Excessive alcohol consumption and dietary folate inadequacy are the main contributors leading to folate deficiency (FD). The present study was planned to study regulation of folate transport in conditions of FD and ethanol exposure in human embryonic kidney cell line. Also, the reversible nature of effects mediated by ethanol exposure and FD was determined by folate repletion and ethanol removal. For ethanol treatment, HEK293 cells were grown in medium containing 100 mM ethanol, and after treatment, one group of cells was shifted on medium that was free from ethanol. For FD treatment, cells were grown in folate-deficient medium followed by shifting of one group of cells on folate containing medium. FD as well as ethanol exposure resulted in an increase in folate uptake which was due to an increase in expression of folate transporters, i.e., reduced folate carrier, proton-coupled folate transporter, and folate receptor, both at the mRNA and protein level. The effects mediated by ethanol exposure and FD were reversible on removal of treatment. Promoter region methylation of folate transporters remained unaffected after FD and ethanol exposure. As far as transcription rate of folate transporters is concerned, an increase in rate of synthesis was observed in both ethanol exposure and FD conditions. Additionally, mRNA life of folate transporters was observed to be reduced by FD. An increased expression of folate transporters under ethanol exposure and FD conditions can be attributed to enhanced rate of synthesis of folate transporters.
Reduced binding of SP1 to the promoter region of folate transporters may be a part of the regulatory mechanism resulting in decreased expression of folate transporters on ethanol exposure.
Chronic infection with HBV has been reported to be associated with the development of HCC. The in ammation mounted by cytokine mediated immune system plays an important role in the pathogenesis of HBV associated HCC. IL-18 is a pro-in ammatory cytokine whose role in the development of HBV associated chronic to malignant disease state has not been much studied. The present study was conceived to determine the role of genetic polymorphisms in IL-18, serum levels of IL-18 and expression level of its signal transducers in the HBV disease progression. A total of 403 subjects were enrolled for this study including 102 healthy subjects and 301 patients with HBV infection in different diseased categories. Polymorphism was determined using PCR-RFLP. Genotypic distributions between the groups were compared using odd's ratio and 95% CI were calculated to express the relative risk. Circulating IL-18 levels were determined by ELISA. Expression level of pSTAT1 and pNF B were determined by western blotting. In case of IL-18(-607C > A), the heterozygous genotype (CA) was found to be a protective factor while in case of IL-18(-137G > C) the heterozygous genotype (GC) acted as a risk factor for disease progression from HBV to HCC. Moreover, serum IL-18 levels were signi cantly increased during HBV disease progression to HCC as compared to controls. Also the levels of activated signal transducers (pSTAT1 and pNF-κB) of IL-18 in stimulated PBMCs were signi cantly increased during HBV to HCC disease progression. These ndings suggest that IL-18 has the potential to act as a biomarker of HBV related disease progression to HCC.
India is enriched in diversity of flora since ages. The ancient professionals have kept records of their work related to the plants. These works are a source of research today. Sariva is a well known herb since it is most commonly used in Ayurveda for its various therapeutic uses. Later on controversies erupt as locals in different parts of India used different plant species are considered in the name Sariva across India. From the data available, four species are being used as sariva in different regions. Hemidesmus indicus is a botanical name of true sariva. Cryptolepis buchanani and Ichnocarpus are also collectively known as Sariva in ayurveda. In south India Decalepis hamiltonii is being used as true Sariva. Sariva is a widely used herbal drug in the management of cognitive disorders from the times of Aacharya Charaka till today. Hemidesmus indicus, also known in ancient Ayurvedic medicine as "Sugandi" or "Sariva", has been revealed for its medicinal properties since nearly a thousand years. True Sariva traditionally used in various preparations. There is a greater chance of real material been adulterated or substituted by similar looking, cheaper material. Therefore present study is launched to carry out a complete pharmacognostic evaluation of Hemidesmus indicus and its possible adulterants or substitutes which are being used as true sariva in different regions of India. These diagnostic characters will be useful to screen out original crude drug material at the point purchasing.
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