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Purpose: One of the most important challenges of the medical community is to find out the success rate of coronary artery bypass surgery and control complications after surgery, including acute kidney injury (AKI). The present study was conducted with the aim of determining the predictive effect of serum uric acid (SUA) (UA) level in patients undergoing off‐pump coronary artery bypass (OCABG) surgery. Methods: The present descriptive‐analytical study included 144 patients who underwent OCABG and met the inclusion criteria. SUA and related indicators, duration of hospitalization and stay in ICU, AKI and in‐hospital mortality, and 6‐month follow‐up mortality were investigated. Results: Patients were divided into high and normal groups based on SUA levels. The prevalence of postoperative AKI was 20% and was significantly associated with the preoperative UA levels (OR: 2.04; CI: 95%; 1.03–4.20). The mortality rate of patients was between 2% and 9%, which increased to 13% in patients with high SUA (p value ~0.224). The average duration of ICU and hospitalization in patients with high UA was longer than the other group (p value ~0.06 and p value ~0.002, respectively). Conclusion: SUA levels are independently associated with a higher risk of AKI and outcome complications after off‐pump CABG, and confounding factors at specific cutoffs affect the odds ratio of UA for AKI occurrence. [ABSTRACT FROM AUTHOR]

Background: DNA methylation is catalyzed by DNA methyltransferases (DNMTs) which are encoded by DNMT1, DNMT3A, and DNMT3B. DNMTs play a major role in the abnormal methylation of tumor suppressors and cancer-related genes. Herein, this study explored the expression profile of DNMTs in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), before and after methotrexate (MTX)/mercaptopurine (6-MP) treatment. Materials and Methods: This before-after prospective study included 30 matched children in sex and age (20 children with B-cell ALL and 10 healthy children used as a control or calibrator group). The expression profile of DNMTs was assessed at two-time points; at the diagnosis time and after MTX/6-MP treatment in the consolidation-maintenance phase of therapy. Notable, all pediatric patients included in this study continued the therapy without adverse events, except two children who were excluded from the study. Results: The average age of the patient group was 7.1 ± 1.3 years (in the range of 4-9 years), and the average age of the control group was 8.3 ± 1.7 years (6-10 years). The expression profile of DNMTs in B-cell ALL children was obtained completely different from that in the healthy group. After MTX/6-MP treatment of B-cell ALL children, the expression levels of DNMT1 and 3A were increased (p <0.01 & 0.04, respectively), and the expression level of DNMT3B was decreased (p <0.01), significantly. Conclusions: In ALL, the expression profile of DNMTs would be changed whereby contribute to abnormal growth and maturation capacity of leukemic stem cells and MTX/6-MP treatment could reverse this profile from a cancerous phenotype to the normal one. [ABSTRACT FROM AUTHOR]

Pandemics such as coronavirus disease 2019 (COVID-19) can manifest as systemic infections that affect multiple organs and show laboratory manifestations. We aimed to analyze laboratory findings to understand possible mechanisms of organ dysfunction and risk stratification of hospitalized patients in these epidemics. Methods. This retrospective study was conducted among patients admitted to COVID-19 referral treatment center, Shahid Sadoughi Hospital, Yazd, Iran, from April 21 to November 21, 2021. It was the fifth peak of COVID-19 in Iran, and Delta (VOC-21APR-02; B.1-617.2) was the dominant and most concerning strain. All cases were positive for COVID-19 by RT-PCR test. Lab information of included patients and association of sex, age, and outcome were analyzed, on admission. Results. A total of 466 COVID-19 patients were included in the study, the majority of whom were women (68.9%). The average age of hospitalized patients in male and female patients was 57.68 and 41.32 years, respectively (p < 0.01). During hospitalization, abnormality in hematological and biochemical parameters was significant and was associated with the outcome of death in patients. There was incidence of lymphopenia, neutrophilia, anemia, and thrombocytopenia. The changes in neutrophil/lymphocyte (N/L) and hematocrit/albumin (Het/Alb) ratio and potassium and calcium levels were significant. Conclusion. Based on these results, new biochemical and hematological parameters can be used to predict the spread of infection and the underlying molecular mechanism. Viral infection may spread through blood cells and the immune system. [ABSTRACT FROM AUTHOR]

