The neuroprotective effects of the anti-diabetic drug linagliptin against Aβ-induced neurotoxicity

Impaired insulin signaling in Alzheimer’s disease（AD）brains：The insulin signaling pathway is a fundamental physiological mechanism that presents in nearly all vertebrate cells.However,sometimes cells stop responding properly to insulin stimulation.This condition is known as insulin resistance,which is a hallmark of two very common conditions,metabolic syndrome and type 2 diabetes（T2D）.

Late Protective Effects of the Anticalmodulin Drug Fluphenazine on Carbon Tetrachloride-induced Liver Necrosis

Fluphenazine (FP) treatment (50mg/kg bw, ip in saline) 30 min before or 6 or 10 h after CCl4 administration (1 ml/kg ip in olive oil) significantly prevented the liver necrosis produced by the hepatotoxin at 24 h. FP had enhancing effects on the covalent binding of CCl4 reactive metabolites to cellular constituents and on CCl4 induced lipid peroaldation.FP lowered bOdy temperature of the CCl4-poisoned animals during the 24 h observation period. The obtained results are compatible but do not prove the hypothesis that calmodulin (CaM) had participation in late occurring events preceding necrosis. FP lowering action on body temperature, however, might also play a role in the effects of this drug on the onset of CCl4 induced liver necrosis. FP levels in liver tissue as determined by gas chromatography-mass spectrometry evidenced the presence of the drug in amounts suffi cient to inhibit CaM and that suggests that not all preventive effects of FP are due to its indirect actions on the central nervous system via decreased body temperature

Efficacy of Bee Products(Anzer Honey,Pollen and Propolis)in Detection and Healing of Damage Induced by Antidiabetic Drug Vildagliptin/Metformin Hydrochloride in Healthy Human Pancreatic Cells:Cytotoxic,Genotoxic and Biochemical Studies

Background and Objective Although drugs are powerful therapeutic agents,they have a range of side effects.These side effects are sometimes cellular and not clinically noticeable.Vildagliptin/metformin hydrochloride is one of the most widely used oral antidiabetic drugs with two active ingredients.In this study,we investigated its harmful effects on the metabolic activation system in healthy human pancreatic cells“hTERT-HPNE”,and we aimed to improve these harmful effects by natural products.To benefit from the healing effect,we used the unique natural products produced by the bees of the Anzer Plateau in the Eastern Black Sea Region of Turkey.Methods Cytotoxic and genotoxic effects of the drug were investigated by different tests,such as MTT,flow cytometry-apoptosis and comet assays.Anzer honey,pollen and propolis were analyzed by gas chromatography/mass spectrometry(G/C-MS).A total of 19 compounds were detected,constituting 99.9%of the samples.Results The decrease in cell viability at all drug concentrations was statistically significant compared to the negative control(P<0.05).A statistically significant decrease was detected in the apoptosis caused by vildagliptin/metformin hydrochloride with the supplementation of Anzer honey,pollen and propolis in hTERT-HPNE cells(P<0.05).Conclusion This study can contribute to other studies testing the healing properties of natural products against the side effects of oral antidiabetics in human cells.In particular,Anzer honey,pollen and propolis can be used as additional foods to maintain cell viability and improve heal damage and can be evaluated against side effects in other drug studies.

Effects of “Caulis Sargentodoxae Formula” on Experimental Endometriosis in Rat

Objective To study the drug effects of ＂Caulis Sargentodoxae Formula＂ which dears away heat and blood clot on experimental endometriosis in rat, and to compare this effect with Danazol＇s effects. Method The model of endometriosis rat was induced by transplanting with endometrium surgically The rats were divided into 6 groups randomly： the non-treatment group, the castrate group, Danazol group（80 mg/kg）, ＂Caulis Sargentodoxae Formula＂ group （110 g/kg）, the medium dose group（77.5 g/kg） and the low dose group（55 g/kg）. After 3 weeks＇ treatment, the volume ofendometrium was detected by cutting the rats＇ belly open, drawing the materials from endometrium for tissue section, and doing the quantity analysis of endometrium by semiautomatic image analysis machine.Results There was no significant difference of the endometrium volumes between the low dose group and the non-treatment group（P〉O.05）, other groups＇ endometrium volumes were significantly lower than those of the non-treatment group（P〈0. 05）. And apart from the low dose group, all other groups＇ heights of the endometrium epithelia were significantly lower than that of the non-treatment group（p〈0.01）. Conclusion ＂Caulis Sargentodoxae Formula＂ can refrain the growth of the endometrium, and the effects are better than that of Danazol＇s.

