Serum Tumor Necrosis Factor-α Research Articles

Cang-ai volatile oil alleviates nasal inflammation via Th1/Th2 cell imbalance regulation in a rat model of ovalbumin-induced allergic rhinitis

We previously revealed that Cang-ai volatile oil (CAVO) regulates T-cell activity, enhancing the immune response in people with chronic respiratory diseases. However, the effects of CAVO on allergic rhinitis (AR) have not been investigated. Herein, we established an ovalbumin (OVA)-induced AR rat model to determine these effects. Sprague–Dawley (SD) rats were exposed to OVA for 3 weeks. CAVO or loratadine (positive control) was given orally once daily for 2 weeks to OVA-exposed rats. Behavior modeling nasal allergies was observed. Nasal mucosa, serum, and spleen samples of AR rats were analyzed. CAVO treatment significantly reduced the number of nose rubs and sneezes, and ameliorated several hallmarks of nasal mucosa tissue remodeling: inflammation, eosinophilic infiltration, goblet cell metaplasia, and mast cell hyperplasia. CAVO administration markedly upregulated expressions of interferon-γ, interleukin (IL)-2, and IL-12, and downregulated expressions of serum tumor necrosis factor-α, IL-4, IL-5, IL-6, IL-13, immunoglobulin-E, and histamine. CAVO therapy also increased production of IFN-γ and T-helper type 1 (Th1)-specific T-box transcription factor (T-bet) of the cluster of differentiation-4+ T-cells in splenic lymphocytes, and protein and mRNA expressions of T-bet in nasal mucosa. In contrast, levels of the Th2 cytokine IL-4 and Th2-specific transcription factor GATA binding protein-3 were suppressed by CAVO. These cumulative findings demonstrate that CAVO therapy can alleviate AR by regulating the balance between Th1 and Th2 cells.

Amygdalin ameliorates alopecia areata on C3H/HeJ mice by inhibiting inflammation through JAK2/STAT3 pathway

BackgroundEvidence has demonstrated that Chinese medicine formula Xuefu Zhuyu decoction can markedly promote the formation of new hair in patients and mice with alopecia areata (AA). Amygdalin is one of the active components of Xuefu Zhuyu decoction, but its therapeutic effects and the underlying mechanisms on AA remains largely unrevealed. PurposeTherefore, this study aims to investigate the therapeutic effects and to probe its molecular mechanisms of inflammation and immune regulation on AA model of C3H/HeJ mice. Study designThe C3H/HeJ female mice were divided into control, AA, rusolitinib (60 mg/kg), and amygdalin groups (60, 90, and 120 mg/kg, 0.2 ml/10 g, i.g.). MethodsThe optical microscope was used to observe the feature of the local skin, and the number of lanugo and terminal hair. H&E staining was performed to determine the degree of pathological damage to the skin. ELISA was performed to detect levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in mice serum. Flow cytometry was carried out to analyze the CD4+CD25+FOXP3+, CD4+ and CD8+ of skin tissue. And the levels of CD4+ and CD8+, p-JAK/JAK2, p-STAT3/STAT, and SOCS3 were detected by immunohistochemistry. Western blot and qRT-PCR were employed to examine the expression levels of IL-6, TNF-α, IFN-γ, JAK2, p-JAK, STAT, p-STAT3 and SOCS3 proteins and genes in skin tissues. ResultsCompared with AA group, amygdalin immensely increased the number of vellus hairs and decreased the number of terminal hairs determined by skin microscopy and H&E staining. ELISA, Western blot and qRT-PCR data showed that the levels of IL-6, TNF-α and IFN-γ in serum and skin tissues of AA mice were significantly increased, while amygdalin administration dramatically restrained the contents of the three pro-inflammatory factors. Flow cytometry and immunohistochemistry hinted that amygdalin observably enhanced the number of CD4+CD25+FOXP3+ and CD4+ cells, while inhibited the number of CD8+ positive cells in mice with AA. Moreover, amygdalin signally reduced JAK2/STAT3 pathway-related protein and gene levels in AA mice. ConclusionAmygdalin could inhibit inflammatory response and improve immune function in the treatment of AA. The underlying molecular mechanism may be related to inhibition of JAK2/STAT3 pathway.

Effects of Dietary Callicarpa nudiflora Aqueous Extract Supplementation on Growth Performance, Growth Hormone, Antioxidant and Immune Function, and Intestinal Health of Broilers.

