Influence of applying VARK learning styles on enhancing teaching skills: application of learning theories.

BACKGROUND: Social media in our networks have been exploited as dynamic learning tools and free platforms. AIMS: The main objective of this study is to determine the impact of VARK learning styles (visual (V), aural (A), read/write (R), and kinesthetic (K)) in enhancing parasitological laboratory skills using social media and various learning theories. METHODS: A research sample of 100 chemists working in Mega Alfa labs underwent online learning of laboratory parasitology skills via Facebook posts and WhatsApp dictated messages for an average of 7 weeks. All posts served various VARK learning styles and were designed based on Zeigarnik's effect (conducting information with tactical breaks), memory storage and retrieval strength theories (repetition of information). Trainees were classified according to their VARK learning style preferences and were evaluated through pre/post-tests. Data on VARK learning styles were summarized using frequency (count) and relative frequency (percentage). Data of pre-test and post-test scores were summarized using mean and standard deviation. T-test was used to compare pre-test and post-test scores. The difference between the pre-test results, the post-test results and the preferred learning style was analyzed using ANOVA with Tukey's post-hoc testing. P-values less than 0.05 were considered statistically significant. RESULTS: In a total of 100 trainees, tri-modal and multimodal learning styles were preferred by 40% and 30% of the trainees respectively; on the contrary, the unimodal and bimodal learning styles were the least preferred. In the trimodal and multimodal groups, the post-test results showed significant increase when compared with the pre-test results. Also, using the ANOVA test and a Tukey's post-hoc comparison, the assemblage of multiple learning styles (tri-modal and multimodal) appeared to significantly improve the learning performance in the post-test results when compared with the unimodal and bimodal groups. CONCLUSION: The tri-modal and multimodal learning styles were found to influence the acquirement of the laboratory parasitology skills much better than the unimodal and bimodal learning styles. Kinesthetic learning should have a special emphasis in training.

Forced Swimming-Induced Depressive-like Behavior and Anxiety Are Reduced by Chlorpheniramine via Suppression of Oxidative and Inflammatory Mediators and Activating the Nrf2-BDNF Signaling Pathway.

The first-generation antihistamine chlorpheniramine (CPA) is believed to have both anxiolytic and antidepressant properties. The current study sought to assess the mechanisms behind the antidepressant and anxiolytic effects of CPA therapy concerning oxidative stress, inflammation, and nuclear factor p45 for erythroid 2-Brain-derived neurotrophic factor (Nrf2-BDNF) signaling pathway in forced swimming-induced depressive-like behavior and anxiety. Eighteen male Wistar rats (180-200 gm) rats were separated into three groups (n = 6): a stressed group (acute stress) that underwent the forced swimming test (FST) and a stressed group that received pretreatment with CPA (10 mg/kg body weight) for 3 weeks (CPA + acute stress). Animals were subsequently put through the following behavioral tests after undergoing a forced swim test (FST) for 5 min: an immobility test, open field test, and elevated plus maze test. Serum cortisol levels were measured when the rats were euthanized at the end of the experiments. Brain neurotransmitters (cortisol, serotonin, and noradrenaline), oxidative stress (SOD and MDA), inflammatory (IL-6 and IL-1) biomarkers, and the Nrf2-BDNF signaling pathway in the hippocampus and cerebral cortex tissues was determined. CPA prevented stress-induced increases in cortisol levels (p < 0.0001), decreased brain neurotransmitters, and increased oxidative stress and inflammation. CPA also upregulated the Nrf2-BDNF signaling pathway. Thus, CPA mitigates depressive-like behavior and anxiety by inhibiting oxidative stress and inflammation and upregulating the Nrf2-BDNF signaling pathway in the brain tissues.

Comparing Effectiveness of Hyaluronic Acid-Chitosan Nanoparticles Encapsulation Versus Hyaluronic Acid Monotherapy in Osteoarthritis Rat Model: Microarray Screening for miR-140.

