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AIM: To evaluate the role of semaphorin 7A (Sema7A) and its associated regulatory mechanisms in modulating the barrier function of cultured human corneal epithelial cells (HCEs). METHODS: Barrier models of HCEs were treated with recombinant human Sema7A at concentrations of 0, 125, 250, or 500 ng/mL for 24, 48, or 72h in vitro. Transepithelial electrical resistance (TEER) as well as Dextran-fluorescein isothiocyanate (FITC) permeability assays were conducted to assess barrier function. To quantify tight junctions (TJs) such as occludin and zonula occludens-1 (ZO-1) at the mRNA level, reverse transcription-polymerase chain reaction (RT-PCR) analysis was performed. Immunoblotting was used to examine the activity of the nuclear factor-kappa B (NF-κB) signaling pathway and the production of TJs proteins. Immunofluorescence analyses were employed to localize the TJs. Enzyme-linked immunosorbent assay (ELISA) and RT-PCR were utilized to observe changes in interleukin (IL)-1β levels. To investigate the role of NF-κB signaling activation and IL-1β in Sema7A's anti-barrier mechanism, we employed 0.1 µmol/L IκB kinase 2 (IKK2) inhibitor IV or 500 ng/mL IL-1 receptor (IL-1R) antagonist. RESULTS: Treatment with Sema7A resulted in decreased TEER and increased permeability of Dextran-FITC in HCEs through down-regulating mRNA and protein levels of TJs in a time- and dose-dependent manner, as well as altering the localization of TJs. Furthermore, Sema7A stimulated the activation of inhibitor of kappa B alpha (IκBα) and expression of IL-1β. The anti-barrier function of Sema7A was significantly suppressed by treatment with IKK2 inhibitor IV or IL-1R antagonists. CONCLUSION: Sema7A disrupts barrier function through its influence on NF-κB-mediated expression of TJ proteins, as well as the expression of IL-1β. These findings suggest that Sema7A could be a potential therapeutic target for the diseases in corneal epithelium.

Backgrounds: Poorly regulated mitosis and chromosomal instability are common characteristics in malignant tumor cells. Kinesin family member 2 C (KIF2C), also known as mitotic centromere-associated kinesin (MCAK) is an essential component during mitotic regulation. In recent years, KIF2C was shown to be dysregulated in several tumors and was involved in many aspects of tumor self-regulation. Research on KIF2C may be a new direction and target for anti-tumor therapy. Object: The article aims at reviewing current literatures and summarizing the research status of KIF2C in malignant tumors as well as the oncogenic signaling pathways associated with KIF2C and its role in immune infiltration. Result: In this review, we summarize the KIF2C mechanisms and signaling pathways in different malignant tumors, and briefly describe its involvement in pathways related to classical chemotherapeutic drug resistance, such as MEK/ERK, mTOR, Wnt/β-catenin, P53 and TGF-β1/Smad pathways. KIF2C upregulation was shown to promote tumor cell migration, invasion, chemotherapy resistance and inhibit DNA damage repair. It was also highly correlated with microRNAs, and CD4 +T cell and CD8 +T cell tumor immune infiltration. Conclusion: This review shows that KIF2C may function as a new anticancer drug target with great potential for malignant tumor treatment and the mitigation of chemotherapy resistance.

