OsMBTB32, a MATH-BTB domain-containing protein that interacts with OsCUL1s to regulate salt tolerance in rice.

MATH-BTB proteins are involved in a variety of cellular processes that regulate cell homeostasis and developmental processes. Previous studies reported the involvement of BTB proteins in the development of various organs in plants; however, the function of BTB proteins in salt stress is less studied. Here, we found a novel MATH-BTB domain-containing OsMBTB32 protein that was highly expressed in leaf, root, and shoot. The up-regulation of the OsMBTB32 transcript in 2-week-old seedlings under salt stress suggests the significant role of the OsMBTB32 gene in salinity. The OsMBTB32 transgenic seedlings (OE and RNAi) exhibited significant differences in various phenotypes, including plumule, radical, primary root, and shoot length, compared to WT seedlings. We further found that OsCUL1 proteins, particularly OsCUL1-1 and OsCUL1-3, interact with OsMBTB32 and may suppress the function of OsMBTB32 during salt stress. Moreover, OsWRKY42, a homolog of ZmWRKY114 which negatively regulates salt stress in rice, directly binds to the W-box of OsCUL1-1 and OsCUL1-3 promoters to promote the interaction of OsCUL1-1 and OsCUL1-3 with OsMBTB32 protein in rice. The overexpression of OsMBTB32 and OsCUL1-3 further confirmed the function of OsMBTB32 and OsCUL1s in salt tolerance in Arabidopsis. Overall, the findings of the present study provide promising knowledge regarding the MATH-BTB domain-containing proteins and their role in enhancing the growth and development of rice under salt stress.MATH-BTB proteins are involved in a variety of cellular processes that regulate cell homeostasis and developmental processes. Previous studies reported the involvement of BTB proteins in the development of various organs in plants; however, the function of BTB proteins in salt stress is less studied. Here, we found a novel MATH-BTB domain-containing OsMBTB32 protein that was highly expressed in leaf, root, and shoot. The up-regulation of the OsMBTB32 transcript in 2-week-old seedlings under salt stress suggests the significant role of the OsMBTB32 gene in salinity. The OsMBTB32 transgenic seedlings (OE and RNAi) exhibited significant differences in various phenotypes, including plumule, radical, primary root, and shoot length, compared to WT seedlings. We further found that OsCUL1 proteins, particularly OsCUL1-1 and OsCUL1-3, interact with OsMBTB32 and may suppress the function of OsMBTB32 during salt stress. Moreover, OsWRKY42, a homolog of ZmWRKY114 which negatively regulates salt stress in rice, directly binds to the W-box of OsCUL1-1 and OsCUL1-3 promoters to promote the interaction of OsCUL1-1 and OsCUL1-3 with OsMBTB32 protein in rice. The overexpression of OsMBTB32 and OsCUL1-3 further confirmed the function of OsMBTB32 and OsCUL1s in salt tolerance in Arabidopsis. Overall, the findings of the present study provide promising knowledge regarding the MATH-BTB domain-containing proteins and their role in enhancing the growth and development of rice under salt stress.

LOXL2 reduces 5-FU sensitivity through the Hedgehog/BCL2 signaling pathway in colorectal cancer.