Oxidative stress can damage cells and cause age-related illnesses such as Alzheimer's, Parkinson's, and Huntington's. This study looked at newly synthesized isoindole derivatives and their effects on SH-SY5Y as a neuroblastoma cell under oxidative stress through the NRF2 signaling pathway. NRF2 transcription factor plays a vital role in the oxidative stress response and cellular homeostasis. Three isoindoline-dione derivatives were synthesized by reacting phthalic anhydrides with 4-(2-aminoethyl)-1-benzyl piperidine. Their structures were confirmed through FT-IR, NMR, and Mass spectroscopy. The derivatives were then tested on human SH-SY5Y cells under an oxidative stress model induced by hydrogen peroxide (H2O2). The cell viability, ROS levels, protein carbonyl content, and gene expression of NRF2 and phase II antioxidative enzymes were measured after 24 h. Three isoindoline derivatives (3a–3c) were observed to increase the viability of SH-SY5Y cells by protective against oxidative stress, reducing intracellular reactive oxygen species and carbonylated proteins, and increasing gene expression levels of NRF2 and associated genes such as NQO-1, and GSTK1. Isoindoline derivatives demonstrated a neuroprotective effect on SH-SY5Y cells through various neuroprotective mechanisms, although more studies are needed. [ABSTRACT FROM AUTHOR]

A period of about a decade has been estimated to pass for the emergence of a new infectious strain of a virus that may lead to the occurrence of a pandemic one. It is now suggested that the variants of the 1918 H1N1 and coronavirus disease-19 pandemics could have existed in humans after the initial cross-species introduction to humans and underwent multiple low-level seasonal epidemics before the occurrence of their outbreaks. They share similarities in the continuation, widespreadness due to high transmissibility, high fatality rate and clinical symptoms. They are assumed to share a similar principle of a zoonotic source and a cross-species pathway for transmission. They show some similarities in their pathogenesis with other enveloped viruses: Severe Acute Respiratory Syndrome Coronavirus-1 (SARS-CoV-1), Middle East respiratory syndrome coronavirus (MERS-CoV), human immunodeficiency virus, Ebola, Lassa and measles viruses. The highly pathogenic nature of these viruses and their genetic variants may depend on their binding affinity for host cell receptors, whereby they efficiently circumvent or block host cell immune responses triggered by cytokines (interferon). High transmission rates and viral pathogenicity are attributed to glycan moieties that facilitate virus binding to host multiple receptors and cell entry, thereby helping viruses to evade immune recognition and response. Also, mucosa glycotopes are a matter of concern that play as primary sites for virus attachment and body entry. Finding general lectins or ligands that block the viral–host receptors interaction or identifying individual glycotopes is the therapeutic and prognosis topic that demands the main focus. [ABSTRACT FROM AUTHOR]

Background: Prostate cancer is known as one of the most prevalent health disorders in the male population globally. The aim of the current study was to evaluate the effects of separate and concomitant use of MK- 2206 and salinomycin on prostate cancer cell line. Methods: The antitumor potential of separate and concomitant use of MK-2206 and salinomycin was evaluated in a panel of prostate cancer cell line (PC-3). To get insights into the underlying mechanism of action, different assays including the rate of apoptosis, cell viability, and gene expression were performed in treated prostate cancer cells. Results: A significant reduction was detected in the viability percentage of prostate cancer cells (p< 0.001) and the rate of Akt expression (p< 0.001) in all salinomycin, MK-2206, and salinomycin+MK-2206 groups compared to the negative control group. Furthermore, in comparison with the negative control group, there was a notable increase in both the rate of Bad expression (p< 0.001) and prostate cancer cells apoptosis after salinomycin, MK-2206, and salinomycin+MK-2206 treatments. Moreover, the concomitant use of salinomycin+MK-2206 revealed synergistic improvements regarding the viability of prostate cancer cells and the rate of the Akt and Bad expressions compared to the separate administration of salinomycin and MK-2206 (all p< 0.05) Conclusions: The findings of the present study may contribute to improving the efficacy of the therapies regarding the management of prostate cancer and providing a beneficial strategy in clinical trials. [ABSTRACT FROM AUTHOR]