Abstract Understanding the complex pathogenesis in myocardial ischemia/reperfusion (I/R) injury (IRI) is an urgent problem in clinical trials. Increasing pieces of evidence have suggested that miRNAs are involved in the occurrence and development of heart diseases by regulating mitochondria-related gene expression. Mitochondria have been acknowledged as the key triggers of cardiac I/R injury. However, the potential impact of miR-130a on mitochondria remains unclear in myocardial IRI. Exploring the regulatory mechanism of miR-130a on mitochondria may provide a new target for IRI therapy. In the present study, we found that miR-130a significantly increased in acute myocardial infarction (AMI) patients and myocardial I/R rats. MiR-130a could downregulate the viability of cardiomyocytes and the knockdown of miR-130a could protect the viability of cardiomyocytes under hypoxia-reoxygenation (HR). Over-expression of miR-130a resulted in mitochondrial dysfunction. It was evidenced by decreases in mitochondrial ATP production, mitochondrial membrane potential (MMP), and an increase in reactive oxygen species (ROS) production. However, suppression of miR-130a could protect against mitochondrial damage, show elevation of mitochondrial ATP production rate and MMP, and reduce ROS production. We further explored the effect of miR-130a on the mitochondrial quality control (QMC) system by determining mitochondrial-protein-specific proteases and analyzed mitochondrial morphology by fluorescence imaging and electron microscopy, respectively. It was noted that miR-130a could suppress mitochondrial fusion and FUNDC1-mediated mitophagy to accelerate myocardial IRI. Moreover, we investigated the potential miR-130a targeted mitochondria-related genes to understand the regulatory mechanism of miR-130a in the setting of myocardial IRI. It was revealed that miR-130a targeted GJA1, and GJA1 rescued IRI by enhancing ATP production rate and oxidative phosphorylation, meanwhile protecting cell viability, MMP, and activating mitophagy. In addition, the knockdown of miR-130a significantly activated FUNDC1-mediated mitophagy, while the knockdown of GJA1 reversed the relevant response. Collectively, our findings suggest that miR-130a regulates FUNDC1-mediated mitophagy by targeting GJA1 in myocardial IRI.

Background: RNA modification is one of the epigenetic mechanisms that regulates post-transcriptional gene expression, and abnormal RNA modifications have been reported to play important roles in tumorigenesis. N7-methylguanosine (m7G) is an essential modification at the 5′ cap of human mRNA. However, a systematic and pan-cancer analysis of the clinical relevance of m7G related regulatory genes is still lacking.Methods: We used univariate Cox model and Kaplan-Meier analysis to generate the forest plot of OS, PFI, DSS and identified the correlation between the altered expression of m7G regulators and patient survival in 33 cancer types from the TCGA and GTEx databases. Then, the “estimate” R-package, ssGSEA and CIBERSORT were used to depict the pan-cancer immune landscape. Through Spearman’s correlation test, we analyzed the correlation between m7G regulators and the tumor microenvironment (TME), immune subtype, and drug sensitivity of the tumors, which was further validated in NSCLC. We also assessed the changes in the expression of m7G related regulatory genes in NSCLC with regards to the genetic and transcriptional aspects and evaluated the correlation of METTL1 and WDR4 expression with TMB, MSI and immunotherapy in pan-cancer.Results: High expression of most of the m7G regulators was significantly associated with worse prognosis. Correlation analyses revealed that the expression of majority of the m7G regulators was correlated with tumor immune infiltration and tumor stem cell scores. Drug sensitivity analysis showed that the expression of CYFP1,2 was closely related to drug sensitivity for various anticancer agents (p < 0.001). Analysis of the pan-cancer immune subtype revealed significant differences in the expression of m7G regulators between different immune subtypes (p < 0.001). Additionally, the types and proportions of mutations in METTL1 and WDR4 and their relevance to immunotherapy were further described.Conclusion: Our study is the first to evaluate the correlation between the altered expression of m7G regulators and patient survival, the degree of immune infiltration, TME and drug sensitivity in pan-cancer datasets.

