Effect of cold atmospheric plasma on changing of biomolecular structures involved in apoptosis pathways of melanoma cancer.

BACKGROUND: Cold atmospheric plasma (CAP), is a technology based on non-thermal ionized gas that is used for cancer therapy in research. We evaluated the effect of CAP on malignant melanoma cancer cell line (B16) in comparison with normal cells (L929). METHODS: The effect of CAP on the cytotoxicity of B16 and L929 cell lines was assayed by the MTT method and inverted microscopy. The induction of apoptosis in cells was evaluated using a fluorescence microscope. FTIR monitored the CAP effect in biomacromolecules changes in these cell lines. QPCR assayed gene expression of BAX, BCL-2, and Caspase-3 (CASP-3). RESULTS: The results of the MTT test showed CAP has a cytotoxic effect on the B16 cancer cell line more than L929 normal cells (p < 0.0001). The results of invert and fluorescence microscopy showed CAP-induced apoptotic morphology on cancerous cells. FTIR spectroscopy indicated CAP changes biomacromolecules structure. Evaluation of gene expression showed CAP increased BAX and CASP-3 gene expression. Also, it decreased BCL-2 gene expression. CONCLUSIONS: Taken together, CAP may change biomacromolecule structures involved in apoptosis pathways, decrease proliferation and induce apoptosis in cancer cells.

Cold atmospheric pressure plasma treatment combined with starvation increases autophagy and apoptosis in melanoma in vitro and in vivo.

Despite advances in therapy, malignant melanoma remains a fatal disease. Among several emerging approaches to combat cancer, cold atmospheric pressure plasma (CAP) has shown promising results as a novel antitumor agent in preclinical models so far. The technology mainly relies on the emittance of various reactive oxygen and nitrogen species (ROS/RNS) that are tumor-toxic at high concentrations. Moreover, malignant melanoma has a metabolic dimension that can be targeted by mild starvation. To this end, we investigated the combined effect of starvation and CAP treatment on melanoma in vitro and in vivo. In vitro, starvation+CAP led to cell morphology changes, decreased metabolic activity and increased lipid peroxidation accompanied by apoptosis and DNA fragmentation in murine B16 melanoma cells but not murine non-malignant L929 fibroblasts. This was paralleled by increased apoptosis (Bax, Bcl-2 and Caspase-3) and autophagy (Lc3 and Atg5)-related gene expression. In vivo, starvation reduced tumor burden. Combination with CAP treatment augmented this effect significantly, albeit there was no difference of combination treatment to CAP exposure alone. Interestingly, there was an overall greater increase of Lc3 and Atg5 in the tumor tissue compared to CAP exposure alone, while starvation-induced autophagy-related gene expression was similar to in the combination group. These data collectively suggest that CAP-derived ROS/RNS treatment and autophagy-induction augment antitumor effects in malignant melanoma in vitro and in vivo.

Tuberculosis comorbidity with rheumatoid arthritis: Gene signatures, associated biomarkers, and screening.

Rheumatoid arthritis (RA) is known to be related to an elevated risk of infections because of its pathobiology and the use of immunosuppressive therapies. Reactivation of latent tuberculosis (TB) infection is a serious issue in patients with RA, especially after receiving anti-TNFs therapy. TNF blocking reinforces the TB granuloma formation and maintenance and the growth of Mycobacterium tuberculosis (Mtb). After intercurrent of TB infection, the standard recommendation is that the treatment with TNF inhibitors to be withheld despite its impressive effect on suppression of inflammation until the infection has resolved. Knowing pathways and mechanisms that are common between two diseases might help to find the mechanistic basis of this comorbidity, as well as provide us a new approach to apply them as therapeutic targets or diagnostic biomarkers. Also, screening for latent TB before initiation of an anti-TNF therapy can minimize complications. This review summarizes the shared gene signature between TB and RA and discusses the biomarkers for early detection of this infection, and screening procedures as well.

