Serum Levels Of TNF-α Research Articles

PCSK9 and its relationship with HMGB1, TLR4, and TNFα in non-statin and statin-treated coronary artery disease patients.

Despite statin use in coronary artery disease (CAD), significant risk remains, potentially due to increased proprotein convertase subtilisin/kexin-type 9 (PCSK9) production, which raises LDL-C levels and induces inflammation. The exact relationship between PCSK9, inflammatory markers like TNFα, TLR4, CRP, and HMGB1, and monocyte subsets is poorly understood. This study aimed to explore these relationships in non-statin and statin-taking CAD patients. This case-control study included 91 controls and 91 stable CAD patients, divided into no-statin (NS, n = 25), low-dose statin (LDS, n = 25), and high-dose statin (HDS, n = 41) groups. Serum levels of LDL-C, CRP, PCSK9, TLR4, HMGB1, and TNFα were measured. Monocyte subsets were classified using flow cytometry into classical monocytes (CM), intermediate monocytes (IM), and non-classical monocytes (NCM). CAD patients showed elevated PCSK9, LDL-C, and inflammatory markers compared to controls. Statin groups (LDS, HDS) had lower LDL-C and inflammatory markers but higher PCSK9 than the NS group, with the HDS group showing the lowest LDL-C and inflammatory markers but the highest PCSK9. In the NS group, PCSK9 positively correlated with inflammatory markers (HMGB1, TNFα, TLR4, CRP) and monocyte subsets (IM%, NCM%). In the total statin group (LDS + HDS), PCSK9 negatively correlated with HMGB1, TLR4, and NCM%, for each, respectively, and positively with CM%. Multivariable linear regression showed significant associations between PCSK9 and HMGB1, NCM%, and IM% in the NS group, and HMGB1, NCM%, and TLR4 in the total statin group. In conclusion, we recommend combining PCSK9 inhibitors with statins in high-risk CAD patients. This may enhance statin efficacy, reduce LDL-C, and inhibit the TLR4/NF-кB inflammatory pathway, decreasing atherosclerotic inflammation.

Protective effects of YCHD on the autoimmune hepatitis mice model induced by Ad-CYP2D6 through modulating the Th1/Treg ratio and intestinal flora

BackgroundAutoimmune hepatitis (AIH) is a chronic liver inflammatory disease mediated by autoimmune reactions, the pathogenesis of AIH is probably related to the imbalance of intestinal flora. Yinchenhao decoction (YCHD) has been used to relieve AIH. However, the mechanisms underpinning YCHD’s hepatoprotective effects with the gut microbito have not been fully revealed.ObjectiveTo explore the potential mechanism of YCHD in treating AIH based on changes in the intestinal flora and Th1/Treg ratio in the spleen and hepatic hilar lymph nodes.MethodsThe AIH mice model induced by the adenovirus vectors that overexpress human cytochrome P450 family 2 subfamily D member 6 (Ad-CYP2D6) was established (untreated group). One week after the Ad-CYP2D6 injection, the AIH model mice were treated by administering YCHD by gavage for 14 days (YCHD-treated group). The therapeutic efficacy of YCHD on AIH was evaluated by detecting the histopathological changes of the liver, serum transaminases (ALT and AST), inflammatory factors (TNF-α,IL-17 and IFN-γ), and autoantibodies (including LKM-1 and LC-1). The ratio of Th1 to Treg within the spleen and hepatic hilar lymph nodes of the mice was detected by flow cytometry. The changes in the species and abundance of intestinal flora and intestinal flora metabolites were analyzed via 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC/MS) to reveal the protective mechanism of YCHD on liver injury.ResultYCHD decreased the transaminase activity (AST and ALT), the content of autoantibodies (LC-1 and LKM-1), and the serum TNF-α, IL-12, and IL-17 levels in AIH mice. The degree of inflammatory infiltration in the YCHD-treated group was significantly less than that in the untreated group. YCHD can effectively reverse the abundance and diversity of intestinal flora in AIH mice and affect the release of short-chain fatty acids (SCFAs), especially butyric acid. Moreover, the flow cytometry results showed that YCHD could also decline the ratio of Th1/Treg, which probably be induced by SCFAs via the G protein-coupled receptor (GPR).ConclusionYCHD may affect the release of SCFAs by regulating the intestinal microbiota, thereby affecting the differentiation of Th1 and Treg, and achieving the effect of alleviating liver damage.

