Probiotics ameliorate endocrine disorders via modulating inflammatory pathways: a systematic review.

Probiotics has offered a new prospect to treat and manage a variety of endocrine disorders such as obesity, diabetes, non- alcoholic fatty liver disease and metabolic syndrome. The precise mechanisms by which probiotics exert their beneficial effects on endocrine disorders and its associated problems are still indecisive. It seems that regulating the immune system and suppressing pro-inflammatory pathways like tumor necrosis factor-α and interleukin-6 or triggering anti-inflammatory pathways like interleukin-4 and 10 may be one of the potential mechanisms in the managing of endocrine disorders. In this systematic review, we hypothesized that various probiotic strains (Lactobacillus, Biofidiobacteria, Streptococcus, Entrococcus, Clostridium, and Bacillus) alone or in combination with each other could manage endocrine disorders via modulating inflammatory pathways such as suppressing pro-inflammatory cytokines (IL-6, IL-12, TNF-α, TNF-ß, NFκB, and MCP-1), stimulating anti-inflammatory cytokines (IL-4,IL-6, IL-22, IL-23, IL-33, and TGF-ß) and maintaining other factors like C-reactive protein, Toll like receptors, LPS, and NK cells. Data source this search was performed in PubMed and Scopus. Both human and animal studies were included. Among more than 15,000 papers, 25 studies were identified as eligible for more assessments. Quality assessment of the studies was cheeked by two researchers independently by title and abstract screening, then article which have inclusion criteria were included, and data retrieved from the included full text studies as the authors had originally reported. Results specified that Lactobacillus has been the most widely used probiotic as well as which one exhibiting the extend of the therapeutic effects on endocrine disorders, especially obesity by modulating immune responses. Also, most studies have revealed that probiotics through suppressing pro-inflammatory pathways specially via reducing levels TNF-α cytokine exhibited protective or beneficial effects on endocrine diseases particularly obesity as well as through decreasing level of IL-6 induced therapeutic effects in diabetes. This systematic review suggests that probiotics could ameliorate endocrine disorders via their immunomodulatory effects.

The Efficiency of Stem Cells (SCs) Differentiation into Functional Hepatocytes for Treating Liver Disorders: A Systematic Review.

Stem cells provided new opportunity to treat various diseases, including liver disorders. Stem cells are unspecialized cells, stimulating influential research interest be indebted to their multipotent self-renewal capacity and differentiation characteristics into several specialized cell types. Many factors contribute to their differentiation into different cell types such as insulin producing cells, osteoblast, and hepatocytes. Accordingly, wide range methods and materials have been used to transform stem cells into hepatocytes, but effectiveness of differentiation is different and depends on several factors such as cell-to-cell adhesion, cell-to-cell contact, and cell biological change. Search was done in PubMed, Scopus, and WOS to evaluate results of studies about stem cells differentiation for higher efficacy. Among more than 28000 papers, 51 studies were considered eligible for more evaluations. Results indicated that most studies were performed on mesenchymal stem cells compared with other types. Acute liver failure was the most investigated liver disorder, and tissue engineering was the most investigated differentiation methods. Also, functional parameters were the most evaluated parameters in assessing differentiation efficacy. We summarize recent advances in increasing efficiency of stem cells differentiation using varied materials, since promising results of this review, further studies are needed to assess efficiency and safety of these cells transplantation in some liver disease treatment.

Synchronized Laparoscopic Bilateral Adrenalectomy for Pheochromocytoma in Multiple Endocrine Neoplasia Syndrome: A Case Report.

Pheochromocytomas are tumors producing catecholamines that arise from chromaffin cells in the adrenal medulla. They are usually benign in multiple endocrine neoplasia type 2 (MEN2) syndrome, but they tend to present bilaterally in 50-80% of the patients. Few researchers have reported success with simultaneous laparoscopic bilateral adrenalectomy. Hence, we report a 48-year-old woman who presented with a panic attack, headache, and abdominal discomfort that had started 10 years ago. The computed tomography (CT) scan showed a large bilateral cystic lesion in both adrenal glands in favor of pheochromocytomas (30 × 22 mm and 18 × 15 mm on the right side and 40 × 33 mm and 35 × 28 mm on the left side). The patient underwent bilateral laparoscopic adrenalectomy without intraoperative or postoperative complications. The total blood loss was 50 cc, and the operative time was 4 h. The histopathology of the specimen revealed pheochromocytomas of adrenal masses. In conclusion, our case demonstrates that synchronized laparoscopic bilateral adrenalectomy can be a safe and feasible treatment option for pheochromocytomas in MEN2 patients.

