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BACKGROUND: Internal heat-type acupuncture therapy is a new treatment technique that combines acupuncture therapy with hyperthermia. It has good clinical effects on steroid-induced osteonecrosis of the femoral head, but the mechanism of action is still not fully clear. OBJECTIVE: To explore the possible mechanism of internal heat-type acupuncture therapy in treating steroid-induced osteonecrosis of the femoral head in rabbits. METHODS: Thirty-two New Zealand rabbits were randomly divided into blank group, model group, internal heat-type acupuncture group and shock wave group using a random number table method, with 8 rabbits in each group. The model group, internal heat-type acupuncture group and shock wave group were modeled using methylprednisolone sodium succinate combined with Escherichia coli endotoxin. The internal heat-type acupuncture group received an internal heat-type acupuncture intervention on the buttocks of rabbits, once a week, for 20 minutes each time. The shock wave group received shock wave intervention on the buttocks of rabbits, once a week, with 2 000 beats per session. The blank group and model group were not given any treatment. After 4 weeks of intervention, blood samples and bilateral femoral head samples were collected from experimental rabbits. The levels of tumor necrosis factor-α and interleukin-6 in serum were detected by ELISA; the histomorphology of the femoral head was observed using hematoxylin-eosin staining and the rate of empty lacunae was calculated; the protein expressions of matrix metalloproteinase 2, matrix metalloproteinase 9, matrix metalloproteinase tissue inhibitor 1, and matrix metalloproteinase tissue inhibitor 2 were detected by immunohistochemistry and western blot. RESULTS AND CONCLUSION: Compared with the blank group, the model rabbits showed reduced food intake, mental fatigue, and decreased activity; compared with the model group, the above performance of the experimental rabbits was significantly improved after internal heat-type acupuncture and shock wave treatment. Compared with the blank group, the histomorphology of the femoral head in the model group deteriorated significantly and the rate of empty bone lacuna increased (P < 0.001), while the histomorphology of the femoral head in the internal heat-type acupuncture group and shock wave group was significantly improved compared with the model group, and the rate of empty bone lacuna was reduced (P < 0.001). The serum levels of tumor necrosis factor-α and interleukin-6 in the model group were significantly higher than those in the blank group (P < 0.05), while the serum levels of tumor necrosis factor-α and interleukin-6 in the internal heat-type acupuncture group and the shock wave group were significantly lower than those in the model group (P < 0.05). Compared with the blank group, the expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 in the femoral head of the model group were significantly increased, while the expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly decreased (P < 0.001); compared with the model group, the protein expression levels of matrix metalloproteinase 2 and matrix metalloproteinase 9 were significantly decreased, while the protein expression levels of matrix metalloproteinase tissue inhibitor 1 and matrix metalloproteinase tissue inhibitor 2 were significantly increased in the internal heat-type acupuncture group and the shock wave group (P < 0.001). Overall, these findings indicate that internal heattype acupuncture may promote the repair of the necrotic femoral head by regulating the levels of matrix metalloproteinases/matrix metalloproteinase tissue inhibitors and serum inflammatory factors, thus treating early steroid-induced osteonecrosis of the femoral head. [ABSTRACT FROM AUTHOR]

Introduction: Traditionally and empirically, Hibiscus sabdariffa L. has been used in treating diabetes mellitus due to its antioxidant activity. This study aimed to investigate the effect of administering the ethyl acetate fraction of hibiscus calyxes (EAFHCs) on malondialdehyde (MDA) levels, tumor necrosis factor-α (TNF-α) levels, bleeding time, and platelet count in male white rats induced with streptozotocin-induced diabetes. Method: Thirty-six Wistar Kyoto rats were induced with intraperitoneal streptozotocin at 55 mg/kg BW and stabilized for 5 days to obtain diabetic conditions. Diabetic animals were divided into four groups; the diabetic group was given vehicle, the glibenclamide group was given 0.45 mg/kg BW of glibenclamide, and two groups were administered the EAFHCs at doses of 100 mg/kg BW and 200 mg/kg BW for 5 days. Subsequently, the MDA, TNF-α, bleeding time and platelet count levels were examined on days 1, 3, and 5, respectively. All data were analyzed using two-way ANOVA followed by the Duncan Multiple Range Test (DMRT). Results: EAFHC significantly reduced MDA and TNF-α levels (p < 0.05). Additionally, this fraction appeared to shorten bleeding time and decrease platelet count in diabetic rats. Administration of the EAFHC for 5 days effectively lowered MDA and TNF-α levels significantly, decreased platelet counts and prolonged coagulation (p < 0.05) in diabetic rats. Conclusion: This study demonstrates that EAFHC effectively reduces MDA and TNF-α levels and reduces the risk of hypercoagulability in diabetic model. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lycium barbarum polysaccharide has many biological activities and has been found to have potential effects on promoting wound healing. OBJECTIVE: To investigate the mechanism of lycium barbarum polysaccharide in tumor necrosis factor-α-mediated keratinocyte apoptosis and its effect on the healing of burn wounds. METHODS: (1) In vitro experiment: Keratinocytes were divided into four groups: cells were cultured in the α-MEM medium (complete medium) containing 15% fetal bovine serum and 1% glutamine in normal group, cultured in the complete medium containing lycium barbarum polysaccharide in positive control group, cultured in the complete medium containing tumor necrosis factor-α in model group, and cultured in the complete medium containing lycium barbarum polysaccharide and tumor necrosis factor-α in experimental group. After 24 hours of culture, cell proliferation was detected using cell counting kit8 assay; Cleaved caspase-8, TNF R1, FADD, and LC3 were detected using western blot. Then an autophagy inhibitor group (the complete medium containing 3-methyladenine) and an autophagy inhibitor+lycium barbarum polysaccharide group (the complete medium containing lycium barbarum polysaccharide, tumor necrosis factor-α, and 3-methyladenine) were set up. After 24 hours of culture, keratinocyte apoptosis was detected by flow cytometry. (2) In vivo experiment: Six Sprague-Dawley rats were randomly divided into a control group and an experimental group, with three rats in each group. Four deep II degree burn wounds with a diameter of 2 cm were made on the back of each rat. At 24 hours after modeling, mice in the control and experimental groups were coated with normal saline and lycium barbarum polysaccharide solution, respectively, once a day. Wound healing was observed regularly after treatment. Samples were taken 28 days after treatment and the pathologic pattern of the wound was observed. RESULTS AND CONCLUSION: (1) In vitro experiment: Addition of lycium barbarum polysaccharide alone did not affect cell proliferation and apoptosis and the expression of apoptotic and autophagic proteins in keratinocytes. After the addition of tumor necrosis factor α, the proliferation of keratinocytes was inhibited, the apoptotic rate increased, and the expression of apoptotic and autophagic proteins was elevated, while lycium barbarum polysaccharide could antagonize the above effects of tumor necrosis factor-α. Lycium barbarum polysaccharide combined with autophagy inhibitors further reduced the apoptotic rate of keratinocytes. (2) In vivo experiment: The wound healing rate of rats in the experimental group was higher than that of the control group at 12, 16, 20, 24, and 28 days after treatment (P < 0.05, P < 0.01). Hematoxylin-eosin staining results at 28 days after treatment showed an intact and well-defined epidermis of the wound in the experimental group compared with the control group. To conclude, lycium barbarum polysaccharide protects the integrity of skin epidermal tissue and promotes wound healing by inhibiting autophagy and apoptosis of keratinocytes. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the effects of low‐intensity pulsed ultrasound (LIPUS) on the proliferation, differentiation, and tumor necrosis factor‐α (TNF‐α)‐induced lipolysis of 3T3‐L1 cells, and to explore the feasibility of regulating the release of free fatty acids (FFA) to prevent lipotoxicity. Methods: Different intensities (30, 60, 90, and 120 mW/cm2) of LIPUS were applied to 3T3‐L1 preadipocytes for different durations (5, 10, 15, 20, 25, and 30 minutes). Appropriate parameters for subsequent experiments were selected by assessing cell viability. The effect of LIPUS on the proliferation and differentiation of 3T3‐L1 cells was evaluated by microscope observation, flow cytometry, and lipid content determination. After treated with LIPUS and TNF‐α (50 ng/mL), the degree of lipolysis was assessed by measuring the extracellular FFA content. Quantitative real‐time polymerase chain reaction (qRT‐PCR) was used to detect the mRNA expression of relevant genes. Results: Different parameters of LIPUS significantly enhance the viability of 3T3‐L1 cells (P <.05), with 20 minutes and 30 mW/cm2 as the most suitable settings. After LIPUS treatment, 3T3‐L1 cell proliferation accelerated, apoptosis rate and G1 phase cell proportion decreased, the content of lipid droplets and TG was increased in differentiated cells, while FFA release decreased (P <.05). The expression of PCNA, PPARγ, C/EBPα, Perilipin A mRNA increased, and the expression of TNF‐α, ATGL, HSL mRNA decreased (P <.05). Conclusions: LIPUS could promote the proliferation and differentiation of 3T3‐L1 cells and inhibit TNF‐α‐induced lipolysis, indicating its potential as a therapy for mitigating lipotoxicity caused by decompensated adipocytes. [ABSTRACT FROM AUTHOR]

