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IntroductionIntensive agriculture, despite high production, has adverse environmental effects, mainly due to the use of pesticides and chemical fertilizers. Therefore, we need alternative agricultural systems that are more economically and environmentally sustainable to produce crops. One of the sustainable methods in the production of agricultural products is intercropping. Intercropping of two or more species in a plot of land can increase biodiversity and resource utilization as agricultural perspective, which in turn can lead to increased yield stability. Intercropping uses resources more efficiently than monoculture, preventing the growth and spread of weeds by shading and suffocating weeds, and in some cases with allelopathic. Intercropping of cereals and legumes is recommended for the development of sustainable food production systems, especially in planting systems based on reduced consumption of foreign inputs. The importance of these systems depends on the nitrogen stabilized by the legumes. The aim of this experiment was to study the effects of row intercropping of barley and vetch and different levels of ammonium nitrate fertilizer on weed biomass, yield components and yield of two species in Karaj climatic condition.Materials and MethodsThis experiment was performed as a factorial split plot based on randomized complete block design in 2019-2020 cropping year in the research farm of the Agriculture and Natural Resources, University of Tehran. Main plots included three levels of ammonium nitrate fertilizer (0, 35 and 70 kg.ha-1) and sub-plots include different ratios of barley and vetch (100% barley, 80% barley: 20% vetch, 80% barley: 45% vetch, 80% barley: 70% vetch, 100% vetch, 80% vetch: 20% barley, 80% vetch: 45% barley, 80% vetch: 70% barley) weeding and non-weeding were in three replications. Plant density in sole barley and vetch were 250 plants per square meter. The method of cultivation in this study was additive intercropping. Seeds were sown on November 6th. The first stage of fertilization was done simultaneously with planting and one third was added to each plot and the second and third stages of fertilization were performed in two stages of stem emergence and spike emergence, respectively from ammonium nitrate fertilizer source. The final harvest was done on July 28th. Data were analyzed using SAS 9.1 software. The least significant difference test (P≤0.05) was used to compare the means.Results and DiscussionThe highest barley grain yield (432.44 g) was related to sole barley, 70 kg ammonium nitrate and weed control, which was not significantly different with 80% B: 45%V, 70 kg ammonium nitrate and weed control. Also, the highest yield of vetch grain (161.47 g) was obtained in sole vetch, application of 70 kg ammonium nitrate and weed control treatment, which was not significantly different with 80%V: 20%B intercropping, application of 70 kg ammonium nitrate and weed control treatment. Weeds in this experiment include: Wild oats (Avena fatua), ryegrass (Lolium temulentum), Bromus (Bromus tectorum), Fox tail (Alopecurus myosuroides), Wild mustard (Sinapis arvensis), Creeping Thistle (Cirsium arvense), London rocket (Sisymbrium irio), Cockspur grass (Echinochloa crus-galli) and Cornflower (Centaurea cyanus). The highest dry weight of weed (231.62 g) was observed in sole vetch, application of 70 kg.ha-1 ammonium nitrate fertilizer treatment. The highest land equivalent ratio LER (1.68) is related to 80% V: 70%B, non-application of ammonium nitrate fertilizer in weed control condition. Intercropping was successful in controlling weeds and using resources, thereby increasing the yield of plants in the experiment.ConclusionThe results obtained from the experiment showed that all different systems of barley and vetch intercropping had land equivalent ratio higher than one, which indicates the superiority of intercropping over pure crops in the land use and crop production. Intercropping treatments were also able to control weeds. Intercropping with high ability to suppress weeds were able to use more resources. On the other hand, vetch biologically stabilized nitrogen was able to reduce the need for fertilizer in plants.

