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Pelgipeptins, tridecaptins, and elgicins are among the antimicrobials produced by Paenibacillus elgii. Growth in complex media is commonly applied to obtain lipopeptides from culture's supernatant, but it requires further purification. This study aimed to improve the yield of pelgipeptins and tridecaptins using chemically defined media. The kinetics of antimicrobial lipopeptide yield in chemically defined media were evaluated in P. elgii AC13. Pelgipeptins were detected in the supernatant and the culture pellet, but tridecaptins were mainly associated with cell debris or endospores. We investigated whether removing Ca2+ would impair P. elgii sporogenesis, consequently improving the yield of tridecaptin. The kinetics of both lipopeptides in the presence and absence of Ca2+ were quantitatively and qualitatively evaluated and further correlated with the cell cycle. The impairment of P. elgii AC13 sporogenesis had no effect on tridecaptin production, which remained undetected in the supernatant of the culture. On the other hand, the yield of pelgipeptin in a Ca2+-free medium increased. We showed for the first time that the removal of Ca2+ interrupted the sporogenesis in P. elgii and improved the yield of pelgipeptins. However, Ca2+ absence had no effect on tridecaptin yield, which is possibly degraded or associated with other cell debris components., (© The Author(s) 2024. Published by Oxford University Press on behalf of Applied Microbiology International.)

Patients with active acromegaly have a higher percentage of lean body mass, a lower percentage of fat body mass, and an increase in their extracellular water compartment compared to healthy individuals. However, muscle function appears to be compromised in patients with acromegaly, with some experiencing worsened physical performance and sarcopenia. Myokine alterations, insulin resistance, dysregulation of protein metabolism, muscle oxidative stress, neuromuscular junction impairment, and increased ectopic intramuscular fat deposits may play roles in muscle dysfunction in patients with acromegaly.

Erythrina velutina is a Brazilian native tree of the Caatinga (a unique semiarid biome). It is widely used in traditional medicine showing anti-inflammatory and central nervous system modulating activities. The species is a rich source of specialized metabolites, mostly alkaloids and flavonoids. To date, genomic information, biosynthesis, and regulation of flavonoids remain unknown in this woody plant. As part of a larger ongoing research goal to better understand specialized metabolism in plants inhabiting the harsh conditions of the Caatinga, the present study focused on this important class of bioactive phenolics. Leaves and seeds of plants growing in their natural habitat had their metabolic and proteomic profiles analyzed and integrated with transcriptome data. As a result, 96 metabolites (including 43 flavonoids) were annotated. Transcripts of the flavonoid pathway totaled 27, of which EvCHI, EvCHR, EvCHS, EvCYP75A and EvCYP75B1 were identified as putative main targets for modulating the accumulation of these metabolites. The highest correspondence of mRNA vs. protein was observed in the differentially expressed transcripts. In addition, 394 candidate transcripts encoding for transcription factors distributed among the bHLH, ERF, and MYB families were annotated. Based on interaction network analyses, several putative genes of the flavonoid pathway and transcription factors were related, particularly TFs of the MYB family. Expression patterns of transcripts involved in flavonoid biosynthesis and those involved in responses to biotic and abiotic stresses were discussed in detail. Overall, these findings provide a base for the understanding of molecular and metabolic responses in this medicinally important species. Moreover, the identification of key regulatory targets for future studies aiming at bioactive metabolite production will be facilitated., 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 Chacon, Santos, Bonilauri, Vilasboa, da Costa, da Silva, Torres, de Araújo, Roque, Pilon, Selegatto, Freire, Reginaldo, Voigt, Zuanazzi, Scortecci, Cavalheiro, Lopes, Ferreira, Santos, Fontes, Sousa, Carvalho, Fett-Neto and Giordani.)

