课程文献中心 更多>>

关键词： Nanomaterials   Green synthesis   In-silico analysis   Rheumatoid arthritis   TNF-a  

摘要： Nanotechnology is widely recognised as one of the most important advances in science from the last decades. Its numerous applications and rapidly expanding demand have led the way for innovative approaches to the synthesis of nanomaterials of higher quality. Green synthesis of silver nanoparticles (AgNPs) using the Dimorphocalyx glabellus (Sny. Tritaxis glabella Thwaites *** & Welzen var. glabella) which has many medicinal properties including treatment of psoriasis and it also has anti-diabetic, anti-diuretic and anti-rheumatic property. The present study assessed with methanolic extract leaves of D. glabellus and its characterization through GC-MS analysis to identify the phyto-constituents. Moreover, AgNPs were synthesized using the leaf extract of D. glabellus and subsequently characterized using UV-Vis Spectrophotometer, Scanning Electron Microscope (SEM), and Fourier Transform Infrared Spectroscopy (FTIR) techniques to verify the formation of AgNPs within the plant extract. The analysis of FTIR spectra revealed the presence of various functional groups such as carboxyl, amine, and phenolic compounds which play a vital role in the reduction of silver ions in the leaf extract of D. glabellus. Furthermore, the phyto-constituents compounds in the plant extract were studied in-silico for possible interaction with TNF-alpha, vital for rheumatoid arthritis and other diseases. This suggests the potential use of these phyto-constituents of D. glabellus as a natural remedy for the treatment of Rheumatoid Arthritis, offering a promising alternative to traditional medications. (c) 2025 SAAB. Published by Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

摘要： Background Pemphigus is a life-threatening autoimmune disease mediated by anti-desmoglein (Dsg) autoantibodies. Ectopic lymphoid-like structures (ELS) are frequently found in chronic skin lesions and are thought to contribute to local autoantibody production. However, the mechanisms driving ELS formation at lesion sites remain *** To investigate the role of myeloid cells in the formation of ELS in pemphigus lesions, and to identify potential therapeutic targets by better understanding the underlying mechanisms that contribute to this *** We used single-cell RNA sequencing (scRNA-seq) to identify the myeloid subpopulations in pemphigus lesions and study their functions. Immunohistochemistry (IHC), immunofluorescence and flow cytometry were used to validate the presence of interleukin (IL)-1 beta-producing myeloid cells. Culture, bulk RNA-seq and transwell chemotaxis experiments were conducted to assess the effects of IL-34 and tumour necrosis factor (TNF)-alpha on monocytes. Additionally, the high expression of IL-34 in pemphigus keratinocytes was validated by *** We first confirmed the abundant presence of myeloid cells within ELS in pemphigus skin lesions, including pemphigus vulgaris and pemphigus foliaceus. Single-cell RNA-seq revealed that IL-1 beta-producing macrophages ('IL1B_Macro') is the dominant myeloid subpopulation in pemphigus lesions, originating from classical monocytes. These cells have a strong inflammatory and chemotactic transcriptomic profile, expressing high levels of IL-1 beta, IL-6 and chemokines such as CCL20, CCL3, CCL5 and CXCL5, promoting leucocyte infiltration. Ex vivo experiments showed that IL1B_Macro differentiation is enhanced by the synergistic action of IL-34 and TNF-alpha, which can be attenuated by a colony-stimulating factor 1 receptor (CSF-1R) inhibitor. IL-34 alone also promotes IL-1 beta and CCL20 expression, and keratinocytes were found to be the major source of elevated IL-34 in pemphigus l

关键词： Large yellow croaker ( Larimichthys crocea )   Pro-inflammatory factor   Interleukin-18   Bacterial infection  

摘要： Interleukin-18 (IL-18), a pro-inflammatory cytokine of the IL-1 family, is crucial for protecting the host against pathogen infection in mammals. In this study, a IL-18 homolog gene was cloned from large yellow croaker (Larimichthys crocea) (LcIL-18), which has an open reading frame (ORF) of 609 bp that encodes a polypeptide of 202 amino acids. The LcIL-18 C-terminus contains a typical IL-1 family signature and a caspase cleavage site. Phylogenetic analysis showed that LcIL-18 was most closely related to IL-18 of Miichthys miiuy. It was found that LcIL-18 was constitutively expressed in all 12 tissues tested of large yellow croakers, with the highest expression in gills. The expression of LcIL-18 in head kidney, spleen, skin, gills, and liver showed a differential pattern following infection with Pseudomonas plecoglossicida and Vibrio alginolyticus. P. plecoglossicida strongly induced LcIL-18 expression in these tissues. Conversely, in the early stage of infection, V. alginolyticus significantly inhibited LcIL-18 expression in head kidney, spleen, skin, and gills, but not in the liver. In vitro, LPS, Poly(I:C), P. plecoglossicida, and V. alginolyticus significantly upregulated the expression of the LcIL-18 in large yellow croaker head kidney (LYCK) cells. Furthermore, recombinant LcIL-18 (rLcIL-18) significantly increased cell viability and upregulated the expression of pro-inflammatory cytokines (LcIL-1 beta, LcIL-6, and LcTNF-alpha 1) in LYCK cells. Our findings therefore indicated that LcIL-18 was involved in pro-inflammatory response induced by pathogenic bacteria.

