DREADD: A Chemogenetic GPCR Signaling Platform

Recently, we created a family of engineered G protein-coupled receptors (GPCRs) called DREADD (designer receptors exclusively activated by designer drugs) which can precisely control three major GPCR signaling pathways (Gq, Gi, and Gs). DREADD technology has been successfully applied in a variety of in vivo studies to control GPCR signaling, and here we describe recent advances of DREADD technology and discuss its potential application in drug discovery, gene therapy, and tissue engineering.     

Therapeutic effects of puerarin on polycystic ovary syndrome: A randomized trial in Chinese women

Background:This study aims to assess the therapeutic effects of a well-known component (puerarin) obtained from a Chinese herb root in patients with polycystic ovary syndrome (PCOS).Methods:Women with premature ovarian failure (POF) were assigned to the obese group (body mass index [BMI] ≥24 kg/m² and waist hip ratio [WHR] >0.85) or non-obese group (group 3, n = 21). Obese patients were further randomly assigned to the obese treatment group (group 1, n = 15) and obese control group (group 1, n = 15). All patients received standard treatment (Diane-35, 1 tablet/d, orally, plus metformin, 1.5 g/d, orally). In addition to the standard modality, patients in group 1 and group 3 also orally received 150 mg/d of puerarin tablets for 3 months. Venous blood was drawn before and after treatment. Then, the metabolic and antioxidant biomarkers were measured. The normality of distribution of the data was tested using the Kolmogorov–Smirnov method. The baseline characteristics were analyzed using one-factor analysis of variance (ANOVA), and post-hoc was performed using the least significance difference (LSD)-t test.Results:Significantly improved blood levels of sex hormone binding globulin (SHBG) and superoxide dismutase (SOD) were observed in patients who received the additional treatment of puerarin, regardless of their lean or obese status, while these were not observed in patients who did not receive puerarin. Furthermore, obese patients with PCOS had significantly lower systolic blood pressure, total cholesterol, and testosterone blood levels, when compared with before treatment.Conclusion:The addition of puerarin to the present treatment protocol can be considered for the management of metabolic disorders and hyperandrogenism in PCOS patients.     

Clinical features and viral RNA shedding of imported and local cases with COVID-19 in Wenzhou,China

Wenzhou had the highest number of confirmed novel coronavirus 2019 (COVID-19) cases outside the Hubei province. The aim of this study was to identify the difference in clinical features and viral RNA shedding between the imported and local COVID-19 cases in Wenzhou.All patients with confirmed COVID-19 admitted to Wenzhou Sixth People''s Hospital, Wenzhou Central Hospital Medical Group, from January 17 to February 11, 2020, were enrolled in this study. Data was analyzed and compared for the imported and local cases with regard to epidemiological, demographic, clinical, radiological features, and laboratory findings. Outcomes for the enrolled participants were followed up until May 7, 2020.Of the 136 cases, 50 were imported from Wuhan. The median age was 45 years and 73 (53.7%) were men. The most common symptoms at onset were fever (104 [76.5%]) and cough (85[62.5%]). Pleural effusion was more common among imported cases compared to local cases. The white blood cell count, neutrophil count, lymphocyte count and platelet count of the imported cases were significantly lower than those of the local cases, while the prothrombin time was significantly longer than that of the local cases. Severe and critically ill patients accounted for 15.4% and 2.9%, respectively. The median duration of SARS-CoV-2 RNA shedding from symptom onset was 26 days (IQR 17–32.3 days) and there were no significant differences in duration of viral RNA shedding between the two groups.The study findings suggest that imported cases from Wuhan were more likely to be severe compared to the local cases in Wenzhou. However, there was no difference between imported and local cases on the viral shedding among the COVID patients.     

Long-term renal outcomes of mesangial proliferative lupus nephritis in Chinese patients

Clinical Rheumatology - This study aimed to explore the long-term outcomes of mesangial proliferative lupus nephritis (LN class II) and the factors associated with its relapse and histological...     

Interstitial nephritis without glomerulonephritis in ANCA-associated vasculitis: a case series and literature review

Clinical Rheumatology - The typical nephrological presentation of antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) is rapidly progressive glomerulonephritis....     

The clinical pattern differentiates ANCA-positive infective endocarditis patients from ANCA-associated vasculitis patients: a 23 years’ retrospective cohort study in China and follow-ups

Clinical Rheumatology - Patients with infective endocarditis (IE) may present rheumatic manifestations concurrent with various autoantibodies and thus mimic antineutrophil cytoplasmic antibody...     

Synthesis of Novel Chain‐End‐Functionalized Polyethylenes via Thiol‐ene Click Chemistry

Chain‐end‐functionalized polyethylenes (Cef‐PEs: PE? S? SH (Cef₁), PE? S? furfuryl (Cef₂), PE? S? NH₂ (Cef₄), PE? S? NH₂?HCl (Cef₅), PE? S? COONa (Cef₆), PE? S? CHA(Cef₇), PE? S? SO₃Na (Cef₈), PE? S? OH (Cef₉) and PE? S? COOH (Cef₁₀)) are synthesized by thiol‐ene addition of vinyl‐terminated polyethylene (v‐PE) with 1,2‐ethanedithiol, furfurylmercaptan, cysteamine, cysteamine hydrochloride, sodium thioglycolate, L‐cysteine hydrochloride, sodium 2‐mercaptoethanesulfonate, mercaptoethanol, and thioglycolic acid, respectively. PE? S? t? NCO (Cef₃) is obtained by subsequent reaction of Cef₉ with anhydrous 4,4′‐MDI. Cef‐PE_1–8 are reported for the first time. The conversions of all the reactions are up to 95%–100%. All the Cef‐PEs are characterized by NMR, GPC, DSC, FT‐IR, and TGA. In the experiments, it is found that alkaline mercaptans and solvents are adverse to the thiol‐ene click reactions.

     

Inhibition of mouse hepatocyte apoptosis via anti-Fas ribozyme

AIM: To investigate the effects of anti-Fas ribozyme on Fas expression and apoptosis in primary cultured mouse hepatocytes. METHODS: Mouse hepatocytes were isolated by using collagenase irrigation. A hammerhead ribozyme targeting the Fas mRNA was constructed, and transfected into mouse hepatocytes via Effectene. Then Fas expression in mouse hepatocytes was detected by RT-PCR and western blotting. After being treated with anti-Fas antibody (JO2), hepatocytes viability was measured with MTT assay. Caspase-3 proteolytic activity was detected, and cell apoptosis was measured according to Annexin V-FITC apoptosis detection kit. RESULTS: Fas expressed in primary mouse hepatocytes. Fas expression in hepatocytes transfected with anti-Fas ribozyme was decreased remarkably and correlated with the resistance to Fas-mediated apoptosis as determined by flow cytometry and caspase-3 proteolytic activity. CONCLUSION: Anti-Fas ribozyme can remarkably decrease the Fas expression in mouse hepatocytes, thus inhibit Fas-mediated apoptosis in hepatocytes. It is suggested that anti-Fas ribozyme could significantly increase the resistance of transplanted hepatocytes to apoptosis and improve the survival of transplanted hepatocytes.