Feasibility and reproducibility of cardiovascular magnetic resonance-feature tracking for quantitative right atrial function in dilated cardiomyopathy patients.

Background: The importance of right heart assessment in dilated cardiomyopathy (DCM) is increasingly recognized. The development of cardiovascular magnetic resonance-feature tracking (CMR-FT) has provided a novel approach to quantify myocardial deformation and evaluate cardiac function. In this study, we aimed to evaluate the feasibility and reproducibility of CMR-FT for the quantitative derivation of right atrial (RA) strain and strain rate (SR) in patients with DCM. Methods: A total of 68 DCM patients (84% male; aged 50.6±13.2 years) and 58 healthy controls (81% male; aged 48.4±11.2 years) were retrospectively enrolled from September 2018 to August 2022 at the First Affiliated Hospital of Zhejiang Chinese Medical University and Shenzhen Clinical Medical College of Guangzhou University of Chinese Medicine. RA reservoir, conduit, and booster strain (εs, εe, and εa) and peak positive, peak early negative, and peak late negative SR (SRs, SRe, and SRa) were measured using CMR-FT and compared between 2 groups using Student's t-test. Intra- and inter-observer reproducibility was evaluated using intraclass correlation coefficients (ICC) and Bland-Altman plots. Results: Compared to healthy controls, DCM patients showed significantly lower RA strain (εs: 19.7%±9.0% vs. 44.4%±9.7%; εe: 7.9%±5.3% vs. 25.8%±8.6%; εa: 11.8%±6.2% vs. 18.6%±5.1%, all P<0.001) and SR (SRs: 1.17±0.48 vs. 1.92±0.62 s-1; SRe: -0.85±0.56 vs. -1.94±0.63 s-1; SRa: -1.39±0.71 vs. -2.01±0.65 s-1, all P<0.001). There was no significant difference in RA maximum volume index between the 2 groups. Simple linear regression analysis demonstrated a significant correlation between N-terminal B-type natriuretic peptide (NT-proBNP), RA emptying fraction passive (RAEF passive), and RA εe [(NT-proBNP and εe): r=-0.48, P<0.001, 95% confidence interval (CI): -0.64 to -0.26; and (RAEF passive and εe): r=0.41, P=0.001, 95% CI: 0.22 to 0.56, respectively] in DCM patients. Intra- and inter-observer reproducibility was excellent (all ICCs >0.85) for RA deformation measurements. Conclusions: CMR-FT is a promising, noninvasive approach for the quantitative assessment of RA phasic function in patients with DCM. DCM patients exhibit impaired RA reservoir, conduit, and booster pump function prior to visible RA enlargement.

Hypoxia inhibits ferritinophagy-mediated ferroptosis in esophageal squamous cell carcinoma via the USP2-NCOA4 axis.

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy of the digestive system. Hypoxia is a crucial player in tumor ferroptosis resistance. However, the molecular mechanism of hypoxia-mediated ferroptosis resistance in ESCC remains unclear. Here, USP2 expression was decreased in ESCC cell lines subjected to hypoxia treatment and was lowly expressed in clinical ESCC specimens. Ubiquitin-specific protease 2 (USP2) depletion facilitated cell growth, which was blocked in USP2-overexpressing cells. Moreover, USP2 silencing enhanced the iron ion concentration and lipid peroxidation accumulation as well as suppressed ferroptosis, while upregulating USP2 promoted ferroptotic cell death in ESCC cells. Furthermore, knockout of USP2 in ESCC models discloses the essential role of USP2 in promoting ESCC tumorigenesis and inhibiting ferroptosis. In contrast, overexpression of USP2 contributes to antitumor effect and ferroptosis events in vivo. Specifically, USP2 stably bound to and suppressed the degradation of nuclear receptor coactivator 4 (NCOA4) by eliminating the Lys48-linked chain, which in turn triggered ferritinophagy and ferroptosis in ESCC cells. Our findings suggest that USP2 plays a crucial role in iron metabolism and ferroptosis and that the USP2/NCOA4 axis is a promising therapeutic target for the management of ESCC.

Opportunities and challenges for human papillomavirus vaccination in China.

