The role of MoS2 QDs coated with DSPE-PEG-TPP in the protection of protein secondary structure of the brain tissues in an Alzheimer's disease model.

In this investigation, we have explored the protective capacity of MoS2 QDs coated with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol) -2000] (DSPE-PEG) linked with (3-carboxypropyl) triphenylphosphonium-bromide (TPP), on the secondary structure of proteins in Alzheimer's disease (AD)-affected brain tissues. Using a cohort of fifteen male SWR/J mice, we establish three groups: a control group, a second group induced with AD through daily doses of AlCl3 and D-galactose for 49 consecutive days, and a third group receiving the same AD-inducing doses but treated with DSPE-PEG-TPP-MoS2 QDs. Brain tissues are meticulously separated from the skull, and their molecular structures are analyzed via FTIR spectroscopy. Employing the curve fitting method on the amide I peak, we delve into the nuances of protein secondary structure. The FTIR analysis reveals a marked increase in ß-sheet structures and a concurrent decline in turn and α-helix structures in the AD group in comparison to the control group. Notably, no statistically significant differences emerge between the treated and control mice. Furthermore, multivariate analysis of the FTIR spectral region, encompassing protein amide molecular structures, underscores a remarkable similarity between the treated and normal mice. This study elucidates the potential of DSPE-PEG-TPP-MoS2 QDs in shielding brain tissue proteins against the pathogenic influences of AD.

Modified TPP-MoS2 QD Blend as a Bio-Functional Model for Normalizing Microglial Dysfunction in Alzheimer's Disease.

Alzheimer's disease (AD) is the most prevalent neurodegenerative disease of old age. Accumulation of ß-amyloid peptide (Aß) and mitochondrial dysfunction results in chronic microglial activation, which enhances neuroinflammation and promotes neurodegeneration. Microglia are resident macrophages of the brain and spinal cord which play an important role in maintaining brain homeostasis through a variety of phenotypes, including the pro-inflammatory phenotype and anti-inflammatory phenotypes. However, persistently activated microglial cells generate reactive species and neurotoxic mediators. Therefore, inhibitors of microglial activation are seen to have promise in AD control. The modified TPP/MoS2 QD blend is a mitochondrion-targeted nanomaterial that exhibits cytoprotective activities and antioxidant properties through scavenging free radicals. In the present study, the cell viability and cytotoxicity of the DSPE-PEG-TPP/MoS2 QD blend on microglial cells stimulated by Aß were investigated. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were also assessed. In addition, pro-inflammatory and anti-inflammatory cytokines, such as tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), transforming growth factor beta (TGF-ß), inducible nitric oxide synthase (iNOS) and arginase-1 (Arg-I) were measured in the presence or absence of the DSPE-PEG-TPP/MoS2 QD blend on an immortalized microglia cells activated by accumulation of Aß. We found that the DSPE-PEG-TPP/MoS2 QD blend was biocompatible and nontoxic at specific concentrations. Furthermore, the modified TPP/MoS2 QD blend significantly reduced the release of free radicals and improved the mitochondrial function through the upregulation of MMP in a dose-dependent manner on microglial cells treated with Aß. In addition, pre-treatment of microglia with the DSPE-PEG-TPP/MoS2 QD blend at concentrations of 25 and 50 µg/mL prior to Aß stimulation significantly inhibited the release and expression of pro-inflammatory cytokines, such as IL-1ß, IL-6, TNF-α, and iNOS. Nevertheless, the anti-inflammatory cytokines TGF-ß and Arg-I were activated. These findings suggest that the modified TPP/MoS2 QD blend reduced oxidative stress, inflammation and improved the mitochondrial function in the immortalized microglial cells (IMG) activated by Aß. Overall, our research shows that the DSPE-PEG-TPP/MoS2 QD blend has therapeutic promise for managing AD and can impact microglia polarization.

Analysis of MIR27A (rs11671784) Variant Association with Systemic Lupus Erythematous.

