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1.
Adv Rheumatol ; 63: 42, 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1513562

RESUMO

Abstract Background The etiology of systemic lupus erythematosus is complex and incurable. A large number of systematic reviews have studied the risk factors of it. Mendelian randomization is an analytical method that uses genetic data as tool variables to evaluate the causal relationship between exposure and outcome. Objective To review the systematic reviews and Mendelian randomization studies that focused on the risk factors of systemic lupus erythematosus and shed light on the development of treatments for its prevention and intervention. Methods From inception to January 2022, we systematically searched MEDLINE (via PubMed) and Embase for related systematic reviews and Mendelian randomization studies. Extract relevant main data for studies that meet inclusion criteria. The quality of systematic reviews was assessed by using Assessment of Multiple Systematic Reviews 2 (AMSTAR-2). Finally, the risk factors are scored comprehensively according to the results' quantity, quality, and consistency. Results Our study involved 64 systematic reviews and 12 Mendelian randomization studies. The results of systematic reviews showed that diseases (endometriosis, atopic dermatitis, allergic rhinitis), lifestyle (smoking, drinking, vaccination), and gene polymorphism influenced the incidence of systemic lupus erythematosus. The results of Mendelian randomization studies identified the role of disease (periodontitis, celiac disease), trace elements (selenium, iron), cytokines (growth differentiation factor 15), and gut microbiome in the pathogenesis of systemic lupus erythematosus. Conclusion We should pay attention to preventing and treating systemic lupus erythematosus in patients with endometriosis, celiac disease, and periodontitis. Take appropriate dietary supplements to increase serum iron and selenium levels to reduce the risk of systemic lupus erythematosus. There should be no excessive intervention in lifestyles such as smoking and drinking.

2.
China Journal of Chinese Materia Medica ; (24): 5-12, 2023.
Artigo em Chinês | WPRIM | ID: wpr-970495

RESUMO

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.


Assuntos
Humanos , Esclerose Múltipla/patologia , Remielinização/fisiologia , Bainha de Mielina/patologia , Inflamação/tratamento farmacológico , Homeostase
3.
China Journal of Chinese Materia Medica ; (24): 311-320, 2023.
Artigo em Chinês | WPRIM | ID: wpr-970467

RESUMO

Atherosclerosis(AS) is the common pathological basis of many ischemic cardiovascular diseases, and its formation process involves various aspects such as vascular endothelial injury and platelet activation. Vascular endothelial injury is the initiating factor of AS plaque. Monocytes are recruited to differentiate into macrophages at the damaged endothelial cells, which absorb oxidized low-density lipoprotein(ox-LDL) and slowly transform into foam cells. Smooth muscle cells(SMCs) proliferate and migrate continuously. As the only cell producing interstitial collagen fibers in the fibrous cap, SMCs largely determine whether the plaque ruptured or not. The amplifying inflammatory response during the formation of AS recruits platelets to adhere to the damaged area of vascular endothelium and stimulates excessive platelet aggregation. Autophagy activity is associated with vascular lesions and abnormal platelet activation, and excessive autophagy is considered to be a negative factor for plaque stability. Therefore, precise regulation of different types of vascular autophagy and platelet autophagy to treat AS may provide a new therapeutic perspective for the prevention and treatment of atherosclerotic ischemic cardiovascular disease. Currently, treatment strategies for AS still focus on lowering lipid levels with high-intensity statins, which often cause significant side effects. Therefore, the development of safer and more effective drugs and treatment modes is the focus of current research. Traditional Chinese medicine and natural compounds have the potential to treat AS by targeted autophagy, and have been playing an increasingly important role in the prevention and treatment of cardiovascular diseases in China. This paper summarizes the experimental studies on different vascular cell types and platelet autophagy in AS, and sums up the published research results on targeted autophagy of traditional Chinese medicine and natural plant compounds to regulate AS, providing new ideas for further research.


