TNF-α Concentrations Research Articles

Observation of clinical efficacy of acupuncture combined with bloodletting therapy and Qingwen Xiere decoction in mild to moderate COVID-19 patients.

To evaluate the clinical efficacy and safety of acupuncture combined with bloodletting therapy and Qingwen Xiere decoction in mild to moderate COVID-19 patients. A total of 100 mild to moderate COVID-19 patients collected from December 2022 to February 2023 were randomly divided into control and observation groups, with 50 patients in each group. Patients in the control group received oral Qingwen Xiere decoction for 6 days. The observation group received acupuncture combined with bloodletting therapy in addition to oral Qingwen Xiere decoction, with the acupuncture (at Kongzui ［LU6］, Hegu ［LI4］, Quchi ［LI11］, Feishu ［BL13］, Zhongwan ［CV12］, Qihai ［CV6］, Yinlingquan ［SP9］) administered 30 min each day for 6 days, and bloodletting (at Shaoshang ［LU11］, Shangyang ［LI1］, Dazhui ［GV14］) administered every other day for 3 times. Traditional Chinese medicine syndrome scores and pulmonary CT scores were recorded before and after treatment. Serum contents of C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) were measured using ELISA. Anxiety and depression degree were assessed using the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA). Safety of the treatments was evaluated in both groups. Compared with before treatment, after treatment, the control group showed improvement in fever, dry cough, sore throat, and total traditional Chinese medicine syndrome scores (P<0.01), but no significant improvement in muscle pain or fatigue；the observation group showed significant improvement in total traditional Chinese medicine syndrome and individual symptoms scores (P<0.01)；both groups demonstrated reductions in pulmonary CT scores, HAMA score, HAMD score and serum contents of CRP and IL-6 (P<0.01)；serum TNF-α content significantly decreased in the observation group (P<0.01). All outcome measures were superior in the observation group to the control group (P<0.01, P<0.05). No adverse reactions were reported in either group. Acupuncture combined with bloodletting therapy and oral Qingwen Xiere decoction effectively improves clinical symptoms, alleviates pulmonary inflammatory injury, reduces inflammatory cytokine contents, and mitigates anxiety and depression in mild to moderate COVID-19 patients, and without adverse effects.

Uncovering the mechanisms of Zhubi decoction against rheumatoid arthritis through an integrated study of network pharmacology, metabolomics, and intestinal flora

Ethnopharmacological relevanceZhubi Decoction (ZBD) is a modified formulation derived from the classic traditional Chinese medicine prescription “Er-Xian Decoction” documented in the esteemed “Clinical Manual of Chinese Medical Prescription”. While the utilization of ZBD has exhibited promising clinical outcomes in treating rheumatoid arthritis (RA), the precise bioactive chemical constituents and the underlying mechanisms involved in its therapeutic efficacy remain to be comprehensively determined. Aim of the studyThis study aims to systematically examine ZBD's pharmacological effects and molecular mechanisms for RA alleviation. Materials and methodsUtilizing the collagen-induced arthritis (CIA) rat model, we comprehensively evaluated the anti-rheumatoid arthritis effects of ZBD in vivo through various indices, such as paw edema, arthritis index, ankle diameter, inflammatory cytokine levels, pathological conditions, and micro-CT analysis. The UPLC-MS/MS technique was utilized to analyze the compounds of ZBD. The potential therapeutic targets and signaling pathways of ZBD in the management of RA were predicted using network pharmacology. To analyze comprehensive metabolic profiles and identify underlying metabolic pathways, we conducted a serum-based widely targeted metabolomics analysis utilizing LC-MS technology. Key targets and predicted pathways were further validated using immunofluorescent staining, which integrated findings from serum metabolomics and network pharmacology analysis. Additionally, we analyzed the gut microbiota composition in rats employing 16 S rDNA sequencing and investigated the effects of ZBD on the microbiota of CIA rats through bioinformatics and statistical methods. ResultsZBD exhibited remarkable efficacy in alleviating RA symptoms in CIA rats without notable side effects. This included reduced paw redness and swelling, minimized joint damage, improved the histopathology of cartilage and synovium, mitigated the inflammatory state, and lowered serum concentrations of cytokines TNF-α, IL-1β and IL-6. Notably, the effectiveness of ZBD was comparable to MTX. Network pharmacology analysis revealed inflammation and immunity-related signaling pathways, such as PI3K/AKT, MAPK, IL-17, and TNF signaling pathways, as vital mediators in the effectual mechanisms of ZBD. Immunofluorescence analysis validated ZBD's ability to inhibit PI3K/AKT pathway proteins. Serum metabolomics studies revealed that ZBD modulates 170 differential metabolites, partially restored disrupted metabolic profiles in CIA rats. With a notable impact on amino acids and their metabolites, and lipids and lipid-like molecules. Integrated analysis of metabolomics and network pharmacology identified 6 pivotal metabolite pathways and 3 crucial targets: PTGS2, GSTP1, and ALDH2. Additionally, 16 S rDNA sequencing illuminated that ZBD mitigated gut microbiota dysbiosis in the CIA group, highlighting key genera such as Ligilactobacillus, Prevotella_9, unclassified_Bacilli, and unclassified_rumen_bacterium_JW32. Correlation analysis disclosed a significant link between 47 distinct metabolites and specific bacterial species. ConclusionZBD is a safe and efficacious TCM formulation, demonstrates efficacy in treating RA through its multi-component, multi-target, and multi-pathway mechanisms. The regulation of inflammation and immunity-related signaling pathways constitutes a crucial mechanism of ZBD's efficacy. Furthermore, ZBD modulates host metabolism and intestinal flora. The integrated analysis presents experimental evidence of ZBD for the management of RA.

