The research advance on subtypes and relevant therapy of Parkinson's disease / 药学学报

Parkinson's disease (PD) is a progressive neurodegenerative disease with a high clinical heterogeneity. According to its motor symptoms, PD patients are divided into predominant tremor-dominant, postural instability and gait difficulty-dominant/akinetic-rigid and mixed subtypes. Different subtypes show different prognostic characteristics and different sensitivities to drugs. Therefore, the early classification of PD is of great significance for the treatment and prognosis of the disease. This paper reviews the clinical classification methods of different subtypes of PD, summarizes the latest biochemical markers and imaging features, and analyzed the differences in incidence, prognosis and pathological mechanism. The current clinical treatment drugs and methods have been preliminarily targeted for treatment based on PD classification, and there are many animal models of PD subtypes have been studied, providing new methods and strategies for mechanism research and preclinical pharmacodynamics evaluation of PD subtypes.

Based on plasma metabonomics and network analysis to research the mechanisms of Chaigui granules for treating depression / 药学学报

The purpose of this study was to systematically analyze the antidepressant mechanism of Chaigui granules from the perspective of biological metabolic network by using integrated metabolomics and biological network analysis tools. The model of chronic unpredictable mild stress (CUMS) depression rat was established, and LC-MS-based plasma metabolomics was used to identify the key metabolites and analyze metabolic pathways underlying the antidepressant effects of Chaigui Granules. The key metabolites regulated by Chaigui granules was integrated with biological network analysis tools to further focus on the key metabolic pathways and explore the potential targets of the antidepressant effect of Chaigui granules. The results showed that there were significant differences in the plasma levels of 20 metabolites in the model group compared with the control group (P < 0.05), Chaigui granules significantly regulated 12 metabolites including docosatrienoic acid, 3-hydroxybutyric acid, 4-hydroxybenzaldehyde, chenodeoxycholic acid, cholic acid, L-glutamine, glycocholic acid, linoleyl carnitine, L-tyrosine, N-acetylvaline, palmitoylcarnitine, arachidonic acid. Further network analysis of the key metabolites regulated by Chaigui granules indicated that plasma arachidonic acid metabolism might be the core pathway for the antidepressant effect of Chaigui granules, with 10 proteins were potential targets for the antidepressant effect of Chaigui granules, including CYP2B6, CYP2E1, CYP2C9, CYP2C8, PLA2G6, PTGS2, ALOX15B, PTGS1, ALOX12 and ALOX5. The animal experimental operations involved in this paper was followed the regulations of the Animal Ethics Committee of Shanxi University and passed the animal experimental ethical review (Approval No. SXULL2020028).

Puerarin reduces oxidative damage to vascular endothelial cells by improving mitochondrial respiratory function / 药学学报

This study investigated the effect of puerarin on human umbilical vein endothelial cells (HUVEC) injured with hydrogen peroxide (H2O2). HUVEC were divided into three groups: a control group, a model group (H2O2 400 μmol·L-1) and a puerarin-treated group (3, 10, 30 and 100 μmol·L-1). HUVEC were cultured with varied concentration of puerarin for 2 h and treated with H2O2 for another 24 h. Cell proliferation was detected by a CCK-8 assay. The mitochondrial membrane potential was measured by a JC-1 fluorescent probe. A transwell chamber assay was adopted to observe cell migration ability. Mitochondrial respiratory function was measured in a two-chamber titration injection respirometer (Oxygraph-2k). The expression of interleukin-1β (IL-1β), interleukin-18 (IL-18) and tumor necrosis factor-α (TNF-α) was detected by quantitative real-time PCR. The expression of pyroptosis-mediated proteins, including cleaved-cysteinyl aspartate-specific proteinase-1 (caspase-1), N-gasdermin D (N-GSDMD), NOD-like receptor protein 3 (NLRP3) and purinergic ligand-gated ion channel 7 receptor (P2X7R) was detected by Western blot. The results show that 400 μmol·L-1 H2O2 treatment for 24 h causes obvious damage to HUVEC. Compared with the model group, puerarin protected against cellular injury in a dose-dependent manner, with the greatest effect at a dose of 30 and 100 μmol·L-1. Puerarin significantly decreased the mitochondrial membrane potential and improved mitochondrial function. Puerarin inhibited cell migration induced by H2O2, suppressed the expression of IL-1β, IL-18 and TNF-α, and down-regulated the pyroptosis-mediated protein. These changes are statistically significant (P < 0.05). These findings demonstrate that puerarin has a protective effect against H2O2-induced oxidative damage of HUVEC by inhibiting the migration of HUVEC cells. The mechanism may be related to improved mitochondrial respiratory function and inhibition of pyroptosis.