Assuntos
Humanos , Células Endoteliais/metabolismo , Doenças Cardiovasculares , Medicina Tradicional Chinesa , Aterosclerose/prevenção & controle , Lipoproteínas LDL/metabolismo , Endotélio Vascular , Placa Aterosclerótica , Autofagia
4.
Chinese Journal of Contemporary Pediatrics ; (12): 205-209, 2023.
Artigo em Chinês | WPRIM | ID: wpr-971061

RESUMO

Extracorporeal carbon dioxide removal is an artificial lung auxiliary technique based on extrapulmonary gas exchange and can effectively remove carbon dioxide and provide oxygenation to a certain extent, and it is one of the effective treatment techniques for hypercapnia developed after mechanical ventilation and extracorporeal membrane oxygenation in recent years and has wide application prospect. This article elaborates on the development, working principle, advantages, classification, complications, and clinical application of extracorporeal carbon dioxide removal, so as to provide a new choice for extracorporeal carbon dioxide removal in clinical practice.


Assuntos
Humanos , Dióxido de Carbono , Oxigenação por Membrana Extracorpórea , Diálise Renal , Respiração Artificial
5.
China Journal of Chinese Materia Medica ; (24): 2360-2367, 2023.
Artigo em Chinês | WPRIM | ID: wpr-981312

RESUMO

This study explored the effect and underlying mechanism of Stellera chamaejasme extract(SCE) on multidrug resistance of breast cancer. The chemotherapy-sensitive breast cancer cell line MCF-7 and adriamycin(ADR)-resistant cell line MCF-7/ADR were used as experimental subjects. MTT assay was used to detect cell proliferation activity. Pi staining was used to detect the cell cycle. 4',6-Diamidino-2-phenylindole, dihydrochloride(DAPI) staining and flow cytometry were used to detect apoptosis. Dansylcadaverine(MDC) staining and GFP-LC3B-Mcherry adenovirus transfection were used to detect autophagy. The protein expression of Bcl-2, Bax, caspase-9, caspase-3, LC3B, p62, and Beclin-1 was detected by Western blot. The results showed that SCE could significantly inhibit the proliferation of both sensitive and resistant breast cancer cell lines. The drug resistance factor was 0.53, which was significantly lower than 59 of ADR. Meanwhile, the proportion of sensitive/resistant cells in the G_0/G_1 phase increased significantly after SCE treatment. In addition, DAPI staining showed that a series of apoptosis phenomena such as nuclear pyknosis, staining deepening, and nuclear fragmentation appeared in sensitive/resistant cell lines after SCE administration. Moreover, the results of flow cytometry double staining showed that the proportion of apoptotic cells in sensitive/resistant cell lines increased significantly after SCE administration. Besides, Western blot showed that the protein expression levels of caspase-3, caspase-9, and Bcl-2 significantly decreased and the expression level of Bax protein significantly increased in both breast cancer cell lines after SCE administration. Furthermore, SCE could also increase the positive fluorescent spots after MDC staining and yellow fluorescent spots after GFP-LC3B-mcherry transfection, and up-regulate the expression levels of autophagy-related proteins LC3B-Ⅱ, p62, and Beclin-1 in breast cancer cells. In summary, SCE may play the role of anti-multidrug resistance by blocking the cell cycle of breast cancer multidrug-resistant cells, blocking autophagy flow, and ultimately interfering with the apoptosis resistance of drug-resistant cells.


Assuntos
Humanos , Feminino , Neoplasias da Mama/metabolismo , Células MCF-7 , Caspase 3/metabolismo , Caspase 9/metabolismo , Proteína Beclina-1/farmacologia , Apoptose , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Proliferação de Células
6.
Chinese Medical Sciences Journal ; (4): 77-93, 2023.
Artigo em Inglês | WPRIM | ID: wpr-981599

