Identification and validation of a costimulatory molecule-related signature to predict the prognosis for uveal melanoma patients.

Uveal melanoma (UVM) is the most common primary tumor in adult human eyes. Costimulatory molecules (CMs) are important in maintaining T cell biological functions and regulating immune responses. To investigate the role of CMs in UVM and exploit prognostic signature by bioinformatics analysis. This study aimed to identify and validate a CMs associated signature and investigate its role in the progression and prognosis of UVM. The expression profile data of training cohort and validation cohort were downloaded from The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) dataset. 60 CM genes were identified, and 34 genes were associated with prognosis by univariate Cox regression. A prognostic signature was established with six CM genes. Further, high- and low-risk groups were divided by the median, and Kaplan-Meier (K-M) curves indicated that high-risk patients presented a poorer prognosis. We analyzed the correlation of gender, age, stage, and risk score on prognosis by univariate and multivariate regression analysis. We found that risk score was the only risk factor for prognosis. Through the integration of the tumor immune microenvironment (TIME), it was found that the high-risk group presented more immune cell infiltration and expression of immune checkpoints and obtained higher immune scores. Enrichment analysis of the biological functions of the two groups revealed that the differential parts were mainly related to cell-cell adhesion, regulation of T-cell activation, and cytokine-cytokine receptor interaction. No differences in tumor mutation burden (TMB) were found between the two groups. GNA11 and BAP1 have higher mutation frequencies in high-risk patients. Finally, based on the Genomics of Drug Sensitivity in Cancer 2 (GDSC2) dataset, drug sensitivity analysis found that high-risk patients may be potential beneficiaries of the treatment of crizotinib or temozolomide. Taken together, our CM-related prognostic signature is a reliable biomarker that may provide ideas for future treatments for the disease.

Cysteine protease inhibitor S promotes lymph node metastasis of esophageal cancer cells via VEGF-MAPK/ERK-MMP9/2 pathway.

Cysteine protease inhibitor S (CST4) plays a pivotal role in the regulation of growth, invasion, and metastasis of a variety of malignancies. However, the potential mechanism behind how CST4 contributes to CST4 in lymph node metastasis (LNM) and tumor-associated lymphangiogenesis of esophageal cancer (EC) cells has not been elucidated previously. Short hairpin RNA technique was utilized to upregulate the CST4 gene expression. Different experiments, including the tubule formation assay and immunofluorescence, were conducted to observe the cellular behavior. Enzyme-linked immunosorbent assay (ELISA) and Western blot analyses were employed to determine the expression levels of relevant proteins. In our study, we discovered that high expression of CST4 in EC cells had multiple effects. It stimulated cell proliferation, invasion, and migration and caused epithelial-mesenchymal transition (EMT). Moreover, it also inhibited the apoptosis of EC cells and caused them to stagnate in the G2/M phase. High expression of CST4 promoted the secretion of lymphangiogenic markers (TGFß1, VEGF, VEGF-C/D) in EC cells. In addition, high expression of CST4 in EC cells not only enhanced the proliferation and migration of HLECs, but also stimulated the lumen formation and F-actin expression and rearrangement of HLECs. The elevated expression of CST4 also facilitated the secretion of p-ERK1/2, MMP9, and MMP-2 in HLECs. However, various tumor-promoting effects of high expression of CST4 on HLECs could be inhibited by VEGF inhibitors in EC cells. Overall, our findings indicate that CST4 plays a significant role in the accumulation, migration, and EMT of EC cells. CST4 can activate the VEGF-MAPK/ERK-MMP9/2 signaling axis to promote LNM and lymphangiogenesis in EC.

[Acacetin protects rats from cerebral ischemia-reperfusion injury by regulating TLR4/NLRP3 signaling pathway].