Multiple microRNAs (miRs) are associated with systemic autoimmune disease susceptibility/phenotype, including systemic lupus erythematosus (SLE). With this work, we aimed to unravel the association of the miR-27a gene (MIR27A) rs11671784G/A variant with SLE risk/severity. One-hundred sixty-three adult patients with SLE and matched controls were included. A TaqMan allelic discrimination assay was applied for MIR27A genotyping. Logistic regression models were run to test the association with SLE susceptibility/risk. Genotyping of 326 participants revealed that the heterozygote form was the most common genotype among the study cohort, accounting for 72% of the population (n = 234), while A/A and G/G represented 15% (n = 49) and 13% (n = 43), respectively. Similarly, the most prevalent genotype among cases was the A/G genotype, which was present in approximately 93.3% of cases (n = 152). In contrast, only eight and three patients had A/A and G/G genotypes, respectively. The MIR27A rs11671784 variant conferred protection against the development of SLE in several genetic models, including heterozygous (G/A vs. A/A; OR = 0.10, 95% CI = 0.05-0.23), dominant (G/A + G/G vs. AA; OR = 0.15, 95% CI = 0.07-0.34), and overdominant (G/A vs. A/A + G/G; OR = 0.07, 95% CI = 0.04-0.14) models. However, the G/G genotype was associated with increased SLE risk in the recessive model (G/G vs. A/A+ G/G; OR = 17.34, 95% CI = 5.24-57.38). Furthermore, the variant showed significant associations with musculoskeletal and mucocutaneous manifestations in the patient cohort (p = 0.035 and 0.009, respectively) and platelet and white blood cell counts (p = 0.034 and 0.049, respectively). In conclusion, the MIR27A rs11671784 variant showed a potentially significant association with SLE susceptibility/risk in the studied population. Larger-scale studies on multiethnic populations are recommended to verify the results.

HSP70 Expression Signature in Renal Cell Carcinoma: A Clinical and Bioinformatic Analysis Approach.

Heat shock proteins (HSPs) are cytoprotective against stressful conditions, as in the case of cancer cell metabolism. Scientists proposed that HSP70 might be implicated in increased cancer cell survival. This study aimed to investigate the HSP70 (HSPA4) gene expression signature in patients with renal cell carcinoma (RCC) in correlation to cancer subtype, stage, grade, and recurrence, combining both clinicopathological and in silico analysis approaches. One hundred and thirty archived formalin-fixed paraffin-embedded samples, including 65 RCC tissue specimens and their paired non-cancerous tissues, were included in the study. Total RNA was extracted from each sample and analyzed using TaqMan quantitative Real-Time Polymerase Chain Reaction. Correlation and validation to the available clinicopathological data and results were executed. Upregulated HSP70 (HSPA4) gene expression was evident in RCC compared to non-cancer tissues in the studied cohort and was validated by in silico analysis. Furthermore, HSP70 expression levels showed significant positive correlations with cancer size, grade, and capsule infiltration, as well as recurrence in RCC patients. The expression levels negatively correlated with the overall survival (r = -0.87, p < 0.001). Kaplan-Meier curves showed lower survival rates in high HSP70 expressor group compared to the low expressors. In conclusion, the HSP70 expression levels are associated with poor RCC prognosis in terms of advanced grade, capsule infiltration, recurrence, and short survival.

Deciphering the immunoboosting potential of macro and micronutrients in COVID support therapy.

The immune system protects human health from the effects of pathogenic organisms; however, its activity is affected when individuals become infected. These activities require a series of molecules, substrates, and energy sources that are derived from diets. The consumed nutrients from diets help to enhance the immunity of infected individuals as it relates to COVID-19 patients. This study aims to review and highlight requirement and role of macro- and micronutrients of COVID-19 patients in enhancing their immune systems. Series of studies were found to have demonstrated the enhancing potentials of macronutrients (carbohydrates, proteins, and fats) and micronutrients (vitamins, copper, zinc, iron, calcium, magnesium, and selenium) in supporting the immune system's fight against respiratory infections. Each of these nutrients performs a vital role as an antiviral defense in COVID-19 patients. Appropriate consumption or intake of dietary sources that yield these nutrients will help provide the daily requirement to support the immune system in its fight against pathogenic viruses such as COVID-19.

WITHDRAWN: Common NLRP3 inflammasome inhibitors and Covid-19: Divide and Conquer.

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

Covid-19-Induced Dysautonomia: A Menace of Sympathetic Storm.

