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Abstract Background The production of functional hepatocyte cells in enough quantities is of paramount importance for the replacement of lost hepatocytes. In this investigation, a series of 7-mimic microRNAs was harnessed to induce the differentiation of Wharton’s jelly-derived mesenchymal stromal cells (WJ-MSCs) into hepatocyte-like cells (HLC) through the application of two distinct techniques: transfection agents and electroporation. The results were then compared with those of HLCs differentiated through the consumption of chemical compounds. Results Different time points (48 h, 72 h, and 96 h), unlike concentrations of mimic miRNAs (100 pM, and 200 pM), and dissimilar combinations of mimic-miRNAs (4-mimic and 7-mimic miRNAs) were selected to assess the stage of differentiated cells through electroporation and lipofection methods. For chemical differentiation, a two-step chemical hepatic differentiation protocol was used (for 21 days). The expression level of eleven key genes that were selected to estimate the stage of produced HLCs by each method were tested at different time points, concentrations and combination of mimic-miRNA. Results demonstrated that the 7-miR-mimics/72 h culture method by electroporation, then the 7-miR-mimics/72 h culture method by lipofection, and finally the chemical differentiation (72 h culture) showed the best result for differentiation. Furthermore, the period in which HLCs are maintained under culture conditions is important, as prolonged culture (more than 72 h) leads to cell loss. Conclusion In conclusion, the results demonstrated that the 7-miR cocktail delivered by electroporation after 72 h effectively promoted the acquisition of hepatocyte-like characteristics which was evidenced by a significant decrease in the Oct4 stemness factor and an increase in the expression of ALB, TAT, AAT, CYP, G6P and HNF4A.

BackgroundMale infertility is a multifaceted issue that has gained scientific interest due to its increasing rate. Studies have demonstrated that oxidative stress is involved in male infertility development. Furthermore, metabolic disorders, including obesity, diabetes, hypo- and hyperthyroidism, are risk factors for male infertility, and oxidative stress is believed to contribute to this association. Melatonin, functioning as an oxidative scavenger, may represent a promising therapeutic approach for the prevention and treatment of metabolic disorder-associated male infertility.Material and methodsWe systematically searched three online databases (PubMed, Scopus, and Web of Science) for studies that evaluated the effects of melatonin therapy on metabolic disorders-induce infertility in male rodents. The favorable outcomes were histopathological parameters of testicular tissue, reproductive hormones, and markers of oxidative stress. Then, meta-analyses were done for each outcome. The results are reported as standardized mean difference (Cohen’s d) and 95% confidence interval.Results24 studies with 31 outcomes were included. Rats and mice were the subjects. Studies have employed obesity, diabetes, hypothyroidism, hyperthyroidism, hyperlipidemia, and food deprivation as metabolic disorders. To induce these disorders, a high-fat diet, high‐fructose diet, leptin, streptozotocin, alloxan, carbimazole, and levothyroxine were used. The outcomes included histopathologic characteristics (abnormal sperm morphology, apoptotic cells, apoptotic index, Johnsen’s testicular biopsy score, seminiferous epithelial height, tubular basement membrane thickness, tubular diameter, sperm count, and motility), weight-related measurements (absolute epididymis, testis, and body weight, body weight gain, epididymal adipose tissue weight, and relative testis to body weight), hormonal characteristics (androgen receptor expression, serum FSH, LH, and testosterone level), markers of oxidative stress (tissue and serum GPx and MDA activity, tissue CAT, GSH, and SOD activity), and exploratory outcomes (serum HDL, LDL, total cholesterol, triglyceride, and blood glucose level). The overall pooled effect sizes were statistically significant for all histopathological characteristics and some markers of oxidative stress.ConclusionsMelatonin can reduce damage to male rodents’ gonadal tissue and improve sperm count, motility, and morphology in metabolic diseases. Future clinical studies and randomized controlled trials are needed to evaluate the safety and effectiveness of melatonin for male infertility in patients with metabolic diseases.

Extracellular vesicles include exosomes, microvesicles, and apoptotic bodies. Their cargos contain a diverse variety of lipids, proteins, and nucleic acids that are involved in both normal physiology and pathology of the ocular system. Thus, studying extracellular vesicles may lead to a more comprehensive understanding of the pathogenesis, diagnosis, and even potential treatments for various diseases. The roles of extracellular vesicles in inflammatory eye disorders have been widely investigated in recent years. The term “inflammatory eye diseases” refers to a variety of eye conditions such as inflammation-related diseases, degenerative conditions with remarkable inflammatory components, neuropathy, and tumors. This study presents an overview of extracellular vesicles’ and exosomes’ pathogenic, diagnostic, and therapeutic values in inflammatory eye diseases, as well as existing and potential challenges.

