Ferulic Acid Inhibits Arsenic-Induced Colon Injury by Improving Intestinal Barrier Function.

The prolonged exposure to arsenic results in intestinal barrier dysfunction, which is strongly concerned with detrimental processes such as oxidative stress and the inflammatory response. Ferulic acid (FA), as a phenolic acid, possesses the capability to mitigate arsenic-induced liver damage and cardiotoxic effects dependent on inhibition of oxidative stress and inflammatory responses. FA can mitigate testicular tissue damage and alveolar epithelial dysfunction, the mechanism of which may rely on nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) activation and nuclear factor-kappa B (NF-κB) pathway blocking. Based on the antioxidant and anti-inflammatory properties of FA, we speculated that FA might have the potential to inhibit arsenic-induced intestinal damage. To confirm this scientific hypothesis, mice exposed to sodium arsenite were treated with FA to observe colonic histopathology and TJ protein levels, and oxidative stress and TJ protein levels in Caco-2 cells exposed to sodium arsenite were assessed after FA intervention. In addition, molecular levels of NF-κB and Nrf2/HO-1 pathway in colon and Caco-2 cells were also detected. As shown in our data, FA inhibited arsenic-induced colon injury, which was reflected in the improvement of mucosal integrity, the decrease of down-regulated expression of tight junction (TJ) proteins (Claudin-1, Occludin, and ZO-1) and the inhibition of oxidative stress. Similarly, treatment with FA attenuated the inhibitory effect of arsenic on TJ protein expression in Caco-2 cells. In addition to suppressing the activation of NF-κB pathway, FA retrieved the activation of Nrf2/HO-1 pathway in colon and intestinal epithelial cells induced by arsenic. In summary, our findings propose that FA has the potential to mitigate arsenic-induced intestinal damage by preserving the integrity of intestinal epithelial TJs and suppressing oxidative stress. These results lay the groundwork for the potential use of FA in treating colon injuries caused by arsenic.

Nerve growth factor alleviates arsenic-induced testicular injury by enhancing the function of Sertoli cells.

Sertoli cells (SCs) maintain testicular homeostasis and promote spermatogenesis by forming the blood-testis barrier (BTB) and secreting growth factors. The pro-proliferative and anti-apoptotic effects of nerve growth factor (NGF) on SCs have been proved previously. It is still unclear whether the damage effect of arsenic on testis is related to the inhibition of NGF expression, and whether NGF can mitigate arsenic-induced testicular damage by decreasing the damage of SCs induced by arsenic. Here, the lower expression of NGF in testes of arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO2) was observed through detection of Western blot and Real-time PCR. Subsequently, hematoxylin and eosin (HE) staining, Evans blue staining and transmission electron microscopy were used to evaluate the pathology, BTB permeability and tight junction integrity in testes of control mice, arsenic exposed mice (freely drinking water containing 15 mg/l of NaAsO2) and arsenic + NGF treated mice (freely drinking water containing 15 mg/l of NaAsO2 + intraperitoneal injection with 30 µg/kg of NGF), respectively. Evidently, spermatogenic tubule epithelial cells in testis of arsenic exposed mice were disordered and the number of cell layers was reduced, accompanied by increased permeability and damaged integrity of the tight junction in BTB, but these changes were less obvious in testes of mice treated with arsenic + NGF. In addition, the sperm count, motility and malformation rate of mice treated with arsenic + NGF were also improved. On the basis of the above experiments, the viability and apoptosis of primary cultured SCs treated with arsenic (10 µM NaAsO2) or arsenic + NGF (10 µM NaAsO2 + 100 ng/mL NGF) were detected by Cell counting kit-8 (CCK8) and transferase-mediated DUTP-biotin nick end labeling (TUNEL) staining, respectively. It is found that NGF ameliorated the decline of growth activity and the increase of apoptosis in arsenic-induced SCs. This remarkable biological effect that NGF inhibited the increase of Bax expression and the decrease of Bcl-2 expression in arsenic-induced SCs was also determined by western blot and Real-time PCR. Moreover, the decrease in transmembrane resistance (TEER) and the expression of tight junction proteins ZO-1 and occludin was mitigated in SCs induced by arsenic due to NGF treatment. In conclusion, the above results confirmed that NGF could ameliorate the injury effects of arsenic on testis, which might be related to the function of NGF to inhibit arsenic-induced SCs injury.

Macrophages in head and neck squamous cell carcinoma: A bibliometric analysis.