Glioma is a highly lethal brain cancer in humans. Despite advancements in treatment, the prognosis for patients remains unfavorable. Epigenetic factors, along with their interactions and non-coding RNAs (ncRNAs), are crucial in glioma cells' development and aggressive characteristics. MicroRNAs (miRNAs) are a class of small non-coding RNAs (ncRNAs) that modulate the expression of various genes by binding to target mRNA molecules. They play a critical role in regulating essential biological mechanisms such as cell proliferation and differentiation, cell cycle, and apoptosis. MiR-146a/miR-146b is a significant and prevalent miRNA whose expression alterations are linked to various pathological changes in cancer cells, as well as the modulation of several cellular signaling pathways, including NF-κB, TGF-β, PI3K/Akt, and Notch-1. Scientists may identify novel targets in clinical settings by studying the complicated link between Mir-146a/mir-146b, drug resistance, molecular pathways, and pharmacological intervention in gliomas. Additionally, its interactions with other ncRNAs, such as circular RNA and long non-coding RNA, contribute to the pathogenesis of glioma. As well as miR-146 holds potential as both a diagnostic and therapeutic biomarker for patients with this condition. In the current review, we investigate the significance of miRNAs in the context of glioma, with a particular focus on the critical role of Mir-146a/mir-146b in glioma tumors. Additionally, we examined the clinical relevance of this miRNA, highlighting its potential implications for diagnosis and treatment., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Background: Metastatic Triple-negative Breast Cancer (mTNBC) is the most aggressive form of breast cancer, with a greater risk of metastasis and recurrence. Research studies have published in-depth analyses of the advantages and disadvantages of pembrolizumab, and early data from numerous trials suggests that patients with mTNBC have had remarkable outcomes. This meta-analysis compares the data from numerous relevant studies in order to evaluate the safety and efficacy of pembrolizumab monotherapy or combination therapies for mTNBC., Methods: To identify eligible RCTs, a thorough literature search was carried out using electronic databases. CMA software was utilized to perform heterogeneity tests using fixed and random-effects models., Results: According to our pooled data, the median Progression-free Survival (PFS) was 2.66 months, and the median overall survival (OS) was 12.26 months. Furthermore, by comparing efficacy indicators between PD-L1-positive and PD-L1-negative groups, a correlation was found between the overexpression of PD-L1 with OS, PFS, and ORR. Patients with PD-L1-positive tumors had a higher response rate, with an ORR of 21.1%, compared to the patients with PD-L1-negative tumors. The ORR for first-line immunotherapy was higher than that of ≥second-line immunotherapy. In addition, pembrolizumab plus combination treatment resulted in a pooled incidence of immune- related adverse events of 22.7%., Conclusion: A modest response to pembrolizumab monotherapy was detected in the mTNBC patients. Furthermore, a better outcome from pembrolizumab treatment may be predicted by PD-L1-- positive status, non-liver/lung metastases, combination therapy, and first-line immunotherapy. Pembrolizumab, in combination with chemotherapy, may be more beneficial for patients whose tumors are PD-L1 positive., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Preoperative hemorrhage can be reduced using anti-fibrinolytic medicine tranexamic acid (TXA). During surgical procedures, local administration is being used more and more frequently, either as an intra-articular infusion or as a perioperative rinse. Serious harm to adult soft tissues can be detrimental to the individual since they possess a weak ability for regeneration. Synovial tissues and primary fibroblast-like synoviocytes (FLS) isolated from patients were examined using TXA treatment in this investigation. FLS is obtained from rheumatoid arthritis (RA), osteoarthritis (OA), and anterior cruciate ligament (ACL)-ruptured patients. The in vitro effect of TXA on primary FLS was investigated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell viability assays for cell death, annexin V/propidium iodide (PI) staining for apoptotic rate, real-time PCR for p65 and MMP-3 expression, and enzyme-linked immunosorbent assay (ELISA) for IL-6 measurement. MTT assays revealed a significant decrease in cell viability in FLS of all groups of patients following treatment with 0.8-60 mg/ml of TXA within 24 h. There was a significant increase in cell apoptosis after 24 h of exposure to TXA (15 mg/ml) in all groups, especially in RA-FLS. TXA increases the expression of MMP-3 and p65 expression. There was no significant change in IL-6 production after TXA treatment. An increase in receptor activator of nuclear factor kappa-Β ligand (RANK-L) production was seen only in RA-FLS. This study demonstrates that TXA caused significant synovial tissue toxicity via the increase in cell death and elevation of inflammatory and invasive gene expression in FLS cells., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Rheumatoid arthritis (RA) is a common inflammatory joint disease. Because inflammation and nitrosative stress play an important role in the pathogenesis of RA, drugs that have antioxidant and anti-inflammatory effects can be effective as adjuvant treatment in these patients. Selenium is a compound that has been shown in recent studies to have anti-inflammatory and antioxidant effects. Therefore, the aim of this study was to investigate the effect of oral selenium on the reduction of clinical symptoms and joint pain in patients with RA. Fifty-one patients with moderate and severe RA were randomly divided into selenium and placebo groups. The first group of patients received selenium at a dose of 200 μg twice a day for 12 weeks along with standard RA interventions and treatments, and the second group received standard treatments of RA along with a placebo. Clinical symptoms were evaluated with standard indicators to evaluate disease activity before and after the intervention in the 12th week. Examination of clinical symptoms at the end of the study showed that in the selenium group and after 12 weeks, a reduction in clinical symptoms and joint pain were observed, which was statistically significant compared with before the study began. Meanwhile, no significant changes were observed in the patients of the placebo group in terms of reducing symptoms and joint pains. A dose of 200 μg of oral selenium twice a day for 12 weeks can significantly reduce clinical symptoms and joint pain in patients with RA., (© 2023, The American College of Clinical Pharmacology.)

The main challenge of the twenty-first century is to find a balance between environmental sustainability and crop productivity in a world with a rapidly growing population. Soil health is the backbone of a resilient environment and stable food production systems. In recent years, the use of biochar to bind nutrients, sorption of pollutants, and increase crop productivity has gained popularity. This article reviews key recent studies on the environmental impacts of biochar and the benefits of its unique physicochemical features in paddy soils. This review provides critical information on the role of biochar properties on environmental pollutants, carbon and nitrogen cycling, plant growth regulation, and microbial activities. Biochar improves the soil properties of paddy soils through increasing microbial activities and nutrient availability, accelerating carbon and nitrogen cycle, and reducing the availability of heavy metals and micropollutants. For example, a study showed that the application of a maximum of 40 t ha -1 of biochar from rice husks prior to cultivation (at high temperature and slow pyrolysis) increases nutrient utilization and rice grain yield by 40%. Biochar can be used to minimize the use of chemical fertilizers to ensure sustainable food production., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Lung cancer continues to be the leading cause of cancer-related death worldwide. In the last decade, significant advancements in the diagnosis and treatment of lung cancer, particularly NSCLC, have been achieved with the help of molecular translational research. Among the hopeful breakthroughs in therapeutic approaches, advances in targeted therapy have brought the most successful outcomes in NSCLC treatment. In targeted therapy, antagonists target the specific genes, proteins, or the microenvironment of tumors supporting cancer growth and survival. Indeed, cancer can be managed by blocking the target genes related to tumor cell progression without causing noticeable damage to normal cells. Currently, efforts have been focused on improving the targeted therapy aspects regarding the encouraging outcomes in cancer treatment and the quality of life of patients. Treatment with targeted therapy for NSCLC is changing rapidly due to the pace of scientific research. Accordingly, this updated study aimed to discuss the tumor target antigens comprehensively and targeted therapy-related agents in NSCLC. The current study also summarized the available clinical trial studies for NSCLC patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

