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Introduction: Thiophene derivatives have been widely studied as promising options for the treatment of solid tumors. Previous studies have shown that thiophene derivatives have antileishmanial activity and cytotoxic activity against breast, colon, and ovarian cancer cells. Method: In our study, we evaluated the anticancer activities of three aminothiophene derivatives: SB-44, SB-83, and SB-200, in prostate and cervical adenocarcinoma cells. Several in vitro methods were performed, including cytotoxicity, clonogenic migration, mutagenic, and cleaved Poly (ADP-ribose) polymerase (PARP) assays and annexin V staining. Results: Significant cytotoxicity was observed in cell lines with IC50 values less than 35 μM (15.38-34.04 μM). All aminothiophene derivatives significantly reduced clone formation but had no effect on cell motility. SB-83 and SB-44 induced a significant increase in the percentage of cells in the sub-G1 phase, while SB-200 derivatives significantly decreased the percentage of S/G2/M as well as induced apoptosis, with an increase of cleaved PARP. SBs compounds also showed significant mutagenic potential. Beyond that, in silico analyses revealed that all three thiophene derivatives fulfilled the criteria for oral druggability, which underscores the potential of using them in anticancer therapies. Conclusion: Our findings show that the thiophene nucleus may be used to treat solid tumors, including prostate cancer and cervical adenocarcinoma.

Resumo Fundamento A oncostatina M (OSM) é uma citocina pleiotrópica que, após lesão arterial, demonstra ser expressa rapidamente. Objetivos Correlacionar os níveis séricos da OSM, do receptor solúvel de oncostatina M (sOSMR) e da fração solúvel de glicoproteína 130 (sgp130) em pacientes com doença arterial coronariana (DAC) a parâmetros clínicos. Métodos Os níveis de sOSMR e sgp130 foram avaliados por ELISA, enquanto os de OSM foram avaliados por Western Blot, em pacientes com SCC (n=100), pacientes com SCA (n=70) e 64 voluntários do grupo de controle sem manifestações clínicas da doença. Valores de p

In recent years, the SARS-CoV-2 viruses emerged and spread around the world, leaving a large death toll and long-lasting impact on survivors. As of January 2023, Brazil is still among the countries with the highest number of registered deaths. This continental-size and pluralistic country experienced a heterogenous implementation of non-pharmacological and pharmacological interventions which, associated with large socioeconomic differences between the country regions, has led to distinct virus spread dynamics across the country. Here we investigate the spatiotemporal dispersion of emerging SARS-CoV-2 lineages and its dynamics in distinct epidemiological scenarios in the first two years of the pandemics in the Pernambuco state (Northeast Brazil). We generated a total of 1389 new SARS-CoV-2 genomes from June 2020 to August 2021 covering all major regions of the state. This sampling captured the arrival, communitary transmission and the circulation of the B1.1, B.1.1.28 and B.1.1.33 lineages in the first eight months of the pandemics, the emergence of the former variant of interest P.2 and the emergence and fast replacement of all previous variants by the more transmissible variant of concern P.1 (Gamma) lineage. Based on the incidence and lineage spread pattern we observed that there was an East-to-West to inner state pattern of transmission which is in agreement with the transmission of more populous metropolitan areas to medium and small size country-side cities in the state. Such transmission patterns may be partially explained by the main routes of traffic across municipalities in the state. Nevertheless, inter-state traffic was also another important source of lineage introduction and spread into the state. Our results highlight that the fine grained intrastate analysis of lineages and incidence spread can provide actionable insights for planning future non-pharmacological intervention for air-borne transmissible human pathogens.

