Bee Venom Toxic Effect on MDA-MB-231 Breast Cancer Cells and Caenorhabditis Elegans.

INTRODUCTION: Bee venom has therapeutics and pharmacological properties. Further toxicological studies on animal models are necessary due to the severe allergic reactions caused by this product. METHOD: Here, Caenorhabditis elegans was used as an in vivo toxicity model, while breast cancer cells were used to evaluate the pharmacological benefits. The bee venom utilized in this research was collected from Apis mellifera species found in Northeast Brazil. The cytotoxicity caused by bee venom was measured by MTT assay on MDA-MB-231 and J774 A.1 cells during 24 - 72 hours of exposure. C. elegans at the L4 larval stage were exposed for three hours to M9 buffer or bee venom. Survival, behavioral parameters, reproduction, DAF-16 transcription factor translocation, the expression of superoxide dismutase (SOD), and metabolomics were analyzed. Bee venom suppressed the growth of MDA-MB-231 cancer cells and exhibited cytotoxic effects on macrophages. Also, decreased C. elegans survival impacted its behaviors by decreasing C. elegans feeding behavior, movement, and reproduction. RESULTS: Bee venom did not increase the expression of SOD-3, but it enhanced DAF-16 translocation from the cytoplasm to the nucleus. C. elegans metabolites differed after bee venom exposure, primarily related to aminoacyl- tRNA biosynthesis, glycine, serine and threonine metabolism, and sphingolipid and purine metabolic pathways. Our findings indicate that exposure to bee venom resulted in harmful effects on the cells and animal models examined. CONCLUSION: Thus, due to its potential toxic effect and induction of allergic reactions, using bee venom as a therapeutic approach has been limited. The development of controlled-release drug strategies to improve this natural product's efficacy and safety should be intensified.

Performance of collagen-based matrices from Nile tilapia skin: A pilot proteomic study in a murine model of wound healing.

Full-thickness cutaneous trauma, due to the lack of dermis, leads to difficulty in epithelialization by keratinocytes, developing a fibrotic scar, with less elasticity than the original skin, which may have disorders in predisposed individuals, resulting in hypertrophic scar and keloids. Biomedical materials have excellent characteristics, such as good biocompatibility and low immunogenicity, which can temporarily replace traditional materials used as primary dressings. In this work, we developed two dermal matrices based on Nile tilapia collagen, with (M_GAG) and without (M) glycosaminoglycans, using a sugarcane polymer membrane as a matrix support. To assess the molecular mechanisms driving wound healing, we performed qualitative proteomic analysis on the wound bed in an in vivo study involving immunocompetent murine models at 14 and 21 days post-full-thickness skin injury. Gene Ontology and Pathway analysis revealed that both skins were markedly represented by modulation of the immune system, emphasizing controlling the acute inflammation response at 14 and 21 days post-injury. Furthermore, both groups showed significant enrichment of pathways related to RNA and protein metabolism, suggesting an increase in protein synthesis required for tissue repair and proper wound closure. Other pathways, such as keratinization and vitamin D3 metabolism, were also enriched in the groups treated with M matrix. Finally, both matrices improved wound healing in a full post-thick skin lesion. However, our preliminary molecular data reveals that the collagen-mediated healing matrix lacking glycosaminoglycan (M) exhibited a phenotype more favorable to tissue repair, making it more suitable for use before skin grafts.

Narrowing the Relationship between Human CCR5 Gene Polymorphisms and Chagas Disease: Systematic Review and Meta-Analysis.

Our aim was to carry out a qualitative and quantitative synthesis of the influence of CCR5 genetic variants on Chagas disease (CD) through a systematic review. A total of 1197 articles were analyzed, and eleven were included in the review. A meta-analysis was conducted along with principal component analyses (PCAs). The polymorphisms found were analyzed using the SNP2TFBS tool to identify possible variants that influence the interaction with gene binding sites. Eleven studied variants were identified: rs2856758, rs2734648, rs1799987, rs1799988, rs41469351, rs1800023, rs1800024, Δ32/rs333, rs3176763, rs3087253 and rs11575815. The studies analyzed were published between 2001 and 2019, conducted in Argentina, Brazil, Spain, Colombia and Venezuela, and included Argentine, Brazilian, Colombian, Peruvian and Venezuelan patients. Eight polymorphisms were subjected to the meta-analysis, of which six were associated with the development of the cardiac form of CD: rs1799987-G/G and G/A in the dominance model and G/G in the recessiveness model; rs2856758-A/G in the codominance model; rs2734648-T/T and T/G in the dominance model; rs1799988-T/T in both the codominance and recessiveness models; rs1800023-G allele and the G/G genotype in the codominance and recessiveness models, and the G/G and G/A genotypes in the dominance model; and rs1800024-T allele. The PCA analyses were able to indicate the relationships between the alleles and the genotypes of the polymorphisms. The SNP2TFBS tool identified rs1800023 as an influencer of the Spi1 transcription factor (p < 0.05). A correlation was established between the alleles associated with the cardiac form of CD in this review, members of the C haplotype of the gene (HHC-TGTG), and the cardiac form of CD.

