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Background: We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with chemotherapy in patients with metastatic nasopharyngeal carcinoma (mNPC) who have progressed on prior anti-PD1 therapy. Patients and Methods: We enrolled patients with mNPC who received chemotherapy combined with PD-1 immune-checkpoint inhibitors (ICIs) or chemotherapy alone after prior progression of anti-PD1 therapy. The primary endpoint was progress-free survival (PFS), and the secondary endpoints included overall survival (OS), disease control rate (DCR) and objective response rate (ORR). Results: A total of 96 patients were eligible between January 2015 and December 2020. Thirty-seven (38.5%) were in the PD-1 ICIs re-challenge group, while the remaining 59 patients (61.5%) were in the chemotherapy group. The ORR and DCR of PD-1 ICIs group and chemotherapy group were 37.8% vs 23.7% and 86.5% vs.74.5%, respectively. After a median follow-up period of 21.1 months (IQR 16.1-28.7), the log-rank analysis demonstrated a significantly improved PFS in the PD-1 ICIs re-challenge group compared to the chemotherapy group (8.4 months [95% CI 4.3-14.0] vs 5.0 months [95% CI 2.8-7.2], P = 0.03). However, no significant difference in OS was observed between the two groups (28.3 vs 24.1 months, P = 0.09). The two groups had similar adverse reactions, but the incidence of grade 3 or 4 thrombocytopenia was significantly higher in the PD-1 ICIs re-challenge group (18.9% vs 3.4%, P = 0.025). Conclusion: mNPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with chemotherapy. However, further validation is needed.
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BACKGROUND: This retrospective study aimed to determine the optimal metronomic chemotherapy duration (MTCD) as adjuvant therapy for patients with locally advanced nasopharyngeal carcinoma (LANPC). METHODS: This study involved LANPC patients treated with metronomic chemotherapy (MTC) using a 5-FU prodrug (S1, capecitabine, or tegafur) from May 2013 to September 2020. The optimal MTCD threshold was established using X-tile Bioinformatics software. The overall survival (OS), progression-free survival (PFS), distant metastasis-free survival (DMFS), and locoregional relapse-free survival (LRRFS) were compared between short-term and long-term groups using propensity score matching (PSM). RESULTS: A total of 546 patients were analyzed. MTCD was an independent prognostic factor for OS, PFS, and DMFS (all P < 0.05). Patients were categorized into long-term (>3 months) and short-term (≤3 months) MTCD groups. After a median follow-up of 48 months, significant differences were observed in 4-year OS (97.0 % vs. 87.1 %; P < 0.01), PFS (84.6 % vs. 70.9 %; P < 0.01), DMFS (87.3 % vs. 78.8 %; P < 0.01), and LRRFS (95.3 % vs. 87.4 %; P < 0.01) between the long-term and short-term groups. In the PSM-matched cohort of 196 patients per group, the long-term group demonstrated superior 4-year OS and LRRFS (97.3 % vs. 87.1 %, P < 0.01; 95.2 % vs. 90.0 %, P < 0.05). No significant differences in acute toxicities were observed between the groups (P > 0.05). CONCLUSION: Extended MTC with a 5-FU prodrug (>3 months) may benefit NPC patients. Further prospective studies are needed to validate these findings.
