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1.
Anal Bioanal Chem ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32185442

RESUMO

GC/MS coupled metabolomics analysis, using a simplified and much less expensive silylation process with trimethylsilyl cyanide (TMSCN), was conducted to investigate metabolic abnormalities in stomach cancer cells. Under optimized conditions for derivatization by TMSCN and methanol extraction, 228 metabolites were detected using GC/MS spectrometry analysis, and 89 metabolites were identified using standard compounds and the NIST database. Ten metabolite levels were found to be lower in stomach cancer cells relative to normal cells. Among those ten metabolites, four metabolites-ribose, proline, pyroglutamic acid, and glucose-were known to be linked to cancers. In particular, pyroglutamic acid level showed a drastic reduction of 22-fold in stomach cancer cells. Since glutamine and glutamic acid are known to undergo cyclization to pyroglutamic acid, the 22-fold reduction might be the actual reduction in the levels of glutamine and/or glutamic acid-both known to be cancer-related. Hence, the marked reduction in pyroglutamic acid level might serve as a biomarker to aid early detection of stomach cancer. Graphical abstract.

2.
Org Lett ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186193

RESUMO

Hyperprins A (1) and B (2), two polyprenylated acylphloroglucinol related meroterpenoids with undescribed carbon skeletons, were isolated from Hypericum przewalskii. Compound 1 possesses a new 6/6/6/6/5/5 hexacyclic system with an unprecedented tetracyclo[10.3.1.03,8.08,12]hexadecane motif. Compound 2 features a unique 6/8/6/6 tetracyclic scaffold. Their structures were determined by spectroscopic data, chemical method, and X-ray crystallography. Compound 1 showed antiproliferation activity against the MV-4-11 cell line, and the p-bromobenzoate derivative of 2 displayed PTP1B inhibition.

3.
Carbohydr Polym ; 236: 115972, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32172827

RESUMO

An environmentally friendly octenylsuccinic anhydride modified pH-sensitive chitosan-octenylsuccinic anhydride (OSA-CS) was synthesized. The critical micelle concentration (CMC) of the modified chitosan was 27 µg/mL, the graft polymers can form solubilized curcumin (CUR) and quercetin (QUE) nanoparticles. The drug-loaded nanoparticles had high encapsulation efficiency and drug loading content, the self-assembly of graft polymers formed spherical uniform nanoparticles with an approximate diameter of 150-180 nm. The nanoparticles were stable under storage conditions and in serum. The results revealed that OSA-CS exhibited excellent biocompatibility, no cytotoxicity. Additionally, the results of pH sensitivity and drug release experiments showed that the nanoparticles were highly sensitive to weakly acidic conditions (pH 6.0) and showed a faster release rate, while they were reasonably stable at physiological conditions (pH 7.4). The drug-loaded nanoparticles exhibited higher cellular uptake in vitro, and exhibited stronger anti-inflammatory and antioxidant efficacy. Therefore, OSA-CS-based nanoparticles are a promising hydrophobic drug delivery system for pH-response targeting therapy.

4.
Technol Cancer Res Treat ; 19: 1533033820905824, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32174262

RESUMO

PURPOSE: Triple-negative breast cancer is characterized by fast progression with high possible for metastasis and poor survival. Dysfunction of microRNAs plays an important role in the initiation and progression of cancer. Our previous microRNA-seq data indicated the downregulation of miR-331-3p in triple-negative breast cancer tissues compared with that of the noncancer tissues. However, the function of miR-331-3p in triple-negative breast cancer remains largely unknown. Herein, the involvement of miR-331-3p in triple-negative breast cancer was investigated and the therapeutic potential of miR-331-3p was also explored. METHODS: Real-time quantitative polymerase chain reaction was performed to detect the expression of miR-331-3p in triple-negative breast cancer tissues and cell lines. The cell proliferation was determined by the cell counting kit-8 assay. Apoptosis of triple-negative breast cancer cells was examined by annexin V/propidium iodide staining. miRDB database was used to predict the potential targets of miR-331-3p. Western blot was performed to examine the expression of the target protein. RESULTS: miR-331-3p was significantly downregulated in triple-negative breast cancer tissues and cell line. Lower miR-331-3p expression was significantly correlated with the tumor size, TNM stage, and lymph node metastasis of patients with triple-negative breast cancer. Functional experiments showed that the overexpression of miR-331-3p inhibited the proliferation and increased apoptosis of triple-negative breast cancer cells. Neuropilin-2 was identified as a target of miR-331-3p, which harbored binding site of miR-331-3p in its 3'-untranslated region. Overexpression of miR-331-3p decreased the messenger RNA and protein levels of neuropilin-2 in triple-negative breast cancer cells. Restoration of neuropilin-2 partially reversed the inhibitory effects of miR-331-3p on the proliferation of triple-negative breast cancer cells. CONCLUSIONS: Our results demonstrated the novel function of miR-331-3p/neuropilin-2 signaling in regulating the malignant behaviors of triple-negative breast cancer cells, which suggested miR-331-3p as a potential target for the treatment of triple-negative breast cancer.