Perfil ginecológico e obstétrico de usuárias que realizam o exame papanicolau / Gynecological and obstetric profile of users who perform the pap smear / Perfil ginecológico y obstétrico de las usuarias que realizan la prueba de papanicolaou

Objetivo: Identificar o perfil ginecológico e obstétrico de mulheres que realizam o exame Papanicolau em uma população do Nordeste, Brasil. Métodos: Estudo descritivo com abordagem quantitativa, realizado em unidades básicas de saúde entre os anos de 2014 e 2018. Resultados: Do total de 724 mulheres atendidas, 33,7% (n=244) tinham idade ≥48 anos e 64,2% (n=465) se autodeclararam pardas. A faixa etária mais prevalente da menarca foi de 13 a 15 anos, com 46,1% (n=334), e a da coitarca foi de 16 a 18 anos, com 39,1% (n=283). Os dados ainda evidenciaram que 58,6% (n=424) tiveram de 1 a 5 gestações e 32% (n=232) relataram a primeira gestação entre 18 e 21 anos. Conclusão: Conhecer o perfil desta população é de suma importância para identificação das principais vulnerabilidades do grupo, de modo que as estratégias de promoção, proteção e recuperação da saúde sejam condizentes com a realidade vivenciada por essas mulheres (AU).

Objective: To identify the gynecological and obstetrical profile of women who undergo the Pap smear in a population in Northeast Brazil. Methods: Descriptive study with a quantitative approach, carried out in basic health units between 2014 and 2018. Results: Of the total of 724 women assisted, 33.7% (n=244) were aged ≥48 years and 64.2% (n=465) self-declared brown. The most prevalent age group at menarche was 13 to 15 years old, with 46.1% (n=334), and that of coitarche was 16 to 18 years old, with 39.1% (n=283). The data also showed that 58.6% (n=424) had 1 to 5 pregnancies and 32% (n=232) reported their first pregnancy between 18 and 21 years old. Conclusion: Knowing the profile of this population is of paramount importance for identifying the main vulnerabilities of the group, so that health promotion, protection and recovery strategies are consistent with the reality experienced by these women (AU).

Objetivo: Identificar el perfil ginecoobstétrico de mujeres que se realizan el Papanicolaou en una población del Nordeste de Brasil. Métodos: Estudio descriptivo con abordaje cuantitativo, realizado en unidades básicas de salud entre 2014 y 2018. Resultados: Del total de 724 mujeres atendidas, 33,7% (n=244) tenían edad ≥48 años y 64,2% (n=465) marrón autodeclarado. El grupo etario más prevalente de menarquia fue de 13 a 15 años, con 46,1% (n=334), y el de coitarquia fue de 16 a 18 años, con 39,1% (n=283). Los datos también mostraron que el 58,6% (n=424) tuvo de 1 a 5 embarazos y el 32% (n=232) reportó su primer embarazo entre los 18 y los 21 años. Conclusión: Conocer el perfil de esta población es de suma importancia para identificar las principales vulnerabilidades del grupo, para que las estrategias de promoción, protección y recuperación de la salud sean acordes a la realidad que viven estas mujeres (AU).

Exploring metabolism in scleroderma reveals opportunities for pharmacological intervention for therapy in fibrosis.