Vincamine exerts hepato-protective activity during colon ligation puncture-induced sepsis by modulating oxidative stress, apoptosis, and TNFα/Nrf-2/Keap-1 signaling pathways

Sepsis is a pathological and biochemical disorder induced by numerous infections, leading to critical illness and a high mortality rate worldwide. Vincamine is an indole alkaloid compound obtained from the leaves of Vinca minor. The present study aims to investigate the hepato-protective activity of vincamine during colon ligation puncture (CLP)-induced sepsis at the molecular level. Sepsis was induced using the CLP model. Liver function enzymes such as ALT and AST were analyzed. The hepatic antioxidant status (SOD and GSH), lipid peroxidation (MDA), the pro-inflammatory cytokines (TNFα, IL-6, and IL-1β), bax, bcl2, and cleaved caspase 3 proteins were estimated. Nrf-2 and Keap-1 protein expression was evaluated using western blotting. Histopathological investigation of liver tissues was also performed. CLP-induced sepsis led to liver injury through the elevation of ALT and AST liver enzymes. Oxidative stress was initiated during CLP via the suppression of hepatic GSH content and SOD activity and the elevation of MDA. The inflammatory condition was activated by the upregulation of TNFα, IL-6, IL-1β, and Keap-1 and the downregulation of Nrf-2 proteins. The apoptosis was initiated through the activation of bax and cleaved caspase 3 protein expression and inhibition of bcl2 protein expression. However, vincamine significantly improved the hepatic histological abnormalities and decreased liver enzymes (ALT and AST). It ameliorated oxidative stress, as evidenced by reducing the hepatic MDA content and increasing the SOD activity and GSH content. Moreover, vincamine reduced the hepatic content of TNFα, IL-6, IL-1β, and Keap-1 and increased Nrf-2 protein expression. Additionally, it upregulated bcl2 protein expression and downregulated bax and cleaved caspase 3 protein expression. Vincamine exhibited hepato-protective potential during CLP-induced sepsis via the cross-connection of antioxidant, anti-inflammatory, and anti-apoptotic activities by modulating TNFα/IL-6/IL-1β/Nrf-2/Keap-1 and regulating bax/bcl2/cleaved caspase 3 signaling pathways.

TNFα-Induced Inflammation Model-Evaluation of Concentration and Passage-Dependent Effects on Bovine Chondrocytes.

Inflammation models are widely used in the in vitro investigation of new therapeutic approaches for osteoarthritis. TNFα (tumor necrosis factor alpha) plays an important role in the inflammatory process. Current inflammation models lack uniformity and make comparisons difficult. Therefore, this study aimed to systematically investigate whether the effects of TNFα are concentration-dependent and whether chondrocyte expansion has an effect on the inflammatory model. Bovine chondrocytes were enzymatically isolated, expanded to passages 1-3, and transferred into a 3D pellet culture. Chondrocyte pellets were stimulated with recombinant bovine TNFα at different concentrations for 48 h to induce inflammation. Gene expression of anabolic (collagen 2, aggrecan, cartilage oligomeric protein (COMP)), catabolic (matrix metalloproteinases (MMP3, MMP13)), dedifferentiation (collagen 1) markers, inflammation markers (interleukin-6 (IL-6), nuclear factor kappa B (NFkB), cyclooxygenase-2 (COX), prostaglandin-E-synthase-2 (PTGES2)), and the apoptosis marker caspase 3 was determined. At the protein level, concentrations of IL-6, nitric oxide (NO), and sulfated glycosaminoglycans (GAG) were evaluated. Statistical analysis was performed using the independent t-test, and significance was defined as p < 0.05. In general, TNFα caused a decrease in anabolic markers and an increase in the expression of catabolic and inflammatory markers. There was a concentration-dependent threshold of 10 ng/mL to induce significant inflammatory effects. Most of the markers analyzed showed TNFα concentration-dependent effects (COMP, PRG4, AGN, Col1, MMP3, and NFkB). There was a statistical influence of selected gene expression markers from different passages on the TNFα chondrocyte inflammation model, including Col2, MMP13, IL-6, NFkB, COX2, and PTGES2. Considering the expression of collagen 2 and MMP3, passage 3 chondrocytes showed a higher sensitivity to TNFα stimulation compared to passages 1 and 2. On the other hand, MMP13, IL-6, NFkB, and caspase 3 gene expression were lower in P3 chondrocytes compared to the other passages. On the protein level, inflammatory effects showed a similar pattern, with cytokine effects starting at 10 ng/mL and differences between the passages. TNFα had a detrimental effect on cartilage, with a clear threshold observed at 10 ng/mL. Although TNFα effects showed concentration-dependent patterns, this was not consistent for all markers. The selected passage showed a clear influence, especially on inflammation markers. Further experiments were warranted to explore the effects of TNFα concentration and passage in long-term stimulation.

