[Effect of Notch1 on extracellular matrix deposition in the renal tubulointerstitium of diabetes].

The aim of the present study was to observe the effects of Notch1 and autophagy on extracellular matrix deposition in renal tubulointerstitium of diabetes and to explore the mechanism. The mice were randomly divided into normal control group (db/m mice) and diabetes group (db/db mice). After 12 weeks of feeding, the mice were sacrificed and the corresponding biochemical indexes were measured. Rat renal tubular epithelial cells NRK52E were cultured under normal glucose (NG) and high glucose (HG) respectively, and the expression of Notch1 and LC3 proteins were detected by Western blotting. Autophagosomes in NRK52E cells with overexpressed and knockdown Notch1 under NG and HG conditions were observed by confocal microscope, and the expression changes of Notch1, Collagen-I and III protein were detected by immunofluorescence. The results showed that the Notch1 and Collagen-III expressions were increased (P < 0.01) and the LC3 expression was decreased (P < 0.05) in db/db mice compared with db/m mice. In vitro, the Notch1 was increased (P < 0.01) and the LC3 expression was decreased significantly (P < 0.01) in NRK52E cells of HG group compared with NG group. There was no significant change of Notch1 and LC3 expression between the mannitol (MA) group and the NG group. Autophagy was decreased and extracellular matrix deposition was aggravated when Notch1 was overexpressed. In contrast, autophagy was increased and extracellular matrix deposition was relieved by knockdown of Notch1 under HG conditions. In conclusion, Notch1 protein expression was increased and autophagy was reduced in renal tissue of diabetes and renal tubular epithelial cells under HG. The extracellular matrix deposition in the renal tubulointerstitium was relieved by regulating autophagy after the knockdown of Notch1.

The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status.

An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to ß-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

The relaxing effect of Poncirus fructus and its flavonoid content on porcine coronary artery / 한국실험동물학회지

Coronary artery disease is a common occurrence in human, and causes enormous social cost. Poncirus fructus (PF), the dried immature fruits of Poncirus trifoliata Rafinesquem, is used in the treatment of womb contraction and dyspepsia, as a prokinetic, and in improving blood circulation. This study was performed to investigate the effects of PF and some of its flavonoids components on the coronary from the pig. The arterial ring was suspended by a pair of stainless steel stirrups in an organ bath. The end of the upper stirrup was connected to an isometric force transducer. A dose-dependent induction of relaxation was observed by both water and 70% ethanol extracts of PF in the porcine coronary artery precontracted with U46619 (100 nM), a stable analogue of the potent vasoconstrictor thromboxane A2. The 70% ethanol extract showed more efficacy than the water extract. Pretreatment of the artery with L-NAME (100 microM), a nitric oxide synthase inhibitor, resulted in a significant reduction in the relaxation induced by PF extract. In addition, ODQ (10 microM), a soluble guanylate cyclase inhibitor, also significantly reduced the effects of PF extracts. Hesperidin, a flavonoid present in PF, induced very weak relaxation of the porcine coronary artery at a high concentration (100 microM), while its aglycone, hesperetin, demonstrated a dose-dependent relaxation. In conclusion, PF extracts induced relaxation in the porcine coronary artery, partially through the nitric oxide-cGMP pathway, and the aglycones of flavonoids might be also involved in the relaxation of the same artery.

[Inhibitory effects of small interfering RNA targeting c-myc in combination with 5-fluorouracil on the growth in vitro and in vivo].

OBJECTIVE: To observe the effects of small interfere RNA (siRNA) targeting the c-myc in combination with 5-fluorouracil (5-Fu) on the growth of Hep-2 cells in vitro and in vivo. METHODS: Hep-2 cells transfected with or without c-myc siRNA were treated with 5-Fu for 48 h. C-myc protein levels in Hep-2 cells were detected using the Western blot. The cell cycle was analyzed by flow cytometry. Hep-2 cells were subcutaneously inoculated into the back of BALB/c nude mice to establish the implanted laryngeal squamous carcinoma model. PBS, c-myc siRNA, and 5-Fu, alone or in combinations were administered i.p. The mice were sacrificed after the treatments and the tumor masses were removed to determine the tumor volume and weight. The inhibitory rate was calculated. Expression of c-myc in tumor tissue was detected by immunocytochemistry and cell apoptosis was analyzed by terminal transferase dUTP nick end labeling (TUNEL). RESULTS: The protein levels of c-myc decreased after transfected with c-myc siRNA. C-myc siRNA-transfected cells showed an increase in the percentage of cells in the GO-G1 phase and a decrease in the percentage of cells in the S phase. When combined with 5-Fu, the results were improved. The tumor growth was faster in the control group and was significantly slower in the c-myc siRNA plus 5-Fu group than that in the c-myc siRNA group or 5-Fu group (P < 0.05). The tumor weight in the c-myc siRNA plus 5-Fu group was significantly smaller than that in the c-myc siRNA or 5-Fu group (P < 0.05). Immunohistochemistry showed that c-myc siRNA inhibited the expression of c-myc in tumor tissues in the c-myc siRNA group and c-myc siRNA plus 5-Fu group (P < 0.05). The number of apoptotic cells in the c-myc siRNA plus 5-Fu group was higher than those in the c-myc siRNA groups (P < 0.05). CONCLUSIONS: C-myc siRNA inhibits the expression of c-myc in Hep-2 cells and in the tumor tissues of nude mice. C-myc siRNA combined with 5-Fu inhibits the growth of implanted laryngeal squamous carcinoma and promotes cell apoptosis. C-myc could become a novel target for the treatment of laryngeal squamous carcinoma.