Circ_0001490/miR-579-3p/FSTL1 axis modulates the survival of mycobacteria and the viability, apoptosis and inflammatory response in Mycobacterium tuberculosis-infected macrophages.

BACKGROUND: Macrophages play an important role in the host immune response against mycobacterial infection, and this process is regulated by various factors, including circular RNAs (circRNAs). We intended to explore the role of circ_0001490 in tuberculosis (TB) using Mycobacterium tuberculosis (M.tb)-infected THP-1 macrophages. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to measure RNA and protein expression, respectively. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was conducted to analyze the viability of THP-1 macrophages. Flow cytometry was performed to analyze the apoptosis rate of THP-1 macrophages. Enzyme-linked immunosorbent assay (ELISA) was conducted to assess the release of inflammatory cytokines. Colony-forming unit (CFU) assay was conducted to analyze the survival of M.tb in THP-1 macrophages. Intermolecular target interaction was verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. RESULTS: Circ_0001490 expression was down-regulated in the serum samples of TB patients and M.tb-infected THP-1 macrophages. Circ_0001490 overexpression suppressed M.tb survival and promoted the viability and inflammatory response of THP-1 macrophages. Circ_0001490 interacted with microRNA-579-3p (miR-579-3p), and circ_0001490 overexpression-induced protective effects in M.tb-infected THP-1 macrophages were largely overturned by the overexpression of miR-579-3p. miR-579-3p interacted with the 3' untranslated region (3'UTR) of follistatin-like protein 1 (FSTL1). FSTL1 silencing largely overturned miR-579-3p knockdown-induced effects in M.tb-infected THP-1 macrophages. Circ_0001490 acted as miR-579-3p sponge to up-regulate FSTL1 in THP-1 macrophages. CONCLUSION: In conclusion, our results demonstrated that circ_0001490 suppressed M.tb survival and promoted the viability and inflammatory response of M.tb-infected THP-1 macrophages partly by regulating miR-579-3p/FSTL1 axis.

Effect of dydrogesterone and progesterone on threatened miscarriage due to corpus luteum insufficiency.

OBJECTIVE: To investigate the efficacy and safety of dydrogesterone and progesterone in the treatment of threatened miscarriage due to corpus luteum insufficiency. METHODS: A prospective cohort study was designed and a total of 1,285 patients with threatened miscarriage due to corpus luteum insufficiency were recruited, in which 665 participants received dydrogesterone treatment (dydrogesterone group), and the other 620 received progesterone treatment (progesterone group). The time for clinical symptom relief, changes of sex hormone levels in serum, the rate of miscarriage prevention, delivery outcome, and adverse effects were compared between the two groups. XGBoost algorithm was applied to analyze the factors impacting the efficacy and safety of each treatment. RESULTS: There was no significant difference regarding the time for clinical symptom relief and the rate of miscarriage prevention between the two groups (P>0.05, RR=1.01, 95% CI: 0.97-1.06, P=0.566). However, after 4 weeks of treatment, compared with the progesterone group, the level of sex hormones was significantly upregulated, while the preterm birth rate (9.65% vs. 14.04%), the postpartum hemorrhage rate (3.10% vs. 5.62%), and the incidence of adverse effects (17.44% vs. 32.58%) were considerably reduced in the dydrogesterone group (all P<0.05). XGBoost algorithm analysis demonstrated that dydrogesterone treatment was correlated with a lower incidence of preterm birth rate, postpartum hemorrhage, and adverse effects, ranking the 3rd, 2nd and 1st, respectively, in the weight of dependent variables. CONCLUSION: Compared with progesterone, dydrogesterone can improve the delivery outcome and demonstrate a higher safety in the treatment of threatened miscarriage due to corpus luteum insufficiency.

The TCM prescription Ma-xing-shi-gan-tang inhibits Streptococcus pneumoniae pathogenesis by targeting pneumolysin.

