LncRNA MEG3 inhibits renal fibrinoid necrosis of diabetic nephropathy via the MEG3/miR-21/ORAI1 axis.

INTRODUCTION: Diabetic nephropathy (DN) is one of the most common and lethal diabetic complications worldwide and is associated with a high risk of mortality. However, the exact mechanism behind its development is unknown. The mesangial cells (MCs) and non-coding RNAs are critical for DN, but it is unknown whether a MEG3/miR-21/ORAI1 regulatory axis exists in MCs. Hence, in this study, we aimed to understand whether the MEG3/miR-21/ORAI1 regulatory axis has a role in the pathophysiology of DN. RESULTS: We demonstrated that high-glucose stimuli downregulated MEG3 and ORAI1 expression while enhancing miR-21 expression. Exogenous miR-21 mimics inhibited ORAI1 expression, which was partially salvaged or reversed by MEG3 overexpression. Furthermore, RIP assay demonstrated that the beads labeled with AGO2 antibody could enrich more miR-21 and MEG3 than those labeled with control IgG antibody; both of them formed the RNA-induced silencing complex. Further, the biochemical indicators of db/db mice significantly improved, and renal fibrinoid necrosis was ameliorated using a miR-21 inhibitor. CONCLUSION: The MEG3/miR-21/ORAI1 axis regulates the manifestation of DN in diabetic mice and MCs, and the miR-21 inhibitor can be a potential therapeutic strategy to alleviate DN, once the presence of such an axis is found in humans.

miR-885-5p plays an accomplice role in liver cancer by instigating TIGAR expression via targeting its promoter.

TIGAR (TP53-induced glycolysis and apoptosis regulator) is a p53-inducible gene and its expression resulted in controlling metabolism and protection from apoptosis. Furthermore, TIGAR participated in promoting the pentose phosphate pathway and help in lowering intracellular reactive oxygen species. miR-885-5p has also been reported to be involved in liver tumorigenesis, but whether miR-885-5p has a regulatory effect on TIGAR expression is unknown. In this study, we found that their levels were correlated to each other and positively related to cell malignancy. Exogenous miR-885-5p induced TIGAR expression through a p53-independent pathway. The promoter region of TIGAR harbors two tandem putative miR-885-5p target sites. Cotransfection of synthetic miR-885 with TIGAR promoter reporter constructs significantly enhanced TIGAR promoter activity via binding with target sites. Furthermore, miR-885-5p and its precursor pre-miR-885 had the same stimulatory impact on TIGAR expression. Chromatin immunoprecipitation analysis further verified that increased miR-885-5p potentiated the accessibility of TIGAR promoter chromatin to transcriptional factors and facilitated TIGAR expression. miR-885-5p and its precursor both can interact mechanically with TIGAR promoter binding site and alter local chromatin structure, and subsequently upregulate TIGAR expression and participate in liver tumorigenesis.

Real-time surveillance for abnormal events: the case of influenza outbreaks.

This paper introduces a method of surveillance using deviations from probabilistic forecasts. Realised observations are compared with probabilistic forecasts, and the "deviation" metric is based on low probability events. If an alert is declared, the algorithm continues to monitor until an all-clear is announced. Specifically, this article addresses the problem of syndromic surveillance for influenza (flu) with the intention of detecting outbreaks, due to new strains of viruses, over and above the normal seasonal pattern. The syndrome is hospital admissions for flu-like illness, and hence, the data are low counts. In accordance with the count properties of the observations, an integer-valued autoregressive process is used to model flu occurrences. Monte Carlo evidence suggests the method works well in stylised but somewhat realistic situations. An application to real flu data indicates that the ideas may have promise. The model estimated on a short run of training data did not declare false alarms when used with new observations deemed in control, ex post. The model easily detected the 2009 H1N1 outbreak. Copyright © 2016 John Wiley & Sons, Ltd.

Preparation and Adsorption Properties of Novel Porous Microspheres with Different Concentrations of Bilirubin.

