Background:Polymethoxylatedflavones(PMFs)are compounds present in citrus peels and other Rutaceae plants,which exhibit diverse biological activities,including robust antitumor and antioxidant effects.However,the mechan...Background:Polymethoxylatedflavones(PMFs)are compounds present in citrus peels and other Rutaceae plants,which exhibit diverse biological activities,including robust antitumor and antioxidant effects.However,the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown.In the present study,we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs.Methods:MTT Cell viability assay and colony formation assay were used to investigate the effect of PMFs combined with PTX in reversing HCT8/T cell resistance ex vivo;the mRNA and protein levels of the target were detected by SDS-PAGE(sodium dodecyl sulfate-polyacrylamide gel electrophoresis),quantitative real-timefluorescence polymerase chain reaction(qRT-PCR)and Western blot protein immunoblotting(WB);An HCT8/T cell xenograft model was established to investigate the MDR reversal activity of PMFs in vivo;The extracellular acidification rate(ECAR)and the oxygen consumption rate(OCR)were detected to assess the cellular oxygen consumption rate and glycolytic process.Results:HCT8/T cells demonstrated significant resistance to PTX,up-regulating the expression levels of ABCB1 mRNA,P-gp,LC3-I,and LC3-II protein,and increasing intracellular reactive oxygen species(ROS)content.PMFs mainly contain two active ingredients,nobiletin,and tangeretin,which were able to reverse drug resistance in HCT8/T cells in a concentration-dependent manner.PMFs exhibited high tolerance in the HCT8/T nude mouse model while increasing the sensitivity of PTX-resistant cells and suppressing tumor growth significantly.PMFs combined with PTX reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)in HCT8/T cells.Additionally,PMFs reduced intracellular ROS content,down-regulated the expression levels of autophagy-related proteins LC3-I,LC3-II,Beclin1,and ATG7,and significantly reduced the number of autophagosomes in HCT8/T cells.Conclusions:The present study demonstrated that PMFs could potentially reverse PTX resistance in colon cancer by regulating the aerobic glycolysis-ROS-autophagy signaling axis,which indicated that PMFs would be potential potentiators for future chemotherapeutic agents in colon cancer.展开更多
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 respondi...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).展开更多
Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as wel...Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR,ERK,MEK phosphorylation and tumor stemness marker gene expression.Results:LR004-VC-MMAE with a DAR of 4.02 were obtained.The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells(P<0.01).LR004-VC-MMAE inhibited the proliferation of EGFRpositive TNBC cells,and the ICvalues of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were(0.13±0.02)nmol/L and(0.66±0.06)nmol/L,respectively,which were significantly lower than that of cells treated with MMAE[(3.20±0.60)nmol/L,P<0.01,and(6.60±0.50)nmol/L,P<0.001].LR004-VC-MMAE effectively inhibited migration and invasion of MDA-MB-468 and MDA-MB-231 cells.Moreover,LR004-VC-MMAE also killed tumor stem cells in EGFR-positive TNBC cells and impaired their tumorsphere-forming ability.In TNBC xenograft models,LR004-VC-MMAE at 10 mg/kg significantly suppressed tumor growth and achieved complete tumor regression on day 36.Surprisingly,tumor recurrence was not observed until the end of the experiment on day 52.In a mechanistic study,we found that LR004-VC-MMAE significantly induced cell apoptosis and cell cycle arrest at G/M phase in MDAMB-468[(34±5)%vs.(12±2)%,P<0.001]and MDA-MB-231[(27±4)%vs.(18±3)%,P<0.01]cells.LR004-VC-MMAE also inhibited the activation of EGFR signaling and the expression of cancer stemness marker genes such as Oct4,Sox2,KLF4 and EpCAM.Conclusions:LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes.It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC.展开更多
Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical f...Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery.These orphan excipients could enhance formulatability of highly lipophilic compounds.Additionally,they are safe in preclinical species when used below the LD50 values.However,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix effects.Excipients invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of exposures.Thus,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited.Furthermore,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport proteins.Although it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results.In this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.展开更多
There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system(RAS) inhibitors and s...There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system(RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials(RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios(HR) regarding the treatment effects of these drugs for cardiovascular disease(CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions.展开更多
The paper was to explore the preventive effects of five drugs on mycoplasma pneumonia of swine (MPS) and to provide reference for clinical medication of pig farms in Hainan Province. A total of 444 health piglets we...The paper was to explore the preventive effects of five drugs on mycoplasma pneumonia of swine (MPS) and to provide reference for clinical medication of pig farms in Hainan Province. A total of 444 health piglets were randomly divided into 6 groups, including five medication groups (72 piglets in group A, 74 pig- lets in group B, 72 piglets in group C, 76 piglets in group D, 76 piglets in group E) and one control group (74 piglets). The piglets in experimental groups were treated drugs once a day for successive 5 days at 30, 60, 90, 120 and 150 of age. The piglets in control group were free of medication. At 70 and 140 days of age, 15 piglets of each group were randomly selected to collect their blood