Coronavirus disease 2019 (COVID-19) is a global pandemic caused by novel coronavirus SARS-CoV-2. Angiotensin-converting enzyme 2 (ACE2) is a key player in the pathophysiology of COVID-19, as it facilitates the cellular viral entry, which in turn causes upregulation of Angiotensin II (Ang II) which correlates with the severity of infection and inflammation. Assessing the serum levels of Ang-II among COVID-19 patients, and correlate it with disease severity. Eighty patients of COVID- 19 and 80 healthy subjects were enrolled in this cross sectional study. COVID-19 patients was divided to 4 groups; mild, moderate, severe, and critical groups, according to WHO classification of severity of the disease .Beside clinical, laboratory (CBC, CRP, D-dimer, liver and kidney function tests) and imaging assessment, Ang II level was measured using ELISA kits. Levels of Ang-II are significantly higher in COVID-19 patients (281.82 ± 114.54 pg/dl) compared to control (72.53 ± 21.86 pg/dl), with a p-value < 0.001. Significant higher levels were detected in severe and critical cases, which were 347.65 ± 37.70 and 436.06 ± 53.00, respectively, as compared to mild and moderate cases, which were 132.16 ± 27.98 and 216.44 ± 49.47 pg/dl, respectively. An ROC curve for detection of the cutoff value of Ang II level was 115.5 pg/dl with an AUC of 0.990. Moreover, a cutoff value of Ang II for determining the severe and critical cases was 300.05 pg/dl with an AUC of 1.000. Ang-II may be a potential biomarker that could aid in determining the severity of cases aiming at the development of therapeutic strategies to mitigate disease severity.

Globally, hepatocellular carcinoma (HCC) presents a clinical and financial burden, as it is often diagnosed at a later stage. Cisplatin is one of the most commonly used chemotherapeutics for treating various types of solid tumours; however, it is a double-edged sword due to its cytotoxic effects. Consequently, we hypothesized that combining cisplatin with melatonin could be effective in treating HCC. Additionally, melatonin may mitigate the severe adverse effects of cisplatin on normal cells through its cellular protection, immunomodulation, and antioxidant activities. Forty male adult Wistar rats were randomly divided into five groups: Group 1(n = 8), negative control group. HCC was induced in 32 rats with diethyl nitrosamine and carbon tetrachloride injection. Following induction, rats were divided into group 2 (HCC): diseased control; group 3 (HCC-Cis): HCC rats received cisplatin (2.5 mg/kg I.P. once every week for 3 weeks); group 4 (HCC-Melatonin): HCC rats received melatonin in drinking water (20 mg/L for 3 weeks); and group 5 (HCC-Cis-Melatonin; Combined therapy): the HCC rats received both cisplatin and melatonin. HCC group revealed significant elevation in ALT, AST, and AFP associated with increased TNF-α and MDA levels. Hepatic tissue exhibited a significant increase in VEGF, MDM2, COX-2, and miR-155, and a decrease in caspase-3 associated with hepatic damage, ballooning of hepatocytes, and increased BCL-2 and CD68 immunostaining. Although cisplatin was able to induce HCC apoptosis by COX-2 and MDM2/p53/ miR-155 modulation, it aggravated normal hepatocytic damage that was improved by the antioxidant and anti-inflammatory effects of melatonin. In conclusion, melatonin and cisplatin co-administration may be a viable strategy to preserve liver function by shielding healthy hepatocytes from the cytotoxic effects of cisplatin.

