Health Effects of Oral Contraceptives on Periodontal Disease and Gingivitis: A Cross-Sectional Questionnaire-Based Study Among Saudi Women in Jeddah.

Background: Sex hormones strongly influence the health and ailment of the oral cavity. For instance, a woman's oral health is influenced by her menstrual cycle, menopause, pregnancy, and usage of oral contraceptives. The use of various therapeutic medication results in intraoral alterations. Oral contraceptive pills (OCPs) are among the drugs that produce intraoral alterations. The study's objective was to evaluate attitudes and oral health conditions of Saudi women's utilizing OCPs in Jeddah, Saudi Arabia. Methods: A cross-sectional questionnaire-based study was conducted among Saudi women in Jeddah, Saudi Arabia. The self-administered questionnaire was made and sent to women to evaluate the attitude and oral health condition of women utilizing OCPs. The women using OCPs were asked to self-administer 17 questions to evaluate attitudes and oral health conditions. The questionnaire had multiple-choice questions and was consisted of four sections. Results: The number of participants who used contraceptives was 125 (35.9%) women; of them, only 94 (75.2%) used oral contraceptives. The duration of using oral contraceptives mainly was 1-5 years (39.4%), then > 5 years (34.0%), and <1 year (26.6%). Of the 94 women, 34 (36.2%) had gingival diseases, 23 (24.5%) treated their gums; and 13 (13.8%) cleaned their gums at a dental clinic regularly. Times of teeth brushing per day were one time in 32 women (34%), twice in 47 women (50.0%), and three times in 15 (16.0%). Of the 94 women, 4 (4.3%) were smoking, 24 (25.5%) took medication other than OCPs, and 16 (17.02%) had chronic diseases. Common oral complications noticed by participants were gum bleeding after brushing (51.6%), dental caries (25.5%), and oral ulcers (10.6%). Conclusion: Females on OCPs had a high rate of gingival bleeding, dental caries, and oral ulcers. OCPs users had poor periodontal and gingival health. Establishing an oral hygiene program was necessary to treat gingival and periodontal inflammation that exacerbated by OCPs.

The potential protective effects of melatonin and omega-3 on the male rat optic nerve exposed to 900 MHz electromagnetic radiation during the prenatal period.

BACKGROUND: Due to children and adolescents' widespread use of electronic devices, researchers have focused on pre-and early postnatal electromagnetic field (EMF) exposure. However, little is known about the effects of EMF exposure on the optic nerve. The aim of study was to investigate the changes occurring in the optic nerve and the protective effects of melatonin (mel) and omega 3 (ω-3) in rats. METHODS: Thirty-five pregnant rats were divided into seven groups, Cont, Sham, EMF, EMF + melatonin (EMF + Mel), EMF + ω3, Mel, and ω3. The EMF groups were exposed to 900 megahertz (MHz) EMF daily for two hours during pregnancy. After the experiment, the right optic nerve of each offspring rat was removed and fixed in glutaraldehyde. Thin and semi-thin sections were taken for electron microscopic and stereological analyses. Myelinated axon numbers, myelin sheath thicknesses, and axonal areas were estimated using stereological methods. RESULTS: The groups had no significant differences regarding mean numbers of axons, mean axonal areas, or mean myelin sheath thicknesses (p > 0.05). Histological observations revealed impaired lamellae in the myelin sheath of most axons, and vacuolization was frequently observed between the myelin sheath and axon in the EMF-exposed group. The Mel and ω-3-treated EMF groups exhibited well-preserved myelinated nerve fibers and intact astrocytes and oligodendrocytes. CONCLUSIONS: At the ultrastructural level, Mel and ω3 exhibits a neuroprotective effect on the optic nerve exposed to prenatal EMF. The protective effects of these antioxidants on oligodendrocytes, which play an essential role in myelin formation in the central nervous system, now require detailed investigation.

Promoter Methylation-Regulated Differentially Expressed Genes in Breast Cancer.