5.
Trials ; 21(1): 287, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32197640

RESUMO

BACKGROUND: Coronary heart disease (CHD) has become a common cardiovascular disease that seriously threatens the health of people. As reperfusion in the early phase and drug therapy, especially percutaneous coronary intervention (PCI), have become widely used in the clinic, the mortality of acute myocardial infarction in the short term has been reduced significantly. In addition, in 40%-56% of patients who experience myocardial infarction, cardiac dysfunction occurs and about 25%-33% develop heart failure. METHODS: This study was designed as a multicenter, double-blind, randomized, placebo-controlled, parallel-group, superiority trial. Participants were randomly assigned in a 1:1 ratio through a centrally controlled, computer-generated, simple randomization schedule. The primary outcome was left ventricular end-diastolic volume index = left ventricular end-diastolic volume/body surface area. The combined secondary outcomes include traditional Chinese medicine syndrome score, echocardiogram results, 6-minute walk test results, Seattle Angina Questionnaire score, cardiac magnetic resonance imaging results, biological indicators, dynamic electrocardiogram results, and experiment event rate. Assessments will be performed at baseline and at 4, 8, and 12 weeks after randomization. DISCUSSION: This trial will demonstrate that the addition of a Tongmai Yangxin pill (TMYX) to conventional treatment will intervene in the development of cardiac remodeling and cardiac dysfunction. TRIAL REGISTRATION: This study was registered in the Chinese Clinical Trial Registry on 7 May 2019. The registration number is ChiCRT1900023023 (http://www.chictr.org.cn/showproj.aspx?proj=12370).

6.
Pharmazie ; 75(1): 18-22, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-32033628

RESUMO

Salvia miltiorrhiza (Danshen) is typically used in the treatment of diabetic complications and is often co-prescribed with gliquidone in China. However, whether danshen affects the absorption of gliquidone has not been elucidated. In this study, the effects of an aqueous extract of danshen (danshen injection, DSI) and its primary compounds (danshensu, protocatechuic aldehyde, rosmarinic acid and salvianolic acid B) on gliquidone transport across Caco-2 monolayer cells was investigated. DSI enhanced the transport of gliquidone in Caco-2 cell monolayers from the apical (AP) to basolateral (BL) sides and from the BL to AP sides. Rosmarinic acid (RA) also significantly increased the Papp (AP-BL) value for gliquidone transport. Verapamil (a P-gp inhibitor) and Ko143 (a BCRP inhibitor) inhibited the BL-AP transport of gliquidone and promoted the AP-BL transport of gliquidone, whereas MK571 (an MRP1 inhibitor), probenecid (an MRP2 inhibitor), and benzbromarone (an MRP3 inhibitor) had no effect on gliquidone transport. RA also enhanced the intracellular accumulation of Rho123 and Hoechst 33342. The expression of P-gp and BCRP was significantly downregulated, and P-gp ATPase activity was promoted by RA in a dose-dependent manner. These results indicate that an aqueous extract of danshen can increase the transport of gliquidone in Caco-2 cell monolayers and that RA may be the primary compound associated with this activity, which is in agreement with RA simultaneously suppressing the function and expression of P-gp and BCRP.

