Yong Chen

Hydroxysafflor yellow A (HSYA), the principal bioactive compound of safflower, is clinically used for ischemic cerebrovascular disease. However, the current sources of HSYA are limited and inadequate for clinical applications. In this study, we synthesized 8,9-dihydrohydroxysafflor yellow A (dh-HSYA), an analogue of HSYA, via a chemo-enzymatic approach and investigated its neuroprotective activity. The precursor phloretin-di-C-glucoside (PDG) was biosynthesized de novo in yeast, reaching a titer of 301.15 mg L^-1. Furthermore, efficient production of PDG was achieved by supplementing with phloretin, resulting in a titer of 2.39 g L^-1. Subsequently, dh-HSYA was synthesized from PDG via chemical oxidation, with a yield of 29.02%. The dh-HSYA exerted protective effects on BV2 and HT22 cells under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions and attenuated brain injury in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R). This study provides a promising strategy for the sustainable production of dh-HSYA, which could potentially serve as a more scalable substitute for HSYA.

Spirocitromycetin, an antiosteoporotic polyketide bearing a unique spirocycle, was characterized from a human mucus sputum-derived Penicillium velutinum. Its structure and absolute configuration were elucidated spectrally, with its biosynthetic pathway likely mediated via polivione, a reported heptaketide. Spirocitromycetin was shown to be antiosteoporotic at 0.1 μM in the prednisolone-induced osteoporotic zebrafish model. A combination of spirocitromycetin variant synthesis and bioassay has identified 5'-methyl-3'H-spiro[chromane-3,2'-furan]-3',4-dione as an unreported antiosteroporotic pharmacophore. Collectively, this work offers new starting (sub)structures that may be of significance for antiosteoporotic drug discovery.

The thyrotroph embryonic factor gene is a circadian clock-controlled gene. The rs738499 polymorphism of this gene has been suggested to be associated with depression and sleep disturbance in Parkinson’s disease in previous cross-sectional studies. We aimed to investigate whether this single nucleotide polymorphism is associated with the progression rates of various motor and non-motor symptoms in patients with Parkinson’s disease. We recruited 186 patients with Parkinson’s disease for a longitudinal study. Motor and non-motor symptoms were assessed at baseline and follow-up, and 170 Parkinson’s disease patients completed the clinical evaluation twice with an average follow-up period of 3.3 ± 1.1 years. A stepwise linear regression model was used to validate factors associated with Parkinson’s disease symptoms’ annual progression rates. Faster annual worsening rates of sleep quality and Hoehn-Yahr stage were found in carriers with the homozygous dominant (TT). After adjustment for related clinical factors, the rs738499 polymorphism showed a contribution of 3.1% to the annual decline rate on the Parkinson’s Disease Sleep Scale score and a contribution of 5.5% to the annual increase rate of the Hoehn-Yahr stage. Additionally, anxiety and axial symptoms predicted the progression of sleep disturbances and motor staging. The TT genotype of rs738499 might be a potential predictor of rapid deterioration in sleep quality and Hoehn-Yahr stage in patients with Parkinson’s disease and may advance the understanding of the genetic contributions to Parkinson’s disease.

Objective. We sought to investigate the efficacy and safety of Infliximab for prevention of postoperative recurrence in patients with Crohn’s disease (CD), in a meta-analysis of clinical trial results. Methods. The Medline, Embase, PubMed, and Web of Science databases were systematically searched for suitable studies. A meta-analysis of enrolled studies was performed to analyze the efficacy of Infliximab on outcomes regarding the prevention of postoperative recurrence of CD. A Galbraith radial plot was used to quantify the heterogeneity. Funnel plot and Egger test were performed to describe the bias of publication. A Forest plot was prepared to indicate the efficacy outcomes. Results. A total of 7 prospective trials were included in our meta-analysis (N=455). The Funnel plot and Egger test showed there was no significant bias in the included publications. The Cochrane collaboration tool indicated that all 7 prospective trials were of high quality. The results of Galbraith radial plot showed that no study was the source of heterogeneity. Compared with the placebo group, Infliximab decreased the rates of endoscopic recurrence (RR =0.421; 95% CI 0.328 to 0.539; p p=0.001). Furthermore, Infliximab treatment did not show adverse effects as other systematic therapeutic drugs, indicating that Infliximab treatment is effective and well tolerated. Conclusion. Compared with the controls, Infliximab is a promising therapeutic agent for the management of CD patients.

The quantitative analysis of amino acids, nucleosides and nucleobases is important for the quality evaluation of the popular fruit Annona squamosa L. obtained from different regions in China. To establish a repeatable and accurate LC-QTRAP-MS/MS method for the simultaneous determination of 23 target components in fruitages obtained from 5 different regions, chromatographic separation was carried out on an amide column with gradient elution using water and acetonitrile. The method is rapid and completed in less than 6 min and has acceptable linearity in the range of the tested concentration. The average recoveries of the 23 components were 95.30–104.53% with the relative standard deviations of 1.01–3.90%. The results show that the qualities of AAs and NNs in the A. squamosa fruit obtained from the Guangxi province are optimal. The contents of these targets in the Annona squamosa fruitages obtained from 5 regions are significantly different, which might be due to their environment and species.

Claoxylon indicum Hassk. (Euphorbiaceae), named Diu Le Bang, have functions of dehumidification and relieving swelling pain, and is used as a folk medicine to treat Rheumatoid arthritis (RA), lumbocrural pain and foot edema in the south of China. The aim of the present study was to investigate the anti-arthritic activity of the ethanol extract of Claoxylon indicum (CIE) on mice with adjuvant induced joint arthritis. Adjuvant arthritis was induced in mice by subcutaneous injection of complete Freund’s adjuvant into the plantar surface of right hind paw. Arthritis severity was evaluated by arthritic score, hind paws oedema and spleen index, and histological examinations. Serum samples were collected for determination of malondialdehyde (MDA) and alkaline phosphatase (ALP) levels. The expression of interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) in the specimens of knee joints was determined by standard immunohistochemical techniques. CIE administration (0.4 and 0.8 g/kg) suppressed the inflammatory responses in the joints of adjuvant-induced arthritis (AIA) mice, suggested by the modulatory effects on paw swelling, hyperplasia of lymphatic tissues and synovial membrane. It also decreased the levels of MDA and ALP in serum and downregulated the expression of IL-1β and TNF-α in the arthritic joints of AIA mice. These results suggested that CIE possessed substantial anti-arthritic activity due to immumodepression and regulation of cytokines. CIE may be a potential candidate for the treatment of RA.