Resection of Bilateral Symmetrical Multiple Level Cervical Ganglioneuroma in a 43-Year-Old Man, a Probable Case of Neurofibromatosis Type-1: Report of a Case and Review of Literature.

Ganglioneuroma is a benign tumor, originating from sympathetic nervous system. Intradural and dumbbell shape spinal ganglioneuroma has been reported in the literature. In this study, we intend to present our case, a 43-year-old man with multiple cutaneous dimples-probably a Neurofibromatosis type-1 (NF-1) case-and subacute myelopathy, who presented with bilateral symmetric dumbbell shape C2/C3 and C4/C5 intradural extramedullary tumors. After resection, the pathologic feature was revealed as ganglioneuroma. We also reviewed the literature for similar cases, which revealed our case to be the 9th bilateral and symmetrical spinal GN, all of which in cervical region; the 5th involving multiple level (the 3rd multiple bilateral symmetrical involvement), the 3rd extending intradurally, and the first case of involving all cervical nerve root ganglions in different sizes. Bilateral symmetrical spinal GNs have also appeared to have different body location, geographic, and gender distribution.

The cryoprotective effect of vitamins on human spermatozoa quality: a systematic review and meta-analysis.

The Cryopreservation of spermatozoa ensures preserving fertility potential after some medical treatments such as chemotherapy and radiotherapy in cancer patients. However, many spermatozoa encounter serious damages, and their motility and viability decrease considerably after thawing. The excessive production of reactive oxygen species is one of the major causes of these damages. The supplementation of cryopreservation media with vitamins, which are well-known antioxidants, can reduce cryopreservation-induced damages. In this systematic review, we aimed to evaluate the cryoprotective effect of various vitamins on the quality of cryopreserved-thawed human spermatozoa. Two researchers searched PubMed, ISI, and Scopus databases up to March 2020. All original articles using vitamins in human spermatozoa cryopreservation media were included. We used a standardized form to extract sample size and to determine sample quality, the type and dose of vitamins, and the cryopreservation methods and their effects. We performed a meta-analysis on studies with available data (Mean + SD in cryoprotectant and cryoprotectant + cryoprotectant groups). We also performed a test of between-study heterogeneity, subgroup analysis, and meta-regression. Out of 258 studies, 16 articles were included for the analysis. Our meta-analysis revealed that using vitamins in cryopreservation media could increase motility by 4.60% (95% CI 6.16, 3.05; P = 0.0001), viability by 5.71% (95% CI 9.71, 1.72; P = 0.0001), and DNA integrity by 10.20% (95% CI 12.98, 7.42; P = 0.0001) in cryopreserved-thawed spermatozoa. We found a significant correlation between using vitamins and improved spermatozoa quality; the sperm motility and viability were improved and DNA fragmentation was reduced after thawing by vitamins. However, we could not emphasize on any type or dose of vitamins but we conclude that the anti-oxidative function of vitamins is the main reason for these benefits.

Progesterone and anandamide diminish the inhibitory effect of zinc on mature human sperm.

Zinc ion (Zn2+) homeostasis is very important for sperm capacitation and hyperactivation. Zn2+ is a specific inhibitor of the voltage-dependent proton channel (Hv1). Intracellular alkalisation of human spermatozoa is mainly dependent on opening of Hv1. Anandamide may affect spermatozoa through activation of Hv1. An increase in intracellular pH and progesterone (P4) activate cation channels of spermatozoa (CatSper). This study was designed to elucidate the interaction between ZnCl2, P4 and anandamide on human sperm function and intracellular calcium concentrations ([Ca2+]i). Human normal semen samples (n = 30) were diluted (20 × 106 spermatozoa mL-1) and divided into control and ethanol (0.01%)-, anandamide (1 nM)-, ZnCl2 (1 mM)-, P4 (10µM)-, anandamide+ZnCl2- and P4+ZnCl2-treated groups. Sperm kinematics, viability, acrosome status and [Ca2+]i were assessed. The percentage of viable and motile spermatozoa and sperm velocity was reduced in the ZnCl2-treated groups. Anandamide and P4 attenuated the inhibitory effects of ZnCl2 on sperm kinematics. Loss of the acrosome membrane was observed in all experimental groups. P4 and anandamide are present naturally in secretions of the female reproductive tract and modulate the inhibitory effects of ZnCl2 on sperm kinematics. This attenuation is probably due to a change in [Ca2+]i and prevention of Hv1 inactivation by P4 and anandamide respectively.

Efficiency of Stem Cell (SC) Differentiation into Insulin-Producing Cells for Treating Diabetes: a Systematic Review.