7.
Int J Pharm ; 578: 119177, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32105724

RESUMO

Bacterial therapy is emerging for the treatment of cancers though some scientific and clinical problems have not been addressed. Here, a live drug-loaded carrier, paclitaxel-in-liposome-in-bacteria (LPB), was prepared for inhalation treatment of primary lung cancer, where liposomal paclitaxel (LP) was highly effectively internalized into bacteria (E. coli or L. casei) to get LP-in-E. coli (LPE) or LP-in-L. casei (LPL) by electroporation that had no influence on the growth of these bacteria. Bacteria, LP, the simple mixture of LP and bacteria, and LPB remarkably inhibited the proliferation of A549 lung cancer cells, where LPE was the strongest one. Drug-loaded bacteria delivered the cargos into the cells more quickly than the mixture of drugs and bacteria and the cargos alone. LPE also showed the highest anticancer effect on the rat primary lung cancer among them with the downregulation of VEGF and HIF-1α and the improvement of cancer cell apoptosis after intratracheal administration. Moreover, the bacterial formulations significantly enhanced the expressions of immune markers (TNF-α, IL-4, and IFN-γ) and immune cells (leukocytes and neutrophils). LPB showed much higher bacterial distribution in the lung than other organs after intratracheal administration. LPB is a promising medicine for inhalation treatment of primary lung cancer.

8.
Artigo em Inglês | MEDLINE | ID: mdl-32093473

RESUMO

Mesoporous-structure perovskite solar cells (meso-PVKSCs) have been widely utilized due to the achieved high efficiency for which the TiO2 layer usually suffers from sufficient electron trap states, low electron mobility, and inavoidable catalytic activity. Herein, a mesoporous TiO2 (m-TiO2) layer is modified by tetraethylammonium p-toluenesulfonate (abbreviated as TEATS) for the first time, leading to a significant photoelectric conversion efficiency enhancement from 19.14 to 20.69% for Cs0.05MA0.12FA0.83PbI2.55Br0.45 (abbreviated as CsMAFA) meso-PVKSCs. In particular, the obtained champion open-circuit voltage (Voc) is 1.18 V, which is a record high value for meso-PVKSCs with CsMAFA triple cation mixed perovskite. A series of measurements were employed to investigate the influences of TEATS modification on the energy band structures of TiO2 as well as the CsMAFA perovskite layer atop, unveiling that TEATS modification benefits defect passivation of the TiO2 film along with a decrease in the work function of TiO2. Besides, TEATS modification helps to improve the wettability of perovskite precursors on the m-TiO2 substrate, affording improved film quality of perovskite with enhanced crystallinity and grain size. Consequently, the trap states existed in the perovskite film can be passivated, and the interfacial charge recombination is suppressed. This further benefits the improvement of the ambient stability of devices.

9.
Nanoscale ; 12(9): 5353-5358, 2020 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-32100771

RESUMO

To push the limit of synthetic control, we create a thin layer (5 nm) of silica on the surface of drug nanocrystals, achieving a loading content (88%) that approaches the theoretical limit. The uniform silica shell provides a tailored diffusion barrier for controlled drug release. The method can be generally applied to 11 organic crystals, including 4 drugs.

10.
Viruses ; 12(2)2020 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-32079099

RESUMO

Tetherin is an interferon-inducible type II transmembrane glycoprotein which inhibits the release of viruses, including retroviruses, through a "physical tethering" model. However, the role that the glycosylation of tetherin plays in its antiviral activity remains controversial. In this study, we found that mutation of N-glycosylation sites resulted in an attenuation of the antiviral activity of equine tetherin (eqTHN), as well as a reduction in the expression of eqTHN at the plasma membrane (PM). In addition, eqTHN N-glycosylation mutants colocalize obviously with ER, CD63, LAMP1 and endosomes, while WT eqTHN do not. Furthermore, we also found that N-glycosylation impacts the transport of eqTHN in the cell not by affecting the endocytosis, but rather by influencing the anterograde trafficking of the protein. These results suggest that the N-glycosylation of eqTHN is important for the antiviral activity of the protein through regulating its normal subcellular localization. This finding will enhance our understanding of the function of this important restriction factor.

11.
Chem Commun (Camb) ; 56(17): 2610-2613, 2020 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-32016272

RESUMO

We have synthesized a turn-on fluorescent probe, termed NB4OH, to detect cellular hypochlorite. NB4OH is mainly localized in the endoplasmic reticulum and detects ClO- in foam cells. The fluorescence change of the probe was explained by theoretical calculation as a PET process. The probe holds great promise for application in biomedical research, including atherosclerosis research.

