In vitro transcribed (IVT) mRNA drugs: technical progress and application prospect / 药学学报

The in vitro transcribed (IVT) mRNA technology has progressed rapidly and the application of mRNA vaccines in the COVID-19 pandemic made it become the most talked-about topic. Compared with protein drugs, IVT mRNA has a lower cost; it can be modular produced and its sequence can be modified easily, so it has a broad application prospect. However, due to its short history, mRNA drugs face the problem of lacking sufficient clinical data, and there is no quality control standard for mRNA drugs except mRNA vaccines. We overview the sequence design, delivery vectors, administration, application prospect and safety considerations of mRNA drugs. We also discussed the quality control of mRNA drugs briefly.

Meta-analysis of efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs in treatment of liver fibrosis and cirrhosis in chronic hepatitis B / 中国中药杂志

The present study evaluated the clinical efficacy and safety of Liuwei Wuling Tablets combined with conventional drugs for the treatment of liver fibrosis and cirrhosis in chronic hepatitis B. CNKI, Wanfang, VIP, CBM, PubMed, EMbase and Cochrane Library were searched for the relevant randomized controlled trials(RCTs) published from database inception to February 2021. All the retrieved papers were independently screened, extracted and evaluated by two researchers, followed by Meta-analysis by Review Manager 5.4. Finally, 18 RCTs were included, involving 2 168 patients(1 106 in the treatment group and 1 062 in the control group). The Meta-analysis results showed that compared with conventional drugs alone, Liuwei Wuling Tablets combined with conventional drugs could increase the effective rate of clinical treatment by reducing serum hyaluronic acid(HA), laminin(LN), procollagen type Ⅲ(PCⅢ), and type Ⅳ collagen(Ⅳ-C) to improve liver function, decreasing the levels of total bilirubin(TBiL), alanine amino-transferase(ALT), and aspartate aminotransferase(AST), and improving the negative conversion ratio of hepatitis B virus(HBV) DNA. In terms of safety, there were no serious adverse reactions in the treatment group and the control group. The results showed that Liuwei Wuling Tablets combined with antiviral or other conventional liver-protecting drugs could improve liver function, treat liver cirrhosis, and reduce liver fibrosis with high safety. However, due to the influence of literature quality and quantity, multi-center and high-quality RCTs with large sample size are needed for verification.

Research progress of circadian rhythm / 中国中药杂志

Circadian rhythm disorder is a common society issue caused by jet lag,shift work,sleep disruption and changes in food consumption. Light is the major factor affecting the circadian rhythm system. Disruption of the circadian rhythm system can cause damage to the body,leading to some diseases. Maintaining a normal circadian system is of great importance for good health. Ideal therapeutic effect can not only alleviate symptoms of the diseases,but also recovery the disturbed circadian rhythm to normal. The paper summarizes the modeling methods of animal circadian rhythm disorder,diseases of circadian rhythm abnormality,regulation of circadian clock genes and medicine which are related to circadian rhythm to diseases of circadian rhythm disorder.

Averrhoa Carambola L. Roots DMDD alleviates myocardial injury in diabetes mellitus mice by regulating ROS-mediated autophagy pathway / 中国药理学通报

Aim To evaluate the protective effect of Averrhoa Carambola L. Roots DMDD alleviating myocardial injury in diabetes mellitus (DM) mice and its mechanism. Methods SD mice were given high-glucose-high-fat diet combined with streptozotocin to induce DM model, and were administered with DMDD. The fasting blood glucose (FBG) was recorded. The left ventricular end-diastolic pressure (LVEDP), left ventricular systolic pressure (LVSP), maximum upstroke velocity of left ventricular pressure (+ dp/dt

A new polyketide from endophytic fungus Aspergillus oryzae derived from Paris polyphylla var. yunnanensis / 中草药

Objective: To study the secondary metabolites of the endophytic fungus Aspergillus oryzae from Paris polyphylla var. yunnanensis in order to find new compounds. Methods: The endophytic fungus A. oryzae was fermented by liquid fermentation. After extraction, silica gel and macroporous adsorption resin were used to separate and purify the extract. The structures of the compounds were identified according to their physical and chemical properties and spectroscopic data. Results: Three compounds were isolated and their structures were identified as 3-amino-4,5-dihydroxy-4,6-dimethyl-2-(2-methylbutanoyl)cyclohex-2-enone (1), 12-N-methyl- cyclo-(L-tryptophyl-L-phenylalanyl) (2) and ditryptophenaline (3). Conclusion: Compound 1 is a new polyketide named asperpolyketide A.

