IN VITRO EVALUATION OF CYTOTOXIC AND GENOTOXIC EFFECTS OF PLANT EXTRACTS FROM NOTHAPODYTES FOETIDA (WIGHT) SLEUMER (FAMILY: ICACINACEAE)

Objective: The objective of this study is to investigate cytotoxic and genotoxic properties of aqueous and methanolic extracts of the aerial parts of Nothapodytes foetida (Wight) Sleumer plant.Methods: The cytotoxic effects of aqueous and methanol extract of leaves and stem bark on cell viability of HeLa, MCF7, and HCT-15 cell lines was determined by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazoliumbromide assay. We also confirmed the genotoxic effects of plant extracts through DNA fragmentation in cancer cells and expression pattern of apoptotic genes including p53 and caspase-3 analyzed by semiquantitative reverse transcription-polymerase chain reaction and western blotting techniques.Results: The present study revealed that, when plant extract was tested for cytotoxic activity, the data obtained from cell viability results of HeLa and MCF7 cells revealed that methanol extract of leaves and stem bark exhibited a range of significant cytotoxic activities in a dose-dependent manner varying from 2.5 to 25 μg/mL, whereas an aqueous extract of leaves and stem bark showed decreased cell viability with an increase in the concentration of both the extracts from 5 to 50 μg/mL.Conclusion: These results indicated that the crude extract aerial parts of N. foetida plant contain promising substances having a potential as cytotoxic agent

Association of genetic polymorphisms in XRCC4, XRCC5, XRCC6 and XRCC7 in cervical cancer susceptibility from rural population: a hospital based case-control study

Background: Cervical cancer is a major concern of health risk, moreover the leading cause of cancer causing deaths in women of rural India. This study was aimed to assess the risk of cervical cancer development in association with polymorphisms in XRCC4, XRCC5, XRCC6 and XRCC7 genes in rural population of south-western Maharashtra.Methods: This study included 350 cervical cancer proven cases and 400 age and sex matched controls. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze the association XRCC4, XRCC6 and XRCC7 gene polymorphisms with cervical cancer development in women of Western Maharashtra.Results: The result from our study showed that allele frequencies of selected genes were not statistically different between the groups for XRCC4, XRCC5 and XRCC6. 6721 >T allele of XRCC7 (6721G>T) (OR= 2.34; 95% CI= (2.34 (1.60-3.43); p= <0.0001) significantly increased the risk of cervical cancer.Conclusions: This study indicates that XRCC7 gene polymorphisms play a role in modifying genetic susceptibility of individuals towards cervical cancer among women from rural Maharashtra. This case-control study also revealed negative association of XRCC6 gene in cervical carcinogenesis in the rural Indian population

Assessment of role of genetic polymorphisms in XRCC1, XRCC2 and XRCC3 genes in cervical cancer susceptibility from a rural population: a hospital based case-control study from Maharashtra, India

Background: Cervical cancer is a major concern of health risk, moreover the leading cause of cancer causing deaths in women of rural parts of India. This study was aimed to assess the risk of cervical cancer development in association with polymorphisms in X-Ray Cross Complementing Group (XRCC1, XRCC2 and XRCC3) genes in the rural population of south-western Maharashtra. We focused to determine the frequency of polymorphisms in DNA repair genes including XRCC1 at codon (cd) 194, cd 280, cd 399, XRCC2 at cd 188 and XRCC3 at cd 241 and their plausible role in cervical cancer risk from rural parts of India.Methods: This study included 350 proven cases with cervical cancer and 400 age and sex matched controls. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze the association XRCC1, XRCC2 and XRCC3 gene polymorphisms with cervical cancer development in women of South-Western Maharashtra.Results: The result from our study showed that allele frequencies of selected genes were not statistically different between the groups for XRCC1 Trp194, XRCC2 His188 and XRCC3 Met241. XRCC1 His280 (OR= 4.36; 95% CI= (3.20-5.95); p= <0.0001) and XRCC1 Gln399 (OR= 2.99; 95% CI= (1.60-5.56); p= <0.0001) genotypes significantly increased the risk of cervical cancer.Conclusions: This study indicates that polymorphisms in cd 280 of exon 9 and cd 399 of exon 10 of XRCC1 gene could play a role in modifying genetic susceptibility of individuals towards cervical cancer among women from rural Maharashtra. This case-control study suggest that selected DNA repair genes represent genetic determinants in cervical carcinogenesis along with other risk factors in the rural Indian population