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Administração Metronômica , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Pontuação de Propensão , Humanos , Masculino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Feminino , Pessoa de Meia-Idade , Quimioterapia Adjuvante/métodos , Estudos Retrospectivos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/mortalidade , Adulto , Idoso , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
OBJECTIVE: To compare the effectiveness and safety of nab-paclitaxel, cisplatin, and capecitabine (nab-TPC) with gemcitabine and cisplatin as an alternative first line treatment option for recurrent or metastatic nasopharyngeal carcinoma. DESIGN: Phase 3, open label, multicentre, randomised trial. SETTING: Four hospitals located in China between September 2019 and August 2022. PARTICIPANTS: Adults (≥18 years) with recurrent or metastatic nasopharyngeal carcinoma. INTERVENTIONS: Patients were randomised in a 1:1 ratio to treatment with either nab-paclitaxel (200 g/m2 on day 1), cisplatin (60 mg/m2 on day 1), and capecitabine (1000 mg/m2 twice on days 1-14) or gemcitabine (1 g/m2 on days 1 and 8) and cisplatin (80 mg/m2 on day 1). MAIN OUTCOME MEASURES: Progression-free survival was evaluated by the independent review committee as the primary endpoint in the intention-to-treat population. RESULTS: The median follow-up was 15.8 months in the prespecified interim analysis (31 October 2022). As assessed by the independent review committee, the median progression-free survival was 11.3 (95% confidence interval 9.7 to 12.9) months in the nab-TPC cohort compared with 7.7 (6.5 to 9.0) months in the gemcitabine and cisplatin cohort. The hazard ratio was 0.43 (95% confidence interval 0.25 to 0.73; P=0.002). The objective response rate in the nab-TPC cohort was 83% (34/41) versus 63% (25/40) in the gemcitabine and cisplatin cohort (P=0.05), and the duration of response was 10.8 months in the nab-TPC cohort compared with 6.9 months in the gemcitabine and cisplatin cohort (P=0.009). Treatment related grade 3 or 4 adverse events, including leukopenia (4/41 (10%) v 13/40 (33%); P=0.02), neutropenia (6/41 (15%) v 16/40 (40%); P=0.01), and anaemia (1/41 (2%) v 8/40 (20%); P=0.01), were higher in the gemcitabine and cisplatin cohort than in the nab-TPC cohort. No deaths related to treatment occurred in either treatment group. Survival and long term toxicity are still being evaluated with longer follow-up. CONCLUSION: The nab-TPC regimen showed a superior antitumoural efficacy and favourable safety profile compared with gemcitabine and cisplatin for recurrent or metastatic nasopharyngeal carcinoma. Nab-TPC should be considered the standard first line treatment for recurrent or metastatic nasopharyngeal carcinoma. Longer follow-up is needed to confirm the benefits for overall survival. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1900027112.
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Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Cisplatino , Desoxicitidina , Gencitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Paclitaxel , Humanos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Cisplatino/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Capecitabina/uso terapêutico , Capecitabina/administração & dosagem , Adulto , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Recidiva Local de Neoplasia/tratamento farmacológico , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Paclitaxel/efeitos adversos , Albuminas/administração & dosagem , Albuminas/efeitos adversos , Albuminas/uso terapêutico , Idoso , Intervalo Livre de Progressão , China , Metástase NeoplásicaRESUMO
Introduction: Chondrocyte degeneration and senescence are characteristics of osteoarthritis (OA) and other joint degenerative diseases, and ferroptosis has been observed to regulate the development of OA. However, the role of the N6-methyladenosine (m6A) modification in OA ferroptosis remains unclear. Methods: This study performed series of assays to investigate the function of the m6A reader IGF2BP1 in OA ferroptosis, including m6A quantitative analysis, Iron (Fe2+) release analysis, Malondialdehyde (MDA) measurement, lipid peroxidation (ROS) detection and Glutathione (GSH) measurement. The molecular interaction and mechanism analysis was performed by Luciferase reporter assay, mRNA stability analysis and RNA immunoprecipitation (RIP) assay. Results: These results indicate that IGF2BP1 is upregulated in IL-1ß-induced chondrocytes. Functionally, IGF2BP1 silencing represses ferroptosis, including iron (Fe2+) accumulation, malondialdehyde, and reactive oxygen species (ROS). Mechanistically, among the potential downstream targets, matrix metalloproteinase-3 (MMP3) was observed to harbor a significant m6A modified site in the 3'-UTR. IGF2BP1 combines with MMP3 through the binding of m6A sites, thereby enhancing MMP3 mRNA stability. Discussion: In conclusion, our findings revealed the functions and mechanisms of m6A regulator IGF2BP1 in OA chondrocyte's ferroptosis, providing a novel target for OA treatment.
