Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3

Purpose: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. Methods: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. Results: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. Conclusions: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

Research progress and therapeutic perspective of iron transport balance based on "iron-inflammation" homeostatic coupling theory / 药学学报

The iron and inflammation homeostasis are closely coupled, forming an integrated functional unit under physiological conditions. "Iron transport balance" has become the key mechanism to maintain iron homeostasis through bidirectional regulation of iron uptake and release and dynamic management of transmembrane concentration. It is also the physiological basis for the inflammatory balance between promotion and resolution. Under pathological conditions, represented by inflammatory bowel disease (IBD), disturbed iron transportation was highly involved in almost every step of inflammatory diseases. Therefore, the iron transporting rebalancing provides the mechanistic basis and effective approach for the normalization of inflammatory microenvironment. Macrophage is the key regulator of inflammation homeostasis and determinant for iron transport balance. Unfortunately, the current clinical transformation based on iron transport balance theory has still been insufficient. Sometimes, this strategy even showed high complexity and contradiction, severely restricting its clinical application. By summarizing the theoretical research progress of iron transport balance, especially its relevance to macrophage phenotypic polarization, this review aims to explore the therapeutic value in inflammation intervention by targeting iron transporting balance. This review will provide the necessary knowledge and hints for the research and development of candidate drugs in treating inflammatory diseases.

Reporting and methodological quality of meta-analyses of acupuncture for patients with migraine: A methodological investigation with evidence map / 中西医结合学报

BACKGROUND@#Acupuncture has been widely used to relieve migraine-related symptoms. However, the findings of previous systematic reviews (SRs) and meta-analyses (MAs) are still not completely consistent. Their quality is also unknown, so a comprehensive study is needed.@*OBJECTIVE@#To evaluate the reporting and methodological quality of these MAs concerning acupuncture for migraine, and summarize evidence about the efficacy and safety of acupuncture for migraine.@*SEARCH STRATEGY@#PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Databases, Wanfang Data, and VIP databases were searched from inception to September 2020, with a comprehensive search strategy.@*INCLUSION CRITERIA@#The pairwise MAs of randomized controlled trials (RCTs) concerning migraine treated by acupuncture or acupuncture-based therapies, with a control group that received sham acupuncture, medication, no treatment, or acupuncture at different acupoints were included.@*DATA EXTRACTION AND ANALYSIS@#Two independent investigators screened studies, extracted relevant data, and assessed reporting and methodological quality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 and A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), then all results were cross-checked. Spearman correlation test was used to evaluate the correlation between reporting and methodological quality scores.@*RESULTS@#A total of 20 MAs were included in this study. The included MAs indicated that acupuncture was efficacious and safe in preventing and treating migraine when compared with control intervention. There was a high correlation between reporting and methodological quality scores (rs = 0.87, P < 0.001). The quality of the included SRs needs to be improved mainly with regard to protocol and prospective registration, using a comprehensive search strategy, summarizing the strength of evidence body for key outcomes, a full list of excluded studies with reasons for exclusion, reporting of RCTs' funding sources, and assessing the potential impact of risk of bias in RCTs on MA results.@*CONCLUSION@#Acupuncture is an effective and safe intervention for preventing and treating migraine, and could be considered as a good option for patients with migraine. However, the reporting and methodological quality of MAs included in this overview is suboptimal. In the future, AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.

Clinicopathological features of very well-differentiated adenocarcinoma of the stomach / 中华病理学杂志