Abstract Background Apatinib, a novel vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor, has been approved for the treatment of metastatic gastric cancer and other tumors. Apatinib exerts antiproliferative and proapoptotic effects in different kinds of cancer cells. However, the molecular mechanisms by which apatinib effective against esophageal squamous cell carcinoma (ESCC) have only been partially researched and whether it has a sensitizing effect on paclitaxel remains unclear. Materials and methods The effects of apatinib or paclitaxel on endoplasmic reticulum (ER) stress, autophagy, apoptosis and proliferation of ESCC cell lines were evaluated. Western blot and immunohistochemistry analyses were performed to detect the expression of related genes. The weight and volume of xenograft tumors in mice were measured. Results In the current study, we elucidated the antiproliferative and ER-stress-mediated autophagy-inducing effects of apatinib on ECA-109 and KYSE-150 esophageal squamous cancer cells and identified the underlying mechanisms of its action. We demonstrated that apatinib not only inhibited the proliferation and induced the apoptosis of ESCC cells, but also activated ER stress and triggered protective autophagy. Moreover, inhibiting autophagy by chloroquine (CQ) enhanced the apatinib-induced apoptosis of ESCC cells through the IRE-1α–AKT–mTOR pathway. In addition, we showed, for the first time, the paclitaxel combined with apatinib and CQ exhibited the best antitumor effect on ESCC both in vivo and in vitro via the IRE-1α–AKT–mTOR pathway. Conclusions Our data showed that apatinib induced ER stress, autophagy and apoptosis in ESCC. Inhibiting autophagy by CQ enhanced apatinib-induced apoptosis. The combination of apatinib and CQ sensitized ESCC cells to paclitaxel to induce apoptosis through the IRE-1α–AKT–mTOR signaling pathway, thus providing the basis for its use in innovative anticancer therapeutic strategies. Graphic abstract

Abstract Background Alzheimer’s disease (AD) is a major clinical problem, but there is a distinct lack of effective therapeutic drugs for this disease. We investigated the potential therapeutic effects of zerumbone, a subtropical ginger sesquiterpene, in transgenic APP/PS1 mice, rodent models of AD which exhibit cerebral amyloidosis and neuroinflammation. Methods The N9 microglial cell line and primary microglial cells were cultured to investigate the effects of zerumbone on microglia. APP/PS1 mice were treated with zerumbone, and non-cognitive and cognitive behavioral impairments were assessed and compared between the treatment and control groups. The animals were then sacrificed, and tissues were collected for further analysis. The potential therapeutic mechanism of zerumbone and the signaling pathways involved were also investigated by RT-PCR, western blot, nitric oxide detection, enzyme-linked immunosorbent assay, immunohistochemistry, immunofluorescence, and flow cytometry analysis. Results Zerumbone suppressed the expression of pro-inflammatory cytokines and induced a switch in microglial phenotype from the classic inflammatory phenotype to the alternative anti-inflammatory phenotype by inhibiting the mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B signaling pathway in vitro. After a treatment period of 20 days, zerumbone significantly ameliorated deficits in both non-cognitive and cognitive behaviors in transgenic APP/PS1 mice. Zerumbone significantly reduced β-amyloid deposition and attenuated pro-inflammatory microglial activation in the cortex and hippocampus. Interestingly, zerumbone significantly increased the proportion of anti-inflammatory microglia among all activated microglia, potentially contributing to reduced β-amyloid deposition by enhancing phagocytosis. Meanwhile, zerumbone also reduced the expression of key molecules of the MAPK pathway, such as p38 and extracellular signal-regulated kinase. Conclusions Overall, zerumbone effectively ameliorated behavioral impairments, attenuated neuroinflammation, and reduced β-amyloid deposition in transgenic APP/PS1 mice. Zerumbone exhibited substantial anti-inflammatory activity in microglial cells and induced a phenotypic switch in microglia from the pro-inflammatory phenotype to the anti-inflammatory phenotype by inhibiting the MAPK signaling pathway, which may play an important role in its neuroprotective effects. Our results suggest that zerumbone is a potential therapeutic agent for human neuroinflammatory and neurodegenerative diseases, in particular AD.

Abstract Background This study aims to evaluate the ADL(activity of daily living) of patients with acute cerebral infarction through BI scoring, in order to observe its predictive value in the prognosis of these patients. Methods According to the inclusion and exclusion criteria, patients with acute anterior circulation cerebral infarction were included in the present study. Then, the BI scoring was analyzed through five grades, in order to further investigate the dose-response relationship between BI scoring and mortality risk in patients with cerebral infarction. The receiver operating characteristic (ROC) curves for BI-scored patients were drawn, and the predictive authenticity of the Barthel scale in prognostic prediction for patients with cerebral infarction was estimated. Results The difference in BI scores between the survival group and death group were statistically significant (t = 10.029, P