Paenibacillus elgii AC13 produces antimicrobial lipopeptides of agricultural and pharmaceutical importance. It secretes four cyclic lipopeptides named pelgipeptins, previously characterized in P. elgii B69. These lipopeptides result from the expression of a nonribosomal peptide gene cluster. P. elgii AC13 also produced two linear lipopeptides with ratios of [M + H] + 1105 and 1119 m/z. These compounds were previously observed in Paenibacillus sp. strain OSY-N, but due to purification difficulties, their characterization was executed using synthetically produced linear pelgipeptins. In the present study, purification was achieved from the supernatants of cultures from three complex media by high-performance liquid chromatography. The partial characterization of linear pelgipeptins revealed the similar antimicrobial activity and cytotoxicity of their synthetically produced counterparts, known as paenipeptins. Cyclic forms were highly stable to changes in pH, temperature, and organic extraction with n-butanol as shown by mass spectrometry (MALDI-TOF); therefore, these steps did not cause the hydrolysis of pelgipeptins. A low-activity thioesterase could also generate the linear isoforms observed; this enzyme catalyzes the cyclization process and is coded in the same gene cluster. Alternatively, the cyclic forms were hydrolyzed by an unknown protease produced during growth in the complex medium used in the present study. Although culture conditions are known to produce pelgipeptins with different yields and amino acid compositions, the occurrence of linear and cyclic forms simultaneously has not yet been reported. A mixture of cyclic and linear pelgipeptins presents a potential advantage of the higher antimicrobial activity of cyclic forms combined with the lower cytotoxicity of linear isoforms., (© 2021. Sociedade Brasileira de Microbiologia.)

Objective: to analyze the relationship between affective and sexual experiences and the intensity of physical and psychological symptoms of older adults., Methods: observational, cross-sectional and analytical study, guided by the STROBE tool, carried out in a geriatric outpatient clinic. Sociodemographic and health questionnaire, Affective and Sexual Experiences Scale for Elderly, Edmonton Symptom Assessment Scale were used. Descriptive statistical analysis and Spearman correlation were performed., Results: forty-five older adults participated, with a mean age of 73.8 years; most (91.1%) were married. The highest averages of symptom intensity were pain (4.9), anxiety (4.8), drowsiness (4.5), and a feeling of well-being (4.5). There was a negative correlation between sadness and the dimensions of sexual activity and affective relationships (rs=-0.365; p=0.014 and rs=-0.386; p=0.009) and between anxiety and sexual activity (rs=-0.308; p=0.040)., Conclusion: as sadness increases, affective and sexual experiences are less. The greater the anxiety intensity, the lower the sexual experiences.

Introduction: Natural products of pharmaceutical interest often do not reach the drug market due to the associated low yields and difficult extraction. Knowledge of biosynthetic pathways is a key element in the development of biotechnological strategies for plant specialized metabolite production. Erythrina species are mainly used as central nervous system depressants in folk medicine and are important sources of bioactive tetracyclic benzylisoquinoline alkaloids (BIAs), which can act on several pathology-related biological targets., Objectives: In this sense, in an unprecedented approach used with a non-model Fabaceae species grown in its unique arid natural habitat, a combined transcriptome and metabolome analyses (seeds and leaves) is presented., Methods: The Next Generation Sequencing-based transcriptome ( de novo RNA sequencing) was carried out in a NextSeq 500 platform. Regarding metabolite profiling, the High-resolution Liquid Chromatography was coupled to DAD and a micrOTOF-QII mass spectrometer by using electrospray ionization (ESI) and Time of Flight (TOF) analyzer. The tandem MS/MS data were processed and analyzed through Molecular Networking approach., Results: This detailed macro and micromolecular approach applied to seeds and leaves of E. velutina revealed 42 alkaloids, several of them unique. Based on the combined evidence, 24 gene candidates were put together in a putative pathway leading to the singular alkaloid diversity of this species., Conclusion: Overall, these results could contribute by indicating potential biotechnological targets for modulation of erythrina alkaloids biosynthesis as well as improve molecular databases with omic data from a non-model medicinal plant, and reveal an interesting chemical diversity of Erythrina BIA harvested in Caatinga., Competing Interests: 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., (© 2021 The Authors. Published by Elsevier B.V. on behalf of Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).)