BACKGROUND: Tumor necrosis factor-α is a broadly acting inflammatory cytokine that plays an important role in the immune inflammatory response of the body. The current study concluded that tumor necrosis factor-α has significant biological effects on a variety of bone tissue cells. OBJECTIVE: To summarize the expression and action pathways of tumor necrosis factor-α in osteoblastic and osteoclastic cells to further elucidate the regulatory role of tumor necrosis factor-α on bone tissue cells. METHODS: PubMed and CNKI were searched until March 2023, and the Chinese search terms included “tumor necrosis factor α, osteoblast, osteoclast, osteoclast, osteoprogenitor”; the English search terms included “TNF-α, osteoblast, osteoclast, osteocyte, osteoprogenitor cell”. The corresponding criteria were established according to the research needs, and the final literature was screened. Finally, 77 articles were included for review. RESULTS AND CONCLUSION: (1) Tumor necrosis factor-α is participating in regulating the recruitment, appreciation, and differentiation of osteoprogenitor cells, but leads to osteoprogenitor cell stripping and death under specific environments. It also participates in bone resorption directly or indirectly through secreted enzymes. (2) Tumor necrosis factor-α can increase the level of inflammatory factors in the environment by activating relevant signaling pathways in osteoclast lineage cells or directly induce the generation of osteoclasts in specific environments. (3) Tumor necrosis factor-α can inhibit osteogenic differentiation by activating nuclear factor-κB signaling pathway, inhibiting the expression of transcription factors such as RUNX2 and Osterix, and inducing apoptosis and necrotizing apoptosis in osteoblasts. (4) Tumor necrosis factor-α inhibits osteogenesis and promotes osteoclastogenesis by activating the nuclear factor-κB signaling pathway in osteocytes and inducing cytokines such as RANKL, SOST, and DKK1, while enhancing apoptosis of the osteocytes, as well as bone resorption around the apoptotic bone tissue. (5) Taken together, the effect of tumor necrosis factor-α in bone tissue is mainly to inhibit osteogenesis and promote osteoclastosis. The biological effect of tumor necrosis factor-α in bone tissue cells is usually dependent on the activation of tumor necrosis factor receptor and nuclear factor-κB signaling pathways. (6) The interaction of tumor necrosis factor-α with other tissue cell types surrounding bone tissue and its role in bone immune regulation still deserve attention in future studies. [ABSTRACT FROM AUTHOR]

Objective To investigate the characteristics of pulmonary artery diameter in patients with human immunodeficiency virus (HIV) infection-associated pulmonary hypertension (PAH), and to explore the clinical significance of pulmonary artery diameter correlation indices combined with tumor necrosis factor-α (TNF-α) for early screening and diagnosis of HIV-associated pulmonary hypertension, aiming to provide valuable clinical insights. Methods A retrospective analysis was conducted on 65 HIV-infected patients admitted to the Eighth Hospital Affiliated to Guangzhou Medical University between May 2017 and December 2023. Based on echocardiography findings, the patients were categorized into an observation group (23 cases with PAH) and a control group (42 cases without PAH) . Measurements of pulmonary artery diameter (PA), distal pulmonary artery diameter (dPA), and aortic diameter were obtained in both groups, and the ratio of dPA to aortic diameter (rPA) was calculated. Additionally, serum TNF-α levels were recorded. The clinical significance of each index in early screening and diagnosis of HIV-related pulmonary hypertension was analyzed. Results The PA, dPA, rPA, and TNF- α levels in the observation group were significantly higher compared to those in the control group. Pearson linear correlation analysis revealed a significant positive correlation between TNF-α and both dPA and rPA. Two-column correlation analysis demonstrated a significant association between HIV-PAH and PA, dPA, rPA, as well as TNF-α (P < 0.05). The combined measurement of serum TNF-α with dPA and rPA exhibited an area under the curve (AUC) of 0.891 for diagnosing HIV-APAH, with a sensitivity of 0.870 and specificity of 0.881. Conclusion The combination of pulmonary artery diameter and TNF- α provides a more accurate indication of the presence of HIVPAH, enabling early screening, follow-up, or intervention in high-risk patients. This finding holds significant implications for enhancing patient prognosis. [ABSTRACT FROM AUTHOR]

Tumor necrosis factor-α (TNFα) is a master cytokine which induces expression of chemokines and adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), in endothelial cells to initiate the vascular inflammatory response. In this study, we identified neuropilin1 (NRP1), a co-receptor of several structurally diverse ligands, as a modulator of TNFα-induced inflammatory response of endothelial cells. NRP1 shRNA expression suppressed TNFα-stimulated leukocyte adhesion and expression of ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (HUVECs). Likewise, it reduced TNFα-induced phosphorylation of MAPK p38 but did not significantly affect other TNF-induced signaling pathways, such as the classical NFκB and the AKT pathway. Immunofluorescent staining demonstrated colocalization of NRP1 with the two receptors of TNF, TNFR1 and TNFR2. Coimmunoprecipitation further confirmed that NRP1 was in the same protein complex or membrane compartment as TNFR1 and TNFR2, respectively. Modulation of NRP1 expression, however, neither affected TNFR levels in the cell membrane nor the receptor binding affinities of TNFα. Although a direct interface between NRP1 and TNFα/TNFR1 appeared possible from a protein docking model, a direct interaction was not supported by binding assays in cell-free microplates and cultured cells. Furthermore, TNFα was shown to downregulate NRP1 in a time-dependent manner through TNFR1-NFκB pathway in HUVECs. Taken together, our study reveals a novel reciprocal crosstalk between NRP1 and TNFα in vascular endothelial cells. [ABSTRACT FROM AUTHOR]

Background: Surgery through different mechanisms causes immunosuppression in the postoperative period. Objectives: This study aimed to investigate the effects of preoperative administration of propranolol on blood levels of interleukin-2 (IL-2), interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and hematological parameters, such as white blood cells (WBCs) and lymphocytes. Methods: Forty-five Wistar male rats were divided into three groups. Group 1 (normal control) was injected with normal saline. Groups 2 and 3 were injected subcutaneously with 4 mg/kg of the propranolol (P4) and 8 mg/kg of the propranolol (P8), respectively. Blood samples were collected (before, immediately, 6, 24, and 72 hours after surgery). Then, the IL-2, IFN-γ, TNF-α, WBCs, and lymphocytes levels were determined at different time points. The data were analyzed by one-way ANOVA and the Pearson-test at a significant level of P≤0.05. Results: The results showed a higher level of IL-2 in the P8 and P4 groups with a significant difference compared to the control group (P≤0.05). TNF-α was decreased significantly in the P8 compared to the P4 and control groups (P≤0.05). The P4 has shown a lower level of IFN-γ compared to the P8 and control groups with a significant diference (P≤0.05). Conclusion: It appears that propranolol has considerable immunomodulatory effects on immune responses. Therefore, perioperative use of propranolol may improve immune system function. [ABSTRACT FROM AUTHOR]

Introduction: Antiphospholipid syndrome is one of the most common causes of acquired hypercoagulable conditions which is correlated with ocular conditions not least of which is retinal ischemia due to arterial or venous occlusive insults. Case Presentation: We describe a case of unilateral retinal ischemia in the setting of combined central retinal artery and vein occlusion with associated proliferation of retinal pigment epithelium. The patient was worked-up for the etiology of her presentation which was found to be antiphospholipid syndrome. Conclusion: Although pigment epithelial proliferation occurs commonly after retinal ischemia, no study has reported complete multimodal imaging of such a pathology or proposed the possible mechanisms explaining such an association.

Objective To employ next-generation sequencing (NGS) to analyze differentially expressed mRNAs in the gingival tissue of hypertensive rats with or without periodontitis to provide a theoretical basis for the prevention and treatment of hypertension with periodontitis. Methods After obtaining approval from the Animal Experiment Ethics Committee, a hypertensive rat model was established by administering high-salt feed containing 8%（w/w） NaCl, and a periodontitis rat model was established by ligating the first molar of the mandibular region using 3-0 sterile silk thread. Rat models of the normal control (N), hypertension (H), and hypertension with periodontitis (PH) groups were established. The blood pressure, heart rate, alveolar bone resorption, and number of osteoclasts in the alveolar bone were measured, before harvesting the gingival tissues from the three groups for NGS to analyze the expression of significantly different genes. Gene ontology (GO) enrichment analysis was performed for all significantly differentially expressed genes between the H and PH groups. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis was performed. Key genes were screened by protein-protein interaction (PPI) networks, and the key gene expression in each group was verified using immunohistochemistry (IHC). The expression of key genes in the systemic circulation of each group was analyzed using enzyme-linked immunosorbent assay (ELISA). Results At the end of the experiment (11th week), the blood pressure was higher in both the H and PH groups than that in the N group (PPPP

Gastric inflammation-related disorders are commonly observed digestive system illnesses characterized by the activation of proinflammatory cytokines, particularly tumor necrosis factor-α (TNF-α). This results in the induction of cyclooxygenase-2 (COX-2)/prostaglandin E2 (PEG2) and matrix metallopeptidase-9 (MMP-9). These factors contribute to the pathogenesis of gastric inflammation disorders. We examined the preventive effects of Lonicera japonica Thunb. ethanol extract (Lj-EtOH) on gastric inflammation induced by TNF-α in normal human gastric mucosa epithelial cells (GES-1). The GES-1 cell line was used to establish a model that simulated the overexpression of COX-2/PGE2 and MMP-9 proteins induced by TNF-α to examine the anti-inflammatory properties of Lj extracts. The results indicated that Lj-EtOH exhibits significant inhibitory effects on COX-2/PEG2 and MMP-9 activity, attenuates cell migration, and provides protection against TNF-α-induced gastric inflammation. The protective effects of Lj-EtOH are associated with the modulation of COX-2/PEG2 and MMP-9 through the activation of TNFR–ERK 1/2 signaling pathways as well as the involvement of c-Fos and nuclear factor kappa B (NF-κB) signaling pathways. Based on our findings, Lj-EtOH exhibits a preventive effect on human gastric epithelial cells. Consequently, it may represent a novel treatment for the management of gastric inflammation.