Effects of coenzyme Q10 supplementation on inflammation, angiogenesis, and oxidative stress in breast cancer patients: a systematic review and meta-analysis of randomized controlled- trials.

BACKGROUND/OBJECTIVE: Systemic inflammation and oxidative stress (OS) are associated with breast cancer. CoQ10 as an adjuvant treatment with conventional anti-cancer chemotherapy has been demonstrated to help in the inflammatory process and OS. This systematic review and meta-analysis of randomized clinical trials (RCTs) aimed to evaluate the efficacy of CoQ10 supplementation on levels of inflammatory markers, OS parameters, and matrix metalloproteinases/tissue inhibitor of metalloproteinases (MMPs/TIMPs) in patients with breast cancer. METHODS: A systematic literature search was carried out using electronic databases, including PubMed, Web of Science, Scopus, Google Scholar, and Embase, up to December 2020 to identify eligible RCTs evaluating the effect of CoQ10 supplementation on OS biomarkers, inflammatory cytokines, and MMPs/TIMPs. From 827 potential reports, 5 eligible studies consisting of 9 trials were finally included in the current meta-analysis. Quality assessment and heterogeneity tests of the selected trials were performed using the PRISMA checklist protocol and the I2 statistic, respectively. Fixed and random-effects models were assessed based on the heterogeneity tests, and pooled data were determined as the standardized mean difference (SMD) with a 95% confidence interval (CI). RESULTS: Our meta-analysis of the pooled findings for inflammatory biomarkers of OS and MMPs showed that CoQ10 supplementation (100 mg/day for 45-90 days) significantly decreased the levels of VEGF [SMD: - 1.88, 95% CI: (- 2. 62 to - 1.13); I2 = 93.1%, p < 0.001], IL-8 [SMD: - 2.24, 95% CI: (- 2.68 to - 1.8); I2 = 79.6%, p = 0.001], MMP-2 [SMD: - 1.49, 95% CI: (- 1.85 to - 1.14); I2 = 76.3%, p = 0.005] and MMP-9 [SMD: - 1.58, 95% CI: (- 1.97 to - 1.19); I2 = 79.6%, p = 0.002], but no significant difference was observed between CoQ10 supplementation and control group on TNF-α [SMD: - 2.30, 95% CI: (- 2.50 to - 2.11); I2 = 21.8%, p = 0.280], IL-6 [SMD: - 1.56, 95% CI: (- 1.73 to - 1.39); I2 = 0.0%, p = 0.683], IL-1ß [SMD: - 3.34, 95% CI: (- 3.58 to - 3.11); I2 = 0.0%, p = 0.561], catalase (CAT) [SMD: 1.40, 95% CI: (1.15 to 1.65); I2 = 0.0%, p = 0.598], superoxide dismutase (SOD) [SMD: 2.42, 95% CI: (2.12 to 2.71); I2 = 0.0%, p = 0.986], glutathione peroxidase (GPx) [SMD: 2.80, 95% CI: (2.49 to 3.11); I2 = 0.0%, p = 0.543]], glutathione (GSH) [SMD: 4.71, 95% CI: (4.26 to 5.16); I2 = 6.1%, p = 0.302] and thiobarbituric acid reactive substances (TBARS) [SMD: - 3.20, 95% CI: (- 3.53 to - 2.86); I2 = 29.7%, p = 0.233]. CONCLUSION: Overall, the findings showed that CoQ10 supplementation reduced some of the important markers of inflammation and MMPs in patients with breast cancer. However, further studies with controlled trials for other types of cancer are needed to better understand and confirm the effect of CoQ10 on tumor therapy.

LncRNAs as potential diagnostic and prognostic biomarkers in gastric cancer: A novel approach to personalized medicine.