BACKGROUND: Plasma perfusion was widely used to clear toxic substances of plasma. Particle size and uniformity of adsorbent microspheres also affect the absorption rate. METHODS: Conventional suspension polymerization was improved using a pre-dispersion homogenizer to obtain novel adsorbent microspheres, named ERM-0100. Microsphere-related characteristics and attributes were analysed. RESULT: The ERM-0100 microspheres efficiently adsorbed different bilirubin concentrations, with a maximum rate of 59.72 ± 1.08%. At high bilirubin concentrations, ERM-0100 exhibited similar adsorption rate with BRS350 and BS330 (p = 0.303, p = 1.000, relatively), and higher than HB-H-6 (p = 0.000). At different concentration, ERM-0100 showed good adsorption performance. The ERM-0100 had no significant adsorption for electrolyte; for TP and ALB, the loss rates of ERM-0100 were 15.65 ± 0.36 and 23.23 ± 1.11%, respectively. In addition, ERM-0100 showed good blood compatibility. CONCLUSION: The ERM-0100 is a potential biomedical material for plasma perfusion for good effect, less costs and more safety. The microspheres may be coated to reduce its protein adsorption.

Efficacy and safety of bevacizumab and platinum­based chemotherapy as neoadjuvant regimen for stage­IIIA non­squamous non­small cell lung cancer: A retrospective study.

Bevacizumab plus platinum-based chemotherapy provides modest benefits in non-squamous non-small cell lung cancer (NSCLC), while its application as a neoadjuvant regimen has yet to be validated. The present study aimed to assess the efficacy of neoadjuvant bevacizumab plus platinum-based chemotherapy in patients with stage-IIIA non-squamous NSCLC. Data from 110 patients with stage-IIIA non-squamous NSCLC with negative driver genes, who received neoadjuvant bevacizumab plus platinum-based chemotherapy (n=50) or neoadjuvant platinum-based chemotherapy alone (n=60), and tumor resection, were retrospectively reviewed in the current study. In addition, the data on pathological response, disease-free survival (DFS), overall survival (OS) and adverse events were obtained. The results demonstrated that neoadjuvant bevacizumab plus chemotherapy did not significantly increase the pathological complete response (pCR) rate in comparison with neoadjuvant chemotherapy alone (18.0 vs. 8.3%; P=0.130). However, neoadjuvant bevacizumab plus chemotherapy significantly increased the rates of DFS (P=0.007) and OS (P=0.049) compared with neoadjuvant chemotherapy alone. Adjustments were then performed using multivariate logistic or Cox regression analyses, which demonstrated that neoadjuvant bevacizumab plus chemotherapy in comparison with neoadjuvant chemotherapy alone only significantly independently prolonged DFS [hazard ratio (HR)=0.251; P=0.042], but did not significantly affect pCR (odds ratio=2.897; P=0.117) or OS (HR=0.297; P=0.158). Furthermore, no significant differences were demonstrated between the number of adverse events in patients receiving neoadjuvant bevacizumab plus chemotherapy in comparison with those receiving neoadjuvant chemotherapy alone (all P>0.05). In conclusion, neoadjuvant bevacizumab plus platinum-based chemotherapy was only associated with a significant improvement in the rate of DFS, but showed limited efficacy in improving pCR and OS rates in comparison with neoadjuvant chemotherapy alone in patients with stage-IIIA non-squamous NSCLC. Therefore, a larger sample size and randomized controlled studies are needed for further validation of the findings of the present study.

Testing serial correlation in a general d-factor model with possible infinite variance.

It is well-known that the presence of serial correlation may result in an inefficient or even biased estimation in time series analysis. In this paper, we consider testing serial correlation in a general d-factor model when the model errors follow the GARCH process, which is frequently used in modeling financial data. Two empirical likelihood-based testing statistics are suggested as a way to deal with problems that might come up with infinite variance. Both statistics are shown to be chi-squared distributed asymptotically under mild conditions. Simulations confirm the excellent finite-sample performance of both tests. Finally, to emphasize the importance of using our tests, we explore the impact of the exchange rate on the stock return using both monthly and daily data from eight countries.