The mechanisms of type 2 diabetic skeletal muscle atrophy and the effects of commonly used hypoglycemic drugs: a review / 药学学报

Type 2 diabetes is a hypermetabolic disease characterized with disorders of glucose/lipid metabolism, absolute or relative lack of insulin, and can induce skeletal muscle atrophy. Hyperglycemia, hyperlipidemia, insulin resistance, and abnormal release of inflammatory factors can lead to abnormal signal transduction in skeletal muscle, thus make protein synthesis and degradation imbalance and eventually causing muscle atrophy. Under normal conditions, insulin-like growth factor 1 (IGF-1)/insulin can activate phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT). AKT not only increases protein synthesis through mammalian target protein of rapamycin (mTOR), but also phosphorylates forkhead box O (FoxO) transcription factor and then inhibits the transcription of several ubiquitin ligases (such as MAFbx/atrogin-1 and MuRF1), or autophagy related genes. The weakened IGF-1/PI3K/AKT pathway in type 2 diabetes is an important factor leading to skeletal muscle atrophy. Studies have shown that the commonly used anti-type 2 diabetic drugs have different effects in regulating the synthesis and degradation of skeletal muscle protein. Studies reported that drugs with effect of anti-diabetic muscle atrophy include thiazolidinediones, glucagon-like peptide analogs, glucose-sodium cotransporter 2 inhibitors, etc.; drugs that are still in controversial or even promote skeletal muscle atrophy include metformin, and some sulfonylurea or non-sulfonylurea insulin secretagogues. This article overviewed and analyzed the currently commonly used drugs for type 2 diabetes and summarized the related mechanisms, with the aim to provide references for the rational applications of drugs for type 2 diabetes.

Research progress of cystine/glutamate antiporter as drug targets / 药学学报

Cystine/glutamate antiporter [system Xc(-)] is a sodium independent amino acid transporter, which is a heterodimer composed of light chain subunit xCT and heavy chain subunit 4F2hc (CD98) through covalent disulfide bond. System Xc(-) typically mediates cystine uptake and glutamate output, helps to maintain the balance of glutamate, cystine and cysteine inside and outside the cell, regulates the level of glutamate inside and outside the membrane and the synthesis of intracellular glutathione, thus affecting oxidative stress and glutamate neurotoxicity. This review expounds the structure and function of system Xc(-), analyzes the role of the transporter in physiology and pathology, discusses the role and mechanism in different diseases, and discusses the specific research progress of system Xc(-) as a drug target. This review summarizes the research status of system Xc(-) and provides theoretical guidance for further research on system Xc(-) and drug discovery.

Identification of multi-target anti-cancer agents from TCM formula by in silico prediction and in vitro validation / 中国天然药物

Cancer is a complex disease associated with multiple gene mutations and malignant phenotypes, and multi-target drugs provide a promising therapy idea for the treatment of cancer. Natural products with abundant chemical structure types and rich pharmacological characteristics could be ideal sources for screening multi-target antineoplastic drugs. In this paper, 50 tumor-related targets were collected by searching the Therapeutic Target Database and Thomson Reuters Integrity database, and a multi-target anti-cancer prediction system based on mt-QSAR models was constructed by using naïve Bayesian and recursive partitioning algorithm for the first time. Through the multi-target anti-cancer prediction system, some dominant fragments that act on multiple tumor-related targets were analyzed, which could be helpful in designing multi-target anti-cancer drugs. Anti-cancer traditional Chinese medicine (TCM) and its natural products were collected to form a TCM formula-based natural products library, and the potential targets of the natural products in the library were predicted by multi-target anti-cancer prediction system. As a result, alkaloids, flavonoids and terpenoids were predicted to act on multiple tumor-related targets. The predicted targets of some representative compounds were verified according to literature review and most of the selected natural compounds were found to exert certain anti-cancer activity in vitro biological experiments. In conclusion, the multi-target anti-cancer prediction system is very effective and reliable, and it could be further used for elucidating the functional mechanism of anti-cancer TCM formula and screening for multi-target anti-cancer drugs. The anti-cancer natural compounds found in this paper will lay important information for further study.

