Protective effect of Petroselinum crispum methanolic extract against acrylamide-induced reproductive toxicity in male rats through NF-ĸB, kinesin, steroidogenesis pathways.

This study examined the protective effects of a Petroselinum crispum (P. crispum) methanolic extract on reproductive dysfunction induced by acrylamide in male rats. A total of 40 rats were divided into four groups (n=10). The control group received distilled water, the acrylamide group received 10 mg/kg of acrylamide, the P. crispum group received 100 mg/kg of P. crispum extract, and the combined group was pretreated with P. crispum for two weeks before co-administration of P. crispum and acrylamide. All administrations were administered orally using a gastric tube for eight weeks. Acrylamide decreased testosterone levels but did not affect levels of FSH or LH. It also increased testicular levels of (MDA) malondialdehyde and reduced activity of (SOD) superoxide dismutase and impairment of sperm parameters. Furthermore, the administration of acrylamide resulted in an elevation of tumor necrosis factor-alpha (TNF-α) levels and a reduction in the levels of steroidogenic acute regulatory protein (STAR) and cytochrome P450scc (P450scc). Acrylamide negatively affected the histopathological outcomes, Johnsen's score, the diameter of seminiferous tubules, and the thickness of the germinal epithelium. It also upregulated the expression of NF-ĸB P65 and downregulated the expression of kinesin motor protein. In contrast, treatment with P. crispum extract restored the levels of antioxidant enzymes, improved sperm parameters, and normalized the gene expression of TNF-α, IL-10, IL-6, iNOS, NF-ĸB, STAR, CYP17A1, 17ß-HSD and P450scc. It also recovered testicular histological parameters and immunoexpression of NF-ĸB P65 and kinesin altered by acrylamide. P. crispum showed protective effects against acrylamide-induced reproductive toxicity by suppressing oxidative damage and inflammatory pathways.

The long coiled-coil protein NECC2 regulates oxLDL-induced endothelial oxidative damage and exacerbates atherosclerosis development in apolipoprotein E -/- mice.

Oxidized low density lipoprotein (oxLDL)-induced endothelial oxidative damage promotes the development of atherosclerosis. Caveolae play an essential role in maintaining the survival and function of vascular endothelial cell (VEC). It is reported that the long coiled-coil protein NECC2 is localized in caveolae and is associated with neural cell differentiation and adipocyte formation, but its role in VECs needs to be clarified. Our results showed NECC2 expression increased in the endothelium of plaque-loaded aortas and oxLDL-treated HUVECs. Down-regulation of NECC2 by NECC2 siRNA or compound YF-307 significantly inhibited oxLDL-induced VEC apoptosis and the adhesion factors expression. Remarkably, inhibition of NECC2 expression in the endothelium of apoE-/- mice by adeno-associated virus (AAV)-carrying NECC2 shRNA or compound YF-307 alleviated endothelium injury and restricted atherosclerosis development. The immunoprecipitation results confirmed that NECC2 interacted with Tyk2 and caveolin-1(Cav-1) in VECs, and NECC2 further promoted the phosphorylation of Cav-1 at Tyr14 b y activating Tyk2 phosphorylation. On the other hand, inhibiting NECC2 levels suppressed oxLDL-induced phosphorylation of Cav-1, uptake of oxLDL by VECs, accumulation of intracellular reactive oxygen species and activation of NF-κB. Our findings suggest that NECC2 may contribute to oxLDL-induced VEC injury and atherosclerosis via modulating Cav-1 phosphorylation through Tyk2. This work provides a new concept and drug target for treating atherosclerosis.

CAR-T cell therapeutic avenue for fighting cardiac fibrosis: Roadblocks and perspectives.

Heart diseases remain the primary cause of human mortality in the world. Although conventional therapeutic opportunities fail to halt or recover cardiac fibrosis, the promising clinical results and therapeutic efficacy of engineered chimeric antigen receptor (CAR) T cell therapy show several advancements. However, the current models of CAR-T cells need further improvement since the T cells are associated with the triggering of excessive inflammatory cytokines that directly affect cardiac functions. Thus, the current study highlights the critical function of heart immune cells in tissue fibrosis and repair. The study also confirms CAR-T cell as an emerging therapeutic for treating cardiac fibrosis, explores the current roadblocks to CAR-T cell therapy, and considers future outlooks for research development.