sermn. The Mycoplasma hyopneumoniae (M-Hyo) antibodies in serum were measured by en- zyme-linked immunosorbent assay (ELISA). During the experiment, the incidence rates of respiratory disease, lung lesion, feed conversion rate, average daily gain (ADG), and mortality rate of pigs were also observed and recorded. The results showed that the five drugs had significant difference in preventative effects. Group C (Zhiyuanjing group) received the best preventive effect and the highest economic benefits. Compared with control group, the ADG and feed conversion rate in group C were increased by 7.53% and 9.09%, respectively; the incidence rate of respiratory disease was reduced by 13.44% and lung lesion was alleviated by 81.43% ; and the earnings of each pig could rise by 132.70 yuan. The preventative effect and economic benefit of the drugs was sequenced by Chansu Kechuanling and Bingchan Kechuanwang. Wante Feilin and amoxicillin had weaker preventive effects against MPS but greatly influenced growth performance of pigs, so they should be used alternatively with other drugs.展开更多
In the twenty first century research works, there may be a need to achieve a more reliable research result through a synergy between engineers and biological researchers. The peak absorbance data for various interacti...In the twenty first century research works, there may be a need to achieve a more reliable research result through a synergy between engineers and biological researchers. The peak absorbance data for various interacting systems were measured. These were used to show that the antiretroviral drug has the effect of increasing the peak absorbance values of both the uninfected and infected blood components, i.e., the drugs are made able to increase the light absorption capacity of the blood cells. For drug 2 that contains three components including Efavirenz, the drug effect on lymphocytes was increased by about 38% for patients that had been on antiretroviral drug treatment. Mathematical models were proposed and used in determining the coating effectiveness of antiretroviral drugs in the presence and absence of HIV. The use of the findings of this work by pharmaceutical industries may help in the search for more effective antiretroviral drugs for the treatment of HIV patients.展开更多
Ciprofloxacin (CFX) was loaded on Bana clay (Cameroon) and CFX loaded-clays have been evaluated as drug delivery system. Raw clays and CFX loaded compounds have been characterized by some physico-chemicals methods. &l...Ciprofloxacin (CFX) was loaded on Bana clay (Cameroon) and CFX loaded-clays have been evaluated as drug delivery system. Raw clays and CFX loaded compounds have been characterized by some physico-chemicals methods. <i>In vitro</i> release studies have been done in gastric and phosphate buffer experimental mediums;bacteriological studies have been made up on <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>. X-ray diffractometry patterns of loaded compounds show a basal spacing increasing due to CFX intercalation. On Fourier-Transformed Infrared spectrometry spectra, appearance of CFX characteristic bands and shifting of certain bands already presents on clay confirmed CFX intercalation. After 96 h of CFX released from release mediums, prolonged and continue profiles have been observed. Diffusion tests displayed an inhibition radius of ~2 cm on gelose seeded with <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> due to CFX. The overall results show a modified release of ciprofloxacin with an effective antibacterial activity, giving the way for a new ciprofloxacin drug delivery system using Bana clay as carrier.展开更多
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 ...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展开更多
Background:To study the energy pharmacological effects of chemical drugs.Methods:The energy pharmacological effects of chemical drugs were studied using a literature induction method.Results:Chemical drugs have energy...Background:To study the energy pharmacological effects of chemical drugs.Methods:The energy pharmacological effects of chemical drugs were studied using a literature induction method.Results:Chemical drugs have energy properties,which can be expressed in terms of cold,hot,warm,and cool.The energy properties of chemical drugs have energy pharmacological effects,which are related to the bond energy release and absorption of intermolecular chemical bonds,where the release of energy from chemical bonds indicates a warm-hot energy pharmacological effect and the absorption of energy indicates a cold energy pharmacological effect.The mechanisms of chemical drug energy may be related to the presence of temperature-sensitive ion channels in the body.Conclusion:Chemical drugs exhibit energy pharmacological effects.展开更多
Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly ...Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly assigned to five drug treatment regimens. Results: Combination therapy with doxycycline, rifampin and sulfamethoxazole for 56 consecutive days showed the highest cure rate of 20% after a single course and of 85% after a double course with affectivity rates of 55% and 95%. Cure rate and affectivity rate was significant better (P 0.05) than for patients receiving doxycycline, rifampin and streptomycin for the same period and regimens containing doxycycline were significant better than regimens without this drug. Conclusion: Combination therapy of doxycycline, rifampin and sulfamethoxazole for 8 weeks using one or two full courses should be recommended for Brucella spondylitis.展开更多