Among the plethora of debilitating neurological disorders of COVID-19 syndrome in survivors, the scope of SARS-CoV-2-induced dysautonomia (DNS) is yet to be understood, though the implications are enormous. Herein, we present an inclusive mini-review of SARS-CoV-2-induced DNS and its associated complications. Although, the direct link between Covid-19 and DSN is still speculative, the hypothetical links are thought to be either a direct neuronal injury of the autonomic pathway or a para/post-infectious immune-induced mechanism. SARS-CoV-2 infection-induced stress may activate the sympathetic nervous system (SNS) leading to neuro-hormonal stimulation and activation of pro-inflammatory cytokines with further development of sympathetic storm. Sympathetic over-activation in Covid-19 is correlated with increase in capillary pulmonary leakage, alveolar damage, and development of acute respiratory distress syndrome. Furthermore, SARS-CoV-2 can spread through pulmonary mechanoreceptors and chemoreceptors to medullary respiratory center in a retrograde manner resulting in sudden respiratory failure. Taken together, DSN in Covid-19 is developed due to sympathetic storm and inhibition of Parasympathetic nervous system-mediated anti-inflammatory effect with development of cytokine storm. Therefore, sympathetic and cytokine storms together with activation of Renin-Angiotensin-System are the chief final pathway involved in the development of DSN in Covid-19.

Covid-19 and development of heart failure: mystery and truth.

Coronavirus disease 2019 (Covid-19) is a novel worldwide pandemic caused by a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). During Covid-19 pandemic, socioeconomic deprivation, social isolation, and reduced physical activities may induce heart failure (HF), destabilization, and cause more complications. HF appears as a potential hazard due to SARS-CoV-2 infection, chiefly in elderly patients with underlying comorbidities. In reality, the expression of cardiac ACE2 is implicated as a target point for SARS-CoV-2-induced acute cardiac injury. In SARS-CoV-2 infection, like other febrile illnesses, high blood viscosity, exaggerated pro-inflammatory response, multisystem inflammatory syndrome, and endothelial dysfunction-induced coagulation disorders may increase risk of HF development. Hypoxic respiratory failure, as in pulmonary edema, severe acute lung injury (ALI), and acute respiratory distress syndrome (ARDS) may affect heart hemodynamic stability due to the development of pulmonary hypertension. Indeed, Covid-19-induced HF could be through the development of cytokine storm, characterized by high proliferation pro-inflammatory cytokines. In cytokine storm-mediated cardiac dysfunction, there is a positive correlation between levels of pro-inflammatory cytokine and myocarditis-induced acute cardiac injury biomarkers. Therefore, Covid-19-induced HF is more complex and related from a molecular background in releasing pro-inflammatory cytokines to the neuro-metabolic derangements that together affect cardiomyocyte functions and development of HF. Anti-heart failure medications, mainly digoxin and carvedilol, have potent anti-SARS-CoV-2 and anti-inflammatory properties that may mitigate Covid-19 severity and development of HF. In conclusion, SARS-CoV-2 infection may lead to the development of HF due to direct acute cardiac injury or through the development of cytokine storms, which depress cardiomyocyte function and cardiac contractility. Anti-heart failure drugs, mainly digoxin and carvedilol, may attenuate severity of HF by reducing the infectivity of SARS-CoV-2 and prevent the development of cytokine storms in severely affected Covid-19 patients.

Impacting the Remedial Potential of Nano Delivery-Based Flavonoids for Breast Cancer Treatment.