The optimal cut-off level of lactoferrin in ascitic fluid is debatable for identification of spontaneous bacterial peritonitis (SBP). This study aimed to detect the cut-off level of lactoferrin in ascitic fluid and its role in the diagnosis of SBP in patients with liver cirrhosis. This case–control study was conducted on 100 adult cirrhotic patients of both sexes, with ascites. Group A included 50 patients without SBP, while Group B included 50 patients with SBP. The Child–Pugh score was calculated. Lactoferrin levels in ascitic fluid were evaluated. Optimal cut-off values for lactoferrin levels and ascitic polymorphonuclear cells (PMNs) were determined using area under the curve (AUC) and receiver operator characteristic (ROC) analysis. Ascitic PMNs and lactoferrin levels were significantly higher in group B (p-value < 0.001). Based on the ROC curve, ascitic PMNs and lactoferrin can be used to discriminate patients of SBP at a cut-off level of > 203 cells/mm3 and > 29.1 µg/mL, AUC = 0.99 and 0.91, respectively. A negative bacterial culture was detected in 68

BACKGROUND:Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by a variety of clinical manifestations and a relapsing-remitting course. MiR-338-3p has emerged as a significant regulator of the immune response in the pathogenesis of SLE. Hsa_circ_0049356 is a circular RNA that may serve as a potential biological or clinical marker for autoimmune disorders. PURPOSE OF THE STUDY:This study aims to evaluate the potential role of hsa_circ_0049356 and miR-338-3p in the pathogenesis of SLE by analyzing their expression patterns and assessing their impact on the ERK/MAPK signaling pathway. Understanding these interactions may provide novel insights into the pathogenesis of SLE and identify potential diagnostic or therapeutic targets. METHODS:This study included 100 participants, divided into two groups: healthy controls and SLE patients. Comprehensive clinical evaluations, including history taking, physical examination, and laboratory investigations, were performed. The expression levels of hsa_circ_0049356 and miR-338-3p were determined using RT-PCR. Additionally, the levels of SIRT6, ERK, MAPK, and MEK-1 were measured using Enzyme Linked Immunosorbent Assay. RESULTS:The expression of hsa_circ_0049356 and the level of SIRT6 were significantly decreased in SLE patients. Moreover, SLE patients exhibited increased miR-338-3p expression and higher levels of ERK, MAPK, and MEK-1 compared to healthy controls. CONCLUSION:This study suggests that the release of sponge effect of hsa_circ_0049356 on miR-338-3p leads to an increase in miR-338-3p, which may contribute to the pathogenesis of SLE by modulating the ERK/MAPK pathway.

OBJECTIVE:Systemic sclerosis (SSc) is a multisystem autoimmune disease of heterogeneous pathogenesis, including vascular, immunologic, genetic, epigenetic, and environmental factors. Progressive fibrosis is the hallmark of SSc. Intense research has been conducted to unveil new tools for early diagnosis and management, thus reducing morbidity and mortality. miR-21 has recently been considered to play an important role in the fibrosis of SSc. The objective of this study was to evaluate miR-21 levels in SSc patients and study its correlation to the extent of skin fibrosis and association with various clinical characteristics. METHODS:A total of 25 patients with SSc who fulfilled the American College of Rheumatology/European Alliance of Associations for Rheumatology 2013 classification criteria, as well as 25 controls, were enrolled in a cross-sectional study. The extent of skin fibrosis was evaluated using the modified Rodnan skin score, and disease severity was assessed using the Medsger severity score. The levels of miR-21 were measured by quantitative real-time polymerase chain reaction. The 2-ΔΔCt method was used for analysis. SSc patients affected by diabetes mellitus, hypertension, renal impairment, heart disease, malignancy, other autoimmune diseases, or a history of serious acute infection within 6 weeks were excluded. RESULTS:There was a high statistically significant difference in miR-21 levels between cases and controls (p<0.001). At a cut-off level of 2.55, miR21 could discriminate between SSc patients and controls with sensitivity 92% and specificity 100%. There was no significant correlation between miR-21 levels and the degree of skin fibrosis. There was a significant positive association between miR-21 levels and the presence of arthritis in SSc patients (p=0.007). CONCLUSIONS:miR-21 was suggested as a robust diagnostic biomarker in SSc with superiority over the traditionally utilized antibodies. Additionally, due to its association with arthritis, it is supposed to play a proinflammatory role in addition to its pronounced profibrotic effects. Interestingly, the profibrotic miR-21 may not reflect the extent of skin fibrosis.

