Blood TNF-α Levels Research Articles

Cytomegalovirus viral interleukin-10 in patients with Aspergillus infection and effects on clinical outcome.

Human cytomegalovirus (CMV) is associated with aspergillosis, but the simultaneous presence of CMV viral interleukin-10 (cmvIL-10) and aspergillosis has never been investigated. CmvIL-10 is produced by CMV-infected cells and acts as an immune modulator during CMV infection. The aim of this study was to evaluate cmvIL-10 levels in peripheral blood and its influence on the clinical outcomes of Aspergillus infection. Patients who visited or were admitted to the hospital with suspected Aspergillus infection, including invasive aspergillosis (IA) and chronic pulmonary aspergillosis (CPA), were prospectively enrolled. The cmvIL-10, human IL-10 (hIL-10), IL-1B, IL-6, IL-8, IFN-γ, and TNF-α levels in peripheral blood were measured. Patients with Aspergillus infection had a higher level of cmvIL-10 than the control group (158 ± 305 vs 27.9 ± 30.4pg/ml, p < .05). The level of cmvIL-10 was not correlated with CMV viremia or end-organ disease. The cmvIL-10 but not hIL-10 level was positively correlated with the IFN-γ level (p < .05) and marginally negatively correlated with IL-1B and IL-8 levels (p < .1). In patients with CPA, a high level of cmvIL-10 (≥100 pg/ml) was a poor prognostic factor for long-term survival (p < .05). In contrast, CMV viremia or end-organ disease was associated with poor survival in patients with IA (p=.05). Aspergillus infection was associated with CMV coinfection with cmvIL-10 in blood. A cmvIL-10 concentration ≥100 pg/ml was a predictor for unfavourable outcome in CPA patients.

Probiotics improves abnormal behavior and hippocampal injury in pregnant-stressed offspring rats.

During pregnancy, pregnant women are prone to stress reactions due to external stimuli, affecting their own health and fetal development. At present, there is no good treatment for the stress reactions from pregnant women during pregnancy. This study aims to explore the effect of probiotics on abnormal behavior and hippocampal injury in pregnant stressed offspring. SD pregnant rats were divided into a control group, a stress group, and a probiotics group, with 6 rats in each group. The control group was untreated; the stress group was given restraint stress on the 15th-20th day of pregnancy; the probiotics group was given both bifidobacterium trisporus capsules and restraint stress on the 15th-20th day of pregnancy, and the offspring continued to be fed with probiotics until 60 days after birth (P60). The offspring rats completed behavioral tests such as the open field test, the elevated plus maze test, the new object recognition test, and the barnes maze test at 60-70 d postnatally. Nissl's staining was used to reflect the injury of hippocampal neurons; immunohistochemical staining was used to detect the expression of microglia marker ionized calcium binding adapter molecule 1 (IBA-1) which can reflect microglia activation; ELISA was used to detect the content of plasma TNF-α and IL-1β; Western blotting was used to detect the expression of Bax, Bcl-2, and caspase-3. The retention time of offspring rats in the stress group in the central area of the open field was significantly less than that in the control group (P<0.01), and the retention time of offspring rats in the probiotic group in the central area of the open field was significantly more than that in the stress group (P<0.05). The offspring rats in the stress group stayed in the open arm for a shorter time than the control group (P<0.05) and entered the open arm less often than the control group (P<0.01); the offspring rats in the probiotic group stayed in the open arm for a longer time than the stress group and entered the open arm more often than the stress group (both P<0.05). The discrimination ratio for new to old objects in the offspring rats of the stress group was significantly lower than that of the control group (P<0.01), and the discrimination ratio for new to old objects in the offspring rats of the probiotic group was significantly higher than that of the stress group (P<0.05). The offspring rats in the stress group made significantly more mistakes than the control group (P<0.05), and the offspring rats in the probiotic group made significantly fewer mistakes than the stress group (P<0.05). Compared with the control group, the numbers of Nissl bodies in CA1, CA3, and DG area were significantly reduced in the offspring rats of the stress group (all P<0.001), the number of activated microglia in DG area of hippocampus was significantly increased (P<0.01), the contents of TNF-α and IL-1β in peripheral blood were significantly increased (P<0.05 or P<0.01), the protein expression level of Bcl-2 was significantly down-regulated, and the protein expression levels of Bax and caspase-3 were significantly up-regulated (all P<0.001). Compared with the stress group, the numbers of Nissl bodies in CA1, CA3, and DG area were significantly increased in the probiotic group offspring rats (P<0.001, P<0.01, P<0.05), the number of activated microglia in the DG area of hippocampus was significantly reduced (P<0.05), and the TNF-α and IL-1β levels in peripheral blood were significantly decreased (both P<0.05), the protein expression level of Bcl-2 was significantly up-regulated, and the protein expression levels of Bax and caspase-3 were significantly down-regulated (all P<0.001). Probiotic intervention partially ameliorated anxiety and cognitive impairment in rats offspring of pregnancy stress, and the mechanism may be related to increasing the number of neurons, inhibiting the activation of hippocampal microglia, and reducing inflammation and apoptosis.

