Heavy metal exposure and metabolomics analysis: an emerging frontier in environmental health.

Exposure to heavy metals in various populations can lead to extensive damage to different organs, as these metals infiltrate and bioaccumulate in the human body, causing metabolic disruptions in various organs. To comprehensively understand the metal homeostasis, inter-organ "traffic," and extensive metabolic alterations resulting from heavy metal exposure, employing complementary analytical methods is crucial. Metabolomics is pivotal in unraveling the intricacies of disease vulnerability by furnishing thorough understandings of metabolic changes linked to different metabolic diseases. This field offers exciting prospects for enhancing the disease prevention, early detection, and tailoring treatment approaches to individual needs. This article consolidates the existing knowledge on disease-linked metabolic pathways affected by the exposure of diverse heavy metals providing concise overview of the underlying impact mechanisms. The main aim is to investigate the connection between the altered metabolic pathways and long-term complex health conditions induced by heavy metals such as diabetes mellitus, cardiovascular diseases, renal disorders, inflammation, neurodegenerative diseases, reproductive risks, and organ damage. Further exploration of common pathways may unveil the shared targets for treating associated pathological conditions. In this article, the role of metabolomics in disease susceptibility is emphasized that metabolomics is expected to be routinely utilized for the diagnosis and monitoring of diseases and practical value of biomarkers derived from metabolomics, as well as determining their appropriate integration into extensive clinical settings.

Biochemical Investigation of Therapeutic Efficacy of Berberine-Enriched Extract in Streptozotocin-Induced Metabolic Impairment.

Metabolic disorders pose significant global health challenges, necessitating innovative therapeutic approaches. This study focused on the multifaceted therapeutic potential of berberine-enriched extract (BEE) in mitigating metabolic impairment induced by streptozotocin (STZ) in a rat model and compared the effects of BEE with berberine (BBR) and metformin (MET) to comprehensively evaluate their impact on various biochemical parameters. Our investigation reveals that BEE surpasses the effects of BBR and MET in ameliorating metabolic impairment, making it a promising candidate for managing metabolic disorders. For this, 30 male Wistar rats were divided into five groups (n = 6): control (CN), STZ, STZ + MET, STZ + BBR, and STZ + BEE. The treatment duration was extended over 4 weeks, during which various biochemical parameters were monitored, including fasting blood glucose (FBG), lipid profiles, inflammation, liver and kidney function biomarkers, and gene expressions of various metabolizing enzymes. The induction of metabolic impairment by STZ was evident through an elevated FBG level and disrupted lipid profiles. The enriched extract effectively regulated glucose homeostasis, as evidenced by the restoration of FBG levels, superior to both BBR and MET. Furthermore, BEE demonstrated potent effects on insulin sensitivity, upregulating the key genes involved in carbohydrate metabolism: GCK, IGF-1, and GLUT2. This highlights its potential in enhancing glucose utilization and insulin responsiveness. Dyslipidemia, a common occurrence in metabolic disorders, was effectively managed by BEE. The extract exhibited superior efficacy in regulating lipid profiles. Additionally, BEE exhibited significant anti-inflammatory properties, surpassing the effects of BBR and MET in lowering the levels of inflammatory biomarkers (IL-6 and TNF-α), thereby ameliorating insulin resistance and systemic inflammation. The extract's superior hepatoprotective and nephroprotective effects, indicated by the restoration of liver and kidney function biomarkers, further highlight its potential in maintaining organ health. Moreover, BEE demonstrated potent antioxidant properties, reducing oxidative stress and lipid peroxidation in liver tissue homogenates. Histopathological examination of the pancreas underscored the protective effects of BEE, preserving and recovering pancreatic ß-cells damaged by STZ. This collective evidence positions BEE as a promising therapeutic candidate for managing metabolic disorders and offers potential benefits beyond current treatments. In conclusion, our findings emphasize the remarkable therapeutic efficacy of BEE and provide a foundation for further research into its mechanisms, long-term safety, and clinical translation.

Biosynthesis and Multifaceted Characterization of Breynia nivosa-Derived Silver Nanoparticles: An Eco-Friendly Approach for Biomedical Applications.

