Journal of pharmacological and toxicological methods, Jan 20, 2016
A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the di... more A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg(-1) body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day. Controls (n=15 males; n=15 females) were fed normal balanced diet without administration of STZ. Successful induction of diabetes mellitus was confirmed by testing for fasting blood glucose, intraperitoneal glucose tolerance and intraperitoneal insulin sensitivity. Diabetic mice were administered vildagliptin (10mgkg(-1) bw daily) and metformin (50mgkg(-1) bw daily) orally for 4weeks. Control, diabetic, vildagliptin and metformin-treated diabetic mice were evaluated for alterations in lipid profile using blood serum and histopathology ...
Background: Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM... more Background: Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study. Methods: Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted. Results: Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the r...
Cancers of the upper aero-digestive and gastrointestinal tract are one of the major causes of mor... more Cancers of the upper aero-digestive and gastrointestinal tract are one of the major causes of mortality around the world. DNA repair genes play a vital role in preventing carcinogenesis by maintaining genomic integrity. Polymor-phisms in the nucleotide sequence of DNA repair genes are often reported to be associated with an increased risk for different cancers. The OGG1 gene encodes the enzyme 8-oxoguanine DNA glycosylase which removes oxidatively damaged bases of DNA. Several studies report that the OGG1 Ser326Cys polymorphism increases the risk for cancers of the upper aero-digestive and gastrointestinal tract. However, other studies provide evidence that such an association does not exist. A meta-analysis to assess the role of OGG1 Ser326Cys polymorphism in the cancers of the upper aero-digestive and gastrointestinal tract was therefore undertaken in order to resolve this ambiguity. Seventeen studies were recruited for this meta-analysis after screening 58 articles with a total of 5533 cases and 6834 controls for which the odds ratio with 95 % confidence interval was calculated. Begg's funnel test and Egger's test were performed for calculating publication bias. Our study reveals an association between OGG1 Ser326Cys polymorphism and cancer susceptibility of the upper aero-digestive and gastrointestinal tract (CG + GG vs CC; odds ratio, OR 1.22; 95 % CI 1.05–1.41; GG vs CG + CC; OR 1.36; 95 % CI 1.09–1.70; GG vs CC; OR 1.46; 95 % CI 1.12–1.92). Subgroup analysis based on cancer types and ethnicity also revealed the association of OGG1 Ser326Cys polymorphism to the risk for upper aero-digestive and gastrointestinal tract cancers among both the Asian and the Caucasian populations. No risk was however observed for smoking habits and OGG1 Ser326Cys polymorphism. In conclusion, OGG1 Ser326Cys polymorphism may be associated with the increased risk for aero-digestive tract and gastro-intestinal cancers in both Asian and Caucasian populations.
A number of different epidemiological studies have measured the association between the risk of d... more A number of different epidemiological studies have measured the association between the risk of different cancers and polymorphism at promoter region of 5′ untranslated region (5′-UTR) of the Ataxia-telangiectasia mutated (ATM) gene. However the results were contentious rather than conclusive. The current study was aimed at evaluating the association between the SNP (rs189037 G>A) and the risk of head and neck cancer and lung cancer by conducting ameta-analysis. A total of 9 case–control studieswere considered for this quantitative analysis. Stats Direct Statistical software (version 2.7.2)was used to evaluate the crude odds ratio (OR) with their 95% confidence interval (CI). The dominant model (GG vs. GA+ AA) showed no heterogeneity and the fixed effects pooled OR was found to be significant (OR = 1.14, 95% CI = 1.05–1.25) at p = 0.003. The pooled OR for fixed effects of heterozygote and homozygote mutant allele (GA vs. AA) model was significant (OR = 1.17, 95% CI = 1.04–1.30, p=0.006) and no heterogeneity was observed for this model. The current meta-analysis manifested that ATM rs189037 G>A genetic polymorphismmay contribute increased risk of head and neck and lung cancer. Moreover, the AA mutant allele was found to be related significantly with the prognosis of lung cancer and head and neck cancer
MicroRNAs: a new ray of hope for diabetes mellitus, Jul 4, 2012
Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major chal... more Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major challenge to global health. Characterized by high levels of blood glucose (hyperglycemia), diabetes usually results from a loss of insulin-producing β-cells in the pancreas, leading to a deficiency of insulin (type 1 diabetes), or loss of insulin sensitivity (type 2 diabetes). Both types of diabetes have serious secondary complications, such as microvascular abnormalities, cardiovascular dysfunction, and kidney failure. Various complex factors, such as genetic and environmental factors, are associated with the pathophysiology of diabetes. Over the past two decades, the role of small, single-stranded noncoding microRNAs in various metabolic disorders, especially diabetes mellitus and its complications, has gained widespread attention in the scientific community. Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans, these small RNAs post-transcriptionally suppress mRNA target expression. In this review, we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.
