Evaluation of SARS-CoV-2 interferon gamma release assay in BNT162b2 vaccinated healthcare workers.

To predict protective immunity to SARS-CoV-2, cellular immunity seems to be more sensitive than humoral immunity. Through an Interferon-Gamma (IFN-γ) Release Assay (IGRA), we show that, despite a marked decrease in total antibodies, 94.3% of 123 healthcare workers have a positive cellular response 6 months after inoculation with the 2nd dose of BNT162b2 vaccine. Despite the qualitative relationship found, we did not observe a quantitative correlation between IFN-γ and IgG levels against SARS-CoV-2. Using stimulated whole blood from a subset of participants, we confirmed the specific T-cell response to SARS-CoV-2 by dosing elevated levels of the IL-6, IL-10 and TNF-α. Through a 20-month follow-up, we found that none of the infected participants had severe COVID-19 and that the first positive cases were only 12 months after the 2nd dose inoculation. Future studies are needed to understand if IGRA-SARS-CoV-2 can be a powerful diagnostic tool to predict future COVID-19 severe disease, guiding vaccination policies.

Ratio of plasma IL-13/TNF- ∝ and CXCL10/CCL17 predicts mepolizumab and omalizumab response in asthma better than eosinophil count or immunoglobulin E level.

To date, most studies to identify biomarkers associated with response to the anti-interleukin 5 agent, mepolizumab, and to the anti-immunoglobulin E agent, omalizumab have focused on clinically available biomarkers, such as the peripheral blood eosinophil counts (BEC) and total immunoglobulin E (IgE). However, these biomarkers often have low predictive accuracy, with many patients with eosinophilic or allergic asthma failing to demonstrate clinical response to mepolizumab or omalizumab respectively. In this study, we evaluated the association of baseline pre-biologic plasma levels of 26 cytokines and chemokines, including T-helper 1 (Th1)-, Th2-, Th17-related cytokines, and their ratios with subsequent clinical response to mepolizumab or omalizumab. We defined clinical response as a reduction in the baseline annual exacerbation rate by half or more over the one-year period following initiation of the biologic. Baseline levels of plasma IL-13 were differentially elevated in responders versus non-responders to mepolizumab and plasma CXCL10 levels were differentially elevated in responders to omalizumab. The ratio of IL-13/TNF-α had the best sensitivity and specificity in predicting response to mepolizumab and CXCL10/CCL17 to omalizumab, and these performed better as predictive biomarkers of response than BEC and IgE. Cytokines and chemokines associated with airway eosinophilia, allergic inflammation, or Th2 inflammation, such as IL-13 and CXCL10, may be better predictors of clinical response to mepolizumab and omalizumab, than IL-5 or IgE, the targets of mepolizumab and omalizumab.

Anti-inflammatory properties and characterization of water extracts obtained from Callicarpa kwangtungensis Chun using in vitro and in vivo rat models.

Callicarpa kwangtungensis Chun (CK) is a common remedy exhibits anti-inflammatory properties and has been used in Chinese herbal formulations, such as KangGongYan tablets. It is the main component of KangGongYan tablets, which has been used to treat chronic cervicitis caused by damp heat, red and white bands, cervical erosion, and bleeding. However, the anti-inflammatory effects of CK water extract remains unknown. This study assessed the anti-inflammatory effects of CK in vivo and in vitro, characterized its main components in the serum of rats and verified the anti-inflammatory effects of serum containing CK. Nitric oxide (NO), tumour necrosis factor α (TNF-α) and interleukin-6 (IL-6) release by RAW264.7 cells was examined by ELISA and Griess reagents. Inflammation-related protein expression in LPS-stimulated RAW264.7 cells was measured by western blotting. Furthermore, rat model of foot swelling induced by λ-carrageenan and a collagen-induced arthritis (CIA) rat model were used to explore the anti-inflammatory effects of CK. The components of CK were characterized by LC-MS, and the effects of CK-containing serum on proinflammatory factors levels and the expression of inflammation-related proteins were examined by ELISA, Griess reagents and Western blotting. CK suppressed IL-6, TNF-α, and NO production, and iNOS protein expression in LPS-stimulated RAW264.7 cells. Mechanistic studies showed that CK inhibited the phosphorylation of ERK, P38 and JNK in the MAPK signaling pathway, promoted the expression of IκBα in the NF-κB signaling pathway, and subsequently inhibited the expression of iNOS, thereby exerting anti-inflammatory effects. Moreover, CK reduced the swelling rates with λ-carrageenan induced foot swelling, and reduced the arthritis score and incidence in the collagen-induced arthritis (CIA) rat model. A total of 68 compounds in CK water extract and 31 components in rat serum after intragastric administration of CK were characterized. Serum pharmacological analysis showed that CK-containing serum suppressed iNOS protein expression and NO, TNF-α, and IL-6 release. CK may be an anti-inflammatory agent with therapeutic potential for acute and chronic inflammatory diseases, especially inflammatory diseases associated with MAPK activation.

