, Hypertrophy, Left Ventricular prevention & control, Losartan pharmacology
- Abstract
Background: Left ventricular hypertrophy (LVH) is an endpoint of hypertensive cardiac alterations. Renin-angiotensin-aldosterone system (RAAS) blockers are among the most effective on LVH regression. Physical exercise combined to antihypertensive drug contributes to arterial pressure (AP) control and LVH prevention. We evaluated the effects of physical exercise combined to captopril or losartan during eight weeks for spontaneously hypertensive rats (SHR) on some cardiac parameters. Methods: SHR (n=5-6 per group) were sedentary or trained 5 days a week in treadmill during 8 weeks; and they were treated with daily oral captopril (12.5, 25, or 50mg/kg), losartan (2.5, 5, or 10mg/kg), or vehicle. At the end, it was obtained systolic AP (SAP), electrocardiogram (ECG), and hearts metalloproteinase 2 (MMP-2) activity and histology. Results: Captopril 25 and 50 mg/kg, and losartan 10 mg/kg lowered SAP of sedentary and trained SHR. Losartan 5 mg/kg combined with physical exercise also lowered SAP. Combined with exercise, captopril 50 mg/kg lowered 13.6% of QT interval, 14.2% of QTc interval, and 22.8% of Tpeak-Tend compared to sedentary SHR. Losartan 5 and 10mg/kg lowered QT interval of sedentary and trained SHR. Losartan 2.5, 5 and 10mg/kg combined with physical exercise lowered respectively 25.4%, 24.8%, and 31.8% of MMP-2 activity. Losartan (10mg/kg) combined with exercise reduced cardiomyocyte diameter. Conclusion: These data support the hypothesis of physical exercise combined with RAAS blockers could improve the benefits on hypertensive LVH treatment.
- Published
- 2021
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32. Bauhinia holophylla (Bong.) Steud. leaves-derived extracts as potent anti-dengue serotype 2.
- Author
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Dos Santos M, Teixeira TR, Santos FRDS, Lima WG, Ferraz AC, Silva NL, Leite FJ, Siqueira JM, Luyten W, de Castro AHF, de Magalhães JC, and Ferreira JMS
- Subjects
- Animals, Cells, Cultured, Dengue drug therapy, Humans, Plant Leaves chemistry, Serogroup, Antiviral Agents isolation & purification, Antiviral Agents pharmacology, Bauhinia chemistry, Dengue Virus drug effects, Plant Extracts pharmacology
- Abstract
Dengue virus (DENV) is the most prevalent mosquito-borne viral pathogen and made the disease a major health concern worldwide. However, specific antiviral drugs against this arbovirose or vaccines are not yet available for treatment or prevention. Thus, here we aimed to study the antiviral activity of hydroethanolic extract, fraction ethyl acetate and subfractions of the leaves of Bauhinia holophylla (Fabaceae:Cercideae), a native plant of the Brazilian Cerrado, against DENV-2 by methylthiazolyldiphenyl-tetrazolium bromide (MTT) method in mammalian cells culture. As results, the hydroethanolic extract showed the most potent effect, with an inhibitory concentration (IC
50 ) of 3.2 μg mL-1 and selectivity index (SI) of 27.6, approximately 16-times higher anti-DENV-2 activity than of the ribavirin (IC50 52.8 μg mL-1 ). Our results showed in this study appointed that B. holophylla has a promising anti-dengue activity, which was associated mainly with the presence of flavonoids.- Published
- 2021
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33. Oral administration of angiotensin-(1-7) decreases muscle damage and prevents the fibrosis in rats after eccentric exercise.
- Author
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Totou NL, de Moura SS, Martins Júnior FAD, de Sousa FB, Coelho DB, de Oliveira EC, Dos Santos RAS, Becker LK, and de Lima WG
- Subjects
- Administration, Oral, Angiotensin I, Animals, Fibrosis, Male, Muscle, Skeletal physiology, Peptide Fragments, Rats, Rats, Wistar, Physical Conditioning, Animal physiology
- Abstract
New Findings: What is the central question of this study? Eccentric contraction exercises cause damage to muscle fibres and induce inflammatory responses. The exacerbation of this process can induce deposition of fibrous connective tissue, leading to decreased muscle function. The aim of this study was to examine the role of angiotensin-(1-7) in this context. What is the main finding and its importance? Our results show that oral treatment with angiotensin-(1-7) decreases muscle damage induced by eccentric exercise, reducing inflammation and fibrosis in the gastrocnemius and soleus muscles. This study shows a potential effect of angiotensin-(1-7) for the prevention of muscle injuries induced by physical exercise., Abstract: Eccentric contraction exercises cause damage to the muscle fibres and induce an inflammatory reaction. The protective effect of angiotensin-(1-7) [Ang-(1-7)] in skeletal muscle has led us to examine the role of this peptide in modifying processes associated with inflammation and fibrogenesis induced by eccentric exercise. In this study, we sought to investigate the effects of oral administration of Ang-(1-7) formulated in hydroxypropyl β-cyclodextrin (HPβ-CD) in prevention and treatment of muscle damage after downhill running. Male Wistar rats were divided into three groups: control (untreated and not exercised; n = 10); treated/exercised HPβ-CD Ang-(1-7) (n = 40); and treated/exercised HPβ-CD (n = 40). Exercised groups were subjected to a single eccentric contraction exercise session on a treadmill inclined to -13° at a constant speed of 20 m/min, for 60 min. Oral administration of HPβ-CD Ang-(1-7) and HPβ-CD was performed 3 h before the exercise protocol and daily as a single dose, until the end of the experiment. Samples were collected 4, 12, 24, 48 and 72 h after the exercise session. The animals treated with the Ang-(1-7) showed lower levels of creatine kinase, lower levels of tumor necrosis factor-α in soleus muscle and increased levels of interleukin-10 cytokines. The inflammatory cells and deposition of fibrous connective tissue in soleus and gastrocnemius muscles were lower in the group treated with Ang-(1-7). The results of this study show that treatment with an oral formulation of Ang-(1-7) enhances the process of repair of muscle injury induced by eccentric exercise., (© 2021 The Authors. Experimental Physiology © 2021 The Physiological Society.)
