Objective:Perform a literary review of the interference in the results of biochemical laboratory tests caused by antihypertensive drugs.Methods:This is a review of the scientific literature with descriptive research p...Objective:Perform a literary review of the interference in the results of biochemical laboratory tests caused by antihypertensive drugs.Methods:This is a review of the scientific literature with descriptive research performed according to the PRISMA model using the databases PUBMED,SCIELO,MEDLINE,LILACS,and searches of Brazilian Ministry of Health and Federal Pharmacy Council publications,reagent kits and package inserts approved by ANVISA.Literature and papers in Portuguese and English were selected,prioritizing the years 2010 to 2020.Results:The diuretic class of antihypertensive drugs causes decreases glucose tolerance,thus resulting in an increase in triglycerides.In long-term use,the drug captopril can increase serum levels of potassium,creatine kinase and decreases blood sodium.Methyldopa causes an increase in AST levels.Propranolol is associated with an increase in triglyceride levels and a decrease in HDL and glucose levels.The constant use of losartan results in an increase in HDL,a decrease in uric acid levels and a slight and transient increase in transaminases.In the Gold Analisa,Bioclin and Labtest reagent kits,most of the alterations occur due to the increase in levels of serum biomarkers according to the class of the antihypertensive drug.Conclusions:Biochemical alterations in serum can result in false-positive or false-negative reports,since it can be observed that most of the dosages caused increases due to the physiological effect of the drugs.The antihypertensive drugs that showed the highest incidence of interference were captopril,atenolol,losartan and propranolol.展开更多
Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,...Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.展开更多
Organelle integrity and maintenance of protein homeostasis and purpose is essential for fundamental equilibrium and survivability.Autophagy is the primary process which regulates the distribution of different cell loa...Organelle integrity and maintenance of protein homeostasis and purpose is essential for fundamental equilibrium and survivability.Autophagy is the primary process which regulates the distribution of different cell loads to lysosomes for destruction and reuse.Extensive research illustrates the protective functions of autophagy against various diseases.Though in cancer,noticeably contrasting functions of autophagy have been evaluated in the prohibition of preliminary tumor evolution vs the continuance and,anabolic and catabolic variations of wellestablished and invasive tumors.Autophagy possesses numerous roles in tumor microenvironment(TME)establishment and associated immune cells function which is addressed in recent studies.Autophagic machinery which is employed in different autophagy-related pathways contributes to metastatic diseases and are distinct from classical autophagy.Therapeutic strategies based on the inhibition or induction of autophagy and related processes has helped in the designing of efficient anticancer drugs.According to the review,we evaluate and decipher the various purposes of autophagy and its association with autophagy mechanisms in course of tumor development,invasion and progression.We summarize the latest findings involving the role of these activities including tumor cells and TME and define further breakthrough in therapy aiming at autophagic activities in cancer.展开更多
BACKGROUND Gestational diabetes mellitus(GDM)is a metabolic disorder causing hyperglycemia during pregnancy.Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progr...BACKGROUND Gestational diabetes mellitus(GDM)is a metabolic disorder causing hyperglycemia during pregnancy.Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progression of GDM.CD36 is a membrane glycoprotein involved in lipid metabolism and insulin sensitivity.Studies indicate that the CD36 gene is substantially linked to type 2 diabetes mellitus(T2DM)and could also influence GDM susceptibility.Insulin resistance and decreased insulin secretion are the hallmarks of T2DM,which is thought to have a similar genetic pathophysiology in GDM.AIM To investigate the impact of CD36 gene polymorphisms[rs1761667(G/A)and rs75326924(C/T)]and mRNA expression in GDM women.METHODS The case-control study involved a total of 400 pregnant women,(200 healthy controls and 200 GDM cases).The study of CD36 gene polymorphisms G/A(rs1761667)and C/T(rs75326924))were determined by polymerase chain reaction-restriction fragment length polymorphism.The mRNA expression study of CD36 gene was analyzed by quantitative polymerase chain reaction/quantitative real-time polymerase chain reaction followed by statistical analysis done using GraphPad Prism8 software(ver.8.0).RESULTS The study revealed statistically significant association(P<0.05)in anthropometric/biochemical parameters(age,gestational age,body mass index,fasting prandial glucose,post-prandial glucose,triglyceride,low-density lipoprotein)between GDM cases and healthy controls.CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms were significantly associated with GDM cases.The heterozygous genotypes(GA and CT)of both variants showed significant association(P=0.0001 and P=0.0025,odds ratio=2.683 and 2.022 respectively).Allele frequency of‘T’allele in CD36 C/T(rs75326924)polymorphism was also found to be significant(P=0.0046).CD36 gene was upregulated in individuals with GDM as compared to healthy controls(P=0.0001).However,the upregulation of gene expression was not significantly associated with the genotypes of CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms.CONCLUSION Heterozygous genotypes GA and CT of CD36 gene variants and expression are linked to GDM,potentially serving as predictive biomarkers for GDM susceptibility;further exploration needed in diverse ethnic communities.展开更多
Gestational diabetes mellitus(GDM)is a metabolic condition caused by chronic insulin resistance during pregnancy,affecting millions of women globally and causing significant health concerns.Its consequences are far-re...Gestational diabetes mellitus(GDM)is a metabolic condition caused by chronic insulin resistance during pregnancy,affecting millions of women globally and causing significant health concerns.Its consequences are far-reaching,associated with poor feto-maternal outcomes.GDM has serious implications on metabolic health in both mother and child.Early diagnosis and management of GDM are crucial to prevent related consequences.Traditional diagnostic and predictive biomarkers for GDM,including oral glucose tolerance test,adiponectin,resistin,etc.,have limitations.Recent advances in research have identified novel biomarkers for GDM,offering promising alternatives for early diagnosis and prediction to prevent the associated adverse pediatric outcomes.Emerging biomarkers include microRNAs,cell-free DNA,exosomes,glycolytic intermediates,inflammatory biomarkers(C-reactive protein and interleukin-6),metabolic biomarkers(Betatrophin,fetuin-A,etc.),etc.Emerging bidirectional communication pathway(gut microbiota gut-brain-axis)plays a crucial role in GDM pathophysiology,and could be a promising biomarker.Emerging technologies such as next-generation seque-ncing,metabolomics,and proteomics have enabled the discovery of novel bio-markers for GDM and related pediatric outcomes.This review aims to summarize the current state of knowledge on emerging biomarkers for GDM,including their diagnostic accuracy,predictive value,and potential clinical applications to improve feto-maternal outcomes by personalized medicine approaches.展开更多