The potential anti-Alzheimer's activity of Oxalis corniculata Linn. Methanolic extract in experimental rats: Role of APOE4/LRP1, TLR4/NF-κß/NLRP3, Wnt 3/ß-catenin/GSK-3ß, autophagy and apoptotic cues.

ETHNOPHARMACOLOGICAL RELEVANCE: Oxalis corniculata (O. corniculata) is a member of Oxalidaceae family, widely distributed in Asia, Europe, America, and Africa, used extensively as food and its traditional folkloric uses include management of epilepsy, gastric disorders, and neurodegenerative diseases, together with its use in enhancing health. Numerous pharmacological benefits of O. corniculata are linked to its anti-inflammatory and antioxidant abilities. One of the most prevalent neurodegenerative disorders is Alzheimer's disease (AD) in which neuroinflammation and oxidative stress are its main pathogenic processes. AIM OF THE STUDY: Our research aimed to study the neuroprotective effect of the methanolic extract of Oxalis corniculata Linn. (O. corniculata ME), compared to selenium (Se) against AlCl3-induced AD. MATERIALS AND METHODS: Forty male albino rats were allocated into four groups (Gps). Gp I a control group, the rest of the animals received AlCl3 (Gp II-Gp IV). Rats in Gp III and IV were treated with Se and O. corniculata ME, respectively. RESULTS: The chemical profile of O. corniculata ME was studied using ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry, allowing the tentative identification of sixty-six compounds, including organic acids, phenolics and others, cinnamic acid and its derivatives, fatty acids, and flavonoids. AlCl3 showed deterioration in short-term memory and brain histological pictures. Our findings showed that O. corniculata ME and selenium helped to combat oxidative stress produced by accumulation of AlCl3 in the brain and in prophylaxis against AD. Thus, Selenium (Se) and O. corniculata ME restored antioxidant defense, via enhancing Nrf2/HO-1 hub, hampered neuroinflammation, via TLR4/NF-κß/NLRP3, along with dampening apoptosis, Aß generation, tau hyperphosphorylation, BACE1, ApoE4 and LRP1 levels. Treatments also promoted autophagy and modulated Wnt 3/ß-catenin/GSK3ß cue. CONCLUSIONS: It was noted that O. corniculata ME showed a notable ameliorative effect compared to Se on Nrf2/HO-1, TLR4/NF-κß/NLRP3, APOE4/LRP1, Wnt 3/ß-catenin/GSK-3ß and PERK axes.

Red blood cell alloimmunization in blood transfusion-dependent ß thalassemia major patients in Sana'a City-Yemen.

The development of erythrocyte alloantibodies complicates transfusion therapy in ß thalassemia major patients. These antibodies increase the need for blood and intensify transfusion complications. Data on erythrocyte alloimmunization is scarce in Yemeni thalassemia patients. We studied the frequency of alloimmunization in multitransfused ß-thalassemia major patients and investigated risk factors that affect antibody formation. Blood samples were taken from 100 ß thalassemia major patients who received multitransfused leukodepleted packed red-blood cells. Antibody screening and identification were performed by indirect antiglobulin test using the gel column technique. All patients were tested for autoantibodies using autocontrol and direct antiglobulin test. No adsorption test was done as no autoantibodies were detected in any patient. In our study of 100 ß-thalassemia patients, 50 were male and 50 were female with ages ranging from 1 to 30 years. Alloantibodies were present in 6% of patients, while no autoantibodies were detected. Of the 17 alloantibodies identified, the majority were directed against Kell (41.2%) and Rh (29.4%) blood groups. Alloimmunization was significantly associated with age group and sex (p = 0.013, p = 0.030), respectively in ß thalassemia major patients. The development of alloantibodies was not significantly associated with duration, total number of transfusions and splenectomy (P = 0.445, P = 0.125, P = 0.647). No autoantibodies found in patients with ß thalassemia major. The study found low rates of erythrocyte alloimmunization in multitransfused ß-thalassemia major patients, but significant alloantibodies were produced primarily from Kell and Rh blood groups, suggesting the need for providing phenotypically matched cells for selective antigens to improve transfusion efficiency.

Novel Therapeutic Agents for Management of Diabetes Mellitus: A Hope for Drug Designing against Diabetes Mellitus.