There is always a need for new approaches for the control of virus burdens caused by seasonal outbreaks, the emergence of novel viruses with pandemic potential and the development of resistance to current antiviral drugs. The outbreak of the 2019 novel coronavirus-disease COVID-19 represented a pandemic threat and declared a public health emergency of international concern. Herein, the role of glycans for the development of new drugs or vaccines, as a host-targeted approach, is discussed where may provide a front-line prophylactic or threats to protect against the current and any future respiratory-infecting virus and possibly against other respiratory pathogens. As a prototype, the role of glycans in the coronavirus infection, as well as, galectins (Gal) as the glycan-recognition agents (GRAs) in drug design are here summarized. Galectins, in particular, Gal-1 and Gal-3 are ubiquitous and important to biological systems, whose interactions with viral glycans modulate host immunity and homeostatic balance. [ABSTRACT FROM AUTHOR]

Purpose: There are two signal transduction pathways related to glucose metabolism in C2C12 mouse myoblast cells; one through AMP-activated protein kinase (AMPK), and the other through phosphoinositide 3-kinase (PI3K). Ginger is reported to have hypoglycemic effects. The aim of this study was to determine the exact mechanism of action of ginger in those pathways. Methods: C2C12 cells were seeded to four separate experimental groups; Control: treated with 50 μg/mL DMSO in the absence of any inhibitor; Treatment 1: treated with 50 μg/mL ethyl acetate ginger extract without any inhibitor; Treatment 2: treated with 50 μg/mL extract in the presence of 20 μM AMPK inhibitor; Treatment 3: treated with 50 μg/mL extract in the presence of 25 μM PI3K inhibitor. The amount of GLUT-4 protein (an important glucose transporter) was determined in cytosolic and membrane fractions using sodium dodecyl sulfate polyacrylamide gel electrophoresis and Western blotting. Results: GLUT-4 concentration was significantly higher in the membrane fraction of cells treated with ethyl acetate ginger extract in the absence of any inhibitor in comparison with cells treated with this extract in the presence of each of the inhibitors (P-value < 0.05). GLUT-4 quantity in the membrane fractions in all groups was more than cytosolic fractions. The amount of GLUT-4 in membrane fraction of treated cells in the presence of PI3K inhibitor was higher than in the cells treated with this extract in the presence of AMPK inhibitor (P-value < 0.05). Conclusion: Ethyl acetate ginger extract affects the amount of GLUT-4 protein in membrane and cytosolic fractions of C2C12 myoblast cells mostly through AMPK pathway but less via PI3K. [ABSTRACT FROM AUTHOR]

Background: Decitabine (5-aza-2'-deoxycytidine, DAC) is a deoxycytidine analog currently used as an effective drug against myelodysplastic syndromes and acute myeloid leukemia. Although various studies have pointed out the epigenetic effects of this drug, its epigenetic mechanisms in different leukemic cell lines are not specified. In this lab trial study, possible epigenetic effects of decitabine on leukemia cell lines Hl-60 (acute promyelocytic leukemia) and Nalm-6 (acute pre-B cell lymphoblastic leukemia) vs. normal peripheral blood mononuclear cells (PBMCs) are compared. Materias and Methods: At the logarithmic phase of growth, the cultured cells Hl-60 and Nalm-6 obtained from Tehran Pasteur Institute, Iran, were treated for 24 hr with 1 µM of decitabine, a dose selected from literature and the MTT viability assay. Normal PBMCs were obtained from a pool of 3 healthy adult volunteer males, and cultured simultaneously in the same manner. The gene expressions of epigenetic enzymes DNA methyltransferases (DNMTs) were assessed with the real-time PCR technique before and after treatment. The GAPDH gene expression served as the calibrator, while normal PBMCs were used for comparison. Results: The expressions of DNMT1 and DNMT3B in lymphoblasts were significantly (p=0.0017 and p=0.0489, respectively) decreased after treatment with decitabine, while the expression of DNMT3A was significantly (p=0.0022) increased. In leukemic promyelocytes the expressions of DNMT1 and DNMT3B in lymphoblasts were significantly (p=0.0222 and p=0.0452, respectively) decreased after treatment with decitabine, while the expression of DNMT3A was significantly (p=0.0013) increased. Conclusion: One of the mechanisms by decitabine to inhibit the proliferation of both myeloid and lymphoid acute leukemia cells maybe by altering the gene expression of DNMTs. [ABSTRACT FROM AUTHOR]

