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1.
Vis Comput Ind Biomed Art ; 7(1): 16, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38967824

RESUMO

Active surveillance (AS) is the primary strategy for managing patients with low or favorable-intermediate risk prostate cancer (PCa). Identifying patients who may benefit from AS relies on unpleasant prostate biopsies, which entail the risk of bleeding and infection. In the current study, we aimed to develop a radiomics model based on prostate magnetic resonance images to identify AS candidates non-invasively. A total of 956 PCa patients with complete biopsy reports from six hospitals were included in the current multicenter retrospective study. The National Comprehensive Cancer Network (NCCN) guidelines were used as reference standards to determine the AS candidacy. To discriminate between AS and non-AS candidates, five radiomics models (i.e., eXtreme Gradient Boosting (XGBoost) AS classifier (XGB-AS), logistic regression (LR) AS classifier, random forest (RF) AS classifier, adaptive boosting (AdaBoost) AS classifier, and decision tree (DT) AS classifier) were developed and externally validated using a three-fold cross-center validation based on five classifiers: XGBoost, LR, RF, AdaBoost, and DT. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity (SEN), and specificity (SPE) were calculated to evaluate the performance of these models. XGB-AS exhibited an average of AUC of 0.803, ACC of 0.693, SEN of 0.668, and SPE of 0.841, showing a better comprehensive performance than those of the other included radiomic models. Additionally, the XGB-AS model also presented a promising performance for identifying AS candidates from the intermediate-risk cases and the ambiguous cases with diagnostic discordance between the NCCN guidelines and the Prostate Imaging-Reporting and Data System assessment. These results suggest that the XGB-AS model has the potential to help identify patients who are suitable for AS and allow non-invasive monitoring of patients on AS, thereby reducing the number of annual biopsies and the associated risks of bleeding and infection.

5.
Front Chem ; 12: 1388545, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38680458

RESUMO

Andrographolide is one of the main biologically active molecules isolated from Andrographis paniculata (A. paniculata), which is a traditional Chinese herb used extensively throughout Eastern Asia, India, and China. Pseudomonas aeruginosa, often known as P. aeruginosa, is a common clinical opportunistic pathogen with remarkable adaptability to harsh settings and resistance to antibiotics. P. aeruginosa possesses a wide array of virulence traits, one of which is biofilm formation, which contributes to its pathogenicity. One of the main modulators of the P. aeruginosa-controlled intramembrane proteolysis pathway is AlgW, a membrane-bound periplasmic serine protease. In this work, we have used a set of density functional theory (DFT) calculations to understand the variety of chemical parameters in detail between andrographolide and levofloxacin, which show strong bactericidal activity against P. aeruginosa. Additionally, the stability and interaction of andrographolide and levofloxacin with the protein AlgW have been investigated by molecular docking and molecular dynamics (MD) simulations . Moreover, the growth and inhibition of biofilm production by P. aeruginosa experiments were also investigated, providing insight that andrographolide could be a potential natural product to inhibit P. aeruginosa.

6.
Sensors (Basel) ; 24(3)2024 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-38339567

RESUMO

The point cloud segmentation method plays an important role in practical applications, such as remote sensing, mobile robots, and 3D modeling. However, there are still some limitations to the current point cloud data segmentation method when applied to large-scale scenes. Therefore, this paper proposes an adaptive clustering segmentation method. In this method, the threshold for clustering points within the point cloud is calculated using the characteristic parameters of adjacent points. After completing the preliminary segmentation of the point cloud, the segmentation results are further refined according to the standard deviation of the cluster points. Then, the cluster points whose number does not meet the conditions are further segmented, and, finally, scene point cloud data segmentation is realized. To test the superiority of this method, this study was based on point cloud data from a park in Guilin, Guangxi, China. The experimental results showed that this method is more practical and efficient than other methods, and it can effectively segment all ground objects and ground point cloud data in a scene. Compared with other segmentation methods that are easily affected by parameters, this method has strong robustness. In order to verify the universality of the method proposed in this paper, we test a public data set provided by ISPRS. The method achieves good segmentation results for multiple sample data, and it can distinguish noise points in a scene.