Diabetes mellitus (DM) is characterized by an absolute decline in insulin secretion and peripheral resistance and is the most prevalent metabolic and endocrine disorder. However, the pathogenesis of DM also includes adipocyte insulin resistance, increased glucagon secretion, increased renal glomerular glucose absorption, and neurotransmitter dysfunction. Although there is a wide spectrum of therapeutics available for glycemic control, owing to the identification of various pathogenic determinants of DM, management of DM remains challenging and complex. Current therapeutic interventions against DM focus mostly on glycemic control without considering the other pathological determinants that eventually lead to treatment failure and the progression of DM. Furthermore, long-term use of these conventionally available anti-diabetic drugs leads to various side effects, henceforth development of novel drugs against DM remains an unending search strategy for researchers. Various studies conducted in various parts of the world have proposed that these novel therapeutic interventions target multiple and alternate pathogenic hotspots involved in DM. The current review article discusses novel therapeutic options that hold particular promise to support their safety and discuss the side effects resulting from their use so that these novel candidate drugs can be effectively fabricated into potential drugs for the treatment of DM.

Application of 2D MoS2 Nanoflower for the Removal of Emerging Pollutants from Water.

Two-dimensional (2D) nanomaterial-MoS2 (molybdenum disulfide) has gained interest among researchers, owing to its exceptional mechanical, biological, and physiochemical properties. This paper reports on the removal of organic dyes and an emerging contaminant, Ciprofloxacin, by a 2D MoS2 nanoflower as an adsorbent. The material was prepared by a green hydrothermal technique, and its high Brunauer-Emmett-Teller-specific area of 185.541m2/g contributed to the removal of 96% rhodamine-B dye and 85% Ciprofloxacin. Various characterizations, such as X-ray diffraction, scanning electron microscopy linked with energy-dispersive spectroscopy, and transmission electron microscopy, revealed the nanoflower structure with good crystallinity. The feasibility and efficacy of 2D MoS2 nanoflower as a promising adsorbent candidate for the removal of emerging pollutants was confirmed in-depth in batch investigations, such as the effects of adsorption time, MoS2 dosages, solution pH, and temperature. The adsorption mechanism was further investigated based on thermodynamic calculations, adsorption kinetics, and isotherm modeling. The results confirmed the exothermic nature of the enthalpy-driven adsorption as well as the fast kinetics and physisorption-controlled adsorption process. The recyclability potential of 2D MoS2 exceeds four regeneration recycles. MoS2 nanoflower has been shown to be an effective organic pollutant removal adsorbent in water treatment.

In silico and in vivo analysis of the relationship between ADHD and social isolation in pups rat model: Implication of redox mechanisms, and the neuroprotective impact of Punicalagin.

Attention deficit hyperactivity disorder (ADHD) has high incidence rate among children which may be due to excessive monosodium glutamate (MSG) consumption and social isolation (SI). AIM: We aimed to explore the relationships between MSG, SI, and ADHD development and to evaluate the neuroprotective potential of Punicalagin (PUN). METHODS: Eighty male rat pups randomly distributed into eight groups. Group I is the control, and Group II is socially engaged rats treated with PUN. Groups III to VII were exposed to ADHD-inducing factors: Group III to SI, Group IV to MSG, and Group V to both SI and MSG. Furthermore, Groups VI to VIII were the same Groups III to V but additionally received PUN treatment. KEY FINDINGS: Exposure to MSG and/or SI led to pronounced behavioral anomalies, histological changes and indicative of ADHD-like symptoms in rat pups which is accompanied by inhibition of the nuclear factor erythroid 2-related factor 2 (Nrf2)/Heme-oxygenase 1 (HO-1)/Glutathione (GSH) pathway, decline of the brain-derived neurotrophic factor (BDNF) expression and activation of the Toll-like receptor 4 (TLR4)/Nuclear factor kappa B (NF-kB)/NLR Family Pyrin Domain Containing 3 (NLRP3) pathway. This resulted in elevated inflammatory biomarker levels, neuronal apoptosis, and disrupted neurotransmitter equilibrium. Meanwhile, pretreatment with PUN protected against all the previous alterations. SIGNIFICANCE: We established compelling associations between MSG consumption, SI, and ADHD progression. Moreover, we proved that PUN is a promising neuroprotective agent against all risk factors of ADHD.