Construction and analysis of a lysosome-dependent cell death score-based prediction model for non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common type of tumor globally and the leading cause of cancer-related deaths. Although treatment strategies such as immune checkpoint inhibitors and chemotherapy have advanced, the heterogeneity among NSCLC patients results in significant variability in treatment outcomes. Studies have shown that certain patients respond poorly to immune checkpoint inhibitors, indicating that treatment response is closely related to multiple factors. Therefore, it is necessary to develop predictive models to stratify patients based on gene expression and clinical characteristics, aiming for precision therapy. OBJECTIVE: This study aims to construct a stratified prognostic model for NSCLC patients based on lysosome-dependent cell death (LDCD) scoring by integrating single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data. By analyzing the immune-related characteristics of high-risk and low-risk groups, we further explored the impact of cell death patterns on lung cancer and identified potential therapeutic targets. METHODS: This study obtained single-cell RNA sequencing data and gene expression data of NSCLC patients and normal lung tissues from the GEO and TCGA databases. We used R packages such as Seurat and CellChat for data preprocessing and analysis, and performed dimensionality reduction and visualization through Principal Component Analysis (PCA) and UMAP algorithms. LASSO regression analysis was used to construct the predictive model, followed by cross-validation and ROC curve analysis. The model's effectiveness was validated through survival analysis and immune microenvironment analysis. RESULTS: The study showed a significant increase in the proportion of monocytes in NSCLC tissues, suggesting their important role in cancer progression. Cell communication analysis indicated that macrophages, smooth muscle cells, and myeloid cells exhibit strong intercellular communication during cancer progression. Using the constructed prognostic model based on 12 LDCD-related genes, we found significant differences in overall survival and immune microenvironment between the high-risk and low-risk groups.

Aristolone in Nardostachys jatamansi DC. induces mesenteric vasodilation and ameliorates hypertension via activation of the KATP channel and PDK1-Akt-eNOS pathway.

BACKGROUND: Nardostachys jatamansi DC. is a common medicinal herb used to treat cardiovascular diseases, particularly hypertension. Previously, our lab characterized the chemical compounds of N. jatamansi. However, the bioactive compounds of N. jatamansi and their mechanisms of action on blood pressure and blood vessels are unknown. PURPOSE: The vasorelaxant effects of the methanolic extract (MeOH ext.) of the roots and rhizomes of N. jatamansi, its main compounds, and their underlying mode of action, were investigated. METHODS: The main compounds of N. jatamansi were isolated and identified using UHPLC-TOF MS. The antihypertensive effect of N. jatamansi extracts and (-)-aristolone were determined using spontaneously hypertensive rats. The extracts, fractions, and compounds were also evaluated for their vasorelaxant effects on U46619 contractile responses in isolated thoracic aortic and mesenteric arterial rings. The endothelial-dependent relaxation, as well as the regulatory pathways and targets of (-)-aristolone, were studied in-vitro and ex-vivo. Molecular docking and biophysical characterization (Surface plasmon resonance) studies were utilized to investigate the molecular interaction between (-)-aristolone and the target protein. RESULTS: MeOH ext. (200 mg/kg) reduces the systolic and diastolic blood pressure in spontaneously hypertensive rats. MeOH ext. and its ethyl acetate fraction (EtOAc Fr.), but not the H2O fraction, had a significant relaxing effect on the thoracic aorta. (-)-aristolone and kanshone H from EtOAc Fr. induced vasorelaxation of the thoracic aorta and mesenteric artery. In human umbilical vein endothelial cells, (-)-aristolone treatment upregulated phosphorylation of Akt (T308) and eNOS. Molecular docking and surface plasmon resonance experiments revealed an interaction between (-)-aristolone and phosphoinositide-dependent protein kinase 1 (PDK1), an upstream protein kinase that phosphorylates Akt at T308. Treatment with PDK1 inhibitor PHT-427 and eNOS inhibitor L-NAME consistently inhibited (-)-aristolone-induced vasorelaxation. In addition, KATP channel inhibitor glibenclamide dramatically inhibited the vasorelaxant effects of (-)-aristolone and kanshone H in the endothelium-denuded thoracic aorta. Finally, (-)-aristolone lowers hypertensive rats' systolic and diastolic blood pressure. CONCLUSIONS: The extracts of N. jatamansi promote vasorelaxation and alleviate hypertension. The essential chemicals responsible for producing vasorelaxation effects are (-)-aristolone and kanshone H, which activate the PDK1-Akt-eNOS-NO relaxing pathway and stimulate the opening of the KATP channel. These findings point to N. jatamansi and aristolone as possible antihypertensive agents.

Public and private sectors collective response to combat COVID-19 in Malaysia.