Relationship between pesticide exposure and lipid metabolism in population / 中华劳动卫生职业病杂志

Objective: To investigate the effect of pesticides and herbicides on lipid metabolism. Methods: In November 2020, Based on the data of the national health and Nutrition Survey (NHANES) (2011-2014) , select the population aged 20~65 who have demographic information, pesticide use and data of four lipid metabolism indicators [total cholesterol (TC) , triglyceride (TG) , high density lipoprotein cholesterol (HDLC) and low density lipoprotein cholesterol (LDLC) ] (n=3039) . The subjects were divided into insecticide group (320 people) and non insecticide group (2719) according to the use of insecticides, and herbicide group (156 people) and non herbicide group according to the use of herbicides. Results: Among the 3039 subjects, the males and female were 1509 (49.7%) and 1530 (50.3%) respectively. The males age was (39.7±12.0) years and the females age was (40.2±12.0) years The concentration of HDLC in the NHANES (55.4±15.0) mg/dl was lower than that of (58.2±14.2) mg/dL in the non herbicide group (P<0.05) (b=-0.044, P<0.05) . The results showed that the use of herbicides was related to the decrease of HDLC and the increase of LDLC and LDLC/HDLC in female population (b=-0.050, 0.062, 0.067, all P<0.05) . Conclusion: Herbicide exposure can cause the change of lipid metabolism, and the effect on female population is more obvious.

Changes in the morphology and function of the meibomian glands in patients with type 2 diabetes mellitus and their effects on the function of tear film / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes of morphology and function of meibomian glands in patients with type 2 diabetes mellitus and its influence on the tear film. METHODS: A total of 52 patients(104 eyes)with type 2 diabetes mellitus who came to our hospital from January 2018 to January 2020 were selected. Then they were divided into non-diabetic retinopathy group(NDR group, 31 cases with 62 eyes)and diabetic retinopathy group(DR group, 21 cases with 42 eyes)according to the fundus changes. While 38 cases(76 eyes)of diabetic-free cataract patients who treated at the same time were selected as the control group. The differences of three groups were compared with the morphology and the scores of the function of lid edge and meibomian glands, the scores of fluorescence staining of cornea, break-up time(BUT)of tear film, lipid layer thickness(LLT), blink times(BT)and partial blink rate(PBR).RESULTS: The morphology and the scores of function of lid edge and meibomian glands, the scores of fluorescence staining of cornea were significantly higher than the control group, and the DR group was significantly higher than the NDR group(all P<0.05). The BUT in the DR group and NDR group was significantly lower than that in the control group, and the DR group was significantly lower than that in the NDR group(all P<0.05). There were differences in LLT, BT and PBR among the three groups(P<0.05). The LLT and BT in the DR group and NDR group were significantly lower than those in the control group, and PBR was significantly higher than that in control group(all P<0.05), but there was no significant difference between the DR group and the NDR group(all P>0.05). Type 2 diabetes mellitus patients with morphology abnormalities of meibomian gland have a higher incidence of abnormal tear film function.CONCLUSION: Patients with type 2 diabetes mellitus are prone to shortening and loss of meibomian glands, which is easy to cause the dysfunction of the meibomian gland and decrease the stability of the tear film. While the patients with DR, the morphology abnormalities and dysfunction of the meibomian glands are more pronounced, and the stability of the tear film is worse.