Current estimates of the HPV infection rate in China vary by geographic region (9.6-23.6%), with two age peaks in prevalence in women ≤20-25 years of age and 50-60 years of age. HPV-16, 52 and 58 are the most commonly-detected HPV genotypes in the Chinese population. In China, five HPV vaccines are licensed and several others are undergoing clinical trials. Multiple RCTs have shown the efficacy and safety of the bvHPV (Cervarix), Escherichia coli-produced bvHPV (Cecolin), Pichia pastoris-produced bvHPV (Walrinvax), qvHPV (Gardasil) and 9vHPV (Gardasil-9) vaccines in Chinese populations, including two studies showing long-term efficacy (≥8 years) for the bvHPV and qvHPV vaccines. Real-world data from China are scarce. Although modeling studies in China show HPV vaccination is cost-effective, uptake and population coverage are relatively low. Various policies have been implemented to raise awareness and increase vaccine coverage, with the long-term aim of eliminating cervical cancer in China.

Comprehensive pan-cancer analysis of 33 human cancers reveals immunotherapeutic value of focal adhesion tyrosine kinase.

The immune environment in tumors is the key factor affecting the survival and immunotherapeutic response of patients. This research aimed to explore the underlying association between focal adhesion tyrosine kinase (FAK/PTK2) and cancer immunotherapy in 33 human cancers. Gene expression data and clinical features of 33 cancers were retrieved from the Cancer Genome Atlas Database. The immunotherapy cohorts included GSE67501, GSE78220, and IMVIGOR210, which were derived from the comprehensive gene expression database or from previous studies. Clinical parameters including patient age, gender, survival rate, and tumor stage were analyzed to evaluate the prognostic value of FAK/PTK2. FAK/PTK2 activity was detected by single-sample gene set enrichment analysis and used to compare the difference between FAK/PTK2 transcriptome and protein expression levels. To better understand the role of FAK/PTK2 in cancer immunotherapy, we analyzed its correlations with tumor microenvironment and with immune processes/elements (e.g., immune cell infiltration, immunosuppressants, and stimulants) and major histocompatible complexes. Potential pathways associated with FAK/PTK2 signaling in cancers were also explored. Correlations between FAK/PTK2 and 2 immunotherapeutic biomarkers (tumor mutation load and microsatellite instability) were studied. Finally, the 3 independent immunotherapy cohorts were used to study the relationship between FAK/PTK2 and immunotherapeutic response. Although FAK/PTK2 is not closely associated with age (13/33), gender (5/33), or tumor stage (5/33) in any of the studied human cancers, it has potential prognostic value for predicting patient survival. Consistency between FAK/PTK2 activity and expression exists in some cancers (3/33). Generally, FAK/PTK2 is robustly correlated with immune cell infiltration, immune modulators, and immunotherapeutic markers. Moreover, high FAK/PTK2 expression is significantly related to immune-relevant pathways. However, FAK/PTK2 is not significantly correlated with the immunotherapeutic response. Research on the immunotherapeutic value of FAK/PTK2 in 33 human cancers provides evidence regarding the function of FAK/PTK2 and its role in clinical treatment. However, given the use of a bioinformatics approach, our results are preliminary and require further validation.

Unveiling the mechanism of high sugar diet induced advanced glycosylation end products damage skin structure via extracellular matrix-receptor interaction pathway.

BACKGROUND: AGEs accumulate in the skin as a result of a high-sugar diet and play an important role in the skin aging process. OBJECTIVES: The aim of this study was to characterize the mechanism underlying the effect of a high-sugar diet on skin aging damage at a holistic level. METHODS: We established a high-sugar diet mouse model to compare and analyze differences in physiological indexes. The effect of a high-sugar diet on skin aging damage was analyzed by means of a transcriptome study and staining of pathological sections. Furthermore, the differences in the protein expression of AGEs and ECM components between the HSD and control groups were further verified by immunohistochemistry. RESULTS: The skin in the HSD group mice tended toward a red, yellow, dark, and deep color. In addition, the epidermis was irregular with anomalous phenomena, the epidermis was thinned, and the dermis lost its normal structure and showed vacuolated changes. Transcriptomics results revealed significant downregulation of the ECM-receptor interaction pathway, significant upregulation of the expression of AGEs and significant downregulation of the expression levels of COLI, FN1, LM5, and TNC, among others ECM proteins and ECM receptors. CONCLUSIONS: High-sugar diets cause skin aging damage by inducing the accumulation of AGEs, disrupting the expression of ECM proteins and their receptors, and downregulating the ECM-receptor interaction pathway, which affects cellular behavioral functions such as cell proliferation, migration, and adhesion, as well as normal skin tissue structure.