This study aims to investigate the mechanism of acacetin in protecting rats from cerebral ischemia-reperfusion injury via the Toll-like receptor 4(TLR4)/NOD-like receptor protein 3(NLRP3) signaling pathway. Wistar rats were randomized into sham, model, low-and high-dose acacetin, and nimodipine groups, with 10 rats in each group. The rat model of middle cerebral artery occlusion(MCAO) was established with the improved suture method in other groups except the sham group. The neurological deficit score and cerebral infarction volume of each group were evaluated 24 h after modeling. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1ß(IL-1ß), IL-6, tumor necrosis factor-α(TNF-α), malondialdehyde(MDA), supe-roxide dismutase(SOD), and glutathione(GSH). Western blot was employed to determine the expression levels of B-cell lymphonoma-2(Bcl-2), Bcl-2-associated X protein(Bax), and TLR4/NLRP3 signaling pathway-related proteins(TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1ß, and cleaved IL-1ß) in the rat brain tissue. Hematoxylin-eosin(HE) staining was employed to reveal the histopathological changes in the ischemic area. Compared with the sham group, the modeling of MCAO increased the neurological deficit score and cerebral infarction volume, elevated the IL-1ß, IL-6, TNF-α, and MDA levels and lowered the SOD and GSH levels in the brain tissue(P<0.05). Compared with the MCAO model group, low-and high-dose acacetin and nimodipine decreased the neurological deficit score and cerebral infarction volume, lowered the IL-1ß, IL-6, TNF-α, and MDA levels and elevated the SOD and GSH levels in the brain tissue(P<0.05). Compared with the sham group, the model group showed up-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1ß, and cleaved IL-1ß and down-regulated protein level of Bcl-2 in the brain tissue(P<0.05). Compared with the MCAO model group, the acacetin and nimodipine groups showed down-regulated protein levels of Bax, TLR4, p-NF-κB/NF-κB, NLRP3, pro-caspase-1, cleaved caspase-1, pro-IL-1ß, and cleaved IL-1ß and up-regulated protein level of Bcl-2 in the brain tissue(P<0.05). In conclusion, acacetin regulates the TLR4/NLRP3 signaling pathway to inhibit neuroinflammatory response and oxidative stress, thus exerting the protective effect on cerebral ischemia-reperfusion injury in rats.

Visual impairment and blindness caused by retinal diseases: A nationwide register-based study.

Background: Retinal disorders cause substantial visual burden globally. Accurate estimates of the vision loss due to retinal diseases are pivotal to inform optimal eye health care planning and allocation of medical resources. The purpose of this study is to describe the proportion of visual impairment and blindness caused by major retinal diseases in China. Methods: A nationwide register-based study of vitreoretinal disease covering all 31 provinces (51 treating centres) of mainland China. A total of 28 320 adults diagnosed with retinal diseases were included. Participants underwent standardised ocular examinations, which included best-corrected visual acuity (BCVA), dilated-fundus assessments, and optical coherence tomography. Visual impairment and blindness are defined using BCVA according to the World Health Organization (WHO) (visual impairment: <20/63-≥20/400; blindness: <20/400) and the United States (visual impairment: <20/40-≥20/200; blindness: <20/200) definitions. The risk factors of vision loss were explored by logistic regression analyses. Results: Based on the WHO definitions, the proportions for unilateral visual impairment and blindness were 46% and 18%, respectively, whereas those for bilateral visual impairment and blindness were 31% and 3.3%, respectively. Diabetic retinopathy (DR) accounts for the largest proportion of patients with visual impairment (unilateral visual impairment: 32%, bilateral visual impairment: 60%) and blindness (unilateral blindness: 35%; bilateral blindness: 64%). Other retinal diseases that contributed significantly to vision loss included age-related macular degeneration, myopic maculopathy, retinal vein occlusion, and rhegmatogenous retinal detachment and other macular diseases. Women (bilateral vision loss: P = 0.011), aged patients (unilateral vision loss: 45-64 years: P < 0.001, ≥65 years: P < 0.001; bilateral vision loss: 45-64 years: P = 0.003, ≥65 years: P < 0.001 (reference: 18-44 years)) and those from Midwest China (unilateral and bilateral vision loss: both P < 0.001) were more likely to suffer from vision loss. Conclusions: Retinal disorders cause substantial visual burden among patients with retinal diseases in China. DR, the predominant retinal disease, is accountable for the most prevalent visual disabilities. Better control of diabetes and scaled-up screenings are warranted to prevent DR. Specific attention should be paid to women, aged patients, and less developed regions.

miR-144 negatively regulates the effect of CCNB1 protein on the biological behavior of hepatoma cells.