Elevated expression of lysyl oxidase-like 2 (LOXL2) contributes to the malignant tumor progression in multiple cancers. However, the role of LOXL2 in the 5-fluorouracil (5-FU) resistance of colorectal cancer (CRC) remains unclear. This study aimed to explore the effects of LOXL2 on 5-FU sensitivity in CRC. The mRNA and protein levels of LOXL2 were explored in public databases by bioinformatics, validated in clinical tissues using immunohistochemistry, and detected in 5-FU treated cell lines. The 50% inhibitory concentrations (IC50) values were quantified based on the cell viability at different concentrations of 5-FU with CCK-8 assays. Colony formation and flow cytometry assays were performed to measure the proliferation and apoptosis rates. Gene set enrichment and correlation analyses were conducted to identify the probable mechanism of LOXL2 in TCGA samples. Critical molecules of the Hedgehog signaling pathway and anti-apoptotic BCL2 in protein levels were detected with Western blotting. It concluded that LOXL2 was up-regulated and positively linked to the unfavorable prognosis of CRC patients. The LOXL2 expression increased with the rising 5-FU concentrations, especially at 20 and 40 µM. Elevated LOXL2 promoted the resistance to 5-FU, augmented the proliferation, and inhibited 5-FU-induced apoptosis of CRC cells. LOXL2 activated the Hedgehog signaling pathway by promoting the expression of SMO, GLI1, and GLI2, leading to the upregulation of downstream target gene BCL2 in CRC cells. Moreover, the Hedgehog signaling pathway inhibitor cyclopamine blocked the BCL2 upregulation mediated by LOXL2. This study has demonstrated that LOXL2 can reduce 5-FU sensitivity through the Hedgehog/BCL2 signaling pathway in CRC.

Corrigendum: Comprehensive analysis of the transcriptome-wide m6A methylome in lung adenocarcinoma by MeRIP sequencing.

[This corrects the article DOI: 10.3389/fonc.2022.791332.].

Copper-catalyzed radical trans-selective hydroboration of ynamides with N-heterocyclic carbene boranes.

Vinylboron compounds are important compounds in organic chemistry and biology. In this communication, we developed a copper(I)-catalyzed, highly regio- and stereoselective radical trans-hydroboration of ynamides with N-heterocyclic carbene (NHC)-ligated borane is reported, which leads to a series of trans-boryl enmides that can be conveniently transformed into various multi-substituted enamides. Further investigation showcased that our method is robust and scalable. The mechanism of this unique reaction is studied and discussed.

Comprehensive Analysis of the Transcriptome-wide m6A Methylome in Lung Adenocarcinoma by MeRIP Sequencing.

N6-methyladenosine (m6A) is the most abundant internal modification on eukaryotic mRNAs. There is increasing evidence that m6A plays a key role in tumor progression, so it is important to analyze m6A modifications within the transcriptome-wide in lung adenocarcinoma (LUAD). Three pairs of LUAD samples and tumor-adjacent normal tissues were obtained from the South University of Science and Technology Hospital. And then methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were used to identify differential m6A modifications between tumor and tumor-adjacent normal tissues. We identified 4041 aberrant m6A peaks, of which 1192 m6A peaks were upregulated and 2849 m6A peaks downregulated. It was found that genes with the dysregulated m6A peaks were enriched in the pathways in cancer, Rap1 signaling pathway, and insulin resistance. Additionally, 612 genes with abnormal regulation of m6A peaks and RNA expression were identified by combining MeRIP-seq and RNA-seq data. Through KEGG analysis, the 612 genes were enriched in cancer-related signaling pathways, such as the cGMP-PKG signaling pathway, and the Rap1 signaling pathway. What's more, GSEA enrichment analysis showed these genes were enriched in cell cycle phase transition, cell division, cellular response to DNA damage stimulus, and chromosome organization. To further explore the relationship between differential m6A modified genes and clinical parameters of LUAD patients, we searched The Cancer Genome Atlas (TCGA) and identified 2 genes (FCRL5 and GPRIN1) that were associated with the prognosis and diagnosis of LUAD patients. Furthermore, we found a positive correlation between GPRIN1 and m6A reader YTHDF1 in the GEPIA2 database. It was verified that YTHDF1 binds to GPRIN1 mRNA and regulates its expression. Our study results suggest that m6A modification plays important role in the progression and prognosis of LUAD and maybe a potential new therapeutic target for LUAD patients in the future.

Improvement of chronic non-bacterial prostatitis by Jiedu Huoxue decoction through inhibiting TGF-ß/SMAD signaling pathway.