Objective: To investigate the clinicopathological features of very well-differentiated adenocarcinoma (VWDA) of the stomach. Methods: The clinicopathological data of 12 cases of VWDA of the stomach were collected retrospectively at the People's Liberation Army Joint Logistics Support Force 989 Hospital (formerly 152 Hospital), Pingdingshan, China, from January 2013 to May 2021. The histological characteristics and immunophenotypes were observed and analyzed with review of current literature. Results: There were 8 males and 4 females with a median age of 63 years (range 47 to 80 years). The tumor involved in the upper part of the stomach in 6 cases, the middle part in 2 cases, and the lower part in 4 cases. The median diameter of the tumors was 17 mm (range 5-65 mm). The tumor cells were similar to absorbent cells, Paneth cells, foveolar epithelial cells, and goblet cells. The cells were arranged in a single layer, and the nuclei were slightly enlarged and located at the base. The nuclei were fusiform to slightly irregular, with loss of nuclear polarity. Early tubular VWDA was found in 9 cases, and the tumor glands were similar to intestinal metaplasia. In two cases the tumors infiltrated into the submucosa. The lesions in the mucosa and submucosa showed the glands with cystic expansion, bending, branching, spiky and abortive growth pattern. One case of early papillary tubular VWDA was confined to the mucosal layer and composed of foveolar-type epithelial cells. There were two cases of advanced papillary tubular VWDA, which consisted of foveolar-type epithelial, pyloric glands, or mucinous neck cells and were associated with intra-lymphatic cancer embolus and lymph node metastases. Background mucosal atrophy and intestinal metaplasia were observed in all cases. Immunohistochemical staining showed intestinal type VWDA in 1 case, mixed gastrointestinal type VWDA in 9 cases, and gastric type VWDA in 2 cases. The Ki-67 proliferation index of 8 cases limited to the mucosa was 40%-70%, 2 cases of infiltration into the submucosa and 2 cases of advanced carcinoma was 10%-25%. All the tumors showed a wild type of p53 protein expression pattern and negative HER2. Adenocarcinoma or high-grade dysplasia was diagnosed on preoperative biopsy in 5 cases, and chronic atrophic gastritis with intestinal metaplasia in 7 cases. The median follow-up time was 28 months (range 12-72 months). No recurrence was found in the 10 patients with early cancer. Of the two patients with advanced carcinoma, one patient had lung metastases and the other died. Conclusions: Gastric VWDA is a rare low-grade malignancy with structural features of highly differentiated adenocarcinoma and extremely low cytological atypia. The diagnostic value of structural abnormality is significantly greater than cytological atypia. The invasive growth of irregular glands in the deep mucosa and submucosa is reliable evidence for diagnosis. The diagnosis of intramucosal VWDA is challenging and very difficult in some biopsy specimens.

Current drug research on intestinal mucosal healing in inflammatory bowel disease based on macrophage regulation / 药学学报

Complete healing of the intestinal mucosa is the most ideal goal in the treatment of inflammatory bowel disease (IBD). The intestinal mucosa healing not only significantly alters the course of the disease and relieves clinical symptoms, but also markedly reduces the occurrence of complications and prevents recurrence of IBD. As chronic inflammation associated with peptic ulcer damage is the main pathological feature of IBD, clinical treatment is mainly based on anti-inflammatory therapy, but such therapy cannot promote the healing of the intestinal mucosa of patients. Therefore, how to achieve long-term remission of IBD is still an urgent challenge. In the process of intestinal mucosal repair, the polarization of macrophages maintains the homeostasis of the intestinal microenvironment, which is a representative process that promotes mucosal inflammatory-repair. It is a key part of initiating tissue regeneration that should not be underestimated. In this paper, we reviewed the literature of the past decade, focusing on the promotion of intestinal mucosal healing in IBD. The discussion will highlight the importance and feasibility of regulating macrophages to promote intestinal mucosal repair. Following this thought, we discuss the shortcomings of current clinical treatments and summarize the relevant drugs which have potential to promote intestinal mucosal repair. The aim is to provide effective potential drugs and therapeutic targets for the treatment of IBD.

Respiratory infectious diseases and tissue "damage-repair" balance:pathological characteristics, treatment, and characteristics of traditional Chinese medicine / 中国中药杂志

Respiratory infectious diseases are important diseases causing major public safety events, posing a great threat to life, health, and social development. Effective control and scientific treatment of the diseases is the key basis for ensuring the stability and long-term development of the community of a shared future for human health. Although the pathogens of respiratory viral infectious diseases are diverse and the process is complex, the common pathological basis of their pathogenesis is characterized by the "damage-repair" functional imbalance of the immune microenvironment of the lesions, which leads to the subsequent structural and functional destruction of important organs. Therefore, the treatment should focus on antivirus and immunological regulation, strengthen the protection against immune injury, and promote the functional repair of damaged tissues. The above conclusions are the scientific core of host-directed therapies(HDT), which coincides with "human-disease co-treatment and healthy qi and pathogen interaction" in traditional Chinese medicine(TCM) theories. Under the support of TCM and western medicine theories, the complete pathological chain "infection-immunity-injury" of respiratory viral infectious diseases is integrated with dynamic change in "healthy qi-pathogen" in TCM to transform the treatment focus from the diseases to the patients. It is possible to fundamentally correct the "damage-repair" imbalance in the disease state, change the environment for disease development, and bring benefits to patients by strengthening human intervention, maintaining immune homeostasis, enhancing the protection of tissues and organs, and promoting the repair and regeneration of damaged tissues. This study focused on the common and key pathological processes of respiratory infectious diseases, especially the immune damage caused by the viral infection, to seek effective prevention and treatment strategies, review relevant theoretical progress, summarize effective drug candidates, prospect future research and development, and highlight the therapeutic characteristics of TCM.

