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关键词： Acute pancreatitis   Gastrointestinal injury   Severity   IL-23   C-reactive protein/albumin ratio  

摘要： Objective. To explore the effect of C-reactive protein/albumin ratio (CAR) combined with IL-23 on early prediction of acute gastrointestinal injury (AGI) in patients with acute pancreatitis (AP). Methods. The clinical data of 120 AP patients were retrospectively analyzed, of which 103 patients were in the non-severe AP group and 20 were in the severe AP group (SAP group). The medical records and clinical indicators of all the patients were collected and statistically analyzed. Results. At admission, there was no statistically significant difference in temperature, respiratory rate, alanine aminotransferase, aspartate aminotransferase, LPS, and total bilirubin, and there was a statistically significant difference in heart rate, IL-23, procalcitonin, blood creatinine, CRP, blood urea nitrogen, serum albumin, blood glucose, and CAR. Multifactorial logistic regression analysis revealed that CAR and IL-23 were significant predictors of SAP. CAR and IL-23 at admission were positively correlated with BISAP score (r=0.301, P<0.001;r=0.295, P<0.01). ROC curves showed that the area under the curve of CAR was 0.732 (95% CI: 0.770-0.901), with a sensitivity of 75.00% and a specificity of 85.9%, respectively, and the area under the curve of IL-23 was 0.848 (95% CI: 0.731-0.887), with a sensitivity of 80% and a specificity of 71.4%, respectively. The area under the curve of CAR and IL-23 was 0.899 (95% CI: 0.846-0.936), with a sensitivity of 78% and a specificity of 86.2%. Conclusion. CAR and IL-23 have significant advantages in predicting the severity of AGI in patients with AP, and their predictive efficacy is further increased especially when they are combined.

关键词： agomelatine   inflammation   insulin resistance   kidney injury   necroptosis   obesity  

摘要： Obesity is a risk factor for chronic kidney disease. The expansion of adipose tissues in obesity induces insulin resistance and low-grade systemic inflammation, promoting kidney damage. Our previous studies have demonstrated that agomelatine (AGOM) exerts renoprotective effects in experimental models of obesity and insulin resistance through various mechanisms, including the attenuation of ER stress and oxidative stress. This study aimed to further explore the effects of agomelatine on renal inflammation, insulin signaling, and necroptosis in obese, insulin-resistant rats. Obesity was induced in rats with a high-fat diet for 16 weeks, followed by 4 weeks of treatment with 20 mg kg-1 day-1 of AGOM or 10 mg kg-1 day-1 of pioglitazone (PIO). The results showed that insulin resistance was improved after treatment with AGOM and PIO, as demonstrated by the reduction in fasting plasma glucose, insulin, and HOMA-IR. Both treatments restored the levels of renal insulin signaling proteins. Moreover, AGOM inhibited TNF alpha, TNFR1, NF-& kgreen;B, COX2, and IL1 beta, which attenuated the necroptosis-related proteins RIPK3 and MLKL. AGOM also prevented kidney DNA fragmentation, as detected by the TUNEL assay. In an obese condition, the level of the tight junction protein claudin-1 (CLDN1) was enhanced after being treated with AGOM. In conclusion, the novel mechanisms associated with AGOM and involved in limiting kidney injury were the inhibition of the TNF alpha/NF-& kgreen;B/p-RIPK3 pathway and a reduction in inflammation and necroptosis. This suggested that AGOM could be an effective treatment for inhibiting kidney dysfunction in cases of obesity and insulin resistance. These findings open new avenues for the management of renal dysfunction, with implications for personalized medicine.

