Determination of Toxic Elements in Cannabinoid and Opioid Drugs and Their Impact on Addicts' Health: A Comparative Study.

Drug addiction is associated with significant health risks, including cardiovascular complications, cancer, and mental disorders. Illicit drugs, such as cannabinoids and opioids, including prescription medications, are widely consumed and have profound health consequences. Understanding the health effects of the toxic elements in these substances is critical for overdose prevention and effective recovery strategies. This study aimed to determine toxic elements, including arsenic (As), cadmium (Cd), mercury (Hg), and nickel (Ni), in cannabinoid and opioid drugs and in biological samples (whole blood, scalp hair, and serum) from 311 male drug abuse patients aged 15-60 years with a history of drug abuse. The participants were categorized into three age groups. The comparative analysis involved 113 reference subjects of the same age groups. The sample preparation employed microwave-assisted acid digestion, and the toxic elements were quantified using atomic absorption spectrophotometry. Accuracy was ensured using certified reference materials for hair, whole blood, and serum samples. Drug-addicted subjects had significantly higher concentrations of toxic elements (arsenic, cadmium, mercury, and nickel) in biological samples than referent subjects (p > 0.001). Elevated levels of these toxic elements may increase susceptibility to infections, possibly due to malnutrition, drug-related effects, and additional contaminants. These findings necessitate further studies to explore the long-term health outcomes, potential treatment options, and broader socioeconomic impacts of substance abuse. This study serves as a baseline for future research in this critical public health field.

A novel NPHP4 homozygous missense variant identified in infertile brothers with multiple morphological abnormalities of the sperm flagella.

PURPOSE: Asthenozoospermia is an important cause of male infertility, and the most serious type is characterized by multiple morphological abnormalities of the sperm flagella (MMAF). However, the precise etiology of MMAF remains unknown. In the current study, we recruited a consanguineous Pakistani family with two infertile brothers suffering from primary infertility due to MMAF without obvious signs of PCD. METHODS: We performed whole-exome sequencing on DNAs of the patients, their parents, and a fertile brother and identified the homozygous missense variant (c.1490C > G (p.P497R) in NPHP4 as the candidate mutation for male infertility in this family. RESULTS: Sanger sequencing confirmed that this mutation recessively co-segregated with the MMAF in this family. In silico analysis revealed that the mutation site is conserved across different species, and the identified mutation also causes abnormalities in the structure and hydrophobic interactions of the NPHP4 protein. Different bioinformatics tools predict that NPHP4p.P497R mutation is pathogenic. Furthermore, Papanicolaou staining and scanning electron microscopy of sperm revealed that affected individuals displayed typical MMAF phenotype with a high percentage of coiled, bent, short, absent, and/or irregular flagella. Transmission electron microscopy images of the patient's spermatozoa revealed significant anomalies in the sperm flagella with the absence of a central pair of microtubules (9 + 0) in every section scored. CONCLUSIONS: Taken together, these results show that the homozygous missense mutation in NPHP4 is associated with MMAF.

In silico and in vitro study of bioactive compounds of Nigella sativa for targeting neuropilins in breast cancer.

Introduction: Breast cancer poses a significant global challenge, prompting researchers to explore novel approaches for potential treatments. Material and Methods: For in vitro study we used thin layer chromatography (TAC) for phytochemical screening, total antioxidant capacity (TLC) assay for antioxidant capacity, and hemolytic activity test for toxicity of Neuropilins (NRPs). We performed bioinformatic analyses to predict protein structures, molecular docking, pharmacophore modeling, and virtual screening to reveal interactions with oncogenes. We conducted 200 ns Molecular Dynamics (MD) simulations and MMGBSA calculations to assess the complex dynamics and stability. Results: We identified phytochemical constituents in Nigella sativa leaves, including tannins, saponins, steroids, and cardiac glycosides, while phlobatannins and terpenoids were absent. The leaves contained 9.4% ± 0.04% alkaloids and 1.9% ± 0.05% saponins. Methanol extract exhibited the highest yield and antioxidant capacity, with Total Flavonoid Content at 127.51 ± 0.76 mg/100 g and Total Phenolic Content at 134.39 ± 0.589 mg GAE/100 g. Hemolysis testing showed varying degrees of hemolysis for different extracts. In-silico analysis indicated stable Neuropilin complexes with key signaling pathways relevant for anti-cancer therapy. Molecular docking scores at different possesses (0, C-50, C -80, C-120,C -150, C -200 ns) revealed strong hydrogen bonding in the complexes and showed -12.9, -11.6, and -11.2 binding Affinities (kcal/mol) to support their stability. Our MD simulations analysis at 200ns confirmed the stability of Neuropilin complexes with the signaling pathways protein PI3K. The calculated binding free energies using MMGBSA provided valuable quantitative information on ligand potency on different time steps. These findings highlight the potential health benefits of N. sativa leaves and their possible role in anti-cancer treatments targeting angiogenesis. Conclusion: Nigella sativa leaves have shown significant medical potential due to their bioactive compounds, which exhibit strong properties in supporting organogenic processes related to cancer. Furthermore, studies have highlighted the promising role of neuropilins in anticancer treatment, demonstrating stable interactions and potential as targeted therapy specifically for breast cancer.