Qualitative Analysis of Multiple Cumarins in Angelicae Sinensis Radix Based on HPLC-Q-TOF-MS/MS / 中国实验方剂学杂志

Objective:To systematically and comprehensively analyze coumarin components in Angelicae Sihensis Radix by an efficient and stable HPLC-Q-TOF-MS/MS method,in order to offer the theoretical basis to develop coumarin,establish the quality control standard and apply in clinic. Method:The separation effect of coumarin components was extracted by adjusting the column,temperature,mobile phase,flow rate,sample concentration and other conditions,and various coumarin components in Angelicae Sihensis Radix were identified by corresponding standards,precise molecular mass,polarity,pyrolysis pattern. Result:In this study,a high-efficiency and stable coumarin separation method was established that can be used to separate complex components,and 14 coumarin components were identified in this study,including phellopterin and osthenol that were rarely reported as effective components in Angelicae Sihensis Radix. Major fragment ions of coumarin components were analyzed. The cleavage in methoxy bond or anisole bond on the parent nucleus was the primary pattern for coumarin components, which was summarized for detecting unknowing coumarins. Conclusion:Abundant coumarins were contained in Angelicae Sihensis Radix. Further qualitative and quantitative analysis of coumarins are conducive to improving the quality standards of Angelicae Sihensis Radix,and providing reference for the development of coumarins and clinical application of Angelicae Sinensis Radix.

Effects of high energy enteral nutrition on nutritional status and immune function in patients with pulmonary heart failure / 中国中西医结合急救杂志

Objective To investigate the effects of high energy enteral nutrition (EN) on nutritional status and immune function in patients with heart failure caused by pulmonary cardiac disease. Methods Eighty-six patients with heart failure caused by pulmonary heart disease were continuously collected from March 2017 to March 2018 in the Department of Critical Care Medicine of Taizhou First People's Hospital, and they were divided into a high-energy EN group and a standard EN group according to the different use of EN preparations, each group with 43 cases. The high-energy EN group were treated with high energy EN solution TPF-T (Ruineng), and the standard EN group were treated with standard EN solution TP (Ruisu); the initial EN infusion velocity in all the patients was 25 mL/h, the calorific calorie would reach the target to 104.6-125.5 kJ·kg-1·d-1, and the protein would target to 1.5-2 g·kg-1·d-1 within 3 days;the blood glucose was controlled within the scope of 7.8-11.1 mmol/L. The differences in rates of calorie and protein goal targeting situations, nutritional status, inflammatory response and immune function were compared between the two groups. Results From the 3rd day to 7th day after EN application, the rates of calorie and protein goal targeted in the high-energy EN group were significantly higher than those in the standard EN group [calorie targeted rate: 69.77% (30/43) vs. 41.86% (18/43), protein targeted rate: 25.58% (11/43) vs. 11.63% (5/43), all P < 0.05]. With the extension of EN application, nutritional indexes such as albumin (Alb), prealbumin (PA), transferrin (TRF), etc. and the immune indexes such as human leucocyte antigen (HLA)-DR positive rate, immunoglobulins (IgA, IgG), etc. were persistently increased in both groups, reaching the peak values on the 7th day, and the indexes in high-energy EN group were significantly higher than those in the standard EN group [Alb (g/L): 36.43±5.81 vs. 33.79±5.34, PA (mg/L): 278.83±47.56 vs. 251.67±41.92, TRF (mg/L): 3.58±0.64 vs. 3.26±0.81, HLA-RD positive rate: (53.22±6.11)% vs. (50.21±5.69)%, IgA(mg/L): 165.34±40.13 vs. 141.54±38.76, IgG (mg/L): 4 990.68±881.66 vs. 4 211.75±861.54, all P < 0.05]. However, the levels of inflammatory factors such as C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) in both groups were gradually decreased, reaching the valley values on the 7th day, and the indexes in high-energy EN group were significantly lower than those in the standard EN group [TNF-α(ng/L): 14.43±8.69 vs. 20.59±9.45, CRP (mg/L): 21.33±6.35 vs. 27.36±7.83, all P < 0.05]. Conclusion High energy EN not only can improve the nutritional status in patients with pulmonary heart failure, but also can reduce patients’ inflammation response and elevate their immune function.