Effect of acupuncture combined with bloodletting therapy on mast cell degranulation in urticaria rats

To observe the effects of acupuncture combined with bloodletting on the expression of inflammatory factors in serum, the morphology of sensitized skin tissue and the mast cell degranulation in urticaria rats, and to explore the potential mechanism of this therapy for urticaria. Among 42 SD rats of SPF grade, 6 rats were randomly collected for the preparation of sensitized antiserum; and the rest 36 rats were randomized into a blank group, a model group, a positive drug group, an acupuncture group, a bloodletting group and a combined treatment group (acupuncture + bloodletting), 6 rats in each one. The rat model of urticaria was established by passive cutaneous anaphylaxis. In the positive drug group, loratadine (1 mg•kg-1) by gavage was administered once a day. In the acupuncture group, 1 h after gavage with 0.9% NaCl (1 mL), acupuncture was delivered at "Baihui" (GV 20), "Zhongwan" (CV 12), and bilateral "Quchi" (LI 11) and "Xuehai" (SP 10) for 15 min, once daily . In the bloodletting group, 1 h after gavage with 0.9% NaCl (1 mL), bloodletting was operated at "Dazhui" (GV 14) and bilateral "Geshu" (BL 17), around 0.1 mL of bleeding volume at each point, once daily. In the combined treatment group, 1 h after gavage with 0.9% NaCl (1 mL), the interventions as the acupuncture group and the bloodletting group were adopted, once daily. All the interventions started on day 6 of modeling, lasting 2 weeks. After intervention completion, antigenic stimulation was performed in the rats of each group. Using ELISA, the levels of serum immunoglobulin E (IgE), tryptase (TPS), interleukin-4 (IL-4), interleukin-5 (IL-5), tumor necrosis factor-α (TNF-α) were detected. The diameter of the blue spots of the sensitized skin on the back was measured with ruler in each rat. The morphology of sensitized skin tissue was observed using HE staining, and the degranulation of mast cells was observed using Toluidine blue staining. Compared with the blank group, in the model group, the levels of serum IgE, TPS, IL-4, IL-5 and TNF-α increased (P<0.01), the diameter of blue spot on the sensitized part of the rat back was larger (P<0.01), the degranulation rate of mast cells was elevated (P<0.01), and there were obvious inflammatory cell infiltration and edema in the dermis of sensitized skin tissue on the rat back. Compared with the model group, the serum levels of IgE, TPS, IL-4, IL-5 and TNF-α were reduced in the positive drug group, the acupuncture group, the bloodletting group and the combined treatment group (P<0.01, P<0.05); skin blue spot diameter was smaller in the positive drug group and the combined treatment group (P<0.05); the degranulation rate of mast cells decreased in the positive drug group, the acupuncture group, the bloodletting group and the combined treatment group (P<0.01); and the dermal edema, inflammatory infiltration were attenuated in the positive drug group, the acupuncture group, the bloodletting group and the combined treatment group. Compared with the acupuncture group and the bloodletting group, the serum levels of IgE, TPS, IL-4, IL-5 and TNF-α, as well as the degranulation rate of mast cells in the sensitized tissue were lower in the positive drug group and the combined treatment group (P<0.05). Acupuncture combined with bloodletting effectively suppress mast cell degranulation in the sensitized skin tissue on the back of urticaria rats, and ameliorate the histopathological morphology. Its effect mechanism may be related to inhibiting the differentiation and proliferation of helper T cells 2 and regulating the humoral immune response.

Melatonin attenuates cardiac dysfunction and inflammation in dilated cardiomyopathy via M2 macrophage polarization.

Melatonin is a neuroendocrine hormone that exerts protective effects on the heart. Increasing evidence suggests that macrophage M2-type polarization improves myocardial regeneration and repair. Therefore, this study investigated whether melatonin ameliorates dilated cardiomyopathy (DCM) by modulating M2-type polarization. DCM mice were established by induction with doxorubicin and then treated with melatonin. Cardiac dysfunction was determined by measuring left ventricular ejection fraction (LVEF) and left ventricular internal dimensions at end-diastole and end-systole. Heart injury and fibrosis were determined by hematoxylin and eosin staining and Sirius Red staining, respectively. Serum concentrations of melatonin, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) were measured through enzyme-linked immunosorbent assays. M2-type macrophages were analyzed by flow cytometry. Relative mRNA and protein levels were determined by reverse transcription quantitative polymerase chain reaction and western blotting, respectively. Circulating melatonin levels were significantly decreased in DCM mice and were associated with LVEF. Treatment with melatonin markedly ameliorated cardiac dysfunction, improved survival, and alleviated pathological changes and collagen deposition in DCM mice. Furthermore, melatonin-treated DCM mice displayed lower serum and cardiac levels of IL-1β, IL-6, and TNF-α, as well as higher numbers of M2-type macrophages in cardiac tissue, indicating that melatonin treatment could decrease inflammatory responses and facilitate M2 macrophage polarization in DCM mice. Thus, melatonin treatment alleviated cardiac dysfunction and inflammatory responses by promoting M2 macrophage polarization in the DCM mouse model.