Kai Yu Zhong Yu recipe mitigates stress-induced accelerated follicle loss in mice by regulating the interplay between apoptosis and autophagy via the SIRT1/FOXO1/3 pathway

BackgroundPsychological stress-related infertility is often attributed to a decline in both the quality and quantity of oocytes. Kai Yu Zhong Yu (KYZY) recipe, a classic herbal formula in Traditional Chinese Medicine (TCM), has been employed for centuries to address stress-related infertility. Our previous studies have demonstrated its effectiveness in counteracting the reduction in oocyte competence induced by psychological stress. PurposeTo investigate the mechanism by which KYZY mitigates the adverse effects of stress. MethodsFemale ICR mice were randomly assigned to one of five groups: control, CUMS, KYZY-H, KYZY-M, and KYZY-L. Except for the control group, the other groups underwent a six-week Chronic Unpredictable Mild Stress (CUMS) procedure. Following CUMS, the three KYZY groups were received high (38.2 g kg-1), medium (19.1 g kg-1), and low (9.6 g kg-1) doses of the KYZY recipe intragastrically for four weeks. Additionally, RNA interference was used to reduce Sirt1 expression in the ovary to assess the involvement of the SIRT1 pathway. ELISA, HE staining, follicle counting, TUNEL staining, and Western blot were conducted to explore the mechanism of KYZY in treatment of stress-related infertility. ResultsKYZY treatment significantly reduced concentrations of IL-6, IL-1β and TNF-α, reversed the loss of small follicles, and alleviated follicular apoptosis and autophagy. KYZY also elevated SIRT1/FOXO1/3 activity, reduced BAX expression, increased BCL-2 expression, and restored Beclin-1-dependent autophagy. Sirt1 silencing downregulated the activity of the SIRT1/FOXO1/3 pathway and triggered Caspase-3-mediated cleavage of Beclin-1 in mouse ovary. Conversely, Sirt1 silencing nullified the effect of KYZY recipe on inflammation and the regulation of apoptosis and autophagy. ConclusionKYZY enhances SIRT1/FOXO1/3 pathway activity, shifting the balance from apoptosis towards autophagy to safeguard oocyte capacity against the effects of psychological stress.

Effects of parecoxib sodium on early cognitive impairment and inflammation levels in burned rats.

To study the effect of parecoxib sodium in alleviating inflammation in burned rats and restoring cognitive function in burned rats. 30 SPF grade SD rats were randomly divided into 6 groups: (1) Blank control group (Group C). (2) Sham surgery group (Group Sham). (3) Second-degree burn model (Group B). (4) Low-dose (1mg/kg/d) parecoxib sodium (Group L+B). (5) Medium-dose (10mg/kg/d) parecoxib sodium (Group M+B). (6) High-dose (20mg/kg/d) parecoxib sodium (Group H+B). ELISA measures inflammatory factor IL-2, IL-6, TNF-α and IFN-γ, cognitive function factor NSE, cortisol and S-100β. Combined with water maze and dark avoidance experiments to further verify the recovery of cognitive function in rats. The contents of IL-2, TNF-α and IL-6 in Group M+B were significantly lower than those in Group Sham (P<0.05), and the content of IFN-γ was significantly lower than that in Group Sham (P<0.05). The cognitive markers NSE, S-100β and cortisol levels in Group M+B were significantly higher than those in Group Sham at 2h, 1d, 5d and 10d after operation (P<0.05). In the Group M+B dark-avoidance experiment, the number of probes and errors were not significantly different than those in Group Sham and Group C (P>0.05), and the number of times Group M+B found a platform in the water maze experiment and crossed the platform was second only to Group B and Group C. Parecoxib sodium can effectively reduce inflammation in burn rats and promote cognitive recovery in burn rats, and the optimal dose of parecoxib sodium for burn rats is 10mg/kg.

NDRG2 Deficiency Exacerbates UVB-Induced Skin Inflammation and Oxidative Stress Damage.

UVB radiation induces inflammatory and oxidative stress responses, contributing to skin damage, yet the underlying mechanisms are not fully understood. N-Myc downstream-regulated gene 2 (NDRG2), an emerging stress-associated gene, remains unexplored in UVB-induced skin injury. In this study, we detected skin NDRG2 expression after UVB irradiation for the first time and further used Ndrg2 knockout mice to clarify the role of NDRG2 in UVB-induced skin injury. Three-month-old male Ndrg2+/+ and Ndrg2-/- mice (16-18g) were exposed to UVB to induce acute skin damage, and then dorsal skin samples were collected for subsequent analyses. UVB-induced skin damage was scored. Western Blot Analysis, immunofluorescence (IF) double labeling, and immunohistochemistry (IHC) were employed to assess NDRG2 expression and/or distribution. The concentrations of TNF-α, IL-6, IL-1β, MPO, MMP8, superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH) were quantitatively assessed using enzyme-linked immunosorbent assay (ELISA). Hematoxylin and eosin (HE) staining were employed to determine pathological changes. RNA sequencing and analysis were performed to estimate transcript expression levels and analyze mRNA expression. DESeq2 software was employed to identify differentially expressed genes (DEGs). DEGs were visualized using volcanic and heat maps. Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed to identify primary biological functions, metabolic pathways, or signal transduction pathways associated with DEGs. UVB-challenged Ndrg2-/- mice exhibited significantly exacerbated skin damage (erythema, edema, and erosion), neutrophil infiltration, and apoptosis compared to Ndrg2+/+ mice. Furthermore, UVB-challenged Ndrg2-/- mice displayed significantly elevated pro-inflammatory cytokines, myeloperoxidase (MPO), matrix metalloproteinase-8 (MMP8), and reduced antioxidant expression. RNA sequencing identified 1091 significantly differentially expressed genes enriched in inflammation, immune response, and oxidative stress pathways. In conclusion, the deficiency of Ndrg2 markedly exacerbated UVB-induced skin damage by promoting inflammatory responses and inhibiting antioxidant responses. This suggests that stabilizing NDRG2 expression holds promise as a therapeutic strategy for protecting against UVB-induced skin damage.