The TLR4/NF-κB/MAGI-2 signaling pathway mediates postoperative delirium.

Purpose: To evaluate the TLR4/NF-κB/MAGI-2 signaling pathway in postoperative delirium.Methods: Elderly patients aged 65-80 years who received unilateral hip arthroplasty under subarachnoid anesthesia were included. Pre-anesthesia cerebrospinal fluid and perioperative blood samples were collected. After follow-up, patients were divided into two groups according to the occurrence of postoperative delirium (POD) after surgery. The potential differentially expressed proteins in the two groups were determined by proteomics assay and subsequent western blot validation. A POD model of aged mice was established, and the TLR4/NF-κB/MAGI-2 signaling pathway was determined.Main findings: The IL-1β and TNF-α levels in pre-anesthesia cerebrospinal fluid and postoperative blood were higher in patients who developed POD than in those patients who did not. Compared with non-POD patients, MAGI-2 was highly expressed in POD patients, as validated by proteomics assays and western blotting. Higher p-NF-κB-p65, TLR4 and MAGI-2 in POD patients were detected by western blot. The POD model in aged mice was successfully established and verified by three behavioral tests. Postoperative inflammatory cytokines and the TLR4/NF-κB/MAGI-2 signaling pathway were increased in mice with POD. Inhibiting TLR4/NF-κB/MAGI-2 signaling pathway could reduce postoperative delirium.Conclusions: The TLR4/NF-κB/MAGI-2 signaling pathway mediates POD.

Engineering a curcumol-loaded porphyrinic metal-organic framework for enhanced cancer photodynamic therapy

Photodynamic therapy (PDT), a non-invasive and safe treatment, is a clinical promising alternative strategy for certain cancers. Although PDT can trigger tumor specific immunity, the immunosuppressive tumor microenvironment severely limits the efficacy of photodynamic immunotherapy. Curcumol (CUR), extracted from essential oils of traditional Chinese medicine, has potential immune activation effect for cancer immunotherapy. Considering the fat solubility and volatility hinder the in vivo application of essential oils, a metal-organic framework system (Named as CuTPyP/F68) composed of porphyrin and Cu2+ was constructed for delivering CUR (Named as CUR@CuTPyP/F68). The in vitro assays proved that CUR@CuTPyP/F68 could directly kill tumor cells by the released CUR and singlet oxygen (1O2) generated under laser irradiation (marked as ‘+’). Moreover, CUR@CuTPyP/F68 had superior tumor targeting and retention capabilities, which effectively inhibited tumor growth in vivo with only a single dose. Finally, the mechanism of CUR-mediated enhanced PDT had been firstly proposed: (1) CUR@CuTPyP/F68(+)-treated group exhibited more CD4+ and CD8+ T cells infiltration in tumor tissue; (2) CUR@CuTPyP/F68(+)-treated group exhibited high level of IFN-γ, IL-12 and TNF-α in blood. Overall, we believe the PDT-immunotherapy strategy has great potential for the treatment of breast cancer, and this work will provide a reference for the clinical application of essential oils in cancer immunotherapy.