Gastric cancer is the third leading cause of cancer death with 5-year survival rate of about 30-35%. Since early detection is associated with decreased mortality, identification of novel biomarkers for early diagnosis and proper management of patients with the best response to therapy is urgently needed. Long noncoding RNAs (lncRNAs) due to their high specificity, easy accessibility in a noninvasive manner, as well as their aberrant expression under different pathological and physiological conditions, have received a great attention as potential diagnostic, prognostic, or predictive biomarkers. They may also serve as targets for treating gastric cancer. In this review, we highlighted the role of lncRNAs as tumor suppressors or oncogenes that make them potential biomarkers for the diagnosis and prognosis of gastric cancer. Relatively, lncRNAs such as H19, HOTAIR, UCA1, PVT1, tissue differentiation-inducing nonprotein coding, and LINC00152 could be potential diagnostic and prognostic markers in patients with gastric cancer. Also, the impact of lncRNAs such as ecCEBPA, MLK7-AS1, TUG1, HOXA11-AS, GAPLINC, LEIGC, multidrug resistance-related and upregulated lncRNA, PVT1 on gastric cancer epigenetic and drug resistance as well as their potential as therapeutic targets for personalized medicine was discussed.

IL-35, a double-edged sword in cancer.

Interleukin 35 (IL-35), a cytokine mainly produced by regulatory T cells (Treg cells), is composed of an Epstein-Barr virus-induced gene 3 ß-chain and an IL-12 p35 α-chain. IL-35 causes tumorigenicity in cancer, protects cancer cells against apoptosis, and facilitates cancer progression. However, a few reports have referred to its contradictory roles in cancer prevention. Therefore, the exact purpose of this cytokine in cancer development has become a fundamental question that needs to be answered. In this review, we explain the structure of IL-35 and its receptors and their different signaling pathways. Finally, the function of IL-35 in some cancers and the possible application of this cytokine in approaches for cancer therapy have been discussed.

Infection-associated epigenetic alterations in gastric cancer: New insight in cancer therapy.

Gastric cancer risk is higher for malignancies motivated by bacterial and viral infections. Epigenetic abnormalities including DNA methylation, histone modifications, and noncoding RNAs are important regulatory key players in gastric cancer development in infected patients. Epigenetic memory restoration is an extremely interesting phenomenon which should be considered in therapeutic approaches. In vitro and in vivo antiviral treatments in combination with epigenetic therapeutic strategies along with standard chemotherapy revealed promising outcomes in gastric cancer prevention and treatment. This review summarizes our current understanding of the gastric cancer infections and epigenetic alterations caused by these agents. We focus on studies highlighting recent advances in epigenetic restoration by target specific drugs and present also a comprehensive overview of effective antiviral drug treatments against gastric cancer.

Effects of Aloe vera and Eucalyptus methanolic extracts on experimental toxoplasmosis in vitro and in vivo.

Toxoplasmosis is a worldwide disease caused by the protozoan parasite Toxoplasma gondii (T. gondii), which is most commonly treated by pyrimethamine and sulfadiazine. However, this treatment presents several adverse side effects; Thus, new drugs with lower toxicities are urgently needed. In this study the anti-T. gondii activity of A. vera and Eucalyptus extracts were evaluated in vitro using a MTT (3-(4, 5-dimethylthiazol-2-yl) 2, 5-diphenyltetrazolium bromide) assay and in vivo by measuring the survival rates of mice infected with 2 × 103 tachyzoites of RH strain of T. gondii and then injected intraperitoneally by different concentrations of extracts for 4 days. Biochemical parameters such as Ferric Reducing Antioxidant Potential (FRAP) and malondialdehyde (MDA) assay were also evaluated. As results, in the in vitro assay, the IC50 values were 13.2, 24.7, 2.63 µg/ml, and the selectivity indexes were 3.3, 2.4, 3.03 for the A. vera, Eucalyptus and pyrimethamine, respectively. The mice treated with Eucalyptus showed a better survival rate than others (P < 0.05). The increased weight of liver and spleen, due to infection, was reduced by treatments. In FRAP assay Eucalyptus showed a better antioxidant activity than the other extracts. MDA levels in both liver and spleen were reduced by treatment. The results show that A. Vera and Eucalyptus possess anti-T. gondii activities in vitro and in vivo, in addition, Eucalyptus shows antioxidant activity with a higher survival rate. Therefore, Eucalyptus may be a useful candidate for treating Toxoplasma infection. Moreover, further studies are required to investigate the fractionations of this plant against T. gondii.