Albumina é o expansor plasmático mais importante da circulação sanguínea. Na forma de medicamento, deve ser prescrito após minuciosa avaliação dos pacientes, baseando seu uso de acordo com a literatura, pois apresenta contraindicações, como hemorragias em pacientes pós-cirúrgicos, além de ser um medicamento de alto custo. Assim, o objetivo deste trabalho foi realizar um levantamento das indicações terapêuticas contidas nas prescrições de albumina humana (AH) 20% de um Hospital Escola da cidade do Recife, Pernambuco, Brasil, a fim de avaliar se tais indicações apresentam embasamento científico, além de ser realizado um levantamento dos custos relacionados à aquisição deste medicamento. Foi feito um estudo transversal, retrospectivo, fundamentado na análise das prescrições receitadas aos pacientes, no período de maio de 2015 a maio de 2017. As indicações terapêuticas encontradas foram: paracentese de alívio (29%), síndrome hepatorrenal (SHR) (22,9%), hipovolemia (20,6%), choque séptico (8,7%), peritonite bacteriana espontânea (PBE) (6,4%), hipoalbuminemia (6,1%), ascite (4,1%), neoplasia (1,2%) e encefalopatia hepática (EH) (0,6%). Após levantamento bibliográfico, a AH 20% apresenta respaldo científico para o tratamento de paracentese, SHR e PBE, o que corresponde a 63,1% das prescrições e não apresenta respaldo científico para o tratamento da hipovolemia, choque séptico, hipoalbuminemia, câncer e EH (36,9%), podendo ser substituída por outros expansores plasmáticos. Com isso, destaca-se a importância de basear a prescrição da AH 20% de acordo com a literatura, visando sempre o uso racional de medicamentos. Albumin is the most important plasma expander in the bloodstream. In the form of medication, it must be prescribed after a thorough evaluation of the patients, basing its use according to the literature, as it has contraindications, such as bleeding in post-surgical patients, in addition to being a high-cost medication. Thus, the objective of this work was to carry out a survey of the therapeutic indications contained in the prescriptions of human albumin (HA) 20% of a Teaching Hospital in the city of Recife, Pernambuco, Brazil, in order to assess whether such indications have scientific basis, in addition to a survey of the costs related to the acquisition of this drug should be carried out. A cross-sectional, retrospective study was carried out, based on the analysis of prescriptions prescribed to patients, from May 2015 to May 2017. The therapeutic indications found were: relief paracentesis (29%), hepatorenal syndrome (HRS) (22,9%), hypovolemia (20.6%), septic shock (8.7%), spontaneous bacterial peritonitis (SBP) (6.4%), hypoalbuminemia (6.1%), ascites (4.1%), neoplasia (1.2%) and hepatic encephalopathy (HE) (0.6%). After a literature review, HA 20% has scientific support for the treatment of paracentesis, SHR and PBE, which corresponds to 63.1% of prescriptions and has no scientific support for the treatment of hypovolemia, septic shock, hypoalbuminemia, cancer and HE (36.9%), which can be replaced by other plasma expanders. Thus, the importance of basing the prescription of 20% HA according to the literature is highlighted, always aiming at the rational use of medicines. La albúmina es el expansor de plasma más importante en el torrente sanguíneo. En forma de medicamento, debe prescribirse después de una evaluación minuciosa de los pacientes, basando su uso de acuerdo con la literatura, ya que tiene contraindicaciones, como sangrado en pacientes posquirúrgicos, además de ser un medicamento de alto costo. Así, el objetivo de este trabajo fue realizar un levantamiento de las indicaciones terapéuticas contenidas en las prescripciones de albúmina humana (HA) 20% de un Hospital Escuela en la ciudad de Recife, Pernambuco, Brasil, con el fin de evaluar si tales indicaciones tener base científica, además de realizar un relevamiento de los costos relacionados con la adquisición de este fármaco. Se realizó un estudio transversal, retrospectivo, a partir del análisis de las recetas prescritas a los pacientes, desde mayo de 2015 hasta mayo de 2017. Las indicaciones terapéuticas encontradas fueron: paracentesis de alivio (29%), síndrome hepatorrenal (SHR) (22,9 %), hipovolemia (20,6%), shock séptico (8,7%), peritonitis bacteriana espontánea (PBE) (6,4%), hipoalbuminemia (6,1%), ascitis (4,1%), neoplasia (1,2%) y encefalopatía hepática (EH) (0,6%). Después de una revisión de la literatura, HA 20% tiene respaldo científico para el tratamiento de paracentesis, SHR y PBE, lo que corresponde al 63,1% de las prescripciones y no tiene respaldo científico para el tratamiento de hipovolemia, shock séptico, hipoalbuminemia, cáncer y HE (36,9%), que pueden ser reemplazados por otros expansores de plasma. Así, se destaca la importancia de fundamentar la prescripción de AH al 20% de acuerdo con la literatura, siempre visando el uso racional de los medicamentos.

The combination of pharmacophoric nuclei with different targets has been a strategy for the development of new drugs aimed at improving cancer treatment. A series of ten novel phthalimido-thiazolidine-2-4-dione derivatives were synthesized by two different synthetic routes. The compounds were tested and evaluated in vitro, through antineoplastic activities against cancer cells. Cell cycle analysis and clonogenic assay were also performed. The synthesized FT-12 compound (9j) exhibited antiproliferative activity against Panc-1, Sk-mel-28, and PC-3 cells. FT-12 reduced the ability to form new clones, also caused irreversibility in cell cycle, inducing arrest in the S phase. Besides, the compound (FT-12) induced necrosis and apoptosis. The results suggest that phthalimido-thiazolidine derivatives may be useful in cancer therapy, highlighting compound FT-12 (9j) as a promising candidate. However, more studies must be carried out to confirm its viability.

RESUMO As tecnologias em saúde têm revolucionado a assistência médica e a gestão em saúde. A Comissão Nacional de Incorporação de Tecnologias no SUS (Conitec) é o órgão do Ministério da Saúde que assessora na incorporação, exclusão ou alteração de novas tecnologias no Sistema Único de Saúde (SUS). O presente estudo objetivou descrever o perfil das tecnologias incorporadas no SUS de 1 de janeiro de 2012 a 30 de setembro de 2019. Os dados foram coletados no site da Conitec. Na análise estatística, foi utilizado o teste Qui-quadrado de Pearson e o Teste Exato de Fisher. Os resultados demonstram que foram incorporadas 380 tecnologias, prevalecendo os medicamentos (46,6%). Em relação aos demandantes, os de origem interna superaram os demais (82,4%), principalmente secretarias do Ministério da Saúde (p

As a result of its broad clinical presentation – from asymptomatic infection to severe acute respiratory syndrome (SARS), COVID-19 has emerged as a broadcasting pandemic worldwide. A viral test tells you if you have a current infection. Confirmation of a high-risk for COVID-19 patient has been prioritized in containment efforts. The current diagnostic methods for COVID-19 rely on higher sensitivity, specificity, and faster results. Two types of diagnostic methods have been considered: nucleic acid amplification tests and serological tests. Whereas the first one confirms infection, the second might disclose outcomes from past infection or immunological parameters left by the contamination. Here we collect emerging understanding of the underlying role of molecular and serological tests incorporated in the routine of COVID-19 diagnosis and outline some features related to the methodologies.