BACKGROUND: Unicompartmental knee arthroplasty has been paid more and more attention because of its advantages of fewer traumas, less blood loss, less complications, faster recovery, excellent knee function and high prosthetic survival rate. Most of the relevant reports focused on its clinical effect, but the changes in the levels of relevant inflammatory cytokines in patients after unicompartmental knee arthroplasty were rarely reported. OBJECTIVE: To investigate the effect of unicompartmental knee arthroplasty in patients with medial compartment osteoarthritis of the knee and the changes of interleukin-1, interleukin-6, and tumor necrosis factor-α levels. METHODS: A total of 30 patients with medial compartment osteoarthritis of the knee who received unicompartmental knee arthroplasty from September 2021 to March 2023 and met the inclusion criteria were selected as the study subjects. Medial angle of proximal tibia, femoral and tibial angle, pain visual analog scale score, hospital for special surgery score, knee joint range of motion, synovial fluid interleukin-1, interleukin-6, and tumor necrosis factor-α levels before and after surgery were compared and statistically analyzed. RESULTS AND CONCLUSION: (1) All 30 patients had grade I wound healing. All patients were followed up for more than 6 months after surgery. There were no complications such as prosthesis loosening and dislocation of prosthesis liner in all patients. (2) The medial proximal tibia angle and the femoral and tibial angles measured after operation were significantly improved (P < 0.05). (3) The visual analog scale score, hospital for special surgery score and range of motion measured at 1, 3, and 6 months after operation were better than those before operation (P < 0.05), and showed a gradual improvement (P < 0.05). (4) The levels of interleukin-1, interleukin-6, and tumor necrosis factor-α in synovial fluid at 3 and 6 months after operation were decreased gradually compared with those before operation (P < 0.05) and showed a gradual downward trend at each time point after operation. (5) It is indicated that unicompartmental knee arthroplasty can effectively treat medial compartment osteoarthritis of the knee, significantly relieve pain, restore knee joint function, improve knee varus deformity and lower limb strength line, and reduce the levels of inflammatory cytokines interleukin-1, interleukin-6, and tumor necrosis factor-α in joints to a certain extent. [ABSTRACT FROM AUTHOR]

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Objective To investigate the levels of serum soluble CD14 subtype (Presepsin) and growth differentiation factor 15 (GDF-15) in patients with acute myocarditis and their correlation with inflammation factor levels and cardiac function indexes. Methods Fifty patients with acute myocarditis diagnosed and treated in the Affiliated Hospital of Inner Mongolia Medical University from October 2020 to October 2021 were selected as the case group, and 80 healthy people who received physical examination in the same period were selected as the control group. Enzyme linked immunosorbent assay (ELISA) was used to determine the serum levels of Presepsin, GDF-15, and inflammatory factors ［tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), hypersensitive C-reactive protein (hs-CRP)］. The indexes of cardiac function ［left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), and left ventricular end diastolic diameter (LVEDD)］ were measured by echocardiography. Pearson method was used to measure and analyze the correlation between serum Presepsin and GDF-15 levels in patients with myocarditis, and the correlation of the two indexes levels with the inflammation and cardiac function. ROC curve was applied to determine the diagnostic value of serum Presepsin and GDF-15 levels for acute myocarditis. Results Compared with the control group, the proportion of hypercholesterolemia, the serum levels of Presepsin, GDF-15, IL-6, TNF-α, hs-CRP and the values of LVEDD and LVMI in the case group were significantly higher （P＜0.05）, but LVEF was significantly lower （P＜0.05）. Pearson analysis showed that serum Presepsin was positively correlated with GDF-15 levels in patients with acute myocarditis (P＜0.05), and they were respectively correlated with IL-6, TNF- α, hs-CRP, LVEDD and LVMI levels, while negatively correlated with LVEF (P＜0.05). ROC curve analysis showed that the area under the curve of serum Presepsin and GDF-15 levels in diagnosis of acute myocarditis was 0.873 and 0.816, respectively. When the optimal cut-off values was 77.62 pg/mL and 96.80 pg/mL, the sensitivity was 68.00% and 80.00% and the specificity was 95.00% and 70.00%, respectively. The area under the curve, sensitivity and specificity of the combined diagnosis for acute myocarditis were 0.908, 86.00% and 81.25%, respectively. Conclusion The levels of serum Presepsin and GDF-15 in patients with acute myocarditis are obviously increased, which are closely related to the level of inflammation and left ventricular remodeling. The two indexes have certain diagnostic value for the occurrence of acute myocarditis, and their combined diagnostic value is higher.

Introduction. Gamma-glutamyltransferase (GGT) is a liver enzyme involved in inflammation and oxidative stress. It is already known that MCP-1 (Monocyte Chemoattractant Protein-1) and TNF-α (tumour necrosis factor) as inflammatory markers, ICAM-1 (Intercellular Adhesion Molecule-1) as an endothelial dysfunctional marker, and glutathione, as an antioxidant, have abnormal levels in type 2 diabetic patients. The aim of this study was to evaluate the specific biological picture of type 2 diabetic patients that also associate higher GGT activity.

Abstract Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) pathways. The pro-inflammatory cytokine TNF-α may be secreted by stromal cells, tumor-associated macrophages, and by cancer cells, indicating a prominent role in the tumor microenvironment (TME). However, tumors manage to adapt, escape immune surveillance, and ultimately develop resistance to the cytotoxic effects of TNF-α. The mechanisms by which cancer cells evade host immunity is a central topic of current cancer research. Resistance to TNF-α is mediated by diverse molecular mechanisms, such as mutation or downregulation of TNF/TRAIL receptors, as well as activation of anti-apoptotic enzymes and transcription factors. TNF-α signaling is also mediated by sphingosine kinases (SphK1 and SphK2), which are responsible for synthesis of the growth-stimulating phospholipid, sphingosine-1-phosphate (S1P). Multiple studies have demonstrated the crucial role of S1P and its transmembrane receptors (S1PR) in both the regulation of inflammatory responses and progression of cancer. Considering that the SphK/S1P/S1PR axis mediates cancer resistance, this sphingolipid signaling pathway is of mechanistic significance when considering immunotherapy-resistant malignancies. However, the exact mechanism by which sphingolipids contribute to the evasion of immune surveillance and abrogation of TNF-α-induced apoptosis remains largely unclear. This study reviews mechanisms of TNF-α-resistance in cancer cells, with emphasis on the pro-survival and immunomodulatory effects of sphingolipids. Inhibition of SphK/S1P-linked pro-survival branch may facilitate reactivation of the pro-apoptotic TNF superfamily effects, although the role of SphK/S1P inhibitors in the regulation of the TME and lymphocyte trafficking should be thoroughly assessed in future studies.

AbstractObjectiveMethodsResultsConclusionsProtein kinase C (PKC) has been implicated in the increased contraction of human airway smooth muscle cells (HASMCs) in asthma. Using the three-dimensional collagen gel contraction system, the study aimed to determine the effects of LY333531, a specific inhibitor of the PKC-β isoform, on the contraction of tumor necrosis factor (TNF)-α-sensitized HASMCs.Cultured HASMCs were divided into five groups: the control group received no treatment, and the cells in the TNF-α group were sensitized with 10 ng/mL TNF-α for 48 h, while TNF-α was administered to sensitize HASMCs in the presence of 0.1, 0.2, and 0.5 μM LY333531 for 48 h in the 0.1LY, 0.2LY, and 0.5LY groups, respectively. Following this, HASMCs contraction was stimulated with 1 mM acetylcholine (ACh) for up to 24 h in each group and assessed using a three-dimensional collagen gel contraction assay. Furthermore, western blot and immunofluorescence analysis were performed.The collagen gel contraction assay revealed that TNF-α increased the protein expression of phosphorylated PKC-β2, CPI-17, and MLC while exacerbating ACh-induced HASMCs contraction. LY333531 significantly attenuated HASMCs contraction and downregulated the protein expression of both p-CPI-17 and p-MLC.At least in part by regulating CPI-17 and MLC phosphorylation, LY333531 attenuates augmented contraction of TNF-α-sensitized HASMCs in a collagen gel contraction system. [ABSTRACT FROM AUTHOR]

Anticancer immune surveillance and immunotherapies trigger activation of cytotoxic cytokine signaling, including tumor necrosis factor-α (TNF-α) and TNF-related apoptosis-inducing ligand (TRAIL) pathways. The pro-inflammatory cytokine TNF-α may be secreted by stromal cells, tumor-associated macrophages, and by cancer cells, indicating a prominent role in the tumor microenvironment (TME). However, tumors manage to adapt, escape immune surveillance, and ultimately develop resistance to the cytotoxic effects of TNF-α. The mechanisms by which cancer cells evade host immunity is a central topic of current cancer research. Resistance to TNF-α is mediated by diverse molecular mechanisms, such as mutation or downregulation of TNF/TRAIL receptors, as well as activation of anti-apoptotic enzymes and transcription factors. TNF-α signaling is also mediated by sphingosine kinases (SphK1 and SphK2), which are responsible for synthesis of the growth-stimulating phospholipid, sphingosine-1-phosphate (S1P). Multiple studies have demonstrated the crucial role of S1P and its transmembrane receptors (S1PR) in both the regulation of inflammatory responses and progression of cancer. Considering that the SphK/S1P/S1PR axis mediates cancer resistance, this sphingolipid signaling pathway is of mechanistic significance when considering immunotherapy-resistant malignancies. However, the exact mechanism by which sphingolipids contribute to the evasion of immune surveillance and abrogation of TNF-α-induced apoptosis remains largely unclear. This study reviews mechanisms of TNF-α-resistance in cancer cells, with emphasis on the pro-survival and immunomodulatory effects of sphingolipids. Inhibition of SphK/S1P-linked pro-survival branch may facilitate reactivation of the pro-apoptotic TNF superfamily effects, although the role of SphK/S1P inhibitors in the regulation of the TME and lymphocyte trafficking should be thoroughly assessed in future studies. [ABSTRACT FROM AUTHOR]