AIM To observe the effect of octreotide (OT) and somatostatin (SS) on gallbladder pressure and myoelectric activity of SO in rabbits. METHODS Male rabbits fasted for 15h - 18h and anesthetized with urethane. ...AIM To observe the effect of octreotide (OT) and somatostatin (SS) on gallbladder pressure and myoelectric activity of SO in rabbits. METHODS Male rabbits fasted for 15h - 18h and anesthetized with urethane. The mean gallbladder pressure (GP) and myoelectric activity of SO were simultaneously measured with a frog bladder connected to a transducer and a pair of copper electrodes. RESULTS After injection of OT (10μg/kg, iv), the GP decreased in 2min and reached the lowest value in about 60min ( P <0 01, n =19), and completely or partially returned to the normal level in 120min. The frequency of myoelectric activity of SO was reduced, even disappeared in 2min ( P <0 01, n =19) and returned to normal in about 20min . Injection of SS (10μg/kg, iv) also decreased GP and myoelectric activity of SO ( P <0 01, n =7); Before and after injection of OT or SS, injection of CCK 8 ( 100ng or 200ng ) caused similar increase in myoelectric activity of SO and GP ( P >0 05). Before and after injection of OT, there were no significant differences in increases of myoelectric activity of SO and GP caused by electric stimulation of dorsal motor nucleus of vagus ( P >0 05). CONCLUSION OT and SS decreased GP and myoelectric activity of SO, demonstrating that effects of OT were similar to those of SS. Intravenous injection of OT did not affect the increase of myoelectric activity of SO and GP caused by CCK 8 or electric stimulation of dorsal motor nucleus of vagus.展开更多
Objective:To evaluate the efficacy and side effects of praziquantel(PZQ) in the treatment of schistosomiasis in Ethiopia.Methods:In a cross-sectional study,stool specimens were collected from randomly selected 299 sch...Objective:To evaluate the efficacy and side effects of praziquantel(PZQ) in the treatment of schistosomiasis in Ethiopia.Methods:In a cross-sectional study,stool specimens were collected from randomly selected 299 school children in Shesha Kekele Elementary School,Wondo Genet, Southern Ethiopia,in April 2010.Stool specimens were examined using a single Kato-Katz thick smear for Schistosoma mansoni(5.mansoni) ova.Children who were found positive for S.mansoni were treated with a single oral dose of PZQ at 40 mg/kg bw and interviewed for treatment-related symptoms 24 hours after drug administration.Four weeks post-treatment,stool specimens were collected from the same children and examined following the same procedure as in the pretreatment.Drug efficacy was determined based on cure and egg reduction rates.Results:Pretreatment prevalence of S.mansoni infection was 74.9%with geometric mean egg count of 268. The evaluated generic PZQ produced an overall cure rate of 73.6%(P<0.000 1,OR:8.33,CI:5.3-13.1) and egg reduction rate of 68.2%(P=0.03,F=0.64).The cure rate showed significant association with age(x^2=H,P=0.004),the highest rate being observed in the 15-22 age group.83%of S. mansoni infected children showed various treatment-related symptoms,the most frerjiient being headache,nausea,and abdominal pain.These symptoms were associated with age(P<0.001) and pre-treatment intensity of infection(P<0.05).Conclusions:The present observations revealed relatively lower cure and egg reduction rates of the PZQ evaluated as compared to previous reports for other PZQ brands in Ethiopia.Hence,in depth studies are recommended to clarify whether the present relatively lower cure rate is the actual cure rate of the praziquantel evaluated,treatment failure,or reduced susceptibility of the parasite.Treatment-related side effects observed were transient and tolerable.展开更多
Background: Stroke is a worldwide health problem, the world’s second-leading cause of death and third-leading cause of disability. Currently, the majority of stroke patients are ischemic stroke patients. It is necess...Background: Stroke is a worldwide health problem, the world’s second-leading cause of death and third-leading cause of disability. Currently, the majority of stroke patients are ischemic stroke patients. It is necessary to evaluate risk factors to prevent ischemic stroke. Data and Methods: The risk factors for stroke in the previous fiscal year were analyzed. They were divided into nonmodifiable and modifiable factors. The probit and ordered probit models were used in the study, with 59341 and 50542 observations used in the estimation of the models, respectively. Results: Among the nonmodifiable factors, age, gender and cerebrovascular disease history are important risk factors. The history of cerebrovascular diseases is considered to be an especially important factor. Among the modifiable factors, taking antihypertensive drugs and recent large weight change are negative risk factors;however, sleeping well significantly reduces the probability of ischemic stroke. Conclusion: It is very important to ensure that medical personnel know a patient’s history of cerebrovascular diseases for proper treatments. Ischemic stroke might be considered an important side effect of antihypertensive drugs. Limitations: The dataset was observatory. There are various types of antihypertension drugs, and their effects are not analyzed.展开更多
Parkinson’s disease(PD),a neurodegenerative disease that shows a high incidence in older individuals,is becoming increasingly prevalent.Unfortunately,there is no clinical cure for PD,and novel anti-PD drugs are there...Parkinson’s disease(PD),a neurodegenerative disease that shows a high incidence in older individuals,is becoming increasingly prevalent.Unfortunately,there is no clinical cure for PD,and novel anti-PD drugs are therefore urgently required.However,the selective permeability of the blood–brain barrier(BBB)poses a huge challenge in the development of such drugs.Fortunately,through strategies based on the physiological characteristics of the BBB and other modifications,including enhancement of BBB permeability,nanotechnology can offer a solution to this problem and facilitate drug delivery across the BBB.Although nanomaterials are often used as carriers for PD treatment,their biological activity is ignored.Several studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio effects.In this review,we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD treatment.Subsequently,we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological effects.Finally,we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this field.Our review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.展开更多