This study presents an environmentally friendly synthesis of stable silver nanoparticles (Ag-NPs) using the methanolic extract of Breynia nivosa. Initial phytochemical analysis of the extract revealed the presence of alkaloids, flavonoids, glycosides, saponins, and tannins. Further characterization through high-performance liquid chromatography (HPLC) and gas chromatography-mass spectrometry (GC-MS) analyses identified a diverse array of bioactive compounds, including hydroquinone, stearic acid, neophytadiene, 9,12-octadecadienoic acid (Z,Z), methyl ester, and others. The addition of B. nivosa methanolic extract to an AgNO3 solution resulted in a color change, confirming the green synthesis of Ag-NPs through the reduction of AgNO3, as made evident by ultraviolet-visible (UV-vis) spectroscopy. X-ray diffraction (XRD) analysis provided valuable insights into the crystal structure, and scanning electron microscopy (SEM) analysis visualized the predominantly spherical shape of the Ag-NPs. However, the zeta (ζ)-potential and dynamic light scattering (DLS) analyses confirmed the stability and nanoscale dimensions of the synthesized Ag-NPs. Meanwhile, Fourier transform infrared (FT-IR) spectra exhibited peaks indicative of various functional groups, including carboxylic acids, phenols, alkanes, and isocyanates. These functional groups played a crucial role in both the reduction and capping processes of the Ag-NPs. The study further explored the antioxidant activity, cytotoxicity, acetylcholinesterase inhibition, and α-amylase inhibition activities of the Ag-NPs of the B. nivosa extract, demonstrating their potential for biomedical and therapeutic applications. In conclusion, this environmentally sustainable synthesis of Ag-NPs from the B. nivosa extract, enriched with bioactive secondary metabolites detected through HPLC and GC-MS analysis, holds promise for diverse applications in the burgeoning field of green nanotechnology.

Real-time fluorescent monitoring of phase I xenobiotic-metabolizing enzymes.

This article explores the intricate landscape of advanced fluorescent probes crafted for the detection and real-time monitoring of phase I xenobiotic-metabolizing enzymes. Employing state-of-the-art technologies, such as fluorescence resonance energy transfer, intramolecular charge transfer, and solid-state luminescence enhancement, this article unfolds a multifaceted approach to unraveling the dynamics of enzymatic processes within living systems. This encompassing study involves the development and application of a diverse range of fluorescent probes, each intricately designed with tailored mechanisms to heighten sensitivity, providing dynamic insights into phase I xenobiotic-metabolizing enzymes. Understanding the role of phase I xenobiotic-metabolizing enzymes in these pathophysiological processes, is essential for both medical research and clinical practice. This knowledge can guide the development of approaches to prevent, diagnose, and treat a broad spectrum of diseases and conditions. This adaptability underscores their potential clinical applications in cancer diagnosis and personalized medicine. Noteworthy are the trifunctional fluorogenic probes, uniquely designed not only for fluorescence-based cellular imaging but also for the isolation of cellular glycosidases. This innovative feature opens novel avenues for comprehensive studies in enzyme biology, paving the way for potential therapeutic interventions. The research accentuates the selectivity and specificity of the probes, showcasing their proficiency in distinguishing various enzymes and their isoforms. The sophisticated design and successful deployment of these fluorescent probes mark significant advancements in enzymology, providing powerful tools for both researchers and clinicians. Beyond their immediate applications, these probes offer illuminating insights into disease mechanisms, facilitating early detection, and catalyzing the development of targeted therapeutic interventions. This work represents a substantial leap forward in the field, promising transformative implications for understanding and addressing complex biological processes. In essence, this research heralds a new era in the development of fluorescent probes, presenting a comprehensive and innovative approach that not only expands the understanding of cellular enzyme activities but also holds great promise for practical applications in clinical settings and therapeutic endeavors.

Modulation of Metabolic Pathways and Protection against Cadmium-Induced Disruptions with Taxifolin-Enriched Extract.

