Association Of Statin Therapy On Clinical Outcomes In Covid-19 Patients: An Updated Systematic Review And Meta-Analysis On All Related Evidences

Background: Statins is a class of lipid-lowering drugs and our previous investigations showed that statins have antiviral effects and have a wound healing effect in the lung. This systematic review and meta-analysis aimed to evaluate the effects of statin therapy on mortality and clinical outcomes in COVID-19 patients. Methods: A comprehensive search was conducted in international databases, including MEDLINE, Scopus, Web of Science, and Embase from December 1, 2019 until January 26, 2022 without any restriction in language. The random-effects model was used to estimate the pooled odds ratio (OR). Results: The statin therapy overally was associated with decrease in odds of ventilation [pooled OR (95% CI): 0.85 (0.70 to 0.99)] and mortality [pooled OR (95% CI): 0.73 (0.66 to 0.81)] but had no effects on the  ICU admission [pooled OR (95% CI):  0.93 (0.77 to 1.12)], oxygen therapy [pooled OR (95% CI): 0.85 (0.70 to 0.99)], recovery [pooled OR (95% CI): 1.85 (0.35 to 9.92)], kidney failure [pooled OR (95% CI): 1.01 (0.73 to 1.40)], hospitalization [pooled OR (95% CI): 1.45 (0.88 to 2.36)], asymptomatic disease [pooled OR (95% CI): 1.33 (0.24 to 7.44)], and ARDS [pooled OR (95% CI): 1.15 (0.88 to 1.49)]. Conclusions: The present meta-analysis showed that statin therapy was associated with a reduced risk of mortality and ventilation in patients with COVID-19 but had no effects on other clinical outcomes

Therapeutic Effects of Laser on Partial Osteotomy in the Rat Model of Hypothyroidism

Introduction: Several experimental studies have displayed positive result for laser radiation on stimulating bone regeneration in recent years. The purpose of this experimental study was to determine low-level laser (LLL) effects on partial bone defects in hypothyroidism male rat.Methods: Forty male Wistar rats were randomly distributed as below groups: hypothyroidism + laser (Hypo + laser), hypothyroidism (Hypo), and control. Four weeks after surgery, the tibia bone was removed. Biomechanical and histological examinations were performed immediately.Results: Our results showed significant reduction in the absorption of energy, resistance in bending deformation (bending stiffness), maximum force, high stress load, trabecular bone volume, and number of osteocytes, osteoblasts and osteoclasts in the osteotomy site in hypothyroidism rats compared to hypothyroidism + laser group (P < 0.05).Conclusion: The results indicated that using laser may improve fracture regeneration and it may accelerate bone healing in hypothyroidism rat

Di-(2-ethylhexyl) Phthalate-Induced Hippocampus-Derived Neural Stem Cells Proliferation

The brain and spinal cord have a limited capacity for self-repair under damaged conditions. One of the best options to overcome these limitations involves the use of phytochemicals as potential therapeutic agents. In this study, we have aimed to investigate the effects of di-(2-ethylhexyl) phthalate (DEHP) on hippocampus-derived neural stem cells (NSCs) proliferation to search phytochemical candidates for possible treatment of neurological diseases using endogenous capacity. In this experimental study, neonatal rat hippocampus-derived NSCs were cultured and treated with various concentrations of DEHP (0, 100, 200, 400 and 600 µM) and Cirsium vulgare (C. vulgare) hydroethanolic extract (0, 200, 400, 600, 800 and 1000 µg/ml) for 48 hours under in vitro conditions. Cell proliferation rates and quantitative Sox2 gene expression were evaluated using MTT assay and real-time reverse transcription polymerase chain reaction (RT-PCR). We observed the highest average growth rate in the 400 µM DEHP and 800 µg/ml C. vulgare extract treated groups. Sox2 expression in the DEHP-treated NSCs significantly increased compared to the control group. Gas chromatography/mass spectrometry (GC/ MS) results demonstrated that the active ingredients that naturally occurred in the C. vulgare hydroethanolic extract were 2-ethyl-1-hexanamine, n-heptacosane, 1-cyclopentanecarboxylic acid, 1-heptadecanamine, 2,6-octadien-1-ol,2,6,10,14,18,22-tetracosahexaene, and DEHP. DEHP profoundly stimulated NSCs proliferation through Sox2 gene overexpression. These results provide and opportunity for further use of the C. vulgure phytochemicals for prevention and/or treatment of neurological diseases via phytochemical mediated-proliferation of endogenous adult NSCs

Trehalose Activates Autophagy and Prevents Hydrogen Peroxide-Induced Apoptosis in the Bone Marrow Stromal Cells