C. nudiflora is notably rich in flavonoids and phenylethanoid glycosides, making it a significant natural source of antioxidants. We examined the effects of C. nudiflora aqueous extract (CNE) on growth performance, antioxidant function, immunity, intestinal barrier function, nutrient transporters, and microbiota of broilers. A total of 360 one-day-old broilers were randomly assigned to four treatment groups: a basal diet with 0 (control, CON), 300 mg/kg (CNEL), 500 mg/kg (CNEM), and 700 mg/kg (CNEH) CNE for 42 days. CNEL and CNEM groups quadratically increased body weight and average daily gain but decreased feed-to-gain ratios during the starter and whole phases. Regarding the immune response of broilers, CNE treatment linearly down-regulated jejunal myeloid differentiation factor 88 (MyD88) expression and interleukin-1β (IL-1β) and interferon-γ expression in the liver (d 21), while decreasing jejunal IL-1β expression and the concentration of serum tumor necrosis factor-α and interleukin-6 (d 42). The CNEM and CNEH groups had lower MyD88 and nuclear factor kappa B expression in the liver (d 21) compared to the CON group. Broilers in the CNEL and CNEM groups had higher spleen index and thymus index (d 21) and interleukin-10 expression from the liver and jejunal mucosa (d 42) than that in the CON group. For the antioxidant capacity of broilers, CNE treatment linearly decreased the content of malonaldehyde and increased the activity of total antioxidant capacity in serum (d 42). CNEM and CNEH groups linearly increased the activity of superoxide dismutase in serum and heme oxygenase-1 expression in the liver, while increasing the activity of glutathione peroxidase in serum, jejunal nuclear factor E2-related factor 2 expression, and NAD(P)H quinone oxidoreductase 1 expression in the liver (d 42). As for the growth hormone of broilers, CNEM group increased the level of serum insulin-like growth factor 1 and up-regulated jejunal glucagon-like peptide 2 (GLP-2) expression (d 21). Broilers in the CNEM and CNEH groups had higher jejunal GLP-2 expression and growth hormone (GH) expression in the liver and the level of serum GH (d 42) than that in the CON group. Additionally, the villus height and jejunal Occludin and Claudin-1 expression in the CNEM group increased. CNE-containing diets resulted in a linear increase in the expression of jejunal zonula occluden-1 (d 21), villus height to crypt depth ratio, jejunal Occludin, excitatory amino acid transporters-3, and peptide-transporter 1 (d 42). The regulation of Oscillospira, Ruminococcaceae_Ruminococcus, and Butyricicoccus genera indicated that CNEH altered the composition of the cecal microbiota. In general, supplementing broilers with C. nudiflora aqueous extract could boost hormones, immune and antioxidant function, and gut health, improving their growth performance. Hence, CNE was a promising poultry feed additive, with 500 mg/kg appearing to be the optimal dose.

The Effect of Different Anesthesia Depths on Postoperative Cognitive Function of Tumor Patients Monitored by Narcotrend

Abstract Objectives The study aimed to examine the influence of different anesthesia depths monitored by Narcotrend on postoperative cognitive dysfunction (POCD) in elderly patients undergoing radical resection of gastrointestinal malignancies. Methods Individuals in the control group (n = 40) maintained the Narcotrend index (NTI) at 50 to 59 monitored by Narcotrend, whereas the experimental group at 30 to 39. The mini-mental state examination (MMSE) scale and serum S100β concentration were used to evaluate the cognitive function. Cerebral oxygen metabolism and inflammation were evaluated, presenting as regional oxygen saturations of brain (rSO2) and cerebral oxygen uptake rate (CERO2), serum tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Results Experimental group presented prominently high levels of rSO2 and low levels of CERO2 relative to controls, meanwhile with reduced serum TNF-α and IL-6. Individuals receiving deep anesthesia owned low levels of S100β and enhanced MMSE score, which showed negative correlation. Low incidence rate of POCD was detected in the experimental group. Both age (hazard ratio = 5.219, 95% confidence interval = 1.813–15.025) and NTI score (hazard ratio = 3.707, 95% confidence interval = 1.292–10.633) were independent influence factors for the onset of POCD. Conclusion NTI maintained at 30 to 39 can reduce the incidence of POCD in the early postoperative period for elderly patients receiving gastrointestinal tumors surgery, the contribution might be attributed to the improvement of perioperative cerebral oxygen metabolism and inflammatory stress response.