ETHNOPHARMACOLOGICAL RELEVANCE: Ma-xing-shi-gan-tang (MXSGT), which is documented in the Treatise on Febrile Diseases and is a therapeutic drug, is a well-known classic prescription in China and has been widely studied. Previous studies have shown that MXSGT has various pharmacological activities, including anti-influenza virus activity, and ameliorates microvascular hyperpermeability and inflammatory reactions. However, no study has reported the effect of MXSGT in the treatment of bacterial pneumonia. AIM OF THE STUDY: In this study, the potential inhibition of MXSGT against the virulence of S. pneumoniae by targeting PLY was investigated. MATERIALS AND METHODS: First, HPLC analysis was used to determine the main components of MXSGT. Then PLY protein was constructed and used for hemolysis assay and western blot to test the ability of MXSGT to inhibit PLY activity, production and widowed characteristics. The growth curve of S. pneumoniae was drawled with or without MXSGT treatment. In addition, the inhibition of MXSGT against PLY-mediated A549 cell death was examined by cytotoxicity assay. Finally, the mouse experiment was used to verify the effect of MXSGT on mouse lungs. RESULTS: This work has discovered that MXSGT, a TCM prescription, is an effective inhibitor of PLY, an important virulence factor that is essential for S. pneumoniae pathogenicity. MXSGT inhibits the oligomerization of PLY without affecting S. pneumoniae growth and PLY production. In addition, experimental MXSGT treatment was effective against S. pneumoniae infection both in vitro and in vivo. CONCLUSION: These findings directly demonstrate the potential mechanism of the Chinese herbal formula MXSGT in the treatment of pneumococcal disease and provide additional evidence for promotion of the wide use of MXSGT in the clinic.

A randomized, double-blind, placebo-controlled, multicenter clinical trial for efficacy and safety of traditional Chinese medicine combined with antibiotics in the treatment of bacterial pneumonia in children.

BACKGROUND: Pneumonia is the second leading cause of death in children worldwide after preterm birth and certification. Bacteria, viruses, mycoplasma, and other microorganisms are known to be the main causes of pneumonia, of which bacterial pathogenic factors account for 12.5% of cases. The invention and application of antibiotics have improved the prognosis of children with community-acquired bacterial pneumonia (CABP) to a certain extent, but with the emergence of antibiotic resistance worldwide, the mortality of children with CABP is still high. "Maxing Shigan Decoction" and "Qingfei Decoction" have significant efficacy in the treatment of CABP in children, but there is no standardized randomized controlled trial to systematically evaluate the outcomes. METHODS: This study is a randomized, double-blind, placebo-controlled, multicenter clinical trial that will randomize 240 patients with CABP to group of Oral Maxing Shigan Decoction, group of Qingfei Decoction or group of placebos administered 3 times a day for 7 days. This study will observe a wide range of clinically relevant endpoints that have been used in clinical trials of pneumonia, including but not limited to clinical cure rate, antibiotic application days, complete antipyretic rate, complete antipyretic days, disease efficacy, traditional Chinese medicine syndrome effect, and antibiotic upgrade treatment rates. Safety will be assessed by monitoring for the incidence of adverse events during the study. DISCUSSION: This clinical trial is the first to evaluate the efficacy and safety of "Maxing Shigan Decoction" and "Qingfei Decoction" in the treatment of children with CABP. The research results will provide a reference for future research design. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR1900025354. Registered on 14th October 2019-Retrospectively registered, http://www.chictr.org.cn/.

[Effect of jiawei mojie tablet on plasma oxytocin level in patients with primary dysmenorrhea in menstrual period].

OBJECTIVE: To investigate the therapeutic mechanism of Jiawei Mojie Tablet (JMT) in treating primary dysmenorrhea (PD) by observing its effect on plasma oxytocin (OT) level in patients in menstrual period. METHODS: Sixty-three patients with PD enrolled in the study were randomly divided into the JMT group (n = 33) and the control Group (n = 30, treated with Yueyueshu Granule) to observe the change of OT level in the menstrual period before and after treatment. RESULTS: OT level in patients with PD was obviously higher than that in healthy subjects (P < 0.01), and was positively correlated with the degree of pain (r = 0.738, P < 0.01). OT level reduced significantly after treatment (P < 0.01), the reduction was more significant in the JMT group than that in the control group (P < 0.01). CONCLUSION: JMT could reduce the OT level in menstrual period.