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.

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.

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.

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.

Gestation and breastfeeding in schistosomotic mice differentially alters the expression of histone deacetylases (HDACs) in adult offspring.

BACKGROUND: Breastfeeding or gestation in schistosomotic mothers can cause long-term alterations in the immune response of offspring. OBJECTIVES: Evaluate the expression of histone deacetylases (HDACs) (all classes), the production of cytokines by T and B lymphocytes and macrophages, and the frequency of CD4+CD25+FoxP3+-cells in adult offspring born and/or suckled by schistosomotic mothers. METHODS: We harvested splenocytes from offspring born to (BIM), suckled by (SIM), or born to/suckled by (BSIM) schistosomotic mothers and animals from noninfected mothers (Control) at seven-weeks old and cultured them with/without Concanavalin A. HDAC expression was evaluated by real-time quantitative polymerase chain reaction (qPCR), and cytokines and membrane markers were evaluated by fluorescence-activated cell sorting (FACS). FINDINGS: Compared to Control, BIM mice showed increased expression of HDAC9 and frequency of CD4+IL-10+-cells. The SIM group had increased expression of HDAC1, HDAC2, HDAC6, HDAC7, HDAC10, Sirt2, Sirt5, Sirt6, and Sirt7. The BSIM group only had increased HDAC10 expression. The SIM and BSIM groups exhibited decreased frequencies of CD4+IL-4+-cells and CD4+CD25+FoxP3+-cells, along with a higher frequency of CD14+IL-10+-cells and an increase in CD45R/B220+IL-10+-cells. The BSIM group also showed a high frequency of CD4+IL10+-cells. MAIN CONCLUSIONS: Breastfeeding induced the expression of HDACs from various classes involved in reducing inflammatory responses. However, gestation enhanced the expression of a single HDAC and breastfeeding or gestation appears to favour multiple IL-10-dependent pathways, but not cells with a regulatory phenotype.

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.

Gender differences in the prevalence of congenital heart disease in Down's syndrome: a brief meta-analysis.

BACKGROUND: Down's syndrome (DS) affects one per 700 live births and congenital heart disease (CHD) occurs in 40-60% of these patients. Contributing factors to the association between DS and CHD are being unraveled. Gender could be one of them. METHODS: We performed a meta-analysis of CHD prevalence in DS, separated by gender. Three search engines were used and 578 articles were reviewed. Twelve articles were included. RESULTS: Quantitative analysis showed a higher prevalence of CHD, particularly atrioventricular septal defects (AVSD), in female patients. No differences were found in others forms of CHD. CONCLUSION: CHD, particularly AVSD, are more common in the female gender of Down's syndrome patients.

Purification and characterization of a collagenase from Penicillium sp. UCP 1286 by polyethylene glycol-phosphate aqueous two-phase system.

Collagenases are proteolytic enzymes capable of degrading both native and denatured collagen, reported to be applied in industrial, medical and biotechnological sectors. Liquid-liquid extraction using aqueous two-phase system (ATPS) is one of the most promising bioseparation techniques, which can substitute difficult solid-liquid separation processes, offering many advantages over conventional methods including low-processing time, low-cost material and low-energy consumption. The collagenase produced by Penicillium sp. UCP 1286 showed a stronger affinity for the bottom salt-rich phase, where the highest levels of collagenolytic activity were observed at the center point runs, using 15.0% (w/w) PEG 3350 g/mol and 12.5% (w/w) phosphate salt at pH 7.0 and concentration. The enzyme was characterized by thermal stability, pH tolerance and effect of inhibitors, showing optimal collagenolytic activity at 37 °C and pH 9.0 and proved to be a serine protease. ATPS showed high efficiency in the collagenase purification, confirmed by a single band in SDS/PAGE, and can in fact be applied as a quick and inexpensive alternative method.

Selective cathepsin S inhibition attenuates atherosclerosis in apolipoprotein E-deficient mice with chronic renal disease.

