Ameliorating effects of adropin on letrozole-induced polycystic ovary syndrome via regulating steroidogenesis and the microbiota inflammatory axis in rats.

Growing evidence supports the role of gut microbiota in chronic inflammation, insulin resistance (IR) and sex hormone production in polycystic ovary syndrome (PCOS). Adropin plays a pivotal role in the regulation of glucose and lipid metabolism and is negatively correlated with IR, which affects intestinal microbiota and sex hormones. However, the effect of adropin administration in PCOS has yet to be investigated. The present study aimed to assess the effects of adropin on letrozole (LTZ)-induced PCOS in rats and the potential underlying mechanisms. The experimental groups were normal, adropin, letrozole and LTZ + adropin. At the end of the experiment, adropin significantly ameliorated PCOS, as evidenced by restoring the normal ovarian structure, decreasing the theca cell thickness in antral follicles, as well as serum testosterone and luteinizing hormone levels and luteinizing hormone/follicle-stimulating hormone ratios, at the same time as increasing granulosa cell thickness in antral follicles, oestradiol and follicle-stimulating hormone levels. The ameliorating effect could be attributed to its effect on sex hormone-binding globulin, key steroidogenic genes STAR and CYP11A1, IR, lipid profile, gut microbiota metabolites-brain-ovary axis components (short chain fatty acids, free fatty acid receptor 3 and peptide YY), intestinal permeability marker (zonulin and tight junction protein claudin-1), lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B inflammatory pathway and oxidative stress makers (malondialdehyde and total antioxidant capacity). In conclusion, adropin has a promising therapeutic effect on PCOS by regulating steroidogenesis, IR, lipid profile, the gut microbiota inflammatory axis and redox homeostasis. KEY POINTS: Adropin treatment reversed endocrine and ovarian morphology disorders in polycystic ovary syndrome (PCOS). Adropin regulated the ovarian steroidogenesis and sex hormone-binding globulin in PCOS. Adropin improved lipid profile and decreased insulin resistance in PCOS. Adropin modulated the components of the gut-brain-ovary axis (short chain fatty acids, free fatty acid receptor 3 and peptide YY) in PCOS. Adropin improved intestinal barrier integrity, suppressed of lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B signalling pathway and oxidative stress in PCOS.

Ulinastatin ameliorated streptozotocin-induced diabetic nephropathy: Potential effects via modulating the components of gut-kidney axis and restoring mitochondrial homeostasis.

Growing evidence supports the role of the gut-kidney axis and persistent mitochondrial dysfunction in the pathogenesis of diabetic nephropathy (DN). Ulinastatin (UTI) has a potent anti-inflammatory effect, protecting the kidney and the gut barrier in sepsis, but its effect on DN has yet to be investigated. This study aimed to assess the potential mitigating effect of UTI on DN and investigate the possible involvement of gut-kidney axis and mitochondrial homeostasis in this effect. Forty male Wistar rats were divided equally into four groups: normal; UTI-treated control; untreated DN; and UTI-treated DN. At the end of the experiment, UTI ameliorated DN by modulating the gut-kidney axis as it improved serum and urinary creatinine, urine volume, creatinine clearance, blood urea nitrogen, urinary albumin, intestinal morphology including villus height, crypt depth, and number of goblet cells, with upregulating the expression of intestinal tight-junction protein claudin-1, and counteracting kidney changes as indicated by significantly decreasing glomerular tuft area and periglomerular and peritubular collagen deposition. In addition, it significantly reduced intestinal and renal nuclear factor kappa B (NF-κB), serum Complement 5a (C5a), renal monocyte chemoattractant protein-1 (MCP-1), renal intercellular adhesion molecule 1 (ICAM1), and renal signal transducer and activator of transcription 3 (STAT3), mitochondrial dynamin related protein 1 (Drp1), mitochondrial fission 1 protein (FIS1), mitochondrial reactive oxygen species (ROS), renal hydrogen peroxide (H2O2), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Furthermore, it significantly increased serum short chain fatty acids (SCFAs), and mitochondrial ATP levels and mitochondrial transmembrane potential. Moreover, there were significant correlations between measured markers of gut components of the gut-kidney axis and renal function tests in UTI-treated DN group. In conclusion, UTI has a promising therapeutic effect on DN by modulating the gut-kidney axis and improving renal mitochondrial dynamics and redox equilibrium.

