Facile Synthesis of S-doped Carbon Quantum Dots and Their Application in the Detection of Sudan I in Saffron.

This study employed citric acid as a carbon source and thiourea as a sulphur source to conduct a straightforward one-step microwave synthesis of sulphur-doped carbon quantum dots (SCQDs). For the characterization of as-synthesized SCQDs, several methods such as fluorescence spectroscopy, X-Ray photoelectron spectroscopy (XPS), X-Ray diffraction (XRD), and zeta potential analyzer were utilized. XRD and XPS spectroscopy are used to examine the chemical composition and morphological aspects. These QDs have a limited size distribution spanning up to 5.89 nm, with a maximum distribution at 7 nm, according to zeta size analyser examinations. At an excitation wavelength of 340 nm, the highest fluorescence intensity (FL intensity) of SCQDs was attained. With a detection limit of 0.77 M, the synthesized SCQDs were employed as an efficient fluorescent probe for the detection of Sudan I in saffron samples.

Algae-Mediated Removal of Prevalent Genotoxic Antibiotics: Molecular Perspective on Algae-Bacteria Consortia and Bioreactor-Based Strategies.

Antibiotic pollution poses a potential risk of genotoxicity, as antibiotics released into the environment can induce DNA damage and mutagenesis in various organisms. This pollution, stemming from pharmaceutical manufacturing, agriculture, and improper disposal, can disrupt aquatic ecosystems and potentially impact human health through the consumption of contaminated water and food. The removal of genotoxic antibiotics using algae-mediated approaches has gained considerable attention due to its potential for mitigating the environmental and health risks associated with these compounds. The paper provides an in-depth examination of the molecular aspects concerning algae and bioreactor-driven methodologies utilized for the elimination of deleterious antibiotics. The molecular analysis encompasses diverse facets, encompassing the discernment and profiling of algae species proficient in antibiotic degradation, the explication of enzymatic degradation pathways, and the refinement of bioreactor configurations to augment removal efficacy. Emphasizing the significance of investigating algal approaches for mitigating antibiotic pollution, this paper underscores their potential as a sustainable solution, safeguarding both the environment and human health.

Histomorphometric lung density evaluation of Immulina treatment using a murine influenza pneumonia model.

Histomorphometric lung density measurements were used to evaluate the effects of Immulina on mouse pneumonia. Mice were intra-nasally exposed to H1N1 influenza virus at a dose of 5 × 104 PFU/50 µL/mouse. Lung density was measured using the NIH ImageJ software program. Density values were compared to semiquantitative pneumonia severity scores. Lung photomicrographs were evaluated at 25-×, 40-× and 400-× magnification. The study included viral inoculated controls (IC) and non-inoculated controls (NC) and mice either treated or not treated with Immulina. Three doses of Immulina were included (25, 50 or 100 mg/kg) and administered using 3 protocols: prophylactic treatment (P), prodromal treatment (PD) and therapeutic treatment (TH) (note that in most of the evaluations of the data for the three treatment protocols were combined). Groups of mice were evaluated on days 3, 5, 7, 10 and 15 following exposure. The occurrence of "digital pneumonia" (DP) was defined as a density measurement above the 95% confidence limit of the corresponding NC values. A significant reduction in the occurrence of DP with Immulina treatment at the higher doses compared to IC was seen as early as day 3 and persisted up to day 15. There were also statistically significant dose-variable reductions in lung density in response to Immulina. The study suggests early administration of Immulina (P or PD protocols) may enhance resistance against influenza-induced viral pneumonia. A moderate correlation between pneumonia severity scores and lung density was observed for the 25-× and 40-× images (R = 0.56 and 0.53 respectively), and a strong correlation (R = 0.68) for 400-× images.

Is Baikiain in Tara Flour a Causative Agent for the Adverse Events Associated with the Recalled Frozen French Lentil & Leek Crumbles Food Product? - A Working Hypothesis.

The French Lentil & Leek Crumbles frozen food product was recently recalled due to reports of gastrointestinal issues. So far, 393 adverse illness complaints and 133 hospitalizations have been reported from consumption of this food, and the tara (Tara spinosa) protein flour ingredient is hypothesized to be responsible. A multipronged approach resulted in identification of (S)-(-)-baikiain in tara as a compound of interest due to its abundance, possible metabolic fate, and close resemblance to irreversible inhibitors of L-pipecolate oxidase. Oral administration of baikiain in ND4 mice showed a statistically significant increase in blood ALT levels and a reduction in liver GSH.

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.

Chemical Composition Analysis, Cytotoxic, Antimicrobial and Antioxidant Activities of Physalis angulata L.: A Comparative Study of Leaves and Fruit.