Clinical effect of Xuebijing combined with thymosinα1 on patients with severe pneumonia complicated with sepsis and its effect on serum inflammatory factors.

This study aimed to research the clinical effect of Xuebijing combined with thymosin α1 on patients with severe pneumonia complicated with sepsis, and its effect on serum inflammatory factors. For this purpose, 81 cases of severe pneumonia complicated with sepsis were collected. All patients were given early treatments. 41 cases who received Xuebijing injection by intravenous drip were selected as the control group. 40 cases who were treated through subcutaneous injection of thymosin α1 based on Xuebijing injection by intravenous drip were selected as the study group. The body temperature, respiration, heart rate, leukocytes, other general conditions, blood gas indexes, serum IL-6, TNF-α and CRP levels, bacterial clearance rate and therapy effect were recorded and compared before and after treatment. Results showed that after treatment, the body temperature, respiration, heart rate, leukocytes and other general conditions of the study group were lower than those in the control group (all p<0.05). The blood gas indexes pH and PaCO2 levels of the study group were lower than those of the control group. The levels of serum interleukin-6 (IL-6), serum tumor necrosis factor α (TNF-α) and C-reactive protein (CRP) in the study group were lower than those in the control group (all p<0.05). The bacterial clearance rate of the study group was lower than that of the control group (all p<0.05). The total effective rate of treatment of patients in the study group was higher than that of patients in the control group (all p<0.05). In general, Thymosin α1 and Xuebijing injection can improve the therapy effect of severe pneumonia complicated with sepsis, improve the hemorheology condition of patients, effectively remove bacteria and reduce the expression level of serum CRP, TNF-α, IL-6, IL-8 and other inflammatory factors in patients, which is worthy of clinical promotion.

Effect of Placenta-Derived Mesenchymal Stromal Cells Conditioned Media on an LPS-Induced Mouse Model of Preeclampsia.

We tested the pro-angiogenic and anti-inflammatory effects of human placenta-derived mesenchymal stromal cells (hPDMSCs)-derived conditioned media (CM) on a mouse model of preeclampsia (PE), a severe human pregnancy-related syndrome characterized by maternal hypertension, proteinuria, endothelial damage, inflammation, often associated with fetal growth restriction (FGR). At d11 of pregnancy, PE was induced in pregnant C57BL/6N mice by bacterial lipopolysaccharide (LPS) intravenous injection. At d12, 300 μL of unconditioned media (control group) or 300 μL PDMSCs-CM (CM group) were injected. Maternal systolic blood pressure was measured from 9 to 18 days of pregnancy. Urine protein content were analyzed at days 12, 13, and 17 of pregnancy. At d19, mice were sacrificed. Number of fetuses, FGR, fetal reabsorption, and placental weight were evaluated. Placentae were analyzed for sFlt-1, IL-6, and TNF-α gene and protein expressions. No FGR and/or reabsorbed fetuses were delivered by PDMSCs-CM-treated PE mice, while five FGR fetuses were found in the control group accompanied by a lower placental weight. PDMSCs-CM injection significantly decreased maternal systolic blood pressure, proteinuria, sFlt-1, IL-6, and TNF-α levels in PE mice. Our data indicate that hPDMSCs-CM can reverse PE-like features during pregnancy, suggesting a therapeutic role for hPDMSCs for the treatment of preeclampsia.

Risk Factors Analysis of Thoracic Trauma Complicated With Acute Respiratory Distress Syndrome and Observation of Curative Effect of Lung-Protective Ventilation.