- Published
- 2021
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34. Repositioning of Tamoxifen in Surface-Modified Nanocapsules as a Promising Oral Treatment for Visceral Leishmaniasis.
- Author
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Silva DF, Reis LES, Machado MGC, Dophine DD, de Andrade VR, de Lima WG, Andrade MS, Vilela JMC, Reis AB, Pound-Lana G, Rezende SA, and Mosqueira VCF
- Abstract
Standards of care for human visceral leishmaniasis (VL) are based on drugs used parenterally, and oral treatment options are urgently needed. In the present study, a repurposing strategy was used associating tamoxifen (TMX) with polyethylene glycol- block -polylactide nanocapsules (NC) and its anti-leishmanial efficacy was reported in vivo. Stable surface modified-NC (5 mg/mL of TMX) exhibited 200 nm in size, +42 mV of zeta potential, and 98% encapsulation efficiency. Atomic force microscopy evidenced core-shell-NC. Treatment with TMX-NC reduced parasite-DNA quantified in liver and spleen compared to free-TMX; and provided a similar reduction of parasite burden compared with meglumine antimoniate in mice and hamster models. Image-guided biodistribution showed accumulation of NC in liver and spleen after 30 min post-administration. TMX-NC reduced the number of liver granulomas and restored the aspect of capsules and trabeculae in the spleen of infected animals. TMX-NC was tested for the first time against VL models, indicating a promising formulation for oral treatment.
- Published
- 2021
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35. A short synthetic peptide, based on LyeTx I from Lycosa erythrognatha venom, shows potential to treat pneumonia caused by carbapenem-resistant Acinetobacter baumannii without detectable resistance.
- Author
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Lima WG, Brito JCM, de Lima ME, Pizarro ACST, Vianna MAMM, de Paiva MC, de Assis DCS, Cardoso VN, and Fernandes SOA
- Subjects
- Acinetobacter Infections drug therapy, Acinetobacter Infections microbiology, Acinetobacter baumannii isolation & purification, Animals, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents toxicity, Biofilms drug effects, Carbapenems pharmacology, Chlorocebus aethiops, Drug Resistance, Bacterial drug effects, Drug Stability, Drug Synergism, Female, Humans, Mice, Inbred BALB C, Microbial Sensitivity Tests, Peptides chemistry, Pneumonia, Bacterial microbiology, Vero Cells, Mice, Acinetobacter baumannii drug effects, Anti-Bacterial Agents pharmacology, Peptides pharmacology, Pneumonia, Bacterial drug therapy, Spider Venoms chemistry
- Abstract
The emergence of antibiotic-resistant bacteria, especially carbapenem-resistant Acinetobacter baumannii (CRAB), together with relative stagnation in the development of effective antibiotics, has led to enormous health and economic problems. In this study, we aimed to describe the antibacterial spectrum of LyeTx I mnΔK, a short synthetic peptide based on LyeTx I from Lycosa erythrognatha venom, against CRAB. LyeTx I mnΔK showed considerable antibacterial activity against extensively resistant A. baumannii, with minimum inhibitory and bactericidal concentrations ranging from 1 to 16 µM and 2 to 32 µM, respectively. This peptide significantly increased the release of 260 nm-absorbing intracellular material from CRAB, suggesting bacteriolysis. LyeTx I mnΔK was shown to act synergistically with meropenem and colistin against CRAB. The cytotoxic concentration of LyeTx I mnΔK against Vero cells (CC
50 = 55.31 ± 5.00 µM) and its hemolytic activity (HC50 = 77.07 ± 4.00 µM) were considerably low; however, its antibacterial activity was significantly reduced in the presence of human and animal serum and trypsin. Nevertheless, the inhalation of this peptide was effective in reducing pulmonary bacterial load in a mouse model of CRAB infection. Altogether, these results demonstrate that the peptide LyeTx I mnΔK is a potential prototype for the development of new effective and safe antibacterial agents against CRAB.- Published
- 2021
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36. High-Density-Immune-Complex Regulatory Macrophages Promote Recovery of Experimental Colitis in Mice.
