Cold Atmospheric Plasma Jet Irradiation Decreases the Survival and the Expression of Oncogenic miRNAs of Oral Carcinoma Cells.

Despite recent advancements, therapies against advanced oral squamous cell carcinoma (OSCC) remain ineffective, resulting in unsatisfactory therapeutic outcomes. Cold atmospheric plasma (CAP) offers a promising approach in the treatment of malignant neoplasms. Although the effects of CAP in abrogating OSCC have been explored, the exact mechanisms driving CAP-induced cancer cell death and the changes in microRNA (miRNA) expression are not fully understood. We fabricated and calibrated an argon-CAP device to explore the effects of CAP irradiation on the growth and expression of oncogenic miRNAs in OSCC. The analysis revealed that, in OSCC cell lines following CAP irradiation, there was a significant reduction in viability; a downregulation of miR-21, miR-31, miR-134, miR-146a, and miR-211 expression; and an inactivation of the v-akt murine thymoma viral oncogene homolog (AKT) and extracellular signal-regulated kinase (ERK) signals. Pretreatment with blockers of apoptosis, autophagy, and ferroptosis synergistically reduced CAP-induced cell death, indicating a combined induction of variable death pathways via CAP. Combined treatments using death inhibitors and miRNA mimics, alongside the activation of AKT and ERK following the exogenous expression, counteracted the cell mortality associated with CAP. The CAP-induced downregulation of miR-21, miR-31, miR-187, and miR-211 expression was rescued through survival signaling. Additionally, CAP irradiation notably inhibited the growth of SAS OSCC cell xenografts on nude mice. The reduced expression of oncogenic miRNAs in vivo aligned with in vitro findings. In conclusion, our study provides new lines of evidence demonstrating that CAP irradiation diminishes OSCC cell viability by abrogating survival signals and oncogenic miRNA expression.

SilenceREIN: seeking silencers on anchors of chromatin loops by deep graph neural networks.

Silencers are repressive cis-regulatory elements that play crucial roles in transcriptional regulation. Experimental methods for identifying silencers are always costly and time-consuming. Computational methods, which relies on genomic sequence features, have been introduced as alternative approaches. However, silencers do not have significant epigenomic signature. Therefore, we explore a new way to computationally identify silencers, by incorporating chromatin structural information. We propose the SilenceREIN method, which focuses on finding silencers on anchors of chromatin loops. By using graph neural networks, we extracted chromatin structural information from a regulatory element interaction network. SilenceREIN integrated the chromatin structural information with linear genomic signatures to find silencers. The predictive performance of SilenceREIN is comparable or better than other states-of-the-art methods. We performed a genome-wide scanning to systematically find silencers in human genome. Results suggest that silencers are widespread on anchors of chromatin loops. In addition, enrichment analysis of transcription factor binding motif support our prediction results. As far as we can tell, this is the first attempt to incorporate chromatin structural information in finding silencers. All datasets and source codes of SilenceREIN have been deposited in a GitHub repository (https://github.com/JianHPan/SilenceREIN).

Reciprocal regulation of CIP2A and AR expression in prostate cancer cells.

Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncoprotein overexpressed in human malignancies, including prostate cancer (PCa). In this study, we aimed to explore the oncogenic function of CIP2A in PCa cells and its underlying mechanism. We showed that 63.3% (38/60 cases) of PCa tissues exhibited a high CIP2A immunostaining, compared to 25% (3/12 cases) of BPH samples (p = 0.023). Furthermore, the protein level of CIP2A was positively correlated with patients' short survival time and nuclear AR levels in PCa tissues. Compared to PZ-HPV-7, an immortalized prostate cell line, androgen-sensitive LNCaP C-33, androgen-independent LNCaP C-81, or 22Rv1 cells exhibited a high CIP2A level, associated with high protein and phosphorylation levels of AR. While AR expression and activity modulated CIP2A expression, manipulating CIP2A expression in PCa cells regulated their AR protein levels and proliferation. The reduction of CIP2A expression also enhanced the sensitivity of PCa cells toward Enzalutamide treatment. Our data further showed that depletion of polo-kinase 1 (PLK1) expression or activity in C-81 or 22Rv1 cells caused reduced protein levels of c-Myc and AR. Notably, inhibition of PLK1 activity could abolish CIP2A-promoted expressions in c-Myc, AR, and prostate-specific antigen (PSA) in C-33 cells under an androgen-deprived condition, suggesting the role of PLK1 activity in CIP2A-promoted AR expression. In summary, our data showed the existence of a novel regulation between CIP2A and AR protein levels, which is critical for promoting PCa malignancy. Thus, CIP2A could serve as a therapeutic target for PCa.