Chronic renal disease (CRD) accelerates the development of atherosclerosis. The potent protease cathepsin S cleaves elastin and generates bioactive elastin peptides, thus promoting vascular inflammation and calcification. We hypothesized that selective cathepsin S inhibition attenuates atherogenesis in hypercholesterolemic mice with CRD. CRD was induced by 5/6 nephrectomy in high-fat high-cholesterol fed apolipoprotein E-deficient mice. CRD mice received a diet admixed with 6.6 or 60 mg/kg of the potent and selective cathepsin S inhibitor RO5444101 or a control diet. CRD mice had significantly higher plasma levels of osteopontin, osteocalcin, and osteoprotegerin (204%, 148%, and 55%, respectively; P < 0.05), which were inhibited by RO5444101 (60%, 40%, and 36%, respectively; P < 0.05). Near-infrared fluorescence molecular imaging revealed a significant reduction in cathepsin activity in treated mice. RO5444101 decreased osteogenic activity. Histologic assessment in atherosclerotic plaque demonstrated that RO5444101 reduced immunoreactive cathepsin S (P < 0.05), elastin degradation (P = 0.01), plaque size (P = 0.01), macrophage accumulation (P < 0.01), growth differentiation factor-15 (P = 0.0001), and calcification (alkaline phosphatase activity, P < 0.01; osteocalcin, P < 0.05). Furthermore, cathepsin S inhibitor or siRNA significantly decreased expression of growth differentiation factor-15 and monocyte chemotactic protein-1 in a murine macrophage cell line and human primary macrophages. Systemic inhibition of cathepsin S attenuates the progression of atherosclerotic lesions in 5/6 nephrectomized mice, serving as a potential treatment for atherosclerosis in patients with CRD.

Immunocytochemical study of TOP2A and Ki-67 in cervical smears from women under routine gynecological care.

BACKGROUND: Cervical cancer is one of the most common female cancers and is caused by human papillomavirus (HPV). Viral infection leads to cell cycle deregulation by inactivating p53 and retinoblastoma protein by viral oncoproteins E6 and E7, respectively. Then, nuclear proteins such as DNA topoisomerase type IIa (TOP2A) and Ki-67 show increased expression because of increased cell division. These molecules are used as biomarkers for immunohistochemistry analysis of cervical tissue. METHODS: In this cross-sectional study, we recruited 110 women receiving regular gynecological surveillance at public health centers in Olinda - PE, Brazil. Cervicovaginal cells were collected to determine the presence of cytological abnormalities and HPV infection. Pap smear slides were used to evaluate the expression of TOP2A and Ki-67 using immunocytochemistry techniques. RESULTS: Of the 110 women, 75.4 % showed HPV-DNA(+) infection (83/110) and 29.1 % showed cellular abnormalities (32/110). Two atypical cells of undetermined significance, one low-grade squamous intraepithelial lesion, and one high-grade squamous intraepithelial lesion samples showed no HPV-DNA. TOP2A was positive in 71.9 % of samples, while Ki-67 was positive in 81.2 %. Immunocytochemistry results were positive in 4 of 5 atypical cells of undetermined significance samples. In HPV-DNA(+) samples with cytological abnormalities, immunocytochemistry results were positive 96.4 % of samples (p < 0.0001; odds ratio = 28.0). Among the samples infected with HR-HPV, TOP2A(+) was effective in 71 % samples, while and Ki-67(+) was 77.4 %. Ki-67 and TOP2A were positive for all samples infected with HPV6, HPV11, and HPV18. Ki-67 was also positive for all HPV16 samples, except for one negative sample in cytopathology analysis. CONCLUSIONS: TOP2A and Ki-67 antibodies may be used in combination for cervical cancer screening in immunocytochemistry assays.

A telemedicine network for remote paediatric cardiology services in north-east Brazil.