Mechanism of Bacillus coagulans T242 in prevention of Salmonella infection in mice

Salmonella is recognized as an important foodborne pathogen, which seriously threatens human safety. Bacillus coagulans T242 (T242) could prevent the growth of Salmonella and alleviate Salmonella infection in Caco-2 cells in vitro. The main objective of this study was to investigate the mechanism of action of T242 in preventing Salmonella infection in mice. Both T242 vegetative cells and spore prevention groups could reduce the bacterial loads in the ileum, liver and spleen of Salmonella typhimurium (S. typhi) SL1344 infected mice, and reduce the levels of Interleukin-10 (IL-10) and tumor necrosis factor-α (TNF-α) in serum and also increase the expression of Interleukin-1β (IL-1β) in serum, Monocyte chemoattractant protein-1 (MCP-1) and Inducible nitric oxide synthase (iNOS) in the liver, Interleukin-22 (IL-22) and Interleukin-23 (IL-23) in the ileum, and tight junction proteins (Claudin-1, Occludin and ZO-1) in the colon, and regulate intestinal flora. Pretreatment of T242 spores could downregulate the relative abundance of Desulfovibrionaceae in Salmonella infected mice. The relative abundance of Ruminococcus in Salmonella-infected mice was down-regulated by T242 vegetative cells preconditioning. The results showed that T242 prevented the systemic spread of Salmonella by regulating intestinal flora and enhancing intestinal barrier function against Salmonella invasion, inducing anti-inflammatory effects and regulating immune responses. T242 had great potential in controlling the epidemic of foodborne pathogens and was expected to be an effective alternative to antibiotic therapy, which is of great significance for the control and defense of Salmonella infection.

Effects of Rhodiola rosea injection on intrapulmonary shunt and blood IL-6 and TNF-α levels during single lung ventilation in patients undergoing radical resection of esophageal cancer

To explore the effects of Rhodiola rosea injection on pulmonary shunt and serum interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels during single lung ventilation in patients undergoing radical resection of esophageal cancer. Forty-six patients undergoing radical operation for esophageal cancer were randomized equally into control group and Rhodiola rosea injection group. In the Rhodiola group, 10 mL of Rhodiola rosea injection was added into 250 mL of normal saline or 5% glucose solution for slow intravenous infusion, and normal saline of the same volume was used in the control group after the patients entered the operation room. At T0, T1 and T3, PaO2 of the patient was recorded and 2 mL of deep venous blood was collected for determination of serum TNF-α and IL-6 levels. The incidence of postoperative atelectasis of the patients was recorded. Compared with those in the control group, the patients receiving Rhodiola rosea injection had significantly higher PaO2 and Qs/Qt at T1 and T2 (P<0.05) and lower serum IL-6 and TNF-α levels at T3 (P<0.05). No significant difference in the incidence of postoperative atelectasis was observed between the two groups (P>0.05). Rhodiola rosea injection before anesthesia induction can reduce intrapulmonary shunt during single lung ventilation, improve oxygenation, reduce serum IL-6 and TNF-α levels, and alleviate intraoperative lung injury in patients undergoing radical resection of esophageal cancer.

Significant improvements in the olfactory sensitivity of bipolar I disorder patients during euthymia versus manic episodes: a longitudinal study.

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. 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 TNF-α, 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. 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). 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.

Inflammation and Connexin 43 profiles in the prefrontal cortex are relevant to stress susceptibility and resilience in mice

Depression is a major chronic mental illness worldwide, characterized by anhedonia and pessimism. Exposed to the same stressful stimuli, some people behave normally, while others exhibit negative behaviors and psychology. The exact molecular mechanisms linking stress-induced depressive susceptibility and resilience remain unclear. Connexin 43 (Cx43) forms gap junction channels between the astrocytes, acting as a crucial role in the pathogenesis of depression. Cx43 dysfunction could lead to depressive behaviors, and depression down-regulates the expression of Cx43 in the prefrontal cortex (PFC). Besides, accumulating evidence indicates that inflammation is one of the most common pathological features of the central nervous system dysfunction. However, the roles of Cx43 and peripheral inflammation in stress-susceptible and stress-resilient individuals have rarely been investigated. Thus, animals were classified into the chronic unpredictable stress (CUS)-susceptible group and the CUS-resilient group based on the performance of behavioral tests following the CUS protocol in this study. The protein expression of Cx43 in the PFC, the Cx43 functional changes in the PFC, and the expression levels including interleukin (IL)-1β, tumor necrosis factor-α, IL-6, IL-2, IL-10, and IL-18 in the peripheral serum were detected. Here, we found that stress exposure triggered a significant reduction in Cx43 protein expression in the CUS-susceptible mice but not in the CUS-resilient mice accompanied by various Cx43 phosphorylation expression and the changes of inflammatory signals. Stress resilience is associated with Cx43 in the PFC and fluctuation in inflammatory signaling, showing that therapeutic targeting of these pathways might promote stress resilience.