Cadmium, a ubiquitous environmental pollutant, has been implicated in the disruption of various metabolic pathways, contributing to the development of insulin resistance, glucose intolerance, and associated metabolic disorders. This study aimed to investigate the cadmium chloride (CdCl2) exposure on metabolic pathways and to assess the potential therapeutic efficacy of the taxifolin-enriched extract in mitigating these disruptions by modulating biochemical pathways. Taxifolin-enriched extract (TEE) was prepared from Pinus roxburghii bark using a green extraction method. About 60 Wistar albino rats were divided into six groups: the control group (n = 10), the CdCl2 group (30 mg/kg) (n = 10), and four groups (each comprises n = 10) treated with 30 mg/kg CdCl2 in combination with metformin (100 mg/kg), ascorbic acid, taxifolin (30 mg/kg), and TEE (30 mg/kg), respectively. After the treatment period of 1 month, a comprehensive assessment of metabolic biomarkers and gene expressions that regulate the metabolism of carbohydrates and lipids was conducted to evaluate the impact of CdCl2 exposure and the potential protective effects of TEE. The results revealed that CdCl2 exposure significantly increased (P < 0.001) serum levels of α-glucosidase, α-amylase, insulin, G6PC, hexokinases, TGs, LDL, HMG-CoA reductase, and pro-inflammatory cytokines such as IL-6 and TNF-α. Conversely, CdCl2 exposure led to a reduction in HDL, antioxidant enzyme levels, phosphofructokinases, and glucose-6-phosphatase dehydrogenase. However, the administration of TEE alongside CdCl2 substantially mitigated (P < 0.001) these fluctuations in metabolic and inflammatory biomarker levels induced by CdCl2 exposure. Both TEE and taxifolin treatment effectively lowered the elevated levels of α-amylase, α-glucosidase, G6PC, insulin, TGs, HMG-CoA reductase, leptin, ALT, AST, blood urea nitrogen, creatinine, and pro-inflammatory cytokines while simultaneously enhancing levels of HDL cholesterol and antioxidant enzymes. Moreover, CdCl2 exposure suppressed mRNA expression of critical metabolic biomarkers such as glucose transporter 2 (GLUT2), insulin-like growth factor 1 (IGF-1), lactate dehydrogenase, and HMG-CoA lyases while upregulating the mRNA expression of angiotensin receptor 2 and vasopressin, key metabolic biomarkers involved in glucose metabolism and insulin regulation. TEE demonstrated the potential to restore normal metabolic functions and reduce the adverse impacts caused by CdCl2 exposure by mitigating disturbances in several metabolic pathways and restoring gene expression of critical metabolic biomarkers related to glucose metabolism and insulin regulation. Nevertheless, further investigation is warranted to comprehensively understand the underlying mechanisms and optimize the appropriate dosage and duration of TEE treatment for achieving the most effective therapeutic outcomes.

Therapeutic Intervention of Serine Protease Inhibitors against Hepatitis C Virus.

Hepatitis C virus (HCV) is a globally prevalent and hazardous disorder that is responsible for inducing several persistent and potentially fatal liver diseases. Current treatment strategies offer limited efficacy, often accompanied by severe and debilitating adverse effects. Consequently, there is an urgent and compelling need to develop novel therapeutic interventions that can provide maximum efficacy in combating HCV while minimizing the burden of adverse effects on patients. One promising target against HCV is the NS3-4A serine protease, a complex composed of two HCV-encoded proteins. This non-covalent heterodimer is crucial in the viral life cycle and has become a primary focus for therapeutic interventions. Although peginterferon, combined with ribavirin, is commonly employed for HCV treatment, its efficacy is hampered by significant adverse effects that can profoundly impact patients' quality of life. In recent years, the development of direct-acting antiviral agents (DAAs) has emerged as a breakthrough in HCV therapy. These agents exhibit remarkable potency against the virus and have demonstrated fewer adverse effects when combined with other DAAs. However, it is important to note that there is a potential for developing resistance to DAAs due to alterations in the amino acid position of the NS3-4A protease. This emphasizes the need for ongoing research to identify strategies that can minimize the emergence of resistance and ensure long-term effectiveness. While the combination of DAAs holds promise for HCV treatment, it is crucial to consider the possibility of drug-drug interactions. These interactions may occur when different DAAs are used concurrently, potentially compromising their therapeutic efficacy. Therefore, carefully evaluating and monitoring potential drug interactions are vital to optimize treatment outcomes. In the pursuit of novel therapeutic interventions for HCV, the field of computational biology and bioinformatics has emerged as a valuable tool. These advanced technologies and methodologies enable the development and design of new drugs and therapeutic agents that exhibit maximum efficacy, reduced risk of resistance, and minimal adverse effects. By leveraging computational approaches, researchers can efficiently screen and optimize potential candidates, accelerating the discovery and development of highly effective treatments for HCV, treatments.

Investigating the biochemical association of gestational diabetes mellitus with dyslipidemia and hemoglobin.