Starved human fibroblasts secrete acidic proteins inducing post re-feeding proliferation and in vitro cell migration: a potential tool for wound healing.

BACKGROUND INFORMATION: There are several reports indicating that starved fibroblasts show higher proliferation rates when re-fed with foetal bovine serum. We have evidence demonstrating that this phenomenon is related to secretory proteins which may be beneficial to wound healing. RESULTS: After re-feeding, 16 and 72 h serum-starved fibroblasts showed the highest and lowest proliferation rates, 1.59 and 0.51-fold difference compared to the non-starved control, respectively (P < 0.05). However, the latest value could be normalised by incubating cells with 16 h-starved fibroblast cell culture supernatant (16-SFS), prior to re-feeding. A strong correlation was found between total protein level in starved fibroblast culture supernatants and post re-feeding proliferation rates (r(2) = 0.90, P < 0.001). Two-dimensional gel electrophoresis analysis of 16-SFS confirmed the presence of proteins with relative molecular weights of 10-120 kDa and pI ranging from 4 to 6. A significant difference in calcium influx course was found between 16-SFS and the negative control (Dulbecco's Modified Eagle Medium) (P < 0.05). There was no significant difference in Ca(2+) concentrations after 1 h between non-starved controls and 16-SFS-treated fibroblasts. The scratch test demonstrated that the 16-SFS is able to induce fibroblast migration. CONCLUSIONS: We concluded that human starved fibroblasts secrete proteins that are able to induce post re-feeding cell proliferation and fibroblasts migration, probably through the induction of a sustained calcium influx. This is worth being considered as a potential tool for wound healing.

Proteome analysis, bioinformatic prediction and experimental evidence revealed immune response down-regulation function for serum-starved human fibroblasts.

Emerging evidence indicates that fibroblasts play pivotal roles in immunoregulation by producing various proteins under health and disease states. In the present study, for the first time, we compared the proteomes of serum-starved human skin fibroblasts and peripheral blood mononuclear cells (PBMCs) using Nano-LC-ESI-tandem mass spectrometry. This analysis contributes to a better understanding of the underlying molecular mechanisms of chronic inflammation and cancer, which are intrinsically accompanied by growth factor deficiency.The proteomes of starved fibroblasts and PBMCs consisted of 307 and 294 proteins, respectively, which are involved in lymphocyte migration, complement activation, inflammation, acute phase response, and immune regulation. Starved fibroblasts predominantly produced extracellular matrix-related proteins such as collagen/collagenase, while PBMCs produced focal adhesion-related proteins like beta-parvin and vinculin which are involved in lymphocyte migration. PBMCs produced a more diverse set of inflammatory molecules like heat shock proteins, while fibroblasts produced human leukocytes antigen-G and -E that are known as main immunomodulatory molecules. Fifty-four proteins were commonly found in both proteomes, including serum albumin, amyloid-beta, heat shock cognate 71 kDa, and complement C3. GeneMANIA bioinformatic tool predicted 418 functions for PBMCs, including reactive oxygen species metabolic processes and 241 functions for starved fibroblasts such as antigen processing and presentation including non-classical MHC -Ib pathway, and negative regulation of the immune response. Protein-protein interactions network analysis indicated the immunosuppressive function for starved fibroblasts-derived human leucocytes antigen-G and -E. Moreover, in an in vitro model of allogeneic transplantation, the immunosuppressive activity of starved fibroblasts was experimentally documented. Conclusion: Under serum starvation-induced metabolic stress, both PBMCs and fibroblasts produced molecules like heat shock proteins and amyloid-beta, which can have pathogenic roles in auto-inflammatory diseases such as rheumatoid arthritis, type 1 diabetes mellitus, systemic lupus erythematosus, aging, and cancer. However, starved fibroblasts showed immunosuppressive activity in an in vitro model of allogeneic transplantation, suggesting their potential to modify such adverse reactions by down-regulating the immune system.