Clinical efficacy of nano-hydroxyapatite combined with one-time root canal therapy in the treatment of pulpitis

This study investigates the clinical efficacy of nano-hydroxyapatite (nHA) combined with one-time root canal therapy in the treatment of pulpitis. A total of 92 patients diagnosed with pulpitis and treated at our hospital between September 2021 and November 2022 were selected and randomly designed into a control group filled with calcium hydroxide paste and gutta-percha (n = 46) or an observation group filled with nHA and gutta-percha (n = 46). We compare the cure rate, complication rate, and recurrence rate between the two groups. After treatment, the total effective rate of patients in the observation group was 96.70%, which was significantly higher than 86.00% in the control group. Additionally, the observation group demonstrated lower Visual Analog Scale and Oral Health Impact Profile-14 scores than those of the control group. After treatment, both groups showed reduced serum levels of various inflammatory factors compared to pretreatment values. However, the observation group displayed notably lower levels of serum tumor necrosis factor-α, interleukin-6, and high-sensitivity C-reactive protein compared to their baseline levels. Furthermore, the occlusal force, gingival sulcus bleeding index, and gingival index were significantly lower in the observation group when compared with those in the control group. The incidence of adverse reactions after 6 months of treatment was only 4.30% in the observation group, which was markedly lower than that observed in the control group (18.5%). In summary, we demonstrate the remarkable clinical efficacy of n-HA combined with one-time root canal therapy in the treatment of pulpitis, highlighting its significant potential for clinical application.

Association of left ventricular diastolic dysfunction with inflammatory activity, renal dysfunction, and liver-related mortality in patients with cirrhosis and ascites.

Left ventricular diastolic dysfunction (LVDD) is the predominant cardiac abnormality in cirrhosis. We investigated the association of LVDD with systemic inflammation and its impact on renal function, occurrence of hepatorenal syndrome (HRS) and survival in patients with cirrhosis and ascites. We prospectively enrolled 215 patients with cirrhosis and ascites. We evaluated the diagnosis and grading of LVDD by Doppler echocardiography, inflammatory markers, systemic hemodynamics, vasoactive factors, radioisotope-assessed renal function and blood flow, HRS development and liver-related mortality. LVDD was diagnosed in 142 (66%) patients [grade 2/3: n = 61 (43%)]. Serum lipopolysaccharide-binding protein (LBP), plasma renin activity (PRA) and glomerular filtration rate (GFR) were independently associated with the presence of grade 2/3 LVDD and the severity of diastolic dysfunction. Serum tumor necrosis factor-α, cardiac output and plasma noradrenaline were also independently associated with the presence of grade 2/3 LVDD. The diastolic function marker E/e' was strongly correlated with serum LBP (r = 0.731; P < 0.001), PRA (r = 0.714; P < 0.001) and GFR (r = -0.609; P < 0.001) among patients with LVDD. The 5-year risk of HRS development and death was significantly higher in patients with grade 2/3 LVDD compared to those with grade 1 (35.5 vs. 14.4%; P = 0.01 and 53.3 vs. 28.2%; P = 0.03, respectively). The occurrence and severity of LVDD in patients with cirrhosis and ascites is closely related to inflammatory activity. Advanced LVDD is associated with baseline circulatory and renal dysfunction, favoring HRS development, and increased mortality.

Rosemary leaf powder improves egg quality, antioxidant status, gut barrier function, and cecal microbiota and metabolites of late-phase laying hens

This study sought to determine the effects of rosemary leaf powder (RP) on laying performance, egg quality, serum indices, gut barrier function, and cecal microbiota and metabolites of late-phase laying hens. A total of 84 “Jing Tint 6” laying hens at 65-week old were randomly divided into 2 groups and fed either a basal diet (CON) or a basal diet supplemented with 0.3% RP. Our study revealed that RP improved the Haugh unit and decreased yolk n-6/n-3 polyunsaturated fatty acid (PUFA) ratio of laying hens, increased serum superoxide dismutase (SOD), jejunal activities of SOD and catalase (CAT), and jejunal zonula occludens-1 (ZO-1) expression, as well as decreased serum tumor necrosis factor-α (TNF-α) level and jejunal TNF-α mRNA expression. Rosemary leaf powder markedly enhanced (P < 0.05) cecal abundances of Rikenellaceae, Rikenellaceae_RC9_gut_group, and Turicibacter, tended to promote (P = 0.076) butyrate concentration, and reduced (P < 0.05) cecal abundances of Erysipelatoclostridiaceae, Sutterellaceae, Fusobacteriaceae, Campylobacteraceae, Sutterella, Campylobacter, and Fusobacterium, which were closely linked with Haugh unit, yolk n-6/n-3 PUFA ratio, serum SOD and TNF-α. In addition, RP altered the metabolic functions of cecal microbiota and enhanced the abundances of butyrate-synthesizing enzymes, including lysine 2,3-aminomutase, β-lysine 5,6-aminomutase, and 3-oxoacid CoA-transferase. Together, 0.3% RP has the potential to enhance egg quality by partially modulating serum antioxidant status, jejunal barrier function, and cecal microbiota structure and metabolites, indicating that RP could be considered a promising feed additive to promote the production performance of late-phase laying hens.

