Study on Active Principle and Modernization of Chinese Drugs

The people as a whole cannot live for one day without drug, and the requirement of drugs would never come to an end or stay on the same level. Pharmaceutical industry, being of great significance, has become a new and important one in economic growth in the 21st century. Therefore, the modernization of Chinese drugs has also become a hot spot in public opinion in recent years.

An Assessment of the Level of Knowledge of HIV-Infected Patients about Highly Active Antireteroviral Therapy and Waiting Times and Their Influence on Antiretroviral Therapy Adherence at a Primary Healthcare Centre of South Africa

Objectives： The study assessed if the level of knowledge of HIV-infected about HAART and waiting-times in the PHC （primary healthcare） clinic have an influence on antiretroviral adherence. Methods： A descriptive-cross-sectional study was conducted in South Africa. Data collected uses a standardized-questionnaire and face-to-face-exit interviews. Pill-count technique was performed and a value of≥ 95% acceptable. Data were analysed using SPSS. Univariate-factors associated with poor-adherence to knowledge about HAART and waiting times were assessed using ANOVA and p ≤ 0.05 considered statistically significant. Key findings： Of 86 enrolled, 63（73.3%） were females and 23（26.7%） males, with mean-age （± SD） of 35.6（±9.6） years and on HAART for 35.5（± 31.8） months ranging from 1-137. Of these, 27（31.40%） and 25（29.07%） were on WHO stages 2 and 3 respectively. Adherence-rates computed from 32 patients, 23（71.9%） revealed poor adherence-rates. The level of knowledge about HAART in terms of names of tablets, correct-dose, frequency, adverse-effects had no influence on ARV-adherence （p _〉 0.05）. Of 23 non-compliant, 10 （40%） gave the reason of drugs-unavailability, 7（30%） adverse-effects, 5（20%） drugs＇ complexity, and 1（10%） too busy to take them. Waiting areas associated with poor ARV-adherence were reception （p = 0.028）, doctors （p = 0.027）, while nurse＇s station （p = 0.29） and pharmacy （p = 0.43） revealed acceptable ARV-adherence.

EFFECT OF ANTITUMOR DRUGS ON THE ACTIVITY OF DNA TOPOISOMERASE I

The activity of DNA topoisomerase Ⅱ prepared from either normal or tumor tissues were compared. It was found that the unknotting activity of the enzyme in malignant tumor cells was higher than that in normal cells. We selected some antitumor drugs including Chinese traditional medicine, and observed their effects on the unknotting activity of topoisomerase Ⅱ. The results showed that inhibition of the unknotting activity of the enzyme required very low concentrations of drugs, but much higher concentrations were required for other tested. Some antitumor drugs had no effect on the enzyme were also proved. It is interesting that carrageenan, an antiviral drug, strongly blocked the unknotting activity although its antitumor activity has not been reported.

PROGRESS OF RESEARCH IN THE PREPARATION OF CHINESE TRADITIONAL AND HERBAL DRUGS WITH ANTICANCER ACTIVITY

Research into anticancer substances madefrom Chinese herbal drugs and their clinicalapplication is gaining international attention bythe medical profession of the more than 20analogues of camptothecine isolated from Camp-totheca tree in China, most exhibited anticanceractivity. Among them, 10-hydroxycamptothe-cine has a wide anticancer spectrum and is lesstoxic. In suspension, it exhibits some therapeu-tic effects on primary hepatic cancer, gastriccarcinoma, cancer of the urinary bladder andleukemia.

Meta-analysis about Western Medicine combined with activating blood drugs on modulating blood glucose and lipids in diabetic patients

OBJECTIVE： To assess the effect of activating blood drugs （AB drugs） on blood glucose and lipid levels of diabetic patients METHODS： Systematic searches were conducted on 6 electronic databases and the search time was cut off in May 2016. Randomized controlled trials （RCTs） were included if they investigated diabetic patients who received Western medicine combined withAB drugs in the experimental groups and solitary usage of corresponding Western medicine or placebo in the control groups. 6 outcome measures, which were considered as inclusion, were changes in fasting blood glucose （FBG）, glycosylated haemoglobin A1 c （HbA 1 c）, total triglyceride （TG）, total cholesterol （TC）, low density lipoprotein cholesterol （LDL-c） and high density lipoprotein cholesterol （HDL-c）. The literature quality was assessed by Cochrane score for risk of bias in Review Manager 5.2, as well as meta-analysis was performed. RESULTS： 7 RCTs comprising 999 patients met all inclusion criteria. Meta-analysis showed beneficial effects of Western medicine combined with AB drugs on modulating FBG, TC, LDL-c and HDL-c compared with Western medicine or placebo （P〈0.05）, while no difference was observed in HbAlc, and TG （P〉0.05）. To some extent, the therapeutic effects of Western medicine combined with AB drugs were better than that of solitary usage of Western medicine or placebo. Besides, AB drugs were safe and reliable with little toxic and side-effects. CONCLUSIONS： The meta-analysis suggests beneficial effects of Western medicine combined with AB drugs on modulating blood glucose and lipids in diabetic patients.