Effect of neoadjuvant chemotherapy on breast invasive ductal carcinoma and changes of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 and Ki67 in tissues / 中国综合临床

Objective:To observe the clinical effect on patients of invasive ductal carcinoma of the breast by neoadjuvant chemotherapy, and to analyze the changes of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER-2) and Ki67 in neoplasm.Methods:A total of 83 patients which were treated by neoadjuvant chemotherapy in breast invasive ductal carcinoma diagnosed were selected in North China University of Science and Technology Affiliated Hopital from January 2014 to December 2020. There were 30 cases of Luminal type A, 31 cases of Luminal type B, 10 cases of HER-2 positive type and 12 cases of triple negative type. To observe the clinical effect of different molecular subtypes, detect the expression of Er, PR, HER-2 and Ki67 in pathological tissues before and after neoadjuvant chemotherapy, and conduct a retrospective case-control study. Comparison between the two groups use χ2 test, matched χ2 and accurate probability method. Results:Fifty-eight cases were clinically effective, the total effective rate was 69.8% (58/83), and 9 cases were pathological complete response (pCR), accounting for 10.8% (9/83). After neoadjuvant chemotherapy, the highest clinical efficacy was luminal type B in 26 cases, and the highest PCR was triple negative type in 3 cases. The pathological results showed that the expression of ER (6 cases of positive expression were increased, χ2=1.03, P=0.310), PR (8 cases of positive expression were increased, χ2=1.56, P=0.210) and HER-2 (2 cases of positive expression were decreased, χ2=0.10, P=0.748) was not different before and after neoadjuvant chemotherapy. The expression of Ki67 was decreased in 25 cases (30.1%) after chemotherapy compared with 59 cases (71.1%) before chemotherapy (34 cases of positive expression were decreased, χ2=27.85, P<0.001). Five cases were added among Luminal type A after chemotherapy, all of which were transformed from Luminal type B, but the kappa value was 0.919 (>0.75), the consistency rate was 91.9%. The consistency was idea before and after chemotherapy. Five cases were added after Luminal type A chemotherapy, all of which were transformed from Luminal type B, but the kappa value was 0.919 ( P>0.75), and the consistency rate was 91.9%,The consistency before and after chemotherapy was good. After chemotherapy, HER-2 expression remained unchanged in 59 cases (clinically effective in 48 cases), up-regulated in 9 cases (clinically effective in 4 cases) and down regulated in 15 cases (clinically effective in 6 cases)( χ2=12.82, P=0.002). Ki67 expression remained unchanged in 35 cases (20 cases were clinically effective), up-regulated in 7 cases (2 cases were clinically effective) and down regulated in 41 cases (36 cases were clinically effective)( χ2=14.63, P=0.001). Conclusion:The clinical effect of neoadjuvant chemotherapy in the treatment of breast invasive ductal carcinoma is ideal. The clinical effective rate of Luminal B type is the highest, and the pCR rate of triple negative type is the highest.And it can significantly reduce the expression of Ki67. The down-regulation of HER-2 and Ki67 is significant for clinical efficiency.

Use of network pharmacology to analyze compound reserpine and triamterene tablets in the treatment of hypertension / 药学学报

Compound reserpine and triamterene tablets (CRTT), a compound antihypertensive drug developed by Chinese scientists, is still widely used in clinical practice. However, the mechanisms by which CRTT treats hypertension remain to be fully understood. This study used network pharmacology to analyze CRTT's antihypertensive mechanisms with in vitro experiments. The targets of the four chemical components of CRTT were collected from the Swiss Target Prediction database; 1 828 protein targets related to hypertension were collected from the Therapeutic Target Database (TTD) and Online Mendelian Inheritance in Man (OMIM) database. The CRTT-hypertension network model was constructed using a search tool for recurring instances of neighbouring genes (STRING). Gene ontology (GO) and pathway enrichment analysis of targets of interest was conducted with the Metascape database. In the in vitro study, human umbilical vein endothelial cells (HUVEC) and vascular smooth muscle cells (VSMC) were treated with 1 μmol·L-1 angiotensin Ⅱ (AngⅡ) and CRTT was administered at concentrations of 0.01, 0.1, and 1 μmol·L-1. Changes in the phosphatidylinositol-3-kinase/protein serine threonine kinase/endothelial nitric oxide synthase (PI3K/Akt/eNOS) pathway in HUVEC and the cyclic guanosine monophosphate/cGMP-dependent protein kinase (cGMP/PKG) pathway in VSMC were determined by Western blot. Network pharmacological analysis revealed that the antihypertensive effect of CRTT is closely associated with biological pathways such as vascular tone regulation, adrenergic receptor activation, protein kinase activity and signaling pathways such as the cGMP/PKG signaling pathway, vascular smooth muscle contraction, neuroactive ligand-receptor interaction, adrenergic signaling in cardiomyocytes and calcium signaling pathways. The in vitro study confirmed that CRTT increased the levels of phosphorylated phosphatidylinositol-3-kinase (p-PI3K), phosphorylated protein serine threonine kinase (p-Akt), phosphorylated endothelial nitric oxide synthase (p-eNOS) in HUVEC and the levels of eNOS, phosphorylated vasodilator-stimulated phosphoprotein (p-VASP), and PKG in VSMC through multiple targets and pathways. These results suggest that the activation of PI3K/Akt/eNOS pathway and endothelial-dependent NO/cGMP signaling may be involved in the CRTT-mediated hypotensive effect.

