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UNASSIGNED: To reveal changes in choroidal thickness, retinal vessel density, and serum HIF-1α and TNF-α levels in obstructive sleep apnea syndrome (OSAS) and their correlation.
UNASSIGNED: This prospective case-control study included 118 patients divided into mild-to-moderate OSAS (n = 40), severe OSAS (n = 39), and a control group (n = 39). Choroidal thickness was evaluated with OCT, vessel density with OCTA, AHI index with polysomnography, and serum HIF-1α and TNF-α levels were analyzed using the enzyme-linked immunosorbent assay.
UNASSIGNED: The serum HIF-1α values of the participants in the mild-moderate OSAS and severe OSAS groups were [893.25(406.7-2068) and 1027(453-2527), respectively], and were both significantly higher than the control group [(521.5(231.6-2741))] (p < 0.001). Serum TNF-α levels did not differ significantly between the groups (p = 0.051).). Subfoveal choroidal thickness (SFCT) values of the severe OSAS groups were significantly lower than the control group (p < 0.05). The superficial and deep capillary plexus vascular density (SVD and DVD) values of the severe OSAS group were lower than the control group (p < 0.05). Serum HIF-1α and TNF-α levels of all participants were negatively correlated with both their SVD values (p < 0.05, r: -0.220 and p < 0.05, r: -0.252, respectively) and their DVD values (p < 0.001, r: -0.324 and p = 0.001, r: -0.299, respectively).
UNASSIGNED: Increased serum levels of inflammatory mediators (HIF-1α ve TNF-α) in OSAS cause a decrease in SFCT, SVD, and DVD, which is an indication of systemic vascular damage. Further research on developing treatment strategies to modulate TNF-α ve HIF-1α may help recede vascular morbidity in OSAS patients.

As the eponymous mediators of the cytokine storm syndrome, cytokines are a pleomorphic and diverse set of soluble molecules that activate or suppress immune functions in a wide variety of ways. The relevant cytokines for each CSS are likely a result of differing combinations of environmental triggers and host susceptibilities. Because cytokines or their receptors may be specifically targeted by biologic therapeutics, understanding which cytokines are relevant for disease initiation and propagation for each unique CSS is of major clinical importance. This chapter will review what is known about the role of cytokines across the spectrum of CSS.

Non-alcoholic fatty liver disease (NAFLD) is associated with abnormal bone metabolism, potentially mediated by elevated levels of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-ɑ) and interleukin 6 (IL-6). This study aims to investigate the direct regulatory effects of liver tissues on osteoblast and osteoclast functions in vitro, focusing on the liver-bone axis in NAFLD. Twelve-week-old C57BL/6 mice were fed either a control diet or a high-fat diet (HFD) for 12 weeks. Bone structural parameters were assessed using microCT. Primary hepatocyte cultures were established from control and HFD-fed C57BL/6 mice, as well as IL-6-/- and TNF-α-/- mice. The supernatants from these hepatocyte cultures were used to induce differentiation in bone marrow cell-derived osteoblasts and osteoclasts in vitro. Results showed that mice on a HFD exhibited increased lipid infiltration in liver and bone marrow tissues, alongside reduced bone mass. Moreover, the supernatants from hepatocyte cultures from mice on a HFD displayed elevated TNF-α and IL-6 levels. These supernatants, particularly those derived from HFD-fed and IL-6-/- mice, significantly enhanced osteoclast differentiation in vitro. In contrast, supernatants from TNF-α-/- mice did not significantly affect osteoblast or osteoclast differentiation in vitro. In conclusions, this current study suggested that fatty liver tissues may negatively impact bone metabolism. Additionally, knockout of TNF-α and IL-6 genes revealed distinct influence on osteoblast and osteoclast functions, highlighting the complex interplay between live pathology and bone health.