The influencing factor model and empirical research of TikTok charity live streaming impact users' online charitable donation.

The "live streaming + charity" model is a new model for China's philanthropy, accelerating the new development of China's philanthropy, but there is still a relative paucity of research in the academic community on how charity live streaming affects online charitable donations. In this sense, this study aims to identify the construction of a model of the factors influencing charity live streaming on online charitable donations. This study selected TikTok Live, based on the UTAUT model, combining perceived risk and perceived interactivity, recovered 607 valid questionnaires, and concluded and structural equation modeling to construct an influence factor model to analyze their correlation. The results show that users' performance expectancy, effort expectancy, perceived interactivity, facilitating conditions, and social influence are significantly positively correlated with online charitable donations, and perceived risk does not negatively affect users' intentions to make online charitable donations. Our findings can provide a basis for live-streaming platforms and relevant social organizations and government departments to develop charity communication strategies.

Predictive values of the hemoglobin, albumin, lymphocyte and platelet score (HALP) and the modified -Gustave Roussy immune score for esophageal squamous cell carcinoma patients undergoing concurrent chemoradiotherapy.

The hemoglobin, albumin, lymphocyte and platelet (HALP) score and the Gustave Roussy immune score (GRIm⁃Score) are prognostic markers in several types of malignant tumors. The prognostic values of HALP score and GRIm⁃Score in concurrent chemoradiotherapy for unresectable esophageal cancer remain unknown. METHODS: We enrolled 150 esophageal squamous cell carcinoma (ESCC) patients who underwent concurrent chemoradiotherapy in our institution between 2013 and 2018. The cutoff values for HALP, and GRIm⁃Score were defined by using receiver's operating characteristic curves. Survival was analyzed with the Kaplan- Meier method, with differences analyzed with the log-rank test. Multivariate Cox proportional-hazards models were used to evaluate the prognostic significance of HALP and GRIm for ESCC. RESULTS: HALP was significantly associated with the Zubrod ECOG WHO performance status, tumor location, and the clinical tumor, node, metastasis stage. Modified GRIm (mGRIm) was only significantly associated with metastasis / recurrence before radiotherapy (χ2 = 6.25). Univariate Cox regression analysis showed that higher mGRIm (HR 1.9 95%CI 1.3-2.9) and lower HALP (HR 2.4 95%CI 1.6-3.7) were all associated with worse OS. Multivariate COX analysis found that higher mGRIm score (HR 1.7 95%CI 1.1-2.6), and lower HALP score (HR 2 95%CI 1.3-3.2) were both independent risk factors of overall survival. The nomogram c-index in inside validation was 0.66. CONCLUSION: Both HALP and mGRIm are independent prognostic factors for patients with unresectable ESCC.

Effect of indwelling depth of peripheral intravenous catheters on thrombophlebitis.

To clarify the effect of catheter indwelling depth on the occurrence of thrombophlebitis, a total of 339 hospitalized patients were randomly enrolled and divided by the catheter indwelling depth into 2 groups. Then the effect of indwelling depth on thrombophlebitis was analyzed, and the independent influence factors on the occurrence of thrombophlebitis were clarified. There were 49 cases of thrombophlebitis, including 8 tumor-bearing patients and 41 patients with lung infection. Thirteen of the 135 patients with indwelling depth of 1 cm, and 36 of the 204 patients with indwelling depth of 1.9 cm suffered thrombophlebitis. The relationship between incidence rate of thrombophlebitis and clinicopathological parameters was analyzed. It was found the incidence of thrombophlebitis was significantly correlated with males (X2 = 5.77), lung infection (X2 = 7.79), and indwelling depth of 1.9 cm (X2 = 4.223). Multifactor analysis of variance showed the significant independent risk factors of thrombophlebitis were male [hazard ratio (HR) 3.12 (1.39-6.98)], and lung infection (HR 0.22 [0.06-0.69]), and the indwelling depth of 1.9 cm affected the occurrence of thrombophlebitis (HR 0.79 [0.42 -3.09]) but was not an independent risk factor. In our treatment center, while appropriate fixation was ensured, the catheter indwelling depth shall be as short as possible, so as to reduce the occurrence of thrombophlebitis. For patients with lung infection, nursing at the intubation site shall be strengthened, so as to decrease thrombophlebitis.

