Cornichon protein CNIH4 is not essential for mice gametogenesis and fertility.

BACKGROUND: Cornichon is a functionally conserved transmembrane protein family that generally acts as a cargo-sorting receptor and cycles between the ER and the Golgi. Four Cornichon family members (CNIH1-4) have been identified. The key residues responsible for CNIH1-3 to bind to AMPA receptors are not conserved in CNIH4. Additionally, the function of CNIH1-3 in GPCR signaling is less established, while more established in case of CNIH4 protein that interact with GPCR and control their exportation. Many GPCRs are known for their essential roles in male and female gonad development. But whether CNIH4 plays a role in gametogenesis remains unknown. DESIGN: Mice carrying the Cnih4 knockout allele (Cnih4tm1a-/-) were generated by insertion of a LacZ reporter and a polyadenylation site after exon 1. Western blot, Immunofluorescence, computer-aided sperm analysis and other methods were used in the functional analysis. RESULTS: We identified that both Cnih4tm1a-/- male and female mice have normal fertility. Though, the sperm count, morphology, and motility of Cnih4tm1a-/- mice were slightly impaired compared to those of wild-type mice, the testes to body weight ratio and testicular histology were similar to those in control mice. Histological examination of Cnih4tm1a-/- ovaries detected follicles from primordial to antral stages and the numbers of follicles at each stage were also comparable to wild-type controls. Normal fertility was noticed after six-month fertility tests. That was likely due to the compensatory role of Chin3, which significantly upregulated in the Cnih4tm1a-/- mice to preserve the fertility role. CONCLUSION: Despite CNIH4 showing enriched expression in mouse germ cells, our genetic knockout studies demonstrated that CNIH4 is not essential for gametogenesis and fertility in mice although with a slight reduction in count, motility and morphology of sperm in male mice.

Multifunctional role of nanoparticles for the diagnosis and therapeutics of cardiovascular diseases.

The increasing burden of cardiovascular disease (CVD) remains responsible for morbidity and mortality worldwide; their effective diagnostic or treatment methods are of great interest to researchers. The use of NPs and nanocarriers in cardiology has drawn much interest. The present comprehensive review provides deep insights into the use of current and innovative approaches in CVD diagnostics to offer practical ways to utilize nanotechnological interventions and the critical elements in the CVD diagnosis, associated risk factors, and management strategies of patients with chronic CVDs. We proposed a decision tree-based solution by discussing the emerging applications of NPs for the higher number of rules to increase efficiency in treating CVDs. This review-based study explores the screening methods, tests, and toxicity to provide a unique way of creating a multi-parametric feature that includes cutting-edge techniques for identifying cardiovascular problems and their treatments. We discussed the benefits and drawbacks of various NPs in the context of cost, space, time and complexity that have been previously suggested in the literature for the diagnosis of CVDs risk factors. Also, we highlighted the advances in using NPs for targeted and improved drug delivery and discussed the evolution toward the nano-cardiovascular potential for medical science. Finally, we also examined the mixed-based diagnostic approaches crucial for treating cardiovascular disorders, broad applications and the potential future applications of nanotechnology in medical sciences.

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.

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.

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.

In silico analysis of a novel pathogenic variant c.7G > A in C14orf39 gene identified by WES in a Pakistani family with azoospermia.

Infertility is a multifactorial disorder that affects approximately 12% of couples of childbearing ages worldwide. Few studies have been conducted to understand the genetic causes of infertility in depth. The synaptonemal complex (SC), which is essential for the progression of meiosis, is a conserved tripartite structure that binds homologous chromosomes together and is thus required for fertility. This study investigated genetic causes of infertility in a Pakistani consanguineous family containing two patients suffering from non-obstructive azoospermia (NOA). We performed whole-exome sequencing, followed by Sanger sequencing, and identified a novel pathogenic variant (c.7G > A [p.D3N]) in the SC coding gene C14orf39, which was recessively co-segregated with NOA. In silico analysis revealed that charges on wild-type residues were lost, which may result in loss of interactions with other molecules and residues, and a reduction in protein stability occurred, which was caused by the p.D3N mutation. The novel variant generated the mutant protein C14ORF39D3N, and homozygous mutations in C14orf39 resulted in NOA. The transcriptome profile of C14ORF39 shows that it is specifically expressed in early brain development, which suggests that research in this area is required to study other functions of C14ORF39 in addition to its role in the germline. This research highlights the conserved role of C14orf39/SIX6OS1 in assembly of the SC and its indispensable role in facilitating genetic diagnosis in patients with infertility, which may enable the development of future treatments.