12.
Arch Gynecol Obstet ; 301(3): 707-714, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31903498

RESUMO

PURPOSE: Recent studies have demonstrated the differential expression of micro(mi)RNAs in endometriosis. Previously, we reported the low expression of miR-141 in patients with this disease. Epithelial-to-mesenchymal transition (EMT) and the transforming growth factor-beta1 (TGF-ß1)-induced SMAD2 signalling pathway are central to tumour proliferation and invasion. However, the role of miR-141 in regulating the TGF-ß1/SMAD2 signalling pathway and the associated EMT to be elucidated. METHODS: The levels of TGF-ß1/SMAD2 signalling and EMT markers expression in eutopic and ectopic endometria of endometriosis were determined by immunohistochemistry and western blot analyses. MiR-141 expression was analysed by quantitative reverse-transcription polymerase chain reaction. Cellular invasion and proliferation were determined by transwell and CCK-8 assays, respectively. Functional assay of miR-141 was performed using plasmid and shRNA transfection methods. RESULT: The presence of miR-141, EMT, and TGF-ß1/SMAD2 signalling markers were detected in eutopic and ectopic endometria of endometriosis. TGF-ß1-induced EMT in Ishikawa (ISK) cells by activating the SMAD2 signalling pathway, whereas miR-141 inhibited the TGF-ß1-induced EMT, proliferation and invasion abilities of these cells. CONCLUSION: These data identify miR-141 as a novel driver of EMT in endometriosis, implicates the link between miR-141 and TGF-ß1/SMAD2 signalling pathway in the context of endometriosis, and underscore the role of EMT in the development of endometriosis.

13.
Clin Cancer Res ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919135

RESUMO

PURPOSE: Application of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with hematological disorders is limited by the development of graft-versus-host-disease (GVHD). Separation of GVHD and graft-versus-leukemia (GVL) remains a great challenge in the field. We investigated the contribution of individual pathways involved in the complement cascade in GVH and GVL responses in order to identify specific targets by which to separate these two processes. EXPERIMENTAL DESIGN: We used multiple preclinical murine and human-to-mouse xenograft models involving allo-HCT recipients lacking components of the AP or CP/LP to dissect the role of each individual pathway in GVHD pathogenesis and the GVL effect. For translational purposes, we used the AP-specific complement inhibitor, CR2-fH, which localizes in injured target organs to allow specific blockade of complement activation at sites of inflammation. RESULTS: Complement deposition was evident in intestines of mice and patients with GVHD. In a preclinical setting, ablation of the AP, but not the CL/LP, significantly improved GVHD outcomes. Complement activation through the AP in host hematopoietic cells, and specifically dendritic cells (DCs), was required for GVHD progression. AP-deficiency in recipients decreased donor T-cell migration and Th1/Th2 differentiation, while increasing the generation of regulatory T-cells. This was due to decreased activation and stimulatory activity of recipient DCs in GVHD target organs. Treatment with CR2-fH effectively prevented GVHD while preserving GVL activity. CONCLUSIONS: This study highlights the AP as a new therapeutic target to prevent GVHD and tumor relapse after allo-HCT. Targeting the AP by CR2-fH represents a promising therapeutic approach for GVHD treatment.

14.
Viruses ; 12(1)2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31963559

RESUMO

Orf is a zoonotic disease that has caused huge economic losses globally. Systematical analysis of dysregulated cellular micro RNAs (miRNAs) in response to Orf virus (ORFV) infection has not been reported. In the current study, miRNA sequencing and RNA sequencing (RNA-seq) were performed in goat skin fibroblast (GSF) cells at 0, 18, and 30 h post infection (h.p.i). We identified 140 and 221 differentially expressed (DE) miRNAs at 18 and 30 h.p.i, respectively. We also identified 729 and 3961 DE genes (DEGs) at 18 and 30 h.p.i, respectively. GO enrichment analysis indicates enrichment of apoptotic regulation, defense response to virus, immune response, and inflammatory response at both time points. DE miRNAs and DEGs with reverse expression were used to construct miRNA-gene networks. Seven DE miRNAs and seven DEGs related to "negative regulation of viral genome replication" were identified. These were validated by RT-qPCR. Cfa-let-7a, a significantly upregulated miRNA, was found to repress Thrombospondin 1 (THBS1) mRNA and protein expression by directly targeting the THBS1 3' untranslated region. THBS1 has been reported to induce apoptosis; therefore, the cfa-let-7a-THBS1 axis may play an important role in cellular apoptosis during ORFV infection. This study provides new insights into ORFV and host cell interaction mechanisms.