Human visceral leishmaniasis (VL) and canine leishmaniasis (CanL) in countries of South and Central America are caused by Leishmania infantum and has been endemic in Brazil for several years. The parasite biodiversity as well as the pharmacologic properties of drugs and the host species, are involved in the efficacy or inefficacy of leishmaniasis treatments. Although there are substantial number of reports describing the genetic characterization of the clinical field isolates of L. infantum,the phenotypic parameters have been less studied. In this study isolates from human and canine leishmaniasis (Hum1 and Can1) obtained in Campinas, São Paulo state, Brazil were identified as L. infantum. The Hum1 and Can1 isolates exhibited typical promastigote growth pattern. Regarding morphological features Can1 isolate differed in cell size. The infectivity in vitro of both isolatesis lower compared to the reference strain of L. infantum. Moreover, the in vivo infectivity of the three parasites is similar in Balb/c mice. The Hum1 isolate is more sensitive to leishmanial drugs (amphotericin B, miltefosine and glucantime) than the Can1 isolate when inside human macrophages, but not when inside canine macrophages. These findings indicated that L. infantum isolates differs in some phenotypic characteristics., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Leishmania infantum infection may cause visceral leishmaniasis (VL), a fatal disease having worldwide distribution, that may be silent or asymptomatic. The latter indicates that immunity is naturally developed in some individuals, and, therefore, a vaccine against VL would be possible. Molecular mechanisms of gene expression are being understood in Leishmania, and this knowledge may be useful for vaccine development. The aim of this study was developing an attenuated strain by regulating the expression of toxic proteins in a stage specific manner. For that purpose, the 3' UTR of an amastin gene, known by its increased expression in the amastigote phase, was selected for direct the expression of exogenous proteins. This construct (pFL-AMA), firstly, was proved effective for the expression of mCherry specifically in the intracellular form of L. infantum, as demonstrated by fluorescence microscopy, flow cytometry and Western blotting. Afterwards, mCherry coding sequence was replaced, in the pFL-AMA plasmid, by either egg avidin or the active form of bovine trypsin. Viability of transfected parasites was evaluated in promastigote axenic cultures and in in vitro infection of macrophages. Both lines of transfected parasites showed a limited capacity to multiply inside macrophages. BALB/c mice were inoculated intraperitoneally (i.p.) with a single dose consisting of 2 × 10 6 L. infantum promastigotes transfected with plasmids bearing the toxic genes. After 10 weeks post-inoculation, no parasites were recovered by limiting dilution in either liver or spleen, but a specific immunological response was detected. The immunization with transfected parasites induced cellular and humoral immune responses with activation of TCD4 + , TCD8 + and B cells, having a TH1-type response with increased levels of pro-inflammatory cytokines such as IFN-γ, TNF-α and IL-6. In parallel groups of mice, a challenge consisting on 1 × 10 6 virulent parasites of either L. infantum (inoculated i.p.) or L. amazonensis subcutaneously (s.c.) was performed. Vaccinated mice, challenged with L. infantum, showed lower parasite burdens in liver, spleen and bone marrow than infected mice with WT L. infantum (non-vaccinated); similarly, vaccinated mice developed smaller footpad inflammation than control group. These data support this strategy as an efficient immunization system aimed to the development of vaccines against different forms of leishmaniasis., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Protium heptaphyllum is a plant widely distributed in Brazilian ecosystems that produce a resin which has pharmacological activities. In this study, the chemical composition, antimicrobial and antibiofilm activity, and the possible mechanism of action against the bacterium V. parahaemolyticus of essential oil from P. heptaphyllum (EOPH) were investigated. Twenty-two components were detected in EOPH, and β -phellandrene (60.68%) had the majority. The inhibition halo, MIC, and MBC values were 11 mm, 2 mg/mL, and 8 mg/mL, respectively. Biofilm biomass inhibition and biomass reduction of the preformed biofilm were detected at 4 mg/mL EOPH concentration. The assays of cell constituent release and membrane permeability indicated that EOPH may disrupt the cell membrane, leading to leakage of intracellular constituent as reducing sugars and materials with an absorbance of 260 nm., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2019 Josiane Lima Mendes et al.)

