The Role of Gut Microbiota in Inflammatory Bowel Disease-Current State of the Art.

The human microbiome comprises the genomes of the microbiota that live on and within humans, such as protozoa, archaea, eukaryotes, viruses, and most bacteria. Gastrointestinal disorders such as inflammatory bowel disease, colon cancer, celiac disease, and irritable bowel syndrome can all be triggered by a change in gut flora. The alteration of the gut microbiota (also known as "gut dysbiosis") is affected by host genetics, nutrition, antibiotics, and inflammation, and it is associated with the development of inflammatory bowel disease (IBD). Also, intestinal epithelial dysfunction, altered autophagy, and immune hyperactivation are frequently detected in individuals with severe IBD, which may be attributed to impaired miRNA expression functions. While the exact mechanisms of how Gut Microbiota may cause IBD and intestinal epithelial dysfunction are still debated, recent data point toward the possibility that hormones, gender and miRNAs expression are modifiable contributors to IBD. This review summarizes the current evidence for an association between hormones, gender and miRNAs and Gut Microbiota in IBD and discusses potential mechanisms by which gut microbiota may impact IBD. The study also outlines critical unanswered topics that need to be solved to enhance IBD prevention and treatment in people with gut dysbiosis.

Recent findings on the role of microRNAs in genetic kidney diseases.

BACKGROUND: MicroRNAs (miRNAs) are non-coding, endogenous, single-stranded, small (21-25 nucleotides) RNAs. Various target genes at the post-transcriptional stage are modulated by miRNAs that are involved in the regulation of a variety of biological processes such as embryonic development, differentiation, proliferation, apoptosis, inflammation, and metabolic homeostasis. Abnormal miRNA expression is strongly associated with the pathogenesis of multiple common human diseases including cardiovascular diseases, cancer, hepatitis, and metabolic diseases. METHODS AND RESULTS: Various signaling pathways including transforming growth factor-ß, apoptosis, and Wnt signaling pathways have also been characterized to play an essential role in kidney diseases. Most importantly, miRNA-targeted pharmaceutical manipulation has represented a promising new therapeutic approach against kidney diseases. Furthermore, miRNAs such as miR-30e-5p, miR-98-5p, miR-30d-5p, miR-30a-5p, miR-194-5p, and miR-192-5p may be potentially employed as biomarkers for various human kidney diseases. CONCLUSIONS: A significant correlation has also been found between some miRNAs and the clinical markers of renal function like baseline estimated glomerular filtration rate (eGFR). Classification of miRNAs in different genetic renal disorders may promote discoveries in developing innovative therapeutic interventions and treatment tools. Herein, the recent advances in miRNAs associated with renal pathogenesis, emphasizing genetic kidney diseases and development, have been summarized.

The interaction between sexual reward/ deprivation and the acquisition, extinction and reinstatement of morphine-seeking behavior.

Natural rewards and abused drugs affect the function of the common brain's reward system. Interaction between social and drug rewards can change the vulnerability to development of drug addiction. Here, we investigate the effects of sexual experience and sex deprivation on the acquisition, maintenance, and drug prime-induced reinstatement of morphine-seeking behavior in male mice using conditioned place preference (CPP). CPP induced with morphine (3, 5, 7 mg/kg, s.c. for 3 days) lasted for 10 days after cessation of morphine treatment and priming dose of morphine (2 mg/kg, s.c.) reinstated the extinguished CPP. In the post-test phase, sexually experienced animals showed a lower preference for morphine compared to sex-deprived males. In the extinction phase, sex deprivation shortened maintenance time compared to control animals. The preference for morphine in sexually experienced animals did not diminish by the seventeenth extinction day. In both groups, the priming injection of morphine after the extinction period could reinstate the extinguished morphine-induced CPP. Together, these data showed the interaction between sex and drug reward and that sexual behavior -a natural rewarding stimulus- can prolong, whereas sex deprivation can block the maintenance of morphine-seeking behaviors. Sexual experience may induce functional and morphological alterations in brain reward areas particularly the mesolimbic system similar to repeated exposure to abused drugs which can affect morphine-seeking behaviors.

Cholangiocarcinoma and liver transplantation: What we know so far?

Cholangiocarcinoma (CCA) is a type of cancer with increasing prevalence around the world that originates from cholangiocytes, the epithelial cells of the bile duct. The tumor begins insidiously and is distinguished by high grade neoplasm, poor outcome, and high risk for recurrence. Liver transplantation has become broadly accepted as a treatment option for CCA. Liver transplantation is expected to play a crucial role as palliative and curative therapy for unresectable hilar CCA and intrahepatic CCA. The purpose of this study was to determine which cases with CCA should be subjected to liver transplantation instead of resection, although reported post-transplant recurrence rate averages approximately 20%. This review also aims to highlight the molecular current frontiers of CCA and directions of liver transplantation for CCA.