- Author
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Lopes TCM, Almeida GG, Souza IA, Borges DC, de Lima WG, Prazeres PHDM, Birbrair A, Arantes RME, Mosser DM, and Goncalves R
- Subjects
- Animals, Cells, Cultured, Colitis chemically induced, Colitis immunology, Colitis metabolism, Colon metabolism, Colon pathology, Dextran Sulfate, Disease Models, Animal, Interleukin-10 metabolism, Lipopolysaccharides pharmacology, Macrophages immunology, Macrophages metabolism, Male, Mice, Inbred C57BL, Phenotype, Mice, Adoptive Transfer, Antigen-Antibody Complex pharmacology, Colitis therapy, Colon immunology, Macrophage Activation drug effects, Macrophages drug effects, Macrophages transplantation
- Abstract
Macrophages not only play a fundamental role in the pathogenesis of inflammatory bowel disease (IBD), but they also play a major role in preserving intestinal homeostasis. In this work, we evaluated the role of macrophages in IBD and investigated whether the functional reprogramming of macrophages to a very specific phenotype could decrease disease pathogenesis. Thus, macrophages were stimulated in the presence of high-density immune complexes which strongly upregulate their production of IL-10 and downregulate pro-inflammatory cytokines. The transfer of these high-density-immune-complex regulatory macrophages into mice with colitis was examined as a potential therapy proposal to control the disease. Animals subjected to colitis induction received these high-density-immune-complex regulatory macrophages, and then the Disease Activity Index (DAI), and macroscopic and microscopic lesions were measured. The treated group showed a dramatic improvement in all parameters analyzed, with no difference with the control group. The colon was macroscopically normal in appearance and size, and microscopically colon architecture was preserved. The immunofluorescence migration assay showed that these cells migrated to the inflamed intestine, being able to locally produce the cytokine IL-10, which could explain the dramatic improvement in the clinical and pathological condition of the animals. Thus, our results demonstrate that the polarization of macrophages to a high IL-10 producer profile after stimulation with high-density immune complexes was decisive in controlling experimental colitis, and that macrophages are a potential therapeutic target to be explored in the control of colitis.
- Published
- 2021
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37. Epilepsy in children with Congenital Zika Syndrome: A systematic review and meta-analysis.
- Author
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Maia CQ, Lima WG, Nizer WSDC, and Ferreira JMS
- Subjects
- Child, Humans, Incidence, Epilepsy epidemiology, Epilepsy virology, Zika Virus Infection complications, Zika Virus Infection congenital
- Abstract
Objectives: To estimate the overall frequency of epilepsy in children with congenital Zika syndrome (CZS) and describe the profile of seizures and the response rate to anti-epileptic treatment in this group of patients., Methods: A systematic review and meta-analysis were conducted following the Cochrane Handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. PubMed/MEDLINE, Scopus, Cochrane Library, SciELO, and LILACS were searched until June 23, 2020. Observational studies that evaluated the frequency of epilepsy in children diagnosed with CZS according to international criteria were included in the study., Results: Fourteen studies evaluating 903 patients diagnosed with CZS were pooled in a meta-analysis. All studies were conducted in Brazil, with reports published between 2016 and 2020, and included children diagnosed with CSZ from 0 to 40 months of age. The overall rate of epilepsy in children diagnosed with CZS was estimated at 60% (95% confidence interval [CI] 0.51-0.68). The studies included in this review show that the frequency of epilepsy in patients with CSZ varies with age, with higher rates in older children. Epileptic spasms was the primary type of seizure observed in this group, followed by focal and generalized crisis. The response rate to anti-epileptic drugs was considerably low, ranging from 20% of seizure control in the first year and 30% in the second year., Significance: Children with CZS presented a high cumulative incidence of epilepsy episodes with increased severity and a low response to anti-epileptic therapy, which is associated with the extensive damage caused by the Zika virus on the cortical structures of patients., (© 2021 International League Against Epilepsy.)
- Published
- 2021
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38. Shiga toxin-producing Escherichia coli (STEC) in bovine meat and meat products over the last 15 years in Brazil: A systematic review and meta-analysis.
- Author
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de Assis DCS, da Silva TML, Brito RF, da Silva LCG, Lima WG, and Brito JCM
- Subjects
- Animals, Brazil, Cattle, Food Contamination analysis, Meat Products microbiology, Red Meat microbiology, Shiga-Toxigenic Escherichia coli isolation & purification
- Abstract
We conducted a systematic review and meta-analysis to determine the rate of contamination in bovine meat and meat products with Shiga toxin-producing Escherichia coli (STEC) in Brazil over the last fifteen years. Data were obtained from online databases in February 2020, and 25 papers were selected from 1036 articles identified in the literature search and 13 articles from gray literature, totaling 4286 samples analyzed. The overall rate of STEC was estimated to be 1% in Brazil. The highest rate (9%) was observed in Mato Grosso, followed by Rio Grande do Sul (1%), Goiás (1%), and São Paulo (1%). Regarding the sample type analyzed, hot carcasses had the highest rate (8%) of positive samples for STEC, followed by cold carcasses (2%) and beef samples (1%). As the available data were concentrated in the São Paulo state, the findings of this meta-analysis reveal the need for further studies in Brazil to allow better risk assessment and prevention of human STEC infections., (Copyright © 2020 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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39. Pristimerin isolated from Salacia crassifolia (Mart. Ex. Schult.) G. Don. (Celastraceae) roots as a potential antibacterial agent against Staphylococcus aureus.