Lung cancer is the leading cause of cancer death in both men and women and is the second most common type in both. It generally has a poor prognosis, with 75 percent of patients being diagnosed at an advanced stage. The diagnostic tools typically in use are insufficiently sensitive and do not allow for early disease detection. As a result, finding alternative ways of early and accurate lung cancer diagnosis is critical for successful management. CT imaging, sputum cytology, biopsy, and bronchoscopy are examples of traditional procedures that have been adjusted over time to improve sensitivity and accuracy. Lung biopsy is a reliable procedure performed to help define the treatment strategy for patients with lung cancer. The use of computed tomography (CT), EBUS, EUS and bronchoscopy allowed the collection of specimens for a greater number of patients through minimally invasive procedures. The recent advances in molecular technologies and analytic platforms have made it possible to investigate the gene variations that contribute to tumorigenesis and become potential lung cancer biomarkers. Furthermore, liquid biopsies tend to be a safe alternative to traditional biopsies and can offer both accurate molecular data and a less invasive method of evaluating tumor activity, which could further improve the clinical management of lung cancer patients. This chapter provides an overview of the different traditional and emerging diagnostic tools for lung cancer. We need to understand the characteristics of these procedures that could have predictive, prognostic and therapeutic implications.

The present study aimed to evaluate the mechanism of action of the antineoplastic activity of an oxazolidine derivative, LPSF/NB-3 (5-(4-cloro-benzilideno)-3-etil-2-tioxo-oxazolidin-4-ona). Cytotoxicity assays were performed in peripheral blood mononuclear cells (PBMCs) and resistant acute leukemia cell line (HL-60/MX1) by the MTT method. LPSF/NB-3 exhibited cytotoxicity in HL-60/MX1, but it was not toxic to healthy cells in the highest dose tested (100 μM). The protein extract of HL-60/MX1 cells treated with LPSF/NB-3 was subjected to proteomic analysis using two-dimensional chromatography coupled to mass spectrometry. We could identify a total of 2652 proteins, in which 633 were statistically modulated. Within the group of protein considered for the quantitative analysis with the established criteria, 262 were differentially expressed, 146 with increased expression and 116 with decreased expression in the sample treated with LPSF/NB-3 compared to the control. The following differentially expressed pathways were found: involving regulation of the cytoskeleton, DNA damage, and transduce cellular signals. Networks that were highlighted are related to the immune system. The ELISA technique was used to assess the immunomodulatory potential of LPSF/NB-3 in PBMCs. We observed significant decrease of IFNγ (p < 0.01) and dose-response pattern of the cytokines IL-6, IL-17A, IL-22, and IL-10. Therefore, results suggest that LPSF/NB-3 appears to modulate important pathways, including cell cycle and immune system regulatory pathways.

Aim and Objective: In the last decades, cancer has become a major problem in public health all around the globe. Chimeric chemical structures have been established as an important trend on medicinal chemistry in the last years. Thiazacridines are hybrid molecules composed of a thiazolidine and acridine nucleus, both pharmacophores that act on important biological targets for cancer. By the fact it is a serious disease, seven new 3-acridin-9-ylmethyl-thiazolidine-2,4-dione derivatives were synthesized, characterized, analyzed by computer simulation and tested in tumor cells. In order to find out if the compounds have therapeutic potential. Materials and Methods: Seven new 3-acridin-9-ylmethyl-thiazolidine-2,4-dione derivatives were synthesized through Michael addition and Knoevenagel condensation strategies. Characterization was performed by NMR and Infrared spectroscopy techniques. Regarding biological activity, thiazacridines were tested against solid and hematopoietic tumoral cell lines, namely Jurkat (acute T-cell leukemia); HL-60 (acute promyelocytic leukemia); DU 145 (prostate cancer); MOLT-4 (acute lymphoblastic leukemia); RAJI (Burkitt's lymphoma); K562 (chronic myelogenous leukemia) and normal cells PBMC (healthy volunteers). Molecular docking analysis was also performed in order to assess major targets of these new compounds. Cell cycle and clonogenic assay were also performed. Results: Compound LPSF/AA-62 (9f) exhibited the most potent anticancer activity against HL-60 (IC50 3,7±1,7 μM), MOLT-4 (IC50 5,7±1,1 μM), Jurkat (IC50 18,6 μM), Du-145 (IC50 20±5 μM) and Raji (IC50 52,3±9,2 μM). While the compound LPSF/AA-57 (9b) exhibited anticancer activity against the K562 cell line (IC50 51,8±7,8 μM). Derivative LPSF/AA-62 (9f) did not interfere in the cell cycle phases of the Molt-4 lineage. However, the LPSF/AA-62 (9f) derivative significantly reduced the formation of prostate cancer cell clones. The compound LPSF/AA-62 (9f) has shown strong anchorage stability with enzymes topoisomerases 1 and 2, in particular due the presence of chlorine favored hydrogen bonds with topoisomerase 1. Conclusion: The 3-(acridin-9-ylmethyl)-5-((10-chloroanthracen-9-yl)methylene)thiazolidine-2,4-dione (LPSF/AA-62) presented the most promising results, showing anti-tumor activity in 5 of the 6 cell types tested, especially inhibiting the formation of colonies of prostate tumor cells (DU-145).