Extracellular Vesicles (EVs) are a collection of vesicles released from cells that play an important role in intercellular communication. Microbial infections are known as one of the major problems in the medical field. Considering the increasing resistance of strains to routine drug treatments, the need for new therapies seems to be more than ever. Recent studies have shown that the EVs released from immune cells during microbial infections had anti-microbial effects or were able to induce neighbouring cells to display anti-microbial effects. This mini-review aimed to explore the latest studies on immune cell-derived EVs in viral, bacterial, fungal, and parasitic infections. Review of the literature demonstrated that specific cargos in EVs were involved in the fight against pathogenic infections. Additionally, the transport of appropriate bioactive molecules including miRNAs, mRNAs, and proteins via EVs could mediate the anti-microbial process. Thus, it could be a proof-of-principle that therapeutic approaches based on EVs derived from immune cells could offer a promising path forward, which is still in early stages and needs further assessments.

Occurrence of a malignant sebaceous tumor in the setting of ovarian mature cystic teratoma is exceptionally rare in gynecological pathology; to date, 11 cases have been documented in the literature. Here, we present the case of a 71 year-old lady with an aggressive stage III ovarian sebaceous carcinoma arising in a long standing mature teratoma which harbors aberrant p53 expression and discuss its clinicopathological findings with a review of literature. Additionally, we commented on possible prognostic significance of aberrant p53 expression in this rare entity.

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.

Exosomes, as the smallest extracellular vesicles that carry a cargo of nucleic acids, lipids, and proteins and mediate intercellular communication, have attracted much attention in diagnosis and treatment in the field of medicine. The contents of exosomes vary depending on the cell type and physiological conditions. Among exosomes derived from several cell types, stem cell-derived exosomes (stem cell-Exo) are increasingly being explored due to their immunomodulatory properties, regenerative capacity, anti-inflammatory and anti-microbial functions. Administration of stem cell-Exo, as a cell-free therapy for various diseases, has gained great promise. Indeed, the advantages of exosomes secreted from stem cells outweigh those of their parent cells owing to their small size, high stability, less immunogenicity, no risk of tumorigenesis, and easier condition for storage. Recently, the use of stem cell-Exo has been proposed in the field of microbial diseases. Pathogens including bacteria, viruses, fungi, and parasites can cause various diseases in humans with acute and chronic complications, sometimes resulting in mortality. On the other hand, treatments based on antibiotics and other chemical compounds have many side effects and the strains become resistant to drugs in some cases. Hence, this review aimed to highlight the effect of stem cell-derived extracellular vesicles including stem cell-Exo on microbial diseases. Although most published studies are preclinical, the avenue of clinical application of stem cell-Exo is under way to reach clinical applications. The challenges ahead of this cell-free treatment that might be applied as a therapeutic alternative to stem cells for translation from bench to bed were emphasized, as well.

Objective(s): Liver transplantation is the most important therapy for end-stage liver disease and ischemia reperfusion (I/R) injury is indeed a risk factor for hepatic failure after grafting. The role of miRNAs in I/R is not completely understood. The aim of this study was to investigate the potential protective role of the mesenchymal stem cells (MSCs) and ischemic preconditioning on miR-370 expression and tissue injury in hepatic I/R injury. Materials and Methods: In this study, 24 BALB/c mice were divided into 4 groups, including sham, I/R, I/R mouse that received MSCs (I/R+MSC) and ischemia preconditioning (IPC) The expression levels of hepatic miR-370, Bcl2 and BAX in male BALB/c mice in different groups including hepatic I/R, hepatic I/R received MSCs, and hepatic I/R with IPC were assessed by quantitative real-time PCR. The effect of miR-370 on hepatic I/R was investigated by serum liver enzyme analysis and histological examination. Results: The expression of miR-370 was significantly up-regulated in the mice subjected to hepatic I/R injury as compared with the sham operated mice. Injection of MSCs led to the down-regulation of the serum liver enzymes, expression of miR-370 and BAX, up-regulation of Bcl2 as well as the improvement of hepatic histological damage. IPC led to similar results, but the difference was not significant. Conclusion: Our data suggest that miR-370 affected the Blc2/BAX pathway in hepatic I/R injury, and down- regulation of miR-370 by BM-MSCs efficiently attenuated the liver damage.