Liver cancer poses a great threat to the life safety of patients, which is a common malignant tumor worldwide. This study aims to explore the effect of miR-144 negatively regulating CCNB1 on the biological behavior of liver cancer cells, including the proliferation, apoptosis and migration of liver cancer cells, so as to provide a sufficient biological basis for the treatment of liver cancer. A 3 armour hospital at the records of 100 patients with liver cancer in 2015-2019 as the research object, and resection of the liver cancer cells and tissue adjacent to carcinoma as the research samples, using polymerase chain reaction (PCR) for the organization of miR-144 gene and detect CCNB1 protein expression level, and by using a technique called RNA interference to silence the CCNB1 gene, and try to transfer by transfection CCNB1 protein, thus all kinds of biological behaviour of hepatocellular carcinoma cells. The liver tissue of miR-144 is low, the level of gene expression CCNB1 protein expression level is higher, the expression level in liver cancer cells directly influences the curative effect of hepatocellular carcinoma patients, the miR-144 gene can negative regulation CCNB1 protein, through this kind of negative adjustment to the biological behavior of liver cancer cells have a profound impact.

Prevalence of Parkinson's Disease in Adults Aged 65 Years and Older in China: A Multicenter Population-Based Survey.

BACKGROUND: Parkinson's disease (PD) is a common neurodegenerative disease. With the aging of the Chinese population, it is important to understand the prevalence of PD in the elderly. OBJECTIVE: Little data are available on the current prevalence of PD in China. The aim of this study was to determine the prevalence of PD in Chinese individuals aged 65 years and older and to analyze associated risk factors. METHODS: We performed a population-based cross-sectional survey using a multistage cluster sampling design. Residents aged 65 years and older were drawn from 11 urban districts and 10 rural counties across China. Data were entered into spreadsheets and analyzed using SPSS 24. RESULTS: We identified 151 patients with PD among 8,124 residents aged 65 years and over, including 75 men and 76 women. The overall prevalence of PD in the study population was 1.86%, and the standardized prevalence of PD was 1.60%. The crude prevalence in men (2.12%) was higher than that in women (1.66%) and the standardized prevalence in urban areas (1.98%) was higher than that in rural areas (1.48%). Logistic regression analysis showed that independent risk factors for PD were older age, heavy metal or pesticide exposure, urban residence, rapid eye movement sleep behavior disorder, and heart disease. CONCLUSIONS: The prevalence of PD among individuals aged 65 years and older in China has remained constant. The prevalence of PD is higher in men than in women and higher in urban areas than in rural areas.

CIGAR-seq, a CRISPR/Cas-based method for unbiased screening of novel mRNA modification regulators.

Cellular RNA is decorated with over 170 types of chemical modifications. Many modifications in mRNA, including m6 A and m5 C, have been associated with critical cellular functions under physiological and/or pathological conditions. To understand the biological functions of these modifications, it is vital to identify the regulators that modulate the modification rate. However, a high-throughput method for unbiased screening of these regulators is so far lacking. Here, we report such a method combining pooled CRISPR screen and reporters with RNA modification readout, termed CRISPR integrated gRNA and reporter sequencing (CIGAR-seq). Using CIGAR-seq, we discovered NSUN6 as a novel mRNA m5 C methyltransferase. Subsequent mRNA bisulfite sequencing in HAP1 cells without or with NSUN6 and/or NSUN2 knockout showed that NSUN6 and NSUN2 worked on non-overlapping subsets of mRNA m5 C sites and together contributed to almost all the m5 C modification in mRNA. Finally, using m1 A as an example, we demonstrated that CIGAR-seq can be easily adapted for identifying regulators of other mRNA modification.

1H-NMR analysis of amino acid metabolism in aqueous humor of patients with cataract, according to diabetes status.

OBJECTIVE: To investigate the differences in amino acid metabolism in aqueous humor of patients with cataract, according to diabetes status, using a 1H-nuclear magnetic resonance approach. METHODS: Aqueous humor samples from patients with age-related cataract, with or without diabetes, were collected during cataract surgery. All samples underwent nuclear magnetic resonance spectra analysis to characterize their metabolic function. Potential metabolic pathways were analyzed via MetaboAnalyst 3.0. RESULTS: This study included eight aqueous humor samples from patients with cataract and diabetes and eight aqueous humor samples from age- and sex-matched patients with cataract alone. Four metabolites were found to significantly differ in the aqueous humor of patients with cataract and diabetes, relative to patients with cataract alone; these metabolites were glucose (higher in patients with diabetes), valine, lysine, and tyrosine (all lower in patients with diabetes). Aminoacyl-tRNA biosynthesis was presumed to be involved in the metabolic differences observed in patients with cataract, according to diabetes status. CONCLUSIONS: The amino acid metabolic profile in the aqueous humor differed among patients with cataract, according to diabetes status. Disturbance of amino acid metabolism in the aqueous humor may be related to cataract formation in patients with diabetes.