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.

PREDICTION OF THE THERAPEUTIC EFFECTIVENESS OF NEW DRUGS FROM CLINICAL PHARMACOLOGY STUDIES

The development of new drugs for therapeutic purposes has become very expensive and time-consuming in American and European countries.It is estimated that on the average 50 to 100 million dollars and 10 or more years from the time of patenting are required to make a new drug available for general prescription. Every new drug needs to be charac-

Analysis on Therapeutic Effect of Western and Chinese Drug in Treating Intrahepatic Cholestasis of Pregnancy

Objective: To evaluate the therapeutic effect of Yinchenghao decoction (YCHD, 茵陈蒿汤) and S-adenosy-L-methionine (SAM) in treating intra-hepatic cholestasis of pregnancy (TCP) and improving prognosis of perinatal newborn babies. Methods: Sixty in-patients of TCP were randomly divided into two groups, the group A treated with YCHD and the group B treated with SAM. The symptom of itching and serum biochemical indexes, including glycocholic acid, bilirubin and transaminase, were observed after 3 weeks treat-ment, and the prognosis of perinatal newborn babies between the two groups was compared after delivery. Results: After treatment, the symptom of itching, serum levels of glycocholic acid, bilirubin and transaminase improved significantly (P< 0.05) in both groups, and the prognosis of newborn in the two groups was similar (P>0. 05). Conclusion: Both YCHD and SAM could effectively treat ICP. The former is rather cheaper, so it is more feasible for spreading.Original article on CJITWM (Chin) 2004 ;24(4): 309

Improvement of lenvatinib-induced nephrotic syndrome after adaptation to sorafenib in thyroid cancer:A case report

BACKGROUND Target therapy is licensed by United States Food and Drug Administration on certain cancers.Both sorafenib and lenvatinib are tyrosine kinase inhibitor and indicated on radioactive iodine(RAI)-refractory differentiated thyroid cancer(DTC).Lenvatinib is more effective in cancers'control than sorafenib,but causes more nephrotoxicity than sorafenib does.This case is the second published case about the serial adaptions from lenvatinib to sorafenib for improving the proteinuria and,meanwhile,achieving the therapeutic goal.CASE SUMMARY A 56-year-old man suffered from bilateral edematous lower extremities after 1-mo prescription of lenvatinib of 20 mg/d for RAI-refractory DTC.Aside from this symptom,he also developed hypertension.His laboratory showed grade-3 proteinuria(estimated 24-h urine protein:9993 mg),hypoalbuminemia and hypercholesterolemia.Anti-vascular endothelial growth factor(VEGF)therapyinduced nephrotic syndrome was impressed.After reduced dosage of lenvatinib of 10 mg/d and related symptomatic drugs,limited improvement was observed in both adverse effects and caner control.Under this condition,we substituted sorafenib of 400 mg/d for lenvatinib of 10 mg/d.After a 5-mo prescription,not only hypertension and peripheral edema were greatly improved,but also proteinuria was improved from grade three to grade one(estimated 24-h urine protein:962 mg).At the same time the cancer control was achieved,judged from computed tomography and laboratory evidence[thyroglobulin(Tg)before prescription of sorafenib:354.7 ng/m L;Tg after prescription of sorafenib:108.9 ng/m L].CONCLUSION Adaption from lenvatinib to sorafenib is a feasible method to improve the antiVEGF therapy-induced nephrotic syndrome and achieve the therapeutic goal at the same time.