INTRODUCTION: The tumor microenvironment in head and neck squamous cell carcinoma (HNSCC) is densely infiltrated by macrophages. Utilizing bibliometric analysis, the characteristics, hotspots for research, and research frontiers related to macrophages in HNSCC were reviewed. METHODS: The Web of Science Core Collection database was queried for relevant articles published from 2000 to 2022. VOSviewer and CiteSpace software were utilized to evaluate and visualize macrophage-related HNSCC research trends and hotspots. RESULTS: Assessment of original articles revealed that the annual number of publications regarding the role of macrophages in HNSCC has increased steadily over the past 23 years. China produced the most articles, whereas the United States had the highest number of citations and highest H-index. Wuhan University and Oral Oncology were the most productive affiliation and journal, respectively. The paper published by Bray et al in the CA-A Cancer Journal for Clinicians in 2018 had the greatest number of citations. The keywords "expression," "cancer," and "tumor-associated macrophages (TAMs)" occurred most frequently. CONCLUSIONS: This bibliometric investigation discovered that publications about macrophages in HNSCC are steadily increasing. The majority of studies focused on macrophage polarization, macrophage markers, and inflammation in the tumor microenvironment. Furthermore, our bibliometric analysis revealed that the immunosuppressive role of tumor-associated macrophages in the tumor microenvironment and resistance to therapy in HNSCC have recently received attention.

All-Printed 3D Solid-State Rechargeable Zinc-Air Microbatteries.

Lightweight, compact, integrated, and miniaturized energy devices are under high pursuit for portable and wearable electronics. However, improving the energy density per area still remains a long-standing challenge. Herein, we report the design and fabrication of a solid-state zinc-air microbattery (ZAmB) by a facile 3D direct printing technique. The interdigital electrodes, gel electrolyte, and encapsulation frame are all printed with a customized design by optimzing the composition of the printing inks to obtain the best battery performance. Multiple layers of interdigital electrodes are sequentially printed with a fine overlap to achieve an ultrahigh thickness of 2.5 mm for a remarkably increased specific areal energy of up to 77.2 mWh cm-2. To meet the practical powering requirements for different output voltages and currents, battery modules consisting of individual ZAmBs connected in series or parallel or a combination of the two are printed with a facile integration to external loads. Powering of LEDs, digital watch, and a miniature rotary motor and even charging of a smartphone by the printed ZAmB modules are successfully demonstrated. The versatile 3D direct printing technique enables the fabricated ZAmBs with an adjustable form factor and integration capability with other electronics, paving the way for exploring new energy systems with diverse structures and extended functionalities.

The Construction and Analysis of Immune Infiltration and Competing Endogenous RNA Network in Acute Ischemic Stroke.

Acute ischemic stroke (AIS) is a common neurological disease that seriously endangers both the physical and mental health of human. After AIS, activated immune cells are recruited to the stroke site, where inflammatory mediators are released locally, and severe immune inflammatory reactions occur within a short time, which affects the progress and prognosis of IS. Circular RNA (circRNA) is a type of non-coding RNA (ncRNA) with a closed-loop structure and high stability. Studies have found that circRNA can affect the course of IS. However, there is no report on ceRNA's pathogenesis in AIS that is mediated by circRNA. In this study, the CIBERSORT algorithm was used to analyze the distribution of immune cells in patients with AIS. mRNA dataset was downloaded from the GEO database, and the weighted gene co-expression network analysis (WGCNA) method was used to construct weighted gene co-expression to determine 668 target genes, using GO, KEGG enrichment analysis, construction of protein-protein interaction (PPI) network analysis, and molecular complex detection (MCODE) plug-in analysis. The results showed that the biological function of the target gene was in line with the activation and immune regulation of neutrophils; signal pathways were mostly enriched in immune inflammation-related pathways. A Venn diagram was used to obtain 52 intersection genes between target genes and disease genes. By analyzing the correlation between the intersection genes and immune cells, we found that the top 5 hub genes were TOM1, STAT3, RAB3D, MDM2, and FOS, which were all significantly positively correlated with neutrophils and significantly negatively correlated with eosinophils. A total of 52 intersection genes and the related circRNA and miRNA were used as input for Cytoscape software to construct a circRNA-mediated ceRNA competition endogenous network, where a total of 18 circRNAs were found. Further analysis of the correlation between circRNA and immune cells found that 4 circRNAs are positively correlated with neutrophils. Therefore, we speculate that there may be a regulatory relationship between circRNA-mediated ceRNA and the immune mechanism in AIS. This study has important guiding significance for the progress, outcome of AIS, and the development of new medicine.

Construction of a Joint Prediction Model for the Occurrence of Ischemic Stroke and Acute Myocardial Infarction Based on Bioinformatic Analysis.

Ischemic stroke (IS) has imposed significant threat to both middle-aged and elderly people worldwide. Acute myocardial infarction (AMI) is a rare but serious complication following IS, which can further increase patient disability and mortality rates. With the development of intravenous thrombolysis and endovascular treatment, the prognosis of IS has been greatly improved. However, the pathogenesis of IS complicated with AMI is still unclear. To fill this gap, this work uses bioinformatic analysis, where IS and AMI datasets were combined for differential gene analysis, and then, a ROC prediction model for target gene analysis was constructed. It is found that OSM gene has the highest prediction accuracy (AUC = 0.793), followed by IL6ST, IL6, JAK1, IL6R, and JAK2 genes. Joint prediction model showed higher accuracy in predicting the outcome of control and case (AUC = 0.918). The etiology of ischemic stroke and acute myocardial infarction is complicated. Their cooccurring pathological mechanisms and the conversion between the two diseases could not be explained by a single gene. Therefore, the joint prediction model in this work can provide a better prediction accuracy for research purpose.