The Symptoms and Factors Associated With Posttraumatic Stress Disorder for Burns Nurses: A Cross-Sectional Study From Guangdong Province in China.

The symptoms of posttraumatic stress disorder (PTSD) among medical staff have become a significant issue. Environments related to burns are highly stressful for nurses and can lead to PTSD, thus affecting their mental health. It is vital to consider that the quality of burns care, and the outcomes of such treatments, may be threatened if nurses experience PTSD. We evaluated PTSD symptoms in burns nurses and explored the correlations between demographic characteristics, work-related characteristics, professional identity, turnover intention, and PTSD symptoms. This was a cross-sectional study involving 273 nurses working in the burns unit from Guangdong, China, between July and August 2019. Nurses were recruited from 30 hospitals and completed three validated psychological questionnaires: Posttraumatic Stress Disorder Checklist-Civilian Version (PCL-C), Professional Identity Scale (PIS) for nurses, and Turnover Intention Questionnaire (TIQ). We also collated information relating to sociodemographic and work-related characteristics. The cutoff point for the PCL-C was defined as 38 points; 17.22% (n = 47) of participants scored higher than or equal to 38. The PCL-C score was negatively correlated with professional identity level (P < .01) and positively correlated with turnover intention (P < .01). The workplace, mean monthly income, experience of workplace violence, and professional identity level were important factors and all associated with the severity of PTSD. PTSD symptoms were common in burns nurses. Attention should be paid to the mental well-being of these staff. Screening processes need to be initiated to identify individuals suffering from PTSD and take appropriate early interventional action.

Rapidly Progressive, Fata Infection Caused by Bacillus Cereus in a Patient with Acute Lymphoblastic Leukemia.

BACKGROUND: We herein report a fatal case of fulminant septicemia caused by Bacillus cereus in a 49-year-old female with T-cell acute lymphoblastic leukemia receiving chemotherapy. METHODS: Her two blood culture sets were positive for Gram-positive, rod-shaped bacterium. Bacillus cereus was identified by high-throughput MALDI-TOF mass spectrometry and 16S ribosomal RNA gene sequencing. RESULTS: The patient died within 12 hours from the onset of B cereus infection. CONCLUSIONS: Patients with acute leukemia presented with fever and unexplained multiple organ lesions, especially accompanied by CNS symptoms, should alert to the possibility of Bacillus cereus infection.

Efficacy of lifestyle interventions in patients with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: The current meta-analysis evaluated the outcomes of various lifestyle interventions, including diet modifications (DIET), physical activity (PA), and patient education (EDU) in reducing the risk of cardiovascular disease in patients with type 2 diabetes. METHODS: Randomized clinical trials comparing lifestyle intervention with "usual care" (control) in type 2 diabetes patients were hand-searched from medical databases by two independent reviewers using the terms "diabetes, cardiovascular risk, lifestyle, health education, dietary, exercise/physical activities, and behavior intervention". RESULTS: Of the 235 studies identified, 17 were chosen for the meta-analysis. The average age of patients ranged from 50-67.3 years. Results reveal no significant difference between the groups, with respect to BMI, while PA and DIET yielded a greater reduction in HbA1c. Significant reduction in both systolic and diastolic pressures in the DIET group, and diastolic pressure in the PA group, was observed. HDL-c in the DIET group was significantly higher than the control group, while no change in LDL-c levels, was seen in all three intervention subtypes. There was no difference between the EDU vs. the control group in terms of HbA1c, blood pressure or HDL-c and LDL-c. CONCLUSION: DIET intervention showed an improvement in HbA1c, systolic/diastolic blood pressure and HDL-c, with an exception of LDL-c and BMI, suggesting that nutritional intervention had a significant impact on the quality of life by reducing the cardiovascular risk in type 2 diabetes patients.

[Effect of epigallocatechin gallate against exercise-induced fatigue in mice].

