Synergistic effects of mesenchymal stem cell-derived extracellular vesicles and dexamethasone on macrophage polarization under inflammatory conditions.

The undesirable inflammation and the excessive M1 macrophage activity may lead to inflammatory diseases. Corticosteroids and stem cell therapy are used in clinical practice to promote anti-inflammatory responses. However, this protocol has limitations and is associated with numerous side effects. In this study, the synergistic anti-inflammatory effects of dexamethasone (Dex) and mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) were evaluated to enhance the polarization of M1 inflammatory macrophages into the anti-inflammatory (M2) phenotype. Hence, we designed different combinations of Dex and EVs using three methods, including EVs isolated from Dex-preconditioned MSCs (Pre-Dex-EVs), EVs loaded with Dex (L-Dex-EVs), and EVs and Dex co-administration (Dex + EVs). All designed EVs had a significant effect on reducing the expression of M1-related genes (iNOS, Stat1, and IRF5), cytokines (IL6 and TNF-a), and CD markers (CD86) in lipopolysaccharide-stimulated macrophages. On the other hand, these combinations promoted the expression of alternative-activated M2-related genes (Arg-1, Stat6, and IRF4), cytokine (IL10), and CD markers (CD206).The combination of Dex and MSC-EVs enhances the effectiveness of both and synergistically promotes the conversion of inflammatory macrophages into an anti-inflammatory state.

The role of curcumin during pregnancy on the exposed fetuses' tissues of Wistar rats to electromagnetic field.

To investigate curcumin (CUR) as the protector against the harmful effects of low-frequency electromagnetic field(LF- EMF, 50 Hz) during pregnancy period, 5 males and 15 females of Wistar rat mated and vaginal plaques were observed. Then, the pregnant rats were divided into six groups. During pregnancy(21 days), the EMF group was exposed to EMF for 30 min/day, the CUR group received a single dose of 50 mg/kg/daily CUR intraperitoneal, the EMF+CUR group was injected CUR and exposed to EMF daily. The DMSO(dimethyl sulfoxide) group was injected solvent of CUR (DMSO) intraperitoneal with the same volume of CUR solvent, the sham group was placed through the solenoid in the same conditions as the first group without exposure and the control group was kept in their cage in normal condition. After four weeks, babies born were divided according to the mother groups and sacrificed. Then, the three tissues injuries were investigated. EMF exposure led to an increase in outstanding necrotic areas in hippocampal tissue, an increase in the amount of hyperemia(p = 0.017) and necrotic(p = 0.005) in kidneys, and degeneration in liver tissue(p = 0.007) in the EMF group compared with EMF+CUR groups. A single dose of CUR daily during pregnancy can protect these tissues from injuries caused by LF-EMF exposure in rat fetuses.

Electromagnetic fields (EMFs) are able to penetrate and be absorbed by the body. The researchers showed that these radiations might be harmful and lead to cancers, cardiovascular diseases, mental disorders, and fetal abnormalities. Curcumin as an active component in turmeric has anti-inflammatory, antioxidant and anti-hyperlipidemia properties. It can protect the body against diseases such as arthritis, anxiety, and metabolic syndrome. This study examined the effects of curcumin as the protector against the harmful effects of EMF (50Hz) during pregnancy period. So the pregnant rats were divided into six groups. During pregnancy, a group was exposed to EMF for 30 min/day, the second group was injected a dose of curcumin 50mg/kg/daily, the third group was injected curcumin and exposed to EMF daily. The fourth group was injected a curcumin solvent dose, the sham group was placed through the field generator in the same conditions as the first group without exposure and the control group was kept in their cage in normal condition. After four weeks, babies born were divided according to the mother groups and sacrificed. Then, the liver, kidney, and hippocampal tissues were investigated. EMF exposure led to an outstanding increase in necrotic areas in hippocampal tissue, a notable increase in the amount of hyperemia and necrosis in kidneys, and degeneration in liver tissue(p=0.007) in the EMF group compared with the third group that was exposed to EMF and received curcumin. A single dose of curcumin daily during pregnancy can protect these tissues from injuries caused by EMF(50Hz) exposure in rat fetuses.

Effects of isoflavone supplementation on endometrial thickness, endometrial hyperplasia, and cancer in ovariectomized cats.