Punicalagin's Protective Effects on Parkinson's Progression in Socially Isolated and Socialized Rats: Insights into Multifaceted Pathway.

Parkinson's disease (PD) is a gradual deterioration of dopaminergic neurons, leading to motor impairments. Social isolation (SI), a recognized stressor, has recently gained attention as a potential influencing factor in the progress of neurodegenerative illnesses. We aimed to investigate the intricate relationship between SI and PD progression, both independently and in the presence of manganese chloride (MnCl2), while evaluating the punicalagin (PUN) therapeutic effects, a natural compound established for its cytoprotective, anti-inflammatory, and anti-apoptotic activities. In this five-week experiment, seven groups of male albino rats were organized: G1 (normal control), G2 (SI), G3 (MnCl2), G4 (SI + MnCl2), G5 (SI + PUN), G6 (MnCl2 + PUN), and G7 (SI + PUN + MnCl2). The results revealed significant changes in behavior, biochemistry, and histopathology in rats exposed to SI and/or MnCl2, with the most pronounced effects detected in the SI rats concurrently exposed to MnCl2. These effects were associated with augmented oxidative stress biomarkers and reduced antioxidant activity of the Nrf2/HO-1 pathway. Additionally, inflammatory pathways (HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1 and JAK-2/STAT-3) were upregulated, while dysregulation of signaling pathways (PI3K/AKT/GSK-3ß/CREB), sustained endoplasmic reticulum stress by activation PERK/CHOP/Bcl-2, and impaired autophagy (AMPK/SIRT-1/Beclin-1 axis) were observed. Apoptosis induction and a decrease in monoamine levels were also noted. Remarkably, treatment with PUN effectively alleviated behaviour, histopathological changes, and biochemical alterations induced by SI and/or MnCl2. These findings emphasize the role of SI in PD progress and propose PUN as a potential therapeutic intervention to mitigate PD. PUN's mechanisms of action involve modulation of pathways such as HMGB1/RAGE/TLR4/NF-ᴋB/NLRP3/Caspase-1, JAK-2/STAT-3, PI3K/AKT/GSK-3ß/CREB, AMPK/SIRT-1, Nrf2/HO-1, and PERK/CHOP/Bcl-2.

Investigation of Simultaneous and Sequential Cooperative Homotropic Inhibitor Binding to the Catalytic Chamber of SARS-CoV-2 RNA-dependent RNA Polymerase (RdRp).

In our previous report, the unique architecture of the catalytic chamber of the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp), which harbours two distinctive binding sites, was fully characterized at molecular level. The significant differences in the two binding sites BS1 and BS2 in terms of binding pockets motif, as well as the preferential affinities of eight anti-viral drugs to each of the two binding sites were described. Recent Cryogenic Electron Microscopy (Cryo-EM) studies on the RdRp revealed that two suramin molecules, a SARS-CoV-2 inhibitor, bind to RdRp in two different sites with distinctive interaction landscape. Here, we provide the first account of investigating the combined inhibitor binding to both binding sites, and whether the binding of two inhibitors molecules concurrently is "Cooperative binding" or not. It should be noted that the binding of inhibitors to different sites do not necessary constitute mutually independent events, therefore, we investigated two scenarios to better understand cooperativity: simultaneous binding and sequential binding. It has been demonstrated by binding free energy calculations (MM/PBSA) and piecewise linear potential (PLP) interaction energy analysis that the co-binding of two suramin molecules is not cooperative in nature; rather, when compared to individual binding, both molecules adversely affect one another's binding affinities. This observation appeared to be primarily due to RdRp's rigidity, which prevented both ligands from fitting comfortably within the catalytic chamber. Instead, the suramin molecules showed a tendency to change their orientation within the binding pockets in order to maintain their binding to the protein, but at the expense of the ligand internal energies. Although co-binding resulted in the loss of several important key interactions, a few interactions were conserved, and these appear to be crucial in preserving the binding of ligands in the active site. The structural and mechanistic details of this study will be useful for future research on creating and developing RdRp inhibitors against SARS-CoV-2.

Near Green Synthesis of Porous Graphene from Graphite Using an Encapsulated Ferrate(VI) Oxidant.