Aims: To investigate the biochemical correlation of hemoglobin (Hb), dyslipidemia, and HbA1c with gestational diabetes mellitus (GDM). Background: GDM is a condition that develops during pregnancy and is characterized by high blood sugar levels. Biochemical parameters such as hemoglobin (Hb), dyslipidemia, and HbA1c have been implicated in the development of GDM. Understanding the correlation between these biochemical parameters and GDM can provide insights into the underlying mechanisms and potential diagnostic markers for the condition. Objective: The objective of this study was to evaluate the correlation of various biochemical parameters, including Hb, dyslipidemia, and HbA1c, in pregnant women with and without GDM. Method: A cross-sectional study design was used. Pregnant females attending a tertiary care hospital in Faisalabad between September 1st, 2021, and June 25th, 2022, were included in the study. The participants were divided into two groups: those with GDM (GDM group) and those without GDM (non-GDM group). Blood glucose, Hb, and lipid levels were compared between the two groups using statistical tests, including chi-square, independent sample t-test, and Pearson's correlation. Result: Out of the 500 participants, 261 were in the 2nd trimester and 239 in the 3rd trimester. Maternal age showed a significant difference between the GDM and non-GDM groups. The levels of Hb, TC, HDL, LDL, and HbA1c significantly differed (p < 0.05) between the two groups. TC (r = 0.397), TG (r = 0.290), and LDL (r = 0.509) showed a statistically significant and moderately positive correlation with GDM. HDL (r = -0.394) and Hb (r = -0.294) showed a moderate negative correlation with GDM. Conclusion: Increased levels of HbA1c, TC, and LDL, along with decreased levels of HDL and Hb, were identified as contributing factors to GDM. The levels of TC, TG, and LDL were positively correlated with GDM, while HDL and Hb were negatively correlated. The findings of this study suggest that monitoring and managing hemoglobin, dyslipidemia, and HbA1c levels during pregnancy may be important in identifying and potentially preventing or managing GDM. Further research is needed to explore the underlying mechanisms and potential interventions targeting these biochemical parameters in relation to GDM.

Neuroprotective and Cardiometabolic Role of Vitamin E: Alleviating Neuroinflammation and Metabolic Disturbance Induced by AlCl3 in Rat Models.

Cardiovascular diseases (CVDs) and neurodegenerative disorders, such as diabetes mellitus and Alzheimer's disease, share a common pathophysiological link involving insulin resistance (IR), inflammation, and hypertension. Aluminium chloride (AlCl3), a known neurotoxicant, has been associated with neurodegeneration, cognitive impairment, and various organ dysfunctions due to the production of reactive oxygen species (ROS) and oxidative stress. In this study, we aimed to investigate the potential protective effects of metformin and vitamin E against AlCl3-induced neuroinflammation and cardiometabolic disturbances in rat models. Rats were divided into five groups: a normal control group, an AlCl3-treated diseased group without any treatment, and three groups exposed to AlCl3 and subsequently administered with metformin (100 mg/kg/day) alone, vitamin E (150 mg/kg/day) orally alone, or a combination of metformin (100 mg/kg/day) and vitamin E (150 mg/kg/day) for 45 days. We analyzed serum biomarkers and histopathological changes in brain, heart, and pancreatic tissues using H&E and Masson's trichrome staining and immunohistochemistry (IHC). Electrocardiogram (ECG) patterns were observed for all groups. The AlCl3-treated group showed elevated levels of inflammatory biomarkers, MDA, and disturbances in glycemic and lipid profiles, along with reduced insulin levels. However, treatment with the combination of metformin and vitamin E resulted in significantly reduced glucose, cholesterol, LDL, and TG levels, accompanied by increased insulin and HDL levels compared to the individual treatment groups. Histopathological analyses revealed that combination therapy preserved neuronal structures, muscle cell nuclei, and normal morphology in the brain, heart, and pancreatic tissues. IHC demonstrated reduced amyloid plaques and neurofibrillary tangles in the combination-treated group compared to the AlCl3-treated group. Moreover, the combination group showed a normal ECG pattern, contrasting the altered pattern observed in the AlCl3-treated group. Overall, our findings suggest that metformin and vitamin E, in combination, possess neuroprotective and cardiometabolic effects, alleviating AlCl3-induced neuroinflammation and metabolic disturbances.

Tetra-ARMS PCR analysis of angiotensinogen AGT T174M (rs4762) genetic polymorphism in diabetic patients: a comprehensive study.