This study was conducted to investigate the effects of Spirulina and ferrous fumarate supplementations into diets on growth parameters, pigmentation, digestive enzyme activity, antioxidant enzyme activity and fatty acids composition of Yellow River carp. Three experimental groups included control, Spirulina (diet 1), mixture of Spirulina and ferrous fumarate treatments (diet 2) in 3 replications in 9 aquariums. Fifteen fish in each aquarium were fed twice a day for six weeks. Compared to the control group, the Yellow River carp fed with the Spirulina and ferrous fumarate had a higher specific growth rate (P < 0.05). The total carotenoids content in Yellow River carp skin and scale was significantly higher for fish fed diet with Spirulina and ferrous fumarate relative to all other diets (P < 0.05). The color parameters of L *, a *, b*, Hue (Hab°) and Chroma (ch*) were calculated for all treatments. Obtain findings revealed that the Spirulina and ferrous fumarate treatment could provide the desired skin color exactly of Yellow River carp. The Spirulina and ferrous fumarate supplementation significantly elevated intestinal digestive capacity by increasing amylase, lipase, and trypsin enzyme activities (P < 0.05). The results obtained indicated that Spirulina and ferrous fumarate supplementation could improve intestinal health through enhancing intestinal digestive enzyme activity and reducing tissue peroxidation. In addition, the Spirulina and ferrous fumarate has a satisfactory nutritional value of improving the fatty acid profile. Therefore, the use of Spirulina and ferrous fumarate as feed additive could be practiced in the aquaculture species.

An unprecedented solvent-tuned electrochemical method for selective C(sp³)--H bond activation towards the synthesis of C3 functionalized chromone derivatives has been developed. This electrosynthesis protocol provides an efficient and green way to access various C3-functionalized chromones by avoiding traditionally employed transition metals and high temperatures. The swappable chemoselectivity was controlled mainly by altering the solvent and the current. A plausible reaction mechanism has been proposed with the help of radical capture and cyclic voltammetry experiments. [ABSTRACT FROM AUTHOR]

Aim. To explore the expression of long noncoding RNA (LncRNA) LUCAT1 in adult patients with Crohn’s disease (CD) and evaluate the relationship between LncRNA LUCAT1 and the disease activity in Chinese patients with CD. Methods. Patients with CD and healthy participants (≥18 years old) were enrolled in this study between January 2018 and December 2019. The expression of LncRNA LUCAT1 in plasma samples was evaluated by quantitative reverse transcription-polymerase chain reaction. Basic characteristics of patients with CD were collected, including gender, age, clinical stage, disease behavior, disease location, C-reactive protein (CRP), platelet (PLT), erythrocyte sedimentation rate (ESR), fecal calprotectin (FC), Crohn’s disease activity index (CDAI) score, and simplified Crohn’s disease endoscopic score (SES-CD). Results. In total, 168 patients with CD and 65 healthy participants (≥18 years old) were enrolled in this study. Among them, ninety patients with clinically active CD, seventy-eight patients with CD in clinical remission, forty-eight patients with endoscopically active CD, thirty patients with endoscopically inactive CD, and sixty-five healthy participants. LncRNA LUCAT1 was increased in plasma of patients with CD compared with the control group. The plasma LncRNA LUCAT1 level of patients with CD both in the clinical and endoscopic active phase was higher than that of both the clinical and endoscopic remission phase. The plasma level of LncRNA LUCAT1 in patients with CD was positively correlated with ESR, CRP, FC, CDAI, and SES-CD. There was no significant correlation between the level of LUCAT1 and platelets. The plasma LncRNA LUCAT1 level in patients with CD had significant differences between severe active patients and mild/moderate active patients. Conclusion. The plasma LncRNA LUCAT1 is positively associated with the disease activity in patients with CD, and it may act as a noninvasive biomarker to identify the degree of disease activity.