COVID-19 vaccines exhibit high levels of immunogenicity in the overall population. Data on the effects of immunomodulators on the consequences of COVID-19 in patients with Immune-mediated inflammatory diseases (IMIDs) remains scarce. This systematic review aimed to evaluate the immune responses to the COVID-19 vaccines in IMID patients receiving methotrexate (MTX) compared to healthy individuals. A comprehensive literature search was carried out using electronic databases such as PubMed, Web of Science, Scopus, Google Scholar, and Embase up to August 2022 to identify eligible RCTs evaluating the effect of MTX on immune responses in patients with COVID-19. The PRISMA checklist protocol was applied for the quality assessment of the selected trials. Our findings demonstrated that MTX lowered the responses of T cells and antibodies in IMID patients compared to healthy controls. We also discovered that young age (<60 years) was the main parameter influencing the antibody response after vaccination, while MTX had little effect. Following vaccination, MTX-hold and age were considered the main factors influencing the antibody response. In patients older than 60 years of age, the time point of 10 days of MTX discontinuation was critical to boosting the humoral response to anti-SARS-CoV-2 IgG. Because many IMID patients did not have adequate humoral and cellular responses, our findings highlighted the importance of second or booster doses of vaccine and temporary MTX discontinuation. As a result, it implies that individuals with IMIDs should be subjected to more research, particularly humoral and cellular immunity efficiency trials after COVID-19 vaccination, until credible information is achieved., Competing Interests: Declaration of Competing Interest The authors declared that they have no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