BACKGROUND:The presumed implication of thromboembolic and oxidative stress pathways in parkinsonism guided the current research toward the exploration of the anticoagulant dabigatran etexilate (DE) as a thrombin inhibitor in the cobalt chloride (CoCl2)-induced parkinsonism (CIP) model, a model of significance to industrial toxins-related health issues. METHODS:Oral CoCl2 (12.5 mg/kg) was administered daily for 60 days, with the introduction of benztropine mesylate (BM) (10 mg/kg) and/or DE (3 mg/kg) on day 31. Rearing, postural instability, and pasta handling were evaluated, followed by histopathologic examination of the substantia nigra (SN) and striatum (STR). The expressions of brain dopamine receptor 2 (D2 ), adenosine receptor 1 (A1) and 2A (A2A), and protease-activated receptor 1 (PAR1), as well as the brain levels of dopamine (DA), endothelin 1 (ET1), malondialdehyde (MDA), and glutathione (GSH), were assessed. RESULTS:BM+DE restored the number of rears to the control level, compared to being reduced in the CIP model. BM+DE restored the first, second, third, and average displacement distances to the control level, compared to being reduced in the CIP model. BM+DE was superior to either BM or DE in restoring the time to finish eating pasta and the number of adjustments of forepaws while eating to control levels after being affected in the CIP model. BM+DE restored DA to the control level and was superior to DE in restoring D2  to the control level. BM+DE was superior to BM in restoring A1 and A2A , increasing A1/A2A beyond the control level. BM+DE was superior to BM in restoring PAR1 and ET1 to control levels. BM+DE was superior to BM in restoring MDA to the control level and was superior to both BM and DE in increasing GSH beyond the control level. BM+DE exhibited the highest percentage of preserved neurons in SN, which was negatively correlated with MDA. CONCLUSION:BM+DE offers a therapeutic potential for parkinsonism triggered by chronic exposure to CoCl2. The implication of thrombin-related factors and oxidative stress in the modulation of the dopaminergic-adenosinergic crosstalk is plausible.

Background: Necroinflammation loop is a pathologic hallmark of organ dysfunction. That is owed to a distorted balance between the pro-inflammatory (M1) and the anti-inflammatory (M2) macrophages. We aimed to explore whether low-intensity pulsed ultrasound (LIPUS) and/or splenectomy could ameliorate necroinflammation by increasing M2 macrophages and modulating the exosomes-related proteins. Method: Rats were allocated into 2 groups: Sham and splenectomy (Splen). After that, rats were divided into LIPUS untreated and treated subgroups. Rats in each subgroup were subjected to either vehicle (sham, sham + LIPUS) or gentamicin (GM) (GM, GM + LIPUS, Splen + GM, Splen + GM + LIPUS). Biochemical and immunohistological analyses assessed macrophage polarization, necroptosis, exosomes-related markers, and exosomes-related proteins. Results: We found that LIPUS successfully reversed the effects of GM, LIPUS significantly-decreased (p < 0.05) necroinflammation markers through significant downshifting (p < 0.05) of M1 macrophage polarization, and noticeable modification (p < 0.05) of the exosome-related proteins (Milk fat globule-EGF factor 8 (MFG-E8), heat shock protein 70 (Hsp70)). Conclusion: Spleen could be a promising target for LIPUS via restoring M1/M2 balance and modulation of exosomes-related proteins.