BACKGROUND: Chronic non-bacterial prostatitis (CNBP) accounts for more than 90 % of clinical prostatitis cases, and there is no specific and effective treatment for CNBP. The regulatory role of Jiedu Huoxue decoction (JDHXD)in CNBP remains unclear. We investigated if JDHXD could improve CNBP METHODS: The animal model of CNBP was established by carrageenan injection with 1 % carrageenan (50 µL). The prostate index, epithelial thickness, lumen area, and pain response time were investigated. The apoptosis levels were measured with TUNEL staining and flow cytometry, respectively. Inflammatory factors in the serum were measured with ELISA method. RESULTS: Treatment with JDHXD significantly improve prostate tissues injury in CNBP rats. Some parameters, such as prostate index, and pain response time, reflecting the prostate function were improved by JDHXD. Inhibition of apoptosis, reactive oxygen species (ROS), and inflammatory response were achieved by JDHXD in vivo. JDHXD markedly suppressed the TGF-ß/SMAD signaling pathway, and activation of TGF-ß/SMAD signaling pathway could reverse the improvement of CNBP injury by JDHXD. The anti-inflammatory, anti-oxidative and anti-apoptotic effects of JDHXD were proved. CONCLUSION: JDHXD might improve CNBP injury through suppressing inflammation response, ROS, and apoptosis by targeting TGF-ß/SMAD signaling pathway. This research might provide a new thought for the prevention and treatment of CNBP through inhibiting TGF-ß/SMAD signaling pathway.

Jiedu Huoxue decoction improves chronic abacterial prostatitis/chronic pelvic pain syndrome through activating Wnt/GSKß/ß-catenin signaling pathway and alleviating apoptosis.

BACKGROUND: Chronic abacterial prostatitis/chronic pelvic pain syndrome (CP/CPPS) accounts for 90% of clinical prostatitis, and there is no specific and effective treatment for it. Jiedu Huoxue decoction (JDHXD) has been believed to be an effective agent for CP/CPPS, but the specific mechanism remains unclear. METHODS: Carrageenan and LPS were used to established the animal and cell models of CP/CPPS, respectively. The prostate index, urine volume, lumen area, epithelial thickness, and pain response time were investigated. TUNEL staining and flow cytometry were applied to measure apoptosis levels in vivo and in vitro. RESULTS: JDHXD improved CP/CPPS recovery in a dose-dependent manner. JDHXD restrained apoptosis and activated Wnt/GSK-3ß/ß-catenin signaling pathway in the CP/CPPS animal model. Inhibition of Wnt/GSK-3ß/ß-catenin signaling pathway remarkably aggravated apoptosis and suppressed the improvement of CP/CPPS by JDHXD. XAX939 markedly reversed the suppression of cell apoptosis and ROS level caused by JDHXD in vitro. CONCLUSION: Jiedu Huoxue decoction improved CP/CPPS through activating Wnt/GSKß/ß-catenin signaling pathway and inhibiting apoptosis. This study might provide a novel insight for the prevention and treatment of CP/CPPS through activating Wnt/GSK-3ß/ß-catenin signaling pathway.

Efficacy of acupuncture combined with traditional Chinese medicine on chronic prostatitis: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic prostatitis is a common andrological disease, which brings many troubles to the lives of middle-aged and elderly male patients. With the increase of modern life pressure, the incidence of chronic prostatitis tends to younger, but its etiology and pathogenesis are not fully elucidated. Which seriously affects men's health? Relevant studies have shown that acupuncture combined with traditional Chinese medicine (TCM) has a good effect on the treatment of chronic prostatitis compared with conventional western medicine; however, there is no consistent conclusion at present. The main purpose of this study is to explore whether acupuncture combined with TCM is effective in treating chronic prostatitis. METHODS: The collection of randomized controlled trials related to acupuncture and TCM for chronic prostatitis will search the following electronic databases, including: PubMed, Web of Science, the Cochrane Database, EMBASE, Chinese National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, Weipu. There are 8 electronic databases including the VIP Chinese Science and Technology Periodical Database and the China Biomedical Literature Database. The cure rate and total effective rate are the main indicators, and the recurrence rate and adverse events are the secondary indicators. Meta-analysis using RevMan5.4 provided by Cochrane Collaboration. RESULTS: This study will provide the latest evidence of efficacy for the acupuncture combined with TCM in the treatment of chronic prostatitis. CONCLUSION: The effectiveness of acupuncture combined with TCM for chronic prostatitis will be evaluated. UNIQUE INPLASY NUMBER: INPLASY202130083.