Short exposure to collagenase and coculture with mouse embryonic pancreas improve human dermal fibroblast culture.

The dermal fibroblast as a major component of connective tissue has attracted much attention in the past few years, and application of these very fast growing cells in several fields has been intensively studied. Isolating dermal fibroblasts is an appropriate way to expand these fast growing cells in vitro. Although using a dissociated fibroblast culture method is more convenient than skin explant culture, its enzymatic digestion is critical because a large number of cells can be lost over prolonged exposure to collagenase. This study was performed to increase the number of viable cells after digestion of fresh human foreskin of donors aged from 1 to 3 months with collagenase and also by to design a coculture system for resuscitation of the injured fibroblast. Our results demonstrate that we can maximize cell yield while maintaining cell viability by cutting the specimens into very small pieces (1-2 mm³) after removing the epidermal layer with dispase II and also by collecting released cells every 20 Min subsequent to digesting the dermal layer with collagenase. Moreover, our data strongly indicate that coculturing of isolated fibroblasts with embryonic pancreas explants can enhance the rate of proliferation in cultured fibroblasts.

The immunogenicity of an inactivated vaccine against SARS-CoV-2 in healthy individuals: A systematic review and meta-analysis.

OBJECTIVE: Inactivated (killed) vaccines against COVID-19 have been widely used for the control of the pandemic condition. We performed a systematic and meta-analysis review of randomized, double-blind, placebo-controlled trials of the immunogenicity of inactivated vaccines against SARS-CoV-2 in healthy individuals. METHODS: In the present study, all research and evidence were extracted from the available online databases. Two researchers randomly evaluated the assessment of the research sensitivity. Finally, after quality assessment and regarding the specific inclusion and exclusion criteria, the eligible articles were entered for meta-analysis. The heterogeneity between the results of the studies was measured using test statistics (Cochran's Q) and the I2 index. The forest plots illustrated the point and pooled estimates with 95% confidence intervals (crossed lines). All statistical analyses were performed using Comprehensive meta-Analysis V.2 software. RESULTS: This meta-analysis included six primary studies investigating the immunogenicity of inactivated vaccines against SARS-CoV-2 in healthy individuals. According to the pooled prevalence (95% confidence interval), neutralizing antibody responses 28 days after receiving the second dose regarding different ages and micrograms per dose was 95.50% (CI: 93.2-97.1%). Our results showed that antibody levels were higher in the 6 µg group than in other groups. 98.3% (CI: 94.2-99.5%). CONCLUSION: Since the rapid development of vaccinations has sparked widespread public anxiety regarding vaccine efficacy. Governments and unvaccinated individuals, particularly those with vaccination reluctance, will be interested in and benefit from the findings of this systematic study.

Role of Frizzled receptor expression on patients' survival with gastrointestinal cancers: A systematic review with meta-analysis.