Inflammation impairs cognitive function in healthy individuals and people with psychiatric disorders, such as bipolar disorder (BD). This effect may also impact emotion recognition, a fundamental element of social cognition. Our study aimed to investigate the relationships between pro-inflammatory cytokines and emotion recognition in euthymic BD patients and healthy controls (HCs). We recruited forty-four euthymic BD patients and forty healthy controls (HCs) and measured their inflammatory markers, including high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and TNF-α. We applied validated cognitive tasks, the Wisconsin Card-Sorting Test (WCST) and Continuous Performance Test (CPT), and a social cognitive task for emotion recognition, Diagnostic Analyses of Nonverbal Accuracy, Taiwanese Version (DANVA-2-TW). We analyzed the relationships between cytokines and cognition and then explored possible predictive factors of sadness recognition accuracy. Regarding pro-inflammatory cytokines, TNF-α was elevated in euthymic BD patients relative to HCs. In euthymic BD patients only, higher TNF-α levels were associated with lower accuracy of sadness recognition. Regression analysis revealed that TNF-α was an independent predictive factor of sadness recognition in patients with euthymic BD when neurocognition was controlled for. Conclusions : We demonstrated that enhanced inflammation, indicated by increased TNF-α, was an independent predictive factor of impaired sadness recognition in BD patients but not in HCs. Our findings suggested a direct influence of TNF-α on sadness recognition and indicated vulnerability to depression in euthymic BD patients with chronic inflammation. [ABSTRACT FROM AUTHOR]

Objective: To explore the mechanism of paeoniflorin (PF) on osteoarthritis (OA) synovial inflammation from network pharmacology to experimental pharmacology. Methods: Targets of OA were constructed by detecting the database of network database platforms (Therapeutic Target database, DrugBank and GeneCards), and the targets of PF were constructed by PubChem and Herbal Ingredients' Targets database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these co-targeted genes were conducted via Database for Annotation, Visualization, and Integrated Discovery (DAVID) database, and protein-protein interaction (PPI) networks were conducted via the search tool for the retrieval of interacting genes (STRING) database. Cell counting kit-8 (CCK-8) assay was performed to assess the potential toxicity of PF on human OA fibroblast-like synoviocytes (FLS), quantitative real-time polymerase chain reaction (qPCR), enzyme-linked immunosorbent assay (ELISA) and Western blot were used to verify the potential mechanism of PF in synovial inflammation. Results: Twenty-six co-targeted genes were identified. GO enrichment results showed that these co-targeted genes were most likely localized in the cytoplasm, and the biological processes mainly involved 'cellular response to hypoxia' 'lipopolysaccharide (LPS)-mediated signaling pathway' and 'positive regulation of gene expression'. KEGG pathway analysis indicated that these co-targeted genes may function through pathways associated with 'hypoxia-inducible factor-1 (HIF-1) signaling pathway' and 'tumor-necrosis factor (TNF) signaling pathway'. The PPI network showed that the top 3 hub genes were TP53, TNF, and CASP3. Molecular docking results showed that PF was well docking with TNF. CCK-8 showed no potential toxicity of 10, 20 and 50 µmol/L PF on human OA FLS. And PF significantly decreased the expression levels of interleukin-1 β, interleukin-6, TNF-α matrix metalloproteinase 13 (MMP13), and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) and TNF-α in LPS-induced OA FLS. Conclusion: PF exhibited potent anti-inflammatory effect in OA synovial inflammation. [ABSTRACT FROM AUTHOR]

Introduction: There is no useful method to discriminate between latent tuberculosis infection (LTBI) and active pulmonary tuberculosis (PTB). This study aimed to investigate the potential of cytokine profiles to discriminate between LTBI and active PTB using whole-blood stimulation with Mycobacterium tuberculosis (MTB) antigens, including latency-associated antigens. Materials and methods: Patients with active PTB, household contacts of active PTB patients and community exposure subjects were recruited in Manila, the Philippines. Peripheral blood was collected from the participants and used for whole-blood stimulation (WBS) with either the early secretory antigenic target and the 10-kDa culture filtrate protein (ESAT-6/CFP-10), Rv3879c or latency-associated MTB antigens, includingmycobacterial DNA-binding protein 1 (MDP-1), α-crystallin (Acr) and heparin-binding hemagglutinin (HBHA). Multiple cytokine concentrations were analyzed using the Bio-Plex™ multiplex cytokine assay. Results: A total of 78 participants consisting of 15 active PTB patients, 48 household contacts and 15 community exposure subjects were eligible. The MDP-1-specific IFN-γ level in the active PTB group was significantly lower than that in the household contact group (p < 0.001) and the community exposure group (p < 0.001). The Acr-specific TNF-α and IL-10 levels in the active PTB group were significantly higher than those in the household contact (TNF-α; p = 0.001, IL-10; p = 0.001) and community exposure (TNF-α; p < 0.001, IL-10; p = 0.01) groups. However, there was no significant difference in the ESAT-6/CFP- 10-specific IFN-γ levels among the groups. Conclusion: The patterns of cytokine profiles induced by latency-associated MTB antigens using WBS have the potential to discriminate between LTBI and active PTB. In particular, combinations of IFN-γ and MDP-1, TNF-α and Acr, and IL-10 and Acr are promising. This study provides the first demonstration of the utility of MDP-1-specific cytokine responses in WBS. [ABSTRACT FROM AUTHOR]

Introduction: Research has indicated that individuals diagnosed with bipolar disorder (BD) might experience alterations in their olfaction or levels of serum tumor necrosis factor-α (TNF-α), but no studies have investigated olfactory function and serum TNF-α in BD patients simultaneously. Moreover, there is a lack of existing research that compares the longitudinal olfactory function between individuals with manic and euthymic BD I. Methods: Patients with manic BD I (BDM, n=44) and healthy controls (HCs, n=32) were evaluated symptoms (measured via the Young Manic Rating Scale, YRMS), social function (measured via the Global Assessment Function, GAF), serum TNFa, and olfactory function (via the Sniffin’ Sticks test) including olfactory sensitivity (OS) and olfactory identification (OI). The BDM patients were followed up to the remission period and re-evaluated again. We compared OS, OI and serum TNF-α in manic and euthymic patients with BD I and HCs. We examined the correlation between olfactory function and symptoms, social function, and serum TNF-α in patients with BD I. Results: The BDM patients exhibited significantly lower OS and OI compared to the HCs (Z = −2.235, P = 0.025; t = −6.005, P < 0.001), while a positive correlation was observed between OS and GAF score (r = 0.313, P = 0.039). The OS in the BD I remission group (n=25) exhibited significantly superior performance compared to the BDM group (t = −4.056, P < 0.001), and the same as that in the HCs (P = 0.503). The change in OS showed a positive correlation with the decrease in YMRS score (r = 0.445, P = 0.026), and a negative correlation with the course of disease (r = -0.594, P = 0.002). The TNF-α in BD I patients was significantly lower compared to HCs (P < 0.001), and not significantly correlated with olfactory function (all P > 0.05). Conclusion: The findings suggest that OS and OI are impaired in BDM patients, and the impaired OS in those patients can be recovered in the remission stage. OI may serve as a potential characteristic marker of BD. OS might be useful as an index for BDM treatment efficacy and prognosis. [ABSTRACT FROM AUTHOR]

Obejective: To explore the relationship between plasma thrombomodulin (TM), thrombin activated fibrinolytic inhibitor (TAFI), interleukin-6 (IL-6) and tumor necrosis factor-琢 (TNF-α) levels and infarct volume in patients with acute cerebral infarction in ultra-early stage and their diagnostic value for infarct volume. Method(s): 75 patients with ultra-early acute cerebral infarction admitted to the Second Affiliated Hospital of Xi'an Medical University from Jun 2018 to Sep 2019 were included in the observation group, and 75 patients with outmoded cerebral infarction admitted in the same period were included in the control group. The plasma TM, TAFI, IL-6 and TNF-α levels of patients before treatment (and within 6 hours of onset), 3 days after treatment and 7 days after treatment in the observation group, and those of patients at admission in the control group were detected. The difference of the above indexes before treatment between the observation group and the control group was compared. The patients in the observation group were divided into small volume infarction group (n=27), medium volume infarction group (n=30) and large volume infarction group (n=18) according to infarction volume. The change trend and difference of the levels of the above indexes before treatment, 3 days after treatment and 7 days after treatment among the three groups were compared. The correlation between the above indexes before treatment and the volume of infarction was analyzed by ordinal Logistic regression; The diagnostic value of the above indexes before treatment for large volume infarction was analyzed by ROC. Result(s): The plasma levels of TM, TAFI, IL-6 and TNF-α of patients before treatment (and within 6 hours of onset) in the observation group were higher than those of patients in the control group (P＜0.05). With the progression of the disease course, the levels of the above indexes in patients with small volume infarction, medium volume infarction and large volume infarction decreased after 3 days of treatment compared to pre-treatment levels (P＜0.05), and after 7 days of treatment, these levels continued to decrease compared to the levels at 3 days (P＜0.05). However, the overall levels of the above indexes in patients with large volume infarction were consistently higher than those in patients with medium volume infarction (P＜0.05) at each time point, and the levels in patients with medium volume infarction were higher than those in patients with small volume infarction for the aforementioned indicators (P＜0.05). Ordered Logistic regression analysis showed that the above indexes before treatment had a significant positive effect on infarction volume. It can be seen from ROC analysis that the above indexes before treatment can be used to diagnose large volume infarction, and the diagnostic value of combined detection is better. Conclusion(s): The levels of plasma TM, TAFI, IL-6 and TNF-α in patients with acute cerebral infarction increased, but decreased with the prolongation of the course of the disease, which are of great significances in the development of acute cerebral infarction; In the ultra-early stage of acute cerebral infarction, the levels of the above indexes of patients may be used to assist in diagnosing the infarction volume. [ABSTRACT FROM AUTHOR]

