Notoginsenoside R1 Facilitates Cell Angiogenesis by Inactivating the Notch Signaling During Wound Healing.

The development of chronic, nonhealing wounds is a persistent medical problem that drives patient morbidity and increases healthcare costs. Angiogenesis is a critical accompanying activity in the proliferation stage during the wound healing process. Notoginsenoside R1 (NGR1) isolated from Radix notoginseng has been reported to alleviate diabetic ulcers by promoting angiogenesis and decreasing inflammatory responses and apoptosis. In the present study, we investigated the effect of NGR1 on angiogenesis and its therapeutic functions in cutaneous wound healing. For in vitro evaluation, cell counting kit-8 assays, migration assays, Matrigel-based angiogenic assays, and western blotting were conducted. The experimental results showed that NGR1 (10-50 µM) had no cytotoxicity to human skin fibroblasts (HSFs) and human microvascular endothelial cells (HMEC), and NGR1 treatment facilitated the migration of HSFs and enhanced angiogenesis in HMECs. Mechanistically, NGR1 treatment inhibited the activation of Notch signaling in HMECs. For in vivo analysis, hematoxylin-eosin staining, immunostaining, and Masson's trichrome staining were performed, and we found that NGR1 treatment promoted angiogenesis, reduced wound widths, and facilitated wound healing. Furthermore, HMECs were treated with N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT; a Notch inhibitor), and DAPT treatment was found to exert pro-angiogenic effects. Simultaneously, DAPT was administrated into experimental cutaneous wound healing model, and we found that DAPT administration prevented the development of cutaneous wounds. Collectively, NGR1 promotes angiogenesis and wound repair via activation of the Notch pathway and exhibits therapeutic effects on cutaneous wound healing.

AIn4S6Cl (A = Rb and Cs) and Pb5Sn3Q10Cl2 (Q = S and Se): quaternary chalcohalides with mixed anionic coordination exhibit photocurrent responses.

Mixed-anionic compounds have caught considerable attention due to their flexible coordination manners and abundant physical properties. Four new chalcohalides RbIn4S6Cl (1), CsIn4S6Cl (2), Pb5Sn3S10Cl2 (3) and Pb5Sn3Se10Cl2 (4) were successfully obtained by the high-temperature halide salt flux method. Compounds 1 and 2 have layered structures that consist of octahedral InS6 and aliovalent-anionic InS3Cl units. Compounds 3 and 4 feature 3-D structural frameworks built by [Pb4SnQ8Cl4]6- and [PbSn2Q6]2- (Q = S and Se) polyhedral chains, in which partial Pb2+ cations are coordinated by Q2- and Cl- anions. Compounds 1-4 have optical band gaps close to the wavelength range of visible light and exhibit significant photocurrent responses of 28.75 nA cm-2, 55.12 nA cm-2, 19.58 mA cm-2, and 36.12 µA cm-2 with on/off ratios 30.0, 2.5, 15.7 and 2.6, respectively, implying their potential for photovoltaic applications. To the best of our knowledge, compound 3 has the largest photocurrent response among all non-oxides. In addition, the activation energies of 1-4 are well below 0.3 eV, which makes these compounds interesting for potential applications in electrochemical devices. This work sheds light on the exploration of promising photocurrent response materials in the mixed-anionic compound system.

Efficacy of 125I seed implantation combined with intermittent hormonal therapy on moderate- and high-risk non-metastatic prostate cancer.

PURPOSE: Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1-214 transcript (PVT1-214) is a notable lncRNA involved in gastric cancer and colorectal cancer (CRC) so far. Nowadays, the biological function of PVT1-214 on the response of CRC to chemotherapy is still unclear. We aimed to explore the molecular mechanism of PVT1-214 and its regulatory mechanism in advanced CRC. METHODS: The levels of PVT1-214, microRNA (miR)-128, and interferon regulatory factor-1 (IRF-1) in CRC tissues and cell lines were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Log-rank test was applied to evaluate the role of high PVT1-214 levels in shortening the overall survival of CRC patients. Chi-square test was to assess the relation between PVT1-214 expression and clinicopathological features of CRC patients. CCK8 assays tested the cell proliferation of oxaliplatin-resistant CRC cells (HCT116/Oxa and SW480/Oxa) with PVT1-214 knockdown. The underlying regulatory mechanism between PVT1-214 and miR-128 was predicted by bioinformatics and verified by RNA transfection, qRT-PCR and western blotting. Chromatin immunoprecipitation (ChIP) assay was done to examine the relationship between or IRF-1 and the PVT1-214 gene. RESULTS: High levels of PVT1-214 expression were more likely to be present in patients with late-stage (IV), chemotherapy resistance, and inferior overall survival. PVT1-214 was aberrantly elevated in oxaliplatin-resistant CRC tissues and cell lines (HCT116/Oxa and SW480/Oxa). PVT1-214 knockdown reduced cell proliferation, migration and invasion of oxaliplatin-resistant CRC cells in vitro. Moreover, IRF-1 was found to be a negative transcription regulator of PVT1-214 and decreased PVT1-214 levels in oxaliplatin-resistant CRC cells. Besides, PVT1-214 repressed miR-128 function by binding to the complementary sites of miR-128. CONCLUSIONS: IRF-1/PVT1-214 may markedly boost the oxaliplatin-resistance of CRC, resulting in the late TNM stage and poor survival. These findings suggest that the IRF-1/PVT1-214 axis may be a helpful target for intervention in CRC.

MiR-539-5p alleviates sepsis-induced acute lung injury by targeting ROCK1.

INTRODUCTION: Sepsis-induced acute lung injury (ALI) is an inflammatory process involved with simultaneous production of inflammatory cytokines and chemokines. In this study, we investigated the regulatory role of miR-539-5p in sepsis-induced ALI using a mouse model of cecal ligation puncture (CLP) and an in vitro model of primary murine pulmonary microvascular endothelial cells (MPVECs). MATERIAL AND METHODS: Adult male C57BL/6 mice were intravenously injected with or without miR-539-5p agomir or scrambled control one week before CLP operation. MPVECs were transfected with miR-539-5p mimics or control mimics, followed by lipopolysaccharide (LPS) stimulation. ROCK1 was predicted and confirmed as a direct target of miR-539-5p using dual-luciferase reporter assay. In rescue experiment, MPVECs were co-transfected with lentiviral vector expressing ROCK1 (or empty vector) and miR-539-5p mimics 24 h before LPS treatment. The transcriptional activity of caspase-3, the apoptosis ratio, the levels of miR-539-5p, interleukin-1b (IL-1b), interleukin-6 (IL-6), and ROCK1 were assessed. RESULTS: Compared to sham group, mice following CLP showed pulmonary morphological abnormalities, elevated production of IL-1b and IL-6, and increased caspase-3 activity and apoptosis ratio in the lung. In MPVECs, LPS stimulation resulted in a significant induction of inflammatory cytokine levels and apoptosis compared to untreated cells. The overexpression of miR-539-5p in septic mice alleviated sepsis-induced pulmonary injury, apoptosis, and inflammation. MiR-539-5p also demonstrated anti-apoptotic and anti-inflammatory effect in LPS-treated MPVECs. The upregulation of ROCK1 in MPVECs recovered miR-539-5p-suppressed caspase-3 activity and proinflammatory cytokine production. CONCLUSION: In conclusion, miR-539-5p alleviated sepsis-induced ALI via suppressing its downstream target ROCK1, suggesting a therapeutic potential of miR-539-5p for the management of sepsis-induced ALI.