The role of non-protein-coding RNAs in ischemic acute kidney injury.

Acute kidney injury (AKI) is a condition characterized by a rapid decline in kidney function within a span of 48 hours. It is influenced by various factors including inflammation, oxidative stress, excessive calcium levels within cells, activation of the renin-angiotensin system, and dysfunction in microcirculation. Ischemia-reperfusion injury (IRI) is recognized as a major cause of AKI; however, the precise mechanisms behind this process are not yet fully understood and effective treatments are still needed. To enhance the accuracy of diagnosing AKI during its early stages, the utilization of innovative markers is crucial. Numerous studies suggest that certain noncoding RNAs (ncRNAs), such as long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), play a central role in regulating gene expression and protein synthesis. These ncRNAs are closely associated with the development and recovery of AKI and have been detected in both kidney tissue and bodily fluids. Furthermore, specific ncRNAs may serve as diagnostic markers and potential targets for therapeutic interventions in AKI. This review aims to summarize the functional roles and changes observed in noncoding RNAs during ischemic AKI, as well as explore their therapeutic potential.

Protective effects of melatonin against physical injuries to testicular tissue: A systematic review and meta-analysis of animal models.

Background: Modern societies face infertility as a global challenge. There are certain environmental conditions and disorders that damage testicular tissue and may cause male infertility. Melatonin, as a potential antioxidant, may protect testicular tissue. Therefore, we conducted this systematic review and meta-analysis to evaluate the effects of melatonin in animal models against physical, heat, and ischemic damage to the testicular tissue. Methods: PubMed, Scopus, and Web of Science were systematically searched to identify animal trials evaluating the protective effect of melatonin therapy on rodent testicular tissue when it is exposed to physical, thermal, ischemic, or hypobaric oxygen stress. Random-effect modeling was used to estimate the standardized mean difference and 95% confidence intervals based on the pooled data. Additionally, the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) tool was used to assess the risk of bias. The study protocol was prospectively registered in PROSPERO (CRD42022354599). Results: A total of 41 studies were eligible for review out of 10039 records. Studies employed direct heat, cryptorchidism, varicocele, torsion-detorsion, testicular vascular occlusion, hypobaric hypoxia, ischemia-reperfusion, stress by excessive or restraint activity, spinal cord injury, and trauma to induce stress in the subjects. The histopathological characteristics of testicular tissue were generally improved in rodents by melatonin therapy. Based on the pooled data, sperm count, morphology, forward motility, viability, Johnsen's biopsy score, testicular tissue glutathione peroxidase, and superoxide dismutase levels were higher in the melatonin treatment rodent arms. In contrast, the malondialdehyde level in testicular tissue was lower in the treatment rodent arms. The included studies suffered from a high risk of bias in most of the SYRCLE domains. Conclusion: This study concludes that melatonin therapy was associated with improved testicular histopathological characteristics, reproductive hormonal panel, and tissue markers of oxidative stress in male rodents with physical, ischemic, and thermal testicular injuries. In this regard, melatonin deserves scientific investigations as a potential protective drug against rodent male infertility. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42022354599.

Indirect co-culture of islet cells in 3D biocompatible collagen/laminin scaffold with angiomiRs transfected mesenchymal stem cells.

Diabetes is an autoimmune disease in which the pancreatic islets produce insufficient insulin. One of the treatment strategies is islet isolation, which may damage these cells as they lack vasculature. Biocompatible scaffolds are one of the efficient techniques for dealing with this issue. The current study is aimed to determine the effect of transfected BM-MSCS with angiomiR-126 and -210 on the survival and functionality of islets loaded into a 3D scaffold via laminin (LMN). AngiomiRs/Poly Ethylenimine polyplexes were transfected into bone marrow-mesenchymal stem cells (BM-MSCs), followed by 3-day indirect co-culturing with islets laden in collagen (Col)-based hydrogel scaffolds containing LMN. Islet proliferation and viability were significantly increased in LMN-containing scaffolds, particularly in the miRNA-126 treated group. Insulin gene expression was superior in Col scaffolds, especially, in the BM-MSCs/miRNA-126 treated group. VEGF was upregulated in the LMN-containing scaffolds in both miRNA-treated groups, specifically in the miRNA-210, leading to VEGF secretion. MiRNAs' target genes showed no downregulation in LMN-free scaffolds; while a drastic downregulation was seen in the LMN-containing scaffolds. The highest insulin secretion was recorded in the Oxidized dextran (Odex)/ColLMN+ group with miRNA-126. LMN-containing biocompatible scaffolds, once combined with angiomiRs and their downstream effectors, promote islets survival and restore function, leading to enhanced angiogenesis and glycemic status.