Garcinia dulcis (GD) extract possesses anti-hypertensive property that are poorly characterized. This study aimed to investigate an anti-inflammatory effect of GD flower extract in the 2-kidney-1-clip (2K1C) hypertensive compared to sham operative (SO) rat. Male Wistar rats were divided into 2 groups; the 2K1C group in which a silver clip was placed around renal artery to induce hypertension, and the SO normotensive group. Four weeks later, each group of rats were further divided into 2 subgroups, each subgroup was orally gavaged of either corn oil (vehicle) or 50 mg/kg BW GD extract daily for 4 weeks. The malondialdehyde (MDA) levels in serum, liver, and kidney were determined. Hematoxylin and eosin staining was carried out for histological examination, Periodic acid – Schiff staining for glomerular injury, Masson's trichrome staining for renal fibrosis, and immunohistochemistry for either tumor necrosis factor alpha (TNF-α) or endothelial nitric oxide synthase (eNOS) investigation. Taken together, our results demonstrated that GD flower extract decreased the MDA level in both serum and liver and kidney tissue and suppressed the expression of TNF-α in both liver and kidney of 2K1C hypertensive rats. Mesangial cell proliferation, expansion of mesangial matrix, widening Bowman's capsule space, congestion of glomerular capillary and vessel, cloudy swelling of renal tubular epithelial cell, and renal fibrosis were observed in the kidneys of 2K1C rats. Therefore, we concluded that GD flower extract can alleviate liver and kidney inflammation in which partially attenuates the glomerular injury in the 2K1C rat. [ABSTRACT FROM AUTHOR]

Background: Fertility in male animals is an important issue in veterinary medicine. Exposure to severe crowding and fattening may affect the fertility of these animals. Objectives: This study compares the effect of oxidative stress caused by overcrowding or obesity on testicular tissue in male albino mice. Methods: A total of 30 male mice were divided into 3 groups. The first was a control group. The second group was subjected to crowding by cramming 20 mice in a small cage. The third group was fattened by eating a high-fat diet. Morphometric cells and histological measurements of the seminiferous tubule diameter, epithelium thickness, and Sertoli and Leydig cell counts were taken. Results: The crowding group testes showed the presence of necrosis and degeneration of spermatocytes, Sertoli, and Leydig cells. The obese group's spermatocytes, Sertoli, and Leydig cells had shown severe necrosis, degeneration, and giant cell invasion. Histomorphometric measurements of seminiferous tubule diameter, epithelium-thickness, and Sertoli and Leydig cell counts revealed a considerable reduction in the obese group compared to the other groups. Furthermore, in the crowding and fattening groups, measurements of oxidative stress indicators revealed a decrease in glutathione value in the obese group compared to the control, whereas malondialdehyde rose in the overcrowded and obese groups compared to the control. The results of the immunohistochemical expressions for tumor necrosis factor-α (TNF-α) in the testes of mice revealed weak TNF-α positive expression in the control group, moderate expression in the crowding group, and strong expression in the obesity group. Conclusion: The study suggests that both obesity and crowding can impair testicular function, with obesity having the most significant impact. More research into the mechanisms underlying these effects, as well as potential interventions to improve testicular function in obese or overcrowded animals, is required. [ABSTRACT FROM AUTHOR]

Background: Chronic obstructive pulmonary disease (COPD) is a progressive airflow limitation that is preventable but not curable. It is associated with persistent symptoms that cause a considerable burden on individual productivity at work, and daily activities, and reduced quality of life, also burdening the healthcare system and society. Objectives: The study aims to measure the burden of COPD on patients in terms of daily activities and work productivity. It also seeks to investigate some inflammatory biomarkers' levels and their correlation with selected outcomes. Patients and Methods: A cross-sectional study on 120 stable COPD patients who were diagnosed and treated according to the GOLD guidelines at Kirkuk General Hospital's chest and Internal Medicine consultation clinics, and in private internist clinics in Kirkuk City, Iraq between January and April 2023. The Work Productivity and Activity Impairment Questionnaire (WPAI-COPD) measured the Burden of COPD. The symptom burden was assessed by the COPD assessment test (CAT). The level of IL-6 monoclonal antibodies was measured via a Roche Cobas 6000 analyzer and TNF-α using the ELISA sandwich technique. All these devices and machines were authorized by the Ministry of Health, Iraq. Results: The mean age was (54.1 ± 8.12) years, 62.5% being males and 37.5% being females; 41.7% were public sector employees, and 39.2% were self-employed. Due to COPD, the overall work loss was (45.9±18.91) days, the mean percentage of absenteeism was (10.9% ± 12.31%), activity impairment was (47.5% ±17.79%) among all patients, presenteeism was (40.8 ± 15.05%,) and COPD-related retirees were 14.2% of the study group. The mean CAT score (19.3±5.63) was high and the most troubling symptom among patients was chest tightness. WPAI-COPD scores were higher in older age and longer disease duration. The levels of biomarkers were above the reference ranges, the mean IL-6 level was (69.4 ± 35.29) pg/ml, and the mean TNF-α was (72.3 ± 22.45) pg/ ml. Conclusions: COPD patients exhibit a disease burden in terms of productivity loss at work and activity impairment that increases with aging and disease duration. COPD patients with low BMI are more prone to a decline in lung functions and to worse symptoms.

The heavy metals and bioreactivity properties of endotoxin in personal exposure to fine particulate matter (PM2.5) were characterized in the analysis. The average personal exposure concentrations to PM2.5 were ranged from 6.8 to 96.6 μg/m3. The mean personal PM2.5 concentrations in spring, summer, autumn, and winter were 32.1±15.8, 22.4±11.8, 35.3±11.9, and 50.2±19.9 μg/m3, respectively. There were 85 % of study targets exceeded the World Health Organization (WHO) PM2.5 threshold (24 hours). The mean endotoxin concentrations ranged from 1.086 ± 0.384–1.912 ± 0.419 EU/m3, with a geometric mean (GM) varied from 1.034 to 1.869. The concentration of iron (Fe) (0.008–1.16 μg/m3) was one of the most abundant transition metals in the samples that could affect endotoxin toxicity under Toll-Like Receptor 4 (TLR4) stimulation. In summer, the interleukin 6 (IL-6) levels showed statistically significant differences compared to other seasons. Spearman correlation analysis showed endotoxin concentrations were positively correlated with chromium (Cr) and nickel (Ni), implying possible roles as nutrients and further transport via adhering to the surface of fine inorganic particles. Mixed-effects model analysis demonstrated that Tumor necrosis factor-α (TNF-α) production was positively associated with endotoxin concentration and Cr as a combined exposure factor. The Cr contained the highest combined effect (0.205–0.262), suggesting that Cr can potentially exacerbate the effect of endotoxin on inflammation and oxidative stress. The findings will be useful for practical policies for mitigating air pollution to protect the public health of the citizens.

Abstract Background Inflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology. Methods The study enrolled 31 TRS and 49 cm male patients, and 53 healthy controls. Serum MMP-2 and TNF-α levels were measured by the Luminex liquid suspension chip detection method. Positive and Negative Syndrome Scale (PANSS) scores were used to evaluate symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status was used to assess cognitive function. Results Serum TNF-α and MMP-2 levels differed significantly between TRS, CMS and healthy control patients (F = 4.289, P = 0.016; F = 4.682, P = 0.011, respectively). Bonferroni correction demonstrated that serum TNF-α levels were significantly elevated in CMS patients (P = 0.022) and MMP-2 levels were significantly higher in TRS patients (P = 0.014) compared to healthy controls. In TRS patients, TNF-α was negatively correlated with age (r=-0.435, P = 0.015) and age of onset (r=-0.409, P = 0.022). In CMS patients, MMP-2 and TNF-α were negatively correlated with PANSS negative and total scores, and TNF-α was negatively correlated with PANSS general psychopathology scores (all P 0.05). Conclusion The results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted.

Abstract Background A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-α (TNF-α) expression in granulocyte–macrophage colony-stimulating factor-induced macrophages (GM-CSF MΦ) and the TNF-α expression ratio in GM-CSF MΦ/M-CSF MΦ (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed. Methods To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese. Results Our results of co-culture experiments showed that GM-CSF MΦ affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1α and TNF-α. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals. Limitations The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals. Conclusions Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF MΦ in individuals with ASD on neurons, mediated by interleukin-1α and TNF-α. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology.

Abstract Background Oral lichen planus (OLP) is a T-cell-mediated autoimmune disease that affects the epithelial cells of the oral cavity. This study was performed to investigate any possible relationship between − 1031(T/C) polymorphism (rs1799964) of the tumor necrosis factor α (TNF-α) gene with the risk and severity of oral lichen planus (OLP) disease among an Iranian population. Method Saliva samples were collected from 100 patients with OLP and a similar number of healthy controls (age and sex-matched). Then, DNA was extracted from the collected samples for genotyping TNF-α-1031 T/C polymorphism using the PCR-CTPP method. The results were assessed using SPSS software. Results The findings revealed a significantly higher prevalence of the C allele in OLP patients (53%) compared to healthy controls (36%), suggesting an association between TNF-alpha gene polymorphism and OLP. A multivariate logistic regression analysis supported this finding, as the presence of the C allele was significantly associated with an increased risk of OLP [χ2 = 4.17, p = 0.04, 95% CI = 1.01–2.65, OR = 1.64]. However, our data indicated no significant association between TNF-alpha-1031 T/C gene polymorphism and OLP severity. Conclusions These findings provide the first evidence supporting a possible role of TNF-α-1031 T/C gene polymorphism in OLP susceptibility in the Iranian population. The findings of this study demonstrate a positive association between TNF-α-1031 C/T allele distribution and the risk of OLP disease in the Iranian population. Therefore, carrying the C allele may increase the susceptibility to OLP disease.