Characterization analysis and overexpressed vector construction of the circular RNA hsa_circ_0082626 derived from the antiviral gene ZC3HAV1 / 医学研究生学报

Objective Circular RNA is a research hotspot of non-coding RNAs. The purpose of this study was to investigate the basic characteristics and expression effect of the overexpression vectors of circular RNA hsa_circ_0082626 transcribed from antiviral gene ZC3HAV1. Methods The basic characteristics of hsa_circ_0082626 were studied by the verification of reverse cleavage site, RNase digestion assay and intracellular distribution location with extraction of cytoplasmic and nuclear RNA. In the RNase digestion assay, samples were divided into RNase R treatment group and control group. RNase. 20 U (2 U/μg) of RNase R was added to the R treatment group, and the control group was replaced with an equivalent amount of ddH2O to detect changes in expression levels after RNase treatment. The cells were divided into 2 groups: overexpression group and negative control group. At 24, 48 and 72 h after transfection, cells were collected to detect the expression of circular RNA by RT-qPCR. Results Compared with the control group, the expression of ZC3HAV1, CDR1as and GAPDH in the RNase R treatment group was increased (0.144±0.002 vs 1.000±0.016, 0.772±0.058 vs 1.000±0.122, 0.077±0.009 vs 1.000±0.164, P<0.05). Hsa_circ_0082626 could resist the treatment of RNase R and was mainly distributed in cytoplasm. The expression level of hsa_circ_0082626 in the overexpression group was significantly higher than that in the negative control group, and the expression level was the highest at 48 h after transfection. Conclusion The characteristics of hsa_circ_0082626 reverse cleavage site, RNase resistance and expression in cells were successfully analyzed, which proved that hsa_circ_0082626 does have a circular structure. The overexpression vector of hsa_circ_0082626 was successfully constructed to provide an experimental basis for the biological function and mechanism of RNA hsa_circ_0082626.

Clinical Study on Dilong Jiangya Capsule in Treatment of Essential Hypertension with Subclinical Atherosclerosis of Hyperactivity of Liver Yang Type / 中国中医药信息杂志

Objective To investigate the synergistic antihypertensive effect of Dilong Jiangya Capsules on patients with essential hypertension with subclinical atherosclerosis of liver yang hyperactivity type and its effect on arteriosclerosis. Methods Totally 120 patients with essential hypertension with subclinical atherosclerosis were randomly divided into treatment group (60 cases) and control group (60 cases). Control group received antihypertensive treatment by following the individual, low-dose, long-term, combined principle, while treatment group was given Dilong Jiangya Capsules on the basis of control group, one capsule per time, twice a day, orally taken during early morning and bedtime. The treatment for both groups lasted for six weeks. Blood pressure, carotid artery intima-media thickness (IMT), pulse wave velocity (PWV) and ankle-brachial index (ABI) were observed before and 2, 4 and 6 weeks after treatment. Blood pressure clinical efficacy was evaluated. Results Two and three cases were lost in the treatment group and control group, respectively. The total effective rate was 91.38% (53/58) in the treatment group and 82.46% (47/57) in the control group, and the treatment group was significantly better than the control group (P<0.05). Compared with before treatment, the blood pressure of the two groups was significantly lower (P<0.05), and the treatment group was significantly lower than the control group (P<0.05). Compared with before treatment, the levels of IMT and PWV in both groups significantly decreased at 2 and 4 weeks of treatment, and ABI at 2, 4 and 6 weeks of treatment decreased significantly (P<0.05). There was statistical difference in IMT and PWV between the two groups at 4 weeks of treatment (P<0.05). There was statistical difference in ABI between the two groups at 2 and 4 weeks of treatment (P<0.05). There was statistical difference in IMT, PWV and ABI between the two groups at 6 weeks of treatment (P<0.05). Conclusion Dilong Jiangya Capsules combined with conventional antihypertensive treatment of essential hypertension with subclinical atherosclerosis can enhance the antihypertensive effect, and improve IMT, PWV and ABI to some extent.