Side-effects associated with the cancer chemotherapy limit the scope of chemotherapeutic drugs and no data was available about these side effects in Pakistan. Moreover starvation based differential chemotherapy has be...Side-effects associated with the cancer chemotherapy limit the scope of chemotherapeutic drugs and no data was available about these side effects in Pakistan. Moreover starvation based differential chemotherapy has been proved to greatly reduce the side effects of chemotherapy depending on starvation time. The current study was conducted to survey the common side effects of the chemotherapeutic drugs and the role of starvation to reduce them. The study included total 100 subjects with multiple carcinomas. A comprehensive questionnaire about starvation inquiry, chemotherapy side effects and their basic information was filled by interviewers as told by patients. There were 48% patients with breast cancer and 11% with uterine cancer. Out of these patients 30%, 28%, 9% and 9% patients were agreed to starve for 12, 24, 36 and 48 hours respectively. The survey regarding the side effects of chemotherapy showed that 43% patients were suffering from headache, fatigue 90%, weakness 95%, hair loss 76%, nausea 77%, vomiting 75%, diarrhea 31%, abdominal cramps 40%, mouth sores 47%, dry mouth 74%, memory impairment 14%?and numbness 49%. Breast cancer is the most common cancer in Pakistan. Only 18% of the total patients were agreed to starve for more than one day. Chemotherapy-associated side effects vary greatly and it does not depend upon cancer type. But these side effects depend on multiple factors such as the type and dose of chemotherapeutic drug, patient’s health status and stage of cancer.展开更多
This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 ...This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 Tibetan veterinary drugs, Veronica ciliate Fisch, Usnea diffracta Vain, Sophoraflavescens var. flavescens, Lamiophlomis rotata ( Benth. ) Kudo on 14 common diarrheagenic bacteria were detected by K-B diffusion method and micro-broth dilution method. Optimization was performed on prescriptions of the 4 Tibetan veterinary drugs using orthogonal design software, and a mouse bacterial diarrhea model was established with a clinical isolate, Salmonella blegdam. According to the LD50 value of the optimal prescription of the 4 Tibetan veterinary drugs, the established mouse bacterial diarrhea model was treated in 3 dose groups, i. e. , the high, middle and low dose groups (0. 060, 0. 030 and 0. 020 g/ml, respectively). The results showed that the 4 Tibetan veterinary drugs had very good inhibitory effects on most of the tested diarrheagenic bacteria, and among them, U. diffracta had better inhibitory effects on all the tested bacteria. The optimal prescription of the d Tibetan veterinary drugs (high dose, 0.06 g/ml) exhibited very good inhibitory effect on mouse diarrhea, indicating that the prescription has very good anti-diarrhea effect, which is beneficial to the clinical treatment of such disease and the development of Tibetan veterinary drugs.展开更多
Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs...Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.展开更多
基金supported by National Natural Science Foundation of China(82104446)Guangdong Basic and Applied Basic Research Foundation(2023A1515011961)+3 种基金Guangdong Province Characteristic Innovation Project of Universities(2022KTSCX100)Guangzhou University(College)-(High Level University/Deng feng Hospital)Basic and Applied Basic Research Project(2023A03J0397)Guangdong Medical Science and Technology Research Foundation(A2023460)Plan on Enhancing Scientific Research in GMU(2024SRP117).
文摘Background:Polymethoxylatedflavones(PMFs)are compounds present in citrus peels and other Rutaceae plants,which exhibit diverse biological activities,including robust antitumor and antioxidant effects.However,the mechanism of PMFs in reversing drug resistance to colon cancer remains unknown.In the present study,we aimed to investigate the potential connection between the aerobic glycolysis-ROS-autophagy signaling axis and the reversal of PTX resistance in colon cancer by PMFs.Methods:MTT Cell viability assay and colony formation assay were used to investigate the effect of PMFs combined with PTX in reversing HCT8/T cell resistance ex vivo;the mRNA and protein levels of the target were detected by SDS-PAGE(sodium dodecyl sulfate-polyacrylamide gel electrophoresis),quantitative real-timefluorescence polymerase chain reaction(qRT-PCR)and Western blot protein immunoblotting(WB);An HCT8/T cell xenograft model was established to investigate the MDR reversal activity of PMFs in vivo;The extracellular acidification rate(ECAR)and the oxygen consumption rate(OCR)were detected to assess the cellular oxygen consumption rate and glycolytic process.Results:HCT8/T cells demonstrated significant resistance to PTX,up-regulating the expression levels of ABCB1 mRNA,P-gp,LC3-I,and LC3-II protein,and increasing intracellular reactive oxygen species(ROS)content.PMFs mainly contain two active ingredients,nobiletin,and tangeretin,which were able to reverse drug resistance in HCT8/T cells in a concentration-dependent manner.PMFs exhibited high tolerance in the HCT8/T nude mouse model while increasing the sensitivity of PTX-resistant cells and suppressing tumor growth significantly.PMFs combined with PTX reduced extracellular acidification rate(ECAR)and oxygen consumption rate(OCR)in HCT8/T cells.Additionally,PMFs reduced intracellular ROS content,down-regulated the expression levels of autophagy-related proteins LC3-I,LC3-II,Beclin1,and ATG7,and significantly reduced the number of autophagosomes in HCT8/T cells.Conclusions:The present study demonstrated that PMFs could potentially reverse PTX resistance in colon cancer by regulating the aerobic glycolysis-ROS-autophagy signaling axis,which indicated that PMFs would be potential potentiators for future chemotherapeutic agents in colon cancer.
文摘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).