Osteoarthritis is a debilitating, progressive joint disease linked to lower quality of life and higher health care costs. This study compared hyaluronic acid-chitosan nanoparticle encapsulation to hyaluronic-acid monotherapy in a rat model of knee osteoarthritis. Four groups of 40 adult male albino rats were designed. Group (Gp) I: control; Gp II (osteoarthritis model): intra-articular injection of monoiodoacetate; Gp III (hyaluronic acid-treated): intra-articular injections of hyaluronic-acid on days 14 and 21 after monoiodoacetate injection; and Gp IV (hyaluronic acid-chitosan nanoparticle-treated): intra-articular injections of hyaluronic acid-chitosan nanoparticle on days 14 and 21 after monoiodoacetate injection. After 28 days, knee joints were examined using H&E, Safranin O, and immunohistochemistry for nuclear factor kappa beta (NF-κB), inducible nitric oxide synthase (iNOS), and matrix metalloproteinase (MMP)-13. Quantification for gene expression of collagen-II, aggrecan, and micro-RNA-140; ELISA for interleukin (IL)-1ß and IL-8; and western blotting for IKBα and NF-κB was estimated. Osteoarthritis-knee joints showed a severe cartilage damage and synovial inflammation with increased NF-κB, iNOS, and MMP-13 immunostaining, decreased miR-140, collagen II, and aggrecan levels, and increased inflammatory markers' gene expressions. The hyaluronic acid-chitosan nanoparticle significantly improved knee joint structure and reduced inflammatory cytokines compared to hyaluronic acid monotherapy. Intra-articular injection of hyaluronic acid-chitosan nanoparticle encapsulation revealed a significant improvement in the knee joint structure compared to hyaluronic-acid in a rat model of osteoarthritis.

Metformin Suppresses Thioacetamide-Induced Chronic Kidney Disease in Association with the Upregulation of AMPK and Downregulation of Oxidative Stress and Inflammation as Well as Dyslipidemia and Hypertension.

Toxic chemicals such as carbon tetrachloride and thioacetamide (TAA) are reported to induce hepato-nephrotoxicity. The potential protective outcome of the antidiabetic and pleiotropic drug metformin against TAA-induced chronic kidney disease in association with the modulation of AMP-activated protein kinase (AMPK), oxidative stress, inflammation, dyslipidemia, and systemic hypertension has not been investigated before. Therefore, 200 mg/kg TAA was injected (via the intraperitoneal route) in a model group of rats twice a week starting at week 3 for 8 weeks. The control rats were injected with the vehicle for the same period. The metformin-treated group received 200 mg/kg metformin daily for 10 weeks, beginning week 1, and received TAA injections with dosage and timing similar to those of the model group. All rats were culled at week 10. It was observed that TAA induced substantial renal injury, as demonstrated by significant kidney tissue damage and fibrosis, as well as augmented blood and kidney tissue levels of urea, creatinine, inflammation, oxidative stress, dyslipidemia, tissue inhibitor of metalloproteinases-1 (TIMP-1), and hypertension. TAA nephrotoxicity substantially inhibited the renal expression of phosphorylated AMPK. All these markers were significantly protected by metformin administration. In addition, a link between kidney fibrosis and these parameters was observed. Thus, metformin provides profound protection against TAA-induced kidney damage and fibrosis associated with the augmentation of the tissue protective enzyme AMPK and inhibition of oxidative stress, inflammation, the profibrogenic gene TIMP-1, dyslipidemia, and hypertension for a period of 10 weeks in rats.

Lipopolysaccharide induces acute lung injury and alveolar haemorrhage in association with the cytokine storm, coagulopathy and AT1R/JAK/STAT augmentation in a rat model that mimics moderate and severe Covid-19 pathology.

Progress in the study of Covid-19 disease in rodents has been hampered by the lack of angiotensin-converting enzyme 2 (ACE2; virus entry route to the target cell) affinities for the virus spike proteins across species. Therefore, we sought to determine whether a modified protocol of lipopolysaccharide (LPS)-induced acute respiratory distress syndrome in rats can mimic both cell signalling pathways as well as severe disease phenotypes of Covid-19 disease. Rats were injected via intratracheal (IT) instillation with either 15 mg/kg of LPS (model group) or saline (control group) before being killed after 3 days. A severe acute respiratory syndrome (SARS)-like effect was observed in the model group as demonstrated by the development of a "cytokine storm" (>2.7 fold increase in blood levels of IL-6, IL-17A, GM-CSF, and TNF-α), high blood ferritin, demonstrable coagulopathy, including elevated D-dimer (approximately 10-fold increase), PAI-1, PT, and APTT (p < 0.0001). In addition, LPS increased the expression of lung angiotensin II type I receptor (AT1R)-JAK-STAT axis (>4 fold increase). Chest imaging revealed bilateral small patchy opacities of the lungs. Severe lung injury was noted by the presence of both, alveolar collapse and haemorrhage, desquamation of epithelial cells in the airway lumen, infiltration of inflammatory cells (CD45+ leukocytes), widespread thickening of the interalveolar septa, and ultrastructural alterations similar to Covid-19. Thus, these findings demonstrate that IT injection of 15 mg/kg LPS into rats, induced an AT1R/JAK/STAT-mediated cytokine storm with resultant pneumonia and coagulopathy that was commensurate with moderate and severe Covid-19 disease noted in humans.