The heart is one of the most important vital organs, and any malfunctioning of the heart and its ... more The heart is one of the most important vital organs, and any malfunctioning of the heart and its blood vessels may contribute to cardiovascular disorders. Diseases of the cardiovascular system represent the most common cause of human morbidity and mortality around the globe. Thus, there is always a need for innovative new therapies and diagnostics for cardiovascular disorders. In the past decades, a plethora of tiny, endogenous, singlestranded RNA sequences called microRNAs (miRNAs) has been studied meticulously in cardiovascular development and pathophysiology, providing a new dimension to the heart’s biology. miRNAs posttranscriptional inhibit the gene expression of specific mRNA targets through Watson– Crick base pairing between the miRNA “seed region” and the 3′ untranslated regions (UTRs) of target mRNAs. Better recognized as “master switches”, miRNAs are emerging as vital regulators of mammalian cardiovascular development and disease and thus are helpful in understanding therapeutic targets and diagnostics for a variety of cardiovascular disorders. In this review, a detailed discussion of the roles of various microRNAs in cardiovascular development and pathophysiology with potential therapeutics is considered.
Journal of pharmacological and toxicological methods, Jan 20, 2016
A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the di... more A murine model of type 2 diabetes mellitus was used to compare the antidiabetic effects of the dipeptidyl peptidase-4 (DPP4) inhibitor vildagliptin and biguanide, metformin. Swiss albino mice (n=20 males; n=25 females) were given high fat diet (HFD) ad libitum for 3weeks followed by low dose (40mgkg(-1) body weight, bw daily) of streptozotocin (STZ) intraperitoneally five times from the 22nd day of treatment onwards, with HFD continued up to 26th day. Controls (n=15 males; n=15 females) were fed normal balanced diet without administration of STZ. Successful induction of diabetes mellitus was confirmed by testing for fasting blood glucose, intraperitoneal glucose tolerance and intraperitoneal insulin sensitivity. Diabetic mice were administered vildagliptin (10mgkg(-1) bw daily) and metformin (50mgkg(-1) bw daily) orally for 4weeks. Control, diabetic, vildagliptin and metformin-treated diabetic mice were evaluated for alterations in lipid profile using blood serum and histopathology ...
Background: Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM... more Background: Studies pertaining to association of GSTM1 and GSTT1 null genotypes with risk of T2DM and its complications were often inconclusive, thus spurring the present study. Methods: Meta-analysis of 25 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in determining the risk for T2DM and 17 studies for evaluating the role of GSTM1/GSTT1 null polymorphisms in development of T2DM related complications were conducted. Results: Our study revealed an association between GSTM1 and GSTT1 null polymorphism with T2DM (GSTM1; OR=1.37;95% CI =1.10-1.70 and GSTT1; OR=1.29;95% CI =1.04-1.61) with an amplified risk of 2.02 fold for combined GSTM1-GSTT1 null genotypes. Furthermore, the GSTT1 null (OR=1.56;95%CI=1.38-1.77) and combined GSTM1-GSTT1 null genotypes (OR=1.91;95%CI=1.25- 2.94) increased the risk for development of T2DM related complications, but not the GSTM1 null genotype. Stratified analyses based on ethnicity revealed GSTM1 and GSTT1 null genotypes increase the r...