- Author
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Nizer WSDC, Ferraz AC, Moraes TFS, Lima WG, Santos JPD, Duarte LP, Ferreira JMS, de Brito Magalhães CL, Vieira-Filho SA, Andrade ACDSP, Rodrigues RAL, Abrahão JS, and Magalhães JC
- Subjects
- Animals, Anti-Bacterial Agents isolation & purification, Biofilms drug effects, Chlorocebus aethiops, Gram-Positive Bacteria drug effects, Microbial Sensitivity Tests, Pentacyclic Triterpenes, Plant Roots, Staphylococcal Infections drug therapy, Triterpenes isolation & purification, Vero Cells, Anti-Bacterial Agents pharmacology, Salacia chemistry, Staphylococcus aureus drug effects, Triterpenes pharmacology
- Abstract
Ethnopharmacological Relevance: Pristimerin is a triterpenoid considered the main component of Salacia crassifolia extracts. This terpene has shown promising antitumor, anti-inflammatory, and antimicrobial effects. Likewise, S. crassifolia has been used in traditional medicine to treat cancer and as an antimicrobial and anti-inflammatory agent., Aim of the Study: This study aimed to evaluate the antibacterial activity of the hexane extract of Salacia crassifolia roots (HER) and its isolate, pristimerin, against pathogenic bacteria., Materials and Methods: First, we evaluated the spectrum of action of HER and pristimerin by the determination of the minimum inhibitory concentration (MIC) and the minimal bactericidal concentration (MBC). Subsequently, we analyzed the time-kill curve of these plant-derived compounds against Staphylococcus aureus. Then, we examined their mode of action by three different assays: the crystal violet methodology, the release of intracellular material, and transmission electron microscopy methods (TEM). Finally, we evaluated the effect of HER and pristimerin on the pre-formed biofilm of S. aureus by the crystal violet assay, the synergistic effect by the checkerboard method, the cytotoxicity against Vero cells, and the in silico activity using the online software PASS., Results: HER and pristimerin presented a narrow spectrum of action against Gram-positive bacteria (MIC 0.195-25 μg/mL), and their primary mode of action is the alteration of membrane permeability of S. aureus. Our results show that the compounds disrupted the pre-formed biofilm of S. aureus in a dose-dependent manner. Furthermore, HER and pristimerin presented a significant synergic effect after the combination with well-known antibiotics, which was associated with the ability of these phytomedicines to change membrane permeability. Regarding the cytotoxic effect, the selective index (SI) of HER ranged from 0.37 to 11.86, and the SI of pristimerin varied from 0.24 to 30.87, according to the bacteria tested., Conclusions: Overall, HER and pristimerin showed a promising antibacterial effect in vitro through the alteration of membrane permeability of S. aureus., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
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40. Rate of exposure to Mayaro virus (MAYV) in Brazil between 1955 and 2018: a systematic review and meta-analysis.
- Author
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Lima WG, Pereira RS, da Cruz Nizer WS, Brito JCM, Godói IP, Cardoso VN, Fernandes SOA, and Ferreira JMS
- Subjects
- Alphavirus pathogenicity, Animals, Brazil epidemiology, Disease Outbreaks, Humans, Alphavirus Infections epidemiology, Alphavirus Infections virology
- Abstract
Mayaro fever is an infection caused by Mayaro virus (MAYV) that stands out among the neglected diseases transmitted by arthropods. Brazil is the country with the highest number of confirmed cases of MAYV infection. However, epidemiological surveillance studies conducted in Brazil are decentralized and focus on small outbreaks and unconfirmed cases. Thus, the aim of this review was to determine the general epidemiological profile of MAYV infections in Brazil. Several medical databases (i.e., PUBMED/MEDLINE, Scopus, Cochrane Library, LILACS, SciELO, and Biblioteca Virtual em Saúde) were searched for studies reporting cases of MAYV infections in Brazilian patients. Then, the rate of exposure to MAYV in Brazil was analyzed using RStudio® Software. We identified 37 studies published from 1957 to 2019, containing data of 12,374 patients from 1955 to 2018. The general rate of exposure to MAYV in Brazil was 10% (95% CI; 0.04-0.22), with 1,304 reported cases. The highest incidence of MAYV infection was found in the northern region (13%; 95% CI; 0.05-0.29), with 1,142 cases (88% of all cases). Furthermore, autochthonous MAYV cases have also been reported in the Central West (8%; 95% CI; 0.03-0.18) and Southeast (0.4%; 95% CI; 0.00-0.28). The states with the highest number of cases are Amazonas (490 cases), Pará (276 cases), and Goiás (87 cases). In conclusion, the general rate of exposure to MAYV in Brazil between 1955 and 2018 was considerable, especially in the Legal Amazon, in which 93% of cases were reported.
- Published
- 2021
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41. Bee products as a source of promising therapeutic and chemoprophylaxis strategies against COVID-19 (SARS-CoV-2).
