Metronidazole, acyclovir and tetrahydrobiopterin may be promising to treat COVID-19 patients, through interaction with interleukin-12.

COVID-19 patients have shown overexpressed serum levels of several pro-inflammatory cytokines, leading to a high mortality rate due to numerous complications. Also, previous studies demonstrated that the metronidazole (MTZ) administration reduced pro-inflammatory cytokines and improved the treatment outcomes for inflammatory disorders. However, the effect and mechanism of action of MTZ on cytokines have not been studied yet. Thus, the current study aimed to identify anti-cytokine therapeutics for the treatment of COVID-19 patients with cytokine storm. The interaction of MTZ with key cytokines was investigated using molecular docking studies. MTZ-analogues, and its structurally similar FDA-approved drugs were also virtually screened against interleukin-12 (IL-12). Moreover, their mechanism of inhibition regarding IL-12 binding to IL-12 receptor was investigated by measuring the change in volume and area. IL-12-metronidazole complex is found to be more stable than all other cytokines under study. Our study also revealed that the active sites of IL-12 are inhibited from binding to its target, IL-12 receptor, by modifying the position of the methyl and hydroxyl functional groups in MTZ. Three MTZ analogues, metronidazole phosphate, metronidazole benzoate, 1-[1-(2-Hydroxyethyl)-5-nitroimidazol-2-yl]-N-methylmethanimine-oxide, and two FDA-approved drugs acyclovir (ACV), and tetrahydrobiopterin (THB) were also found to prevent binding of IL-12 to IL-12 receptor similar to MTZ by changing the surface and volume of IL-12 upon IL-12-drug/ligand complex formation. According to the RMSD results, after 100 ns MD simulations of human IL-12-MTZ/ACV/THB drug complexes, it was also observed that each complex was swinging within a few Å compared to their corresponding docking poses, indicating that the docking poses were reliable. The current study demonstrates that three FDA-approved drugs, namely, metronidazole, acyclovir and tetrahydrobiopterin, are potential repurposable treatment options for overexpressed serum cytokines found in COVID-19 patients. Similar approach is also useful to develop therapeutics against other human disorders.Communicated by Ramaswamy H. Sarma.

Recent advances in cold atmospheric plasma (CAP) for breast cancer therapy.

The serious problems of conventional breast cancer therapy strategies such as drug resistance, severe side effects, and lack of selectivity prompted the development of various cold atmospheric plasma (CAP) devices. Due to its advanced technology, CAP can produce a unique environment rich in reactive oxygen and nitrogen species (RONS), photons, charged ions, and an electric field, making it a promising revolutionary platform for cancer therapy. Despite substantial technological successes, CAP-based therapeutic systems are encounter with distinct limitations, including low control of the generated RONS, poor knowledge about its anticancer mechanisms, and challenges concerning designing, manufacturing, clinical translation, and commercialization, which must be resolved. The latest developments in CAP-based therapeutic systems for breast cancer treatment are discussed in this review. More significantly, the integration of CAP-based medicine approaches with other breast cancer therapies, including chemo- and nanotherapy is thoroughly addressed.

Protective effects of summer savory (Satureja hortensis) oil on growth, biochemical, and immune system performance of common carp exposed to pretilachlor herbicide.

There are many reports on the deleterious effects of herbicides on aquatic organisms which lead to tremendous biological, environmental and economical damage. In this regard, in the present study, the protective effect of summer savory (Satureja hortensis) essential oil (SEO) against pretilachlor, one of the most used herbicides was investigated in common carp (Cyprinus carpio). The fish assigned to six treatment groups (T1: control treatment; T2: 25% LC50 pretilachlor herbicide; T3: 50% LC50 pretilachlor herbicide; T4: 1% SEO; T5: 25% LC50 pretilachlor herbicide + 1% SEO; and T6: 25% LC50 pretilachlor herbicide + 1% SEO) for 21 days. The results showed that the SEO-containing treatments significantly increased the survival rate (SR) (P < 0.05). The highest final weight (FW), specific growth rate (SGR), and feed conversion ratio (FCR) were observed in the T4 treatment (P < 0.05). There was a significant increase in glucose (GLU) level in pretilachlor treatments and a significant decrease in SEO-containing treatments compared to the control (P < 0.05). The significantly highest total protein (TP) content was observed in T4 treatment containing SEO. Cholesterol (CHOL) and triglyceride (TRIG) levels decreased in SEO-containing treatments with the lowest level in T4 treatment (P < 0.05). Alternative complement pathway activity (ACH50), activity levels of superoxide dismutase (SOD), and glutathione peroxidase (GPX) showed an increasing trend in SEO-containing treatments with the highest level in T4 treatment (P < 0.05). The activity of liver enzymes showed a significantly lowest level in T4 treatment. To conclude, our findings revealed that the use of SEO in fish exposed to pretilachlor herbicide could improve growth, strengthen the immune system and exert a protective effect on common carp.

