Hesperidin Supplementation Improves Altered PON -1, LDL Oxidation, Inflammatory Response and Hepatic Function in an Experimental Rat Model of Hyperlipidemia.

In this study, we have examined the effect of hesperidin on rats fed on an experimental high-fat diet. Male Wistar rats were given a high-fat diet orally for one month for developing an HFD (High fat- diet) model. Rats were also supplemented with hesperidin (100 mg/kg body weight) for one month. We determined serum LDL (Low-density lipoprotein) oxidation, Paraoxonase-1 (PON-1) activity, and histopathological profile of the liver. Inflammatory cytokines levels were also measured in serum. HFD induced significant changes in LDL oxidation and PON-1 activity. Liver tissue histopathology and gene expression of inflammatory markers (Il-6(Interleukin-6), TNF- alpha (Tumor necrosis factor alpha), NF-KB (Nuclear factor kappa B) show that significant changes occur in the hyperlipidemic model of rats. We also show that hesperidin can effectively improve plasma antioxidant, LDL oxidation, and inflammatory cytokine expression in rats already subjected to hyperlipidemic stress. We conclude that hesperidin may protect the liver from oxidative stress by improving hepatic function.

A Potential Link Between Visceral Obesity and Risk of Alzheimer's Disease.

Alzheimer's disease (AD) is the most common type of dementia characterized by the deposition of amyloid beta (Aß) plaques and tau-neurofibrillary tangles in the brain. Visceral obesity (VO) is usually associated with low-grade inflammation due to higher expression of pro-inflammatory cytokines by adipose tissue. The objective of the present review was to evaluate the potential link between VO and the development of AD. Tissue hypoxia in obesity promotes tissue injury, production of adipocytokines, and release of pro-inflammatory cytokines leading to an oxidative-inflammatory loop with induction of insulin resistance. Importantly, brain insulin signaling is involved in the pathogenesis of AD and lower cognitive function. Obesity and enlargement of visceral adipose tissue are associated with the deposition of Aß. All of this is consonant with VO increasing the risk of AD through the dysregulation of adipocytokines which affect the development of AD. The activated nuclear factor kappa B (NF-κB) pathway in VO might be a potential link in the development of AD. Likewise, the higher concentration of advanced glycation end-products in VO could be implicated in the pathogenesis of AD. Taken together, different inflammatory signaling pathways are activated in VO that all have a negative impact on the cognitive function and progression of AD except hypoxia-inducible factor 1 which has beneficial and neuroprotective effects in mitigating the progression of AD. In addition, VO-mediated hypoadiponectinemia and leptin resistance may promote the progression of Aß formation and tau phosphorylation with the development of AD. In conclusion, VO-induced AD is mainly mediated through the induction of oxidative stress, inflammatory changes, leptin resistance, and hypoadiponectinemia that collectively trigger Aß formation and neuroinflammation. Thus, early recognition of VO by visceral adiposity index with appropriate management could be a preventive measure against the development of AD in patients with VO.

Bioactive Compounds, Pharmacological Actions, and Pharmacokinetics of Genus Acacia.

Plants are a promising source of bioactive compounds that can be used to tackle many emerging diseases both infectious and non-infectious. Among different plants, Acacia is a very large genus and exhibits a diverse array of bioactive agents with remarkable pharmacological properties against different diseases. Acacia, a herb found all over the world, contains approximately more than 1200 species of the Fabaceae family. In the present review, we have collected detailed information on biochemical as well as pharmacological properties. The data were retrieved using different databases, such as Elsevier, PubMed, Science Direct, Google Scholar, and Scopus, and an extensive literature survey was carried out. Studies have shown that Acacia possesses several secondary metabolites, including amines, cyanogenic glycosides, flavonoids, alkaloids, seed oils, cyclitols, fluoroacetate, gums, non-protein amino acids, diterpenes, fatty acids, terpenes, hydrolyzable tannins, and condensed tannins. These compounds exhibit a wide range of pharmaceutical applications such as anti-inflammatory, antioxidant, antidiarrheal, antidiabetic, anticancer, antiviral, liver protective effects, and so on. Thus, the literature shows the tremendous phytochemical impact of the genus Acacia in medicine. Overall, we recommend that more research should be conducted on the medicinal value and isolation and purification of the effective therapeutic agents from Acacia species for the treatment of various ailments.