PROBLEM: Providing health care for children with congenital heart diseases remains a major challenge in low- and middle-income countries. APPROACH: In October 2011, the Government of Paraíba, Brazil, established a paediatric cardiology network in partnership with the nongovernmental organization Círculo do Coração. A cardiology team supervised all network activities, using the Internet to keep in contact with remote health facilities. The network developed protocols for screening heart defects. Echocardiograms were performed by physicians under direct online supervision of a cardiologist; alternatively, a video recording of the examination was subsequently reviewed by a cardiologist. Cardiovascular surgeons came to a paediatric hospital in the state capital once a week to perform heart surgeries. LOCAL SETTING: Until 2011, the State of Paraíba had no structured programme to care for children with heart disease. This often resulted in missed or late diagnosis, with adverse health consequences for the children. RELEVANT CHANGES: From 2012 to 2014, 73,751 babies were screened for heart defects and 857 abnormalities were identified. Detection of congenital heart diseases increased from 4.09 to 11.62 per 1000 live births (P < 0.001). Over 6000 consultations and echocardiograms were supervised via the Internet. Time to diagnosis, transfers and hospital stays were greatly reduced. A total of 330 operations were carried out with 6.7% (22/330) mortality. LESSONS LEARNT: Access to an echocardiography machine with remote supervision by a cardiologist improves the detection of congenital heart disease by neonatologists; virtual outpatient clinics facilitate clinical management; the use of Internet technology with simple screening techniques allows resources to be allocated more efficiently.

Site of infections associated with human papillomavirus.

INTRODUCTION: Human papillomavirus (HPV) is the most clinically common sexually transmitted infection due to its carcinogenic power and the high number of lesions that it causes at different sites of the human body. MATERIAL AND METHODS: Genital tract organs are the most common sites where the virus can be found, but by increasing the sensitivity of diagnostic technique, it is possible to identify viral presence in different regions of the body such as the stomach, the lung, and the urinary tract. These findings break with the traditional HPV skin/genital tropic profile and demonstrate that the virus is capable of infecting a wide variety of cells, tissues, and organs or can, at least, survive in these areas. The widespread presence of the HPV in the human body, often in latent form, led us to consider the hypothesis that HPV latency may be associated with no disease. CONCLUSION: This observation raises further questions about the possibility of the virus not causing disease in specific sites of the human body, but rather, behaving like a commensal/opportunistic microorganism.

Nanoencapsulation of quercetin and resveratrol into elastic liposomes.

Based on the fact that quercetin (QUE) and resveratrol (RES) induce a synergic inhibition of the adipogenesis and increase apoptosis in adipocytes, and that sodium deoxycholate (SDC) has necrotic effects, the nanoencapsulation of QUE and RES into SDC-elastic liposomes is proposed as a new approach for dissolving the subcutaneous fat. The concentration of constituents and the effect of the drug incorporation into cyclodextrin inclusion complexes on the stability of QUE/RES-loaded liposomes were studied. The best liposomal formulation reduced the use of phosphatidylcholine and cholesterol in 17.7% and 68.4%, respectively. Liposomes presented a mean diameter of 149nm with a polydispersion index of 0.3. The zeta potential of liposomes was slightly negative (-13.3mV) due to the presence of SDC in the phospholipid bilayer. Encapsulation efficiency of QUE and RES into liposomes was almost 97%. To summarize, QUE/RES-loaded elastic liposomes are stable and suitable for subcutaneous injection, thereby providing a new strategy for reducing subcutaneous fat.

Advancing arbovirus diagnosis in Brazil: strengthening diagnostic strategies and public health data collection.

