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Objective Elevated serum levels of sialic acid (SA) have been verified in patients with various inflammatory conditions. The association between the Crohn's disease (CD) activity and serum SA has been insufficiently studied. Materials and Methods Serum SA concentrations were determined using an enzymatic colorimetric assay method, and the correlation of SA with the Harvey-Bradshaw Index (HBI) and other inflammation activity markers was evaluated using the Spearman correlation. The predictive value of SA in estimating CD disease activity was assessed using the receiver operating characteristic. Results The SA levels were positively correlated with HBI and C-reactive protein (CRP) levels. The correlation of SA with the HBI was superior to that of CRP with the HBI. The area under the curve for SA was higher than that for CRP, with an optimal cutoff value of 53.14 mg/dL for active CD. Conclusion Serum SA correlates with the HBI score better and has better predictive value in monitoring CD disease activity than CRP or other inflammatory markers. [ABSTRACT FROM AUTHOR]

Research has been conducted on the role of viral mutations in HIV-infected drug addicts. Results indicate that opiate can increase HIV mutation in lymphocytes and decrease the abilities of these lymphocytes to repair DNA damage caused by chemical mutagens producing single-strand adducts.

NOD‐like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. Previous reports have shown that NLRC3 is expressed in dendritic cells (DCs). However, the role of NLRC3 in DC activation and immunogenicity is unclear. In the present study, we find that NLRC3 attenuates the antigen‐presenting function of DCs and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets. Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced experimental autoimmune encephalomyelitis (EAE) development. NLRC3 negatively regulates the antigen‐presenting function of DCs via p38 signaling pathway. Vaccination with NLRC3‐overexpressed DCs reduces EAE progression. Our findings support that NLRC3 serves as a potential target for treating adaptive immune responses driving multiple sclerosis and other autoimmune disorders. Synopsis: The innate immune sensor NLRC3 negatively regulates dendritic cell activation to affect Th1 and Th17 cell differentiation and experimental autoimmune encephalomyelitis. NLRC3 attenuates the antigen‐presenting function of DCs and their ability to activate and polarize CD4+ T cells into Th1 and Th17 subsets.Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced EAE development.NLRC3 negatively regulates the antigen‐presenting function of DCs via p38 signaling pathway. [ABSTRACT FROM AUTHOR]

Electrolytes are essential parts of the environment for all life forms, where proteins, water, and solutes interplay to support vital activities. However, a fundamental understanding of the effect of ionic solutes on proteins remains elusive for more than a century. Here we show how some ionic solutes can serve as potent denaturants despite the absence of direct protein-ion interactions. We demonstrate dramatic differences between denaturation potency of different ionic solutes with lithium bromide (LiBr) being the strongest denaturant and sodium bromide (NaBr) being the least potent. Experiments and simulations indicate the presence of certain ions disrupts the structure of water network, thereby induce protein denaturation indirectly via an entropy-driven mechanism. We further introduce a scalable strategy for protein waste revalorization, distinguished by the closed-loop recycling of denaturants, straightforward protein separation, and facile manufacturing, all enabled by the entropy-driven denaturation by LiBr. Through successful isolation and systematic study of indirect solute effects, our findings suggest a unified and generally applicable framework for decoding of the protein-water-solute nexus, where all current studies can be easily incorporated. Besides, our regeneration approach underscores the feasibility of repurposing protein waste into valuable biomaterials in a sustainable way with wide-reaching application potential.

Objective: To analyze the effectiveness of binocular loupe assisted mini-lateral and medial incisions in lateral position for the release of elbow stiffness., Methods: The clinical data of 16 patients with elbow stiffness treated with binocular loupe assisted mini-internal and external incisions in lateral position release between January 2021 and December 2022 were retrospectively analyzed. There were 9 males and 7 females, aged from 19 to 57 years, with a median age of 33.5 years. Etiologies included olecranon fracture in 6 cases, elbow dislocation in 4 cases, medial epicondyle fracture in 2 cases, radial head fracture in 4 cases, terrible triad of elbow joint in 2 cases, supracondylar fracture of humerus in 1 case, coronoid process fracture of ulna in 1 case, and humerus fracture in 1 case, with 5 cases presenting a combination of two etiologies. The duration of symptoms ranged from 5 to 60 months, with a median of 8 months. Preoperatively, 12 cases had concomitant ulnar nerve numbness, and 6 cases exhibited ectopic ossification. The preoperative range of motion for elbow flexion and extension was (58.63±22.30)°, the visual analogue scale (VAS) score was 4.3±1.6, and the Mayo score was 71.9±7.5. Incision lengths for both lateral and medial approaches were recorded, as well as the occurrence of complications. Clinical outcomes were evaluated using Mayo scores, VAS scores, and elbow range of motion both preoperatively and postoperatively., Results: The lateral incision lengths for all patients ranged from 3.0 to 4.8 cm, with an average of 4.1 cm. The medial incision lengths ranged from 2.4 to 4.2 cm, with an average of 3.0 cm. The follow-up duration ranged from 6 to 19 months and a mean of 9.2 months. At last follow-up, 1 patient reported moderate elbow joint pain, and 3 cases exhibited residual mild ulnar nerve numbness. The other patients had no complications such as new heterotopic ossification and ulnar nerve paralysis, which hindered the movement of elbow joint. At last follow-up, the elbow range of motion was (130.44±9.75)°, the VAS score was 1.1±1.0, and the Mayo score was 99.1±3.8, which significantly improved when compared to the preoperative ones ( t =-12.418, P <0.001; t =6.419, P <0.001; t =-13.330, P <0.001)., Conclusion: The binocular loupe assisted mini-lateral and medial incisions in lateral position integrated the advantages of traditional open and arthroscopic technique, which demonstrated satisfying safety and effectivity for the release of elbow contracture, but it is not indicated for patients with posterior medial heterolateral heterotopic ossification.