Da Chaihutang Protects Liver Mitochondrial Function of Nutritionally Obese Rats via CREB/PGC-1α Pathway / 中国实验方剂学杂志

Objective:To observe the effects of Da Chaihutang on Cyclic adenosine monophosphate （cAMP）-response element binding protein （CREB）/peroxisome proliferator-activated receptor-gamma coactivator-1 alpha （PGC-1<italic>α</italic>） pathway in nutritionally obese rats and the protective mechanism on liver mitochondria. Method:A total of 120 8-week-old male SD rats were randomly divided into a control group （<italic>n</italic>=20） and an experimental group （<italic>n</italic>=100）. The rats in the control group were fed on a normal diet， while those in the experimental group were administered with a high-fat feed. Successfully modeled rats were randomly divided into a model group， a positive drug （metformin） group， and low-， medium- and high-dose Da Chaihutang groups （4.25， 8.5， and 17 g∙kg^-1， respectively）， with 20 rats in each group. After treatment with Da Chaihutang， the body weight， Lee's index， liver mitochondrial membrane potential and mitochondrial ultrastructure， PGC-1<italic>α </italic>expression and CREB phosphorylation of each group were measured and compared. Result:Compared with the control group， the model group showed increased body weight and Lee's index （<italic>P</italic><0.01）， whereas decreased mitochondrial membrane potential， PGC-1<italic>α</italic> expression， and CREB phosphorylation level （<italic>P</italic><0.01）. As compared with the model group， Da Chaihutang significantly reduced the body weight and Lee's index of obese rats （<italic>P</italic><0.05， <italic>P</italic><0.01）， enhanced liver mitochondrial membrane potential （<italic>P</italic><0.05， <italic>P</italic><0.01） to protect the integrity of mitochondrial structure， up-regulated PGC-1<italic>α</italic> expression and promoted CREB phosphorylation （<italic>P</italic><0.05， <italic>P</italic><0.01）. Conclusion:Da Chaihutang protects the structure and function of mitochondria and inhibits weight gain in obese rats by activating the CREB/PGC-1<italic>α</italic> pathway.

Polarized activation affects iron metabolism in macrophages / 生理学报

The aim of this study was to investigate the effects of polarization program on the ability of macrophages to regulate iron metabolism. M1 and M2 macrophages were propagated in vitro from porcine alveolar macrophages 3D4/2 and polarized by cytokines. The 3D4/2 macrophages were treated with 20 ng/mL interferon gamma (IFN-γ) and 10 ng/mL interleukin-4 (IL-4) combined with 10 ng/mL macrophage colony-stimulating factor (M-CSF) to induce polarization to M1 and M2, respectively. After incubation for 24 h, the expression levels of inflammatory factors and iron-metabolism genes were determined using real-time qPCR, Western bot and immunofluorescence. The M1/M2 macrophages culture media supernatant was collected and used to treat porcine intestinal epithelial cells IPEC-J2. The proliferation ability of IPEC-J2 was detected using CCK-8 assay kit. Following exogenous addition of ammonium ferric citrate (FAC) to M1/M2 macrophages, the phagocytic function of macrophages was detected using fluorescein isothiocyanate-dextran (FITC-dextran) and flow cytometry. The results showed that, compared with control, M1 macrophages had higher mRNA levels of iron storage proteins (ferritin heavy and light polypeptide, i.e. FtH and FtL), hepcidin and lipocalin-2, as well as iron content. Moreover, iron enhanced the ability of M1 macrophages to phagocytize FITC-dextran. There was no significant change in these mRNA expression levels in M2 macrophages, but the mRNA expression levels of ferroportin and transferrin receptor were up-regulated. In addition, the conditioned media supernatant from M2 macrophages promoted cell proliferation of IPEC-J2. These findings indicate that M1 macrophages tend to lock iron in the cell and reduce extracellular iron content, thereby inhibiting the proliferation of extracellular bacteria. While M2 macrophages tend to excrete iron, which contributes to the proliferation of surrounding cells and thus promotes tissue repair.