BACKGROUND: Frizzled receptors (FZD) play a pivotal role in the initiation and progression of a wide array of cancers. Dysregulated expression of FZD receptors is correlated with higher metastasis and invasive potential, as well as short survival in many malignancies. In this meta-analysis, we aimed to verify the prognostic value of FZD receptor expression on patients' survival with different types of gastrointestinal (GI) cancers, including gastric, colorectal, and esophageal cancers. METHODS: A systematic search was performed using PubMed, Scopus, and Web of Science from 2000 to November 2020. Fourteen studies, including 2997 patients met our inclusion criteria, in which nine articles were considered FZD7 while the rest were about other FZD members. The fixed-effect model was used to estimate the pooled hazard ratio (HR) and the 5-year overall survival (OS) rate. We used the Newcastle-Ottawa scale of cohort articles to determine the quality of included studies. RESULTS: The results showed that high expression of FZD receptors is associated with the poor survival in patients with GI cancers (HR= 1.83, 95% CI: 1.5-2.17). Moreover, multivariate analysis indicated that FZD receptors could be considered as an independent prognostic factor (HR = 1.76, 95% CI: 1.37-2.16). CONCLUSION: According to our results, overexpression of FZD receptors predicts a poor prognosis in patients with GI cancers and could be used as a useful therapeutic target.

Synthesis and characterization of amino sulfonic acid functionalized graphene oxide as a potential carrier for quercetin.

In this investigation, a new nanocomposite as a nanocarrier based on functionalized graphene oxide was synthesized by reaction of tetraethylenepentamine and chlorosulfonic acid with functional groups on the surface of GO. The synthesized nanocomposite was characterized by FT-IR, XRD TGA, FE-SEM, EDAX, TEM, and AFM analysis. To explore the potential of nanocomposites in drug delivery, the loading and releases of quercetin as an anticancer drug were investigated. The result displayed that more than 90% of the drug was loaded on the nanocarrier and the release of the drug is depending on the pH of the environment such that the releases of the drug in Gastric and intestinal conditions were up to 50% and 30%, respectively. The analysis of toxicity effect on the normal and cancer cells indicated that the nanocarrier with the drug has potential for cancer cells therapy without cytotoxic effect on normal cells in IC50 concentration.

Inhibitory Effects of Cold Atmospheric Plasma on Inflammation and Tumor-Like Feature of Fibroblast-Like Synoviocytes from Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic, debilitating systemic disease characterized by chronic inflammation and progressive joint destruction. Fibroblast-like synoviocytes (FLSs) are one of the most important players in the pathophysiology of RA, acting like tumor cells and secreting inflammatory cytokines. Previous research has shown that cold atmospheric plasma (CAP) inhibits cancer cells and may have anti-inflammatory properties. This study examined the effects of argon plasma jet-produced CAP on the suppression of invasion and inflammation caused by cultured RA-FLS. The findings revealed that CAP reduced cell viability and elevated the percentage of apoptotic RA-FLS by producing reactive oxygen species. Carboxyfluorescein diacetate succinimidyl ester (CFSE) staining confirmed that CAP could decrease the proliferation of RA-FLS. Furthermore, CAP effectively reduced the production of inflammatory factors (e.g., NF-κB and IL-6) as well as destructive factors like receptor activator of nuclear factor kappa-B ligand (RANKL) and matrix metalloproteinases-3 (MMP-3). These data suggest that CAP could be a promising treatment for slowing the progression of RA by reducing tumor-like features and inflammation in RA-FLS.

Dimethylaminoparthenolide (DMAPT) as an alternative approach for treatment of Familial Mediterranean Fever (FMF).