Background: Recent evidence has indicated that alterations in energy metabolism play a critical role in the pathogenesis of fibrotic diseases. Studies have suggested that 'metabolic reprogramming' involving the glycolysis and oxidative phosphorylation (OXPHOS) in cells lead to an enhanced generation of energy and biosynthesis. The aim of this study was to assess the molecular basis of changes in fibrotic metabolism in systemic sclerosis (Scleroderma; SSc) and highlight the most appropriate targets for anti-fibrotic therapies. Materials and methods: Dermal fibroblasts were isolated from five SSc patients and five healthy donors. Cells were cultured in medium with/without TGF-ß1 and with/without ALK5, pan-PIM or ATM kinase inhibitors. Extracellular flux analyses were performed to evaluate glycolytic and mitochondrial respiratory function. The mitochondrial network in TMRM-stained cells was visualized by confocal laser-scanning microscopy, followed by semi-automatic analysis on the ImageJ platform. Protein expression of ECM and fibroblast components, glycolytic enzymes, subunits of the five OXPHOS complexes, and dynamin-related GTPases and receptors involved in mitochondrial fission/fusion were assessed by western blotting. Results: Enhanced mitochondrial respiration coupled to ATP production was observed in SSc fibroblasts at the expense of spare respiratory capacity. Although no difference was found in glycolysis when comparing SSc with healthy control fibroblasts, levels of phophofructokinase-1 isoform PFKM were significantly lower in SSc fibroblasts (P<0.05). Our results suggest that the number of respirasomes is decreased in the SSc mitochondria; however, the organelles formed a hyperfused network, which is thought to increase mitochondrial ATP production through complementation. The increased mitochondrial fusion correlated with a change in expression levels of regulators of mitochondrial morphology, including decreased levels of DRP1, increased levels of MIEF2 and changes in OPA1 isoform ratios. TGF-ß1 treatment strongly stimulated glycolysis and mitochondrial respiration and induced the expression of fibrotic markers. The pan-PIM kinase inhibitor had no effect, whereas both ALK5 and ATM kinase inhibition abrogated TGF-ß1-mediated fibroblast activation, and upregulation of glycolysis and respiration. Conclusions: Our data provide evidence for a novel mechanism(s) by which SSc fibroblasts exhibit altered metabolic programs and highlight changes in respiration and dysregulated mitochondrial morphology and function, which can be selectively targeted by small molecule kinase inhibitors.

Sarcopenia in Non-Dialysis Chronic Kidney Disease Patients: Prevalence and Associated Factors.

Background: Sarcopenia is related to morbidity and mortality in non-dialysis Chronic Kidney Disease (ND-CKD) patients; however, the pathophysiology of sarcopenia remains unclear. The study aimed to assess the prevalence and factors associated with sarcopenia in ND-CKD individuals. Methods: We cross-sectionally evaluated 139 prevalent ND-CKD patients attending our outpatient clinic at Hospital das Clínicas of the Federal University of Pernambuco, between April and October 2019. Patients older than 18 years old and at G3-G5 CKD stages were included. Hand grip strength, Muscle Mass appendicular Index, and Gait Speed (GS) were defined by the standards of the European Working Group on Sarcopenia in Older People 2 guideline. Results: Sarcopenia prevalence was 20.9% and severe sarcopenia 2.9%. Sarcopenic were mostly found in elderly ones (64.8 ± 13.5 years vs. 54.9 ± 12.8 years, p < 0.001), revealing lower body mass index [26.1 (6.8) vs. 28.6 (6.2), p = 0.023], lower phase angle (PhA) [4.50 (1.10) vs. 5.60 (1.20), p < 0.001] and lower GS [1.00 (0.50) vs. 1.40 (0.4), p < 0.001]. They also presented lower serum creatinine levels [2.40 (1.50) vs. 3.0 (1.8), p = 0.032], lower Albumin-to-Creatinine Ratio [72.60 (1008.30) vs. 342.30 (1172.1), p = 0.039] and Hemoglobin levels [11.45 (1.8) vs. 12.60 (2.40), p = 0.003], and higher levels of C-reactive protein [0.2 (0.80) vs. 0.03 (0.3), p = 0.045] compared to non-sarcopenic. Under Poisson Multivariate Model, PhA [Relative precision (RP): 0.364, Confidence Interval (CI) (95%):0.259-0.511, p < 0.001], Interleukin six (IL-6) [RP: 1.006, CI (95%):1.001-1.01, p = 0.02] and serum creatinine levels [RP: 0.788, CI (95%): 0.641-0.969, p = 0.024] were associated with sarcopenia. Conclusions: Sarcopenia predominance was identified in our ND-CKD population, and was associated with lower PhA values, higher IL-6 levels, and lower serum creatinine levels.

The impact of supervised physical exercise on chemokines and cytokines in recovered COVID-19 patients.