OBJECTIVE: To investigate the effects of epigallocatechin gallate (EGCG)against exercise-induced fatigue in mice. METHODS: Total 120 mice were randomly divided into three groups and tested separately. For each test, there were 30 mice subdivided into high dose (50 mg/kg . d EGCG) and low dose (10 mg/kg . d EGCG) groups as well as saline control group(1 ml/kg . d) with 10 in each. Burden swimming, running wheel endurance, stick climbing and hypoxia tolerance exercise were used to establish fatigue mice training model in three groups. And intraperitoneal injection with different doses of EGCG per day for consecutively 28 days and the mice in the control group were treated with normal saline. After the last each test, the blood lactic acid (BLA), blood urea nitrogen (BUN), blood lactate dehydrogenase (LDH), muscle glycogen (MG) and liver glycogen (LG) of each group of mice were determined. RESULTS: EGCG treatment groups(B and C)revealed a prolonged the mice survival time of burden swimming test, hypoxia tolerance, running wheel time and the ability of stick climbing(P < 0.05 or P <0.01), and increased LDH activity and MG and LG contents, reduced contents of BLA and BUN. High dose group had an obviously increase effect than lower dose group(P <0.05). CONCLUSION: EGCG has significant effects against exercise-induced fatigue in mice.

Astragaloside IV attenuates proteinuria in streptozotocin-induced diabetic nephropathy via the inhibition of endoplasmic reticulum stress.

BACKGROUND: Diabetic nephropathy (DN) is a major cause of Chronic Kidney Disease and End-Stage Renal Disease throughout the world; however, the reversibility of diabetic nephropathy remains controversial. Endoplasmic reticulum (ER) stress plays an important role in the pathogenesis of DN. Astragaloside IV (AS-IV) is derived from Astragalus membranaceus (Fisch) Bge, a widely used traditional herbal medicine in China, and has diverse pharmacological activities including the attenuation of podocyte injury and amelioration of proteinuria in idiopathic nephrotic syndrome. The present study aimed to investigate the effect and mechanism of AS-IV on proteinuria in the rat streptozotocin (STZ)-induced model of diabetes. METHODS: Male Sprague-Dawley (SD) rats were randomly divided into four groups: normal control (Normal group), diabetic nephropathy (Model group), diabetic nephropathy plus AS-IV treatment (AS-IV group) and diabetic nephropathy plus 4-phenyl butyric acid treatment (PBA group). ER stress was induced in cultured human podocytes, pretreated with or without AS-IV, with tunicamycin (TM). At the end of 8 weeks, serum creatinine (Scr), blood urea nitrogen (BUN) and 24-hour urinary protein excretion rate (UAER) were determined. Renal morphology was examined after periodic acid-Schiff staining of kidney sections. Apoptosis of podocytes was measured by flow cytometry. The total expression and phosphorylation of eIF2α, PERK and JNK, and the expression of CHOP and cleaved caspase-3 were determined by western blotting. The expression of glucose-regulated protein 78 (GRP78) and 150 kDa oxygen-regulated protein (ORP150) mRNA and protein was determined by real-time PCR and western blotting respectively. RESULTS: AS-IV treatment significantly reduced urinary albumin excretion, plasma creatinine and blood urea nitrogen levels, and prevented the mesangial matrix expansion and increase in mean mesangial induced by STZ. AS-IV also prevented the phosphorylation of eIF2α, PERK and JNK, and inhibited the expression of GRP78 and ORP150 markedly, both in vivo and in vitro. AS-IV inhibited the TM-induced apoptosis of podocytes, concomitant with decreased CHOP expression and cleaved caspase-3. CONCLUSIONS: This study supports the hypothesis that AS-IV reduces proteinuria and attenuates diabetes, which is associated with decreased ER stress. This might be an important mechanism in the renoprotective function of AS-IV in the pathogenesis of DN.

Comparative genomic study of gastric epithelial cells co-cultured with Helicobacter pylori.