Mechanisms of gene regulation by histone degradation in adaptation of yeast: an overview of recent advances.

Histones are important component of eukaryotic cells chromatin and consist of arginine and lysine residues. Histones play an important role in the protection of DNA. Their contents significantly affect high-level chromatin structure formation, gene expression, DNA replication, and other important life activities. Protein degradation is an important regulatory mechanism of histone content. Recent studies have revealed that modification of amino acid sequence is directly related to histone breakdown. In addition, histone degradation is closely related to covalent modifications, such as ubiquitination and acetylation, which are considered to be driving factors in gene regulation. Gene regulation is an important mechanism in adaptation to the environment and survival of species. With the introduction of highly efficient technology, various mutations in histones have been identified in yeast. In the field of epigenetics and the transmission of chromatin states, two widely used model organisms are the budding yeast Saccharomyces cerevisiae and Schizosaccharomyces pombe. Higher eukaryotes can use their silent loci to maintain their epigenetic states and providing the base to investigate mechanisms underlying development. Therfore, both species have contributed a plethora of information on these mechanisms in both yeast and higher eukaryotes. This study focuses on the role of histone modifications in controlling telomeric silencing in Saccharomyces cerevisiae and centromeric silencing in S. pombe as examples of genetic loci that demonstrate epigenetic inheritance. In view of recent advances, this review focuses on the post-translational modification of histone amino acid residues and reviews the relationship between histone degradation and amino acid residue modification.

Testis-specific fascin component FSCN3 is dispensable for mouse spermatogenesis and fertility.

BACKGROUND: Fascins belong to a family of actin-bundling proteins that are involved in a wide range of biological functions. FSCN3, a newly identified testis-specific actin-bundling protein, is specifically expressed in elongated spermatids. However, its in vivo function in mouse spermiogenesis remains unknown. METHODS AND RESULTS: We generated Fscn3 knockout mice through CRISPR/Cas9 gene-editing technology. Fscn3-/- mice displayed normal testis morphology and testis to bodyweight ratio, and sperm concentrations did not differ significantly between Fscn3+/+ and Fscn3-/- mice. Fertility assays consistently revealed that Fscn3-/- mice are completely fertile and their reproductive status does not differ from that of wild-type. Moreover, hematoxylin and eosin staining of the testis sections of Fscn3-/- mice detected various germ cells, ranging from spermatogonia to mature spermatozoa. Furthermore, the swimming velocity of the sperm of Fscn3-/- mice was comparable to that of their wild-type littermates. Both Fscn3+/+ and Fscn3-/-mice had normal sperm morphology, indicating that the disruption of Fscn3 does not affect sperm morphology. The analysis of meiotic prophase I progression demonstrated normal prophase-I phases (leptonema to diplonema) in both Fscn3+/+ and Fscn3-/- mice, suggesting that Fscn3 is not essential for meiosis I. CONCLUSION: Our study provides the first evidence that FSCN3 is a testis-specific actin-bundling protein that is not required for mouse spermatogenesis. Our results will help reproductive biologists focus their efforts on genes that are crucial for fertility and avoid research duplication.

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.

Determination of Electrolytes and Trace Elements in Biological Samples from Patients with Altered Semen Parameters: a Correlational Analysis.

