Papers by Md. Abu Baker Siddique
Infectious Diseases and Therapy, 2021
Introduction: The mounting incidence of multidrug-resistant bacterial strains and the dearth of n... more Introduction: The mounting incidence of multidrug-resistant bacterial strains and the dearth of novel antibiotics demand alternate therapies to manage the infections caused by resistant superbugs. Bacteriophages and pha-ge=derived proteins are considered as potential alternates to treat such infections, and have several applications in health care systems. The aim of this review is to explore the hidden potential of bacteriophage proteins which may be a practical alternative approach to manage the threat of antibiotic resistance. Results: Clinical trials are in progress for the use of phage therapy as a tool for routine medical use; however, the existing regulations may hamper their development of routine antimicrobial agents. The advancement of molecular techniques and the advent of sequencing have opened new potentials for the design of engineered bacteriophages as well as recombinant bacteriophage proteins. The phage enzymes and proteins encoded by the lysis cassette genes, especially endolysins, holins, and spanins, have shown plausible potentials as therapeutic candidates. Conclusion: This review offers an integrated viewpoint that aims to decipher the insights and abilities of bacteriophages and their derived proteins as potential alternatives to antibiotics.
Journal of Occupational and Environmental Medicine, 2005
Learning Objectives • Describe, in this Bangladeshi population that has been chronically exposed ... more Learning Objectives • Describe, in this Bangladeshi population that has been chronically exposed to arsenic in drinking water, any associations between various measures of exposure and vibrotactile thresholds measured in the great toe and index finger (the primary outcome). • Recall the degree of correlation, if any, between exposure to arsenic and several tasks of neurological function that served as secondary outcomes. • Conclude whether the presence and concentration of manganese in drinking water influenced the association between arsenic exposure and signs of subclinical peripheral neuropathy.
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, Feb 20, 2016
Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinog... more Posttranslational histone modifications (PTHMs) are altered by arsenic, an environmental carcinogen. PTHMs are also influenced by nutritional methyl donors involved in one-carbon metabolism (OCM), which may protect against epigenetic dysregulation. We measured global levels of three PTHMs, which are dysregulated in cancers (H3K36me2, H3K36me3, H3K79me2), in peripheral blood mononuclear cells (PBMCs) from 324 participants enrolled in the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults. Sex-specific associations between several blood OCM indices (folate, vitamin B12, choline, betaine, homocysteine) and PTHMs were examined at baseline using regression models, adjusted for multiple tests by controlling for the false discovery rate (PFDR). We also evaluated the effects of FA supplementation (400 µg/day for 12 weeks), compared with placebo, on PTHMs. Associations between choline and H3K36me2 and between vitamin B12 and H3K79me2, differed significant...
The Journal of nutrition, May 6, 2016
Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A b... more Folic acid (FA) supplementation facilitates urinary excretion of arsenic, a human carcinogen. A better understanding of interactions between one-carbon metabolism intermediates may improve the ability to design nutrition interventions that further facilitate arsenic excretion. The objective was to determine if FA and/or creatine supplementation increase choline and betaine and decrease dimethylglycine (DMG). We conducted a secondary analysis of the Folic Acid and Creatine Trial, a randomized trial in arsenic-exposed Bangladeshi adults (n= 605, aged 24-55 y, 50.3% male) who received arsenic-removal water filters. We examined treatment effects of FA and/or creatine supplementation on plasma choline, betaine, and DMG concentrations, measured by LC-tandem mass spectrometry at baseline and at week 12. Group comparisons were between1) 400 and 800 μg FA/d (FA400 and FA800, respectively) compared with placebo,2) creatine (3 g/d) compared with placebo, and3) creatine plus FA400 compared with...
Cancer Epidemiology, Biomarkers & Prevention, 2015
Background: Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and ... more Background: Depletion of global 5-hydroxymethylcytosine (5-hmC) is observed in human cancers and is strongly implicated in skin cancer development. Although arsenic (As)—a class I human carcinogen linked to skin lesion and cancer risk—is known to be associated with changes in global %5-methylcytosine (%5-mC), its influence on 5-hmC has not been widely studied. Methods: We evaluated associations of As in drinking water, urine, and blood with global %5-mC and %5-hmC in two studies of Bangladeshi adults: (i) leukocyte DNA in the Nutritional Influences on Arsenic Toxicity study (n = 196; 49% male, 19–66 years); and (ii) peripheral blood mononuclear cell DNA in the Folate and Oxidative Stress study (n = 375; 49% male, 30–63 years). Results: Overall, As was not associated with global %5-mC or %5-hmC. Sex-specific analyses showed that associations of As exposure with global %5-hmC were positive in males and negative in females (P for interaction < 0.01). Analyses examining interactions ...
