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Naturally occurring compounds are reported as effective candidates for prevention and treatment of various cancers. Breviscapine (BVP) is a mixture of flavonoid glycosides, derived from the Chinese herbs. Previous researches have indicated that BVP has comprehensive pharmacological functions. However, little is known about whether BVP has preventive effects on human prostate cancer. Here, we attempted to explore if BVP inhibits human prostate cancer in vitro and in vivo in a comprehensive manner. We found that BVP triggered cytotoxicity in prostate cancer cell lines dose-dependently. BVP-induced DNA damage caused the cell cycle arrest and apoptosis and further induced cell death. High expression of MCM-7 was reduced in BVP-treated cancer cells and tumor tissues, and also the DNA damage response marker of γH2AX is down-regulated by BVP, associated with MCM-7 expression through regulating retinoblastoma protein (Rb) and checkpoint control proteins expression. Additionally, BVP induced apoptotic response in prostate cancer cells and tumors via activating Caspase-3 and PARP. In vivo studies indicated that BVP impeded tumor growth in xenograft animal models. In conclusion, our data indicates that breviscapine (BVP) can be further explored for its potential, which might be used in human prostate cancer therapeutics. [ABSTRACT FROM AUTHOR]

Papillary and non-papillary are two histological patterns of bladder carcinogenesis and are considered as dual-track oncogenic pathways, which have different genetic alterations. The TCGA-bladder cancer (BLCA) database contains clinicopathological, genomic and survival data from over 400 muscle-invasive bladder cancer patients. In this study, using data from this database, we performed a systematic screening of gene expression to identify the protein-coding gene that might have prognostic value in papillary and non-papillary muscle-invasive bladder cancer (MIBC). The data of patients with primary MIBC in TCGA-BLCA was acquired from the UCSC Xena project (http://xena.ucsc.edu) for re-analysis. By setting |log2 fold change|≥2 and adjusted p value <0.01 as the screening criteria, we found 751 significantly dysregulated genes, including 183 overexpressed and 568 downregulated genes. HMMR was identified as a potential prognostic marker with unique expression. Multivariate analysis showed that its expression was an independent prognostic indicator of shorter progression-free survival (PFS) (HR: 1.400, 95%CI: 1.021–1.920, p = 0.037) in the papillary subtype. ENST00000393915.8 and ENST00000358715.3, two transcripts that contain all 18 exons and encode the full length of HMMR , were significantly upregulated in cancer tissues compared with normal bladder tissues. None of the 17 CpG sites in its DNA locus was relevant to HMMR expression. 26/403 (6.5%) MIBC cases had HMMR gene-level amplification, which was associated with upregulated HMMR expression compared with the copy-neutral and deletion groups. Gene set enrichment analysis (GSEA) in papillary MIBC found that the high HMMR expression group was associated with upregulated genes enriched in multiple gene sets with well-established role in BC development, including G2M checkpoint, E2 F Targets, Myc Targets V1, Myc Targets V2 and Glycolysis. Based on these findings, we infer that HMMR expression might be a specific prognostic marker in terms of PFS in papillary MIBC. DNA amplification might be an important mechanism of its elevation. [ABSTRACT FROM AUTHOR]

Airway remodeling, as a predominant characteristic of asthma, refers to the structural changes that occurred both in the large and small airways. These pathological changes not only contribute to airway hyperresponsiveness and airway obstruction, but also predict poor outcomes of patients. In vitro models are the alternatives to animal models that facilitate airway remodeling research. Current approaches to mimic airway remodeling in vitro include mono cultures of cell lines and primary cells that are derived from the respiratory tract, and co-culture systems that consist of different cell subpopulations. Moreover, recent advances in microfluid chips and organoids show promise in simulating the complex architecture and functionality of native organs. According, they enable highly physiological-relevant investigations of human diseases in vitro. Here we aim to detail the current human cell-based models regarding their key pros and cons, and to discuss how they may be used to facilitate our understanding of airway remodeling in asthma. • Provide an introduction to airway remodeling in asthma. • Review of current experimental models and phenotypic assays in the airway remodeling research. • Highlight current microfluidic chip and organoids technologies and address outstanding questions that need to be investigated. [ABSTRACT FROM AUTHOR]