COVID-19 is an infectious disease caused by the SARS-CoV-2 virus, which induces a high release of pro-inflammatory chemokines and cytokines, leading to severe systemic disorders. Further, evidence has shown that recovered COVID-19 patients still have some symptoms and disorders from COVID-19. Physical exercise can have many health benefits. It is known to be a potent regulator of the immune system, which includes frequency, intensity, duration, and supervised by a professional. Given the confinement and social isolation or hospitalization of COVID-19 patients, the population became sedentary or opted for physical exercise at home, assuming the guarantee of the beneficial effects of physical exercise and reducing exposure to SARS-CoV-2. This study aimed to investigate the effects of a supervised exercise protocol and a home-based unsupervised exercise protocol on chemokine and cytokine serum levels in recovered COVID-19 patients. This study was a prospective, parallel, two-arm clinical trial. Twenty-four patients who had moderate to severe COVID-19 concluded the intervention protocols of this study. Participants were submitted to either supervised exercise protocol at the Clinical Hospital of the Federal University of Pernambuco or home-based unsupervised exercise for 12 weeks. We analyzed serum levels of chemokines (CXCL8/IL-8, CCL5/RANTES, CXCL9/MIG, CCL2/MCP-1, and CXCL10/IP-10) and cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, and IFN-γ). Before the interventions, no significant differences were observed in the serum levels of chemokines and cytokines between the supervised and home-based unsupervised exercise groups. The CXCL8/IL-8 (p = 0.04), CCL2/MCP-1 (p = 0.03), and IFN-γ (p = 0.004) levels decreased after 12 weeks of supervised exercise. In parallel, an increase in IL-2 (p = 0.02), IL-6 (p = 0.03), IL-4 (p = 0.006), and IL-10 (p = 0.04) was observed after the supervised protocol compared to pre-intervention levels. No significant differences in all the chemokines and cytokines were found after 12 weeks of the home-based unsupervised exercise protocol. Given the results, the present study observed that supervised exercise was able to modulate the immune response in individuals with post-COVID-19, suggesting that supervised exercise can mitigate the inflammatory process associated with COVID-19 and its disorders. Clinical trial registration: https://ensaiosclinicos.gov.br/rg/RBR-7z3kxjk, identifier U1111-1272-4730.

A proteomics evaluation of the primary and secondary immune response of Biomphalaria straminea challenged by Schistosoma mansoni.

Biomphalaria spp. snails are intermediary hosts of Schistosoma mansoni, etiologic agent of intestinal schistosomiasis, one of the most important neglected tropical diseases. Biomphalaria straminea is an important intermediary host that possess a different phenotype to parasite infection but shows a large geographic distribution and high capacity of new ecologic niche invasion. Our purpose was to characterize for the first time the differentially expressed proteome in B. straminea during two times intervals after primary and secondary exposure to S. mansoni. The hemolymph was collected at 1 and 15 days after primary and secondary exposure of snails to the parasite. Total proteins were extracted and digested with trypsin. LC-MS/MS label-free quantification was performed and analyzed using Maxquant and Perseus software. Proteins were identified and annotated using Blast2GO tools. After 1 day of exposure, most of upregulated proteins are hemoglobin type 2, C and H type lectins, molecules related to cell adhesion, and response to oxidative stress. After 15 days, we found a similar pattern of upregulated proteins but some fibrinogen-related proteins (FREPs) and TEPs homologs were downregulated. Regarding the differentially expressed proteins during secondary response, the principal immune-related proteins upregulated were C and H type lectins, cellular adhesion molecules, biomphalysin, and FREP3. We noted a several upregulated biological processes during both responses that could be the one of the key points of efficacy in the immune response to parasite. Our data suggests different immune mechanisms used by B. straminea snails challenged with S. mansoni.

Outcomes of critically ill patients with acute kidney injury in COVID-19 infection: an observational study.

