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关键词： Indole   TNF-alpha   Docking   Anti-inflammatory activity  

摘要： A novel series of eleven aryl ethers (S-1-S-11) based on 5-nitroindole were prepared, confirmed, and screened out for their in vitro and in vivo anti-inflammatory response. The prepared aryl ethers were synthesized by reacting 5-chloro-2-(5-nitro-1H-indol-1-yl) aniline with various phenols in acetonitrile. Structural characterization of all aryl ethers was established and confirmed by FT-IR, 1H NMR, 13C NMR, and mass spectrometry. The ADMET studies were carried out by web software. Lipinski's rule of five was applied to find out the drug-likeness property. A docking study was done to emphasize the binding site of the Tumor Necrosis Factor-alpha (TNF alpha) and newly synthesized aryl ether compounds. In the series, the synthesized compound showed the highest binding affinity, -10.6 kcal/mol. The prepared aryl ether compounds were evaluated for their anti-inflammatory activity by albumin denaturation inhibitory assay and the carrageenan-induced rat paw edema method. Among them, compound S-7 showed a higher anti-inflammatory effect than indomethacin.

关键词： Zhizi-Bopi decoction   cholestatic liver injury   network pharmacology   single-cell RNA sequencing   IL-17/NF-κB signaling pathway  

摘要： Background:ZhiZi-BoPi Decoction(ZZBPD),a traditional prescription for liver and gallbladder protection,has garnered significant clinical interest due to its hepatoprotective *** its proven efficacy in mitigating intrahepatic cholestasis,the precise mechanisms underlying its therapeutic effects remain inadequately *** study aims to comprehensively investigate the pharmacological mechanisms underlying the therapeutic effects of ZZBPD in cholestatic liver injury(CLI).Methods:Firstly,we evaluated the hepatoprotective effects of ZZBPD on mice with CLI induced byα-naphthylisothiocyanate(ANIT),by measuring biochemical markers,inflammatory factors,and bile acid ***,we employed network pharmacology and single-cell RNA sequencing(scRNA-seq)to identify key targets and potential signaling pathways for the prevention and treatment of ***,we further validated the mechanism of action of ZZBPD on these key targets through molecular docking,western blotting,and immunofluorescence ***:ZZBPD notably improved serum liver function,reduced hepatic inflammation,and restored bile acid *** network pharmacology and scRNA-seq analysis,48 core targets were identified,including TNF,IL-6,and NFKB1,all of which are linked to the IL-17 and NF-κB signaling pathways,as shown by KEGG enrichment *** docking further confirmed stable interactions between ZZBPD’s key active components and molecules such as IL-6,IL-17,and NF-κ***,western blotting and immunofluorescence validated the downregulation of IL-17 and NF-κB protein expression in liver ***:ZZBPD effectively treats CLI by activating pathways related to the bile acid receptor FXR,while also modulating the IL-17/NF-κB signaling *** dual action enhances bile secretion and alleviates liver *** findings offer important insights into the pharmacological mechanisms of ZZBPD and underscore its potential as a promisin

关键词： Adjuvanted vaccine   Injection vaccination   Protective efficacy   Streptococcosis   Vaccine development  

摘要：

关键词： 急性淋巴细胞白血病   异基因移植   费城染色体   BCR/ABL基因   酪氨酸激酶抑制剂   微小残留病   早期干预   复发  

摘要： 背景:BCR/ABL基因是Ph染色体阳性急性淋巴细胞白血病的特异性基因,其表达水平已经成为异基因造血干细胞移植前后微小残留病监测的敏感指标。然而,移植前BCR/ABL基因表达水平是否影响移植疗效,移植后如何指导酪氨酸激酶抑制剂进行复发的早期干预尚无定论。目的:探讨Ph染色体阳性急性淋巴细胞白血病患者行亲缘间、异基因造血干细胞移植前后BCR/ABL基因表达与复发的关系。方法:选择2015年1月至2022年12月期间华北理工大学附属医院收治的24例达到血液学完全缓解后行亲缘间异基因造血干细胞移植的Ph染色体阳性急性淋巴细胞白血病患者,应用实时荧光定量聚合酶链反应动态监测治疗期间BCR/ABL基因表达水平,以此代表微小残留病。依据BCR/ABL基因表达,移植前给予酪氨酸激酶抑制剂联合化疗,选择异基因造血干细胞移植时机;移植后评估疾病状态,指导酪氨酸激酶抑制剂的应用,制定早期干预复发的方案。结果与结论:随访至2023年12月,中位随访时间为49(12-82)个月,8例血液学复发,复发的中位时间为14(8-39)个月,累积复发率为33%(8/24)。单因素分析显示,异基因造血干细胞移植后血液学复发与性别、年龄、髓外并发症、诊断至移植时间、HLA配型、急性移植物抗宿主病、慢性移植物抗宿主病无明显相关性(P>0.05);与移植前缓解疗程及微小残留病水平有明显相关性,移植前第2次血液学完全缓解、微小残留病阳性患者有更高的血液学复发率(P<0.05)。预期移植后3年累积复发率、无病生存率、总生存率分别为27%,63%,74%;5年累积复发率、无病生存率、总生存率分别为38%,57%,74%。结果表明,异基因造血干细胞移植前BCR/ABL基因阳性Ph染色体阳性急性淋巴细胞白血病患者有更高的复发率;移植后BCR/ABL基因表达可指导酪氨酸激酶抑制剂应用,做为早期干预复发的依据。

