Boosting therapeutic efficacy of mesenchymal stem cells in pulmonary fibrosis: The role of genetic modification and preconditioning strategies.

Pulmonary fibrosis (PF) is the end stage of severe lung diseases, in which the lung parenchyma is replaced by fibrous scar tissue. The result is a remarkable reduction in pulmonary compliance, which may lead to respiratory failure and even death. Idiopathic pulmonary fibrosis (IPF) is the most prevalent form of PF, with no reasonable etiology. However, some factors are believed to be behind the etiology of PF, including prolonged administration of several medications (e.g., bleomycin and amiodarone), environmental contaminant exposure (e.g., gases, asbestos, and silica), and certain systemic diseases (e.g., systemic lupus erythematosus). Despite significant developments in the diagnostic approach to PF in the last few years, efforts to find more effective treatments remain challenging. With their immunomodulatory, anti-inflammatory, and anti-fibrotic properties, stem cells may provide a promising approach for treating a broad spectrum of fibrotic conditions. However, they may lose their biological functions after long-term in vitro culture or exposure to harsh in vivo situations. To overcome these limitations, numerous modification techniques, such as genetic modification, preconditioning, and optimization of cultivation methods for stem cell therapy, have been adopted. Herein, we summarize the previous investigations that have been designed to assess the effects of stem cell preconditioning or genetic modification on the regenerative capacity of stem cells in PF.

Carbon Quantum Dots as Multi-Purpose Nanomaterial in Stem Cell Therapy.

Some issues, such as their obscure fate or low survival rate into the body during stem cell therapy, should be addressed to boost efficiency. Nanotechnology offers a suitable solution to combat such limitations. Carbon quantum dots (CQDs) are carbon-based nanomaterials and may be used as multi-purpose compounds in stem cell therapy. CQDs are excellent choices for stem cell labeling thanks to their special features such as optical properties and good biocompatibility. Besides, they can modulate the biological function of stem cells, such as their proliferation, homing ability, and differentiation properties. Considering the charismatic feature of CQDs and their broad unique effect on stem cells, the current review aims to summarize the advancements in this field. Hence, we first focused on CQDs synthesis and their applications. In the next section, the stem cell categories will be discussed, and the final part is dedicated to the recent research evaluating the impact of CQDs on stem cell therapy.

Compliance of imipenem and meropenem administration with the national antimicrobial stewardship program in a referral teaching hospital in Iran.

INTRODUCTION: Considering the great significance of antimicrobial resistance, implementation of antimicrobial stewardship programs (ASPs) in healthcare facilities is of particular importance. This study aimed to evaluate the compliance of imipenem and meropenem administration with the ASP guidelines in a referral teaching hospital in Iran. METHODS: In this retrospective cross-sectional study, the medical records of patients, who received either imipenem or meropenem at xx Hospital in Semnan, Iran, from 21 March 2017 until 20 March 2019, were reviewed using the developed ASP, according to the instructions issued by the Ministry of Health of Iran. The obtained findings were recorded in a checklist consisted of six items. If the action taken for the patient complied with the item requirement specified in the ASP, it would receive a score of one; otherwise, a score of zero. The sum of scores (range: 0-6) was reported and analyzed. Data were analyzed in SPSS version 23, using Chi-square, ANOVA, and independent t-test, and P < 0.05 was considered as significant. RESULTS: The mean duration of imipenem/meropenem administration was 9.2 ± 8.0 days. A total of 6,032 imipenem/meropenem vials (1 g/vial) were prescribed during the study (meropenem for 210 patients and imipenem for 87 patients). In 64.2% of the patients, there was no indication, and the mean score of the subjects was 1.55 ± 1.2. The obtained score was three in 53 (17.8%) records and four in 18 (6.1%) records. The mean score of ASP in the intensive care units was higher, while it was lower in the surgical ward as compared to the other wards (P = 0.002). DISCUSSION: Antibiotic prescription was inappropriate in our center, and compliance with the ASP guidelines was very low, especially in the surgical wards. It seems necessary to take effective steps for planning continuing education programs on rational antibiotic prescription and supervision of prescription patterns.