Over the recent years, the use of stem cells has provided a new opportunity to treat various disorders including diabetes. Stem cells are unspecialized cells with a capacity for self-renewal and differentiation into more specialized cell types. Many factors contribute to the differentiation of SCs and thus play an important role in regulating the fate of stem cells. Accordingly, a wide range of protocols has been used to differentiate SCs to insulin-producing cells but the effectiveness of SC differentiation varies. The aim of this systematic review was to evaluate the results obtained from different studies on SC differentiation for higher efficacy to treat diabetes. This search was done in PubMed, Web of Science (WOS), and Scopus using keywords "insulin-producing cell (IPC)," "pancreatic B cell," "insulin-secreting cell," "stem cell," "progenitor cells," "mother cell," and "colony-forming unit." Among more than 3646 papers, 32 studies were considered eligible for more evaluations. The obtained results indicated that most of the studies were performed on the mesenchymal stem cells (MSCs) derived from different tissues as compared with other types of SCs. Different evaluations of in vitro studies as well as animal models supported their role in the recovery of diabetes. In the present review, we summarize and discuss recent advances in increasing the efficiency of SC differentiation using different materials, but despite the promising results of this systematic review, further studies are needed to assess the efficiency and safety of transplantation of these cells in diabetes recovery.

Calprotectin, an available prognostic biomarker in systemic sclerosis: a systematic review.

BACKGROUND: Finding easier and less invasive biologic biomarker in the clinical specimen of systemic sclerosis (SSc) patients can be effective in diagnosing and treating SSc-associated multisystem diseases. The complex of S100A8 and S100A9 (Calprotectin) is an easily available prognostic biomarker that secretes from immune cells and is necessary for initiating the immune response to noninfectious inflammation processes. The present study aims to evaluate the effectiveness of Calprotectin in specimen of SSc patients. We reviewed the evidence for Calprotectin in diagnostic and prognostic of SSc patients. METHODS: This systematic review was done to identify studies on "Calprotectin" within "SSc" patients. PubMed, Web of knowledge, and Scopus were searched for this purpose. A standardized form was used to extract diseases, sample size, biomarkers identified, source of biomarker, and its effects. RESULTS: Overall, the 16 articles selected show that the main sources of Calprotectin were plasma, bronchoalveolar lavage fluid, and especially stool. CONCLUSION: The best source of Calprotectin was fecal Calprotectin that could show the inflammation and small intestinal bacterial overgrowth (SIBO) on SSc patients. Also, the most arguable source is plasma because of its low sample size. Comparing the Calprotectin level in different rheumatic diseases showed the specificity of fecal Calprotectin for SSc disease. Nevertheless, it has to be noted that Calprotectin correlates with some other factors such as age, PIP drug, and nonsteroidal anti-inflammatory drugs.

NADPH oxidase 5 activation; a novel approach to human sperm cryoinjury.

Sperm cryopreservation leads to various structural and functional damages, some of which induce by oxidative stress. The reactive oxygen species (ROS) generates by mitochondria and membrane NADPH oxidases (NOXs). Among the NOXs, only NOX5 has been identified in the cell membrane of human sperm. This study was designed to clarify the possible role of NOX5 on sperm cryoinjury. Forty human semen samples were washed and randomly divided into fresh and cryopreserved groups. Each group was divided into 4 subgroups containing Ham's F10 (control), 0.1% DMSO (vehicle), 100 nM of PMA (phorbol 12-myristate 13-acetate) and 1 µM of DPI (diphenyleneiodonium), as NOX5 activator and inhibitor. The samples of cryopreserved groups were preserved in liquid nitrogen for 1 month. The sperm kinematics, membrane integrity, ROS production, apoptosis rate, mitochondrial membrane potential (MMP), intracellular ATP and calcium concentration [Ca2+]i were evaluated. The percent of sperm with intact membrane and motile sperm reduced significantly after thawing (p ≤ 0.01). The ROS production (p ≤ 0.01) and the apoptotic rate increased, MMP dissipated, and the percentage of live cells with high [Ca2+]i decreased significantly in the cryopreserved control group relative to the fresh control group. DPI, in contrast to PMA, improved sperm progressive motility (p ≤ 0.01), membrane integrity in fresh and cryopreserved groups and reduced the ROS amount in cryopreserved group (p ≤ 0.01). Apoptotic rate, [Ca2+]i, ATP, and MMP did not change with DPI and PMA in cryopreserved groups. We conclude that NOX5 activity in fresh sperm is low, and it increases during cryopreservation. NOX5 inhibition improves the cryopreserved sperm quality.