Physalis angulata L. belongs to the family Solanaceae and is distributed throughout the tropical and subtropical regions. Physalis angulata leaf and fruit extracts were assessed for in vitro anticancer, antioxidant activity, and total phenolic and flavonoid content. The GC-MS technique investigated the chemical composition and structure of bioactive chemicals reported in extracts. The anticancer activity results revealed a decrease in the percentage of anticancer cells' viability in a concentration- and time-dependent way. We also noticed morphological alterations in the cells, which we believe are related to Physalis angulata extracts. Under light microscopy, we observed that as the concentration of ethanolic extract (fruit and leaves) treated HeLa cells increased, the number of cells began to decrease.

A Multitarget Approach to Evaluate the Efficacy of Aquilaria sinensis Flower Extract against Metabolic Syndrome.

Aquilaria sinensis (Lour.) Spreng is known for its resinous secretion (agarwood), often secreted in defense against injuries. We investigated the effects of A. sinensis flower extract (AF) on peroxisome proliferator-activated receptors alpha and gamma (PPARα and PPARγ), liver X receptor (LXR), glucose uptake, and lipid accumulation (adipogenesis). Activation of PPARα, PPARγ and LXR was determined in hepatic (HepG2) cells by reporter gene assays. Glucose uptake was determined in differentiated muscle (C2C12) cells using 2-NBDG (2-deoxy-2-[(7-nitro-2,1,3-benzoxadiazol-4-yl)amino]-D-glucose). Adipogenesis was determined in adipocytes (3T3-L1 cells) by Oil red O staining. At a concentration of 50 µg/mL, AF caused 12.2-fold activation of PPARα and 5.7-fold activation of PPARγ, while the activation of LXR was only 1.7-fold. AF inhibited (28%) the adipogenic effect induced by rosiglitazone in adipocytes and increased glucose uptake (32.8%) in muscle cells at 50 µg/mL. It was concluded that AF acted as a PPARα/γ dual agonist without the undesired effect of adipogenesis and exhibited the property of enhancing glucose uptake. This is the first report to reveal the PPARα/γ dual agonistic action and glucose uptake enhancing property of AF along with its antiadipogenic effect, indicating its potential in ameliorating the symptoms of metabolic syndrome.

Milk-Compositional Study of Metabolites and Pathogens in the Milk of Bovine Animals Affected with Subclinical Mastitis.

Bovine milk is an important food component in the human diet due to its nutrient-rich metabolites. However, bovine subclinical mastitis alters the composition and quality of milk. In present study, California mastitis testing, somatic cell count, pH, and electrical conductivity were used as confirmatory tests to detect subclinical mastitis. The primary goal was to study metabolome and identify major pathogens in cows with subclinical mastitis. In this study, 29 metabolites were detected in milk using gas chromatography−mass spectrometry. Volatile acidic compounds, such as hexanoic acid, hexadecanoic acid, lauric acid, octanoic acid, n-decanoic acid, tricosanoic acid, tetradecanoic acid, and hypogeic acid were found in milk samples, and these impart good flavor to the milk. Metaboanalyst tool was used for metabolic pathway analysis and principal component estimation. In this study, EC and pH values in milk were significantly increased (p < 0.0001), whereas fat (p < 0.04) and protein (p < 0.0002) significantly decreased in animals with subclinical mastitis in comparison to healthy animals. Staphylococcus aureus was the predominant pathogen found (n = 54), followed by Escherichia coli (n = 30). Furthermore, antibiotic sensitivity revealed that Staphylococcus aureus was more sensitive to gentamicin (79.6%), whereas Escherichia coli showed more sensitivity to doxycycline hydrochloride (80%).

Verona integron-encoded metallo-Beta-lactamase (VIM) and Vietnam extended-spectrum Beta-lactamase (VEB) producing pseudomonas balearica from a clinical specimen.

Pseudomonas balearica, a saprophyte found in marshy and marine habitats, is not routinely differentiated from P. aeruginosa and P. stutzeri using automated systems and hence has not been reported from clinical samples. This study describes the identification of P. balearica using MALDI-TOF-MS and 16S rDNA sequence from a patient admitted to an intensive care unit (I.C.U.). The isolate was found to be Verona integron-mediated Metallo-b-lactamase (V.I.M.), and Vietnam extended-spectrum b-lactamase (V.E.B.) producer and resistant to Ceftriaxone, Imipenem, and Tobramycin. P. balearica can be a source for horizontal transfer of blaVEB and blaVIM. Its pathogenesis has yet to be understood.