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BACKGROUND: The long-term prognosis of colon cancer patients remains little changed with relatively high mortality and morbidity. Since the most widely used prognostic parameter TNM staging system is less satisfactory in predicting prognosis in early-stage cancers, numerous clinicopathological factors, including tumor necrosis, have been proposed for prognosis stratification, but substantial evidences are still lacking for early-stage colon cancer. MATERIALS AND METHODS: In the retrospective study, a total of eligible 173 stage I-II colon cancer patients, who received tumor radical resection and lymphadenectomy in the local hospital between January 1, 2010, and December 31, 2018, were enrolled for analyzing the prognostic role of tumor necrosis. The primary endpoints included 5-year overall survival (OS) and progression-free survival (PFS). RESULTS: The median follow-up of enrolled early-stage colon cancer patients was 58.3 months. The 2-year and 5-year OS rates were 88.3% and 68.2%, respectively, and the 2-year and 5-year PFS rates were 85.6% and 62.7%, respectively. Seventy-eight patients (45.1%) were diagnosed with tumor necrosis by pathological examination. Demographic analysis revealed a significant association of tumor necrosis with larger tumor size and a marginal association with vascular invasion. Kaplan-Meier survival curves demonstrated that tumor necrosis was associated with worse OS (log-rank P = 0.003) and PFS (log-rank P = 0.002). The independent unfavorable prognostic effect of tumor necrosis was further validated in univariate and multivariate Cox regression analysis (hazard ratio = 1.91 (1.52-2.40), P = 0.004). CONCLUSIONS: The current study confirmed the independent prognostic role of tumor necrosis from pathological review in early-stage colon cancer patients. This pathological criterion promises to help in identifying high-risk subgroup from early-stage colon cancer patients, who may benefit from strict follow-up and adjuvant therapy.
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The antiangiogenic agent apatinib has been shown to clinically improve responses to immune checkpoint inhibitors in several cancer types. Patients with N3 nasopharyngeal carcinoma have a high risk of distant metastasis, however, if the addition of immunotherapy to standard treatment could improve efficacy is unclear. In this phase II clinical trial (ChiCTR2000032317), 49 patients with stage TanyN3M0 nasopharyngeal carcinoma were enrolled and received the combination of three cycles of induction chemotherapy, camrelizumab and apatinib followed by chemoradiotherapy. Here we report on the primary outcome of distant metastasis-free survival and secondary end points of objective response rate, failure-free survival, locoregional recurrence-free survival, overall survival and toxicity profile. After induction therapy, all patients had objective response, including 13 patients (26.5%) with complete response. After a median follow-up of 28.7 months, the primary endpoint of 1-year distant metastasis-free survival was met for the cohort (1-year DMFS rate: 98%). Grade≥3 toxicity appeared in 32 (65.3%) patients, with the most common being mucositis (14[28.6%]) and nausea/vomiting (9[18.4%]). In this work, camrelizumab and apatinib in combination with induction chemotherapy show promising distant metastasis control with acceptable safety profile in patients with stage TanyN3M0 nasopharyngeal carcinoma.
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Anticorpos Monoclonais Humanizados , Quimioterapia de Indução , Neoplasias Nasofaríngeas , Piridinas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Quimioterapia de Indução/efeitos adversos , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/uso terapêutico , Quimiorradioterapia/efeitos adversosRESUMO
Eight structurally diverse components, including six undescribed ones, (±)-daphuarin A (1a/1b), daphuarin B (2), daphuarin D-E (4-6), together with a pair of new natural products (±)-daphuarin C (3a/3b) were isolated from the herb of Daphne bholua Buch.-Ham. ex D. Don. Their planar structures were elucidated by extensive spectroscopic analyses. The configurations were established with the assistance of quantum chemical calculations, together with the Custom DP4+ method. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated.