A Paenibacillus elgii strain isolated from soil samples from Cerrado, Brazil, showed antimicrobial activity. Its genome sequence was acquired (GS20 FLX Titanium 454 platform) and comprises 108 contigs ( N 50 , 198,427 bp) and 6,810 predicted sequences. Here, we shed some light on the antimicrobial genes of the strain, including a nonribosomal peptide synthetase (NRPS) module identified as part of a pelgipeptin gene cluster., (Copyright © 2018 Ortega et al.)

Objective: Analyzing statements of health professionals from a Street Clinic regarding care of a homeless population with tuberculosis., Method: This is a qualitative research, conducted in the central region of São Paulo at three basic health units in the period of November to December 2014. A semi-structured interview guideline was implemented for data collection and all interviews were recorded using a digital recorder., Results: Six health professionals were interviewed. According to the Discourse Analysis perspective, three discursive segments emerged: experiences on care in the streets; weaknesses inherent to the treatment process; and incentives as a means of maintaining sick people in treatment., Conclusion: Caring for a the homeless population with tuberculosis constitutes a new and challenging experience. It involves difficulties in dealing with the reality of a miserable social context, a lack and inadequacy of services, as well as care limitations for treatment and treatment dropout, which reinforces multiresistance. However, the investigated Street Clinic teams seek to expand access to health and social care services to this population., Objetivo: Analisar os discursos dos profissionais de saúde do Consultório na Rua em relação ao cuidado à pessoa em situação de rua com tuberculose., Método: Trata-se de uma pesquisa qualitativa, realizada na região central do município de São Paulo, em três Unidades Básicas de Saúde, no período de novembro a dezembro de 2014. Utilizou-se de um roteiro de entrevista semiestruturada para a coleta de dados e todas as entrevistas foram gravadas com recurso a um gravador digital., Resultados: Foram entrevistados seis profissionais de saúde. Segundo a perspectiva da Análise de Discurso, emergiram três blocos discursivos: experiência sobre o cuidar na rua; fragilidades inerentes ao processo de tratamento e incentivos como meio para a permanência do sujeito doente no tratamento., Conclusão: Cuidar da pessoa com tuberculose e em situação de rua constitui uma experiência nova e desafiadora, implica dificuldades em lidar com a realidade de um contexto social miserável, falta e inadequação de serviços, bem como limitações do cuidado para a cura e abandono do tratamento, podendo reforçar a multirresistência. Contudo, as equipes de Consultório na Rua investigadas buscam ampliar o acesso aos serviços de saúde e assistência social a essa população.

Our study describes the clinical, epidemiologic, pathologic, immunohistochemical, and molecular aspects PCR of a case of cutaneous pythiosis in a donkey (Equus asinus) from Brazil. During a dry period, the animal grazed for 4 months around a pond where the vegetation remained green. Skin lesions were nodular, multifocal, and disseminated, mainly involving the legs, ventral chest, and mammary gland. On cut surface, there were multifocal to coalescent discrete yellow foci, and occasional small cavitations with a few kunkers. Ulcerative nodular pyogranulomatous and eosinophilic dermatitis with folliculitis and furunculosis were observed histologically. Hyphae were observed in sections stained with Gomori methenamine silver. Immunohistochemistry with Pythium insidiosum antibodies yielded strong immunostaining of hyphae. P. insidiosum DNA was extracted from tissues in paraffin blocks by amplification of a fragment of 105 bp, which targets the 5.8S ribosomal gene. After the diagnosis of pythiosis, the larger skin lesions were excised and treated as second intention healing wounds, which were completely healed 30 days after resection. Small skin lesions regressed spontaneously in ~60 days. The granulomatous inflammation and outcome of the disease in this donkey were similar to cases of pythiosis in cattle., (© 2016 The Author(s).)