Effect of Saccharomyces boulardii on Liver Diseases: A Systematic Review.

We aimed to systematize the results of published studies on the use of Saccharomyces boulardii (SB) for the treatment of various liver disorders (CRD42022378050). Searches were conducted using PubMed and Scopus on 1 August 2022. The PubMed search was updated on 15 June 2024. The review included sixteen studies: ten experimental animal studies (EASs) and six randomized controlled trials (RCTs). The CNCM I-745 strain was used in 68.8% of the included studies. SB reduced the severity of many manifestations of cirrhosis, and lowered the Child-Pugh scores in RCT. SB reduced the serum concentrations of TNF-α, IL-1β, IL-6, and IL-4 in animals with metabolic dysfunction-associated steatotic liver disease (MASLD); lowered the serum TNF-α and IL-6 levels in experimental cirrhosis in rats; and reduced the CRP levels in decompensated cirrhosis. The EAS of MASLD revealed that SB reduced liver steatosis and inflammation and lowered the liver expression of genes of TNF-α, IL-1β, interferon-γ, and IL-10. In studies on experimental cirrhosis and MASLD, SB reduced the liver expression of genes of TGF-β, α-SMA, and collagen as well as liver fibrosis. SB reduced the abundance of Escherichia (Proteobacteria), increased the abundance of Bacteroidetes in the gut microbiota, prevented an increase in intestinal barrier permeability, and reduced bacterial translocation and endotoxemia.

Reduced plasma interleukin-6 concentration after transcranial direct current stimulation to the prefrontal cortex

ObjectivesTranscranial direct stimulation (tDCS) targeted to the dorsolateral prefrontal cortex (DLPFC) reduces food intake and hunger, but its effects on circulating factors are unclear. We assessed the effect of repeated administration of tDCS to the left DLPFC (L-DLPFC) on concentrations of pro/anti-inflammatory and appetitive hormone concentrations. Materials and methodsTwenty-nine healthy adults with obesity (12 M; 42±11 y; BMI=39±8 kg/m2) received 3 consecutive inpatient sessions of either anodal or sham tDCS targeted to the L-DLPFC during a period of ad libitum food intake. Fasting plasma concentrations of IL-6, orexin, cortisol, TNF-α, IL-1β, ghrelin, PYY, and GLP-1 were measured before the initial and after the final tDCS sessions. ResultsIL-6 (β=-0.92 pg/ml p=0.03) decreased in the anodal group compared with sham, even after adjusting for kcal intake; there were no changes in other hormones. Mean kcal intake was associated with higher IL-1β and ghrelin concentrations after the ad libitum period (β=0.00018 pg/ml/kcal, p=0.03; β=0.00011 pg/ml/kcal, p=0.02; respectively), but not differ by intervention groups. ConclusionsIL-6 concentrations were reduced following anodal tDCS to the L-DLPFC independent of ad libitum intake. IL-6 concentrations reflect the inflammatory state of adiposity and may affect eating behavior and weight gain. These findings provide evidence of therapeutic benefit of tDCS.

Neuroprotective effects of Aframomum pruinosum seed extract against stroke in rat: Role of antioxidant and anti-inflammatory mechanisms

BackgroundStroke is a major cause of disability and neurological impairment worldwide. Effective prevention and management strategies are needed to reduce its burden. This study aimed to investigate the therapeutic effect of the seed ethanolic extract of Aframomum pruinosum (EEAP) on stroke and its related motor and cognitive deficits in rats. Materials and methodsStroke was induced by either middle cerebral artery occlusion (MCAO) or bilateral common carotid artery occlusion (BCCAO). In the MCAO model, rats received EEAP (75, 150, or 300 mg kg-1) or N-acetyl-L-cysteine (100 mg kg-1) orally for one week before 2 h of occlusion, followed by reperfusion. Twenty-four hours after ischemia, brain was collected for infarct size using 2, 3, 5 -TriphenylTetrazolium Chloride (TTC) staining, oxidative stress markers and inflammatory cytokines (TNF-α, IL-1β) measurements. In the BCCAO model, rats underwent occlusion for 30 min and received EEAP or quercetin (25 mg kg-1) for 7 days post-induction. Behavioral parameters were evaluated at the end of the treatment. Oxidative stress and inflammatory markers were measured in the cerebrum and cerebellum. ResultsMCAO caused significant brain infarction, and increased lipid peroxidation, TNF-α and IL-1β contents. EEAP, rich in nerolidol, prevented these changes in a dose-dependent manner. BCCAO impaired the neurological function, mobility, and muscle strength of rats. It also increased lipid peroxidation and inflammatory cytokines in the cerebellum. EEAP significantly ameliorated these impairments. ConclusionEEAP exerts preventive and curative neuroprotective effects against ischemic stroke and its associated motor impairments at least partially through its antioxidant and anti-inflammatory properties, and its nerolidol content.