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Daphne , Daphne/química , Daphne/metabolismo , Estrutura Molecular , Acetilcolinesterase/metabolismoRESUMO
To assess the efficacy and safety of the combination of immune checkpoint inhibitors (ICIs) and target therapy (anti-angiogenesis or EGFR inhibitors) as a second-line or subsequent treatment for recurrent or metastatic nasopharyngeal carcinoma (R/M NPC), we conducted a retrospective study. In this study, previously treated R/M NPC patients were administered one of the following treatment: ICIs combined with target therapy and chemotherapy (ITC), ICIs combined with target therapy alone (IT), ICIs combined with chemotherapy (IC), or chemotherapy alone (C). The primary endpoint under consideration was progression-free survival (PFS), while secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety measures. A total of 226 patients participated in this study, with 70 receiving the ITC regimen, 48 receiving IT, 48 treated with IC, and 60 undergoing C alone. The median PFS for the four cohorts was 20.67, 13.63, 12.47, and 7.93 months respectively. Notably, ITC regimen yielded the most favorable PFS among these cohorts. The ITC cohort exhibited a comparable tumor response and safety profile to the IT and IC cohorts (p > 0.05), but superior tumor response compared to the C cohort (p < 0.05). The ITC regimen also conferred a significant improvement in OS when comparing to C alone (HR 0.336, 95%CI 0.123-0.915, p = 0.033). The IT and IC regimens achieved a nearly identical PFS (HR 0.955, 95%CI 0.515-1.77, p = 0.884), although the IT regimen was associated with a lower occurrence of SAEs in contrast to the IC regimen (p < 0.05). In addition, the IT regimen demonstrated superior PFS (HR 0.583, 95%CI 0.345-0.985, p = 0.044) and fewer SAEs when compared to C alone (p < 0.05). These findings collectively support the notion that the combination of ICIs, target and chemotherapy exhibits robust antitumor activity in previously treated R/M NPC patients, without a significant increase in adverse events.
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Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Estudos Retrospectivos , Recidiva Local de Neoplasia/tratamento farmacológico , Irinotecano , Imunoterapia , Neoplasias Nasofaríngeas/tratamento farmacológicoRESUMO
This experiment was conducted to investigate the effects of noni fruit extract (NFE) on growth performance, ruminal and colonic fermentation, nutrient digestion, and subacute rumen acidosis (SARA) of cashmere goats with the high-concentrate diet. Twenty-four cashmere kids (17.9 ± 1.45 kg of BW ± SD) were randomly assigned to three treatments: low-concentrate diet, high-concentrate (HC) diet, or HC diet supplemented with NFE at 1 g per kg DM (0.1%). The results showed that although the HC diet improved the average daily gain (ADG) and feed conversion rate (FCR), it was accompanied by SARA with a decreased pH and an increased lactic acid of both rumen and colon, and decreased digestibility of neutral detergent fiber (NDF)and acid detergent fiber (ADF). The supplementation of 0.10% NFE in the HC diet could not only effectively alleviate SARA symptoms and colon fermentation disorders, such as reversing the decrease of pH and alleviating the increase of lactic acid in rumen and colon, but also mitigate the decline of fiber digestibility caused by long-term feeding in the HC diet, and increase the digestibility of crude protein(CP) and dry matter (DM), which improved the ADG and FCR of cashmere kids. Thus, NFE provides new strategies for alleviating SARA and promoting cashmere goat growth.
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Three undescribed compounds elephantopuscabers A-C, along with one previously reported compound spirowallichiione, were isolated from Elephantopus scaber L. Their structures were determined via extensive NMR spectroscopic analysis, quantum chemical calculations, and single-crystal X-ray diffraction crystallography. A plausible biosynthetic pathway for spirowallichiione was proposed. All the isolated compounds were tested for their acetylcholinesterase inhibitory activities. Among them, elephantopuscaber B and C displayed promising inhibitory activities against AChE, and the binding sites were predicted by molecular docking.