Background: Diabetes poses a global threat, leading to hospitalizations and premature death if not managed properly. It involves tumor necrosis factor-α (TNF-α), an inflammatory cytokine, which binds to TNF-α receptor-1, triggering sphingomyelinase, and ceramide production. Vitamin D acts as an anti-inflammatory agent, reducing inflammatory cytokines and proinflammatory cell growth, and benefiting diabetes mellitus (DM). Aims and Objectives: The primary objective was to compare serum Vitamin D and TNF-α levels in diabetics and non-diabetics. The secondary objective was to explore Vitamin D and TNF-α correlation in newly diagnosed type 2 diabetes. Materials and Methods: A case–control study involved 92 subjects in each group. Data included demographics, clinical assessments, glycemic parameters, Vitamin D, and TNF-α. Statistical analysis used student’s t-test and Pearson correlation (P

Background: Osteophyte development is a common characteristic of inflammatory skeletal diseases. Elevated osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) participates in pathological osteogenesis. Integrin-linked kinase (ILK) positively regulates the osteoblastic differentiation of osteoprogenitors, but whether the ILK blockage prevents osteophytes and its potential mechanism is still unknown. Furthermore, the low-dose tumor necrosis factor-α (TNF-α) promotes osteogenic differentiation, but a lack of study reports on the relationship between this cytokine and ILK. OSU-T315 is a small ILK inhibitor, which was used to determine the effect of ILK inhibition on osteogenesis and osteophyte formation. Methods and results: The osteogenesis of BMSCs was evaluated using Alizarin red S staining, alkaline phosphatase, collagen type I alpha 2 chain, and bone gamma-carboxyglutamate protein. The expression and phosphorylation of protein were assessed through western blot. Immunofluorescence was employed to display the distribution of β-catenin. microCT, hematoxylin-eosin, and safranin O/fast green staining were utilized to observe the osteophyte formation in collagen antibody-induced arthritis mice. We found that ILK blockage significantly declined calcium deposition and osteoblastic markers in a dose- and time-dependent manner. Furthermore, it lowered osteogenesis in the TNF-α-induced inflammatory microenvironment by diminishing the effect of ILK and inactivating the Akt/ GSK-3β/ β-catenin pathway. Nuclear β-catenin was descended by OSU-T315 as well. Finally, the ILK suppression restrained osteophyte formation but not inflammation in vivo. Conclusions: ILK inhibition lowered osteogenesis in TNF-α-related inflammatory conditions by deactivating the Akt/ GSK-3β/ β-catenin pathway. This may be a potential strategy to alleviate osteophyte development in addition to anti-inflammatory treatment. [ABSTRACT FROM AUTHOR]

Current work has been designed to investigate the immunomodulatory efficacy with particular reference to humoral, cell-mediated and cytokine-modulating potential of hot aqueous extract of Neolamarckia cadamba (HAENC) fruits in Wistar albino rats. The effect of different concentrations of HAENC fruits over cell-mediated immune response was assessed using six groups (Gp-I as control, Gp-II with 20 µg/mL, Gp-III with 50 µg/mL, Gp-IV with 100 µg/mL, Gp-V with 250 µg/mL, and Gp-VI with 500 µg/mL) of Wistar albino rats having six animals in each. The amount of tumor necrosis factor-α (TNF-α) and interleukin (IL)-10 was measured by sandwich ELISA with different concentrations of HAENC (50–500 µg/mL) in splenocyte culture supernatant and their expression was determined by qRT-PCR Humoral immune response was determined by measuring the serum antibody titer of Wistar albino rats against Salmonella typhimurium 'O' antigen using four groups containing six animals each (Gp-I as control, Gp II, III & IV were respectively fed orally with 125, 250, and 500 mg/Kg body weight using HAENC fruits). LC–MS analysis suggested the presence of cadambine, chlorogenic acid, cadambagenic acid, stearic acid, octadecanoic acid ethyl ether, and 7-hydroxy-5,2'-4'-trimethoxyflavonon in the extract based on their m/z ratio. The result suggested significant (p < 0.01) dose-dependent proliferation of Concanavalin A (Con A)-treated splenocytes, depicting cell-mediated immunostimulatory potential of HAENC fruits. A dose-dependent significant decrease (p < 0.01) was found in the amount of TNF-α and IL-10 was found to increase significantly (p < 0.01) as extract concentrations increased. TNF-α and IL-10 expressions were confirmed at the molecular level by qRT-PCR analysis of mRNA transcripts of TNF-α and IL-10 genes. Fold expression of TNF-α and IL-10 gene was 0.197 and 3.58 at 250 µg/mL, 0.02 and 20.11 at 500 µg/mL concentrations of HAENC respectively in comparison to control. Serum antibody titer was significantly increased (p < 0.01) in animals fed with different doses of HAENC fruits. The present study suggested the anti-inflammatory effect of HAENC fruits which also influences the networking of cytokines, implying that it may play a role in regulating the activity of the host's immune system and can serve as a potent herbal drug with immuno-stimulatory potential. [ABSTRACT FROM AUTHOR]

Objective To analyze the changes of serum intercellular adhesion molecule-1 (ICAM-1), interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) levels in burn patients and the relationship between them and the degree of wound healing. Methods A total of 120 burn patients admitted to Department of Burn, Zhangjiakou First Hospital, from January 2020 to February 2023 were selected, and the serum levels of ICAM-1, IL-10 and TNF-α at 1, 28 days after admission were compared. According to the median levels of serum ICAM-1, IL-10 and TNF-α, the patients were divided into high expression group and low expression group, and the degree of wound healing between the groups was compared. Pearson correlation was used to analyze the correlation between the degree of wound healing and serum ICAM-1, IL-10 and TNF-α in burn patients. According to the wound healing quality of burn patients, the predictive value of serum ICAM-1, IL-10 and TNF-α on wound healing quality of burn patients was evaluated by ROC curve. Results On the 1, 28 day after admission, the serum levels of ICAM-1, IL-10 and TNF-α in burn patients were significantly different (P<0.05). The wound healing degree of ICAM-1 high expression group was significantly lower than that of ICAM-1 low expression group (P<0.05). The wound healing degree of high IL-10 expression group was significantly lower than that of low IL-10 expression group (P<0.05). The wound healing degree of high TNF-α expression group was significantly lower than that of low TNF-α expression group (P<0.05). Pearson correlation analysis showed that the degree of wound healing in burn patients was negatively correlated with serum ICAM-1, IL-10 and TNF-α (P< 0.05). ROC curve results showed that the area under the curve of serum ICAM-1, IL-10 and TNF-α on the 28 day after admission was greater than that of serum ICAM-1, IL-10 and TNF-α on the 1 day after admission, and the area under the curve of combined detection of the three was greater than that of any single detection. These results indicated that the combined detection of the three methods could be used as an effective indicator to predict the quality of wound healing in burn patients, and the predictive value of serum ICAM-1, IL-10 and TNF-α after treatment was higher. Conclusion Serum ICAM-1, IL-10 and TNF-α were negatively correlated with the degree of wound healing in burn patients, and the combined detection of the three could provide a reference for clinical prediction of wound healing quality. [ABSTRACT FROM AUTHOR]

Background: Inflammation has an important role in the pathogenesis of schizophrenia. The aim of this study was to investigate the levels of tumor necrosis factor (TNF) and matrix metalloproteinase-2 (MMP-2) in male patients with treatment-resistant schizophrenia (TRS) and chronic medicated schizophrenia (CMS), and the relationship with psychopathology. Methods: The study enrolled 31 TRS and 49 cm male patients, and 53 healthy controls. Serum MMP-2 and TNF-α levels were measured by the Luminex liquid suspension chip detection method. Positive and Negative Syndrome Scale (PANSS) scores were used to evaluate symptom severity and Repeatable Battery for the Assessment of Neuropsychological Status was used to assess cognitive function. Results: Serum TNF-α and MMP-2 levels differed significantly between TRS, CMS and healthy control patients (F = 4.289, P = 0.016; F = 4.682, P = 0.011, respectively). Bonferroni correction demonstrated that serum TNF-α levels were significantly elevated in CMS patients (P = 0.022) and MMP-2 levels were significantly higher in TRS patients (P = 0.014) compared to healthy controls. In TRS patients, TNF-α was negatively correlated with age (r=-0.435, P = 0.015) and age of onset (r=-0.409, P = 0.022). In CMS patients, MMP-2 and TNF-α were negatively correlated with PANSS negative and total scores, and TNF-α was negatively correlated with PANSS general psychopathology scores (all P < 0.05). MMP-2 levels were positively correlated with TNF-α levels (P < 0.05), but not with cognitive function (P > 0.05). Conclusion: The results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Chondrocyte apoptosis as a prominent characteristic is usually accompanied by cartilage degeneration in osteoarthritis (OA). Herein, we aimed to determine the roles of miR-149-5p in tumor necrosis factor-α (TNF-α)-induced chondrocyte apoptosis. Material and methods: Human chondrocytes were cultured with TNF-α to establish an apoptosis cell model in vitro. After transfection with miR-149- 5p mimics or co-expression with TRADD in chondrocytes, cell viability, apoptosis, inflammatory cytokines, mRNA and protein expression were measured using CCK8, Annexin V-FITC double staining, ELISA assays, RT-qPCR and western blotting, respectively. Results: TNF-α-induced chondrocyte apoptosis occurred in association with the inhibition of cell proliferation, the elevation of inflammatory cytokine levels and the activation of TRADD and caspase-3/8 signaling. The post-transcriptional regulatory mechanism suggested that TRADD was a direct target of miR-149-5p, and overexpression of miR-149-5p resulted in the down-regulation of TRADD protein expression in chondrocytes. In addition, miR-149-5p mimics had the ability to attenuate TNF-α-induced inflammation and apoptosis, while transfection with TRADD vector neutralized the protective effects of miR-149-5p on TNF-α-induced chondrocyte dysfunction. Conclusions: miR-149-5p inversely regulated TNF-α-mediated chondrocyte damage by inhibiting TRADD-modulated caspases signaling. The miR-149- 5p/TRADD signaling pathway might be a promising therapeutic target for the treatment of OA. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) express tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) following activation by various molecules and have antitumor effects against several cancer types. In particular, preactivation of MSCs with tumor necrosis factor-α (TNF-α) enhances TRAIL expression. We focused on the application of human periodontal ligament-derived stem cells (hPDLSCs) to stem cell-based cancer therapy, and evaluated their effects on head and neck squamous cell carcinoma (HNSCC) cells. TRAIL expression in hPDLSCs preactivated with TNF-α (A-hPDLSCs) was evaluated using real-time PCR, western blotting, and fluorescent immunocytochemistry. Subsequently, non-treated hPDLSCs (N-hPDLSCs) or A-hPDLSCs were cocultured with three types of HNSCC cells: HSC2, HSC3, and HSC4, and HNSCC cell apoptosis was assessed using flow cytometry. The migration ability of N-hPDLSCs and A-hPDLSCs toward HNSCC cells was also evaluated using a 3D gel invasion assay. In addition, conditioned medium (CM) derived from A-hPDLSCs was added to HNSCC cells, and cell proliferation ability was measured. A-hPDLSCs preactivated with 10 ng/mL TNF-α significantly upregulated the expression of TRAIL, increased apoptosis in HNSCC cells, and exhibited increased migration toward HNSCC cells compared to N-hPDLSCs. However, CM derived from A-hPDLSCs neither increased apoptosis nor suppressed HNSCC cell proliferation. hPDLSCs are proposed to be beneficial for stem cell therapies for HNSCC. Upon TNF-α preactivation, hPDLSCs may migrate toward HNSCC cells and directly induce apoptosis. [ABSTRACT FROM AUTHOR]