PurposeTo explore the risk factors of acute respiratory distress syndrome (ARDS) secondary to thoracic trauma and the therapeutic effect of protective lung ventilation in patients with acute respiratory distress syndrome complicated with thoracic trauma.MethodsWe collected 206 patients with thoracic trauma admitted to our hospital from September 2017 to March 2021, counted the incidence of ARDS and analyzed the risk factors of ARDS. To observe the clinical efficacy of the application of lung-protective ventilation therapy in patients with thoracic trauma combined with ARDS.ResultsAmong 206 patients with thoracic trauma, there were 82 cases of combined ARDS, and its incidence was 39.81%. The 82 patients with ARDS were randomly divided into the control group and the observation group with 42 cases each, and different ventilation methods were used for treatment. The results showed that the mechanical ventilation time (MVT) was shorter in the observation group than in the control group, and the incidence of ventilator-associated lung injury (VALI) and case fatality rate (CFR) were lower than those in the control group (P < 0.05). Arterial partial pressure of oxygen (Pa02), arterial blood carbon dioxide partial pressure (PaCO2), and Oxygenation index (arterial partial pressure of oxygen/Fraction of inspiration O2, PaO2/FiO2) were significantly improved better in both groups after treatment; compared with the control group, patients in the observation group had higher Pa02 levels and lower PaCO2 levels at 8 h and 24 h after ventilation (P < 0.05). Multivariate analysis revealed that blunt trauma, massive blood transfusion, procalcitonin (PCT) level, tumor necrosis factor-α (TNF-α) level, and acute physiology and chronic health score (APACHE II) were all risk factors for Thoracic trauma with ARDS.ConclusionRisk factors for the development of ARDS after thoracic trauma are blunt injuries, massive blood transfusion, high PCT and TNF-α levels, and high APACHE II scores, which can be given active interventions in the early stage of clinical practice to improve patient prognosis. The use of protective lung ventilation therapy can improve the clinical outcome of patients with thoracic trauma combined with ARDS, which is important for improving the ventilation effect and respiratory function of patients.

Gastrodin injection alleviates lung injury caused by focal cerebral ischemia in rats through NGF/TrkA pathway-mediated activation of the anti-inflammatory pathway

To investigate the therapeutic mechanism of gastrodin injection for alleviating lung injury caused by focal cerebral ischemia in rats and the role of the NGF-TrkA pathway in mediating this effect. Forty SD rats were equally randomized into normal group, sham-operated group, model group and gastrodin group, and in the latter two groups, rat models of focal cerebral ischemia were established by embolization of the right middle cerebral artery. After successful modeling, the rats were treated with intraperitoneal injection of gastrodin injection at the daily dose of 10 mg/kg for 14 days. After the treatment, the wet/dry weight ratio of the lung tissue was determined, the pathological changes in the lung tissue were observed using HE staining, and the levels of IL-10 and TNF-α in the arterial blood were detected with ELISA. The expressions of NF-κB p65 and TNF-α in the lung tissue were detected with Western blotting, and the expressions of NGF and TrkA were detected using immunohistochemical staining and Western blotting. Compared with the normal control and sham-operated groups, the rats in the model group showed obvious inflammatory lung injury, significantly increased wet/ dry weight ratio of the lungs (P < 0.01), increased TNF-α level in arterial blood (P < 0.01), and significantly up-regulated protein expressions of NF-κB p65 (P < 0.01), TNF-α (P < 0.01), NGF (P < 0.05) and TrkA(P < 0.05) in the lung tissue. Treatment with gastrodin injection obviously alleviated lung inflammation, decreased the wet/dry weight ratio of the lungs (P < 0.05), and significantly lowered TNF-α level (P < 0.01) and increased IL-10 level in the arterial blood in the rat models (P < 0.01); gastrodin injection also significantly decreased the protein expressions of NF-κB p65 and TNF-α (P < 0.05) and up-regulated the expressions of NGF and TrkA in the lung tissue of the rats (P < 0.05). The NGF/TrkA pathway may participate in cerebral ischemia-induced inflammatory lung injury, which can be obviously alleviated by gastrodin through the activation of the anti-inflammatory pathway mediated by the NGF/TrkA pathway.