Background: Vulvovaginal candidiasis (VVC) is a common cause of significant morbidity, affecting millions of women worldwide. It is estimated that approximately 75%of women of childbearing age will have at least one e...Background: Vulvovaginal candidiasis (VVC) is a common cause of significant morbidity, affecting millions of women worldwide. It is estimated that approximately 75%of women of childbearing age will have at least one episode of candidiasis in their lifetime. In the last decades, resistance to azoles has become a public health problem. Although studies on vulvovaginitis have been done, there is lack of VVC studies in our area. The aim of this study was to describe the etiological and resistance profiles of vulvovaginal candidiasis to standard antifungus at the Saint Camille Hospital of Ouagadougou (HOSCO), Burkina Faso. Methods: We conducted a prospective study from January 2018 to December 2022. From vulvovaginal swabs, Candida species were identified using the ChromID® Candida Agar medium and the API® Candida gallery. Antifungal susceptibility testing was performed using Kirby-Bauer agar disk diffusion. Results: A total of 4789 women were sampled. The average age of sexually active women was 27.80+/−6.77 years, with extremes ranging from 15 to 64 years. Vaginal Candida infections accounted for 74.16% of the cases. The 20 - 29 age group was the most affected by vulvovaginal candidiasis. Pregnant women accounted for 28.76% of our study population. Women in the second (2nd) trimester of pregnancy had more Candida infections. Candida albicans was the most isolated species (55.12%), followed by Candida glabrata (27.64%), Candida tropicalis (6.91%), Candida famata (6.67%), Candida krusei (2.56%). All the Candida species isolated showed very high of resistance to Fluconazole (45.2%), Miconazole (23.7%) and Clotrimazole (45.7%). Conclusion: Species-specific antifungal results should always be considered to avoid antifungal resistance associated with vulvovaginal candidiasis. Identifying the causative species using vaginal fungal cultures can help guide therapy and improve outcomes for these patients.展开更多
BACKGROUND Breast cancer is a prominent contributor to female cancer-related mortality.Early detection and accurate diagnosis are essential for effective management.AIM To evaluate the diagnostic relevance of a panel ...BACKGROUND Breast cancer is a prominent contributor to female cancer-related mortality.Early detection and accurate diagnosis are essential for effective management.AIM To evaluate the diagnostic relevance of a panel of circulating microRNAs(miRNAs)independently or in combination with other tumor biomarkers and evaluate their sensitivity and specificity in classifying breast cancer patients by grade.METHODS In the present study,we analyzed the aberrant expression of miR-21,miR-221,miR-1246,miR-145,and miR-382,in addition to the tumor biomarkers cancer antigen 15-3(CA15-3)and 8-hydroxy-2′-deoxyguanosine(8-OHdG)in breast cancer patients with varying grades.RESULTS Our results revealed distinct expression patterns of these miRNAs between grade II and III patients.Specifically,miR-21,miR-221,and miR-1246 were significantly elevated, while miR-145 and miR-382 were downregulated. Elevated serum levels of CA15-3 and 8-OHdG wereobserved in breast cancer patients compared to healthy controls, with CA15-3 showing greater diagnostic efficacyin differentiating between grades. Our study revealed strong correlations among evaluated miRNAs, suggestingtheir interconnected roles in breast cancer progression. Receiver operating characteristic curve analysisdemonstrated high diagnostic accuracy for all investigated miRNAs, with miR-21 and miR-1246 showing thehighest diagnostic power for differentiating patients from healthy individuals and distinguishing breast cancergrades. Moreover, the combination of multiple miRNAs and conventional tumor biomarkers revealed enhanceddiagnostic accuracy and sensitivity.CONCLUSIONThese findings suggest that circulating miRNAs may play a significant role in distinguishing breast cancer patientsbased on tumor grade, with superior diagnostic performance over some tumor biomarkers, supporting thedevelopment of multi-analyte liquid biopsy approaches in the diagnostic process and personalized management ofbreast cancer patients.展开更多
BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both brea...BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both breast cancer(BC)clinicopathological characteristics and tumor sensitivity to chemotherapy.However,the concordance of PDCD1 LG1 expression scoring with immunohistochemical(IHC)tests approved for clinical use and with the polymerase chain reaction(PCR)method has not been previously studied.AIM To evaluate the concordance of methods for assessing PD-L1 expression,IHC tests with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and PCR.METHODS This prospective single-center observational cohort study included 148 patients with BC.PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and by PCR.The concordance of PD-L1 scores between tests was assessed with positive percentage agreement(PPA)and negative percentage agreement(NPA).The strength of the agreement between the methods was calculated via the Cohen kappa index.P<0.05 was considered statistically significant.RESULTS Regardless of the method used to assess marker expression,PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status,human epidermal growth factor receptor-2-positive(HER2+)status,luminal B HER+BC,nonluminal HER+BC and triple-negative BC.PPA and NPA were 38.3%and 70.4%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(SP142);26.3%and 63.3%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(PCR);and 36.5%and 74.4%,respectively,for PD-L1(SP142)and PD-L1(PCR).Cohen's kappa index for PD-L1(PDCD1 LG1)and PD-L1(SP142)was 0.385(95%CI:0.304–0.466),that for PD-L1(PDCD1 LG1)and PD-L1(PCR)was 0.207(95%CI:0.127–0.287),and that for PD-L1(SP142)and PD-L1(PCR)was 0.389(95%CI:0.309–0.469).CONCLUSION Thus,all three markers of PD-L1 expression are associated with the characteristics of aggressive BC,demonstrating moderate concordance between the tests.展开更多
Background Oxidative stress can impair intestinal barrier function and cause liver damage,resulting in reduced animal productivity.Paraquat(PQ)induces significant oxidative stress in weaned piglets.The antioxidant,ant...Background Oxidative stress can impair intestinal barrier function and cause liver damage,resulting in reduced animal productivity.Paraquat(PQ)induces significant oxidative stress in weaned piglets.The antioxidant,anti-inflammatory,and metabolic regulatory functions of taurine(Tau),a free amino acid that is widely distributed in the body,have been extensively studied.However,the mechanisms by which dietary Tau alleviates oxidative stress and gut-liver axis damage in weaned piglets remain unclear.Methods Forty weaned piglets(20 males and 20 females;6.41±0.11 kg;25 days old;Duroc×Landrace×Yorkshire)were used in a 2×2 factorial design to investigate the mechanism by which dietary Tau(0%or 0.4%)alleviates PQ-induced oxidative stress and gut-liver axis damage.We analyzed key biomarkers related to gut barrier function,mucosal damage repair,liver damage,gut-liver immunity,antioxidant capacity,systemic immune homeostasis,antioxidant levels,and gut microbiota diversity in piglets under normal and acute oxidative stress.In particular,we evaluated the coordinated regulation of gut-liver axis function mediated by Tau through the Nrf2/Keap1(antioxidant)and TLR4/NF-κB(immune modulation)signaling pathways.Partial least squares path modeling and molecular docking were used to explore the intrinsic relationship between PQ,Tau,and the gut-liver axis.Results PQ exposure impaired gut barrier function,increased the liver fibrosis area,and markedly affected gut microbial diversity(P<0.05).Tau effectively alleviated PQ-induced oxidative stress by activating the Nrf2/Keap1 pathway and inhibiting the TLR4/NF-κB pathway.This enhanced gut barrier function,promoted mucosal repair,and significantly suppressed the concentration and circulation of lipopolysaccharides in the blood,consequently reducing liver damage(P<0.05).This further facilitated the optimization of gut microbiota composition,thereby supporting the positive regulation of the gut-liver axis and improving systemic immune and antioxidant functions.Conclusions Tau improved the health status of weaned piglets under both normal and stressed conditions by modulating the Nrf2/Keap1 and TLR4/NF-κB pathways,offering a potential new nutritional strategy for alleviating gut-liver damage.展开更多