RESUMO

Background In mainland China, patients with neovascular age-related macular degeneration (nAMD) have approximately an 40% prevalence of polypoidal choroidal vasculopathy (PCV). This disease leads to recurrent retinal pigment epithelium detachment (PED), extensive subretinal or vitreous hemorrhages, and severe vision loss. China has introduced various treatment modalities in the past years and gained comprehensive experience in treating PCV.Methods A total of 14 retinal specialists nationwide with expertise in PCV were empaneled to prioritize six questions and address their corresponding outcomes, regarding opinions on inactive PCV, choices of anti-vascular endothelial growth factor (anti-VEGF) monotherapy, photodynamic therapy (PDT) monotherapy or combined therapy, patients with persistent subretinal fluid (SRF) or intraretinal fluid (IRF) after loading dose anti-VEGF, and patients with massive subretinal hemorrhage. An evidence synthesis team conducted systematic reviews, which informed the recommendations that address these questions. This guideline used the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach to assess the certainty of evidence and grade the strengths of recommendations. Results The panel proposed the following six conditional recommendations regarding treatment choices. (1) For patients with inactive PCV, we suggest observation over treatment. (2) For treatment-na?ve PCV patients, we suggest either anti-VEGF monotherapy or combined anti-VEGF and PDT rather than PDT monotherapy. (3) For patients with PCV who plan to initiate combined anti-VEGF and PDT treatment, we suggest later/rescue PDT over initiate PDT. (4) For PCV patients who plan to initiate anti-VEGF monotherapy, we suggest the treat and extend (T&E) regimen rather than the pro re nata (PRN) regimen following three monthly loading doses. (5) For patients with persistent SRF or IRF on optical coherence tomography (OCT) after three monthly anti-VEGF treatments, we suggest proceeding with anti-VEGF treatment rather than observation. (6) For PCV patients with massive subretinal hemorrhage (equal to or more than four optic disc areas) involving the central macula, we suggest surgery (vitrectomy in combination with tissue-plasminogen activator (tPA) intraocular injection and gas tamponade) rather than anti-VEGF monotherapy. Conclusions Six evidence-based recommendations support optimal care for PCV patients' management.

7.
Acta Pharmaceutica Sinica ; (12): 1593-1603, 2022.
Artigo em Chinês | WPRIM | ID: wpr-929433

RESUMO

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.

8.
Acta Pharmaceutica Sinica ; (12): 1887-1894, 2022.
Artigo em Chinês | WPRIM | ID: wpr-929416

RESUMO

This study aims to construct a dynamic two-dimensional characterization technique for the hygroscopicity of traditional Chinese medicine extracts and investigate the effect of material properties of powders on hygroscopicity. The dynamic hygroscopicity-time curves of the powders were measured at 25 ℃ and 75% humidity, and the semi-equilibrium hygroscopicity time (t1/2) and equilibrium hygroscopicity (F∞) were derived as two-dimensional evaluation indicators. Finally, the correlation between the material properties and the hygroscopic behavior was analyzed by principal component analysis (PCA) and partial least squares analysis (PLS). The results showed that the dynamic two-dimensional characterization system of hygroscopicity constructed with 1/t1/2 = 0.1 h-1 and F∞ = 15% as the center can classify the hygroscopic behavior of traditional Chinese medicine extracts into four categories: fast hygroscopicity with strong hygroscopicity, slow hygroscopicity with strong hygroscopicity, fast hygroscopicity with weak hygroscopicity and slow hygroscopicity with weak hygroscopicity. The moisture absorption was negatively correlated with D50, D90, ρb and ρt; the moisture absorption rate was negatively correlated with D10, D50, D90, ρb, ρt, and positively correlated with moisture content. The hygroscopicity dynamic two-dimensional characterization indicators of Chinese medicine extracts (CMEs) constructed in this study matched with the physical properties. The method of dynamic multi-dimensional characterization technology is feasible and scientific, and the idea has strong promotional value.

9.
Protein & Cell ; (12): 26-46, 2022.
Artigo em Inglês | WPRIM | ID: wpr-922494

RESUMO

In vitro studies have established the prevalent theory that the mitochondrial kinase PINK1 protects neurodegeneration by removing damaged mitochondria in Parkinson's disease (PD). However, difficulty in detecting endogenous PINK1 protein in rodent brains and cell lines has prevented the rigorous investigation of the in vivo role of PINK1. Here we report that PINK1 kinase form is selectively expressed in the human and monkey brains. CRISPR/Cas9-mediated deficiency of PINK1 causes similar neurodegeneration in the brains of fetal and adult monkeys as well as cultured monkey neurons without affecting mitochondrial protein expression and morphology. Importantly, PINK1 mutations in the primate brain and human cells reduce protein phosphorylation that is important for neuronal function and survival. Our findings suggest that PINK1 kinase activity rather than its mitochondrial function is essential for the neuronal survival in the primate brains and that its kinase dysfunction could be involved in the pathogenesis of PD.