Susceptibility to Metabolic Diseases in COVID-19: To be or Not to be an Issue.

Despite the passage of more than 17 months from the beginning of the COVID-19 pandemic, challenges regarding the disease and its related complications still continue in recovered patients. Thus, various studies are underway to assay the long-term effects of COVID-19. Some patients, especially those with severe symptoms, experience susceptibility to a range of diseases and substantial organ dysfunction after recovery. Although COVID-19 primarily affects the lungs, multiple reports exist on the effect of this infection on the kidneys, cardiovascular system, and gastrointestinal tract. Studies have also indicated the increased risk of severe COVID-19 in patients with diabetes. On the other hand, COVID-19 may predispose patients to diabetes, as the most common metabolic disease. Recent studies have shown that Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) binds to Angiotensin-Converting Enzyme 2 (ACE2) receptors, which are expressed in the tissues and organs involved in regulating the metabolic status including pancreas, adipose tissue, gastrointestinal tract, and kidneys. Therefore, SARS-CoV-2 may result in metabolic disturbance. However, there are still many unknowns about SARS-CoV-2, which are required to be explored in basic studies. In this context, special attention to molecular pathways is warranted for understanding the pathogenesis of the disease and achieving therapeutic opportunities. Hence, the present review aims to focus on the molecular mechanisms associated with the susceptibility to metabolic diseases amongst patients recovered from COVID-19.

microRNAs Alterations of Myocardium and Brain Ischemia-Reperfusion Injury: Insight to Improve Infarction.

Heart and cerebral infarctions, as two important ischemic diseases, lead to the death of tissues due to inadequate blood supply and high mortality worldwide. These statuses are started via blockage of vessels and depletion of oxygen and nutrients which affected these areas. After reperfusion and restoration of oxygen supply, more severe injury was mediated by multifaceted cascades of inflammation and oxidative stress. microRNAs (miRNAs) as the regulator of biological and pathological pathways can adjust these conditions by interaction with their targets. Also, miRNAs can be modulated by preconditioning and external agents that may improve the functional outcome after IRI. miRNAs might be considered as therapeutic approaches to improve the symptoms of patients after myocardial infarction and cerebral ischemic stroke.

microRNAs in liver and kidney ischemia reperfusion injury: insight to improve transplantation outcome.

Ischemia reperfusion injury (IRI) is a condition that occurs wherever blood flow and oxygen is reduced or absent, such as trauma, vascular disease, stroke, and solid organ transplantation. This condition can lead to tissue damage, especially during organ transplantation. Under such circumstances, some signaling pathways are activated, leading to up- or down- regulation of several genes such as microRNAs (miRNAs) that might attenuate or ameliorate this status. Therefore, by manipulating miRNAs level, they can be used as a biomarker for early diagnosis of IRI or suggestive to be therapeutic agents in clinical situation in future.

Hypoxia-Preconditioned Wharton's Jelly-Derived Mesenchymal Stem Cells Mitigate Stress-Induced Apoptosis and Ameliorate Human Islet Survival and Function in Direct Contact Coculture System.

