RESUMEN

The process of tumorigenesis is highly associated with the disruption of cell-cycle regulators and derangement of various signaling pathways, which end up with the inhibition of apoptosis and hyper-activation of survival pathways. The PI3K medicated AKT/mTOR pathway is the widely explained mechanism for cancer cell survival which causes the overexpression of MDM2 and downregulates the p53-BAX mediated apoptotic pathway. Curcumin (CUR), the phyto-compound, derived from Curcuma longa is currently being focused on for its anticancer activities against breast cancer cells, MDA-MB-231, not only because of its minimal cytotoxicity against healthy cells (HEK293) but also because it synergistically sensitizes the activity of Doxorubicin (DOXO) in lower doses, which can be a promising source for complementary drug development. This study aims to investigate the combinatorial effect of CUR and DOXO on PI3K/AKT/mTOR pathway proteins by sequential molecular docking analysis and MD simulation studies. The lower binding affinity of the sequentially docked protein-ligand complex proves the increasing binding affinity of CUR and DOXO in the combinatorial dose. The mRNA expressions of different genes of this pathway are observed and quantified using rt-qPCR, where the decreasing fold change (2-∆∆Ct) indicates the suppression of the AKT/mTOR pathway after co-treatment of CUR and DOXO against MDA-MB-231 cells. These in silico and in vitro findings can be a new horizon for further in vitro and clinical trials of breast cancer treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00231-2.

RESUMEN

Diabetes is known to increase susceptibility to hypertension due to increase in inflammation, oxidative stress, and endothelial dysfunction, leading to vascular stiffness. The polytherapy might lead to several drug-drug interactions (DDIs), which cause certain life-threatening complications such as diabetic nephropathy and hypoglycaemia. So, in this review we focused on drug-drug interactions and impact of genetic factors on drug responses for better disease management. Drug-drug interactions (DDIs) may act either synergistically or antagonistically. For instance, a combination of metformin with angiotensin II receptor antagonist or angiotensin-converting enzyme inhibitors (ACEIs) synergistically improves glucose absorption, whereas the same hypertensive drug combination with sulphonylurea might cause severe hypoglycaemia sometimes. Thiazolidinediones (TDZs) can cause fluid retention and heart failure when taken alone, but a combination of angiotensin II receptor antagonist with TZDs prevents these side effects. Interindividual genetic variation affects the DDI response. We found two prominent genes, GLUT4 and PPAR-γ, which are common targets for most of the drug. So, all of these findings established a connection between drug-drug interaction and genetics, which might be used for effective disease management.

Asunto(s)

Diabetes Mellitus , Hipertensión , Hipoglucemia , Humanos , Farmacogenética , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/genética , Hipertensión/tratamiento farmacológico , Hipertensión/genética , Antagonistas de Receptores de Angiotensina/efectos adversos

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Coronavirus disease-2019 (COVID-19) is pro-inflammatory disorder characterized by acute respiratory distress syndrome. Interleukin-6, a cytokine secreted by macrophages, which mediates an inflammatory response, is frequently increased and associated with the severity in COVID-19 patients. The differential expression of IL6 cytokine in COVID-19 patients may be associated with the presence of single nucleotide polymorphisms (SNPs) in regulatory region of cytokine genes. The aim of this study is to investigate the role of two promoter polymorphisms of the IL6 gene (-597G > A and -174G > C) with the severity of COVID-19. The study included 242 patients, out of which 97 patients with severe symptoms and 145 patients with mild symptoms of COVID-19. Genotyping of two selected SNPs, rs1800795 (-174G > C) and rs1800797 (-597G > A) of promoter region of IL6 gene, was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). In our study, individuals with GC genotypes of IL6 (-174G > C) polymorphism showed significantly higher risk of severity [adjusted odds (OR) 3.86, p <.001] but we did not observe any association of COVID-19 severity with rs1800797 (-597G > A) polymorphism. The COVID-19 severity was significantly higher in individuals having 'C' allele of IL6 (-174G > C) polymorphism (p = .014). Linkage disequilibrium between rs1800795 (-174G > C) and rs1800797 (-597G > A) showed that individuals having AC* haplotype significantly association with COVID-19 severity (p = .034). Our results suggest that 'C' allele of rs1800795 (-174G > C) polymorphism of IL6 may be the risk allele for severity of COVID-19 in North Indian population.

