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关键词： Anti-TNF-alpha   Immune-mediated polyneuropathies   Demyelination   Conduction block  

摘要： BackgroundThere is growing evidence that anti-TNF-alpha therapies may trigger immune-mediated polyneuropathies. However, the clinical spectrum, therapeutic strategies, and long-term outcomes remain insufficiently defined. This systematic review aims to address these gaps by collecting published case-reports and describing two additional cases of anti-TNF-alpha-induced *** total of 99 cases from the literature and two from our center were included (n = 101). Clinical, neurophysiological, therapeutic, and outcome data were summarized. Predictors of poor neurological outcomes were identified using univariate and multivariate logistic *** percent of neuropathies typically developed within the first 24 months of treatment (median: 6 (IQR: 3-14) months), with Infliximab as the most frequently implicated agent (63.4%). Motor impairment, either isolated (29.7%) or with sensory symptoms (55.4%), was the predominant presentation. Neurophysiological studies showed conduction blocks (41%) or demyelination (39%). TNF-alpha therapy was discontinued in 94.8% of cases, and rescue immunotherapy was used in 73%. Complete recovery occurred in 39.6%, while 31.7% developed a chronic inflammatory demyelinating polyneuropathy-like *** analysis identified sensory-motor involvement, demyelination, and conduction blocks as predictors of poor outcome;multivariate analysis confirmed sensory-motor involvement as an independent predictor (OR = 5.14;95% CI: 1.24-21.34;p = 0.024). Symptom recurrence was evident in 7 re-exposed patients, while no relapse was observed in 2 patients who underwent dose reduction or different anti-TNF-alpha *** percent of neuropathies typically developed within the first 24 months of treatment (median: 6 (IQR: 3-14) months), with Infliximab as the most frequently implicated agent (63.4%). Motor impairment, either isolated (29.7%) or with sensory symptoms (55.4%), was the predominant presentation. Neur

关键词： Atherosclerosis   omics   biological DMARD   Comorbidities   Cardiovascular system  

关键词： mRNA vaccine   IL-15   Immunotherapy   Lung cancer   Biomimetic hybrid  

摘要： CD8+T cells-based mRNA vaccines represent a promising strategy for cancer immunotherapy. However, their development is significantly limited by the low-expression of major histocompatibility complex (MHC) I on tumor cells, which impairs effective antigen presentation and T cells recognition. Given that natural killer (NK) cells can kill tumors in an MHC-independent manner, dual activation of T cells and NK cells has the potential to enhance the efficacy of immunotherapy. Herein, we developed an IL-15 functionalized biomimetic hybrid mRNA vaccine (LMPR) that activates NK cells in collaboration with CD8+T cells, compensating the MHC-dependent limitation to boost antitumor therapy. Once vaccinated, LMPR is effectively taken up by dendritic cells (DCs) and successfully translated into antigenic proteins to initiate antigen-specific T-cell immune responses. Meanwhile, IL-15/IL-15 receptor alpha (IL-15R alpha) induces oxidative stress tolerance of NK cells by regulating the balance of thioredoxin system, thereby promoting the proliferation of NK cells and synergistically exerting anti-tumor effect with CD8+T cells. Upon intranasal administration to lewis lung cancer (LLC)-bearing mice, LMPR signifcantly promotes infiltration of CD8+T cells and NK cells, accompanied by elevated level of interferon-gamma (IFN-gamma) and Granzyme B (GZMB), exhibiting superior cytotoxicity in suppressing tumor growth. Notably, LMPR potently facilitates the up-regulation of T-bet, thus enriching the differentiation of effector memory T cell (Tem) to inhibit tumor recurrence. Therefore, this innovative approach elicits dual activation by CD8+T cells and NK cells, holding great potential for potentiating therapeutic mRNA vaccination antitumor immunity.

摘要： [This retracts the article DOI: 10.3892/etm.2019.8192.].

关键词： Imaging   Enthesitis   Ultrasound   biological DMARD  

摘要： Background: Among the various clinical presentations of psoriatic arthritis (PsA), distal interphalangeal predominant psoriatic arthritis (DIP-PsA) is particularly challenging due to its specific involvement of the distal interphalangeal joints, which can significantly affect patient prognosis and quality of life. Nailfold videocapillaroscopy is a non-invasive tool that allows for the assessment of capillary morphology, potentially providing insights into microvascular changes related to disease activity and treatment response. Objectives: This study aimed to determine the correlation between capillary alterations, DIP joint extensor tendon enthesopathy and DIP synovitis in patients with PsA and Psoriasis (PsO) treated with TNF inhibitors. Methods: A total of 65 patients were included in this retrospective study: 35 patients with DIP predominat PsA and 30 patients with psoriasis who were prescribed anti-TNF therapies. Patients were evaluated using nailfold videocapillaroscopy and Power Doppler ultrasound before and after 6 months of treatment. Inclusion criteria: patients with positive cutaneous biopsy suggestive of psoriasis and PsA patients (who met the CASPAR criteria) who were prescribed anti TNF treatment. Exclusion criteria: age under 18 years old, Raynaud's syndrome, history of smoking or alcoholism, patients with prior biological treatment. Results: Among the PsA group, 37% of patients had enthesitis of the DIP joints, and all of them had DIP joint synovitis. We observed that 45% of them exhibited grade 1 synovitis, while 30% presented with grade 2, and 25% were classified with grade 3. In the PsO group, 31% had enthesitis, while 13% exhibited subclinical synovitis. Our observations revealed that among patients with psoriatic arthritis exhibiting enthesitis, 31% had capillaroscopic abnormalities (reduced capillary density and dilated capillaries). In those diagnosed with synovitis, 22% showed similar capillaroscopic findings, characterized by decreased capil