Current cancer therapies and their influence on glucose control

This review focuses on the development of hyperglycemia arising from widely used cancer therapies spanning four drug classes.These groups of medications were selected due to their significant association with new onset hyperglycemia,or of potentially severe clinical consequences when present.These classes include glucocorticoids that are frequently used in addition to chemotherapy treatments,and the antimetabolite class of 5-fluorouracil-related drugs.Both of these classes have been in use in cancer therapy since the 1950s.Also considered are the phosphatidyl inositol-3-kinase(PI3K)/AKT/mammalian target of rapamycin(mTOR)-inhibitors that provide cancer response advantages by disrupting cell growth,proliferation and survival signaling pathways,and have been in clinical use as early as 2007.The final class to be reviewed are the monoclonal antibodies selected to function as immune checkpoint inhibitors(ICIs).These were first used in 2011 for advanced melanoma and are rapidly becoming widely utilized in many solid tumors.For each drug class,the literature has been reviewed to answer relevant questions about these medications related specifically to the characteristics of the hyperglycemia that develops with use.The incidence of new glucose elevations in euglycemic individuals,as well as glycemic changes in those with established diabetes has been considered,as has the expected onset of hyperglycemia from their first use.This comparison emphasizes that some classes exhibit very immediate impacts on glucose levels,whereas other classes can have lengthy delays of up to 1 year.A comparison of the spectrum of severity of hyperglycemic consequences stresses that the appearance of diabetic ketoacidosis is rare for all classes except for the ICIs.There are distinct differences in the reversibility of glucose elevations after treatment is stopped,as the mTOR inhibitors and ICI classes have persistent hyperglycemia long term.These four highlighted drug categories differ in their underlying mechanisms driving hyperglycemia,with clinical presentations ranging from potent yet transient insulin resistant states[type 2 diabetes mellitus(T2DM)-like]to rare permanent insulin-deficient causes of hyperglycemia.Knowledge of the relative incidence of new onset hyperglycemia and the underlying causes are critical to appreciate how and when to best screen and treat patients taking any of these cancer drug therapies.

Intellectual Property Protection and High Quality Development of Radix Glycyrrhizae for Treatment of COVID-19

Radix Glycyrrhizae is the dominant native medicinal material variety in the north and northwestern medicinal materials producing areas.It is a main Chinese medicine of effective TCM drugs and formulas for the treatment of new coronavirus disease(COVID-19).This paper introduces the medicinal value of Radix Glycyrrhizae,involving the labeling,cultural heritage,and creative intellectual property rights of the Chinese medicinal materials,analyzes the poverty-stricken areas that are ecologically suitable for Radix Glycyrrhizae cultivation,and the superior counties and production bases of the Chinese medicinal materials.Besides,mainly from the aspects of perfect intellectual property rights,the establishment of authentic medicinal material production bases,and the construction of quality control systems,etc.,it discusses the rural revitalization strategy and the development strategy of traditional Chinese medicine(TCM),agricultural intellectual property protection and high-quality development strategy of Radix Glycyrrhizae.

FIRST STEP VIEW OF THE EFFICACY OF ANTINEOPLASTIC AGENTS

A human K562 leukaemia call and acute adult leudaemia patient samples have been used to test the efficacy of antineoplastic agents with MTT assay.All 18 drugs were invoved.According to the purpose of experiment these durgs were applied at different opportunities or combinations.The drug efficacy has been observed and summarized as four different conditions:1.the change of the time(△ T )closely related with drug effacacy, during the duration the change of drug concentration(△ C) at certain extent has almost no influence; 2the △ C closely related with the efficacy, the △ T has no influence;3. The △ C and △ T effect the results together;and 4.the △ C and △ T effect not the result. And then draw a conclution that the process or drug effacacy has a multiple function with flat distrtct.