Objectives: identify the diagnostic accuracy of tissue Cystatin (SA) in diagnosis of oral lichen planusMethodology: The present study included 58 Patients divided into 2 groups, group I: 29 healthy control patients and group II: 29 Patients clinically diagnosed with oral lichen planus. Tissue biopsy was taken and the production of tissue cystatin SA was determined by enzyme immunoassay. We described and compared the protein profiles (Cystatin SA) in the tissues, from patients who presented with oral lichen planus and from healthy controls. Data were presented as mean and standard deviation values and were analyzed using independent t-test. Correlations were analyzed using Spearman's rank order correlation coefficient.Results: The Oral Lichen Planus group had a significantly higher Cystatin-SA level than the control group (p<0.001). The mean value of the cystatin SA in the Oral Lichen Planus group was 19.68±3.69, whereas the mean value of the cystatin SA in the control group was 7.22±1.6, suggesting a role for the cystatin SA in the diagnosi of Oral Lichen Planus.Conclusions: Cystatin-SA expression in Oral Lichen Planus patients was more outstanding than in healthy control subjects.Key words: Biopsy, autoimmune disease, immunoassay

Background Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder mainly affecting joints, yet the systemic inflammation can influence other organs and tissues. The objective of this study was to unravel the ameliorative capability of Ondansetron (O) or β-sitosterol (BS) against inflammatory reactions and oxidative stress that complicates Extra-articular manifestations (EAM) in liver, kidney, lung, and heart of arthritic and arthritic irradiated rats. Methods This was accomplished by exposing adjuvant-induced arthritis (AIA) rats to successive weekly fractions of total body γ-irradiation (2 Gray (Gy)/fraction once per week for four weeks, up to a total dose of 8 Gy). Arthritic and/or arthritic irradiated rats were either treated with BS (40 mg/kg b.wt. /day, orally) or O (2 mg/kg) was given ip) or were kept untreated as model groups. Results Body weight changes, paw circumference, oxidative stress indices, inflammatory response biomarkers, expression of Janus kinase-2 (JAK-2), Signal transducer and activator of transcription 3 (STAT3), high mobility group box1 (HMGB1), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), as well as pro- and anti-inflammatory mediators in the target organs, besides histopathological examination of ankle joints and extra-articular tissues. Treatment of arthritic and/or arthritic irradiated rats with BS or O powerfully alleviated changes in body weight gain, paw swelling, oxidative stress, inflammatory reactions, and histopathological degenerative alterations in articular and non-articular tissues. Conclusion The obtained data imply that BS or O improved the articular and EAM by regulating oxidative and inflammatory indices in arthritic and arthritic irradiated rats.

Background Varicocele is considered a common and correctable cause of male infertility. This is established by the improvement of sperm parameters after surgical correction. Endoglin (Eng) is presented in two forms, a membrane and soluble forms, and the equilibrium between these forms depends on the oxidative status. Eng is linked to several pathological conditions common in varicocele as hypoxia and apoptosis. Aim This study aimed to evaluate the seminal level of soluble Eng in infertile oligoasthenoteratozoospermic (OAT) men associated with varicocele. Methods Sixty men were enrolled in this study. They were divided into two groups: infertile OAT men with varicocele and healthy fertile men as a control group. These participants were subjected to complete history taking, clinical and genital examination, semen analysis, and assessment of soluble Eng pre- and 6 months after the surgical intervention. Results The results showed a significant elevation of seminal soluble Eng in infertile OAT men associated with varicocele than in fertile control. Six months postsurgical correction, there was a significant improvement in semen parameters accompanied by a significant decrease in the seminal level of soluble Eng. Conclusions It was concluded that seminal soluble Eng is elevated in infertile OAT men linked to varicocele concurrent with the negative effect on sperm parameters. The surgical correction of varicocele in these cases shows significant improvement in these criteria.