Role of NQO1 gene involvement and susceptibility of T2DM among Saudi Arabia population.

NQO1 disruption enhances susceptibility to oxidative stress during hyperglycemia. As a significant contributor to the development and progression of diabetes.Oxidative stress has been linked to a number of symptoms, including hyperglycemia, reactive oxygen species buildup, high blood pressure, and the expression of inflammatory markers. Therefore, present research work aimed to evaluate the genetic abnormality of NQO1 gene polymorphism, expression and vitamin-D level assessment among the T2DM patients. Present research study included 100 newly diagnosed T2DM cases and 100 healthy individuals as healthy control. Total RNA was extracted from the whole blood using the Trizol method and further cDNA was synthesized and expression was evaluated. Significant difference in NQO1 genotypes distribution among the T2DM patients and healthy controls (p=0.04). Compared to NQO1 CC wild type genotype, NQO1 CT heterozygous genotype had odds ratio of 1.96 (1.08-3.55), and NQO1 TT mutant type genotype had odds ratio of 3.31 (0.61-17.77). Significantly decreased expression of NQO1 mRNA was observed with heterozygous CT (p<0.0001) and homozygous mutant TT genotype (p=0.0004), compared to homozygous wild type CC genotype. NQO1 mRNA expression level was also compared with respect to vitamin-D level among the T2DM patients. T2DM patients with vitamin-D deficiency had 1.83 fold NQO1 mRNA expression while vitamin-D insufficient and sufficient T2DM cases had 3.31 fold (p<0.0001) and 3.70 fold (p<0.0001) NQO1 mRNA expression. Results concluded that NQO1 (C609T) CT and TT genotypes played significant role in worseness of type II diabetes mellitus and decreased expression of NQO1 mRNA expression could be important factor for disease worseness as well as hypermethylation could be factor for decreased expression leading to disease severity. As the decreased NQO1 mRNA expression with heterozygous CT and mutant TT genotype as well as associated with vitamin-D deficiency may contribute to disease progression.

Pesticides impacts on human health and the environment with their mechanisms of action and possible countermeasures.

Pesticides are chemical constituents used to prevent or control pests, including insects, rodents, fungi, weeds, and other unwanted organisms. Despite their advantages in crop production and disease management, the use of pesticides poses significant hazards to the environment and public health. Pesticide elements have now perpetually entered our atmosphere and subsequently contaminated water, food, and soil, leading to health threats ranging from acute to chronic toxicities. Pesticides can cause acute toxicity if a high dose is inhaled, ingested, or comes into contact with the skin or eyes, while prolonged or recurrent exposure to pesticides leads to chronic toxicity. Pesticides produce different types of toxicity, for instance, neurotoxicity, mutagenicity, carcinogenicity, teratogenicity, and endocrine disruption. The toxicity of a pesticide formulation may depend on the specific active ingredient and the presence of synergistic or inert compounds that can enhance or modify its toxicity. Safety concerns are the need of the hour to control contemporary pesticide-induced health hazards. The effectiveness and implementation of the current legislature in providing ample protection for human health and the environment are key concerns. This review explored a comprehensive summary of pesticides regarding their updated impacts on human health and advanced safety concerns with legislation. Implementing regulations, proper training, and education can help mitigate the negative impacts of pesticide use and promote safer and more sustainable agricultural practices.

Ganoderma lucidum: Multifaceted mechanisms to combat diabetes through polysaccharides and triterpenoids: A comprehensive review.