Bone marrow stromal stem cells (BMSCs) play a significant role in cell therapy. These cells quickly die after transplantation to the affected area due to oxidative stress. The natural disaccharide, trehalose which can be known as autophagy inducer. The present study aimed to investigate the role of trehalose in preventing BMSCs from oxidative stress caused by H2O2. BMSCs were isolated from the adult rats. The cells were divided into three groups: (a) control; (b) 100 μM H2O2; (c) 100 μM H2O2 and trehalose 3%. The morality rate was analyzed by viability test. Immunocytochemistry and Western blot was used in order to evaluate p62 protein and LC3II/LC3I ratio, respectively. In order to evaluate apoptosis, cleaved caspase-3 protein was used. In viability test, the survival rate for BMSCs after 8 h were 82%, 72%, 49%, and 39% (for groups who received 50, 100, 200, and 400 μM H2O2, respectively) compared to the control group. Pre-treatment with the use of trehalose 3% increased cell survivals. The levels of p62 protein, were increased in the cells under H2O2 treatment, while the levels of p62 protein in the cytoplasm, as autophagy inclusions, reduced for the group with trehalose pre-treatment. In addition, trehalose caused to increase LC3II/LC3I ratio and decreased the expression of cleaved caspase-3. Trehalose decreased apoptosis and increased the autophagy and survival levels of the cells against H2O2. Due to the unique properties of trehalose and its low toxicity, it can be used as a pharmaceutical agent in cellular transplantation to reduce oxidative stress. Keywords: Stress oxidative; Autophagy; Apoptosis; Bone marrow stromal cells; Trehalose

Route exposure and adverse effects monitoring of Aflatoxin B1 in the workers of wet waste management, the role of body redox system modulation

Exposure to dust, containing different fungi metabolites such as aflatoxins is a risk factor for developing liver and kidney health abnormalities. Occupational evaluation of the aflatoxin's exposure-induced health abnormalities should include the monitoring of bioaerosols in the workplace and personal air, and applying of appropriate blood biomarkers to assess Aflatoxin B1 (AFB1) detrimental effects on a worker’s health. However, to the best of our knowledge, these appropriate methods, especially determining the associated-adverse effects on health, following exposure, haven't been well documented in the literature at the wet waste handling sites. In the current study, the AFB1 quantity in the area, personal, and settled dust in wet household waste handling samples and AFB1-Albumin levels in the serum of workers in comparison with the control group were determined using high-pressure liquid chromatography with a fluorescent detector (HPLC-FLD) methods. Moreover, the adverse effects of AFB1 on the liver and kidney biochemical profiles of the exposed workers and its relation to antioxidant capacity in the household wet waste sorting were recorded in a consolidated investigation. The results demonstrated that the average airborne dust concentration and its associated AFB1 content were significantly higher in wet waste management sections as compared to the control place, corresponding to the serum AFB1-Albumin levels of workers. Furthermore, AFB1-induced changes in the serum biochemicals evaluating liver and kidney function tests and antioxidant profiles of workers in wet waste handling sections were indicative of their function abnormalities. The results imply AFB1-induced adverse effects on the liver and kidney functions may be mediated through the body redox system modulation

Human wild-type superoxide dismutase 1 gene delivery to rat bone marrow stromal cells: its importance and potential future trends

Objective(s): Human superoxide dismutase 1 (SOD1) is the cytosolic form of this enzyme it detoxifies superoxide anions and attenuates their toxicities and concomitant detrimental effects on the cells. It is believed that the amount of these enzymes present in the oxidative stress-induced diseases is crucial for preventing disease progression. Transfection of rat bone marrow stromal cells (BMSCs) by a constructed vector carrying the human wild-type SOD1 gene, a non-viral gene transfer method, was the main aim of this study. Materials and Methods: For this purpose, the rat BMSCs were transfected with the vector using Turbofect reagent and then stabilized. Western-blot and real-time PCR were also used for evaluation of SOD1 expression. Results: Data analysis from RT-PCR and Western-blot techniques revealed that the stable transfected cells could secrete human wild-type SOD1 in the supernatant. Also, the total activity of SOD1 was about 0.5±0.09 U/ml and 0.005±0.002 U/ml in the supernatants of the transfected and not-transfected of rat BMSCs, respectively. Conclusion: This study showed that expansion of the stable transfected rat BMSCs by a constructed vector carrying the human wild-type SOD1 gene is capable of secreting the active SOD1 enzyme under ex-vivo conditions.  The recommendation of this study is that the same experiment would be applicable for expression of the other form of this enzyme, SOD3, as well. More valuable information could probably be provided about the variety of the diseases caused by superoxide anions toxicities by intervention and application of the non-viral method for expressions of SOD1 and SOD3 enzymes

The Effect of bisphenol A and Photobiomodulation Therapy on Autophagy-Related Genes Induction in Adipose Tissue-Derived Stem Cells: Effects of Bisphenol A and Photobiomodulation Treatments on Autophagy