Background: Breast cancer is one of the most common malignancies among women. Recent studies revealed that differentially methylated regions (DMRs) are implicated in regulating gene expression. The goal of this research was to determine which genes and pathways are dysregulated in breast cancer when their promoters are methylated in an abnormal way, leading to differential expression. Whole-genome bisulfite sequencing was applied to analyze DMRs for eight peripheral blood samples collected from five Saudi females diagnosed with stages I and II of breast cancer aligned with three normal females. Three of those patients and three normal samples were used to determine differentially expressed genes (DEG) using Illumina platform NovaSeq PE150. Results: Based on ontology (GO) and KEGG pathways, the analysis indicated that DMGs and DEG are closely related to associated processes, such as ubiquitin-protein transferase activity, ubiquitin-mediated proteolysis, and oxidative phosphorylation. The findings indicated a potentially significant association between global hypomethylation and breast cancer in Saudi patients. Our results revealed 81 differentially promoter-methylated and expressed genes. The most significant differentially methylated and expressed genes found in gene ontology (GO) are pumilio RNA binding family member 1 (PUM1) and zinc finger AN1-type containing 2B (ZFAND2B) also known as (AIRAPL). Conclusion: The essential outcomes of this study suggested that aberrant hypermethylation at crucial genes that have significant parts in the molecular pathways of breast cancer could be used as a potential prognostic biomarker for breast cancer.

Expression of Tie2 (angiopoietin receptor) on the monocyte subpopulations from ischemic stroke patients: Histological and flowcytometric studies.

INTRODUCTION: Different subpopulations of monocytes play roles in phagocytosis, inflammation, and angiogenic processes e.g., Tie2-expressing monocytes (TEMs). The brain is flooded with macrophages that are derived from monocytes within 3-7 days after a stroke. This study aimed to determine the expression level of Tie2 (an angiopoietin receptor) on monocytes and their subpopulations in ischemic stroke patients using the histological and immunohistological study of bone marrow biopsies and blood flow cytometry examination. METHODS: Ischemic stroke patients within two days were selected. Participants in the control group were healthy volunteers of matched age and gender. Sample collection was performed within 24 to 48 hours after medical consultants confirmed the stroke diagnosis. An iliac crest bone marrow biopsy was obtained and fixed for histological and immunohistological staining with antiCD14 and antiCD68. Flow cytometry was used to determine the total monocyte population, monocyte subpopulations, and TEMs after staining with monoclonal antibodies to CD45, CD14, CD16, and Tie2. RESULTS: Post-stroke patients' bone marrow cells were hypercellular. There was an apparent increase in CD68 and CD14-positive cells. Ischemic stroke patients exhibited low percentages of nonclassical monocytes CD14lowCD16++, with an increase in intermediate monocytes CD14highCD16+. Moreover, ischemic stroke patients had significantly higher levels of TEMs than control group. CONCLUSIONS: The results of this study demonstrate dysregulation of angiogenesis in monocyte subsets in ischemic stroke patients, which could be used as an early diagnostic marker of neurovascular damage and may need angiogenic therapy or improved medications to prevent further damage of blood vessels.

Neuroprotective Effect of Red Sea Marine Sponge Xestospongia testudinaria Extract Using In Vitro and In Vivo Diabetic Peripheral Neuropathy Models.

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes. Oxidative stress plays an important role in the pathophysiology of DPN. Red Sea marine sponge Xestospongia testudinaria extract has a promising neuroprotective effect, presumably owing to its antioxidant and anti-inflammatory properties. Thus, this study aimed to investigate the neuroprotective effect of the sponge X. testudinaria extract on in vitro and in vivo models of DPN. Mice dorsal root ganglia (DRG) were cultured with high glucose (HG) media and used as an in vitro model of DPN. Some of the DRGs were pre-treated with 2 mg/mL of X. testudinaria. The X. testudinaria extract significantly improved the HG-induced decreased neuronal viability and the neurite length. It improved the oxidative stress biomarkers in DRG cultures. The DPN model was induced in vivo by an injection of streptozotocin at a dose of 150 mg/kg in mice. After 35 days, 0.75 mg/kg of the X. testudinaria extract improved the hot hyperalgesia and the DRG histology. Although the sponge extract did not reduce hyperglycemia, it ameliorated the oxidative stress markers and pro-inflammatory markers in the DRG. In conclusion, the current study demonstrates the neuroprotective effect of Red Sea sponge X. testudinaria extract against experimentally induced DPN through its antioxidant and anti-inflammatory mechanisms.

Is Vitamin B12 Level a Reliable Predictor of Psychosis Severity in Male Patients with Megaloblastic Anemia at a Single Tertiary Hospital?