基金supported by the CAMS Innovation Fund for Medical Sciences(CIFMS)(2021-1-I2M-026)the Beijing Natural Science Foundation(7202133)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2021-RW350-002)。
文摘Background:Triple-negative breast cancer(TNBC)is the most aggressive subtype and occurs in approximately 15%–20%of diagnosed breast cancers.TNBC is characterized by its highly metastatic and recurrent features,as well as a lack of specific targets and targeted therapeutics.Epidermal growth factor receptor(EGFR)is highly expressed in a variety of tumors,especially in TNBC.LR004-VC-MMAE is a new EGFR-targeting antibody–drug conjugate produced by our laboratory.This study aimed to evaluate its antitumor activities against EGFR-positive TNBC and further studied its possible mechanism of antitumor action.Methods:LR004-VC-MMAE was prepared by coupling a cytotoxic payload(MMAE)to an anti-EGFR antibody(LR004)via a linker,and the drug-to-antibody ratio(DAR)was analyzed by HIC-HPLC.The gene expression of EGFR in a series of breast cancer cell lines was assessed using a publicly available microarray dataset(GSE41313)and Western blotting.MDA-MB-468 and MDA-MB-231 cells were treated with LR004-VC-MMAE(0,0.0066,0.066,0.66,6.6 nmol/L),and the inhibitory effects of LR004-VC-MMAE on cell proliferation were examined by CCK-8 and colony formation.The migration and invasion capacity of MDA-MB-468 and MDA-MB-231 cells were tested at different LR004-VCMMAE concentrations(2.5 and 5 nmol/L)with wound healing and Transwell invasion assays.Flow cytometric analysis and tumorsphere-forming assays were used to detect the killing effects of LR004-VC-MMAE on cancer stem cells(MDA-MB-468 and MDA-MB-231 cells).The mouse xenograft models were also used to evaluate the antitumor efficacy of LR004-VC-MMAE in vivo.Briefly,BALB/c nude mice were subcutaneously inoculated with MDA-MB-468 or MDAMB-231 cells.Then they were randomly divided into 4 groups(n=6 per group)and treated with PBS,naked LR004(10 mg/kg),LR004-VC-MMAE(10 mg/kg),or doxorubicin,respectively.Tumor sizes and the body weights of mice were measured every 4 d.The effects of LR004-VC-MMAE on apoptosis and cell cycle distribution were analyzed by flow cytometry.Western blotting was used to detect the effects of LR004-VC-MMAE on EGFR,ERK,MEK phosphorylation and tumor stemness marker gene expression.Results:LR004-VC-MMAE with a DAR of 4.02 were obtained.The expression of EGFR was found to be significantly higher in TNBC cells compared with non-TNBC cells(P<0.01).LR004-VC-MMAE inhibited the proliferation of EGFRpositive TNBC cells,and the ICvalues of MDA-MB-468 and MDA-MB-231 cells treated with LR004-VC-MMAE for 72 h were(0.13±0.02)nmol/L and(0.66±0.06)nmol/L,respectively,which were significantly lower than that of cells treated with MMAE[(3.20±0.60)nmol/L,P<0.01,and(6.60±0.50)nmol/L,P<0.001].LR004-VC-MMAE effectively inhibited migration and invasion of MDA-MB-468 and MDA-MB-231 cells.Moreover,LR004-VC-MMAE also killed tumor stem cells in EGFR-positive TNBC cells and impaired their tumorsphere-forming ability.In TNBC xenograft models,LR004-VC-MMAE at 10 mg/kg significantly suppressed tumor growth and achieved complete tumor regression on day 36.Surprisingly,tumor recurrence was not observed until the end of the experiment on day 52.In a mechanistic study,we found that LR004-VC-MMAE significantly induced cell apoptosis and cell cycle arrest at G/M phase in MDAMB-468[(34±5)%vs.(12±2)%,P<0.001]and MDA-MB-231[(27±4)%vs.(18±3)%,P<0.01]cells.LR004-VC-MMAE also inhibited the activation of EGFR signaling and the expression of cancer stemness marker genes such as Oct4,Sox2,KLF4 and EpCAM.Conclusions:LR004-VC-MMAE showed effective antitumor activity by inhibiting the activation of EGFR signaling and the expression of cancer stemness marker genes.It might be a promising therapeutic candidate and provides a potential therapeutic avenue for the treatment of EGFR-positive TNBC.
文摘Formulation/pharmaceutical excipients play a major role in formulating drug candidates,with the objectives of ease of administration,targeted delivery and complete availability.Many excipients used in pharmaceutical formulations are orphanized in preclinical drug discovery.These orphan excipients could enhance formulatability of highly lipophilic compounds.Additionally,they are safe in preclinical species when used below the LD50 values.However,when the excipients are used in formulating compounds with diverse physico-chemical properties,they pose challenges by modulating study results through their bioanalytical matrix effects.Excipients invariably present in study samples and not in the calibration curve standards cause over-/under-estimation of exposures.Thus,the mechanism by which excipients cause matrix effects and strategies to nullify these effects needs to be revisited.Furthermore,formulation excipients cause drug interactions by moderating the pathways of drug metabolizing enzymes and drug transport proteins.Although it is not possible to get rid of excipient driven interactions,it is always advised to be aware of these interactions and apply the knowledge to draw meaningful conclusions from study results.In this review,we will comprehensively discuss a)orphan excipients that have wider applications in preclinical formulations,b)bioanalytical matrix effects and possible approaches to mitigating these effects,and c)excipient driven drug interactions and strategies to alleviate the impacts of drug interactions.