7.
World J Urol ; 42(1): 14, 2024 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-38189837

RESUMO

PURPOSE: Bladder neck contracture (BNC) is a rare but intolerant complication after transurethral surgery of prostate. The present study aims to investigate the incidence and risk factors of BNC in patients diagnosed benign prostate hyperplasia (BPH) and following transurethral resection or enucleation of the prostate (TURP/TUEP). METHODS: This retrospective study included 1008 BPH individuals who underwent transurethral surgery of the prostate between January 2017 and January 2022. Patients' demographics, medical comorbidities, urologic characteristics, perioperative parameters, and the presence of BNC were documented. Univariate and multivariate analyses were conducted to identify the risk factors. RESULTS: A total of 2% (20/1008) BPH patients developed BNC postoperatively and the median occurring time was 5.8 months. Particularly, the incidences of BNC were 4.7% and 1.3% in patients underwent Bipolar-TURP and TUEP respectively. Preoperative urinary tract infection (UTI), elevated PSA, smaller prostate volume (PV), bladder diverticulum (BD), and B-TURP were significantly associated with BNC in the univariate analysis. Further multivariate logistic regression demonstrated preoperative UTI (OR 4.04, 95% CI 2.25 to 17.42, p < 0.001), BD (OR 7.40, 95% CI 1.83 to 31.66, p < 0.001), and B-TURP (OR 3.97, 95% CI 1.55 to 10.18, p = 0.004) as independent risk factors. All BNC patients were treated with transurethral incision of the bladder neck (TUIBN) combined with local multisite injection of betamethasone. During a median follow-up of 35.8 months, 35% (7/20) of BNC patients recurred at a median time of 1.8 months. CONCLUSION: BNC was a low-frequency complication following transurethral surgery of prostate. Preoperative UTI, BD, and B-TURP were likely independent risk factors of BNC. TUIBN combined with local multisite injection of betamethasone may be promising choice for BNC treatment.


Assuntos
Contratura , Hiperplasia Prostática , Masculino , Humanos , Bexiga Urinária , Próstata , Estudos Retrospectivos , Hiperplasia Prostática/cirurgia , Contratura/epidemiologia , Contratura/etiologia , Betametasona
8.
J Endourol ; 38(4): 340-346, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38243842

RESUMO

Background: The objective of this study was to explore the perioperative outcomes of single-plane posterior retroperitoneoscopic adrenalectomy (SPRA) guided by indocyanine green dye (ICG) fluorescence imaging. Methods: A retrospective analysis of patients who underwent SPRA from April to September 2023 in our center was conducted. Patients were divided into the ICG group and the non-ICG group, based on whether they received intraoperative ICG fluorescence guided or not. Baseline and perioperative data were recorded and analyzed by R software (R 4.3.1). Results: A total of 23 patients were enrolled in the study, with 12 in the ICG group and 11 in the non-ICG group. The demographics including age, gender, body mass index, or American Society of Anesthesiologists classification showed no significant differences between groups. There were obvious advantages in shortening adrenal gland localization time and total operative time, as well as reducing estimated blood loss in the ICG group compared with the non-ICG group (5.58 ± 0.36 minutes vs 7.55 ± 0.62 minutes, p < 0.001; 27.50 ± 5.46 minutes vs 45.00 ± 10.99 minutes, p < 0.001; 22.91 ± 7.57 mL vs 54.54 ± 18.90 mL, p < 0.001; respectively). Furthermore, patients in the ICG group exhibited significantly lower visual analog pain scale scores at 24 hours postoperatively and at discharge (p = 0.001 and p = 0.006, respectively). The oral intake intervals, hospital stays, and perioperative complications were comparable between groups. Conclusions: ICG-guided SPRA could be a safe and effective procedure for patients with adrenal tumors. This technique improves the accuracy and efficacy of adrenal gland localization and has shown benefits in perioperative outcomes. The use of ICG fluorescence guidance represents a promising clinical application.


Assuntos
Neoplasias das Glândulas Suprarrenais , Laparoscopia , Humanos , Verde de Indocianina , Adrenalectomia/métodos , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/cirurgia , Tempo de Internação , Laparoscopia/métodos
9.
BMC Chem ; 17(1): 111, 2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37700296