Airway hyperresponsiveness(AHR) is a major clinical phenomenon in lung diseases (asthma, COPD and pulmonary fibrosis) and not only a high-risk factor for perioperative airway spasm leading to hypoxaemia, haemodynamic instability and even "silent lung", but also a potential risk for increased mortality from underlying diseases (e.g. asthma, COPD). Airway reactivity is closely linked to airway inflammation, remodelling and increased mucus secretion, and endoplasmic reticulum stress is an important mechanism for the development of these pathologies. This review, therefore, focuses on the effects of endoplasmic reticulum stress on the immune cells involved in airway hyperreactivity (epithelial cells, dendritic cells, eosinophils and neutrophils) in inflammation and mucus & sputum secretion; and on the differentiation and remodelling of airway smooth muscle cells and epithelial cells. The aim is to clarify the mechanisms associated with endoplasmic reticulum stress in airway hyperresponsiveness and to find new ideas and methods for the prevention of airway hyperresponsiveness in the perioperative period. [ABSTRACT FROM AUTHOR]

Colistin (polymyxin E) is an antibiotic that is effective against multidrug-resistant gram-negative bacteria. However, the high incidence of nephrotoxicity caused by colistin limits its clinical use. To identify compounds that might ameliorate colistin-induced nephrotoxicity, we obtained 1707 compounds from the Korea Chemical Bank and used a high-content screening (HCS) imaging-based assay. In this way, we found that bimatoprost (one of prostaglandin F2α analogue) ameliorated colistin-induced nephrotoxicity. To further assess the effects of bimatoprost on colistin-induced nephrotoxicity, we used in vitro and in vivo models. In cultured human proximal tubular cells (HK-2), colistin induced dose-dependent cytotoxicity. The number of terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL)-positive cells, indicative of apoptosis, was higher in colistin-treated cells, but this effect of colistin was ameliorated by cotreatment with bimatoprost. The generation of reactive oxygen species, assessed using 2,7-dichlorodihydrofluorescein diacetate, was less marked in cells treated with both colistin and bimatoprost than in those treated with colistin alone. Female C57BL/6 mice (n = 10 per group) that were intraperitoneally injected with colistin (10 mg/kg/12 hr) for 14 days showed high blood urea nitrogen and serum creatinine concentrations that were reduced by the coadministration of bimatoprost (0.5 mg/kg/12 hr). In addition, kidney injury molecule-1 (KIM1) and Neutrophil gelatinase-associated lipocalin (NGAL) expression also reduced by bimatoprost administration. Further investigation in tubuloid and kidney organoids also showed that bimatoprost attenuated the nephrotoxicity by colistin, showing dose-dependent reducing effect of KIM1 expression. In this study, we have identified bimatoprost, prostaglandin F2α analogue as a drug that ameliorates colistin-induced nephrotoxicity. [Display omitted] • Colistin treats multidrug-resistant bacterial infections, but its nephrotoxicity risk limits use. • High-Content Screening reveals Bimatoprost as a potential protector against colistin's nephrotoxicity. • Bimatoprost might be a protective drug for nephrotoxicity, its systemic use needs more study. [ABSTRACT FROM AUTHOR]