Comparison of Secnidazole and Fenbendazole for the Treatment of Asymptomatic Giardia Infection in Dogs

The objetive of this study was to compare a single dose of secnidazole versus multiple doses of fenbendazole for the treatment of dogs with asymptomatic Giardia infection.Materials and methods:Twenty-four asymptomatic dogs with a positive test result for Giardia spp were randomized in two equal groups to receive a single dose of secnidazole at 30 mg/kg PO,or fenbendazole at 50 mg/kg PO q24h for 3 days.Hematological parameters were evaluated before and 8 days after treatment,and feces were re-examined at days 8,15,and 30 post-treatment by fecal flotation and antigen test.Results:The number of positive dogs in the fenbendazole group was:1(day 8)and 3(days 15 and 30).In the secnidazole group,the number of positive cases were:4(day 8),3(day 15),and 1(day 30).Conclusion:Treatment with secnidazole or fenbendazole,were effective between 75%and 92%to eliminate the excretion of Giardia cysts in canines together with hygienic measures to control,like disinfection with quaternary ammonium of patients and their environment.Further studies that include more animals and multiple fecal exams on consecutive days would be necessary to confirm its efficacy in dogs.

Dexmedetomidine May Produce Extra Protective Effects on Sepsis-induced Diaphragm Injury

Objective：The objective was to evaluate the protective effects ofdexmedetomidine （DEX）,a selective agonist of α2-adrenergic receptor,on sepsis-induced diaphragm injury and the underlying molecular mechanisms.Data Sources：The data used in this review were mainly from PubMed articles published in English from 1990 to 2015.Study Selection：Clinical or basic research articles were selected mainly according to their level of relevance to this topic.Results：Sepsis could induce severe diaphragm dysfunction and exacerbate respiratory weakness.The mechanism of sepsis-induced diaphragm injury includes the increased inflammatory cytokines and excessive oxidative stress and superfluous production of nitric oxide （NO）.DEX can reduce inflammatory cytokines,inhibit nuclear factor-kappaB signaling pathways,suppress the activation of caspase-3,furthermore decrease oxidative stress and inhibit NO synthase.On the basis of these mechanisms,DEX may result in a shorter period of mechanical ventilation in septic patients in clinical practice.Conclusions：Based on this current available evidence,DEX may produce extra protective effects on sepsis-induced diaphragm injury.Further direct evidence and more specific studies are still required to confirm these beneficial effects.

Growth inhibiting effects of terazosin on androgen-independent prostate cancer cell lines

Objective To study the effects of an α1-adrenoceptor antagonist, terazosin on the androgen-independent prostate cancer cell lines PC-3 and DU145.Methods Two androgen independent cell lines, PC-3 and DU145, were used to determine cell viability, colony-forming ability, as well as cell cycle distribution, after exposure to terazosin. Western blot analysis was used to determine the expression of p21 WAF1 and p27KIP1.Results This study shows that terazosin inhibits not only prostate cancer cell growth but also its colony forming ability, both of which are main targets of clinical treatment. In addition, terazosin is shown to inhibit cell growth through G1 phase cell cycle arrest and the up-regulation of p27KIP1.Conclusion This study provides evidence that the α1-adrenoceptor antagonist terazosin may have therapeutic potential in the treatment of advanced hormone refractory prostate cancer.

EFFECT OF ANTIHYDATID DRUGS ON CARBOHYDRATE METABOLISM OF METACESTODE OF ECHINOCOCCUS GRANULOSUS

A biochemical some enzymes of glycolysis and a partial reversed tricarboxylic acid cycle together with hydrolytic enzymes in the cyst wall of Echinococcus granulosus was carried out. Lactate dehydrogenase (LDH), pyruvate kinase (PK), phosphoenolpyruvate carboxykinase (PEPCK), and adenosine triphosphatase (ATPase) showed their high level of activity, suggesting that the proliferation of E. granulosus cyst wall is an energy-dependent process and the major pathways for glucose metabolism is glycolysis. Treatment of E. granulosus-in-fected mice with mebendazole and albendazole resulted in marked inhibition of PK, PEPCK and ATPase of E. granulosus cyst wall, whereas praziquantel had no effect, indicating that PK, PEPCK, and ATPase might be chemotherapeutic targets and the differences in the inhibitory effects might account for the efficacy of the three antihydatid drugs.