Graphene oxide (GO) is a conventional yet vital precursor for the synthesis of porous graphene (PG). Several strong oxidizing agents such as potassium permanganate and perchlorates are typically used for oxidization of graphite. However, they expose toxic reactants/products that harm the environment. Therefore, a greener approach is desperately needed to oxidize and exfoliate graphite. This study reports for the first time on successful oxidation of graphite by ferrate(VI) compounds via an encapsulation approach. By further reducing GO prepared from this near green route with vitamin C, PG anticipated by many highly important and expanding areas such as water treatment could be readily achieved. X-ray diffraction (XRD), Fourier transform infrared (FTIR) and UV-vis spectroscopy, and scanning electronic microscopy (SEM) along with energy-dispersive spectroscopy confirmed the high yield of GO from the oxidation of graphite. Raman spectroscopy, XRD, and TEM confirmed the formation of high-quality few-layered PG from the reduction of as-prepared GO. The above results demonstrated the practicality of using encapsulated ferrate(VI) compounds to realize green oxidation of graphite and resolve the paradox about the oxidation capability of ferrate(VI). To further illustrate its potential for the removal of emerging and crucial contaminants from water, as-prepared PG was further examined against the contaminants of methyl orange (MeO) dye and ibuprofen (IBU). Taken together, the results revealed that more than 90% removal efficiency could be achieved at a high PG dosage against MeO and IBU. This ground-breaking greener approach opens the door to risk-free, extensive graphene environmental applications.

The protective effects of sesamol and/or the probiotic, Lactobacillus rhamnosus, against aluminum chloride-induced neurotoxicity and hepatotoxicity in rats: Modulation of Wnt/ß-catenin/GSK-3ß, JAK-2/STAT-3, PPAR-γ, inflammatory, and apoptotic pathways.

Introduction: Aluminium (Al) is accumulated in the brain causing neurotoxicity and neurodegenerative disease like Alzheimer's disease (AD), multiple sclerosis, autism and epilepsy. Hence, attenuation of Al-induced neurotoxicity has become a "hot topic" in looking for an intervention that slow down the progression of neurodegenerative diseases. Objective: Our study aims to introduce a new strategy for hampering aluminum chloride (AlCl3)-induced neurotoxicity using a combination of sesamol with the probiotic bacteria; Lactobacillus rhamnosus (L. rhamnosus) and also to test their possible ameliorative effects on AlCl3-induced hepatotoxicity. Methods: Sprague-Dawley male rats were randomly divided into five groups (n = 10/group) which are control, AlCl3, AlCl3 + Sesamol, AlCl3 + L. rhamnosus and AlCl3 + Sesamol + L. rhamnosus. We surveilled the behavioral, biochemical, and histopathological alterations centrally in the brain and peripherally in liver. Results: This work revealed that the combined therapy of sesamol and L. rhamnosus produced marked reduction in brain amyloid-ß, p-tau, GSK-3ß, inflammatory and apoptotic biomarkers, along with marked elevation in brain free ß-catenin and Wnt3a, compared to AlCl3-intoxicated rats. Also, the combined therapy exerted pronounced reduction in hepatic expressions of JAK-2/STAT-3, inflammatory (TNF-α, IL-6, NF-κB), fibrotic (MMP-2, TIMP-1, α-SMA) and apoptotic markers, (caspase-3), together with marked elevation in hepatic PPAR-γ expression, compared to AlCl3 -intoxicated rats. Behavioral and histopathological assessments substantiated the efficiency of this combined regimen in halting the effect of neurotoxicity. Discussion: Probiotics can be used as an add-on therapy with sesamol ameliorate AlCl3 -mediated neurotoxicity and hepatotoxicity.

Anti-Alzheimer Activity of Combinations of Cocoa with Vinpocetine or Other Nutraceuticals in Rat Model: Modulation of Wnt3/ß-Catenin/GSK-3ß/Nrf2/HO-1 and PERK/CHOP/Bcl-2 Pathways.