The prospective effect of fucoidan on splenic dysfunction caused by oxaliplatin in male rats through endoplasmic stress dynamics.

Fucoidans (FUCs) are highly sulfated polysaccharides demonstrating multiple actions in different systems. Oxaliplatin (OXA) is a platinum-containing chemotherapeutic agent with several side effects that restrict its usage. The current study aimed to determine the potential effect of FUC in male rats with splenic dysfunction induced by OXA. Eighty adult male rats aged (8-9 weeks) weighing (190-230 g) were divided into four groups: (Group I: the control group): Rats were administrated normal saline; (Group II: controls treated by FUC): Rats were treated with FUC; (Group III: Splenic dysfunction group): Rats were treated with 8 mg/kg OXA. (IV: Splenic dysfunction treated by FUC): Rats were treated by OXA as Group III, then fucoidan was given. At the end of the experiment, blood was collected to determine red blood cells and white blood cells. Splenic tissues were divided into one part for biochemical assays, oxidative stress markers as MDA and catalase, inflammatory markers (TNF-alpha, IL6), and apoptotic markers (caspase 3) and gene expression of Nrf2, Mapk1 gene expression, and endoplasmic stress parameters and the other part was used for immunohistochemical and histopathological analysis. Compared to the OXA-induced splenic dysfunction group, FUC significantly decreased high levels of MDA, TNF- alpha, IL6, caspase-3, Mapk1, endoplasmic stress induced by OXA, and increased the level of catalase and Nrf2. Fucoidan has corrected the histopathological and immunohistochemical changes compared to the OXA-induced splenic dysfunction group. In conclusion, our findings suggest that fucoidan has a significant role in the treatment of splenic dysfunction induced by OXA.

Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions.

BACKGROUND: Pancreatic cystic lesions (PCLs) are common in clinical practice. The accurate classification and diagnosis of these lesions are crucial to avoid unnecessary treatment of benign lesions and missed opportunities for early treatment of potentially malignant lesions. AIM: To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens [e.g., cancer antigen (CA)19-9, CA72-4], carcinoembryonic antigen (CEA), serine protease inhibitor Kazal-type 1 (SPINK1), interleukin 1 beta (IL1-ß), vascular endothelial growth factor A (VEGF-A), and prostaglandin E2 (PGE2)], amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions. METHODS: This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent endoscopic ultrasound (EUS) and EUS-fine needle aspiration (EUS-FNA) for characterization and sampling of different PCLs. RESULTS: The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1ß, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in cystic pancreatic lesions. CONCLUSION: EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.

Impact of sustained virologic response in regression of portal hypertension in Egyptian patients with hepatitis C virus-associated cirrhosis and portal hypertension.