To evaluate the relationship of obstructive sleep apnea with chronic periodontitis and its association with coronary artery disease by assessing serum tumor necrosis factor-α

The periodontal tissue initiates an immune-inflammatory response against bacteria and their products at the site of periodontal infection, and systemic attack by these pathogens triggers an acute phase response that contributes to the systemic inflammatory burden. Obstructive sleep apnea (OSA) and periodontal diseases share many common risk factors and are therefore disorders associated with, and possibly related to, systemic inflammation.Objectives 1.) To evaluate the severity of infection-causing chronic periodontitis subjects leading to Coronary Artery Disease (CAD) risk.2.) To evaluate specific Inflammatory marker TNF-α in coronary artery disease (CAD) subjects with chronic periodontitis and obstructive sleep apnea.Methods A total of 5 ml of the venous blood was collected from each participant which was separated out by centrifugation at 3000 rpm for 5–10 min at room temperature for the estimation of inflammatory markers. Collected samples were labeled and stored at − 20 °C in a deep freezer. The estimation of human TNF-α (tumor necrosis factor-alpha) levels was determined using an ELISA kit based on the Sandwich-ELISA principle.Conclusion TNF-α may serve as important markers for the diagnosis of chronic periodontitis and obstructive sleep apnea and the prediction of the severity of cardiovascular diseases. Cardiovascular disease can be efficiently circumvented with a biomarker-based approach to treatment, which also benefits patients' quality of life.Results The result of our study showed that TNF-α is involved in the onset and progression of obstructive sleep apnea leading to coronary artery disease since the expression levels of TNF in the case group were considerably higher than those in the control group.

Mesencephalic astrocyte-derived neurotrophic factor ameliorates inflammatory response in polycystic ovary syndrome via inhibiting TLR4-NF-κB-NLRP3 pathway

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disorder in women of reproductive age, which often leads to female infertility. Chronic inflammation is a significant factor in the development of PCOS. Our study aimed to explore the impact of mesencephalic astrocyte-derived neurotrophic factor (MANF), a scientifically validated anti-inflammatory factor, on 99 diagnosed PCOS patients. We also investigated its effects on PCOS mice induced with dehydroepiandrosterone (DHEA) and KGN cells induced with dihydrotestosterone (DHT). Our findings revealed a decrease in serum MANF levels in PCOS patients, which were negatively associated with serum tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) levels. The administration of recombinant human MANF (rhMANF) in PCOS mice demonstrated a decrease in pro-inflammatory cytokines and monocytes/macrophages in both peripheral blood and ovarian tissues. Furthermore, the inclusion of rhMANF notably ameliorated DHEA-induced ovarian dysfunction and fibrosis by negatively regulating the toll-like receptor 4 (TLR4)-nuclear factor kappa B (NF-κB)-NLR family, pyrin domain containing protein 3 (NLRP3) pathway. Additionally, in vitro experiments showed that the up-regulation of MANF offset DHT-induced inhibition of viability and apoptosis in KGN cells. Collectively, this study highlights the anti-inflammatory properties of MANF in PCOS and suggests its potential as a therapeutic approach for the management of PCOS.

Benefits of heat-killed Lactobacillus acidophilus on growth performance, nutrient digestibility, antioxidant status, immunity, and cecal microbiota of rabbits.