- Author
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Lima WG, Brito JCM, and da Cruz Nizer WS
- Subjects
- Animals, Antiviral Agents metabolism, Antiviral Agents therapeutic use, Biological Products metabolism, COVID-19 epidemiology, Fatty Acids physiology, Honey, Humans, Pollen physiology, Propolis metabolism, Propolis therapeutic use, SARS-CoV-2 physiology, Waxes metabolism, Waxes therapeutic use, Apitherapy methods, Apitherapy trends, Bees metabolism, Biological Products therapeutic use, COVID-19 prevention & control, Chemoprevention methods, SARS-CoV-2 drug effects
- Abstract
The emergence of novel coronavirus (SARS-CoV-2) in 2019 in China marked the third outbreak of a highly pathogenic coronavirus infecting humans. The novel coronavirus disease (COVID-19) spread worldwide, becoming an emergency of major international concern. However, even after a decade of coronavirus research, there are still no licensed vaccines or therapeutic agents to treat the coronavirus infection. In this context, apitherapy presents as a promising source of pharmacological and nutraceutical agents for the treatment and/or prophylaxis of COVID-19. For instance, several honeybee products, such as honey, pollen, propolis, royal jelly, beeswax, and bee venom, have shown potent antiviral activity against pathogens that cause severe respiratory syndromes, including those caused by human coronaviruses. In addition, the benefits of these natural products to the immune system are remarkable, and many of them are involved in the induction of antibody production, maturation of immune cells, and stimulation of the innate and adaptive immune responses. Thus, in the absence of specific antivirals against SARS-CoV-2, apitherapy could offer one hope toward mitigating some of the risks associated with COVID-19., (© 2020 John Wiley & Sons Ltd.)
- Published
- 2021
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42. Swimming training improves cardiovascular autonomic dysfunctions and prevents renal damage in rats fed a high-sodium diet from weaning.
- Author
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de Souza JA, Becker LK, Batista MAC, de Assis Braga DC, Gomes PM, Alzamora AC, Vieira MAR, de Lima WG, Andrade MGC, de Lima Sanches B, Totou NL, de Assis Dias Martins Júnior F, de Oliveira LB, Antunes VR, and Cardoso LM
- Subjects
- Animals, Autonomic Nervous System pathology, Diet, Heart Rate physiology, Hypertension pathology, Kidney pathology, Male, Physical Conditioning, Animal, Rats, Rats, Wistar, Swimming, Water-Electrolyte Balance, Autonomic Nervous System physiopathology, Blood Pressure physiology, Hypertension physiopathology, Kidney physiopathology, Sodium, Dietary
- Abstract
New Findings: What is the central question of this study? How does swimming exercise training impact hydro-electrolytic balance, renal function, sympathetic contribution to resting blood pressure and cerebrospinal fluid (CSF) [Na
+ ] in rats fed a high-sodium diet from weaning? What is the main finding and its importance? An exercise-dependent reduction in blood pressure was associated with decreased CSF [Na+ ], sympathetically driven vasomotor tonus and renal fibrosis indicating that the anti-hypertensive effects of swimming training in rats fed a high-sodium diet might involve neurogenic mechanisms regulated by sodium levels in the CSF rather than changes in blood volume., Abstract: High sodium intake is an important factor associated with hypertension. High-sodium intake with exercise training can modify homeostatic hydro-electrolytic balance, but the effects of this association are mostly unknown. In this study, we sought to investigate the effects of swimming training (ST) on cerebrospinal fluid (CSF) Na+ concentration, sympathetic drive, blood pressure (BP) and renal function of rats fed a 0.9% Na+ (equivalent to 2% NaCl) diet with free access to water for 22 weeks after weaning. Male Wistar rats were assigned to two cohorts: (1) fed standard diet (SD) and (2) fed high-sodium (HS) diet. Each cohort was further divided into trained and sedentary groups. ST normalised BP levels of HS rats as well as the higher sympathetically related pressor activity assessed by pharmacological blockade of ganglionic transmission (hexamethonium). ST preserved the renal function and attenuated the glomerular shrinkage elicited by HS. No change in blood volume was found among the groups. CSF [Na+ ] levels were higher in sedentary HS rats but were reduced by ST. Our findings showed that ST effectively normalised BP of HS rats, independent of its effects on hydro-electrolytic balance, which might involve neurogenic mechanisms regulated by Na+ levels in the CSF as well as renal protection., (© 2020 The Authors. Experimental Physiology © 2020 The Physiological Society.)- Published
- 2021
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43. Circulating Leptin Levels as a Potential Biomarker in Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis.
