Therapeutic Effects of Mesenchymal Stem Cells Derived from Bone Marrow and Adipose Tissue in a Rat Model of Temporomandibular Osteoarthritis.

OBJECTIVES: To examine the potential of intra-articular administration of mesenchymal stem cells (MSCs) derived from bone marrow or adipose tissue to mitigate synovial inflammation in a rat model of temporomandibular joint (TMJ) osteoarthritis (OA). METHODS: In this experimental study, 40 rats were divided into 4 groups: (1) Control group; (2) Untreated TMJ-OA group; (3) TMJ-OA group treated with bone marrow-derived MSCs; (4) TMJ-OA group treated with adipose tissue-derived MSCs. The TMJ-OA model was established by inducing synovial inflammation through the intra-articular administration of complete Freund's adjuvant (CFA). After 8 weeks of TMJ-OA establishment, the animals were sacrificed and each mandibular condyle was extracted for histological evaluation. RESULTS: The untreated TMJ-OA group had significantly higher synovial inflammation, as indicated microscopically by higher grades of synovial membrane hyperplasia and adhesion, vascular vasodilation, and fibrin deposition than the control group (p < 0.001). Both TMJ-OA groups treated with MSCs had lower grades of synovial inflammation and less severe synovitis than the untreated TMJ-OA group (p < 0.001). The TMJ-OA group treated with adipose tissue-derived MSCs showed lower grades of synovial membrane hyperplasia and higher grades of fibrin deposition than the that treated with bone marrow-derived MSCs (p < 0.001). Other indicators of synovial inflammation and synovitis severity were comparable between the two treatment groups. CONCLUSIONS: Administration of CFA to the TMJ-OA rat model augmented synovial inflammation. Intra-articular administration of MSCs derived from either bone marrow or adipose tissue attenuated the microscopic manifestations of this inflammation, indicating the therapeutic potential of this treatment for TMJ-OA.

The therapeutic effect of MSCs and their extracellular vesicles on neuroblastoma.

Neuroblastoma is a common inflammatory-related cancer during infancy. Standard treatment modalities including surgical interventions, high-dose chemotherapy, radiotherapy, and immunotherapy are not able to increase survival rate and reduce tumor relapse in high-risk patients. Mesenchymal stem cells (MSCs) are known for their tumor-targeting and immunomodulating properties. MSCs could be engineered to express anticancer agents (i.e., growth factors, cytokines, pro-apoptotic agents) or deliver oncolytic viruses in the tumor microenvironment. As many functions of MSCs are mediated through their secretome, researchers have tried to use extracellular vesicles (EVs) from MSCs for targeted therapy of neuroblastoma. Here, we reviewed the studies to figure out whether the use of MSCs could be worthwhile in neuroblastoma therapy or not. Native MSCs have shown a promoting or inhibiting role in cancers including neuroblastoma. Therefore, MSCs are proposed as a vehicle to deliver anticancer agents such as oncolytic viruses to the neuroblastoma tumor microenvironment. Although modified MSCs or their EVs have been shown to suppress the tumorigenesis of neuroblastoma, further pre-clinical and clinical studies are required to come to a conclusion.

Roles of Mesenchymal Stem Cells in Breast Cancer Therapy: Engineered Stem Cells and Exosomal Cell-Free Based Therapy.

Breast cancer has a high prevalence among women, with a high mortality rate. The number of people who suffer from breast cancer disease is increasing, whereas metastatic cancers are mostly incurable, and existing therapies have unfavorable side effects. For an extended duration, scientists have dedicated their efforts to exploring the potential of mesenchymal stem cells (MSCs) for the treatment of metastatic cancers, including breast cancer. MSCs could be genetically engineered to boost their anticancer potency. Furthermore, MSCs can transport oncolytic viruses, suicide genes, and anticancer medicines to tumors. Extracellular vesicles (EVs) are MSC products that have attracted scientist's attention as a cell-free treatment. This study narratively reviews the current state of knowledge on engineered MSCs and their EVs as promising treatments for breast cancer.

The Effects of Remdesivir and Dexamethasone on Renal Sirtuin-1 Expression and Renal Function in Male Rats.