[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].

OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Dynamic indicators of acute respiratory diseases treatment in children after correction.

OBJECTIVE: Aim: To study the Respiratory pathology of the upper respiratory tract, markers of the inflammatory response of the organism, Oxidative stress, Metabolic adaptation and possibilities of correction. PATIENTS AND METHODS: Materials and Methods: The study group (n=111) included school-aged children (10-14 years old). The general group of inflammatory diseases of the respiratory tract (J000-J06) was considered, with a diagnosis of acute respiratory infection (ARI) of viral and bacterial origin and included local inflammationof the upper respiratory tract with presentation of acute pharyngitis (68.0%), acute bronchitis (22,0%), acute tonsillitis (10,0%). RESULTS: Results: Dynamic observation of groups of children who received optimized (group 1, n=60) and basic (group 2, n=51) treatment was carried out. The level of the erythrocyte pool correlated with IL-1 (r=-0,29, p=0,03), IL-4 (r=0,32, p=0,01), TNF-α (r=-0,35 , p=0,006). Creatinine value correlated with IL-10 (r=0,3, p=0,005), γ-IFN (r=0,42, p=0,001), TNF-α (r=0,25, p=0,05). Correlations of ferritin presented positive correlation values with the level of total protein (r=0,26, p=0,04) and TNF-α (r=0,41, p=0,001). CONCLUSION: Conclusions: After the optimized treatment, there was a significant decrease in the reliable levels of CRP and γ-IFN by 7 and 4,4 times (by groups) and 5,8 and 3,2 times (by groups), respectively. Correlation relationships of urea levels with IL-2,4 were detected. The level of the erythrocyte pool correlated with IL-1,4, TNF-α, Ferritin presented positive correlation values with the level of total protein,TNF-α .

A Patented Dietary Supplement (Hydroxy-Methyl-Butyrate, Carnosine, Magnesium, Butyrate, Lactoferrin) Is a Promising Therapeutic Target for Age-Related Sarcopenia through the Regulation of Gut Permeability: A Randomized Controlled Trial.

Adequate diet, physical activity, and dietary supplementation with muscle-targeted food for special medical purposes (FSMP) or dietary supplement (DS) are currently considered fundamental pillars in sarcopenia treatment. The aim of this study is to evaluate the effectiveness of a DS (containing hydroxy-methyl-butyrate, carnosine, and magnesium, for its action on muscle function and protein synthesis and butyrate and lactoferrin for their contribution to the regulation of gut permeability and antioxidant/anti-inflammation activity) on muscle mass (assessed by dual X-ray absorptiometry (DXA)), muscle function (by handgrip test, chair test, short physical performance battery (SPPB) test, and walking speed test), inflammation (tumor necrosis factor-alpha (TNF-a), C-reactive protein (CRP), and visceral adipose tissue (VAT)) and gut axis (by zonulin). A total of 59 participants (age 79.7 ± 4.8 years, body mass index 20.99 ± 2.12 kg/m2) were enrolled and randomly assigned to intervention (n = 30) or placebo (n = 28). The skeletal muscle index (SMI) significantly improved in the supplemented group compared to the placebo one, +1.02 (CI 95%: -0.77; 1.26), p = 0.001; a significant reduction in VAT was observed in the intervention group, -70.91 g (-13.13; -4.70), p = 0.036. Regarding muscle function, all the tests significantly improved (p = 0.001) in the supplemented group compared to the placebo one. CRP, zonulin, and TNF-alpha significantly decreased (p = 0.001) in intervention, compared to placebo, -0.74 mg/dL (CI 95%: -1.30; -0.18), -0.30 ng/mL (CI 95%: -0.37; -0.23), -6.45 pg/mL (CI 95%: -8.71; -4.18), respectively. This DS improves muscle mass and function, and the gut muscle has emerged as a new intervention target for sarcopenia.

Effects of ketamine on penile tissues in an experimental priapism model in rats.