This report presents incidental finding of early colorectal cancer in an adult patient with gunshot injury. The patient was a 41 y/o man, transferred to our center due to gunshot wound to his abdomen and back. A well differentiated adenocarcinoma, stage I, was incidentally identified during pathologic examination on his segmental proctectomy specimen. This singular case highlights the necessity of caring for all removed tissues, indicating how important they are for both clinicians and pathologists.

Bilateral ovarian dermoid tumor with invasion to surrounding organ is a rare entity. We report the case of a 63-year-old woman with prolonged dysuria and hematuria who had bilateral ovarian dermoid cysts with urinary bladder involvement.

Background: Proliferation markers, especially Ki67, are increasingly important in diagnosis and prognosis. The best method for calculating Ki67 is still the subject of debate. Materials and Methods: We evaluated an image analysis tool for quantitative interpretation of Ki67 in neuroendocrine tumors and compared it to manual counts. We expanded a primary digital pathology platform to include the Leica Biosystems image analysis nuclear algorithm. Slides were digitized using a Leica Aperio AT2 Scanner and accessed through the Cerner CoPath LIS interfaced with Aperio eSlideManager through Aperio ImageScope. Selected regions of interest (ROIs) were manually defined and annotated to include tumor cells only; they were then analyzed with the algorithm and by four pathologists counting on printed images. After validation, the algorithm was used to examine the impact of the size and number of areas selected as ROIs. Results: The algorithm provided reproducible results that were obtained within seconds, compared to up to 55 min of manual counting that varied between users. Benefits of image analysis identified by users included accuracy, time savings, and ease of viewing. Access to the algorithm allowed rapid comparisons of Ki67 counts in ROIs that varied in numbers of cells and selection of fields, the outputs demonstrated that the results vary around defined cutoffs that provide tumor grade depending on the number of cells and ROIs counted. Conclusions: Digital image analysis provides accurate and reproducible quantitative data faster than manual counts. However, access to this tool allows multiple analyses of a single sample to use variable numbers of cells and selection of variable ROIs that can alter the result in clinically significant ways. This study highlights the potential risk of hard cutoffs of continuous variables and indicates that standardization of number of cells and number of regions selected for analysis should be incorporated into guidelines for Ki67 calculations.

Mesoblastic nephroma is a rare entity in adulthood. We report a case of mesoblastic nephroma in a 35-year-old woman who presented with left flank pain. Computed tomography images favored a soft tissue mass in the upper pole of the left kidney. The lesion was excised and sent for pathological analysis. Pathological and immunohisto-chemical studies favored a diagnosis of mesoblastic nephroma.

The development of malignancies after solid organ transplants is a well-known complication. Cancer is associated with significant consequences for the organ transplant patient. It is expected that cancer will surpass cardiovascular complications as the leading cause of death in transplant patients within the next few years. We report on a 36-year-old male patient who developed mixed germ-cell testicular tumor seven years after liver transplantation for alcoholic cirrhosis. He was treated with orchiectomy, retroperitoneal lymph node dissection and post-operative chemotherapy.

This is a rare case of metastatic follicular carcinoma of thyroid in a patient with no history of thyroid problem. A frontal bone mass was examined microscopically and showed the pattern of metastatic follicular carcinoma. Thyroid ultrasonography then revealed a nodule in left lobe. Total thyroidectomy was done for the patient and microscopic examination confirmed the diagnosis.

Papillary serous cystadenocarcinoma of the ovary is a common tumor but occurrence of ovarian type papillary serous cystadenocarcinoma in the testis is very rare. Herein we report such a case in a 49-year-old man presenting with testicular swelling. In this tumor, mesothelioma of tunica vaginalis should be excluded by immunohistochemistry. The best treatment is radial orchiectomy and it is very resistant to chemoradiation. Our case was well after orchiectomy and now after a year he is doing well and completely symptom free.

Introduction Extramedullary hematopoiesis (EMH) commonly occurs in the spleen, liver and lymph nodes. Rare cases of EMH in the adrenal gland have been reported. Case Presentation We report the case of a 33-year-old man from the South of Iran suffering from major β-thalassemia, who underwent open left adrenalectomy and the histopathology revealed EMH. Conclusions In patients in which a history of hematologic disorders exists, careful imaging and hormonal assay should be done to certify a diagnosis of EMH. However, the surgical management becomes inevitable in certain cases.