关键词： inflammatory bowel disease   Crohn's disease   ulcerative colitis   early treatment   anti-TNF-alpha   biosimilar  

摘要： Data indicate that earlier initiation of anti-tumor necrosis factor alpha (anti-TNF-alpha) biologic medicines may prevent progression to irreversible bowel damage and improve outcomes for patients with inflammatory bowel disease (IBD), particularly Crohn's disease. However, the high cost of such therapies may restrict access and prevent timely treatment of IBD. Biosimilar anti-TNF-alpha medicines may represent a valuable opportunity for cost savings and optimized patient outcomes by improving access to advanced therapies and allowing earlier anti-TNF-alpha treatment initiation. Biosimilar anti-TNF-alpha medicines have been shown to offer consistent therapeutic outcomes to their reference medicines, yet despite entering the IBD treatment armamentarium over 10 years ago, their implementation in clinical practice remains suboptimal. Factors limiting the 'real' use of biosimilar anti-TNF-alpha medicines may include an ongoing lack of understanding and acceptance of biosimilars by both healthcare professionals (HCPs) and patients, as well as systemic factors such as formulary decisions outside of the control of the prescriber. In this review, an expert panel of gastroenterologists discusses HCP-level considerations to improve biosimilar anti-TNF-alpha utilization in IBD in order to support early anti-TNF-alpha initiation and maximize patient outcomes.

关键词： Calcitriol   Immune system   Cytokine   Vitamin D receptor   Muscle-immune-crosstalk   Immunosenescence  

摘要： Besides its classical skeletal function, vitamin D plays a critical role in both skeletal muscle and the immune system. Interleukin-15 (IL-15), which is highly expressed, and secreted complexed with its receptor, IL-15R alpha, by skeletal muscle, stimulates the development of immune cells and affects myogenesis and muscle mass. However, little is known about possible regulators of this myokine. To test whether vitamin D could be a regulator of muscle IL-15 and IL-15R alpha expression, C2C12 myotubes were treated with vitamin D3 metabolites and analysis were performed in gastrocnemius muscles of rats treated with a single intraperitoneal dose of 1,25(OH)2D3. The role of VDR was investigated by siRNA technique in C2C12 myotubes and in gastrocnemius muscles of vitamin D receptor knockout (Vdr-KO) mice. Treatment of C2C12 myotubes with 1,25(OH)2D3 or 25(OH)D3 increased Il-15 gene expression in a dose-dependent manner and 1,25(OH)2D3 also moderately increased the relative Il-15 protein amount. Rats treated with a single dose of 1,25(OH)2D3 demonstrated a higher mRNA abundance of muscle Il-15 than controls. The 1,25(OH)2D3 effect on Il-15 was considerably weaker in C2C12 myotubes treated with Vdr-specific siRNA. Vdr-KO mice showed significantly lower muscle Il-15 mRNA than WT mice. Il-15Ra mRNA and Il-15/Il-15R alpha protein abundance were unaffected by 1,25(OH)2D3-treatment or VDR functionality, and Cyp27b1 activity is not required for 25(OH)D3-mediated Il-15 gene expression. The results provide evidence for a regulatory role of hydroxyvitamin D3 metabolites on the Il-15 synthesis in skeletal muscle cells, which is largely mediated by the VDR.

关键词： Temporal high-glucose   Inflammatory cytokine   BRD4   Histone acetylation   Macrophage   Type 2 diabetes mellitus  

