Comparison of the efficacy of human umbilical cord mesenchymal stem cells conditioned medium and platelet-rich plasma on the hippocampus of STZ-induced rat model of Alzheimer's disease: A behavioral and stereological study.

Introduction: Alzheimer's disease (AD) is accompanied by progressive cognitive disorders and memory loss. This study aims to determine the combined effects of conditioned medium of human umbilical cord mesenchymal stem cells (CM) and platelet-rich plasma (PRP) on AD model rats. Methods: Forty-eight male Sprague Dawley rats were classified into 6 groups: Control, Sham, AD, and three treatment groups. AD was induced by streptozotocin(STZ; 3 mg/kg, intracerebroventricular (ICV)) and the treatment groups received injections of CM [(200 µl, intraperitoneally (i.p.), and/or PRP (100 µl, intravenously(i.v)] for 8 days. Behavioral tests (Morris water maze and novel objective recognition) were used to assess learning ability and memory. At the end of the behavioral tests, the rats were sacrificed and their brain was entirely removed, sectioned, and stained with cresyl violet. The hippocampus volume and number of neurons were evaluated by stereological techniques. Results: In the AD group, the discrimination ratio, time spent in the target zone, volume of Cornu Ammonis1 (CA1) and Dentate Gyrus (DG), and the number of pyramidal and granular cells decreased significantly compared to the Sham group. The mentioned parameters increased in the CM and CM+PRP groups compared to the AD group (p < 0.01). PRP did not have any noticeable effect on the examined parameters. Conclusions: CM may be beneficial in the treatment of AD as it led to better improvement in STZ-induced learning and memory impairments as well as the structure of the hippocampus.

The improving effects of the amnion and chorion membranes on tissue regeneration in periodontal disorders: A systematic review.

Background, recently, amnion-chorion membranes (ACMs), has provided new strategy to induce tissue regeneration in periodontal disorders. These biomaterials are rich sources of various biomarkers such as growth factors, proteins, and stem cells (SCs) which can accelerate regeneration. Numerous studies have been investigated beneficial effects of these materials on periodontal disorders9 tissue regeneration. Objective, the aim of this review was to evaluate therapeutic efficacy of these biomaterials, (combination of different effective biomarkers and SCs), more cost-effectiveness and with lower immune adverse effects on tissue regenerating in periodontal diseases. Methods, inclusion criterion was the English language and full text publications. Reviews, or strategies other than ACMs application for periodontal disorders treatment, and mechanism other than tissue regeneration were excluded. Data source, this search was done in PubMed, web of science (WOS) and Scopus using keywords. The search were repeated in May 2023 to identify any report that emerged during the time to develop the manuscript. After assessing bias, total of 151 articles were initially identified. After deleting duplication (30) using hand- screening, 121 papers met all inclusion criteria and were selected. Moreover, 31 papers were reviewed and excluded. Among remained articles (90), 57 articles excluded due to unrelated, 33 articles were assessed for the efficacy of ACMs on treating periodontal disorders. The most of studies used this material in the coronally flap technique. Miller recession defects was the most investigated periodontal disorder and clinical parameters were the most evaluated parameters in assessing the efficacy of ACMs. Discussion, different findings might be explained by different study designs, application techniques, or periodontal disorders in these studies. In the present review, we summarize the impacts of ACMs on tissues regeneration in treating periodontal disorders, but despite the promising and ameliorating results of this review, further studies are needed to assess these beneficial effects tissue to clarify the their helpfulness in clinical management of periodontal disorders. This review did not receive any funding.

Evaluation of the osteoconductive properties of scaffold containing platete-enriched-fibrin (PRF) with three calcium phosphate (TCP) in the alveolar socket repair after tooth extraction: An animal study.

Bone regeneration can be accomplished through osteogenesis, osteoinduction, and osteoconduction mechanisms. This study aimed to investigate the properties of the PRF scaffold with tricalcium phosphate nanoparticles in socket preservation in an animal model. Fabrication of PRF performed. In this experimental study, 18 rats were divided into three negative control, PRF, and PRF/TCP groups. The mechanical and chemical tests including swelling rate, degradation time, and MTT tests were applied to the scaffolds. In each animal, the first maxillary right molar was extracted, and extraction sites of test groups were filled with a resorbable biocompatible biomaterial in situ hardening bone substitute. After 2 and 4 weeks all animals were sacrificed and examined histopathologically and with qRT-PCR. Histological results showed TCP in combination with PRF accelerates bone regeneration with the highest amount of lamellar bone and collagen formation compared to the control and PRF alone. Mechanical and chemical tests on the scaffolds showed the addition of TCP to the PRF scaffold decreases the swelling rate and increases the degradation time. qRT-PCR showed expression of osteogenic genes increased significantly (p < 0.05) in PRF/TCP and PRF, respectively. In conclusion, the gelatin hydrogel containing PRF/TCP scaffold led to more bone formation after tooth extraction. Therefore, the injectable PRF\TCP hydrogel is a promising candidate for bone repair and regeneration.