Objective This study aimed to evaluate the joint monitoring of somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) in vertebral canal decompression surgery for acute spinal cord injury. Methods Twenty-four patients, who were admitted to the hospital for the surgical treatment of spinal cord injury with SEP and MEP monitoring, were assigned to the intraoperative monitoring group (group I). In addition, 24 patients who were admitted to the hospital for the surgical treatment of spinal cord injury without SEP or MEP monitoring were assigned to the control group (group C). Results In group I, there were significant changes before and after decompression surgery in the P40 latency and amplitude, and in the latency of MEP in the abductor hallucis brevis (AHB), in patients with improved spinal nerve function following surgery. In contrast, there were no significant differences in the P40 latency or amplitude, or the latency of MEP in the AHB, in patients who showed no improvement after surgery. Conclusion In vertebral canal decompression surgery for acute spinal cord injury, the application of joint MEP and SEP monitoring can timely reflect changes in spinal cord function.

Objective: The present study aimed to evaluate the prognostic value of Acute Physiology and Chronic Health Evaluation (APACHE; II and III), Chinese Stroke Scale (CSS), National Institutes of Health Stroke Score (NIHSS), activities of daily living (ADL) (Barthel index, BI), and Glasgow Coma Scale (GCS) scores for stroke patients.Methods: A total of 352 stroke patients were evaluated using APACHE II, APACHE III, CSS, NIHSS, ADL, and GCS scores within 24 h after admission. And these patients were consecutive admissions to the hospital. The endpoint was in-hospital death. The scores of these scales were compared between the survival group and death group, and the receiver operating characteristic (ROC) curves were drawn. The ability of each scoring system to predict the prognosis of patients was evaluated using the area under the ROC curve, and the areas under the curves (AUCs) of these six scales were compared.Results: The AUCs of the APACHE II, APACHE III, CSS, NIHSS, ADL, and GCS scores were 0.882, 0.867, 0.832, 0.859, 0.838, and 0.819, respectively.Conclusion: APACHE II, APACHE III, CSS, NIHSS, ADL, and GCS scores have good predictive values in the prognosis of stroke patients. APACHE II is superior among the other five scales.

AIM: To determine if tranilast affects human corneal fibroblast (HCFs) contraction. METHODS: HCFs cultured in a three-dimensional type I collagen gel were treated with or without transforming growth factor beta (TGF-β) or tranilast. Gel diameter was measured as an indicator for collagen contraction. Immunoblot was performed to evaluate myosin light chain (MLC) and paxillin phosphorylation. Confocal microscopy was employed to examine the focal adhesions and actin stress fiber formation. Immunoblot analysis and gelatin zymography were performed to detect tissue inhibitors of metalloproteinases and matrix metalloproteinases (MMPs) in supernatant. RESULTS: The inhibitory effect of tranilast on HCFs-mediated collagen gel contraction induced by TGF-β was dose-dependent. The significant effect of tranilast was started from 100 μmol/L and maximized at 300 μmol/L. The peak effect of 300 μmol/L tranilast also relied on the duration of treatment, which showed statistical significance from day 2. TGF-β-induced paxillin and MLC phosphorylation, stress fiber formation, focal adhesions, and MMP-1, MMP-2, and MMP-3 secretion in HCFs were also inhibited by tranilast. CONCLUSION: Tranilast suppresses the HCFs-cultured collagen gel contraction induced by TGF-β. It attenuates actin stress fibers formation, focal adhesions, and the secretion of MMPs, with these actions likely contributing to the inhibitory effect on HCF contractility. By attenuating the contractility of corneal fibroblasts, tranilast treatment may inhibit corneal scarring.

Objective: This study aims to evaluate the effects of combining Acute Physiology and Chronic Health Disease Classification System II (APACHE II) scores and the NIHSS score for short-term prognosis of cerebral hemorrhage patients.Methods: APACHE II and NIHSS scores were respectively carried out for 189 acute cerebral hemorrhage patients who were admitted to the hospital for 24 h, and the area under ROC curve was used to measure the ability of these score systems to forecast the prognosis, in order to find the best dividing value. The discriminant analysis method should be used to carry out a comprehensive analysis of these two score methods and establish the mathematical model to provide a reasonable basis for accurately mastering these illness conditions, and its prognosis.Results: The areas under the ROC curve of APACHE II and NIHSS scores in forecasting cerebral hemorrhage prognosis was 0.853 and 0.845, respectively, the dividing value was 15 and 17, respectively, and the forecasting accuracy was 77.2 and 79.9%, respectively; The forecasting accuracy of the combined discrimination model was 85.96%.Conclusion: APACHE II and NIHSS scores have good forecasting value to the short-term prognosis of acute cerebral hemorrhage patients, and the combination of these two can provide a higher forecasting value.