Background: Portal hypertension (PH) is a common consequence in hepatitis C virus cirrhotic patients. With interferon alpha-based therapy, SVR was linked to improved PH and fibrosis regression. SVR to oral antiviral regimens is linked to reduced portal pressure in patients with clinically significant portal hypertension (CSPH) at baseline. However, CSPH continues in most of the patients. This study aims to assess the reversibility and/or improvement of PH in Egyptian patients with HCV-related cirrhosis and CSPH after achieving SVR with DAAs. The second aim is to evaluate performance of the noninvasive markers of fibrosis in prediction of the presence and/or reversibility of the CSPH in correlation to radiological and endoscopic parameters. Subjects and methods: We evaluated noninvasive parameters, radiological and endoscopic signs of PH at baseline, and/or SVR 24 and SVR 48 post-DAA therapy in 40 patients with cirrhosis and CSPH (group A) and another 40 patients with cirrhosis only (group B). Results: In group A, the spleen diameter decreased from baseline (15.74 ± 1.53 cm), and SVR 24 (15.48 ± 1.51), to SVR 48 (15.35 ± 1.49 cm). No ascites detected at SVR 48 in 62.5%. Portal vein diameter and portal vein blood velocity reduced to 13.53 ± 1.07 mm and 14.14 ± 2.2 cm/s at SVR 48, with reversibility of hepatic vein waveform towards the triphasic pattern. Medium to large esophageal varices regressed from 52.5% to 2.5%, and up to 70% of patients showed no EVs at SVR 48. In group A, 24 patients showed complete reversibility of CSPH, and 16 patients showed improvement of CSPH. Child-Pugh score, FIB-4 index, King's score, and Lok index revealed higher significance for detection of the presence of PH. Child-Pugh score, PC/SD ratio, and Lok index revealed higher significance for detection of reversibility of PH. Conclusion: We concluded that CSPH improved after SVR with DAAs and completely regressed in some patients. Upon predicting the presence of PH, Child-Pugh score, FIB-4 index, King's score, and Lok index were the most significant noninvasive scores. While for predicting the reversibility of PH, Child-Pugh score, PC/SD ratio, and Lok index were the most significant scores.

Effect of Ramadan fasting on Muslim recipients after living donor liver transplantation: A single center study.

BACKGROUND AND STUDY AIMS: Several factors affect the quality of life and personal well-being of transplant recipients, including Ramadan fasting for Muslims. This study aimed to assess the effect of Ramadan fasting on the renal and liver functions of liver transplantation recipients and to propose a protocol for adapting an Immunosuppression regimen and follow-up schedule for patients wishing to fast after liver transplantation. PATIENTS AND METHODS: This prospective study was conducted on 45 recipients who wished to fast Ramadan from 17th May to 14th June 2018, at Ain Shams Center for Organ Transplantation, Cairo, Egypt. RESULTS: The mean age of the patients was 55.5 ± 7.2 (37-68) years, and 84.4% were males; the mean time from liver transplantation was 51.6 ± 28 months (14-117). Thirty-seven patients (82.2%) completed Ramadan fasting, three patients (6.6%) had interrupted fasting, and five patients (11.1%) had to stop fasting because of an unacceptable rise in renal function. There was a statistically significant difference between the pre- and post-fasting states in terms of the serum creatinine level (p = 0.004).However, the serum creatinine did not exceed the upper normal value in the patients who completed fasting. CONCLUSION: Our data seem promising for Ramadan fasting with an adapted immunosuppression protocol and regular follow-up for recipients wishing to fast. Further multicentre studies on a larger number of patients are warranted.

Neuroprotective effects of minocycline and progesterone on white matter injury after focal cerebral ischemia.

Stroke induced white matter injury can induce marked neurological deficits even after relatively small infarcts, due to the tightly packed nature of white matter tracts especially in certain areas in the brain. Many drugs which were successful in the pre-clinical trials failed in clinical trials, which was attributed in part to the focus on grey matter injury completely and ignoring their effect on white matter. In this work we selected two known neuroprotective drugs (minocycline and progesterone) and examined their effect on white matter injury after focal cerebral ischemia/reperfusion injury in rats. Focal cerebral ischemia was induced in male Wistar rats (one-hour ischemia followed by reperfusion). Progesterone and minocycline were administered immediately after reperfusion onset. Infarct size, microglial activation and white matter injury were assessed and compared between the treatment and no-treatment groups and Sham operated animals. Our data showed that both progesterone and minocycline reduced infarct size, microglial activation and white matter injury. This work shows a new neuroprotective mechanism of both drugs, via white matter injury reduction, that can be exploited for stroke management. While the utility of either drugs as a sole agent in the management of stroke is questionable, there is a value of using either drugs as an adjuvant therapy to traditional stroke therapy, making use of the white matter protective effect that would improve outcome and facilitate healing after stroke.