[Effect of Met kinase inhibitor BMS-777607 on proliferation and apoptosis of tongue cell line CAL 27 squamous cell carcinoma].

PURPOSE: To investigate the effect of Met kinase inhibitor BMS-777607 on proliferation and apoptosis of tongue squamous cell carcinoma cell line CAL27. METHODS: The effect of BMS-777607 on proliferation of CAL27 was detected by MTT method, clone formation assay and EdU cell imaging. Morphological changes of apoptosis of CAL27 cells induced by BMS-777607 were observed by Heochst33342 staining. JC-1 staining was used to detect the changes of mitochondrial membrane potential of CAL27 cells treated with BMS-777607. Western blot was used to detect the effect of BMS-777607 on the expression of proliferation protein Akt, p-Akt and apoptosis-related proteins Bcl-2, Cleaved caspase-3, Bax and Parp in CAL27 cells. The data were analyzed using SPSS 22.0 software package. RESULTS: BMS-777607 inhibited proliferation and promoted apoptosis of CAL27 cells in a concentration-dependent manner（P＜0.05）. It also inhibited the expression of Bcl-2 and p-Akt and promoted the expression of Bax, Cleaved caspase-3 and Parp protein (P＜0.05). CONCLUSIONS: BMS-777607 can inhibit proliferation and promote apoptosis of CAL27 cells.

[Effect of enhancer of zeste homolog 2 inhibitor GSK126 on the proliferation and apoptosis of tongue squamous cell carcinoma].

OBJECTIVE: This study aims to study the effect of the enhancer of zeste homolog 2 (EZH2) inhibitor GSK126 on the proliferation and apoptosis of human tongue squamous cell carcinoma cells in vitro and explore its related mechanisms in order to obtain insights into the clinical treatment of tongue squamous cell carcinoma. METHODS: Different concentrations of GSK126 were applied to CAL-27 cells of tongue squamous cell carcinoma, and the effects of drugs on cell proliferation were detected through methyl thiazolyl tetrazolium (MTT) assay, colony formation assay, and 5-ethynyl-2'-deoxyuridine (EdU) fluorescence staining. Hoechst33342 fluorescence staining and the JC-1 method were used in observing apoptosis. The expression levels of extracellular regulated protein kinases (ERK), phospho-extracellular regulated protein kinases (p-ERK), Bax, Bcl-2, and Cleaved caspase-9 in Cal-27 cells were detected through Western blot. RESULTS: GSK126 inhibited CAL-27 cell proliferation and promoted apoptosis. GSK126 down-regulated the expression of p-ERK and Bcl-2 and increased the expression of Bax and Cleaved caspase-9 (P<0.05). CONCLUSIONS: GSK126 can inhibit the proliferation of CAL-27 cells in tongue squamous cell carcinoma and promote its apoptosis, and the related mechanism may be associated with the inhibition of the MEK/ERK signaling pathway and activation of the Bax/Bcl-2 pathway.

Serum uric acid levels in patients with Parkinson's disease: A meta-analysis.

BACKGROUND: Lower serum uric acid (UA) levels have been reported as a risk factor in Parkinson's disease (PD). However, the results have been inconsistent so far. OBJECTIVES: The aim of the present study was to clarify the potential relationship of uric acid with PD. METHODS: Comprehensive electronic search in pubmed, web of science, and the Cochrane Library database to find original articles about the association between PD and serum uric acid levels published before Dec 2015. Literature quality assessment was performed with the Newcastle-Ottawa Scale. Random-effects model was used to estimate the standardized mean differences (SMDs) with 95% confidence intervals (CIs). Heterogeneity across studies was assessed using I2 and H2 statistics. Sensitivity analyses to assess the influence of individual studies on the pooled estimate. Publication bias was investigated using funnel plots and Egger's regression test. Analyses were performed by using Review Manager 5.3 and Stata 11.0. RESULTS: Thirteen studies with a total of 4646 participants (2379 PD patients and 2267 controls) were included in this meta-analysis. The current results showed that the serum UA levels in PD patients were significantly lower compared to sex and age-matched healthy controls (SMD: -0.49, 95% CI: [-0.67, -0.30], Z = 5.20, P < 0.001) and these results showed no geographic regional (Asia: SMD = -0.65, 95% CI [-0.84, -0.46], Z = 6.75, p <0.001; Non-Asia: SMD = -0.25, 95% CI [-0.43, -0.07], Z = 2.70, p = 0.007) and sex differences (women: SMD = -0.53, 95% CI [-0.70, -0.35], z = 5.98, p <0.001; men: SMD = -0.66, 95% CI [-0.87, -0.44], z = 6.03, p <0.001). Serum UA levels in middle-late stage PD patients with higher H&Y scales were significantly lower than early stage PD patients with lower H&Y scales (SMD = 0.63, 95% CI [0.36,0.89], z = 4.64, p <0.001). CONCLUSIONS: Our study showed that the serum UA levels are significantly lower in PD and the level is further decreased as the disease progresses. Thus it might be a potential biomarker to indicate the risk and progression of PD.