Hydrogen sulfide and mesenchymal stem cells-extracted microvesicles attenuate LPS-induced Alzheimer's disease.

Both hydrogen sulfide (H2 S) and mesenchymal stem cells (MSCs) extracted microvesicles (MVs) are potent anti-inflammatory molecules. They play an essential role in lowering the production of tumor necrosis factor-alpha (TNF-α). The latter could strongly stimulate MiR-155 that contributes to neurodegeneration and Alzheimer's disease (AD). miR-155 could repress the expression of inositol 5-phosphatase-1 (SHIP-1) leading eventually to activation of Akt kinase and neurofibrillary development in AD. The current study was conducted to evaluate the role of miR-155 in a rat model of lipopolysaccharide (LPS)-induced AD and to investigate the effect of using MVs and H2 S that were given either separately or combined in regulating pro-inflammatory signaling. Thirty female Wistar albino rats aged 6 months to 1 year were equally divided into five groups; control group, LPS-induced AD group, LPS + MVs group, LPS + NaHS group, and LPS + MVs and NaHS group. The increased miR-155 level was associated with decreased SHIP-1 level and positively correlated with TNF-α. In addition, treatment with MVs and/or NaHS resulted in attenuation of inflammation, decreasing miR-155, pAkt levels, and downregulation of apoptosis along with improvement of the hippocampal and cortical histopathological alterations. LPS enhanced production of malondialdehyde (MDA) and reduced glutathione (GSH) levels indicating oxidative stress-induced neural damage, whereas MVs and NaHS could mitigate oxidative damage and accelerate antioxidant capacity via increasing catalase enzyme. In conclusion, downregulation of TNF-α, miR-155, and pAkt and increased SHIP-1 could improve the neuro-inflammatory state and cognitive function of LPS-induced Alzheimer's disease.

Metformin impairs homing ability and efficacy of mesenchymal stem cells for cardiac repair in streptozotocin-induced diabetic cardiomyopathy in rats.

Bone marrow-derived mesenchymal stem cells (BM-MSCs) have demonstrated potential in treating diabetic cardiomyopathy. However, patients with diabetes are on multiple drugs and there is a lack of understanding of how transplanted stem cells would respond in presence of such drugs. Metformin is an AMP kinase (AMPK) activator, the widest used antidiabetic drug. In this study, we investigated the effect of metformin on the efficacy of stem cell therapy in a diabetic cardiomyopathy animal model using streptozotocin (STZ) in male Wistar rats. To comprehend the effect of metformin on the efficacy of BM-MSCs, we transplanted BM-MSCs (1 million cells/rat) with or without metformin. Our data demonstrate that transplantation of BM-MSCs prevented cardiac fibrosis and promoted angiogenesis in diabetic hearts. However, metformin supplementation downregulated BM-MSC-mediated cardioprotection. Interestingly, both BM-MSCs and metformin treatment individually improved cardiac function with no synergistic effect of metformin supplementation along with BM-MSCs. Investigating the mechanisms of loss of efficacy of BM-MSCs in the presence of metformin, we found that metformin treatment impairs homing of implanted BM-MSCs in the heart and leads to poor survival of transplanted cells. Furthermore, our data demonstrate that metformin-mediated activation of AMPK is responsible for poor homing and survival of BM-MSCs in the diabetic heart. Hence, the current study confirms that a conflict arises between metformin and BM-MSCs for treating diabetic cardiomyopathy. Approximately 10% of the world population is diabetic to which metformin is prescribed very commonly. Hence, future cell replacement therapies in combination with AMPK inhibitors may be more effective for patients with diabetes.NEW & NOTEWORTHY Metformin treatment reduces the efficacy of mesenchymal stem cell therapy for cardiac repair during diabetic cardiomyopathy. Stem cell therapy in diabetics may be more effective in combination with AMPK inhibitors.

Hypoxia-induced downregulation of cyclooxygenase 2 leads to the loss of immunoprivilege of allogeneic mesenchymal stem cells.