Long non-coding RNA SNHG5 affects the invasion and apoptosis of renal cell carcinoma by regulating the miR-363-3p-Twist1 interaction.

Non-coding RNA dysregulation is associated with many human diseases, including cancer. This study explored the effects of lncRNA SNHG5 on clear cell renal cell carcinoma (ccRCC). We found that lncRNA SNHG5 is upregulated in human ccRCC tissues and that lncRNA SNHG5 inhibition reduced ccRCC cell invasion and promoted apoptosis in vitro. Bioinformatics database searching revealed that lncRNA SNHG5 is predicted to regulate the interaction between miR-363-3p and Twist1. We further verified a ccRCC biomarker panel, which consists of lncRNA SNHG5, miR-363-3p, and Twist1 in ccRCC tissue samples. The direct SNHG5-miR-363-3p and Twist1-miR-363-3p interactions were confirmed via dual-luciferase reporter assays. Additionally, functional assays demonstrated that SNHG5 promotes cell invasion and inhibits apoptosis, while miR-363-3p inhibits cell invasion and promotes apoptosis via an interaction with Twist1. Furthermore, we found that Twist1 promotes tumor metastasis by regulating matrix metalloproteinase (MMP)2 and MMP9 levels. Together, these results suggest that lncRNA SNHG5 may predict ccRCC patient clinical outcome and serve as a novel anti-ccRCC therapeutic target.

[Establishment of RIG-I knockout 293T cell line and its effect on the replication of influenza B virus].

The CRISPR/Cas9 gene editing technology directs Cas9 protein to recognize, bind and cleave the target site specifically by using artificial single-guide RNA (sgRNA), through non-homologous end joining or homologous end-recombinant repair mechanisms of cells, which can be engineered to knockout or knock-in of genomes. RIG-I is a pattern recognition receptor that recognizes the 5'-triphosphate-containing RNA in the cytoplasm and activates IRF3/7 and NF-κB by interacting with the downstream signaling molecule MAVS, thus initiating the expression of type I interferons and inflammatory factors. Previous studies found that influenza B virus (IBV) can up-regulate the expression of RIG-I. In the present study, to explore whether RIG-I is the major receptor for IBV to active the antiviral innate immune response and its effect on IBV replication, RIG-I gene in 293T cells was knocked out by CRISPR-Cas9 system, and a stable RIG-I knockout 293T (RIG-I(-/-) 293T) cell line was screened by puromycin pressure. The results of Western blotting showed that RIG-I was not expressed in this cell line after IBV or Sendai virus (SeV) infection, indicating that the RIG-I(-/-) 293T cell line was successfully constructed. The transcription levels of interferons, inflammatory factors and interferon-stimulated genes in RIG-I(-/-) 293T cells which were infected by IBV decreased significantly compared with those in wild-type 293T cells. Moreover, the phosphorylation of p65 and IRF3 were not detected in IBV or SeV infected RIG-I(-/-) 293T cells. It is indicated that the expression of cytokines mainly depends on the RIG-I-mediated signaling pathway at the early stage of IBV infection. Furthermore, the multi-step growth curves of IBV in the wild type and RIG-I(-/-) 293T cells showed that RIG-I inhibited the replication of IBV. Collectively, the RIG-I knockout 293T cell line was successfully constructed. We found that RIG-I is the main receptor for IBV to active the antiviral innate immune response and is critical for inhibiting IBV replication, which lays the foundation for further study of IBV infection mechanism.

Icariin Attenuates Diabetic Cardiomyopathy and Downregulates Extracellular Matrix Proteins in Heart Tissue of Type 2 Diabetic Rats.