Diabetes is a chronic metabolic disorder. Diabetes complications can affect many organs and systems in the body. Ganoderma lucidum (G. lucidum) contains various compounds that have been studied for their potential antidiabetic effects, including polysaccharides, triterpenoids (ganoderic acids, ganoderol B), proteoglycans, and G. lucidum extracts. G. lucidum polysaccharides (GLPs) and triterpenoids have been shown to act through distinct mechanisms, such as improving glucose metabolism, modulating the mitogen-activated protein kinase (MAPK) system, inhibiting the nuclear factor-kappa B (NF-κB) pathway, and protecting the pancreatic beta cells. While GLPs exhibit a significant role in controlling diabetic nephropathy and other associated complications. This review states the G. lucidum antidiabetic mechanisms of action and potential biologically active compounds that contribute to diabetes management and associated complications. To make G. lucidum an appropriate replacement for the treatment of diabetes with fewer side effects, more study is required to completely comprehend the number of physiologically active compounds present in it as well as the underlying cellular mechanisms that influence their effects on diabetes.

Exercise modulates APOE expression in brain cortex of female APOE3 and APOE4 targeted replacement mice.

Apolipoprotein E (ApoE) is the main cholesterol carrier of the brain and the ε4 gene variant (APOE4) is the most prevalent genetic risk factor for Alzheimer's disease (AD), increasing risk up to 15-fold. Several studies indicate that APOE4 modulates critical factors for neuronal function, including brain-derived neurotrophic factor (BDNF) and peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). Both proteins show exercise-induced upregulation, which is presumed to mediate many of the beneficial effects of physical activity including improved cognition; however, there is variability in results between individuals potentially in-part due to genetic variations including APOE isoform. This study aimed to determine if the two most prevalent human APOE isoforms influence adaptive responses to exercise-training. Targeted replacement mice, homozygous for either APOE3 or APOE4 were randomized into exercised and sedentary groups. Baseline locomotor function and voluntary wheel-running behavior was reduced in APOE4 mice. Exercised groups were subjected to daily treadmill running for 8 weeks. ApoE protein in brain cortex was significantly increased by exercise in both genotypes. PGC-1α mRNA levels in brain cortex were significantly lower in APOE4 mice, and only tended to increase with exercise in both genotypes. Hippocampal BDNF protein were similar between genotypes and was not significantly modulated by treadmill running. Behavioral and biochemical variations between APOE3 and APOE4 mice likely contribute to the differential risk for neurological and vascular diseases and the exercise-induced increase in ApoE levels suggests an added feature of the potential efficacy of physical activity as a preventative and therapeutic strategy for neurogenerative processes in both genotypes.

Formulation Development and Investigations on Therapeutic Potential of Nanogel from Beta vulgaris L. Extract in Testosterone-Induced Alopecia.

The objective of the present study was to develop a novel nanogel containing Beta vulgaris L. hydroalcoholic extract and assess its efficacy for treating testosterone-induced alopecia. Beta vulgaris L. leaf hydroalcoholic extract nanogel (BVEN) was prepared by ionic gelation method, incorporated in carbopol 934 gel. Optimization of particle size and entrapment efficiency as the responses was carried out by central composite design response surface methodology. Prepared nanoparticles were evaluated for entrapment efficiency, particle size, zeta potential, polydispersity index, Fourier transform infrared spectroscopy, transmission electron microscopy, and differential scanning calorimetry. Nanogel was evaluated for pH, colour, appearance and homogeneity, viscosity, spreadability, in vitro release study, and stability studies. Further, 2.5% and 5% BVEN were also evaluated for antialopecic activity in Swiss albino mice by using parameters as hair growth initiation, testosterone content, total protein, prostate weight measurement, hair follicular density, anagen/telogen ratio, and histopathological studies. The resulting nanoparticles had better entrapment efficiency with particle size of 274 nm, polydispersity index of 0.259, and zeta potential of +28.8. BVEN pH 6.5, drug content, i.e., quercetin 99.84 ± 1.30% and stigmasterol 99.89 ± 1.52%, spreadability 20.3 ± 0.5925 g cm/sec, and viscosity 110 × 105 cps were observed. Stability studies showed that nanogel was stable at 4°C ± 2°C/60% ± 5% RH. It was found that 5% BVEN showed better antialopecic activity as compared to 2.5% BVEN.