- Author
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de Carvalho LGF, Lima WG, Coelho LGV, Cardoso VN, and Fernandes SOA
- Subjects
- Biomarkers blood, Humans, Colitis, Ulcerative diagnosis, Crohn Disease diagnosis, Leptin blood
- Abstract
Background: The differential diagnosis of inflammatory bowel diseases (IBDs) between Crohn's disease (CD) and ulcerative colitis (UC) is important for designing an effective therapeutic regimen. However, without any adequate gold standard method for differential diagnosis currently, therapeutic design remains a major challenge in clinical practice. In this context, recent studies have showed that circulating leptin stands out as a potential biomarker for the categorization of IBDs. Thus, we aimed to summarize the current understanding of the prognostic and diagnostic value of serum leptin in patients with IBDs., Methods: A systematic search was performed in PubMed/MEDLINE, Scopus, Cochrane Library, and Web of Science databases. Articles that aimed to study the relationship between circulating levels of leptin and IBDs were included. Finally, the meta-analysis was performed with the mean serum leptin levels in patients with IBDs and healthy controls using RevMan 5.3 software, with I2 > 50% as a criterion for substantial heterogeneity., Results: Nineteen studies were included. Serum leptin levels among patients with IBDs and healthy controls did not show a significant difference (95% CI, -2.15 to 0.57; I2, 86%, P ≤ 0.00001). Similarly, there was no association of leptin levels with the activity of IBDs (95% CI, -0.24 to 0.06; I2, 50%; P = 0.13). However, serum leptin levels were significantly higher in patients with CD than those in patients with UC (95% CI, -2.09 to -0.37; I2, 7%; P ≤ 0.36)., Conclusion: This review suggested that serum leptin levels might be a promising biomarker to help in the differentiation between CD and UC., (© 2020 Crohn’s & Colitis Foundation. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
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44. Design, synthesis, and biodistribution studies of new analogues of marine alkaloids: Potent in vitro and in vivo fungicidal agents against Candida spp.
- Author
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Andrade JT, Lima WG, Sousa JF, Saldanha AA, Nívea Pereira De Sá, Morais FB, Prates Silva MK, Ribeiro Viana GH, Johann S, Soares AC, Araújo LA, Antunes Fernandes SO, Cardoso VN, and Siqueira Ferreira JM
- Subjects
- Alkaloids chemical synthesis, Alkaloids chemistry, Antifungal Agents chemical synthesis, Antifungal Agents chemistry, Dose-Response Relationship, Drug, Fungicides, Industrial chemical synthesis, Fungicides, Industrial chemistry, Microbial Sensitivity Tests, Molecular Structure, Structure-Activity Relationship, Alkaloids pharmacology, Antifungal Agents pharmacology, Candida drug effects, Drug Design, Fungicides, Industrial pharmacology
- Abstract
Invasive candidiasis, such as intra-abdominal candidiasis (IAC), is a significant cause of morbidity and mortality worldwide. IAC is still poorly understood, and its treatment represents a challenge for public health. In this study, we showed the in vitro anti-Candida activity of four alkaloid synthetic derivatives and their antifungal potential in a murine model of IAC. The biological effects of alkaloids were evaluated against Candida spp. through the determination of the minimum inhibitory concentration (MIC). For the alkaloids that showed antifungal activity, the fungicidal concentration, time-kill curve, synergism with azoles and polyenes, phenotypic effects, and the effect against virulence factors were also determined. The most active alkaloids were selected for in vivo assays. The compounds 6a and 6b were active against C. albicans, C. glabrata, and C. tropicalis (MIC 7.8 μg/mL) and showed promising antifungal activity against C. krusei (MIC 3.9 μg/mL). The compound 6a presented a potent fungicidal effect in vitro, eliminating the yeast C. albicans after 8 h of incubation at MIC. An important in vitro synergistic effect with ketoconazole was observed for these two alkaloids. They also induced the lysis of fungal cells by binding to the ergosterol of the membrane. Besides that, 6a and 6b were able to reduce yeast-to-hyphal transition in C. albicans, as well as inhibit the biofilm formation of this pathogen. In the in vivo assay, the compound 6a did not show acute toxicity and was mainly absorbed by the liver, spleen, and lung after a parenteral administration. Also, this analogue significantly reduced the fungal load of C. albicans on the kidney and spleen of animals with IAC. Therefore, these results showed that the compound 6a is a potent anti-Candida agent in vitro and in vivo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
- Published
- 2021
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45. In-depth characterization of antibacterial activity of melittin against Staphylococcus aureus and use in a model of non-surgical MRSA-infected skin wounds.
- Author
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Lima WG, de Brito JCM, Cardoso VN, and Fernandes SOA
- Subjects
- Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Humans, Melitten pharmacology, Microbial Sensitivity Tests, Staphylococcus aureus, Methicillin-Resistant Staphylococcus aureus, Staphylococcal Infections drug therapy
- Abstract
Skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) require the development of new and effective topical antibiotics. In this context, melittin, the main component of apitoxin, has a potent antibacterial effect. However, little is known regarding the anti-inflammatory potential this peptide in infection models, or its ability to induce clinically important resistance. Here, we aimed to conduct an in-depth characterization of the antibacterial potential of melittin in vitro and evaluate the pharmaceutical potential of an ointment containing melittin for the treatment of non-surgical infections induced by MRSA. The minimum inhibitory concentration of melittin varied from 0.12 to 4 μM. The antibacterial effect was mainly bactericidal and fast (approximately 0.5 h after incubation) and was maintained even in stationary cells and mature MRSA biofilms. Melittin interacts synergistically with beta-lactams and aminoglycosides, and its ability to form pores in the membrane reverses the resistance of vancomycin-intermediate Staphylococcus aureus (VISA) to amoxicillin, and vancomycin. Its ability to induce resistance in vitro was absent, and melittin was stable in several conditions often associated with infected wounds. In vivo, aointment containing melittin reduced bacterial load and the content of pro-inflammatory cytokines, such as tumor necrosis factor-α, interleukin-6 (IL-6), and IL-1 beta. Collectively, these data point to melittin as a potential candidate for topical formulations aimed at the treatment of non-surgical infections caused by MRSA., (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Published
- 2021
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46. Ventilator-associated pneumonia (VAP) caused by carbapenem-resistant Acinetobacter baumannii in patients with COVID-19: Two problems, one solution?
