Therapeutic role of extracellular vesicles derived from stem cells in cutaneous wound models: A systematic review.

A growing body of evidence has shown that extracellular vesicles can be efficient as experimental therapeutics in pre-clinical models of skin wounds, but there is a significant unmet need to translate this to clinical utilization. The objectives of the current systematic review were to identify the strength of the therapeutic effects of EVs derived from stem cells in cutaneous wounds and to assess which EV-mediated mechanisms could be involved in the therapeutic response. PubMed, ISI Web of Science, and Scopus databases were systematically searched. We retrieved English-language articles published through June 2020. In vivo studies which applied stem cell-derived EVs were included for further analysis. The Risk of bias was assessed by the SYRCLE tool. We identified thirty-nine pre-clinical studies that evaluated the effects of EVs on the wound healing process. The included studies varied greatly in EVs isolation techniques, route of administration, EVs producing cells, and follow-up time. In vivo application revealed beneficial effects of EVs on accelerating wound closure and re-epithelialization in a dose-dependent manner. Elevated angiogenesis was reported in twelve eligible studies through multiple signaling pathways such as PI3K/Akt, MAPK/ERK, and JAK/STAT. The well-known signaling pathway to inhibit scar formation was TGF-ß2/SMAD2. However, all included studies were not blinded enough which may have introduced bias. Therefore, the transition of EV's efficacy into the clinics is deeply rooted in the following important factors: 1) pre-clinical studies with a lower risk of bias and longer follow-up time, and 2) consistent, reproducible, and feasible manufacturing of EVs production in a large-scale commercial program.

Evaluation of salivary acetylcholinesterase and pseudocholinesterase in patients with Alzheimer's disease: A case-control study.

AIM: The aim of this study was to evaluate acetylcholinesterase (AChE) and pseudocholinesterase (PChE) in whole saliva in patients with Alzheimer's disease (AD) and in healthy subjects. Saliva has a high potential for keeping track of general health and diseases. AD is a type of dementia with reduction in brain cholinergic markers that causes memory, thinking, and behavior problems. Up to 90% decrease in AChE activity has been observed in AD. METHODS AND RESULTS: Thirty healthy subjects and 30 patients with AD participated in this study. Saliva samples were collected from 8 to 10 am. AChE and PChE of saliva were assessed by the Ellman method. Statistical comparison was performed using SPSS 16 for t-test. The activity of AChE and PChE significantly increased in the group with AD compared to the healthy subjects. Sex had no effect on the activities of these enzymes. No correlation existed between the duration of illness and enzymatic activity. The enzyme levels reduced with age. CONCLUSION: AChE and PChE levels were increased in saliva samples of patients with AD. Therefore, saliva has the potential for being used for the purpose of biomarker evaluation to replace cerebrospinal fluid in patients with AD.

Effect of Antioxidants on Testicular iNOS and eNOS after High-Fat Diet in Rat.

BACKGROUND AND OBJECTIVE: Spermatogenesis is a process by which germ cells produce spermatozoa and can be disturbed at every level. Nitric Oxide Synthases (NOS), implicate in interactions with Oxidative Stress (OS) which is one of the main factors in the etiology of male infertility. The High Fat Diet (HFD) is a major factor of obesity which in turn is important for enhancing OS. Antioxidants and garlic could attenuate or reverse effects of HFD. The aim of the study was to investigate the effects of dietary antioxidants and garlic on testicular inducible NOS (iNOS) and endothelial NOS (eNOS) in Wistar albino rats fed on HFD. MATERIALS AND METHODS: Groups (each n = 8) were: SD (100% access to standard diet), F-HFD, (100% access to HFD) and R-HFD (70% access to HFD), F-HFD +antioxidants, F-HFD+garlic and R-HFD+antioxidants. The HFD consisted of a 60% fatty diet in 3 forms: Without antioxidants, with antioxidants and with garlic. The testicular iNOS and eNOS were studied by immunohistochemical (IHC) method. Also used ANOVA, repeated measures ANOVA, t-tests and Tukey's test (where necessary) to analyze the data (p<0.05). RESULTS: The iNOS increased in the F-HFD and R-HFD+antioxidants groups. The eNOS increased in R-HFD,F-HFD and F-HFD+garlic groups. The H-E evaluation in R-HFD group showed a decrease in spermatogenesis score count and seminiferous tubules diameters (µm) in comparison with the SD and F-HFD groups. R-HFD+antioxidants group had lower score than F-HFD+antioxidants and F-HFD+garlic groups. CONCLUSION: Restricted fat diet consumption causes increase in weight and impairs spermatogenesis. Results of this study reveal that adding the antioxidants can't improve histological changes of testis. The iNOS expression in seminiferous tubules in restricted fat diet along with antioxidants, suggest a potential role of iNOS in spermatogenesis and male infertility.