Breast cancer persists as a diffuse source of cancer despite persistent detection and treatment. Flavonoids, a type of polyphenol, appear to be a productive option in the treatment of breast cancer, because of their capacity to regulate the tumor related functions of class of compounds. Plant polyphenols are flavonoids that appear to exhibit properties which are beneficial for breast cancer therapy. Numerous epidemiologic studies have been performed on the dynamic effect of plant polyphenols in the prevention of breast cancer. There are also subclasses of flavonoids that have antioxidant and anticarcinogenic activity. These can regulate the scavenging activity of reactive oxygen species (ROS) which help in cell cycle arrest and suppress the uncontrolled division of cancer cells. Numerous studies have also been performed at the population level, one of which reported a connection between cancer risk and intake of dietary flavonoids. Breast cancer appears to show intertumoral heterogeneity with estrogen receptor positive and negative cells. This review describes breast cancer, its various factors, and the function of flavonoids in the prevention and treatment of breast cancer, namely, how flavonoids and their subtypes are used in treatment. This review proposes that cancer risk can be reduced, and that cancer can be even cured by improving dietary intake. A large number of studies also suggested that the intake of fruit and vegetables is associated with reduced breast cancer and paper also includes the role and the use of nanodelivery of flavonoids in the healing of breast cancer. In addition, the therapeutic potential of orally administered phyto-bioactive compounds (PBCs) is narrowed because of poor stability and oral bioavailability of compounds in the gastrointestinal tract (GIT), and solubility also affects bioavailability. In recent years, creative nanotechnology-based approaches have been advised to enhance the activity of PBCs. Nanotechnology also offers the potential to become aware of disease at earlier stages, such as the detection of hidden or unconcealed metastasis colonies in patients diagnosed with lung, colon, prostate, ovarian, and breast cancer. However, nanoformulation-related effects and safety must not be overlooked. This review gives a brief discussion of nanoformulations and the effect of nanotechnology on herbal drugs.

Arginine vasopressin and pathophysiology of COVID-19: An innovative perspective.

In Covid-19, systemic disturbances may progress due to development of cytokine storm and dysregulation of and plasma osmolarility due to high release of pro-inflammatory cytokines and neuro-hormonal disorders. Arginine vasopressin (AVP) which is involve in the regulation of body osmotic system, body water content, blood pressure and plasma volume, that are highly disturbed in Covid-19 and linked with poor clinical outcomes. Therefore, this present study aimed to find the potential association between AVP serum level and inflammatory disorders in Covid-19. It has been observed by different recent studies that physiological response due to fever, pain, hypovolemia, dehydration, and psychological stress is characterized by activation release of AVP to counter-balance high blood viscosity in Covid-19 patients. In addition, activated immune cells mainly T and B lymphocytes and released pro-inflammatory cytokines stimulate discharge of stored AVP from immune cells, which in a vicious cycle trigger release of pro-inflammatory cytokines. Vasopressin receptor antagonists have antiviral and anti-inflammatory effects that may inhibit AVP-induced hyponatremia and release of pro-inflammatory cytokines in Covid-19. In conclusion, release of AVP from hypothalamus is augmented in Covid-19 due to stress, high pro-inflammatory cytokines, high circulating AngII and inhibition of GABAergic neurons. In turn, high AVP level leads to induction of hyponatremia, inflammatory disorders, and development of complications in Covid-19 by activation of NF-κB and NLRP3 inflammasome with release of pro-inflammatory cytokines. Therefore, AVP antagonists might be novel potential therapeutic modality in treating Covid-19 through mitigation of AVP-mediated inflammatory disorders and hyponatremia.

Curcumin Nanoparticles as Promising Therapeutic Agents for Drug Targets.

Curcuma longa is very well-known medicinal plant not only in the Asian hemisphere but also known across the globe for its therapeutic and medicinal benefits. The active moiety of Curcuma longa is curcumin and has gained importance in various treatments of various disorders such as antibacterial, antiprotozoal, cancer, obesity, diabetics and wound healing applications. Several techniques had been exploited as reported by researchers for increasing the therapeutic potential and its pharmacological activity. Here, the dictum is the new room for the development of physicochemical, as well as biological, studies for the efficacy in target specificity. Here, we discussed nanoformulation techniques, which lend support to upgrade the characters to the curcumin such as enhancing bioavailability, increasing solubility, modifying metabolisms, and target specificity, prolonged circulation, enhanced permeation. Our manuscript tried to seek the attention of the researcher by framing some solutions of some existing troubleshoots of this bioactive component for enhanced applications and making the formulations feasible at an industrial production scale. This manuscript focuses on recent inventions as well, which can further be implemented at the community level.

The Rise of SARS-CoV-2 Variants and the Role of Convalescent Plasma Therapy for Management of Infections.