The effects of important nutrients such as calcium (Ca), copper (Cu), iron (Fe), magnesium (Mg), selenium (Se), and zinc (Zn) have been investigated in relation to male fertility due to their roles in proper spermatogenesis, sperm maturation, motility, and optimal sperm function. An imbalance between these elements has been associated with several pathologic conditions and male reproductive issues. The purpose of this study was to determine the essential trace and electrolytes elements, such as Ca, Cu, Fe, Mg, Se, and Zn, in human biological samples (blood, serum, and semen) from patients with male infertility. This study used correlational analysis to determine the potential associations between these elements and male fertility. Imbalances in these elements have been linked to various pathological conditions and male reproductive issues. One hundred eighty referent male adults and two hundred twenty-nine patients diagnosed with subtypes of infertility were included in the study, divided into two age groups. Acid digestion was controlled using a microwave oven, and the essential trace elements and electrolytes in the oxidized biological samples were determined using atomic absorption spectrometry. Certified reference materials of blood and serum were used to validate the accuracy of the methodology. The results showed that the concentrations of Ca, Cu, Fe, Mg, Se, and Zn in the blood, serum, and seminal plasma of male adults in all age groups were higher than those in patients with different infertility phenotypes. Essential element deficiency in all biological fluid samples may significantly negatively affect human reproductive health and lead to male infertility. Through a multidimensional approach, our study sought to unravel the intricate biochemical signatures associated with OAT, providing insights that may shape the landscape of diagnostic and therapeutic strategies for male reproductive health.

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 homozygous TSGA10 missense variant causes acephalic spermatozoa syndrome in a Pakistani family.

BACKGROUND: Acephalic spermatozoa syndrome is a rare type of teratozoospermia causing male infertility due to detachment of the sperm head and flagellum, which precludes fertilization potential. Although loss-of-function variations in several genes, including TSGA10, have been associated with acephalic spermatozoa syndrome, the genetic cause of many cases remains unclear. RESULTS: We recruited a Pakistani family with two infertile brothers who suffered from acephalic spermatozoa syndrome. Through whole-exome sequencing (WES) followed by Sanger sequencing, we identified a novel missense variant in TSGA10 (c.1112T > C, p. Leu371Pro), which recessively co-segregated with the acephalic spermatozoa syndrome within this family. Ultrastructural analyses of spermatozoa from the patient revealed that 98% of flagellar cross-sections displayed abnormal axonemal ultrastructure, in addition to the head-flagellum detachment. Real-time quantitative PCR analysis revealed almost no detectable TSAG10 mRNA and western blot analysis also failed to detect TSAG10 protein in patient's sperm samples while TSGA10 expression was clearly detected in control samples. Consistently, immunofluorescence analysis demonstrated the presence of TSGA10 signal in the midpiece of sperm from the control but a complete absence of TSGA10 signal in sperm from the patient. CONCLUSION: Altogether, our study identifies a novel TSGA10 pathogenic variant as a cause of acephalic spermatozoa syndrome in this family and provides information regarding the clinical manifestations associated with TSGA10 variants in human.