Abstract Obesity-related health problems are getting worse in various societies worldwide. Artemisia anuua L. (AA) has distinctive health benefits, including anti-inflammatory, antioxidant, and insulin-sensitizing properties; however, its major constituents' limitedsolubility and bioavailability constrain its absorption. This study aimed to use a sonochemical technique to nano-formulate the AA ethanolic extract (AAE) to produce AAE nanoparticles (AAEN) and to compare their efficacy in modulating obesity-related complications in hypercaloric (high-fat /high-sucrose, HF/HS) diet-induced obese rats. Forty-eight Sprague Dawley adult rats were divided into two main groups and fed a basal or hypercaloric diet for twelve weeks. Starting from the eighth week, each main group was subdivided into three subgroups and treated orally with either saline, AAE, or AAEN till the end of the experiment (12 weeks). AAE and AAEN exerted antiadipogenic effects. They reduced body weight and epididymal fat, mitigated dyslipidemia, improved glucose utilization, reduced insulin resistance and hyperleptinemia, increased serum adiponectin, and decreased oxidative stress andinflammatory markers. These results were mediated by controlling the expression of critical genes contributing to lipids and carbohydrate metabolism.AAEN produced more expressive ameliorating effects than the conventional extract. In conclusion, nanoformulation of Artemisia annua L. extract boosted its antiadipogenic efficacy.

A common anthracycline antibiotic used to treat cancer patients is doxorubicin (DOX). One of the effects of DOX therapy is skeletal muscle fatigue. Our goal in this research was to study the beneficial effect of exercise on DOX-induced damaged muscle fibers and compare the effect of different exercise strategies (prophylactic, post- toxicity and combined) on DOX toxicity. Five groups were created from 40 male rats: group I, control group; group II, DOX was administered intraperitoneally for 2 weeks over 6 equal injections (each 2.5 mg/kg); group III, rats trained for 3 weeks before DOX; group IV, rats trained for 8 weeks after DOX; and group V, rats were trained for 3 weeks before DOX followed by 8 weeks after. Measures of oxidative damage (H 2 O 2 , catalase), inflammation (TNF-α), and glucose transporter 4 (GLUT4) expression on skeletal muscle were assessed. Also, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was estimated. Skeletal performance was evaluated by contraction time (CT), half relaxation time (1/2 RT), and force-frequency relationship by the end of this research. The current study demonstrated a detrimental effect of DOX on skeletal performance as evidenced by a significant increase in CT and 1/2 RT compared to control; in addition, H 2 O 2 , TNF-α, and HOMA-IR were significantly increased with a significant decrease in GLUT4 expression and catalase activity. Combined exercise therapy showed a remarkable improvement in skeletal muscle performance, compared to DOX, CT, and 1/2 RT which were significantly decreased; H 2 O 2 and TNF-α were significantly decreased unlike catalase antioxidant activity that significantly increased; in addition, skeletal muscle glucose metabolism was significantly improved as GLUT4 expression significantly increased and HOMA-IR was significantly decreased. Exercise therapy showed significant improvement in all measured parameters relative to DOX. However, combined exercise therapy showed the best improvement relative to both pre-exercise and post-exercise groups.

Caloric restriction (CR) alongside its ability to increase longevity, exerts inhibitory effects against various tumors. The purpose of this current research was to investigate the conceivable implications of CR, either independently or in ion conjunctwith a cyclooxygenase 2 inhibitor (Celecoxib), on the pathophysiology of induced hepatocellular carcinoma (HCC). Forty adult malestar Wi rats were allocated into four groups: Control, HCC; induced by injecting diethylnitrosamine intraperitoneally, then subsequntly give a weekly subcutaneous injection of carbon tetrachloride (CCl4) once a week for 6 consecutive weeks, CR group, and CR-Celecoxiboup. gr The results revealed enhanced serum insulin growth factor-I (IGF-I) and- II (IGF-II) levels, along with a significant in increaseCOX-2 and IL-6 gene expression as well as acceleration of pathological changes, glycogen depletion, enhanced fibrosis, and decreasedcaspase 3 expression in the liver. However, both IGF-I, II, and alpha-fetoprotein (AFP) were significantly decreased in the CR group-treated co with Celecoxib which was positively reflected on the liver architecture. We concluded that combined CR and COX-2 inhibition interferes with the pathogenesis of HCC.