Floral color and scent are crucial for plant-environment interactions,especially in reproduction by attracting pollinators for fertilization.They also have wide applications in cosmetic,pharmaceutical,and nutraceutica...Floral color and scent are crucial for plant-environment interactions,especially in reproduction by attracting pollinators for fertilization.They also have wide applications in cosmetic,pharmaceutical,and nutraceutical industries.Plant pigments are typically classified as chlorophylls,flavonoids,carotenoids,and betalains,while volatile organic compounds(VOCs)are grouped as terpenes,phenylpropanoids/benzenoids,and fatty acid derivatives.Significant progresses have been made in understanding the biosynthesis and regulation of these floral pigments and VOCs.Despite differences in their biosynthetic pathways,floral pigments and VOCs are biochemically connected and exhibit synergistic interactions during flower development and in response to biotic and abiotic stresses,suggesting the existence of pleiotropic regulators or complex mechanisms co-regulating their biosynthesis.In this review,we summarize and outline the metabolite pathways mainly integrating flavonoids,carotenoids,terpenes,and phenylpropanoids/benzenoids.We also provide a series of scenarios illustrating the coordinated regulation of floral color and scent.Finally,we suggest areas for future research.We hope this review will spark interest in this research direction and stimulate further studies.展开更多
Nicotiana tabacum(2n=4x=48),an economically important non-food crop and a model plant for genetic studies,faces challenges in efficient genotyping of novel germplasm.To address this,we developed the Ta-LD-SC,a 20K SNP...Nicotiana tabacum(2n=4x=48),an economically important non-food crop and a model plant for genetic studies,faces challenges in efficient genotyping of novel germplasm.To address this,we developed the Ta-LD-SC,a 20K SNP Affymetrix Axiom array,based on resequencing data from 150 tobacco accessions.A total of 20,213 unique SNPs were carefully selected,achieving coverage of over 90%of the tobacco genome(Nitab4.5 and NtaSR1)with a uniform probe distribution,limiting density to no more than 5 SNPs per 200 kb.The array underwent extensive validation using 866 tobacco accessions(NP panel)and 288 F2 individuals from a cross between K326 and Oxford 26(GP panel).Performance metrics demonstrated its robustness,with high SNP call rates(93.6%-99.8%),a low technical error rate(<1%),and a superior PolyHighResolution SNP rate(79.79%)compared to other crop SNP arrays.Population structure analysis of the NP panel revealed two major introductions of foreign germplasm that have significantly influenced the genetic diversity of Chinese tobacco resources.Using the array,a genome-wide association study(GWAS)identified 62 genes linked to eight agronomic traits,and a high-density genetic map encompassing 4553 SNPs across 6606.08 cM was constructed.The Ta-LD-SC array provides a valuable tool for rapid,high-quality genotyping offering supporting marker annotations that may benefit genetic research and breeding of tobacco.展开更多
Objective:To assess the effect of quercetin(flavonoid) against lindane induced alterations in lipid profile of wistar rats.Methods:Rats were administered orally with lindane(100 mg/kg body weight) and quercetin(10 mg/...Objective:To assess the effect of quercetin(flavonoid) against lindane induced alterations in lipid profile of wistar rats.Methods:Rats were administered orally with lindane(100 mg/kg body weight) and quercetin(10 mg/kg body weight) for 30 days.After the end of treatment period lipid profile was estimated in serum and tissue.Results:Elevated levels of serum cholesterol, triglycerides,low density lipoprotein(LDL),very Low Density Lipoprotein(VLDL) and tissue triglycerides,cholesterol with concomitant decrease in serum HDL and tissue phospholipids were decreased in lindane treated rats were found to be significantly decreased in the quercetin and lindane co-treated rats.Conclusions:Our study suggests that quercetin has hypolipidemic effect and offers protection against lindane induced toxicity in liver by restoring the altered levels of lipids.The quercetin cotreatment along with lindane for 30 days reversed these biochemical alterations in lipids induced by lindane.展开更多
We evaluated the genotypes of the serotonin transporter gene （5-HTT） in patients with premature ejaculation （PE） to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the ...We evaluated the genotypes of the serotonin transporter gene （5-HTT） in patients with premature ejaculation （PE） to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene （5-HTTLPR） were determined. The 5-HTTLPR （serotonin transporter promoter gene） genotypes in PE patients vs. controls were distributed as follows： L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene： LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short （S） allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls （P 〈 0.05）. We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup （such as primary and secondary PE） responses to selective serotonin reuptake inhibitors as well as ethnic differences.展开更多
Helicobacter pylori(H. pylori) infection is present in more than half the world's population and has been associated with several gastric disorders, such as gastritis, peptic ulceration, and gastric adenocarcinoma...Helicobacter pylori(H. pylori) infection is present in more than half the world's population and has been associated with several gastric disorders, such as gastritis, peptic ulceration, and gastric adenocarcinoma.The clinical outcome of this infection depends on host and bacterial factors where H. pylori virulence genes seem to play a relevant role. Studies of cag A and vac A genes established that they were determining factors in gastric pathogenesis. However, there are gastric cancer cases that are cag A-negative. Several other virulence genes have been searched for, but these genes remain less well known that cag A and vac A. Thus, this review aimed to establish which genes have been suggested as potentially relevant virulence factors for H. pylori-associated gastrointestinal diseases. We focused on the cag-pathogenicity island, genes with adherence and motility functions, and ice A based on the relevance shown in several studies in the literature.展开更多
Infectious diseases are indeed a lifelong threat to everyone irrespective of age, sex, lifestyle and socio-economic status. The infectious diseases have persisted among the prominent causes of death globally. Recently...Infectious diseases are indeed a lifelong threat to everyone irrespective of age, sex, lifestyle and socio-economic status. The infectious diseases have persisted among the prominent causes of death globally. Recently, re-emergence of Chikungunya viral infection harmed many in Asian and African countries. Chikungunya was considered as a major threat in developing and underdeveloped countries; the recent epidemiological outbreak of Chikungunya in La Reunion urges the global researchers to develop effective vaccine against this viral disease. In this review, Chikungunya, pathogenesis and epidemiology were briefly described.展开更多
Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a...Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.展开更多
Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a project...Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.展开更多
Colorectal cancer(CRC) is fourth most common cancer in men and third in women worldwide. Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of CRC is recognised as to be crucial...Colorectal cancer(CRC) is fourth most common cancer in men and third in women worldwide. Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of CRC is recognised as to be crucial for early initial diagnosis, which in turn leads to better long term survival. Most of the research on novel potential CRC biomarkers in the last 2 decades has been focussed on stool DNA analysis. In this paper, we describe the recent advances in non-invasive CRC screening and more specifically in molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions. In several research papers these markers showed superior rates for sensitivity and specificity in comparison to previously described assays. These tests detected the majority of adenomas ≥ 1 cm in size and the detection rates progressively increased with larger adenomas. The methylation status of the BMP3 and NDRG4 promoters demonstrated effective detection of neoplasms at all sites throughout the colon and was not affected by common clinical variables. Recently, a multitarget stool DNA test consisting of molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, mutant KRAS and immunochemical assay for human haemoglobin has been made commercially available and is currently reimbursed in the United States. Although this is the most sensitive noninvasive CRC screening test, there is the need for further research in several areas- establishment of the best timeframe for repeated DNA stool testing; validation of the results in populations outside of North America; usefulness for surveillance and prognosis of patients; cost-effectiveness of DNA stool testing in real-life populations.展开更多
AIM: To investigate chromosome 8 numerical aberra- tions, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histo- pathological characteristics of gastric tumors. MET...AIM: To investigate chromosome 8 numerical aberra- tions, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histo- pathological characteristics of gastric tumors. METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immu- nostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases showed chromosome 8 aneu- ploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level ofchromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification, like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Structural rearrangement of C-MYC, like translocation, was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinal- type the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic path- ways.展开更多
文摘Objective:Perform a literary review of the interference in the results of biochemical laboratory tests caused by antihypertensive drugs.Methods:This is a review of the scientific literature with descriptive research performed according to the PRISMA model using the databases PUBMED,SCIELO,MEDLINE,LILACS,and searches of Brazilian Ministry of Health and Federal Pharmacy Council publications,reagent kits and package inserts approved by ANVISA.Literature and papers in Portuguese and English were selected,prioritizing the years 2010 to 2020.Results:The diuretic class of antihypertensive drugs causes decreases glucose tolerance,thus resulting in an increase in triglycerides.In long-term use,the drug captopril can increase serum levels of potassium,creatine kinase and decreases blood sodium.Methyldopa causes an increase in AST levels.Propranolol is associated with an increase in triglyceride levels and a decrease in HDL and glucose levels.The constant use of losartan results in an increase in HDL,a decrease in uric acid levels and a slight and transient increase in transaminases.In the Gold Analisa,Bioclin and Labtest reagent kits,most of the alterations occur due to the increase in levels of serum biomarkers according to the class of the antihypertensive drug.Conclusions:Biochemical alterations in serum can result in false-positive or false-negative reports,since it can be observed that most of the dosages caused increases due to the physiological effect of the drugs.The antihypertensive drugs that showed the highest incidence of interference were captopril,atenolol,losartan and propranolol.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,and Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022).
文摘Gestational diabetes mellitus(GDM)is a metabolic disorder,recognised during 24-28 weeks of pregnancy.GDM is linked with adverse newborn outcomes such as macrosomia,premature delivery,metabolic disorder,cardiovascular,and neurological disorders.Recent investigations have focused on the correlation of genetic factors such asβ-cell function and insulin secretary genes(transcription factor 7 like 2,potassium voltage-gated channel subfamily q member 1,adipo-nectin etc.)on maternal metabolism during gestation leading to GDM.Epigenetic alterations like DNA methylation,histone modification,and miRNA expression can influence gene expression and play a dominant role in feto-maternal meta-bolic pathways.Interactions between genes and environment,resulting in differ-ential gene expression patterns may lead to GDM.Researchers suggested that GDM women are more susceptible to insulin resistance,which alters intrauterine surroundings,resulting hyperglycemia and hyperinsulinemia.Epigenetic modi-fications in genes affecting neuroendocrine activities,and metabolism,increase the risk of obesity and type 2 diabetes in offspring.There is currently no treatment or effective preventive method for GDM,since the molecular processes of insulin resistance are not well understood.The present review was undertaken to un-derstand the pathophysiology of GDM and its effects on adverse neonatal out-comes.In addition,the study of genetic and epigenetic alterations will provide lead to researchers in the search for predictive molecular biomarkers.
基金Supported by DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level Ⅱ),No.TG BT/INF/22/SP47623/2022.
文摘Organelle integrity and maintenance of protein homeostasis and purpose is essential for fundamental equilibrium and survivability.Autophagy is the primary process which regulates the distribution of different cell loads to lysosomes for destruction and reuse.Extensive research illustrates the protective functions of autophagy against various diseases.Though in cancer,noticeably contrasting functions of autophagy have been evaluated in the prohibition of preliminary tumor evolution vs the continuance and,anabolic and catabolic variations of wellestablished and invasive tumors.Autophagy possesses numerous roles in tumor microenvironment(TME)establishment and associated immune cells function which is addressed in recent studies.Autophagic machinery which is employed in different autophagy-related pathways contributes to metastatic diseases and are distinct from classical autophagy.Therapeutic strategies based on the inhibition or induction of autophagy and related processes has helped in the designing of efficient anticancer drugs.According to the review,we evaluate and decipher the various purposes of autophagy and its association with autophagy mechanisms in course of tumor development,invasion and progression.We summarize the latest findings involving the role of these activities including tumor cells and TME and define further breakthrough in therapy aiming at autophagic activities in cancer.