10.
China Journal of Chinese Materia Medica ; (24): 3402-3409, 2021.
Artigo em Chinês | WPRIM | ID: wpr-887991

RESUMO

This study aimed to investigate the effect and the possible mechanism of Shenlian( SL) extract on tumor necrosis factor-α( TNF-α)-induced ECV304 injury. After the establishment of TNF-α-induced ECV304 cells injure model,MTT assay was used to detect cell viability and the level of reactive oxygen species( ROS) was measured by flow cytometry. The contents of superoxide dismutase( SOD),malondialdehyde( MDA),nitric oxide( NO),endothelin-1( ET-1) and interleukin-1β( IL-1β) in the supernatant were detected by biochemical method and enzyme linked immunosorbent assay( ELISA). The expression levels of apoptosis-related proteins B-lymphoma-2 gene( Bcl-2),Bcl-2 associated X protein( Bax),caspase-3,caspase-9 and nuclear factor E2 associated factor2( Nrf2)/Kelch like epichlorohydrin associated protein-1( Keap1) signaling pathway related proteins Nrf2,Keap1,quinone oxidoreductase( NQO1) and heme oxygenase 1( HO-1) were detected by Western blot. The results showed that 50 μg·L-1 TNF-α significantly damaged ECV304 cells,induced the impairment of cell viability( P<0. 01),the increase of ROS production,the decrease of SOD activity,and the increase of MDA,NO,ET-1 and IL-1β( P<0. 01),meanwhile,it caused the up-regulation of Keap1,caspase-9 and Bax protein expression,and down-regulation of NQO1 and Bcl-2 protein expression( P<0. 05) compared with the control group.Compared with the model group,SL extract reduced the damage of ECV304 cells induced by TNF-α,improved cell viability,reduced ROS production,increased SOD activity and decreased MDA,NO,ET-1,IL-1β content( P<0. 01 or P<0. 05). In addition,SL extract also down-regulated the protein expression levels of Keap1,caspase-3,caspase-9 and Bax,and increased the protein expressions of Nrf2,NQO1,HO-1 and Bcl-2( P<0. 01 or P<0. 05). The above results indicate that SL extract can provide protective effect on ECV304 cells injury induced by TNF-α,alleviate oxidative stress injury,inflammation and apoptosis,and its mechanism may be related to regulating Nrf2/Keap1 signaling pathway.


Assuntos
Apoptose , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Extratos Vegetais , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética
11.
Acta Pharmaceutica Sinica ; (12): 2048-2058, 2021.
Artigo em Chinês | WPRIM | ID: wpr-887059

RESUMO

At present, the modernization of Chinese medicine preparations (CMPs) is still a challenging task. The 3 typical Chinese medicine materials (CMMs) used for preparing CMPs are the powders, extracts, and components of Chinese medicine and their properties of CMMs are important for designing CMPs. Basing on our long term research, we have established a property system for CMMs according to the state of CMMs under an exactly condition and according to the interaction characteristics between substances. The property system could be divided into 5 categories: material composition, spatial structure, body property, surface property, physicochemical properties, and they could also be divided into 18 subcategories. Furthermore, we also established the corresponding index and characterization system, where the 61 indexes and characterization techniques were systematically summarized. At last, we hope that the article will promote the modernization of CMPs.