Asunto(s)

COVID-19 , Interleucina-6 , Humanos , Interleucina-6/genética , Predisposición Genética a la Enfermedad , COVID-19/genética , Genotipo , Polimorfismo de Nucleótido Simple , Frecuencia de los Genes

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Tuberculosis (TB) continues to be a major infectious disease affecting individuals worldwide. Current TB treatment strategy recommends the standard short-course chemotherapy regimen containing first-line drug, i.e., isoniazid, rifampicin, pyrazinamide, and ethambutol to treat patients suffering from drug-susceptible TB. Although Mycobacterium tuberculosis , the causing agent, is susceptible to drugs, some patients do not respond to the treatment or treatment may result in serious adverse reactions. Many studies revealed that anti-TB drug-related toxicity is associated with genetic variations, and these variations may also influence attaining maximum drug concentration. Thus, inter-individual diversities play a characteristic role by influencing the genes involved in drug metabolism pathways. The development of pharmacogenomics could bring a revolution in the field of treatment, and the understanding of germline variants may give rise to optimized targeted treatments and refine the response to standard therapy. In this review, we briefly introduced the field of pharmacogenomics with the evolution in genetics and discussed the pharmacogenetic impact of genetic variations on genes involved in the activities, such as anti-TB drug transportation, metabolism, and gene regulation.

RESUMEN

Objectives Cervical cancer (CC) is one of the most destructive disease caused by persistent HPV infection which affects women worldwide, especially in developing countries. The genetic basis of host immune response especially cytokine function has been shown to influence CC susceptibility. Studies have demonstrated that IL-10 gene polymorphism have been associated with numerous malignancies, but in context to CC results were inconclusive. Though, aim of our study to investigate the association between IL-10 -1082A/G and -819C/T promoter polymorphism and CC susceptibility. Material and Methods This study comprised 192 women with CC and 200 controls. HPV detection was done by RT-PCR and genotyping was assessed through PCR-RFLP method. Serum concentration of IL-10 measured by ELISA. Results Women with AG and AG+GG genotypes of IL-10 -1082A/G had two-fold increased risk of CC [OR, 2.35 (95% CI, 1.54-3.58), p  = 0.005], [OR, 2.03 (95% CI, 1.36-3.04), p  = 0.0005] compared to controls. Women with G allele of -1082A/G polymorphism had linked with CC susceptibility [OR, 1.39 (95% CI, 1.02-1.88), p  = 0.036] compared to controls. No significant difference was found between patients and controls in the genotype or allele frequencies of IL-10 -819C/T polymorphism [OR, 1.00 (95% CI, 0.63-1.58), p  = 0.99]. The level of serum concentration of IL-10 was significantly higher in cases compared to controls. Conclusion These findings help to understand that polymorphism of IL-10 -1082A/G gene is associated with increased risk of CC development and can serve as a marker of genetic susceptibility to CC.

RESUMEN

Cancer progression is linked to abnormal epigenetic alterations such as DNA methylation and histone modifications. Since epigenetic alterations, unlike genetic changes, are heritable and reversible, they have been considered as interesting targets for cancer prevention and therapy by dietary compounds such as luteolin. In this study, epigenetic modulatory behaviour of luteolin was analysed on HeLa cells. Various assays including colony forming and migration assays, followed by biochemical assays of epigenetic enzymes including DNA methyltransferase, histone methyl transferase, histone acetyl transferase, and histone deacetylases assays were performed. Furthermore, global DNA methylation and methylation-specific PCR for examining the methylation status of CpG promoters of various tumour suppressor genes (TSGs) and the expression of these TSGs at transcript and protein level were performed. It was observed that luteolin inhibited migration and colony formation in HeLa cells. It also modulated DNA methylation at promoters of TSGs and the enzymatic activity of DNMT, HDAC, HMT, and HAT and reduced the global DNA methylation. Decrease in methylation resulted in the reactivation of silenced tumour suppressor genes including FHIT, DAPK1, PTEN, CDH1, SOCS1, TIMPS, VHL, TP53, TP73, etc. Hence, luteolin-targeted epigenetic alterations provide a promising approach for cancer prevention and intervention.