Over the past years, several zoonotic viruses have crossed the species barrier into humans and have been causing outbreaks of severe, and often fatal, respiratory illness. The 21st century has seen the worldwide spread of three recognized coronaviruses (CoVs) which can cause pneumonia and severe acute respiratory symptoms (SARSs), SARS, MERS, and recently SARS-CoV-2. Herein, it is raising concerns about the dissemination of another new and highly lethal pandemic outbreak. Preparing for a pandemic outbreak involves a great deal of awareness necessary to stop initial outbreaks, through recognizing the molecular mechanisms underlying virus transmission and pathogenicity. CoV spike protein S is the key determinant of host tropism and viral pathogenicity which can undergo variations and makes the CoV a highly pathogenic and diffusible virus capable of sustained human-to-human transmission and spread easily. The three mentioned CoVs exhibit some similarities in S protein whereby constitute a promising target for the development of prophylactics and therapeutics in the future. [ABSTRACT FROM AUTHOR]

Objective: Insulin resistance (IR) is the major cause in Type 2 diabetes mellitus (T2DM). Expression of some miRNAs can be changed in response to a drug treatment for IR, and used as the biomarker in IR. This study set out to determine the effect of cinnamon extract (cinnamaldehyde) on some miRNAs expression in IR adipocytes. Materials and Methods: In this In-vitro study the 3T3L1 cells were expanded in Dulbecco's modified Eagle's medium (DMEM), differentiated into adipocytes phenotype and insulin resistant with high glucose medium, then the cells were treated with cinnamaldehyde. To determine of the miRNAs profiling in 3T3L1 adipocytes, insulin-resistant adipocytes and treated insulin-resistant adipocytes quantitative real-time PCR method was performed. Results: IR adipocytes exhibited a significantly increase in miRs 29a, 223 and 320 expression, and decrease in miR26-b expression in compare to the normal adipocytes (P-value<0.001 and P-value= 0.024 respectively). However in response to cinnamaldehyde in IR adipocytes, expression of miRs 29a, 223 and 320 were down-regulated while expression of miR26-b was up-regulated neared it to the normal level (P-value= 0.003 and P-value= 0.002 respectively). Conclusion: IR changes expression of intended miRs, so that cinnamaldehyde treatment helps to improve and normalize the changes. Cinnamon as the herbal product can be helpful for IR particular in adipose tissue. [ABSTRACT FROM AUTHOR]

Background: 6-thioguanine (6-TG) is one of the thiopurine drugs with successful use in oncology, especially for acute lymphoblastic leukemia (ALL). 6-TG is proposed to act as an epigenetic drug affecting DNA methylation. The aim of this study was to clarify the effect of 6-TG on the proliferation, viability and expression of genes coding for the enzymes DNA methyltransferase 3A and DNA methyltransferase 3B (DNMTs) as well as histone deacetylase 3 (HDAC3) in the human B cell-ALL cell line Nalm6. Materials and Methods: In this experimental study, Nalm6 cells and also normal peripheral blood mononuclear cells (PBMCs) were grown in RPMI 1640 medium containing 10% fetal bovine serum. They were then treated with 6-TG at their exponential growth phase. Cell viability was monitored using the Cell Counting Kit-8 assay with an enzyme-linked immunosorbent assay (ELISA) reader. The expressions of the abovementioned 3 genes were quantified using real-time PCR. Results: 6-TG could inhibit the proliferation of Nalm6 cells and decrease their viability. In Nalm6 cells, as compared to normal PBMCs, 6-TG significantly decreased HDAC3 (p = 0.008) as well as DNMT3B (p = 0.003) gene expressions, but increased the expression of DNMT3A gene (p = 0.02) after normalization to GAPDH, as the housekeeping gene. Conclusion: These findings suggested that the altered expression of DNMT3A, DNMT3B and HDAC3 genes was responsible for at least part of the antitumoral properties of 6-TG, providing an insight into mechanism of its action as an epigenetic drug. [ABSTRACT FROM AUTHOR]