- Author
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Lima WG, Brito JCM, and da Cruz Nizer WS
- Subjects
- Acinetobacter baumannii, Coinfection, Colistin metabolism, Humans, Models, Theoretical, Acinetobacter Infections complications, Anti-Bacterial Agents pharmacology, COVID-19 complications, Carbapenems pharmacology, Drug Resistance, Bacterial, Pneumonia, Ventilator-Associated complications, Pneumonia, Ventilator-Associated microbiology
- Published
- 2020
- Full Text
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47. Epidemiological Impact and Hospitalization costs applied to dengue in the Midwest region of Minas Gerais state, Brazil, from SUS perspective.
- Author
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Morais MVF, de Andrade CR, da Silva GH, de Abreu E Silva M, Parreira AG, de Lima WG, and Dias-Godói IP
- Subjects
- Adolescent, Adult, Brazil epidemiology, Hospitalization, Humans, Young Adult, Chikungunya Fever, Dengue epidemiology, Zika Virus, Zika Virus Infection
- Abstract
Background & Objectives: Dengue is considered one of the greatest public health challenges in the world, especially, for tropical and subtropical countries. Brazil highlights with considerable number of registers associated with this arbovirus, with emphasis on the state of Minas Gerais and its municipalities in regions such as the midwest. We aimed to evaluate the economic and epidemiological impact of dengue in the midwest region of minas Gerais, from SUS perspective., Methods: Our study evaluated the epidemiological impact of dengue fever in the midwest region of Minas Gerais using data applied to Divinópolis city from SUS perspective between 2000 to 2015 considering SIH/SUS database (hospitalization registers) and 2007 to 2017 using the SINAN database (notification cases). We analyzed the number of notification registers and hospital services, as well as their costs, from a SUS perspective associated with this infection., Results: There were 26,516 notifications associated with dengue, with 21,953 cases being confirmed by SEMUSA, with a median incidence of 211 cases/100,000 inhabitants of dengue notifications between 2007 and 2017. The southeast and southwest regions in the municipality are highlighted with high number of cases. Additionally, 160 hospitalizations were recorded with 33.79% in individuals between 15 and 34 years old and expenses of USD 53,737.21 for SUS between 2000 and 2015., Interpretation & Conclusion: Divinópolis is the reference (social and economic) municipality of the midwest region in Minas Gerais state. Our study is the first conducted involving a long period of follow up applied to dengue context in this locality, especially, including the costs associated with hospitalization services. We hope to contribute to the discussions regarding the coping strategies of the disease, considering the impact in its different regions, highlighting the need for continued efforts and initiatives aimed at combating the vector of this and other arboviruses such as Zika and chikungunya., Competing Interests: None
- Published
- 2020
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48. Silymarin Attenuates Hepatic and Pancreatic Redox Imbalance Independent of Glycemic Regulation in the Alloxan-induced Diabetic Rat Model.
- Author
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Miranda LMO, Agostini LDC, Lima WG, Camini FC, and Costa DC
- Subjects
- Alloxan pharmacology, Animals, Diabetes Mellitus, Type 1 metabolism, Liver drug effects, Oxidation-Reduction, Pancreas drug effects, Antioxidants pharmacology, Diabetes Mellitus, Experimental metabolism, Liver metabolism, Pancreas metabolism, Protective Agents pharmacology, Silymarin pharmacology
- Abstract
Objective: To evaluate the efficiency of silymarin (SMN) in modulating metabolic parameters and redox status in rats with type 1 diabetes mellitus (T1DM)., Methods: Diabetes was induced by intraperitoneal injection of alloxan. The diabetic rats were administered with SMN at doses of 50 and 100 mg/kg body weight/d for 30 consecutive days. The rats were divided into the following four groups: vehicle control, diabetic (alloxan-treated), DS50 (alloxan + 50 mg/kg body weight/d of SMN), and DS100 (alloxan + 100 mg/kg body weight/d of SMN) groups. The bodyweight and food and water intake were evaluated. After 30 d, the animals were euthanized and the blood was collected for measuring the serum levels of glucose, triacylglycerol (TAG), urea, and creatinine. The liver and pancreas were collected for measuring the activities of superoxide dismutase (SOD) and catalase (CAT), and the levels of carbonylated protein (PC). The pancreas sample was also used for histological analysis., Results: SMN reduced hepatic ( P < 0.001) and pancreatic ( P < 0.001) protein damage and creatinine levels ( P = 0.0141) in addition to decreasing food ( P < 0.001) and water intake ( P < 0.001). However, treatment with SMN did not improve beta-cell function or decrease blood glucose levels in diabetic rats., Conclusion: SMN improved polyphagia and polydipsia, renal function, and protected the liver and pancreas against protein damage without affecting hyperglycemia in diabetic animals., (Copyright © 2020 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)
- Published
- 2020
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49. Effect of probiotics on the maintenance of intestinal homeostasis after chemotherapy: systematic review and meta-analysis of pre-clinical studies.