Allogeneic mesenchymal stem cells (MSCs) from young and healthy donors are reported to hold the potential to treat several immunological and degenerative disorders. However, recent data from animal studies and clinical trials demonstrate that immunogenicity and poor survival of transplanted MSCs impaired the efficacy of cells for regenerative applications. It is reported that initially immunoprivileged under in vitro conditions, MSCs are targeted by the host immune system after transplantation in the ischemic tissues in vivo. We performed in vitro (in MSCs) and in vivo (in the rat model of myocardial infarction [MI]) studies to elucidate the mechanisms responsible for the change in the immunophenotype of MSCs from immunoprivileged to immunogenic under ischemic conditions. We have recently reported that a soluble factor prostaglandin E2 (PGE2) preserves the immunoprivilege of allogeneic MSCs. In the current study, we found that PGE2 levels, which were elevated during normoxia, decreased in MSCs following exposure to hypoxia. Further, we found that proteasome-mediated degradation of cyclooxygenase-2 (COX2, rate-limiting enzyme in PGE2 biosynthesis) in hypoxic MSCs is responsible for PGE2 decrease and loss of immunoprivilege of MSCs. While investigating the mechanisms of COX2 degradation in hypoxic MSCs, we found that in normoxic MSCs, COP9 signalosome subunit 5 (CSN5) binds to COX2 and prevents its degradation by the proteasome. However, exposure to hypoxia leads to a decrease in CSN5 levels and its binding to COX2, rendering COX2 protein susceptible to proteasome-mediated degradation. This subsequently causes PGE2 downregulation and loss of immunoprivilege of MSCs. Maintaining COX2 levels in MSCs preserves immunoprivilege in vitro and improves the survival of transplanted MSCs in a rat model of MI. These data provide novel mechanistic evidence that PGE2 is downregulated in hypoxic MSCs which is responsible for the post-transplantation rejection of allogeneic MSCs. Therefore, our data suggest that the new strategies that target CSN5-COX2 signaling may improve survival and utility of transplanted allogeneic MSCs in the ischemic heart.

Hypoxia-induced increase in Sug1 leads to poor post-transplantation survival of allogeneic mesenchymal stem cells.

Allogeneic mesenchymal stem cells (MSCs) from young and healthy donors are immunoprivileged and have the potential to treat numerous degenerative diseases. However, recent reviews of clinical trials report poor long-term survival of transplanted cells in the recipient that turned down the enthusiasm regarding MSC therapies. Increasing evidence now confirm that though initially immunoprivileged, MSCs eventually become immunogenic after transplantation in the ischemic or hypoxic environment of diseased tissues and are rejected by the host immune system. We performed in vitro (in rat and human cells) and in vivo (in a rat model) investigations to understand the mechanisms of the immune switch in the phenotype of MSCs. The immunoprivilege of MSCs is preserved by the absence of cell surface immune antigen, major histocompatibility complex II (MHC-II) molecule. We found that the ATPase subunit of 19S proteasome "Sug1" regulates MHC-II biosynthesis in MSCs. Exposure to hypoxia upregulates Sug1 in MSCs and its binding to class II transactivator (CIITA), a coactivator of MHC-II transcription. Sug1 binding to CIITA in hypoxic MSCs promotes the acetylation and K63 ubiquitination of CIITA leading to its activation and translocation to the nucleus, and ultimately MHC-II upregulation. In both rat and human MSCs, knocking down Sug1 inactivated MHC-II and preserved immunoprivilege even following hypoxia. In a rat model of myocardial infarction, transplantation of Sug1-knockdown MSCs in ischemic heart preserved immunoprivilege and improved the survival of transplanted cells. Therefore, the current study provides novel mechanisms of post-transplantation loss of immunoprivilege of MSCs. This study may help in facilitating better planning for future clinical trials.

Resveratrol suppresses cholestasis-induced liver injury and fibrosis in rats associated with the inhibition of TGFß1-Smad3-miR21 axis and profibrogenic and hepatic injury biomarkers.

Cholestasis caused by slowing or blockage of bile flow is a serious liver disease that can lead to liver fibrosis and cirrhosis. The link between transforming growth factor beta 1 (TGFß1), Smad family member 3 (Smad3), and microRNA 21 (miR21) in bile duct ligation (BDL)-induced liver fibrosis in the presence and absence of the anti-inflammatory and antioxidant compound, resveratrol (RSV), has not been previously studied. Therefore, we tested whether RSV can protect against BDL-induced liver fibrosis associated with the inhibition of the TGFß1-Smad3-miR21 axis and profibrogenic and hepatic injury biomarkers. The model group of rats had their bile duct ligated (BDL) for 3 weeks before being killed, whereas, the BDL-treated rats were separated into three groups that received 10, 20, and 30 mg/kg RSV daily until the end of the experiment. Using light microscopy and ultrasound examinations, we documented in the BDL group, the development of hepatic injury and fibrosis as demonstrated by hepatocytes necrosis, bile duct hyperplasia, collagen deposition, enlarged liver with increased echogenicity, irregular nodular border and dilated common bile duct, which were more effectively inhibited by the highest used RSV dosage. In addition, RSV significantly (p ≤ 0.0027) inhibited BDL-induced hepatic TGFß1, Smad3, miR21, the profibrogenic biomarker tissue inhibitor of metalloproteinases-1 (TIMP-1), malondialdehyde (MDA), interleukin-17a (IL-17a), and blood levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin. These findings show that RSV at 30 mg/kg substantially protects against BDL-induced liver injuries, which is associated with the inhibition of TGFß1-Smad3-miR21 axis, and biomarkers of profibrogenesis, oxidative stress, and inflammation.