关键词： GBP1   IFN-γ   IL-2   Mycobacterium tuberculosis   Non-tuberculous mycobacteria  

摘要：

关键词： Identity leadership   Social identity   Nested organizations   Elite sports   Multigroup dynamics   Coach leadership effectiveness  

摘要：

关键词： B细胞血液恶性肿瘤   嵌合抗原受体T细胞   免疫疗法   治疗靶点   长期疗效   毒副作用   复发  

摘要： 背景:嵌合抗原受体T(chimeric antigen receptor T,CAR-T)细胞疗法是治疗B细胞血液恶性肿瘤的前沿方法,其能高效且特异性地识别并杀伤肿瘤细胞,不受主要组织相容性复合体限制。目的:旨在梳理CAR-T细胞的结构、发展历程及上市产品进展,总结CAR-T细胞治疗B细胞血液恶性肿瘤的长期疗效,并探讨治疗后的毒副作用、复发性及解决策略,同时综述潜在靶点治疗B细胞血液恶性肿瘤的进展。方法:以“嵌合抗原受体T细胞,B细胞恶性肿瘤,毒副作用,免疫疗法”为中文检索词,以“CAR-T、B cell hematological malignancies,Toxic side effects,Immunotherapy”为英文检索词在中国知网、万方数据库、PubMed数据库检索CAR-T细胞相关靶点治疗B细胞恶性肿瘤的文献。结果与结论:①美国食品药品监督管理局和中国国家药品监督管理局共批准11款CAR-T细胞产品,主要针对B细胞血液恶性肿瘤的CD19和B细胞成熟抗原靶点;②长期随访数据显示,CAR-T细胞治疗为B细胞血液恶性肿瘤患者带来高缓解率和持久反应,但存在抗原丢失或下调导致的复发问题;③CAR-T细胞治疗存在高毒副作用、高复发率和耐药性等问题,限制了其广泛应用;④未来研究的方向包括开发新的靶点、联合治疗等策略,以提高CAR-T细胞的持久性和抗肿瘤活性。

关键词： Batatasin III   Enteric nervous system   Microbiota–gut–brain axis   NLRP3   Slow transit constipation  

摘要：

关键词： BD   bipolar disorder   M.I.N.I   Mini-International Neuropsychiatric Interview   HAMD-24   Hamilton Depression Rating Scale-24 items   YMRS   Young Mania Rating Scale   MADRS   Montgomery-Åsberg Depression Rating Scale   BSSI   Beck Scale for Suicide Ideation   ORs   odd ratio   CI   confidence interval   IL   interleukin   TNF   tumor necrosis factor   IFN   interferon   FT4   free thyroxine 4   FT3   free thyroxine 3   TT4   total thyroxine 4   TT3   total thyroxine 3   TSH   thyroid stimulating hormone   aTPO   anti-thyroid peroxidase antibody   aTG   anti-thyroglobulin   CRP   C-reaction protein   DSM-5   the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition   ICD-11   the International Classification of Diseases, 11th Revision   PHQ-9   Patient Health Questionnaire-9 items   GAD-7   Generalized Anxiety Disorder-7 items   HAMA   Hamilton Anxiety Rating Scale   SI-C   current suicidal ideation   SI-W   the severity of suicidal thoughts at their worst point   NK cell   natural killer cell   BMI   body mass index   FDR   false discovery rate   Bipolar disorder   Suicide risk   Machine learning   Thyroid function   Biomarkers  

摘要：

关键词： Breast cancer   P18   interleukin 24   fusion protein   molecular docking   MD simulations  

摘要： Breast cancer is the second leading cause of cancer-related deaths throughout the world, and it remains one of the significant health challenges due to treatment limitations such as drug resistance and adverse side effects. Instead of developing novel treatment approaches, including radiotherapy and chemotherapy, their efficacy is trapped by non-specific toxicity and resistance. This study includes designing a novel chimeric protein combining Interleukin-24 (IL-24) and p18 peptides that are well-being to exhibit significant anticancer properties. The fusion protein, IL-24-P18, was developed to enhance specificity and minimize off-target effects in breast cancer treatment. We used silico techniques to predict this novel fusion protein construct's structural, functional and therapeutic properties. The P18 peptide was fused to the N-terminal of IL-24 using an AEAAAKEAAAKA linker. The fusion protein was found to be nontoxic, non-allergenic and non-antigenic. The fusion protein was hydrophilic with a neutral charge, exhibiting soluble expression in E. coli and stable at varying conditions. Secondary and tertiary structure predictions showed well-defined alpha-helices and a stable 3D conformation. Molecular docking and interaction analysis further confirmed strong binding affinities with a score of -847.5 Kcal/mol between IL-24-P18 and breast cancer receptor proteins, indicating the potential for selective targeting. Moreover, the MD simulation results revealed the interaction stability of the designed fusion protein and receptor. The overall results of this Insilco study showed that IL-24-P18 fusion is a prospective novel candidate against breast cancer that has the potential to inhibit breast cancer with higher accuracy and fewer side effects as compared to already available treatments. Further, in vitro and clinical studies are required to validate its clinical applicability.