RéSUMé: CONTEXTE: Le syndrome des spermatozoïdes acéphaliques est un type rare de tératozoospermie provoquant une infertilité masculine en raison du détachement de la tête et du flagelle des spermatozoïdes, ce qui exclut une potentielle fécondation. Bien que des variations de perte de fonction dans plusieurs gènes, y compris TSGA10, aient été associées au syndrome des spermatozoïdes acéphaliques, la cause génétique de nombreux cas reste incertaine. RéSULTATS: Nous avons recruté une famille pakistanaise avec deux frères infertiles qui souffraient du syndrome des spermatozoïdes acéphaliques. Grâce au séquençage de l'exome entier (WES) suivi du séquençage Sanger, nous avons identifié un nouveau variant faux-sens dans TSGA10 (c.1112T > C, p. Leu371Pro), qui co-ségréguait de manière récessive avec le syndrome des spermatozoïdes acéphaliques au sein de cette famille. Les analyses ultrastructurales des spermatozoïdes des patients ont révélé que 98% des coupes transversales flagellaires présentaient une ultrastructure axonémiques anormales, en plus du décollement tête-flagelle. L'analyse quantitative par PCR en temps réel n'a révélé presque aucun ARNm TSAG10 détectable; l'analyse par transfert Western n'a pas non plus réussi à détecter la protéine TSAG10 dans les échantillons de sperme des patients, tandis que l'expression de TSGA10 a été clairement détectée dans les échantillons du témoin. De manière cohérente, l'analyse par immunofluorescence a démontré la présence du signal TSGA10 dans la partie médiane des spermatozoïdes du témoin, mais une absence totale de signal TSGA10 chez ceux des patients. CONCLUSION: Dans l'ensemble, notre étude identifie un nouveau variant pathogène de TSGA10 comme cause du syndrome des spermatozoïdes acéphaliques dans cette famille et fournit des informations concernant les manifestations cliniques associées aux variants de TSGA10 chez l'homme. MOTS-CLéS: Infertilité, TSGA10, Spermatozoïdes acéphaliques, Variations faux-sens.

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.

Pathophysiology of Disseminated Intravascular Coagulation in Sepsis: A Clinically Focused Overview.

Sepsis is a major global health problem that results from a dysregulated and uncontrolled host response to infection, causing organ failure. Despite effective anti-infective therapy and supportive treatments, the mortality rate of sepsis remains high. Approximately 30-80% of patients with sepsis may develop disseminated intravascular coagulation (DIC), which can double the mortality rate. There is currently no definitive treatment approach for sepsis, with etiologic treatment being the cornerstone of therapy for sepsis-associated DIC. Early detection, diagnosis, and treatment are critical factors that impact the prognosis of sepsis-related DIC. Over the past several decades, researchers have made continuous efforts to better understand the mechanisms of DIC in sepsis, as well as improve its quantitative diagnosis and treatment. This article aims to provide a comprehensive overview of the current understanding of sepsis-related DIC, focusing on common causes and diagnoses, with the goal of guiding healthcare providers in the care of patients with sepsis.

Decoding Sepsis-Induced Disseminated Intravascular Coagulation: A Comprehensive Review of Existing and Emerging Therapies.

Disseminated intravascular coagulation (DIC) is a recurrent complication of sepsis. Since DIC not only promotes organ dysfunction but also represents a strong prognostic factor, it is important to diagnose DIC as early as possible. When coagulation is activated, fibrinolysis is inhibited, blood thinners are consumed, and a condition is created that promotes blood clotting, making it more difficult for the body to remove fibrin or prevent it from being deposited in the blood vessels. This leads to microvascular thrombosis, which plays a role in organ dysfunction. Despite efforts to understand the underlying mechanisms of sepsis-induced DIC, healthcare providers worldwide still face challenges in effectively treating this condition. In this review, we provide an in-depth analysis of the available strategies for sepsis-induced DIC, considering their effectiveness, limitations, and potential for future advances. Corticosteroids (CS), recombinant thrombomodulin (rTM), vitamin C, fibrinolytic therapy, and platelet transfusion are among the treatments discussed in the review. In addition, we are specifically addressing immunomodulatory therapy (IMT) by investigating treatments such as granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interferon gamma (IFN-γ), and mesenchymal stem cell therapy (MSC). Finally, we also examined how these therapies might affect COVID-19 cases, which often present with sepsis-induced DIC. The review suggests that targeted experiments with randomization are needed to verify the effectiveness of these treatments and to discover novel approaches to treat sepsis-induced DIC. By increasing our knowledge of sepsis-induced DIC, we can develop targeted treatments that have the potential to save lives and improve outcomes.

Mitigating marine hazardous contaminants: A sustainable management perspective.