Fibrinogen-Like Protein 2 Protects the Aggravation of Hypertriglyceridemia on the Severity of Hypertriglyceridemia Acute Pancreatitis by Regulating Macrophages.

The mechanisms underlying the increased severity of hypertriglyceridemia acute pancreatitis (HTG-AP) remain poorly understood. Fibrinogen-like protein 2 (FGL2) has been identified as a regulator of macrophage activity, mediating immune suppression. This study aims to examine the role of FGL2 in the susceptibility to severe conditions of HTG-AP. Both wild-type and FGL2 gene knockout C57BL/6 mice were utilized to establish HTG, AP, and HTG-AP models using P-407 and/or caerulein. Serum levels of triglycerides, total cholesterol, amylase, and lipase were assessed via biochemical analysis. Pancreatic and lung tissue injuries were evaluated using hematoxylin and eosin staining. Tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6) levels in serum and pancreatic tissues were quantified using enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to assess the expression of FGL2, the macrophage marker CD68, and M1/M2 macrophage markers iNOS/CD163. The animal models were successfully established. Compared to wild-type mice, FGL2 knockout resulted in increased pathological injury scores in the pancreas and lungs, as well as elevated TNF-α, IL-1β, and IL-6 levels in serum and pancreatic tissue in the HTG group, with more pronounced effects observed in the HTG-AP group. The AP group alone did not exhibit significant changes due to FGL2 knockout. Further analysis revealed that FGL2 knockout increased CD68 expression but reduced CD163 expression in the pancreatic tissues in the HTG group. In the HTG-AP group, there was a marked increase in CD68 and iNOS expressions, coupled with a reduction in CD163 expression. FGL2 knockout in HTG and HTG-AP mice resulted in increased inflammatory responses and a significant imbalance in M2 macrophages. These findings suggest that FGL2 plays a crucial role in mitigating the aggravation of HTG on the severity of HTG-AP by modulating macrophage activity.

The Impact of Combined Cranberry Supplementation and Weight Loss Diet on Inflammatory, Antioxidant, and Apoptosis Biomarkers in Patients with Non-Alcoholic Fatty Liver Disease: A Randomized, Double-Blinded, Controlled Clinical Trial

Background: Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disease. The aim of this study is to evaluate the effect of combined weight loss diet and cranberry supplementation on anthropometric measurements, inflammation and antioxidant biomarkers in patients with NAFLD. Methods: In this randomized, double-blinded, and controlled clinical trial, 41 NAFLD patients were supplemented with either cranberry or placebo tablets for 12 weeks. Both groups followed a diet of 500-1000 calories less than the estimated energy requirements. Serum levels of total antioxidant capacity (TAC), malondialdehyde (MDA), cytokeratin 18 M30 (CK-18 M30), chemokine C-C motif ligand 2 (CCL2) and tumor necrosis factor alpha (TNF-α) were measured at both baseline and the end of the study. Results: Significant improvements in TAC were observed in the cranberry group and between the two groups (P=0.006 and P=0.011, respectively), but the changes in the placebo group were not significant (P=0.325). There were no statistically significant differences in the serum levels of MDA, CK-18 M30, CCL2 and TNF-α between the cranberry and the placebo groups (P&gt;0.05). Conclusions: It seems that daily consumption of cranberry supplement would be beneficial in increasing serum levels of TAC. Further studies are needed to investigate the effects of anti-inflammatory and antioxidant properties of cranberry on NAFLD.

Study on the Anti-Atherosclerotic Mechanisms of Xin-Tong-Tai Granule Through Network Pharmacology, Molecular Docking, and Experimental Validation.

Xin-Tong-Tai Granule (XTTG), a Chinese medicine (CM) formula, has demonstrated significant therapeutic effects on atherosclerosis (AS) in both clinical and experimental settings. Nonetheless, the mechanisms underlying XTTG's efficacy remain largely unexplored. This study aimed to elucidate the mechanisms through which XTTG acts against AS, employing network pharmacology, molecular docking, and experimental validation techniques. Initially, target identification for the main chemical components of XTTG was conducted using database, followed by determining the intersection targets between these compounds and disease. Protein-protein interaction (PPI) network analysis, Gene Ontology (GO) enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were subsequently utilized to investigate the potential pathways through which XTTG exerts its effects on AS. Molecular docking was done to confirm the binding efficacy of XTTG's active components. Additionally, the effects of XTTG were evaluated in vitro using oxidized low-density lipoprotein (ox-LDL) induced human aortic vascular smooth muscle cells (HAVSMCs) and in vivo in apolipoprotein E gene knockout (ApoE-/-) mice fed a high-fat diet (HFD). 229 therapeutic targets were screened for PPI network and enrichment analysis. Notably, the nuclear factor kappa-B (NF-κB) signaling pathway, along with processes related to inflammation and autophagy, were significantly enriched, highlighting their importance. In vitro studies showed that XTTG repressed cell proliferation and lipid droplet aggregation in ox-LDL-induced HAVSMCs. It also decreased the ratio of phosphorylated NF-κB p65/ NF-κB p65, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, and elevated microtubule-associated protein light chain 3 (LC3) and decreased p62 protein expression. In vivo, XTTG ameliorated blood lipid profiles and aortic pathology in HFD-fed ApoE-/- mice, reduced NF-κB p65 expression and serum levels of TNF-α and IL-6, increased the ratio of LC3II/LC3I while decreasing p62 protein expression. XTTG mitigates AS primarily through anti-inflammatory and autophagy-modulating mechanisms, particularly via inhibition of NF-κB p65 expression. These findings underscore the potential of CM in treating AS and support its further clinical exploration.