The aim of this study was to determine the antimicrobial capacity, minimum inhibitory concentration (MIC), and cytotoxic effects of a Peganum harmala seed extract in comparison to 5.25% sodium hypochlorite (NaOCl). The oral pathogen Enterococcus faecalis was used to evaluate the antimicrobial capacity, and the MIC values were determined through serial dilution. Inhibition zones were measured in millimeter, and the data were analyzed statistically by analysis of variance and the Tukey HSD test. For cytotoxicity testing, P. harmala seed extract and 5.25% NaOCl solution were incubated with L929 fibroblast cells. After 1, 24, and 72 hr of incubation, cells were stained and the optical density determined with an enzyme-linked immunosorbent assay (ELISA) reader. Data were analyzed with Chi-Square statistical test. The significance level was set at p < .05. There was no significant difference between the antimicrobial capacity of 5.25% NaOCl and the P. harmala extract (p > .05; MIC 4 μg/ml). The Microculture Tetrazolium (MTT) assay test showed that the cytotoxic effects of the P. harmala extract were significantly lower than 5.25% NaOCl (p < .05). The results show that 5.25% NaOCl and P. harmala seed extract have similar antimicrobial activity against Enterococcus faecalis; but P. harmala, which shows reduced cytotoxicity, should be considered for further investigation as a safe, phytotherapeutic, intracanal irrigant. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are effector cells of the innate immune system that exert direct cytotoxic functions. Ubiquitously-expressed toll-like receptors (TLRs) have been recognized as one of the major components promoting dendritic cell (DC) maturation, which may induce polarized immune responses beneficial to cancer immunotherapy. TLR-activated NK cells and DCs are prerequisite for robust activation of the innate immune system against tumors. Recently, some medical research and clinical trials have proposed NK cells as a new therapy and potential strategy in both children and adults with those cancers which cannot be cured with the usual treatment modalities. As an example, the importance of DC/NK antitumor immunity in the outcome of breast and other cancers is recently recognized. Therefore, considering strategies which exploit TLR-mediated immunity in concordance with DC/NK system holds strong potential for cancer therapy. This review addresses the current knowledge about the potential role of TLR in tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess plasma levels of endothelium- and heart-associated microRNAs (miRNAs) miR-126 and miR-499, respectively, using quantitative reverse transcriptase polymerase chain reaction. Methods: A two-step analysis was conducted on 75 patients undergoing off-pomp coronary artery bypass graft (CABG) surgery. Five biomarkers of inflammation and cardiac injury were assessed in addition to the abovementioned miRNAs. Results: Plasma concentrations of miRNAs were found to be significantly correlated with plasma levels of cardiac troponin I (cTnI) (miR-499, r 0.49, p~0.002; miR-126, r = 0.30, p~0.001), indicating cardiac damage. Data analysis revealed that miR-499 had higher sensitivity and specificity for cardiac injury than miR-126, which reflects more endothelial activation. Interestingly, a strong correlation was observed between both miRNAs and uric acid (UA) levels with ventricular contractility measured as ejection fraction (EF) (miR-499/EF%, r = 0.58, p~0.004; UA/EF%, r = -0.6, p~0.006; UA/miR-499, r = -0.34; UA/miR-126, r = 0.5, p~0.01). Conclusions: In patients undergoing CABG, circulating miR-126/499 is associated with presentation of traditional risk factors and reflects post-operative response to injury. Plasma pool of miRNAs likely reflects extracellular miRNAs which are proportional to intracellular miRNA levels. Therefore, circulating levels of these miRNAs have prognostic implications in detection of higher risk of future cardiovascular events. [ABSTRACT FROM AUTHOR]

The age-related senescence of adult tissues is associated with the decreased level of angiogenic capability and with the development of a degenerative disease such as atherosclerosis which thereafter result in the deteriorating function of multiple systems. Findings indicate that tissue senescence not only diminishes repair processes but also promotes atherogenesis, serving as a double-edged sword in the development and prognosis of ischaemia-associated diseases. Evidence evokes microRNAs (miRNAs) as molecular switchers that underlie cellular events in different tissues. Here, miRNAs would promote new potential targets for optimizing therapeutic methods in blood flow recovery to the ischaemic area. Effectively beginning an ischaemia therapy, a more characteristic of miRNA changes in adult tissues is prerequisite and in the forefront. It may also be a preliminary phase in treatment strategies by stem cell-based therapy. [ABSTRACT FROM AUTHOR]