Alzheimer's disease (AD) is a devastating illness with limited therapeutic interventions. The aim of this study is to investigate the pathophysiological mechanisms underlying AD and explore the potential neuroprotective effects of cocoa, either alone or in combination with other nutraceuticals, in an animal model of aluminum-induced AD. Rats were divided into nine groups: control, aluminum chloride (AlCl3) alone, AlCl3 with cocoa alone, AlCl3 with vinpocetine (VIN), AlCl3 with epigallocatechin-3-gallate (EGCG), AlCl3 with coenzyme Q10 (CoQ10), AlCl3 with wheatgrass (WG), AlCl3 with vitamin (Vit) B complex, and AlCl3 with a combination of Vit C, Vit E, and selenium (Se). The animals were treated for five weeks, and we assessed behavioral, histopathological, and biochemical changes, focusing on oxidative stress, inflammation, Wnt/GSK-3ß/ß-catenin signaling, ER stress, autophagy, and apoptosis. AlCl3 administration induced oxidative stress, as evidenced by elevated levels of malondialdehyde (MDA) and downregulation of cellular antioxidants (Nrf2, HO-1, SOD, and TAC). AlCl3 also upregulated inflammatory biomarkers (TNF-α and IL-1ß) and GSK-3ß, leading to increased tau phosphorylation, decreased brain-derived neurotrophic factor (BDNF) expression, and downregulation of the Wnt/ß-catenin pathway. Furthermore, AlCl3 intensified C/EBP, p-PERK, GRP-78, and CHOP, indicating sustained ER stress, and decreased Beclin-1 and anti-apoptotic B-cell lymphoma 2 (Bcl-2) expressions. These alterations contributed to the observed behavioral and histological changes in the AlCl3-induced AD model. Administration of cocoa, either alone or in combination with other nutraceuticals, particularly VIN or EGCG, demonstrated remarkable amelioration of all assessed parameters. The combination of cocoa with nutraceuticals attenuated the AD-mediated deterioration by modulating interrelated pathophysiological pathways, including inflammation, antioxidant responses, GSK-3ß-Wnt/ß-catenin signaling, ER stress, and apoptosis. These findings provide insights into the intricate pathogenesis of AD and highlight the neuroprotective effects of nutraceuticals through multiple signaling pathways.

ABO, Lewis blood group systems and secretory status with H.pylori infection in yemeni dyspeptic patients: a cross- sectional study.

BACKGROUND: The ABO and Lewis blood group antigens are potential factors in susceptibility to H. pylori infection. This research aimed to examine the prevalence of Helicobater pylori (H.pylori) infection and its association with ABO, Lewis blood group systems, and secretory status in Yemeni symptomatic patients. METHODS: In a cross-sectional study, 103 patients referred for endoscopy due to dyspepsia were included. H pylori infection was assessed using stool antigen and serum antibody rapid tests. ABO and Lewis blood group systems were examined using hemagglutination assay. Saliva samples were investigated for identification of the secretory phenotype using hemagglutination inhibition test. RESULTS: The prevalence of H. pylori infection was (80.6%), with a higher rate of infection in females than males. The ABO blood groups were found to be significantly different between males and females (p = 0.047). The O blood group was prevalent among H. pylori patients, especially secretors. There was a significant association between ABO blood groups and H. pylori infection (p = 0.001). The Le (a + b+) phenotype was the most common, followed by Le (a + b-), Le (a-b+), and Le (a-b-). Lewis blood group systems and secretory status of symptomatic patients were not associated with H. pylori infection. The results showed that serum Ab test for H. pylori achieved poor sensitivity (68%), specificity of 55%; positive predictive value (PPV) 86%, negative predictive value (NPV) 29% and accuracy 65.1%. CONCLUSION: The prevalence of H. pylori infection was high in Yemeni patients. This infection was linked to the O and Le (a + b+) secretor phenotype. The H. pylori stool Ag test is the most reliable noninvasive diagnostic method for detecting H. pylori infection.

The consumption pattern and perception of using artificial sweeteners among the public in Tabuk region, Saudi Arabia.