Asunto(s)

Luteolina , Neoplasias , Metilación de ADN , Metilasas de Modificación del ADN/genética , Desmetilación , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Células HeLa , Código de Histonas , Histona Desacetilasas/metabolismo , Humanos , Luteolina/farmacología , Neoplasias/tratamiento farmacológico , Neoplasias/genética

RESUMEN

Background: Coronavirus disease 2019 (COVID-19) is an ongoing pandemic which has emerged as a new challenge for the medical sciences. Severity of COVID-19 is mostly determined with overexpressed proinflammatory cytokines eventually leading to endothelial dysfunction causing vital organ injury, especially in the lungs. It has been postulated that various genetic mutations might be associated with an increased risk of disease severity in COVID-19. This study was thus carried out to determine the association of rs1800896 and rs1800872 genetic polymorphism in IL-10 gene in determining COVID-19 severity. Methods: The study included 160 RT-PCR confirmed COVID-19 patients with mild (n = 85) and severe (n = 75) conditions. All subjects were genotyped for Interleukin-10 (rs1800896 and rs1800872) gene polymorphisms using PCR-RFLP technique followed by statistical analysis. Results: This study found a significant gender and age-based discrepancy in COVID-19 severity with 1.85-and 3.81-fold increased risk of COVID-19 in males of mild and severe groups as compared to females (p = 0.046 and p < 0.001) and 4.35-fold high risk in subjects ≥ 50 (p < 0.001). Genotyping analysis showed that IL-10 (rs1800872) gene polymorphism was strongly associated with COVID-19 severity (p = 0.01) whereas, IL-10 rs1800896 polymorphism was not found to confer the risk of COVID-19 severity in our population. Conclusion: In this regard, the present study provided an evidence that IL-10 (rs1800872) gene polymorphism is strongly associated with COVID-19 severity and CC genotype confer a protective role in preventing severe disease progression. More detailed studies with a larger sample size on the genetic variations are required to establish the role of studied IL-10 gene polymorphisms with COVID-19 severity.

RESUMEN

Human papillomaviruses (HPV) infection is a major causative agent and strongly associated with the development of cervical cancer. Understanding the mechanisms of HPV-induced cervical cancer is extremely useful in therapeutic strategies for primary prevention (HPV vaccines) and secondary prevention (screening and diagnosis of precancerous lesions). However, due to the lack of proper implementation of screening programs in developing countries, cervical cancer is usually diagnosed at advanced stages that result in poor treatment responses. Nearly half of the patients will experience disease recurrence within two years post treatment. Therefore, it is vital to identify new tools for early diagnosis, prognosis, and treatment prediction. MicroRNAs (miRNAs) are small non-coding RNAs, implicated in posttranscriptional regulation of gene expression. Growing evidence has shown that abnormal miRNA expression is associated with cervical cancer progression, metastasis, and influences treatment outcomes. In this review, we provide comprehensive information about miRNA and their potential utility in cervical cancer diagnosis, prognosis, and clinical management to improve patient outcomes.

