Gut microbiome and function are altered for individuals living in high fluoride concentration areas in Pakistan.

Background: Endemic fluorosis refers to the condition when individuals are exposed to excessive amounts of fluoride ion due to living in a region characterized by elevated levels of fluorine in the drinking water, food, and/or air. In Pakistan, a substantial proportion of the population is thereby affected, posing a public health concern.

Objectives: Assessing how the gut microbiota and its metabolic profiles are impacted by chronic exposure to fluoride in drinking water (that caused Dental Fluorosis) as well as to perceive how this microbiota is connected to adverse health outcomes prevailing with fluoride exposure.

Exposure to heavy metals, antioxidant status, and the interaction of single nucleotide polymorphisms in the genes CAT rs7943316, GSTP1 rs1695, as well as GSTM1 and GSTT1 genes, among workers in occupational settings.

Individuals working in diverse fields are consistently exposed to work-related pollutants that can impact their overall health. The current study investigated the presence of pollutants in seven different occupational groups and their impact on human health. Biochemical and genetic approaches were employed.

Chronic exposure to electronic waste poses risk to liver toxicity with molecular interaction of GSTM1, GSTT1 null variants, and GSTP1.

Chronic exposure to electronic waste (e-waste) is becoming a serious concern for health among individuals exposed to it. E-waste has been reported to contain heavy metals, trace elements, and persistent organic pollutants which can trigger health issues through different biological pathways. The liver is a major metabolic and detoxifying organ in the body.

Influence of the chronic groundwater fluoride consumption on cholinergic enzymes, ACHE and BCHE gene SNPs and pro-inflammatory cytokines: A study with Pakistani population groups.

Fluoride is one of the abundant elements found in the Earth's crust and is a global environmental issue. The present work aimed to find the impact of chronic consumption of fluoride contained groundwater on human subjects. Five hundred and twelve volunteers from different areas of Pakistan were recruited.

Acetylcholinesterase, pro-inflammatory cytokines, and association of ACHE SNP rs 17228602 with male infertility.

Male infertility is a complex and polygenic reproductive disease. 10-15% of the males are affected by idiopathic infertility conditions. Acetylcholine (ACh), a major neurotransmitter has been reported to play a non-neuronal role as well.

Dysregulation of butyrylcholinesterase, BCHE gene SNP rs1803274, and pro-inflammatory cytokines in occupational workers.

Background: People in different occupations are exposed to a variety of xenobiotics which affect the health and physiological processes of the body. Butyrylcholinesterase (BChE), has been reported to play neuronal and non-neuronal roles, though its exact function is yet to be established. This study aimed to find the status and role of BChE in seven different occupational groups; gasoline fillers, auto-mechanics, carpenters, textile shop workers, furniture shop workers, electricians, and office workers.

Association analysis of miRNA-146a and miRNA-499 polymorphisms with rheumatoid arthritis: a case-control and trio-family study.

Single nucleotide polymorphism is known to alter the expression and processing of miRNAs leading to a variety of diseases including rheumatoid arthritis (RA). However, disagreement is present up to date regarding the association of miRNA-146a and miRNA-499 polymorphisms with RA. The goal of this study was to assess the association of polymorphisms at miRNA-146a and miRNA-499 with the pathogenesis of RA in patients originating from Pakistan.

Association analysis of single nucleotide polymorphisms in autophagy related 7 (ATG7) gene in patients with coronary artery disease.

Recent experimental studies sparked the involvement of autophagy-related 7 (ATG7) in the development of atherosclerosis. However, the genetic variants and their association with coronary artery disease (CAD) are still to be unveiled. Therefore, we aimed to design a retrospective case-control study for the analysis of ATG7 gene polymorphisms and their association with CAD among the subjects originating from Pakistan.

Antioxidant enzymes and association of CAT SNP-21 A/T (rs7943316) with male infertility.