12.
Cancer Research and Treatment ; : 223-232, 2021.
Artigo em Inglês | WPRIM | ID: wpr-874355

RESUMO

Purpose@#The evidence of adherence to cancer prevention guidelines and endometrial cancer (EC) risk has been limited and controversial. This study summarizes and quantifies the relationship between adherence to cancer prevention guidelines and EC risk. @*Materials and Methods@#The online databases PubMed, Web of Science, and EMBASE were searched for relevant publications up to June 2, 2020. This study had been registered at PROSPERO. The registration number is CRD42020149966. Study quality evaluation was performed based on the Newcastle-Ottawa Scale. The I2 statistic was used to estimate heterogeneity among studies. Egger’s and Begg’s tests assessed potential publication bias. Summary hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between adherence to cancer prevention guidelines score was assigned to participants by summarizing individual scores for each lifestyle-related factor. The scores ranged from least healthy (0) to most healthy (20) and the EC risk was calculated using a randomeffects model. @*Results@#Five prospective studies (four cohort studies and one case‑cohort study) consisted of 4,470 EC cases, where 597,047 participants were included. Four studies had a low bias risk and one study had a high bias risk. Summary EC HR for the highest vs. lowest score of adherence to cancer prevention guidelines was 0.54 (95% CI, 0.40 to 0.73) and had a high heterogeneity (I2=86.1%). For the dose-response analysis, an increment of 1 significantly reduced the risk of EC by 6%. No significant publication bias was detected. @*Conclusion@#This study suggested that adherence to cancer prevention guidelines was negatively related to EC risk.

13.
Chinese Journal of Practical Nursing ; (36): 1218-1222, 2021.
Artigo em Chinês | WPRIM | ID: wpr-883136

RESUMO

Objective:To translate the Anticoagulation Knowledge Tool(AKT) into Chinese,and to test its reliability and validity in patients with atrial fibrillation.Methods:After obtaining the authorization of the original author, the Brislin cross-cultural translation method was used to translate from the original, back translate and cross-cultural adaptation of AKT to form the Chinese version of AKT. The reliability and validity were tested in 147 patients with atrial fibrillation from January to June in 2020 in Ruijin Hospital, Shanghai Jiaotong University School of Medicine.Results:The Chinese version retained 20 items of the original questionnaire,with the item content validity index of 0.857-1.000 and the average scale content validity index of 0.85. The Cronbach alpha coefficient was 0.812 and test-retest coefficient was 0.781.Conclusions:The Chinese version of AKT has been proved to be valid and reliable, which can be used to assess anticoagulation knowledge of patients with atrial fibrillation.

14.
China Journal of Chinese Materia Medica ; (24): 6020-6027, 2021.
Artigo em Chinês | WPRIM | ID: wpr-921759

RESUMO

This study was designed to investigate the correlations of the spatial structure properties of Chinese medicinal extracts with hygroscopicity and the anti-hygroscopic techniques. With Poria extract used as the model drug, pregelatinised starch and microcrystalline cellulose at different ratios were added into Poria fluid extract for preparing powder particles with diverse spatial structures using different drying processes. Then, their hygroscopic behaviours were characterized by equilibrium hygroscopicity(F~∞) and semi-hygroscopic time(t_(1/2)). The correlations of the hygroscopicity of each powder with the spatial structure properties such as particle size(D_(90)), porosity(ε), true density(ρ_t), and surface element distribution were analyzed using partial least-squares method. The F~∞ and t_(1/2) values of Poria extract prepared by three drying methods were sorted in a descending order as follows: F~∞(spray drying>drying at ordinary pressure>drying at reduced pressure); t_(1/2)(drying at reduced pressure>drying at ordinary pressure>spray drying). The powder obtained by spray drying showed a spherical structure with the smallest particle size and intra-particle ε but relatively stronger hygroscopicity. The large-scale surface element enrichment of the powders dried by reduced pressure effectively reduced their hygroscopicity. F~∞ and t_(1/2) were negatively correlated with ε but positively with D_(90), and the interactive influence of each spatial structural properties was not significant. There existed a correlation between the spatial structure of the powder particles of Chinese medicine extracts and their hygroscopicity, and the hygroscopicity could be improved by designing the spatial structure. This study has provided some practical basis for developing the moisture-proof technology of Chinese medicinal preparations.