Identification of genetic polymorphisms in DNA repair xenoderma pigmentosum group D gene and its association with head and neck cancer susceptibility in rural Indian population: a hospital based case-control study from south-western Maharashtra, India

Background: Smoking and alcohol related head and neck cancer is a major concern of health risk in developing countries, such as India. In this study, we aimed to determine the frequency of polymorphisms in DNA repair gene, xeroderma pigmentosum complementation group D (XPD) at codon (cd) 156, cd199, cd320, cd751 in patients of oral cancer from South-Western Maharashtra, India and to evaluate their association with oral cancer development.Methods: We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze XPD gene polymorphisms in 320 patients with oral cancer and in 400 age and sex matched disease-free controls.Results: There was no significant difference in the genotype distribution between oral cancer patients and controls for each polymorphism (p>0.05) except XPD199. The result from our study showed that allele frequencies of selected genes were not statistically different between the groups for XPD Arg156, XPD Asn320, XPD Gln751. XPDMet199 (OR=29.44; 95% CI= (18.47-46.92); p≤0.0001) genotypes significantly increased the risk of head and neck cancer.Conclusions: This study indicates that polymorphisms in cd199 of XPD gene could play a role in modifying genetic susceptibility of individual to head and neck cancer inMaharashtra patients. Thus, the case-control study suggest that selected DNA repair genes represent genetic determinants in oral carcinogenesis along with other risk factors in the rural Indian population.

Association of Genetic Variants in XPC and XPG Genes with Cervical Cancer Risk in a Rural Population: A Hospital Based Case Control Study

Background: Cervical cancer is a major concern of health risk in urban and rural parts of India.. Aim and Objectives: This study was aimed to find out frequency of polymorphisms in DNA repair genes including Xeroderma pigmentosum complementation group C (XPC) and Xenoderma pigmentosum complementation group G (XPG) in patients of cervical cancer from Maharashtra and to evaluate their association with risk of cervical cancer. Materials and Methods: We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to examine gene polymorphisms in 350 patients with cancer of cervix and 400 age and sex matched normal controls. Results: The results obtained indicated that there was no significant difference in the genotype distribution between cervical cancer patients and controls for XPC Lys939Gln, -371promoter and XPG His 1104 Asp. The result showed that genotype frequencies of XPC Val 499 Arg of codon 499 in exon 15 (OR=4.26; 95% CI=(3.007-6.03); p= <0.0001) were increased significantly. Conclusion: This study indicates that polymorphisms in Val499Arg haplotype of XPC gene appear to influence genetic susceptibility of individual to cervical cancer in Maharashtrian patients

People–place narratives as knowledge typologies for social sustainability : cases from urban contexts in the Global South

In the dynamic interplay between people and their physical environments, the Global South stands as a mosaic undergoing a multitude of transformative influences in architecture and urbanism, within which examining social sustainability becomes imperative. While the prevailing attention remains on environmental and economic sustainability, this study addresses a persistent gap in the urban literature by focusing on the dynamic and manifold nature of social sustainability. Positioning itself within the context of sustainable development, the study links the pursuit of social aspects of sustainability with selected unique urban contexts from the Global South. Five cases, including Alexandria (Egypt), Tripoli (Libya), Basra (Iraq), Lilongwe (Malawi), and Accra (Ghana), are discussed through multi-layered investigations which involve attitude surveys, interviews, focus groups, participatory systematic observations, and behavioral mapping, engaging directly with inhabitants and stakeholders. Uncovering people–place narratives in the identified contexts, the cases are developed into five knowledge typologies that serve as practical tools for planning and design decision-making, policy formulation, and academic discourse. Discussions are conceived to demonstrate the transformative role people–place narratives play in fostering a more sustainable and equitable urban future. Conclusions are drawn to offer practical insights for stakeholders involved in various capacities in shaping the urban landscape of the Global South

The Spectrum of Beta-Globin Gene Mutations in Thalassemia Patients of South-Western Maharashtra: A Cross Sectional Study