miRNA-877-5p inhibits malignant progression of prostate cancer by directly targeting SSFA2.

In this study, we aimed to investigate the role of miR-877-5p in the malignant phenotypes of prostate cancer (PCa) cells and its underlying mechanism. RT-qPCR analysis was performed to examine the expression of miR-877-5p and sperm-specific antigen 2 (SSFA2) in PCa tissues and cells. Cell counting kit-8 (CCK-8) assay, 5-ethynyl-20-deoxyuridine (EdU) assay, flow cytometry, wound-healing assay, and Transwell invasion assay were performed to determine the functional roles of miR-877-5p in PCa cells. The association of miR-877-5p with SSFA2 was determined by luciferase reporter and RNA pull-down assays. In this study, we found that the expression level of miR-877-5p was decreased in PCa tissues and cells. Functionally, overexpression of miR-877-5p exerted tumor suppressor properties in PCa cells. Mechanistically, SSFA2 was identified as a target gene of miR-877-5p, while overexpression of SSFA2 could abrogate the anti-tumor effects of miR-877-5p in PCa cells. These findings demonstrated that miR-877-5p/SSFA2 axis functioned as a potential target for PCa treatment.

RBBP4 Enhances Platinum Chemo Resistance in Lung Adenocarcinoma.

BACKGROUND: The majority of lung cancers are adenocarcinomas, with the proportion being 40%. The patients are mostly diagnosed in the middle and late stages with metastasis and easy recurrence, which poses great challenge to the treatment and prognosis. Platinum-based chemotherapy is a primary treatment for adenocarcinoma, which frequently causes drug resistance. As a result, it is important to uncover the mechanisms of the chemoresponse of adenocarcinoma to platinum-based chemotherapy. METHODS: The genes from the dataset GSE7880 were gathered into gene modules with the assistance of weighted gene coexpression network analysis (WGCNA), the gene trait significance absolute value (|GS|), and gene module memberships (MM). The genes from hub gene modules were calculated with a protein-protein interaction (PPI) network analysis in order to obtain a screening map of hub genes. The hub genes with both a high |GS| and MM and a high degree were selected. Furthermore, genes in the hub gene modules also went through a Gene Ontology (GO) functional enrichment analysis. RESULTS: 11 hub genes in four hub gene modules (LY86, ACTR2, CDK2, CKAP4, KPNB1, RBBP4, SMAD4, MYL6, RPS27, TSPAN2, and VAMP2) were chosen as the significant hub genes. Through the GO function enrichment analysis, it was indicated that four modules were abundant in immune system functions (floralwhite), amino acid biosynthetic process (lightpink4), cell chemotaxis (navajowhite2), and targeting protein (paleturquoise). Four hub genes with the highest |GS| were verified by prognostic analysis.

Oxidative stress and antioxidant defense in detoxification systems of snake venom-induced toxicity.

BACKGROUND: Snakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required. METHODS: Cases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database. RESULTS: Principal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity. CONCLUSIONS: Our results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.

The effect of Jiedu Huoxue decoction on rat model of experimental nonbacterial prostatitis via regulation of miRNAs.