Combined treatment with systemic resveratrol and resveratrol preconditioned mesenchymal stem cells, maximizes antifibrotic action in diabetic cardiomyopathy.

Wnt/ß-catenin signaling pathway plays a crucial role in diabetic cardiomyopathy (DCM), thus we aimed at investigating the effect of one therapeutic approach with resveratrol (RSV) given systemically and combined treatment of RSV with mesenchymal stem cells (MSCs) that was either RSV-preconditioned or not on Wnt/ß-catenin signaling pathway in streptozotocin-induced DCM, and to evaluate effects of RSV preconditioning on MSCs therapeutic potential. The rats were divided into control (C, n = 8), diabetic (DM, n = 8), diabetic treated with systemic RSV (DM-RSV, n = 8), diabetic treated with RSV and nonconditioned MSCs (DM-RSV-MSCs, n = 8), diabetic treated with RSV and RSV-incubated with MSCs (DM-RSV-MSCc, n = 8) and diabetic treated with RSV-conditioned MSCs (DM-MSCc, n = 8). Echocardiography (Echo) showed significant improvement of cardiac functions in all groups treated with RSV either systemic or added in culture media. Data of ejection fraction (EF%) of DM-RSV-MSCc (81.50; interquartile range [IQR], 80.00-83.00) was comparable to both DM-RSV-MSCs (77.50; IQR, 71.50-79.00), and DM-MSCc (71.50; IQR, 70.00-74.50). Histological examination of the left ventricles was performed for all groups. DM group revealed significant myocardial hypertrophy, apoptosis, interstitial fibrosis, and microvascular affection. All treated groups were associated, in variable degrees, with attenuation of cardiac hypertrophy and fibrosis, decreased area% for cardiac immunostaining of secreted frizzled-related protein (sFRP2) and Wnt/ß-catenin and improvement of the microvasculature. In conclusion, MSCs pretreated with resveratrol for 7 days showed increased 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and combined use of RSV (systemically and in culture media) significantly could improve cardiac remodeling capacity of MSCs via attenuation of sFRP2-mediated fibrosis and the downstream Wnt/ß-catenin pathway.

Contribution of volume overload to progression of cardiovascular disease in a rat model of chronic kidney disease.

Volume overload is a common phenomenon in patients with chronic kidney disease that is associated with cardiovascular risk factors. However, its contribution to the development of adverse cardiovascular outcomes in those patients is not fully understood. Thus, the present work investigated the effect of salt-induced volume overload on cardiac functions and geometry in a rat model of chronic kidney disease. Thirty adult male Sprague-Dawley rats were randomly divided. One set of animals received a sham operation, while another set of animals underwent uninephrectomy. Rats were then fed either a normal-salt (0.4%) or high-salt (8.0%) diet for 6 weeks. The salt-loaded, uninephrectomized rats were treated with indapamide (3 mg·kg-1·day-1, orally) for 6 weeks. We found that uninephrectomized rats subjected to a high-salt diet (8.0%) for 6 weeks presented with hypertension, proteinuria, decreased renal Klotho expression, and deterioration in cardiac hemodynamics and histology. Echocardiography to assess cardiac function showed that ejection fraction and fractional shortening were positively correlated with relative renal Klotho expression. In conclusion, salt-induced volume overload in a rat model of chronic kidney disease has an adverse cardiovascular outcome and is associated with inflammatory activation and decrease in renal Klotho expression.

Amelioration of cisplatin-induced neurodegenerative changes in rats and restoration of mitochondrial biogenesis by 6-bromoindirubin-3'-oxime: The implication of the GSK-3ß/PGC1-α axis.