Necrotic related-lncRNAs: Prediction of prognosis and differentiation between cold and hot tumors in head and neck squamous cell carcinoma.

Treatment of head and neck squamous cell carcinoma (HNSCC) is a substantial clinical challenge due to the high local recurrence rate and chemotherapeutic resistance. This project seeks to identify new potential biomarkers of prognosis prediction and precision medicine to improve this condition. A synthetic data matrix for RNA transcriptome datasets and relevant clinical information on HNSCC and normal tissues was downloaded from the Genotypic Tissue Expression Project and The Cancer Genome Atlas (TCGA). The necrosis-associated long-chain noncoding RNAs (lncRNAs) were identified by Pearson correlation analysis. Then 8-necrotic-lncRNA models in the training, testing and entire sets were established through univariate Cox (uni-Cox) regression and Lasso-Cox regression. Finally, the prognostic ability of the 8-necrotic-lncRNA model was evaluated via survival analysis, nomogram, Cox regression, clinicopathological correlation analysis, and receiver operating characteristic (ROC) curve. Gene enrichment analysis, principal component analysis, immune analysis and prediction of risk group semi-maximum inhibitory concentration (IC50) were also conducted. Correlations between characteristic risk score and immune cell infiltration, immune checkpoint molecules, somatic gene mutations, and anti-cancer drug sensitivity were analyzed. Eight necrosis-associated lncRNAs (AC099850.3, AC243829.2, AL139095.4, SAP30L-AS1, C5orf66-AS1, LIN02084, LIN00996, MIR4435-2HG) were developed to improve the prognosis prediction of HNSCC patients. The risk score distribution, survival status, survival time, and relevant expression standards of these lncRNAs were compared between low- and high-risk groups in the training, testing and entire sets. Kaplan-Meier analysis showed the low-risk patients had significantly better prognosis. The ROC curves revealed the model had an acceptable predictive value in the TCGA training and testing sets. Cox regression and stratified survival analysis indicated that the 8 necrosis-associated lncRNAs were risk factors independent of various clinical parameters. We recombined the patients into 2 clusters through Consensus ClusterPlus R package according to the expressions of necrotic lncRNAs. Significant differences were found in immune cell infiltration, immune checkpoint molecules, and IC50 between clusters, suggesting these characteristics can be used to evaluate the clinical efficacy of chemotherapy and immunotherapy. This risk model may serve as a prognostic signature and provide clues for individualized immunotherapy for HNSCC patients.

Identification and verification of aging-related lncRNAs for prognosis prediction and immune microenvironment in patients with head and neck squamous carcinoma.

Aging is highly associated with tumor formation and progression. However, little research has explored the association of aging-related lncRNAs (ARLs) with the prognosis and tumor immune microenvironment (TIME) of head and neck squamous cell carcinoma (HNSCC). RNA sequences and clinicopathological data of HNSCC patients and normal subjects were downloaded from The Cancer Genome Atlas. In the training group, we used Pearson correlation, univariate Cox regression, least absolute shrinkage/selection operator regression analyses, and multivariate Cox regression to build a prognostic model. In the test group, we evaluated the model. Multivariate Cox regression was done to screen out independent prognostic factors, with which we constructed a nomogram. Afterward, we demonstrated the predictive value of the risk scores based on the model and the nomogram using time-dependent receiver operating characteristics. Gene set enrichment analysis, immune correlation analysis, and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno- and chemo-therapeutic responses. The most important LINC00861 in the model was examined in HNE1, CNE1, and CNE2 nasopharyngeal carcinoma cell lines and transfected into the cell lines CNE1 and CNE2 using the LINC00861-pcDNA3.1 construct plasmid. In addition, CCK-8, Edu, and SA-ß-gal staining assays were conducted to test the biofunction of LINC00861 in the CNE1 and CNE2 cells. The signature based on nine ARLs has a good predictive value in survival time, immune infiltration, immune checkpoint expression, and sensitivity to multiple drugs. LINC00861 expression in CNE2 was significantly lower than in the HNE1 and CNE1 cells, and LINC00861 overexpression significantly inhibited the proliferation and increased the senescence of nasopharyngeal carcinoma cell lines. This work built and verified a new prognostic model for HNSCC based on ARLs and mapped the immune landscape in HNSCC. LINC00861 is a protective factor for the development of HNSCC.