Effect of tomato consumption on inflammatory markers in health and disease status: A systematic review and meta-analysis of clinical trials.

BACKGROUND AND AIMS: Inflammation is a major cause of chronic diseases. Several studies have investigated the effects of tomato intake on inflammatory biomarkers; however, the results are equivocal. Therefore, the present study aimed to systematically review and analyses randomized clinical trials (RCTs) assessing the effects of tomato intake on inflammatory biomarkers in adults. METHODS: A systematic search was performed in PubMed, Scopus, ISI Web of Science, and Cochrane Library databases to find RCTs related to the effect of tomato intake on inflammatory markers, including C-reactive protein (CRP), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), up to November 2021. Meta-analyses were performed using the random-effects model. RESULTS: A total of 465 subjects sourced from seven eligible RCTs (8 treatment arms) were entered into the analysis. Pooled effect size of articles indicated that tomato intake was not significantly effective on CRP (WMD: 0.13 mg/dL, 95% CI: -0.09 to 0.36; P = 0.23, I2: 83.9%) and IL-6 (Hedges' g = -0.12; 95% CI -0.36, 0.13; P = 0.34, I2: 0.0%) levels compared to the control group. But it can significantly reduce TNF-α (Hedges' g = -0.45; 95% CI -0.76, -0.13; P = 0.005, I2: 0.0%) levels. CONCLUSION: Generally, the present study showed that tomato intake has no significant effect on serum CRP, and IL-6 concentrations, but can reduce serum TNF-α levels significantly. However, additional well-designed studies that include more diverse populations and longer duration are warranted.

Various types of electrochemical biosensors for leukemia detection and therapeutic approaches.

Leukemia often initiates following dysfunctions in hematopoietic stem cells lineages. Various types of leukemia, including acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML), acute promyelocytic leukemia (APL), and human T-cell leukemia/lymphoma virus type 1 (HTLV-1) can thus call for different diagnosis and treatment options. One of the most important subjects in leukemia is the early detection of the disease for effective therapeutic purposes. In this respect, biosensors detecting the molecules of deoxyribonucleic acid (DNA) as analytes are called genosensors or DNA biosensors. Electrochemical sensors, as the most significant approach, also involve reacting of chemical solutions with sensors to generate electrical signals proportional to analyte concentrations. Biosensors can further help detect cancer cells in the early stages of the disease. Moreover, electrochemical biosensors, developed based on various nanomaterials (NMs), can increase sensitivity to the detection of leukemia-related genes, e.g., BCR/ABL as a fusion gene and promyelocytic leukemia/retinoic acid receptor alpha (PML/RARα). Therefore, the present review reflects on previous studies recruiting different NMs for leukemia detection.

Transfer hydrogenation of nitroarenes using cellulose filter paper-supported Pd/C by filtration as well as sealed methods.

A reductive filter paper for selective nitro reduction has been prepared by modification of a pristine cellulose filter paper by Pd/C nanoparticles, as a portable catalyst. The reaction was performed in two different set-ups including (i) filtration and (ii) sealed systems, in the presence of ammonium formate and ex situ generated hydrogen gas reducing agents, respectively. In the sealed system in the presence of H2 gas, the halogenated nitroarenes were completely reduced, while in the filtration system, different derivatives of the nitroarenes were selectively reduced to aryl amines. In both systems, the reduction of nitroarenes to aryl amines was performed with high efficiency and selectivity, comparable to a heterogeneous system. Reaction parameters were comprehensively designed using Design Expert software and then studied. The properties of the catalytic filter paper were studied in detail from the points of view of swellability, shrinkage, reusability, and stability against acidic, alkaline, and oxidative reagents.

Assessment effects and risk of nosocomial infection and needle sticks injuries among patents and health care worker.