BACKGROUND: The cognitive deficits observed after treatment with chemotherapeutic drugs are obvious clinical problems. For treating chemotherapy-induced cognitive deficits (CICD), the treatment modalities must target its underlying mechanisms. Specifically, cisplatin may activate glycogen synthase kinase-3ß (GSK-3ß), thereby enhancing neuronal apoptosis. 6-bromoindirubin-3'-oxime (6BIO) was not investigated previously in a model of CICD. Therefore, this investigation aimed to address the impacts of GSK3 inhibition on regulating cell signaling, which contributes to neurodegeneration and cognitive impairment. METHODS: Thirty adult male Wistar rats were randomly allocated into control groups, while two experimental groups were exposed to repeated cisplatin injections (2 mg/kg intraperitoneally (ip), twice weekly, nine injections), termed chemobrain groups. The rats in the two experimental groups were equally divided into the chemobrain group (untreated) and the chemobrain-6BIO group (treated with 6BIO at a dose of 8.5 µg/kg ip every two days, started after the last dose of cisplatin and continued for two weeks). RESULTS: Repeated exposure to cisplatin led to a marked decline in cognitive functions. GSK3 inhibition exerted neuroprotection by decreasing the expression of p-tau and amyloid ß, thereby improving cognition. 6BIO, the GSK-3ß inhibitor, restored mitochondrial biogenesis by augmenting the protein levels of PGC1-α and increasing the number of mitochondria in the cerebral cortex and hippocampus. CONCLUSION: 6BIO provided neuroprotection and exhibited anti-apoptotic and anti-oxidative effects in a rat model of chemobrain.

Comparing the therapeutic potentials of Lactobacillus johnsonii vs. Lactobacillus acidophilus against vulvovaginal candidiasis in female rats: an in vivo study.

Background: Vulvovaginal candidiasis (VVC) is a highly prevalent illness affecting women globally. Lactobacilli, which make up the majority of healthy vaginal microbiota (VMB), serve as a powerful barrier against infections. Probiotic therapy has been recommended for the treatment or prevention of VVC. Aim of work: To compare the in vivo therapeutic effects of Lactobacillus johnsonii (B-2178) vs. Lactobacillus acidophilus (LA-5®) on VVC in a rat model, particularly highlighting the immune response of the host vaginal epithelium. Methods: In total, 30 female Sprague-Dawley rats were divided into 5 groups; Group 1: no intervention, Group 2: ovariectomy group, while animals in Groups 3-5 were subjected to ovariectomy and an intravaginal inoculation of Candida albicans (C. albicans) to establish VVC. The animals in Groups 4 and 5 received intravaginal lactobacilli treatment with L. acidophilus (LA-5®) and L. johnsonii (B-2178) strains, respectively, for 7 days. C. albicans load was measured in a vaginal lavage 1, 3, and 7 days after the stoppage of the treatment. Histological, morphometric, and immunohistochemical studies of the vaginal tissues were done. IFN-γ, IL-4, and IL-17 were measured in the vaginal tissue. Results: Both L. johnsonii and L. acidophilus significantly reduced C. albicans vaginal load (250 ± 77.46 and 133.33 ± 40.82 CFU/mL) compared to the count before treatment in both groups (4,850 ± 1419.51 and 4966.67 ± 852.45 CFU/mL) even after 7 days of stoppage of lactobacilli treatment. A statistically significant reduction of the pro-inflammatory cytokines IL-17 and IFN-γ was reported in both treated groups compared to the infected untreated group. L. johnsonii has a significant effect on the reduction of hyphae formation of C. albicans as well as the nuclear factor kappa B (NF-κB) immunostaining density of vaginal tissue compared to L. acidophilus. Moreover, treatment with L. johnsonii significantly minimized the epithelium damage triggered by C. albicans infection and restored normal vaginal architecture as evidenced by the histologic and morphometric studies when compared to L. acidophilus. Conclusion: Through maintaining an immune tolerant state in the vaginal epithelium and ameliorating the undesirable uncontrolled inflammatory response in the vaginal tissue, L. johnsonii (B-2178) has the potential to be utilized alone or in combination with other lactobacilli species in probiotic clinical trials to treat or prevent VVC.

Beneficial Effect of Erythropoietin on Ameliorating Propionic Acid-Induced Autistic-Like Features in Young Rats.