UNASSIGNED: The correlation of adiponectin and serum tumor necrosis factor alpha (TNFα) with glucometabolic parameters in diabetes mellitus (DM) needs further studies. We aimed in this study to evaluate the relationship between adiponectin and TNFα with glucometabolic parameters in patients with type 2 DM (T2DM).
UNASSIGNED: We conducted a cross-sectional study in the Department of Physiology, College of Medicine, King Saud University, Saudi Arabia. The sample size was 117 from the diabetes clinic of King Abdul-Aziz University hospital through the convenience sampling technique. Subjects were grouped into control (healthy) subjects (53) with no chronic diseases and the diabetic group (64) with confirmed T2DM. Socio-demographic data were collected along with the serum blood sample to analyze the variables.
UNASSIGNED: Adiponectin was significantly high in healthy subjects compared to the diabetic group (control: 14.4 ± 4.3, T2DM: 11.0 ± 4.1, P = 0.000), while TNFα was higher in the T2DM group (7.8 ± 2.7) than in the control group (6.6 ± 2.9, P = 0.024). TNFα was negatively correlated with adiponectin in the control group (-0.279) and in diabetic subjects (-0.311) and positively correlated with HbA1c in the diabetic group (0.319) and triglycerides (0.252). Adiponectin was positively correlated with HDL in the control group (0.252) and in diabetic subjects (0.326). There was an inverse correlation between TNFα and adiponectin.
UNASSIGNED: Adiponectin is higher in healthy subjects than in diabetic patients, while TNFα is higher in diabetic patients. In addition, adiponectin is positively correlated with HDL in healthy as well as diabetic patients. TNFα is positively correlated with HbA1c and triglycerides.

UNASSIGNED: Tumor necrosis factor alpha (TNF-α) is an inflammatory cytokine implicated in pathological changes to the retinal pigment epithelium that are similar to changes in geographic atrophy (GA), an advanced form of age related macular degeneration (AMD). TNF-α also modulates expression of other cytokines including vascular endothelial growth factor (VEGF), leading to choroidal atrophy in models of AMD. The purpose of this study was to investigate systemic TNF-α and VEGF in patients with GA and intermediate AMD (iAMD) compared to controls without AMD.
UNASSIGNED: We examined plasma levels of TNF-α and VEGF in patients with GA, iAMD, and controls without AMD from the University of Colorado AMD registry (2014 to 2021). Cases and controls were characterized by multimodal imaging. TNF-α and VEGF were measured via multiplex immunoassay and data were analyzed using a non-parametric rank based linear regression model fit to plasma biomarkers.
UNASSIGNED: There were 97 GA, 199 iAMD patients and 139 controls. TNF-α was significantly increased in GA (Median:9.9pg/ml, IQR:7.3-11.8) compared to iAMD (Median:7.4, IQR:5.3-9.1) and in both GA and iAMD compared to controls (Median:6.4, IQR:5.3-7.8), p<0.01 for all comparisons. VEGF was significantly increased in iAMD (Median:8.9, IQR:4.8-14.3) compared to controls (Median:7.7, IQR:4.6-11.1), p<0.01. There was a significant positive correlation between TNF-α and VEGF in GA (0.46, p<0.01), and iAMD (0.20, p=0.01) with no significant interaction between TNF-α and VEGF in any group.
UNASSIGNED: These findings suggest TNF-α and VEGF may contribute to systemic inflammatory processes associated with iAMD and GA. TNF-α and VEGF may function as systemic biomarkers for disease development.

Introduction: Despite the established role of peripheral adenosine receptors in sepsis-induced organ dysfunction, little or no data is available on the interaction of central adenosine receptors with sepsis. The current study tested the hypothesis that central adenosine A3 receptors (A3ARs) modulate the cardiovascular aberrations and neuroinflammation triggered by sepsis and their counteraction by the cholinergic antiinflammatory pathway. Methods: Sepsis was induced by cecal ligation and puncture (CLP) in rats pre-instrumented with femoral and intracisternal (i.c.) catheters for hemodynamic monitoring and central drug administration, respectively. Results: The CLP-induced hypotension, reduction in overall heart rate variability (HRV) and sympathovagal imbalance towards parasympathetic predominance were abolished by i.v. nicotine (100 μg/kg) or i.c. VUF5574 (A3AR antagonist, 2 µg/rat). In addition, the selective A3AR agonist, 3-iodobenzyl-5\'-N-methylcarboxamidoadenosine IB-MECA, 4 µg/rat, i.c.) exaggerated the hypotension and cardiac autonomic dysfunction induced by sepsis and opposed the favorable nicotine actions against these septic manifestations. Immunohistochemically, IB-MECA abolished the nicotine-mediated downregulation of NFκB and NOX2 expression in rostral ventrolateral medullary areas (RVLM) of brainstem of septic rats. The inhibitory actions of IB-MECA on nicotine responses disappeared after i.c. administration of PD98059 (MAPK-ERK inhibitor), SP600125 (MAPK-JNK inhibitor) or wortmannin (PI3K inhibitor). Moreover, infliximab (TNFα inhibitor) eliminated the IB-MECA-induced rises in RVLM-NFκB expression and falls in HRV, but not blood pressure. Conclusion: Central PI3K/MAPKs pathway mediates the A3AR counteraction of cholinergic defenses against cardiovascular and neuroinflammatory aberrations in sepsis.

