A novel necroptosis related gene signature and regulatory network for overall survival prediction in lung adenocarcinoma.

We downloaded the mRNA expression profiles of patients with LUAD and corresponding clinical data from The Cancer Genome Atlas (TCGA) database and used the Least Absolute Shrinkage and Selection Operator Cox regression model to construct a multigene signature in the TCGA cohort, which was validated with patient data from the GEO cohort. Results showed differences in the expression levels of 120 necroptosis-related genes between normal and tumor tissues. An eight-gene signature (CYLD, FADD, H2AX, RBCK1, PPIA, PPID, VDAC1, and VDAC2) was constructed through univariate Cox regression, and patients were divided into two risk groups. The overall survival of patients in the high-risk group was significantly lower than of the patients in the low-risk group in the TCGA and GEO cohorts, indicating that the signature has a good predictive effect. The time-ROC curves revealed that the signature had a reliable predictive role in both the TCGA and GEO cohorts. Enrichment analysis showed that differential genes in the risk subgroups were associated with tumor immunity and antitumor drug sensitivity. We then constructed an mRNA-miRNA-lncRNA regulatory network, which identified lncRNA AL590666. 2/let-7c-5p/PPIA as a regulatory axis for LUAD. Real-time quantitative PCR (RT-qPCR) was used to validate the expression of the 8-gene signature. In conclusion, necroptosis-related genes are important factors for predicting the prognosis of LUAD and potential therapeutic targets.

Chemical constituents, pharmacological effects, toxicology, processing and compatibility of Fuzi (lateral root of Aconitum carmichaelii Debx): A review.

ETHNOPHARMACOLOGICAL RELEVANCE: The lateral root of Aconitum carmichaelii Debx is known as Fuzi in Chinese. It is traditionally valued and used for dispelling cold, relieving pain effects, restoring 'Yang,' and treating shock despite its high toxicity. This review aims to provide comprehensive information on the chemical composition, pharmacological research, preparation, and compatibility of Fuzi to help reduce its toxicity and increase its efficiency, based on the scientific literature. In addition, this review will establish a new foundation for further studies on Fuzi. MATERIALS AND METHODS: A systematic review of the literature on Fuzi was performed using several resources, namely classic books on Chinese herbal medicine and various scientific databases, such as PubMed, the Web of Science, and the China Knowledge Resource Integrated databases. RESULTS: Fuzi extracts contain diester-type alkaloids, monoester-type alkaloids, other types of alkaloids, and non-alkaloids types, and have various pharmacological activities, such as strong heart effect, effect on blood vessels, and antidepressant, anti-diabetes, anti-inflammatory, pain-relieving, antitumor, immunomodulatory, and other therapeutic effects. However, these extracts can also lead to various toxicities such as cardiotoxicity, neurotoxicity, reproductive toxicity, hepatotoxicity, and embryonic toxicity. In vivo and in vitro experiments have demonstrated that different processing methods and suitable compatibility with other herbs can effectively reduce the toxicities and increase the efficiency of Fuzi. CONCLUSION: The therapeutic potential of Fuzi has been demonstrated in conditions, such as heart failure, various pains, inflammation, and tumors, which is attributed to the diester-type alkaloids, monoester-type alkaloids, other types of alkaloids, and non-alkaloid types. In contrast, they are also toxic components. Proper processing and suitable compatibility can effectively reduce toxicity and increase the efficiency of Fuzi. Thus more pharmacological and toxicological mechanisms on main active compounds are necessary to be explored.

A comprehensive review of emodin in fibrosis treatment.

Emodin is the main pharmacodynamic components of rhubarb, with significant pharmacological effects and clinical efficacy.Emodin has a variety of therapy effects, such as anti-cancer, anti-fibrosis effects, and is widely used to treat encephalitis, diabetic cataract and organ fibrosis. Several studies have shown that emodin has a good treatment effect on organ fibrosis, but the mechanism is complex. Moreover, the evidence of some studies is conflicting and confusing. This paper reviewed the mechanism, pharmacokinetics and toxicology of emodin in fibrosis treatment, and briefly discussed relevant cutting-edge new formulations to improve the efficacy, the result can provide some reference for future study.

Role of TRPV1 in respiratory disease and association with traditional Chinese medicine: A literature review.