Novel therapies for the treatment of COVID-19 are continuing to emerge as the SARS-Cov-2 pandemic progresses. PCR remains the standard benchmark for initial diagnosis of COVID-19 infection, while advances in immunological profiling are guiding clinical treatment. The SARS-Cov-2 virus has undergone multiple mutations since its emergence in 2019, resulting in changes in virulence that have impacted on disease severity globally. The emergence of more virulent variants of SARS-Cov-2 remains challenging for effective disease control during this pandemic. Major variants identified to date include B.1.1.7, B.1.351; P.1; B.1.617.2; B.1.427; P.2; P.3; B.1.525; and C.37. Globally, large unvaccinated populations increase the risk of more and more variants arising. With successive waves of COVID-19 emerging, strategies that mitigate against community transmission need to be implemented, including increased vaccination coverage. For treatment, convalescent plasma therapy, successfully deployed during recent Ebola outbreaks and for H1N1 influenza, can increase survival rates and improve host responses to viral challenge. Convalescent plasma is rich with cytokines (IL-1ß, IL-2, IL-6, IL-17, and IL-8), CCL2, and TNFα, neutralizing antibodies, and clotting factors essential for the management of SARS-CoV-2 infection. Clinical trials can inform and guide treatment policy, leading to mainstream adoption of convalescent therapy. This review examines the limited number of clinical trials published, to date that have deployed this therapy and explores clinical trials in progress for the treatment of COVID-19.

Herbal drugs and natural bioactive products as potential therapeutics: A review on pro-cognitives and brain boosters perspectives.

Memory, one of the most vital aspects of the human brain, is necessary for the effective survival of an individual. 'Memory' can be defined in various ways but in an overall view, memory is the retention of the information that the brain grasps. Different factors are responsible for the disbalance in the brain's hippocampus region and the acetylcholine level, which masters the memory and cognitive functions. Plants are a source of pharmacologically potent drug molecules of high efficacy. Recently herbal medicine has evolved rapidly, gaining great acceptance worldwide due to their natural origin and fewer side effects. In this review, the authors have discussed the mechanisms and pharmacological action of herbal bioactive compounds to boost memory. Moreover, this review presents an update of different herbs and natural products that could act as memory enhancers and how they can be potentially utilized in the near future for the treatment of severe brain disorders. In addition, the authors also discuss the differences in biological activity of the same herb and emphasize the requirement for a higher standardization in cultivation methods and plant processing. The demand for further studies evaluating the interactions of herbal drugs is mentioned.

Glutathione S-Transferase (GSTT1 rs17856199) and Nitric Oxide Synthase (NOS2 rs2297518) Genotype Combination as Potential Oxidative Stress-Related Molecular Markers for Type 2 Diabetes Mellitus.

BACKGROUND: Deregulation of the antioxidant enzymes was implicated in pathogenesis and complications of type 2 diabetes mellitus (T2DM). The data relate the genetic variants of these enzymes to T2DM are inconsistent among various populations. PURPOSE: We aimed to explore the association of 13 genetic variants of "superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and nitric oxide synthase (NOS)" with T2DM susceptibility and the available clinical laboratory data. SUBJECTS AND METHODS: A total of 384 individuals were enrolled in this work. Different genotypes of the genes mentioned above were characterized using TaqMan OpenArray Genotyping assays on a Real-Time polymerase chain reaction system. RESULTS: After age- and sex-adjustment, among the studied 13 variants, GSTT1 rs17856199 was associated with T2DM under homozygote (OR=3.42; 95% CI:1.04-11.2, p=0.031), and recessive (OR=3.57; 95% CI: 1.11-11.4, p=0.029) comparison models. The NOS2 rs2297518*A allele was more frequent among the T2DM cohort (58.1% vs 35.4%, p<0.001) and showed a dose-response effect; being heterozygote was associated with higher odds for developing DM (OR=4.06, 95% CI=2.13-7.73, p<0.001), whereas being AA homozygote had double the risk (OR=9.06, 95% CI=3.41-24.1, p<0.001). Combined NOS2 rs2297518*A and either GSTT1 rs17856199*A or *C genotype carriers were more likely to develop T2DM. Different associations with sex, BMI, hyperglycemia, and/or hyperlipidemia were evident. The principal component analysis revealed NOS2 rs2297518*G, old age, dyslipidemia, high systolic blood pressure, and elevated HbA1c were the main classifiers of T2DM patients. CONCLUSION: The oxidative stress-related molecular markers, GSTT1 rs17856199 and NOS2 rs2297518 variants were significantly associated with T2DM risk and phenotype in the study population.