Asunto(s)

MicroARNs/farmacología , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/etiología , Detección Precoz del Cáncer/métodos , Femenino , Humanos , MicroARNs/administración & dosificación , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/tratamiento farmacológico , Pronóstico

RESUMEN

Severe acute respiratory syndrome corona virus-2 (SARS-CoV-2) has first emerged from China in December 2019 and causes coronavirus induced disease 19 (COVID-19). Since then researchers worldwide have been struggling to detect the possible pathogenesis of this disease. COVID-19 showed a wide range of clinical behavior from asymptomatic to severe acute respiratory disease syndrome. However, the etiology of susceptibility to severe lung injury is not yet fully understood. Angiotensin-converting enzyme1 (ACE1) convert angiotensin I into Angiotensin II that was further metabolized by ACE 2 (ACE2). The binding ACE2 receptor to SARS-CoV-2 facilitate its enter into the host cell. The interaction and imbalance between ACE1 and ACE2 play a crucial role in the pathogenesis of lung injury. Thus, the aim of this study was to investigate the association of ACE1 I/D polymorphism with severity of Covid-19. The study included RT-PCR confirmed 269 cases of Covid-19. All cases were genotyped for ACE1 I/D polymorphism using polymerase chain reaction and followed by statistical analysis (SPSS, version 15.0). We found that ACE1 DD genotype, frequency of D allele, older age (≥46 years), unmarried status, and presence of diabetes and hypertension were significantly higher in severe COVID-19 patient. ACE1 ID genotype was significantly independently associated with high socio-economic COVID-19 patients (OR: 2.48, 95% CI: 1.331-4.609). These data suggest that the ACE1 genotype may impact the incidence and clinical outcome of COVID-19 and serve as a predictive marker for COVID-19 risk and severity.

Asunto(s)

Sustitución de Aminoácidos , COVID-19/epidemiología , COVID-19/genética , Predisposición Genética a la Enfermedad , Peptidil-Dipeptidasa A/genética , Polimorfismo Genético , SARS-CoV-2/patogenicidad , Adulto , Factores de Edad , Anciano , Alelos , Enzima Convertidora de Angiotensina 2/genética , Enzima Convertidora de Angiotensina 2/metabolismo , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Enfermedades Asintomáticas , COVID-19/mortalidad , COVID-19/virología , Comorbilidad , Diabetes Mellitus , Femenino , Regulación de la Expresión Génica , Frecuencia de los Genes , Interacciones Huésped-Patógeno/genética , Humanos , Hipertensión , India/epidemiología , Isoleucina/genética , Isoleucina/metabolismo , Masculino , Persona de Mediana Edad , Peptidil-Dipeptidasa A/metabolismo , Factores de Riesgo , SARS-CoV-2/fisiología , Índice de Severidad de la Enfermedad , Análisis de Supervivencia

RESUMEN

BACKGROUND: Endothelial nitric oxide synthase (eNOS) and potassium voltage-gated channel subfamily J member 11 (KCNJ11) could be the candidate genes for coronary artery disease (CAD). This study investigated the relationship of the eNOS (rs1799983) and KCNJ11 (rs5219) polymorphisms with the presence and severity of CAD in the North Indian population. METHODS: This study included 300 subjects, 150 CAD cases and 150 healthy controls. Single nucleotide polymorphism was evaluated by Polymerase chain reaction and Restriction fragment length polymorphism (PCR-RFLP). Analysis was performed by SPSS (version 21.0). RESULTS: We observed that KK genotype of KCNJ11E23K (rs5219) polymorphism (P=0.0001) genotypes and K allele (P=0.0001) was found to be a positive risk factor and strongly associated with CAD. In the case of eNOSG894T (rs1799983) there was no association found with CAD. CONCLUSION: These results illustrate the probability of associations between SNPs and CAD although specific genetic polymorphisms affecting ion channel function and expression have still to be clarified by further investigations involving larger cohorts.