Evaluation of the hepatotoxic potential of Tinospora crispa and its isolated borapetosides B, C and F in a murine model.

The hepatotoxic potential of the methanolic extract of the stems of Tinospora crispa and of its furano-diterpenoid-borapetosides B, C, and F-was investigated in normal and health-compromised mice. Health-compromised condition was established by a single intraperitoneal injection of LPS (6 mg/kg). Two different sets of experiments were conducted to evaluate the hepatotoxic potential. A 21-day study where the mice were dosed with the extract of T. crispa (1 gm/kg b. wt./day) or standardized combination of borapetosides B, C and F (500 mg/kg b. wt.) with or without a single dose of LPS (1 gm/kg b. wt./day). In the acute toxicity study, mice were dosed with borapetosides B, C, and F (500 mg/kg b. wt.). Results showed that the ALT levels were normal and liver histopathology unaltered. No conclusive hepatotoxicity was observed in the methanolic extract or pure compounds tested under the given experimental conditions.

Box-Behnken Response Surface Design of Polysaccharide Extraction from Rhododendron arboreum and the Evaluation of Its Antioxidant Potential.

In the present investigation, the ultrasound-assisted extraction (UAE) conditions and optimization of Rhododendron arboreum polysaccharide (RAP) yield were studied by a Box-Behnken response surface design and the evaluation of its antioxidant potential. Three parameters that affect the productivity of UAE, such as extraction temperature (50-90 °C), extraction time (10-30 min), and solid-liquid ratio (1-2 g/mL), were examined to optimize the yield of the polysaccharide percentage. The chromatographic analysis revealed that the composition of monosaccharides was found to be glucose, galactose, mannose, arabinose, and fucose. The data were fitted to polynomial response models, applying multiple regression analysis with a high coefficient of determination value (R2 = 0.999). The data exhibited that the extraction parameters have significant effects on the extraction yield of polysaccharide percentage. Derringer's desirability prediction tool was attained under the optimal extraction conditions (extraction temperature 66.75 °C, extraction time 19.72 min, and liquid-solid ratio 1.66 mL/g) with a desirability value of 1 yielded the highest polysaccharide percentage (11.56%), which was confirmed through validation experiments. An average of 11.09 ± 1.65% of polysaccharide yield was obtained in optimized extraction conditions with a 95.43% validity. The in vitro antioxidant effect of polysaccharides of R. arboreum was studied. The results showed that the RAP extract exhibited a strong potential against free radical damage.

Pharmacokinetics and Tissue Distribution of Aegeline after Oral Administration in Mice.

Aegeline is claimed to be a biologically active constituent of Aegle marmelos. Preclinical studies have reported possible therapeutic potential for aegeline against obesity and diabetes. In recent years, aegeline has been added to several weight loss products. However, the consumption of aegeline-containing supplements such as OxyELITE Pro and VERSA-1 has been linked to multiple cases of acute and chronic liver failure. This study was carried out to evaluate the pharmacokinetics and tissue distribution of aegeline in ND4 mice. Two doses of aegeline, a human equivalent dose (1×) 30 mg/kg and a 10× dose (300 mg/kg), were orally administered to the mice, and blood and tissue samples were collected over 8 h. The quantitative analysis of plasma and tissue homogenates (liver, kidney, and brain) was done by UHPLC-QTOF to determine aegeline concentrations. The peak plasma level of aegeline was achieved at a Tmax of 0.5 h, indicating its rapid absorption from the gastrointestinal tract. Aegeline was not detected in the plasma at 8 h after oral administration, with a half-life of 1.4 ± 0.01 and 1.3 ± 0.07 h for the 30 and 300 mg/kg doses, respectively. The half-life of aegeline in the liver was 1.2 h and 1.7 h for 30 and 300 mg/kg doses, respectively, with a Tmax of 1.9 h, which indicates relatively fast elimination of aegeline from the liver.

Introduction of Inactivated Polio Vaccine, Withdrawal of Type 2 Oral Polio Vaccine, and Routine Immunization Strengthening in the Eastern Mediterranean Region.

