Plastic compounds and liver diseases: Whether bisphenol A is the only culprit.

Plastics, while providing modern conveniences, have become an inescapable source of global concern due to their role in environmental pollution. Particularly, the focus on bisphenol A (BPA) reveals its biohazardous nature and association with liver issues, specifically steatosis. However, research indicates that BPA is just one facet of the problem, as other bisphenol analogues, microplastics, nanoplastics and additional plastic derivatives also pose potential risks. Notably, BPA is implicated in every stage of non-alcoholic fatty liver disease (NAFLD) onset and progression, surpassing hepatitis B virus as a primary cause of chronic liver disease worldwide. As plastic contamination tops the environmental contaminants list, urgent action is needed to assess causative factors and mitigate their impact. This review delves into the molecular disruptions linking plastic pollutant exposure to liver diseases, emphasizing the broader connection between plastics and the rising prevalence of NAFLD.

Melamine Exacerbates Neurotoxicity in D-Galactose-Induced Neuronal SH-SY5Y Cells.

Numerous studies have depicted the role of diet and environmental toxins in aging. Melamine (Mel) is a globally known notorious food adulterant, and its toxicity has been shown in several organs including the brain. However, till now, there are no reports regarding Mel neurotoxicity in aging neurons. So, this study examined the in vitro neurotoxicity caused by Mel in the D-galactose (DG)-induced aging model of neuronal SH-SY5Y cells. In the present study, the neuronal SH-SY5Y cells were treated with DG and Mel separately and in combination to assess the neurotoxicity potential using MTT assay and neurite length measurement. Further, the superoxide dismutase (SOD), catalase (CAT), and total antioxidant activities were evaluated followed by the determination of the intracellular reactive oxygen species (ROS), mitochondrial membrane potential (MMP), and caspase3 (Casp3) activity. The cotreatment of Mel and DG in neuronal SH-SY5Y cells showed maximum cell death than the cells treated with DG or Mel individually and untreated control cells. The neurite length shrinkage and ROS production were maximum in the DG and Mel cotreated cells showing exacerbated toxicity of Mel. The activity of SOD, CAT, and total antioxidants was also found to be lowered in the cotreatment group (Mel + DG) than in Mel- or DG-treated and untreated cells. Further, the combined toxicity of Mel and DG also elevated the Casp3 activity more than any other group. This is the first study showing the increased neurotoxic potential of Mel in an aging model of neuronal SH-SY5Y cells which implicates that Mel consumption by the elderly may lead to increased incidences of neurodegeneration like Alzheimer's disease and Parkinson's disease.

Organophosphorus and carbamate pesticides: Molecular toxicology and laboratory testing.

Population and food requirements are increasing daily throughout the world. To fulfil these requirements application of pesticides is also increasing. Organophosphorous (OP) and Organocarbamate (OC) compounds are widely used pesticides. These pesticides are used for suicidal purposes too. Both inhibit Acetylcholinesterase (AChE) and cholinergic symptoms are mainly used for the diagnosis of pesticide poisoning. Although the symptoms of the intoxication of OP and OC are similar, recent research has described different targets for OP and OC pesticides. Researchers believe the distinction of OP/OC poisoning will be beneficial for the management of pesticide exposure. OP compounds produce adducts with several proteins. There is a new generation of OP compounds like glyphosate that do not inhibit AChE. Therefore, it's high time to develop biomarkers that can distinguish OP poisoning from OC poisoning.

Electrophoresis of Amplicons is a Better Method to Understand the Performance of Loop-mediated Isothermal Amplification Assay for Screening the Presence of Escherichia coli in Water.

SUMMARY: LAMP assay is widely used for detecting pathogens. We observed that the conventional and gradient polymerase chain reaction (PCR) could not detect the extracted Escherichia coli DNA; real-time PCR was able to detect up to a certain limit (10-8 bacterial dilution). At the same time, the LAMP assay could detect the bacteria at a much lower concentration (10-14 dilution). The results of the LAMP assay were evaluated using agarose gel electrophoresis and DNA binding dye (PicoGreen), but only gel electrophoresis gave reliable results. Therefore, we propose using electrophoresis-based amplicon detection to overcome the limitations of dye-based detection. We believe that this amplicon detection will go a long way in the screening of potable drinking water.

Molecular docking analysis of melamine with nuclear factor erythroid 2-related factor 2 and succinate dehydrogenase.

Melamine consumption causes oxidative stress by an unknown mechanism. Therefore, it is of interest to analyze the interaction of melamine with two important proteins involved in oxidative stress biology namely, nuclear factor erythroid 2-related factor 2 and succinate dehydrogenase. The molecular docking data shows the melamine binding with these two proteins at critical residues. These interactions can be logically perceived for the causation of melamine induced oxidative stress.