Asunto(s)

Enfermedad de la Arteria Coronaria , Óxido Nítrico Sintasa de Tipo III , Pueblo Asiatico , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Óxido Nítrico Sintasa de Tipo III/genética , Óxido Nítrico Sintasa de Tipo III/metabolismo , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Factores de Riesgo

RESUMEN

BACKGROUNDS: Cervical cancer (CC) is one of the leading cause of death in women worldwide, HPV infection is the major risk factor in the disease development, 0and however other risk factor such as chemical carcinogens, genetic susceptibility and altered immune system are also a cause of the disease progression. In the light of the above statement we studied the base excision repair pathway (BER). METHODS: We identified and studied the association of Single Nucleotide polymorphisms in the DNA repair genes of XRCC1 (Arg194Trp, Arg399G,) and APE-1Asp/148Glu to the susceptibility of cervical cancer (CC) in North Indian population. In our study of cases (n=102). Controls (n=109) were recruited from among women without cervical abnormalities. Genotypes were determined by PCR-CTPP method, Taking DNA from peripheral blood in a case control study. RESULTS: A positive association was observed between the polymorphisms of XRCC1 genes, that is, in codons 194 (P=0.03, odds ratio (OR) =2.39, 95% confidence interval (CI)=5.2-1.1), 280 (P=0.01, OR=4.1, 95% CI=11.5-1.3) and 399 (P=0.01, OR=3.4, 95% CI=8.6-1.3) while APE-1 genotype GG (p=0.03,odds ratio(OR)=0.2,95% confidence interval (CI)=0.97-0.004) we observed a statistically significant protective role in developing cervical cancer. CONCLUSION: Our results suggested that, XRCC1 gene is an important candidate gene for susceptibility to cervical cancer. Although the sample size was small, the present study indicate a statistical association between cervical cancer and XRCC1 SNPs. Future studies are needed that may provide a better understanding of the association between gene polymorphism and cervical carcinoma risk.
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Asunto(s)

Adenocarcinoma/epidemiología , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/epidemiología , Reparación del ADN , ADN-(Sitio Apurínico o Apirimidínico) Liasa/genética , Neoplasias del Cuello Uterino/epidemiología , Proteína 1 de Reparación por Escisión del Grupo de Complementación Cruzada de las Lesiones por Rayos X/genética , Adenocarcinoma/genética , Adenocarcinoma/patología , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Pronóstico , Neoplasias del Cuello Uterino/genética , Neoplasias del Cuello Uterino/patología

RESUMEN

Genetic factors in combination with environmental factors play a critical role in the development type 2 diabetes mellitus (T2DM) which is growing as an epidemic globally. In present study we aim to assess the association of eNOS (G894T, rs1799983) and NET (G1287A, rs5569) genes polymorphism with T2DM. A case-control study including a total of 400 North Indian subjects (200 T2DM cases and 200 controls) was performed using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach to analyze genetic polymorphism. Alleles/genotype frequencies between cases and controls were compared using χ2 and Student's t-tests. Odds ratios and 95% confidence intervals were calculated by logistic regression to assess the relative association between disease and genotypes. In case of NET gene, GG (P = 0.002 in T2DM males, 0.053 in overall T2DM cases) genotype and G allele (P = 0.003 in T2DM males, 0.027 in overall T2DM cases) were found to be a positive risk factors and AG genotype (P = 0.012 in T2DM males) and A allele (P = 0.003 in T2DM males, P = 0.027 in overall T2DM cases) as negative risk factor for T2DM. No association of eNOS gene polymorphism was found with T2DM (P values of all genotypes and alleles were greater than 0.05). NET gene polymorphism might be associated with the risk of T2DM whereas; eNOS gene polymorphism do not confer any risk of T2DM in North Indian Ethnic group. It is hoped that understanding genetic causes of T2DM will lead to earlier diagnosis, preventive measures and more effective and specific treatment.