关键词： Eruca vesicaria essential oil   Acetamiprid   Nephrotoxicity   GC-MS analysis   Oxidative stress   Biochemical/molecular analysis  

摘要： Acetamiprid (Aceta) is a neonicotinoid insecticide utilized extensively worldwide, and its environmental and human health risks are of concern. Eruca vesicaria is an edible year-round plant that contains a lot of healthpromoting phytochemicals and is an excellent source of antioxidants. So, the present investigation was planned to assess the effect of E. vesicaria seed essential oil versus acetamiprid-induced toxicity in rats. Animals were partitioned into 4 groups of seven each: control, E. vesicaria seeds essential oil (ESEO;0.17 mL/kg), acetamiprid (Aceta;21.7 mg/kg), and ESEO plus Aceta, respectively. Doses were given orally and daily for 14 days. Results revealed that ESEO has many phytochemical components with high antioxidant activity. Data showed that treatment with Aceta increased lipid peroxidation and decreased the activities of "enzymatic and non-enzymatic antioxidants" in kidney homogenate. Also, disturbance of kidney and liver function biomarkers, lipid profile, and protein content were observed. These are confirmed by the histological, molecular (Cox-2, TNF-alpha, and PPAR-alpha), and renal damage biomarkers (KIM-1 and Cystatin C) examination. On the other hand, rats administered ESEO and then treated with Aceta showed significant amelioration in most of the examined indices. To sum up, ESEO has a potent anti-inflammatory, anti-apoptotic, and antioxidant activity that protects against the pronounced harmful effects of Aceta in rat kidneys due to its health-promoting phytochemicals.

关键词： Biomarker interaction   Peripheral biomarkers   Treatment-resistant depression   Therapeutic drug monitoring  

摘要： We read with great interest the article by Cho et al. (2025), which prospectively examined the interplay between serum interleukin-1β (sIL-1β) and brain-derived neurotrophic factor (sBDNF) in predicting antidepressant treatment response( Cho et al...

关键词： Lung inflammation   Interleukin-17A   IL-17 receptor   Animal model   IL-17-Act1 pathway  

摘要： IL-17A is a potent proinflammatory cytokine that plays a crucial role in the pathogenesis of various lung diseases. This study focused on the evaluation of the role of IL-17 receptor signaling through one-week intranasal exposure of IL-17A in lung tissues of BALB/c mice. IL-17A triggered inflammatory responses in the mice lungs and led to changes in the morphological alveolar arrangements. Exposure of IL-17A induced redox imbalance by triggering an increase in the level of the pro-oxidants (reactive oxygen species, nitrite and malondialdehyde) and reduction of the levels of antioxidant proteins (glutathione, superoxide dismutase and catalase) in the lung tissue. IL-17A also caused a significant elevation in the levels of proinflammatory cytokines lines including TNF-alpha, IL-1 beta and IL-6, in lung tissue as well as in plasma. More interestingly, these changes were accompanied by the alterations in IL-17 receptor downstream signaling through activation of IL-17R-Act1-TRAF6-IKB alpha-mediated pathway. IL-17A exposure also caused lung tissue injury, recruitment and polarization of immune cells from anti-inflammatory to pro-inflammatory. This study clearly demonstrated the role of IL-17A-induced signaling in worsening lung inflammatory diseases, and hence points towards its emergence as an important therapeutic target to control lung inflammation.

关键词： CD317/tetherin   extracellular vesicles   immune modulation   mesenchymal stromal cells  

摘要： In spite of the numerous clinical trials conducted on mesenchymal stromal cells and their extracellular vesicles (MSC-EVs) across a wide range of diseases, the field faces challenges in reaching a consensus on crucial parameters such as source, marker definition, and culture conditions, adding to heterogeneous efficiencies. Nevertheless, there is widespread acceptance of the pro-inflammatory activation of MSCs with IFN-γ and TNF-α to enhance immune modulation. Our study highlights the impact of activation duration on MSC-EV-mediated immune modulation of macrophages. Extended activation periods (24 h) revealed elevated levels of IFN-γ-induced CD317 on the MSC surface. CD317 is known to tether enveloped viral particles to the cell membrane, impeding viral diffusion and spread. We demonstrated the accumulation of EVs on the MSC cell surface following activation or lentiviral CD317 overexpression. In contrast, CD317 knockdown eliminated the enrichment of EVs on the cell surface, significantly enhancing the MSC-EV-mediated immune modulation of macrophages. Considering the pivotal role of IFN-γ in MSC immune modulation and its inevitable contact in patients, our findings propose CD317 as a potential modulator of MSC-based therapy efficacy in clinical applications.