Spectrofluorimetric-based approach to screen urine contamination in drinking water: A step toward the development of screening method for leptospirosis.

Hygiene hypothesis and sanitization are two important pivots of modern civilization. The drinking water should be free from urine and stool contamination. Coliform test is popular for understanding feces contamination. However, understanding urine contamination in drinking water is a difficult task. On the other hand, urine contamination can cause disease like leptospirosis. It occurs mainly in animals and infects humans through contaminated water, food, and soil and causes serious consequences. Rat urine is the most common source of such disease outbreaks. Further, sophisticated laboratories with high-end technologies may not be present at the site of disease outbreaks. In this context, we have proposed a spectrofluorimetric approach to screen urine contamination in water. The screening method can sense up to 156 nl/ml of rat urine.

Fluorimetric method for specific detection of human serum albumin in urine using its pseudoesterase property.

Detection of microalbuminuria is an analytical challenge. There are dye-based methods and immunochemical methods. However, these methods are less specific and sensitive respectively. So, people are trying new approaches for microalbuminuria detection. In this context, we have developed a fluorescent spectroscopic method to detect human serum albumin using its pseudoesterase property. Recently, we had discovered that neostigmine does not inhibit Human serum albumin pseudoesterase activity. Using such a phenomenon, we have devised a specific fluorimetric detection method of HSA using 2NA as a substrate for the pseudoesterase activity. The developed method can sense as low as 0.1 µM of HSA in the urine matrix without dye or antibody. We have proposed a scheme of automation of the proposed method.

Acute aluminum phosphide poisoning: The menace of phosphine exposure.

Aluminum phosphide (AlP) is a popular fumigant used widely for the safe storage of food grain. Although A1P is free from toxic residues, it releases phosphine which acts on mitochondrial components of almost all types of pests. Unfortunately A1P is also a common suicidal agent in developing countries with no known antidote. In addition, accidental exposure to phosphine may also occur. AlP poisoning affects cardiac and vascular tissue directly and can result in multiorgan system failure leading to death in severe cases. There is no specific biomarker for diagnosing AlP poisoning and management depends on a high level of clinical suspicion. Although acetylcholinesterase has been suggested as a surrogate biomarker of AlP exposure, there are opposing views. In this review, we analyzed the relevant published material with emphasis on the need to recognize and explore the use of plasma mitochondrial enzyme activity as a potential biomarker for AlP exposure.

Application of Tucatinib and Trastuzumab: Dual Anti HER2 Therapy Against HER2 Positive Breast Cancer.

Synergism in action of tucatinib and trastumab is reported in breast cancer management. However, its molecular basis is yet to be determined. In this context we attempted to provide an explanation at the molecular level by performing in silico experimentation and coupling its result with already available published observations. Our study will provide basis for planning further experimental study for unravelling the truth.

Pseudosterase activity-based specific detection of human serum albumin on gel.

Human serum albumin (HSA) has pseudoesterase activity. So far on gel specific detection of such property of HSA is never reported. Moreover, protein binding dyes are non-specific for albumin. However, many of such dyes are used for HSA detection. So, dye-based albumin detection on the gel is expected to generate false-positive results for HSA. In this context, we have discovered that Fast Blue BB (FBBB, 0.12%) stains specifically HSA pseudoesterase activity with 2 Naphthyl acetate (2NA) as an ester substrate. Further, neostigmine has not inhibited the pseudoesterase activity associated with HSA. Neostigmine is a known inhibitor of many true esterases like acetylcholinesterase. So, neostigmine addition offers specificity to the method developed for staining of HSA. Additionally, 2NA stains HSA better than bovine serum albumin (BSA). Exploring all these novel findings, we have devised a simple method of HSA detection on the gel, accurately where other esterases are not detected. To the best of our knowledge, our method is the first to detect HSA pseudoesterase activity specifically on gel without getting interfered by any other esterase activity. The method detects HSA better than BSA. We feel that this method will go a long way for the specific detection of HSA on the gel. It is also relevant for understanding the purity of donor human milk matrix and pharmaceutical preparation of HSA. Our method can detect 7 µM of added HSA in human urine. Therefore, our method can be proceeded further for microalbuminuria detection in days to come.

Metformin and Rifampicin combination augments active to latent tuberculosis conversion: A computational study.