Ovariectomy is identified as a standard treatment in different European countries. Isoflavones, as nonsteroidal compounds in plants, are common constituents of soy and soy products. Some available cat diets contain different concentrations of soy products. This study aimed to examine the effects of isoflavone supplementation on endometrial hyperplasia and endometrial thickness in ovariectomized cats. Fifteen neutered adult cats were divided into control, estradiol, and isoflavone groups (five cats per group). Subcutaneous injection of estradiol (0.5 µg) in sesame oil (100 µL) was done for 30 days in estradiol-treated cats. Isoflavone-treated cats ingested a single oral tablet of soy extract for 30 days, while the controls received subcutaneous injections of the vehicle and oral placebo for 30 days. Histopathological findings of hematoxylin and eosin-stained sections revealed a significant difference between the estradiol group and other groups in terms of hyperplastic epithelium and simple hyperplasia. Thickness of myometrium was greater in the estradiol group compared to the isoflavone and control groups. Higher concentrations of estrogen can affect the endometrium and myometrium, while 30-day ingestion of isoflavone didn't have any uterine effect.

Adipose-derived mesenchymal stem cell-secreted exosome alleviates dextran sulfate sodium-induced acute colitis by Treg cell induction and inflammatory cytokine reduction.

Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is an inflammatory condition that results in gastrointestinal tract damage. Various factors, including environmental and genetic agents, disrupt the function of the intestinal immune system that can lead to IBD. Mesenchymal stem cells (MSCs) display an immunoregulatory function and demonstrate regenerative potential by paracrine action. In this study, we evaluated the immunomodulatory effects of MSCs' derived exosomes in the acute form of dextran sulfate sodium (DSS)-induced colitis. Exosomes were isolated from adipose-derived MSCs. Acute colitis was induced by DSS. The exosome was used by intraperitoneal injection into mice with acute colitis. Stool consistency, body weight changes, bleeding severity, colon length, and weight were examined. At the experimental endpoint (Day 7), the changes in the colon tissue were evaluated. The level of cytokines of interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17), IL-4, IL-12, transforming growth factor-ß (TGF-ß) and, IL-10, and Treg cells percentage were assayed. Results showed that exosome administration diminished colon shortening, bodyweight loss, bleeding, and colon injury. The levels of IFN-γ, TNF-α, IL-12, and IL-17 were decreased, and the level of TGF-ß, IL-4, and IL-10 were increased in lymph node and spleen of mice treated with exosome.  Percentages of CD4+ CD25+ Foxp3+ Treg cells were grown in the lymph node and spleen of mice treated with exosomes. Overall, current data suggest that MSC-derived exosome could regulate the Treg population and improves inflammation in DSS-induced acute colitis.

Imipenem alters systemic and liver inflammatory responses in CLP- induced sepsis mice in a dose-dependent manner.

BACKGROUND: Considering the role of inflammation in the outcome of sepsis and the widespread use of imipenem in the disease, this study was designed to assess the effect of imipenem on the dynamics of inflammatory responses in the sepsis mouse model. METHODS: Cecal Ligation and Puncture (CLP) model was used to induce sepsis in mice. C57BL/6 mice were divided into sham, CLP-induced sepsis mice, CLP-induced sepsis mice receiving 25 mg/kg, and 125 mg/kg imipenem. Blood and liver samples were obtained and bacterial load, endotoxin level, and liver enzymes were evaluated. The concentration and mRNA expression of cytokines were also determined. RESULTS: Sepsis mice treated with a high dose (125 mg/kg) of imipenem showed a significant reduction in bacterial load, while increased liver enzymes, endotoxin level, and inflammatory cytokine production in plasma and liver. In contrast, significant reduction in the liver enzymes, bacterial load, endotoxin levels, and inflammatory cytokine levels was observed in the mice treated with a low dose (25 mg/kg) of imipenem compared with other mice groups. Liver tissue pathology of mice indicated little tissue destruction in the sepsis mice treated with 25 mg/kg of imipenem compared to other groups. Mice receiving 25 mg/kg of imipenem had better survival rate. CONCLUSIONS: Our results demonstrated the dose-dependent effect of subcutaneous administration of imipenem on the inflammatory responses in sepsis mice. A dose of 25 mg/kg imipenem resulted in better pathology, lower inflammatory mediators, and increased survival rate in sepsis mice.

Effect of fullerene nanoemulsion on the repair of wrinkles induced by UVB radiation: A c57bl6 mice model.