Oral warty dyskeratoma: An unusual presentation.

Warty dyskeratoma is an uncommon benign skin lesion, which is mostly limited to the head or neck and is rarely seen in other areas of the skin or mucous membranes. Although it is clinically similar to many skin lesions, its distinctive histopathologic features help distinguish it from other identical lesions. Herein, we report a case of warty dyskeratoma in a very unusual site (lateral border of the tongue) in a 56-year-old woman.

The Effects of EGTA on the Quality of Fresh and Cryopreserved-Thawed Human Spermatozoa.

BACKGROUND: Sperm cryopreservation-thawing process has damaging effects on the structure and function of sperm, namely cryoinjury. Calcium overload has been reported as a postulated mechanism for sperm damage during the first steps after thawing. This study was designed to assess the intracellular calcium (Ca2+ i) after cryopreservation and to clarify the role of a calcium chelator ethylene glycol-bis (2-aminoethyl ether)-N, N, N', N'-tetraacetic acid (EGTA) on human sperm quality. METHODS: Forty semen samples were obtained from fertile men (March 2017 to 2018). The samples were randomly divided into fresh (F) and cryopreserved-thawed (CT) groups. The F and CT samples were divided into control and 1 mM EGTA-treated groups. Sperm kinematics and membrane integrity were assessed. The reactive oxygen species (ROS) and adenosine triphosphate (ATP) were measured by luminescent methods. Ca2+ i, apoptotic rate, and mitochondrial membrane potential (MMP) were evaluated using flow cytometric methods. Data were compared using SPSS software, version 16.0 by ANOVA and Kruskal-Wallis test. P<0.05 was considered as significant. RESULTS: Cryopreservation decreased sperm motility, viability, membrane integrity, Ca2+ i, MMP, and induced cell apoptosis and ROS production. EGTA could not protect the cryopreserved sperm from cryoinjury. It was found to have destructive effects on fresh sperm motility and viability (P=0.009) relative to cryopreserved sperm. ATP was reduced (P=0.02) and ROS production (P=0.0001) was increased in the EGTA-treated F and CT sperms. CONCLUSION: Despite Ca2+ i reduction by EGTA, it had no protective effects on fresh or cryopreserved sperm. We concluded that sperm cryoinjury was not dependent on calcium overload, and it was suggested that cryoinjury was mainly related to cell membranes damage.

Comparing Human Sperm Quality Preserved at Two Different Temperatures; Effect of Trolox, Coenzyme Q10 and Extracellular Adenosine Triphosphate.

Cooling method was proposed to maintain the sperm quality for several days. Nevertheless, during this procedure, sperm is encountered to "cold shock", and its quality decreases time-dependently. This study was designed to improve the in vitro sperm preservation methods. Thirty normal semen samples were examined in Shiraz, Iran, 2017. Fifteen samples were incubated at 22-27 °C and 15 samples were cooled moderately to 4 °C. Each sample was divided into five subgroups; control, solvent, 200 µM Trolox, 40 µM Coenzyme Q10, and 10 mM ATP. ATP was added only 15 minutes before the analysis. Assessments of motility parameters and sperm viability were done every 24 hours. Statistical analysis was performed using SPSS 16 software. The differences between two main groups and subgroups were compared by t test and one-way ANOVA, respectively. The effect of time was analyzed by repeated measurement test. Sperm motility and viability were the same in both groups until 24 hours, except the straight line velocity was greater in the cold group. Even after 48 hours, progressive motility and sperm velocity, but not viability, were still the same. The greatest reduction in progressive motility occurred on the second day; and after 72 hours, sperm quality was better preserved in 22-27 °C. Treatment with Trolox, coenzyme-Q10, and extracellular ATP did not have effect on sperm quality. Cold temperature is recommended for in-vitro sperm preservation up to 24 hours, and 22-27 °C is preferred for longer time storage. The sperm does not need antioxidant therapy for quality maintenance, but the extender media must be supplied with nutrients and antibiotics.

Satureja khuzestanica prevents the development of morphine analgesic tolerance through suppression of spinal glial cell activation in rats.