OBJECTIVE: Diabetic cardiomyopathy (DCM) is a serious complication of type 2 diabetes mellitus (T2DM), resulting in unfavorable prognosis. Icariin (ICA) is a major flavonoid isolated from the traditional oriental herbal medicine Epimedium that has been recently proved to show potential therapeutic efficacy on T2DM. The aim of this study was to investigate the underlying mechanism of how ICA improved DCM in rat models. METHODS: To corroborate myocardial improvement by ICA, we managed to establish the T2DM rat model by streptozotocin (STZ) administration and high-glucose-high-fat diet. RESULTS: The rats with T2DM showed severe insulin resistance, left ventricular dysfunction, aberrant lipids deposition, cardiac inflammation, and fibrosis compared with the control group. All these pathological symptoms were ameliorated by the treatment of ICA. The levels of extracellular matrix proteins of heart tissue significantly declined in ICA-treated rats. CONCLUSION: ICA may exert as a protector in T2DM-induced DCM by reducing extracellular matrix proteins in the heart tissue, implicating its potential role for the treatment of human DCM.

SFI Enhances Therapeutic Efficiency of Gefitinib: An Insight into Reversal of Resistance to Targeted Therapy in Non-small Cell Lung Cancer Cells.

Background: The clinical application of EGFR tyrosine kinase inhibitors is always accompanied by inevitable drug resistance. However, the mechanism remains elusive. In the present study, we investigate the involvement of MAPK/SREBP1 pathway in NSCLC gefitinib resistance and evaluate the synergistic effects of shenqi fuzheng injection (SFI) and gefitinib on NSCLC cells. Methods: To investigate the MAPK/SREBP1 pathway involved in gefitinib resistance, Western blotting was used to examine p-MEK, p-ERK and SREBP1 expression in PC-9 and PC-9/GR cells, MTT was used on cell proliferation, wound healing assay was used on cell migration. To detect the cooperative effects of SFI and gefitinib, clonogenic assay was used on cell proliferation. Apoptosis assay was analyzed by flow cytometry. Immunofluorescence was used to detect gefitinib binding to EGFR. Western blotting was used to detect whether SFI regulate the resistance to gefitinib via the suppression of MAPK/SREBP1 pathway. Results: Our results showed that MAPK/SREBP1 pathway mediated resistance to gefitinib in NSCLC cells. MAPK pathway was found to directly target SREBP1 and inhibition of SREBP1 increased gefitinib sensitivity. In addition, SFI showed cooperative anti-proliferation and pro-apoptosis impacts on gefitinib resistant cells via down-regulating MAPK/SREBP1 pathway. Moreover, the combination of SFI and gefitinib enhanced gefitinib binding to EGFR resulting in the restoration of sensitivity to gefitinib. Conclusions: Taken together, MAPK/SREBP1 pathway could be regarded as the potential treatment target for overcoming resistance to EGFR-TKIs in NSCLC and adjuvant therapy of SFI could be a potential therapeutic strategy for gefitinib resistant treatment.

Trocar opening: silicone oil removal with phacoemulsification and intraocular lens implantation.

AIM: To evaluate the efficacy and safety of a modified technique [trocar opening (TO)] for silicone oil removal (SOR) in combination with phacoemulsification and intraocular lens (IOL) implantation. METHODS: A total of 60 eyes of 60 patients with cataract and silicone oil-filled eyes were enrolled in this study. The patients were divided into two groups: the patients in the control group underwent 23-gauge pars plana active SOR surgery with phacoemulsification and IOL implantation, while the patients in the TO group underwent TO methods during surgery. Best corrected visual acuity (BCVA), surgery time, intraocular pressure, and operative complications were observed 6mo after surgery. RESULTS: There was no significant difference between the two groups in terms of age, gender, preoperative, intraocular pressure, or time of silicone oil stay. Prior to surgery, the mean BCVA for the control and TO groups was 1.34±0.44 and 1.36±0.42. At 6mo following surgery, the mean BCVA improved to 0.74±0.36 and 0.77±0.32, respectively (P<0.001). There was no significant difference between the two groups. The mean SOR time was 6.9±2.3min and 4.8±1.2min in the control and TO groups (P=0.008). The total operation time was 28.2±8.5min and 24.6±6.4min, respectively (P=0.035). Posterior capsule rupture occurred in four eyes of control and none of TO group (P<0.01). Late recurrent retinal detachment occurred in one eye in the control group (2mo after surgery) and in one eye in the TO group (4mo after surgery). CONCLUSION: TO is a simple, effective, time-saving, and safe method for SOR combined with phacoemulsification and IOL implantation.