Asunto(s)

Diabetes Mellitus Tipo 2/genética , Óxido Nítrico Sintasa de Tipo III/genética , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/genética , Adulto , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/enzimología , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Óxido Nítrico Sintasa de Tipo III/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Factores de Riesgo

RESUMEN

Background: MicroRNAs (miRNAs) are non-coding RNAs that regulate multiple cellular processes during cancer progression, identified to be involved in tumorgenesis of several cancers including cancers of digestive system. However its role in gallbladder inflammatory disease (GID) and gallbladder cancer (GBC) has not been well documented. The present study was aimed to investigate the clinical significance of hsa-miRNA-335-5p (miR-335) in GBC and GID. Subjects and Methods: This prospective case control study, conducted from July 1, 2014 to December 1, 2017 in Era's Lucknow Medical College & Hospital, India, evaluated miR-335 expression by real-time polymerase chain reaction. Hundred tissue samples GID (control; n=50) and GBC (case; n=50) were studied. Relative quantification of target miR-335 expression was examined using the comparative cycle threshold method. Their expression was correlated with different clinicopathological parameters. Fishers' exact test, Student's t-test, and Chi-square test were used as appropriate for data analysis. Kaplan-Meier methods were used to calculate overall and disease-free survival rate. Two sided P<0.05 was considered as significant. Results: miR-335 expression was found to be significantly low in GBC lesions when compared with GID lesions (P<0.001). The low expression level of miR-335 was correlated with histological grade (P=0.007), clinical stage (P<0.001), lymph node metastasis (P<0.001) and liver metastasis (P=0.016). Reduced expression of miRNA-335 was associated with a shorter median overall survival (7 months vs. 25 months) in GBC patients (P<0.001). Conclusions: Down regulation of miR-335 is associated with the severity of the disease and thus indicate that miR-335 expression may serve as prognostic marker for GBC.

Asunto(s)

Biomarcadores de Tumor/genética , Neoplasias de la Vesícula Biliar/genética , Neoplasias de la Vesícula Biliar/patología , MicroARNs/genética , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Neoplasias de la Vesícula Biliar/cirugía , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia , Adulto Joven

RESUMEN

Lung carcinoma is the leading cause of cancer-related death worldwide; it has been regarded as the origin of death by melanoma universally. Frequently, lung carcinomas identified in progressive phase and have lowermost roots of existence in any category of the cancer. MicroRNAs (miRNAs) are small having 18-25 nucleotides extended noncoding RNAs regulating gene expression and elaborate in a wide assortment of cellular progressions also. Cumulative indications propose that, miRNA plays imperative and multifarious roles in cases of human lung cancer genetics. Collective studies concern with research related to lung sarcoma by using biomarkers which determine phenotypic signatures on behalf of diagnostic, prognostic, as well as therapeutic rationale. Furthermore, a number of aspects are indispensable to be deliberated while opting for miRNAs as clinical biomarkers in lung cancers, which have been recognized as imperative targets for therapeutic interventions in recent times. This review focuses inclusive information over the biogenesis of miRNA and considerable risk dynamics associated with the genetics of human lung cancer.

Asunto(s)

Carcinogénesis/genética , Carcinoma/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Pulmonares/genética , MicroARNs/genética , Animales , Biomarcadores de Tumor , Carcinoma/metabolismo , Carcinoma/patología , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Pronóstico , Interferencia de ARN