Prognostic value of modified-Gustave-Roussy Immunity Score in resectable proximal gastric cancer.

The prognostic evaluation of GRIm score has been confirmed in many tumor species. The purpose of this study is to clarify the value of GRIm score in the prognostic evaluation of patients with resectable proximal gastric cancer. A single center retrospective study was conducted in 174 patients with proximal gastric cancer who underwent radical total gastrectomy. An in-depth analysis was carried out to explore the prognostic differences between high and low GRIm, and the influencing factors of disease-free survival rates and overall survival rates were analyzed by Cox regression model and Kaplan-Meier method. A total of 174 patients were divided into two groups: 135 patients were marked in L-mGRIm and 39 patients in H-mGRIm groups respectively. The median OS of the H-mGRIm and L-mGRIm groups were 23.2 and 38.6 months, respectively. The median DFS of the H-mGRIm and L-mGRIm groups was 16.9 and 31.7 months, respectively. Both DFS and OS were significantly different between groups (P = .000, P = .000). In multivariate analysis, ZPS (2 vs 0-1: HR 1.99 95% CI 1.05-3.76 P = .035), LDH (≥193 vs <193:HR 0.6; 95% CI 0.38-0.95 P = .028), mGRIm score (2-3 vs 0-1: HR 2.4; 95% CI 1.09-5.23 P = .029) was independent risk factors of OS. The age (>65 vs ≤65 years HR 0.63; 95% CI 0.4-0.95 P = .003), LDH (>193 U/L vs ≤193 U/L: HR 0.55; 95% CI 0.37-0.82 P = .004) and mGRIm score (2-3 vs 0-1: HR 4.74; 95% CI 2.24-9.9 P = .000) as an independent risk factor for DFS. mGRIm score is a novel, simple and effective index for prognosis evaluation of resectable cardiac cancer and can be used as a part of the risk stratification process.

MicroRNA-205-5p: A potential therapeutic target for influenza A.

We are committed to finding host targets for influenza A therapeutics. The nucleoprotein (NP) plays an important role in influenza A virus replication and is an indispensable part of viral transcription and replication. Exploring endogenous substances that can modulate NP is critical for finding host targets. MicroRNAs (miRNAs, miR) are a novel class of powerful, endogenous gene expression regulators. Herein, we used miRanda to analyse the base complementarity between the NP gene and the 14 host miRNAs reported previously by us. MiRanda predicted that miR-431-5p, miR-744-3p and miR-205-5p could complement the NP gene. To understand the effect of these miRNAs on NP expression, we co-transfected 293 T cells with NP gene sequence containing above miRNAs binding site or full sequence of NP gene (transfected into pmirGlo or pcDNA3.1 vectors, respectively), and mimics of miR-205-5p, miR-431-5p and miR-744-3p. Dual luciferase reporter gene or Western blotting assays confirmed that miR-205-5p and miR-431-5p inhibit NP expression by binding with the miRNA binding site of NP gene. Further, we infected Mouse Lung Epithelial (MLE-12) cells overexpressing miR-205-5p and miR-431-5p with influenza A virus and performed Western blotting to examine NP expression. We found that NP expression was significantly reduced in MLE-12 cells overexpressing miR-205-5p during influenza A infection. The miR-205-5p overexpression-induced inhibition of influenza A replication could be attributed to the inhibition of NP expression. Further, we administered oseltamivir and Jinchai Antiviral Capsules (JC, an anti-influenza Chinese medicine) to influenza A virus-infected MLE-12 cells and mice. We found that miR-205-5p was significantly decreased increased in infected cells and lung tissues, and oseltamivir and JC could up-regulate miR-205-5p. In conclusion, we provide new evidence that miR-205-5p plays a role in regulating viral NP protein expression in combating influenza A and may be a potential target for influenza A therapy.

Identification of Immune and Hypoxia Risk Classifier to Estimate Immune Microenvironment and Prognosis in Cervical Cancer.