15.
Naunyn Schmiedebergs Arch Pharmacol ; 393(3): 469-480, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31655854

RESUMO

In the present study, we explored the anti-tumor and anti-angiogenesis effects of chrysophanol, and to investigate the underlying mechanism of the chrysophanol on anti-tumor and anti-angiogenesis in human lung cancer. The viability of cells was measured by CCK-8 assay, cell apoptosis was measured by Annexin-FITC/PI staining assay, and the cell migration and invasion were analyzed by wound-healing assay and transwell assay. ROS generation and mitochondrial membrane potential were analyzed by DCFH-DA probe and mitochondrial staining kit. Angiogenesis was analyzed by tube formation assay. The expression of CD31 was analyzed by immunofluorescence. The levels of proteins were measured by western blot assay. The anti-tumor effects of chrysophanol in vivo were detected by established xenograft mice model. In this study, we found that the cell proliferation, migration, invasion, tube formation, the mitochondrial membrane potential, and the expression of CD31 were inhibited by chrysophanol in a dose-dependent manner, but cell apoptotic ratios and ROS levels were increased by chrysophanol in a dose-dependent manner. Furthermore, the effects of chrysophanol on A549, H738, and HUVEC cell apoptotic rates were reversed by the ROS inhibitor NAC. Besides, the effects of chrysophanol on HUVEC cell tube formation were reversed by the HIF-1α inhibitor KC7F2 and the VEGF inhibitor axitinib in vitro. Moreover, tumor growth was reduced by chrysophanol, and the expression of CD31, CD34, and angiogenin was suppressed by chrysophanol in vivo. Our finding demonstrated that chrysophanol is a highly effective and low-toxic drug for inhibition of tumor growth especially in high vascularized lung cancer.

16.
J Fish Dis ; 43(2): 215-225, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31770821

RESUMO

LuxR-type transcriptional factors are essential in many bacterial physiological processes. However, there have been no reports on their roles in Aeromonas hydrophila. In this study, six stable silent strains were constructed using shRNA. Significant decreases in the expression levels of luxR05 , luxR08 , luxR19 , luxR11 , luxR164 and luxR165 were shown in their respective strains by qRT-PCR. The luxR05 -RNAi and luxR164 -RNAi exhibit the most significant changes in sensitivity to kanamycin and gentamicin. The luxR05 -RNAi showed minimum biofilm formation and the least motility, while luxR164 -RNAi showed minimum biofilm formation, adhesion, growth and extracellular protease activity compared to the wild-type strain. In summary, the results of this paper suggest that all six luxR genes are involved in multiple physiological processes in A. hydrophila and that the roles of luxR05 and luxR164 are highly significant. The sensitivity of luxR05 -RNAi and luxR164 -RNAi to drugs may be closely related to biofilm formation. The luxR05 may play an important role in the pathogenicity of A. hydrophila by regulating the movement, adhesion and biofilm formation of bacteria, whereas luxR164 may be involved in similar functions by regulating bacterial adhesion, extracellular enzyme activity and growth. These results help further our understanding of the drug resistance and pathogenesis of A. hydrophila.

17.
Mol Pharm ; 17(1): 338-348, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31793786

RESUMO

The synergy of chemotherapy and antiangiogenesis therapy is a new strategy for cancer treatment. In this paper, a well-developed core-shell nanoparticle loaded with gambogic acid (GA), heparin (HP), and the immunoadjuvant cytosine-phosphate-guanine oligonucleotide (CpG ODN), called GHC NP, was constructed to treat hepatocellular carcinoma. GHC NPs with liver targeting activity can effectively inhibit tumor cell proliferation and angiogenesis. With the delivery of nanocarriers and the assistance of GA and HP, the GHC NPs can more effectively upregulate cytotoxic T cell (CTL) levels, promote helper T cell (Th cell) differentiation, and induce Th1 immune responses in long-term treatment compared with single CpG ODN. This synergistically enhanced immunotherapy might have universal application in cancer treatments.