PURPOSE Patients submitted to radiotherapy (RT) may present in their healthy tissues surrounding the treated tumor, some typical acute inflammatory reactions induced by ionizing radiation (IR). The manifestation of inflammatory processes is a result of exacerbation of the immune system, as a response to radiation exposure, and this can be a limiting factor for RT protocols. To counteract this, some thiazolidinediones, such as LPSF/GQ-16, may be useful for modulating the patient's radioinduced inflammatory response in normal tissues. In this context, the present work aims to evaluate the activity of LPSF/GQ-16 on the levels of cytokines and the expression of the gene PPARγ in mononuclear cells irradiated in vitro, to analyze the immunomodulatory activity of the molecule and its action on radiomitigation. MATERIALS AND METHODS For this, blood samples from eight donors were collected and irradiated with 2 Gy, then the PBMC (peripheral blood mononuclear cells) were cultured and treated with LPSF/GQ-16. The levels of cytokines TNF-α, IFN-γ, IL-2 and IL-4 were quantified by CBA, while the genes of TNF-α, IFN-γ and PPARγ were analyzed by RT-PCR. RESULTS LPSF/GQ-16 significantly reduced the expression of proinflammatory cytokines (IFN-γ and TNF-α) in irradiated and nonirradiated groups. There was no significant reduction of anti-inflammatory cytokines (IL-2 and IL-4) by LPSF/GQ-16. The mRNA expression of PPAR-γ, IFN-γ and TNF-α in the presence of LPSF/GQ-16 was higher in the nonirradiated sample. CONCLUSION LPSF/GQ-16 showed effective activity after irradiation, with an important immunomodulatory activity in irradiated PBMCs.

Coronavirus disease 2019 (Covid‐19) is an emerging novel respiratory infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) that rapidly spread worldwide. In addition to lung injury, Covid‐19 patients may develop extrapulmonary symptoms, including cardiac, liver, kidney, digestive tract, and neurological injuries. Angiotensin converting enzyme 2 is the major receptor for the entry of SARS‐CoV‐2 into host cells. The specific mechanisms that lead to cell death in different tissues during infection by SARS‐CoV‐2 remains unknown. Based on data of the previous human coronavirus SARS‐CoV together with information about SARS‐CoV‐2, this review provides a summary of the mechanisms involved in cell death, including apoptosis, autophagy, and necrosis, provoked by severe acute respiratory syndrome coronavirus.

The combination of pharmacophoric nuclei with different targets has been a strategy for the development of new drugs aimed at improving cancer treatment. A series of ten novel phthalimido-thiazolidine-2-4-dione derivatives were synthesized by two different synthetic routes. The compounds were tested and evaluated in vitro, through antineoplastic activities against cancer cells. Cell cycle analyzes and clonogenic assay were also performed. In addition to these tests, in silico predictions were performed. The synthesized FT-12 compound (9j) exhibited antiproliferative activity against Panc-1, Sk-mel-28 and PC-3 cells. FT-12 reduced the ability to form new clones, also caused irreversibility in cell cycle, inducing arrest in phase S. Besides, the compound (FT-12) caused necrosis and apoptosis. The results suggest that phthalimido-thiazolidine derivatives may be useful in cancer therapy, highlighting compound FT-12 (9j) as a promising candidate. More studies must be carried out to confirm the viability.

Background/purpose Although many patients with chikungunya virus disease (CHIKVD), an arboviral disease characterized by sudden fever and incapacitating poliartralgia, develop chronic articular symptoms, the mechanisms involved in CHIKVD’s chronification and its possible biomarkers remain poorly understood. Interleukin (IL)-17A, IL-21, IL-22, IL-29, and transforming growth factor (TGF)-β have been implicated in the pathogenesis of other inflammatory joint diseases, including rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis. Since chronic manifestations of CHIKVD share many clinical and immunological characteristics with those diseases, we assessed the serum levels of those cytokines and analyzed their associations with clinical manifestations in patients with CHIKVD. Methods We evaluated 45 patients (36 female, mean age: 55.2 ± 13.8 years) with CHIKVD serologically confirmed by enzyme-linked immunosorbent assay (ELISA), articular manifestations upon evaluation, and no previous history of inflammatory rheumatologic diseases, along with 49 healthy age- and sex-matched controls. We tested anti-Chikungunya IgM and IgG antibodies and measured IL-17A, IL-21, IL-22, IL-27, IL-29, and TGF-β serum levels with specific ELISA kits. Results IL-27, IL-17A, and IL-29 appeared in most patients but not in controls. IL-27 serum levels were higher in patients with chronic symptoms (median: 523.0 pg/mL [62.5–1,048]) than in ones in the acute or subacute stage (median: 62.5 pg/mL [62.5–483.8], p = .008). In patients with CHIKVD, we found significant correlations between IL-27 levels and tender joint counts (r = .32, p = .006), along with associations between IL-17A levels and swollen joint counts (r = .315, p = .0352). Furthermore, patients with arthritis had higher IL-17A levels (median: 23.14 pg/mL [20.6–25.86]) than ones without (median: 20.29 pg/mL [3.91–22.43], p = .0352). We did not detect IL-22 in either group or IL-21 in patients with CHIKVD. Conclusion Serum levels of IL-17A, IL-27, and IL-29 were high in patients with CHIKVD and had important associations with articular manifestations, which might indicate the inflammatory nature of Chikungunya infection in patients with joint symptoms and the roles of those cytokines in the disease’s pathophysiology.