BACKGROUND: Early reports indicate that AKI is common during COVID-19 infection. Different mortality rates of AKI due to SARS-CoV-2 have been reported, based on the degree of organic dysfunction and varying from public to private hospitals. However, there is a lack of data about AKI among critically ill patients with COVID-19. METHODS: We conducted a multicenter cohort study of 424 critically ill adults with severe acute respiratory syndrome (SARS) and AKI, both associated with SARS-CoV-2, admitted to six public ICUs in Brazil. We used multivariable logistic regression to identify risk factors for AKI severity and in-hospital mortality. RESULTS: The average age was 66.42 ± 13.79 years, 90.3% were on mechanical ventilation (MV), 76.6% were at KDIGO stage 3, and 79% underwent hemodialysis. The overall mortality was 90.1%. We found a higher frequency of dialysis (82.7% versus 45.2%), MV (95% versus 47.6%), vasopressors (81.2% versus 35.7%) (p < 0.001) and severe AKI (79.3% versus 52.4%; p = 0.002) in nonsurvivors. MV, vasopressors, dialysis, sepsis-associated AKI, and death (p < 0.001) were more frequent in KDIGO 3. Logistic regression for death demonstrated an association with MV (OR = 8.44; CI 3.43-20.74) and vasopressors (OR = 2.93; CI 1.28-6.71; p < 0.001). Severe AKI and dialysis need were not independent risk factors for death. MV (OR = 2.60; CI 1.23-5.45) and vasopressors (OR = 1.95; CI 1.12-3.99) were also independent risk factors for KDIGO 3 (p < 0.001). CONCLUSION: Critically ill patients with SARS and AKI due to COVID-19 had high mortality in this cohort. Mortality was largely determined by the need for mechanical ventilation and vasopressors rather than AKI severity.

A first, naturally occurring substitution at the second pyrethroid receptor of voltage-gated sodium channel of Aedes aegypti.

BACKGROUND: Aedes aegypti is a remarkably effective mosquito vector of epidemiologically important arboviral diseases including dengue fever, yellow fever and Zika. The present spread of resistance against pyrethroids, the primary insecticides used for mosquito control, in global populations of this species is of great concern. The voltage-gated sodium channel (VGSC) in the nervous system is the known target site of pyrethroids in insects. Past studies have revealed several amino-acid substitutions in this channel that confer pyrethroid resistance, which are known as knockdown resistance (kdr) mutations. RESULTS: This study investigated a laboratory colony of Ae. aegypti, MCNaeg, established from larvae collected in Rio de Janeiro, Brazil in 2016. The MCNaeg colony showed strong resistance against pyrethroids without laboratory selection. Of the two VGSC gene haplotypes present within this colony, one harbored three known kdr mutations, V410L, V1016I, and F1534C, and the other harbored only the known F1534C mutation. In latter haplotype, we also found novel amino-acid substations including V253F. Previous molecular modeling and electrophysiological studies suggest that this residue serves a pyrethroid-sensing site in the second receptor, PyR2. Our genetical analysis showed that the haplotype harboring V253F and F1534C is associated with equal or slightly stronger resistance than the other triple kdr haplotype to both Type I and Type II pyrethroids. CONCLUSION: The novel substitution V253F is potentially involved in pyrethroid resistance in Ae. aegypti. Further studies are needed to elucidate the role of this substitution in the pyrethroid susceptibility of VGSC. © 2021 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

miRNA-195 expression in the tumor tissues of female Brazilian breast cancer patients with operable disease.

OBJECTIVE: This study aimed to assess miRNA-195 expression in the tumor tissues from a cohort of Brazilian female breast cancer patients undergoing neoadjuvant chemotherapy (NAC) and evaluate its correlation with various clinicopathological markers. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the miRNA-195 expression in tumor tissues from a cohort of female breast cancer patients undergoing NAC. This expression was then correlated with the occurrence of several distinct breast cancer molecular subtypes and other clinicopathological variables. RESULTS: A total of 55 patients were included in this study, 28 (50.9%) of whom were treated using NAC. Tumor miRNA-195 expression was suppressed in breast cancer patients, regardless of their exposure to systemic treatments, histological grade, size, nodal status, and tumor-node-metastasis (TNM) staging. This was more pronounced in luminal and triple-negative patients, and patient's response to NAC was correlated with an increase in miRNA-195 expression. CONCLUSION: miRNA-195 is downregulated in the tumor tissues of Brazilian breast cancer patients regardless of NAC exposure; this reinforces its role as a tumor suppressor and a potential biomarker for chemotherapy response.

Chikungunya Virus Infection Outcome: A Systematic Review of Host Genetics.