Cancers of the upper aero-digestive and gastrointestinal tract are one of the major causes of mor... more Cancers of the upper aero-digestive and gastrointestinal tract are one of the major causes of mortality around the world. DNA repair genes play a vital role in preventing carcinogenesis by maintaining genomic integrity. Polymor-phisms in the nucleotide sequence of DNA repair genes are often reported to be associated with an increased risk for different cancers. The OGG1 gene encodes the enzyme 8-oxoguanine DNA glycosylase which removes oxidatively damaged bases of DNA. Several studies report that the OGG1 Ser326Cys polymorphism increases the risk for cancers of the upper aero-digestive and gastrointestinal tract. However, other studies provide evidence that such an association does not exist. A meta-analysis to assess the role of OGG1 Ser326Cys polymorphism in the cancers of the upper aero-digestive and gastrointestinal tract was therefore undertaken in order to resolve this ambiguity. Seventeen studies were recruited for this meta-analysis after screening 58 articles with a total of 5533 cases and 6834 controls for which the odds ratio with 95 % confidence interval was calculated. Begg's funnel test and Egger's test were performed for calculating publication bias. Our study reveals an association between OGG1 Ser326Cys polymorphism and cancer susceptibility of the upper aero-digestive and gastrointestinal tract (CG + GG vs CC; odds ratio, OR 1.22; 95 % CI 1.05–1.41; GG vs CG + CC; OR 1.36; 95 % CI 1.09–1.70; GG vs CC; OR 1.46; 95 % CI 1.12–1.92). Subgroup analysis based on cancer types and ethnicity also revealed the association of OGG1 Ser326Cys polymorphism to the risk for upper aero-digestive and gastrointestinal tract cancers among both the Asian and the Caucasian populations. No risk was however observed for smoking habits and OGG1 Ser326Cys polymorphism. In conclusion, OGG1 Ser326Cys polymorphism may be associated with the increased risk for aero-digestive tract and gastro-intestinal cancers in both Asian and Caucasian populations.
A number of different epidemiological studies have measured the association between the risk of d... more A number of different epidemiological studies have measured the association between the risk of different cancers and polymorphism at promoter region of 5′ untranslated region (5′-UTR) of the Ataxia-telangiectasia mutated (ATM) gene. However the results were contentious rather than conclusive. The current study was aimed at evaluating the association between the SNP (rs189037 G>A) and the risk of head and neck cancer and lung cancer by conducting ameta-analysis. A total of 9 case–control studieswere considered for this quantitative analysis. Stats Direct Statistical software (version 2.7.2)was used to evaluate the crude odds ratio (OR) with their 95% confidence interval (CI). The dominant model (GG vs. GA+ AA) showed no heterogeneity and the fixed effects pooled OR was found to be significant (OR = 1.14, 95% CI = 1.05–1.25) at p = 0.003. The pooled OR for fixed effects of heterozygote and homozygote mutant allele (GA vs. AA) model was significant (OR = 1.17, 95% CI = 1.04–1.30, p=0.006) and no heterogeneity was observed for this model. The current meta-analysis manifested that ATM rs189037 G>A genetic polymorphismmay contribute increased risk of head and neck and lung cancer. Moreover, the AA mutant allele was found to be related significantly with the prognosis of lung cancer and head and neck cancer
MicroRNAs: a new ray of hope for diabetes mellitus, Jul 4, 2012
Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major chal... more Diabetes mellitus has become one of the most common chronic diseases, thereby posing a major challenge to global health. Characterized by high levels of blood glucose (hyperglycemia), diabetes usually results from a loss of insulin-producing β-cells in the pancreas, leading to a deficiency of insulin (type 1 diabetes), or loss of insulin sensitivity (type 2 diabetes). Both types of diabetes have serious secondary complications, such as microvascular abnormalities, cardiovascular dysfunction, and kidney failure. Various complex factors, such as genetic and environmental factors, are associated with the pathophysiology of diabetes. Over the past two decades, the role of small, single-stranded noncoding microRNAs in various metabolic disorders, especially diabetes mellitus and its complications, has gained widespread attention in the scientific community. Discovered first as an endogenous regulator of development in the nematode Caenorhabditis elegans, these small RNAs post-transcriptionally suppress mRNA target expression. In this review, we discuss the potential roles of different microRNAs in diabetes and diabetes-related complications.