Mechanism of Propofol-Lidocaine Hydrochloride Nano-Emulsion on Retinal Ganglion Cytopathic Effect in Diabetic Rats

The study drew attention to the influence mechanism of propofol and lidocaine hydrochloride nanoemulsion (NE) in the retinal ganglion cell pathology in diabetic rats. Specifically, the propofollidocaine hydrochloride NE was prepared using the emulsification method. The microscope and laser particle size analyser were used to observe the morphology and particle size of NE, respectively. Also, the viscosity of the NE and the recovery rate of the main ingredient were explored. 45 adult male Wistar rats were randomly divided into control group (PBS control), model group (diabetes model), and test group (diabetes model+propofol-lidocaine hydrochloride NE), with 15 rats in each group. The three groups were compared for the blood glucose, body weight, TNF-α and IL-1β mRNA levels in retinal tissue, and the number and apoptosis rate of ganglion cells. It was found that the average particle size of the NE was 89.76 nm, the maximum absorption wavelength was 280.0 nm, and the viscosity was 106.49 N/m/s. The average recovery rate of propofol in NE was 99.91%, and that of lidocaine hydrochloride was 99.80%. At 12th week after modeling, the blood glucose of the test group was lower versus the model group (P &lt; 0.05); the blood glucose and body weight of rats in the control group were lower than those in the other two groups (P &lt; 0.001). The test group exhibited lower mRNA levels of TNF-α and IL-1β and apoptosis index of retinal ganglion cells versus the model group (P &lt; 0.05). The model group showed a lower number of retinal ganglion cells versus the other two groups (P &lt; 0.05). It was inferred that propofol-lidocaine hydrochloride NE of a small particle size and good syringeability can notably reduce blood glucose, TNF-α and IL-1β mRNA levels, and retinal ganglion cell apoptosis index, and at the same time increase the number of retinal ganglion cells.

EFFECT OF DATE FRUIT (PHOENIX DACTYLIFERA L.) EXTRACT ON TNFα LEVELS AND BRAIN WEIGHT OF ALZHEIMER’S MODEL RATS

Background: Alzheimer's disease (AD) is a neurodegenerative disorder marked by brain inflammation resulted in structural damage and brain dysfunction. Tumor necrosis factor α (TNFα) is a cytokine that plays an important role in inflammation. Dates fruit may help to fight oxidative stress and inflammation in the brain. Objective: To determine the effect of date fruit extracts on blood TNFα levels and brain weight of alzheimer’s model rats. Methods: This research is a laboratory experimental study by post-test only with control group design using alzheimer model rats. This study used 6 treatment groups with simple randomization. Each treatment group was represented by 8 Sprague Dawley rats. The normal control group (KN) was not induced by Hcy and was not given date palm extract, the negative control group (K-) was the Alzheimer's experimental rats which was not given the date palm extract, the positive group was the Alzheimer's experimental rats which was given the Donepezil (K+). Groups P1, P2, P3 were Alzheimer's experimental rats that were given date palm extract at a dose of 200, 400,800 mg / kgBW / day. The effect of date palm extract dosage on TNFα levels and brain weight were analyzed using the One Way Anova test followed by Tukey's post hoc test. Results: The difference in TNFα levels between groups showed a significant difference (p = 0.00). Meanwhile there was no significant difference in brain weight among all groups (p &gt; 0,05). Conclusion: Date palm extract at doses of 200, 400, 800 mg / kgBW can decrease blood TNFα levels of Alzheimer’s model rats.

White saffron (Curcuma mangga Val.) attenuates diabetes and improves pancreatic β-cell regeneration in streptozotocin-induced diabetic rats

Diabetes is a chronic disease caused by an imbalance of insulin release to the bloodstream in response to excessive glucose influx, which causes hyperglycemia. White saffron (Curcuma mangga Val.), an Indonesian aromatic spice, contains essential phytochemicals and has a number of potential health benefits. Here, we examined the effects of oral administration of white saffron powder (WSP): 1.5 and 4.5 g (WSP 1.5 and WSP 4.5) in streptozotocin (STZ)-induced diabetic rats. WSP was administered orally on a daily basis for one month and its antidiabetic, anti-inflammatory, and antioxidative effects were investigated by measuring the concentrations of blood glucose, insulin, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), interleukin 8 (IL-8), malondialdehyde (MDA), and superoxide dismutase (SOD) activity. In response to high WSP intervention (WSP 4.5), treated rats showed increased insulin level and SOD activity and reduced blood glucose, IL-6, IL-8, TNF-α, and MDA levels, which were closely related to the positive control (PC) group. In addition, Hematoxylin and Eosin (H&E) staining of the pancreatic tissues showed that WSP 4.5-treated rats had significant improvement in β-cell regeneration, which taken together reflected the antidiabetic potential of Curcuma mangga Val.