Remdesivir (REM) and dexamethasone (DEX) both have been used to treat coronavirus disease 2019 (COVID-19). The present study aimed to evaluate the effects of REM and DEX on kidney structure and function with particular focus on the probable renal sirtuin-1 (SIRT1) expression alteration in rats. Twenty-four male Wistar rats were divided into four groups, as follows: group A (control) received normal saline (5 mL/kg/day for 10 days); group B (REM) received REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days); group C (REM + DEX) received both REM (17 mg/kg/day on the first day, and 8.5 mg/kg/day on the 2nd-10th days) and DEX (7 mg/kg/day, for 10 days); group D (DEX) received DEX (7 mg/kg/day for 10 days). Renal SIRT1 expression and kidney structure and function-related factors were evaluated by standard methods. The mean levels of urea in the REM + DEX group (60.83 ± 6.77, mg/dL) were significantly higher than in the control (48.33 ± 3.01, mg/dL; p = 0.002) and DEX (51.22 ± 4.99, mg/dL; p = 0.018) groups. The mean levels of creatinine in the REM (0.48 ± 0.08, mg/dL) and REM + DEX (0.50 ± 0.04, mg/dL) groups were higher than in the control group (48.33 ± 3.0 mg/dL) significantly (p = 0.022 and p = 0.010, respectively). The renal SIRT1 expression was significantly (p = 0.018) lower in the REM + DEX group (0.36 ± 0.35) than in the control group (1.34 ± 0.48). Tubulointerstitial damage (TID) scores in REM + DEX-treated rats (2.60 ± 0.24) were significantly higher than in the control (0.17 ± 0.17, p = 0.001) and DEX (0.50 ± 0.29, p = 0.005) groups. The administration of DEX and REM might lead to kidney injury associated with SIRT1 downregulation.

Role of cancer stem cell-derived extracellular vesicles in cancer progression and metastasis.

Cancer is one of the leading causes of mortality worldwide. Numerous strategies have been developed for cancer treatment. Metastasis, heterogeneity, chemotherapy resistance, recurrence, and evasion of immune surveillance are the primary reasons for the failure of cancer treatment. Cancer stem cells (CSCs) can give rise to tumors via self-renewal and differentiation into various cell types. They show resistance to chemotherapy and radiotherapy and have a strong capability of invasion and metastasis. Extracellular vesicles (EVs) are bilayered vesicles that carry biological molecules and are released under both healthy and unhealthy conditions. It has been shown that one of the leading causes of cancer treatment failure is cancer stem cell-derived EVs (CSC-EVs). CSC-EVs have essential roles in tumor progression, metastasis, tumor angiogenesis, chemoresistance, and immunosuppressants. In the future, controlling EV production in CSCs may be one of the most promising strategies to stop cancer treatment failures.

Association of serum kynurenine/tryptophan ratio with poor glycemic control in patients with type2 diabetes.

PURPOSE: The role of indoleamine 2,3-dioxygenase (IDO) has been shown in insulin resistance and metabolic syndrome. The present study aimed to measure serum IDO activity in patients with type 2 diabetes (T2DM) and to determine its association with glycemic control, oxidative stress, and insulin resistance. METHODS: Seventy-four patients with T2DM and 74 healthy subjects were selected to participate in this study. Fasting serum biochemical parameters including fasting blood sugar (FBS), HbA1c, insulin, uric acid, albumin, tryptophan, kynurenine, and total antioxidant capacity (TAC) were measured. HOMA-IR, QUICKI, and HOMA-B were calculated using serum FBS and insulin values. IDO activity was estimated using kynurenine/tryptophan ratio (KTR). Data were analyzed using SPSS software (Version 15) and p < 0.05 was considered as a significant difference. RESULTS: The findings showed higher levels of FBS, HbA1c, HOMA-IR, and KTR in the patients compared to the controls. TAC and HOMA-B were significantly lowered in the T2DM patients compared to controls. KTR was significantly correlated with the level of HbA1c, and T2DM patients with poor glycemic control (HbA1c ≤ 8) had significantly higher level of KTR. HOMA-B was significantly correlated with serum tryptophan and inversely correlated with HbA1c. CONCLUSION: Serum KTR is increased in T2DM patients with poor glycemic control. Potential clinical implications and possible pathogenic roles of IDO in T2DM development should be further elucidated.

Developing a model to predict air pollution (case study: Tehran City).

The technology development, population growth, development of metropolises and subsequent pollution are serious threats to the environment and public health. Therefore, monitoring and evaluation of various emissions and their sources, and also providing practical strategies of pollution reduction, are necessary to solve these problems. In this regard, the use of modern methods to predict the concentration of pollutants can improve decision-making and provide appropriate solutions. Tehran has been ranked as one of the most polluted cities in Iran. In this study, the meteorological monthly data were employed to achieve potent models based on a Box-Jenkins method for the modelling of concentration level of five major air pollutants in Tehran such as NO2, PM10, O3, SO2, CO, and Pollutant Standard Index. The best models were selected using goodness of fit criteria such as Akaike Information Criterion (AIC) and Schwartz Bayesian Criterion (SBC) and least prediction error. Prediction of concentrations of those pollutants can be a powerful tool in order to take preventive measures, such as the reduction of emissions and alerting the affected population. The results indicated that the concentration of pollutants in each period was influenced by their level and shocks they received during previous periods, which is mainly explained by special climatic and geographic conditions of Tehran that accumulates the pollution over time. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40201-020-00582-w.