The heart is one of the most important vital organs, and any malfunctioning of the heart and its ... more The heart is one of the most important vital organs, and any malfunctioning of the heart and its blood vessels may contribute to cardiovascular disorders. Diseases of the cardiovascular system represent the most common cause of human morbidity and mortality around the globe. Thus, there is always a need for innovative new therapies and diagnostics for cardiovascular disorders. In the past decades, a plethora of tiny, endogenous, singlestranded RNA sequences called microRNAs (miRNAs) has been studied meticulously in cardiovascular development and pathophysiology, providing a new dimension to the heart’s biology. miRNAs posttranscriptional inhibit the gene expression of specific mRNA targets through Watson– Crick base pairing between the miRNA “seed region” and the 3′ untranslated regions (UTRs) of target mRNAs. Better recognized as “master switches”, miRNAs are emerging as vital regulators of mammalian cardiovascular development and disease and thus are helpful in understanding therapeutic targets and diagnostics for a variety of cardiovascular disorders. In this review, a detailed discussion of the roles of various microRNAs in cardiovascular development and pathophysiology with potential therapeutics is considered.
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Papers by SAYANTAN NATH
and polymorphism at promoter region of 5′ untranslated region (5′-UTR) of the Ataxia-telangiectasia mutated
(ATM) gene. However the results were contentious rather than conclusive. The current study was aimed
at evaluating the association between the SNP (rs189037 G>A) and the risk of head and neck cancer and lung
cancer by conducting ameta-analysis. A total of 9 case–control studieswere considered for this quantitative analysis.
Stats Direct Statistical software (version 2.7.2)was used to evaluate the crude odds ratio (OR) with their 95%
confidence interval (CI). The dominant model (GG vs. GA+ AA) showed no heterogeneity and the fixed effects
pooled OR was found to be significant (OR = 1.14, 95% CI = 1.05–1.25) at p = 0.003. The pooled OR for fixed
effects of heterozygote and homozygote mutant allele (GA vs. AA) model was significant (OR = 1.17, 95% CI =
1.04–1.30, p=0.006) and no heterogeneity was observed for this model. The current meta-analysis manifested
that ATM rs189037 G>A genetic polymorphismmay contribute increased risk of head and neck and lung cancer.
Moreover, the AA mutant allele was found to be related significantly with the prognosis of lung cancer and head
and neck cancer
and polymorphism at promoter region of 5′ untranslated region (5′-UTR) of the Ataxia-telangiectasia mutated
(ATM) gene. However the results were contentious rather than conclusive. The current study was aimed
at evaluating the association between the SNP (rs189037 G>A) and the risk of head and neck cancer and lung
cancer by conducting ameta-analysis. A total of 9 case–control studieswere considered for this quantitative analysis.
Stats Direct Statistical software (version 2.7.2)was used to evaluate the crude odds ratio (OR) with their 95%
confidence interval (CI). The dominant model (GG vs. GA+ AA) showed no heterogeneity and the fixed effects
pooled OR was found to be significant (OR = 1.14, 95% CI = 1.05–1.25) at p = 0.003. The pooled OR for fixed
effects of heterozygote and homozygote mutant allele (GA vs. AA) model was significant (OR = 1.17, 95% CI =
1.04–1.30, p=0.006) and no heterogeneity was observed for this model. The current meta-analysis manifested
that ATM rs189037 G>A genetic polymorphismmay contribute increased risk of head and neck and lung cancer.
Moreover, the AA mutant allele was found to be related significantly with the prognosis of lung cancer and head
and neck cancer