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关键词： Inflammation   CRP   TNF   weight loss   ketogenic diet  

摘要： Background: Lipedema is considered an inflammation-related disease, and low-carbohydrate ketogenic diets may help reduce inflammation. However, no randomized controlled trials have investigated the effect of a low-carbohydrate ketogenic diet on inflammatory markers in females with lipedema. Objectives: To compare changes in inflammatory and fibrosis-associated markers after a low-energy low-carbohydrate diet (LCD) compared with a low-fat diet in females with lipedema, and to explore potential associations between changes in pain and changes in inflammatory and fibrosis-associated markers. Methods: Females with lipedema and obesity were randomly assigned to either an LCD or low-fat diet (both 1200 kcal/d) for 8 weeks. Body composition [fat mass (FM) and fat-free mass] and the plasma concentrations of high-sensitivity C-reactive protein (hsCRP), cytokines, and fibrosis-associated markers were measured pre- and postintervention. Results: A total of 70 females were included (35/group) (mean age: 47.3 f 10.9 y, BMI: 36.9 f 4.9 kg/m2). Both groups lost weight and FM (kg and %), with a greater reduction in the LCD group. A reduction in macrophage inflammatory protein-1 ss, tumor necrosis factor-alpha, and hsCRP was seen in the LCD group only, despite no significant differences between groups. No associations were found between changes in pain and changes in cytokines and fibrosis-associated markers. Conclusions: Changes in cytokines and fibrosis-associated markers did not differ between low-energy LCD and low-fat diets in females with lipedema, despite a beneficial profile in the LCD group. Inflammation does not seem to be involved in pain reduction following LCD in this patient group. Trial registration number: This trial was registered at *** as NCT04632810.

关键词： DC-SIGN   IL-10   anti-inflammatory effects   veterinary autoimmune diseases   veterinary immune-mediated diseases   DC-SIGN ligands   DC-SIGN homologues in animals   comparative medicine   translational research  

摘要： DC-SIGN (dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin) is a C-type lectin receptor expressed on dendritic cells and M2 macrophages, playing a key role in immune regulation and pathogen recognition. Its ability to mediate anti-inflammatory effects by interacting with specific ligands triggers pathways that suppress pro-inflammatory responses and promote tissue repair, making it a potential therapeutic target for inflammatory and autoimmune diseases. DC-SIGN homologs in various animal species share structural similarities and perform comparable immune functions, offering valuable insights into its broader application across species. By recognizing carbohydrate ligands on pathogens, DC-SIGN facilitates immune modulation, which can be harnessed for developing therapies aimed at controlling inflammation. In veterinary medicine, autoimmune and inflammatory diseases, such as rheumatoid arthritis and inflammatory bowel disease, represent significant challenges, and the anti-inflammatory properties of DC-SIGN could provide new therapeutic options to improve disease management and enhance animal health. Future investigations should focus on the structural and functional analysis of DC-SIGN homologs in various species, as well as the development of preclinical models to translate these findings into clinical interventions bridging veterinary and human health.

关键词： "Tuberculosis   Circulating cytokines   Pro-inflammation   Anti-inflammatory  

摘要： Background: In human tuberculosis, Mycobacterium tuberculosis elicits immunopathology characterized by abnormal expression of plasma cytokines. This immunopathology may influence the severity of illness and the efficacy of prolonged anti-mycobacterial treatment. Methods: The study analysed TNF-alpha, IL-10, and TGF-(3 levels in 90 pulmonary tuberculosis patients and compared them with 90 healthy individuals. The tuberculosis patients were categorized as mild, moderate, or advanced based on chest x-ray results, and the ratio of pro-inflammatory to anti-inflammatory cytokines was compared. Results: All three cytokines were present in most tuberculosis patients, and their concentrations were noticeably higher than in healthy individuals. The ratio of TNF-alpha/IL-0 and TNF-alpha/TGF-(3 demonstrated the most powerful discriminatory ability in determining the severity of tuberculosis. The levels of TNF-alpha/IL-0 and TNF-alpha/ TGF-(3 in individuals with moderate and advanced tuberculosis were markedly elevated compared to those with mild cases. The area under the curve (AUC) for TNF-alpha/TGF-(3 and TNF-alpha/IL-0 was determined to be 0.823 and 0.814, respectively. Conclusions: The elevated ratio of TNF-alpha/IL-0 and TNF-alpha/TGF-(3 in the sera of TB patients may contribute to an excessive pro-inflammatory response, whereas a lower ratio may regulate excessive inflammation. Both the TNF-alpha/IL-0 and TNF-alpha/TGF-(3 ratios may effectively categorize the tuberculosis severity and have the potential to serve as biomarkers for evaluating the early response to treatment.