Background: Megaloblastic anemia (MA) occurs due to ineffective erythropoiesis, which results from impaired DNA synthesis in the hematopoietic precursors and intramedullary hemolysis. MA's most common cause is nutritional deficiencies of either cobalamin (vitamin B12) or folate (vitamin B6). This study aims to determine the association between MA caused by vitamin B12 deficiency and psychosis among psychotic male patients in Mental Health Hospital at Taif, Saudi Arabia. Methods: Fifty psychotic male patients, aged 48.58±1.72, were recruited from the Mental Health Hospital at Taif, Saudi Arabia, in addition to 54 sex-matched healthy controls. The following tests were run: complete blood count (CBC), liver function tests (LFT), serum levels of vitamin B12, folate, and C-reactive protein (CRP). Results: The CBC showed that RBCs count, haemoglobin, haematocrit, platelets count, mean platelets volume (MPV), and absolute lymphocyte count were significantly lower in psychotic patients versus healthy controls (P=0.007, P=0.002, P=0.001, P=0.004, P=0.0001, and P=0.005, respectively). In contrast, the eosinophil absolute count and basophil percentage were significantly higher in psychotic patients versus controls (P=0.009, P=0.0001, respectively). Vitamin B12 levels were insignificantly decreased in psychotic patients versus healthy group. There were significant negative correlations between serum levels of VitB12 and negative symptoms (r=-0.381, P=0.006) and hallucination (r=-0.297, P=0.036). Conclusion: These findings indicate no link between MA induced by VitB12 insufficiency and psychosis among psychotic patients. However, low serum VitB12 can predict the severity of some psychosis signs, including hallucinations and negative symptoms. Therefore, monitoring VitB12 levels and its supplementation in psychotic patients is recommended to improve their symptoms.

Multiple Recurrent Copy Number Variations (CNVs) in Chromosome 22 Including 22q11.2 Associated with Autism Spectrum Disorder.

Introduction: Autism spectrum disorder (ASD) is a developmental disorder that can cause substantial social, communication, and behavioral challenges. Genetic factors play a significant role in ASD, where the risk of ASD has been increased for unclear reasons. Twin studies have shown important evidence of both genetic and environmental contributions in ASD, where the level of contribution of these factors has not been proven yet. It has been suggested that copy number variation (CNV) duplication and the deletion of many genes in chromosome 22 (Ch22) may have a strong association with ASD. This study screened the CNVs in Ch22 in autistic Saudi children and assessed the candidate gene in the CNVs region of Ch22 that is most associated with ASD. Methods: This study included 15 autistic Saudi children as well as 4 healthy children as controls; DNA was extracted from samples and analyzed using array comparative genomic hybridization (aCGH) and DNA sequencing. Results: The aCGH detected (in only 6 autistic samples) deletion and duplication in many regions of Ch22, including some critical genes. Moreover, DNA sequencing determined a genetic mutation in the TBX1 gene sequence in autistic samples. This study, carried out using aCGH, found that six autistic patients had CNVs in Ch22, and DNA sequencing revealed mutations in the TBX1 gene in autistic samples but none in the control. Conclusion: CNV deletion and the duplication of the TBX1 gene could be related to ASD; therefore, this gene needs more analysis in terms of expression levels.

A Possible Novel Protective Effect of Piceatannol against Isoproterenol (ISO)-Induced Histopathological, Histochemical, and Immunohistochemical Changes in Male Wistar Rats.

Dry mouth is characterized by lower saliva production and changes in saliva composition. In patients with some salivary gland function remaining, pharmaceutical treatments are not recommended; therefore, new, more effective methods of promoting saliva production are needed. Hence, this study aimed to provide an overview of the histological changes in the salivary gland in the model of isoproterenol (ISO)-induced degenerative changes in male Wistar rats and to evaluate the protective effect of piceatannol. Thirty-two male Wistar rats were randomly divided into four groups: the control group, the ISO group, and the piceatannol (PIC)-1, and -2 groups. After the third day of the experiment, Iso (0.8 mg/100 g) was injected intraperitoneally (IP) twice daily into the animals. PIC was given IP in different daily doses (20 and 40 mg/kg) for three days before ISO and seven days with ISO injection. The salivary glands were rapidly dissected and processed for histological, histochemical, immunohistochemical (Ki-67), and morphometric analysis. Upon seven days of treatment with ISO, marked hypertrophy was observed, along with an increased number of positive Ki-67 cells. Proliferation was increased in some endothelial cells as well as in ducts themselves. Despite the significant decrease in proliferation activity, the control group did not return to the usual activity level after treatment with low-dose PIC. Treatment with a high dose of PIC reduced proliferative activity to the point where it was substantially identical to the results seen in the control group. An ISO-driven xerostomia model showed a novel protective effect of piceatannol. A new era of regenerative medicine is dawning around PIC's promising role.