Assuntos
China , Tamanho da Partícula , Extratos Vegetais , Pós , Tecnologia , Molhabilidade
15.
Chinese Journal of Pharmacology and Toxicology ; (6): 765-766, 2021.
Artigo em Chinês | WPRIM | ID: wpr-909599

RESUMO

OBJECTIVE To explore the potential molecular mechanism of Shenlian (SL) on myocardial ischemia (MI) on the basis of network pharmacology. METHODS Firstly, the main active ingredients of SL were screened in the Traditional Chinese Medicine Integrated Database, and the MI-associated targets were collected from the DisGeNET database. Then, we used compound-target and target-pathway networks to uncover the therapeutic mechanisms of SL. On the basis of network pharmacology analysis results, we assessed the effects of SL in MI rat model and oxygen glu?cose deprivation model of H9c2 cells and validated the possible molecular mechanisms of SL on myocardial injury in vivo and in vitro. RESULTS The network pharmacology results showed that 37 potential targets were recognized, including TNF-α, Bcl-2, STAT3, PI3K, and MMP2. The pathways revealed that the possible targets of SL were involved in the reg?ulation of inflammation and apoptosis signaling pathway. Then, in vivo experiments indicated that SL significantly reduced the myocardial infarction size of MI rats. Serum CK-MB, cTnT, CK, LDH, and AST levels were significantly decreased by SL (P<0.05 or P<0.01). In vitro, SL significantly increased H9c2 cell viability. The levels of inflammation factors including TNF-α and MMP2 were significantly decreased by SL (P<0.05 or P<0.01). TUNEL and Annexin V/propidium iodide assays indicated that SL could significantly decrease the cell apoptotic rate in vivo and in vitro (P<0.05 or P<0.01). The remarkable upregulation of anti-apoptotic Bcl-2 and downregulation of pro-apoptotic Bax protein level further confirmed this result. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the PI3K-Akt and JAK2-STAT3 pathways were significantly enriched in SL. Compared with the model group, SL treatment significantly activated the PI3K-Akt and JAK2-STAT3 pathways in vivo and in vitro according to Western blotting analyses. CONCLU?SION SL could protect the myocardium from MI injury. The underlying mechanism may be related to the reduction of inflammation and apoptosis by activating the PI3K/Akt and JAK2/STAT3 pathways.

16.
Acta Pharmaceutica Sinica ; (12): 3540-3546, 2021.
Artigo em Chinês | WPRIM | ID: wpr-906839

RESUMO

ZSP1601, a novel pan-phosphodiesterase inhibitor is in development for the treatment of nonalcoholic steatohepatitis. A physiologically-based pharmacokinetic (PBPK) model was developed to predict the pharmacokinetics of ZSP1601 in human. The PBPK model following intravenous and oral dose of ZSP1601 in rats and dogs was firstly built using preclinical in vitro and in vivo data. The PBPK model in human was then built based on models in animal. The in vitro-in vivo extrapolation (IVIVE) method and some allometric scaling methods were used to predict the clearance in human, respectively. The PBPK models using IVIVE and allometry of unbound CL plus the rule of exponents methods predicted the pharmacokinetics of ZSP1601 in healthy Chinese subjects successfully. The predicted parameters Cmax and AUC following single oral dose administration were within 0.5-2 folds of the observed data. The model was optimized and the final model was used to predict the pharmacokinetics of ZSP1601 in North European Caucasian, Geriatrics, Obese and Morbidly Obese, respectively. Animal studies were approved by the Animal Management and Use Committee of Suzhou AppTec Inc., and the approved No. is SZ20140916.

17.
Acta Pharmaceutica Sinica ; (12): 3392-3400, 2021.
Artigo em Chinês | WPRIM | ID: wpr-906821

RESUMO

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.