CONTEXT: The underlying mechanisms of Jiedu Huoxue decoction (JDHXD) in treating chronic prostatitis have not been fully explored. OBJECTIVE: This study investigates the miRNAs as potential biomarkers and the effect of JDHXD on the rat model of experimental nonbacterial prostatitis. MATERIALS AND METHODS: Fifty-four Sprague-Dawley male rats were randomly divided into normal control, model, JDHXD low dose (0.5 g/kg/day), medium dose (1 g/kg/day), high dose (2 g/kg/day) and western medicine (cernilton 0.094 g/kg/day) groups, and intragastrically administered once daily for 30 days. The control and model (upon successful establishment) groups received distilled water. Differential expression of miRNAs was analysed with high-throughput miRNA sequencing and validated with qRT-PCR and Northern blot. Prediction of specific target genes and functional enrichment analysis were performed with bioinformatics. RESULTS: LD50 test showed no sign of toxicity with maximum feasible dose 4 g/kg JDHXD. Compared with control, 495 miRNAs showed expression changes in CAP/CPPS rats, of which 211 were significantly different and 37 were prostatic-related. There were 181 differentially expressed miRNAs between the model and high dose JDHXD groups, of which 23 were identical with the control and model groups. Compared with control, miR-146a, miR-423 and miR-205 expression increased significantly in the model group, decreased dose-dependently in the JDHXD groups (p < 0.05), and vice-versa for miR-96 (p < 0.05). The effect of low dose JDHXD was comparable to cernilton (p > 0.05). DISCUSSION AND CONCLUSIONS: Future studies may explore the contributions of the active components in JDHXD. The study design is generalisable. The effect can be repeatedly verified in clinical trials.

Network Pharmacology and Experimental Evidence Reveal Dioscin Suppresses Proliferation, Invasion, and EMT via AKT/GSK3b/mTOR Signaling in Lung Adenocarcinoma.

PURPOSE: Dioscin, a natural glycoside derived from many plants, has been proved to exert anti-cancer activity. Several studies have found that it reverses TGF-ß1-induced epithelial-mesenchymal transition (EMT). Whether dioscin can reverse EMT by pathways other than TGF-ß is still unknown. METHODS: We used network-based pharmacological methods to systematically explore the potential mechanisms by which dioscin acts on lung cancer. Cell Counting Kit-8 assay, scratch healing, Transwell assay, Matrigel invasion assay, immunofluorescence assay, and Western blotting were employed to confirm the prediction of key targets and the effects of dioscin on EMT. RESULTS: Here, using network-based pharmacological methods, we found 42 possible lung cancer-related targets of dioscin, which were assigned to 98 KEGG pathways. Among the 20 with the lowest p-values, the PI3K-AKT signaling pathway is involved and significantly related to EMT. AKT1 and mTOR, with high degrees (reflecting higher connectivity) in the compound-target analysis, participate in the PI3K-AKT signaling pathway. Molecular docking indicated the occurrence of dioscin-AKT1 and dioscin-mTOR binding. Functional experiments demonstrated that dioscin suppressed the proliferation, migration, invasion, and EMT of human lung adenocarcinoma cells in a dose-dependent manner, without TGF-ß stimulation. Furthermore, we determined that dioscin downregulated p-AKT, p-mTOR and p-GSK3ß in human lung adenocarcinoma cells without affecting their total protein levels. The PI3K inhibitor LY294002 augmented these changes. CONCLUSION: Dioscin suppressed proliferation, invasion and EMT of lung adenocarcinoma cells via the inactivation of AKT/mTOR/GSK3ß signaling, probably by binding to AKT and mTOR, and inhibiting their phosphorylation.