基金Supported by Maulana Azad National Fellowship,University Grants Commission,New Delhi,Department of Biotechnology,New Delhi,No.AS[82-27/2019(SA III)]DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level II),No.TG(BT/INF/22/SP47623/2022)Department of Science and Technology-SERB Power Grant Scheme,No.SPG/2021/00545.
文摘BACKGROUND Gestational diabetes mellitus(GDM)is a metabolic disorder causing hyperglycemia during pregnancy.Insulin resistance and decreased insulin secretion are linked to altered lipid metabolism that leads to progression of GDM.CD36 is a membrane glycoprotein involved in lipid metabolism and insulin sensitivity.Studies indicate that the CD36 gene is substantially linked to type 2 diabetes mellitus(T2DM)and could also influence GDM susceptibility.Insulin resistance and decreased insulin secretion are the hallmarks of T2DM,which is thought to have a similar genetic pathophysiology in GDM.AIM To investigate the impact of CD36 gene polymorphisms[rs1761667(G/A)and rs75326924(C/T)]and mRNA expression in GDM women.METHODS The case-control study involved a total of 400 pregnant women,(200 healthy controls and 200 GDM cases).The study of CD36 gene polymorphisms G/A(rs1761667)and C/T(rs75326924))were determined by polymerase chain reaction-restriction fragment length polymorphism.The mRNA expression study of CD36 gene was analyzed by quantitative polymerase chain reaction/quantitative real-time polymerase chain reaction followed by statistical analysis done using GraphPad Prism8 software(ver.8.0).RESULTS The study revealed statistically significant association(P<0.05)in anthropometric/biochemical parameters(age,gestational age,body mass index,fasting prandial glucose,post-prandial glucose,triglyceride,low-density lipoprotein)between GDM cases and healthy controls.CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms were significantly associated with GDM cases.The heterozygous genotypes(GA and CT)of both variants showed significant association(P=0.0001 and P=0.0025,odds ratio=2.683 and 2.022 respectively).Allele frequency of‘T’allele in CD36 C/T(rs75326924)polymorphism was also found to be significant(P=0.0046).CD36 gene was upregulated in individuals with GDM as compared to healthy controls(P=0.0001).However,the upregulation of gene expression was not significantly associated with the genotypes of CD36 G/A(rs1761667)and CD36 C/T(rs75326924)polymorphisms.CONCLUSION Heterozygous genotypes GA and CT of CD36 gene variants and expression are linked to GDM,potentially serving as predictive biomarkers for GDM susceptibility;further exploration needed in diverse ethnic communities.
基金Supported by DBT-BUILDER-University of Lucknow Interdisciplinary Life Science Programme for Advance Research and Education(Level Ⅱ),No.TG BT/INF/22/SP47623/2022Maulana Azad National Fellowship,University Grants Commission,New Delhi,Department of Biotechnology,New Delhi,No.F.82-27/2019(SA Ⅲ).
文摘Gestational diabetes mellitus(GDM)is a metabolic condition caused by chronic insulin resistance during pregnancy,affecting millions of women globally and causing significant health concerns.Its consequences are far-reaching,associated with poor feto-maternal outcomes.GDM has serious implications on metabolic health in both mother and child.Early diagnosis and management of GDM are crucial to prevent related consequences.Traditional diagnostic and predictive biomarkers for GDM,including oral glucose tolerance test,adiponectin,resistin,etc.,have limitations.Recent advances in research have identified novel biomarkers for GDM,offering promising alternatives for early diagnosis and prediction to prevent the associated adverse pediatric outcomes.Emerging biomarkers include microRNAs,cell-free DNA,exosomes,glycolytic intermediates,inflammatory biomarkers(C-reactive protein and interleukin-6),metabolic biomarkers(Betatrophin,fetuin-A,etc.),etc.Emerging bidirectional communication pathway(gut microbiota gut-brain-axis)plays a crucial role in GDM pathophysiology,and could be a promising biomarker.Emerging technologies such as next-generation seque-ncing,metabolomics,and proteomics have enabled the discovery of novel bio-markers for GDM and related pediatric outcomes.This review aims to summarize the current state of knowledge on emerging biomarkers for GDM,including their diagnostic accuracy,predictive value,and potential clinical applications to improve feto-maternal outcomes by personalized medicine approaches.
文摘Background: Vulvovaginal candidiasis (VVC) is a common cause of significant morbidity, affecting millions of women worldwide. It is estimated that approximately 75%of women of childbearing age will have at least one episode of candidiasis in their lifetime. In the last decades, resistance to azoles has become a public health problem. Although studies on vulvovaginitis have been done, there is lack of VVC studies in our area. The aim of this study was to describe the etiological and resistance profiles of vulvovaginal candidiasis to standard antifungus at the Saint Camille Hospital of Ouagadougou (HOSCO), Burkina Faso. Methods: We conducted a prospective study from January 2018 to December 2022. From vulvovaginal swabs, Candida species were identified using the ChromID® Candida Agar medium and the API® Candida gallery. Antifungal susceptibility testing was performed using Kirby-Bauer agar disk diffusion. Results: A total of 4789 women were sampled. The average age of sexually active women was 27.80+/−6.77 years, with extremes ranging from 15 to 64 years. Vaginal Candida infections accounted for 74.16% of the cases. The 20 - 29 age group was the most affected by vulvovaginal candidiasis. Pregnant women accounted for 28.76% of our study population. Women in the second (2nd) trimester of pregnancy had more Candida infections. Candida albicans was the most isolated species (55.12%), followed by Candida glabrata (27.64%), Candida tropicalis (6.91%), Candida famata (6.67%), Candida krusei (2.56%). All the Candida species isolated showed very high of resistance to Fluconazole (45.2%), Miconazole (23.7%) and Clotrimazole (45.7%). Conclusion: Species-specific antifungal results should always be considered to avoid antifungal resistance associated with vulvovaginal candidiasis. Identifying the causative species using vaginal fungal cultures can help guide therapy and improve outcomes for these patients.