关键词： aspergillosis   Candida spp.   candidemia   cryptococcosis   deep fungal infection   immunodeficiency   pityriasis versicolor   systemic infection  

摘要： TNF-alpha inhibitors, including infliximab, adalimumab and etanercept, are used to treat various inflammatory diseases, such as arthritis, psoriasis and ankylosing spondylitis. However, these treatments may predispose patients to fungal infections, including histoplasmosis, candidiasis and aspergillosis. In this study, we systematically reviewed case reports to critically examine the correlations between anti-TNF-alpha therapies and the occurrence of invasive and superficial fungal infections. Infliximab was the most commonly used TNF-alpha inhibitor (50.65%). The highest number of fungal infections during anti-TNF34 alpha therapy was reported in the USA (84.25%). The conditions treated primarily included rheumatoid arthritis. A total of 517 invasive fungal infections were identified, including histoplasmosis, invasive candidiasis and aspergillosis, with histoplasmosis being the most common. Most studies were conducted in higher-income countries, highlighting the critical lack of research on the use of immunobiologicals in relation to fungal diseases in African countries, which requires further attention. Logistic regression analysis revealed significant associations between adalimumab use and increased risks of candidiasis, coccidioidomycosis, onychomycosis and pityriasis versicolor. For etanercept, significant associations were found with aspergillosis, coccidioidomycosis, cryptococcosis, dermatophytosis, invasive candidiasis, pityriasis versicolor and onychomycosis. Infliximab use was significantly associated with coccidioidomycosis, onychomycosis, aspergillosis, cryptococcosis, histoplasmosis and invasive candidiasis. The data presented in this study clearly demonstrate an association between the use of TNF-alpha inhibitors and an increased risk of fungal infections. It is imperative that healthcare professionals maintain a high level of vigilance when managing patients on these medications. Regular monitoring and proactive management strategies are essential to

关键词： Allergic rhinitis   FABP4   Inflammatory response   Barrier dysfunction   Ferroptosis  

摘要： This study was conducted to investigate the role and the mechanism of fatty acid-binding protein 4 (FABP4) in allergic rhinitis (AR). To induce AR in vitro, human nasal epithelial cells (hNECs) were treated by interleukin (IL)-13. Real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot were used to detect FABP4 expression. Enzyme-linked immunosorbent assay (ELISA) was used to detect the inflammatory level while inflammation-related proteins were detected by western blot. Immunofluorescence (IF) assay was used to detect mucin-5AC (MUC5AC) and zonula occludens-1 (ZO-1) level. The expressions of tight junction proteins were detected by western blot. Lipid reactive oxygen species (ROS) was detected using a BODIPY 581/591 C11 kit and iron level was detected by corresponding assay kits. Ferroptosis-related proteins were detected by western blot. With the goal of investigating the mechanism of FABP4 associated with ferroptosis, cells were pretreated by ferroptosis inducer erastin (30 mM) and rescue experiments were implemented. In this work, FABP4 expression was increased in hNECs treated by IL-13. After FABP4 was knocked down, the inflammation, mucus production, barrier dysfunction and ferroptosis induced by IL-13 in hNECs were all repressed. Nevertheless, erastin pre-treatment partially counteracted the protective role of FABP4 depletion against inflammation, mucus production and barrier dysfunction in IL-13-treated hNECs. In summary, FABP4 deficiency ameliorated IL-13-induced inflammatory response and barrier dysfunction in nasal mucosal epithelial cells through the regulation of ferroptosis.

关键词： Cement hydration   limestone   strength gain   Type IL cement  

摘要： This article reviews the impact of limestone on cement hydration and strength gain;discusses the fresh, mechanical, and durability properties of concrete containing Type IL cement;and suggests strategies to help precast, prestressed concrete producers make the switch to Type IL cement.