RESUMO

Inert allyl-type monomers have been widely documented due to reduce degradation chain transfer. Recently, we and others discovered that the [3 + 2] cyclization reaction process by a photo-driven radical reaction, which can accelerate the polymerization. It was discovered that allyl ether monomers had much higher reactivity than other allyl monomers in the suspension photopolymerization initiated by Type I photoinitiator. Since the hydrogen abstraction reaction (HAR) is the initial step of cyclization, and in order to clarify the influence of solvents effect, three allyl-type monomers were employed, containing "O", "N" and "S" atom as hydrogen donors. The benzoyl radical obtained from cleavage of photoinitiator was chosen as hydrogen acceptors. We explored the hydrogen abstraction reaction in different solvents (methanol, water and DMSO) by quantum chemistry for geometry and energy. An investigation was undertaken regarding the structural orbital by electrostatic potential (ESP) and topological analysis (ELF and LOL). The findings were also combined with the distortion model and transition state theory. We obtained the molecular interactions used independent gradient method in the Hirshfeld molecular density partition (IGMH). The Eckart's correction allowed to examine the driving factors of the hydrogen abstraction reaction tunnels and these reactions constant rates are determined in the range of 500-2500 K depending on the modified Arrhenius form in different solvents effect. Our results can provide an answer for the different reactivities.

10.
Sensors (Basel) ; 23(13)2023 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-37447907

RESUMO

With the rapid development of Lidar technology, the use of Lidar for underwater terrain detection has become feasible. There is still a challenge in the process of signal resolution: the underwater laser echo signal is different to propagating in the air, and it is easy to produce weak waves and superimposed waves. However, existing waveform decomposition methods are not effective in processing these waveform signals, and the underwater waveform signal cannot be correctly decomposed, resulting in subsequent data-processing errors. To address these issues, this study used a drone equipped with a 532 nm laser to detect a pond as the study background. This paper proposes an improved inflection point selection decomposition method to estimate the parameter. By comparing it with other decomposition methods, we found that the RMSE is 2.544 and R2 is 0.995975, which is more stable and accurate. After estimating the parameters, this study used oscillating particle swarm optimization (OPSO) and the Levenberg-Marquardt algorithm (LM) to optimize the estimated parameters; the final results show that the method in this paper is closer to the original waveform. In order to verify the processing effect of the method on complex waveform, this paper decomposes and optimizes the simulated complex waveforms; the final RMSE is 0.0016, R2 is 1, and the Gaussian component after decomposition can fully represent the original waveform. This method is better than other decomposition methods in complex waveform decomposition, especially regarding weak waves and superimposed waves.


Assuntos
Algoritmos , Luz , Distribuição Normal
11.
Front Microbiol ; 14: 1133782, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37089532

RESUMO

Objective: Increasing evidence suggests that gut microbiota is involved in the occurrence and progression of urinary system diseases such as clear cell renal cell carcinoma (ccRCC). However, the mechanism of how alteration of gut metagenome promotes ccRCC remains unclear. Here we aim to elucidate the association of specific gut bacteria and their metabolites with ccRCC. Methods: In a pilot case-control study among 30 ccRCC patients (RCC group) and 30 healthy controls (Control group), 16S ribosomal RNA (rRNA) gene sequencing were analyzed from fecal samples collected prior to surgery or hospitalization. Alpha diversity and beta diversity analysis of the gut microbiota were performed, and differential taxa were identified by multivariate statistics. Meanwhile, serum metabolism was measured by UHPLC-MS, and differential genes were identified based on the TCGA database. Results: Alpha diversity found there were no significant microbial diversity differences of gut microbiota between the RCC group and the Control group. However, beta diversity analysis showed that the overall structures of the two groups were significantly separated (p = 0.008). Random Forests revealed the relative abundances of 20 species differed significantly between the RCC group and the Control group, among which nine species were enriched in the RCC group such as Desulfovibrionaceae, and 11 species were less abundant such as four kinds of Lactobacillus. Concomitantly, serum level of taurine, which was considered to be consumed by Desulfovibrionaceae and released by Lactobacillus, has decreased in the RCC group. In addition, macrophage-related genes such as Gabbr1 was upregulated in ccRCC patients. Conclusion: Reduction of protective bacteria, proliferation of sulfide-degrading bacteria Desulfovibrionaceae, reduction of taurine, and enrichment of macrophage related genes might be the risk predictors of ccRCC.