Experience in Applying Zhigancao Decoction in Treatment of Respiratory Diseases / 中国中医药信息杂志

Zhigancao Decoction is from Shang Han Lun,which is widely used to treat cardiovascular diseases nowadays,such as arrhythmia,myocarditis,heart failure and so on.Moreover,according to records in Wai Tai Mi Yao:Zhigancao Decoction can also be used to treat lung"atrophy". This article introduced application of Zhigancao Decoction in treating respiratory diseases with good efficacy, which could provide new ideas for the TCM treatment of advanced respiratory diseases.

Effects of doxorubicin on neuropathic pain in chronic sciatic nerve constriction injury rats and its underlying mechanism / 中国药理学通报

Aim To observe the analgesic effect of doxorubicin ( DOX) on chronic sciatic nerve constric-tion injury (CCI) rat model, and analyze the underly-ing mechanism from the ultrastructure of sciatic nerve ganglion and the expressions of some apoptotic pro-teins.Methods A total of 60 SD rats were randomly divided into four groups: sham operation group ( Sham ) , CCI model group ( Model ) , sham operation+DOX 5 mg· kg -1 group ( Sham+DOX) , CCI mod-el +DOX 5 mg· kg -1 group (Model+DOX).DOX was given by caudal vein injection after model estab-lishment .Sham group and model group were given the same amount of saline . The mechanical withdrawal threshold and thermal withdrawal latency were deter-mined by behavioral test .The ultrastructural changes of L4-5 DRG were examined by light microscopy and scanning electron microscopy , respectively .The pro-tein expression levels of Bax , Bcl-2 , PKCɑ, PKCδand PKCε in DRG tissues were determined by Western blot.Results The fluorescence of DOX was found in DRG after DOX was given intravenously .In compari-son with sham group , the thermal and mechanical pain thresholds had no obvious changes in sham +DOX group, while the thresholds were decreased obviously seven days after surgery in model group .In comparison with model group , the pain thresholds in model +DOX group increased significantly , which lasted for the en-tire observation time of six days .The ultra-structure of tissues was damaged obviously in both sham +DOX group and model+DOX group.The protein expression of Bax/Bcl-2 increased, while the expressions of PKCδand PKCεdecreased with DOX injection .Conclusions DOX can retrograde and reach the DRG tissues after intravenous administration . The attenuation effect of DOX on neuropathic pain is related to the apoptosis in-duced by the down-regulation of PKCδ and PKCε in DRG cells.

Comparison and discussion of different surgical methods used to treat vesicovaginal fistulas / 北京大学学报(医学版)

Objective:To compare the feasibility and prognosis of different surgical methods used for vesicovaginal fistulas and to explore the value of electrocoagulation treating small ones.Methods:The medical data of 19 patients who had undertaken transvaginal VVF repairs in Peking University People's Hospital between October 2008 and November 2016 were retrospectively collected.The follow-ups were performed.The patients' age ranged from 31 to 55 years with the median age of 48 years and the history length ranged from 1 month to 24 months with the median length of 3 months.Their fistula situation,surgical methods and prognosis were analyzed and the differences and similarities were compared.Results:Three patients (15.79％) was performed by electrocoagulation,4 (21.05％) by transvaginal repair,5 (21.32％) by laparoscopic repair and 7(36.84％) by open operation.Except one patient who rejected urinary catheter and D-J catheters,the rest of the patients discharged with catheters.Twelve patients (63.2％) got full satisfaction with one operation.One of the 3 patients who undertook electrocoagulation repeated the operation for twice and got completely cured within 1 month while the other two undertook the operation once and got dry within 1 month.Three patients who undertook transvaginal repair got dry within 1 month.Two of the 5 patients who undertook laparoscopic repair had readmission for a second operation and the other 3 got dry after operation.Five of the 7 open repair patients got dry while the other 2 attempted other center for treatment.Conclusion:Transvaginal repair has been the main surgery procedure for VVF,but it is limited by the location of fistula and the condition of vaginal.For patients not suitable for transvaginal repair,laparoscopic repair and open surgery are feasible.However both laparoscopic repair and open surgery are more invasive.Based on that,electrocoagnlation becomes a better choice.In our research,patients with small and high location fistula treated by electrocoagulation got a higher cure rate and bear less surgical trauma.Electrocoagulation used in the treatment of VVF showed advantages of less trauma,less bleeding and better satisfaction.Fistulas with low location were more suitable for transvaginal repair.Complex VVF,especially with narrow ureteral open and ureteral fistulas,were more suitable for open and laparoscopic repair.As for single and small fistula,the electrocoagulation can be the first choice.