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Terpenos , Triterpenos , Terpenos/farmacologia , Acetilcolinesterase , Simulação de Acoplamento Molecular , Estrutura MolecularRESUMO
The fungus Nectria sp. MHHJ-3 was isolated from Illigera rhodantha. A molecular networking-guided the secondary metabolites investigation of Nectria sp. MHHJ-3 led to the isolation of ten metabolites (1-10), including two new naphthalenone derivatives, nectrianaphthalenones A (1) and B (2), and two new steroids, nectriasteroids A (3) and B (4). Their structures were elucidated by extensive spectroscopic analysis including the HRESIMS, 1D/2D NMR and electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for 1-2 was proposed. Compounds 1 and 2 exhibited moderate acetylcholinesterase (AChE) inhibitory activities. Compounds 3 and 4 showed significant cytotoxic activity against selected tumor cells. Particularly, compound 3 exhibited the strongest activity against A549 cells with an IC50 value of 13.73 ± 0.03 µM, which was at the same grade with that of positive control cisplatin.
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Antineoplásicos , Nectria , Estrutura Molecular , Nectria/química , Acetilcolinesterase , Fungos , Antineoplásicos/farmacologiaRESUMO
As a chronic inflammatory autoimmune disease, rheumatoid arthritis (RA) causes significant destruction to joints and cartilage. So far, from RA patients, the synovial cells and subsynovial tissues reflected the positive expression of IL-18, IL-1ß, Caspase-1 and NLRP3, with the synovial tissues of those patients also expressing the zinc finger protein A20 at a significantly lower level compared with osteoarthritis (OA) ones. Thus, the inhibition of the NLRP3/caspase-1 signaling pathway can effectively down-regulate the expression of IL-1ß, but when NLRP3 inflammasomes are activated, they can also shear GSDMD and induce pyroptosis. These suggest that the Gasdermin family of proteins, downstream of the NLRP3 inflammasome, could be involved in pyroptosis. Previous studies have shown that A20 contributes largely as an anti-inflammatory factor in many inflammatory diseases, but it remains unclear whether zinc finger protein A20, as an inhibitor of NLRP3 inflammasomes, can play a protective role against RA by inhibiting NLRP3 inflammasome-mediated pyroptosis. Therefore, this study aimed to verify the effects of zinc finger protein A20 on NLRP3/ Caspase-1-mediated pyroptosis in rheumatoid arthritis synovial fibroblasts (HFLS-RA) cells through cell experiments and clinical bidirectional verification, aim to understand the regulatory mechanism of A20 on RA. The results of clinical trials showed that NLRP3, Caspase-1, IL-1ß and IL-18 were positively scattered in RA synovial cells and subsynovial tissue. The expression level of the zinc finger protein A20 in RA synovial tissues was significantly lower than that in OA synovial tissue and was negative, while zinc finger protein A20 was strongly positive in OA synovial tissue. In addition, HFLS-RA cells with siRNA-interfering zinc finger protein A20 were constructed at the cellular level, with the results also confirming that zinc finger protein A20 can play a protective role against RA by inhibiting NLRP3 inflammasome-mediated pyroptosis. In conclusion, this study is of great significance for understanding the role of the NLRP3-caspase-1-IL-1ß/ pyroptosis signaling pathway in the occurrence and development of RA. It is expected that the results will provide a theoretical basis for the immune regulation of innate immunity in the occurrence and development of RA, while providing a new therapeutic target for the clinical treatment of RA.