AIM: To investigate the association between collagen type I alpha 1 (COL1A1) gene and high myopia. METHODS: In this Meta-analysis, we examined 5 published case-control studies that involved 1942 high myopia cases and 2929 healthy controls to assess the association between the COL1A1 rs2075555 polymorphism and high myopia risk. We calculated the pooled odds ratios (ORs) of COL1A1 rs2075555 polymorphism in high myopia cases vs healthy controls to evaluate the strength of the association. RESULTS: Overall, there was no significant difference both in the genotype and allele distributions of COL1A1 rs2075555 polymorphism between high myopia cases and healthy controls: CC vs AA OR=1.10, 95% confidence interval (CI)=0.76-1.58; AC vs AA OR=0.98, 95%CI 0.80-1.20; CC/AC vs AA/OR=1.01, 95%CI 0.84-1.22; CC vs AC/AA OR=1.06, 95%CI=0.93-1.20; C vs A OR=1.06, 95%CI 0.91-1.23). In addition, in the stratified analyses by ethnicity, no significant associations were found in any genetic model both in European and Asia cohorts. CONCLUSION: Our results indicate that the COL1A1 rs2075555 polymorphism may not affect susceptibility to high myopia.

Background The major clinical presentation of severe subclavian artery stenosis is subclavian steal syndrome (SSS). At present, stent implantation has become a promising method for this disease. The aim of this article is to investigate the effectiveness and safeness of stent implantation in the treatment for symptomatic severe subclavian artery stenosis. Methods Clinical data of 20 patients with symptomatic severe subclavian artery stenosis treated via angioplasty and stenting from June 2012 to November 2012 were retrospectively analyzed. Results The procedure was technically successful in all of the 20 cases. Postoperative digital subtraction angiography (DSA) suggested the residual ratio of subclavian artery stenosis was < 20% . Straight-forward blood flow in vertebral artery, disappeared subclavian steal symptom and fluent blood flow in intracranial segment of ipsilateral vertebral artery were also seen. After procedure no stent⁃related complications were found. During the follow-up study from 10 days to 6 months, vessel ultrasound and computed tomography angiography (CTA) showed no in-stent restenosis, vessels with good form and fluent blood flow. Conclusion Percutaneous angioplasty and stenting is a minimally invasive, safe and effective method in the treatment for severe subclavian artery stenosis.

AIM: To study the correlation between visual display terminal(VDT)exposure time and ocular symptoms.METHODS: By use of questionnaire, a survey was carried out in 1218 undergraduate students from 3 universities in Zhuhai to find out their VDT exposure time and their eye symptoms. VDT exposure time at different grades and ocular symptom scores in different exposure intensity crowd were compared, the relationship between VDT exposure time and ocular symptoms were investigated.RESULTS: On average, VDT exposure time in all students of the three universities was 3.72±2.17h, the mean exposure time increased with grade. And the ocular symptoms scores increased with exposure time, VDT has a positive correlation with VDT exposure time.CONCLUSION: Long-time exposure to VDT is harmful to visual health, eye health education should be strengthened to avoid or reduce the health damages caused by VDT exposure.

AIM: To investigate the effect of anterior chamber puncture combined trabeculectomy in the treatment of high intraocular pressure continued state of acute angle-closure glaucoma. METHODS: Totally 80 cases with angle-closure glaucoma from March 2011 to June 2012 in our hospital were retrospectively analyzed, and 40 cases were given trabeculectomy after anterior chamber decompression(observation group)while 40 cases were received trabeculectomy after drugs decompression(control group). The clinical efficacy was compared between the two groups. RESULTS: The postoperative vision recovery, anterior chamber angle and pupil improvement were better than the control group, and the incidence of complications were less than the control group, the difference was statistically significant(P