基金Supported by National Research Centre,Egypt,No.E120504.
文摘BACKGROUND Breast cancer is a prominent contributor to female cancer-related mortality.Early detection and accurate diagnosis are essential for effective management.AIM To evaluate the diagnostic relevance of a panel of circulating microRNAs(miRNAs)independently or in combination with other tumor biomarkers and evaluate their sensitivity and specificity in classifying breast cancer patients by grade.METHODS In the present study,we analyzed the aberrant expression of miR-21,miR-221,miR-1246,miR-145,and miR-382,in addition to the tumor biomarkers cancer antigen 15-3(CA15-3)and 8-hydroxy-2′-deoxyguanosine(8-OHdG)in breast cancer patients with varying grades.RESULTS Our results revealed distinct expression patterns of these miRNAs between grade II and III patients.Specifically,miR-21,miR-221,and miR-1246 were significantly elevated, while miR-145 and miR-382 were downregulated. Elevated serum levels of CA15-3 and 8-OHdG wereobserved in breast cancer patients compared to healthy controls, with CA15-3 showing greater diagnostic efficacyin differentiating between grades. Our study revealed strong correlations among evaluated miRNAs, suggestingtheir interconnected roles in breast cancer progression. Receiver operating characteristic curve analysisdemonstrated high diagnostic accuracy for all investigated miRNAs, with miR-21 and miR-1246 showing thehighest diagnostic power for differentiating patients from healthy individuals and distinguishing breast cancergrades. Moreover, the combination of multiple miRNAs and conventional tumor biomarkers revealed enhanceddiagnostic accuracy and sensitivity.CONCLUSIONThese findings suggest that circulating miRNAs may play a significant role in distinguishing breast cancer patientsbased on tumor grade, with superior diagnostic performance over some tumor biomarkers, supporting thedevelopment of multi-analyte liquid biopsy approaches in the diagnostic process and personalized management ofbreast cancer patients.
基金Supported by Russian Science Foundation,No.23-25-00183.
文摘BACKGROUND We previously demonstrated that the antibody against programmed cell death protein 1 ligand 1(PDCD1 LG1)is a promising new marker of programmed death-ligand 1(PD-L1)expression that correlates with both breast cancer(BC)clinicopathological characteristics and tumor sensitivity to chemotherapy.However,the concordance of PDCD1 LG1 expression scoring with immunohistochemical(IHC)tests approved for clinical use and with the polymerase chain reaction(PCR)method has not been previously studied.AIM To evaluate the concordance of methods for assessing PD-L1 expression,IHC tests with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and PCR.METHODS This prospective single-center observational cohort study included 148 patients with BC.PD-L1 expression in immune cells was assessed by the IHC method with anti-PD-L1(PDCD1 LG1)and anti-PD-L1(SP142)antibodies and by PCR.The concordance of PD-L1 scores between tests was assessed with positive percentage agreement(PPA)and negative percentage agreement(NPA).The strength of the agreement between the methods was calculated via the Cohen kappa index.P<0.05 was considered statistically significant.RESULTS Regardless of the method used to assess marker expression,PD-L1 expression was significantly more often detected in patients with negative estrogen receptor status,human epidermal growth factor receptor-2-positive(HER2+)status,luminal B HER+BC,nonluminal HER+BC and triple-negative BC.PPA and NPA were 38.3%and 70.4%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(SP142);26.3%and 63.3%,respectively,for PD-L1(PDCD1 LG1)and PD-L1(PCR);and 36.5%and 74.4%,respectively,for PD-L1(SP142)and PD-L1(PCR).Cohen's kappa index for PD-L1(PDCD1 LG1)and PD-L1(SP142)was 0.385(95%CI:0.304–0.466),that for PD-L1(PDCD1 LG1)and PD-L1(PCR)was 0.207(95%CI:0.127–0.287),and that for PD-L1(SP142)and PD-L1(PCR)was 0.389(95%CI:0.309–0.469).CONCLUSION Thus,all three markers of PD-L1 expression are associated with the characteristics of aggressive BC,demonstrating moderate concordance between the tests.
基金supported by the National Natural Science Foundation of China(32372894)Key Project of Science and Technology Research Program of Chongqing Municipal Education Commission(KJZD-K202300209)+1 种基金Fundamental Research Funds for National Key R&D Program of China(SQ2022YFD1300007)Innovation Research 2035 Pilot Program of Southwest University(SWU-XDPY22005).
文摘Background Oxidative stress can impair intestinal barrier function and cause liver damage,resulting in reduced animal productivity.Paraquat(PQ)induces significant oxidative stress in weaned piglets.The antioxidant,anti-inflammatory,and metabolic regulatory functions of taurine(Tau),a free amino acid that is widely distributed in the body,have been extensively studied.However,the mechanisms by which dietary Tau alleviates oxidative stress and gut-liver axis damage in weaned piglets remain unclear.Methods Forty weaned piglets(20 males and 20 females;6.41±0.11 kg;25 days old;Duroc×Landrace×Yorkshire)were used in a 2×2 factorial design to investigate the mechanism by which dietary Tau(0%or 0.4%)alleviates PQ-induced oxidative stress and gut-liver axis damage.We analyzed key biomarkers related to gut barrier function,mucosal damage repair,liver damage,gut-liver immunity,antioxidant capacity,systemic immune homeostasis,antioxidant levels,and gut microbiota diversity in piglets under normal and acute oxidative stress.In particular,we evaluated the coordinated regulation of gut-liver axis function mediated by Tau through the Nrf2/Keap1(antioxidant)and TLR4/NF-κB(immune modulation)signaling pathways.Partial least squares path modeling and molecular docking were used to explore the intrinsic relationship between PQ,Tau,and the gut-liver axis.Results PQ exposure impaired gut barrier function,increased the liver fibrosis area,and markedly affected gut microbial diversity(P<0.05).Tau effectively alleviated PQ-induced oxidative stress by activating the Nrf2/Keap1 pathway and inhibiting the TLR4/NF-κB pathway.This enhanced gut barrier function,promoted mucosal repair,and significantly suppressed the concentration and circulation of lipopolysaccharides in the blood,consequently reducing liver damage(P<0.05).This further facilitated the optimization of gut microbiota composition,thereby supporting the positive regulation of the gut-liver axis and improving systemic immune and antioxidant functions.Conclusions Tau improved the health status of weaned piglets under both normal and stressed conditions by modulating the Nrf2/Keap1 and TLR4/NF-κB pathways,offering a potential new nutritional strategy for alleviating gut-liver damage.