The Journal of nutrition, Jan 26, 2015
Creatine synthesis from guanidinoacetate consumes ∼50% of s-adenosylmethionine (SAM)-derived meth... more Creatine synthesis from guanidinoacetate consumes ∼50% of s-adenosylmethionine (SAM)-derived methyl groups, accounting for an equivalent proportion of s-adenosylhomocysteine (SAH) and total homocysteine (tHcys) synthesis. Dietary creatine inhibits the synthesis of guanidinoacetate, thereby lowering plasma tHcys in rats. We tested the hypotheses that creatine supplementation lowers plasma guanidinoacetate, increases blood SAM, lowers blood SAH, and lowers plasma tHcys. Bangladeshi adults were randomly assigned to receive 1 of 4 treatments for 12 wk: placebo (n = 101), 3 g/d creatine (Cr; n = 101), 400 μg/d folic acid (FA; n = 153), or 3 g/d creatine plus 400 μg/d folic acid (Cr+FA; n = 103). The outcomes of plasma guanidinoacetate and tHcys, as well as whole blood SAM and SAH, were analyzed at baseline and week 12 by HPLC. Treatment effects of creatine supplementation were examined with the use of the group comparisons of Cr vs. placebo and Cr+FA vs. FA. Plasma guanidinoacetate decli...
Free Radical Biology and Medicine, 2015
Exposure to arsenic (As) in drinking water is a widespread public health problem leading to incre... more Exposure to arsenic (As) in drinking water is a widespread public health problem leading to increased risk for multiple outcomes such as cancer, cardiovascular disease, and possibly renal disease; potential mechanisms include inflammation and oxidative stress. We tested the hypothesis that As exposure is associated with increased inflammation and decreased estimated glomerular filtration rate (eGFR) and examined whether the effects of As were modified by plasma glutathione (GSH), glutathione disulfide (GSSG), or the reduction potential of the GSSG/2GSH pair (E h GSH). In a cross-sectional study of N = 374 Bangladeshi adults having a wide range of As exposure, we measured markers of inflammation (plasma C-reactive protein (CRP), α-1 acid glycoprotein (AGP)), renal function (eGFR), GSH, and GSSG. In covariate-adjusted models, a 10% increase in water As, urinary As adjusted for specific gravity (uAs), or blood As (bAs) was associated with a 0.74% (p = 0.01), 0.90% (p = 0.16), and 1.39% (p = 0.07) increase in CRP, respectively; there was no association with AGP. A 10% increase in uAs or bAs was associated with an average reduction in eGFR of 0.16 (p = 0.12) and 0.21 ml/min/1.73 m 2 (p = 0.08), respectively. In stratified analyses, the effect of As exposure on CRP was observed only in participants having E h GSH > median (uAs p Wald = 0.03; bAs p Wald = 0.05). This was primarily driven by stronger effects of As exposure on CRP in participants with lower plasma GSH. The effects of As exposure on eGFR were not modified significantly by E h GSH, GSH, or GSSG. These data suggest that participants having lower plasma GSH and a more oxidized plasma E h GSH are at increased risk for As-induced inflammation. Future studies should evaluate whether antioxidant treatment lowers plasma E h GSH and reduces risk for As-induced diseases.
The Journal of Nutrition, 2014
Chronic exposure to inorganic arsenic (InAs) through drinking water is a major problem worldwide.... more Chronic exposure to inorganic arsenic (InAs) through drinking water is a major problem worldwide. InAs undergoes hepatic methylation to form mono-and dimethyl arsenical species (MMA and DMA, respectively), facilitating arsenic elimination. Both reactions are catalyzed by arsenic (13 oxidation state) methyltransferase (AS3MT) using S-adenosylmethionine (SAM) as the methyl donor, yielding the methylated product and S-adenosylhomocysteine (SAH), a potent product-inhibitor of AS3MT. SAM biosynthesis depends on folate-and cobalamin-dependent one-carbon metabolism. With the use of samples from 353 participants in the Folate and Oxidative Stress Study, our objective was to test the hypotheses that blood SAM and SAH concentrations are associated with arsenic methylation and that these associations differ by folate and cobalamin nutritional status. Blood SAM and SAH were measured by HPLC. Arsenic metabolites in blood and urine were measured by HPLC coupled to dynamic reaction cell inductively coupled plasma MS. In linear regression analyses, SAH was not associated with any of the arsenic metabolites. However, log(SAM) was negatively associated with log(% urinary InAs) (b: 20.11; 95% CI: 20.19, 20.02; P = 0.01), and folate and cobalamin nutritional status significantly modified associations between SAM and percentage of blood MMA (%bMMA) and percentage of blood DMA (%bDMA) (P = 0.02 and P = 0.01, respectively). In folate-and cobalamin-deficient individuals, log(SAM) was positively associated with %bMMA (b: 6.96; 95% CI: 1.86, 12.05; P < 0.01) and negatively associated with %bDMA (b: 26.19; 95% CI: 212.71, 0.32; P = 0.06). These findings suggest that when exposure to InAs is high, and methyl groups are limiting, SAM is used primarily for MMA synthesis rather than for DMA synthesis, contributing additional evidence that nutritional status may explain some of the interindividual differences in arsenic metabolism and, consequently, susceptibility to arsenic toxicity.