12.
Transl Androl Urol ; 11(8): 1130-1147, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36092848

RESUMO

Background: Ferroptosis-related genes (FRGs) play vital roles in survival and prognosis of prostate cancer (PCa) patients. We establish a ferroptosis-related prediction model through bioinformatics analysis for overall survival (OS) and disease-free survival (DFS), so as to evaluate the clinical survival status through the characteristics of immune cell infiltration (ICI), which could provide information for treatment monitoring. Methods: At first, 268 FRGs were obtained from previous studies. Differentially expressed FRGs were identified based on The Cancer Genome Atlas (TCGA) database, and FRG enrichment analysis was performed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then performed univariate, least absolute shrinkage and selection operator (LASSO), and multivariate Cox regression analyses to establish OS- and DFS-related prognostic prediction models. The association of the model and clinicopathological features was further analyzed. Subsequently, unique genomic signatures of immune cell subsets were obtained through the KEGG database. Based on specific genes associated with ferroptosis and their association with ICI, immune infiltration was assessed in patients in different risk groups. Results: We constructed an OS- and an DFS-prognostic model through bioinformatics analysis. The predicted values of OS and DFS-related models were higher in T3-4 than in T1-2 (P=0.0057, P<0.001), and the predicted value of the DFS model in N0 stage was higher than that in N1 stage (P=0.0136). Results of Single-sample gene set enrichment analysis (ssGSEA) on the basis of the KEGG dataset showed p53 signaling being the most enriched signal in the high-risk group, while endocytosis was the most enriched signal in the low-risk group. M2 macrophages (P=0.007) and neutrophils (P=0.024) were enriched in the high-risk group, and CD4-activated memory T cells were significantly accumulated in the low-risk group (P=0.017). Conclusions: The OS- and DFS-related model based on FRGs and ICI create new insights into the disease state assessment of PCa patients., which may aid in the development of individualized and precise treatment in the future.

13.
Front Chem ; 10: 967836, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36118315

RESUMO

The photodriven radical-mediated [3 + 2] cyclization reaction was found to yield polymers efficiently without being hindered by degradative chain transfer. The first reaction is a hydrogen abstraction process in which one hydrogen atom migrates from the α-methylene group of an allyl monomer to the triplet state (or fragments) of the photoinitiator, thus yielding primary allyl radicals as primary radicals and then begins chain propagation via a 3 + 2 cyclization reaction. Allyl ether monomers were found to be significantly higher than other allyl monomers even with the absence of amine-like synergists. In order to clarify the procedure of the hydrogen abstraction mechanism, we used four allyl-type monomers as hydrogen donors and three thioxanthone photoinitiators as hydrogen acceptors by the quantum chemistry method in terms of geometry and energy. The results were interpreted with transition-state theory and the interaction/deformation model. Then, the tunneling factors of hydrogen abstraction reactions were also investigated by Eckart's correction. The results show allyl ether systems are more reactive than other allyl systems, and it would provide us with new insights into these hydrogen abstractions.

14.
Front Chem ; 10: 962355, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35936101

RESUMO

The palladium-catalyzed decarboxylative reactions of phenols and vinyl ethylene carbonate to produce allylic aryl ethers under mild conditions have been established. Adopting an inexpensive PdCl2(dppf) catalyst promotes the efficient conversion of phenols to the corresponding allylic aryl ethers via the formation of a new C-O bond in good isolated yields with complete regioselectivities, acceptable functional group tolerance and operational simplicity. The robust procedure could be completed smoothly by conducting a scaled-up reaction with comparable efficiency to afford the target product.

15.
Front Bioeng Biotechnol ; 10: 852482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35387298

RESUMO

Hypertrophic scarring, which is characterized by excessive extracellular matrix deposition and abnormal fibroblast homeostasis, is an undesirable outcome of dermal wound healing. Once formed, the scar will replace the normal function of local skin, and there are few noninvasive clinical treatments that can cure it. Se@SiO2 nanoparticles were synthesized to suppress oxidative stress, which induced the presence and activation of myofibroblasts during wound recovery. The characterization, antioxidant capacity and biological safety of Se@SiO2 NPs were evaluated. A full-thickness excisional wound model was established, and the wounds were divided into three groups. The re-epithelization and distribution of collagen fibers were assessed using hematoxylin and eosin staining and Masson's trichome staining after specific treatments. Our results revealed that the Se@SiO2 NPs accelerated dermal wound healing and suppressed the formation of hypertrophic scars, accompanied by oxidative stress inhibition. Moreover, we found that Se@SiO2 NPs worked by activating the PI3K/Akt pathway and upregulating the phosphorylation of Akt. The findings of our study provide a new method to promote dermal scar-free wound healing by suppressing excessive oxidative stress and through PI3K/Akt pathway activation.