COVID-19 vaccines approved by the Food and Drug Administration have been studied mainly in healthy individuals and there is limited information on their immunogenicity in patients with autoimmune diseases. Therefore, the current systematic review and meta-analysis study, aimed to comprehensively investigate the immunogenicity of these vaccines in patients with autoimmune inflammatory rheumatoid diseases (AIRDs). A comprehensive literature search was performed on various databases, including Google Scholar, PubMed, Web of Science, EMBASE, and Cochrane Library, to select cohort and randomized clinical trial (RCT) studies up to January 2022. Also, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist protocol and the I 2 statistic were used for quality assessment and heterogeneity tests of the selected studies. Fixed and random-effects models were estimated based on the heterogeneity tests, and pooled data were determined as the ratio of mean (ROM) with a 95% confidence interval (CI). As a result, we found that vaccines can cause favorable immunogenicity and antibody response in vaccinated AIRD patients; however, older age and the concomitant consumption of conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and biologic DMARDs (bDMARDs) could significantly reduce the vaccine immunogenicity. Consequently, our findings revealed significant humoral responses (seropositive) in AIRD patients following the administration of COVID-19 vaccines., (© 2023 Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Rheumatoid arthritis (RA) as a chronic inflammatory disorder affects around 1% of the world population. Fibroblast-like synoviocyte (FLS), one of the main cells in RA pathogenesis is characterized by hyperproliferation and resistance to apoptosis resulting to synovial hyperplasia. Dimethyl fumarate (DMF) has been licensed for the treatment of multiple sclerosis (MS) and psoriasis; however, its role in RA is unknown. DMF has immunomodulatory properties and may be considered as therapeutic approach in RA treatment. In this study, we aimed to investigate the effect of DMF on controlling FLS-mediated synovial inflammation and joint destruction in RA. FLSs were isolated from synovial tissues of 8 patients with RA and treated with DMF. Apoptosis rate was analyzed by Annexin V-FITC. Cell proliferation was measured by carboxyfluorescein succinimidyl ester (CFSE) dye. The matrix metalloproteinase 3 (MMP3) and NF-кB pathway protein (p65) mRNA expression were evaluated by RT-PCR. Also, the IL-6 production and lactate release were measured in FLS supernatant. DMF treatment decreased the cell proliferation and increased apoptosis in a dose dependent manner. DMF-treated FLS showed a reduction in IL-6 and lactate release. Moreover, it was revealed that DMF inhibited the expression of p65 and MMP3. Our data demonstrate that DMF treatment suppresses the aggressive and inflammatory features of RA FLSs. Our Results suggest that DMF might be expected to be evaluated as a therapy for RA., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Several successful attempts have been recorded with PD-L1 blockade via atezolizumab monotherapy or combination therapy with chemotherapy in patients with metastatic triple-negative breast cancer (mTNBC). Due to the lack of a large-scale study, we present a meta-analysis aimed at evaluating the safety and efficacy of this promising strategy in patients with mTNBC., Methods: A comprehensive literature search was conducted using electronic databases to identify eligible RCTs. Twelve studies, including 2479 mTBNC patients treated with atezolizumab monotherapy or in combination with chemotherapy, were included up to January 2022. The PRISMA checklist protocol and the I2 statistic were applied for quality assessment and heterogeneity tests of the selected trials, respectively. Fixed and random-effects models were estimated based on the heterogeneity tests, and statistical analysis was performed using CMA., Results: Our pooled findings demonstrated that the median overall survival (OS) and progression-free survival (PFS) were 16.526 and 5.814 months in mTNBC patients, respectively. Furthermore, when comparing efficacy indicators between PD-L1-positive and PD-L1-negative groups, mTNBC patients with PD-L1 had better OS, PFS, and ORR than PD-L1-negative patients. Also, the immune-related adverse event incident for alopecia was higher (51.9%) than other complications across atezolizumab therapy., Conclusion: Moreover, the pooled analysis indicated that the overall rate of lung metastasis following atezolizumab therapy was 42.8%, which was higher than the rates of metastasis in bone (26.9%), brain (5.4%), and lymph node (6.5%). Atezolizumab showed a manageable safety profile and had promising and durable anti-tumor efficacy in TMBC patients. Higher PD-L1 expression may be closely correlated with better clinical efficacy., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background/objective: Naringenin is a member of the flavonoid family that can perform many biological processes to treat a wide range of inflammatory diseases and pathological conditions related to oxidative stress (OS). Naringenin immunomodulatory activities have been the subject of recent research as an effective alternative treatment for autoimmune disorders. The effects of naringenin on the levels of inflammatory biomarkers and OS factors in animal models of autoimmune disorders (ADs) were studied in this meta-analysis., Methods: Up until January 2022, electronic databases such as Cochrane Library and EMBASE, PubMed, Web of Science, and Scopus were used to conduct a comprehensive literature search in English language. To evaluate the effect of naringenin on inflammatory mediators, such as TNF-α, IL-6, IL-β, IFN-γ, NF-κB, and nitric oxide, and OS biomarkers, such as CAT, SOD, GPx, GSH and MDA, in AD models, we measured the quality assessment and heterogeneity test using the PRISMA checklist protocol and I 2 statistic, respectively. A random-effects model was employed based on the heterogeneity test, and then pooled data were standardized as mean difference (SMD) with a 95% confident interval (CI)., Results: We excluded all clinical trials, cell experiment studies, animal studies with different parameters, non-autoimmune disease models, and an inadequate series of studies for quantitative synthesis. Finally, from 627 potentially reports, 12 eligible studies were included in the meta-analysis. Data were collected from several groups. Of these, 153 were in the naringenin group and 149 were in the control group. Our meta-analysis of the pooled data for the parameters of inflammation and OS indicated that naringenin significantly reduced the levels of NF-κB (SMD - 3.77, 95% CI [- 6.03 to - 1.51]; I 2  = 80.1%, p = 0.002), IFN-γ (SMD - 6.18, 95% CI [- 8.73 to - 3.62]; I 2  = 53.7%, p = 0.115), and NO (SMD - 3.97, 95% CI [- 5.50 to - 2.45]; I 2  = 73.4%, p = 0.005), IL-1β (SMD - 4.23, 95% CI [- 5.09 to - 3.37]; I 2  = 0.0%, p = 0.462), IL-6 (SMD - 5.84, 95% CI [- 7.83 to - 3.85]; I 2  = 86.5%, p < 0.001), and TNF-α (SMD - 5.10, 95% CI [- 6.34 to - 3.86]; I 2  = 74.7%, p < 0.001). These findings also demonstrated the efficacy of naringenin on increasing the levels of CAT (SMD 4.19, 95% CI [1.33 to 7.06]; I 2  = 79.9%, p = 0.007), GSH (SMD 4.58, 95% CI [1.64 to 7.51]; I 2  = 90.5%, p < 0.001), and GPx (SMD 9.65, 95% CI [2.56 to 16.74]; I 2  = 86.6%, p = 0.001) and decreasing the levels of MDA (SMD - 3.65, 95% CI [- 4.80 to - 2.51]; I 2  = 69.4%, p = 0.001) than control groups. However, treatment with naringenin showed no statistically difference in SOD activity (SMD 1.89, 95% CI [- 1.11 to 4.89]; I 2  = 93.6%, p < 0.001)., Conclusion: Overall, our findings revealed the immunomodulatory potential of naringenin as an alternative treatment on inhibition of inflammation and OS in several autoimmune-related diseases. Nevertheless, regarding the limitation of clinical trials, strong preclinical models and clinical settings in the future are needed that address the effects of naringenin on ADs. Before large-scale clinical studies, precise human pharmacokinetic investigations are required to determine the dosage ranges and evaluate the initial safety profile of naringenin., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Various reports show the beneficial effect of naringenin on the development of cancer. We hypothesized that naringenin suppresses cancer cells by activating intrinsic and extrinsic apoptosis pathways. This systematic review and meta-analysis was performed to reveal the effect of naringenin on cancer inhibition in vitro and in vivo by altering apoptotic factors. Literature search was carried out using electronic databases including PubMed, Web of Science, Scopus, Google Scholar, and Embase up to February 2021. The heterogeneity test of the included studies was performed using the PRISMA checklist protocol and I 2 statistic, respectively. Pooled standard mean difference and effect size (ES) with 95% confident interval (CI) were used to evaluate each relationship. A total of 32 articles were enrolled in our final analysis. Meta-analysis of the pooled findings for apoptosis, viability percentage, and apoptotic factors determined that treatment with naringenin affects viability and apoptosis in cancer cells in vitro and in vivo. Moreover, the results of in vitro experiments showed that naringenin increases the activity of caspase-3 (ES, 5.04; 95% CI, 2.61-7.47; I 2  = 99.9), caspase-9 (ES, 2.99; 95% CI, 2.47-3.51; I 2  = 93.7%), caspase-8 (ES, 2.86; 95% CI, 1.11-4.61; I 2  = 99.7%), and Bax expression (ES, 2.73; 95% CI, 1.91-3.55; I 2  = 99.4%) in cancer cells. It also increased the apoptotic rate and the activity of caspase-3 and caspase-9 in tumor-bearing animals. Overall, our findings highlight the potential therapeutic effects of naringenin in cancer inhibition through caspases cascade., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background/objective: Apigenin is a member of the flavonoid family that can regulate various biological processes, which is characterized as a treatment of different inflammatory disorders and pathological problems associated with oxidative stress (OS). Recent research has focused on apigenin immunomodulatory properties as a potential treatment for different types of lung injuries. This meta-analysis was designed to determine the impact of apigenin treatment on inflammatory markers and OS parameters in animal models of lung injuries., Methods: The comprehensive literature search was conducted using electronic databases such as Google Scholar, PubMed, Web of Science, Scopus, and Embase up to August 2021. To assess apigenin's effect on inflammatory mediators and OS biomarkers in lung injury animal models, we used the I 2 statistic to determine the heterogeneity. We then pooled data as standardized mean difference (SMD) with a 95% confidence interval (CI)., Results: Our meta-analysis of the pooled data for inflammatory biomarkers demonstrated that the apigenin administration significantly decreased the NF-κB expression (SMD - 1.60, 95% CI [- 2.93 to - 0.26]; I 2  = 89.0%, p < 0.001), IL-1β (SMD - 4.30, 95% CI [- 6.24 to - 2.37]; I 2  = 67.3%, p = 0.047), IL-6 (SMD - 4.10, 95% CI [- 5.04 to - 3.16]; I 2  = 72.6%, p < 0.001), TNF-α (SMD - 3.74, 95% CI [- 4.67 to - 2.82]; I 2  = 84.1%, p < 0.001), and TNF-α gene expression (SMD - 3.44, 95% CI [- 4.44 to - 2.43]; I 2  = 0.0%, p = 0.622). This study also indicated the efficacy of apigenin in increasing the level of CAT (SMD 4.56, 95% CI [3.57 to 5.55]; I 2  = 15.3%, p = 3.15), GSH (SMD 5.12, 95% CI [3.53 to 6.70]; I 2  = 77.6%, p < 0.001), and SOD (SMD 3.45, 95% CI [2.50 to 4.40]; I 2  = 79.2%, p < 0.001), and decreasing the level of MDA (SMD - 3.87, 95% CI [- 5.25 to - 2.49]; I 2  = 80.3%, p < 0.001) and MPO (SMD - 4.02, 95% CI [- 5.64 to - 2.40]; I 2  = 88.9%, p < 0.001), TGF- β (SMD - 3.81, 95% CI [- 4.91 to - 2.70]; I 2  = 73.4%, p = 0.001) and W/D level (SMD - 3.22, 95% CI [- 4.47 to - 1.97]; I 2  = 82.1%, p < 0.001) than control groups., Conclusion: Overall, our findings showed the immunomodulatory potential of apigenin as an alternative treatment for the suppression of inflammatory responses and OS in different types of lung injury diseases. Nevertheless, due to the paucity of clinical studies, reliable preclinical models, and clinical settings, evaluating the influence of apigenin on lung injury is required in the future. Before conducting large-scale clinical trials, detailed human pharmacokinetic studies are also needed to establish dosage ranges and determine the initial safety and tolerability of apigenin., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Despite recent advances in therapy, cancer still is a devastating and life-threatening disease, motivating novel research lines in oncology. Cold physical plasma, a partially ionized gas, is a new modality in cancer research. Physical plasma produces various physicochemical factors, primarily reactive oxygen and nitrogen species (ROS/RNS), causing cancer cell death when supplied at supraphysiological concentrations. This review outlines the biomedical consequences of plasma treatment in experimental cancer therapy, including cell death modalities. It also summarizes current knowledge on intracellular signaling pathways triggered by plasma treatment to induce cancer cell death. Besides the inactivation of tumor cells, an equally important aspect is the inflammatory context in which cell death occurs to suppress or promote the responses of immune cells. This is mainly governed by the release of damage-associated molecular patterns (DAMPs) to provoke immunogenic cancer cell death (ICD) that, in turn, activates cells of the innate immune system to promote adaptive antitumor immunity. The pivotal role of the immune system in cancer treatment, in general, is highlighted by many clinical trials and success stories on using checkpoint immunotherapy. Hence, the potential of plasma treatment to induce ICD in tumor cells to promote immunity targeting cancer lesions systemically is also discussed., Competing Interests: The authors declare that no conflict of interest exists with the publication of this article., (Copyright © 2021 Fatemeh Faramarzi et al.)