Evaluation of Honey as a Topical Therapy for Intraoral Wound Healing in Rats.

OBJECTIVE: Honey is one of the oldest known medicines. Its medical and therapeutic importance has been recently rediscovered. Honey is an effective treatment for infected wounds and ulcers. The aim of this study was to determine the effect of honey as a topical therapy for intraoral wound healing in rats. MATERIALS AND METHODS: Thirty-two male rats were divided into experimental and control groups (consisting of 16 rats, 4 animals in each group). A 2-mm mucosal defect was made to the depth of the periosteum using punch biopsy. Honey was applied to the wound every day, and the ulcer size was measured daily. On days 2, 4, 6, and 8, four rats were euthanized from each group (experimental and control groups), and tissues were histopathologically evaluated. Healing processes were studied as follows: the size of ulcer, inflammatory response, reepithelialization, and granulation tissue formation. RESULTS: The mean rank of wound size was significantly reduced in the honey group (2.50), as compared to the control group (6.50). Reepithelialization and granulation tissue formation mean rank were significantly higher in the honey group (6.50) than in the control group (2.50). Inflammation mean rank was statistically lower in the honey group (2.63) compared with the control group (6.38). CONCLUSION: Honey was shown to have a beneficial effect on the healing of oral ulcers in rats in this model. Further research may shed light on the effects of honey on different types of ulcers in humans.

Dimethyloxalylglycine may be enhance the capacity of neural-like cells in treatment of Alzheimer disease.

Although using differentiated stem cells is the best proposed option for the treatment of Alzheimer disease (AD), an efficient differentiation and cell therapy require enhanced cell survival and homing and decreased apoptosis. It seems that hypoxia preconditioning via Dimethyloxalylglycine (DMOG) may increase the capacity of MSC to induce neural like stem cells (NSCs). Furthermore, it can likely improve the viability of NSCs when transplanted into the brain of AD rats.

Effect of a high fat diet on ovary morphology, in vitro development, in vitro fertilisation rate and oocyte quality in mice.

INTRODUCTION: The aim of this study was to determine the effect of a high-fat diet (HFD) on oocyte maturation and quality in a mouse model. METHODS: Female BALB/c mice were allocated to one of the following groups: (a) control group (n = 40), which received a controlled diet; or (b) HFD group (n = 40), which received an HFD for 12 weeks. Sections of the ovary were examined histologically. The number of follicles and corpora lutea were counted. In vitro maturation and in vitro fertilisation (IVF) were assessed in germinal vesicle (GV) and metaphase II (MII) oocytes, respectively. The expression of bone morphogenetic protein 15 (BMP15) and leptin receptor genes in GV and MII oocytes was evaluated using reverse transcription real-time polymerase chain reactions. RESULTS: In the HFD group, there was a decreased number of primordial and Graafian follicles, as well as corpora lutea (p < 0.05). The rate of oocyte development to the MII stage was also reduced (p < 0.001). Cumulus expansion was observed more frequently in the control group than the HFD group (p < 0.05). The IVF rate in the HFD group was lower than that in the control group (p < 0.05). In the HFD group, BMP15 and leptin receptor genes were upregulated in the GV stage (p > 0.05) and MII stage (p < 0.05), compared to the control group. CONCLUSION: An HFD reduces folliculogenesis in the primordial and Graafian stages, in vitro maturation and in vitro fertilisation rates, as well as oocyte quality in mice.