Dietary patterns and their associations with glycemic control among type 2 diabetic patients in Jazan, Saudi Arabia: A cross-sectional study.

Diabetes is an important global health concern. According to the World Health Organization, the Kingdom of Saudi Arabia (KSA) has 2.8 to 4.3 million diabetic patients between the ages of 27 to 60 in the year 2022. Medical nutrition therapy an essential component of diabetes management, helps improve diabetes outcomes by assisting patients in achieving a target glycated hemoglobin (HbA1c) level of <7. This study aimed to describe the pattern of food consumption in the study population and determine its association with glycemic control. This was a cross-sectional study among health facility attendees at the Endocrinology and Diabetes Center (EDC) in Jazan, KSA. A total of 315 patients with type 2 diabetes (T2D) were enrolled using a systematic random sampling technique. Sociodemographic and dietary habit information gathered through face-to-face interviews, anthropometric measurements, and HbA1c were collected from medical records. Participants were mostly females (55.6%), and more than half of them were above 50 years of age. More than 90% of the patients had poor HbA1c levels, and 2-thirds of the patients were overweight and obese (43.8% and 37.1%, respectively). The most consumed foods were bread (8 times/week) and coffee/tea and vegetables (7 times per week), and the least consumed was soda beverages (once/week). Multivariate logistic regression revealed that the consumption of fruits (consumed 5 times/week) significantly decreased HbA1c, while the consumption of pastries/pizza (consumed twice/week) significantly increased it. The pattern of consumption of fruits and vegetables in the study population conformed to the recommended levels, and that of fruits showed a statistically significant association with the control of HbA1c. Another food item that has a significant negative effect on HbA1c is pastries/pizza. Further studies that include more potentially confounding variables, such as treatment type, are needed.

Advanced glycation end product signaling and metabolic complications: Dietary approach.

Advanced glycation end products (AGEs) are a heterogeneous collection of compounds formed during industrial processing and home cooking through a sequence of nonenzymatic glycation reactions. The modern western diet is full of heat-treated foods that contribute to AGE intake. Foods high in AGEs in the contemporary diet include processed cereal products. Due to industrialization and marketing strategies, restaurant meals are modified rather than being traditionally or conventionally cooked. Fried, grilled, baked, and boiled foods have the greatest AGE levels. Higher AGE-content foods include dry nuts, roasted walnuts, sunflower seeds, fried chicken, bacon, and beef. Animal proteins and processed plant foods contain furosine, acrylamide, heterocyclic amines, and 5-hydroxymethylfurfural. Furosine (2-furoil-methyl-lysine) is an amino acid found in cooked meat products and other processed foods. High concentrations of carboxymethyl-lysine, carboxyethyl-lysine, and methylglyoxal-O are found in heat-treated nonvegetarian foods, peanut butter, and cereal items. Increased plasma levels of AGEs, which are harmful chemicals that lead to age-related diseases and physiological aging, diabetes, and autoimmune/inflammatory rheumatic diseases such as systemic lupus erythematosus and rheumatoid arthritis. AGEs in the pathophysiology of metabolic diseases have been linked to individuals with diabetes mellitus who have peripheral nerves with high amounts of AGEs and diabetes has been linked to increased myelin glycation. Insulin resistance and hyperglycemia can impact numerous human tissues and organs, leading to long-term difficulties in a number of systems and organs, including the cardiovascular system. Plasma AGE levels are linked to all-cause mortality in individuals with diabetes who have fatal or nonfatal coronary artery disease, such as ventricular dysfunction. High levels of tissue AGEs are independently associated with cardiac systolic dysfunction in diabetic patients with heart failure compared with diabetic patients without heart failure. It is widely recognized that AGEs and oxidative stress play a key role in the cardiovascular complications of diabetes because they both influence and are impacted by oxidative stress. All chronic illnesses involve protein, lipid, or nucleic acid modifications including crosslinked and nondegradable aggregates known as AGEs. Endogenous AGE formation or dietary AGE uptake can result in additional protein modifications and stimulation of several inflammatory signaling pathways. Many of these systems, however, require additional explanation because they are not entirely obvious. This review summarizes the current evidence regarding dietary sources of AGEs and metabolism-related complications associated with AGEs.