Objective: Tumor necrosis factor‐α (TNF‐α) can induce left ventricular remodeling. In this study, we investigated whether the TNF‐α‐308G>A polymorphism is associated with left ventricular geometry (LVG) and left ventricular functional abnormalities in obstructive sleep apnea (OSA) subjects. Methods: Two hundred and seventy‐eight subjects were enrolled. Echocardiography and genetic data were assessed in all patients. Geometric patterns of the left ventricle were determined from the relative wall thickness and left ventricular mass index (LVMI). Genetic analysis for the TNF‐α‐308G>A SNP rs1800629 was identified by Sanger sequencing. The correlations of the TNF‐α‐308G>A polymorphism with LVG and left ventricular function were analyzed by difference analysis and logistic regression. Results: The chi‐square test showed that there were differences in genotype distributions among the four groups (p = 0.033), such that the frequency of GA+AA genotypes was significantly higher in the concentric hypertrophy group than in the normal geometry group (p < 0.05). Independent sample T tests showed that the GA+AA genotypes had higher IVST, LVPWT, LVMI, E/e' values, and lower e' values than those of the GG genotype (p < 0.05). Logistic regression analysis showed that the TNF‐α‐308G>A polymorphism was independently correlated with eccentric hypertrophy (OR = 2.456, p = 0.047) and concentric hypertrophy (OR = 2.456, p = 0.047). Conclusion: In OSA patients, the TNF‐α‐308G>A polymorphism was linked to LVG and abnormal left ventricular diastolic function, suggesting that the TNF‐α‐308G>A polymorphism may have an important influence on LVG alterations. [ABSTRACT FROM AUTHOR]

We propose a new strategy using a sandwich approach for the detection of two HF biomarkers: tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10). For this purpose, magnetic nanoparticles (MNPs) (MNPs@aminodextran) were biofunctionalized with monoclonal antibodies (mAbs) using bis (sulfosuccinimidyl) suberate (BS3) as a cross-linker for the pre-concentration of two biomarkers (TNF-α and IL-10). In addition, our ISFETs were biofunctionalized with polyclonal antibodies (pAbs) (TNF-α and IL-10). The biorecognition between pAbs immobilized on the ISFET and the pre-concentrate antigen (Ag) on MNPs was monitored using electrochemical impedance spectroscopy (EIS). Our developed ImmunoFET showed a low detection limit (0.03 pg/mL) toward our target analyte when compared to previously published electrochemical immunosensors. It showed a higher sensitivity than for other HF biomarkers. Finally, the standard addition method was used to determine the unknown concentration in artificial saliva. The results matched with the expected values well. [ABSTRACT FROM AUTHOR]

Curcuma longa L. extract (CLE) exerts various biological functions including antioxidant, anti-inflammation, anticancer, and antiallergenic effects. However, its immune-enhancing capacity remains unclear. Therefore, the immune-enhancing effect of CLE was investigated in RAW 264.7 cells and cyclophosphamide (CPP)-induced immunosuppression model. CLE upregulated nitric oxide (NO) and reactive oxygen species production and increased inducible nitric oxide synthase and cyclooxygenase-2 expression without affecting the RAW 264.7 cells viability. The results of quantitative real-time reverse transcription polymerase chain reaction and sandwich enzyme-linked immunosorbent assay showed that CLE increased the gene expression and protein levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β in RAW 264.7 cells. Moreover, CLE upregulated p65, I kappa B kinase α/β, and I kappa B α (IκBα) phosphorylation and downregulated IκBα expression in RAW 264.7 cells. CLE also increased p65 translocation from the cytoplasmic to the nucleus in RAW 264.7 cells. The oral administration of CLE increased organ indexes (including the spleen and thymus) and NO production in peritoneal macrophages and improved natural killer cell activity in CPP-induced immunosuppression BALB/c mice. Overall, CLE could be a useful health functional food material that can improve innate immunity via macrophage activation. [ABSTRACT FROM AUTHOR]

Objective To observe the regulatory role of receptor tyrosine kinase Mer （Mertk） in the proliferation of the rat Schwann cell line RSC96 under high glucose condition. Methods RSC96 cells were divided into groups one, two, three, four and five and were cultured in medium containing 25（normal glucose concentration）, 50, 75, 100 and 125 mmol/L glucose, respectively, and Mertk was detected in cells of each group by Western blotting at 48 h of incubation, and the highest concentration of Mertk protein relative expression was selected to be the high-glucose concentration for the subsequent study. RSC96 cells were starved for 4 h, and were placed in the glucose medium containing 100 mmol/ L glucose, and then were cultured for 0, 24, 36, 48, and 60 h. Western blotting was used to detect the Mertk of cells in each group, and the time with the highest relative expression of Mertk protein was screened as the time of culture for the subsequent study. RSC96 cells were taken and divided into the control group, high glucose group, high glucose knock‐ down group and knockdown group： cells in the high glucose group were starved for 4 h and cultured in medium containing 100 mmol/L glucose; cells in the high glucose knockdown group were starved for 4 h, and were placed in medium contain‐ ing 100 mmol/L glucose, and then, 5 µL of siRNA solution with knockdown of Mertk expression was added; cells in the knockdown group were starved for 4 h, and 5 µL of siRNA with knockdown of Mertk expression was added; cells in the control group were cultured in the normal medium. The cells in each group were taken at 48 h of culture, and the proliferation of each group was measured by Edu method, and Mertk, phosphorylated nuclear transcription factor-κB （P65） and tumor necrosis factor-α（TNF-α） in each group were detected by Western blotting. Results Compared with the group one, the relative expression levels of Mertk protein were higher in cells of groups four and five （all P<0. 05); the relative expression of Mertk was higher in RSC96 cells at 48 and 60 h of culture in comparison with that at 0 of culture （all P<0. 05). Compared with the control group, the proliferation activity of cells in the high glucose group was lower （P<0. 05), and the proliferation activity of cells in the knockdown group was higher （P<0. 05); compared with the control group, the relative expression levels of P65 and TNF-α of cells in the high glucose knockdown group were higher （both P<0. 05), the relative expression of Mertk of cells in the knockdown group was lower, the relative expression levels of P65 and TNF-α of cells in the knockdown group were higher （all P<0. 05), and the relative expression levels of Mertk, P65, and TNF-α of cells in the high glucose group were higher （all P<0. 05). Conclusions RSC96 cells cultured in high glucose environment with knockdown of Mertk gene expression has high proliferative capacity and high cellular P65 and TNF-α expression. Mertk may promote the proliferation of RSC96 cells cultured in high glucose environment by promoting cellular P65 and TNF-α expression. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence suggests that immune dysfunction and inflammation in the peripheral tissues as well as the central nervous system are associated with the neurodevelopmental deficits observed in autism spectrum disorder (ASD). Elevated expression of pro-inflammatory cytokines in the plasma, serum, and peripheral blood mononuclear cells of ASD has been reported. These cytokine expression levels are associated with the severity of behavioral impairments and symptoms in ASD. In a prior study, our group reported that tumor necrosis factor-α (TNF-α) expression in granulocyte–macrophage colony-stimulating factor-induced macrophages (GM-CSF MΦ) and the TNF-α expression ratio in GM-CSF MΦ/M-CSF MΦ (macrophage colony-stimulating factor-induced macrophages) was markedly higher in individuals with ASD than in typically developed (TD) individuals. However, the mechanisms of how the macrophages and the highly expressed cytokines affect neurons remain to be addressed. Methods: To elucidate the effect of macrophages on human neurons, we used a co-culture system of control human-induced pluripotent stem cell-derived neurons and differentiated macrophages obtained from the peripheral blood mononuclear cells of five TD individuals and five individuals with ASD. All participants were male and ethnically Japanese. Results: Our results of co-culture experiments showed that GM-CSF MΦ affect the dendritic outgrowth of neurons through the secretion of pro-inflammatory cytokines, interleukin-1α and TNF-α. Macrophages derived from individuals with ASD exerted more severe effects than those derived from TD individuals. Limitations: The main limitations of our study were the small sample size with a gender bias toward males, the use of artificially polarized macrophages, and the inability to directly observe the interaction between neurons and macrophages from the same individuals. Conclusions: Our co-culture system revealed the non-cell autonomous adverse effects of GM-CSF MΦ in individuals with ASD on neurons, mediated by interleukin-1α and TNF-α. These results may support the immune dysfunction hypothesis of ASD, providing new insights into its pathology. [ABSTRACT FROM AUTHOR]