Protection of isolated pancreatic islets against hypoxic and oxidative damage-induced apoptosis is essential during a pretransplantation culture period. A beneficial approach to maintain viable and functional islets is the coculture period with mesenchymal stem cells (MSCs). Hypoxia preconditioning of MSCs (Hpc-MSCs) for a short time stimulates the expression and secretion of antiapoptotic, antioxidant, and prosurvival factors. The aim of the present study was to evaluate the survival and function of human islets cocultured with Hpc-MSCs. Wharton's jelly-derived MSCs were subjected to hypoxia (5% O2: Hpc) or normoxia (20% O2: Nc) for 24 hours and then cocultured with isolated human islets in direct and indirect systems. Assays of viability and apoptosis, along with the production of reactive oxygen species (ROS), hypoxia-inducible factor 1-alpha (HIF-1α), apoptotic pathway markers, and vascular endothelial growth factor (VEGF) in the islets, were performed. Insulin and C-peptide secretions as islet function were also evaluated. Hpc-MSCs and Nc-MSCs significantly reduced the ROS production and HIF-1α protein aggregation, as well as downregulation of proapoptotic proteins and upregulation of antiapoptotic marker along with increment of VEGF secretion in the cocultured islet. However, the Hpc-MSCs groups were better than Nc-MSCs cocultured islets. Hpc-MSCs in both direct and indirect coculture systems improved the islet survival, while promotion of function was only significant in the direct cocultured cells. Hpc potentiated the cytoprotective and insulinotropic effects of MSCs on human islets through reducing stressful markers, inhibiting apoptosis pathway, enhancing prosurvival factors, and promoting insulin secretion, especially in direct coculture system, suggesting the effective strategy to ameliorate the islet quality for better transplantation outcomes.

Decreased Expression of Arginine-Phenylalanine-Amide-Related Peptide-3 Gene in Dorsomedial Hypothalamic Nucleus of Constant Light Exposure Model of Polycystic Ovarian Syndrome.

BACKGROUND: An abnormality in pulse amplitude and frequency of gonadotropin releasing hormone (GnRH) secretion is the most characteristics of polycystic ovarian syndrome (PCOS). On the other hand, arginine-phenylalanine-amide (RFamide)-related peptide-3 (RFRP3) inhibits the secretion of GnRH in mammalian hypothalamus. The current study performed in order to investigate the expression of RFRP3 mRNA in the dorsomedial hypothalamic nucleus (DMH) after the induction of PCOS in a rat model of constant light exposure, and the possible role of parity on occurrence of PCOS. MATERIALS AND METHODS: In the experimental study, female nulliparous (n=12) and primiparous (n=12) rats were randomly subdivided into control and PCOS subgroups (n=6). PCOS were induced by 90 days exposure to constant light. After 90 days, blood, brain, and ovaries were sampled. Serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), and testosterone were evaluated. In addition, six adult female ovariectomized rats as a control of real-time polymerase chain reaction (PCR) tests were prepared and in the DMH of all rats, the relative mRNA expression of RFRP3 was assessed. RESULTS: Histological evaluation of ovaries represented the polycystic features. In addition, serum concentrations of testosterone in the PCOS subgroups were more than the controls (P<0.05). Furthermore, the relative expression of RFRP3 mRNA in PCOS subgroups was lower than the controls (P<0.05). CONCLUSION: Constant light model of the PCOS-induced rats decreased the gene expression of RFRP3 in the DMH that suggests the decrease of RFRP3 may reduce its inhibitory effect on GnRH during the PCOS pathogenesis. This effect was stronger in the nulliparous rats than the primiparous.

Histomorphometric changes of small intestine in pregnant rat.

Food intake of rats increases during pregnancy. This requires changes in the structure of the small intestine to absorb additional food. The aim of the present study was to investigate the morphological changes in the layers of small intestine in rats during pregnancy. Duodenum, jejunum and ileum of 18 pregnant Sprague-Dawley rats (day 7, 14 and 21 of pregnancy) were collected. Villous height and width and thickness of lamina propria, tunica muscularis entirely and separately (circular and longitudinal layers) were measured on transverse sections. During pregnancy increasing villi length and muscular layer thickness was observed in duodenum. Furthermore, along with the progress of gestation greatest histomorphometric change in small intestine was observed in the jejunum. The reduction in the ileum histomorphologic indices was observed during pregnancy. In conclusion, increase in histomorphologic indices of duodenum and jejunum supplies more capacity of duodenum to digest food intake during pregnancy and decrease in these indices in ileum controls the absorption of excess produced amino acids and glucose by hyperphagia.

The Healing Effect of Licorice on Pseudomonas aeruginosa Infected Burn Wounds in Experimental Rat Model.