Insights on benzodiazepines' potential in Alzheimer's disease.

Alzheimer's disease (AD) is the most frequent type of dementia characterized by the deposition of amyloid beta (Aß) plaque and tau-neurofibrillary tangles (TNTs) in the brain. AD is associated with the disturbances of various neurotransmitters including gamma-aminobutyric acid (GABA). Of note, GABA is reduced in AD, and restoration of GABA effect by benzodiazepines (BDZs) may improve AD outcomes. However, BDZs may adversely affect cognitive functions chiefly in elderly AD patients with sleep disorders. Besides, there is a controversy regarding the use of BDZs in AD. Consequently, the objective of the present review was to disclose the possible role of BDZs on the pathogenesis of AD that might be beneficial, neutral, or detrimental effects on AD. Prolonged use of intermediate-acting BDZ lorazepam exerts amnesic effects due to attenuation of synaptic plasticity and impairment of recognition memory. However, BDZs may have a protective effect against the development of AD by reducing tau phosphorylation, neuroinflammation, and progression of AD neuropathology. On the other side, other findings highlighted that extended use of BDZs was not associated with the development of AD. In conclusion, there are controversial points concerning the use of BDZs and the risk for the progression of AD. Thus, preclinical, and clinical studies are essential in this regard.

Pros and cons for statins use and risk of Parkinson's disease: An updated perspective.

Parkinson's disease (PD) is the second most frequent neurodegenerative brain disease (NBD) after Alzheimer's disease (AD). Statins are the most common lipid-lowering agents used in the management of dyslipidemia and the prevention of primary and secondary cardiovascular diseases (CVD) events. In addition, there is a controversial point regarding the role of serum lipids in the pathogenesis of PD. In this bargain, as statins reduce serum cholesterol so they affect the PD neuropathology in bidirectional ways either protective or harmful. Statins are not used in the management of PD, but they are frequently used in the cardiovascular disorders commonly associated with PD in the elderly population. Therefore, the use of statins in that population may affect PD outcomes. Concerning the potential role of statins on PD neuropathology, there are conflicts and controversies either protective against the development of PD or harmful by increasing the risk for the development of PD. Therefore, this review aimed to clarify the precise role of statins in PD regarding the pros and cons from published studies. Many studies suggest a protective role of statins against PD risk through the modulation of inflammatory and lysosomal signaling pathways. Nevertheless, other observations suggest that statin therapy may increase PD risk by diverse mechanisms including reduction of CoQ10. In conclusion, there are strong controversies regarding the protective role of statins in PD neuropathology. Therefore, retrospective and prospective studies are necessary in this regard.

Ganoderma lucidum: Novel Insight into Hepatoprotective Potential with Mechanisms of Action.

Ganoderma lucidum (G. lucidum) has been widely used for its health benefits as an edible and traditional medicinal mushroom for thousands of years in Asian countries. It is currently used as a nutraceutical and functional food owing to its major bioactive compounds, polysaccharides and triterpenoids. G. lucidum exhibits a broad range of hepatoprotective impacts in various liver disorders, such as hepatic cancer, nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease, hepatitis B, hepatic fibrosis, and liver injury induced by carbon tetrachloride (CCl4) and α-amanitin. G. lucidum protects the liver through a broad range of mechanisms that include the modulation of liver Phase I and II enzymes, the suppression of ß-glucuronidase, antifibrotic and antiviral actions, the regulation of the production of nitric oxide (NO), the maintenance of hepatocellular calcium homeostasis, immunomodulatory activity, and scavenging free radicals. G. lucidum could signify an encouraging approach for the management of various chronic hepatopathies, and its potential mechanisms make it a distinctive agent when used alone or with other drugs and applied as a functional food, nutraceutical supplement, or adjuvant to modern medicine. This review summarizes the hepatoprotective properties of G. lucidum with its various mechanisms of action on different liver ailments. Biologically active substances derived from G. lucidum are still being studied for their potential benefits in treating different liver ailments.