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: India being a multicultural nation, every region of the country offers a distinct culinary flavor and taste. These flavors are attributed to spices and condiments which form the mainstay of Indian cuisine. Most of these spices and condiments are derived from various biodiversity hotspots in India and form the crux of India's multidiverse and multicultural cuisine. Apart from their varying aromas, flavors and tastes, these spices and condiments are known to possess several medicinal properties also. Most of these spices find considerable mention in Ayurveda, the indigenous system of medicine, as panaceas for several aliments. Cinnamomum zeylanicum (CZ), belonging to family Lauraceae and commonly known as cinnamon is one such spice known to have diverse medicinal properties since time immemorial. AIM OF THE STUDY: In the present study, apoptotic and anti-microbial activity of ethanolic extract of CZ was evaluated against human breast cancer cell line MDA-MB-231 and compared for its effect on normal kidney epithelial cell line Vero. MATERIALS AND METHODS: Ethanolic extract of tree bark of CZ was used to determine the cytotoxic effect on MDA-MB-231 using Trypan blue dye exclusion method and cytometry. The tested dose of the extract was 10-100 µg/mL. Antibacterial activity was determined using disc diffusion method against Staphylococcus aureus and Escherichia coli in the range 2-10 mg/mL. Apoptotic activity was determined using DNA fragmentation assay. RESULTS: Ethanolic extract of CZ was found to have an IC50 value of 25 µg/mL against MDA cell line. On the other hand, CZ extract did not have any significant effect on Vero cells even at 100 µg/mL (IC50 > 100 µg/mL). The ethanolic extract of CZ bark showed significant antibacterial activity against S. aureus at 10 mg/mL while no appreciable activity was detected against E. coli. DNA isolated from extract treated cancer cells showed a fragmentation pattern characteristic of apoptosis. However, no DNA fragmentation was observed in DNA isolated from extract treated Vero cells. CONCLUSION: Ethanolic bark extract of CZ could be potentially beneficial in treating breast cancer and may be of interest for future studies in developing integrative cancer therapy against proliferation, metastasis, and migration of breast cancer cells.

Asunto(s)

Antibacterianos/farmacología , Supervivencia Celular/efectos de los fármacos , Cinnamomum zeylanicum , Fitoquímicos/farmacología , Extractos Vegetales/farmacología , Animales , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Línea Celular Tumoral , Supervivencia Celular/fisiología , Chlorocebus aethiops , Relación Dosis-Respuesta a Droga , Evaluación Preclínica de Medicamentos/métodos , Etanol/farmacología , Fitoquímicos/química , Fitoquímicos/aislamiento & purificación , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Células Vero

RESUMEN

Coronary artery disease (CAD) is the leading cause of death worldwide and it is basically caused by atherosclerosis. The atherosclerotic process includes complex events and each one involves a specific biological pathway and different genes. According to World Health Organization report, Cardiovascular diseases will be the largest cause of death and disability by 2020, with an estimated 2.6 million Indians predicted to die due to CAD predominantly with myocardial infarction. Genetic factors are estimated to contribute 30-60% of the CAD risk. The aim of this study is to investigate the association of COL4A1 and CD14 genes polymorphism with CAD. This study included 345 subjects, 185 CAD cases and 160 healthy controls. Single-nucleotide polymorphisms were evaluated by polymerase chain reaction and restriction fragment length polymorphism. Alleles and genotype frequencies between cases and controls were compared using χ2 and Student's t tests. Odds ratios and 95% confidence intervals were calculated by logistic regression to assess the relative association between disease and genotypes. In this study, CD14 (rs2569190), CC (P = 0.008) genotypes, and C allele (P = 0.007) were found to be a positive risk factor, while TT genotype (P = 0.045) and T allele (P = 0.007) as negative risk factor for CAD. Significant differences were not observed in COL4A1 (rs605143 and rs565470) gene polymorphism with CAD. It seems that CD14 gene polymorphism might be associated with the risk of CAD, whereas COL4A1 gene polymorphism was not found to confer any risk of CAD.

Asunto(s)

Colágeno Tipo IV/genética , Enfermedad de la Arteria Coronaria/genética , Predisposición Genética a la Enfermedad , Receptores de Lipopolisacáridos/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Aterosclerosis/complicaciones , Estudios de Casos y Controles , Enfermedad de la Arteria Coronaria/etiología , Frecuencia de los Genes , Genotipo , Humanos , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa , Polimorfismo de Longitud del Fragmento de Restricción