Background: Obesity and weight gain have become major problems worldwide. Thus, several forms of alternative intense sweeteners are extensively used, offering a non-caloric sweet taste. To the best of our knowledge, no research has studied either the consumption pattern or the perception of using artificial sweeteners in Saudi Arabia. Objectives: Our research aimed to study the usage pattern of such artificial sweeteners in the Tabuk region and estimate the knowledge of and attitudes toward their usage among the population. Methods: A cross-sectional study promoted on multiple social media platforms and face-to-face interviews in different malls and hospitals in the Tabuk region. We grouped the participants into two major groups: the users and the non-users of artificial sweeteners. Each group has been subdivided into a healthy subgroup and those with a medical record subgroup. Participants' characteristics and their choice of sweeteners were analyzed using bivariate analysis. The age, gender, and education level of the participants were adjusted using binary logistic regression in order to adjust for potential confounders. Results: A total of 2,760 participants were included in our study. We found that more than 59% of the participants that were over 45 years old were non-hospitalized non-hospitalized diseased irrespective of their usage of artificial sweeteners. Furthermore, females, graduates, diabetics were significantly high irrespective of their subgroup. Moreover, Steviana® is the most commonly used artificial sweetener. In addition, healthy participants showed a greater perception of the usage and adverse effects of artificial sweeteners. Furthermore, bivariate analysis using logistic regression revealed significant associations (p < 0.05) with confounders such as gender, age, and education level. Conclusion: Educational programs and nutritional advice for the safe consumption and the daily permissible doses of artificial sweeteners are essential and should be directed specifically at females.

Effects of Albumin-Chlorogenic Acid Nanoparticles on Apoptosis and PI3K/Akt/mTOR Pathway Inhibitory Activity in MDA-MB-435s Cells.

In this study, we synthesized, characterized, and explored the anti-microbial and anti-cancer effects of albumin-chlorogenic acid nanoparticles (NPs). Characterization studies with a UV-vis spectrophotometer, FTIR, PL spectrum, TEM, FESEM, XRD, and DLA analysis showed patterns confirming the physio-chemical nature of biogenic nanocomposites. Further, anti-microbial studies using bacterial strains Staphylococcus aureus, Streptococcus pneumonia, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Vibrio cholera, and fungal strain Candida albicans showed significant (p < 0.05) anti-bacterial and anti-fungal activities. Next, we used MDA-MB-435s, a human cell line, to evaluate the anti-cancer effects of albumin-chlorogenic acid NPs. Cytotoxic studies revealed its IC50 concentration at 24 µg/mL after a 24 h treatment of MDA-MB-435s cells. We chose this IC50 dose to analyze albumin-chlorogenic acid NPs anti-cancer effects in vitro. MDA-MB-435s cells exposed to our NPs were studied via AO/EtBr staining, cell cycle analyses via PI staining, the status of whole genomic damage via comet assay, levels of apoptotic cells via annexin V/PI staining, ROS generation via DCFH-DA staining, an assay of antioxidant enzymes catalase, superoxide dismutase, and antioxidant GSH, via ELISA analyses of apoptotic markers caspase-3, 8, 9, Bax, Bcl-2, CytC, and p53, PI3/AKT/mTOR pathway. Our results collectively showed albumin-chlorogenic acid NPs induced apoptosis via p53-dependent and PI3/AKT/mTOR inhibition in MDA-MB-435s cells. Our results denote albumin-chlorogenic acid NPs can be used as an effective candidate for anti-microbial and anti-cancer applications; however, further in vivo confirmatory studies are warranted.

Sodium alginate encapsulated iron oxide decorated with thymoquinone nanocomposite induces apoptosis in human breast cancer cells via PI3K-Akt-mTOR pathway.

The present study investigated the cytotoxicity and proapoptotic properties of iron oxide-sodium-alginate-thymoquinone nanocomposites against breast cancer MDA-MB-231 cells in vitro and in silico. This study used chemical synthesis to formulate the nanocomposite. Electron microscopies such as scanning (SEM) and transmission (TEM), Fourier transform infrared (FT-IR), Ultraviolet-Visible, Photoluminescence spectroscopy, selected area (electron) diffraction (SAED), energy dispersive X-ray analysis (EDX), and X-ray diffraction studies (XRD) were used to characterize the synthesized ISAT-NCs and the average size of them was found to be 55 nm. To evaluate the cytotoxic, antiproliferative, and apoptotic potentials of ISAT-NCs on MDA-MB-231 cells, MTT assays, FACS-based cell cycle studies, annexin-V-PI staining, ELISA, and qRT-PCR were used. PI3K-Akt-mTOR receptors and thymoquinone were predicted using in-silico docking studies. Cell proliferation is reduced in MDA-MB-231 cells due to ISAT-NC cytotoxicity. As a result of FACS analysis, ISAT-NCs had nuclear damage, ROS production, and elevated annexin-V levels, which resulted in cell cycle arrest in the S phase. The ISAT-NCs in MDA-MB-231 cells were found to downregulate PI3K-Akt-mTOR regulatory pathways in the presence of inhibitors of PI3K-Akt-mTOR, showing that these regulatory pathways are involved in apoptotic cell death. We also predicted the molecular interaction between thymoquinone and PI3K-Akt-mTOR receptor proteins using in-silico docking studies which also support PI3K-Akt-mTOR signaling inhibition by ISAT-NCs in MDA-MB-231 cells. As a result of this study, we can conclude that ISAT-NCs inhibit the PI3K-Akt-mTOR pathway in breast cancer cell lines, causing apoptotic cell death.