Antioxidants-Related Superoxide Dismutase (SOD), Catalase (CAT), Glutathione Peroxidase (GPX), Glutathione-S-Transferase (GST), and Nitric Oxide Synthase (NOS) Gene Variants Analysis in an Obese Population: A Preliminary Case-Control Study.

Oxidative stress and antioxidants play an important role in obesity etiopathology. Genetic variants, including single nucleotide polymorphisms (SNPs) of the antioxidant-related genes, may impact disease risk in several populations. This preliminary study aimed to explore the association of 12 SNPs related to superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione-S-transferase (GST), and nitric oxide synthase (NOS) genes with obesity susceptibility in a Saudi population. A total of 384 unrelated participants, including 154 (40.1%) obese individuals, were enrolled. TaqMan OpenArray Genotyping assays were used. Six SNPs were significantly more prevalent in obese cohorts: (1) GSTM1 rs1056806*C/T; (2) SOD1 rs2234694*A; (3) SOD2 rs4880*G; (4) SOD3 rs2536512*A; (5) GPX1 rs1800668*A; (6) NOS3 rs1799983*G. Four SNPs were associated with higher obesity risk under heterozygote and dominant models for GSTM1 rs1056806 (C/T), homozygote model for SOD2 rs4880 (A/G), and homozygote and recessive models for GPX1 rs1800668 (A/G). In contrast, SOD3 rs2536512 (A/G) were less likely to be obese under heterozygote and dominant models. The CGAG, CAAA, TGGG, and CGAG combined genotypes showed a higher risk of obesity. In conclusion, the present results suggest that oxidative-stress-related genetic determinants could significantly associate with obesity risk in the study population.

Effects of aluminum chloride and coenzyme Q10 on the molecular structure of lipids and the morphology of the brain hippocampus cells.

Aluminum chloride (AlCl3) is a neurotoxic substance, while coenzyme Q10 (CoQ10) is considered a lipid antioxidant. Herein, their effects on the molecular structure of lipids and the morphology of the hippocampus brain tissue were investigated. Three groups of Wistar albino male rats were used in this study. For four weeks, one group was kept as a control group; the second group was given AlCl3; the third group was given AlCl3/CoQ10. Fourier transform infrared (FTIR) and histopathological examinations were utilized to estimate alterations in the molecular structure of the lipids and the cell morphology, respectively. The FTIR spectra revealed considerable decreases in the CH contents and alterations in the molecular ratios of olefinic[double bond, length as m-dash]CH/νas(CH3), νas(CH2)/νas(CH3), and νas(CH2)/[νas(CH2) + νs(CH2)] in the group given AlCl3. However, no significant changes were detected in those rats given AlCl3/CoQ10. Histopathology images uncovered shrinking and dark centers in the pyramidal cells of brain tissue hippocampal cells. The diameters of the pyramidal cells were estimated to be 4.81 ± 0.55 µm, 4.04 ± 0.71 µm, and 4.63 ± 0.71 µm for the control, AlCl3, and AlCl3/CoQ10 groups, respectively. The study showed that the AlCl3 could cause a shrinking of around 16% in the hippocampus pyramidal cells; besides, CoQ10 is a powerful therapeutic antioxidant to help restore the hippocampal neurons to a regular state.

Correction: Effects of aluminum chloride and coenzyme Q10 on the molecular structure of lipids and the morphology of the brain hippocampus cells.

[This corrects the article DOI: 10.1039/D1RA03786B.].

ATR-IR and EPR spectroscopy for following the membrane restoration of isolated cortical synaptosomes in aluminium-induced Alzheimer's disease - Like rat model.