Glial cell activation and oxidative stress are important factors in the induction of opioid side effects such as tolerance and dependence. It has been demonstrated that Satureja khuzistanica extract (SKE) has antioxidative, antinociceptive and anti-inflammatory properties; however, its influences on opioid analgesic tolerance have not yet been clarified. Adult male Wistar rats were rendered analgesic-tolerant by injection of 10 mg/kg morphine twice daily for 8 days. To determine the effect of SKE on the development of morphine tolerance, different doses of SKE (25, 50 and 100 mg/kg i.p.) were injected simultaneously with morphine. The tail-flick test was used to assess the nociceptive threshold. The lumbar spinal cord was assayed to determine glial fibrillary acidic protein (GFAP) and tumor necrosis factor alpha (TNFα) levels by the Western blotting method. Our results showed that chronic morphine produced tolerance to the antinociceptive effect of morphine. However, SKE could prevent, in a dose-dependent manner, morphine tolerance development. In tolerant animals, a significant increase in GFAP and TNFα levels was observed in the lumbar spinal cord, and was reversed to control levels by 100 mg/kg SKE. Our data revealed that Satureja khuzistanica had beneficial effects in preventing opioid tolerance and the underlying mechanisms of those effects may be due, at least in part, to reduce spinal glial cell activation.

Evaluation of two commonly used temporary skin dressings for the treatment of acute partial-thickness wounds in rats.

OBJECTIVES: There is a broad range of expensive temporary wound dressings that promise better results in wound management. The aim of this study was to compare two commonly used temporary dressings for the treatment of partial-thickness wounds in a rat model. METHODS: Forty-two partial thickness wounds were created on the back of Lewis rats and treated with the dressings; control wounds remained without treatment. Wound size was determined daily by measuring the scabbed area. Three months after the wounds were created, skin elasticity was measured and a histologic evaluation was performed. RESULTS: Wound appearance in the animals in the treated groups did not differ significantly. Wound closure was slower in the control group than in the dressing groups. There was no histologic evidence of inflammation and no suggestion of epidermal changes in any group. CONCLUSION: Using both skin dressings, we observed satisfying results without any significant differences. Because of rising health care expenses, cost should play an essential role in the clinical application of these dressings.

Serum adenosine deaminase in patients with rheumatoid arthritis treated with methotrexate.

OBJECTIVE: Recently, adenosine deaminase (ADA) is introduced as helpful marker in diagnosis, prognosis, and monitoring of treatment in rheumatoid arthritis (RA). The aim of this study was to determine the efficacy of the serum ADA in diagnosis, prognosis, and monitoring of treatment with methotrexate (MTX) in RA. METHODS: This was a self-controlled clinical trial conducted in university hospitals of Isfahan, Iran. The serum level of ADA, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were measured for 70 patients with active RA (Disease Activity Score-28 [DAS28] > 3/2). After three months of MTX treatment and disease remission (DAS28 < 2.6) these markers were measured again. ANCOVA multiregression and paired t-test were used to compare and evaluate the mean level and correlation of ADA, ESR, IgM-RF, and DAS before and after RA remission. FINDINGS: The mean value for ADA activity was significantly higher than the normal one compared with other studies. Significant decreases were seen in values of ADA, ESR, RF, visual analogue scale (VAS), and DAS after remission. Also, the correlation coefficient between the values of ADA with ESR and DAS were statistically significant in baseline. Moreover, the statistically significant correlation between ADA and ESR, VAS, and DAS were seen after remission. No correlation was found in the case of the dosage of MTX with the value of ADA. CONCLUSION: It was concluded that ADA may be considered useful as a marker in diagnosis, prognosis, and monitoring of treatment with Methotrexate in RA.

Serum iron, zinc, and copper concentration in premature graying of hair.

Premature graying of hair with unclear etiology, which is known as premature canities, is a common cause of referrals to the dermatologists. We assessed the relationship between serum iron, copper, and zinc concentrations with premature canities. This study was conducted on patients under 20 years old suffering from premature canities, having a minimum of ten gray hair fibers, and referring to university hospitals of Isfahan (Iran). The results were compared with age-sex-matched controls. Demographic data and disease characteristics were recorded for two groups. We studied serum iron, copper, and zinc concentrations of 66 patients and 66 controls using atomic absorption and Ferrozine methods. The mean age of studied cases was 17.8 ± 2.0 years, and the mean age of the onset of canities was 15.5 ± 3.2 years with no significant difference between males and females (P > 0.05). Serum copper concentration was significantly lower in patients compared with controls (90.7 ± 37.4 vs. 105.3 ± 50.2 µg/dL, P = 0.048), but serum iron concentration was significantly lower in controls compared to patients (88.8 ± 39.5 vs. 108.3 ± 48.4 µg/dL, P = 0.008). Also, there was no significant difference between patients and controls in serum zinc concentration (114.8 ± 67.8 vs. 108.2 ± 49.9 µg/dL, P = 0.285). According to these results, among copper, zinc, and iron, a low serum copper concentration may play a role in premature graying of hairs in our society. Further studies are needed to find the underlying mechanism of this relationship.