Purpose: Cervical cancer (CC) is one of the most common gynecologic neoplasms. Hypoxia is an essential trigger for activating immunosuppressive activity and initiating malignant tumors. However, the determination of the role of immunity and hypoxia on the clinical outcome of CC patients remains unclear. Methods: The CC independent cohort were collected from TCGA database. Consensus cluster analysis was employed to determine a molecular subtype based on immune and hypoxia gene sets. Cox relevant analyses were utilized to set up a risk classifier for prognosis assessment. The underlying pathways of classifier genes were detected by GSEA. Moreover, we conducted CIBERSORT algorithm to mirror the immune status of CC samples. Results: We observed two cluster related to immune and hypoxia status and found the significant difference in outcome of patients between the two clusters. A total of 251 candidate genes were extracted from the two clusters and enrolled into Cox relevant analyses. Then, seven hub genes (CCL20, CXCL2, ITGA5, PLOD2, PTGS2, TGFBI, and VEGFA) were selected to create an immune and hypoxia-based risk classifier (IHBRC). The IHBRC can precisely distinguish patient risk and estimate clinical outcomes. In addition, IHBRC was closely bound up with tumor associated pathways such as hypoxia, P53 signaling and TGF ß signaling. IHBRC was also tightly associated with numerous types of immunocytes. Conclusion: This academic research revealed that IHBRC can be served as predictor for prognosis assessment and cancer treatment estimation in CC.

Cantharidin induces senescence via inhibition of AMP-activated protein kinase and activation of NLRP3 inflammasome in H9c2 cardiomyocytes.

Cantharidin is a natural compound with cardiotoxicity. Cellular senescence and senescence-associated secretory phenotype (SASP) are implicated in chemotherapy-associated cardiotoxicity. We here investigated how cantharidin induced cardiomyocyte senescence. H9c2 cells were treated with cantharidin. Senescence, mitochondrial functions, SASP, NOD-like receptor thermal protein domain associated protein 3 (NLRP3) signaling and AMP-activated protein kinase (AMPK) phosphorylation were examined. Cantharidin inhibited viability and increased expression of senescence-associated ß--galactosidase (SA-ß-Gal), p16 and p21 in H9c2 cells, suggesting occurrence of senescence. Cantharidin impaired mitochondrial functions evidenced by reduction in basal respiration, ATP levels and spare respiratory capacity. Cantharidin also decreased mitochondrial DNA copy number and down-regulated mRNA levels of cytochrome c oxidase-I, -II and -III. Moreover, cantharidin suppressed activity of mitochondria complex-I and -II. Examinations of SASP showed that cantharidin promoted expression and secretion of SASP cytokines interleukin-1ß-, -6 and -8 and tumor necrosis factor-α, associated with activation of NLRP3/caspase-1 pathway. Finally, cantharidin suppressed AMPK phosphorylation. AMPK activator GSK621 abrogated the up-regulation of SA-ß--Gal, p16 and p21 and counteracted the activation of NLRP3 and caspase-1 in cantharidin-challenged H9c2 cells. In conclusion, cantharidin stimulated senescence and SASP in cardiomyocytes through activation of NLRP3 inflammasome and inhibition of AMPK, providing novel molecular insights into cantharidin-induced cardiotoxicity.

An Integrated Analysis Reveals Geniposide Extracted From Gardenia jasminoides J.Ellis Regulates Calcium Signaling Pathway Essential for Influenza A Virus Replication.

Geniposide, an iridoid glycoside purified from the fruit of Gardenia jasminoides J.Ellis, has been reported to possess pleiotropic activity against different diseases. In particular, geniposide possesses a variety of biological activities and exerts good therapeutic effects in the treatment of several strains of the influenza virus. However, the molecular mechanism for the therapeutic effect has not been well defined. This study aimed to investigate the mechanism of geniposide on influenza A virus (IAV). The potential targets and signaling pathways of geniposide in the IAV infection were predicted using network pharmacology analysis. According to the result of network pharmacology analysis, we validated the calcium signaling pathway induced by IAV and investigated the effect of geniposide extracted from Gardenia jasminoides J.Ellis on this pathway. The primary Gene Ontology (GO) biological processes and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways KEGG enrichment analysis indicated that geniposide has a multi-target and multi-pathway inhibitory effect against influenza, and one of the mechanisms involves calcium signaling pathway. In the current study, geniposide treatment greatly decreased the levels of RNA polymerase in HEK-293T cells infected with IAV. Knocking down CAMKII in IAV-infected HEK-293T cells enhanced virus RNA (vRNA) production. Geniposide treatment increased CAMKII expression after IAV infection. Meanwhile, the CREB and c-Fos expressions were inhibited by geniposide after IAV infection. The experimental validation data showed that the geniposide was able to alleviate extracellular Ca2+ influx, dramatically decreased neuraminidase activity, and suppressed IAV replication in vitro via regulating the calcium signaling pathway. These anti-IAV effects might be related to the disrupted interplay between IAV RNA polymerase and CAMKII and the regulation of the downstream calcium signaling pathway essential for IAV replication. Taken together, the findings reveal a new facet of the mechanism by which geniposide fights IAV in a way that depends on CAMKII replication.