Expression of NLRP3 in serum and induced sputum of children with asthma and their relationship with disease severity

ObjectivesThe aim of this cross-sectional study is to investigate the levels of NLRP3 in the serum and induced sputum of children with asthma and their potential association with lung function and disease severity.MethodsThis cross-sectional study included 83 children with bronchial asthma who sought medical care at our hospital from May 2023 to February 2024. Portable spirometry was used to monitor lung function parameters, including forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow. The expression of C-reactive protein (CRP), interleukin (IL)-6, IL-1β, TNF-α, and Nod-like receptor family pyrin domain-containing 3 (NLRP3) in the serum and induced sputum were measured by enzyme-linked immunosorbent assay. Data analysis was performed using SPSS 25.0 and differences with P < 0.05 were considered statistically significant.ResultsChildren with asthma exhibited significantly elevated levels of serum NLRP3, CRP, IL-6, IL-1β, and TNF-α compared to healthy controls. In addition, children with moderate–severe asthma had significantly higher levels of serum and induced sputum NLRP3 and IL-1β compared to children with mild asthma. Spearman’s correlation analysis revealed a positive correlation between induced sputum NLRP3 and IL-6. Moreover, induced sputum NLRP3 was negatively correlated with lung function parameters. The results of receiver operating characteristic curves showed that induced sputum NLRP3 could be used for diagnosing children with moderate–severe asthma, with an AUC was 0.758, cutoff value of 3.33 ng/mL, sensitivity of 66.1%, and specificity of 70.8%. Furthermore, the logistic regression analysis revealed that serum and induced sputum NLRP3, induced sputum IL-6 and IL-1β were risk factors for children with moderate–severe asthma.ConclusionsIn this cross-sectional study, we found a significant increase in NLRP3 levels in induced sputum of children with asthma, which further increased in those with moderate–severe disease. The levels of NLRP3 in induced sputum could serve as potential biomarkers for assessing disease severity.

Rosehip (Rosa rugosa Thunb.) ethanol extract ameliorates liver fibrosis through upregulation of the PPAR signaling pathway

The objective of this study was to examine the effect of rosehip (Rosa rugosa Thunb.) ethanol extract (RRE) on liver fibrosis in mice and the underlying molecular mechanisms. RRE has no acute oral toxicity, and the MTD in mice is 46.14 g/kg. Histopathological analysis showed that RRE significantly ameliorated inflammation, necrosis, and apoptosis of hepatocytes and collagen deposition caused by CCl4. Further assays indicated that RRE significantly suppressed the production of MDA while markedly increasing the levels of SOD and GSH in the liver. The AST, ALT, IL-6, IL-1β, TNF-α, HA, LN, PCIII, and IVC levels in serum were decreased by RRE. Transcriptome analysis shows that RRE significantly upregulates the PPAR signaling pathway. The RT-q PCR results further confirmed the RRE up-regulating Pparγ, Rxrα, and Plin5 in the PPAR signaling pathway. The Western blot and immunohistochemical results indicate that RRE upregulated PPARγ, RXRα, and Perilipin 5 while downregulating α-SMA and COL1A1 expression. The results indicate that RRE can ameliorate liver fibrosis in mice by upregulating the PPAR signaling pathway.

Hemin attenuates bleomycin-induced lung fibrosis in mice by regulating the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/NF-κB pathways.