Infertility is a multifactorial and polygenic disease. A vast majority of infertility is still unexplained despite modern diagnostic techniques. Oxidative stress is considered a factor for male infertility but etiology in terms of functional gene polymorphism and experimental studies on human subjects is scarcely reported.

Genetic Association of Butyrylcholinesterase with Major Depressive Disorder.

Major depressive disorder (MDD) is characterized as clinical depression, which primarily affects the mood and behaviour of an individual. In the present study butyrylcholinesterase (BChE), a co-regulatory cholinergic neurotransmitter enzyme implicated in several putative neuronal and non-neuronal physiological roles was investigated for its role in MDD. Eighty MDD patients and sixty-one healthy controls were recruited for the study.

Experimental and Established Oximes as Pretreatment before Acute Exposure to Azinphos-Methyl.

Poisoning with organophosphorus compounds (OPCs) represents an ongoing threat to civilians and rescue personal. We have previously shown that oximes, when administered prophylactically before exposure to the OPC paraoxon, are able to protect from its toxic effects. In the present study, we have assessed to what degree experimental (K-27; K-48; K-53; K-74; K-75) or established oximes (pralidoxime, obidoxime), when given as pretreatment at an equitoxic dosage of 25% of LD, are able to reduce mortality induced by the OPC azinphos-methyl.

Mixture of Organophosphates Chronic Exposure and Pancreatic Dysregulations in Two Different Population Samples.

Organophosphates (OP) are a major agrochemical. The application of OP pesticides is expected to increase multifold in the coming decades. The etiology of diabetic diseases is attributed to multiple factors including OP pesticide exposure.

Analysis of PON1 gene polymorphisms (rs662 and rs854560) and inflammatory markers in organophosphate pesticides exposed cohorts from two distinct populations.

Background And Objectives: Organophosphate (OPs) anticholinesterases are one of the main groups of pesticides used in agriculture. Harmful effects of OPs on health have been attributed primarily for irreversible inhibition of acetylcholinesterase (AChE) at nerve synapse. However, studies have shown that inhibition of AChE alone cannot explain all the maladies encountered in prolonged exposure to OPs.

Molecular docking analyses of CYP450 monooxygenases of (Herbst) reveal synergism of quercetin with paraoxon and tetraethyl pyrophosphate: studies.

Pest management in stored grain industry is a global issue due to the development of insecticide resistance in stored grain insect pests. Excessive use of insecticides at higher doses poses a serious threat of food contamination and residual toxicity for grain consumers. Since the development of new pesticide incurs heavy costs, identifying an effective synergist can provide a ready and economical tool for controlling resistant pest populations.

Cannabis Constituents and Acetylcholinesterase Interaction: Molecular Docking, In Vitro Studies and Association with rs and .

The study documented here was aimed to find the molecular interactions of some of the cannabinoid constituents of cannabis with acetylcholinesterase (AChE). Molecular docking and LogP determination were performed to predict the AChE inhibitory effect and lipophilicity. AChE enzyme activity was measured in the blood of cannabis addicted human subjects.

Combined Pre- and Posttreatment of Paraoxon Exposure.

Aims: Organophosphates (OPCs), useful agents as pesticides, also represent a serious health hazard. Standard therapy with atropine and established oxime-type enzyme reactivators is unsatisfactory. Experimental data indicate that superior therapeutic results can be obtained when reversible cholinesterase inhibitors are administered before OPC exposure.

Reactivation potency of two novel oximes (K456 and K733) against paraoxon-inhibited acetyl and butyrylcholinesterase: In silico and in vitro models.

Organophosphates (OPs) irreversibly inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes. The reactivation of these inhibited enzymes is paramount for their normal function. Present study evaluates reactivation potency of two newly developed oximes, K456 and K733, against paraoxon (POX)-inhibited human-RBC-AChE and human-plasma-BChE in comparison to reported reactivator, pralidoxime (2-PAM).

Oximes as pretreatment before acute exposure to paraoxon.