Background and purpose: Hypertension (HTN) is a multifactorial chronic disease that poses a significant global health burden and is associated with increased mortality rates. It often coexists with other conditions, such as cardiovascular, liver, and renal diseases, and has a strong association with diabetes mellitus. Insulin resistance and endothelial dysfunction commonly occur in individuals with both HTN and type 2 diabetes mellitus (T2DM). Genetic factors, along with environmental and pathological factors, play a role in the development of HTN. Recent studies have revealed the influence of single nucleotide polymorphisms (SNPs) in various genes on HTN. In this study, we aimed to investigate the genetic polymorphism of angiotensinogen (AGT) T174M (rs4762) and its association with HTN in diabetic patients. Methods: A total of 300 participants were enrolled in this study and divided into three groups: control, hypertensive, and hypertensive diabetic. Blood samples were collected, and predetermined biochemical parameters were assessed. Genotyping of the AGT T174M (rs4762) gene was conducted using Tetra ARMS PCR with specific primers. Results: The study findings revealed a significant association between AGT T174M (rs4762) genotype and HTN in diabetic patients within the Pakistani population. The C/T genotype of AGT T174M (rs4762) was found to be significant in both the hypertensive and hypertensive diabetic participants compared to the control group. This genotype was identified as a risk factor for developing HTN in both the hypertensive and hypertensive diabetic participants. Conclusion: This study demonstrates a significant association between AGT T174M (rs4762) genetic polymorphism and HTN in diabetic patients. The C/T genotype of AGT T174M (rs4762) may serve as a potential marker for identifying individuals at risk of developing HTN, specifically in the hypertensive and hypertensive diabetic populations. Further research is warranted to elucidate the underlying mechanisms and validate these findings in larger cohorts.

Resveratrol Mitigates Bisphenol A-Induced Metabolic Disruptions: Insights from Experimental Studies.

The aim of this study was to investigate the disruptions of metabolic pathways induced by bisphenol A (BPA) and explore the potential therapeutic intervention provided by resveratrol (RSV) in mitigating these disruptions through the modulation of biochemical pathways. Wistar albino rats were divided into three groups: group 1 served as the control, group 2 received 70 mg/Kg of BPA, and group 3 received 70 mg/kg of BPA along with 100 mg/Kg of RSV. After the treatment period, various biomarkers and gene expressions were measured to assess the effects of BPA and the potential protective effects of RSV. The results revealed that BPA exposure significantly increased the serum levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines such as TNF-α and IL-6. Concurrently, BPA exposure led to a reduction in the levels of antioxidant enzymes such as catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD), as well as GLUT4 and HDL cholesterol. However, the administration of RSV along with BPA significantly ameliorated these alterations in the biomarker levels induced through BPA exposure. RSV treatment effectively reduced the elevated levels of α-amylase, α-glucosidase, G6PC, insulin, HbA1c, HMG-CoA reductase, FFAs, TGs, DPP-4, MDA, and proinflammatory cytokines, while increasing the levels of antioxidant enzymes, GLUT4, and HDL cholesterol. Furthermore, BPA exposure suppressed the mRNA expression of glucokinase (GCK), insulin-like growth factor 1 (IGF-1), and glucose transporter 2 (GLUT2) and up-regulated the mRNA expression of uncoupling protein 2 (UCP2), which are all critical biomarkers involved in glucose metabolism and insulin regulation. In contrast, RSV treatment effectively restored the altered mRNA expressions of these biomarkers, indicating its potential to modulate transcriptional pathways and restore normal metabolic function. In conclusion, the findings of this study strongly suggest that RSV holds promise as a therapeutic intervention for BPA-induced metabolic disorders. By mitigating the disruptions in various metabolic pathways and modulating gene expressions related to glucose metabolism and insulin regulation, RSV shows potential in restoring normal metabolic function and counteracting the adverse effects induced by BPA exposure. However, further research is necessary to fully understand the underlying mechanisms and optimize the dosage and duration of RSV treatment for maximum therapeutic benefits.

Metabolomics: a promising tool for deciphering metabolic impairment in heavy metal toxicities.

Heavy metals are the metal compounds found in earth's crust and have densities higher than that of water. Common heavy metals include the lead, arsenic, mercury, cadmium, copper, manganese, chromium, nickel, and aluminum. Their environmental levels are consistently rising above the permissible limits and they are highly toxic as enter living systems via inhalation, ingestion, or inoculation. Prolonged exposures cause the disruption of metabolism, altered gene and/or protein expression, and dysregulated metabolite profiles. Metabolomics is a state of the art analytical tool widely used for pathomolecular inv22estigations, biomarkers, drug discovery and validation of biotransformation pathways in the fields of biomedicine, nutrition, agriculture, and industry. Here, we overview studies using metabolomics as a dynamic tool to decipher the mechanisms of metabolic impairment related to heavy metal toxicities caused by the environmental or experimental exposures in different living systems. These investigations highlight the key role of metabolomics in identifying perturbations in pathways of lipid and amino acid metabolism, with a critical role of oxidative stress in metabolic impairment. We present the conclusions with future perspectives on metabolomics applications in meeting emerging needs.

Toxicological evaluation of bisphenol analogues: preventive measures and therapeutic interventions.