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-3 beta (GSK-3 beta), 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 mu g/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 beta, thereby improving cognition. 6BIO, the GSK-3 beta inhibitor, restored mitochondrial biogenesis by augmenting the protein levels of PGC1-alpha 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.

Single nucleotide polymorphisms (SNPs) of the protein tyrosine phosphatase non-receptor type 2 (PTPN2) gene have been documented to be linked with several autoimmune disorders including Behçet’s disease (BD). PTPN2 SNPs rs2542151 and rs7234029 have been assessed using real-time PCR in 96 BD patients and 50 controls matched by age and gender. Patients were categorized into groups according to the disease phenotypes and severity. A total of 94.8

ABSTRACTParkinson's disease (PD), the second common neurodegenerative disease, is characterized by the loss of the dopaminergic neurons in the substantia nigra (SN). Because of L-dopa's side effects, new therapeutic methods were considered such as stem cells for PD treatment. The major challenge facing stem cell therapy following transplantations is their peripheral sequestration and decreased survival. Thus, the ability of erythropoietin (EPO) and low-level laser therapy (LLLT) to enhance mesenchymal stem cell (MSC) proliferation and therapeutic efficiency for alleviating rotenone-induced PD was investigated. Therefore, we compared the influence of stem cell preconditioning with erythropoietin versus LLLT on MSCs’ homing ability and the chances of survival. Forty-eight male Swiss mice were included in the in vivo protocol and ten in the in vitro work. The mice in the in vivo study were divided randomly into six groups (8 in each); group I; control group and group II; induced PD (untreated) group, group III; L-dopa, group IV; MSCs, group V; EPO-activated MSCs and group VI; laser-activated MSCs. Treatment with MSCs (either preconditioned or not) improved these neurological features by restoring the normal balance between glutamate and GABA neurotransmitters, and dopamine as well as increased tyrosine hydroxylase levels. Stem cell therapy decreased oxidative stress, miRNA-155 levels, enhanced neuronal architecture in SN, and decreased the number of apoptotic cells. LLLT enhanced MSC expression of integrin β1 which was reflected in the homing of PKH26-labelled MSCs into corpus striatum and SN. Thus, the optimum results were achieved with laser-activated MSCs.

BACKGROUND AND AIM:Many attempts to control acute kidney injury (AKI) have failed due to a lack of understanding of its pathophysiological key components. Macrophages are a crucial determinant of AKI, which can be categorized functionally as M1 pro-inflammatory and M2 anti-inflammatory macrophages. Low-intensity pulsed ultrasound (LIPUS) is currently being investigated as an immune modulator. The present study aimed to explore the potential effects of LIPUS on the polarization of renal macrophages, as well as the possible interplay between macrophage polarization and necroptosis in gentamicin-induced acute kidney injury.METHOD:All rats were randomly allocated into one of four groups: control, LIPUS-treated control, gentamicin acute kidney (GM-AKI), and LIPUS-treated GM-AKI. Renal functions, macrophage polarization, necroptosis, and heat shock protein-70 (HSP70) were analyzed using real-time reverse-transcriptase-polymerase chain reaction (rT-PCR), Western Blot, Enzyme-linked immunosorbent assay (ELISA) as well as immunohistological analysis.RESULTS:we found that LIPUS markedly inhibited the expressions of M1 macrophage-related genes and promoted significantly the expression of M2 macrophages related genes. This was accompanied by an inhibition of necroptosis and a marked reduction of HSP-70, resulting in a reversal of gentamicin-induced renal alteration.CONCLUSION:Functional switching of macrophage responses from M1 into M2 seems to be a potential approach to ameliorate necroptosis as well as HSP-70 by low pulsed ultrasound waves in GM-AKI.