文摘There are multiple biases in using observational studies to examine treatment effects such as those from prevalent drug users, immortal time and drug indications. We used renin angiotensin system(RAS) inhibitors and statins as reference drugs with proven efficacies in randomized clinical trials(RCTs) and examined their effectiveness in the prospective Hong Kong Diabetes Registry using adjustment methods proposed in the literature. Using time-dependent exposures to drug treatments yielded greatly inflated hazard ratios(HR) regarding the treatment effects of these drugs for cardiovascular disease(CVD) in type 2 diabetes. These errors were probably due to changing indications to use these drugs during follow up periods, especially at the time of drug commencement making time-dependent analysis extremely problematic. Using time-fixed analysis with exclusion of immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of RAS inhibitors for CVD was comparable to that in RCT. The result supported the use of the Registry for performing pharmacoepidemiological analysis which revealed an attenuated low low-density lipoprotein cholesterol related cancer risk with RAS inhibitors. On the other hand, time-fixed analysis with including immortal time and adjustment for confounders at baseline and/or during follow-up periods, the HR of statins for CVD was similar to that in the RCT. Our results highlight the complexity and difficulty in removing these biases. We call for validations of the methods to cope with immortal time and drug use indications before applying them to particular research questions, so to avoid making erroneous conclusions.
基金National Natural Science Foundation of China(31560696)Special Project of Enterprises-Universities-Researches Integration of Hainan Province(cxy20150008)Special Project of Technology Development in Scientific Research Institutes of Hainan Province(KYYS-2014-32)
文摘The paper was to explore the preventive effects of five drugs on mycoplasma pneumonia of swine (MPS) and to provide reference for clinical medication of pig farms in Hainan Province. A total of 444 health piglets were randomly divided into 6 groups, including five medication groups (72 piglets in group A, 74 pig- lets in group B, 72 piglets in group C, 76 piglets in group D, 76 piglets in group E) and one control group (74 piglets). The piglets in experimental groups were treated drugs once a day for successive 5 days at 30, 60, 90, 120 and 150 of age. The piglets in control group were free of medication. At 70 and 140 days of age, 15 piglets of each group were randomly selected to collect their blood sermn. The Mycoplasma hyopneumoniae (M-Hyo) antibodies in serum were measured by en- zyme-linked immunosorbent assay (ELISA). During the experiment, the incidence rates of respiratory disease, lung lesion, feed conversion rate, average daily gain (ADG), and mortality rate of pigs were also observed and recorded. The results showed that the five drugs had significant difference in preventative effects. Group C (Zhiyuanjing group) received the best preventive effect and the highest economic benefits. Compared with control group, the ADG and feed conversion rate in group C were increased by 7.53% and 9.09%, respectively; the incidence rate of respiratory disease was reduced by 13.44% and lung lesion was alleviated by 81.43% ; and the earnings of each pig could rise by 132.70 yuan. The preventative effect and economic benefit of the drugs was sequenced by Chansu Kechuanling and Bingchan Kechuanwang. Wante Feilin and amoxicillin had weaker preventive effects against MPS but greatly influenced growth performance of pigs, so they should be used alternatively with other drugs.
文摘In the twenty first century research works, there may be a need to achieve a more reliable research result through a synergy between engineers and biological researchers. The peak absorbance data for various interacting systems were measured. These were used to show that the antiretroviral drug has the effect of increasing the peak absorbance values of both the uninfected and infected blood components, i.e., the drugs are made able to increase the light absorption capacity of the blood cells. For drug 2 that contains three components including Efavirenz, the drug effect on lymphocytes was increased by about 38% for patients that had been on antiretroviral drug treatment. Mathematical models were proposed and used in determining the coating effectiveness of antiretroviral drugs in the presence and absence of HIV. The use of the findings of this work by pharmaceutical industries may help in the search for more effective antiretroviral drugs for the treatment of HIV patients.
文摘Ciprofloxacin (CFX) was loaded on Bana clay (Cameroon) and CFX loaded-clays have been evaluated as drug delivery system. Raw clays and CFX loaded compounds have been characterized by some physico-chemicals methods. <i>In vitro</i> release studies have been done in gastric and phosphate buffer experimental mediums;bacteriological studies have been made up on <i>Escherichia coli</i> and <i>Staphylococcus aureus</i>. X-ray diffractometry patterns of loaded compounds show a basal spacing increasing due to CFX intercalation. On Fourier-Transformed Infrared spectrometry spectra, appearance of CFX characteristic bands and shifting of certain bands already presents on clay confirmed CFX intercalation. After 96 h of CFX released from release mediums, prolonged and continue profiles have been observed. Diffusion tests displayed an inhibition radius of ~2 cm on gelose seeded with <i>Escherichia coli</i> and <i>Staphylococcus aureus</i> due to CFX. The overall results show a modified release of ciprofloxacin with an effective antibacterial activity, giving the way for a new ciprofloxacin drug delivery system using Bana clay as carrier.
文摘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
基金the National Natural Science Foundation of China(No.81072974).
文摘Background:To study the energy pharmacological effects of chemical drugs.Methods:The energy pharmacological effects of chemical drugs were studied using a literature induction method.Results:Chemical drugs have energy properties,which can be expressed in terms of cold,hot,warm,and cool.The energy properties of chemical drugs have energy pharmacological effects,which are related to the bond energy release and absorption of intermolecular chemical bonds,where the release of energy from chemical bonds indicates a warm-hot energy pharmacological effect and the absorption of energy indicates a cold energy pharmacological effect.The mechanisms of chemical drug energy may be related to the presence of temperature-sensitive ion channels in the body.Conclusion:Chemical drugs exhibit energy pharmacological effects.