Mortality Predictors Among COVID-19 Elderly in Taif, Saudi Arabia.

Background: By December 2021, the COVID-19 pandemic had caused more than 266 million cases and 5 million deaths, especially among geriatric patients. Objective: To identify determinants of COVID-19-related death in geriatric patients. Methods: This is a comparative retrospective study involving 145 COVID-19 hospitalized patients who are more than 60 years old, conducted at King Faisal Medical Complex in Taif, Saudi Arabia, from June 2020 to August 2020. The main outcome studied was COVID-19-related death. Results: Out of 145 elderly COVID-19 patients, 11% have died. There was a significant difference between those who died and the surviving group regarding hospital stay duration, with a higher duration median among those who died (22 days vs 12 day respectively, p=0.002). Transfer to ICU, mechanical ventilation, low oxygen saturation, shortness of breath, respiratory support, x-ray trend, and prolonged QT interval showed significant statistical differences between them (p<0.001, <0.001, 0.017, 0.045, <0.001, <0.001, 0.004, respectively). After doing logistic regression of predictors for progression to death, putting patients on oxygen only vs mechanical ventilation was statistically significant, with an adjusted odds ratio (AOR) of 0.038 (p=0.012). Worse x-rays vs constant also were statistically significant and had AOR of 23.459 (p=0.001). There was a significant moderate positive correlation between duration of hospital stay and duration from admission to medication start (SP=0.336 and p<0.001). Conclusion: We recommend accurately monitoring patients using x-rays to determine which patients have worse x-rays. However, the cost-benefit of using radiation must be well assessed and needs further research to determine if its benefit outweighs its risks, especially in high-risk patients. Furthermore, mechanically ventilated patients must be carefully monitored. Finally, the duration of hospital stay was highly correlated with the duration from admission to medication start. Therefore, proper treatment must be started as early as possible.

Application and performance of artificial intelligence technology in cytopathology.

Deep learning algorithms and artificial intelligence (AI) are making great progress in their capacity to evaluate and interpret image data recent advancements in computer vision and machine learning. The first use of AI in a pathology lab was in cytopathology, when a computer-assisted Pap test screening was created. Initially designed to diagnose rather than screen, there was a lot of disagreement concerning their wide use to clinical specimens. However, whole-slide imaging of both gynaecological and non-gynaecological histopathology have been the subject of recent AI work. An overview of the literature on AI in cytopathology is provided in this brief review. To be more precise, it intends to emphasize the relevance of applications of AI algorithms to gynaecological and non-gynaecologic cytology. Between January 2000 and December 2021, a search on artificial intelligence in cytopathology was conducted in several well-known databases, including PubMed, Web of Science, Scopus, Embase, and Google Scholar. Only full-text papers that could be accessed online were evaluated.

DNA Methylation Level of Transcription Factor Binding Site in the Promoter Region of Acyl-CoA Synthetase Family Member 3 (ACSF3) in Saudi Autistic Children.

BACKGROUND: DNA methylation (DNAm) is one of the main epigenetic mechanisms that affects gene expression without changing the underlying DNA sequence. Aberrant DNAm has an implication in different human diseases such as cancer, schizophrenia, and autism spectrum disorder (ASD). ASD is a neurodevelopmental disorder that affects behavior, learning, and communication skills. Acyl-CoA synthetase family member 3 (ACSF3) encodes malonyl-CoA synthetase that is involved in the synthesis and oxidation of fatty acids. The dysregulation in such gene has been reported in combined malonic and methylmalonic aciduria associated with neurological symptoms such as memory problems, psychiatric diseases, and/or cognitive decline. This research aims to study DNAm in the transcription factor (TF) binding site of ACSF3 in Saudi autistic children. To determine whether the DNAm of the TF-binding site is a cause or a consequence of transcription regulation of ACSF3. METHODS: RT-qPCR and DNA methylight qPCR were used to determine the expression and DNAm level in the promoter region of ACSF3, respectively. DNA and RNA were extracted from 19 cases of ASD children and 18 control samples from their healthy siblings. RESULTS: The results showed a significant correlation between the gene expression of ACSF3 and specificity protein 1 (SP1) in 17 samples of ASD patients, where both genes were upregulated in 9 samples and downregulated in 8 samples. CONCLUSION: Although this study found no DNAm in the binding site of SP1 within the ACSF3 promoter, the indicated correlation highlights a possible role of ACSF3 and SP1 in ASD patients.