Background: Chikungunya virus (CHIKV) is a global concern, inducing chikungunya fever and trigging an arthritogenic chronic phase beyond some severe forms. Outcomes of CHIKV infections in humans are dependent on genetic variations. Here, a systematic review was performed to show evidence of genetic variations on infection outcomes of patients. Methods: Searches were performed in Scopus, SciELO, MEDLINE/PubMed, Web of Science, OneFile (GALE), Periódicos CAPES and ScienceDirect Journals databases. The PICOS approach was used to assess the eligibility of records. A meta-analysis was also conducted to show an association between described alleles/genes and CHIKV infection outcome. Results: Reviews of genetic variants were conducted on genes: CD 209, OAS1, OAS2, OAS3, MIF, TLR-3, TLR-7, TLR-8, MYD-88, KIR, HLA-B; HLA-C; DRB1 and DQB1. Studies were performed on Gabon, Singapore, and India, including Indians, Malay, Gabonese and Chinese ethnicities and published between 2009-2017. The meta-analysis was performed with DRB1 *01; *03; *04; *07; *10; *11; *13; *14 and *15 and DQB1 *02; *03; *05 and *06 alleles with Indian population sample. Sampling power was >80% and a significant positive association between DRB1*14 and CHIKV infection was found (OR = 1.67, 95% CI = 1.04-2.67; p = .03). Conclusion: Majority of the studies were conducted in India. Meta-analysis suggests that DRB1*14 is related to the susceptibility of symptomatic CHIKV infection in Indian population. The literature about CHIKV infection and genetic variations is scarce. The precise role of genetic variation in CHIKV is not clear yet. Further studies are necessary to provide more concrete evidences.

Association of Polymorphisms in Cytokine genes with susceptibility to Precancerous Lesions and Cervical Cancer: A systematic review with meta-analysis.

Objectives: This study investigated the relationship between single-nucleotide polymorphisms (SNPs) in cytokine genes and the susceptibility to Squamous Intraepithelial Lesions (SIL), cervical cancer and HPV infection through a systematic review with meta-analysis. To verify the effect of SNPs, we also analyzed the transcription factor binding affinity using bioinformatics tools.Methods: Seven electronic databases (MEDLINE, Scielo, BIREME, PubMed, Scopus, Web of Science and Science Direct) were searched for case-control studies.Results: A total of 35 relevant case-control studies were meta-analyzed, including 7 cytokine genes and 15 SNPs. SNPs in IL-17A (rs2275913, rs3748067); IL-17 F (rs763780); IL-12A (rs568408); IL-12B (rs3212227); TNFA (rs1800629, rs361525); IL-1B (rs16944); IL-6 (rs1800795); IL-10 (rs1800896) genes were associated with increased risk for cervical cancer. No association was observed between meta-analyzed polymorphisms and SIL. Additional bioinformatics analysis suggested a possible transcriptional regulation pathway of the TNFA and IL-10 genes through the MZF1 (TNFA -308 G > A and IL-10 - 1082A>G) and ZNF263 (TNFA -238 G > A) transcription factors binding.Conclusion: Overall, 10 SNPs in cytokine genes were associated with increased risk for cervical cancer. Therefore, in our meta-analysis, these SNPs demonstrated to be potential biomarkers for predicting or identifying cases of high risk for SIL and cervical cancer.

Lovastatin producing by wild strain of Aspergillus terreus isolated from Brazil.

Lovastatin is a drug in the statin class which acts as a natural inhibitor of 3-hydroxy-3-methylglutaryl, a coenzyme reductase reported as being a potential therapeutic agent for several diseases: Alzheimer's, multiple sclerosis, osteoporosis and due to its anti-cancer properties. Aspergillus terreus is known for producing a cholesterol reducing drug. This study sets out to evaluate the production of lovastatin by Brazilian wild strains of A. terreus isolated from a biological sample and natural sources. Carbon and nitrogen sources and the best physicochemical conditions using factorial design were also evaluated. The 37 fungal were grown to produce lovastatin by submerged fermentation. A. terreus URM5579 strain was the best lovastatin producer with a level of 13.96 mg/L. Soluble starch and soybean flour were found to be the most suitable substrates for producing lovastatin (41.23 mg/L) and biomass (6.1 mg/mL). The most favorable production conditions were found in run 16 with 60 g/L soluble starch, 15 g/L soybean flour, pH 7.5, 200 rpm and maintaining the solution at 32 °C for 7 days, which led to producing 100.86 mg/L of lovastatin and 17.68 mg/mL of biomass. Using natural strains and economically viable substrates helps to optimize the production of lovastatin and promote its use.

miRNA-195 expression in the tumor tissues of female Brazilian breast cancer patients with operable disease