Bisphenol A (BPA) is a prominent endocrine-disrupting compound that shares structural similarities with estrogen. It is widely used, particularly in the production of food packaging, canned goods, and dental sealants. Of the eight bisphenol analogues, BPA is the most frequently utilized chemical in packaging food items, canned foods and dental sealants. However, chronic exposure to BPA can pose severe health risks, particularly in children. To ensure public safety, it is crucial to adopt proper precautionary measures to minimize BPA exposure. This article explores the toxic effects of bisphenols on various body systems and mechanisms, shedding light on their impact on the reproductive and endocrine system, obesity, albuminuria, and the generation of reactive oxygen species. Understanding the detrimental effects of bisphenols on these systems and mechanisms is vital for developing strategies to mitigate their harmful consequences. Furthermore, the article delves into the biotransformation processes of bisphenols, focusing on their occurrence in vertebrates, invertebrates, plants, and microorganisms. Investigating the biotransformation pathways provides valuable insights into the fate of bisphenols in various organisms and ecosystems. Lastly, the article emphasizes preventive measures to avoid bisphenol exposure and highlights the potential use of plant-based bioactive compounds for treatment strategies. By implementing effective preventive measures, such as utilizing BPA-free products and adopting safer alternatives, individuals can reduce their exposure to bisphenols. Additionally, exploring the potential of plant-based bioactive compounds as therapeutic agents offers promising avenues for addressing the adverse effects of bisphenols. The findings presented herein contribute to a better understanding of the novelty, significance, and potential implications of bisphenol research in the field, aiding in the development of safer practices and interventions to safeguard public health.

Biochemical profiling of berberine-enriched extract in aluminum chloride induced oxidative damage and neuroinflammation.

Despite the numerous treatment strategies used for Alzheimer's disease (AD), only a few cholinesterase inhibitor drugs, such as memantine, are effective in symptomatically relieving the hallmarks of AD, providing momentary recovery of memory and cognitive decline. These available drugs do not treat the underlying causes of AD, and their chronic use is associated with serious adverse effects and disease progression. Berberine is an isoquinoline alkaloid that has been reported to possess therapeutic potential against AD. Therefore, its activity was evaluated against an aluminum chloride (AlCl3)-induced AD rat model, and a berberine-enriched extract (BEE) was used to determine if its activity is equivalent to pure berberine (PB). The rats were administered 300 mg/kg of oral AlCl3 to induce AD and were then treated with oral PB at a dosage of 50 mg/kg, BEE at a dosage of 50 mg/kg, and rivastigmine at a dosage of 1 mg/kg as a standard drug for 21 days. In this study, various parameters were assessed to evaluate cognitive functions, such as behavioral analysis, antioxidant enzyme levels, acetylcholinesterase (AChE) activity, proinflammatory cytokine levels, real-time polymerase chain reaction (RT-PCR) analysis of different biomarkers (AChE, IL-1α, IL-1ß, BACE-1, TNF-α) linked to AD, and histopathological changes in the rats' brains. After 21 days, the disease control group showed a significant decline in cognitive function, decreased levels of antioxidant enzymes, upregulated activity of the AChE enzyme, increased levels of proinflammatory cytokines, and marked elevation in mRNA expression of AD-associated biomarkers. On the other hand, the treatment groups showed significant improvements in memory deficits, elevated levels of antioxidant enzymes, reduced levels of proinflammatory cytokines, decreased AChE activity, and significant downregulation of the expression of predefined biomarkers. Histological examination of the treatment groups showed less neuroinflammation and fewer amyloid plaques compared to the disease control group. In conclusion, both PB and BEE have comparable neuroprotective potential to mitigate the pathological hallmarks of AD. However, controlled clinical trials are needed to assess their efficacy and safety.

Biochemical association of regulatory variant of KLF14 genotype in the pathogenesis of cardiodiabetic patients.