The Effect of Coenzyme Q10 on Liver Injury Induced by Valproic Acid and Its Antiepileptic Activity in Rats.

Valproic acid (VPA) has toxic metabolites that can elevate oxidative stress markers, and the hepatotoxicity of VPA has been reported. Coenzyme Q10 (CoQ10) is one of the most widely used antioxidants. The effect of CoQ10 on epileptogenesis and VPA hepatotoxicity were examined. Rats were randomly divided into five groups: the control group received 0.5% methylcellulose by oral gavages daily and saline by intraperitoneal injection three times weekly. The PTZ group received 1% methylcellulose by gavages daily and 30 mg/kg PTZ by intraperitoneal injection three times weekly. The valproic acid group received 500 mg/kg valproic acid by gavage and 30 mg/kg PTZ, as above. The CoQ10 group received 200 mg/kg CoQ10 by gavages daily and 30 mg/kg PTZ, as above. The Valproic acid + CoQ10 group received valproic acid and CoQ10, as above. Results: CoQ10 exhibited anticonvulsant activity and potentiated the anticonvulsant effect of VPA. CoQ10 combined with VPA induced a more significant reduction in oxidative stress and improved the histopathological changes in the brain and liver compared to VPA treatment. In addition, CoQ10 reduced the level of toxic VPA metabolites. These findings suggest that the co-administration of CoQ10 with VPA in epilepsy might have therapeutic potential by increasing antiepileptic activity and reducing the hepatotoxicity of VPA.

Effect of e-cigarette flavoring agents on the neural retina of chick embryo: histological and gene expression study.

BACKGROUND: An electronic cigarette (e-cigarette) is initially marketed as an assistant product to quit smoking or limit its use. However, recent studies suggest the opposite, describing it as a product that lacks adequate quality and user safety. The present study aimed to investigate the effect of e-cigarette flavoring agent (cinnamon flavor) on the neural retina development of chick embryos and apoptosis induction after the early and late apoptosis stages by quantitative detection of gene expression CASP-3 at both embryonic days E9 and E17. METHODS: Fertilized chicken eggs were divided into two groups: control and treatment, and each group included two embryonic days; E9 and E17. For each treatment stage, two dosages of the treatment were applied, 2% and 5%. The neural retinas were dissected from the sclera and retinal pigment epithelium for subsequent RNA extraction and histological examination. RESULTS: This study indicated that aerosol of the subtle cinnamon flavor e-liquid causes downregulated expression of CASP3 in neural retina development. In addition, the hematoxylin and eosin (H&E)-stained sections showed multiple structural changes in the retinal layers and evidence of apoptotic cell death. CONCLUSION: Cell death was visible and abundant in E9, and E17 concludes that flavor vapor condensate treatment caused neuronal cell death. CASP-3 was downregulated, which indicates that cell death occurred independently of CASP-3.

Angiogenesis Biomarkers in Ischemic Stroke Patients.

INTRODUCTION: Stroke is a global health issue, and ischemic stroke is among the most common strokes affecting many people worldwide. Throughout ischemic stroke, various immune cells counter its effect by releasing cytokines, chemokines, and angiogenic molecules. These molecules can work as potential biomarkers in the diagnosis and monitoring of the progress of ischemic stroke. The current study investigated the use of angiogenic molecules as biomarkers in ischemic stroke patients. METHODS: The samples were obtained from twenty healthy subjects and nineteen patients with ischemic stroke. Multiplex assay was used to measure the serum levels of angiogenic biomarkers, including endoglin, VEGF-A, endothelin-1, G-CSF, and angiopoietin-2. All data were analyzed using an unpaired Student's t-test. Correlations between measured parameters were made using Pearson correlations. RESULTS: Angiopoietin-2, VEGF-A, endothelin-1, and endoglin levels in stroke patients were significantly higher compared to healthy controls. Nevertheless, G-CSF level showed a non-significant increase in patients compared to controls. The correlation coefficient of measured angiogenic biomarkers among patients showed significant correlations between endoglin, angiopoietin, VEGF-A, and endothelin-1. DISCUSSION: The angiogenic factors were significantly increased in patients with ischemic stroke, which may help in the early detection of ischemic stroke and consequently prompt treatment and better prognosis.