The objective of this study was to investigate the protective effect and potential mechanism of action of hemin on bleomycin-induced pulmonary fibrosis in mice. Male C57BL/6 mice were randomly divided into control, bleomycin and bleomycin + hemin groups. Mice in the bleomycin and bleomycin + hemin groups were injected intratracheally with bleomycin to establish the pulmonary fibrosis model. The bleomycin + hemin group mice were injected intraperitoneally with hemin starting 7 days before modeling until the end of Day 21 after modeling. Pathological changes in lung tissue were assessed by HE and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined in lung tissue. Immunohistochemistry was performed to assess the expression of α-SMA and collagen I. The serum levels of IL-6 and TNF-α were measured via ELISA. Western blotting was used to determine the expression of TGF-β1, SIRT1, PGC-1α and HO-1 and the phosphorylation levels of p38, ERK1/2, JNK, AMPK and NF-κB p65 in lung tissue. Hemin significantly reduced lung indices, increased terminal body weight. It also significantly increased SOD and CAT activities; decreased MDA, IL-6 and TNF-α levels; reduced the levels of α-SMA and collagen I-positive cells; upregulated SIRT1, PGC-1α and HO-1 expression; promoted AMPK phosphorylation; and downregulated TGF-β1 expression and p38, ERK1/2, JNK and NF-κB p65 phosphorylation. Hemin might attenuate oxidative damage and inflammatory responses and reduces extracellular matrix deposition by regulating the expression and phosphorylation of proteins associated with the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/NF-κB pathways, thereby alleviating bleomycin-induced pulmonary fibrosis.

F-Box and WD repeat domain containing 7 induces infectious osteomyelitis by regulating MYB stability and ubiquitination.

Osteomyelitis is a bone inflammation initiated by invading pathogens. Macrophages and inflammation play essential roles in osteomyelitis. F-Box and WD repeat domain containing 7 (Fbxw7) is a tumour suppressor and E3 ubiquitin ligase. In the present study, the potential roles of Fbxw7 in osteomyelitis were explored. The mRNA level of Fbxw7 was measured in bone marrow cells from patients with osteomyelitis and Staphylococcus aureus (S. aureus)-infected macrophages. The conditional knockout mice with Fbxw7 deficiency in myeloid cells were generated. The expression of interleukin (IL)-6, IL-23a and nitric oxide synthase 2 (Nos2) was measured in S. aureus-infected Fbxw7-deficient bone marrow-derived macrophages (BMDMs). The body weight loss, bacterial burden, bone loss and formation and serum level of IL-6, IL-23 and TNF-α were measured in S. aureus-infected Fbxw7 conditional KO mice. The interacting partners of Fbxw7 were predicted using STRING and the interaction were tested. Elevated expression of Fbxw7 was observed in bone marrow cells from patients with osteomyelitis and in S. aureus-infected macrophages. The expression of IL-6, IL-23a and Nos2 was remarkably suppressed in S. aureus-infected Fbxw7-deficient BMDMs. Fbxw7 conditional knockout mice had less body weight loss, higher bacterial burden, less bone loss and formation and decreased serum level of cytokines. Fbxw7 interacted with MYB. S. aureus-infected Fbxw7-deficient BMDMs had higher level of MYB and less ubiquitination of MYB. Fbxw7 promotes osteomyelitis symptoms by regulating ubiquitination and stability of MYB.

Correlation of biochemical markers and inflammatory cytokines in autism spectrum disorder (ASD)

IntroductionAutism Spectrum Disorder (ASD) is a disorder that severely affects neurodevelopment, and its underlying causes are not yet entirely understood. Research suggests that there may be a connection between the occurrence of ASD and changes in immune responses. This study aims to know if some biochemical and inflammatory cytokines are promising biomarkers for ASD and whether they are involved in the pathogenesis of ASD.MethodsThe serum levels of CRP, TNF-α, TGF-β, IL-1β, IL-10, 1 L-8, and IL-6 were measured in all of the patients (n = 22) and in the healthy (n = 12) children using ELISA method.ResultsThe serum concentrations of IL-10 and IL-8 were significantly lower in the ASD patients compared to the control group (p < 0.05) and there were not significant differences between CRP, TNF-α, TGF-β, IL-6 and IL-1β levels in two groups. There were positive correlations between CRP and IL-10, also CRP and IL-8, in ASD group. In contrast to the ASD patients, the correlations of IL-8, IL-10, and CRP were not significant in the control group.ConclusionIn conclusion, this study highlights the potential role of certain biochemical markers and inflammatory cytokines in ASD. Specifically, the lower levels of IL-10 and IL-8 in ASD patients, along with the significant correlations between CRP and these cytokines, suggest an altered immune response in individuals with ASD. These findings support the hypothesis that immune dysregulation may be involved in ASD pathogenesis. Further research is needed to explore these biomarkers and their mechanistic links to ASD, which could lead to improved diagnostics or therapeutic strategies.