BACKGROUND: This study aimed to evaluate the histopathological and biochemical effects of ketamine on penile tissues following ischemia-reperfusion injury induced by priapism. METHODS: Twenty-four male rats were randomized into three groups. Group 1 served as the control group. Group 2 underwent the priapism model to induce ischemia-reperfusion injury. Group 3, the treatment group, experienced a similar ischemia-reperfusion model as Group 2; additionally, 50 mg/kg of ketamine was administered intraperitoneally just before reperfusion. Blood biochemical analyses and penile histopathological evaluations were performed. RESULTS: In Group 3, significant improvements were observed in all histopathological scores, including desquamation, edema, inflammation, and vasocongestion compared to Group 2 (p<0.001). Blood biochemical analyses showed that the malondialdehyde (MDA) levels were recorded as 10 in Group 2, with a significant decrease in Group 3 (p=0.013). Similarly, proinflammatory cytokine levels, including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were found to be suppressed in Group 3 compared to Group 2 (p=0.003, p=0.022, and p=0.028, respectively). Antioxidant enzyme activities, such as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), were higher in Group 3 compared to Group 2 (p=0.016 and p=0.024, respec-tively). CONCLUSION: Ketamine is an effective anesthetic agent in alleviating the effects of penile ischemia-reperfusion injury.

[Effect of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer and chronic obstructive pulmonary disease].

Objective: To investigate the impact of peripheral blood inflammatory indicators on the efficacy of immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) complicated with chronic obstructive pulmonary disease (COPD). Methods: A retrospective cohort study was performed to include 178 patients with Ⅲ-Ⅳ NSCLC complicated with COPD who received at least 2 times of immunotherapy in Xinqiao Hospital of the Army Medical University from January 2019 to August 2021. Baseline peripheral blood inflammatory indicators such as interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α) were collected within 2 weeks before the first treatment, with the last one being on or before February 7, 2022. X-tile software was used to determine the optimal cut-off value of peripheral blood inflammatory indicators. The Cox multivariate regression models were used to analyze the factors affecting progression free survival (PFS) and overall survival (OS). Results: Among the 178 patients, there were 174 males (97.8%) and 4 females (2.2%); the age ranged from 42 to 86 (64.3±8.3) years old.There were 30 cases (16.9%) of immunotherapy monotherapy, 114 cases (64.0%) of immunotherapy combined with chemotherapy, 21 cases (11.8%) of immunotherapy combined with antivascular therapy, and 13 cases (7.3%) of immunotherapy combined with radiotherapy. The median follow-up period was 14.5 months (95%CI: 13.6-15.3 months). The objective response rate (ORR) and disease control rate (DCR) were 44.9% (80/178) and 90.4% (161/178) for the whole group, the median PFS was 14.6 months (95%CI: 11.6-17.6 months), and the median OS was 25.7 months (95%CI: 18.0-33.4 months). The results of Cox multivariate analysis showed that IL-6>9.9 ng/L (HR=5.885, 95%CI: 2.558-13.543, P<0.01), TNF-α>8.8 ng/L (HR=3.213, 95%CI: 1.468-7.032, P=0.003), IL-8>202 ng/L (HR=2.614, 95%CI: 1.054-6.482, P=0.038), systemic immune inflammatory index (SII)>2 003.95 (HR=2.976, 95%CI: 1.647-5.379, P<0.001) were risk factors for PFS, and advanced lung cancer inflammation index (ALI)>171.15 was protective factor for PFS (HR=0.545, 95%CI: 0.344-0.863, P=0.010). IL-6>9.9 ng/L(HR=6.124, 95%CI: 1.950-19.228, P<0.002), lactate dehydrogenase (LDH)>190.7 U/L (HR=2.776, 95%CI: 1.020-7.556, P=0.046), SII>2 003.95 (HR=4.521, 95%CI: 2.241-9.120, P<0.001) were risk factors for OS, and ALI>171.15 was a protective factor for OS (HR=0.434, 95%CI: 0.243-0.778, P=0.005). Conclusion: Baseline high levels of IL-6, TNF-α, IL-8, SII, LDH, and low levels of ALI are risk factors for poor prognosis in patients with advanced NSCLC-COPD receiving immunotherapy.

HERV-W upregulation expression in bipolar disorder and schizophrenia: unraveling potential links to systemic immune/inflammation status.

BACKGROUND: Bipolar disorder (BD) and schizophrenia (SZ) are the two main mental disorders with unknown etiology that significantly impact individuals' quality of life. The potential pro-inflammatory role in their pathogenesis is postulated and Human Endogenous Retrovirus W (HERV-W) is an emerging candidate to modulate this pathogenic finding. HERVs, ancient retroviruses in the human genome, may play roles in inflammation and disease pathogenesis. Despite HERVs' involvement in autoimmune diseases, their influence on mental disorders remains underexplored. Therefore, the aim of this study was to assess the level of HERV-W-env expression and the systemic inflammatory profile through the concentration of IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ cytokines in BD and SZ patients. RESULTS: All participants showed HERV-W-env expression, but its expression was higher in mental disorder patients (p < 0.01) than in control. When separated, SZ individuals exhibited higher HERV-W expression than the control group (p < 0.01). Higher serum levels of TNF-α and IL-10 were found in BD (p = 0.0001 and p = 0.001, respectively) and SZ (p = 0.01) and p = 0.01, respectively) than in the control group, while SZ showed decreased levels IFN-γ and IL-2 as compared to controls (p = 0.05) and BD patients (p = 0.05), respectively. Higher TNF-α/IL-4 and TNF-α/IL-10 ratios, and lower IFN-γ/IL-10 were observed in BD and SZ patients than controls. Significant negative correlation between HERV-W-env expression and IL-10 (r=-0.47 p < 0.05), as well as positive correlations between HERV-W-env expression and TNF-α/IL-10 or IFN-γ/IL-10 ratios (r = 0.48 p < 0.05 and r = 0.46 p < 0.05, respectively) were found in BD patients. CONCLUSION: These findings suggest not only a potential link between HERV-W-env expression both in BD and SZ, but also a possible involvement of systemic inflammatory status in BD patients.