Research Progress of Traditional Chinese Medicine in Treating Irritable Bowel Syndrome Based on Network Pharmacology and Molecular Docking Technology

In recent years,using network pharmacology and molecular docking technology to reveal the therapeutic targets of irritable bowel syndrome(IBS)has become a research hotspot.This paper summarizes 31 studies of traditional Chinese medicine for IBS by domestic and foreign scholars,and expounds the action mechanism of single drug,drug pair and compound prescription in the treatment of IBS from the aspects of drug activity,action target,biological process and pathway analysis.It also discusses the shortcomings and prospects of network pharmacology and molecular docking technology in the field of traditional Chinese medicine research,and provides reference for expanding the research ideas of traditional Chinese medicine in treating IBS.

A NEW EXPERIMENTAL AND CLINICAL APPROACH OF COMBINING USAGE OF HIGHLY ACTIVE TUMOR-INFILTRATING LYMPHOCYTES AND HIGHLY SENSITIVE ANTITUMOR DRUGS FOR THE ADVANCED MALIGNANT TUMOR

In recent years, tumor-nfiltrating lymphocytes (TILs) have been reported to be effective for tumors in experimental and clinical research. In order to increase the therapeutical effect, we modified some steps of Rosenberg's approach a. cold digestion with collagenase at 4C for 24 hours; b. sedimentation instead of centrifugation; c. elimination of tumor cells before the cultivation procedure. Compared with the original approach, the proliferation, activity and cytotoxicity of TILs obtained by the modified procedure were much improved. TILs' expansion-old was greater than that with the original approach. Cytotoxicity against rumor cells was more potent. Increased TILs' subsets were CD3 and CD8 cells. Meanwhile, we took tumor cells from tumor tissues to test their in vitro chemosensitivities to different drugs in order to select highly sensitive antitumor drugs for treatment of cases with advanced tumors. According to the design of using highly active TILs and highly sensitive drugs (H & H therapy), preliminary clinical results of 50 cases showed higher response rates than those in treatment with TIL / IL2, LAK / 1L2 and TIL+IL2+CTX. Less toxic side effects were observed in 14 patients.

Synthesis and anti-HBV evaluation of mono L-amino acid ester, mono non-steroid anti-inflammation drug carboxylic ester derivatives of acyclonucleoside phosphonates

A series of mono L-amino acid ester, mono non-steroid anti-inflammation drug （NSAID）, carboxylic ester derivatives of acyclonucleoside phosphonates were prepared by using a ＂one pot synthesis＂ method and their in vitro anti-HBV activity were evaluated in HepG 2.2.15 cells. Compound 9a exhibited more potent anti-HBV activity and lower cytotoxicity than those of adefovir dipivoxil with IC50 and selective index （SI） values of 0.48μmol/L and 763.72, respectively.

Tumor-Selective Cascade-Amplified Dual-Prodrugs Activation for Synergistic Oxidation-Chemotherapy

Efficacy of prodrugs in cancer therapy requires selective and efficient drug activation in cancer cells.Here,we report a novel dual-prodrug delivery system with tumor-selective cascade-amplified prodrug activation for synergistic oxidation-chemotherapy.Cancer cells overexpressing cathepsin B-activatable nearinfrared(NIR)hemicyanine prodrug(CyNH-Citval)were encapsulated by the reactive oxygen species(ROS)-responsive polyprodrug of doxorubicin(DOX)(PTK_(DOX))to obtain PTK_(DOX/Cy).Upon uptake of PTK_(DOX/Cy) by cancer cells and subsequent prodrug CyNH-Citval activation,NIR fluorescence was turned on and toxicity toward mitochondria was restored,thereby elevating intracellular ROS levels,which subsequently activated the polyprodrug PTK_(DOX) to initiate the cascade and amplify DOX.Overall,these results indicate that enzyme-mediated initiation of drug activation and amplification of cascade ROS ultimately causes selective and efficient prodrug activation in tumors with synergistic oxidation and chemotherapy.These findings provide new insights to inform precise cooperative cancer therapy.