RESUMEN

PURPOSE: The present study was carried out to investigate the association of fatty acid-binding protein 2 (FABP2) and fat mass and obesity-associated (FTO) gene polymorphism with primary open-angle glaucoma (POAG) cases and controls. MATERIALS AND METHODS: This study includes 122 POAG cases and 112 controls. FABP2 and FTO gene polymorphisms in cases and controls were evaluated by polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The mean ages were 49.88 ± 12.34 and 53.74 ± 11.87 years in POAG cases and control groups, respectively. The FABP2 gene AA, AT, TT genotype frequencies were 12.90%, 62.40%, 24.80% in POAG cases and 20.60%, 64.70%, 14.70% in healthy controls, respectively. The frequencies of A and T allele in POAG cases were 44.06% and 55.94% as compared to 52.94% and 47.06% in the controls. The FTO gene AA, AT, TT genotype frequencies were 2.00%, 79.20%, 18.80% in cases and 0%, 75.50%, 24.50% in healthy controls, respectively. The frequencies of A and T allele in POAG cases were 41.58% and 58.42% as compared to 37.75% and 62.25% in the controls. No significant difference in the frequencies of FABP2 and FTO genotype was found between POAG cases and controls. CONCLUSION: We could not identify the possible association of FABP2 and FTO gene polymorphism with POAG; however, further studies with larger sample size in different population are require to clarify the role of FABP2 and FTO genes in susceptibility to POAG.

RESUMEN

Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR, FABP2, FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE, FABP2, FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

RESUMEN

CONTEXT: Genetics play a major role in development and pathophysiology of Type 2 diabetes mellitus (T2DM). OBJECTIVE: To asses the association of Guanine nucleotide-binding protein (GNB3) (C825T) gene's polymorphism with T2DM. MATERIALS AND METHODS: A case-control study including 400 North Indians was performed using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) approach to analyze genetic polymorphism. RESULTS: No significant difference was observed in genotype and allele frequencies of GNB3 gene on comparing cases with controls. DISCUSSION: Our study is in agreement with studies on Polish, Japanese, Hispanic-American and Danish populations who observed no significant association between GNB3 (C825T) polymorphism and T2DM. CONCLUSION: GNB3 (C825T) polymorphism is not associated with T2DM.

Asunto(s)

Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad/genética , Proteínas de Unión al GTP Heterotriméricas/genética , Mutación , Alelos , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Genotipo , Humanos , India , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Factores de Riesgo

RESUMEN

BACKGROUND: Senile cataract is the most common type of cataract characterized by gradual progressive thickening of the lens of the eye. Previously, many studies investigated the association between genetic polymorphism and senile cataract. Angiotensin-converting enzyme (ACE) I/D polymorphism is the potential risk factor for many eye-related diseases such as retinopathy and glaucoma. CYP46A1 enzyme converts cholesterol to 24S-hydroxycholesterol; human lens' membranes contain the highest cholesterol content. Defects in enzymes of cholesterol metabolism can be associated with cataracts. Hence, the present study was carried out to investigate the association of ACE and CYP46A1 genes polymorphism with senile cataract cases and controls. MATERIALS AND METHODS: ACE (rs 4646994) and CYP46A1 (rs 754203) genes polymorphism in cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism. RESULTS: This study included 103 senile cataract cases (55 were males and 48 were females) and 102 controls (53 were males and 49 were females). Mean age of cases in this study was 52.02 ± 12.11 years while in control group 53.74 ± 11.87 years. Frequencies of ACE ID, DD, and II genotypes in senile cataract cases were 64.07%, 4.85%, and 31.06% and controls were 61.76%, 26.47%, and 11.76%, respectively. The CYP46A1 gene CT, CC, and TT genotype frequencies were 48.54%, 8.73%, and 42.71% in senile cataract cases and 28.43%, 3.92%, and 67.64% in healthy controls, respectively. ACE DD and II genotypes (P < 0.001,P = 0.0008) and CYP46A1 CT and TT genotypes (P = 0.003,P = 0.0003) were significantly associated with senile cataract cases compared to the controls. CONCLUSION: Findings of this study suggest that ACE and CYP46A1 genes polymorphism may be a predictive marker for early identification of population at risk of senile cataract. This potential role of ACE and CYP46A1 genes polymorphism as a marker of susceptibility to senile cataract needs further validation in studies involving larger number of patients from different regions.