Markers of systemic leukocyte activation for assessing acute and chronic systemic inflammation

The phenomenon of systemic leukocyte activation is a component of systemic inflammation (SI), known as the systemic inflammatory response (SIR). Currently, there are hundreds of molecular markers that can serve as criteria for systemic activation, including soluble receptor to IL-2 (sIL-2R) or CD25, β2-microglobulin, and eosinophil cationic protein (ECP). The objective of our study was to assess whether markers of systemic leukocyte activation can be used as criteria for acute and chronic systemic inflammation. Data from 121 patients with acute critical infectious conditions – intensive care patients with sepsis-2 (according to the 2001 consensus, without MODS) and sepsis-3 (2016 consensus, with MODS) – and 136 patients with non-infectious genesis (polytrauma with and without MODS) were analyzed to study acute SI. Additionally, data from 148 patients with immune-inflammatory rheumatic diseases were analyzed to study chronic SI. The reactivity level (RL) was calculated using the author’s method to assess the intensity of SIR. The development of SI was verified based on the measured concentrations of IL-6, IL-8, IL-10, TNFα, CRP, D-dimers, cortisol, myoglobin, and troponin I. Criteria for leukocyte activation phenomenon were sIL-2R 700 units/mL, β2-microglobulin 3000 ng/mL, and ECP 10 ng/mL. Based on the study results, TNFα, ECP, and β2-microglobulin were identified as the most stable indices for dividing groups with and without systemic vasculitis in both acute and chronic diseases. These indices indicate the typical character of systemic leukocyte activation and can be used to assess the intensity of the described phenomenon when integrated into the SI score. However, it is doubtful that these indices can be independently applied as criteria for the complex process of SI and even the SIR phenomenon. This is because the registration of threshold values for two criteria simultaneously during the acute process of SI was only observed in 40.2% of cases, and in chronic processes, it was only observed in 23.7%. These values were comparable to the group without acute SI. Additionally, all three additional criteria were only determined in acute SI in 20.5% of cases and in chronic SI in 3.4%.

Efficacy of pentoxifylline for the treatment of bipolar I/II patients with treatment-resistant depression: A proof-of-concept, randomized, double-blind, placebo-controlled trial

BackgroundImmune dysregulation can play a role in depression pathophysiology, and immunological antagonists can improve depressive symptoms in treatment-resistant bipolar depression (TRD) patients according to studies. ObjectiveTo evaluate the anti-depressant effects of the anti-inflammatory drug, pentoxifylline (PTX) in TRD bipolar I/II adult subjects. MethodsThis 12-week, randomized, double-blind, placebo-controlled, parallel-group trial of 60 participants was conducted at Hawler Psychiatric Hospital and Private Clinic in Erbil, Iraq. Participants were confirmed as being qualified for bipolar I/II depression based on DSM-5 criteria. Data were analyzed using modified intent-to-treat analysis. ResultsThere were no significant differences between the two groups in Hamilton Rating Scale for Depression-17 (HAM-D-17) scores (χ2=1.9, P =.48) or a significant time × treatment interaction (χ2=7.1, P=.54). Nevertheless, a significant effect of time was observed with both groups’ reduction in HAM-D-17 scores from the start to the endpoint (χ2= 2.11, P=.002). Besides, a significant time × treatment × CRP interaction was found (χ2=3.1, P=0.016), where there was more reduction in HAM-D-17 score in PTX-treated subjects with CRP> 7.1 mg/L. The response rate difference between PTX and the placebo group did not reach a significance level (χ2=0.84, p=0.43). Furthermore, serum concentrations of TNF-α, CRP, and IL-6 significantly reduced at week 12 in the PTX group (P=.007,.04, and <.001, respectively). ConclusionThe current proof of concept study found that in terms of overall anti-depressant effectiveness in bipolar patients with TRD, PTX is not superior to placebo. However, it may improve depressive mood in a subpopulation of subjects with a higher pretreatment inflammatory profile.