16.
Front Chem ; 10: 869860, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35402370

RESUMO

Pyridinones have been adopted as an important block in medicinal chemistry that could serve as hydrogen bond donors and acceptors. With the help of feasible synthesis routes via established condensation reactions, the physicochemical properties of such a scaffold could be manipulated by adjustment of polarity, lipophilicity, and hydrogen bonding, and eventually lead to its wide application in fragment-based drug design, biomolecular mimetics, and kinase hinge-binding motifs. In addition, most pyridinone derivatives exhibit various biological activities ranging from antitumor, antimicrobial, anti-inflammatory, and anticoagulant to cardiotonic effects. This review focuses on recent contributions of pyridinone cores to medicinal chemistry, and addresses the structural features and structure-activity relationships (SARs) of each drug-like molecule. These advancements contribute to an in-depth understanding of the potential of this biologically enriched scaffold and expedite the development of its new applications in drug discovery.

17.
J Proteome Res ; 21(4): 921-929, 2022 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-34851127

RESUMO

Microglia are the main immune cells in the brain playing a critical role in neuroinflammation, and numerous pieces of evidence have proved that energy metabolism is closely associated with inflammation in activated microglia. Salidroside (Sal) isolated from Tibetan medicine Rhodiola crenulate can inhibit microglial hypoxia inflammation (HI). However, whether the inhibition is due to the intervening energy metabolic process in microglia is not clear. In this work, the hypoxic microenvironment of BV2 microglial cells was simulated using deferoxamine (DFO) in vitro and the change of cell metabolites (lactate, succinate, malate, and fumarate) was real-time online investigated based on a cell microfluidic chip-mass spectrometry (CM-MS) system. Meanwhile, for confirming the metabolic mechanism of BV2 cells under hypoxia, the level of HI-related factors (LDH, ROS, HIF-1α, NF-κB p65, TNF-α, IL-1ß, and IL-6) was detected by molecular biotechnology. Integration of the detected results revealed that DFO-induced BV2 cell HI was associated with the process of energy metabolism, in which cell energy metabolism changed from oxidative phosphorylation to glycolysis. Furthermore, administration of Sal treatment could effectively invert this change, and two metabolites of Sal were identified: tyrosol and 4-hydroxyphenylacetic acid. In general, we illustrated a new mechanism of Sal for reducing BV2 cell HI injury and presented a novel analysis strategy that opened a way for real-time online monitoring of the energy metabolic mechanism of the effect of drugs on cells and further provided a superior strategy to screen natural drug candidates for HI-related brain disease treatment.


Assuntos
Microfluídica , Microglia , Glucosídeos , Humanos , Hipóxia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Espectrometria de Massas , Microglia/metabolismo , NF-kappa B/metabolismo , Fenóis , Transdução de Sinais
18.
Artigo em Inglês | MEDLINE | ID: mdl-33927774

RESUMO

Smilax china L. (SCL) is extensively used in the treatment of pelvic inflammatory disease (PID). This study aimed to clarify the potential active ingredients of SCL and mechanisms on PID. SCL was widely distributed in Japan, South Korea, and China, which was traditionally considered heat-clearing, detoxicating, and dampness-eliminating medicine. Systems pharmacology revealed that 32 compounds in SCL may interact with 19 targets for immunoenhancement, antiapoptosis, anti-inflammation, and antioxidant activity of the PID model. Molecular docking revealed that isorhamnetin, moracin M, rutin, and oxyresveratrol may have higher binding potential with prostaglandin-endoperoxide synthase 2 (PTGS2), mitogen-activated protein kinase 1 (MAPK1), siderocalin (LCN2), tumor necrosis factor (TNF), and matrix metalloprotein-9 (MMP9), respectively. Molecular dynamics simulation showed that the binding modes of moracin M-MAPK1, rutin-TNF, and oxyresveratrol-MMP9 complexes were more stable, evidenced by relatively smaller fluctuations in root mean square deviation values. Conclusively, SCL may treat PID by inhibiting inflammatory factors, antitissue fibrosis, and microbial growth.

19.
World J Urol ; 39(9): 3447-3453, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33475762

RESUMO

PURPOSE: To develop and validate a predictive nomogram for early stress urinary incontinence (SUI) after endoscopic enucleation of the prostate (EEP) in patients with benign prostatic hyperplasia (BPH). METHODS: The records of 458 patients who underwent plasmakinetic- or diode-based EEP at our center from March 2016 to December 2019 were reviewed. Among these, 326 and 132 cases were randomly assigned to the training and validation set, respectively. A predictive nomogram was constructed based on multivariate logistic regression analysis. Receiver operating characteristic (ROC) analysis and calibration curves were employed to evaluate its performance. RESULTS: 65 years ≤ age < 70 years, 75 years ≤ age, 25 kg/m2 ≤ BMI < 30 kg/m2, 30 kg/m2 ≤ BMI, 5 years ≤ LUTS duration, and 75 ml ≤ prostate volume were finally selected as independent predictors of early SUI into the multivariate logistics regression model. It was visualized as a concise nomogram with satisfactory discrimination and accuracy in both training and validation sets. CONCLUSIONS: A concise nomogram was developed and validated as a useful clinical tool for predicting early SUI post-EEP.