Oxidative stress and antioxidant defense in detoxification systems of snake venom-induced toxicity

Snakebites remain a major life-threatening event worldwide. It is still difficult to make a positive identification of snake species by clinicians in both Western medicine and Chinese medicine. The main reason for this is a shortage of diagnostic biomarkers and lack of knowledge about pathways of venom-induced toxicity. In traditional Chinese medicine, snakebites are considered to be treated with wind, fire, and wind-fire toxin, but additional studies are required. Methods: Cases of snakebite seen at the Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine were grouped as follows: fire toxin - including four cases of bites by Agkistrodon acutus and three bites by Trimeresurus stejnegeri - and wind-fire toxin - four cases of bites by vipers and three bites by cobras. Serum protein quantification was performed using LC-MS/MS. Differential abundance proteins (DAPs) were identified from comparison of snakebites of each snake species and healthy controls. The protein interaction network was constructed using STITCH database. Results: Principal component analysis and hierarchical clustering of 474 unique proteins exhibited protein expression profiles of wind-fire toxins that are distinct from that of fire toxins. Ninety-three DAPs were identified in each snakebite subgroup as compared with healthy control, of which 38 proteins were found to have significantly different expression levels and 55 proteins displayed no expression in one subgroup, by subgroup comparison. GO analysis revealed that the DAPs participated in bicarbonate/oxygen transport and hydrogen peroxide catabolic process, and affected carbon-oxygen lyase activity and heme binding. Thirty DAPs directly or indirectly acted on hydrogen peroxide in the interaction network of proteins and drug compounds. The network was clustered into four groups: lipid metabolism and transport; IGF-mediated growth; oxygen transport; and innate immunity. Conclusions: Our results show that the pathways of snake venom-induced toxicity may form a protein network of antioxidant defense by regulating oxidative stress through interaction with hydrogen peroxide.(AU)

Association of hemoglobin with arterial stiffness evaluated by carotid-femoral pulse wave velocity among Chinese adults.

OBJECTIVE: Increased hemoglobin (Hb) levels are known to be associated with increased cardiovascular events and mortalities. Therefore, we assumed that high Hb levels were associated with arterial stiffness. Pulse wave velocity (PWV) is a simple and noninvasive method for measuring arterial stiffness to assess cardiovascular disease in general populations. Accordingly, we conducted a cross-sectional study to explore the association of Hb with PWV. METHODS: A total of 6642 adults aged 54.5 ± 11.2 years undergoing physical examinations were enrolled, 71.7% of whom were males. Arterial stiffness was evaluated by carotid-femoral PWV (cfPWV). Multivariable regression analyses were performed to determine the relationship between Hb and increased cfPWV. RESULTS: In this study, the mean Hb (per 10 g/L increase) was 144.7 ± 13.9 g/L, and the mean cfPWV was 15.1 ± 3.1 m/s. cfPWV was significantly higher in high hemoglobin groups ≥15.4 g/L (Quartile 4) than in the lowest hemoglobin group (Quartile 1 ≤ 13.6 g/L; P < 0.001). Multiple linear regression analysis revealed that Hb positively correlated with cfPWV (ß = 0.16, P < 0.01). Univariate Logistic regression analysis revealed that Hb was associated with increased cfPWV, with an odd ratio (OR) of 1.46 (95% confidence interval [CI], 1.39-1.54). After adjusting for potential confounders, Hb and the highest Hb quartile group were also independently associated with increased cfPWV, with a fully adjusted OR of 1.11 (95% CI, 1.02-1.20) and 1.45 (95% CI, 1.01-2.08), respectively. CONCLUSION: This study demonstrated that Hb levels significantly correlate with increased cfPWV.

N-Methylparoxetine Blocked Autophagic Flux and Induced Apoptosis by Activating ROS-MAPK Pathway in Non-Small Cell Lung Cancer Cells.