COVID-19 infection and liver injury: Clinical features, biomarkers, potential mechanisms, treatment, and management challenges.

It is hypothesized that liver impairment caused by coronavirus disease 2019 (COVID-19) infection might play a central role in severe clinical presentations. Liver injury is closely associated with severe disease and, even with antiviral drugs, have a poor prognosis in COVID-19 patients. In addition to the common hepatobiliary disorders caused by COVID-19, patients with pre-existing liver diseases demand special considerations during the current pandemic. Thus, it is vital that upon clinical presentation, patients with concurrent pre-existing liver disease associated with metabolic dysfunction and COVID-19 be managed properly to prevent liver failure. Careful monitoring and early detection of liver damage through biomarkers after hospitalization for COVID-19 is underscored in all cases, particularly in those with pre-existing metabolic liver injury. The purpose of this study was to determine most recent evidence regarding causality, potential risk factors, and challenges, therapeutic options, and management of COVID-19 infection in vulnerable patients with pre-existing liver injury. This review aims to highlight the current frontier of COVID-19 infection and liver injury and the direction of liver injury in these patients.

Kidney diseases and COVID-19 infection: causes and effect, supportive therapeutics and nutritional perspectives.

Recently, the novel coronavirus disease 2019 (COVID-19), has attracted the attention of scientists where it has a high mortality rate among older adults and individuals suffering from chronic diseases, such as chronic kidney diseases (CKD). It is important to elucidate molecular mechanisms by which COVID-19 affects the kidneys and accordingly develop proper nutritional and pharmacological strategies. Although numerous studies have recently recommended several approaches for the management of COVID-19 in CKD, its impact on patients with renal diseases remains the biggest challenge worldwide. In this paper, we review the most recent evidence regarding causality, potential nutritional supplements, therapeutic options, and management of COVID-19 infection in vulnerable individuals and patients with CKD. To date, there is no effective treatment for COVID-19-induced kidney dysfunction, and current treatments are yet limited to anti-inflammatory (e.g. ibuprofen) and anti-viral medications (e.g. Remdesivir, and Chloroquine/Hydroxychloroquine) that may increase the chance of treatment. In conclusion, the knowledge about kidney damage in COVID-19 is very limited, and this review improves our ability to introduce novel approaches for future clinical trials for this contiguous disease.

Protective effects of morphine in a rat model of post-traumatic stress disorder: Role of hypothalamic-pituitary-adrenal axis and beta- adrenergic system.

Post-traumatic stress disorder (PTSD) arises after tremendous traumatic experiences. Recently, we have reported that morphine has time-dependent protective effects against behavioral and morphological deficits in the single prolonged stress (SPS) as an experimental model of PTSD in adult male rats. To find the mechanisms underlying the protective effects of morphine against SPS-induced PTSD-like symptoms, the present study investigated the interaction between morphine and hypothalamic-pituitary-adrenal (HPA) axis and beta - adrenergic system, which crucially involved in the stress response, on PTSD-like symptoms in male rats. The animals were exposed to the SPS procedure (restraint for 2 h, forced swimming for 20 min, and ether anesthesia) and morphine (10 mg/kg) or saline was injected 24 h following the SPS. The glucocorticoid receptor antagonist RU486 (20 mg/kg), the mineralocorticoid receptor antagonist spironolactone (50 mg/kg), and the corticosterone synthesis inhibitor metyrapone (50 mg/kg) were injected 90 min before morphine administration to block the HPA axis activity. The beta - adrenergic receptor blocker propranolol (10 mg/kg) and the peripheral beta-adrenergic receptor blocker nadolol (5 mg/kg) were administered 30 min before morphine injection to block the beta - adrenergic system. Anxiety-like behaviors were evaluated using the elevated plus maze (EPM) 11 days after the SPS. After that, animals were conditioned in a fear-conditioning task and extinction training was performed on days 1, 2, 3, 4 and 11 after fear conditioning. SPS increased anxiety-like behaviors and impaired fear extinction. Morphine injection 24 h after SPS significantly improved anxiety-like behaviors and enhanced fear extinction. The RU486, spironolactone and metyrapone prevented the protective effects of morphine on both SPS-induced anxiety-like behaviors and impaired fear extinction. The propranolol, and nadolol did not prevent the effect of morphine on anxiety-like behaviors, but the propranolol prevented morphine effects on fear extinction in SPS animals. These findings together suggest that the protective effects of morphine on PTSD-like symptoms in rats require a certain level of the HPA axis and central beta - adrenergic activity and any alteration in the function of these systems can impede the protective effects of morphine.