Effectiveness and Safety of Favipiravir Compared to Hydroxychloroquine for Management of Covid-19: A Retrospective Study.

BACKGROUND: Coronavirus disease (COVID-19) is an infectious disease due to SARS-COV-2. Patients with risk factors are vulnerable to severe morbidity and mortality. Favipiravir (FPV) and hydroxychloroquine (HCQ) are considered possible COVID-19 treatments. OBJECTIVE: To investigate the effectiveness and safety of FPV compared to HCQ in patients with COVID-19 as the standard of care approved by the national protocol there. METHODS: This is a retrospective cohort study on patients with COVID-19 who were administered either FPV or HCQ at King Faisal Medical Complex, Taif, Saudi Arabia, from June 2020 to August 2020. RESULTS: In total, 508 patients were included in the analysis. Patients were categorized into three groups by medication. Patients enrolled in this study were 244 (55.8%) on FPV, 193 (44.2%) on HCQ and 71 (13.81%) on neither medication. Patients who received FPV had higher age and greater comorbidity. Most of the patients were discharged on day 14 (n = 303, 59.6%), 26 (36.6%) in neither med, 154 (63.1%) in FPV and 123 (63.7%) in HCQ groups with significant difference between groups (P < 0.0001). Mortality rate was 8.2% (n = 20) in FPV and 7.3% (n = 14) in HCQ groups with significant difference between groups (P = 0.048). Regarding drug safety, 19.7% of patients treated with FPV vs 7.8% HCQ have adverse effects with significant difference between groups (P < 0.0001). Most of the side effects were increase ALT and AST. Meanwhile, prolonged Q-T interval was reported only in the HCQ group (2.6%). From Cox regression modeling, only mechanical ventilation due to Covid 19 was predictive for mortality (HR: 16.598, 95% CI: 7.095-38.828, P < 0.0001). Meanwhile, there was no significant difference in the prediction of discharge of FPV (vs HCQ) (HR: 0.933, 95% CI: 0.729-1.195, P = 0.5843), predictors of mortality were HCQ (vs FPV) (HR: 2.3, 95% CI: 0.994-5.487, P = 0.0518). Kaplan-Meier survival curves showed improved survival time and discharged time among patients in the HCQ versus FPV group with an insignificant difference between them (P = 0.85, P = 0.06, respectively). CONCLUSION: The present study concluded that FPV and HCQ showed comparable efficacy in decrease mortality and oxygen requirements. FPV likely has a more favorable safety profile regarding cardiac toxicity. A randomized clinical trial with large patient numbers is recommended to confirm the effectiveness of these drugs in COVID-19 patients.

Secondary Cerebellar Cortex Injury in Albino Male Rats after MCAO: A Histological and Biochemical Study.