Statins are widely accepted as first-choice agents for the prevention of lipid-related cardiovascular diseases. These drugs have both anti-inflammatory and anti-oxidant properties, which may also make them effective as potential treatment marked by perturbations in these pathways, such as some neuropsychiatric disorders. In this narrative review, we have investigated the effects of statin therapy in individuals suffering from major depressive disorder (MDD), schizophrenia, anxiety, obsessive-compulsive disorder (OCD), bipolar disorder (BD), delirium, and autism spectrum disorders using a broad online search of electronic databases. We also explored the adverse effects of these drugs to obtain insights into the benefits and risks associated with their use in the treatment of these disorders. Lipophilic statins (including simvastatin) because of better brain penetrance may have greater protective effects against MDD and schizophrenia. The significant positive effects of statins in the treatment of anxiety disorders without any serious adverse side effects were shown in numerous studies. In OCD, BD, and delirium, limitations, and contradictions in the available data make it difficult to draw conclusions on any positive effect of statins. The positive effects of simvastatin in autism disorders have been evaluated in only a small number of clinical trials. Although some studies showed positive effect of statins in some neuropsychiatric disorders, further prospective studies are needed to confirm this and define the most effective doses and treatment durations.

CXCR4 is a member of CXC-type and G protein-coupled receptors that can conduce many biological processes, including hemostasis, migration, and adhesion of different types of immune cells. Also, the contribution of CXCR4 in metastasis cascade and development of various malignancies has been addressed in previous reports. This meta-analysis was performed to explore whether the CXCR4 expression affects prognosis and clinicopathologic features in melanoma cancer. Our study involved 656 melanoma patients from 13 reports by detailed literature search from PubMed, Embase, Web of Science, and Google Scholar up to April 2021. To evaluate the association between CXCR4 expression and clinicopathological features of melanoma, we calculated odds ratios (ORs) with its 95% confidence intervals (CIs). We indicated that the CXCR4 overexpression was obviously correlated with ulceration (OR = 0.56, 95% CI: 0.38 to 0.74; I 2  = 0.0%, P = 0.999), tumor thickness (OR = 0.56, 95% CI: 0.38 to 0.74; I 2  = 0.0%, P = 0.999) and lymph node metastasis (OR = 8.54, 95% CI: 1.04 to 16.04; I 2  = 98.9, P < 0.0001). In conclusion, our results reveal that CXCR4 is involved in enhancing the progression and metastasis of melanoma, and further clinical studies are necessary to investigate the role of CXCR4 as a diagnostic and therapeutic biomarker through the progress of melanoma cancer., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objective: Cell culture technology has become a popular method in the field of cell biology, pharmacology, and medical researches. Primary cells represent the normal physiological condition of human cells. Fibroblasts are the most common native cells of connective tissue that play a crucial role in the entire pathogenesis of various disorders, such as rheumatoid arthritis (RA). Fibroblast-like synoviocytes (FLSs), which overlie the loose connective tissue of the synovial sublining, are known to be the central mediators of joint damage. The most routine approach for the isolation of FLS is an enzymatic digestion of synovial tissue. This experimental study is designed to introduce an easy, fast, and high-throughput method compared with enzymatic digestion for isolation of FLS., Methods: The synovial tissue and synovial fluid (SF) samples were collected from eight patients with RA who underwent routine knee replacement surgery. Synovial tissue was incubated with collagenase VIII enzyme, while SF was washed with a similar volume of phosphate-buffered saline. The cells were further subcultured and stored based on the standard protocols. The purity of isolated synoviocytes was confirmed using flow cytometry analysis., Results: Isolation of FLS from SF was more successful with a faster rate, 3-5 days after culture. The morphological assessment and flow cytometry analysis confirmed the purity of SF-derived cells in passage 4., Conclusions: SF could be a more accessible source of FLS than synovial tissue. Obtaining primary FLS from SF is a simple, fast, and cost-effective way to have a large-scale cell during a short time.