Periodontitis Provokes Retinal Neurodegenerative Effects of Metabolic Syndrome: A Cross-Sectional Study

Background: This cross-sectional study aims to investigate the retino-choroidal degenerative effects of periodontitis, metabolic syndrome (Mets), and the combination of these diseases using optical coherence tomography (OCT) measurements. Methods: Ninety-two patients selected according to inclusion criteria were divided into four groups: systemically and periodontally healthy (control), systemically healthy periodontitis (PD), periodontally healthy metabolic syndrome (MetS), and periodontitis and metabolic syndrome combined (PD-MetS). The systemic inflammatory–oxidative effects of periodontitis and MetS were biochemically evaluated using the serum TNF-α level, IL-1β/IL-10 ratio, and oxidative stress index (OSI: TOS/TAS). Retinal (AMT, pRNFLT, and GCL + T) and choroidal (SFCT) morphometric measurements and vascular evaluations (foveal capillary density) were performed via OCT Angio with swept-source technology. Results: Both periodontitis and Mets cause systemic inflammatory stress characterized by significant increases in the IL-1β/IL-10 ratio and OSI (p &lt; 0.05). Compared to the control group, the AMT was significantly thinner in the MetS group, the pRNFLT was significantly thinner in the PD-MetS group, and the SFCT was significantly thinner in both groups (p &lt; 0.05). The GCL+ was slightly thicker in the Mets groups. (p &gt; 0.05) Foveal capillary density did not differ significantly among the groups. (p &gt; 0.05). Conclusions: Periodontitis-related inflammatory stress alone causes changes in retinal and subfoveal choroidal thicknesses that are not statistically significant. On the other hand, when combined with Mets, it may significantly provoke the retinal neurodegenerative effects of this disease.

Traditional Chinese herbal formula, Fuzi-Lizhong pill, produces antidepressant-like effects in chronic restraint stress mice through systemic pharmacology

Ethnopharmacological relevanceFuzi-Lizhong pill (FLP) is a well-validated traditional Chinese medicine (TCM) formula that has long been used in China for gastrointestinal disease and adjunctive therapy for depression. In our previous study, we reported that the principal herb of FLP, Aconitum carmichaelii Debx. (Fuzi), exhibits antidepressant-like effects. However, there have been no reports on whether FLP produces antidepressant-like effects and its potential molecular mechanisms. Aim of the studyWe aim to demonstrate the antidepressant-like effects of FLP in chronic restraint stress (CRS) mice and to explore the associated molecular mechanisms. Materials and methodsThe active components and probable molecular targets of FLP, as well as the targets related to depression, were identified through network pharmacology. A protein-protein interaction (PPI) network was generated using the overlapping targets, followed by the visualization as well as identification of the core targets associated with the antidepressant-like action of FLP. Subsequently, KEGG and GO enrichment analyses were conducted. UHPLC-MS/MS was employed to further detect the active compounds in FLP. Molecular docking was applied to assess the connections between the active components as well as the core targets. The efficacy of FLP in treating depression and its molecular mechanisms were examined using western blotting, ELISA, 16S rRNA sequencing, HE staining, Nissl staining, and Golgi-Cox staining in a CRS-induced mouse model. ResultsNetwork pharmacology and UHPLC-MS/MS analyses indicated that the active compounds of FLP comprised taraxerol, songorine, neokadsuranic acid B, ginkgetin, hispaglabridin B, quercetin, benzoylmesaconine and liquiritin. KEGG pathway analysis implicated that the PI3K/Akt/mTOR as well as MAPK signaling pathways are closely related to the therapeutic effects of FLP on depression. Molecular docking analysis demonstrated that the main components of FLP bind to PI3K, AKT, mTOR, BDNF and MAPK. FLP significantly decreased immobility in mice that were elevated by CRS in the FST and the TST. FLP also significantly increased sucrose preference in mice after CRS in the SPT. FLP upregulated proteins associated with BDNF-TrkB and PI3K/Akt/mTOR signaling and downregulated proteins associated with MAPK signaling. Serum levels of CORT, IL-6, IL-1β, and TNF-α in CRS mice were significantly decreased following treatment with FLP. In addition, FLP ameliorated CRS-induced gut microbiota dysbiosis as demonstrated by 16S rRNA sequencing analysis. FLP ameliorated CRS-induced intestinal inflammation and neuronal damage. Finally, antidepressant-like effects and concomitant increases in dendritic spine density induced by FLP administration were also reduced after rapamycin treatment. ConclusionThese results demonstrate that FLP has antidepressant-like effects in mice exposed to CRS that involve activation of the PI3K/Akt/mTOR signaling pathway, increase in spinogenesis, inhibition of the MAPK signaling pathway, decrease in inflammation, and amelioration of gut microbiota dysbiosis. These findings provide novel evidence for the clinical application of FLP on depression.