Lyophilized equine platelet-rich plasma (L-GFequina) antagonize the Reproductive toxicity and oxidative stress Induced by Cyclophosphamide in female rats.

BACKGROUND: The antineoplastic agent Cyclophosphamide (CP) induces reproductive toxicity. New strategies for protecting ovarian tissue damage in women with chemotherapy-induced reproductive toxicity are essential. This study was designed to evaluate the possible protective effect of combined treatment with L-GFequina on CP-induced reproductive toxicity in the mature female rat. METHODOLOGY: Forty mature female rats were assigned into four groups: First group, control: rats were intraperitoneally injected (IP) with 200 µl sterile saline solution on days 1 and 10; Group 2 (CP): were IP injected with 75 mg/kg on days 1 and 10 to induce POI); Group 3 (CP + L-GFequina): as in group 2 + IP injected with 200 µl rehydrated L-GFequina half-hour after CP injection on day 1 and 10); Group 4 (L-GFequina): rats were IP injected with 200 µl L-GFequina on day 1 and 10). Blood samples were collected for a complete blood picture and determinations of nitric oxide and malondialdehyde. Animals were sacrificed on Day-21, and genitalia was dissected, weighed, and fixed in 10% formalin for histopathological and morphometric evaluation. RESULTS: On day 21 of the experiment, body weight, ovarian parameters (Ovarian weight, uterine weight, the number of ovarian follicles, and corpora lutea (CL) were determined, and histopathological changes, blood profile, as well as antioxidant activity assessment, were performed. CP significantly suppresses ovarian and uterine functions and increased MAD, NO levels, RBCs, hemoglobin, WBCs, and platelet count compared to the control group ( P < 0.05). While, in CP + L-GFequina group, gross, histomorphometry parameters, blood, and biochemical markers were similar to that in the control. IP injection of L-GFequina alone significantly (P < 0.05) increased body weight, and ovarian and uterine morphometry compared with the control. CONCLUSION: co-administration of L-GFequina with CP might protect the reproductive organs in rats through its high antioxidant capacity.

Therapeutic Potential of Albumin Nanoparticles Encapsulated Visnagin in MDA-MB-468 Triple-Negative Breast Cancer Cells.

Breast cancer is among the most recurrent malignancies, and its prevalence is rising. With only a few treatment options available, there is an immediate need to search for better alternatives. In this regard, nanotechnology has been applied to develop potential chemotherapeutic techniques, particularly for cancer therapy. Specifically, albumin-based nanoparticles are a developing platform for the administration of diverse chemotherapy drugs owing to their biocompatibility and non-toxicity. Visnagin, a naturally derived furanochromone, treats cancers, epilepsy, angina, coughs, and inflammatory illnesses. In the current study, the synthesis and characterization of albumin visnagin (AV) nanoparticles (NPs) using a variety of techniques such as transmission electron microscopy, UV-visible, Fourier transform infrared, energy dispersive X-ray composition analysis, field emission scanning electron microscopy, photoluminescence, X-Ray diffraction, and dynamic light scattering analyses have been carried out. The MTT test, dual AO/EB, DCFH-DA, Annexin-V-FITC/PI, Propidium iodide staining techniques as well as analysis of apoptotic proteins, antioxidant enzymes, and PI3K/Akt/mTOR signaling analysis was performed to examine the NPs' efficacy to suppress MDA-MB-468 cell lines. The NPs decreased cell viability increased the amount of ROS in the cells, disrupted membrane integrity, decreased the level of antioxidant enzymes, induced cell cycle arrest, and activated the PI3K/Akt/mTOR signaling cascade, ultimately leading to cell death. Thus, AV NPs possesses huge potential to be employed as a strong anticancer therapy alternative.