Comparison of curative effects of intravitreal injection of Ranibizumab and Conbercept in the treatment of diabetic macular edema / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To comparatively analyze curative effects of intravitreal injection of Ranibizumab and Conbercept in the treatment of diabetic macular edema.METHODS:Retrospectively analyzed the clinical data of 110 patients (110 eyes) with diabetic macular edema treated in our hospital from January 2015 to January 2016,divided them into two groups according to the different treatment.Of these,treated 55 eyes with ranibizumab intravitreal injections (ranibizumab group) and the other with conbercept intravitreal injections (conbercept group),the injection came once a month for 8 continuous months with a 6-month follow-up.Compared the changes of visual acuity,macular thickness,postoperative comfort,clinical efficacy and complications between the two groups after treatment.RESULTS:There was no significant difference in LogMAR visual acuity between the two groups before treatment (P＞ 0.05).The visual acuity of the patients in the ranibizumab group and conbercept group were significantly improved after 1mo treatment,F were 42.06and 64.02 respectively (P＜ 0.01),but there was no significant difference between the two groups after 1mo treatment (P＞0.05).The visual acuity of the conbercept group was significantly higher than that of the ranibizumab group after 3 and 6mo treatment (P＜0.05).There was no significant difference in macular thickness between the two groups before treatment (P＞0.05),the thickness of the macular fovea in the ranibizumab group and conbercept group was lower than that before treatment,there were statistically significant differences (P＜ 0.01);the decline range of conbercept group were more than those of the ranibizumab group after 3 and 6mo (P＜0.05).Patients comfort of the two groups improved with the passage of time after surgery,and there was no significant difference between the two groups (P＞0.05),there were no significant differences in the total effective rate and complication of the ranibizumab group (87.3％,1.8％) and the conbercept group(85.5％,3.6％) (P＞0.05).CONCLUSION:In the treatment of diabetic macular edema,the early vision of patients with diabetic macular edema increases significantly,and the macular thickness decreases significantly.Conbercept works better and has a longer lasting effect after 3 and 6mo treatment,and conbercept is more economical.

Protective effect of sodium butyrate on the neonatal mouse model of necrotizing enterocolitis / 解放军医学杂志

Objective To investigate the protective effect of sodium butyrate on the neonatal mouse model of necrotizing enterocolitis and analyze its possible mechanism.Methods Sixty c57BL/6 neonatal mice were randomly divided into two groups (n=30):PBS group and butyric acid group.At the third day after birth,mice in both groups were respectively given PBS and sodium butyrate solution by gavage once a day for 7 days,and neonatal necrotizing enterocolitis (NEC) model was established by hypoxia,cold stimulation and artificial feeding.The newborn mice were sacrificed overnight after modeling.HE staining and double-blind pathological score were performed to observe the pathological changes of ileocecal intestinal tissue.The mRNA expressions of IL-6,IL-10,TGF-β1 and TNF-a were tested by quantitative real-time PCR.The levels of IL-10 and TGF-β1 in intestine tissues were evaluated using ELISA.Flow cytometry was used to analyze the ratio of regulatory T cells (Treg) on CD4+ T cells in both groups.Results When mice were sacrificed overnight after NEC modeling,the body weight was significantly higher in butyric acid group (4.50 ± 0.42g) than in PBS group (4.16 ± 0.60g,P＜0.05);No significant difference (P＞0.05) existed in survival rate of butyric acid group (76.34％) and PBS group (67.95％).The pathological damage score of intestinal tissue showed that the median score of intestinal injury was significantly lower in butyric acid group [1.33(1.33-1.67)] than in PBS group [2.00(1.67-2.25),P＜0.05].qPCR demonstrated that the expressions of IL-6 and TNF-α mRNA were obviously lower in butyric acid group than in PBS group (0.85 ± 0.30 vs.1.77 ± 0.49 and 0.41 ± 0.25 vs.0.96 ± 0.56,respectively,P＜0.05);and the expressions of IL-10 and TGF-β1 mRNA were markedly higher in butyric acid group than in PBS group (1.91 ± 0.82 vs.0.94 ± 0.43 and 1.46 ± 0.57 vs.0.88 ± 0.29,respectively,P＜0.05);Intestinal tissue ELISA results showed that the expressions of IL-10 and TGF-β1 were higher in butyric acid group than in PBS group (68.60 ± 15.06 vs.37.25 ± 5.81 and 424.93 ± 19.34 vs.127.31 ± 60.83,respectively,P＜0.05);Flow cytometry revealed that the proportion of regulatory T cells (Treg) of CD4+ T cells was higher in butyric acid group than in PBS group (12.68％ ± 6.79％ vs.3.57％ ± 0.88％,P＜0.05).Conclusions Butyric acid plays a protective effect in the intestinal injury of neonatal mouse model of necrotizing enterocolitis.The possible mechanism is that butyrate can down-regulate the expressions of cytokines IL-6 and TNF-o,up-regulate the expressions of cytokines IL-10 and TGF-β1,and promote the differentiation of T cells into Treg cells.