Background and purpose: The study focuses on examining the relationship between a single nucleotide polymorphism (SNP) in KLF14 rs4731702 and risk of type 2 diabetes mellitus (T2DM) and dyslipidemia in different ethnic populations. The purpose of this study was to evaluate the association between KLF14 rs4731702 and serum lipid profile and to determine the frequency distribution of KLF14 rs4731702 among T2DM and cardiometabolic patients. Methods: A total of 300 volunteers were recruited, consisting of three groups: 100 healthy individuals, 100 individuals diagnosed with T2DM, and 100 individuals diagnosed with cardiometabolic disorders. Biochemical analysis of blood samples was conducted to assess various biomarkers related to glycemic control and lipid profile. This involved measuring levels of glucose, triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and ApoA1. Genotyping analysis was performed to investigate KLF14 rs4731702 polymorphism. The Tetra ARMS-PCR method was employed for genotyping analysis. Results: The results of biochemical profiling revealed a significant association between altered glycemic biomarkers and lipid profile in diseased patients compared to healthy participants. The frequencies of KLF14 rs4731702 alleles and genotypes were compared between the control group and T2DM group. A statistically significant difference was observed, indicating a potential association between KLF14 rs4731702 and T2DM. In the dominant inheritance model of KLF14 rs4731702 SNP, a statistically significant difference [odds ratio (95% confidence interval)] of 0.56 (0.34 -0.96) was found between the control and T2DM subjects. This suggests that the presence of certain genotypes influences the risk of T2DM. In T2DM patients, individuals carrying the C allele exhibited compromised insulin sensitivity, decreased HDL-C and ApoA1 levels, and increased serum glucose, TG, and LDL-C concentrations. Conversely, TT genotype carriers demonstrated increased levels of HDL-C and ApoA1, lower insulin resistance, serum glucose, LDL-C, and TG levels. Conclusion: The study's findings indicate that dyslipidemia in T2DM patients is associated with reduced KLF14 functionality due to CC and CT genotypes, leading to insulin resistance and an increased risk of cardiovascular diseases. Additionally, risk of KLF14 rs4731702 polymorphism was found to increase with age and was more prevalent in female than in male individuals. These insights contribute to understanding genetic factors influencing the development and progression of T2DM and dyslipidemia in different ethnic populations.

Soluble laticifer proteins from Calotropis procera as an effective candidates for antimicrobial therapeutics.

Calotropis procera is a latex-producing plant with plenty of pharmacologically active compounds. The principal motivation behind this study was to separate and characterize laticifer proteins to check their antimicrobial potential. Laticifer proteins were separated by gel filtration chromatography (GFC) and investigated using sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The SDS-PAGE assay detected proteins of molecular weights of 10 to 30 kDa but most of them were in the range of 25 to 30 kDa. The soluble laticifer proteins (SLPs) were tested against Gram-positive bacteria i.e., Streptococcus pyogenes and Staphylococcus aureus whereas Escherichia coli and Pseudomonas aeruginosa were tested as Gram-negative bacteria, we determined a profound anti-bacterial activity of these proteins. In addition, SLPs were also investigated against Candida albicans via the agar disc diffusion method which also showed significant anti-fungal activity. SLP exhibited antibacterial activity against P. aeruginosa, E. coli, and S. aureus with a minimum inhibitory concentration (MIC) of 2.5 mg/mL for each, while MIC was found at 0.625 mg/mL for S. pyogenes and 1.25 mg/mL for C. albicans. Moreover, enzymatic activity evaluation of SLP showed the proteolytic nature of these proteins, and this proteolytic activity was greatly enhanced after reduction which might be due to the presence of cysteine residues in the protein structure. The activity of the SLPs obtained from the latex of C. procera can be associated with the involvement of enzymes either proteases or, protease inhibitors and/or peptides.

Technological Advancement in ω-3 Fatty Acids: Their Therapeutic Functions and Novel Delivery Strategies.

Being an important dietary component, omega-3 (ω-3) fatty acids are essential polyunsaturated fatty acids, which play a crucial role in the normal growth and development of an individual. ω-3 fatty acids have been reported to possess therapeutic activities against several diseases, including cardiovascular, neurological, cancer, etc. Due to the unsaturation, ω-3 fatty acids are highly reactive and prone to oxidation, which is the biggest hurdle in their administration, as oxidation produces a foul smell and reduces their therapeutic efficacy. Although numerous supplementation strategies have been developed to enhance the bioavailability, targeted drug delivery, and therapeutic potential, the rate of compliance is low due to difficulty in swallowing and unpleasant aftertaste. To cope with these problems, several novel drug delivery approaches have been developed, which may be used as an alternative to enhance the effectiveness of ω-3 fatty acids when administered alone or in combination therapy. This review focuses on how novel drug delivery approaches can be used to overcome the ω-3 fatty acids stability issues and how to maximize its therapeutic activity.

Macrophages M2 polarization is involved in lapatinib-mediated chemopreventive effects in the lung cancer.