Inflammatory depression is associated with selective glomerular hypofiltration.

BACKGROUND: Systemic low-grade inflammation may be a pathophysiological mechanism in a subtype of depression. In this study we investigate a novel candidate mechanism of inflammatory depression - Selective Glomerular Hypofiltration Syndromes (SGHS) - which are characterized by a reduced estimated glomerular filtration rate (eGFR) based on cystatin C (cysC) relative to eGFR based on creatinine (crea). SGHS have been associated with increased blood levels of pro-inflammatory markers, but have never been investigated in a sample of depressed individuals. METHOD: The prevalence of SGHS was compared between 313 patients with difficult-to-treat depression and 73 controls. Since there is no single established eGFRcysC/eGFRcrea-ratio cut-off to define SGHS, several cut-offs were investigated in relation to a depression diagnosis, inflammation, and symptom severity. Plasma inflammatory markers tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-6, IL-8, and IL-10 were available from 276 depressed patients. We examined mediation effects of IL-6 on the relationship between SGHS and depression. RESULTS: Depressed patients were more likely to have SGHS compared to controls defining SGHS as either eGFRcysC/eGFRcrea-ratio < 0.9 (33.2 % vs 20.5 %, p = 0.035) or < 0.8 (15.7 % vs 5.5 %, p = 0.023). Lower eGFRcysC/eGFRcrea-ratio was associated with higher levels of inflammatory markers in depressed patients. IL-6 partly mediated the relationship between SGHS and depression. CONCLUSION: This is the first study to demonstrate a link between SGHS and inflammatory depression. If replicated in independent and longitudinal cohorts, this may prove to be a relevant pathophysiological mechanism in some cases of depression that could be targeted in future intervention and prevention studies.

Dexmedetomidine Pretreatment Confers Myocardial Protection and Reduces Mechanical Ventilation Duration for Patients Undergoing Cardiac Valve Replacement under Cardiopulmonary Bypass.

PURPOSE: The study aims to assess the effects of dexmedetomidine (Dex) pretreatment on patients during cardiac valve replacement under cardiopulmonary bypass. METHODS: For patients in the Dex group (n = 52), 0.5 µg/kg Dex was given before anesthesia induction, followed by 0.5 µg/kg/h pumping injection before aortic occlusion. For patients in the control group (n = 52), 0.125 ml/kg normal saline was given instead of Dex. RESULTS: The patients in the Dex group had longer time to first dose of rescue propofol than the control group (P = 0.003). The Dex group required less total dosage of propofol than the control group (P = 0.0001). The levels of cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), malondialdehyde (MDA), and tumor necrosis factor-α (TNF-α) were lower in the Dex group than the control group at T4, 8 h after the operation (T5), and 24 h after the operation (T6) (P <0.01). The Dex group required less time for mechanical ventilation than the control group (P = 0.003). CONCLUSION: The study suggests that 0.50 µg/kg Dex pretreatment could reduce propofol use and the duration of mechanical ventilation, and confer myocardial protection without increased adverse events during cardiac valve replacement.

Folic acid supplementation on inflammation and homocysteine in type 2 diabetes mellitus: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: The beneficial effects of folate have been observed under different conditions, but the available evidence on inflammation and reduction of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) is limited. The study aimed to explore the effects of folate on inflammation and homocysteine amongst individuals with T2DM. METHODS: PubMed, Scopus, and Cochrane Library were used to search for evidence. A random-effect model meta-analysis through Review Manager (version 5.4) and metaHun was performed. Results were reported as standardized mean differences (SMD) and 95% confidence intervals graphically using forest and funnel plots. RESULTS: Data from 9 trials with 426 patients living with T2DM were analyzed. Folic acid supplementation significantly revealed a large effect size on homocysteine levels compared to placebo, SMD = -1.53, 95%CI (-2.14,-0.93), p < 0.05. Additionally, we observed a medium marginal effect size on C-reactive protein (SMD = -0.68, 95%CI (-1.34, -0.01), p = 0.05). However, no significant effect on tumor necrosis factor-α (SMD = -0.86, 95%CI (-2.65, 0.93), p = 0.34), and interleukin-6 (SMD = -0.04, 95%CI (-1.08, 1.01), p = 0.95) was observed. CONCLUSION: Evidence analyzed in this study suggests that folic acid supplementation in T2DM reduces homocysteine and may mitigate CVDs. However, its effect on inflammation is inconclusive.