Mitochondrial retrograde signaling: a new option for the treatment of mitochondrially related diseases / 药学学报

Mitochondria play a key role in cell metabolism. In addition to synthesizing ATP, they also participate in many physiological and pathological processes, including apoptosis, inflammation, oxidative stress, neuronal disease, tumor development, and aging. Most gene transcription of mitochondrial proteins occurs in the nucleus, so the biogenesis of mitochondria and the maintenance of mitochondrial homeostasis mainly depend on the expression of nuclear genes (nDNA) and mitochondria-nucleus interactions. Conversely, mitochondria can affect the expression of nuclear genes through nuclear transcription factors, a process called mitochondrial retrograde signaling. This review summarizes the research progress on mitochondria-nucleus retrograde signaling and its regulation, including the ways by which mitochondria regulate nuclear genes and affect biological processes, and discusses new strategies for the treatment of diseases that involve mitochondrial retrograde signaling in disease pathology.

Research advances on the protective effects and mechanism of salvianolic acids against ischemic heart disease / 药学学报

Salvianolic acids are the main water-soluble active compounds of Salvia miltiorrhiza and have been widely used for the treatment of cardiovascular diseases. Based on the latest studies in China and abroad, we summarize the pharmacological effects and mechanism of salvianolic acids on ischemic heart disease by describing how salvianolic acid A and salvianolic acid B protect the vascular endothelium, relax coronary arteries, promote angiogenesis and anti-platelet aggregation, inhibit the inflammatory response, anti-cell apoptosis, and scavenge free radicals. This review provides a theoretical basis for further research on the effects of salvianolic acids on ischemic heart disease and their potential for drug development.

Evaluation of the preventive effect of DL0805-2 against monocrotaline induced rat pulmonary arterial hypertension / 药学学报

In the treatment of hypertensive crisis, the novel Rho kinase inhibitor DL0805-2 can rapidly lower systematic blood pressure, reduce pulmonary artery pressure, and has a significant protective effect on lung injury. This experiment intends to evaluate the efficacy of DL0805-2 against pulmonary arterial hypertension (PAH) and preliminarily reveals its underlying mechanism. Animal welfare and experimental procedures are in accordance with the provision of the Animal Ethics Committee of the Institute of Materia Medica, Chinese Academy of Medical Sciences. Sprague Dawley (SD) rats were randomly divided into DL0805-2 low, medium, and high dose groups (1, 3, and 10 mg·kg-1), bosentan positive control group, model group, and blank control group. The drug was administered daily on the 7th day after model establishment by monocrotaline injection. On the 25th day of the experiment, relevant indicators were examined to observe the therapeutic effect of DL0805-2 on pulmonary hypertension. DL0805-2 significantly relieved the abnormal changes in the physiological parameters related to PAH induced by monocrotaline, including reducing right ventricular systolic pressure, alleviating cardiac damage caused by pressure overload, and reducing the levels of endothelin-1 and inflammatory factors in lung tissues. DL0805-2 also attenuated pulmonary arteries remodeling. It was preliminarily discovered that DL0805-2 exerts preventive and therapeutic effect on PAH through Rho-kinase pathway. Our results suggested that DL0805-2 had good therapeutic effects on monocrotaline-induced PAH rat model. It intervened early in the disease process, effectively prevented the development of the disease, and reduced the mortality of the diseased animals. The mechanism is related to Rho-kinase pathway.