BACKGROUND: The last five decades have seen a surge in viral outbreaks, particularly in tropical and subtropical regions like Brazil, where endemic arboviruses such as Dengue (DENV), Zika (ZIKV), and Chikungunya (CHIKV) pose significant threats. However, current diagnostic strategies exhibit limitations, leading to gaps in infection screening, arbovirus differential diagnoses, DENV serotyping, and life-long infection tracking. This deficiency impedes critical information availability regarding an individual's current infection and past infection history, disease risk assessment, vaccination needs, and policy formulation. Additionally, the availability of point-of-care diagnostics and knowledge regarding immune profiles at the time of infection are crucial considerations. OBJECTIVES: This review underscores the urgent need to strengthen diagnostic methods for arboviruses in Brazil and emphasizes the importance of data collection to inform public health policies for improved diagnostics, surveillance, and policy formulation. METHODS: We evaluated the diagnostic landscape for arboviral infections in Brazil, focusing on tailored, validated methods. We assessed diagnostic methods available for sensitivity and specificity metrics in the context of Brazil. RESULTS: Our review identifies high-sensitivity, high-specificity diagnostic methods for arboviruses and co-infections. Grifols transcription-mediated amplification assays are recommended for DENV, CHIKV, and ZIKV screening, while IgG/IgM ELISA assays outperform Rapid Diagnostic Tests (RDTs). The Triplex real-time RT-PCR assay is recommended for molecular screening due to its sensitivity and specificity. CONCLUSION: Enhanced diagnostic methods, on-going screening, and tracking are urgently needed in Brazil to capture the complex landscape of arboviral infections in the country. Recommendations include nationwide arbovirus differential diagnosis for DENV, ZIKV, and CHIKV, along with increased DENV serotyping, and lifelong infection tracking to combat enduring viral threats and reduce severe presentations.

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.

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.

Association between the genetic polymorphisms of glutathione S-transferase (GSTM1 and GSTT1) and the clinical manifestations in sickle cell anemia.

The hereditary deficiency of antioxidant enzymes when associated with sickle cell anemia (SCA) further contributes to the oxidation of hemoglobin S, which increases the formation of degradation products of this hemoglobin. The glutathione S transferases play an important role in the conjugation of glutathione to endogenous products of peroxidation of lipids and protect cells from the deleterious effects of oxidative stress. We analyzed genomic DNA from 278 patients with sickle cell anemia to correlate the genotypes GSTT1 and/or GSTM1 null (determined by multiplex PCR technique) and the clinical manifestations of the disease. 27% of patients showed absence of the GSTM1 gene and 15% had absence of GSTT1. The GSTM1 and GSTT1 null genotypes were found in 11% of the population. The risk of individuals with the GSTT1 null genotype developing acute chest syndrome and aseptic necrosis of the femoral head were, respectively, 10 and 6.3 times higher when compared with those individuals who had of this gene. Patients with GSTM1 null showed a risk 3.9 times higher to develop stroke and high risk for malleolar ulcers and acute chest syndrome (OR=6.9 and 4.2, respectively). The individuals with the GSTM1 and GSTT1 null genotypes showed a higher chance of developing acute chest syndrome, malleolar ulcer and aseptic necrosis of the femoral head. The absence of GSTT1 and/or GSTM1 was an important risk factor for increasing the morbidity of SCA, especially in regard to acute chest syndrome.

Mannose binding lectin and mannose binding lectin-associated serine protease-2 genes polymorphisms in human T-lymphotropic virus infection.

Variations in genes involved in the immune response pathways may influence the interaction between viruses (such as Human T-lymphotropic virus, HTLV-1) and the host. The mannose binding lectin (MBL) and its associated serine protease type 2 (MASP-2) promote the activation of the lectin pathway of the complement system. As the interaction of complement system with HTLV-1 is not well understood, the MBL2 promoter/exon 1 polymorphisms and a MASP2 missense polymorphism were examined in a Northeast Brazilian population, looking for a possible relationship between these variations and the susceptibility to HTLV-1 infection. The present study describes an association between a polymorphism in the MASP2 gene and susceptibility to HTLV-1 infection, and provides further evidence of an association between the MBL2 gene and HTLV-1 infection. These findings suggest an important role of the complement system activation, via the lectin pathway, in the susceptibility to HTLV-1 infection.