CCN5/WISP2 serum levels in patients with coronary artery disease and type 2 diabetes and its correlation with inflammation and insulin resistance; a machine learning approach

IntroductionStudies have shown various effects of CCN5/WISP2 on metabolic pathways, yet no prior investigation has established a link between its serum levels and CAD and/or T2DM. Therefore, this study seeks to explore the relation between CCN5 and the risk factor of CAD and/or diabetes, in comparison to individuals with good health, marking a pioneering endeavor in this field. MethodsThis case-control study investigates serum levels of CCN5, TNF-α, IL-6, adiponectin, and fasting insulin in a population of 160 individuals recruited into four equal groups (T2DM, CAD, CAD-T2DM, and healthy controls). Statistical tests comprise Chi-square tests, ANOVA, Spearman correlation, and logistic regression. ROC curves were used to represent the diagnostic potential of CCN5. Disease states are predicted by machine learning algorithms: Decision Tree, Gradient Boosted Trees, Random Forest, Naïve Bayes, and KNN. These models' performance was evaluated by various metrics, all of which were ensured to be robust by applying 10-fold cross-validation. Analyses were done in SPSS and GraphPad Prism and RapidMiner software. ResultsThe CAD, T2DM, and CAD-T2DM groups had significantly higher CCN5 concentrations compared to the healthy control group (CAD: 336.87 ± 107.36 ng/mL, T2DM: 367.46 ± 102.15 ng/mL, CAD-T2DM: 404.68 ± 108.15 ng/mL, control: 205.62 ± 63.34 ng/mL; P < 0.001). A positive and significant correlation was observed between CCN5 and cytokines (IL-6 and TNF-α) in all patient groups (P < 0.05). Multinomial logistic regression analysis indicated a significant association between CCN5 and T2DM-CAD, T2DM, and CAD conditions (P < 0.001) even after adjusting for gender, BMI, and age (P < 0.001). Regarding the machine learning models, the Naïve Bayes model showed the best performance for classifying cases of T2DM, achieving an AUC value of 0.938±0.066. For predicting CAD, the Random Forest classifier achieved the highest AUC value of 0.994±0.020. In the case of CAD-T2DM prediction, the Naïve Bayes model demonstrated the highest AUC of 0.981±0.059, along with an Accuracy of 97.50 % ± 7.91 % and an F-measure of 96.67 % ± 10.54 %. ConclusionOur study has revealed, for the first time, a positive connection between CCN5 serum levels and the risk of developing T2DM and CAD. Nonetheless, more research is needed to ascertain whether CCN5 can serve as a predictive marker.

Moringa oleifera Lam. seed lectin (WSMoL) reduces chronic stress-induced anxiety and depression in mice by lessening inflammation and balancing brain chemicals

Phyto-based treatments for anxiety and depression are gaining attention. The efficacy of the water-soluble Moringa oleifera seed lectin (WSMoL) in reducing acute anxiolytic and depressive-like behaviors in mice has been previously demonstrated. In the present study, it was evaluated the effects of WSMoL on reducing anxiety and depressive-like symptoms in a mouse model of unpredictable chronic mild stress (UCMS). The animals were divided into groups and exposed to a four-week UCMS regimen. Following this, the mice received daily intraperitoneal injections of vehicle (non-stressed and UCMS control groups), WSMoL (2 or 4 mg/kg), or fluoxetine (10 mg/kg) for 21 days. Neurobehavioral tests included the open field test and elevated plus maze test to assess anxiety-like behavior, and the tail suspension test and sucrose preference test to evaluate depression-like behavior. Biochemical analyses measured serum corticosterone and cytokines as well brain levels of cytokines and monoamines. All tests indicated that WSMoL significantly (p < 0.05) reversed the anxiety and depression-like behaviors induced by UCMS. The stress protocol increased serum corticosterone levels and WSMoL treatment was not able to normalize corticosterone secretion. WSMoL treatment reduced serum and brain levels of IL-2, IL-6, and TNF-α, indicating reduced neuroinflammation, and increased brain levels of dopamine, serotonin, and noradrenaline. In summary, WSMoL mitigated UCMS-induced anxiety and depression-like behaviors by reducing neuroinflammation and modulating brain monoamine levels.

Evaluation of Adipose Tissue Hormones and Tumor Necrosis factor in Patients with Endometriosis

Objective: To evaluate levels of physiological parameters (Testosterone, follicle stimulating hormone FSH, luteinizing hormone LH, leptin and tumor necrosis factor TNF-α, Adipsin and Ghrelin), Total antioxidant capacity-TAC, Glutathione S transfers -GST in sera of patients with endometriosis. Method: This study involved (85) women within reproductive age (25-40) years, who were distributed into two groups: patientsʹ group (55) women diagnosed with endometriosis, and (30) healthy control women. The study was carried out at Al-Karkh Maternity Hospital/ Baghdad and extended from 20/4/2024 to 20/5/2024. The pathological cases of patients were diagnosed by clinical examinations and confirmed by specialist physician with ultrasound examination. Blood samples were taken from both groups, serum was separated for each individual by a centrifuge. Results: a significant rise in the (FSH, Leptin, TNF -α, Adipisin) while a significant decrease in levels of (Testosterone , LH, GST, TAC, Ghrelin) concentration were found in the sera of patients compered to healthy women , with a probability of P ≤ 0.05. According to Receiver operating characteristic (ROC) statistical analysis, Area under curve (AUC ) for LH, leptin, TNF -α, adipsin, ghrelin, GST, TAC were closely or equal to (1) for patients . Conclusion: serum levels of LH, Leptin, Adipisin, Gherlin, TNF-α and GST can be dependable as prognostic indicator markers that reflect the degree of oxidative stress accompanying endometriosis.