Structural characterization and immune activity evaluation of a polysaccharide from Lyophyllum Decastes

An innovative acidic hydrolysate fingerprinting workflow was proposed for the characterization of Lyophyllum Decastes polysaccharide (LDP) by ultra performance liquid chromatography-mass spectrometry (UPLC-MS). The crude polysaccharides were firstly separated and purified by using DE-52 column and the BRT GPC purification system, respectively. The molecular weight and monosaccharide content of homogeneous polysaccharides were ascertained by utilizing HPGPC and ion chromatography separately. Secondly, the linkage of LDP was identified by methylation analysis and 1D/2D NMR spectra. The UPLC-MS/MS was used to scan and identify the acidic hydrolysate products of LDP using the PGC column. The oligosaccharides were collected by chromatography and identified by mass spectrometry. Thirdly, the expression of IL-1β, IL-6, iNOS, TNF-α and IFNAR-I was measured in order to assess the immunological activity of LDP. Besides, the targeted receptors identification of polysaccharides was performed by screening the expression of TLRs family protein. The results showed that oligosaccharide fragments with different molecular weights can be obtained by partial hydrolysis, which further verified that the structures of LDP polysaccharides was a 1–6-linked β-glucan. Moreover, the LDP polysaccharide can up-regulate the content of IL-1β, IL-6, iNOS, TNF-α and IFNAR-I and plays an important immunoregulation role through TLRs family.

Association of Acute Systemic Inflammation with Patient-Centric Postoperative Pulmonary Complications After Elective Cardiac Surgery.

Postoperative pulmonary complications (PPCs) occur frequently after cardiac surgery. Absolute postoperative values of biomarkers of inflammation (interleukin [IL]-6, IL-8, and tumor necrosis factor-alpha [TNF-α]) and alveolar epithelial injury (soluble receptor for advanced glycation end-products [sRAGE]) have been associated with hypoxia and prolonged ventilation. However, relationships between these biomarkers and PPCs, contextualized to preoperative inflammation and perioperative lung injury risk factors, are uncertain. We aimed to determine associations between perioperative increases in biomarkers of inflammation and alveolar epithelial injury with a patient-centric PPC definition in adult cardiac surgical patients, accounting for the influence of intraoperative risk factors for lung injury. Adults undergoing elective cardiac surgery were eligible for this observational cohort study. Blood concentrations of IL-6, IL-8, TNF-α, and sRAGE were collected after anesthesia induction (baseline) and on postoperative day 1 (POD 1). The primary outcome was the occurrence of moderate or severe PPCs, graded using a validated scale, in POD 0 to 7. We estimated the association between POD 1 IL-6, IL-8, TNF-α, and sRAGE concentrations and moderate/severe PPC presence using separate logistic regression models for each biomarker, adjusted for baseline biomarker values and risk factors for postoperative lung injury (age, baseline PaO2/FiO2, left ventricle ejection fraction [LVEF], procedural type, cardiopulmonary bypass duration, and transfusions). Covariables were chosen based on relevance to lung injury and unadjusted between-group differences among patients with versus without PPCs. The secondary outcome was postoperative ventilation duration, which was log-transformed and analyzed using linear regression, adjusted using the same variables as the primary outcome. We enrolled 204 patients from 2016 to 2018. Biomarkers were analyzed in 2023 among 175 patients with complete data. In adjusted analyses, POD 1 IL-8 and IL-6 were significantly associated with moderate/severe PPCs. The odds ratio (OR) for developing a PPC for every 50 pg/mL increase in POD 1 IL-8 was 7.19 (95% confidence interval [CI], 2.13-28.53, P = .003) and 1.42 (95% CI, 1.13-1.93, P = .01) for every 50 pg/mL increase in POD 1 IL-6. In adjusted analyses, postoperative ventilation duration was significantly associated with POD 1 sRAGE; each 50 pg/mL increase in sRAGE was associated with a 25% (95% CI, 2%-52%, P = .03) multiplicative increase in hours of ventilation. TNF-α was not significantly associated with PPCs or ventilation duration. Acute systemic inflammation is significantly associated with PPCs after elective cardiac surgery in adults when taking into consideration preoperative inflammatory burden and perioperative factors that may influence postoperative lung injury.

Mediators of monocyte chemotaxis and matrix remodeling are associated with mortality and pulmonary fibroproliferation in patients with severe COVID-19.

Acute respiratory distress syndrome (ARDS) has a fibroproliferative phase that may be followed by pulmonary fibrosis. Pulmonary fibrosis following COVID-19 pneumonia has been described at autopsy and following lung transplantation. We hypothesized that protein mediators of tissue remodeling and monocyte chemotaxis are elevated in the plasma and endotracheal aspirates of critically ill patients with COVID-19 who subsequently develop features of pulmonary fibroproliferation. We enrolled COVID-19 patients admitted to the ICU with hypoxemic respiratory failure. (n = 195). Plasma was collected within 24h of ICU admission and at 7d. In mechanically ventilated patients, endotracheal aspirates (ETA) were collected. Protein concentrations were measured by immunoassay. We tested for associations between protein concentrations and respiratory outcomes using logistic regression adjusting for age, sex, treatment with steroids, and APACHE III score. In a subset of patients who had CT scans during hospitalization (n = 75), we tested for associations between protein concentrations and radiographic features of fibroproliferation. Among the entire cohort, plasma IL-6, TNF-α, CCL2, and Amphiregulin levels were significantly associated with in-hospital mortality. In addition, higher plasma concentrations of CCL2, IL-6, TNF-α, Amphiregulin, and CXCL12 were associated with fewer ventilator-free days. We identified 20/75 patients (26%) with features of fibroproliferation. Within 24h of ICU admission, no measured plasma proteins were associated with a fibroproliferative response. However, when measured 96h-128h after admission, Amphiregulin was elevated in those that developed fibroproliferation. ETAs were not correlated with plasma measurements and did not show any association with mortality, ventilator-free days (VFDs), or fibroproliferative response. This cohort study identifies proteins of tissue remodeling and monocyte recruitment are associated with in-hospital mortality, fewer VFDs, and radiographic fibroproliferative response. Measuring changes in these proteins over time may allow for early identification of patients with severe COVID-19 at risk for fibroproliferation.