The main mechanistic function of most chemotherapeutic drugs is mediated by inducing mitochondria-dependent apoptosis. Tumor cells usually respond to upregulate autophagy to eliminate impaired mitochondria for survival. Hypothetically, inhibiting autophagy might promote mitochondria-dependent apoptosis, thus enhancing the efficacy of chemotherapeutic therapies. We previously identified N-methylparoxetine (NMP) as an inducer of mitochondrial fragmentation with subsequent apoptosis in non-small cell lung cancer (NSCLC) cells. We discovered that ROS was accumulated in NMP-treated NSCLC cells, followed by c-Jun N-terminal kinase (JNK) and p38 MAP kinase (p38) activation. This was reversed by the application of a reactive oxygen species (ROS) scavenger, N-acetylcysteine (NAC), leading to a reduction in apoptosis. Our data suggested that NMP induced apoptosis in NSCLC cells by activating mitogen-activated protein kinase (MAPK) pathway. We further speculated that the remarkable increase of ROS in NMP-treated NSCLC cells might result from an inhibition of autophagy. Our current data confirmed that NMP blocked autophagy flux at late stage wherein lysosomal acidification was inhibited. Taken together, this study demonstrated that NMP could exert dual apoptotic functions-mitochondria impairment and, concomitantly, autophagy inhibition. NMP-related excessive ROS accumulation induced apoptosis by activating the MAPK pathway in NSCLC cells.

Myricetin Inhibits Breast Tumor Growth and Angiogenesis by Regulating VEGF/VEGFR2 and p38MAPK Signaling Pathways.

Tumor angiogenesis is an important cause of tumor growth and metastasis. Myricetin is a flavonoid component used in traditional Chinese medicine that has been demonstrated to have anticancer activity. However, to the best of our knowledge, the effect of myricetin on tumor angiogenesis remains unknown. The present study reports the identification of myricetin as a potential chemopreventive agent by reason of its inhibition of tumor angiogenesis and demonstrates the anticancer effects of myricetin in vivo. Cell Counting Kit-8 assays revealed that myricetin inhibits the proliferation of tumor cells but not that of human umbilical vein endothelial cells (HUVECs), and a transwell assay demonstrated that myricetin could inhibit the migration of HUVECs. A rat aortic ring assay revealed that myricetin could also affect the development of microvessels and the formation of vascular networks. Further, an ELISA showed that myricetin reduced the levels of vascular endothelial growth factor (VEGF) in vivo and in vitro. Western blot analysis indicated that myricetin could downregulate VEGFR2 and p38MAPK. Therefore, myricetin could significantly inhibit tumor angiogenesis and has potential as a chemopreventive agent because of its inhibition to angiogenesis. Anat Rec, 302:2186-2192, 2019. © 2019 American Association for Anatomy.

Jiedu Huoxue decoction improves inflammation in rat type III prostatitis: The importance of the NF-κB signalling pathway.

This study aimed to investigate the mechanism of Jiedu Huoxue decoction (JDHXD) in type III prostatitis based on the NF-κB signalling pathway. Twenty-six Sprague-Dawley male rats were divided into blank control, model, positive (Prostate Plus), low-dose JDHXD, medium-dose JDHXD and high-dose JDHXD groups. Type III prostatitis rat model was established and confirmed with HE staining. NF-кB P50 and NF-κB P65 expression was detected with immunohistochemistry. NF-κB mRNA expression was detected with qRT-PCR. Protein expression of NF-κB and its inhibitor Iκ-Bα was detected with Western blot. Compared to the model group, a decrease in glandular hyperplasia and inflammation, and in NF-кB P50 and NF-κB P65 expression in the medium- and high-dose JDHXD groups was observed. NF-κB mRNA expression was significantly increased in the model group compared to control (p < 0.05), and significantly decreased in the JDHXD treatment groups compared to model group (p < 0.05). Protein expression of NF-κB was significantly increased in the model and low-dose JDHXD groups compared to control(p < 0.05), and significantly decreased in the medium- and high-dose JDHXD groups compared to model group (p < 0.05). Protein expression of Iκ-Bα was vice versa. JDHXD could be a potential treatment for type III prostatitis via its regulation of NF-κB and Iκ-Bα expression.