Autism is a neurodevelopmental disorder that impairs communication and social interaction. This study investigated the possible beneficial effects of erythropoietin (EPO) on experimental autistic-like behaviors induced by propionic acid (PPA). Twenty-four rats were distributed into three groups: (i) control; (ii) PPA_Gp: daily injected subcutaneously with PPA for five consecutive days; PPA+EPO-Gp: injected with PPA, then received intraperitoneal injection of EPO once daily for two weeks. Behavioral changes in the rats were assessed. Specimens from the cerebellar hemispheres were subjected to histological and ultrastructure examination, immunohistochemistry for glial fibrillary acidic protein (GFAP) and calbindin-D28K, and biochemical analysis for glutathione peroxidase (GSH-Px), malondialdehyde (MDA), gamma amino-butyric acid (GABA), and serotonin. PPA-Gp showed significant behavioral impairment, with a significant depletion in GSH-px, GABA, and serotonin and a significant increase in MDA. Histological examination revealed reduced Purkinje cell count with ultrastructural degeneration, irregularly arranged nerve fibers in the molecular layer, astrogliosis, and significantly decreased calbindin-immunostaining compared to the control. EPO protected cerebellar structure, increased Purkinje cell count, improved neuronal morphology, reduced PPA-induced autistic-like features, alleviated neuronal oxidative stress, increased intercellular antioxidant levels, and suppressed inflammation. EPO provided significant protection against PPA-induced autistic features in rats, with structural preservation of Purkinje cells.

Vitamin E protects against the modulation of TNF-α-AMPK axis and inhibits pancreas injury in a rat model of L-arginine-induced acute necrotising pancreatitis.

BACKGROUND: Acute pancreatitis (AP) associated with the modulation of TNF-α-AMPK axis in the presence and absence of vitamin E has not been investigated before. MATERIAL AND METHODS: Rats were either injected with L-arginine (2.5 gm/kg) before being sacrificed after 48 h or were pre-treated with vitamin E (60 mg/kg) and continued receiving vitamin E until the end of the experiment. RESULTS: AP was developed as demonstrated by infiltration of inflammatory cells and profound pancreas tissue damage, which were substantially protected by vitamin E. In addition, L-arginine injections significantly (p < .0001) increased the expression of TNF-α mRNA and protein, and decreased phospho-AMPK and IL-10 mRNA and protein that was significantly (p < .0001) protected by vitamin E. Furthermore, vitamin E inhibited L-arginine-induced blood levels of LDH, amylase, and myeloperoxidase. CONCLUSIONS: L-arginine-induced acute pancreatitis modulates TNF-α-AMPK axis, IL-10 and other AP biomarkers, which is protected by vitamin E; thus, may offer therapeutic potential in humans.

Melatonin Mitigates the Progression of Chemically Induced Hepatocellular Carcinoma in Rats via Targeting Wnt/Β-Catenin Pathway, and Small Noncoding miR-let-7b.

Background: Melatonin, the controlling hormone of the sleep-wake cycle, has acquired attention due to its role in immunomodulation, anti-inflammation, as well as its proapoptotic effects. Wnt/ß-catenin signaling can modulate cancer progression by promoting cell division and migration, while miR-let-7b may inhibit cell growth, migration, and invasion by affecting the function of adaptive immune cells. This work was designed to detect the effect of using melatonin as an immunomodulating therapeutic approach to control the progression of chemically induced hepatocellular carcinoma (HCC). Methods: Thirty male rats were equally divided into control, HCC, and melatonin-HCC groups. Animals in the HCC and melatonin-HCC groups were injected with diethylnitrosamine (intraperitoneal single dose) followed by repeated carbon-tetrachloride subcutaneous injection once weekly for six weeks. Melatonin was given from the first week of the study and continued during the process of HCC induction. Results: In the HCC group, the levels of tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), and Wnt/ß-catenin expression significantly increased, while there was a downregulation of microRNA Let7b. Melatonin administration reversed these changes, along with an increase in hepatic content of interleukin-2 (IL-2) and caspase-3. Conclusions: Melatonin exerted hepatic immunomodulating changes, in addition to proapoptotic and antiangiogenic effects, illustrated by increased IL-2, caspase-3, and decreased VEGF levels, respectively. Moreover, the use of melatonin during hepatocarcinogenesis positively modulated the disrupted expression of microRNA let7b and Wnt/ß-catenin significantly.

Hibiscus attenuates renovascular hypertension-induced aortic remodeling dose dependently: the oxidative stress role and Ang II/cyclophilin A/ERK1/2 signaling.