Study of Plasma Biochemistry and Plasma Metabolomics Differences in Montbéliard and Holstein Backcross and Holstein Heifers.

Holstein cattle are the main breed of dairy cattle in China. However, given the high degree of purebred selection of Holstein cattle, Chinese dairy cattle are increasingly being characterized by poor disease resistance, poor quality, and declining fertility. In this study, using Montbéliard × Holstein cattle as females and Montbéliard bulls as males for backcross breeding, we sought to provide a reference for improving the quality and performance of Holstein cattle and enhancing the efficiency of dairy farming. On the basis of similar physiological status and age, we selected 24 Montbéliard and Holstein backcross heifers and 11 Holstein heifers fed the same formula for comparative analyses. Plasma samples collected for plasma biochemical index analyses revealed that the content of ALB and BUN in the Montbéliard and Holstein backcross heifers was 20.83% (31.62 g/L to 26.17 g/L) and 42.36% (6.89 mmol/L to 4.84 mmol/L) higher than in the Holsteins (p < 0.01). The ALB/GLB (0.90 to 0.60, p < 0.05) was significantly higher in Montbéliard and Holstein backcross heifers than in Holstein heifers. Similarly, the activity of CAT in the backcross heifers was 61.28% (4.29 U/mL to 2.66 U/mL) higher than that in the Holstein heifers (p < 0.05). Although the activity of GSH-Px in the backcross heifers also showed an increasing trend, the difference did not reach the level of statistical significance (p = 0.052). Compared with Holstein heifers, the concentrations of IgA, IgG, and IL-4 were elevated by 32.52% (24.90 μg/mL to 18.79 μg/mL, p < 0.01), 13.46% (234.32 μg/mL to 206.53 μg/mL, p < 0.01), and 14.59% (306.27 pg/mL to 267.28 pg/mL, p < 0.05), and the contents of IL-6 and TNF-α were decreased by 15.92% (215.71 pg/mL to 256.55 pg/mL, p < 0.01) and 32.17% (7.17 ng/mL to 10.57 ng/mL, p < 0.01) in the plasma of Montbéliard and Holstein backcross heifers. Among the experimental heifers, five animals from each of the two groups were selected for plasma metabolomic analysis based on untargeted liquid chromatography-mass spectrometry. A comparison of the differential metabolites between the two heifer breeds revealed an up-regulation of d-glucuronic acid, s-glutathionyl-l-cysteine, and oleic acid levels in the backcross cattle compared with those in the Holstein heifers. We speculate that changes in the levels of these metabolites may be associated with an enhancement of the anti-inflammatory, antioxidant, and immune systems in these backcross heifers. Collectively, our findings in this study indicate that compared with 12-month-old purebred Holstein heifers, Montbéliard and Holstein backcross heifers of the same age are characterized by higher antioxidant capacity and immunity.

Impact of different formulations of platelet lysate on proliferative and immune profile of equine mesenchymal stromal cells.

Platelet lysate (PL) is investigated as a potential replacement for fetal bovine serum (FBS) in cell culture. However, there is limited research on its impact on the immune profile of equine mesenchymal stromal cells (eMSCs). This study aimed to evaluate the effects of different PL formulations on the proliferative capacity, multipotentiality, and immune profile of equine adipose tissue-derived MSCs (eAD-MSCs). In vitro growth kinetics and trilineage differentiation of eAD-MSCs (n = 7) were assessed under three culture conditions: medium-concentration PL (MPL), high-concentration PL (HPL), and FBS as a control. The immune profile was evaluated by studying the expression of immunogenic receptors such as MHC I, MHC II, and immunomodulatory molecules IL-6, IL-10, and TNF-α, determined by gene expression, surface marker expression, and cytokine quantification. Both PL formulations, pooled from 5 donors, exhibited 3.3 and 6.5-fold higher platelet counts than baseline plasma for MPL and HPL, respectively. Higher concentrations of TGF-β and PDGF were found in both PL formulations compared to baseline. Furthermore, MPL and HPL subcultures demonstrated proliferative, clonogenic, and multipotent capacities similar to FBS. The immune profile of PL-cultured cells exhibited gene expression levels related to immunogenicity and immunomodulation similar to the reference condition, and the surface antigen presence of MHC II was also similar. However, HPL media exhibited higher IL-6, IL-10, and TNF-α concentrations in the culture supernatant. In conclusion, both PL media contained higher concentrations of growth factors compared to FBS, supporting the in vitro culture of eAD-MSCs with proliferative, clonogenic, and multipotent capacity similar to the reference medium. Nonetheless, PL usage led to a variation in the immunomodulatory cytokine microenvironment, with higher concentrations of IL-6, IL-10, and TNF-α in HPL media compared to MPL and FBS.

Very early and early nutrition in children with pancreatitis-A randomised trial.