Background. Due to the variety of functions that galectins (Gal) possess, it is clear that they participate in the pathogenesis of rheumatoid arthritis (RA). Although some studies demonstrate their functions, there is still no correlation with the clinical data of the disease, having the physiological meaning still unknown. Objectives. To compare serum levels of Gal-1, -4, and -7 in patients with RA and healthy controls and to correlate them with clinical parameters. Methods. Serum samples were collected from patients with RA and healthy donors to determine the serum levels of Gal-1, -4, and -7. Results. Serum levels of Gal-1, -4, and -7 were significantly higher in RA patients compared to controls. We evaluated disease activity (CDAI) with serum levels of galectins and found that patients who were high in disease activity had high levels of galectin compared to the moderate activity group. Galectin-4 had higher levels in patients who were in high activity when compared to the group in remission or low activity. Evaluating the activity of the individual disease (DAS28), patients in high individual activity had high levels of Gal-4 when compared to the group in remission or low activity. We also found an association between positive rheumatoid factor and Gal-1 and Gal-4 levels. Conclusion. Our results show for the first time the relationship between serum levels of galectin and the clinical parameters of patients with RA. Demonstrating their role in pathogenesis, new studies with galectins are needed to assess how they function as a biomarker in RA.

Although several cytokines and chemokines have been investigated as possible mediators of fibrosis in systemic sclerosis (SSc), specific correlation between cytokines and organ involvement have not been found yet, and a cytokine profile characteristic of SSc is far to be identified. We studied the profile of antifibrotic and profibrotic transcripts involved in skin of SSc patients. The mRNA expression was detected by fluorescence-based quantitative real-time PCR (qPCR) in skin's biopsies from 14 patients with SSc and 5 healthy controls. PDGF-A, CTGF, CCL3, IL-6, IL-13, IL-7, IFNγ, IL-17, IL-22 and RORc were analysed in these samples. CCL3, IL-7, IL-13 and IFN-γ were more expressed in skin's biopsy of patients with SSc (P = 0.0002, P = 0.0082, P = 0.0243, P = 0.0335, respectively) when compared with healthy controls. We also found a positive correlation between CCL3 and IL-7 transcripts (P = 0.0050 r = 0.7187). Furthermore, we observed that patients with lung involvement had lower expression of PDGF-A (P = 0.0385). We found an increase in IL-7, IFN-γ, CCL3 and IL-13 relative mRNA expressions on the skin's biopsy of patients with SSc, and a positive correlation between IL-7 and CCL3. These molecules are involved in the pathogenesis of SSc, and how their interactions occur should be the subject of further studies.

Glucocorticoids (GC) are widely used in the treatment of SSc, although there is not much evidence to prove the benefits offered by these drugs in this disease. In this study, we evaluated the effects of a GC on cytokine production in peripheral blood mononuclear cells (PBMC) of SSc patients. The effect of dexamethasone (DEX) was evaluated in PBMC of 21 SSc patients and 10 healthy volunteers after stimulation of cells with anti-CD3 and anti-CD28. Cytokines IL-2, IL-4, IL-6, IL-10, IL-17A, IL-17F, IFN-γ, TNF, and IL-1β were quantified in the culture supernatant by CBA or ELISA. Of the patients evaluated in this study, 8 (38%) were taking corticosteroids, and esophageal dysfunction was more frequent in these patients when compared to those who did not take corticosteroids. DEX (1.000 nM) treatment in PBMC of SSc patients stimulated with anti-CD3 and anti-CD28 promoted a significant reduction in IL-2, IL-4, IL-6, IL-10, IL-17A, IFN-γ, TNF, IL-1β (p

Alzheimer's disease (AD) is the world's leading cause of neurological dysfunction, cognitive decline, and neuronal loss in the elderly. The sedimentation of beta amyloid (Aβ)-containing plaque, and formation of tau-containing neurofibrillary tangles (NFTs) along with extensive neuroinflammation, are the events that characterize the pathogenesis of AD. Galectins (gal) are carbohydrate-containing-ligand molecules recognized as potential modulators of the brain microglia polarization, immunosurveillance, neuroinflammation, and neuroprotection. Galectins 1, 3, 4, 8, and 9 are amongst the 15 members of the galectin family which are expressed in the brain. These galectins possess a significant correlation with neuromodulation through the glial cell-induced cytokine production that plays either a complementary or antagonistic role in the disturbance of the CNS physiology. Therefore, elaborating the hypothesis of galectins in the development of AD is of potential interest. This review aims at discussing the interaction between galectins and the neuropathophysiology of AD. An understanding about how galectins communicate with AD progression could lead to the development of improved diagnostic and therapeutic strategies for this leading cause of dementia worldwide.

Systemic sclerosis (SSc) is a rare complex disease characterized by vascular damage, autoimmunity, and extensive skin and internal organs fibrosis. Galectin-3 (Gal-3) is encoded by geneTo investigate associations amongA case-control study with 88 patients and 151 matched controls was performed.TheThe

INTRODUCTION Herein, the authors describe a simple enhancement to a commercial rapid DNA extraction kit based on simple viral lysis for detecting COVID-19 via RT-qPCR. METHODS After testing several different modifications, the adapted protocol with the best results in preliminary experiments was statistically evaluated in comparison with an automated robotic protocol. RESULTS Processing and testing of 119 nasopharyngeal samples ultimately yielded near-perfect agreement with the automated protocol (κ = 0.981 [95% confidence interval 0.943-1.000]). CONCLUSIONS The low cost and rapidity of the enhanced protocol makes it suitable for adoption in laboratories diagnosing COVID-19, especially those with high demand for examinations.