Free Radical Biology and Medicine, 2014
Inorganic arsenic (InAs) is metabolized through a series of methylation reactions catalyzed by ar... more Inorganic arsenic (InAs) is metabolized through a series of methylation reactions catalyzed by arsenic(III)-methyltransferase (AS3MT), resulting in the generation of monomethylarsonic (MMAs) and dimethylarsinic acids (DMAs). AS3MT activity requires the presence of the methyl donor S-adenosylmethionine (SAM), a product of folate-dependent one-carbon metabolism, and a reductant. Although glutathione (GSH), the primary endogenous antioxidant, is not required for As methylation, GSH stimulates As methylation rates in vitro. However, the relationship between GSH redox and As methylation capacity in humans is unknown. We wished to test the hypothesis that a more oxidized plasma GSH redox status is associated with decreased As methylation capacity, and examine whether these associations are modified by folate nutritional status. Concentrations of plasma GSH and GSSG, plasma folate, total blood As (bAs), total urinary As (uAs), and uAs metabolites were assessed in a cross-sectional study of n = 376 Bangladeshi adults who were chronically exposed to As in drinking water. We observed that a decreased plasma GSH/GSSG ratio (reflecting a more oxidized redox state) was significantly associated with increased urinary %MMA, decreased urinary %DMA, and increased total bAs in folate-deficient individuals (plasma folate ≤ 9.0 nmol/L). Concentrations of plasma GSH and GSSG were independently associated with increased and decreased As methylation capacity, respectively. No
Environmental Health Perspectives, 2011
Environmental Health Perspectives, 2013
Background: Several studies employing cell culture and animal models have suggested that arsenic ... more Background: Several studies employing cell culture and animal models have suggested that arsenic (As) exposure induces global DNA hypomethylation. However, As has been associated with global DNA hypermethylation in human study populations. We hypothesized that this discrepancy may reflect a non linear relationship between As dose and DNA methylation. oBjective: The objective of this study was to examine the dose-response relationship between As and global methylation of peripheral blood mono nuclear cell (PBMC) DNA in apparently healthy Bangladeshi adults chronically exposed to a wide range of As concentrations in drinking water. Methods: Global PBMC DNA methylation, plasma folate, blood S-adenosylmethionine (SAM), and concentrations of As in drinking water, blood, and urine were measured in 320 adults. DNA methylation was measured using the [ 3 H]-methyl incorporation assay, which provides disintegrationper-minute (DPM) values that are negatively associated with global DNA methylation. results: Water, blood, and urinary As were positively correlated with global PBMC DNA methylation (p < 0.05). In multivariable-adjusted models, 1-μg/L increases in water and urinary As were associated with 27.6-unit (95% CI: 6.3, 49.0) and 22.1-unit (95% CI: 0.5, 43.8) decreases in DPM per microgram DNA, respectively. Categorical models indicated that estimated mean levels of PBMC DNA methylation were highest in participants with the highest As exposures. conclusions: These results suggest that As is positively associated with global methylation of PBMC DNA over a wide range of drinking water As concentrations. Further research is necessary to elucidate under lying mechanisms and physiologic implications.
Journal of Occupational & Environmental Medicine, 2014
Objective-To evaluate the dose-response relationship between arsenic exposure and markers of oxid... more Objective-To evaluate the dose-response relationship between arsenic exposure and markers of oxidative damage in Bangladeshi adults. Methods-We recruited 378 participants drinking from wells assigned to five water arsenic exposure categories; the distribution of subjects was as follows: 1) <10 μg/L (n=76); 2) 10-100 μg/L (n=104); 3) 101-200 μg/L (n=86); 4) 201-300 μg/L (n=67); and 5) > 300 μg/L (n=45). Arsenic concentrations were measured in well water, as well as in urine and blood. Urinary 8oxo-2'-deoxyguanosine (8-oxo-dG) and plasma protein carbonyls were measured to assess oxidative damage. Results-None of our measures of arsenic exposure were significantly associated with protein carbonyl or 8-oxo-dG levels. Conclusions-We found no evidence to support a significant relationship between chronic exposure to arsenic-contaminated drinking water and biomarkers of oxidative damage among Bangladeshi adults.
Neuroepidemiology, 2011
Background: Essential tremor (ET) is one of the most common neurological diseases. Few prevalence... more Background: Essential tremor (ET) is one of the most common neurological diseases. Few prevalence studies have been conducted in South Asia, and none in Bangladesh, one of the most populated countries in the world. We estimated the prevalence of ET in a population-based study in Araihazar, Bangladesh. Methods: As part of an in-person evaluation in a health outcomes study, each
Neuroepidemiology, 2011
Background: Essential tremor (ET) is one of the most common neurological diseases. Few prevalence... more Background: Essential tremor (ET) is one of the most common neurological diseases. Few prevalence studies have been conducted in South Asia, and none in Bangladesh, one of the most populated countries in the world. We estimated the prevalence of ET in a population-based study in Araihazar, Bangladesh. Methods: As part of an in-person evaluation in a health outcomes study, each
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Papers by Md. Abu Baker Siddique