18.
Asian-Australas J Anim Sci ; 33(1): 12-23, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31480193

RESUMO

OBJECTIVE: The objective of a conservation program is to maintain maximum genetic diversity and preserve the viability of a breed. However, the efficiency of a program is influenced by the ability to accurately measure and predict genetic diversity. METHODS: To examine this question, we conducted a simulation in which common measures (i.e. heterozygosity) and novel measures (identity-by-descent probabilities and parental genomic components) were used to estimate genetic diversity within a conserved population using double-labeled single nucleotide polymorphism markers. RESULTS: The results showed that the accuracy and sensitivity of identity-by-state probabilities and heterozygosity were close to identity by descent (IBD) probabilities, which reflect the true genetic diversity. Expected heterozygosity most closely aligned with IBD. All common measures suggested that practices used in the current Chinese pig conservation program result in a ~5% loss in genetic diversity every 10 generations. Parental genomic components were also analyzed to monitor real-time changes in genomic components for each male and female ancestor. The analysis showed that ~7.5% of male families and ~30% of female families were lost every 5 generations. After 50 generations of simulated conservation, 4 male families lost ~50% of their initial genomic components, and the genomic components for 24.8% of the female families were lost entirely. CONCLUSION: In summary, compared with the true genetic diversity value obtained using double-labeled markers, expected heterozygosity appears to be the optimal indicator. Parental genomic components analysis provides a more detailed picture of genetic diversity and can be used to guide conservation management practices.

19.
Int J Biol Macromol ; 145: 1080-1090, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31730989

RESUMO

A novel acid polysaccharide (PPRLMF-2) with the Mw of 137,123 Da and a triple-helix conformation was first isolated from the pulp of Rosa laevigata Michx fruit. Structural characterization showed that PPRLMF-2 consisted of rhamnose (7.6%), arabinose (26.5%), xylose (3.5%), mannose (0.9%), glucose (5.7%), galactose (31.9%) and galacturonic acid (23.9%). The methylation and NMR (1D and 2D) analysis revealed that PPRLMF-2 contained 16 types of glycosidic linkages. The immunomodulatory activity assays indicated that PPRLMF-2 could significantly enhance phagocytosis, the secretion and mRNA expression of cytokines in RAW 264.7 cells. Additionally, SR, GR, TLR-2, and TLR-4 were the main pattern recognition receptors (PRRs) of PPRLMF-2 to upregulate the p-ERK, p-JNK, p-p38, and p-p65. These results suggested that PPRLMF-2 could recognize the PRRs of the macrophages to enhance the immunomodulatory activity via activation of the MAPKs and NF-κB signaling pathways. This study provides important implications of PPRLMF-2 as an attractive immunomodulatory functional food.

20.
Biomolecules ; 9(12)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795133

RESUMO

Rheumatoid arthritis (RA) is a known chronic autoimmune disease can cause joint deformity and even loss of joint function. Fibroblast-like synoviocytes (FLS), one of the main cell types in synovial tissues of RA patients, are key effector cells in the development of RA and are considered as promising therapeutic targets for treating RA. Herbal medicines are precious resources for finding novel agents for treating various diseases including RA. It is reported that induction of apoptosis in FLS is an important mechanism for the herbal medicines to treat RA. Consequently, this paper reviewed the current available references on pro-apoptotic effects of herbal medicines on FLS and summarized the related possible signal pathways. Taken together, the main related signal pathways are concluded as death receptors mediated apoptotic pathway, mitochondrial dependent apoptotic pathway, NF-κB mediated apoptotic pathways, mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, PI3K-Akt mediated apoptotic pathway, and other reported pathways such as janus kinase/signal transducers and activators of transcription (JAK-STAT) signal pathway. Understanding the apoptosis induction pathways in FLS of these herbal medicines will not only help clear molecular mechanisms of herbal medicines for treating RA but also be beneficial for finding novel candidate therapeutic drugs from natural herbal medicines. Thus, we expect the present review will highlight the importance of herbal medicines and its components for treating RA via induction of apoptosis in FLS, and provide some directions for the future development of these mentioned herbal medicines as anti-RA drugs in clinical.

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