OBJECTIVE: This study aimed to assess miRNA-195 expression in the tumor tissues from a cohort of Brazilian female breast cancer patients undergoing neoadjuvant chemotherapy (NAC) and evaluate its correlation with various clinicopathological markers. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the miRNA-195 expression in tumor tissues from a cohort of female breast cancer patients undergoing NAC. This expression was then correlated with the occurrence of several distinct breast cancer molecular subtypes and other clinicopathological variables. RESULTS: A total of 55 patients were included in this study, 28 (50.9%) of whom were treated using NAC. Tumor miRNA-195 expression was suppressed in breast cancer patients, regardless of their exposure to systemic treatments, histological grade, size, nodal status, and tumor-node-metastasis (TNM) staging. This was more pronounced in luminal and triple-negative patients, and patient's response to NAC was correlated with an increase in miRNA-195 expression. CONCLUSION: miRNA-195 is downregulated in the tumor tissues of Brazilian breast cancer patients regardless of NAC exposure; this reinforces its role as a tumor suppressor and a potential biomarker for chemotherapy response.

Human papillomavirus infection and risk factors to cervical cancer in asymptomatic women in the region of the Northeast of Brazil / Infecção pelo papillomavirus humano e fatores de risco para o cancer cervical em mulheres assintomáticas em uma região do Nordeste do Brasil

Objective: This study sought to identify the presence of HPV infection and the risk factors related to susceptibility to cervical cancer in asymptomatic women. Methods: It is a cross-sectional study with 428 users attended Basic Health Units, in Arapiraca, Alagoas, Brazil. Sociodemographic, behavioral variables, and cytopathological reports were collected. Molecular detection of the HPV virus was performed by Nested-PCR. Statistical analysis was conducted with SPSS version 22.0. Results: A total of 428 women were studied, HPV DNA detected in 39.2% (n = 168), with a mean age of 41 years old. There was an association of HPV with use of oral contraceptives (p <0.016) and alcoholism (p <0.038). It was showed a higher frequency of positive HPV in women older than 25 years old (88.7%), up to 5 sexual partners (93.4%), up to 3 pregnancies (71.4%), and with the cytopathologic results within the limits of normality (61.9%). HPV was identified in 40.3% (104/258) of the women with results within the limits of normality. Conclusion: Our results suggest that the use of oral contraceptives and alcoholism may be considered as possible risk factors related to cervical oncogenesis. With this, it is necessary to propose interventions aimed at the health education of this population, actions of prevention, and early detection.

Objetivo: Este estudo buscou identificar a presença de infecção pelo HPV e os fatores de risco relacionados à suscetibilidade ao câncer do colo do útero em mulheres assintomáticas. Métodos: Trata-se de um estudo transversal com 428 usuários atendidos em Unidades Básicas de Saúde, em Arapiraca, Alagoas, Brasil. Foram coletados relatórios sociodemográficos, variáveis comportamentais e citopatológicos. A detecção molecular do vírus HPV foi realizada por Nested-PCR. A análise estatística foi realizada com SPSS versão 22.0. Resultados: Foram estudadas 428 mulheres, com DNA de HPV detectado em 39,2% (n =168), com média de idade de 41 anos. Houve associação do HPV com o uso de anticoncepcional oral (p<0,016) e alcoolismo (p <0,038). Foi evidenciada maior frequência de HPV positivo em mulheres maiores de 25 anos (88,7%), até cinco parceiros sexuais (93,4%), até três gestações (71,4%) e com resultados citopatológicos dentro dos limites da normalidade (61,9%). O HPV foi identificado em 40,3% (104/258) das mulheres com resultados dentro dos limites da normalidade. Conclusão: Nossos resultados sugerem que o uso de anticoncepcionais orais e o alcoolismo podem ser considerados como possíveis fatores de risco relacionados à oncogênese cervical. Com isso, é necessário propor intervenções voltadas para a educação em saúde dessa população, ações de prevenção e detecção precoce.

The incidence of NOS3 gene polymorphisms on newborns with large and small birth weight.