Transient receptor potential vanilloid type 1 (TRPV1), involved in multiple pathophysiological processes including inflammation, is a thermally activated, non-selective cation channel. It has been identified that TRPV1 is highly involved in some common respiratory diseases including allergic rhinitis, asthma, chronic obstructive pulmonary disease, and pulmonary infection by participating in neurogenic and immunogenic inflammation, sensitization, and oxidative stress. In recent years, the hypothesis of transient receptor potential (TRP) has been introduced in studies on the theory of five flavors and four properties of Chinese medicinal. However, the hypothesis is undetermined due to the multi-component and multi-target characteristics of Chinese medicinal. This study describes the relations between TRPV1 and four types of respiratory diseases based on the literature in recent five years. In the meantime, the therapeutic effect of Chinese medicinal by intervening TRPV1 was reviewed, in an attempt to provide certain evidence for future studies on the medicinal property-effect relationship, mechanism of drug action, the syndrome differentiation in traditional Chinese medicine (TCM) for respiratory diseases and to help for new drug development.

Mechanism of Action of Strychni Semen for Treating Rheumatoid Arthritis and Methods for Attenuating the Toxicity.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic autoimmune disease, which affects the joints and causes significant pain, impairing patient's quality of life. Strychni semen showed promising results to treat RA. However, there are increasing safety concerns in using strychni semen due to its severe toxicity. AIM AND OBJECTIVE: The purpose of this review is to provide insight into using Strychni semen as an alternative medicine to treat RA, as well as to offer a method for the safe application of Strychni semen through processing and compatibility studies. METHODS: Publications were retrieved and surveyed from CNKI and PubMed relevant to Strychni semen for a literature review. RESULTS: This article summarized the mechanism of function of strychni semen in treating RA with its anti-inflammatory, analgesic, and immunomodulatory effect. Commonly used methods to attenuate the toxicity of Strychni semen were also discussed in this article. CONCLUSION: Strychni semen has a good therapeutic effect on RA, mainly by the modulation of immunity with anti-inflammatory and analgesic effects. Also, the reported toxicity of strychni semen can be effectively reduced by processing and compatibility methods. Hence, as an alternative medicine for RA treatment, strychni semen has a broad prospect.

Calycosin attenuates pulmonary fibrosis by the epithelial-mesenchymal transition repression upon inhibiting the AKT/GSK3ß/ß-catenin signaling pathway.

The precise etiology and pathogenesis of idiopathic pulmonary fibrosis are not completely understood, and no satisfactory treatment exists. This work aimed to examine the effects of calycosin (CA, an isoflavone compound) on pulmonary fibrosis (PF) and explore the underlying mechanism. In this study, we established a mice model of PF induced by 5 mg/mL bleomycin (BLM), and mice were orally administrated with 7 mg/kg or 14 mg/kg CA once a day for three weeks. In vitro, after pretreated with 80 µM CA, MLE-12 cells were stimulated with 10 ng/mL transforming growth factor-ß1 (TGF-ß1) for inducing epithelial-mesenchymal transition (EMT). The results showed that CA treatment ameliorated the severity of fibrosis and the lung tissue damage, as well as suppressed the secretion of inflammation factors in a dose-dependent manner of the PF mice model induced by BLM. Subsequently, CA inhibited the BLM-induced PF progression by repressing EMT, evidenced by the reverse of the downregulation of E-cadherin and the upregulation of vimentin, α-SMA, and fibronectin. Moreover, the elevated phosphorylation of AKT and GSK3ß induced by BLM (or TGF-ß1) was decreased by CA treatment, leading to the rescue of the high expression of ß-catenin. CA prevented the translocation of ß-catenin from the cytoplasm to the nucleus. The repressed effects of CA on the TGF-ß1-induced EMT and the AKT/GSK3ß/ß-catenin axis, as well as the translocation of ß-catenin were all reversed by a AKT activator SC79. Taken together, CA ameliorated PF by the EMT inhibition upon suppressing the AKT/GSK3ß/ß-catenin signaling pathway.

Danshensu alleviates bleomycin-induced pulmonary fibrosis by inhibiting lung fibroblast-to-myofibroblast transition via the MEK/ERK signaling pathway.