Heat-killed probiotics, as a type of inactivated beneficial microorganisms, possess an extended shelf life and broader adaptability compared to their live counterparts. This study aimed to investigate the impact of heat-killed Lactobacillus acidophilus (L. acidophilus, LA) - a deactivated probiotic on the growth performance, digestibility, antioxidant status, immunity and cecal microbiota of rabbits. Two hundred weaned Hyla rabbits were randomly allocated into five equal groups (CON, L200, L400, L600, and L800). Over a 28-day period, the rabbits were fed basal diets supplemented with 0, 200, 400, 600, and 800 mg/kg of heat-killed LA, respectively. Results revealed a significant reduction in the feed-to-gain ratio (F/G) in the L600 and L800 groups (p < 0.05). Additionally, the L800 group exhibited significantly higher apparent digestibility of crude fiber (CF) and crude protein (CP) (p < 0.05). Regarding digestive enzyme activities, enhanced trypsin and fibrinase activities were observed in the L600 and L800 groups (p < 0.05). Concerning the regulation of the body's antioxidant status, the L800 group demonstrated elevated levels of superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) in both serum and ileal tissue (p < 0.05). In terms of immune capacity modulation, serum tumor necrosis factor-α (TNF-α) levels were significantly lower in the L600 and L800 groups (p < 0.05), while immunoglobulin A (IgA) and immunoglobulin M (IgM) levels were higher (p < 0.05). Additionally, the L800 group exhibited a substantial increase in secretory immunoglobulin A (SIgA) levels in the intestinal mucosa (p < 0.05). In comparison to the CON group, the L800 group exhibited a significant increase in the relative abundance of Phascolarctobacterium and Alistipes in the cecum (p < 0.05). Phascolarctobacterium demonstrated a positive correlation with SIgA (p < 0.05), IgM (p < 0.01), and Glutathione peroxidase (GSH-Px) (p < 0.05), while displaying a negative correlation with TNF-α levels (p < 0.05). Concurrently, Alistipes exhibited positive correlations with IgA (p < 0.05), IgM (p < 0.05), SIgA (p < 0.01), GSH-Px (p < 0.05), SOD (p < 0.05), and T-AOC (p < 0.01), and a negative correlation with TNF-α (p < 0.05). In conclusion, the dietary incorporation of 600 mg/kg and 800 mg/kg of heat-killed LA positively influenced the growth performance, nutrient digestibility, antioxidant status, immune capacity and cecal microbiota of rabbits. This highlights the potential benefits of utilizing heat-killed probiotics in animal nutrition.

Association between elevated serum matrix metalloproteinase-2 and tumor necrosis factor-α, and clinical symptoms in male patients with treatment-resistant and chronic medicated schizophrenia

BackgroundInflammation 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.MethodsThe 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.ResultsSerum 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).ConclusionThe results indicate the involvement of inflammation in the etiology of TRS and CMS. Further studies are warranted.

Correlation between the serum FABP4, ANGPTL3, and ANGPTL4 levels and coronary artery disease.

Lipid metabolism related factors, such as angiopoietin-like protein 3 (ANGPTL3), angiopoietin-like 4 (ANGPTL4), fatty acid-binding protein 4 (FABP4) are newly discovered factors that can affect coronary artery disease (CAD). In this study, we aimed to investigate the relationship between CAD and these lipid metabolism factors. ANGPTL3, ANGPTL4, and FABP4 may provide a new method for the control of CAD risk factors and the prevention and treatment of CAD. We enrolled 284 consecutive inpatients with suspected CAD and divided them into CAD and non-CAD groups based on the coronary angiography results. Serum ANGPTL3, ANGPTL4, FABP4, and tumor necrosis factor-α (TNF-α) levels were estimated using the enzyme-linked immunosorbent assay. Multivariate logistic regression was used to assess the risk factors for CAD. The receiver operating characteristic curve was used to determine the cutoff and diagnostic values. The serum TNF-α, FABP4, ANGPTL3, and ANGPTL4 values showed a significant difference between the CAD and non-CAD groups (p < .05). After adjusting for confounding factors, the FABP4, ANGPTL3, and ANGPTL4 levels were independently associated with CAD (p < .05). The ANGPTL3 expression level was an independent risk factor for CAD in patients with hypertension, but not in those without hypertension. The ANGPTL3 > 67.53 ng/mL, ANGPTL4 > 29.95 ng/mL, and FABP4 > 1421.25 ng/L combination had the highest diagnostic value for CAD. ANGPTL3, ANGPTL4, and FABP4 were identified as independent risk factors for CAD and have valuable clinical implications for the diagnosis and treatment of CAD.

Three Artemisia pollens trigger the onset of allergic rhinitis via TLR4/MyD88 signaling pathway.