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Artrite Reumatoide , Osteoartrite , Humanos , Caspase 1 , Piroptose , Inflamassomos , Interleucina-18 , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 Induzida por Fator de Necrose Tumoral alfa , Transdução de SinaisRESUMO
We aim to evaluate the efficacy and safety of anti-PD1 rechallenge in combination with anti-angiogenesis or anti-EGFR treatment in recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) patients who progressed to previous anti-PD1 therapy. Enrolled patients were divided into a combination group and a chemotherapy only group. A total of 145 patients were enrolled. The median progress-free survival (mPFS) was 7.9 months and 4.4 months, respectively for the two groups. The combination group exhibited significantly longer PFS (HR=0.363, p < 0.001), and better disease control ratio (DCR, p = 0.022) compared with the chemotherapy group. Among the combination group, longer PFS was found in those patients who received different PD1 inhibitor from prior therapy, reached object response rate (ORR) from prior anti-PD1 therapy, and EBV DNA ≤ 1500 copy/ml before therapy, comparing to the corresponding other patients. R/M NPC patients who progressed from prior anti-PD1 therapy could benefit from the anti-PD1 rechallenge in combination with anti-angiogenesis or anti-EGFR agents.
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Imunoterapia , Neoplasias Nasofaríngeas , Humanos , Carcinoma Nasofaríngeo/tratamento farmacológico , Inibidores de Checkpoint Imunológico , Neoplasias Nasofaríngeas/tratamento farmacológicoRESUMO
Fractionation motivated by biological activity screening and NMR characteristic signals analysis led to the isolation of seventeen diarylpentanoids from the whole plant of Daphne bholua Buch.-Ham. ex D. Don, among which nine compounds were undescribed. Their structures and stereochemistry were determined by comprehensive spectroscopic data, J-based configurational analysis, and quantum chemical calculations. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated in vitro and in silico.
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Daphne , Daphne/química , Daphne/metabolismo , Estrutura Molecular , Acetilcolinesterase/metabolismo , Espectroscopia de Ressonância MagnéticaRESUMO
The genus Daphne is a treasure-house of secondary metabolites with various biological effects, which inspired Daphne bholua being fully investigated phytochemically and biologically for the first time. Here, seven undescribed guaiane-type sesquiterpenoids (1-7) along with thirteen known analogues (8-20) were targeted and isolated from D. bholua using molecular networking. Their chemical structure and configurations were established via NMR spectroscopy analysis, NMR and ECD calculations, Snatzke's method, along with single-crystal X-ray diffraction technique. Moreover, two pairs of sesquiterpene isomers, either with prominent biological properties or with unprecedented skeleton, were revised by means of computer-assisted structure elucidation, chemical shift calculator using deep learning, etc. The inhibitory potentials of all isolates against acetylcholinesterase were evaluated in vitro and in silico.
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Inibidores da Colinesterase , Daphne , Sesquiterpenos de Guaiano , Acetilcolinesterase/química , Daphne/química , Estrutura Molecular , Sesquiterpenos de Guaiano/química , Sesquiterpenos de Guaiano/isolamento & purificação , Sesquiterpenos de Guaiano/farmacologia , Inibidores da Colinesterase/química , Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologiaRESUMO
In this study, the immunohistochemical EnVision method was applied to detect CD3, CD4 and CD8 in synovial tissues of 40 patients with rheumatoid arthritis (RA) and 10 patients with osteoarthritis (OA). In 92.5% (37/40) RA cases, lymphocytes were focally aggregated, and even germinal centers appeared, forming lymphoid follicle-like structures. The expression of CD3, CD4, and CD8 were high in synovial tissue of RA group, but low in OA group. The number of CD3, CD4+, and CD8+ lymphocytes in OA group were significantly lower than that in RA group (p < 0.05); CD4+lymphocytes in RA accounted for the majority, and mostly were focally distributed. The number of CD8+lymphocytes in the synovial tissue were small, and were mostly scattered. The number of CD4+lymphocytes were significantly higher than CD8+lymphocytes (p<0.05). Compared with the OA group, the number of CD4+T and CD8+T lymphocytes in RA group were higher, and the ratio of CD4/CD8 was higher in RA group (p < 0.05). In conclusion, the CD3, CD4 and CD8 with high level may promote the occurrence and development of RA. The ratio of CD4+/CD8+ may be used as a reference index for the diagnosis and prognosis of RA.