Circulating Tumor Cells in Esophageal Squamous Cell Carcinoma - Mini Review.

Esophageal cancer has high incidence and mortality rates and a low five-year survival rate of <15% owing to its strong capabilities of invasion, relapse and metastasis. The classic view holds that metastasis and diffusion is an advanced event during cancer progression, but recent studies show that distant diffusion of primary cancer cells may actually be an early event. Detection of circulating tumor cells (CTCs) in the circulation may indicate tumor spread, so CTCs are considered to be the key factor of metastatic cascade. In recent years, despite research progress on CTCs, there is a lack of systematic and important evidence to confirm the diagnostic, monitoring and prognostic values of CTCs in esophageal squamous cell carcinoma (ESCC). In this review, we clarify the relationship between CTC values and ESCC and provide more reliable evidence to improve the management and treatment of ESCC.

[Effect of polysaccharides from seeds of Vaccaria segetalis in alleviating urinary tract infection induced bladder injury by inhibiting NLRP3 inflammasome].

To study the mechanism of polysaccharides from seeds of Vaccaria segetalis( PSV) in the treatment of bacterial cystitis through the NLRP3 inflammasome pathway. The rat model of urinary tract infection was used and treated with PSV,and the urine and bladders were collected. The level of interleukin-10( IL-10) in rat urine was detected by enzyme linked immunosorbent assay( ELISA). Western blot and immunofluorescence staining were used to detect the expressions of sonic hedgehog( SHH) and NLRP3 inflammasome [NOD-like receptor thermoprotein domain 3( NLRP3),apoptosis associated speck like protein( ASC) and pro-caspase-1]. The expression of Toll-like receptor pathway was detected by RT-PCR. The death of 5637 cells induced by uropathogenic Escherichia coli( UPEC) and lactate dehydrogenase( LDH) release were evaluated using live/dead staining. The results showed that in the rat bladder,the expressions of SHH,NLRP3 inflammasomes and Toll-like receptors were significantly up-regulated,and NLRP3 inflammasomes were significantly activated by UPEC infection. The administration with PSV could significantly increase the concentration of IL-10 in urine,inhibit the expressions of SHH,NLRP3 inflammasomes and Toll-like receptors in bladder,and inhibit the activation of NLRP3 inflammasomes. A large number of 5637 cells were dead after UPEC infection and caused LDH production. PSV could significantly inhibit the death of 5637 cells and the release of LDH. In conclusion,PSV could inhibit the expression and activation of NLRP3 inflammasomes by inhibiting the Toll-like receptor pathway,thereby mitigating the bladder injury.

Study on mechanism of matrine in treatment of COVID-19 combined with liver injury by network pharmacology and molecular docking technology.

The aim of the present study was to investigate the pharmacological mechanism of matrine in treatment of COVID-19 combined with liver injury. Potential targets related to matrine, COVID-19 and liver injury were identified from several databases. We constructed PPI network and screened the core targets according to the degree value. Then, GO and KEGG enrichment were carried out. Molecular docking technology was used to verify the affinity between matrine and the crystal structure of core target protein. Finally, real-time RT-PCR was used to detect the effects of matrine on hub gene expression in liver tissue of liver injury mice and lung tissue of lung injury mice to further confirm the results of network pharmacological analysis. The results show that six core targets including AKT1, TP53, TNF, IL6, BCL2L1 and ATM were identified. The potential therapeutic mechanism of matrine on COVID-19 combined with liver injury is closely related to regulate antiviral process, improve immune system and regulate the level of inflammatory factors. Molecular docking showed that matrine could spontaneously bind to the receptor protein and had strong binding force. Real-time RT-PCR demonstrated that matrine could significantly reduce the expression of AKT1, TP53, TNF, IL6 and ATM in mice with liver injury or lung injury (P < 0.05), and increase the expression of BCL2L1 to a certain extent (P > 0.05). Our results indicate that matrine can achieve simultaneous intervention of COVID-19 combined with liver injury by multi-dimensional pharmacological mechanism.