Environmental impact of endocrine-disrupting chemicals and heavy metals in biological samples of petrochemical industry workers with perspective management.

Exposure to endocrine disrupting chemicals (EDCs) or heavy metals are synthetic compounds that can lead to negative effect on health, including immune and endocrine system disruption, respiratory problems, metabolic issues, diabetes, obesity, cardiovascular problems, growth impairment, neurological and learning disabilities, and cancer. Petrochemical industry drilling wastes, which contain varying levels of EDCs, are known to pose a significant risk to human health. This study aimed to investigate the levels of toxic elements in biological samples of individuals working in the petrochemical drilling sites. Biological samples, including scalp hair and whole blood, were collected from petrochemical drilling workers, individuals residing in the same residential area, and control age-matched persons from nonindustrial areas. The samples were oxidized by an acid mixture before analysis using atomic absorption spectrophotometry. The accuracy and validity of the methodology were verified through certified reference materials from scalp hair and whole blood. The results showed that the concentrations of toxic elements, such as cadmium and lead, were higher in biological samples of petrochemical drilling employees, while lower essential element levels (iron and zinc) were detected in their samples. This study highlights the significance of adopting better practices to reduce exposure to harmful substances and protect the health of petrochemical drilling workers and the environment. It also suggests that perspective management including policymakers and industry leaders should take measures to minimize exposure to EDCs and heavy metals to promote worker safety and public health. These measures could include the implementation of strict regulations and better occupational health practices to reduce toxic exposure and promote a safer work environment.

The importance of monitoring endocrine-disrupting chemicals and essential elements in biological samples of fertilizer industry workers.

Exposure to endocrine-disrupting chemicals (EDCs) can lead to adverse health effects, including immune and endocrine system disruption, respiratory problems, metabolic issues, diabetes, obesity, cardiovascular problems, growth impairment, neurological and learning disabilities, and cancer. Fertilizers, which contain varying levels of heavy metals, are known to pose a significant risk to human health, especially for those residing or working near fertilizer industries. This study aimed to investigate the levels of toxic elements in biological samples of individuals working in a fertilizer industry's quality control and production units and those residing within 100-500 m of the industry. Biological samples, including scalp hair and whole blood, were collected from fertilizer workers, individuals living in the same residential area, and control age-matched persons from nonindustrial areas. The samples were oxidized by an acid mixture before analysis using atomic absorption spectrophotometry. The accuracy and validity of the methodology were verified through certified reference materials from scalp hair and whole blood. The results showed that the concentrations of toxic elements, such as cadmium and lead, were higher in biological samples of quality control and production employees. In contrast, lower essential element levels (iron and zinc) were detected in their samples. These levels were higher than those found in samples collected from residents living within 10-500 m of the fertilizer manufacturing facilities and unexposed areas. This study highlights the significance of adopting better practices to reduce exposure to harmful substances and protect the health of fertilizer industry workers and the environment. It also suggests that policymakers and industry leaders should take measures to minimize exposure to EDCs and heavy metals to promote worker safety and public health. These measures could include implementing strict regulations and better occupational health practices to reduce toxic exposure and promote a safer work environment.

Adaptive mechanisms in quinoa for coping in stressful environments: an update.

Quinoa (Chenopodium quinoa) is a grain-like, genetically diverse, highly complex, nutritious, and stress-tolerant food that has been used in Andean Indigenous cultures for thousands of years. Over the past several decades, numerous nutraceutical and food companies are using quinoa because of its perceived health benefits. Seeds of quinoa have a superb balance of proteins, lipids, carbohydrates, saponins, vitamins, phenolics, minerals, phytoecdysteroids, glycine betaine, and betalains. Quinoa due to its high nutritional protein contents, minerals, secondary metabolites and lack of gluten, is used as the main food source worldwide. In upcoming years, the frequency of extreme events and climatic variations is projected to increase which will have an impact on reliable and safe production of food. Quinoa due to its high nutritional quality and adaptability has been suggested as a good candidate to offer increased food security in a world with increased climatic variations. Quinoa possesses an exceptional ability to grow and adapt in varied and contrasting environments, including drought, saline soil, cold, heat UV-B radiation, and heavy metals. Adaptations in salinity and drought are the most commonly studied stresses in quinoa and their genetic diversity associated with two stresses has been extensively elucidated. Because of the traditional wide-ranging cultivation area of quinoa, different quinoa cultivars are available that are specifically adapted for specific stress and with broad genetic variability. This review will give a brief overview of the various physiological, morphological and metabolic adaptations in response to several abiotic stresses.