Melatonin potentials against viral infections including COVID-19: Current evidence and new findings.

Viral infections are dangerous diseases for human health worldwide, which lead to significant morbidity and mortality each year. Because of their importance and the lack of effective therapeutic approaches, further attempts should be made to discover appropriate alternative or complementary treatments. Melatonin, a multifunctional neurohormone mainly synthesized and secreted by the pineal gland, plays some roles in the treatment of viral infections. Regarding a deadly outbreak of COVID-19 across the world, we decided to discuss melatonin functions against various viral infections including COVID-19. Therefore, in this review, we summarize current evidence on melatonin therapy for viral infections with focus on possible underlying mechanisms of melatonin actions.

Investigating The Alterations of Oxidative Stress Status, Antioxidant Defense Mechanisms, MAP Kinase and Mitochondrial Apoptotic Pathway in Adipose-Derived Mesenchymal Stem Cells from STZ Diabetic Rats.

OBJECTIVE: This study aimed to investigate the reliability of diabetic adipose-derived stem cells (ADSCs) for autologous cell-based therapies by exploring the functionality of signalling pathways involved in regulating oxidative stress and apoptosis. MATERIALS AND METHODS: In this experimental study, ADSCs were isolated from streptozotocin (STZ)-induced diabetic rats (dADSCs) and normal rats (nADSCs). The colonies derived from dADSCs and nADSCs were compared by colony-forming unit (CFU) assay. Reactive oxygen species (ROS) formation and total antioxidant power (TAP) were also measured. Furthermore, the expression of antioxidant enzymes, including catalase (Cat), superoxide dismutase (Sod)-1 and -3, glutathione peroxidase (Gpx)-1, -3 and -4 was measured at mRNA level by semi-quantitative reverse transcriptase polymerase chain reaction assay. The expression of Bax, Bcl2, caspase-3, total and phosphorylated c-Jun N-terminal kinase (JNK) and P38 Mitogen-Activated Protein Kinase (MAPK) at protein level was analyzed by western blotting. RESULTS: The results of this study indicated that viability and plating efficiency of dADSCs were significantly lower than those of nADSCs. ROS generation and TAP level were respectively higher and lower in dADSCs. The gene expression of antioxidant enzymes, including Cat, Sod-1, Gpx-3 and Gpx-4 in dADSCs was significantly greater than that in nADSCs. However, Sod-3 and Gpx-1 mRNA levels were decreased in dADSCs. Moreover, Bax/Bcl-2 protein ratio, caspase-3 protein expression and phosphorylation of JNK and P38 proteins were increased in dADSCs compared to nADSCs. CONCLUSION: Taken together, diabetes might impair the cellular functions of dADSCs as candidates for autologous cellbased therapies. This impairment seems to be mediated by JNK, P38 MAPKs, and mitochondria pathway of apoptosis and partly by disruption of antioxidant capacity.

Protective effects of atorvastatin on high glucose-induced oxidative stress and mitochondrial apoptotic signaling pathways in cultured chondrocytes.

The high glucose concentration is able to disturb chondrocyte homeostasis and contribute to OA pathogenesis. This study was designed to investigate the protective effects of atorvastatin (ATO) on high glucose (HG)-mediated oxidative stress and mitochondrial apoptosis in C28I2 human chondrocytes. The protective effect of ATO (0.01 and 0.1 µM) on HG (75 mM)-induced oxidative stress and apoptosis was evaluated in C28I2 cells. The effects of ATO on HG-induced intracellular ROS production and lipid peroxidation were detected and the protein expression levels of Bax, Bcl-2, caspase-3, total and phosphorylated JNK and P38 MAPKs were analyzed by Western blotting. The mRNA expression levels of antioxidant enzymes including heme oxygenase-1, NAD(P)H quinine oxidoreductase, glutathione S-transferase-P1, catalase, superoxide dismutase-1, glutathione peroxidase-1, -3, -4 were evaluated by reverse transcription-polymerase chain reaction. Pretreatment with ATO remarkably increased the gene expression levels of antioxidant enzymes and reduced HG-induced elevation of ROS, lipid peroxidation, Bax/Bcl-2 ratio, caspase-3 activation, and JNK and P38 phosphorylation. Atorvastatin could considerably reduce HG-induced oxidative stress and mitochondrial apoptosis through increasing the expression of antioxidant enzymes. Atorvastatin may be considered as a promising agent to prevent high glucose-induced cartilage degradation in OA patients.