The prevalence of allergic rhinitis is high, making it a relatively common chronic condition. Countless patients suffer from seasonal Allergic rhinitis (AR). The objective of this investigation is to examine the potential involvement of common pollen allergens in seasonal allergic rhinitis, and study the proposed mechanism of Toll-like receptor 4 (TLR4)/Myeloid differentiation primary response gene 88 (MyD88) signaling pathway in the induction of AR. A mouse AR model (sensitized group) was constructed with pollen extracts and ovalbumin(OVA) of Artemisia annua (An), Artemisia argyi (Ar) and Artemisia Sieversiana (Si), and thereafter, AR symptom score was performed. After successful modeling, mouse serum and nasal mucosa tissues were extracted for subsequent experiments. The expression levels of immunoglobulin E (IgE), Interleukin (IL)-4, IL-5, IL-13 and Tumor Necrosis Factor-α (TNF-α) in serum were detected using Enzyme-linked immunosorbent assay (ELISA); Hematoxylin-eosin (H&E) staining methods were used to observe the pathological changes of the nasal mucosal tissue; Utilizing immunohistochemistry (IHC) staining, the expression levels of TLR4, MyD88 and Nuclear factor kappa B (NF-κB) p65 in mouse nasal mucosa were quantified; The mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of sensitized mice were detected with Quantitative reverse transcription PCR (qRT-PCR) and Western Blot. Finally, the in vitro culture of Human nasal mucosal epithelial cells (HNEpC) cells was conducted, and cells were treated with 200µg/ml Artemisia annua pollen extractand OVA for 24h. Western Blot assay was used to detect the expression level of TLR4, MyD88 and NF-κB p65 proteins before and after HNEpC cells were treated with MyD88 inhibitor ST-2825. On the second day after AR stimulation, the mice showed obvious AR symptoms. H&E results showed that compared to the control group, the nasal mucosal tissue in the sensitized group was significantly more inflamed. Furthermore, ELISA assay showed increased expression levels of IgE, IL-4, IL-5, IL-13 and TNF-α in serum of mice induced by OVA and Artemisia annua pollen, Artemisia argyi pollen and Artemisia Sieversiana pollen than those of the control group. However, the expression level of IL-2 was lower than that of the control group (P < 0.05). Using Immunohistochemistry staining visually observed the expression levels of TLR4, MyD88 and NF-κB p65 in mouse nasal mucosa tissues and quantitatively analyzed. The expression levels of TLR4, MyD88 and NF-κB p65 in the sensitized group were higher than those in the control group, and the differences were statistically significant (P < 0.05). The results from qRT-PCR and Western Blot showed that the mRNA and protein expression levels of TLR4, MyD88 and NF-κB p65 in nasal mucosa of the sensitized group were significantly higher than those in the control group (P < 0.05). Finally, HNEpC cells were cultured in vitro and analyzed using Western Blot. The expression levels of TLR4, MyD88 and NF-κB p65 in OVA and An groups were significantly increased (P < 0.05). After ST-2825 treatment, TLR4 protein expression was significantly increased (P < 0.05) and MyD88 and NF-κB p65 protein expression were significantly decreased (P < 0.05). To sum up, the occurrence and development of AR induced by OVA and pollen of Artemisia annua, Artemisia argyi and Artemisia Sieversiana were related to TLR4/MyD88 signal pathway.

Effect of electroacupuncture on ventricular structure and function in rats with myocardial ischemia-reperfusion injury.

To observe the effect of electroacupuncture (EA) on changes of ventricular structure and function in rats with myocardial ischemia-reperfusion injury (MIRI), so as to explore its potential mechanisms underlying improvement of ventricular remodeling after MIRI. Forty male SD rats were randomly divided into 4 groups：sham operation group, model group, EA group and medication (sacubactril valsartan, LCZ696) group, with 10 rats in each group. The MIRI model was established by ligation of the left anterior descending coronary artery and reperfusion. EA (2 Hz/100 Hz, 2 mA) was applied to bilateral "Neiguan" (PC6) for 20 min, once every other day for 21 d. Rats of the medication group received gavage of LCZ696 (60 mg·kg-1·d-1). After the intervention, echocardiography was used to detect the ejection fraction (EF) and fractional shortening (FS) of the left ventricle, and the contents of serum tumor necrosis factor-α(TNF-α), vascular cell adhesion molecule-1(VCAM-1) and intercellular cell adhesion molecule-1(ICAM-1) were assayed by enzyme-linked immunosorbent assay. The pathological changes of myocardial tissue were observed after HE staining. The Masson staining was used to evaluate the myocardial collagen deposition and myocardial fibrosis. The mRNA expression levels of collagen Ⅰ and Ⅲ and connective tissue growth factor (CTGF) in the myocardial tissue were detected by quantitative real-time PCR, and the expression levels of IL-1β and IL-18 were detected by Western blot. In contrast to the sham operation group, the EF and FS levels of the left ventricle were ob-viously decreased (P<0.001), while the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, the expression levels of IL-1β and IL-18 were significantly increased (P<0.001, P<0.000 1, P<0.05, P<0.01) in the model group. Compared with the model group, the EF and FS levels were remarkably increased (P<0.01), whereas the contents of serum TNF-α, VCAM-1 and ICAM-1, the proportion of myocardial fibrosis area, the mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF, and the expression levels of IL-1β and IL-18 were significantly down-regulated (P<0.001, P<0.01, P<0.05) in both the medication and EA groups. No significant differences were found between the EA and medication groups in all the indexes mentioned above. EA can improve the left-ventricular fibrosis and function, delay or reverse ventricular remodeling in MIRI rats, which may be related to its functions in down-regulating myocardial inflammatory response and mRNA expression levels of myocardial collagen Ⅰ, collagen Ⅲ and CTGF.