Estrogenic activity of osthole and imperatorin in MCF-7 cells and their osteoblastic effects in Saos-2 cells / 中国天然药物

There is an increasing interest in phytoestrogens due to their potential medical usage in hormone replacement therapy (HRT). The present study was designed to investigate the in vitro effects of estrogen-like activities of two widespread coumarins, osthole and imperatorin, using the MCF-7 cell proliferation assay and their alkaline phosphatase (ALP) activities in osteoblasts Saos-2 cells. The two compounds were found to strongly stimulate the proliferation of MCF-7 cells. The estrogen receptor-regulated ERα, progesterone receptor (PR) and PS2 mRNA levels were increased by treatment with osthole and imperatorin. All these effects were significantly inhibited by the specific estrogen receptor antagonist ICI182, 780. Cell cycle analysis revealed that their proliferation stimulatory effect was associated with a marked increase in the number of MCF-7 cells in S phase, which was similar to that observed with estradiol. It was also observed that they significantly increased ALP activity, which was reversed by ICI182,780. These results suggested that osthole and imperatorin could stimulate osteoblastic activity by displaying estrogenic properties or through the ER pathway. In conclusion, osthole and imperatorin may represent new pharmacological tools for the treatment of osteoporosis.

Observation of the change in ocular anterior segment after pterygium surgery with ultrasound biomicroscopy / 国际眼科杂志(Guoji Yanke Zazhi)

AlM: To observe the effect of anterior chamber depth and angle change after pterygium excision.METHODS:Thirty cases (30 eyes) of primary pterygium were underwent pterygium excision. Central anterior chamber depth, four direction angle open distance ( AOD ) and open angle ( AA ) were measured preoperatively and postoperatively by ultrasound biomicroscopy ( UBM ) and the intraocular pressure was observed.RESULTS:Preoperative and Postoperative intraocular pressure were 15. 17±10. 6 and 16. 23±2. 61mmHg, and the central anterior chamber depth were 2. 28±0. 39 and 2. 33± 0. 24mm. The four directions of AOD and AA were no statistical difference.CONCLUSlON:The anterior chamber depth and the angle change is not obvious after pterygium excision.