Background: Osteosarcoma (OS) is the most common primary malignant tumor of bone tissue, which has an insidious onset and is difficult to detect early, and few early diagnostic markers with high specificity and sensitivity. Therefore, this study aims to identify potential biomarkers that can help diagnose OS in its early stages and improve the prognosis of patients., Methods: The data sets of GSE12789, GSE28424, GSE33382 and GSE36001 were combined and normalized to identify Differentially Expressed Genes (DEGs). The data were analyzed by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genome (KEGG) and Disease Ontology (DO). The hub gene was selected based on the common DEG that was obtained by applying two regression methods: the Least Absolute Shrinkage and Selection Operator (LASSO) and Support vVector Machine (SVM). Then the diagnostic value of the hub gene was evaluated in the GSE42572 data set. Finally, the correlation between immunocyte infiltration and key genes was analyzed by CIBERSORT., Results: The regression analysis results of LASSO and SVM are the following three DEGs: FK501 binding protein 51 (FKBP5), C-C motif chemokine ligand 5 (CCL5), complement component 1 Q subcomponent B chain (C1QB). We evaluated the diagnostic performance of three biomarkers (FKBP5, CCL5 and C1QB) for osteosarcoma using receiver operating characteristic (ROC) analysis. In the training group, the area under the curve (AUC) of FKBP5, CCL5 and C1QB was 0.907, 0.874 and 0.676, respectively. In the validation group, the AUC of FKBP5, CCL5 and C1QB was 0.618, 0.932 and 0.895, respectively. It is noteworthy that these genes were more expressed in tumor tissues than in normal tissues by various immune cell types, such as plasma cells, CD8+ T cells, T regulatory cells (Tregs), activated NK cells, activated dendritic cells and activated mast cells. These immune cell types are also associated with the expression levels of the three diagnostic genes that we identified., Conclusion: We found that CCL5 can be considered an early diagnostic gene of osteosarcoma, and CCL5 interacts with immune cells to influence tumor occurrence and development. These findings have important implications for the early detection of osteosarcoma and the identification of novel therapeutic targets., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Chronic inflammation develops when the immune system is unable to clear a persistent insult. Unresolved chronic inflammation leads to immunosuppression to maintain the internal homeostatic conditions, which is mediated primarily by myeloid-derived suppressor cells (MDSCs). Toll-like receptors 2 (TLR2) has an important role in chronic inflammation and can be activated by a vast number and diversity of TLR2 ligands, for example Pam2CSK4. However, the regulatory effect of TLR2 signaling on MDSCs in chronic inflammation remains controversial. This study demonstrated that heat-killed Mycobacterium bovis BCG-induced pathology-free chronic inflammation triggered suppressive monocytic MDSCs (M-MDSCs) that expressed TLR2. Activation of TLR2 signaling by Pam2CSK4 treatment enhanced immunosuppression of M-MDSCs by upregulating inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production partly through signal transducer and activator of transcription 3 (STAT3) activation. Thus, TLR2 has a fundamental role in promoting the MDSC-mediated immunosuppressive environment during chronic inflammation and might represent a potentially therapeutic target in chronic inflammation disease., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Termedia.)

NOD-like receptor (NLR) family CARD domain containing 3 (NLRC3), an intracellular member of NLR family, is a negative regulator of inflammatory signaling pathways in innate and adaptive immune cells. Previous reports have shown that NLRC3 is expressed in dendritic cells (DCs). However, the role of NLRC3 in DC activation and immunogenicity is unclear. In the present study, we find that NLRC3 attenuates the antigen-presenting function of DCs and their ability to activate and polarize CD4 + T cells into Th1 and Th17 subsets. Loss of NLRC3 promotes pathogenic Th1 and Th17 responses and enhanced experimental autoimmune encephalomyelitis (EAE) development. NLRC3 negatively regulates the antigen-presenting function of DCs via p38 signaling pathway. Vaccination with NLRC3-overexpressed DCs reduces EAE progression. Our findings support that NLRC3 serves as a potential target for treating adaptive immune responses driving multiple sclerosis and other autoimmune disorders., (© 2019 The Authors.)