关键词： Fluoride   Vitamin B2   Enterohepatic circulation   IL-17A   Ileal microbiome  

摘要： Introduction: Fluorosis is a global public health disease affecting more than 50 countries and 500 million people. Excessive fluoride damages the liver and intestines, yet the mechanisms and therapeutic approaches remain unclear. Objectives: To explore the mechanisms by which fluoride-induced intestinal-hepatic damage and vitamin B2 alleviation. Methods: Fluoride and/or vitamin B2-treated IL-17A knockout and wild-type mouse models were established, the morphological and functional changes of liver and gut, total bile acid biosynthesis, metabolism, transport, and regulation of FXR-FGF15 signaling pathways were evaluated, the ileal microbiome was further analyzed by 16S rDNA sequence. Finally, Bifidobacterium supplementation mouse model was designed and re-examined the above indicators. Results: The results demonstrated that fluoride induced hepatointestinal injury and enterohepatic circulation disorder by altering the synthesis, transporters, and FXR-FGF15 pathway regulation of total bile acid. Importantly, the ileum was found to be the most sensitive and fluoride changed ileal microbiome particularly by reducing abundance of Bifidobacterium. While vitamin B2 supplementation attenuated fluoride-induced enterohepatic circulation dysfunction through IL-17A and ileal microbiome, Bifidobacterium supplementation also reversed fluoride-induced hepatointestinal injury. Conclusion: Fluoride induces morphological and functional impairment of liver and gut tissues, as well as enterohepatic circulation disorder by altering total bile acid (TBA) synthesis, transporters, and FXR-FGF15 signaling regulation. Vitamin B2 attenuated fluoride-induced enterohepatic circulation disorder through IL-17A knockout and ileal microbiome regulation. The ileum was found to be the most sensitive to fluoride, leading to changes in ileal microbiome, particularly the reduction of Bifidobacterium. Furthermore, Bifidobacterium supplementation reversed fluoride-induced hepatointestinal injury. This stu

关键词： biological DMARD   Infection  

关键词： Cell differentiation   Interleukin-4   Peptide hydrogel   Skeletal muscle regeneration   Stromal derived factor-1  

摘要： Under specific circumstances, such as extensive injuries, the development of degenerative diseases, or aging, the na & iuml;ve potential of skeletal muscle to regenerate may be limited. For this reason, different tools and approaches are being tested which could result in the improvement of skeletal muscle reconstruction. Among them are hydrogels, investigated also by us, additionally functionalized with fragments of proteins known to support skeletal muscle regeneration, i.e., stromal-derived factor 1 or interleukin 4. In the current study, we evaluated the impact of such custom-designed hydrogels on different human cells important for efficient muscle regeneration, i.e., myoblasts, crucial for myofiber reconstruction, fibroblasts, ensuring ECM formation, and endothelial cells, securing new vessel development in regenerated muscles. Our results indicate that hydrogels functionalized with SDF-1 and IL-4 peptides induce beneficial but diverse effects in analyzed cell types, influencing either their proliferation, migration, or differentiation. Most importantly, hydrogels tested by us do not harm analyzed cell types, indicating that in vivo skeletal muscle regeneration might be improved by them.

关键词： HLA-DQB1*03:19:01:03   HLA-genotyping   Illumina   next generation sequencing   novel allele  

摘要： The HLA-DQB1*03:19:01:03 allele differs from HLA-DQB1*03:19:01:01 by a single nucleotide substitution in intron 2.

关键词： Lung cancer   Curcumin   STAT1   PD-L1   IFN-gamma  

摘要： Background: Immune evasion in non-small cell lung cancer (NSCLC) is largely mediated by programmed death-ligand 1 (PD-L1), which is upregulated by interferon-gamma (IFN-gamma)-induced STAT1 activation. Targeting this pathway may improve immunotherapy outcomes. Curcumin, a natural polyphenol, has been reported to modulate various oncogenic signaling pathways, but its role in inhibiting IFN-gamma-driven PD-L1 expression in NSCLC remains unclear. Methodology: The NSCLC cell line A549 were treated with curcumin (50 mu M) for 2 h before stimulation with IFN-gamma (500 U/ml). Western blot, qRT-PCR, and immunofluorescence microscopy were used to evaluate STAT1 phosphorylation, PD-L1 expression, and the localization of phosphorylated STAT1 (p-STAT1). The expression of interferon-stimulated genes (ISGs), including SOCS1 and ISG15, was also examined. Additionally, the Resazurin assay was performed to assess cell viability. Results: IFN-gamma significantly induced STAT1 phosphorylation, leading to a time-dependent upregulation of PD-L1 expression. Immunofluorescence confirmed that p-STAT1 is translocated to nucleus. Curcumin treatment inhibited STAT1 phosphorylation by 68% (p < 0.001), leading to a marked reduction in PD-L1 expression. Moreover, curcumin suppressed IFN-gamma-induced SOCS1 (63%) and ISG15 (54%) expressions, indicating a broader effect on STAT1-mediated immune evasion. Finally, curcumin enhanced IFN-gamma-mediated growth inhibition, reducing cell viability by 47% at 48 h (p < 0.01). Conclusion: Curcumin effectively inhibits IFN-gamma-induced STAT1 phosphorylation and PD-L1 expression, downregulates ISGs, and enhances IFN-gamma-mediated tumor suppression. These findings suggest that curcumin may serve as a therapeutic adjuvant in NSCLC, potentially improving immune checkpoint inhibitor (ICI) efficacy.