Organophosphates, useful agents as pesticides, also represent a serious danger due to their high acute toxicity. There is indication that oximes, when administered before organophosphate exposure, can protect from these toxic effects. We have tested at equitoxic dosage (25% of LD ) the prophylactic efficacy of five experimental (K-48, K-53, K-74, K-75, K-203) and two established oximes (pralidoxime and obidoxime) to protect from mortality induced by the organophosphate paraoxon.

Capsaicin inhibits the function of α-nicotinic acetylcholine receptors expressed in Xenopus oocytes and rat hippocampal neurons.

Capsaicin is a naturally occurring alkaloid derived from Chili peppers fruits. Using the two-electrode voltage-clamp technique in Xenopus oocyte expression system, actions of capsaicin on the functional properties of α subunit of the human nicotinic acetylcholine (α nACh) receptor were investigated. Ion currents activated by ACh (100 μM) were reversibly inhibited with an IC value of 8.

Association of status of acetylcholinesterase and ACHE gene 3' UTR variants (rs17228602, rs17228616) with drug addiction vulnerability in pakistani population.

Substance addiction is a chronic, relapsing mental disorder Characterized by compulsive drug seeking, and loss of control over drug intake and relapse after prolonged abstinence. Genetics has been shown to contribute towards an individual's vulnerability to addiction. Acetylecholine (ACh), a cholinergic neurotransmitter hydrolyzed by acetylcholinesterase (AChE), is an essential neurotransmitter and neuromodulator in central and peripheral nervous system and has regulatory influence on numerous neuronal functions including addiction.

Biochemical Analysis and Association of Butyrylcholinesterase SNPs rs3495 and rs1803274 with Substance Abuse Disorder.

Addiction is a complex mental and behavioral disorder that changes the neurochemistry and physiology of the brain. Genetics also plays a significant role in the pathophysiology of addiction. Butyrylcholinesterase (BChE), a cholinergic enzyme, has been implicated in the metabolism of various drugs, including cocaine, and an association between single-nucleotide polymorphisms (SNPs) of the butyrylcholinesterase gene (BCHE) and neuronal disorders has been reported.

In silico and in vitro evaluation of two novel oximes (K378 and K727) in comparison to K-27 and pralidoxime against paraoxon-ethyl intoxication.

Organophosphate (OP) poisoning is a major global health issue; while compounds from this group have been used intensively over the last century, an effective antidote is still lacking. Oxime-type acetylcholinesterase (AChE) reactivators are used to reactivate the OP inhibited AChE. Pralidoxime is the only US Food and Drug Administration approved oxime for therapeutic use but its efficacy has been disappointing.

Phenylalanine derivatives with modulating effects on human α1-glycine receptors and anticonvulsant activity in strychnine-induced seizure model in male adult rats.

The critical role of α1-glycine receptor (α1-GLYRs) in pathological conditions such as epilepsy is well known. In the present study, structure-activity relations for a series of phenylalanine derivatives carrying selected hydrogen bond acceptors were investigated on the functional properties of human α1-GLYR expressed in Xenopus oocytes. The results indicate that one particular substitution position appeared to be of special importance for control of ligand activity.

Novel biological therapies for the treatment of diabetic foot ulcers.

The number of people with diabetes mellitus (DM) is estimated to exceed 640 million by the year 2040. Diabetic foot ulcer (DFU) is a debilitating illness that affects more than 2% of DM patients. DFU is caused by DM-induced neural and vascular lesions leading to a reduced sensation and microcirculation.

Thujone inhibits the function of α-nicotinic acetylcholine receptors and impairs nicotine-induced memory enhancement in one-trial passive avoidance paradigm.

Effects of thujone, a major ingredient of absinthe, wormwood oil and some herbal medicines, were tested on the function of α subunit of the human nicotinic acetylcholine (α nACh) receptor expressed in Xenopus oocytes using the two-electrode voltage-clamp technique. Thujone reversibly inhibited ACh (100μM)-induced currents with an IC value of 24.7μM.