MeCP2 triggers diabetic cardiomyopathy and cardiac fibroblast proliferation by inhibiting RASSF1A.

Diabetes causes cardiomyopathy and increases the risk of heart failure independent of hypertension and cardiac fibrosis disease. However, the molecular mechanism of cardiomyopathy caused by diabetic (DCM) is currently unknown. Here we explore the role of the Methyl CpG binding protein 2 (MeCP2) in DCM patients and a type 1 DM (T1DM) rat model. In this study, we employed streptozotocin (STZ)-induced rats DCM and DCM patient and found that MeCP2 triggers cardiac fibroblast proliferation in DCM by inhibiting of RASSF1A expression. Moreover, the in vitro study demonstrated that high glucose inhibited RASSF1A expression, accompanied by the increases of MeCP2 expression and DNA hypermethylation in RASSF1A promoter region. MeCP2 inhibition or knockdown reversed the decrease of RASSF1A transcription induced by high glucose in cardiac fibroblasts. MeCP2 triggers cardiac fibroblasts proliferation through the activation of RASSF1A/ERK1/2 signaling pathways. Our results demonstrated that MeCP2 plays a key role in RASSF1A mediated ERK1/2 activation in DCM. Taken together, these indicate that MeCP2 acts as a key regulator of DCM and cardiac fibroblasts proliferation.

GSK3ß inhibits epithelial-mesenchymal transition via the Wnt/ß-catenin and PI3K/Akt pathways.

AIM: To investigate the regulatory mechanism of glycogen synthase kinase 3ß (GSK3ß) in epithelial-mesenchymal transition (EMT) process after proliferative vitreoretinopathy (PVR) induction. METHODS: Experimental PVR was induced by intravitreal injection of retinal pigment epithelium (RPE) cells in the eyes of rabbits. A PI3K/Akt inhibitor (wortmannin) and a GSK3ß inhibitor (LiCl) were also injected at different time during PVR progress. Electroretinogram (ERG), ocular fundus photographs, and B-scan ultrasonography were used to observe the PVR progress. Western blot test on the extracted retina were performed at 1, 2, 4wk. The expression of the mesenchymal marker vimentin was determined by immunohistochemistry. Toxicity of wortmannin and LiCl were evaluated by ERG and TdT-mediated dUTP nick-end labeling (TUNEL) assay. The vitreous was also collected for metabolomic analysis. RESULTS: Experimental PVR could significantly lead to EMT, along with the suppressed expression of GSK3ß and the activation of Wnt/ß-catenin and PI3K/Akt pathways. It was verified that upregulating the expression of GSK3ß could effectively inhibit EMT process by suppressing Wnt/ß-catenin and PI3K/Akt pathways. CONCLUSION: GSK3ß effectively inhibits EMT via the Wnt/ß-catenin and PI3K/Akt pathways. GSK3ß may be regarded as a promising target of experimental PVR inhibition.

LncRNAs and miRs as epigenetic signatures in diabetic cardiac fibrosis: new advances and perspectives.

PURPOSE: Diabetic cardiomyopathy (DCM) is a serious cardiac complication of diabetes, which further lead to heartfailure. It is known that diabetes-induced cardiac fibrosis is a key pathogenic factor contributing topathological changes in DCM. However, pathogenetic mechanisms underlying diabetes cardiac fibrosis arestill elusive. Recent studies have indicated that noncoding RNAs (ncRNAs) play a key role in diabetescardiac fibrosis. The increasing complexity of epigenetic regulator poses great challenges to ourconventional conceptions regarding how ncRNAs regulate diabetes cardiac fibrosis. METHODS: We searched PubMed, Web of Science, and Scopus for manuscripts published prior to April 2018 using keywords "Diabetic cardiomyopathy" AND " diabetes cardiac fibrosis " OR " noncoding RNAs " OR " longnoncoding RNAs " OR " microRNAs " OR "epigenetic". Manuscripts were collated, studied and carriedforward for discussion where appropriate. RESULTS: Based on the view that during diabetic cardiac fibrosis, ncRNAs are able to regulate diabetic cardiac fibrosisby targeting genes involved in epigenetic pathways. Many studies have focused on ncRNAs, an epigeneticregulator deregulating protein-coding genes in diabetic cardiac fibrosis, to identify potential therapeutictargets. Recent advances and new perspectives have found that long noncoding RNAs and microRNAs,exert their own effects on the progression of diabetic cardiac fibrosis. CONCLUSION: We firstly examine the growing role of ncRNAs characteristics and ncRNAs-regulated genes involved indiabetic cardiac fibrosis. Then, we provide several possible therapeutic strategies and highlight the potentialof molecular mechanisms in which targeting epigenetic regulators are considered as an effective means of treating diabetic cardiac fibrosis.