Dexamethasone enhances glucose uptake by SGLT1 and GLUT1 and boosts ATP generation through the PPP-TCA cycle in bovine neutrophils.

BackgroundClinical dexamethasone (DEX) treatment or stress in bovines results in extensive physiological changes with prominent hyperglycemia and neutrophils dysfunction.ObjectivesTo elucidate the effects of DEX treatment in vivo on cellular energy status and the underlying mechanism in circulating neutrophils.MethodsWe selected eight-month-old male bovines and injected DEX for 3 consecutive days (1 time/d). The levels of glucose, total protein (TP), total cholesterol (TC), and the proinflammatory cytokines interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α in blood were examined, and we then detected glycogen and adenosine triphosphate (ATP) content, phosphofructosekinase-1 (PFK1) and glucose-6-phosphate dehydrogenase (G6PDH) activity, glucose transporter (GLUT)1, GLUT4, sodium/glucose cotransporter (SGLT)1 and citrate synthase (CS) protein expression and autophagy levels in circulating neutrophils.ResultsDEX injection markedly increased blood glucose, TP and TC levels, the Ca2+/P5+ ratio and the neutrophil/lymphocyte ratio and significantly decreased blood IL-1β, IL-6 and TNF-α levels. Particularly in neutrophils, DEX injection inhibited p65-NFκB activation and elevated glycogen and ATP contents and SGLT1, GLUT1 and GR expression while inhibiting PFK1 activity, enhancing G6PDH activity and CS expression and lowering cell autophagy levels.ConclusionsDEX induced neutrophils glucose uptake by enhancing SGLT1 and GLUT1 expression and the transformation of energy metabolism from glycolysis to pentose phosphate pathway (PPP)-tricarboxylic acid (TCA) cycle. This finding gives us a new perspective on deeper understanding of clinical anti-inflammatory effects of DEX on bovine.

Platelet Toll-like Receptor 4-Related Innate Immunity Potentially Participates in Transfusion Reactions Independent of ABO Compatibility: An Ex Vivo Study.

The role of platelet TLR4 in transfusion reactions remains unclear. This study analyzed platelet TLR4 and certain damage-associated molecular patterns (DAMPs) and evaluated how ABO compatibility affected TLR4 expression after a simulated ex vivo transfusion. A blood bank was the source of donor red blood cells. Blood from patients undergoing cardiac surgery was processed to generate a washed platelet suspension to which the donor blood was added in concentrations 1, 5, and 10% (v/v). Blood-mixing experiments were performed on four groups: a 0.9% saline control group (n = 31); a matched-blood-type mixing group (group M, n = 20); an uncross-matched ABO-specific mixing group (group S, n = 20); and an ABO-incompatible blood mixing group (group I, n = 20). TLR4 expression in the platelets was determined after blood mixing. We evaluated levels of TLR4-binding DAMPs (HMGB1, S100A8, S100A9, and SAA), lipopolysaccharide-binding protein, and endpoint proteins in the TLR4 signaling pathway. In the M, S, and I groups, 1, 5, and 10% blood mixtures significantly increased TLR4 expression (all p < 0.001) in a concentration-dependent manner. Groups M, S, and I were not discovered to have significantly differing TLR4 expression (p = 0.148). HMGB1, S100A8, and S100A9 levels were elevated in response to blood mixing, but SAA, lipopolysaccharide-binding protein, TNF-α, IL-1β, and IL-6 levels were not. Blood mixing may elicit innate immune responses by upregulating platelet TLR4 and DAMPs unassociated with ABO compatibility, suggesting that innate immunity through TLR4-mediated signaling may induce transfusion reactions.

Acupuncture Can Regulate the Distribution of Lymphocyte Subsets and the Levels of Inflammatory Cytokines in Patients With Mild to Moderate Vascular Dementia.