OBJECTIVES: Familial Mediterranean Fever (FMF) is a hereditary auto-inflammatory disorder that is caused by mutations in the Mediterranean fever (MEFV) gene and is associated with an increase in pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß) and interleukin-18 (IL-18), leading to excess inflammation. Colchicine is a common drug widely used for treatment of FMF attacks, but about 5-15% of the patients show resistance to the regular colchicine treatment. In this study, we used dimethylamino-parthenolide (DMAPT), as a small molecule inhibitor of Nuclear factor-κB (NF-κB), NLR family Pyrin domain containing 3 (NLRP3), and cysteine-aspartic acid protease 1(Caspase-1) on FMF-derived peripheral blood mononuclear cells (PBMCs). MATERIALS AND METHODS: The effects of DMAPT and colchicine on metabolic activity and apoptosis of FMF-derived PBMCs were evaluated by MTT and Annexin V/PI assays, respectively. Also, the expression levels of NF-κB, NLRP3, MEFV, CASP1, and IL-1ß mRNA were investigated using a TaqMan real-time PCR, and the protein levels of IL-1ß, IL-18, and IL-37 were assessed via an enzyme-linked immunosorbent assay (ELISA) in LPS/ ATP-stimulated PBMCs. RESULTS: DMAPT decreased the expression levels of NFκB (0.38±0.096, P<0.0001), NLRP3 (0.39±0.12, P<0.001), MEFV (0.384±0.145, P<0.001), CASP1 (0.48±0.13, P=0.0023), and IL-1ß (0.09±0.09, P<0.0001) and reduced the secretion levels of IL-1ß (8.92±5.3 vs. 149.85±20.92, P<0.0001), IL-18 (135±32.1 vs. 192±22.18, P=0.01), and IL-37 (27.5±6.3 vs. 78.19±14.3, P<0.0001) as compared to untreated cells. CONCLUSION: Given the obtained results in comparison with previous research, the future clinical development of DMAPT could result in the expansion of new anti-inflammatory therapeutics for FMF disorder.

The Perspective of Therapeutic Antibody Marketing in Iran: Trend and Estimation by 2025.

BACKGROUND: Monoclonal antibodies with high efficiency and specificity are one of the best strategies to diagnose and treat a variety of diseases such as cancer, autoimmunity, and inflammatory diseases. The market for monoclonal therapeutic antibodies (MTAs) has grown dramatically in the past decade. OBJECTIVE: Given the importance of these issues, developing countries spend a high cost on importing or producing MTAs annually. This study intends to examine the market of monoclonal therapeutic antibodies in Iran and predict the future growth rate of this market using the obtained data. METHODS: Data on the status of MTAs in the country (from 2008 to 2018) were obtained from the Food and Drug Deputy of Mazandaran University of Medical Sciences. The market status of MTAs was studied based on the dosage forms, application, and price. Then, the market outlook was predicted up to year 2025. RESULTS: The results showed that 58.8% of all MTAs were humanized, and 86% of all antibody-based drugs were used to treat cancer. Sales of MTA-based medications will reach $454 million by 2025 and are projected to grow significantly in the future. CONCLUSION: Given the increasing technology of the production of MTAs and their use in targeted therapies worldwide, their consumption market in Iran is expected to grow significantly.

The Effect of Arbutin on The Expression of Tumor Suppressor P53, BAX/BCL-2 Ratio and Oxidative Stress Induced by Tert-Butyl Hydroperoxide in Fibroblast and LNcap Cell Lines.

OBJECTIVE: Arbutin (p-hydroxyphenyl-ß-D-glucopyranoside) possesses beneficial functions including antioxidant, antiinflammatory, and anti-tumoral activities. Due to the important role of oxidative stress and apoptosis in the successful treatment of cancer, understanding mechanisms that lead to apoptosis in cancer cells, is essential. The purpose of the current study was to evaluate the effect of arbutin on tert-butyl hydroperoxide (t-BHP)-induced oxidative stress and the related mechanisms in fibroblast and Lymph Node Carcinoma of the Prostate (LNCaP) cells. MATERIALS AND METHODS: In this experimental study, the LNCaP and fibroblast cell lines were pre-treated with arbutin (50, 250 and 1000 µM). After 24 hours, t-BHP (30 and 35 µM) was added to the cells. Viability was measured (at 24 and 48 hours) using MTT assay. The antioxidant effect of arbutin was measured by FRAP assay. The mRNA expression of P53 and BAX/BCL-2 ratio were measured using quantitative polymerase chain reaction (PCR). The percentage of apoptotic or necrotic cells was determined using a double staining annexin V fluorescein isothiocyanate (FITC) apoptosis detection kit. RESULTS: Arbutin pre-treatment increased the total antioxidative power and cell viability in the MTT assay and reduced BAX/BCL-2 ratio, P53 mRNA expression and necrosis in fibroblasts exposed to the oxidative agent (P<0.001). In addition, our results showed that arbutin can decrease cell viability, induce apoptosis and increase BAX/BCL-2 ratio in LNCaP cells at some specific concentrations (P<0.001). CONCLUSION: Arbutin as a potential functional ß-D-glucopyranoside has strong ability to selectively protect fibroblasts against t-BHP-induced cell damage and induce apoptosis in LNCaP cells.