Background: β-thalassemia is a heterogeneous group of inherited hematological disorder. Though the importance of mutations in the beta-globin gene causing β-thalassemia have been reported worldwide, no data are available from rural population of SouthWestern Maharashtra. Objective: In the present study we aimed to characterize the mutations in ß-globin gene from ß-thalassemia patients from rural areas of South-Western Maharashtra. Material and Methods: The patients were analyzed for the ß-globin gene mutations included IVS I-1 (G-T), IVS I-5 (G-C), cd 71/72 (+A), cd 41/42 (-TTCT), codon (cd) 8/9 (+G), cd 17 (A-T), cd 95 (+A), cd 43 (-C), cd 41 (-C), cd 35 (C-A), cd 26 (G-T), cd 19 (A-G), cd 15 (-T), cd 27/28 (+C) and cd 14/15 (+G) with the help of Multiplexed Amplification Refractory Mutation SystemPolymerase Chain Reaction (MARMS-PCR). Results: Out of the common mutations studied the cd 71/72 (21.54%), cd 19 (13.7 %). cd 41/42 (9.68%) and cd 41 (9.6%) showed high prevalence followed by cd17 (7.56 %). 7.27% patients showed IVSI-5 mutations, 6.26 % showed IVSI-1 mutations. Cd 15 mutations were present in 8.69 % patients and only 5.39 % subjects showed cd 8/9 mutations. This study provides the pattern of ß-thalassemia mutations from rural areas of Maharashtra in India. Conclusion: This study provides the pattern of ß-thalassemia mutations from rural population which will open a new avenue for implementation of molecular diagnostics for prenatal diagnosis and prevention of blood disorder by proper counseling in rural areas

The Spectrum of Dystrophin Gene Mutations in Duchene Muscular Dystrophy Patients of South-Western Maharashtra in India

Background: Duchenne muscular dystrophy is the most common neuromuscular disease of childhood caused by deletion or point mutations in the dystrophin gene. Though the importance of deletion mutations in the dystrophin gene causing DMD have been reported worldwide, no data available from rural population of Maharashtra. Objectives: This study specifically aimed at the investigation of deletion mutations in the DMD gene from the patients from South-Western Maharashtra. Material & Methods: Fifty patients with clinically diagnosed DMD were analyzed to screen for intragenic deletions in 21 exons within the DMD gene using the multiplex polymerase chain reaction. Results: Amongst the 50 unrelated DMD patients from South-Western Maharashrra we found DMD gene deletions in 47 cases which represent 94 % mutations in DMD patients. Majority of the deletions (85.10%) were located at distal hot spot region that encompasses exons 42-53 and 10.63% of the deletions were located at the proximal hot spot region (exons 2-19). Exons 50, 51, 52 and 53 are most frequently deleted. Conclusion: It is important to note that we could be the first to search for the most frequent deletions in the exons of DMD gene in from the rural areas of Maharashtra with the help of molecular biology tools

Identification of genetic polymorphisms in DNA repair xenoderma pigmentosum group D gene and its association with head and neck cancer susceptibility in rural Indian population: a hospital based case-control study from south-western Maharashtra, India

Background: Smoking and alcohol related head and neck cancer is a major concern of health risk in developing countries, such as India. In this study, we aimed to determine the frequency of polymorphisms in DNA repair gene, xeroderma pigmentosum complementation group D (XPD) at codon (cd) 156, cd199, cd320, cd751 in patients of oral cancer from South-Western Maharashtra, India and to evaluate their association with oral cancer development.Methods: We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to analyze XPD gene polymorphisms in 320 patients with oral cancer and in 400 age and sex matched disease-free controls.Results: There was no significant difference in the genotype distribution between oral cancer patients and controls for each polymorphism (p&gt;0.05) except XPD199. The result from our study showed that allele frequencies of selected genes were not statistically different between the groups for XPD Arg156, XPD Asn320, XPD Gln751. XPDMet199 (OR=29.44; 95% CI= (18.47-46.92); p≤0.0001) genotypes significantly increased the risk of head and neck cancer.Conclusions: This study indicates that polymorphisms in cd199 of XPD gene could play a role in modifying genetic susceptibility of individual to head and neck cancer inMaharashtra patients. Thus, the case-control study suggest that selected DNA repair genes represent genetic determinants in oral carcinogenesis along with other risk factors in the rural Indian population.