Effect of phospholipid composition on pharmaceutical properties and anti-tumor activity of stealth liposomes containing brucine / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the pharmaceutical properties and the anti-tumor activities of three kinds of stealth liposomes prepared with different phospholipid composition containing brucine.</p><p><b>METHOD</b>Stealth liposomes with different phospholipids composition, such as soybean phosphatidycholine (SPC), hydrogenated soybean phosphatidylcholine (HSPC) and the complex of SPC and HSPC, were prepared by ammonium sulfate transmembrane gradient method. Pharmaceutical properties such as shape, encapsulation efficiency and size of three stealth liposomes were compared intensively. Anti-tumor activity of SPC, HSPC and novel stealth liposomes composed of both SPC and HSPC were compared by established mouse liver cancer H22 model. Meanwhile, the mice body weight and immune organ weight were also compared.</p><p><b>RESULT</b>The encapsulation efficiency of novel, SPC and HSPC stealth liposomes were 77.7%, 64.8% and 74.8%, respectively. The mean diameters of them were less than 100 nm. The tumor inhibition rate of novel, HSPC and SPC stealth liposomes were 57.88%, 49.15%, 23.37%, respectively. The mice body weight, thymus gland index of three stealth liposomes group and spleen index of novel stealth liposomes group had no significant difference with the negative group while SPC and HSPC stealth liposomes group increased the spleen index.</p><p><b>CONCLUSION</b>Phospholipids composition is the key factor which determines the antitumor activity of brucine-loaded stealth liposomes.</p>

Pharmacokinetics of brucine in rats after intravenous administration of liposomes containing total alkaloids from seed of Strychnos nux-vomica / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the pharmacokinetic characteristics of brucine following intravenous administration of liposomes, containing total alkaloids from seed of Strychnos nux-vomica, to rats with different phospholipids composition.</p><p><b>METHOD</b>Liposomes containing the total alkaloids were prepared by the method of ammonium sulfate transmembrane gradients and stealth liposome technique. The contents of total alkaloids and brucine in liposomes were determined and compared after free drug being removed. After intravenous administration of total alkaloids solution or liposomes with different composition, plasma samples were drawn at predetermined time points and the concentrations of brucine were determined by a validated method of HPLC. Pharmacokinetic analysis was performed by 3P97 program.</p><p><b>RESULT</b>The ratios of brucine to total alkaloids in liposomes hardly varied with phospholipids composition. Compared with SPC liposome, AUC of brucine was increased 13.3-fold and apparent volume of distribution was decreased to only 3.6% following intravenous administration of HSPC liposome. In addition, besides that AUC of brucine was slightly increased, most pharmacokinetic parameters were not significantly changed after administration of the novel liposome compared with those of SPC liposome.</p><p><b>CONCLUSION</b>Phospholipids composition has a significant influence on the pharmacokinetics of brucine after intravenous administration of liposomes containing total alkaloids from seed of S. nux-vomica.</p>

Efficient expression of soluble human FGF-21 and its glucose regulation activity / 药学学报

The cDNA of human FGF-21 was subcloned into the pSUMO expression vector and the fusion protein was induced to express in Escherichia coli Rosetta (DE3). The recombinant hFGF-21 was expressed in soluble form in the pSUMO expression system. The recombinant fusion protein was purified by Ni-NTA column. The purified recombinant protein was dialyzed against PBS for re-nature. To obtain pure and active recombinant protein, the fusion protein was subjected to cleavage with SUMO protease I. To examine glucose regulation activity of hFGF-21, 3T3-L1 pre-adipocytes were differentiated into adipocytes, glucose up-take activity of hFGF-21 was examined by glucose oxidase and peroxidase (GOD-POD) assay. Compared with no stimulation control, the recombinant hFGF-21 treatment led to a significant increase in glucose consumption of adipocytes and a significant decrease in concentration of glucose in the medium (P < 0.05, P < 0.001).

Butyl-p-hydroxybenzoate stimulates cystic fibrosis transmembrane conductance regulator Cl- transport / 药学学报

This study is to investigate the activation effect of butyl-p-hydroxybenzoate (Bpb) on cAMP-dependent cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel gating. A stably transfected Fischer rat thyroid (FRT) epithelial cell lines co-expressing human CFTR and a green fluorescent protein mutant with ultra-high halide sensitivity (EYFP) were used to measure CFTR-mediated iodide influx rates. Bpb was identified as an effective activator of wild-type CFTR chloride channel, it can correct delta F508-CFTR gating defects but not processing defect. Bpb can't potentiate G551D-CFTR channel gating. The activity was reversible and dose-dependent. The study also provided clues that Bpb activates CFTR chloride channel through a direct binding mechanism. Our study identified Bpb as a novel structure CFTR activator. Bpb may be useful for probing CFTR channel gating mechanisms and as a lead compound to develop pharmacological therapy for CFTR-related disease.