AIM: To identify genes potentially involved in Helicobacter pylori (H. pylori)-induced gastric carcinogenesis. METHODS: GES-1 cells were co-cultured with H. pylori strains isolated from patients with gastric carcinoma (GC, n = 10) or chronic gastritis (CG, n = 10) for in vitro proliferation and apoptosis assays to identify the most and least virulent strains. These two strains were cagA-genotyped and used for further in vivo carcinogenic virulence assays by infecting Mongolian gerbils for 52 wk, respectively; a broth free of H. pylori was lavaged as control. Genomic profiles of GES-1 cells co-cultured with the most and least virulent strains were determined by microarray analysis. The most differentially expressed genes were further verified using quantitative real-time polymerase chain reaction in GES-1 cells infected with the most and least virulent strains, and by immunohistochemistry in H. pylori positive CG, precancerous diseases, and GC biopsy specimens in an independent experiment. RESULTS: GC-derived H. pylori strains induced a potent proliferative effect in GES-1 cells in co-culture, whereas CG-derived strains did not. The most (from a GC patient) and least (from a CG patient) virulent strains were cagA-positive and negative, respectively. At week 52, CG, atrophy, metaplasia, dysplasia, and GC were observed in 90.0%, 80.0%, 80.0%, 90%, and 60.0%, respectively, of the animals lavaged with the most virulent strain. However, only mild CG was observed in 90% of the animals lavaged with the least virulent strain. On microarray analysis, 800 differentially expressed genes (49 up- and 751 down-regulated), involving those associated with cell cycle regulation, cell apoptosis, cytoskeleton, immune response, and substance and energy metabolisms, were identified in cells co-cultured with the most virulent strain as compared with those co-cultured with the least virulent strain. The six most differentially expressed genes (with a betweenness centrality of 0.1-0.2) were identified among the significant differential gene profile network, including JUN, KRAS, BRCA1, SMAD2, TRAF1, and HDAC6. Quantitative real-time polymerase chain reaction analyses verified that HDAC6 and TRFA1 mRNA expressions were significantly more up-regulated in GES-1 cells co-cultured with the most virulent strain than in those co-cultured with the least virulent strain. Immunohistochemistry of gastric mucosal specimens from H. pylori-positive patients with CG, intestinal metaplasia (IM), dysplasia, and GC showed that moderately positive and strongly positive HDAC6 expression was detected in 21.7% of CG patients, 30.0% of IM patients, 54.5% of dysplasia patients, and 77.8% of GC patients (P < 0.001). The up-regulation of TRAF1 expressions was detected in 34.8%, 53.3%, 72.7%, and 88.9% specimens of CG, IM, dysplasia, and GC, respectively (P < 0.001). CONCLUSION: The overexpression of HDAC6 and TRAF1 in GES-1 cells co-cultured with the GC-derived strain and in H. pylori-positive dysplasia and GC suggests that HDAC6 and TRAF1 may be involved in H. pylori-induced gastric carcinogenesis.

Surface reaction of Bacillus cereus biomass and its biosorption for lead and copper ions.

In this study, the surface chemical functional groups of Bacillus cereus biomass were identified by Fourier transform infrared (FTIR) analytical technique. It had been shown that the B. cereus cells mainly contained carboxyl, hydroxyl, phosphate, amino and amide functional groups. The potentiometric titration was conducted to explain the surface acid-base properties of aqueous B. cereus biomass. The computer program FITEQL 4.0 was used to perform the model calculations. The optimization results indicated that three sites-three pKas model, which assumed the cell surface to have three distinct types of surface organic functional groups based on the IR analysis results, simulated the experimental results very well. Moreover, batch adsorption experiments were performed to investigate biosorption behavior of Cu(II) and Pb(II) ions onto the biomass. Obviously, the adsorption equilibrium data for the two ions were reasonably described by typical Langmuir isotherm.

[Biosorption of Pb2+ by Bacillus cereus biomass].

In this paper, the potentiometric titration and the sorption experiments were applied to investigate the biosorption behavior of Pb2+ on Bacillus cereus biomass. It was shown that the biosorption capacities increased with increasing pH from 3 to 7, and the higher concentration of the biomass in solution was favorable to the sorption of Pb2+. Langmuir model simulated the adsorption data of Pb2+ ion very well, and the saturated sorption capacity for Pb2+ ion achieved 36.7 mg.g-1 dry biomass. According to the result of the potentiometric titration, the Gran plots for the hydroxide back-titration of biomass suspension systems were utilized to derive the specific volume of titrant at the equivalence point (Ve), furthermore, the total surface site concentration was calculated.