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.

New concepts in regulation and function of the FGF23.

In comparison to the regulation of calcium homeostasis, which has been widely studied over the last several decades, phosphate homeostasis is little understood. The parathyroid hormone (PTH)/vitamin D axis has traditionally been used as a conceptual framework for understanding mineral metabolism. Recently, the fundamental regulator of phosphate homeostasis, fibroblast growth factor 23 (FGF23), which is produced by osteocytes and is involved in the hormonal bone-parathyroid-kidney axis, has attracted more attention. The secretion of FGF23 is controlled by diet, serum phosphate levels, PTH, and 1,25(OH)2 vitamin D. FGF-23, the FGF receptors and the obligate co-receptor α-Klotho work in concert to affect FGF-23 actions on targeted organs. Despite all efforts to investigate pleotropic effects of FGF23 in various endocrine organs, many aspects of the regulation and functions of FGF23 and the exact crosstalk among FGF23, serum phosphate, calcium, PTH, and vitamin D in the regulation of mineral homeostasis remain unclear; much efforts need to be established before it can be moved toward therapeutic applications. In this regard, we provide a brief overview of the novel findings in the regulation and function of FGF23 and refer to related questions and hypotheses not answered yet, which can be a window for future projects. We also focus on the current knowledge about the role of FGF23 obtained from our researches in recent years.

Primary hepatocyte urea assessment in the sodium-alginate patterned hydrogel by electrochemical procedure containing umbilical cord conditioned media.

Limitations in liver transplantation and advances in cell therapy methods motivated us to study primary hepatocytes. The main challenge in using primary hepatocytes for liver regeneration is that they lose their functionalities. We aimed to develop a controlled-shape hydrogel and apply the conditioned-media of mesenchymal stromal cells (CM-MSCs) to improve in vitro hepatocyte functions. In this experimental study, following rat hepatocyte isolation by collagenase perfusion and collection of human umbilical cord CM-MSCs, a simple and precise system called electrodeposition was used to produce the patterned alginate hydrogel. To reduce the cytopathic effects, we used an indirect electrodeposition method. For characterizing this structure, mechanical properties, Fourier-transform infrared spectroscopy (FTIR), water uptake, in-vitro degradation, and hydrogel stability were studied. Urea synthesis as a basic function of hepatocytes was assessed in five different groups. Scanning electron microscope (SEM) was utilized to evaluate the primary hepatocyte morphology and their dispersion in the fabricated structure. We observed a significant increase in urea synthesis in the presence of CM-MSCs in patterned hydrogel alginate compared to 2D culture on day 3 (p<0.05). However, there was no significant difference in simple and patterned hydrogel on day 2. We found that the electrodeposition method is appropriate for the rapid fabricating of hydrogel structures with arbitrary patterns for 3D cell culture.

The role of the immune system in the pathogenesis of NAFLD and potential therapeutic impacts of mesenchymal stem cell-derived extracellular vesicles.

Non-Alcoholic Fatty Liver Disease (NAFLD) is characterized by intra-hepatocyte triglyceride accumulation and concomitant involvement of the immune system with subsequent histological changes, tissue damage, and clinical findings. There are various molecular pathways involved in the progression of NAFLD including lipotoxicity, endoplasmic reticulum stress, and the immune response. Both innate and adaptive immune systems are involved in the NAFLD pathogenesis, and crosstalk between the immune cells and liver cells participates in its initiation and progression. Among the various treatments for this disease, new cell based therapies have been proposed. Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSC) (MSC-EVs) are new cell-free vehicles with low immunogenicity, which can suppress detrimental immune responses in inflamed tissues. This review aimed to express the immune system's molecular pathways associated with the initiation and progression of NAFLD. Then, the possible role of MSC-EVs in the treatment of this entity through immune response modulation was discussed. Finally, engineered EVs enhanced by specific therapeutic miRNA were suggested for alleviating the pathological cellular events in liver disease.

Downhill running exercise increases circulating level of myokine meteorin-like hormone in humans.