The present study focused on secondary injury following the middle cerebral artery (MCA) occlusion in rats not linked to the MCA's feeding zone. This entity has been very rarely studied. Additionally, this study investigated the rates of expression of five fundamental angiogenic biomarkers called endoglin, vascular endothelial growth factors-A (VEGF-A), endothelin-1 (ET-1), 2granulocyte colony-stimulating factor (G-CSF), and angiopoietin-using the MCA occlusion (MCAO) model. The random allocation of twelve adult male albino rats was in two groups. As a sham control group, six rats were used. This group was subjected to a sham operation without MCAO. The MCAO group consisted of six rats that were subjected to MCAO operation. After three days, the rats were sacrificed. The cerebellar specimens were immediately processed for light microscopic examination. An angiogenic biomarkers multiplex assay from multiplex was used to assess endoglin levels, VEGF-A, ET-1, angiopoietin-2, and G-CSF in serum samples. Hematoxylin and eosin-stained sections showed that the cerebellar cortex of rats of the MCAO group was more affected than the sham control group. Furthermore, Nissl stain and immunohistochemical analysis revealed an apparent increase in the number of positive immunoreactive in the cerebellar cortex and an evident decrease in Nissl granules in Purkinje cells of the MCAO rats, in contrast to the control rats. In addition, there was a significant increase in angiogenic factors VEGF-A, ET-1, angiopoietin-2, and endoglin. Interestingly, there was an increase in the G-CSF but a non-significant in the MCAO rats compared to the control rats. Furthermore, there was a significant correlation between the angiopoietin-2 and ET-1, and between G-CSF and ET-1. VEGF-A also exhibited significant positive correlations with the G-CSF serum level parameter, Endoglin, and ET-1. Rats subjected to MCAO are a suitable model to study secondary injury away from MCA's feeding zone. Additionally, valuable insights into the association and interaction between altered angiogenic factors and acute ischemic stroke induced by MCAO in rats.

Altered Expression of Angiogenic Biomarkers in Pregnancy Associated with Gestational Diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) typically occurs during the third trimester of pregnancy. Maternal hyperglycemic may influence the expression of pro-and anti-angiogenic factors. Altered levels of angiogenic biomarkers in GDM pregnant women are associated with abnormal placentation. This study aimed to investigate the rates of expression of five angiogenic biomarkers called vascular endothelial growth factor-A (VEGF-A), angiopoietin-2, endoglin, endothelin-1, and granulocyte colony-stimulating factor (G-CSF) in GDM. METHODS: The samples were obtained from normal (n=9) and GDM (n=10) pregnancies. Multiplex assay was used to assess the levels of angiogenic biomarkers including VEGF-A, endoglin, endothelin-1, angiopoietin-2, and G-CSF in serum samples. All data were statistically analyzed using an unpaired Student's t-test. Correlations between measured parameters were made using Pearson correlations. RESULTS: VEGF-A, endoglin, endothelin-1, and angiopoietin-2 levels in GDM were significantly higher (P value = 0.001, 0.042, 0.049, 0.001; respectively) compared to control. However, G-CSF level exhibited a non-significant increase (P=0.466) in GDM compared to healthy controls. There was a significant positive correlation between angiopoietin-2 with endoglin, endothelin-1, and VEGF-A. Moreover, there was a significant positive correlation between VEGF-A with endoglin and endothelin-1. Most interestingly, there was a significant positive correlation between G-CSF with endothelin-1. CONCLUSION: The angiogenic biomarkers were highly altered in pregnant women with GDM. The study provides a novel advance in the field of gestational diabetes, in terms of increase of angiogenic factors that can modify the vascularization of the placenta, the development of fetal vascular system and the insulin resistance itself.

Celecoxib Decrease Seizures Susceptibility in a Rat Model of Inflammation by Inhibiting HMGB1 Translocation.

The risk of developing epilepsy is strongly linked to peripheral inflammatory disorders in humans. High-mobility group box protein 1 (HMGB1) has the most focus for being a suspect in this scenario. The current study aimed to detect the celecoxib effect, an anti-inflammatory drug, on decreasing seizure susceptibility and organ damage in lipopolysaccharides (LPS)/pilocarpine (PILO) pretreated Wistar rats. Rats were divided into 6 groups (8 each): group 1 (control), group 2 (PILO), group 3 (PILO+LPS), group 4 (PILO+LPS+(VPA) Valproic acid), group 5 (PILO+LPS+Celecoxib), and group 6 (PILO+LPS+VPA+Celecoxib). LPS was used to induce sepsis and PILO to induce seizures. Oxidative stress markers, pro-inflammatory cytokines, and HMGB1 levels in serum and brain homogenate were evaluated. Histopathological studies were conducted on the hippocampus, liver, lung, and kidney. Treatment with celecoxib either alone or in combination with VPA significantly reduced Racine score and delays latency to generalized tonic-clonic seizures onset with a significant decrease in hippocampal levels of pro-inflammatory cytokines, oxidative stress markers, and increase in reduced glutathione. In addition, celecoxib treatment either alone or in combination with VPA suppressed HMGB1translocation into peripheral circulation more than treatment with VPA alone. Furthermore, hippocampus, liver, lung, and kidney histopathological changes were improved in contrast to other epileptic groups. Celecoxib either alone or combined with VPA has antiepileptic and multiorgan protective effects on acute seizures and inflammatory models induced by PILO with LPS. It decreased histopathological findings, oxidative, and inflammatory effects induced by VPA and LPS. This might be due to its anti-oxidative, anti-inflammatory and anti-HMGB1 mediated effects.