Perineural invasion (PNI) is characterized by an encounter between the cancer cells and neuronal fibers and holds an extremely poor prognosis for malignant tumors. The exact molecular mechanism behind PNI yet remains to be explored. However, it is worth-noting that an involvement of the neuroactive molecules plays a major part in this process. A complex signaling network comprising the interplay between immunological cascades and neurogenic molecules such as tumor-derived neurotrophins, neuromodulators, and growth factors constitutes an active microenvironment for PNI associated with malignancy. The present review aims at discussing the following points in relation to PNI: a) Communication between PNI and neuroplasticity mechanisms can explain the pathophysiology of poor, short and long-term outcomes in cancer patients; b) Neuroactive molecules can significantly alter the neurons and cancer cells so as to sustain PNI progression; c) Finally, careful manipulation of neurogenic pathways and/or their crosstalk with the immunological molecules implicated in PNI could provide a potential breakthrough in cancer therapeutics.

The sialic acid-binding immunoglobulin-type lectin Siglec-15 is a promising target to cancer immunotherapy in several tumor types. The present study aimed to investigate Siglec-15 expression in gastric cancer (GC) patient tissue and to evaluate its clinical value. Siglec-15 expression was evaluated by immunohistochemistry with 71 patients. Siglec-15 staining was observed in tumor cells of 53 (74.64%) patients, with significant association with histologic classification and angiolymphatic invasion (p

Systemic sclerosis (SSc) is a rare complex disease characterized by vascular damage, autoimmunity, and extensive skin and internal organs fibrosis. Galectin-3 (Gal-3) is encoded by gene LGALS3 (Lectin, Galactoside-Binding, Soluble, 3; 14q22.3) and it has been reported to play a central role in self-tolerance, inflammation, and fibrosis. To investigate associations among LGALS3 single nucleotide polymorphisms (SNPs) and serum levels Gal-3 and SSc susceptibility and their clinical features. A case-control study with 88 patients and 151 matched controls was performed. LGALS3 variants were analyzed by the TaqMan real-time polymerase chain reaction (PCR) system whereas Gal-3 serum levels were measured by sandwich enzyme linked immunosorbent assay (ELISA). Associations among genotypes, clinical features, and Gal-3 levels were performed by univariable and multivariable analysis through statistical packages. The LGALS3 rs4652 A/C genotype was more frequent in SSc patients than controls according to overdominant model [OR 1.89 (CI 95% 1.01 − 3.52); p = .046]. Also, LGALS3 rs4652 C/C polymorphic genotype was associated with lower patient Gal-3 levels (p = .03) and control group (p = 0.005), as noted by generalized linear model (GLM). The LGALS3 rs1009977 G/T controls showed higher Gal-3 levels than wild-type and polymorphic genotypes (p = .03); however, in SSc patients, no difference was found. None of the LGALS3 SNPs or Gal-3 levels was associated with clinical manifestations in SSc patients. Considering only the SSc group, GLM analysis pointed LGALS3 rs4652 and rs2075601, pulmonary arterial hypertension (PAH), myopathy, and health assessment questionnaire (HAQ) and scleroderma health assessment questionnaire (SHAQ) as important predictors for Gal-3 levels. The LGALS3 rs4652 A/C was more frequent in SSc patients and related to lower Gal-3 levels. These findings were corroborated through a GLM to estimate Gal-3 values. Also, by model equations, Gal-3 levels may be predicted by HAQ, SHAQ, PAH, myopathy, and LGALS3 rs4652 and rs2075601 factors. In these ways, we suggest that galectins may be promising biomarkers to identify susceptibility to SSc as well as to identify HAQ, SHAQ, PAH, and myopathy outcomes.

Parkinson's disease (PD) induced by environmental toxins involves a multifactorial cascade of harmful factors, thus motivating the search for therapeutic agents able to act on the greatest number of molecular targets. This study evaluated the efficacy of 50 mg/kg purified anacardic acids (AAs), isolated from cashew nut shell liquid, on multiple steps of oxidative stress and inflammation induced by rotenone in the substantia nigra (SN) and striatum. Adult mice were divided into four groups: Control, rotenone, AAs + rotenone, and AAs alone. Lipoperoxidation, nitric oxide (NO) levels, and reduced glutathione (GSH)/oxidized gluthatione (GSSG) ratio were evaluated. NF-kB-p65, pro-IL-1β, cleaved IL-1β, metalloproteinase-9, Tissue Inhibitory Factor-1 (TIMP-1), tyrosine hydroxylase (TH), and glial fibrillary acidic protein (GFAP) levels were assessed by Western blot. In silico studies were also made using the SwissADME web tool. Rotenone increased lipoperoxidation and NO production and reduced TH levels and GSH/GSSG ratio in both SN and striatum. It also enhanced NF-kB-p65, pro, and cleaved IL-1β, MMP-9, GFAP levels compared to control and AAs groups. The AAs alone reduced pro-IL-1β in the striatum while they augmented TIMP1 and reduced MMP-9 amounts in both regions. AAs reversed rotenone-induced effects on lipoperoxidation, NO production, and GSH/GSSG ratio, as well as increased TH and attenuated pro-IL-1β and MMP-9 levels in both regions, NF-kB-p65 in the SN and GFAP in the striatum. Altogether, the in vivo and in silico analysis reinforced multiple and defined molecular targets of AAs, identifying that they are promising neuroprotective drug candidates for PD, acting against oxidative and inflammatory conditions induced by rotenone.