Protective Effects of Antioxidants on Sperm Parameters and Seminiferous Tubules Epithelium in High Fat-fed Rats.

BACKGROUND: Prescription of antioxidants might increase the quality of sperm parameters and improve the rate of pregnancy in obese people who suffer from infertility. Therefore, the present study investigated protective effects of vitamin A, E and astaxanthin on sperm parameters and seminiferous tubules epithelium in high-fat diet model. METHODS: Thirty-six numbers of 3 months old albino Wistar rats were divided to control, high-fat diet and high-fat diet with antioxidants groups. After 12 weeks, levels of LDL-C and HDL-C were detected in the groups. Sperm was obtained from the tail of epididymis and its parameters (count, vitality, motility and morphology) were analyzed. Testes were fixed in 10% formalin and after tissue processing, stained with Hematoxylin and Eosine (H&E) for histological evaluation. Data were analyzed by a one-way ANOVA and p < 0.05 was considered significant. RESULTS: Our results indicated that viability, motility and normal morphology of sperm in high-fat diet (HFD) decreased significantly compared to high-fat diet with antioxidant (HFD + A) and the control groups (p < 0.05). Also spermatogonium and the number of Sertoli cells increased significantly in HFD + A compared to the control (p < 0.05). CONCLUSION: As it is shown in our study, application of antioxidants decreased serum triglyceride, cholesterol and HDL-C/LDL-C in high-fat diet model and improved the semen parameters. Therefore, it is suggested that the low quality of sperm can be improved in obese men through antioxidant prescription. Finally, it seems that the antioxidants in obese patients with subfertility or infertility is a new and efficient strategy with few side effects.

Failure to thrive severity determination by new design curves in standard growth charts.

Failure to thrive (FTT) is a perplexing disorder commonly seen by primary care physicians. Identification of FTT and an assessment of severity of the undernutrition are important to identify children at risk, and to provide appropriate intervention for preventing malnutrition and developing sequela. One of different anthropometric methods for categorizing undernutrition in childhood is Waterlow and Gomez classifications. Unfortunately, these classifications are not an easy task for the practitioners due to its difficult calculations. In this paper, Waterlow and Gomez classifications have been shown on the Standard Growth Charts (WHO 2006). Using these curves, the practitioners can determine severity of FTT by plotting weight, height and age of the patients without any calculations.

Reversible inactivation and excitation of nucleus raphe magnus can modulate tail blood flow of male Wistar rats in response to hypothermia.

BACKGROUND: The nucleus raphe magnus (NRM) is involved in thermoregulatory processing. There is a correlation between changes in the firing rates of the cells in the NRM and the application of the peripheral thermal stimulus. INTRODUCTION: we examined the effect of reversible inactivation and excitation of NRM on mechanisms involved in tail blood flow (TBF) regulation in hypothermia. METHODS: Hypothermia was induced in Male Wistar rats and cannula was implanted above the NRM. To evaluate the effect of nucleus inactivation on TBF, the amount of TBF was measured by Laser Doppler in hypothermic rats, before and after lidocaine microinjection into NRM. TBF was also measured after glutamate microinjection to assess the effect of nucleus excitation in hypothermic rats. RESULTS: Results indicated that after dropping TBF by hypothermia, microinjection of lidocaine into NRM significantly decreased TBF from 54.43 +- 5.7 to 46.81 +- 3.4, whereas glutamate microinjection caused a significant increase from 44.194 +- 0.6 to 98 +- 10.0 CONCLUSION: These data suggest that NRM have thermoregulatory effect in response to hypothermia.