关键词： breast cancer   ferroptosis   HMGB3   IFN-gamma   immunotherapy  

摘要： Our previous studies showed HMGB3 expression may correlate with immunotherapy efficacy in breast cancer patients. Here, we investigated whether HMGB3 overexpression has an impact on anti-PD-1 therapy in triple-negative breast cancer (TNBC) and its molecular mechanisms. Animal models were established to observe the effect of HMGB3 on sensitivity to anti-PD-1 treatment. Correlation of HMGB3 expression and ferroptosis preventive proteins in TNBC patients' tissues with anti-PD-1 therapy efficacy was analyzed. The impact of HMGB3 on IFN-gamma (Interferon-gamma) inhibitory effects and signaling was examined in human TNBC cells where HMGB3 expression was knocked down using siRNA. Moreover, TNBC cells stably transfected with lentiviral vectors containing cDNA of HMGB3 were also used to confirm the effect of overexpression of HMGB3 on IFN-gamma inhibitory effect and signaling. Effect of HMGB3 on IFN-gamma-driven ferroptosis and ferroptosis-associated protein expression were also investigated. Correlation of HMGB3 and IRF1 and GPX4 expression in patient's cancer tissue were also investigated. Our results demonstrated that HMGB3 expression contributes to resistance to anti-PD-1 therapy in vivo. HMGB3 expression correlated with treatment efficacy of immunotherapy and survival in TNBC patients. HMGB3 silence decreased resistance of breast cancer cells to IFN-gamma cytotoxic effect, while HMGB3 overexpression increased resistance of these cancer cells. HMGB3 silence increased STAT1 phosphorylation and IRF1 expression upon IFN-gamma treatment compared with control. Overexpression of HMGB3 inhibited STAT1 phosphorylation and IFN-gamma signaling in TNBC cells. Moreover, HMGB3 also increased STAT3 activation and had an effect of interaction between STAT1 and STAT3. HMGB3 overexpression decreased IFN-gamma-driven ferroptosis in TNBC cells. HMGB3 increased ferroptosis-inhibitory proteins (SLC7A11, GPX4, and SLC3A2) expression in TNBC cells. Ferroptosis inhibition recovers resistance to

关键词： TNF   XPro1595   Neurodegeneration   Microgliosis   rAAV   alpha-synuclein  

摘要： The underlying cause of neuronal loss in Parkinson's disease (PD) remains unknown, but evidence implicates neuroinflammation in PD pathobiology. The pro-inflammatory cytokine soluble tumor necrosis factor (TNF) seems to play an important role and thus has been proposed as a therapeutic target for modulation of the neuroinflammatory processes in PD. In this regard, dominant-negative TNF (DN-TNF) agents are promising antagonists that selectively inhibit soluble TNF signaling, while preserving the beneficial effects of transmembrane TNF. Previous studies have tested the protective potential of DN-TNF-based therapy in toxin-based PD models. Here we test for the first time the protective potential of a DN-TNF therapeutic against alpha-synucleindriven neurodegeneration in the viral vector-based PD female rat model. To do so, we administered the DN-TNF agent XPro1595 subcutaneously for a period of 12 weeks. In contrast to previous studies using different PD models, neuroprotection was not achieved by systemic XPro1595 treatment. alpha-Synuclein-induced loss of nigrostriatal neurons, accumulation of pathological inclusions and microgliosis was detected in both XPro1595and saline-treated animals. XPro1595 treatment increased the percentage of the hypertrophic/ameboid Iba1+ cells in SN and reduced the striatal MHCII+ expression in the alpha-synuclein-overexpressing animals. However, the treatment did not prevent the MHCII upregulation seen in the SN of the model, nor the increase of CD68+ phagocytic cells. Therefore, despite an apparently immunomodulatory effect, this did not suffice to protect against viral vector-derived alpha-synuclein-induced neurotoxicity. Further studies are warranted to better elucidate the therapeutic potential of soluble TNF inhibitors in PD.

关键词： HLA   HLA-DRB1   nanotype sequencing   novel allele   sequencing-based typing  

摘要： The novel allele HLA-DRB1*13:348 differs from HLA-DRB1*13:02:01:01 by one non-synonymous nucleotide substitution in exon 2.

关键词： cancer-associated fibroblast   interferon-licenced fibroblast   non-small cell lung cancer   secretome   tumour microenvironment  

摘要： Cancer-associated fibroblasts (CAFs) are the dominant nonmalignant component of the tumour microenvironment (TME). CAFs demonstrate a high level of inter- and intra-tumour heterogeneity in solid tumours, though the drivers of CAF subpopulations are not fully understood. Here, we demonstrate that non-small cell lung cancer (NSCLC) patient-derived CAFs upregulate the secretion of inflammatory cytokines (IL6, LIF, IL33, GM-CSF, IL1ra) and chemokines (CCL2, CCL3, CCL4, CCL20, CXCL8, CXCL9, CXCL10, CXCL11) in response to in vitro co-culture with anti-CD3/anti-CD28-stimulated peripheral blood mononuclear cells (PBMCs) via IFN gamma and TNF alpha. Furthermore, T-cell-derived IFN gamma inhibits CXCL12 secretion by CAFs in vitro. Our results highlight the ability of T-cell effector cytokines to modulate the CAF secretome in NSCLC.