Introduction: The high levels of angiotensin II (Ang II) can modify the vascular tone, enhance vascular smooth muscle cells (VSMCs) proliferation and hypertrophy and increase the inflammatory cellular infiltration into the vessel wall. The old herbal nonpharmacological agent, Hibiscus (HS) sabdariffa L has multiple cardioprotective impacts; thus, we investigated the role of HS extract in amelioration of renovascular hypertension (RVH)-induced aortic remodeling. Materials and methods: Thirty-five rats (7/group) were randomly allocated into 5 groups; group: I: Control-sham group, and RVH groups; II, III, IV, and V. The rats in RVH groups were subjected to the modified Goldblatt two-kidneys, one clip (2K1C) for induction of hypertension. In group: II, the rats were left untreated whereas in group III, IV, and V: RVH-rats were treated for 6 weeks with low dose hibiscus (LDH), medium dose hibiscus (MDH), and high dose hibiscus (HDH) respectively. Results: We found that the augmented pro-contractile response of the aortic rings was ameliorated secondary to the in-vivo treatment with HS dose dependently. The cyclophilin A (CyPA) protein levels positively correlated with the vascular adhesion molecule-1 (VCAM-1) and ERK1/2, which, in turn, contribute to the reactive oxygen species (ROS) production. Daily HS intake modified aortic renovation by enhancing the antioxidant capacity, restraining hypertrophy and fibrosis, downregulation of the metastasis associated lung adenocarcinoma transcript (MALAT1), and cyclophilin A (CyPA)/ERK1/2 levels. Discussion: Adding to the multiple beneficial effects, HS aqueous extract was able to inhibit vascular smooth muscle cell proliferation induced by 2K1C model. Thus, adding more privilege for the utilization of the traditional herbal extracts to attenuate RVH-induced aortopathy.

Comparing MitoQ10 and heat therapy: Evaluating mechanisms and therapeutic potential for polycystic ovary syndrome induced by circadian rhythm disruption.

Environmental factors, such as sleep restriction, contribute to polycystic ovary syndrome (PCOS) by causing hyperinsulinemia, hyperandrogenism, insulin resistance, and oligo- or anovulation. This study aimed to evaluate the effects of circadian rhythm disruption on reproductive and metabolic functions and investigate the potential therapeutic benefits of MitoQ10 and hot tub therapy (HTT). Sixty female rats were divided into six groups: control, MitoQ10, HTT, and three groups with PCOS induced by continuous light exposure(L/L). The reproductive, endocrine, and structural manifestations ofL/L-induced PCOS were confirmed by serum biochemical measurements, ultrasound evaluation of ovarian size, and vaginal smear examination at week 14. Subsequently, the rats were divided into the L/L (untreated), L/L+MitoQ10-treated, andL/L+HTT-treated groups. At the end of week 22, all rats were sacrificed. Treatmentwith MitoQ10 or HTT partially reversed the reproductive, endocrine, and structural features of PCOS, leading to a decreased amplitude of isolated uterine contractions, ovarian cystic changes and size, and endometrial thickness. Furthermore, both interventions improved the elevated serum levels of anti-Mullerian hormone (AMH), kisspeptin, Fibulin-1, A disintegrin and metalloproteinase with thrombospondin motifs 19 (ADAMTS-19), lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), oxidative stress markers, androgen receptors (AR) and their transcription target genes, FKBP52 immunostaining in ovarian tissues, and uterine estrogen receptor alpha (ER-α) and PRimmunostaining. In conclusion, MitoQ10 supplementation and HTT demonstrated the potential for ameliorating metabolic, reproductive, and structural perturbations associated with PCOS induced by circadian rhythm disruption. These findings suggest a potential therapeutic role for these interventions in managing PCOS in women.

Metformin Is Associated with the Inhibition of Renal Artery AT1R/ET-1/iNOS Axis in a Rat Model of Diabetic Nephropathy with Suppression of Inflammation and Oxidative Stress and Kidney Injury.

Diabetes is the most common cause of end-stage renal disease, also called kidney failure. The link between the renal artery receptor angiotensin II type I (AT1R) and endothelin-1 (ET-1), involved in vasoconstriction, oxidative stress, inflammation and kidney fibrosis (collagen) in diabetes-induced nephropathy with and without metformin incorporation has not been previously studied. Diabetes (type 2) was induced in rats and another group started metformin (200 mg/kg) treatment 2 weeks prior to the induction of diabetes and continued on metformin until being culled at week 12. Diabetes significantly (p < 0.0001) modulated renal artery tissue levels of AT1R, ET-1, inducible nitric oxide synthase (iNOS), endothelial NOS (eNOS), and the advanced glycation end products that were protected by metformin. In addition, diabetes-induced inflammation, oxidative stress, hypertension, ketonuria, mesangial matrix expansion, and kidney collagen were significantly reduced by metformin. A significant correlation between the AT1R/ET-1/iNOS axis, inflammation, fibrosis and glycemia was observed. Thus, diabetes is associated with the augmentation of the renal artery AT1R/ET-1/iNOS axis as well as renal injury and hypertension while being protected by metformin.