Tuberculosis, a global threat, is a highly infectious disease intensified by the emergence of drug-resistant strains. In tuberculosis disease spectrum, a typical situation is a dormant or latent phase where a person exposed to Mycobacterium tuberculosis has the reservoir of the disease that may or may not result in an active state. Existence of the dormant state is retarding the eradication of tuberculosis. Transcription of several genes helps M. tuberculosis to survive in nonreplicative mode. DosR transcription factor is the hallmark for this genesis. Diabetes mellitus is a predisposition factor leading to the development of tuberculosis and latent tuberculosis. High plasma insulin concentrations in the prediabetic state can increase the tuberculosis bacterium. On the other hand, antidiabetic drug metformin is known to reduce active tuberculosis disease when provided in combination with antitubercular therapy. However, the effect of the same on latent tuberculosis is still unknown. In the present work using tools of computational biology, we have tried to find the consequence of adding metformin in combination with rifampicin, a well-known antitubercular drug, on molecular mechanisms of latent tuberculosis. We have investigated whether metformin and rifampicin interact with DosR machinery or not. Our results indicate that if metformin-bound DosR-DNA complex binds with rifampicin, it will result in the conversion of active tuberculosis to latent tuberculosis.

Hydrochlorothiazide and Indapamide bind the NADPH binding site of bacterial Dihydrofolate Reductase: results of an in-silico study and their implications.

Hypertension is a public health concern. Low dose thiazide diuretics are known to effectively control blood pressure compared to that of other classes of antihypertensive drugs. In this context, we have performed an in-silico study and found that the two Sulphonamide Diuretics Hydrochlorothiazide and Indapamide bound the NADPH binding region of bacterial Dihydrofolate Reductase. Therefore, akin to Sulphonamide Antibiotics, Sulphonamide Diuretics may have antibiotic activity and thereby have the potential to modulate the gut microbiome in a way beneficial to vascular health. The in-silico experiment results were analyzed in the context of the relevant literature. We postulate that Sulphonamide Diuretics exert their antihypertensive role by modulating the gut microbiome, specifically by increasing butyrate-producing taxa in the gut. We recommend extending such work as it is plausible that Indapamide and other Sulphonamide Diuretics may be beneficial for both diabetes and hypertension.

The susceptibility of disulfide bonds towards radiation damage may be explained by S⋯O interactions.

Radiation-induced damage to protein crystals during X-ray diffraction data collection is a major impediment to obtaining accurate structural information on macromolecules. Some of the specific impairments that are inflicted upon highly brilliant X-ray irradiation are metal-ion reduction, disulfide-bond cleavage and a loss of the integrity of the carboxyl groups of acidic residues. With respect to disulfide-bond reduction, previous results have indicated that not all disulfide bridges are equally susceptible to damage. A careful analysis of the chemical environment of disulfide bonds in the structures of elastase, lysozyme, acetylcholinesterase and other proteins suggests that S-S bonds which engage in a close contact with a carbonyl O atom along the extension of the S-S bond vector are more susceptible to reduction than the others. Such an arrangement predisposes electron transfer to occur from the O atom to the disulfide bond, leading to its reduction. The interaction between a nucleophile and an electrophile, akin to hydrogen bonding, stabilizes protein structures, but it also provides a pathway of electron transfer to the S-S bond, leading to its reduction during exposure of the protein crystal to an intense X-ray beam. An otherwise stabilizing interaction can thus be the cause of destabilization under the condition of radiation exposure.

Rifampicin and isoniazid behave as non-creatinine chromogens and interfere with Jaffe's reaction: A phenomenon with the potential to give a false-positive result in creatinine estimation.

Tuberculosis is a health concern worldwide. The anti-tubercular drugs (particularly rifampicin) used for its management offers side effects like acute kidney injury. Creatinine, which is recognised as an important biomarker for the renal function, is commonly estimated with Jaffe's reaction (alkaline picrate reaction). However, interference of Jaffe's reaction with non-creatinine chromogens has been reported. In this context, we have checked the possibility of interference by Rifampicin and Isoniazid at therapeutic concentration with the Jaffe's reaction. Through in-silico study, we have studied the reaction prediction of picric acid with other chemicals/reactant (i.e. Rifampicin, Isoniazid and non-creatinine chromogens) in terms of confidence value. It is observed that the confidence value of reaction prediction between picric acid and INH and Rifampicin is much more than the same of pyruvic acid (non-creatinine chromogen). Further, we have checked the absorbance value of Jaffe's reaction mixture in aqueous media in the presence of both the drugs at 520nm. It is observed that the absorbance of alkaline picric acid increases with an increase in drug concentration. However, the increasing trend of absorbance is much more in the case of rifampicin compared to INH. It appears from our result rifampicin, and isoniazid has the potential to behave as non-creatinine chromogen and can give false positive creatinine results in Jaffe's reaction. Thus, it can cause misdiagnosis in patients consuming these drugs. We recommend study in the biological matrix for further validation of the result.