Alginate from Ericaria crinita Possesses Antioxidant Activity and Attenuates Systemic Inflammation via Downregulation of Pro-Inflammatory Cytokines

Alginates are anionic polysaccharides present in the cell walls of brown seaweeds. Various biological activities of alginate and its derivatives have been described. In this study, we assessed the potential of alginate obtained from Ericaria crinita (formerly Cystoseira crinita) to scavenge free radicals and function as a ferric ion reductor. The anti-inflammatory effect on the serum levels of TNF-α, IL-1β, IL-6, and IL-10 of rats with LPS-induced systemic inflammation after 14 days of treatment was also examined. Ericaria crinita alginate showed antioxidant activities of IC50 = 505 µg/mL (DPPH) and OD700 &gt; 2 (ferric reducing power). A significant decrease in serum levels of IL-1β was observed only in animals treated with the polysaccharide at a dose of 100 mg/kg bw. Both doses of E. crinita alginate (25 and 100 mg/kg bw) significantly reduced the serum concentrations of pro-inflammatory cytokines TNF-α and IL-6, but no statistical significance was observed in the levels of the anti-inflammatory cytokine IL-10. Our findings show the potential of E. crinita alginate to act as an antioxidant and anti-inflammatory agent. It is likely that the exhibited antioxidant ability of the polysaccharide contributes to its antiphlogistic effects. More in-depth studies are needed to fully understand the specific mechanisms and the molecular pathways involved in these activities.

Inflammatory Cytokines and Cognition in Alzheimer's Disease and Its Prodrome.

The aim of this study was to investigate the association between blood levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) and cognitive impairments among elderly individuals. Peripheral concentration of TNF-α and IL-6 were measured in all subjects. To assess individual cognitive function, the Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NP) was used, and standardized scores (z-scores) were calculated for each test. Cytokine levels were compared between the diagnostic groups, and correlations between blood inflammatory factor levels and z-scores were analyzed. The 37 participants included 8 patients with Alzheimer's disease (AD), 15 subjects with mild cognitive impairment (MCI), and 14 cognitively healthy controls. TNF-α and IL-6 levels were higher in patients with AD than in healthy controls. TNF-α levels were higher in the AD group than in the MCI group. However, after adjusting for age, the associations between diagnosis and TNF-α and IL-6 were not significant. The higher the plasma IL-6 level, the lower the z-scores on the Boston Naming Test, Word List Learning, Word List Recognition, and Constructional Recall. The higher the serum TNF-α level, the lower the z-scores on the Word List Learning and Constructional Recall. Negative correlation between serum TNF-α level and the z-score on Word List Learning remained significant when age was adjusted. The difference in the blood levels of TNF-α and IL-6 between the diagnostic groups may be associated with aging. However, elevated TNF-α levels were associated with worse immediate memory performance, even after adjusting for age.

The triple combination DBDx alleviates cytokine storm and related lung injury

Cytokine storm is a life-threatening disorder, and therapeutic treatments are urgently needed. Here, we investigated the anti-cytokine storm efficacy of DBDx, a triple drug combination composed of dipyridamole, ubenimex and dexamethasone. Evaluated by lipopolysaccharide (LPS)-induced cytokine storm murine model, DBDx significantly improved survival rate and prolonged survival time of the model mice. Notably, the efficacy of DBDx was higher than that of dipyridamole, ubenimex and dexamethasone. Determined by ELISA, DBDx significantly reduced the LPS-stimulated serum levels of TNF-α, IL-6 and IL-1β in mice. Luminex assay showed that DBDx suppressed the serum levels of a wide variety of inflammatory cytokines and chemokines, which was more potent than dexamethasone alone. Otherwise, DBDx exerted similar inhibitory effects on cytokine profiles in bronchoalveolar lavage fluid. Histopathological observation showed that DBDx significantly reduced the LPS-induced thickening of alveolar septum, indicating its suppression of capillary congestion, edema and neutrophil infiltration in the lung. Ultra-structure analysis showed that DBDx suppressed the LPS-induced morphological changes of microvilli in type II pneumocytes. In vitro experiment showed that DBDx inhibited IL-6 and TNF-α secretion in THP-1 cells, and downregulated TLR4/NF-κB/HIF-1α signaling pathway. All of these results demonstrate that DBDx, a triple combination of clinical orally-administered drugs, can alleviate cytokine storm and related lung injury. DBDx is beneficial for treating cytokine storm disorders.