A Role of Thyroid Hormones in Acute Myocardial Infarction: An Update.

The acute coronary syndrome is one of the commonest life-threatening illnesses. It encompasses the clinical spectrum of acute myocardial ischemia and includes unstable angina and acute myocardial infarction both with and without ST segment elevation. The acute coronary syndrome can be attributed to a significant hemodynamic insult that leads to atherosclerosis of the epicardial coronary arteries. The main causative risk factors, such as obesity, smoking, and alcohol intake, increase the burden of acute coronary syndrome. Owing to an increase in the utilization of antioxidants, the antioxidant capacity decreases concerning the scavenging of lipid peroxides. Moreover, the thyroid hormones are important regulators of the expression of cardiac genes, and many of the cardiac manifestations of thyroid dysfunction are associated with alterations in triiodothyronine- mediated gene expression. Cardiovascular signs and symptoms of thyroid disease are among the most acute clinically relevant findings that occur in combination with both hypothyroidism and hyperthyroidism. By understanding the cellular mechanism of the action of thyroid hormones on the heart and cardiovascular system, it is possible to explain rhythm disturbances and alterations in cardiac output, blood pressure, cardiac contractility, and vascular resistance that result from thyroid dysfunction. Oxidative stress is thereby induced, together with a decrease in antioxidant capacity for overcoming oxidative stress, which leads to endothelial dysfunction, subsequent atherosclerosis, and, ultimately, acute myocardial infarction. The implications for the identification of the effects of thyroid disease on acute myocardial infarction include the observation that restoration of normal thyroid function repeatedly reverses abnormalities in cardiovascular hemodynamics.

Selenium and mercury concentrations in biological samples from patients with COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a systemic disease affecting multiple organs. Furthermore, viral infection depletes several trace elements and promotes complex biochemical reactions in the body. Smoking has been linked to the incidence of COVID-19 and associated mortality, and it may impact clinical effects, viral and bacterial conversion, and treatment outcomes. OBJECTIVES: To study the relationship between severe acute respiratory syndrome coronavirus type 2 and the elemental concentrations of selenium (Se) and mercury (Hg) in biological samples from smokers and nonsmokers infected with the virus and in healthy individuals. METHOD: We evaluated changes in the concentrations of essential (Se) and toxic (Hg) elements in biological samples (blood, nasal fluid, saliva, sputum, serum, and scalp hair) collected from male smokers and nonsmokers (aged 29-59 years) infected with COVID-19 and from healthy men in the same age group. The patients lived in different cities in Sindh Province, Pakistan. The Se and Hg concentrations were determined using atomic absorption spectrophotometry. RESULTS: Se concentrations in all types of biological samples from smokers and nonsmokers with COVID-19 were lower than those of healthy smokers and nonsmokers. Hg concentrations were elevated in both smokers and nonsmokers with COVID-19. CONCLUSIONS: In the current study, persons infected with COVID-19 had higher concentrations of toxic Hg, which could cause physiological disorders, and low concentrations of essential Se, which can also cause weakness. COVID-19 infection showed positive correlations with levels of mercury and selenium. Thus, additional clinical and experimental investigations are essential.

RP-HPLC Method Development, Validation, and Drug Repurposing of Sofosbuvir Pharmaceutical Dosage Form: A Multidimensional Study.