Nitric oxide and selenium nanoparticles confer changes in growth, metabolism, antioxidant machinery, gene expression, and flowering in chicory (Cichorium intybus L.): potential benefits and risk assessment.

This experiment was conducted to provide a better insight into the plant responses to nitric oxide (NO) and selenium nanoparticle (nSe). Chicory seedlings were sprayed with nSe (0, 4, and 40 mg l-1), and/or NO (0 and 25 µM). NO and/or nSe4 improved shoot and root biomass by an average of 32%. The nSe40 adversely influenced shoot and root biomass (mean = 26%), exhibiting moderate toxicity partly relieved by NO. The nSe and NO treatments transcriptionally stimulated the dehydration response element B1A (DREB1A) gene (mean = 29.6-fold). At the transcriptional level, nSe4 or NO moderately upregulated phenylalanine ammonia-lyase (PAL) and hydroxycinnamoyl-CoA quinate transferase (HCT1) genes (mean = sevenfold). The nSe4 + NO, nSe40, and nSe40 + NO groups drastically induced the expression of PAL and HCT1 genes (mean = 30-fold). With a similar trend, hydroxycinnamoyl-CoA Quinate/shikimate hydroxycinnamoyl transferase (HQT1) gene was also upregulated in response to nSe and/or NO (mean = 25-fold). The activities of nitrate reductase and catalase enzymes were also induced in the nSe- and/or NO-treated seedlings. Likewise, the application of these supplements associated with an increase in ascorbate concentration (mean = 31.5%) reduced glutathione (mean = 35%). NO and/or nSe enhanced the PAL activity (mean = 36.4%) and soluble phenols (mean = 40%). The flowering was also influenced by the supplements in dose and compound dependent manner exhibiting the long-time responses. It appears that the nSe-triggered signaling can associate with a plethora of developmental, physiological, and molecular responses at least in part via the fundamental regulatory roles of transcription factors, like DREB1A as one the most significant genes for conferring tolerance in crops.

Effect of Vitamin D Supplementation on Intracytoplasmic Sperm Injection Outcomes: A Randomized Double-Blind Placebo-Controlled Trial.

BACKGROUND: Despite numerous studies indicating an imperative role for reproduction, however, the role of Vitamin D supplementation on outcomes of assisted reproductive techniques remains controversial. This clinical trial was performed to evaluate the effect of Vitamin D supplementation 6 weeks prior to intracytoplasmic sperm injection (ICSI) on fertility indices. MATERIALS AND METHODS: The present study was a double-blind clinical trial conducted on infertile women was randomly allocated into two groups: Vitamin D supplementation (42 participants) and placebo (43 participants). Serum Vitamin D was measured before and six to eight weeks after treatment, on the day of ovum pick up. Results were analyzed using SPSS16 and fertility indices were compared between the two groups. RESULTS: No significant difference was observed between the intervention and control groups regarding the mean number of oocytes retrieved, percentage mature oocyte, fertilization rate and the rate of good quality embryos (all P>0.05). But, percentages of the individual with suitable endometrium (7-14 mm thickness) were significantly higher in the Vitamin D compared to control group (P=0.011). The rate of chemical (47.6 vs. 25.5%, P=0.013) and clinical pregnancy rate (38.1 vs. 20.9%, P=0.019) were also significantly higher in the Vitamin D compared to control group. CONCLUSION: The present study reveals that consuming Vitamin D for 6 weeks prior to ICSI improves quality of endometrium, rate of chemical and clinical pregnancy (Registration Number: IRCT2015111124999N1).

The effect of aromatherapy massage with lavender oil on severity of primary dysmenorrhea in Arsanjan students.

BACKGROUND: Presently, using complementary therapy such as lavender oil has specific application in medicine. The purpose of this study was to investigate the effect of aromatherapy massage on the severity of primary dysmenorrhea in nursing and midwifery students of Islamic Azad University of Arsanjan, Iran. MATERIALS AND METHODS: This study was performed using clinical trial method on 80 eligible students whose level of pain was measured by visual analogue scale (VAS) before the intervention. Each participant, in the first days of menstruation, randomly received two types of massage with lavender and placebo oil in two consecutive cycles of menstruation. Their level of pain was measured before and 30 min after the intervention. In this study, each group was considered as their self-control group in the next cycle. The data were analyzed by SPSS software. RESULTS: A significant decrease in VAS score after lavender massage was detected in comparison with placebo massage. There was a statistically significant difference between VAS scores after and before placebo massage. In addition, statistically the effect of lavender massage on the severity of primary dysmenorrhea was higher than that of placebo massage (P < 0.001). CONCLUSIONS: Findings of this study showed that lavender oil massage decreases primary dysmenorrhea and it can be used as an effective herbal drug.