Apigetrin-enriched Pulmeria alba extract prevents assault of STZ on pancreatic ß-cells and neuronal oxidative stress with concomitant attenuation of tissue damage and suppression of inflammation in the brain of diabetic rats.

In the present study, in vitro, in vivo, and in silico models were used to evaluate the therapeutic potential of Pulmeria alba methanolic (PAm) extract, and we identified the major phytocompound, apigetrin. Our in vitro studies revealed dose-dependent increased glucose uptake and inhibition of α-amylase (50% inhibitory concentration (IC50)= 217.19 µg/mL), antioxidant (DPPH, ferric-reducing activity of plasma (FRAP), and lipid peroxidation (LPO) [IC50 = 103.23, 58.72, and 114.16 µg/mL respectively]), and anti-inflammatory potential (stabilizes human red blood cell (HRBC) membranes, and inhibits proteinase and protein denaturation [IC50 = 143.73, 131.63, and 198.57 µg/mL]) by the PAm extract. In an in vivo model, PAm treatment reversed hyperglycemia and attenuated insulin deficiency in rats with streptozotocin (STZ)-induced diabetes. A post-treatment tissue analysis revealed that PAm attenuated neuronal oxidative stress, neuronal inflammation, and neuro-cognitive deficiencies. This was evidenced by increased levels of antioxidants enzymes (superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH)), and decreased malondialdehyde (MDA), proinflammatory markers (cyclooxygenase 2 (COX2), nuclear factor (NF)-κB and nitric oxide (NOx)), and acetylcholinesterase (AChE) activities in the brain of PAm-treated rats compared to the STZ-induced diabetic controls. However, no treatment-related changes were observed in levels of neurotransmitters, including serotonin and dopamine. Furthermore, STZ-induced dyslipidemia and alterations in serum biochemical markers of hepatorenal dysfunction were also reversed by PAm treatment. Extract characterization identified apigetrin (retention time: 21,227 s, 30.48%, m/z: 433.15) as the major bioactive compound in the PAm extract. Consequently, we provide in silico insights into the potential of apigetrin to target AChE/COX-2/NOX/NF-κB Altogether the present study provides preclinical evidence of the therapeutic potential of the apigetrin-enriched PAm extract for treating oxidative stress and neuro-inflammation associated with diabetes.

Arsenic Exposure through Dietary Intake and Associated Health Hazards in the Middle East.

Dietary arsenic (As) contamination is a major public health issue. In the Middle East, the food supply relies primarily on the import of food commodities. Among different age groups the main source of As exposure is grains and grain-based food products, particularly rice and rice-based dietary products. Rice and rice products are a rich source of core macronutrients and act as a chief energy source across the world. The rate of rice consumption ranges from 250 to 650 g per day per person in South East Asian countries. The source of carbohydrates through rice is one of the leading causes of human As exposure. The Gulf population consumes primarily rice and ready-to-eat cereals as a large proportion of their meals. Exposure to arsenic leads to an increased risk of non-communicable diseases such as dysbiosis, obesity, metabolic syndrome, diabetes, chronic kidney disease, chronic heart disease, cancer, and maternal and fetal complications. The impact of arsenic-containing food items and their exposure on health outcomes are different among different age groups. In the Middle East countries, neurological deficit disorder (NDD) and autism spectrum disorder (ASD) cases are alarming issues. Arsenic exposure might be a causative factor that should be assessed by screening the population and regulatory bodies rechecking the limits of As among all age groups. Our goals for this review are to outline the source and distribution of arsenic in various foods and water and summarize the health complications linked with arsenic toxicity along with identified modifiers that add heterogeneity in biological responses and suggest improvements for multi-disciplinary interventions to minimize the global influence of arsenic. The development and validation of diverse analytical techniques to evaluate the toxic levels of different As contaminants in our food products is the need of the hour. Furthermore, standard parameters and guidelines for As-containing foods should be developed and implemented.