In medical centers and hospitals one of the most dangers that threaten health care worker and patient are Nosocomial infections (NIs) and Needle stick injuries (NSIs). The aim of this study was to determination the effects of nosocomial infection and needle sticks injuries on patents and health care worker. A review study of literature was conducted to One thousand and fifty manuscripts were retrieved based on various databases: Elsevier, PubMed, Web of Science, Springer, and Google Scholar. Reporting data were used on predetermined consequences nosocomial infection and needle sticks injuries and related to adverse health effects, routes of transmission, control and reduction. The literature signs a notable undesirable affect from potential NIS and NSIs attributed to risk investigated among patents and health care worker. Based on Result this study, the resistance of antibiotics, non-standard personal protective equipment, and Needle recapping can endanger health of human and increase transfer infectious disease risk among exposed patients and health care worker. Useful for health system decision makers and political officials in order to cope with the incidence of nosocomial infections and decrease number of needle stick injuries among patients and health care worker can be the main application the results of this study. Increasing the level of awareness, especially of sensitive groups (patients and HCW), about the ways to prevent nosocomial infections and reduce needle sticks and proper use of personal protective equipment are the main vital managers of the health department actions for decrease the prevalence of NIs. Further research using more sophisticated methodology is warranted. Holding regular and periodic training workshops in connection with standard precautions and prevention of occurrence nosocomial infection and needle sticks injuries can play an important role in increasing the health of patents and health care worker.

Mesenchymal stromal/stem cells and their exosomes application in the treatment of intervertebral disc disease: A promising frontier.

Today, the application of mesenchymal stromal/stem cells (MSCs) and their exosomes to treat degenerative diseases has received attention. Due to the characteristics of these cells, such as self-renewability, differentiative and immunomodulatory effects, their use in laboratory and clinical studies shows promising results. However, the allogeneic transplantation problems of MSCs limit the use of these cells in the clinic. Scientists propose the application of exosomes to use from the therapeutic effect of MSCs and overcome their defects. These vesicles change the target cell behaviour and transcription profile by transferring various cargo such as proteins, mi-RNAs, and lipids. One of the degenerative tissue diseases in which MSCs and their exosomes are used in their treatment is intervertebral disc disease (IDD). Different factors such as genetics, nutrition, ageing, and environmental factors play a significant role in the onset and progression of this disease. These factors affect the cellular and molecular properties of the disc, leading to tissue destruction. Nucleus pulposus cells (NPCs) are among the most important cells involved in the pathogenesis of disc degeneration. MSCs exert their therapeutic effects by differentiating, reducing apoptosis, increasing proliferation, and decreasing senescence in NPCs. In addition, the use of MSCs and their exosomes also affects the annulus fibrosus and cartilaginous endplate cells in disc tissue and prevents disc degeneration progression.

Cloning and Embryo Splitting in Mammalians: Brief History, Methods, and Achievements.

Embryo splitting is one of the newest developed methods in reproductive biotechnology. In this method, after splitting embryos in 2-, 4-, and even 8-cell stages, every single blastomere can be developed separately, but the embryos are genetically identical. Embryo splitting, as an approach in reproductive cloning, is extensively employed in reproductive medicine studies, such as investigating human diseases, treating sterility, embryo donation, and gene therapy. In the present study, cloning in mammalians and cloning approaches are briefly reviewed. In addition, embryo splitting and the methods commonly used in embryo splitting and recent achievements in this field, as well as the applications of embryo splitting into livestock species, primate animals, and humans, are outlined. Finally, a perspective of embryo splitting is provided as the conclusion.

Humoral immune mechanisms involved in protective and pathological immunity during COVID-19.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing COVID-19 is associated with excessive inflammation, as a main reason for severe condition and death. Increased inflammatory cytokines and humoral response to SARS-CoV-2 correlate with COVID-19 immunity and pathogenesis. Importantly, the levels of pro-inflammatory cytokines that increase profoundly in systemic circulation appear as part of the clinical pictures of two overlapping conditions, sepsis and the hemophagocytic syndromes. Both conditions can develop lethal inflammatory responses that lead to tissue damage, however, in many patients hemophagocytic lymphohistiocytosis (HLH) can be differentiated from sepsis. This is a key issue because the life-saving aggressive immunosuppressive treatment, required in the HLH therapy, is absent in sepsis guidelines. This paper aims to describe the pathophysiology and clinical relevance of these distinct entities in the course of COVID-19 that resemble sepsis and further highlights two effector arms of the humoral immune response (inflammatory cytokine and immunoglobulin production) during COVID-19 infection.