Restoring the IL-1ß/NF-κB-induced impaired chondrogenesis by diallyl disulfide in human adipose-derived mesenchymal stem cells via attenuation of reactive oxygen species and elevation of antioxidant enzymes.

Strategies based on mesenchymal stem cell (MSC) therapy for restoring injured articular cartilage are not effective enough in osteoarthritis (OA). Due to the enhanced inflammation and oxidative stress in OA microenvironment, differentiation of MSCs into chondrocytes would be impaired. This study aims to explore the effects of diallyl disulfide (DADS) on IL-1ß-mediated inflammation and oxidative stress in human adipose derived mesenchymal stem cells (hADSCs) during chondrogenesis. MTT assay was employed to examine the effects of various concentrations of DADS on the viability of hADSCs at different time scales to obtain non-cytotoxic concentration range of DADS. The effects of DADS on IL-1ß-induced intracellular ROS generation and lipid peroxidation were evaluated in hADSCs. Western blotting was used to analyze the protein expression levels of IκBα (np), IκBα (p), NF-κB (np) and NF-κB (p). Furthermore, the gene expression levels of antioxidant enzymes in hADSCs and chondrogenic markers at days 7, 14 and 21 of differentiation were measured using qRT-PCR. The results showed that addition of DADS significantly enhanced the mRNA expression levels of antioxidant enzymes as well as reduced ROS elevation, lipid peroxidation, IκBα activation and NF-κB nuclear translocation in hADSCs treated with IL-1ß. In addition, DADS could significantly increase the expression levels of IL-1ß-induced impaired chondrogenic marker genes in differentiated hADSCs. Treatment with DADS may provide an effective approach to prevent the pro-inflammatory cytokines and oxidative stress as catabolic causes of chondrocyte cell death and enhance the protective anabolic effects by promoting chondrogenesis associated gene expressions in hADSCs exposed to OA condition.

Protective Effect of Ginger (Zingiber officinale Roscoe) Extract against Oxidative Stress and Mitochondrial Apoptosis Induced by Interleukin-1ß in Cultured Chondrocytes.

AIMS: The protective effects of ginger (Zingiber officinale Roscoe) extract on IL-1ß-mediated oxidative stress and mitochondrial apoptosis were investigated in C28I2 human chondrocytes. METHODS: The effects of various concentrations of ginger extract on C28I2 human chondrocyte viability were evaluated in order to obtain noncytotoxic concentrations of the drug by methylthiotetrazole assay. The cells were pretreated with 5 and 25 µg/mL ginger extract for 24 h, followed by incubation with IL-1ß (10 ng/mL) for 24 h. The effects of ginger extract on IL-1ß-induced intracellular reactive oxygen species (ROS) production and lipid peroxidation were examined. The mRNA expressions of antioxidant enzymes including catalase, superoxide dismutase-1, glutathione peroxidase-1, glutathione peroxidase-3, and glutathione peroxidase-4 were evaluated by reverse transcription polymerase chain reaction. The protein expressions of Bax, Bcl-2, and caspase-3 were analyzed by Western blotting. RESULTS: No cytotoxicity was observed at any concentration of ginger extract in C28I2 cells. Ginger extract pretreatment remarkably increased the gene expression of antioxidant enzymes and reduced the IL-1ß-induced elevation of ROS, lipid peroxidation, the Bax/Bcl-2 ratio, and caspase-3 activity. CONCLUSIONS: Ginger extract could considerably reduce IL-1ß-induced oxidative stress and consequent mitochondrial apoptosis as the major mechanisms of chondrocyte cell death. These beneficial effects of ginger extract may be due to its antioxidant properties. It may be considered as a natural herbal product to prevent OA-induced cartilage destruction in the clinical setting.