Background Curcumin (CUR) is a Chinese medicine monomer with antioxidant and anti-inflammatory properties. The aim of this study was to investigate the effects and mechanisms of CUR treatment on ventilator-induced lung injury (VILI) in rats. Methods Total 50 SD rats were divided into five groups: sham, VILI, VILI+CUR-50 (CUR 50 mg/kg pretreated intraperitoneal), VILI+CUR-200 (CUR 200 mg/kg pretreated intraperitoneal) and VILI + DXM (5 mg/kg pretreated intraperitoneal). The morphology and ultrastructure were observed by microscope and transmission electron microscope. The wet to dry ratio, protein concentration in bronchoalveolar lavage fluid (BALF), evans blue dye (EBD) content, nuclear factor kappa B (NF-κB) activity, myeloperoxidase (MPO), malondialdehyde (MDA), xanthine oxidase (XO) and total antioxidative capacity (TAOC) levels were measured. Results Histological studies revealed that inflammatory cells infiltration and alveolar edema were significantly severe in VILI as compared to other groups. CUR-200 and DXM treatment reversed lung injury significantly. The wet to dry ratio, protein concentration in BALF, EBD content, MPO activity, tumor necrosis factor (TNF)-α level and NF-κB activity were significantly increased in VILI group as compared to other groups. CUR-200 and DXM treatment significantly suppressed permeability and inflammation induced by ventilation. Furthermore, the significantly higher MDA content in VILI could be markedly decreased by CUR-200 and DXM treatment while the levels of XO and TAOC were markedly recovered only by CUR (200 mg/kg) treatment after VILI. Conclusion CUR could inhibit the inflammatory response and oxidative stress during VILI, which is partly through NF-κB pathway. [ABSTRACT FROM AUTHOR]

Special AT-rich sequence binding protein 1 (SATB1) plays important role in the regulation of chromatin structure and gene expression. Recent studies have indicated oncogenic role of SATB1. However, the function of SATB1 in prostate cancer progression and metastasis remains unclear. In this study SATB1 expression vector or siRNA was employed to modulate the expression level of SATB1 in prostate cancer cells and xenograft tumor in nude mouse model. Immunohistochemical analysis was performed on clinical prostate cancer samples. Silencing SATB1 inhibited the growth of DU-145 cells subcutaneous tumor in nude mice, while SATB1 overexpression promoted the growth of LNCaP cells subcutaneous tumor in nude mice. Immunohistochemical and Western blot analysis of the xenografts showed that silencing SATB1 led to decreased expression of vimentin and MMP2 and increased expression of E-cadherin, while SATB1 overexpression led to increased expression of vimentin and MMP2 and decreased expression of E-cadherin. Furthermore, SATB1, vimentin and MMP2 expression was increased significantly while E-cadherin expression was reduced significantly in clinical samples of prostate carcinoma with metastasis compared to prostate carcinoma without metastasis and benign prostate hyperplasia. Taken together, these findings suggest that the modulation of epithelial–mesenchymal transition by SATB1 may contribute to prostate cancer metastasis. [ABSTRACT FROM AUTHOR]

As a universal Chinese medicine, Rhei Radix et Rhizoma was used for centuries in different fields including pharmaceutical, health care and cosmetics. Chrysophanol (Chr) is one of the most important anthraquinone components isolated from plants of the Rheum genus. Current reports show that in Rheum officinale , Chr is the most abundant free anthraquinone compound [ 1 ] and exerts a number of beneficial effects, such as anti-inflammation, anti-cancer, and anti-depressive effects and offers neuroprotection. We collected information about Chr from the Internet databases PubMed , Web of Science , Europe PMC and CNKI with a combination of keywords including "Chr", "Pharmacology", and "Pharmacokinetics". All data about this ingredient in this review were extracted from articles published before September 2019. Based on the literature found, we concluded that (1) Chr exhibited potential anti-inflammation, anti-cardiovascular disease (CVD)and anti-cancer activities by regulating signaling pathway transduction (NF-κB, MAPK, PI3K/Akt, etc.); (2) compared with free Chr, pharmacokinetic studies revealed that other forms of Chr, such as nanoparticle-based and liposome-based Chr, showed high bioavailability. Nevertheless, we also found that the understanding of the exact differences in the regulation of multiple molecular signaling pathways is in a preliminary stage and needs to be clarified. Moreover, further studies are required to determine the apoptotic mechanism of Chr in cancer cells. Finally, we found that (3) structure modification studies demonstrated potential relationships between structure and drug activity. The purpose of this review is to summarize the pharmacological activities, intracorporal processes and structure-activity relationships of Chr and to provide an up-to-date reference for further research and clinical applications. [ABSTRACT FROM AUTHOR]