Effects of prenatal exposure to chrysotile asbestos on hippocampal neurogenesis and long-term behavioral changes in adult male rat offspring.

Prenatal development is a critical period of life that many environmental pollutants have been suggested to influence fetal growth. Nevertheless, there are still a few investigations into the prenatal exposure to chrysotile asbestos and its neurodevelopmental and behavioral outcome in offspring. In this study, twenty-eight pregnant Wistar rats were divided into four groups and received three-times repeated intraperitoneal injections of normal saline, chrysotile, ascorbic acid and the combination of chrysotile and ascorbic acid on gestational days 11, 14 and 17. The maternal serum levels of malondialdehyde (MDA) and prooxidant-antioxidant balance (PAB) and hippocampal MDA content in adult male offspring were measured. At postnatal day (PND) 60, elevated plus maze was performed to determine anxiety-like behavior, also depression-like behavior was examined using a forced swim test at PND 61- 62. Thereafter, the quantitative analysis of Ki-67, NeuN and GFAP positive cells in the hippocampal dentate gyrus were studied by immunostaining. Our data showed that prenatal exposure to chrysotile increased the maternal serum level of MDA and PAB as well as hippocampal MDA content in adult male offspring, also increased the depression- and anxiety-like behaviors of adult male offspring and decreased the hippocampal Ki-67+, NeuN+ and GFAP+ cells in dantate gyrus of adult male offspring. However, co-administration of ascorbic acid and chrysotile decreased hippocampal lipid peroxidation and increased the Ki-67+, NeuN+ and GFAP+ cells in adult male offspring. In summary, these results indicated that oxidative stress induced by prenatal exposure to chrysotile, lead to the long-lasting decrease of the hippocampal cell proliferation and neuronal differentiation as well as astrogliosis of adult male offspring that exhibit more depression- and anxiety-like behaviors in adulthood and co-treatment of ascorbic acid with chrysotile asbestos attenuated the changes.

Decrease in VEGF-Induced Pericardial Adhesion Formation Using Bevacizumab After Surgery.

OBJECTIVES: Some degrees of postoperative cardiac adhesions occur in response to the first cardiac surgery in patients that may limit surgeons for subsequent operations and increase the risk of heart injury. In this article, we established a model of postoperative pericardial adhesions, and because vascular endothelial growth factor (VEGF) seems to initiate adhesion formation through inflammatory responses, we used an anti-VEGF antibody, that is, bevacizumab, to examine its effects on postoperative adhesion formation. METHODS: Twenty Wistar rats were divided in 2 groups: control and bevacizumab. After chest opening, pericardial sac was opened and the heart was fully exposed. In the bevacizumab group, bevacizumab (2.5 mg/kg) was applied locally on the heart and then the chest was closed. The control group received saline solution as placebo. After 42 days, high-sensitivity C-reactive protein in peripheral blood was measured, and re-sternotomy was performed to measure severity of pericardial adhesions. Then, the hearts were collected from all rats to evaluate percentage of CD-31-positive cells (as a marker of angiogenesis) using immunohistochemical staining. RESULTS: When the bevacizumab group was compared with the control group, we found that the mean score of adhesion (0.89 ± 0.38 vs 2.56 ± 0.41) and CD-31 expression (27.45 ± 3.75% vs 56.26 ± 1.98%) was decreased significantly after bevacizumab administration. However, we did not find any difference in high-sensitivity C-reactive protein levels of control and bevacizumab animals. CONCLUSION: In the current study, bevacizumab administration could effectively reduce adhesion formation after first sternotomy by preventing VEGF-induced angiogenesis through CD-31 downregulation.

A glance at the therapeutic potential of irisin against diseases involving inflammation, oxidative stress, and apoptosis: An introductory review.

Irisin is a hormone-like molecule mainly released by skeletal muscles in response to exercise. Irisin induces browning of the white adipose tissue and has been shown to regulate glucose and lipid homeostasis. Keeping its energy expenditure and metabolic properties in view, numerous studies have focused on its therapeutic potential for the treatment of metabolic disorders like obesity and type 2 diabetes. Recently, the anti-inflammatory, anti-apoptotic and anti-oxidative properties of irisin have received a great deal of attention of the scientific society. These pathogenic processes are often associated with initiation, progression, and prognosis of numerous diseases like myocardial infarction, kidney diseases, cancer, lung injury, inflammatory bowel diseases, atherosclerosis, liver diseases, obesity and type 2 diabetes. In the current review, we present evidence regarding the anti-inflammatory, anti-apoptotic and anti-oxidative potential of irisin pertaining to various pathological conditions. Here, we explore multiple molecular pathways targeted by irisin therapy. Given the promising effects of irisin, many diseases with evident oxidative stress, inflammation and apoptosis can be targeted by irisin.