Diagnostic, Prognostic, and Recurrence Monitoring Value of Plasma CYFRA21-1 and NSE Levels in Patients With Esophageal Squamous Cell Carcinoma.

This study was aimed to evaluate the clinical values of single markers and combination in the diagnosis, short-term efficacy and recurrence risk assessment of esophageal squamous cell carcinoma (ESCC). METHODS: Totally 50 patients with I-IVa stage ESCC, 50 healthy controls and 11 patients with recurrent esophageal cancer after comprehensive treatment were enrolled. Serum biomarkers were collected and evaluated. Serum concentrations of carcinoembryonic antigen (CEA), cytokeratin 19 fragment antigen 21-1 (CYFRA21-1) and neuron specific enolase (NSE) were measured by enzyme-linked immunosorbent assay before and after treatment. RESULTS: The diagnostic efficacy ROC curve area of CEA, CYFRA21-1 and NSE in esophageal cancer was 0.70, 0.71 and 0.64(all P <0.05), respectively, the sensitivity was 80%, 88.89% and 60% respectively, and the specificity was 53%, 58.5% and 58% respectively. The sensitivity and specificity of the combined detection were 68% and 78% respectively. The area under ROC curve was 0.75. CEA, CYFRA21-1 and NSE were significantly higher than the healthy control group and thus can be used as diagnostic markers of esophageal cancer (all P <0.05). After standard treatment, the clinical CR and PR rate of patients with positive CYFRA21-1 or NSE before treatment was significantly lower than that of patients with negative CYFRA21-1 or NSE (X2 = 4.52,P =0.03). A significant negative correlation was found between N stage and clinical efficacy (HR 2.48, 95%CI 1.07-5.73). After comprehensive treatment, the serum CYFRA21-1 and NSE levels in recurrent patients also increased significantly(all P<0.05), indicating these two markers play obvious roles in recurrence monitoring. CONCLUSION: CYFRA21-1 and NSE may help to predict the response of ESCC to CRT, and play important roles in the diagnosis and recurrence monitoring of esophageal cancer. These markers have a diagnostic value of esophageal cancer when combined with CEA.

Polysaccharides extract from Vaccaria segetalis seeds inhibits kidney infection by regulating cathelicidin expression.

ETHNOPHARMACOLOGICAL RELEVANCE: According to the Chinese Pharmacopoeia, the seeds of Vaccaria segetalis, a traditional medicinal herb, can be used for treating urinary diseases. The polysaccharides extract from V. segetalis seeds (VSP) has been shown to prevent urinary tract infections (UTIs). AIM OF THE STUDY: Investigate the effects of VSP on treating kidney infection induced by uropathogenic Escherichia coli (UPEC) and the underlying mechanisms. MATERIALS AND METHODS: Both in vivo and in vitro infection models were established with the UPEC strain CFT073. After oral administration of VSP, the levels of bacterial load, cathelicidin (CRAMP), Toll-like receptors (TLRs) in the kidney were evaluated. The expression of cathelicidin (LL-37) in human renal cell carcinoma cell line (A498) was tested after the treatment of VSP. RESULTS: In the kidneys of infection models, high-titer bacteria was detected. In the kidney of rat model, the expression of CRAMP was down-regulated, no significant change was observed in the levels of TLRs. After oral administration of VSP, the bacterial load was significantly decreased in rat and mouse models, and the levels of CRAMP and TLRs were significantly up-regulated in rat model. In vitro, the expression of LL-37 was significantly inhibited by CFT073. VSP up-regulated the expression of LL-37 in A498 cells. CONCLUSIONS: The up-regulation of cathelicidin expression may contribute to the therapeutic effects of VSP on kidney infection.