Introduction: As adipose tissue-derived stem cells (ADSCs) can divide rapidly and be prepared noninvasively, they have extensively been used in regenerative medicine. On the other hand, a new method of therapy, known as photobiomodulation (PHT), has been used to treat many diseases, such as inflammatory conditions, wound healing and pain. Besides, exposure to chemical substances such as bisphenol A (BPA), at low levels, can lead to autophagy. This study investigated the effects of BPA and PHT on the expression of autophagy-related genes, including LC3, NRF2, and P62, in rat ADSCs as a model.Methods: ADSCs isolation and purification were confirmed by immunocytochemistry (ICC). The cells were then treated with different concentrations of BPA and also subjected to PHT. Reverse transcription polymerase chain reaction (RT-PCR) was used for the evaluation of LC3, NRF2 and P62 gene expressions. Oil red O staining was used for adipogenic vacuole formation.Result: ICC showed that the isolated cells were CD 49-positive but CD 31 and CD 34-negative. The viability test indicated that the number of live cells after 24 hours in the BPA groups at concentrations of 0, 1, 50, 100 and 200 μM was 100%, 93%, 81%, 72%, and 43% respectively. The difference in cell viability between groups 50, 100 and 200 μM was significant as compared with the control groups (P<0.05). Moreover, in the group with 1 μM concentration of BPA, the expressions of LC3, NRF2 and P62 genes were upregulated. However, in the treatment group at the concentration of 200 μM of BPA, the LC3 gene was expressed, but NRF2 and P62 genes were downregulated.Conclusion: BPA and PHT induce autophagy and adiposeness in ADSCs in a dose-dependent manner. Doi:10.34172/jlms.2022.15

Evaluation of the antibacterial activity of the Althaea officinalis L. leaf extract and its wound healing potency in the rat model of excision wound creation

Objectives: Wound is defined simply as the disruption of the biochemical, cellular, and anatomic continuity of a tissue. Plants and their extracts known as phytomedicine have immense potential for the management and treatment of wounds. Materials and Methods: Due to the undesirable side effects, in the control and treatment of the wound infections, it is recommended to use natural materials such as phytochemicals instead of chemically synthesized drugs. Thus, the aim of this research was to study the anti-microbial and wound healing potential of Althaea officinalis L. hydroalchoholic extract in comparison with ciprofloxacin, gentamicin, and penicillin antibiotics on clinical strains as well as pathogenic bacteria such as Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Listeria monocytogenes under in vitro conditions using micro broth dilution and disc diffusion methods. Moreover, MIC and MBC of its hydroalchoholic extract was also evaluated. Results: The results showed that although Althaea officinalis L. extract was not effective on gram-negative bacteria but it was efficacious on gram-positive bacteria. The extract was also tested in the form of topical administration on excision wound model in rats. In the extract-treated wounds, the wound healing percent was significantly increased in comparison with controls. Conclusions: Based on this research, herbal extract of officinalis L. can be a great candidate for the treatment of gram-positive infections and merits further studies

Dopaminergic Neuroprotection with Ginkgolide in 6-Hydroxydopamine Rat Parkinson’s Disease Model

Abstract Background and purpose: Parkinson's disease (PD) is a prevalent movement disorder in elderly with progressive motor complications due to antioxidant defense system deficiency and accumulation of degraded proteins in dopaminergic neurons of midbrain. Ginkgolide is biologically active terpenic lactones as a polyphenol, with potent antioxidant and anti-inflammatory properties. The present study aimed to evaluate the neuroprotective effects of Ginkgolide in 6-hydroxydopamine (6- OHDA) rat model of PD. Materials and methods: Intrastriatal 6-OHDA-parkinson’s disease rat model was pretreated with Ginkgolide at 50 mg/kg/day for 4 weeks. Apomorphine-induced rotation test was applied to evaluate the neuroprotective effects of Ginkgolide. In addition, the antioxidant effects of Ginkgolide were assessed by analyzing the levels of thiobarbituric acid reactive substances (TBARS), Glutathione-S-transferase (GST), reactive oxygen species (ROS) homovanillic acid (HVA), and dopamine (DA). Results: Ginkgolide pretreatment led to reduced nigral and striatal TBARS, and ROS and increased the levels of GST, HVA, and DA. Meanwhile, Ginkgolide attenuates apomorphine-induced rotational bias and reduced contra-lateral rotation in Ginkgolide treatment group. Conclusion: These findings indicated the neuroprotective potential of Ginkgolide in 6- OHDA rat model of PD via amelioration of oxidative stress. Keywords: Parkinson’s disease, 6-hydroxydopamine, ginkgolide, oxidative stres