文摘Objective: To evaluate five drug treatment regimens in the treatment of Brucella spondylitis. Methods: Patients with clinical symptoms compatible and diagnostic test consistent with Brucella spondylitis were randomly assigned to five drug treatment regimens. Results: Combination therapy with doxycycline, rifampin and sulfamethoxazole for 56 consecutive days showed the highest cure rate of 20% after a single course and of 85% after a double course with affectivity rates of 55% and 95%. Cure rate and affectivity rate was significant better (P 0.05) than for patients receiving doxycycline, rifampin and streptomycin for the same period and regimens containing doxycycline were significant better than regimens without this drug. Conclusion: Combination therapy of doxycycline, rifampin and sulfamethoxazole for 8 weeks using one or two full courses should be recommended for Brucella spondylitis.
文摘AIM To observe the effect of octreotide (OT) and somatostatin (SS) on gallbladder pressure and myoelectric activity of SO in rabbits. METHODS Male rabbits fasted for 15h - 18h and anesthetized with urethane. The mean gallbladder pressure (GP) and myoelectric activity of SO were simultaneously measured with a frog bladder connected to a transducer and a pair of copper electrodes. RESULTS After injection of OT (10μg/kg, iv), the GP decreased in 2min and reached the lowest value in about 60min ( P <0 01, n =19), and completely or partially returned to the normal level in 120min. The frequency of myoelectric activity of SO was reduced, even disappeared in 2min ( P <0 01, n =19) and returned to normal in about 20min . Injection of SS (10μg/kg, iv) also decreased GP and myoelectric activity of SO ( P <0 01, n =7); Before and after injection of OT or SS, injection of CCK 8 ( 100ng or 200ng ) caused similar increase in myoelectric activity of SO and GP ( P >0 05). Before and after injection of OT, there were no significant differences in increases of myoelectric activity of SO and GP caused by electric stimulation of dorsal motor nucleus of vagus ( P >0 05). CONCLUSION OT and SS decreased GP and myoelectric activity of SO, demonstrating that effects of OT were similar to those of SS. Intravenous injection of OT did not affect the increase of myoelectric activity of SO and GP caused by CCK 8 or electric stimulation of dorsal motor nucleus of vagus.
基金financially supported by the Vice President Officefor Research and Dean of School of Graduate Studies and Aklilu Lemma Institute of Pathobiology(grant No.RDP/PY-014/09)
文摘Objective:To evaluate the efficacy and side effects of praziquantel(PZQ) in the treatment of schistosomiasis in Ethiopia.Methods:In a cross-sectional study,stool specimens were collected from randomly selected 299 school children in Shesha Kekele Elementary School,Wondo Genet, Southern Ethiopia,in April 2010.Stool specimens were examined using a single Kato-Katz thick smear for Schistosoma mansoni(5.mansoni) ova.Children who were found positive for S.mansoni were treated with a single oral dose of PZQ at 40 mg/kg bw and interviewed for treatment-related symptoms 24 hours after drug administration.Four weeks post-treatment,stool specimens were collected from the same children and examined following the same procedure as in the pretreatment.Drug efficacy was determined based on cure and egg reduction rates.Results:Pretreatment prevalence of S.mansoni infection was 74.9%with geometric mean egg count of 268. The evaluated generic PZQ produced an overall cure rate of 73.6%(P<0.000 1,OR:8.33,CI:5.3-13.1) and egg reduction rate of 68.2%(P=0.03,F=0.64).The cure rate showed significant association with age(x^2=H,P=0.004),the highest rate being observed in the 15-22 age group.83%of S. mansoni infected children showed various treatment-related symptoms,the most frerjiient being headache,nausea,and abdominal pain.These symptoms were associated with age(P<0.001) and pre-treatment intensity of infection(P<0.05).Conclusions:The present observations revealed relatively lower cure and egg reduction rates of the PZQ evaluated as compared to previous reports for other PZQ brands in Ethiopia.Hence,in depth studies are recommended to clarify whether the present relatively lower cure rate is the actual cure rate of the praziquantel evaluated,treatment failure,or reduced susceptibility of the parasite.Treatment-related side effects observed were transient and tolerable.
文摘Background: Stroke is a worldwide health problem, the world’s second-leading cause of death and third-leading cause of disability. Currently, the majority of stroke patients are ischemic stroke patients. It is necessary to evaluate risk factors to prevent ischemic stroke. Data and Methods: The risk factors for stroke in the previous fiscal year were analyzed. They were divided into nonmodifiable and modifiable factors. The probit and ordered probit models were used in the study, with 59341 and 50542 observations used in the estimation of the models, respectively. Results: Among the nonmodifiable factors, age, gender and cerebrovascular disease history are important risk factors. The history of cerebrovascular diseases is considered to be an especially important factor. Among the modifiable factors, taking antihypertensive drugs and recent large weight change are negative risk factors;however, sleeping well significantly reduces the probability of ischemic stroke. Conclusion: It is very important to ensure that medical personnel know a patient’s history of cerebrovascular diseases for proper treatments. Ischemic stroke might be considered an important side effect of antihypertensive drugs. Limitations: The dataset was observatory. There are various types of antihypertension drugs, and their effects are not analyzed.