The NOS3 gene polymorphisms T-786C, G894T and VNTR 4b/a are associated with a predisposition to the development of Metabolic Syndrome (MetS). The NOS3 gene contributes to a normal pregnancy and fetal development. According to their birthweight, newborns can be classified as: small (SGA), adequate (AGA) or large (LGA) for gestational age. The SGA and LGA present a higher risk of developing disorders related to MetS, both during childhood and adulthood. Therefore, the aim of this work is to relate the incidence of G894T, T-786C and VNTR 4b/a on SGA and LGA newborns and their mothers. 204 blood samples were collected from mothers (102) and the umbilical cords of 102 newborns (SGA = 12; AGA = 47; LGA = 43). The genotyping was performed through PCR-RFLP to evaluate presence of the G894T, T-786C and VNTR 4b/a polymorphisms. A significant difference was found between the groups of newborns in the genotypic frequency of T-786C, but without Hardy-Weinberg equilibrium. The VNTR 4b/a and the G894T polymorphisms showed no significance between the groups. The haplotype analysis showed that the SGA newborns presented the higher frequency of 4aGT (9.8%) and of the 4aTT combination (25.4%), while LGA newborns presented the higher frequency of the 4bTT haplotype (23%). Only the SGA newborns and their mothers presented the 4aTC haplotype. In conclusion, the NOS3 polymorphisms do not appear to be a factor to inadequate birth weight. However, the G894T and VNTR 4b/a polymorphisms, and the haplotype 4aTC, seem to influence the occurrence of SGA.

Mirna21 Expression in the Breast Cancer Tumor Tissue is Independent of Neoadjuvant Chemotherapy.

INTRODUCTION: MicroRNA-21 (miRNA-21) has been described as one of the most significantly upregulated miRNAs in human breast cancer. However, limited knowledge exists on miRNA-21 expression in breast cancer tissue after neoadjuvant chemotherapy (NAC). PURPOSE: The aim of this study was to assess miRNA-21 expression in the tumor tissues of Brazilian patients with breast cancer who underwent NAC and its correlation with clinicopathological variables. PATIENTS AND METHODS: Utilizing qRT-PCR, miRNA-21 expression in tumor tissue was measured in a cohort of female patients with breast cancer who underwent NAC. The correlation of miRNA-21 expression with breast cancer molecular subtypes and other clinicopathological variables was also assessed. RESULTS: A total of 55 patients were included in the study, and 28 (50.9%) underwent NAC. miRNA-21 was upregulated in patients with breast cancer, regardless of previous exposure to chemotherapy, molecular subtypes, tumor-node-metastasis (TNM) staging and lymph node status of the axilla. miRNA-21 expression did not differ between patients with breast cancer who achieved a pathologic complete response after NAC and healthy controls. CONCLUSION: miRNA-21 was upregulated in the tumor tissue of Brazilian patients with breast cancer regardless of NAC treatment, which reinforces its role as an "oncomiR" and a potential biomarker.

Whey milk proteomics from Schistosoma mansoni-infected mice reveals proteins involved in immunomodulation of the offspring.

Milk from schistosomotic mothers can modulate the immune response of their offspring. However, its characterization and potential of modulating immunity has not yet been fully elucidated. Thus, the aim of this study was to evaluate whey proteins from the milk of Schistosoma mansoni-infected mice in order to identify the fractions which can act as potential immunomodulatory tools. For this, we did a mass spectrometry (nanoUPLC-MSE) analysis to characterize the proteomic profile of milk from infected (MIM) and non-infected mice (MNIM). It was possible to identify 29 differentially expressed proteins: 15 were only found in MIM, 10 only found in MNIM, and 4 were downregulated in MIM group. Gene Ontology (GO), pathway enrichment analysis, and protein-protein interaction (PPI) analyses indicated differentially expressed proteins linked to biological processes and pathways in MIM group such as the following: fructose 1,6-biphosphate metabolic and glycolytic processes, glucose metabolism, and neutrophil degranulation pathways. The downregulated and unique proteins identified in MNIM group were involved in the positive regulation of B cell activation and receptor signaling pathway, in the innate immune response, complement activation, and phagocytosis. The present findings revealed a protein profile that may be involved in the activation and deactivation of the offspring's immune system in the long term, conferring a protective character due to the previous contact with milk from infected mothers.

A durable murine model of spleen transplantation with arterial and venous anastomoses.

The spleen is a large lymphoid organ located in the abdomen that filters blood and regulates the immune system. The extent of mobilization of splenic immune cells to peripheral tissues in health and disease, however, remains poorly understood. This is due, in large part, to a lack of in vivo, spleen-specific lineage tagging strategies. Here, we describe a detailed practical protocol of spleen transplantation and its evaluation for long-term graft survival. Unlike implantation of splenic morsels in the great omentum, our approach uses arterial and venous anastomoses which rapidly restores blood flow and facilitates long-term survival of the graft. The use of congenic mouse strains permits the use of immunofluorescence and flow cytometry-based methodologies to unambiguously track the migration of spleen-derived cells to peripheral tissues.