摘要： Background: Postprandial hyperglycemia induces expression of inflammatory cytokines including tumor necrosis factor (TNF), which promotes the onset of type 2 diabetes and cardiovascular diseases. In this study, we investigated whether a transient high-glucose culture enhanced sustained expression of TNF, or whether the induction is associated with histone acetylation, and bromodomain protein containing protein 4 (BRD4), which binds acetylated histone, in human juvenile macrophage-like THP-1 cells. Methods: THP-1 cells were cultured in medium with high-glucose in the presence or absence of (+)-JQ1, an inhibitor of bromodomain and extra-terminal domain family, for 24 h (day 0). Thereafter, the cells were returned to a low-glucose medium without (+)-JQ1 and cultured for 2 or 4 days and samples were collected. mRNA expression of inflammation genes, and histone H3 K9/14 acetylation and binding of BRD4 and RNA polymerase II around the TNF gene were measured by RT-qPCR and chromatin immunoprecipitation, respectively. Results: TNF mRNA levels, histone H3 K9/14 acetylation, and bindings of BRD4 and RNA polymerase II to the TNF gene were higher in cells exposed to high-glucose culture for 24 h and subsequently cultured in low-glucose medium for 2-4 days, compared with cells cultured in a low-glucose medium. The addition of (+)-JQ1 to the high-glucose medium for 24 h reduced histone H3 K9/14 acetylation, and BRD4 and RNA polymerase II bindings around TNF gene, and the mRNA levels. Conclusions: Histone H3 K9/14 acetylation and BRD4 binding are associated with the sustained expression of TNF mRNA induced by temporal high-glucose exposure in juvenile macrophage-like THP-1 cells.

关键词： Si photonics   Parallel test   IL   PDL   SOP   Wafer testing  

摘要： We propose a measurement system that enables the rapid measurement of insertion loss and polarizationdependent loss using a parallel test setup with a fiber array, and the calibration procedure to be used within this system. By applying rough scan methods, we have developed a calibration algorithm that efficiently finds the accurately optimized state of polarization in minimal time. Through conducting on-wafer spectral optical power measurements, we compared conventional applications and our proposed algorithms. The results demonstrate that our method enables the almost simultaneous measurement of the spectral responses of multiple optical components. Moreover, the method enables to measure these responses with a well-defined input state of polarization (SOP) applied to each path individually. This novel approach holds promise for enhancing accuracy and cost-effectiveness in insertion loss and polarization-dependent loss measurements.

关键词： Auto-inflammatory disease   Interleukin 18   Hemophagocytic lymphohistiocytosis   Actinopathies   PSTPIP1   XIAP   CDC42   Still disease  

摘要： Autoinflammatory diseases (AIDs) are conditions characterized by dysfunction of innate immunity, causing systemic inflammation and various clinical symptoms. The field of AIDs has expanded due to improved comprehension of pathophysiological mechanisms and advancements in genomics techniques. A new emerging category of AIDs is characterized by a significant increase in interleukin 18 (IL-18), a pro-inflammatory cytokine synthesized in macrophages and activated by caspase 1 via various inflammasomes. IL-18 plays a role in the regulation of innate and adaptive immunity. IL-18 is involved in various functions, such as the proliferation, survival, and differentiation of immune cells, tissue infiltration of immune cells, polarization of immune responses, and production of other pro-inflammatory cytokines. This review analyzes the literature on IL-18 regarding its functions and its implications in the diagnosis and treatment of AIDs. IL-18-associated AIDs comprise Still's disease and diseases associated with mutations in NLRC4, XIAP, CDC42, and PSTPIP1, as well as IL-18BP deficiencies. With the exception of PSTPIP1-associated diseases, these conditions all carry a risk of macrophagic activation syndrome. Measuring IL-18 levels in serum can aid in the diagnosis, prognosis, and monitoring of these diseases. Therapies targeting IL-18 and its signaling pathways are currently under investigation. (c) 2024 Societe Nationale Francaise de Medecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

关键词： HLA   lupus   rheumatoid arthritis   DRB1   autoimmune  

摘要： Objective: A narrative short review has been made aiming to identify the most important immune disorders associated with the HLA DRB1*allele. Material and Methods: Data have been taken from PubMed, and 36 articles have been retrieved. Results: It has been found that DRB1*16:02 is associated with autoimmune diseases with production of autoantibodies, mainly systemic lupus erythematosus and myasthenia gravis. DRB1*04 is associated with lupus erythematosus, bullous pemphigoid, and pemphigus vulgaris. DRB1*is also associated with dermatitis herpetiformis, alopecia areata, acute generalised exanthematous pustulosis, and systemic sclerosis. No association of DRB1 has been found either with psoriasis or with psoriatic arthritis, while the association of Cw6 and DRB1*07 confers less severe joint damage in patients with psoriatic arthritis. Conclusion: DRB1* is associated with lupus erythematosus rheumatoid arthritis and with most immune disorders with skin involvement.