基金This work was financially supported through grants from the Guangdong Basic and Applied Basic Research Foundation(2019B1515120043)National Natural Science Foundation of China(File No.82104354)+2 种基金the Science and Technology Development Fund,Macao SAR(File No.0016/2021/A)and the Open Project of Key Laboratory of Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Chinese Medicine(zdsys-202101)Open access funding provided by Shanghai Jiao Tong University
文摘Parkinson’s disease(PD),a neurodegenerative disease that shows a high incidence in older individuals,is becoming increasingly prevalent.Unfortunately,there is no clinical cure for PD,and novel anti-PD drugs are therefore urgently required.However,the selective permeability of the blood–brain barrier(BBB)poses a huge challenge in the development of such drugs.Fortunately,through strategies based on the physiological characteristics of the BBB and other modifications,including enhancement of BBB permeability,nanotechnology can offer a solution to this problem and facilitate drug delivery across the BBB.Although nanomaterials are often used as carriers for PD treatment,their biological activity is ignored.Several studies in recent years have shown that nanomaterials can improve PD symptoms via their own nano-bio effects.In this review,we first summarize the physiological features of the BBB and then discuss the design of appropriate brain-targeted delivery nanoplatforms for PD treatment.Subsequently,we highlight the emerging strategies for crossing the BBB and the development of novel nanomaterials with anti-PD nano-biological effects.Finally,we discuss the current challenges in nanomaterial-based PD treatment and the future trends in this field.Our review emphasizes the clinical value of nanotechnology in PD treatment based on recent patents and could guide researchers working in this area in the future.
文摘Side-effects associated with the cancer chemotherapy limit the scope of chemotherapeutic drugs and no data was available about these side effects in Pakistan. Moreover starvation based differential chemotherapy has been proved to greatly reduce the side effects of chemotherapy depending on starvation time. The current study was conducted to survey the common side effects of the chemotherapeutic drugs and the role of starvation to reduce them. The study included total 100 subjects with multiple carcinomas. A comprehensive questionnaire about starvation inquiry, chemotherapy side effects and their basic information was filled by interviewers as told by patients. There were 48% patients with breast cancer and 11% with uterine cancer. Out of these patients 30%, 28%, 9% and 9% patients were agreed to starve for 12, 24, 36 and 48 hours respectively. The survey regarding the side effects of chemotherapy showed that 43% patients were suffering from headache, fatigue 90%, weakness 95%, hair loss 76%, nausea 77%, vomiting 75%, diarrhea 31%, abdominal cramps 40%, mouth sores 47%, dry mouth 74%, memory impairment 14%?and numbness 49%. Breast cancer is the most common cancer in Pakistan. Only 18% of the total patients were agreed to starve for more than one day. Chemotherapy-associated side effects vary greatly and it does not depend upon cancer type. But these side effects depend on multiple factors such as the type and dose of chemotherapeutic drug, patient’s health status and stage of cancer.
基金Supported by the Science and Technology Training Plan Project of Sichuan Province(2016KZ0007)the Fundamental Research Funds for the Central Universitiesof Southwest University for Nationalities(2017NZYQN38)
文摘This study was conducted to investigate the effects of extracts of 4 Tibetan veterinary drugs on bacterial diarrhea, and to guide the clinical treatment of the disease. The inhibitory effects of the extracts of the 4 Tibetan veterinary drugs, Veronica ciliate Fisch, Usnea diffracta Vain, Sophoraflavescens var. flavescens, Lamiophlomis rotata ( Benth. ) Kudo on 14 common diarrheagenic bacteria were detected by K-B diffusion method and micro-broth dilution method. Optimization was performed on prescriptions of the 4 Tibetan veterinary drugs using orthogonal design software, and a mouse bacterial diarrhea model was established with a clinical isolate, Salmonella blegdam. According to the LD50 value of the optimal prescription of the 4 Tibetan veterinary drugs, the established mouse bacterial diarrhea model was treated in 3 dose groups, i. e. , the high, middle and low dose groups (0. 060, 0. 030 and 0. 020 g/ml, respectively). The results showed that the 4 Tibetan veterinary drugs had very good inhibitory effects on most of the tested diarrheagenic bacteria, and among them, U. diffracta had better inhibitory effects on all the tested bacteria. The optimal prescription of the d Tibetan veterinary drugs (high dose, 0.06 g/ml) exhibited very good inhibitory effect on mouse diarrhea, indicating that the prescription has very good anti-diarrhea effect, which is beneficial to the clinical treatment of such disease and the development of Tibetan veterinary drugs.
基金Part of this manuscript was supported by Grant from the Instituto Mexicano del Seguro Social,projects FIS/IMSS/PROT/G15/1414
文摘Drug-induced liver injury encompasses a spectrum of diseases ranging from mild biochemical abnormalities to acute liver failure; example of this scenery is hepatotoxicity caused by the first-line antituberculous drugs isoniazid, rifampin and pyrazinamide, which are basic for treatment of drug-sensible and drug-resistant tuberculosis. In the search for pharmacological alternatives to prevent liver damage, antitubercular drugs have been the subject of numerous studies and published reviews, a great majority of them carried out by Asian countries. At the same time, hepatoprotectors from plant source are now emerging as a possible alternative to counteract the toxic effects of these therapeutic agents. The present review aims to highlight the most recent studies on the subject, based information published in scientific databases such as Scopus and Pub Med.