The Global Polio Eradication Initiative has reduced the global incidence of polio by 99% and the number of countries with endemic polio from 125 to 3 countries. The Polio Eradication and Endgame Strategic Plan 2013-2018 (Endgame Plan) was developed to end polio disease. Key elements of the endgame plan include strengthening immunization systems using polio assets, introducing inactivated polio vaccine (IPV), and replacing trivalent oral polio vaccine with bivalent oral polio vaccine ("the switch"). Although coverage in the Eastern Mediterranean Region (EMR) with the third dose of a vaccine containing diphtheria, tetanus, and pertussis antigens (DTP3) was ≥90% in 14 countries in 2015, DTP3 coverage in EMR dropped from 86% in 2010 to 80% in 2015 due to civil disorder in multiple countries. To strengthen their immunization systems, Pakistan, Afghanistan, and Somalia developed draft plans to integrate Polio Eradication Initiative assets, staff, structure, and activities with their Expanded Programmes on Immunization, particularly in high-risk districts and regions. Between 2014 and 2016, 11 EMR countries introduced IPV in their routine immunization program, including all of the countries at highest risk for polio transmission (Afghanistan, Pakistan, Somalia, and Yemen). As a result, by the end of 2016 all EMR countries were using IPV except Egypt, where introduction of IPV was delayed by a global shortage. The switch was successfully implemented in EMR due to the motivation, engagement, and cooperation of immunization staff and decision makers across all national levels. Moreover, the switch succeeded because of the ability of even the immunization systems operating under hardship conditions of conflict to absorb the switch activities.

Alterations in microbiome of COVID-19 patients and its impact on forensic investigations.

The human microbiome is vital for maintaining human health and has garnered substantial attention in recent years, particularly in the context of the coronavirus disease 2019 (COVID-19) outbreak. Studies have underscored significant alterations in the microbiome of COVID-19 patients across various body niches, including the gut, respiratory tract, oral cavity, skin, and vagina. These changes manifest as shifts in microbiota composition, characterized by an increase in opportunistic pathogens and a decrease in beneficial commensal bacteria. Such microbiome transformations may play a pivotal role in influencing the course and severity of COVID-19, potentially contributing to the inflammatory response. This ongoing relationship between COVID-19 and the human microbiome serves as a compelling subject of research, underscoring the necessity for further investigations into the underlying mechanisms and their implications for patient health. Additionally, these alterations in the microbiome may have significant ramifications for forensic investigations, given the microbiome's potential in establishing individual characteristics. Consequently, changes in the microbiome could introduce a level of complexity into forensic determinations. As research progresses, a more profound understanding of the human microbiome within the context of COVID-19 may offer valuable insights into disease prevention, treatment strategies, and its potential applications in forensic science. Consequently, this paper aims to provide an overarching review of microbiome alterations due to COVID-19 and the associated impact on forensic applications, bridging the gap between the altered microbiome of COVID-19 patients and the challenges forensic investigations may encounter when analyzing this microbiome as a forensic biomarker.

Emerging global trends and development in forensic toxicology: A review.

This study conducts a comprehensive analysis of forensic toxicology research trends, publication patterns, author's contributions, and collaboration. Utilizing the Scopus database, we scrutinized 3259 articles across 348 journals spanning from 1975 to 2023. Analysis employed diverse software tools such as VOSviewer, RStudio, MS Excel, and MS Access to dissect various publication aspects. We observed a notable surge in publications post-2007, indicating heightened research interest. Leading contributors included the United States, Germany, and Italy, with Logan B.K. emerging as the most prolific author. Forensic Science International stood out as the primary journal, publishing 888 articles and accruing significant citations. Keyword co-occurrences such as "forensic toxicology," "forensic science," and "toxicology" underscored core thematic areas in the field. Moreover, extensive research collaboration, especially among Western nations in Europe, was evident. This study underscores the imperative for enhanced collaboration between developing and developed nations to foster further advancements in forensic science. Strengthened partnerships can catalyze innovation, facilitate knowledge dissemination, and address emerging challenges, thereby propelling the field of forensic toxicology toward new frontiers of discovery and application.

Immulina® mitigates the development of illness when administered during the prodromal period of influenza viral infection in mice (Part 2).

BACKGROUND: Immulina®, a dietary supplement derived from Limnospira (formerly Arthrospira), is being investigated as a potential agent to increase antiviral resilience. In our recently published manuscript, we described the effects of Immulina® on influenza when taken daily, beginning before infection (prophylaxis) or after the onset of clinical symptoms of viral illness (therapeutic). However, the benefit of Immulina® in infected individuals before the manifestation of any symptoms (prodromal) has not been investigated yet. PURPOSE: To evaluate Immulina®'s potential use to increase the host antiviral immune response using a prodromal therapy regime. STUDY DESIGN: The efficacy of Immulina® extract was evaluated in rodents using a prodromal protocol (test material administered prior to the emergence of viral illness symptoms). METHODS: Immulina® (25, 50 and 100 mg/kg body weight) was orally administered to both genders of mice, 2 h following influenza A viral infection, and continued daily for 14 days. RESULTS: Compared to the infected control mice, animals fed Immulina® exhibited statistically significant reduction in the emergence of various physical symptoms of viral-induced illness and decreased viral RNA levels. The effects are likely mediated through the host immune system since the level of various cytokines (IL-6 and IFN-γ) were significantly increased in lung tissue. CONCLUSION: This study, together with our previous paper, indicate that Immulina® was most effective at enhancing immune antiviral resilience if administered before or soon after initial infection. The data generated can be used to guide additional research using human subjects.