Over the last year, the dangerous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread rapidly around the world. Malaysia has not been excluded from this COVID-19 pandemic. The resurgence of COVID-19 cases has overwhelmed the public healthcare system and overloaded the healthcare resources. Ministry of Health (MOH) Malaysia has adopted an Emergency Ordinance (EO) to instruct private hospitals to receive both COVID-19 and non-COVID-19 patients to reduce the strain on public facilities. The treatment of COVID-19 patients at private hospitals could help to boost the bed and critical care occupancy. However, with the absence of insurance coverage because COVID-19 is categorised as pandemic-related diseases, there are some challenges and opportunities posed by the treatment fees management. Another major issue in the collaboration between public and private hospitals is the willingness of private medical consultants to participate in the management of COVID-19 patients, because medical consultants in private hospitals in Malaysia are not hospital employees, but what are termed "private contractors" who provide patient care services to the hospitals. Other collaborative measures with private healthcare providers, e.g. tele-conferencing by private medical clinics to monitor COVID-19 patients and the rollout of national vaccination programme. The public and private healthcare partnership must be enhanced, and continue to find effective ways to collaborate further to combat the pandemic. The MOH, private healthcare sectors and insurance providers need to have a synergistic COVID-19 treatment plans to ensure public as well as insurance policy holders have equal opportunities for COVID-19 screening tests, vaccinations and treatment.

A review on traditional uses, phytochemistry, pharmacology, toxicology and the analytical methods of the genus Nardostachys.

ETHNOPHARMACOLOGICAL RELEVANCE: The plants of the genus Nardostachys (Caprifoliaceae) have been used for a long history in different cultural systems of medicine, including Chinese, Ayurvedic, Korean folk medicine and Islamic, for treatments of disorders in nervous, digestive, cardiovascular and integumentary systems. AIM OF THE REVIEW: This review aims to provide comprehensive information on Nardostachys plants including botany update, traditional uses, data mining of uses in traditional Chinese medicine (TCM) and current Chinese medicinal patents, chemical constituents, pharmacological effects, toxicity and analytical method studies. MATERIALS AND METHODS: Studies of the genus Nardostachys were collected via Google Scholar and Baidu Scholar, ScienceDirect, SciFinder, Wiley Online Library, ACS Publications, NLM/NCBI, Web of Science, CNKI, WANFANG DATA, EMBASE, Huabeing database and Traditional Chinese Medicine Resource Network and libraries. Some local books, PhD or MS's dissertations were also included. The literatures cited in this review covered the period from 1962 to March 2021. The Plant List and Kew Herbarium Catalogue databases were used to authenticate the scientific name. RESULTS: Botany description of Nardostachys genus is updated. Analysis of the literatures indicates that Nardostachys species are valuable herbs with therapeutic potentials for various disorders. Data mining on ancient TCM prescriptions and current Chinese medicinal patents containing Nardostachys revealed its common compatibility with other herbs in China. Phytochemical studies identified terpenoids and phenolic compounds as the main constituents in the genus Nardostachys and sesquiterpenoids as the major bioactive components. Experimental studies demonstrated that crude extracts, major fractions and the main constituents from Nardostachys species mainly exhibited pharmacological activities on nervous, digestive, cardiovascular and skin systems. Further, in vivo and in vitro toxicological studies demonstrated that Nardostachys plants showed either no or low toxicities, except at high doses. Finally, methods of qualitative and quantitative analyses on chemical constituents of genus Nardostachys were summarized, including TLC/HPTLC, GC and HPLC/UPLC methods, combined with common detectors including PDA, DAD and MS. CONCLUSIONS: This review summarizes the progress on phytochemistry, pharmacology, toxicology and analytical methods of the genus Nardostachys. Studies demonstrate traditional uses of the genus Nardostachys, and reveal novel bioactive effects for clinical uses. These achievements expand our knowledge on the genus Nardostachys and its clinical value.

A robot for image-guided percutaneous intervention: Decoupled motion capability correlated to the positioning and orientation steps of the percutaneous intervention / 中国组织工程研究

The purpose of this study was to develop a robotic system for image-guided percutaneous interventions using ultrasound (US) or computed tomography (CT) for needle biopsy, ablation, cryotherapy, and other needle procedures. The conventional operation of puncture was analyzed firstly, and a compact robot was then designed for manipulating a needle or other slender surgical instrument in the confined space. Its distinctive characteristic is the decoupled motion capability correlated to the positioning and orientation steps of the percutaneous intervention. This approach allowed each step of the intervention to be performed using a separate mechanism of the robot. One major advantage of this kinematic approach was patient safety.