INTRODUCTION: The effect of fullerene nanoemulsion on skin wrinkle repair in an animal model was evaluated using ultrasonic images processing. METHODS: Wrinkles were created in C57BL6 mice during 35 days of UVB radiation. Then, to investigate the therapeutic effect of fullerene nanoemulsions, mice were divided into three groups of control, UVB radiation, and treatment with fullerene nanoemulsion. Stable fullerene nanoemulsions were prepared using shear equalization. The therapeutic effect of fullerene nanoemulsion was investigated by extracting the skin thickness and mechanical parameters. Histology studies were performed to confirm the reliability of the treatment. RESULTS: A significant decrease was observed in the thickness of the epidermis and dermis layers (43% and 36%), Young modulus (27%), and the shear modulus (20%) of the skin on day 28 of the fullerene nanoemulsion treatment. Skin stiffness obtained by tensiometry on day 28 of the treatment showed a 48% reduction in the treatment group compared with the control group. Histological results confirmed the effect of fullerene nanoemulsions on wrinkle repair. CONCLUSION: The healing effect of fullerene nanoemulsion in wrinkle repair was confirmed. To study the skin repair, parameters including Young modulus, the shear modulus, and skin layer thickness can be calculated using ultrasonic images processing.

Non-invasive evaluation of elasticity of skin with the processing of ultrasound images during ultraviolet radiation: An animal photoaging model.

OBJECTIVE: The aim of this study was to provide a non-invasive imaging method to evaluate the physical and mechanical parameters as a novelty method during skin photoaging. METHODS: In order to evaluate the process of skin damage, 25 mice (C57BL6) were exposed to UVB radiation (0.03 mW/cm2 ), 5 times a week for 5 weeks. The thickness of the epidermal and dermal layers was measured weekly from the ultrasound images (40 MHz). The elastic parameters of the skin were estimated from the processing of the sequential ultrasound images with the motion detection algorithm during the injury generation process. RESULTS: The thickening, Young modulus, and shear modulus of the dermal and epidermal layers during the UVB damage process significantly increased during the 5-week study period (P < .05). In addition, the percentage of changes in the thickness of the epidermal layer (0.22 ± 0.01 mm in day 0 to 0.37 ± 0.02 mm in day 35) and dermal layer (0.57 ± 0.05 mm in day 0 to 0.90 ± 0.08 mm in day 35) increased by 68% and 57%, respectively. Furthermore, Young modulus (154.41 ± 8.8 kPa) was 11 times more than that of non-irradiated skin (14.90 ± 2.2 kPa) and the shear modulus (2.33 ± 0.04 kPa) was 2.2 times more than non-irradiated skin (1.06 ± 0.04 kPa). CONCLUSION: With processing the sequential ultrasound images and extracting the thickening, the elasticity of the skin layers can detect skin lesions by UVB radiation.

Low-intensity ultrasound combined with allogenic adipose-derived mesenchymal stem cells (AdMSCs) in radiation-induced skin injury treatment.

Mesenchymal stem cells are mechano-sensitive cells with the potential to restore the function of damaged tissues. Low-intensity ultrasound has been increasingly considered as a bioactive therapeutic apparatus. Optimizing transplantation conditions is a critical aim for radiation-induced skin tissue injury. Therefore, the therapeutic function of adipose-derived mesenchymal stem cells to ultrasound stimulus was examined based on the mechanical index (MI). Mesenchymal stem cells were isolated from the adipose tissues of mature guinea pigs. An ultrasound system (US) was constructed with a 40 kHz frequency. The radiation-induced skin injury model was produced on the abdominal skin of guinea pigs by 60 Gy of radiation. Then, they were divided to 7 groups (n = 42): control, sham, US (MI = 0.7), AdMSCs injection, US AdMSCs (AdMSCs, under US with MI = 0.2), AdMSCs + US (AdMSCs transplantation and US with MI = 0.7) and US AdMSCs + US (combining the last two groups). The homing of stem cells was verified with fluorescence imaging. The groups were followed with serial photography, ultrasound imaging, tensiometry, and histology. The thickness of the skin was analyzed. Functional changes in skin tissue were evaluated with Young's modulus (kPa). One-way ANOVA tests were performed to analyze differences between treatment protocols (p < 0.05). The results of Kumar's score showed that radiation injury was significantly lower in the treatment groups of US AdMSCs and US AdMSCs + US than other groups after 14 days (p < 0.05). There was a significant difference in skin thickness between treatment groups with control, sham, and US groups after 60 Gy radiation and were closer to the thickness of healthy skin. Young's modulus in US AdMSCs + US, US AdMSCs, and AdMSCs + US groups demonstrated a significant difference with the other groups (p < 0.05). Young's modulus in US AdMSCs + US and US AdMSCs treatment groups were closer to Young's modulus of the healthy skin. The histological results confirmed the improvement of acute radiation damage in the combined treatment method, especially in US AdMSCs + US and US AdMSCs groups with increasing the epithelialization and formation of collagen. An ultrasonic treatment plan based on a mechanical index of the target medium could be used to enhance stem cell therapy.