In this article, we present the case of a patient with heart failure with biological aortic valve prosthesis and multiple vascular changes consistent with Takayasu arteritis (TA) who was seen in our department receiving corticosteroids and secondary prevention of rheumatic fever (RF); it was not possible to exclude the association between both diseases., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)

This study aimed to assess the effects of a yacon-based product (YBP) on constipation in adults, including the elderly. Forty-eight individuals were recruited and divided into equal intervention groups named the test and control groups. The YBP (test) and the control (maltodextrin) were dissolved in commercial orange juice. The volunteers for the YBP/test group consumed, on a daily basis, orange juice containing 10 g fructooligosaccharide (FOS)/inulin per day. The control group consumed, on a daily basis, orange juice containing 25 g of maltodextrin. The study had a span of 30 days. We evaluated the participants' frequency of evacuation, consistency of the feces, constipation score, abdominal symptoms (flatulence, pain, and abdominal strain), and effects upon the microbiota, pH, lactate, and short-chain fatty acids (SCFAs) of the feces. The study showed an increased number of evacuations after the consumption of the YBP as well as an improvement in the consistency of the feces and a reduction in the constipation score. After 30 days of intervention, the group that consumed the YBP showed higher counts of Bifidobacterium, lower Clostridium and enterobacteria counts, and lower fecal pH. In relation to SCFAs, no significant change was found after the intervention. However, the lactate concentration was higher in the test group when compared to the post-treatment control group. The YBP was effective in improving constipation symptoms; not only was its functional characteristic in reducing constipation symptoms evident but it also demonstrated usefulness as a potential therapy.

A characteristic feature of Staphylococcus aureus is its ability to acquire resistance to antimicrobial agents. There is a need, therefore, for new approaches to combat this pathogen; for example, employing a combination of plant-derived products and antibiotics to overcome bacterial resistance. Indigofera suffruticosa is a plant popularly used to treat infections and has verified antimicrobial action. Here, we investigate the antimicrobial activity of different extracts from I. suffruticosa against S. aureus and their synergistic effects with erythromycin. Leaves of I. suffruticosa were extracted sequentially using diethyl ether, chloroform and acetone and the antimicrobial activity of each extract then tested against nine clinical isolates of S. aureus. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) were determined by microdilution tests, while the fractional inhibitory concentration (FIC) was assessed by checkerboard assay. All organic solvent extracts showed antimicrobial activity against S. aureus strains. The acetone extract was the most potent inhibitor of S. aureus (MIC and MBC of 0.78 and 3.12 mg/mL), followed by the chloroform extract (MIC and MBC of 3.12 and 6.25 mg/mL). Furthermore, acetone or chloroform extracts of I. suffruticosa enhanced the activity of erythromycin against S. aureus (FIC ≤ 0.5). We conclude that organic extracts from leaves of I. suffruticosa, alone or combined with erythromycin, are promising natural products for the development of new anti-S. aureus formulations.

Iron abnormalities in chronic liver disease may be the result of genetic diseases or secondary factors. The present study aimed to identify subjects with HFE-HH in order to describe the frequency of clinical manifestations, identify risk factors for iron elevation, and compare the iron profile of HFE-HH to other genotypes in liver disease patients. A total of 108 individuals with hepatic disease, transferrin saturation (TS) > 45%, and serum ferritin (SF) > 350 ng/mL were tested for HFE mutations. Two groups were characterized: C282Y/C282Y or C282Y/H63D genotypes (n = 16) were the HFE hereditary hemochromatosis (HFE-HH) group; and C282Y and H63D single heterozygotes, the H63D/H63D genotype, and wild-type were considered group 2 (n = 92). Nonalcoholic liver disease, alcoholism, and chronic hepatitis C were detected more frequently in group 2, whereas arthropathy, hepatocarcinoma, diabetes, and osteoporosis rates were significantly higher in the HFE-HH group. TS > 82%, SF > 2685 ng/mL, and serum iron > 178 μg/dL were the cutoffs for diagnosis of HFE-HH in patients with liver disease. Thus, in non-Caucasian populations with chronic liver disease, HFE-HH diagnosis is more predictable in those with iron levels higher than those proposed in current guidelines for the general population.