Thymoquinone Protects Neurons in the Cerebellum of Rats through Mitigating Oxidative Stress and Inflammation Following High-Fat Diet Supplementation.

High-fat diet (HFD) is a major problem causing neuronal damage. Thymoquinone (TQ) could regulate oxidative stress and the inflammatory process. Hence, the present study elucidated the significant role of TQ on oxidative stress, inflammation, as well as morphological changes in the cerebellum of rats with HFD. Rats were divided into three groups as (1) control, (2) saturated HFD for eight weeks and (3) HFD supplementation (four weeks) followed by TQ 300 mg/kg/day treated (four weeks). After treatment, blood samples were collected to measure oxidative stress markers glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and inflammatory cytokines. Furthermore, neuronal morphological changes were also observed in the cerebellum of the rats. HFD rats show higher body weight (286.5 ± 7.4 g) as compared with the control group (224.67 ± 1.78 g). TQ treatment significantly (p < 0.05) lowered the body weight (225.83 ± 13.15 g). TQ produced a significant (p < 0.05) reduction in cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The antioxidative enzymes significantly reduced in HFD rats (GSH, 1.46 ± 0.36 mol/L and SOD, 99.13 ± 5.41 µmol/mL) as compared with the control group (GSH, 6.25 ± 0.36 mol/L and SOD, 159.67 ± 10.67 µmol/mL). MDA was increased significantly in HFD rats (2.05 ± 0.25 nmol/L) compared to the control group (0.695 ± 0.11 nmol/L). Surprisingly, treatment with TQ could improve the level of GSH, MDA, and SOD. TQ treatment significantly (p < 0.05) reduced the inflammatory markers as compared with HFD alone. TQ treatment minimizes neuronal damage as well as reduces inflammation and improves antioxidant enzymes. TQ can be considered as a promising agent in preventing the neuronal morphological changes in the cerebellum of obese populations.

Role of toll-like receptor 4 antagonist Lipopolysaccharide-Rhodobacter sphaeroides on acute stress-induced voluntary ethanol preference and drinking behaviour: In vivo Swiss Albino mouse model.

The present study focused on investigating the effect of toll-like receptor 4 (TLR4) antagonist Lipopolysaccharide-Rhodobacter sphaeroides(LPS-RS) on acute, stress-induced voluntary ethanol preference and drinking behaviour, neuronal components activation, and gene expression associated with stress and addictive behaviour. This study involved the exposure of restraint stress and social isolation using Swiss Albino mice. Two-bottle choice ethanol preference analysis was used in the evaluation of voluntary ethanol seeking and drinking behaviour. Several behavioural assessments were carried out to assess fear and anxiety-like behaviour, neuromuscular ability, motor coordination and locomotion. Morphological and immunoreactivity analysis and gene expression analysis were done after the completion of behavioural assessments. TLR4 antagonist LPS-RS treated stressed-mice showed a significant decrease in ethanol drinking compared with stressed mice. Behavioural results showed that stress exposure induced fear and anxiety-like behaviour; however; no significant deficit was found on motor coordination, neuromuscular ability, locomotion and exploratory behaviour among groups. Morphological analysis showed no significant change in the prefrontal cortex and hippocampus among all groups, while immunoreactivity analysis showed higher expression of c-Fos in prefrontal cortex and hippocampus, higher TLR4 expression in the prefrontal cortex and glial fibrillary acidic protein (GFAP) in hippocampus among stressed-animals. Stressed-mice also showed significant increase in TLR4, Nuclear Factor-Kappa B (NF-kB), inducible nitric oxide synthase (iNOS), dopamine receptor D2 (DRD2), cyclic adenosine monophosphate (cAMP) response element binding protein-1 (CREB-1) and opioid receptor MU-1 (OPRM-1) genes expression compared with control and LPS-RS treated stressed-mice. As a conclusion, the antagonism of TLR4 could provide therapeutic value in the treatment of stress-induced addiction.