Toll-like receptor family (TLRs), pattern recognition receptors, is expressed not only on immune cells but also on non-immune cells, including cardiomyocytes, fibroblasts, and vascular endothelial cells. One main function of TLRs in the non-immune system is to regulate apoptosis. TLRs are the central mediators in hepatic, pulmonary, brain, and renal ischemic/reperfusion (I/R) injury. Up-regulation of TLRs and their ligation by either exogenous or endogenous danger signals plays critical roles in ischemia/reperfusion-induced tissue damage. Conventional TLR-NF-κB pathways are markedly activated in failing and ischemic myocardium. Recent studies have identified a cross talk between TLR activation and the PI3K/Akt pathway. The activation of TLRs is proposed to be the most potent preconditioning method after ischemia, to improve the cell survival via the mechanism involved the PI3K/Akt signaling pathway and to attenuate the subsequent TLR-NF-κB pathway stimulation. Thus, TLRs could be a great target in the new treatment approaches for myocardial I/R injury. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to determine the association of the Helicobacter pylori virulence factors, cytotoxin-associated gene A (CagA) and vacuolating cytotoxin A (VacA) antibodies, with serum levels of interleukin (IL)-12 and IL-13 in H. pylori-infected duodenal ulcer (DU) patients and H. pylori-infected asymptomatic (AS) carriers in order to elucidate any correlation between them. Methods: A total of 67 DU patients, 48 AS individuals, and 26 healthy H. pylori-negative subjects were enrolled in this study. Serum concentrations of IL-12 and IL-13 were determined by enzyme-linked immunosorbent assay (ELISA) method. Patient sera were tested by Western blot method to determine the presence of serum antibodies to bacterial virulence antigens p120 (CagA) and p95 (VacA). Serum concentrations of IL-12 and IL-13 were compared in 9 groups, including 4 AS phenotypes (CagA+VacA+, CagA+VacA−, CagA−VacA+, CagA−VacA−), 4 DU phenotypes (CagA+VacA+, CagA+VacA−, CagA−VacA+, CagA−VacA−), and 1 control group. Results: The results revealed that DU patients positive for CagA, independent of the anti-VacA antibody status, showed drastically elevated levels of IL-12 (251 ± 43 pg/ml) when compared with the other groups ( p = 0.0001). No significant difference was found between groups regarding levels of IL-13 ( p > 0.05). Conclusions: Our findings indicate that in the DU group, the serum concentrations of IL-12 but not of IL-13 were influenced by bacterial CagA, independent of the VacA status, suggesting that high IL-12 levels may contribute to susceptibility to DU in CagA-positive individuals. These findings could possibly be considered to improve the predictive or prognostic values of inflammatory cytokines for DU, and also to design possible novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Objective: GLUT4 is a type of glucose transporter and plays a central role in whole-body metabolism of carbohydrates. The muscle is the major site of GLUT4 and cell line models, to explore GLUT4 behaviors under new therapeutic approach, such as herbal components, should be evaluated. Here, C2C12 cell line is evaluated for GLUT4 translocation from intracellular compartment into the cell membrane. Materials and Methods: C2C12 cell lines were cultured and differentiated into myotubes. Cinnamon/Turmeric-water soluble extract (CWE and TWE) were prepared and differentiated myotubes were exposed to the 100, 1000 µg/ml CWE, 100 µg/ml TWE or dimethylsulfoxide for 3 hours. Intracellular/cytoplasmic membrane compartments were separated using ultracentrifugation. GLUT4 percentages quantities were measured using western blotting. Data analysis of 3 sample sizes was done by comparing mean±SD of GLUT4 quantities and independent samples t-test. Results: CWE enhances GLUT4 translocation from intracellular compartment into the cytoplasmic membrane; its effect is also dose- dependent meaning that 1000 µg/ml concentration has a more potent effect than 100 µg/ml (p<0.05). However, 100 µg/ml TWE had a reverse effect (p<0.05). Conclusion: Here we have shown that C2C12 is a good model for exploring GLUT4 changes under the effect of herbal extract. Induction or blockade of GLUT4 maybe under control of different signals transduction pathways. Furthermore, although turmeric ingredients are declared to have somewhat anti-diabetic effects, here we have shown that such effect is not applied via TWE effects on GLUT4 intracellular compartments movement into the cell membrane. [ABSTRACT FROM AUTHOR]