Unacylated ghrelin attenuates acute liver injury and hyperlipidemia via its anti-inflammatory and anti-oxidative activities.

Liver injury and hyperlipidemia are major issues that have drawn more and more attention in recent years. The present study aimed to investigate the effects of unacylated ghrelin (UAG) on acute liver injury and hyperlipidemia in mice. UAG was injected intraperitoneally once a day for three days. Three hours after the last administration, acute liver injury was induced by intraperitoneal injection of carbon tetrachloride (CCl4), and acute hyperlipidemia was induced by intraperitoneal injection of poloxamer 407, respectively. Twenty-four hours later, samples were collected for serum biochemistry analysis, histopathological examination, and Western blotting. In acute liver injury mice, UAG significantly decreased liver index, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), reduced malondialdehyde (MDA) concentration and increased superoxide dismutase(SOD) in liver tissue. NF-kappa B (NF-κB) protein expression in the liver was down-regulated. In acute hyperlipidemia mice, UAG significantly decreased serum total cholesterol (TC), triglyceride (TG), ALT, and AST, as well as hepatic TG levels. Meanwhile, hepatic MDA decreased and SOD increased significantly. Moreover, UAG improved the pathological damage in the liver induced by CCl4 and poloxamer 407, respectively. Intraperitoneal injection of UAG exhibited hepatoprotective and lipid-lowering effects on acute liver injury and hyperlipidemia, which is attributed to its anti-inflammatory and anti-oxidant activities.

Hydrogen attenuates endothelial glycocalyx damage associated with partial cardiopulmonary bypass in rats.

Cardiopulmonary bypass (CPB) causes systemic inflammation and endothelial glycocalyx damage. Hydrogen has anti-oxidant and anti-inflammatory properties; therefore, we hypothesized that hydrogen would alleviate endothelial glycocalyx damage caused by CPB. Twenty-eight male Sprague-Dawley rats were randomly divided into four groups (n = 7 per group), as follows: sham, control, 2% hydrogen, and 4% hydrogen. The rats were subjected to 90 minutes of partial CPB followed by 120 minutes of observation. In the hydrogen groups, hydrogen was administered via the ventilator and artificial lung during CPB, and via the ventilator for 60 minutes after CPB. After observation, blood collection, lung extraction, and perfusion fixation were performed, and the heart, lung, and brain endothelial glycocalyx thickness was measured by electron microscopy. The serum syndecan-1 concentration, a glycocalyx component, in the 4% hydrogen group (5.7 ± 4.4 pg/mL) was lower than in the control (19.5 ± 6.6 pg/mL) and 2% hydrogen (19.8 ± 5.0 pg/mL) groups (P < 0.001 for each), but it was not significantly different from the sham group (6.2 ± 4.0 pg/mL, P = 0.999). The endothelial glycocalyces of the heart and lung in the 4% hydrogen group were thicker than in the control group. The 4% hydrogen group had lower inflammatory cytokine concentrations (interleukin-1β and tumor necrosis factor-α) in serum and lung tissue, as well as a lower serum malondialdehyde concentration, than the control group. The 2% hydrogen group showed no significant difference in the serum syndecan-1 concentration compared with the control group. However, non-significant decreases in serum and lung tissue inflammatory cytokine concentrations, as well as in serum malondialdehyde concentration, were observed. Administration of 4% hydrogen via artificial and autologous lungs attenuated endothelial glycocalyx damage caused by partial CPB in rats, which might be mediated by the anti-inflammatory and anti-oxidant properties of hydrogen.