TNF-α: A serological marker for evaluating the severity of hippocampal sclerosis in medial temporal lobe epilepsy?

OBJECTIVE: By analysing the difference in TNF-α levels in the peripheral blood of patients with medial temporal lobe epilepsy (mTLE) with or without hippocampal sclerosis and the correlation between TNF-α and N-acetylaspartate levels in the hippocampus, we explored the relationship between TNF-α and the degree of damage to hippocampal sclerosis neurons in medial temporal lobe epilepsy. METHODS: This is a prospective, population-based study. A total of 71 Patients with medial temporal lobe epilepsy diagnosed by clinical seizures, video-EEG, epileptic sequence MRI, and other imaging examinations were recruited from October 2020 to July 2022 in the Department of Neurology, Affiliated Hospital of Xuzhou Medical University. Twenty age-matched healthy subjects were selected as the control group. The patients were divided into two groups: the medial temporal epilepsy with hippocampal sclerosis group (positive group, mTLE-HS-P group) and the medial temporal epilepsy without hippocampal sclerosis group (negative group, mTLE-HS-N group). The levels of IL-1ß, IL-5, IL-6, IL-8, IL-17, IFN-γ and TNF-α in the peripheral blood of the patients in the three groups were detected by multimicrosphere flow immunofluorescence assay. The level of N-acetylaspartate (NAA) in the hippocampus was measured by 1H-MRS. The differences in cytokine levels among the three groups were analysed, and the correlation between cytokine and NAA levels was analysed. RESULTS: The level of TNF-α in the peripheral blood of the patients in the mTLE-HS-P group was significantly higher than that of the patients in the mTLE-HS-N and healthy control groups, and the level of TNF-α in the patients in the mTLE-HS-N group was significantly higher than that of the patients in the healthy control group. The NAA level in mTLE-HS-P group patients was significantly lower than that of mTLE-HS-N patients and healthy controls, but there was no significant difference between mTLE-HS-N patients and healthy controls (P > 0.05). Spearman correlation analysis showed that TNF-α level (rs = -0.437, P < 0.05) and the longest duration of a single seizure (rs = -0.398, P < 0.05) were negatively correlated with NAA level. Logistic regression analysis showed that there was no significant correlation between the longest duration of a single seizure and hippocampal sclerosis, but TNF-α level was closely related to hippocampal sclerosis in patients with mTLE (OR = 1.315, 95 % CI 1.084-1.595, P = 0.005). CONCLUSION: The level of TNF-α in the peripheral blood of patients with medial temporal lobe epilepsy with hippocampal sclerosis was higher, and it was correlated with NAA and hippocampal sclerosis. The high expression of TNF-α may be of important value in the evaluation of hippocampal sclerosis patients.

Correlation between serum inflammatory factors and cognitive function in patients with high-altitude polycythemia: A case-control study.

The purpose of this study is to investigate the serum inflammatory factors in patients with high-altitude polycythemia (HAPC) and their correlation with cognitive function. The subjects were recruited and placed into a HAPC group and control group. Serum samples were collected, and inflammatory factors (interleukin-1beta [IL-1ß], monocyte chemoattractant protein-1 [MCP-1], and tumor necrosis factor-alpha [TNF-α]) were measured using ELISA kits. The mini-mental State Examination (MMSE) was used to assess cognitive function. According to the MMSE scores, HAPC group was further divided into normal cognitive function group (HNCF) and cognitive dysfunction group (HCDF). In comparison with the control group, the MMSE scores in the HAPC group were significantly low (P < .05), whereas the serum levels of IL-1ß, MCP-1, and TNF-α were significantly high (P < .01). Among the HAPC group (n = 60), 21 belonged to the HCDF and 39 belonged to the HNCF. Compared with the HNCF, the IL-1ß, MCP-1, and TNF-α in the HCDF were significantly increased (P < .01). The Pearson correlation analysis showed that inflammatory factors were positively correlated with hemoglobin, and negatively correlated with MMSE. Serum inflammatory cytokines IL-1, MCP-1, and TNF-α were increased in HAPC, and HAPC exhibited cognitive dysfunction. Considering chronic hypoxia environment influences the change of the red blood cell metabolic and inflammatory factor, red blood cells and inflammatory factor in plateau is likely to be affected by patients with vascular lesions, increase cognitive impairment.