Background: Rheumatoid Arthritis (RA) is a chronic and inflammatory disease that affects about 1% of the world's population. Almost 70% of RA patients have a cardiovascular disease such as Systemic Arterial Hypertension (SAH). Inflammatory cytokines are clearly involved in the pathogenesis of RA and correlated with SAH. Objective: It is necessary to understand whether the antihypertensive drugs have a dual effect as immunomodulators and which one is the best choice for RA SAH patients. Methods: Peripheral Blood Mononuclear Cells (PBMCs) from 16 RA patients were purified and stimulated or not stimulated with anti-CD3 and anti-CD28 mAB and were treated with Enalapril, Losartan and Valsartan at 100μM. Patients were evaluated for clinical and laboratory variables including measures of disease activity by Clinical Disease Activity Index (CDAI) and Disease Activity Score (DAS28). Cytokines were quantified by ELISA sandwich. Results: Losartan was able to reduce levels of IFN-γ (p = 0.0181), IL-6 (p = 0.0056), IL-17F (0.0046) and IL-22 (p = 0.0234) in RA patients. In addition, patients in remission and mild score (DAS28 Conclusion: PBMCs from RA patients are responsive in inhibiting proinflammatory cytokines using Losartan better than Enalapril and Valsartan and it could be a better antihypertensive choice for patients with RA and systemic arterial hypertension treatment.

Chikungunya fever (CHIKF) is an arboviral disease that has caused an epidemic burst of chronic inflammatory joint disease in Latin America in the last few years. Efforts are being spent in understanding the mechanisms by which it may cause such articular damage and in determining possible biomarkers of the disease. Galectins (GAL) are a family of animal lectins with an affinity for beta-galactosides. They have multiple functions including working as receptors in innate immunity and as a control for inflammatory responses in both innate and adaptive immunity. They regulate functions of immune cells, such as lymphocytes and macrophages, which have a main role in the chikungunya inflammatory process. Galectins are also involved in chronification of viral diseases, participate in the immunopathogenesis of chronic joint diseases such as rheumatoid arthritis, and have a role in inflammation in other arboviral diseases, such as dengue. Thus, we intended to determine the serum levels of galectin-1, -3, -4, -7, and -9 in patients with subacute and chronic articular manifestations of CHIKF and to evaluate their associations with clinical manifestations. We evaluated 44 patients with clinical manifestations of CHIKF and serological confirmation with IgM and/or IgG chikungunya virus (CHIKV) antibodies. Forty-nine age- and gender-matched healthy individuals served as controls. Anti-CHIKV IgM and IgG antibodies and galectins serum levels were measured by ELISA. We found higher levels of GAL-9 (patients median 2192 [1500-2631] pg/mL, controls median 46.88 [46.88-46.88] pg/mL, p 0.0001) and lower levels of GAL-3 (patients median 235.5 [175.5-351.8] pg/mL, controls median 2236.0 [1256.0-2236.0] pg/mL, p 0.0001) in patients than in controls. There was no statistical difference in levels of GAL-1, -4 and -7 between patients and control groups. There was no difference in GAL-9 serum levels between patients with subacute or chronic symptoms (median 2148 [1500-2722] pg/mL x 2212 [1844-2500] pg/mL, p = 0.3626). A significant association of GAL-9 with joint stiffness, both in its duration and intensity, was found. These results may reflect the participation of GAL-9 in the immunopathogenesis of the inflammatory process in chikungunya fever, as morning stiffness may reflect the systemic inflammatory process.

Immune dysregulation is a central process in the pathogenesis of systemic sclerosis (SSc). Cytokines produced by lymphocytes and monocytes are important mediators and induce tissue damage, recruit additional inflammatory cells, and promote extracellular matrix production and fibrosis. In the present research, we aimed to study the associations between levels of cytokines in serum and culture supernatants from peripheral blood mononuclear cells (PBMCs) and clinical manifestations in SSc patients. Serum samples were obtained from 56 SSc patients and 56 unrelated age- and gender-matched healthy individuals. Resting and anti-CD3/CD28-stimulated PBMC cultures were obtained from 19 SSc patients and 8 healthy controls. IL-2, IL-4, IL-6, IL-10, IL-17A, TNF, and IFN-γ levels were measured by ELISA or CBA. Serum cytokines, except IL-17A, were below the kit detection limit in most of the patients and controls. In unstimulated PBMC, the production of TNF(p = 0.004), IL-10(p = .048), IL-2(p 0.001), and IL-6 (p = 0.01) was higher in SSc patients than in healthy controls. After anti-CD3/CD28 stimulation, scleroderma PBMCs had lower concentrations of TNF(p = 0.009), IL-10(p = .018), and IL-2(p = .002) than HC. In unstimulated PBMC, IL-2 concentration was higher in patients with esophageal dysmotility (p = 0.04), and IL-10 levels had a positive correlation with modified Rodnan score (p = 0.03). After anti-CD3/CD28 stimulation, higher levels of IL-2 and IL-4 were observed in SSc patients with lung fibrosis (p = 0.01 and 0.006, respectively), and higher levels of IL-10 (p = 0.04) and IL-4 (p = 0.04) in patients with digital ulcers. In conclusion, SSc patients have a different profile of cytokine production and this was associated with clinical manifestations.