- Author
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Lima WG, Pessoa RM, Vital KD, Takenaka IKTM, Cardoso VN, and Fernandes SOA
- Subjects
- Animals, Apoptosis, Cell Proliferation, Cytokines metabolism, Disease Models, Animal, Drug-Related Side Effects and Adverse Reactions, Gastrointestinal Microbiome, Inflammation, Intestinal Mucosa metabolism, Intestinal Mucosa microbiology, Intestinal Mucosa pathology, Mucositis chemically induced, Mucositis prevention & control, Weight Loss, Mucositis therapy, Probiotics therapeutic use
- Abstract
Gastrointestinal mucositis (GIM) is an inflammation caused by antitumor therapy, especially after chemotherapy and radiotherapy. Currently in the clinical practice, only palliative measures are taken to treat GIM, representing the main clinical limitation in the management of this condition. Several studies have highlighted the potential benefits of probiotics for the management of GIM, but the actual role of these microorganisms in the maintenance of intestinal homeostasis remains elusive. In this context, here we aimed to realise a systematic review with meta-analysis to evaluate the effect of probiotics on experimental GIM. The meta-analysis showed that probiotics significantly suppressed the body weight loss related to GIM in rodents (95% confidence interval (CI): -2.67 to -0.70; I
2 =98%, P <0.00). Subgroup analysis showed that pre-treatment (≥7 days before chemotherapy) (95% CI: -8.84 to -0.17; I2 =98%, P <0.04) with a high dose of probiotics (≥ 109 cfu/day) (95% CI: -2.58 to -0.28; I2 =98%, P <0.00) comprising two or more microorganism species (95% CI: -6.49 to -0.28; I2 =96%, P =0.03) remedied GIM more effectively. It was also revealed that fungi (specifically Saccharomyces boullardii ) are more effective in remedying GIM than bacteria ( P =0.03 vs P <0.00), and the mouse models are more receptive than rats to the enteroprotective effects of probiotics (95% CI: -4.76, -0.69; I2 =97%, P =0.01). Qualitative analyses highlighted that probiotics suppress GIM through several mechanisms; they reduce the intestinal permeability, suppress the pro-inflammatory cytokine production while stimulating production and secretion of anti-inflammatory cytokines, inhibit the signalling pathways coupled to inflammation and apoptosis, accelerate the proliferation of enterocytes, reduce the levels of reactive oxygen species, and help maintain the protective mucus layer. In conclusion, this review highlights the therapeutic benefits of probiotics in experimental GIM.- Published
- 2020
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50. The potential of drug repositioning as a short-term strategy for the control and treatment of COVID-19 (SARS-CoV-2): a systematic review.
- Author
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Lima WG, Brito JCM, Overhage J, and Nizer WSDC
- Subjects
- Antiviral Agents pharmacology, COVID-19, Coronavirus Infections prevention & control, Humans, Pandemics prevention & control, Pneumonia, Viral prevention & control, SARS-CoV-2, COVID-19 Drug Treatment, Anti-Bacterial Agents pharmacology, Anti-Retroviral Agents pharmacology, Antimalarials pharmacology, Antineoplastic Agents pharmacology, Betacoronavirus drug effects, Coronavirus Infections drug therapy, Drug Repositioning, Pneumonia, Viral drug therapy
- Abstract
The novel human coronavirus (SARS-CoV-2), the causative agent of COVID-19, has quickly become a threat to the public health and economy worldwide. Despite the severity of some cases, there are no current pathogen-specific antivirals available to treat the disease. Therefore, many studies have focused on the evaluation of the anti-SARS-CoV-2 activity of clinically available drugs. Here, we conducted a systematic review to describe the drug repositioning strategy against SARS-CoV-2 and to discuss the clinical impact of this approach in the current pandemic context. The systematic review was performed on March 23, 2020, using PubMed/MEDLINE, Scopus, Cochrane Library, and Biblioteca Virtual de Saúde (BVS). The data were summarized in tables and critically analyzed. After the database search, 12 relevant studies were identified as eligible for the review. Among the drugs reported in these studies, 57 showed some evidence of antiviral activity. Antivirals, especially antiretrovirals, are the main class of therapeutic agents evaluated against COVID-19. Moreover, studies have reported the anti-SARS-CoV-2 activity of antitumor (16%; 9/57), antimalarial (7%, 4/57), and antibacterial (5%; 3/57) agents. Additionally, seven pharmacological agents (chloroquine, tetrandrine, umifenovir (arbidol), carrimycin, damageprevir, lopinavir/ritonavir) are in phase IV of clinical trials. Due to the evidence of the anti-SARS-CoV-2 activity of various clinically available agents, drug repositioning stands out as a promising strategy for a short-term response in the fight against the novel coronavirus.
- Published
- 2020
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