Carbon Monoxide Alleviates Post-ischemia-reperfusion Skeletal Muscle Injury and Systemic Inflammation.

Restoration of blood flow in skeletal muscle after a prolonged period of ischemia induces muscular ischemia-reperfusion injury, leading to local injury/dysfunction in muscles followed by systemic inflammatory responses. However, preventive/curative agents for skeletal muscle ischemia injury are unavailable in clinics to date. Increasing evidence has validated that carbon monoxide (CO) prevents the progression of ischemia-reperfusion injury in various organs owing to its versatile bioactivity. Previously, we developed a bioinspired CO donor, CO-bound red blood cells (CO-RBC), which mimics the dynamics of RBC-associated CO in the body. In the present study, we have tested the therapeutic potential of CO-RBC in muscular injury/dysfunction and secondary systemic inflammation induced by skeletal muscle ischemia-reperfusion. The results indicate that CO-RBC rather than RBC alone suppressed elevation of plasma creatine phosphokinase, a marker of muscular injury, in rats subjected to both hind limbs ischemia-reperfusion. In addition, the results of the treadmill walking test revealed a significantly decreased muscular motor function in RBC-treated rats subjected to both hind limbs ischemia-reperfusion than that in healthy rats, however, CO-RBC treatment facilitated sustained muscular motor functions after hind limbs ischemia-reperfusion. Furthermore, CO-RBC rather than RBC suppressed the production of tumour necrosis factor (TNF)-α and interleukin (IL)-6, which were upregulated by muscular ischemia-reperfusion. Interestingly, CO-RBC treatment induced higher levels of IL-10 compared to saline or RBC treatments. Based on these findings, we suggest that CO-RBC exhibits a suppressive effect against skeletal muscle injury/dysfunction and systemic inflammatory responses after skeletal muscle ischemia-reperfusion.

Lingering Effects of Early Institutional Rearing and Cytomegalovirus Infection on the Natural Killer Cell Repertoire of Adopted Adolescents.

Adversity during infancy can affect neurobehavioral development and perturb the maturation of physiological systems. Dysregulated immune and inflammatory responses contribute to many of the later effects on health. Whether normalization can occur following a transition to more nurturing, benevolent conditions is unclear. To assess the potential for recovery, blood samples were obtained from 45 adolescents adopted by supportive families after impoverished infancies in institutional settings (post-institutionalized, PI). Their immune profiles were compared to 39 age-matched controls raised by their biological parents (non-adopted, NA). Leukocytes were immunophenotyped, and this analysis focuses on natural killer (NK) cell populations in circulation. Cytomegalovirus (CMV) seropositivity was evaluated to determine if early infection contributed to the impact of an atypical rearing. Associations with tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ), two cytokines released by activated NK cells, were examined. Compared to the NA controls, PI adolescents had a lower percent of CD56bright NK cells in circulation, higher TNF-α levels, and were more likely to be infected with CMV. PI adolescents who were latent carriers of CMV expressed NKG2C and CD57 surface markers on more NK cells, including CD56dim lineages. The NK cell repertoire revealed lingering immune effects of early rearing while still maintaining an overall integrity and resilience.

The relationship between levels of tumor necrosis factor-alpha, interleukin-6, and C-reactive protein in the serum of elderly and acute myocardial infarction.

This study aimed to explore the relationship between the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and hypersensitive C-reactive protein (hs-CRP) and the prognosis of acute myocardial infarction (AMI) patients after percutaneous coronary intervention (PCI) treatment. A total of 118 early-onset AMI patients who successfully received PCI (in the PCI group, blood samples were collected before PCI, 12, 24, 48 h after PCI, and 90 d follow-up period) and 52 AMI patients who received only cardioangiography (CAG) (in the CAG group, blood samples were collected before CAG, 12, 24, 48 h after CAG, and 90 d follow-up period). The serum levels of IL-6, hs-CRP and TNF-α were detected, and the incidence of major adverse cardiac events (MACE) in the PCI group during follow-up was observed. The basic levels of IL-6, hs-CRP, and TNF-α between the PCI group and the CAG group were not statistically different (P>0.05); there was no statistically significant difference in changes of serum IL-6, hs-CRP, and TNF-α in the CAG group before and after CAG (P>0.05); IL-6, hs-CRP, and TNF-α in the PCI group were significantly higher than those before treatment (P<0.01); in the PCI group, the levels of IL-6, hs-CRP and TNF-α between the MACE group and the MACE-free group were statistically different (P<0.05). Serum IL-6, hs-CRP and TNF-α levels in AMI patients after PCI significantly increased in the short term, and PCI may induce an inflammatory response; the high levels of inflammatory cytokines, IL-6, hs-CRP, and TNF-α, in peripheral blood may have an important reference value for MACE and short-term prognosis in early-onset AMI patients after PCI.