BACKGROUND: Meteorin-like hormone (Metrnl) is a myokine with immunoregulatory traits. This study aimed at evaluating the response of the plasma levels of Metrnl to a downhill running exercise (DHRE) in humans. METHODS: Twenty active male college students (aged: 22±1.5 years, BMI: 23.50±2.91 kg/m2) completed this study. They performed a skeletal muscle-damaging exercise protocol e.g., downhill running exercise (DHRE) on treadmill. Blood samples were drawn before and after the exercise protocol to measure plasmatic values of Metrnl, eosinophil count, creatine kinase (CK), and lactate dehydrogenase (LDH). RESULTS: Plasma Metrnl level showed a significantly increased level in response to the DHRE (P=0.007). CK (P=0.004), LDH (P=0.001) and the number of plasma eosinophils (P=0.002) also showed significantly increased values following DHRE. Additionally, we found a significant and positive correlation between changes of plasma Metrnl level with those of the number of eosinophils (P<0.05). CONCLUSIONS: Downhill running exercise associated with noticeable skeletal muscle damage is accompanied by significantly increased plasma Metrnl level as well as eosinophils' number in sedentary humans.

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.

Metformin-Loaded PCL/PVA Fibrous Scaffold Preseeded with Human Endometrial Stem Cells for Effective Guided Bone Regeneration Membranes.

Many studies have been devoted to investigating the potential of guided bone regeneration (GBR) membranes for bone defect reconstruction. Regardless of approaches for treating damaged bone tissues, a beneficial therapeutic strategy has remained a challenge. In this study, a novel GBR membrane with polycaprolactone (PCL) and poly(vinyl alcohol) (PVA) containing different concentrations of metformin (Met) for improving osteogenic properties was developed. The membranes were evaluated for their hydrophilicity, degradation rate, swelling ratio, drug release, mechanical properties, and biological responses. The results showed a significant increase in hydrophilicity, swelling ratio, and degradation rate and no significant changes in mechanical properties of PCL/PVA membranes with Met concentration enhancement. A decrease in cell viability cultured on the surface of the PCL/PVA membrane was seen when the amount of Met was changed from 10 to 15 wt %. The results of the in vitro quantitative real-time polymerase chain reaction (qRT-PCR) also confirmed the higher secretion of osteogenic-related genes in a PCL/PVA/Cell/10 wt % Met scaffold than in the PCL/PVA/Cell sample. Therefore, further in vivo studies were conducted using the electrospun PCL/PVA membrane containing human endometrial stem cells (hEnSCs) and 10% Met. Histopathological and histomorphometric results confirmed that PCL/PVA/hEnSCs/10 wt % Met has excellent potential to differentiate hEnSCs into osteogenic lineages and bone regeneration in calvarial defects of rats. The results of this study confirm the high potential of the PCL/PVA/10 wt % Met fibrous membrane preseeded with hEnSCs in GBR applications.

Shedding light on the role of keratinocyte-derived extracellular vesicles on skin-homing cells.

Extracellular vesicles (EVs) are secretory lipid membranes with the ability to regulate cellular functions by exchanging biological components between different cells. Resident skin cells such as keratinocytes, fibroblasts, melanocytes, and inflammatory cells can secrete different types of EVs depending on their biological state. These vesicles can influence the physiological properties and pathological processes of skin, such as pigmentation, cutaneous immunity, and wound healing. Since keratinocytes constitute the majority of skin cells, secreted EVs from these cells may alter the pathophysiological behavior of other skin cells. This paper reviews the contents of keratinocyte-derived EVs and their impact on fibroblasts, melanocytes, and immune cells to provide an insight for better understanding of the pathophysiological mechanisms of skin disorders and their use in related therapeutic approaches.

Association of Meteorin-Like Hormone with insulin resistance and body composition in healthy Iranian adults.

BACKGROUND AND AIMS: Sedentary behavior and/or physical inactivity are modifiable risk factors for noncommunicable diseases. Myokines are one of the mediators of physical activity health benefits. Relationship between regular physical activity (RPA) and baseline plasma Meteorin-Like Hormone (Metrnl) has not been explored in human. Hence, we compared baseline plasma Metrnl between sedentary individuals and ones with recreational physical activities, and role of Metrnl as a biological messenger between physical activity and insulin resistance and body composition was also explored. METHODS: Forty healthy young men (aged: 21 ± 2.1 yrs; BMI: 23 ± 3.44 kg/m2) completed the study. Participants were equally assigned into two groups of control (sedentary) and case (recreational athletes). Baseline plasma Metrnl, glucose, insulin and body composition components and insulin resistance index (HOMA-IR) were assessed under resting conditions. RESULTS: Except for baseline blood glucose, baseline plasma Metrnl, insulin, HOMA-IR and body mass index and body fat percentage were similar between two groups (P > 0.05). However, after Metrnl correction for the degree of insulin resistance index (Metrnl/HOMA-IR), recreational athletes showed a significantly greater baseline compared to sedentary subjects (P < 0.05). Baseline blood glucose showed a negative and significant correlation with baseline plasma Metrnl (P < 0.05). CONCLUSIONS: Baseline plasma Metrnl is correlated with regular physical activity and insulin sensitivity, but not with body composition parameters. Metrnl may be one possible mediator of the beneficial effects of PA on insulin sensitivity in healthy humans. Hence, increasing awareness of the benefits of physical activity and incorporating physical activity into lifestyle are of great importance for people with non-communicable diseases.