基金supported by the National Natural Science Foundation of China(Grant Nos.32272751,32272750,31972445)the Department of Science and Technology of Jilin Province(Grant Nos.20220508112RC,20210101005JC)+1 种基金the“Pioneer”and“Leading Goose”R&D Program of Zhejiang(Grant No.2023C02028)the China Scholarship Council(Grant No.202006625007)。
文摘Floral color and scent are crucial for plant-environment interactions,especially in reproduction by attracting pollinators for fertilization.They also have wide applications in cosmetic,pharmaceutical,and nutraceutical industries.Plant pigments are typically classified as chlorophylls,flavonoids,carotenoids,and betalains,while volatile organic compounds(VOCs)are grouped as terpenes,phenylpropanoids/benzenoids,and fatty acid derivatives.Significant progresses have been made in understanding the biosynthesis and regulation of these floral pigments and VOCs.Despite differences in their biosynthetic pathways,floral pigments and VOCs are biochemically connected and exhibit synergistic interactions during flower development and in response to biotic and abiotic stresses,suggesting the existence of pleiotropic regulators or complex mechanisms co-regulating their biosynthesis.In this review,we summarize and outline the metabolite pathways mainly integrating flavonoids,carotenoids,terpenes,and phenylpropanoids/benzenoids.We also provide a series of scenarios illustrating the coordinated regulation of floral color and scent.Finally,we suggest areas for future research.We hope this review will spark interest in this research direction and stimulate further studies.
基金supported by the Guizhou Provincial Basic Research Program(Natural Science)[(2024)648]the Program of China National Tobacco Corporation(110202101032(JY-09),110202201003(JY-03))the Program of Guizhou Branch of China National Tobacco Corporation(2023XM02,2021XM05,2022XM05,2024XM01).
文摘Nicotiana tabacum(2n=4x=48),an economically important non-food crop and a model plant for genetic studies,faces challenges in efficient genotyping of novel germplasm.To address this,we developed the Ta-LD-SC,a 20K SNP Affymetrix Axiom array,based on resequencing data from 150 tobacco accessions.A total of 20,213 unique SNPs were carefully selected,achieving coverage of over 90%of the tobacco genome(Nitab4.5 and NtaSR1)with a uniform probe distribution,limiting density to no more than 5 SNPs per 200 kb.The array underwent extensive validation using 866 tobacco accessions(NP panel)and 288 F2 individuals from a cross between K326 and Oxford 26(GP panel).Performance metrics demonstrated its robustness,with high SNP call rates(93.6%-99.8%),a low technical error rate(<1%),and a superior PolyHighResolution SNP rate(79.79%)compared to other crop SNP arrays.Population structure analysis of the NP panel revealed two major introductions of foreign germplasm that have significantly influenced the genetic diversity of Chinese tobacco resources.Using the array,a genome-wide association study(GWAS)identified 62 genes linked to eight agronomic traits,and a high-density genetic map encompassing 4553 SNPs across 6606.08 cM was constructed.The Ta-LD-SC array provides a valuable tool for rapid,high-quality genotyping offering supporting marker annotations that may benefit genetic research and breeding of tobacco.
基金the UGC SAP DRS(Under Graduate students research orientation programme) sponsored by the University Grants Commission,New Delhiwhich supported the present work
文摘Objective:To assess the effect of quercetin(flavonoid) against lindane induced alterations in lipid profile of wistar rats.Methods:Rats were administered orally with lindane(100 mg/kg body weight) and quercetin(10 mg/kg body weight) for 30 days.After the end of treatment period lipid profile was estimated in serum and tissue.Results:Elevated levels of serum cholesterol, triglycerides,low density lipoprotein(LDL),very Low Density Lipoprotein(VLDL) and tissue triglycerides,cholesterol with concomitant decrease in serum HDL and tissue phospholipids were decreased in lindane treated rats were found to be significantly decreased in the quercetin and lindane co-treated rats.Conclusions:Our study suggests that quercetin has hypolipidemic effect and offers protection against lindane induced toxicity in liver by restoring the altered levels of lipids.The quercetin cotreatment along with lindane for 30 days reversed these biochemical alterations in lipids induced by lindane.
文摘We evaluated the genotypes of the serotonin transporter gene （5-HTT） in patients with premature ejaculation （PE） to determine the role of genetic factors in the etiopathogenesis of PE and possibly to identify the patient subgroups. A total of 70 PE patients and 70 controls were included in this study. All men were heterosexual, had no other disorders and were either married or in a stable relationship. PE was defined as ejaculation that occurred within 1 min of vaginal intromission. Genomic DNA from patients and controls was analyzed using polymerase chain reaction, and allelic variations of the promoter region of the serotonin transporter gene （5-HTTLPR） were determined. The 5-HTTLPR （serotonin transporter promoter gene） genotypes in PE patients vs. controls were distributed as follows： L/L 16% vs. 17%, L/S 30% vs. 53% and S/S 54% vs. 28%. We examined the haplotype analysis for three polymorphisms of the 5-HTTLPR gene： LL, LS and SS. The appropriateness of the allele frequencies in the 5-HTTLPR gene was analyzed by the Hardy-Weinberg equilibrium using the Z-test. The short （S） allele of the 5-HTTLPR gene was significantly more frequent in PE patients than in controls （P 〈 0.05）. We suggest that the 5-HTTLPR gene plays a role in the pathophysiology of all primary PE cases. Further studies are needed to evaluate the relationship between 5-HTTLPR gene polymorphism and patient subgroup （such as primary and secondary PE） responses to selective serotonin reuptake inhibitors as well as ethnic differences.
文摘Helicobacter pylori(H. pylori) infection is present in more than half the world's population and has been associated with several gastric disorders, such as gastritis, peptic ulceration, and gastric adenocarcinoma.The clinical outcome of this infection depends on host and bacterial factors where H. pylori virulence genes seem to play a relevant role. Studies of cag A and vac A genes established that they were determining factors in gastric pathogenesis. However, there are gastric cancer cases that are cag A-negative. Several other virulence genes have been searched for, but these genes remain less well known that cag A and vac A. Thus, this review aimed to establish which genes have been suggested as potentially relevant virulence factors for H. pylori-associated gastrointestinal diseases. We focused on the cag-pathogenicity island, genes with adherence and motility functions, and ice A based on the relevance shown in several studies in the literature.