Factor analysis - Eating patterns among khat chewers.

Objectives: Khat is a green leafy plant that grows in many countries, including in the southwest of Saudi Arabia. It is estimated that one third of the people in Jazan chew khat, and the majority are males. The objective of this study was to identify the dietary patterns among khat-chewing students of Jazan University. Methods: A cross-sectional descriptive analytical study was conducted at Jazan University. A total of 620 khat-chewing students participated in the study. Food intakes were collected through a food frequency questionnaire (FFQ). Dietary patterns were assessed by exploratory factor analysis based on the intake of the 17 food groups. A principal component analysis for factor extraction followed by varimax rotation was used. Results: Based on the Kaiser criterion and the scree plot, factor analysis identified three patterns that accounted for 70.2% of the variability within the sample. The first factor (starch) was characterized by rice, bread, pizza, potato, traditional food, burger, snacks, and hot drinks. The second factor (meat products/fruit) included meat products, poultry, fish, cool drinks, and fruit. The third factor (dairy products/vegetables) included dairy, low-fat and fat-free dairy, fat, and vegetables. Conclusion: The present study identified dietary patterns among khat-chewing students via factor analysis. It is now important to identify a correlation between specific patterns and health status to implement dietary interventions.

Untargeted Metabolomics Approach of Cross-Adaptation in Salmonella Enterica Induced by Major Compounds of Essential Oils.

Cross-adaptation phenomena in bacterial populations, induced by sublethal doses of antibacterial solutions, are a major problem in the field of food safety. In this regard, essential oils and their major compounds appear as an effective alternative to common sanitizers in food industry environments. The present study aimed to evaluate the untargeted metabolomics perturbations of Salmonella enterica serovar Enteritidis that has been previously exposed to the sublethal doses of the major components of essential oils: cinnamaldehyde, citral, and linalool (CIN, CIT, and LIN, respectively). Cinnamaldehyde appeared to be the most efficient compound in the assays evaluating the inhibitory effects [0.06% (v/v) as MBC]. Also, preliminary tests exhibited a phenotype of adaptation in planktonic and sessile cells of S. Enteritidis when exposed to sublethal doses of linalool, resulting in tolerance to previously lethal concentrations of citral. A metabolomics approach on S. Enteritidis provided an important insight into the phenomenon of cross-adaptation induced by sublethal doses of major compounds of some essential oils. In addition, according to the results obtained, when single molecules were used, many pathways may be involved in bacterial tolerance, which could be different from the findings revealed in previous studies regarding the use of phytocomplex of essential oils. Orthogonal projection to latent structures (OPLS) proved to be an interesting predictive model to demonstrate the adaptation events in pathogenic bacteria because of the global engagement to prevent and control foodborne outbreaks.

Role of metabolizing MTHFR gene polymorphism (rs1801133) and its mRNA expression among Type 2 Diabetes.