Pulmonary fibrosis (PF) is a chronic pulmonary interstitial disease, and its pathological process is closely related to fibroblast-myofibroblast differentiation. Danshensu (DSS) has been reported to exert an anti-fibrotic effect in heart and liver. However, it is unknown whether DSS has an equally anti-fibrotic effect on lungs. To evaluate the effect of DSS on PF and demonstrate its possible molecular mechanisms, we established an in vitro model on TGF-ß1 (5 ng/mL)-stimulated NIH3T3 cells and in vivo model on bleomycin (BLM) (5 mg/kg)-induced PF mice. In vitro, our results revealed that 50 µM DSS effectively inhibited the fibroblast proliferation, migration and differentiation into myofibroblast. In vivo, our results showed that DSS (28 and 56 mg/kg) reduced damaged lung structures, infiltrated inflammatory cells and accumulated areas of collagen deposition. Moreover, we showed that DSS decreased the fibroblast-specific protein 1 (FSP-1) - and α-SMA-positive areas. Meanwhile, we indicated that DSS reduced the expression of TGF-ß1, α-SMA and COL-I in the lung tissues of mice. To further explore the mechanism of DSS on alleviating PF, we detected the MEK/ERK signaling pathway. Our results showed that DSS reduced the phosphorylation of MEK1/2 and ERK1/2, indicating that DSS might inhibit the MEK/ERK signaling pathway. Taken together, these results demonstrated that DSS could suppress lung fibroblast proliferation, migration and differentiation to myofibroblasts, possibly through suppressing the MEK/ERK signaling pathway, which suggested that DSS might be a potential therapeutic drug for PF treatment.

The association of air pollution with the patients' visits to the department of respiratory diseases.

BACKGROUND: The objective of this study was to evaluate the impact of air particulate matter 2.5 (PM2.5) on the daily number of patients' visits to the Department of Respiratory Diseases in a local general hospital. METHODS: The number of patients in outpatient department of respiratory diseases (ODRD) in a general hospital of Jinan, China, the air quality and meteorological data were collected for 1 year. By controlling the confounding factors such as "day of the week" effects and the meteorological factors, the generalized additive Poisson regression analysis was conducted to evaluate the impact of PM2.5 on the number of patients' visits to the ODRD. RESULTS: Within two consecutive days, if the cumulative PM2.5 was less than 200 µg/m(3), the daily number of patients in the ODRD did not increase significantly; however, it increased dramatically when the concentration of PM2.5 particles reached the range between 200 and 400 µg/m(3). CONCLUSION: There is a non-linear relationship between the concentration of atmospheric PM2.5 particles and the daily number of patients in the ODRD.

[Effects of TCM treatment according to syndrome differentiation on expressions of nuclear factor-kappaB and gamma-glutamylcysteine synthetase in rats with chronic obstructive pulmonary disease of various syndrome types].

OBJECTIVE: To explore the mechanism of traditional Chinese medicine (TCM) treatment according to syndrome differentiation in treating chronic obstructive pulmonary disease (COPD) by observing the changes of nuclear factor-kappaB (NF-kappaB) and gamma-glutamylcysteine synthetase (gamma-GCS) expression levels in rats. METHODS: COPD model was established by modified method of combining fumigation and lipopolysaccharide (LPS) intra-tracheal dripping. Model rats were treated respectively for succesive 14 days according to their syndrome, that is, Xiaoqinglong Decoction to the rats of cold-phlegm accumulation in Fei, Maxing Shigan Decoction to those of heat-phlegm accumulation in Fei, Yupingfeng Decoction to those of Fei-qi deficiency, Liujunzi Decoction to those of Pi-qi deficiency, Renshen Gejie Decoction to those of Shen qi-deficiency. Besides, model rats in the model control group received 2mL normal saline daily, and no intervention was applied in the normal control group. The expression of gamma-GCS and NF-kappaB was detected by immunochemistry before and after treatment. RESULTS: Compared with that in the normal rats, the expressions of gamma-GCS and NF-kappaB in bronchial and alveolar epithelium of COPD rats before treatment were significantly higher, but the positive expression rates were lowered after treatment significantly (P<0.05). CONCLUSION: TCM treatment according to syndrome differentiation could rectify imbalance of oxidation/anti-oxidation and alleviate inflammatory reaction in COPD rats, thus to treat COPD effectively.