The aim of our study was to assess the impact of the very early introduction of refeeding on the course of acute pancreatitis (AP) in children. Additionally, we evaluated the effect of nutrition on inflammatory markers, including cytokines. This prospective randomised study was conducted in three university hospitals in Poland. Patients, aged 1-18 years with AP, were randomised into two groups: A-refeeding within 24 h of hospital admission (very early), and B-refeeding at least 24 h after admission (early nutrition). The severity of AP was assessed after 48 h. The serum concentrations of four cytokines (tumour necrosis factor α [TNFα], interleukin-1β [IL-1β], interleukin-6 [IL-6] and interleukin-8 [IL-8]) and C-reactive protein, as well as the activity of amylase, lipase and aminotransferases, were measured during the first 3 days of hospitalisation. A total of 94 children were recruited to participate in the study. The statistical analysis included 75 patients with mild pancreatitis: 42-group A and 33-group B. The two groups did not differ in the length of hospitalisation (p = 0.22), AP symptoms or results of laboratory tests. Analysis of cytokine levels was conducted for 64 children: 38-group A and 26-group B. We did not find a difference in concentrations of the measured cytokines, except for IL-1β on the third day of hospitalisation (p = 0.01). The time of initiation of oral nutrition within 24 h (very early) or after 24 h (early) from the beginning of hospitalisation had no impact on the length of hospitalisation, concentrations of TNF-α, IL-1β, IL-6 and IL-8, activity of amylase and lipase or occurrence of symptoms in children with mild AP.

Aluminum-induced oxidative stress promotes changes in the structure of the gut microbiota and liver deficiency

As a low-toxicity metal, aluminum has garnered increasing attention in relation to its impact on the human body; however, the specific mechanism of action remains unclear. To bridge this knowledge gap and facilitate practical applications, this study took 8-week-old ICR mice as the research object to study the effects of dietary addition of aluminum potassium sulfate on intestinal flora structure and liver. As the concentration of aluminum increased, it inhibited mice weight growth rate and significantly altered the composition of white blood cells in their bloodstream. Histological examination revealed liver inflammation through HE staining sections. The oxidative stress markers MDA increased, GSH-PX and CAT decreased significantly. And liver function index MAO increased, TC and ALP decreased first and then increased. Moreover, there was a significant increase in pro-inflammatory factor TNF-α content. Further 16S rRNA sequencing analysis demonstrated substantial changes in both composition and structure of mouse intestinal microbiota induced by aluminum exposure; microbial phenotype prediction indicated that aluminum-induced oxidative stress promoted an increase in abundance of oxidation-resistant microbial types. Alterations in gut flora structure also influenced the liver via the gut-liver axis. These findings lay a foundation for further research on the regulation and interaction of aluminum on intestinal flora.

Inflammatory Biomarkers in Patients With Type 2 Diabetes Mellitus and Heart Failure With Preserved Ejection Faction.

To verify the relationship between gene polymorphisms of tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) with inflammation markers and codependent metabolic variables in patients with type 2 diabetes mellitus and chronic heart failure (CHF). This study included 154 patients (mean age, 69.1±3.2 years). The control group consisted of 47 patients with metabolic syndrome (MS) without CHF; the 2nd group included 56 patients with CHF with preserved ejection fraction (CHFpEF); and the 3rd group consisted of 51 patients with CHF with reduced ejection fraction (CHFrEF). The rs1800629 polymorphism of the TNF-α gene (TNF-α: G308A) was studied in real time by the polymerase chain reaction (PCR) method and the rs1800795 polymorphism of the IL-6 gene (IL-6: 174 G&gt;C) was studied by PCR with the electrophoretic detection. The frequencies of polymorphic alleles were compared with the clinical blood test results, plasma concentrations of C-reactive protein (CRP), TNF-α, leptin, and fibrinogen. Differences between the groups were determined using the F test. Relationships between individual studied parameters were identified using the regression analysis. In most patients, the occurrence of gene polymorphisms was eident as increased plasma concentrations of biomarkers. An association was found between the TNF-α gene polymorphism (G308A) and an increase in plasma TNF-α and between the IL-6 gene polymorphism (174 C&gt;G) and an increase in plasma CRP. In the CHFpEF group, the rs1800629 gene polymorphism was observed in 55% of patients, among whom 93% had increased TNF-α. The rs1800795 gene polymorphism was observed in 82% of CHFpEF patients, among whom 21% had increased CRP. In the CHFrEF group, the G308A transition in the TNF-α gene was observed in 53% of patients; an increase in the respective cytokine was noted in 67% of patients; the IL-6 gene polymorphism 174 C&gt;G was found in 78%, however, only 14% of patients with this polymorphism had also increased CRP. In the control group, the TNF-α G308A gene polymorphism was found in 30% of patients, while an increase in free TNF-α was associated with this polymorphism in 50% of patients; the IL-6 174 C&gt;G gene polymorphism was detected in 78%, while no increase in the CRP level was observed in this group. This demonstrates a high probability of the TNF-α G308A gene polymorphism occurrence in patients with CHF. Inflammatory markers are important predictors of CHF. The most significant predictor was the TNF-α G308A gene polymorphism, which was observed in more than 50% of patients, the majority of whom had an increase in plasma TNF-α.