18.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 1-9, 2021.
Artigo em Chinês | WPRIM | ID: wpr-906293

RESUMO

Objective:To compare the therapeutic efficacies of Wujiwan at two different compatibilities (No.1 and No.2) on irritable bowel syndrome (IBS) based on neuro-endocrine-immune network, and provide a theoretical basis for the treatment based on syndrome differentiation in traditional Chinese medicine (TCM). Method:The chronic animal model of IBS with visceral hypersensitivity was established by colon irritation via percutaneous transluminal coronary angioplasty (PTCA) in suckling rats. The animals were randomly divided into a control group, a model group, a dicetel group (0.01 g·kg<sup>-1</sup>), low- (0.335 g·kg<sup>-</sup><bold><sup>1</sup></bold>), medium- (0.67 g·kg<sup>-</sup><bold><sup>1</sup></bold>), and high-dose (1.34 g·kg<sup>-</sup><bold><sup>1</sup></bold>) No. 1 Wujiwan groups, and low- (0.385 g·kg<sup>-</sup><bold><sup>1</sup></bold>), medium- (0.77 g·kg<sup>-</sup><bold><sup>1</sup></bold>), and high-dose (1.54 g·kg<sup>-</sup><bold><sup>1</sup></bold>) No. 2 Wujiwan groups. The thresholds of abdominal elevation and bow back elevation were evaluated to detect the effect of Wujiwan on intestinal sensitivity of IBS. The density of mast cells (MC) in the colonic tissue of model rats was detected by the modified toluidine blue staining method. The concentrations/positive expression of 5-hydroxytryptamine (5-HT), substance P (SP), somatostatin (SS), and vasoactive intestinal peptide (VIP) in the blood/colon tissue were detected by enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry (IHC) assay. Result:There was no significant difference in body weight among different groups. Compared with the control group, the model group exhibited decreased thresholds of abdominal elevation and bow back elevation (<italic>P<</italic>0.01), increased density of MCs in the colon tissue (<italic>P<</italic>0.05), up-regulated levels of 5-HT, SP, and SS in the blood and colon tissue (<italic>P<</italic>0.05, <italic>P<</italic>0.01), and elevated VIP level in the colon tissue (<italic>P</italic><0.05). Compared with the model group, Wujiwan at different compatibilities could increase the thresholds of abdominal elevation and bow back elevation (<italic>P</italic><0.01), diminish the count of MC in the colon tissue (<italic>P</italic><0.05), and reduce the levels of 5-HT, SP, SS, and VIP (<italic>P</italic><0.05). As demonstrated by the comparison of No. 1 and No. 2 Wujiwan, No. 1 was superior to No. 2 in reducing the concentrations of 5-HT, SP, and SS in the blood, especially in 5-HT (<italic>P</italic><0.01). No significant difference between No. 1 and No. 2 in reducing 5-HT positive expression in the colon tissue was observed. Compared to the No. 1 Wujiwan, No. 2 significantly reduced SP expression, and the intensity and range of SS expression in the colon tissue in the No. 2 groups were smaller than those in the No. 1 groups (<italic>P</italic><0.05). Conclusion:Wujiwan at different compatibilities was capable of improving gastrointestinal hormone disorder of IBS to reduce intestinal sensitivity. In terms of systemic effect, No. 1 was superior to No. 2, while in terms of local effect, No. 2 was advantageous. No. 1 Wujiwan was superior to No. 2 in the effect on intestinal dynamics, while No. 2 had an advantageous effect on intestinal sensation over No. 1.

19.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 161-171, 2021.
Artigo em Chinês | WPRIM | ID: wpr-906220