BACKGROUND: Burn is still one of the most devastating injuries in emergency medicine while improvements in wound healing knowledge and technology have resulted into development of new dressings. This study was undertaken to evaluate the healing effect of licorice in Pseudomonas aeruginosa infected burn wounds of experimental rat model. METHODS: One hundred and twenty female Sprague-Dawley rats were randomly allocated to 4 equal groups. Group A received silver sulfadiazine ointment, Group B received 10% licorice extract and Group C was considered as control group and received gel base as the base of medication. Group D did not receive any medication and just underwent burn injury. A standard 3rd degree burn wound was produced by a hot plate with similar size about 20% of total body surface area (TBSA) and at identical temperature. After 24 h of burn production, 10(8) colony forming units (CFU) of toxigenic strains of P. aeruginosa (PA 103) were inoculated subcutaneously into the burnt area. After 3, 7, 14, 21 and 28 days of therapy, the animals were sacrificed and burn areas were macroscopically examined and histologically evaluated. RESULTS: Decrease in size of the burn wounds, in inflammation and re-epithelialization were poor in groups B-D. Infection to P. aeruginosa was still visible in groups B-D but was absent in Group A. The mean histological score, tensile strength, maximum stress, yield strength and stiffness in groups B-D were lower compared with Group A. CONCLUSION: Licorice extract in 10% concentration was shown not to be effective in healing of P. aeruginosa infected burn wounds.

Expression of RFamide-Related Peptide-3 (RFRP-3) mRNA in Dorsomedial Hypothalamic Nucleus and KiSS-1 mRNA in Arcuate Nucleus of Rat during Pregnancy.

BACKGROUND: RFamide-related peptide-3 (RFRP-3) and kisspeptin (KiSS-1) are known to respectively inhibit and stimulate gonadotropin releasing hormone (GnRH) and lute- inizing hormone (LH) secretion in rat. The aim of the present study was to evaluate the relative mRNA expression of RFRP-3 and KiSS-1 in the hypothalamus of pregnant rats. MATERIALS AND METHODS: In a randomized controlled experimental study, the exact preg- nancy day of 18 Sprague-Dawley rats were confirmed using the vaginal smear method and were equally assigned to three groups of days 7, 14 and 21 of pregnancy. Four non- pregnant female rats were ovariectomized and assigned as the control group. All rats were decapitated, and the dorsomedial hypothalamic nucleus (DMH) and the arcuate nucleus (ARC) for detection of KiSS-1 mRNA were separated from their hypothalamus to detect RFRP-3 and KiSS-1 mRNA respectively. Then, their relative expressions were compared between control and pregnant groups using real-time polymerase chain reac- tion (PCR). RESULTS: The relative expression of RFRP-3 mRNA in DMH did not change significantly during pregnancy (p>0.01). However, the relative expression of KiSS-1 mRNA in ARC was at its highest in day 7 of pregnancy and decreased until day 21 of pregnancy (p<0.01). CONCLUSION: Decrease in GnRH and LH secretion during the pregnancy of rat may be controlled by constant expression of RFRP-3 mRNA and reduced expression of KiSS-1 mRNA in hypothalamus.

Molecular and Serological Evaluation of Toxoplasma gondii Infection in Reared Turkeys in Fars Province, Iran.

BACKGROUND: Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. This parasite infects most of warm-blooded animals, including birds. Turkeys are one of these animals which might be infected by this parasite. Little is known about the prevalence of T. gondii in turkeys in Iran. OBJECTIVES: The current study aimed to evaluate the rate of Toxoplasma infection in turkeys in Fars Province, Southern Iran. MATERIALS AND METHODS: Sera and tissues (brain, neck and tongue) of 54 turkeys were collected from Shiraz slaughterhouse in Fars province. Anti-Toxoplasma antibodies were assessed in the collected sera using modified agglutination test (MAT), while tissues were evaluated by polymerase chain reaction (PCR) and bioassay methods. RESULTS: T. gondii antibodies (MAT titer: ≥ 1:40) were found in 89.8% of turkeys. T. gondii DNA was detected in 61.6% of turkey tissues and brain had the highest rate of infection. Brain tissues from each animal were bioassayed and Toxoplasma tissue cysts were found in 11.5% and Toxoplasma DNA in 62% of inoculated mice. CONCLUSIONS: Results of this study validated a relatively high level of Toxoplasma infection in reared turkeys and turkey meat might be considered as an infection sources for human.