This is a series of cases describing the use of citalopram for the treatment of cataplexy in patients with narcolepsy. Cataplexy is the most specific symptom of narcolepsy, being characterized by a sudden and temporary loss of muscle tonus, triggered by episodes of emotion during vigil. Some antidepressants, besides gamma-hydroxybutyrate, are used for the control of cataplexy. As gamma-hydroxybutyrate is not available in Brazil, local treatment is usually done by the use of antidepressants. Citalopram is a selective inhibitor of serotonin reuptake, with reasonable price and with fewer side effects when compared with other drugs of the same type. In this study, we report a series of cases with patients with narcolepsy and cataplexy, treated with citalopram for the control of cataplexy.

Objective: Wilson's disease (WD) is an inborn error of metabolism caused by abnormalities of the copper-transporting protein encoding gene ATP7B. In this study, we examined ATP7B for mutations in a group of patients living in southern Brazil., Methods: 36 WD subjects were studied and classified according to their clinical and epidemiological data. In 23 subjects the ATP7B gene was analyzed., Results: Fourteen distinct mutations were detected in at least one of the alleles. The c.3207C>A substitution at exon 14 was the most common mutation (allelic frequency=37.1%) followed by the c.3402delC at exon 15 (allelic frequency=11.4%). The mutations c.2018-2030del13 at exon 7 and c.4093InsT at exon 20 are being reported for the first time., Conclusion: The c.3207C>A substitution at exon 14, was the most common mutation, with an allelic frequency of 37.1%. This mutation is the most common mutation described in Europe.

Unlabelled: Recurrent cholesteatoma is relatively uncommon. Residual middle ear cholesteatomas account for most of the cases of recurrent disease. The limited role of microscopy in the visualization of tridimensional anatomic alterations of the temporal bone led to the use of endoscopic examination as an additional tool in the realm of ear surgery. Endoscopy has significantly aided in the management of chronic cholesteatomatous otitis media and in the prevention of recurrent disease., Objective: To review the literature and assess the relevance of endoscopy in the surgical treatment of cholesteatomas and in the prevention of relapsing lesions., Method: Searches on databases MedLine and LILACS were carried out between March and June of 2011 to select studies in which endoscopy was used in the management of cholesteatomas., Results: Three studies comparing surgery aided by endoscopy and surgery performed with the aid of a microscope met the inclusion criteria., Conclusion: Endoscopy has positively impacted the management of cholesteatomas and should be used in cholesteatoma surgery.

Crataeva tapia is a plant popularly used for diabetes treatment, in Brazil. Progressive decline in renal and hepatic functions has been described in patients with diabetes mellitus, and mortality rate is increased in patients with chronic liver and renal disease. This study aimed to evaluate whether Crataeva tapia bark lectin (CrataBL) improves hyperglycemia and renal and hepatic damage in diabetic mice. CrataBL was purified by ion exchange chromatography on CM-cellulose, and intraperitoneal administration of CrataBL to alloxan-induced diabetic mice at dose of 10 mg/Kg/day and 20 mg/Kg/day for 10 days significantly reduced serum glucose levels by 14.9% and 55.9%, respectively. Serum urea, creatinine, aspartate aminotransferase, and alanine aminotransferase were also significantly reduced after treatment with both doses of CrataBL. Furthermore, histological analysis of liver, kidney, and pancreas revealed an improvement in the tissue morphology upon treatment with CrataBL. The results suggest that CrataBL has a beneficial hypoglycemic activity and improves the renal and hepatic complications of diabetes. Therefore, this lectin may be a promising agent for the treatment of diabetes, and this might be the basis for its use in the folk medicine as an alternative treatment to manage diabetes-related complications such as hyperglycemia and tissue damage.