[Effect of salvia miltiorrhiza combined with roxadustat on wound healing of full-thickness skin defects in diabetic rats and its mechanism].

Objective: To explore the effect of salvia miltiorrhiza combined with roxadustat on wound healing of full-thickness skin defects in diabetic rats and its mechanism. Methods: This study was an experimental study. Twenty male 8-week-old Sprague-Dawley rats were used to successfully establish diabetic model, then full-thickness skin defect wounds on their backs were made. The rats were divided into normal saline group, roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group according to the random number table, with 5 rats in each group. Immediately after injury, the rats in normal saline group were given 5 mL normal saline by gavage, the rats in roxadustat alone group were given 1.5 mg/mL roxadustat suspension by gavage at 25 mg/kg, the rats in salvia miltiorrhiza alone group were given 18 mg/mL salvia miltiorrhiza suspension by gavage at 300 mg/kg, and the rats in roxadustat+salvia miltiorrhiza group were given 19.5 mg/mL roxadustat and salvia miltiorrhiza suspension at roxadustat 25 mg/kg and salvia miltiorrhiza 300 mg/kg. All were administered once a day for 2 weeks. The wounds at 0 (immediately), 4, 8, and 12 d after injury were observed, and the wound healing rates at 4, 8, and 12 d after injury were calculated (n=5). At 14 d after injury, abdominal aortic blood was collected, and hemoglobin, red cell count, and white blood cell count were detected (n=5). The wound tissue was collected for hematoxylin-eosin staining to observe inflammatory infiltration, skin tissue structure, and neovascularization, for Masson staining to observe the proportion of collagen fiber (n=3), for Western blotting to detect the protein expression levels of vascular endothelial growth factor (VEGF), CD31, interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and IL-1ß (n=3), and for immunohistochemical staining to determine the protein expression levels of epidermal growth factor receptor (EGFR), hypoxia-inducible factor 1α (HIF-1α), and proliferating cell nuclear antigen (PCNA), with sample number of 3. Results: From 0 to 12 d after injury, the wound areas of rats in 4 groups were gradually decreased. At 4 d after injury, the wound healing rates of rats in salvia miltiorrhiza alone group and roxadustat+salvia miltiorrhiza group were significantly higher than those in normal saline group and roxadustat alone group (P<0.05). At 8 d after injury, the wound healing rates of rats in roxadustat alone group and salvia miltiorrhiza alone group were significantly higher than the rate in normal saline group (P<0.05), and the wound healing rate of rats in roxadustat+salvia miltiorrhiza group was significantly higher than the rates in the other 3 groups (with P values all <0.05). At 12 d after injury, the wound healing rates of rats in roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group were significantly higher than the rate in normal saline group (P<0.05). At 14 d after injury, there were no statistically significant differences in the hemoglobin or red blood cell count of rats in 4 groups (P<0.05). The white blood cell count of rats in roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group were respectively (24.3±1.2)×109/L, (26.3±2.4)×109/L, and (15.0±0.7)×109/L, which were significantly lower than (33.8±2.7)×109/L in normal saline group (P<0.05); the white blood cell count of rats in roxadustat+salvia miltiorrhiza group was significantly lower than that in roxadustat alone group and salvia miltiorrhiza alone group (with P values both <0.05). At 14 d after injury, a large number of inflammatory cell infiltration, disordered skin tissue structure, and few new blood vessels were observed in the wounds of rats in normal saline group; while a small amount of inflammatory cell infiltration, tight skin tissue structure, and rich neovascularization were observed in the wounds of rats in the other 3 groups. There were no statistically significant differences in the proportion of collagen fiber of wounds in rats among the 4 groups (P>0.05). At 14 d after injury, the protein expression levels of VEGF and CD31 in the wound tissue of rats in roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group were significantly higher than those in normal saline group (P<0.05), the protein expression level of CD31 in the wound tissue of rats in roxadustat+salvia miltiorrhiza group was significantly higher than the levels in roxadustat alone group and salvia miltiorrhiza alone group (with P values both <0.05). At 14 d after injury, the protein expression levels of IL-6, TNF-α, and IL-1ß in the wound tissue of rats in roxadustat alone group, salvia miltiorrhiza alone group, and roxadustat+salvia miltiorrhiza group were significantly lower than those in normal saline group (P<0.05); the protein expression levels of IL-6 and IL-1ß in the wound tissue of rats in roxadustat+salvia miltiorrhiza group were significantly lower than those in roxadustat alone group and salvia miltiorrhiza alone group (P<0.05); the protein expression level of TNF-α in the wound tissue of rats in roxadustat+salvia miltiorrhiza group was significantly lower than that in salvia miltiorrhiza alone group (P<0.05). At 14 d after injury, the protein expression level of EGFR in the wound tissue of rats in roxadustat+salvia miltiorrhiza group was significantly higher than the levels in the other 3 groups (with P values all <0.05); the protein expression levels of HIF-1α in the wound tissue of rats in roxadustat alone group and roxadustat+salvia miltiorrhiza group were significantly higher than the level in normal saline group (P<0.05), and the protein expression level of HIF-1α in the wound tissue of rats in roxadustat+salvia miltiorrhiza group was significantly higher than that in salvia miltiorrhiza alone group (P<0.05); there were no statistically significant differences in the protein expression level of PCNA in the wound tissue of rats in 4 groups (P>0.05). Conclusions: Roxadustat combined with salvia miltiorrhiza can promote the wound healing of full-thickness skin defects in diabetic rats by promoting blood vessel regeneration and reducing inflammatory response.