Marine hazardous contaminants, such as cadmium (Cd) and lead (Pb), pose significant risks to both human health and aquatic organisms. Traditional methods may not remove contaminants to safe levels, leading to the release of hazardous materials into marine environments. This research proposes polymeric membrane bioreactors as a potential solution to this problem. We determined Cd and Pb levels in three freshwater fish species (Rita, Ompok bimaculatus, and Heteropneustes fossils) from two distinctive regions (Zone 1 and Zone 2). Additionally, Cd and Pb concentrations in feeding materials, water, and sediments were analyzed to estimate daily intake and potential hazardous effects of these contaminants on the fish species. These findings underscore the need for effective regulatory measures and policies to reduce the discharge of hazardous contaminants into freshwater and marine environments, protecting both human health and the environment. Implementing polymeric membrane bioreactors in wastewater treatment and industrial facilities could mitigate the risks associated with consuming contaminated fish species. Significantly, the Cd and Pb levels in all three fish species from both fishponds exceeded the Food and Agriculture Organization's (FAO) maximum permissible limits. These findings carry important implications for policymakers, regulators, and industries, urging them to act appropriately to ensure the safety of the environment and public health. This study suggests that polymeric membrane bioreactors are a promising technological approach to address marine contamination, emphasizing their potential role in safeguarding human health and aquatic ecosystems.

Effect Of Lead On The Skin And Health Of Female Dermatitis Patients Through Cosmetics.

BACKGROUND: Cosmetics have been a part of routine body care not only for the upper classes but also for the middle and lower classes since the dawn of civilization. Cosmetic formulations are in more demand as the public's interest in skin whitening grows. The contamination of cosmetics with heavy metals is a major concern as they containing heavy metals and pose a major risk to human health. This study looks in to the effects of Lead on human skin. METHODS: In this cross sectional study different products were examined. The matrices (scalp hair, blood, serum and nails) of reference and dermatitis cosmetic female patients (seborrhoeic dermatitis, rosacea, allergic contact dermatitis, and irritant contact dermatitis) and cosmetic samples were used in a 2:1 mixture of HNO3 (65%) and H2O2 (30%), and oxidation was performed using a microwave. The oxidized beauty and biological specimen underwent electrothermal atomic emission spectrophotometry after microwave-assisted acid digestion. The validity and precision of the methodology were verified using certified reference materials. Cosmetic products (lipstick, face powder, Eye Liner and Eye shadow) of different brands contain Pb concentrations in the ranges of 50.5-120 µg/g, 14.6-30.7 µg/g, 2.87-4.25 µg/g and 15.3-21.6 µg/g, respectively. RESULTS: In the present study, cosmetic products (lipstick (N=15), face powder (N=13), eye liner (N=11), eye shadow (N=15) and female patients with dermatitis (N=252) residing in Hyderabad city, Sindh, Pakistan, was investigated. The outcome of this investigation showed significantly higher levels of Pb in biological samples (blood and scalp hair) of different types of female dermatitis patients than in reference subjects (p<0.001). CONCLUSIONS: The cosmetic products, especially with regard to heavy metals adulteration, are in use by the female population.

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 novel homozygous frameshift variant in DNAH8 causes multiple morphological abnormalities of the sperm flagella in a consanguineous Pakistani family.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenozoospermia categorized by immotile spermatozoa with abnormal flagella in ejaculate. Whole-exome sequencing (WES) is used to detect pathogenic variants in patients with MMAF. In this study, a novel homozygous frameshift variant (c.6158_6159insT) in dynein axonemal heavy chain 8 (DNAH8) from two infertile brothers with MMAF in a consanguineous Pakistani family was identified by WES. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed DNAH8 mRNA decay in these patients with the DNAH8 mutation. Hematoxylin-eosin staining and transmission electron microscopy revealed highly divergent morphology and ultrastructure of sperm flagella in these patients. Furthermore, an immunofluorescence assay showed the absence of DNAH8 and a reduction in its associated protein DNAH17 in the patients' spermatozoa. Collectively, our study expands the phenotypic spectrum of patients with DNAH8-related MMAF worldwide.