A smooth, exceptionally sensitive, correct, and extra reproducible RP-HPLC technique was developed and demonstrated to estimate Sofosbuvir (SOF) in pharmaceutical dosage formulations. This process was carried out by Agilent High-Pressure Liquid Chromatograph 1260 with GI311C Quat. Pump, Phenomenex Luna C-18 (150 mm × 4.6 mm × 5 µm) (USA), and Photodiode Array Detector (PDA) G1315D. The cell section, including acetonitrile and methanol with 80:20 v/v and solution (B) 0.1% phosphoric acid (40:60), was used for the study. However, 10 µL of the sample was injected with a drift flow of 1 mL/min. The separation occurred at a column temperature of 30 °C, and the eluents used PDA set at 260 nm. The retention time of SOF was 5 min. The calibration curve was modified linearly within the range of 0.05-0.15 mg/mL with a correlation coefficient of 0.99 and genuine linear dating among top vicinity and consciousness in the calibration curve. The detection and quantification restrictions were 0.001 and 0.003 mg/mL, respectively. SOF recovery from pharmaceutical components ranged from 98% to 99%. The percentage assay of SOF was 99%. Analytical validation parameters, such as specificity, linearity, precision, accuracy, and selectivity, were studied, and the percentage relative standard deviation (%RSD) was less than 2%. All other key parameters were observed within the desired thresholds. Hence, the proposed RP-HPLC technique was proven effective for developing SOF in bulk and pharmaceutical pill dosage forms. SOF was found to interact with SARS-COV-2 nsp12, and molecular docking results revealed its high affinity and firm binding within the active site groove of nsp12. The key interacting residues include; LYS-72, GLN-75, MET-80 ALA-99, ASN-99, TRP-100, TYR-101 with ASN-99 and TRP-100 forming hydrogen bonds. Molecular Dynamics simulation of SOF and nsp12 complex elucidated that the system was stable throughout 20ns. Therefore, this drug repurposing strategy for SOF can be used for treating COVID-19 infections by performing animal experiments and accurate clinical trials in the future.

Determining the level of essential elements in patients with Ewing Sarcoma: A correlation.

BACKGROUND: Metal ion aberrant metabolism is essential for health and disease, and its research has sparked a lot of interest. This study aims to compare the critical mineral resources-magnesium (Mg), sodium (Na), calcium (Ca) and potassium (K)-in biological materials (scalp hair, blood, and serum) of 87 Ewing Sarcoma (ES) hypertensive men and women, age range 31-60 years, in an urban area, with 62 nonhypertensive subjects from the same age range and living area. METHODS: An atomic-absorption spectrophotometer was used after microwave-induced acid digestion to determine elemental concentrations. The results' authenticity and precision were verified using a traditional wet acid digestion procedure and accredited reference materials. The average convalesces from all elements have been within the 99.2%-99.7% of certified values. RESULTS: In the biological samples from patients with ES hypertension, the amount of Na was found to be higher than in controls. Patients with ES hypertension had lower Mg, K, and Ca levels in their biological samples (scalp hair and blood) than healthy controls of both genders. CONCLUSIONS: Ca, Mg, and K deficiency can work with other ES hypertension risk factors. These findings will help physicians and other healthcare professionals determine the depletion of essential micronutrients in the biological samples (blood and scalp hair) of patients with hypertension. After microwave-induced acid digestion, the elemental concentration was determined using an atomic absorption spectrophotometer. The results' authenticity and precision were confirmed using a traditional wet-acid digestion procedure and accredited oriented materials. The average recoveries from all elements have been within the 99.2%-99.7% of certified values.

Identification and Functional Investigation of Novel Heterozygous HELQ Mutations in Patients with Sertoli Cell-only Syndrome.

Background: Male infertility is a major health concern in couples of childbearing ages. Nonobstructive azoospermia (NOA) is an extreme form of male infertility that affects ∼1% of adult men, and the etiology remains unknown in most cases. Sertoli cell-only syndrome (SCOS) is the most severe type of NOA. Aims: To explore novel human candidate variants that cause SCOS. Methods: (1) Whole exome sequencing (WES) of 20 men with SCOS, (2) Sanger sequencing of the HELQ gene in an additional 163 men with SCOS, (3) in vitro functional assays, and (4) in vivo studies. Results: WES of 20 patients with SCOS led to the identification of two heterozygous missense mutations (M1 and M2) in two unrelated Chinese patients with infertility. Using subsequent Sanger sequencing covering all the coding regions of the HELQ gene for 163 additional SCOS cases, we identified four additional heterozygous mutations (M3-M6) in unrelated patients. In vitro functional analyses revealed that two of these mutations (M5, c.2538T > G and M6, c.2945G > T) might affect the function of the HELQ protein. Two heterozygous mutant mouse models with mutations similar to those of two patients (M5 and M6) did not show any considerable spermatogenic defects. Conclusion: Assuming that the mouse models accurately reflect the impact of the mutations, heterozygous HELQ variants alone did not lead to the development of the SCOS phenotype in mice. However, we cannot rule out the risk variants in Chinese or other human populations, and a larger dataset is needed to confirm the association between HELQ mutations with SCOS.

Computational analysis of Cyclin D1 gene SNPs and association with breast cancer.

CCND1 encodes for Cyclin D1 protein and single-nucleotide polymorphisms (SNPs) can modulate its activity. In the present study, the impact of CCND1 SNPs on structure and/or function of Cyclin D1 protein using in silico tools was investigated. Our analysis revealed only one splice site SNP (c.1988+5G