Substitutions in thiophene structure give rise to new derivatives with different biological and pharmacological activities. The present study investigated the cytotoxicity activity of some thiophene derivatives in breast cancer cells maintained in two-dimensional (2D) or in three-dimensional (3D) culture and evaluated the anticancer mechanism of these compounds. Cytotoxicity assays were performed against untransformed cells and against breast cancer cell MCF-7. Apoptosis analysis and in-vitro migration assay were also performed to evaluate the mechanism of induction of cell death. All thiophene derivatives reduced the cell viability in breast cancer cells, showing cytotoxic activity (IC5030 µmol/l), and SB-200 compound showed the best selectivity index in MCF-7 cells compared with doxorubicin in 2D culture. All thiophene derivatives significantly induced G0/G1 phase cell cycle arrest. However, only SB-83 treatment was effective against motility of MCF-7 cells in 2D culture (P=0.0059). The SB-200 derivative treatment induced an increased proportion of acridine orange/Hoechst double-stained cells (35.35 vs. 3.14%, P=0.0002) compared with nontreated cells, with apoptosis morphological alterations independent of caspase 7 activation (P0.05). MCF-7 cells became less responsive to SB-200 and to doxorubicin in 3D culture compared with cells in 2D culture (higher IC50 values); however, SB-200 showed a better cytotoxic effect compared with doxorubicin in 3D culture. Therefore, the current study provides an insight into anticancer potential of thiophene derivatives, and further studies should be conducted to understand the mechanism by which thiophene derivatives act on cancer cells.

A alta incidência dos casos de câncer tornou-o evidente problema de saúde pública em todo o mundo. Os gestores da rede pública no Brasil alegam que os recursos repassados não são suficientes para cobrir os custos com os quimioterápicos. Este trabalho trouxe um panorama do serviço ofertado pelo SUS na rede de atenção oncológica em Pernambuco e avaliou a sustentabilidade financeira para garantir o acesso aos medicamentos quimioterápicos em um hospital referência. Tratou-se de um estudo observacional, analítico e retrospectivo, realizado no período de 2015 a 2020. Avaliou-se o custo dos quimioterápicos para o câncer de mama e foram analisadas as incorporações de novos tratamentos pela CONITEC durante o mesmo período. Foram realizados 343.585 procedimentos quimioterápicos nos estabelecimentos avaliados e observou-se que o câncer de mama foi a neoplasia mais onerosa. Observou-se ainda que o financiamento dos tratamentos oncológicos se manteve estável, apesar da evolução inflacionária e epidemiológica, havendo prejuízo na incorporação de tecnologias. Verificou-se que os custos com quimioterápicos para câncer de mama comprometeram 31,23% do valor pago pelo MS, e atualmente, com os reajustes do período, este passou a comprometer 100,75%. Ao projetar os reajustes para os próximos anos, verificou-se que o orçamento estaria comprometido em 121,6%, levando em conta o mesmo cenário inflacionário. Concluiu-se que a atual forma de financiamento do tratamento quimioterápico para o câncer de mama não se mostrou financeiramente sustentável no cenário avaliado e que se novos investimentos não forem aportados, os pacientes do SUS não serão beneficiados com as novas tecnologias de tratamento.

A ampla testagem da população é uma das formas mais eficazes para o controle da disseminação da Covid-19. Portanto, a Universidade Federal de Pernambuco (UFPE), em parceria com outras instituições públicas, forneceu infraestrutura e prestação de serviço para a realização dos exames moleculares do novo coronavírus, ampliando a testagem na população no estado de Pernambuco. Este artigo relata a experiência da UFPE no processo de implementação do teste molecular para a detecção de Covid-19. Para a implementação, foram necessárias articulações conjuntas entre o Gabinete do Reitor da UFPE, a Pró-Reitoria de Pesquisa e Inovação, a Superintendência de Infraestrutura da UFPE, a Fundação de Apoio ao Desenvolvimento da UFPE e professores de diferentes departamentos da universidade. O laboratório foi estruturado conforme as normas e diretrizes da Resolução da Diretoria Colegiada/Agência Nacional de Vigilância Sanitária. Termocicladores para RT-qPCR, ultra freezers e demais insumos foram cotados e adquiridos em um curto espaço de tempo, levando-se em conta as dificuldades de compra e importação de produtos. Após capacitações, implementação da gestão da qualidade e testes de proficiência com certificação, o laboratório iniciou a testagem. Em pouco menos de um ano, a UFPE entregou 89 mil laudos do diagnóstico molecular da Covid-19. Durante o processo de implementação, a urgência para a adequação estrutural e o atraso da chegada dos insumos foram as maiores dificuldades encontradas. A cooperação entre a UFPE, o estado de Pernambuco e as instituições ministeriais federais para a estruturação de um laboratório de apoio para o diagnóstico da Covid-19 pode ser seguida como modelo, pois mostrou-se efetiva considerando o número de testes realizados com confiabilidade, no curto período transcorrido, para dar suporte em tempo hábil aos gestores públicos na tomada de decisões frente à pandemia.