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Artrite Reumatoide , Artrite Reumatoide/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Humanos , Membrana Sinovial/química , Membrana Sinovial/metabolismoRESUMO
Three undescribed acylated sucroses (1-3), one undescribed butenolide analog (4) along with three known compounds (5-7) were isolated from the aqueous EtOH extract of the dried leaves of Tripterygium wilfordii. Their structures were elucidated on the basis of spectroscopic analyses, electron circular dichroism (ECD) techniques, and saccharide hydrolysis. All the isolated compounds were tested for their anti-tyrosinase effects. Among them, 6 exhibited similar inhibitory effects on tyrosinase with IC50 values of 0.073 mM comparing to arbutin. Additionally, the possible mechanism of the interaction between 6 and the active site of tyrosinase was explored by molecular docking.
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Monofenol Mono-Oxigenase , Tripterygium , 4-Butirolactona/análogos & derivados , Simulação de Acoplamento Molecular , Estrutura Molecular , Tripterygium/químicaRESUMO
Quassinoids, originating from the oxidative degradation of tetracyclic tirucallane triterpene, are a diverse class of secondary metabolites identifying from nature mostly in Simaroubaceae family. The crucial pharmacological activities and structural complexity of quassinoids have long fascinated scientists due to their medicinal uses, infamous toxicity, and unique biosynthesis. In the past few decades, 482 quassinoids, assigned to 6 skeletons, have been isolated and identified from plants. The names, classes, molecular formula, and plant sources of these secondary metabolites are collated here. This review will be a detailed update of the naturally occurring quassinoids reported from the plant kingdom, providing an in-depth discussion of their diversity, antitumor activities, structure-activity relationship.
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Quassinas , Simaroubaceae , Extratos Vegetais , Plantas , Quassinas/farmacologia , Relação Estrutura-AtividadeRESUMO
Six undescribed lanostane triterpenoids (1-6), together with three known compounds (7-9) were isolated from Inonotus obliquus. Compounds 3-5 are the rare natural compounds featuring a 4,5-seco-lanostane core with a 5,7,9-trien-21,24-cyclopentane moiety. The structure elucidation of the compounds was conducted by spectroscopic techniques and the ECD method. The absolute configuration of compound 1 was confirmed by single-crystal X-ray diffraction analysis. All isolated compounds were assayed for their neuroprotective activity against H2O2-induced cell injury using human neuroblastoma SH-SY5Y cells. Compound 9 exhibited the most potent neuroprotective activity and the flow cytometry analysis indicated that 9 could protect SH-SY5Y cells from oxidative damage by inhibiting cell apoptosis.
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Antineoplásicos/química , Misturas Complexas/química , Inonotus/química , Lanosterol/química , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/química , Triterpenos/química , Antineoplásicos/farmacologia , Produtos Biológicos/química , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Cromatografia Líquida , Misturas Complexas/farmacologia , Avaliação Pré-Clínica de Medicamentos , Humanos , Peróxido de Hidrogênio/metabolismo , Conformação Molecular , Estrutura Molecular , Fármacos Neuroprotetores/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Triterpenos/farmacologiaRESUMO
Small molecule accurate recognition technology (SMART) is an emerging method for the rapid structural prediction of major constituents from crude extracts and fractions. In the present study, a targeted isolation of an Elephantopus scaber extract by SMART resulted in the obtention of 15 new (1-15) and five known germacranolide sesquiterpenes (16-20). Their structures were assigned by extensively analyzing HRESIMS, NMR, X-ray crystallographic analyses, modified Mosher's method results, and quantum chemical calculate electronic circular dichroism (ECD) spectra. All germacranolide sesquiterpenes were screened to determine their inhibitory effects with two hepatoma cell lines (HepG2 and Hep3B), and compounds 14, 16, 18, 19 and 20 showed significant cytotoxic activities against the HepG2 (IC50, 3.3-9.9 µM) and Hep3B (IC50, 4.5-8.6 µM) cell lines. Further study suggested that 18 can induce the apoptosis of hepatoma cells via mitochondrial dysfunction.