A site-oriented nanosystem for active transcellular chemo-immunotherapy to prevent tumor growth and metastasis

Immunotherapy has shown promising potential in cancer therapy;however, poor delivery by nanocarriers and insufficient immune response in tumors have severely impeded its clinical application. To overcome these disadvantages, a site-specific and active transcellular drug delivery system was developed herein for chemotherapyenhanced immunotherapy. When arriving at the tumor site,the matrix metallopeptidase 2(MMP2)-responsive shell detached from the nanosystem, releasing positively charged cores. The cationic surface of the inner cores induced adsorption-meditated transcytosis, which facilitated transendothelial transportation and transcellular drug delivery into distal tumor cells. PD-L1 antibody and chemotherapeutic drugs were loaded in the outer layer and inner cores of the nanosystem, respectively, to be precisely delivered to target sites, thereby achieving synchronized delivery and siteoriented release of different anticancer agents. PD-L1 antibody released in the tumor microenvironment effectively blocked the binding of PD-L1 to its receptors on the T cell surface. Oxaliplatin and indoximod co-delivered in the cationic cores can induce immunogenic cell death and attenuate the immunosuppressive effect throughout the tumor tissues,recruiting a large amount of T cells and further enhancing the immunotherapy. The resulting synergistic antitumor response could not only efficiently inhibit the growth of primary tumors, but also help prevent metastasis of primary tumor to distant sites. This study offers a novel nano-enabled strategy for chemo-immunotherapy in immunosuppressive tumors.

Constructive strategies for drug delivery systems in antivirus disease therapy by biosafety materials

Due to the coronavirus disease 2019(COVID‐19)pandemic,the development of antiviral drugs has attracted increasing attention.Clinical antiviral drugs show weak solubility,low bioavailability,adverse side effects,or only limited targets.With the advancement of nanotechnology and material science,biosafety nanomaterials have been constructed for drug delivery systems of antiviral disease therapy,such as liposomes,polymers,gold nanoparticles,and graphene.These nanodrug systems can either deliver synthesized antiviral drugs siRNA/miRNA and small molecular compounds,deliver bioactive large molecular drug proteins and mRNA,or show antiviral activity by themselves.Nanodelivery systems could effectively enhance the efficiency of antiviral drugs by increasing drug loading and host cell uptake with a small size and high specific surface area.This review focused on the biosafety nanomaterials used for antiviral therapy and discussed the options for the design of antiviral drugs in the future.

Novel liver-specific nitric oxide(NO) releasing drugs with bile acid as both NO carrier and targeting ligand

Novel liver-specific nitric oxide（NO） releasing drugs with bile acid as both the NO carrier and targeting ligand were designed and synthesized by direct nitration of the hydroxyl group in bile acids or the 3-Ohydroxyl alkyl derivatives,with the intact 24-COOH being preserved for hepatocyte specific recognition.Preliminary biological evaluation revealed that oral administrated targeted conjugates could protect mice against acute liver damage induced by acetaminophen or carbon tetrachloride.The nitrate level in the liver significantly increased after oral administration of 1e while nitrate level in the blood did not significantly change.Co-administration of ursodeoxycholic acid（UDCA） significantly antagonized the increase of nitrate in the liver resulted by administration of 1e.

Antipsychotic drug research and resting-state brain activity in normal adults

In the field of functional MRI,compared to observations of task-related brain activity,a growing number of studies have shown that spontaneous brain activity during the resting state may be more sensitive to defects in the cognitive functions of our brain.

Enoxacin-loaded Poly(lactic-co-glycolic acid) Coating on Porous Magnesium Scaffold as a Drug Delivery System: Antibacterial Properties and Inhibition of Osteoclastic Bone Resorption

Implant-associated infection remains a difficult medical problem in orthopedic surgery. Therefore, the development of multifunctional bone implants for treating infection and regenerating lost bone tissue, which may be a result of infection, is important. In the present study, we report the fabrication of enoxacin- loaded poly （lactic-co-glycolic acid） （PLGA） coating on porous magnesium scaffold （Enox-PLGA-Mg） which combine the favorable properties of magnesium, the antibacterial property and the effect of inhibition of osteoclastic bone resorption of enoxacin. The drug loaded PLGA coating of Mg scaffold enables higher drug loading efficiency （52%-56%） than non-coating enoxacin loaded Mg scaffold （Enox-Mg） （4%-5%）. Enox- PLGA-Mg exhibits sustained drug release for more than 14 days, and this controlled release of enoxacin signifcantly inhibits bacterial adhesion and prevented biofilm formation by Staphylococcus epidermidis （ATCC35984） and Staphylococcus aureus （ATCC25923）. Biocompatibility tests with Balb/c mouse embryo fibroblasts （Balb/c 3T3 cells） indicate that PLGA-Mg has better biocompatibility than Mg. Finally, we also demonstrate that Enox-PLCA-Mg extract potently inhibited osteoclast formation in vitro. Therefore, Enox- PLCA-Mg has the potential to be used as a multifunctional controlled drug delivery system bone scaffolds to prevent and/or treat orthopedic peri-implant infections.

miR-202 contributes to sensitizing MM cells to drug significantly via activing JNK/SAPK signaling pathway

Objective To explore the role of miR-202 in multiple myeloma(MM)cells,and study the regulation of miR-202 on drug sensitivity of MM cells.Methods miR-202 and BAFF mRNA levels were detected by real-time PCR.U266 cells were transfected with miR-202-mimics,miR-202-inhibitor,siB AFF and their negative controls.