关键词： Common cancer antigen   Cancer-specific antigen   Cytotoxic T lymphocyte (CTL)   Peptide vaccine   mRNA vaccine   HLA-A24   HLA-A2  

摘要： Targeting cancer antigens expressed in cancer cells is necessary to develop cancer-specific immunotherapy. We have performed immunohistochemical analysis of various solid cancer specimens, adding ROBO1, AFP, TGFBI, EphB4, CLDN1, and LAT1 to the previously studied glypican-3 (GPC3), HSP105 alpha, FOXM1, and SPARC, and found that these 10 common cancer antigens are sufficient to cover most solid cancers. These antigens were frequently expressed in various solid cancers but shown to be rarely ex-pressed, with some exceptions, in non-cancerous normal organs adjacent to the cancer. In this study, we predicted 72 and 73 peptides that bind to HLA-A24 and -A2 in silico from the full-length amino acid sequences of these 10 common cancer antigens and immunized each HLA transgenic mouse with a cocktail of synthesized peptides together with the poly I:CLC three times weekly to analyze the antigen-specific immune response. As a result, 68 peptide sequences (30 and 38, respectively) were identified that had higher cytotoxic T lymphocyte (CTL) induction ability than GPC3 298-306 and GPC3 144-152 used in the clinical trials. Furthermore, experiments with cocktail peptide vaccines using mouse models expressing subcutaneous tumors of each antigen showed promising results in terms of safety and efficacy. These peptides identified in this study, derived from 10 common cancer antigens covering all solid cancers, are expected to be clinically applicable as cocktail peptide vaccines.

关键词： colorectal cancer   DMH   JAK2   linagliptin   rats   STAT3  

摘要： Colorectal cancer (CRC) is a multicomponent disease and the second most frequent root of cancer-related deaths globally. Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. It has been repurposed in recent experimental studies due to its marked anti-inflammatory activities. This study aimed to evaluate the ameliorative role of linagliptin in 1,2-dimethylhydrazine (DMH)-induced CRC via modulation of NFAT-mediated IL-6 and JAK2/STAT3/NF-kappa B signaling pathways. CRC model has been successfully established via a dose equal 40 mg/kg two times a week of DMH for 8-week duration. Twenty-four Wistar rats were segregated into three groups of eight rats each;normal control, DMH-induced CRC and DMH + linagliptin (10 mg/kg;p.o). Linagliptin attenuated DMH-induced oxidative stress by restoring the declined levels of some antioxidant enzymes. Linagliptin suppressed the elevated nuclear factor kappa B (NF-kappa B) induced by DMH which is highlighted using immunohistochemistry analysis. The anti-inflammatory role of linagliptin has been fortified by the decline in nuclear factor of activated T-cells (NFAT) mRNA expression level along with the reduction in vascular endothelial growth factor (VEGF), interlukin-6 (IL-6) and cyclooxygenase-2 (COX-2) levels. Linagliptin mitigate the protein expression of DMH-activated oncogenic janus-activated kinase/signal transducers and activators of transcription (JAK2/STAT3). Linagliptin exerted a proapoptotic effect to tumor cells manifested by a remarkable decline in B-cell lymphoma 2 (Bcl-2) and a significant elevation in Bcl-2-associated X protein (Bax) expression levels. The histopathological analysis revealed that linagliptin has inhibitory potential against the DMH induced dysplastic aberrant crypt foci (ACF) and adenocarcinoma. Linagliptin ameliorated CRC by modulating NFAT-mediated IL-6 with JAK2/STAT3/NF-kappa B signaling cascades.