α4β2-Nicotine acetylcholine receptor: advances in relevant diseases and drugs / 药学学报

The α4β2-nicotinic acetylcholine receptor (nAChR) is a ligand-gated ion channel that is distributed throughout the nervous system. It is involved in the regulation of various neurotransmitters including acetylcholine, dopamine, γ-aminobutyric acid, and norepinephrine. α4β2-nAChR plays an important role in learning, memory, cognition, attention, inflammation, and pain. A large number of studies have shown that α4β2-nAChR is an important therapeutic target for neurological diseases such as Alzheimer's disease, Parkinson's disease, epilepsy, depression, nicotine dependence, pain, etc. It is an important target in the early diagnosis and curative effect detection of neurodegenerative diseases including Alzheimer's disease. This review summarizes the role, mechanisms and related drug research advances on α4β2-nAChR ligand drugs in neurological diseases, as well as providing a theoretical basis for identifying and developing more suitable α4β2-nAChR-related compounds.

Research progress of circadian rhythm / 中国中药杂志

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

Puerarin protects against myocardial ischemia/reperfusion injury by suppressing NLRP3 inflammasome activation via TLR4/Myd88/NF-κB pathway in rats / 药学学报

This study was to investigate the protective effects of puerarin on myocardial ischemia/reperfusion (MI/R) injury and the underlying mechanism. The MI/R-model was established by ligating the left anterior descending artery (LAD) for 60 min followed by 24 h reperfusion, puerarin (10, 30, and 100 mg·kg-1) was orally administered 20 min before reperfusion. Cardiac function, myocardial infarct index, cardiac damage markers, inflammatory cytokines, and apoptosis index were measured to evaluate the protective effects of puerarin on MI/R injury. The activation of Nod-like receptor protein 3 (NLRP3) inflammasome and Toll like receptor 4 (TLR4)/myeloid differentiation factor 88 (Myd88)/nuclear factor kappa B (NF-κB) pathway were determined by Western blot. All animal experimental procedures were approved by the ethics committee of the Institute of Materia Medica, Peking Union Medical College, Chinese Academy of Medical Sciences. The results showed that puerarin could significantly improve cardiac function, reduce myocardial infarct size, decease the levels of lactic dehydrogenase (LDH), aspartate transaminase (AST), creatine kinase-MB (CK-MB), and cardiac troponin T (cTnT) and suppress cardiomyocyte apoptosis. Meanwhile, puerarin could notably decrease the levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Western blot analysis revealed that puerarin could downregulate the expression of TLR4, Myd88, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), cleaved-caspase 1, cleaved-gasdermin-D (GSDMD), IL-1β, and IL-18, as well as the phosphorylation levels of inhibitor of NF-κB α (IκBα), IκB kinase β (IKKβ), and NF-κB. These findings demonstrated that puerarin could alleviate MI/R injury by suppressing NLRP3 inflammasome activation, possibly via TLR4/Myd88/NF-κB pathway.

Progress on the application of artificial intelligence technology in ligand-based and receptor structure-based drug screening / 药学学报

Artificial intelligence technology is being widely applied in drug screening. This paper introduces the characteristics of artificial intelligence, and summarizes the application and progress of artificial intelligence technology especially deep learning in drug screening, from ligand-based and receptor structure-based aspects. This paper also introduces how to apply artificial intelligence to drug design from these two aspects. Finally, we discuss the main limitations, challenges, and prospects of artificial intelligence technology in the field of drug screening.

Research progress of natural drugs targeting mitochondrial autophagy against ischemic heart disease / 药学学报

Ischemic heart disease (IHD), which has been considered to be exclusively caused by stenosis or occlusion of coronary artery, is a significant cause of morbidity and mortality worldwide. Mitochondrial dysfunction is the main pathological basis of ischemic heart disease and reperfusion injury, and moderate mitochondrial autophagy can selectively remove damage proteins and organelles to maintain intracellular homeostasis, so mitochondrial autophagy is important for maintaining the homeostasis of cardiomyocytes. Natural drugs from plants are widely used in ischemic heart disease. In recent years, more and more natural drugs have been proven to alleviate myocardial cell damage after ischemia/reperfusion through mitochondrial autophagy. This paper reviews the research progress of natural drugs from plants medicines regulating mitochondrial autophagy in the treatment of ischemia heart disease.