基金The Department of Biotechnology,Bharathiar University,Coimbatore,Tamil Nadu,India for supporting this research through DST-FIST (SR/FST/LST-299/2006 Dt:31-01-2007)UGC-SAP (F.No.3-9/2007 (SAP-II) February 2007)
文摘Infectious diseases are indeed a lifelong threat to everyone irrespective of age, sex, lifestyle and socio-economic status. The infectious diseases have persisted among the prominent causes of death globally. Recently, re-emergence of Chikungunya viral infection harmed many in Asian and African countries. Chikungunya was considered as a major threat in developing and underdeveloped countries; the recent epidemiological outbreak of Chikungunya in La Reunion urges the global researchers to develop effective vaccine against this viral disease. In this review, Chikungunya, pathogenesis and epidemiology were briefly described.
基金Supported by Agencies viz Department of Biotechnology(DBT),Indian Council of Medical Research(ICMR),Department of Science and Technology(DST)and Centre of Excellence(COE),UP Government,India for generous grants to our laboratory for diabetes research
文摘Diabetes mellitus is a combined metabolic disorder which includes hyperglycemia,dyslipidemia,stroke and several other complications.Various groups all over the world are relentlessly working out the possible role of a vast number of genes associated with type 2 diabetes(T2DM).Inflammation is an important outcome of any kind of imbalance in the body and is therefore an indicator of several diseases,including T2DM.Various ethnic populations around the world show different levels of variations in single nucleotide polymorphisms(SNPs).The present review was undertaken to explore the association of cytokine gene polymorphisms with T2DM in populations of different ethnicities.This will lead to the understanding of the role of cytokine genes in T2DM risk and development.Association studies of genotypes of SNPs present in cytokine genes will help to identify risk haplotype(s)for disease susceptibility by developing prognostic markers and alter treatment strategies for T2DM and related complications.This will enable individuals at risk to take prior precautionary measures and avoid or delay the onset of the disease.Future challenges will be to understand the genotypic interactions between SNPs in one cytokine gene or several genes at different loci and study their association with T2DM.
文摘Type 2 diabetes mellitus(T2DM) is a silent progressive polygenic metabolic disorder resulting from ineffective insulin cascading in the body. World-wide, about 415 million people are suffering from T2DM with a projected rise to 642 million in 2040. T2DM is treated with several classes of oral antidiabetic drugs(OADs) viz. biguanides, sulfonylureas, thiazolidinediones, meglitinides, etc. Treatment strategies for T2DM are to minimize long-term micro and macro vascular complications by achieving an optimized glycemic control. Genetic variations in the human genome not only disclose the risk of T2DM development but also predict the personalized response to drug therapy. Inter-individual variability in response to OADs is due to polymorphisms in genes encoding drug receptors, transporters, and metabolizing enzymes for example, genetic variants in solute carrier transporters(SLC22A1, SLC22A2, SLC22A3, SLC47A1 and SLC47A2) are actively involved in glycemic/HbA1c management of metformin. In addition, CYP gene encoding Cytochrome P450 enzymes also play a crucial role with respect to metabolism of drugs. Pharmacogenetic studies provide insights on the relationship between individual genetic variants and variable therapeutic outcomes of various OADs. Clinical utility of pharmacogenetic study is to predict the therapeutic dose of various OADs on individual basis. Pharmacogenetics therefore, is a step towards personalized medicine which will greatly improve the efficacy of diabetes treatment.
文摘Colorectal cancer(CRC) is fourth most common cancer in men and third in women worldwide. Developing a diagnostic panel of sensitive and specific biomarkers for the early detection of CRC is recognised as to be crucial for early initial diagnosis, which in turn leads to better long term survival. Most of the research on novel potential CRC biomarkers in the last 2 decades has been focussed on stool DNA analysis. In this paper, we describe the recent advances in non-invasive CRC screening and more specifically in molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions. In several research papers these markers showed superior rates for sensitivity and specificity in comparison to previously described assays. These tests detected the majority of adenomas ≥ 1 cm in size and the detection rates progressively increased with larger adenomas. The methylation status of the BMP3 and NDRG4 promoters demonstrated effective detection of neoplasms at all sites throughout the colon and was not affected by common clinical variables. Recently, a multitarget stool DNA test consisting of molecular assays for aberrantly methylated BMP3 and NDRG4 promoter regions, mutant KRAS and immunochemical assay for human haemoglobin has been made commercially available and is currently reimbursed in the United States. Although this is the most sensitive noninvasive CRC screening test, there is the need for further research in several areas- establishment of the best timeframe for repeated DNA stool testing; validation of the results in populations outside of North America; usefulness for surveillance and prognosis of patients; cost-effectiveness of DNA stool testing in real-life populations.
基金Supported by Financiadora de Estudos e Projetos(FINEP CT-INFRA/FADESP),No.0927-03Fundacao de Amparo a Pesquisa do Estado de Sao Paulo(FAPESP)No.2003/06540-5+1 种基金DQC had a master fellowship,No.151127/2002-6granted by Coordenacao de Aperfeicoamento de Pessoal de Nível Superior
文摘AIM: To investigate chromosome 8 numerical aberra- tions, C-MYC oncogene alterations and its expression in gastric cancer and to correlate these findings with histo- pathological characteristics of gastric tumors. METHODS: Specimens were collected surgically from seven patients with gastric adenocarcinomas. Immu- nostaining for C-MYC and dual-color fluorescence in situ hybridization (FISH) for C-MYC gene and chromosome 8 centromere were performed. RESULTS: All the cases showed chromosome 8 aneu- ploidy and C-MYC amplification, in both the diffuse and intestinal histopathological types of Lauren. No significant difference (P < 0.05) was observed between the level ofchromosome 8 ploidy and the site, stage or histological type of the adenocarcinomas. C-MYC high amplification, like homogeneously stained regions (HSRs) and double minutes (DMs), was observed only in the intestinal-type. Structural rearrangement of C-MYC, like translocation, was observed only in the diffuse type. Regarding C-MYC gene, a significant difference (P < 0.05) was observed between the two histological types. The C-MYC protein was expressed in all the studied cases. In the intestinal- type the C-MYC immunoreactivity was localized only in the nucleus and in the diffuse type in the nucleus and cytoplasm. CONCLUSION: Distinct patterns of alterations between intestinal and diffuse types of gastric tumors support the hypothesis that these types follow different genetic path- ways.