RESUMO

Objective:To analyze active components, its targets and signaling pathways of Shenlian formula based on network pharmacology, and explore the molecular mechanism of Shenlian formula in the treatment of atherosclerotic cardiovascular disease (ASCVD), in order to provide a basis for the rational interpretation of the prescription compatibility of Shenlian formula. Method:Major chemical compounds of the formula were obtained by SymMap and Systematic pharmacology database and analysis platform of Traditional Chinese Medicine (TCMSP), its target proteins were obtained by SymMap and ETCM Databases, and the pathogenic genes responsible for of ASCVD were obtained by DisGeNET and GEO Datebases. Protein targets of drugs and pathogenic genes of diseases were overlapped to obtain predicted targets of Shenlian Formula for ASCVD. Proteins-proteins interactions (PPI) network was built through the String Datebase. The Cytoscape 3.6.0 was used to explore the key compounds and targets of Shenlian formula on ASCVD. Then gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway were analyzed to screen out the key targets of Shenlian Formula. Rat I/R model was adopted as representative disease model of ASCVD for experimental verification. Result:There were 59 candidate compounds, 67 predicted targets and 29 key targets of Shenlian formula on ASCVD. Key targets mainly included cyclooxygenase 2 (PTGS2), estrogen receptor 1 (ESR1) and TP53. GO analysis showed that the biological functions of potential genes of Shenlian formula in treatment of ASCVD were mainly related to apoptotic, nitric oxide biosynthetic process, response to estradiol, angiogenesis, inflammatory response and oxidative stress and acute-phase response. KEGG pathway enrichment results showed that the pathways of potential genes of Shenlian formula in treatment of ASCVD mainly involved TNF signaling pathway, phosphatidylinositol-3 kinase (PI3K)/ protein kinase B (Akt) signaling pathway, hypoxia induction factor-1 (HIF-1) signaling pathway and apoptosis. Among them, the regulatory effect of Shenlian formula on apoptosis may act on not only TP53, but also different signaling pathways of apoptosis respectively, thus playing a synergistic effect. <italic>In vivo</italic> experimentation confirmed that Shenlian formula could significantly reduce the myocardial infarction area, improve the myocardial histopathological changes, and especially reduce myocardial mitochondrial injury. Further analysis showed that Shenlian formula can significantly inhibit the expressions of activated proteins in mitochondrial apoptosis pathway. Conclusion:Anti-atherosclerosis traditional Chinese medicine Shenlian formula could effectively intervene ASCVD, and its effect on mitochondrial apoptosis of myocardial cells is one of its mechanisms in protecting myocardial ischemia-reperfusion injury.

20.
Chinese Journal of Experimental Traditional Medical Formulae ; (24): 124-131, 2021.
Artigo em Chinês | WPRIM | ID: wpr-905997

RESUMO

Objective:To establish an ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) for determining the plasma concentrations of 10 active ingredients in Wujiwan at different time points after oral administration, and to compare the pharmacokinetic characteristics between normal rats and rats with chronic visceral hypersensitive irritable bowel syndrome (CVH-IBS). Method:CVH-IBS rat model was prepared by the neonatal rat colon percutaneous transluminal coronary angioplasty (PTCA) balloon stimulation method. After intragastric administration of Wujiwan (0.245 g·kg<sup>-1</sup>), blood was collected from the jugular vein at different time points, and the plasma concentrations of 10 active ingredients (berberine hydrochloride, palmatine hydrochloride, coptisine hydrochloride, jatrorrhizine hydrochloride, epiberberine, dihydroberberine, evodiamine, evodine, paeoniflorin, albiflorin) in Wujiwan was detected simultaneously by UPLC-MS/MS, the pharmacokinetic parameters of each component in normal rats and CVH-IBS rats were calculated. Result:The established UPLC-MS/MS could sensitively and accurately detect the plasma concentrations of 10 active ingredients of Wujiwan in rats. Compared with the normal group, the absorption rates of these 10 active ingredients of Wujiwan in the blood of CVH-IBS rats all decreased to a certain extent, and the peak time (<italic>t</italic><sub>max</sub>) was prolonged. Among them, the <italic>t</italic><sub>max</sub> of berberine hydrochloride and jatrorrhizine hydrochloride were significantly prolonged from 54 minute and 39 minute to 90 minute, respectively (<italic>P</italic><0.05, <italic>P</italic><0.01). Area under the plasma concentration-time curve (AUC<sub>0-</sub><italic><sub>t</sub></italic>) of each component increased, and evodiamine and paeoniflorin were significantly different (<italic>P</italic><0.05,<italic> P</italic><0.01). The clearance rates (CL/<italic>F</italic>) of these 10 active ingredients were all decreased, among which berberine hydrochloride, palmatine hydrochloride and evodiamine had significant differences (<italic>P</italic><0.05, <italic>P</italic><0.01). Conclusion:There are significant differences in the pharmacokinetic behavior of the active ingredients in Wujiwan between normal rats and CVH-IBS rats, which may be related to the destruction of microstructure of intestinal epithelial cells and the change of activity of liver enzymes under the pathological state of IBS.

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