Prophylactic and therapeutic mouse models for evaluating immunologic resilience to infection with influenza virus by Immulina® (Part 1).

BACKGROUND: Illness resulting from influenza is a global health problem that has significant adverse socioeconomic impact. Although various strategies such as flu vaccination have beneficial effects, the risk of this illness has not been eliminated. The use of botanicals may provide a complementary approach by enhancement of the host antiviral immune response. PURPOSE: Generate preclinical data using rodent models to determine the most effective utility of a Limnospira (formerly Arthrospira)-derived oral supplement (Immulina®) for enhancing host immunity to improve antiviral resilience. STUDY DESIGN: Two non-lethal mouse models (prophylactic and therapeutic) were used to evaluate the impact of Immulina® on increasing host resilience against experimental influenza infection. METHODS: Mice were fed Immulina® only for the 2 weeks prior to viral infection (prophylactic regime) or starting 3 days post-viral infection (at the onset of symptoms, therapeutic design). Three doses of Immulina® were evaluated in each model using both female and male mice. RESULTS: Significant protective effect of Immulina® against viral illness was observed in the prophylactic model (improved clinical scores, less body weight loss, decreased lung/body weight ratio, lower lung viral load, and increased lung IFN-γ and IL-6). Substantially less (minimal) protective effect was observed in the therapeutic model. CONCLUSION: This study demonstrates that Immulina® exerts a protective effect against influenza illness when administered using a prophylactic regime and may not be effective if given after the onset of symptoms. The results will help to optimally design future clinical trials.

The effect of mass immunisation campaigns and new oral poliovirus vaccines on the incidence of poliomyelitis in Pakistan and Afghanistan, 2001-11: a retrospective analysis.

BACKGROUND: Pakistan and Afghanistan are two of the three remaining countries yet to interrupt wild-type poliovirus transmission. The increasing incidence of poliomyelitis in these countries during 2010-11 led the Executive Board of WHO in January, 2012, to declare polio eradication a "programmatic emergency for global public health". We aimed to establish why incidence is rising in these countries despite programme innovations including the introduction of new vaccines. METHODS: We did a matched case-control analysis based on a database of 46,977 children aged 0-14 years with onset of acute flaccid paralysis between Jan 1, 2001, and Dec 31, 2011. The vaccination history of children with poliomyelitis was compared with that of children with acute flaccid paralysis due to other causes to estimate the clinical effectiveness of oral poliovirus vaccines (OPVs) in Afghanistan and Pakistan by conditional logistic regression. We estimated vaccine coverage and serotype-specific vaccine-induced population immunity in children aged 0-2 years and assessed their association with the incidence of poliomyelitis over time in seven regions of Afghanistan and Pakistan. FINDINGS: Between Jan 1, 2001, and Dec 31, 2011, there were 883 cases of serotype 1 poliomyelitis (710 in Pakistan and 173 in Afghanistan) and 272 cases of poliomyelitis serotype 3 (216 in Pakistan and 56 in Afghanistan). The estimated clinical effectiveness of a dose of trivalent OPV against serotype 1 poliomyelitis was 12·5% (95% CI 5·6-18·8) compared with 34·5% (16·1-48·9) for monovalent OPV (p=0·007) and 23·4% (10·4-34·6) for bivalent OPV (p=0·067). Bivalent OPV was non-inferior compared with monovalent OPV (p=0·21). Vaccination coverage decreased during 2006-11 in the Federally Administered Tribal Areas (FATA), Balochistan, and Khyber Pakhtunkhwa in Pakistan and in southern Afghanistan. Although partially mitigated by the use of more effective vaccines, these decreases in coverage resulted in lower vaccine-induced population immunity to poliovirus serotype 1 in FATA and Balochistan and associated increases in the incidence of poliomyelitis. INTERPRETATION: The effectiveness of bivalent OPV is comparable with monovalent OPV and can therefore be used in eradicating serotype 1 poliomyelitis whilst minimising the risks of serotype 3 outbreaks. However, decreases in vaccination coverage in parts of Pakistan and southern Afghanistan have severely limited the effect of this vaccine. FUNDING: Poliovirus Research subcommittee of WHO, Royal Society, and Medical Research Council.

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.