Synaptosomal membrane peroxidation and alteration in its biophysical properties are associated with Aluminium (Al) toxicity that may lead to cognitive dysfunction and Alzheimer's disease (AD) like pathogenesis. Here we investigated the therapeutic potential of Lepedium sativum (LS) as a natural anti-inflammatory, antioxidant and as acetyl cholinesterase inhibitor in treating Al induced AD-like in rat model. We utilized ATR-IR spectroscopy to follow the restoration in the damaged membrane structure of isolated rat cortical synaptosomes and its biophysical properties, electron paramagnetic resonance (EPR) spin trapping to follow NADPH oxidase activity (NOX), and EPR spin labelling in response to LS treatment after Al intoxication. We measured the concentration of Ca2+ ions in rat cortical tissue by inductively coupled plasma (ICP), the brain atrophy/curing and hydrocephalus by magnetic resonance imaging (MRI) besides light microscope histopathology. Our results revealed significant increase in synaptosomal membrane rgidification, order, lipid packing, reactive oxygen species (ROS) production and Ca2+ ion concentration as a result of Al intoxication. The dramatic increase in Ca2+ ion concentration detected in AD group associated with the increase in synaptic membrane polarity and EPR-detected order S-parameter suggest that release of synaptic vesicles into synaptic cleft might be hindered. LS treatment reversed these changes in synaptic membranes, and rescued an observed deficit in the exploratory behaviour of AD group. Our results also strongly suggest that the synaptosomal membrane phospholipids that underwent free radical attacks mediated by AlCl3, due to greater NOX activity, was prevented in the LS group. The results of ATR-IR and EPR spectroscopic techniques recommend LS as a promising therapeutic agent against synaptic membrane alterations opening a new window for AD drug developers.

The Effect Sizes of PPARγ rs1801282, FTO rs9939609, and MC4R rs2229616 Variants on Type 2 Diabetes Mellitus Risk among the Western Saudi Population: A Cross-Sectional Prospective Study.

Type 2 diabetes mellitus (T2DM) is a common polygenic disease with associated comorbidities. Obesity is a major risk factor for the development of T2DM. The aim of this study is to determine the allele and genotype frequency of peroxisome proliferator-activated receptor-γ (PPARγ) rs1801282, fat mass and obesity-associated protein (FTO) rs9939609, and melanocortin 4 receptor (MC4R) rs2229616 polymorphisms and their association with risk of T2DM in the western Saudi population as mediators of adiposity phenotypes. In a cross-sectional prospective study, genomic DNA from control and T2DM patients were isolated and genotyped for these single-nucleotide polymorphisms. There was a significant association of the MC4R rs2229616 variant with T2DM, but no association with T2DM was detected with PPARγ rs1801282 or FTO rs9939609. The combination of C/C for PPARγ rs1801282, A/A for FTO rs9939609, and C/C for MC4R rs2229616 increased the risk of T2DM by 1.82. The A/T genotype for FTO rs9939609 was predicted to decrease the risk of T2DM when combined with C/C for PPARγ rs1801282 and C/C for MC4R rs2229616 or C/C for PPARγ rs1801282 and C/T MC4R rs2229616. In conclusion, our study showed the risk of the assessed variants for the development of T2DM in the Saudi population.

SLC22A1 And ATM Genes Polymorphisms Are Associated With The Risk Of Type 2 Diabetes Mellitus In Western Saudi Arabia: A Case-Control Study.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major global health problem that is progressively affected by genetic and environmental factors. The aim of this study is to determine the influence of solute carrier family 22 member 1 (SLC22A1) rs628031 and rs461473, and ataxia telangiectasia mutated (ATM) rs11212617 polymorphisms on the risk of T2DM in Saudi Arabia by considering many parameters associated with glycemic control of T2DM, such as body mass index (BMI), fasting blood glucose, glycated hemoglobin (HbA1c), and triglyceride. METHODS: In a case-control study, genomic DNA from controls and diabetic groups was isolated and genotyped for each single-nucleotide polymorphism. RESULTS: There were significant correlations between T2DM and both BMI and HbA1c. Significant associations between G/G and A/G genotypes of rs628031 and rs461473 variants of SLC22A1 and high levels of HbA1c were detected. Therefore, G was predicted to be the risk allele among the assessed SLC22A1 variants. A significant correlation was observed between A/A and A/C genotypes of the rs11212617 polymorphism of ATM and elevated HbA1c. Relative risk calculation confirmed A to be the risk allele in the T2DM population. CONCLUSION: Our study showed the risk of the assessed SLC22A1 and ATM variants on glycemic control parameters in diabetic patients.