Mitochondria are ubiquitous membrane-bound organelles that not only play a key role in maintaining cellular energy homeostasis and metabolism but also in signaling and apoptosis. Aryl hydrocarbons receptors (AhRs) are ligand-activated transcription factors that recognize a wide variety of xenobiotics, including polyaromatic hydrocarbons and dioxins, and activate diverse detoxification pathways. These receptors are also activated by natural dietary compounds and endogenous metabolites. In addition, AhRs can modulate the expression of a diverse array of genes related to mitochondrial biogenesis and function. The aim of the present review is to analyze scientific data available on the AhR signaling pathway and its interaction with the intracellular signaling pathways involved in mitochondrial functions, especially those related to cell cycle progression and apoptosis. Various evidence have reported the crosstalk between the AhR signaling pathway and the nuclear factor κB (NF-κB), tyrosine kinase receptor signaling and mitogen-activated protein kinases (MAPKs). The AhR signaling pathway seems to promote cell cycle progression in the absence of exogenous ligands, whereas the presence of exogenous ligands induces cell cycle arrest. However, its effects on apoptosis are controversial since activation or overexpression of AhR has been observed to induce or inhibit apoptosis depending on the cell type. Regarding the mitochondria, although activation by endogenous ligands is related to mitochondrial dysfunction, the effects of endogenous ligands are not well understood but point towards antiapoptotic effects and inducers of mitochondrial biogenesis., (Copyright © 2021 Elsevier B.V. and Mitochondria Research Society. All rights reserved.)

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 I 2 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); I 2  = 93.1%, p < 0.001], IL-8 [SMD: - 2.24, 95% CI: (- 2.68 to - 1.8); I 2  = 79.6%, p = 0.001], MMP-2 [SMD: - 1.49, 95% CI: (- 1.85 to - 1.14); I 2  = 76.3%, p = 0.005] and MMP-9 [SMD: - 1.58, 95% CI: (- 1.97 to - 1.19); I 2  = 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); I 2  = 21.8%, p = 0.280], IL-6 [SMD: - 1.56, 95% CI: (- 1.73 to - 1.39); I 2  = 0.0%, p = 0.683], IL-1β [SMD: - 3.34, 95% CI: (- 3.58 to - 3.11); I 2  = 0.0%, p = 0.561], catalase (CAT) [SMD: 1.40, 95% CI: (1.15 to 1.65); I 2  = 0.0%, p = 0.598], superoxide dismutase (SOD) [SMD: 2.42, 95% CI: (2.12 to 2.71); I 2  = 0.0%, p = 0.986], glutathione peroxidase (GPx) [SMD: 2.80, 95% CI: (2.49 to 3.11); I 2  = 0.0%, p = 0.543]], glutathione (GSH) [SMD: 4.71, 95% CI: (4.26 to 5.16); I 2  = 6.1%, p = 0.302] and thiobarbituric acid reactive substances (TBARS) [SMD: - 3.20, 95% CI: (- 3.53 to - 2.86); I 2  = 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.

Objectives: Despite extensive caffeine use in preterm infants, the pharmacokinetics (PKs) data are limited because of the studies are complicated to do in these patients. This research was investigated the PK profile of two various dosages of caffeine in premature neonates., Materials and Methods: The PK values of caffeine in premature neonates with Apnea were predicted by using all of computer-based simulation (Simcyp ® ), population-based PK, and modeling (P-Pharm ® ). We assayed the plasma levels of caffeine in two groups. The information was analyzed utilizing nonlinear mixed-effects modeling approach. The PK parameters were assessed simulating virtual clinical considers with subjects got 20 mg. kg -1 of caffeine in both groups, which was followed by a 5 mg. kg -1 once daily in Group 1 or 2.5 mg. kg -1 twice daily in Group 2. All statistical analysis was executed utilizing SSPS issue 19 and a P value of 0.05 was chosen significance., Results: In the present study, the means CL, volume of distribution, and T1/2 of caffeine in preterm infants were 0.0476 L. h -1 , 1.1081 L, 16.2284 h, respectively. Whereas our simulated means by Simcyp were 0.090 L. h -1 , 1.841 L, and 14.653 h in Group 1 and 16.223 h in Group 2, respectively., Conclusions: There was overall good agreement between predicted and measured PK values in our study. This study provides an initial demonstration of Simcyp simulation advantage on anticipating of PK parameters., Competing Interests: None

The viral infection due to the new coronavirus or coronavirus disease 2019 (COVID-19), which was reported for the first time in December 2019, was named by the World Health Organization (WHO) as Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV2), because of the very similar genome and also its related symptoms to SARS-CoV1. The ongoing COVID-19 pandemic with significant mortality, morbidity, and socioeconomic impact is considered by the WHO as a global public health emergency. Since there is no specific treatment available for SARS-CoV2 infection, and or COVID-19, several clinical and sub-clinical studies are currently undertaken to find a gold-standard therapeutic regimen with high efficacy and low side effect. Based on the published scientific evidence published to date, we summarized herein the effects of different potential therapies and up-to-date clinical trials. The review is intended to help readers aware of potentially effective COVID-19 treatment and provide useful references for future studies.