Effects of vitamin D3 supplementation for 12 weeks on serum levels of anabolic hormones, anaerobic power, and aerobic performance in active male subjects: A randomized, double-blind, placebo-controlled trial.

Maintenance of the serum 25-hydroxyvitamin D (25-OH-D) concentration at recommended levels is essential due to its role in the regulation of anabolic hormones and athletic performance. However, the results of the clinical experiments in athletes are controversial. The present study aimed to investigate the effect of vitamin D3 supplement on serum levels of anabolic hormones, cortisol, anaerobic and aerobic performance in active males. In this double-blind, randomized controlled trial, 46 active males randomly assigned to vitamin D3 supplement (VDS; 2000 IU/day) or placebo for 12 weeks. The Wingate test, VO2max, and serum levels of 25-OH-D, Parathyroid hormone (PTH), total testosterone, growth hormone (GH), Insulin-like growth factor-1 (IGF-1), and cortisol were assessed. Subjects in the VDS group had a higher serum level of 25-OH-D (p = 0.004), VO2max (p = 0.016), and average power (p = 0.044) compared to the placebo at the end of the study. Also, lower levels of PTH (p = 0.004) and fatigue index (p < 0.001) were observed in VDS group at the end of the study. The serum cortisol levels were reduced significantly only in subjects with vitamin D deficiency in VDS group (p = 0.042). There was a significant reduction in serum testosterone levels in VDS group (p = 0.013). No change was indicated in serum levels of GH and IGF-1 in VDS group compared to the placebo (p > 0.05). The present study showed an improvement in aerobic capacity, anaerobic performance, and vitamin D status following vitamin D3 supplementation. However, more studies are required for the effect of vitamin D3 on serum concentration of anabolic hormones.

Imminent Angiotensin-converting Enzyme Inhibitor from Microbial Source for Cancer Therapy.

BACKGROUND: Drugs targeting Angiotensin I-converting enzyme (ACE) have been used broadly in cancer chemotherapy. The recent past coupled with our results demonstrates the effective use of ACE inhibitors (ACEi) as anticancer agents, and they are potentially relevant in deriving new inhibitors. METHODS: Bacterial strains were isolated from cow milk collected in Coimbatore, Tamil Nadu, India and plated on nutrient agar medium. The identity of the strain was ascertained by 16s rRNA gene sequencing method and was submitted to the NCBI GenBank nucleotide database. Various substrates were screened for ACEi production by the fermentation with the isolated strain. ACEi was purified by sequential steps of ethanol precipitation, ion exchange column chromatography and gel filtration column chromatography. The apparent molecular mass was determined by SDS-PAGE. The anticancer property was analyzed by studying the cytotoxicity effects of ACEi using Breast cancer MCF-7 cell lines. RESULTS: The isolate coded as BUCTL09 was selected and identified as Micrococcus luteus. Among the seven substrates, only beef extract fermented broth showed an inhibition of 79% and was reported as the best substrate. The peptide was purified and molecular mass was determined. The IC50 value of peptide was found to be 59.5 µg/ml. The purified peptide has demonstrated to induce apoptosis of cancer cell. CONCLUSIONS: The results of this study revealed that Peptide has been determined as an active compound that inhibited the activity of ACE. These properties indicate the possibilities of the use of purified protein as a potent anticancer agent.

Synthesis of calcium phosphate-zirconia scaffold and human endometrial adult stem cells for bone tissue engineering.

To address the hypothesis that using a zirconia (ZrO2)/ ß-tricalcium phosphate (ß-TCP) composite might improve both the mechanical properties and cellular compatibility of the porous material, we fabricated ZrO2/ß-TCP composite scaffolds with different ZrO2/ß-TCP ratios, and evaluated their physical and mechanical characteristics, also the effect of three-dimensional (3D) culture (ZrO2/ß-TCP scaffold) on the behavior of human endometrial stem cells. Results showed the porosity of a ZrO2/ß-TCP scaffold can be adjusted from 65% to 84%, and the compressive strength of the scaffold increased from 4.95 to 6.25 MPa when the ZrO2 content increased from 30 to 50 wt%. The cell adhesion and proliferation in the ZrO2/ß-TCP scaffold was greatly improved when ZrO2 decreased. Moreover, in vitro study showed that an osteoblasts-loaded ZrO2/ß-TCP scaffold provided a suitable 3D environment for osteoblast survival and enhanced bone regeneration. We thus showed that a porous ZrO2/ß-TCP composite scaffold has excellent mechanical properties, and cellular/tissue compatibility, and would be a promising substrate to achieve both bone reconstruction and regeneration needed during in vivo study for treatment of large bone defects.