Epigenetic signatures in cardiac fibrosis, special emphasis on DNA methylation and histone modification.

Cardiac fibrosis is defined as excess deposition of extracellular matrix (ECM), resulting in tissue scarring and organ dysfunction. In recent years, despite the underlying mechanisms of cardiac fibrosis are still unknown, numerous studies suggest that epigenetic regulation of cardiac fibrosis. Cardiac fibrosis is regulated by a myriad of factors that converge on the transcription of genes encoding extracellular matrix protein, a process the epigenetic machinery plays a pivotal role. Epigenetic modifications contain three main processes: DNA methylation, histone modifications, and noncoding RNAs. Here, we review recent studies that have illustrated key roles for epigenetic events in the control of pro-fibrotic gene expression, and highlight the potential of molecule mechanisms that target epigenetic regulators as a means of treating cardiac fibrosis.

Possible interference between seasonal epidemics of influenza and other respiratory viruses in Hong Kong, 2014-2017.

BACKGROUND: Unlike influenza viruses, little is known about the prevalence and seasonality of other respiratory viruses because laboratory surveillance for non-influenza respiratory viruses is not well developed or supported in China and other resource-limited countries. We studied the interference between seasonal epidemics of influenza viruses and five other common viruses that cause respiratory illnesses in Hong Kong from 2014 to 2017. METHODS: The weekly laboratory-confirmed positive rates of each virus were analyzed from 2014 to 2017 in Hong Kong to describe the epidemiological trends and interference between influenza viruses, respiratory syncytial virus (RSV), parainfluenza virus (PIV), adenovirus, enterovirus and rhinovirus. A sinusoidal model was established to estimate the peak timing of each virus by phase angle parameters. RESULTS: Seasonal features of the influenza viruses, PIV, enterovirus and adenovirus were obvious, whereas annual peaks of RSV and rhinovirus were not observed. The incidence of the influenza viruses usually peaked in February and July, and the summer peaks in July were generally caused by the H3 subtype of influenza A alone. When influenza viruses were active, other viruses tended to have a low level of activity. The peaks of the influenza viruses were not synchronized. An epidemic of rhinovirus tended to shift the subsequent epidemics of the other viruses. CONCLUSION: The evidence from recent surveillance data in Hong Kong suggests that viral interference during the epidemics of influenza viruses and other common respiratory viruses might affect the timing and duration of subsequent epidemics of a certain or several viruses.

GSK3ß attenuates TGF-ß1 induced epithelial-mesenchymal transition and metabolic alterations in ARPE-19 cells.

While TGF-ß1 is known to induce epithelial-mesenchymal transition (EMT), a major factor in the pathogenesis of proliferative vitreoretinopathy (PVR), in ARPE-19 cells. The molecular pathways involved in EMT formation have not yet to be fully characterized. In this study, we have found that TGF-ß1-mediated induction of EMT in ARPE-19 cells varied in a dose- and time-dependent manner. Specifically, TGF-ß1 inhibited GSK-3ß by accelerating phosphorylation at ser9. GSK-3ß inhibitor or knockdown of GSK-3ß resulted in enhanced TGF-ß1-mediated EMT, migration and collagen contraction in ARPE-19 cells, which were then abrogated by GSK-3ß overexpression and PI3K/AKT inhibitor. Importantly, GSK-3ß also mediated metabolic reprogramming in TGF-ß1-treated cells. Our results indicate that GSK-3ß plays a pivotal role in TGF-ß1-mediated EMT in ARPE-19 cells.