Neurophysiological observations are clarifying how astrocytes can actively participate in information processing and how they can encode information through frequency and amplitude modulation of intracellular Ca 2+ signals. Consequently, hardware realization of astrocytes is important for developing the next generation of bio-inspired computing systems. In this paper, astrocytic calcium oscillations and neuronal firing dynamics are presented by De Pittà and IF (Integrated & Fire) models, respectively. Considering highly nonlinear equations of the astrocyte model, linear approximation and single constant multiplication (SCM) techniques are employed for efficient hardware execution while maintaining the dynamic of the original models. This low-cost hardware architecture for the astrocyte model is able to show the essential features of different types of Ca 2+ modulation such as amplitude modulation (AM), frequency modulation (FM), or both modes (AFM). To show good agreement between the results of original models simulated in MATLAB and the proposed digital circuits executed on FPGA, quantitative, and qualitative analyses including phase plane are done. This new neuromorphic circuit of astrocyte is able to successfully demonstrate AM/FM/AFM calcium signaling in its real operation on FPGA and has applications in self-repairing systems. It also can be employed as a subsystem for linking biological cells to artificial neuronal networks using astrocytic calcium oscillations in future research., (Copyright © 2019 Faramarzi, Azad, Amiri and Linares-Barranco.)

Gastric cancer is the fourth common cancer and the second leading cause of cancer death worldwide. Due to lack of adequate information on the side effects of chemotherapy regimens in treatment of gastric cancer, this study was aimed to determine the side effects of two common chemotherapy regimens of gastric cancer. This prospective study was conducted in Emam Khomeini Educational Hospital and Touba Polyclinic; both are affiliated to Mazandaran University of Medical Sciences. The frequency and severity of side effects of chemotherapy were recorded based on the National Cancer Institution (NCI) Toxicity Criteria (version 2). DCF (Docetaxel, Cisplatin, 5FU) and FOLFOX (Folinic acid, 5FU, Oxaliplatin) adverse reactions were compared using SPSS 16 software. One hundred twenty five chemotherapy cycles administered to seventy four patients were assessed. The most common used regimens were DCF (70%) and FOLFOX (16%). The incidence of vomiting was higher with DCF compared to FOLFOX (P = 0.049). In more than 50% of cycles, DCF regimen caused diarrhea, while in FOLFOX regimen it was less than 9% (P = 0.002). Stomatitis, visual changes, nausea, skin reactions, and constipation were not significantly different between the two regimens. It seems that the adverse drug reactions of FOLFOX regimen were more favorable than DCF regimen. The results of this study may help clinicians choosing a more favorable chemotherapy regimen especially in patients with a low performance status who have difficulties in tolerating a chemotherapy regimen with a more severe adverse effect profile.

Part one of the present study presented practical Islamic jurisprudential rules and investigated their application to performing medical procedures on nearly dead patients. It was contended that a dying patient could be used in medical education in cases where there is no alternative method, provided the patient voluntarily consents and is not offended. Part two of the present study addresses the issue by referring to the opinions of Islamic jurisprudents to find an appropriate solution to a challenging question in medicine, namely, whether clinical training of medical students on the dying person is permissible. For this purpose, istiftas (petitions or requests for a fatwa ) were sent to prominent contemporary Shiite jurisprudents to solicit their opinions on the use of dying patients for medical education. After exploring the existing views, it was finally concluded that the majority of the jurisprudents allowed the practice in cases of "necessity" and provided that the principles of "no harm" and "consent" were strictly observed. All these terms are found in jurisprudential rules, and we reached the conclusion that Shiite jurisprudents considered this type of training permissible under certain circumstances and in accordance with jurisprudential rules.

End-of-life care and protection of the patient in the near-death moments are part of a patient's rights and the duties of the medical staff. As the beginning and end of human life are most sensitive moments, there are various religious rules associated with them. The ethical issues regarding practicing medical procedures on nearly dead patients are of particular complexity and are consistent with invaluable and profoundly religious recommendations. In addition, the purpose of medical training is to provide physicians with the knowledge and skills necessary to practice appropriately and within legal and ethical frameworks. Therefore, respecting patients' cultural and religious beliefs is an ethically accepted principle in the health systems of different countries and is the basis of respect for human dignity. The present study used a qualitative content analysis to explain how to practice medical procedures on a dying or nearly dead patient in accordance with Islamic jurisprudential rules. It was finally concluded that according to the Islamic jurisprudential rules of "authority", "no harm", "necessity", and "public interest", procedures performed on a dying patient could be used for training purposes under certain circumstances. Nevertheless, such activities should only be done with the patient's permission and provided they cause no unnecessary harassment, and they may take place in the absence of alternative methods.

Background: Caffeine is widely used for prevention of apnea and helps successful extubation from mechanical ventilation. It facilitates the transition from invasive to noninvasive support and reduces duration of continuous positive airway pressure (CPAP) in preterm infants. The optimum caffeine dose in preterm infants has not been well-studied in terms of benefits and risks. We compared efficacy and safety of once versus twice-daily caffeine dose in premature infants., Methods: This study was a randomized clinical trial conducted in Bu-Ali Sina Teaching Hospital, Sari. Patients with gestational age of <37 weeks were included. Both groups received 20 mg/kg loading dose of caffeine intravenously followed by maintenance dose of 5 mg/kg/day in group 1 or 2.5 mg/kg every 12 hours in group 2. Extubation failure, CPAP failure and possibly adverse reactions were evaluated., Results: The mean of gestational age and birth weight were 32.27±3.23 (weeks) and 1824.5±702.54 (gr), respectively. The rate of extubation and CPAP failure and length of NICU stay were lower in twice-daily-group with no statistically significant difference. The means of O 2 saturations on the first three days of caffeine therapy were higher in twice-daily-group. Caffeine was generally safe and well tolerated., Conclusions: This study, which assayed short-term effects of caffeine, showed that twice daily caffeine maintenance dose was related to more benefits in facilitating extubation or prevention of CPAP failure in preterm infants. However, there was not statistically significant difference between two groups., Competing Interests: There is no conflict of interest.