Analysis of the Level of Adiponectin and Selected Cytokines in Patients with Knee Osteoarthritis.

Background and Objectives: Knee osteoarthritis (KOA) is a degenerative disease that is continuously targeting people of different ages, but especially the elderly population, the number of which tends to increase continuously at the global level. Apart from age, excess weight can influence the evolution of the disease, with obesity being associated with a weak inflammation stage and an imbalance between pro-inflammatory and anti-inflammatory cytokines. The present work aimed to analyze specific biomarkers, namely ACRP-30, IL-10, TNF-α, and IL-6, in knee synovial fluid, and correlate them with KOA patients' clinical data, radiographic changes, and functional and pain scores. Materials and Methods: 24 subjects with KOA and over 50 years of age participate in the present study. Synovial fluid was harvested using ultrasound guidance from the target knees of the enrolled KOA patients, and the levels of ACRP-30, IL-10, TNF-α, and IL-6 were measured using enzyme-linked immunosorbent assays (ELISA). All patients underwent a supine X-ray at the target knee and were classified using Kellgren-Lawrence (K-L) grading. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) was used to assess self-reported physical function, pain, and stiffness. Results: The obtained results highlighted a significant correlation between age and adiponectin level (p = 0.0451, r = -0.412). Also, the IL-10 values are lower in cases where the intensity of the pain is more pronounced (p = 0.0405, r = -0.421). In addition, analyzing the data by gender, it was observed that in the case of males, stiffness is more related to age (p = 0.0079, r = 0.7993), compared to women (p = 0.0203, r = 0.6223). In the case of women, the progression of the disease tends to increase more intensively the WOMAC score's total values (p = 0.00031, r = 0.8342), compared with men (p = 0.0289, r = 7013). Regarding interleukins and BMI, significant correlations were observed only in the case of men. Conclusions: A significant correlation between age and adiponectin, and adiponectin and IL-6, suggests that advanced age may contribute to adiponectin reduction. Comparing men with women, it was observed that men's age is more related to rigidity, and IL-6 and IL-10 are directly correlated to BMI; in addition, women seem to be more sensitive to pain and stiffness.

Association between Toxoplasma gondii and gestational diabetes with regard to serum leptin and tumor necrosis factor alpha, a preliminary study.

Gestational diabetes (GDM), the onset of any degree of glucose intolerance during pregnancy, increases a wide range of adverse health outcomes for both the mother and the fetus. The aim of the present study was to evaluate the association of Toxoplasma gondii infection with GDM in a case-control study with regard to the levels of leptin and tumor necrosis factor alpha (TNF-α) as two inflammatory biomarkers. Fifty-one pregnant diabetic cases and 109 controls were selected from a prenatal care clinic of a general hospital in Shiraz, southern Iran during July-November 2020. Cases and controls were similar in age, gestational age and number of parturitions. The presence of IgG antibodies against T. gondii, and serum concentrations of leptin and TNF-α were determined by ELISA. Anti-Toxoplasma antibodies were detected in 25 subjects (15.6 %, 95 % CI: 9.9-21.3). Nine (18 %) diabetic cases were infected with Toxoplasma compared to 16 (15 %) healthy controls (P = 0.63). Level of leptin was higher (P = 0.07) while TNF-α was lower in diabetic cases compared to healthy controls (P = 0.08). When subjects were classified according to the combination of GDM and T. gondii, leptin was significantly lower in healthy (non-diabetic, non-infected) subjects compared to diabetics (P = 0.026), and TNF-α was higher in healthy subjects compared to Toxoplasma-infected diabetics (P = 0.032). These findings can be interpreted as both comorbidities being individually associated with increasing serum leptin and decreasing TNF-α concentrations, with modifying effects on each other. The present study opens a new perspective on GDM and its complex pathophysiological mechanism. Future research in this area is needed to better understand the underlying pathway for the development of GDM and the role of T. gondii and inflammatory biomarkers.