Objective: Type 2 Diabetes is a glucose metabolic disorder occurred by insulin insensitivity in which folate metabolism plays an important role. it is believed that polymorphism of Methylenetetrahydrofolate reductase (MTHFR) C677T linked with type 2 diabetes mellitus. However, results are conflicted. therefore, in this study we re-examine the relationship between MTHFR C677T in type 2 diabetes mellitus patients. Methods: Present research work included 100 newly diagnosed type 2 diabetic mellitus (T2DM) cases and 100 healthy individuals. After the blood sample collection all the biochemical parameters were evaluated among the T2DM cases and healthy individuals. DNA and RNA extraction from whole blood was done to study the MTHFR gene polymorphism by allele specific polymerase chain reaction method and its expression analysis was done by quantitative real time polymerase chain reaction method. Results: The significant difference was observed in genotype distribution among case and control group (p=0.0002). Compared with wildtype CC genotype, CT heterozygous (OR=2.95, 95% Cl=1.62-5.38) and TT homozygous (OR=3.20, CI=1.79-5.73) suggest to have effect of MTHFR polymorphism on type 2 mellitus risk. Moreover, relative MTHFR mRNA expression was found for wild type CC genotype 3.02-fold, CT heterozygous genotype 2.57 fold and mutant TT homozygous genotype 0.50-fold which is down regulated (p<0.0001). Conclusion: Our results indicates that the polymorphism in MTHFR C677T plays significant role in type II diabetes risk. MTHFR CT heterozygous and mutant TT genotype showed reduced mRNA expression among the T2DM patients. However, large scale case-control studies are needed to strengthen such conclusion in the future.

Pharmacological Efficacy of Probiotics in Respiratory Viral Infections: A Comprehensive Review.

Mortality and morbidity from influenza and other respiratory viruses are significant causes of concern worldwide. Infections in the respiratory tract are often underappreciated because they tend to be mild and incapacitated. On the other hand, these infections are regarded as a common concern in clinical practice. Antibiotics are used to treat bacterial infections, albeit this is becoming more challenging since many of the more prevalent infection causes have acquired a wide range of antimicrobial resistance. Resistance to frontline treatment medications is constantly rising, necessitating the development of new antiviral agents. Probiotics are one of several medications explored to treat respiratory viral infection (RVI). As a result, certain probiotics effectively prevent gastrointestinal dysbiosis and decrease the likelihood of secondary infections. Various probiotic bacterias and their metabolites have shown immunomodulating and antiviral properties. Unfortunately, the mechanisms by which probiotics are effective in the fight against viral infections are sometimes unclear. This comprehensive review has addressed probiotic strains, dosage regimens, production procedures, delivery systems, and pre-clinical and clinical research. In particular, novel probiotics' fight against RVIs is the impetus for this study. Finally, this review may explore the potential of probiotic bacterias and their metabolites to treat RVIs. It is expected that probiotic-based antiviral research would be benefitted from this review's findings.

Combining the HSP90 inhibitor TAS-116 with metformin effectively degrades the NLRP3 and attenuates inflammasome activation in rats: A new management paradigm for ulcerative colitis.

Ulcerative colitis (UC) is a prevalent type of inflammatory bowel diseases that may predispose patients to acquire colitis-related cancer if treatment was not effective. Despite the presence of an array of established treatment options, current modalities are not successful for a substanial number of patients. The activation of the NLRP3 inflammasome is critical in the development of inflammatory processes in the colon. Additionally, the regulation of NLRP3 via HSP90 inhibition is a potential target to treat UC. Moreover, during inflammation, autophagy allows the turnover of malfunctioning proteins and therefore stands as a viable strategy for inactivating NLRP3 inflammasomes and halting hyperinflammation. Herein, we evaluated the effect of autophagy induction using metformin in the context of HSP90 inhibition by TAS-116 in the dextran sodium sulfate (DSS)-induced UC in rats. We revealed that TAS-116-induced interruption of the protein complex containing HSP90 and NLRP3 might hamper and delay the start of the inflammatory cascade ensued by the NLRP3 inflammasome oligomerization. In such circumstances, the unprotected NLRP3 is subjected to autophagic degradation in an environment of metformin-promoted autophagic signaling. As a result, such dynamic synergy was efficient in combating colon damage and immune-cell infiltration. This was confirmed by the macroscopic and microscopic investigations. Further, biochemical analysis revealed subdued inflammation cascade and oxidative injury. Therefore, simultaneous administration of TAS-116 and metformin is a new management paradigm aimed at inducing malfunction in the NLRP3 followed by augmenting its autophagic degradation, respectively. However, further studies should be conducted to assess the reliability and consistency of this novel approach.