Objective: Recent achievements in stem cell biotechnology, nanotechnology and tissue engineering have led to development of novel approaches in regenerative medicine. Azoospermia is one of the challenging disorders of the reproductive system. Several efforts were made for isolation and culture of testis-derived stem cells to treat male infertility. However, tissue engineering is the best approach to mimic the three dimensional microenvironment of the testis in vitro. We investigated whether human testis-derived cells (hTCs) obtained by testicular sperm extraction (TESE) can be cultured on a homemade scaffold composed of electrospun nanofibers of homogeneous poly (vinyl alcohol)/human serum albumin/gelatin (PVA/HSA/gelatin). Materials and Methods: In this experimental lab study, human TCs underwent two steps of enzymatic cell isolation and five culture passages. Nanofibrous scaffolds were characterized by scanning electron microscopy (SEM) and Fouriertransform infrared spectroscopy (FTIR). Attachment of cells onto the scaffold was shown by hematoxylin and eosin (H&E) staining and SEM. Cell viability study using MTT [3-(4, 5-dimethyl-2-thiazolyl) -2, 5-diphenyl -2H- tetrazolium bromide] assay was performed on days 7 and 14. Results: Visualization by H&E staining and SEM indicated that hTCs were seeded on the scaffold. MTT test showed that the PVA/HSA/gelatin scaffold is not toxic for hTCs. Conclusion: It seems that this PVA/HSA/gelatin scaffold is supportive for growth of hTCs. [ABSTRACT FROM AUTHOR]

Structurally rearranged extrachromosomal circular DNAs (eccDNAs) have been identified in tumor cells, many of which carry regions related to recurrent cancer driver oncogenes (e.g., CCND1 , EGFR, and MYC ). In a tumor cell, eccDNAs are carrying regions associated with oncogene amplification (>10-fold amplified-copy numbers in human tumors) and poor outcome across multiple cancers. Even though dual-delivery of pairs of CRISPR and CRISPR-associated protein 9 (Cas9) guiding RNAs into normal human cells was reported to induce circularization of genes and chromosomes, in bacteria, the CRISPR-Cas9 system primarily targets extrachromosomal rearranged elements. Likewise, in cancer cells, it is expected that a designed CRISPR-Cas9 system would be able to target extrachromosomal copy number amplifications and produce double strand breaks detrimental to cellular fitness by dictating gene-independent copy number loss-of-fitness effects and antiproliferative responses. A system designed against amplified amplicons may provide a novel approach for cancer therapy and propose a practical implication for CRISPR-Cas9 pairs as a pathway in therapeutic strategies of cancer. SIGNIFICANCE STATEMENT: Structurally rearranged extrachromosomal circular DNAs (eccDNAs) have been identified in tumor cells. Many eccDNAs are carrying regions related to recurrent cancer driver oncogenes (e.g. CCND1 , EGFR and MYC) . It is expected that a designed CRISPR-Cas9 system would able to target extrachromosomal recurrent oncogenes., (Copyright © 2022 by The American Society for Pharmacology and Experimental Therapeutics.)

The age-related senescence of adult tissues is associated with the decreased level of angiogenic capability and with the development of a degenerative disease such as atherosclerosis which thereafter result in the deteriorating function of multiple systems. Findings indicate that tissue senescence not only diminishes repair processes but also promotes atherogenesis, serving as a double-edged sword in the development and prognosis of ischaemia-associated diseases. Evidence evokes microRNAs (miRNAs) as molecular switchers that underlie cellular events in different tissues. Here, miRNAs would promote new potential targets for optimizing therapeutic methods in blood flow recovery to the ischaemic area. Effectively beginning an ischaemia therapy, a more characteristic of miRNA changes in adult tissues is prerequisite and in the forefront. It may also be a preliminary phase in treatment strategies by stem cell-based therapy., (© 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)