Acute cutaneous lupus erythematosus (ACLE) is closely associated with systemic symptoms in systemic lupus erythematosus (SLE). This study aimed to identify potential biomarkers for ACLE and explore their association with SLE to enable early prediction of ACLE and identify potential treatment targets for the future. In total, 185 SLE-diagnosed patients were enrolled and categorized into two groups: those with ACLE and those without cutaneous involvement. After conducting logistic regression analysis of the differentiating factors, we concluded that tumor necrosis factor-alpha (TNF-α) is an independent risk factor for ACLE. Analysis of the receiver operating characteristic revealed an area under the curve of 0.716 for TNF-α. Additionally, both TNF-α and ACLE are positively correlated with disease activity. TNF-α shows promise as a biomarker for ACLE, and in SLE patients, ACLE may serve as a clear indicator of moderate-to-severe disease activity.

BACKGROUND: The lack of reliable biomarkers in response to anti-TNFα biologicals hinders personalized therapy for Crohn\'s disease (CD) patients. The motivation behind our study is to shift the paradigm of anti-TNFα biomarker discovery toward specific immune cell sub-populations using single-cell RNA sequencing and an innovative approach designed to uncover PBMCs gene expression signals, which may be masked due to the treatment or ongoing inflammation; Methods: The single-cell RNA sequencing was performed on PBMC samples from CD patients either naïve to biological therapy, in remission while on adalimumab, or while on ustekinumab but previously non-responsive to adalimumab. Sieves for stringent downstream gene selection consisted of gene ontology and independent cohort genomic profiling. Replication and meta-analyses were performed using publicly available raw RNA sequencing files of sorted immune cells and an association analysis summary. Machine learning, Mendelian randomization, and oligogenic risk score methods were deployed to validate DEGs highly relevant to anti-TNFα therapy response; Results: This study found PLCB1 in CD4+ T cells and CRTAM in double-negative T cells, which met the stringent statistical thresholds throughout the analyses. An additional assessment proved causal inference of both genes in response to anti-TNFα therapy; Conclusions: This study, jointly with an innovative design, uncovered novel candidate genes in the anti-TNFα response landscape of CD, potentially obscured by therapy or inflammation.

Ovarian cancer incidence has declined in recent decades, due in part to oral contraceptive (OC) use and tubal ligation. However, intrauterine device (IUD) use has increasingly replaced OC use. As ovarian cancer is an inflammation-related disease, we examined the association of OC use, IUD use, and tubal ligation with plasma levels of C-reactive protein (CRP), interleukin 6 (IL-6), and soluble tumor necrosis factor α receptor 2 (sTNFR2), in the Nurses\' Health Study (NHS) and NHSII. After adjusting for reproductive, hormonal, and lifestyle factors, and mutual adjustment for other methods of contraception, there were no differences in inflammatory markers between ever and never use of each method. However, CRP levels decreased from an average 30.4% (-53.6, 4.4) with every 5 years since initial IUD use (P-trend=0.03), while CRP increased an average 9.9% (95% CI: 5.7, 14.3) with every 5 years of use of OC (P-trend<0.0001) as well as differences by BMI and menopausal status. Our results suggest IUD use and tubal ligation are not associated with higher circulating inflammatory markers long term, although long duration of OC use may increase generalized inflammation, which may in part explain why its protective effect wanes over time.