M2 polarized tumor-associated macrophages (TAMs) have a multifunctional role in cancer initiation, progression, metastasis, and contribute to chemotherapeutic resistance. Therefore, identifying M2 polarized TAMs is a potential target for cancer therapeutic intervention. The underlying mechanism that target the TAMs M2 polarized macrophages remains primarily uncharacterized; however, only a few compounds have been identified that inhibit TAMs M2 polarized macrophages. In this research, we investigated that lapatinib could effectively suppress the expression of IL_13-induced M2 polarized macrophages surface markers i.e., CD163 and CD206, and downregulation of M2 genes such as Fizz1, Mrc1, Arg1, IL-10, Ym1, nd CCL2 in vitro. Moreover, lapatinib abrogated the M2 polarized macrophage-mediated cancer cells invasion and migration. Mechanistically, in our study, lapatinib inhibited IL-13 triggered STAT6 phosphorylation. Furthermore, in LLCs tumor model, lapatinib significantly reduced tumorigenesis, followed by the downregulation of percentages of M2 marker CD206+ and CD68+ in the tumor. This downregulation correlates with chemopreventive effect of lapatinib. All taken together, these results demonstrated that lapatinib effectively prevents the macrophage M2 polarization and indicates a potential mechanism for preventing the tumor growth via M2 polarized polarization intervention.

Nanosuspension of Foeniculum Vulgare Promotes Accelerated Sensory and Motor Function Recovery after Sciatic Nerve Injury.

The seed extract of Foeniculum vulgare (FV) was used for the preparation of a nanosuspension (NS) with an enhanced bioavailability of phytoconstituents. Subsequently, it was employed as a potent source of polyphenols, such as quercetin and kaempferol, to accelerate the regeneration and recovery of motor and sensory function in injured nerves. The NS was administered through daily gauging as NS1 (0.5 mg/mL) and NS2 (15 mg/mL), at a dose rate of 2 g/kg body weight until the end of the study. The NS-mediated retrieval of motor functions was studied by evaluating muscle grip strength and the sciatic functional index. The recovery of sensory functions was assessed by the hotplate test. Several well-integrated biochemical pathways mediate the recovery of function and the regeneration of nerves under controlled blood glucose and oxidative stress. Consequently, the NS-treated groups were screened for blood glucose, total antioxidant capacity (TAC), and total oxidant status (TOS) compared to the control. The NS administration showed a significant potential to enhance the recuperation of motor and sensory functions. Moreover, the oxidative stress was kept under check as a result of NS treatments to facilitate neuronal generation. Thus, the nanoformulation of FV with polyphenolic contents accelerated the reclamation of motor and sensory function after nerve lesion.

Biochemical Activation and Regulatory Functions of Trans-Regulatory KLF14 and Its Association with Genetic Polymorphisms.

Krüpple-Like family of transcription factor-14 (KLF14) is a master trans-regulatory gene that has multiple biological regulatory functions and is involved in many pathological mechanisms. It controls the expressions of several other genes which are involved in multiple regulatory functions. KLF14 plays a significant role in lipid metabolism, glucose regulation and insulin sensitivity. Cell apoptosis, proliferation, and differentiation are regulated by the KLF14 gene, and up-regulation of KLF14 prevents cancer progression. KLF14 has been used as an epigenetic biomarker for the estimation of chronological age due to the presence of different age-related CpG sites on genes that become methylated with age. Different genome-wide association studies have identified several KLF14 variants in adipose tissues. These single nucleotide polymorphisms in KLF14 have been associated with dyslipidemia, insulin resistance, and glucose intolerance. Moreover, the prevalence of genetic polymorphism is different in different populations due to ethnic differences and epigenetic modifications. In addition, environmental and physiological factors such as diet, age, gender, and obesity are also responsible for genetic mutations in KLF14.

Biochemical Association of MTHFR C677T Polymorphism with Myocardial Infarction in the Presence of Diabetes Mellitus as a Risk Factor.

Myocardial infarction (MI) is a cardiovascular disease that occurs due to the blockage of the coronary artery. Subsequently, cardiac muscles receive a lower oxygen supply, which leads to the death of cardiac muscles. The etiology of MI is linked to various environmental, occupational, and genetic factors. Various studies have been conducted on the polymorphism of genes involved in MI. Previous studies have shown that different variants of the methylene tetrahydrofolate reductase (MTHFR) gene are involved in causing MI by altering the metabolism of folate and homocysteine. However, the genetic polymorphism of MTHFR C677T (rs1801133) and its association with MI in the presence of diabetes mellitus (DM) as a risk factor still needs to be investigated. This study recruited 300 participants who were divided into three groups, i.e., the control, MI, and MI-DM. The blood samples collected from the study participants were subjected to various biochemical tests and their clinical parameters were monitored. MTHFR C677T (rs1801133) genotyping was performed by Tetra ARMS PCR using predetermined primers. The MTHFR C677T (rs1801133) polymorphism was associated with MI in the presence of DM as a risk factor among the participants. The MTHFR C677T (rs1801133) T/T homozygous genotype was found to be significant among MI patients in the presence of DM as a risk factor.