(1) Background: Sjögren's syndrome (SS) represents a systemic autoimmune disease whose pathophysiology has yet to be elucidated, though it is known that the inflammatory process encountered in SS is of a systemic nature, with cytokines representing the main mediators for tissue damage. (2) Aim of the study: The aim of the present study is to further the understanding of the link between interleukin serum levels, cytokine serum levels, HRCT findings and the Warrick score (as tools for the evaluation of pulmonary involvement) in patients with pSS. (3) Methods: The present study is a retrospective, observational one aimed at ascertaining the link between SS activity and its clinical implications, as well as how interleukin and TNF-α levels correlate with systemic changes. The study enrolled 112 patients with pSS and 56 healthy subjects, matched for age and gender, as a control group. pSS activity was assessed using the ESSDAI. Cytokine levels and leukocyte and lymphocyte counts were measured in both groups. The focus score was calculated for each patient, HRCT was performed to assess lung function, and the Warrick score was calculated. (4) Conclusions: HRCT revealed NSIP in 13 patients (59.09%) and UIP in 9 patients. The strongest positive correlation was identified upon analyzing the relation between IL-8 and the Warrick score (r = 0.9156, p < 0.00001), followed by a positive correlation between the score and IL-6 levels (r = 0.5738, p < 0.0052). Unsurprisingly, the degree and severity of pulmonary involvement was also positively correlated with the degree of disease activity (r = 0.4345, p = 0.0433). [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) ameliorate graft-versus-host disease (GVHD)-induced tissue damage by exerting immunosuppressive effects. However, the related mechanism remains unclear. Here, we explored the therapeutic effect and mechanism of action of human placental-derived MSCs (hPMSCs) on GVHD-induced mouse liver tissue damage, which shows association with inflammatory responses, fibrosis accompanied by hepatocyte tight junction protein loss, the upregulation of Bax, and the downregulation of Bcl-2. It was observed in GVHD mice and Th1 cell differentiation system that hPMSCs treatment increased IL-10 levels and decreased TNF-α levels in the Th1 subsets via CD73. Moreover, hPMSCs treatment reduced tight junction proteins loss and inhibited hepatocyte apoptosis in the livers of GVHD mice via CD73. ADO level analysis in GVHD mice and the Th1 cell differentiation system showed that hPMSCs could also upregulate ADO levels via CD73. Moreover, hPMSCs enhanced Nrf2 expression and diminished Fyn expression via the CD73/ADO pathway in Th1, TNF-α+, and IL-10+ cells. These results indicated that hPMSCs promoted and inhibited the secretion of IL-10 and TNF-α, respectively, during Th1 cell differentiation through the CD73/ADO/Fyn/Nrf2 axis signaling pathway, thereby alleviating liver tissue injury in GVHD mice. [ABSTRACT FROM AUTHOR]

Background: Oral lichen planus (OLP) is a T-cell-mediated autoimmune disease that affects the epithelial cells of the oral cavity. This study was performed to investigate any possible relationship between − 1031(T/C) polymorphism (rs1799964) of the tumor necrosis factor α (TNF-α) gene with the risk and severity of oral lichen planus (OLP) disease among an Iranian population. Method: Saliva samples were collected from 100 patients with OLP and a similar number of healthy controls (age and sex-matched). Then, DNA was extracted from the collected samples for genotyping TNF-α-1031 T/C polymorphism using the PCR-CTPP method. The results were assessed using SPSS software. Results: The findings revealed a significantly higher prevalence of the C allele in OLP patients (53%) compared to healthy controls (36%), suggesting an association between TNF-alpha gene polymorphism and OLP. A multivariate logistic regression analysis supported this finding, as the presence of the C allele was significantly associated with an increased risk of OLP [χ2 = 4.17, p = 0.04, 95% CI = 1.01–2.65, OR = 1.64]. However, our data indicated no significant association between TNF-alpha-1031 T/C gene polymorphism and OLP severity. Conclusions: These findings provide the first evidence supporting a possible role of TNF-α-1031 T/C gene polymorphism in OLP susceptibility in the Iranian population. The findings of this study demonstrate a positive association between TNF-α-1031 C/T allele distribution and the risk of OLP disease in the Iranian population. Therefore, carrying the C allele may increase the susceptibility to OLP disease. [ABSTRACT FROM AUTHOR]

Areca nut is a major contributor to the high prevalence of oral cancer in Asia. The precise mechanisms by which areca nut stimulates mucosal cells and contributes to the progression of oral cancer urgently require clarification. The current study aimed to assess the effects of arecoline on the normal human gingival epithelium cell line S-G. Cell viability, levels of reactive oxygen species (ROS), protein expression, cellular morphology, and gene expression were evaluated using the MTT test, flow cytometry, Western blot analysis, optical or confocal microscopy, and RT-qPCR. Keratin (KRT6) analysis involved matched normal and cancer tissues from clinical head and neck specimens. The results demonstrated that 12.5 µg/mL of arecoline induced ROS production, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) mRNA expression in S-G cells. This activation of the MAPK/ERK pathway increased KRT6 expression while limiting cell migration. In head and neck cancer tissues, KRT6B gene expression exceeded that of normal tissues. This study confirms that arecoline induces ROS accumulation in normal cells, leading to the secretion of proinflammatory factors and KRT6 expression. This impedes oral mucosal healing, thereby promoting the progression of oral cancer. [ABSTRACT FROM AUTHOR]

Objective: To establish a reliable, stable and clinically realistic model of blunt contusion injury to the rat skeletal muscle. Method: A model of the rat gastrocnemius muscle blunt contusion injury was established by using a weight of 170g, a height of 70cm and a spring with a diameter of 0.5cm at the bottom to buffer the polymeric striking part and guide the fall to hit for 5 consecutive times. The gait changes of rats were evaluated by CatWalk analysis system at 0h, 12h, 24h, 3 days, 7 days and 14 days after modeling；local histopathological changes were observed by HE staining and local ultrastructural changes were observed by transmission electron microscopy. Enzyme-linked immunosorbent assay (ELISA) was used to detect the changes of tumor necrosis factor-α (TNF-α) in local tissues. Result: Compared with the blank group, the mean speed and maximum speed change rate of the model group were significantly decreased, and the difference was statistically significant (P<0.001)； compared with the normal foot group, the maximum contact area, footprint area and standing phase duration of the limb of the injured limb group were significantly decreased, and the difference was statistically significant (P<0.05). A large infiltration of inflammatory cells and massive lysis necrosis of muscle fibers were observed on HE staining after 3 days. By 14 days, although scar tissue was still present, tissue repair with HE staining was almost indistinguishable from that of the blank group. Vacuolation was observed in part of the sarcoplasmic reticulum at 0h after the blow, and lysis of muscle fibers and part of the sarcoplasmic reticulum at 3 days with increased inflammatory response which basically returned to normal by 14 days. The TNF-α level began to rise gradually and reached a peak from 0h to 12h after injury, and remained higher level from 12h to 72h, and the difference was statistically significant compared with the blank group (P<0.05), and basically returned to the normal level by 14 days. Conclusion: The model can cause moderate damage of skeletal muscle in rats, with a 14-day natural recovery time at least. It can provide as one of the methods for for the establishment of the rat skeletal muscle blunt contusion model. [ABSTRACT FROM AUTHOR]

As miR-137 is a regulator of aquaporin (AQP)2 expression and tumor necrosis factor (TNF) inhibits the expression of several extrarenal AQPs, we tested the hypothesis that TNF inhibits AQP2 in the kidney via a miR-137-dependent mechanism. AQP2 mRNA and protein expression decreased ~70% and 53%, respectively, in primary renal inner medullary collecting duct (IMCD) cells transfected with a miRNA mimic of mmu-miR-137, suggesting that miR-137 directly targets AQP2 mRNA in these cells. Exposure of IMCD cells for 2 h to 400 mosmol/kgH2O medium increased mmu-miR-137 mRNA expression about twofold, conditions that also increased TNF production approximately fourfold. To determine if the increase in mmu-miR-137 mRNA expression was related to the concomitant increase in TNF, IMCD cells were transfected with a lentivirus construct to silence TNF. This construct decreased mmu-miR-137 mRNA expression by ~63%, suggesting that TNF upregulates the expression of miR-137. Levels of miR-137 also increased approximately twofold in IMCD tubules isolated from male mice given 1% NaCl in the drinking water for 3 days. Intrarenal lentivirus silencing of TNF increased AQP2 mRNA levels and protein expression concomitant with a decrease in miR-137 levels in tubules isolated from mice given NaCl. The changes in AQP2 expression levels affected the diluting ability of the kidney, which was assessed by measuring urine osmolality and urine volume, as the decrease in these parameters after renal silencing of TNF was prevented on intrarenal administration of miR-137. The study reveals a novel TNF function via a miR-137-dependent mechanism that regulates AQP2 expression and function. [ABSTRACT FROM AUTHOR]