关键词： HLA   autoimmune disease   congenital hypothyroidism without goiter   diabetes mellitus   endocrine pathology   obesity  

摘要： Endocrine disorders represent a serious public health problem and frequently can be caused by genetic factors or their combination with environmental and lifestyle factors. Assessment of relevant genetic factors is important to estimate the risk of endocrine pathologies in an individual before their manifestation. Identification of genetic variations in proteins of the major histocompatibility complex is important with regard to the autoimmune nature of many endocrine pathologies, including type 1 diabetes. In this study, we investigated the relationship between human leukocyte antigen (HLA) genes and 13 endocrine disorders by using experimental whole-exome sequencing profiles obtained for 895 patients from the National Medical Research Center for Endocrinology, Moscow. In addition, the linkage disequilibrium of the identified alleles in the context of the respective diagnoses was assessed. We identified totally 45 statistically significant associations between HLA alleles and specific diagnoses of endocrine pathologies. Among them, 33 were described for the first time and 12 have been previously reported for type 1 diabetes. Overall, 17 alleles were associated with type 1 diabetes and four alleles - with other forms of diabetes. Furthermore, three alleles were associated with obesity, five - with adrenogenital diseases, three - with hypoglycemia, and three - with precocious puberty. Single alleles were found to be associated with congenital hypothyroidism without goiter, hyperfunction of pituitary gland, adrenomedullary hyperfunction, and short stature due to endocrine disorder. The study shows that early HLA typing can help in detecting genetic risk factors of endocrine disorders. In addition, identification of disease associations with specific HLA alleles can broaden our understanding of the mechanisms involved in the pathogenesis of relevant endocrine disorders.

关键词： CAR T-cell therapies   desensitization   kidney transplantation   plasma cell-directed therapies   plasmapheresis  

摘要： Despite development of kidney paired donation programs and prioritization in kidney allocation schemes, transplantation rates are still low and waiting times remain prolonged for highly sensitized kidney transplant recipients with broad human leukocyte antigen antibody reactivity. Desensitization confers an invaluable option improving access to kidney transplantation for sensitized patients who could not benefit from kidney paired donation programs and kidney allocation schemes. Conventional desensitization strategies use intravenous immunoglobulin combined with either plasmapheresis or monoclonal anti-CD20 antibodies. Imlifidase, IL-6 targeting agents, plasma cell-directed therapies, complement inhibitors, chimeric antigen receptor T-cell therapies, and B cell-activating factor inhibitors are emerging new options in the hope of enhancing and sustaining the efficacy of desensitization to improve allograft longevity. In this review, we discuss the rationale and outcome of desensitization with various strategies alone or in combination. Our aim is also to provide some insight for decision when pursuing desensitization might be successful or futile in sensitized patients.

关键词： Biomarker   Tumor microenvironment   Urothelial cancer   Immunology   Interleukin  

摘要： Interleukin-6 (IL-6) is associated with poor outcomes in bladder cancer (BC) patients, including worse overall survival (OS) and cancer-specific survival (CSS). This study analyzed serum IL-6 levels in 179 BC patients undergoing radical cystectomy and IL-6 concentrations in tumor tissue from 20 additional patients. High serum IL-6 was an independent predictor of OS and CSS, and higher levels were linked to advanced tumor stage, lymph node metastasis, and larger tumor size. Tumor tissue IL-6 was significantly elevated in muscle-invasive BC compared to early-stage tumors. These findings underscore the prognostic potential of IL-6 and its relevance in BC theranostics. Background: Interleukin-6 (IL-6) is associated with adverse clinical outcome in cancer patients. In bladder cancer (BC) patients, higher IL-6 serum levels have been linked with adverse pathologic features, worse overall survival (OS) and cancer-specific survival (CSS). IL-6 is being investigated as a therapeutic target. However, concentrations in tumor-tissue are not investigated in detail. Objective of this study is to analyze the prognostic value of IL-6 in BC patients and to investigate its concentration in tumor tissue. Methods: In this single center prospective observational study, preoperative serum samples of 179 BC patients undergoing radical cystectomy were collected between September 2019 and September 2022. Tumor-tissue of additional 20 patients was collected during transurethral resection or radical cystectomy for investigation of IL-6 in tumor tissue supernatant. IL-6 concentration was measured by ELISA. Results: Median serum IL-6 concentration was 5.4 pg/mL. High serum IL-6 was an independent predictor of OS (HR 1.95;95% CI, 1.07-3.55;P = .03) and CSS (HR 2.31;95% CI, 1.14-4.68;P = .02) in multivariate Cox regression analyses. Patients with advanced tumor stage, lymph node metastasis, and larger tumor size had significantly higher preoperative serum IL-6 concentration (all P < .01). In tumor