Assuntos
Endoscopia , Nomogramas , Complicações Pós-Operatórias/diagnóstico , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Incontinência Urinária por Estresse/diagnóstico , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo
20.
J Ethnopharmacol ; 267: 113514, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33223115

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Rhamnella gilgitica Mansf. et Melch. (སེང་ལྡེང་།, RG) is a traditional Tibetan medicinal plant that is currently grown throughout Tibet. According to the theory of Tibetan medicine, RG is efficient for removing rheumatism, reducing swelling, and relieving pain. Hence, it has been used for the treatment of rheumatoid arthritis (RA) in Tibet for many years. However, there are no previous reports on the anti-RA activities of ethyl acetate extract of RG (RGEA). AIM OF THE STUDY: This study aimed to explore the anti-RA effect and mechanism of RGEA on collagen-induced arthritis (CIA) in rats. MATERIALS AND METHODS: The CIA model was established in male Wister rats by intradermal injection of bovine type II collagen and Complete Freund's Adjuvant at the base of the tail and left sole, respectively. The rats were orally administered with RGEA (9.71, 19.43, or 38.85 mg/kg) for 23 days. The body weight, swelling volume, arthritis index score, thymus and spleen indices, and pathological changes were observed to evaluate the effect of RGEA on RA. Furthermore, the inflammatory cytokines in serum, such as interleukin1 beta (IL-1ß), tumor necrosis factor alpha (TNF-α), interleukin6 (IL-6), interleukin17 (IL-17), interferon-γ (INF-γ), interleukin4 (IL-4), and interleukin10 (IL-10) were measured by enzyme linked immunosorbent assay (ELISA) to explore the anti-inflammatory effects of RGEA. The terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) staining was used to examine apoptosis. Finally, the protein and gene expression of B-cell lymphoma-2-associated X (Bax), B-cell lymphoma 2 (Bcl-2), Caspase3, janus-activated kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), suppressor of cytokine signaling1 (SOCS1), and 3 (SOCS3) in synovial tissue were detected using immunohistochemistry and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: After the treatment with RGEA, the body weight of rats was restored, both the arthritis index and paw swelling were suppressed, and spleen and thymus indices were decreased. RGEA reduced the inflammatory cells and synovial hyperplasia in the synovial tissue of the knee joint, and suppressed bone erosion. Meanwhile, RGEA decreased the levels of IL-1ß, IL-6, IL-17, TNF-α, and INF-γ, while increased the levels of IL-4 and IL-10. TUNEL fluorescence apoptosis results confirmed that RGEA obviously promoted the apoptosis of synovial cells. Further studies showed that RGEA inhibited the proteins and mRNAs expression of JAK2 and STAT3 as well as increased the proteins and mRNAs expression of SOCS1 and SOCS3. In addition, RGEA upregulated the expression of Bax and Caspase3, and downregulated the expression of Bcl-2. CONCLUSION: The anti-RA effectof RGEA might be related to the promotion of apoptosis and inhibition of inflammation, which regulated the JAK-STAT pathway.


Assuntos
Antirreumáticos/farmacologia , Artrite Experimental/prevenção & controle , Janus Quinase 2/metabolismo , Articulações/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rhamnaceae , Fator de Transcrição STAT3/metabolismo , Acetatos/química , Animais , Antirreumáticos/isolamento & purificação , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Artrite Experimental/induzido quimicamente , Artrite Experimental/enzimologia , Artrite Experimental/patologia , Colágeno Tipo II , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Janus Quinase 2/genética , Articulações/enzimologia , Articulações/patologia , Masculino , Medicina Tradicional Tibetana , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Rhamnaceae/química , Fator de Transcrição STAT3/genética , Transdução de Sinais , Solventes/química , Proteína 1 Supressora da Sinalização de Citocina/genética , Proteína 1 Supressora da Sinalização de Citocina/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo
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