Purpose: Propranolol is the most widely used treatment for cardiovascular diseases. Dosage range in our patients is usually less than the amount mentioned in references. The aim of the present study was to clarify whether pharmacokinetic differences are able to justify the need for the fewer doses in our patients or not. Methods: Twenty healthy volunteers (10 male) at heart center of Mazandaran University of Medical Sciences were studied. Samples of blood were collected before a single oral dose (40 mg) of Propranolol. Blood samples were taken up to 9 hours after dose. Total plasma concentration of Propranolol was measured by HPLC. Population Pharmacokinetic analysis was performed using population pharmacokinetics modeling software P-Pharm. Results: The mean value for oral plasma clearance (CL/F) was 126.59 ml/hr. The corresponding values for apparent volume of distribution (V/F), t1/2 beta, maximum blood concentration (C max), and time to reach the maximum blood concentration (T max) were 334.12 Lit, 1.98 hr, 40.25 ng/ml, and 1.68 hr, respectively. The observed mean values of V/F of propranolol in the present study were comparable with those reported in the literature. However, the mean values of CL/F of propranolol in current study was significantly higher than those reported in other population (P-value<0.001). Conclusion: This study has confirmed that the pharmacokinetic differences are not able to justify over-responsiveness of Iranian population to propranolol. Pharmacodynamic differences in responding to beta blocker drugs by Renin secretion or having a different sensibility to beta receptors might play a role in making our population have a different response to propranolol.

Background: Atorvastatin is a 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor widely used in treatment of hypercholesterolemia and prevention of coronary heart disease and has various pleiotropic effects. In this study, the efficacy of atorvastatin emulgel (2 %) in reducing postoperative pain at rest, pain during defecation and analgesic requirement after open hemorrhoidectomy was investigated., Methods: A total of 66 patients with third- and fourth-degree hemorrhoids undergoing open hemorrhoidectomy were included in this prospective, double-blind, randomized controlled trial. The patients were randomly assigned to either atorvastatin emulgel or placebo immediately after surgery and then every 12 h for 14 days. The primary outcomes were intensity of pain at rest and during defecation, measured with a visual analog scale, and the analgesic requirement, measured by amount of pethidine and acetaminophen consumption, and percent of wound healing., Results: There was no significant difference in the average postoperative pain scores in the first 48 h (P 12h  = 1, P 24h  = 0.128 and P 48h  = 0.079) after the surgery between the two groups, but at the week 1 the pain scores during defecation were considerably lower in the atorvastatin group than in placebo group (P = 0.004), which also was the same at the week 2 (P = 0.03). There was no significant difference in the average pethidine and acetaminophen (mg) administration at 12 h and 24 h between the two groups after surgery. Regarding the data about wound healing, at the week two the healing was much better in the treatment group than it was in control group and the difference was statistically significant (P = 0.04)., Conclusions: Compared with placebo, atorvastatin emulgel reduced postoperative pain at rest and on defecation and could improve the healing process after open hemorrhoidectomy., Trial Registration Number: IRCT201404013014N8.

Introduction: This in vitro study compared the apical sealing ability of three common root end filling materials namely mineral trioxide aggregate (MTA), intermediate restorative material (IRM) and calcium-enriched mixture (CEM) cement using a bacterial leakage model., Methods and Materials: The study was conducted on 83 single-rooted human teeth. Tooth crowns were cut and root canals were prepared using the step-back technique. Apical 3 mm of the roots were cut and a three-mm-deep cavity was prepared using an ultrasonic instrument. The samples were divided into three groups ( n =25) according to the root-end filling material including MTA, IRM and CEM cement. The roots were inserted into cut-end microtubes. After sterilization with ethylene oxide, microtubes were placed in sterile vials containing 10 mL of Brain Heart Infusion (BHI) broth and incubated at 37 ° C and 0.1 mL of Enterococcus faecalis suspension compatible with 0.5 McFarland standard (1.5×10 8 cell/ ml), which was refreshed daily. This procedure was continued for 70 days. The data were analyzed using the chi-square, Kruskal-Wallis and log rank tests. The level of significance was set at 0.05., Results: No significant difference was found in bacterial microleakage among three groups; MTA showed slightly (but not significantly) less microleakage than IRM and CEM. However, the difference in the mean time of microleakage was significant among the groups ( P <0.04) and in MTA samples leakage occurred in a longer time than CEM ( P <0.012)., Conclusion: The three tested root end filling materials had equal sealing efficacy for preventing bacterial leakage.

Aim: The use of 3D information has shown impact in numerous applications in drug design. However, it is often under-utilized and traditionally limited to specialists. We want to change that, and present an approach making 3D information and molecular modeling accessible and easy-to-use 'for the people'., Methodology/results: A user-friendly and collaborative web-based platform (3D-Lab) for 3D modeling, including a blazingly fast virtual screening capability, was developed. 3D-Lab provides an interface to automatic molecular modeling, like conformer generation, ligand alignments, molecular dockings and simple quantum chemistry protocols. 3D-Lab is designed to be modular, and to facilitate sharing of 3D-information to promote interactions between drug designers. Recent enhancements to our open-source virtual reality tool Molecular Rift are described., Conclusion: The integrated drug-design platform allows drug designers to instantaneously access 3D information and readily apply advanced and automated 3D molecular modeling tasks, with the aim to improve decision-making in drug design projects.

Introduction: This in vitro study aimed to assess the effectiveness of a single-file rotary system (OneShape) in reduction of intracanal bacteria., Methods and Materials: Eighty one single-rooted mandibular first premolars with single canals were used. Six samples were selected as aseptic control group. Seventy five remaining specimens were infected by Enterococcus faecalis and incubated for 72 h at 37(°)C. Then they were randomly divided into three groups (n=25). In each group, cleaning and shaping procedures were done using either two conventional rotary systems (ProTaper and iRace), or the single-file system (OneShape). Microbial samples from the intracanal environment were taken by paper points in two steps, before and after instrumentation. Then, they were diluted and plated in blood agar. In order to compare bacterial reduction and turbidity, the Kruskal-Wallis test was used followed by the Chi-Square and Mann-Whitney tests for pairwise comparison. The level of significance was set at 0.05., Results: The control group didn't show any bacterial growth. The pre- and post-instrumentation samples were significantly different between three groups (P=0.02). Hence, there was no significant differences between turbidity of samples (P>0.05)., Conclusion: OneShape system is efficient in bacterial reduction. In this regard ProTaper is the most effective system in intracanal bacterial reduction followed by iRaCe and OneShape, respectively.