Redox-responsive polymer prodrug/AgNPs hybrid nanoparticles for drug delivery

A drug carrier system of the hybrid nanoparticles based on the redox-responsive P[（2-（（2-（（camptothecin）-oxy）ethyl）disulfanyl）ethylmethacrylate）-co-（2-（D-galactose）methylmethacryl-ate）]（P（MACPTS-co-MAGP）） and AgNPs is developed to deliver the anti-cancer drug camptothecin（CPT） and monitor the drug release by the recovery of the fluorescence of CPT. CPT is linked to the polymer sidechains via a redox-responsive disulfide bond, attaching on the surface of AgNPs and leading to the quenching of CPT fluorescence（ ＂off＂ state） due to the nanoparticle surface energy transfer（NSET） effect.Upon the exposure to glutathione（GSH）, the disulfide bond is cleaved to release CPT, resulting in the recovery of the fluorescence of CPT（＂on＂ state）. The system offers a platform to track the CPT delivery and releasing in real time

The effect of drug position on the properties of paclitaxel-conjugated gold nanoparticles for liver tumor treatment

Structure-efficacy effect of small molecular drug attracts wide attentions,but it has always been ignored in nanomedicine research.To reveal the efficacy modulation of nanomedicine,we developed a new type of paclitaxel(PTX)-conjugated gold nanoparticles(PTX-co njugated GNPs)to investigate the influence of drug position in controlling their in vitro properties and in vivo performance.Two therapeutic ligands(TA-PEG-NH-N=PTX and TA-PTX=N-NH-PEG)were synthesized to conjugate PTX on the surface of GNPs at different positions,locating on the surface of gold conjugate and inserting between GNPs and polyethylene glycol(PEG,molecular weight 1000 Da),respectively.It was found that PEG-PTX@GNPs with PTX located between GNP and PEG exhibited higher aqueous solubility,biocompatibility,and stability.In addition,an acid sensitive hydrazone bond has been inserted between PTX and PEG in both ligands for drug release of PTX and PTX-PEG segment,respectively,at the tumor site.Further release of PTX from PTX-PEG segment is based on the esterase hydrolysis of an ester bond between PTX and PEG.This two-step drug release mechanism offers PEG-PTX@GNPs effective and sustained release behavior for desirable anticancer activity,enhanced therapeutic efficacy,and lower systematic toxicity in Hepsbearing animal models.

Batroxobin reduces intracellular calcium concentration and inhibits proliferation of vascular smooth muscle cells

Background Batroxobin (BX),a serine protease used in defibrinogenation and thrombolysis,also has an effect on c-fos gene and growth factor. This study attempted to determine the effects of BX on the proliferation of vascular smooth muscle cells (VSMCs) and calcium metabolism. Methods VSMCs were treated with BX at concentrations of 0.1,0.3,or 1.0 mmol/L and cell numbers were determined at 0,24,48,and 72 hours. Intracellular calcium concentration ([Ca 2+ ]_i) was measured using direct fluorescence methods. Results BX was found to suppress proliferation of VSMCs in a dose-dependent fashion with inhibition rates of 18% and 31% by 48 and 72 hours,respectively. In addition,BX decreases basal [Ca 2+ ]_i significantly. The basal level in untreated cells was 162.7±33.8 nmol/L,and decreased to 131.5±27.7 nmol/L,128.3±28.5 nmol/L,and 125.6±34.3 nmol/L with the three concentrations of BX,respectively. Noradrenaline (NE)-induced [Ca 2+ ]_i stimulation was also attenuated by BX (0.1 mmol/L BX,20%±8% inhibition; 0.3 mmol/L BX,54%±11% inhibition; 1.0 mmol/L BX,62%±15% inhibition). The ability of NE to stimulate [Ca 2+ ]_i was attenuated in cultures in Ca 2+ -free medium,as was the ability of BX to blunt NE-induced stimulation. Conclusion These findings demonstrate that BX can effectively inhibit proliferation of VSMCs,probably by blocking the release and uptake of Ca 2+ ,thus influencing [Ca 2+ ]_i.

Recommendations on the Clinical Use of Compound Danshen Dripping Pills

Currently in China, about 290 million people have cardiovascular disease （CVD）. Cardiovascular-relevant morbidity and mortality in Chinese population rose quickly, and increasing nunlber of the patients has brought about a serious health problem to the society. CVD has become the leading cause of death in China, and among the overall mortality, two in every five patients have CVD. Fortunately,