Role of drug transporters and metabolizing enzymes in pharmacokinetics of antibiotics / 药物评价研究

In recent years,the research on drag transporters has made great progress,more and more transporters have been found and studied,and they have shown important roles in the transport of drug across the cellular membrane.Various transporters,including uptake transporters and effiux transporters,have important effects on the pharmacokinetics and drug-drug interactions.Studies have shown that the process in vivo of most of the antibiotics was related to transporters and metabolizing enzymes (cytochrome P450 and CYP450).Therefore,this article summarized the latest research progress in pharmacokinetics and drug-drug interactions of transporters and CYP450,so that provides evidence for clinical rational use of antibiotics.

Role of hepatic transporters and metabolic enzymes in chemical substances-induced liver injury / 药物评价研究

Liver is an important metabolic and detoxification organ in the body.Hepatic transporters are a series of functional membrane proteins that are extensively expressed in the liver.They are responsible for the uptake of endogenous and exogenous substances such as medicines into hepatocytes and excretion of their metabolic products into bile.Recent studies have provided that transporters and metabolic enzymes play important roles in the chemical substances-induced liver injury,and its various regulatory mechanisms have become hot topics of research.In this paper,we summarize the classification of hepatic transporters and metabolic enzymes and the changes of transporters and metabolic enzymes in the chemical substances-induced liver injury and its regulatory mechanism.

Mechanism of hepatic transporters and metabolic enzymes in cholestatic liver injury / 药物评价研究

Cholestatic liver injury,which is mainly caused by the disruption of bile acids,is common in the clinic.The pathogenesis of cholestatic liver injury is directly related to the changes of bile acid-related transporters,synthetic and metabolic enzymes.Nuclear receptors play a crucial part in cholestatic liver injury by regulating the expression of transporters and metabolic enzymes that maintaining the homeostasis of bile acids.In this review,we focus on the role of hepatic transporters and metabolic enzymes in cholestatic liver injury and the mechanism of nuclear receptors on the regulation of transporters and metabolic enzymes.

Vital role of transporters in renal drug elimination / 药物评价研究

Transporters are a class of functional membrane proteins which are broadly expressed in the kidney and play a vital role in the reabsorption and secretion of many endogenous and xenobiotic compounds by the kidney.The renal proximal tubule is the primary site of transporter-mediated active transport for many drugs,including organic anion drugs,organic cation drugs and peptide drugs.Transporter-mediated drug-drug interactions may occur in the kidney when some drugs are co-administration.In this review,we focus on the location and function of major transporters in the kidney and summarize their vital role in renal drug elimination.

Vital role of oligopeptide transporters in physiology and drug transport and their clinical relevance / 药物评价研究

The oligopeptide transporters (PEPTs),including PEPT1 and PEPT2,belong to the SLC family and are driven by H+ gradient.PEPT1,the low-affinity and high-capacity transporter,is mainly expressed in small intestine,whereas PEPT2,the high-affinity and low-capacity transporter,is mainly expressed in kidney,brain and lung and has a broader distribution in the organism.The PEPTs are responsible for the absorption and conservation of dietary protein digestion products in intestine and kidney,respectively,and in maintaining homeostasis of neuropeptides in brain.They are also responsible for the absorption and disposition of a number of pharmacologically important compounds including some aminocephalosporins,angiotensin-converting enzyme inhibitors,antiviral prodrugs and others.And PEPTs are also associated with some intestinal diseases and cancer.Therefore,this article summarizes the important role of PEPTs in physiology and drug transport and their clinical relevance.

Progress in effects of rhein on drug transporters and metabolic enzymes / 药物评价研究

Drug transporters and drag metabolic enzymes are crucial factors in the process of drug treatment.Rhein,as the main active component of traditional Chinese medicine rhubarb,has a wide range of pharmacological activities.Previous studies have shown that rhein is closely related to drug transporters and metabolic enzymes,and can directly activate or inhibit the functions of a variety of transporters and their protein expression.Furthermore,rhein can inhibit the function and protein expression of cytochrome P450 (CYP450),a drug metabolizing enzyme.Thus,when rhein is combined with other drugs,the drug-drug interaction (DDI) may occur based on pharmacokinetic.This paper focuses on the distribution of drug transporters,metabolic enzymes,and the effects of rhein on transporters and metabolic enzymes.