The effectiveness of Colchicine as an anti-inflammatory drug in the treatment of coronavirus disease 2019: Meta-analysis.

A recently discovered coronavirus, SARS-CoV-2, caused a global respiratory disease pandemic called COVID-19. Many studies have shown the excessive activation of the innate immune response that leads to the adverse outcomes of COVID-19, and anti-inflammatory drugs are very useful in the treatment and management of this infection. The activities of Colchicine, one of the anti-inflammatory drugs, target several pathways related to excessive inflammation of COVID-19. This study aimed to evaluate the efficacy of Colchicine in the treatment of COVID-19 using a meta-analysis approach. Scopus, Pubmed, Google scholars, Web of Science, and Science direct were used to search all the randomized controlled trials, case-control, and cross-sectional studies that have evaluated the efficacy of Colchicine as a treatment for COVID-19 (up to 28 May 2021). The overall effect of Colchicine versus the control group was determined using a random-effects model meta-analysis where we compared changes (i.e. mean differences-Colchicine group vs Control group) between the two conditions in test scores indicative of hospitalization time (day) and mortality rate. The results illustrated Colchicine therapy is associated with a decreased mortality rate in COVID-19 patients and associated with a decrease in hospitalization time (day) in COVID-19 patients. Present preliminary data shows that Colchicine has a beneficial effect on coronavirus disease care in 2019. Therefore, Colchicine can be a good suggestion in the management of COVID-19.

Patients with Coronary Artery Disease Have Lower Levels of Antibody to Heat-Stressed Fibroblast Derived Proteins, versus Normal Subjects.

Cellular stress response plays an important role in the pathophysiology of coronary artery disease (CAD). Inhibition of cellular stress may provide a novel clinical approach regarding the diagnosis and treatment of CAD. Fibroblasts constitute 60-70% of cardiac cells and have a crucial role in cardiovascular function. Hence, the aim of this study was to show a potential therapeutic application of proteins derived from heat-stressed fibroblast in CAD patients. Fibroblasts were isolated from the foreskin and cultured under heat stress conditions. Surprisingly, 1.06% of the cells exhibited a necrotic death pattern. Furthermore, heat-stressed fibroblasts produced higher level of total proteins than control cells. In SDS-PAGE analysis, a 70 kDa protein band was observed in stressed cell culture supernatants which appeared as two acidic spots with close pI in the two-dimensional electrophoresis. To evaluate the immunogenic properties of fibroblast-derived heat shock proteins (HSPs), the serum immunoglobulin-G (IgG) was measured by ELISA in 50 CAD patients and 50 normal subjects who had been diagnosed through angiography. Interestingly, the level of anti-HSP antibody was significantly higher in non-CAD individuals in comparison with the patient's group (p < 0.05). The odds ratio for CAD was 5.06 (95%CI = 2.15-11.91) in cut-off value of 30 AU/mL of anti-HSP antibody. Moreover, ROC analysis showed that anti-HSP antibodies had a specificity of 74% and a sensitivity of 64%, which is almost equal to 66% sensitivity of exercise stress test (EST) as a CAD diagnostic method. These data revealed that fibroblast-derived HSPs are suitable for the diagnosis and management of CAD through antibody production.