Background: Vascular dementia (VD) is the second most common type of dementia after Alzheimer’s disease, but there is a lack of definitive treatment for VD. Acupuncture treatment is effective in improving the cognitive impairment and behavioral capacity of patients with VD. In recent years, more studies indicated that peripheral inflammation and abnormal peripheral immune function may aggravate neuroinflammation and cognitive dysfunction. However, there are few studies about the acupuncture and the abnormal peripheral immune function of VD. Also, few studies concern the regulating effect of acupuncture on peripheral immunity of patients with VD.Objective: The aim of this study was to explore the effect of the “sanjiao” acupuncture method on peripheral immunity of patients with mild to moderate VD.Methods: A total of 30 patients with VD were involved in the acupuncture group (AG), which was treated with the “sanjiao” acupuncture method once a day for six times a week and lasted for 12 weeks, and 30 healthy elderly people were assigned to the normal group (NG), which had no treatment. The distribution of lymphocyte subsets and the levels of some inflammatory cytokines in the peripheral blood of subjects were evaluated using the flow cytometry (FCM) and the enzyme-linked immunosorbent assay (ELISA).Results: A total of 60 subjects were involved in this study, while 58 subjects completed the entire trial. Before treatment, the levels of CD3+ T, CD4+ T cells, CD4+/CD8+, Tregs, B cells, IFN-γ, and IL-10 in patients with VD were significantly decreased compared with the normal group (all P < 0.05 or P < 0.01). The level of TNF-α in peripheral blood of patients with VD was significantly increased (P < 0.01). After acupuncture treatment, the levels of CD3+ T, CD4+ T cells, and IFN-γ were significantly increased (all P < 0.05 or P < 0.01). The level of TNF-α was significantly decreased (P < 0.01). The proportion of Tregs was increased (P < 0.01), but it was still lower than that of the normal group (P < 0.05).Conclusion: The acupuncture method can increase the proportion of CD3+, CD4+ T cells, and Tregs in peripheral blood of patients with VD. And, it reduces the levels of pro-inflammatory factor TNF-α, which achieves the anti-inflammatory effects and immunostimulation. It suggests that acupuncture can improve the peripheral immune dysfunction of patients with VD by regulating the distribution of lymphocyte subsets and the levels of inflammatory cytokines.Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR-IOR-17012052].

Associations of maternal insulin resistance during pregnancy and offspring inflammation at birth and at 5 years of age: A prospective study in the Gen3G cohort

BackgroundMaternal insulin resistance is associated with greater maternal inflammation during pregnancy, but its relation to inflammation in offspring remains unclear. The goal of this study was to assess the relationship of gestational insulin resistance and other glycemic markers with offspring inflammation at birth and at 5 years of age. MethodsWe included 653 mother–child pairs from the prospective pre-birth Gen3G cohort. We examined maternal insulin and glucose levels measured during the second trimester of pregnancy, from which we derived the homeostatic model of assessment of insulin resistance (HOMA-IR) and the Matsuda index. We assessed offspring inflammation at birth and at 5 years of age by measuring plasma tumor necrosis factor-α (TNFα) concentrations. We conducted multivariable regression models to evaluate associations of each insulin and glucose marker with offspring inflammation adjusting for confounding variables. ResultsHigher levels of fasting insulin were associated with lower TNFα levels at birth (−0.78, 95% CI [−1.45, −0.11]), in the fully adjusted model. We observed similar associations with the HOMA-IR and opposite direction with the Matsuda index. We did not find persistence of the association between maternal fasting insulin and offspring TNFα at 5 years of age. ConclusionsGreater maternal insulin resistance during pregnancy was associated with lower cord blood TNFα levels in newborns. The mechanisms by which maternal insulin resistance may promote lower inflammatory levels in newborns are not fully understood and more research is needed to deepen our understanding of these mechanisms.

Humanized anti‑TLR4 monoclonal antibody ameliorates lipopolysaccharide‑related acute kidney injury by inhibiting TLR4/NF‑κB signaling.

A humanized anti-Toll-like receptor 4 (TLR4) monoclonal antibody (mAb) was previously produced using phage antibody library technology, and it was found that the mAb could effectively ameliorate lipopolysaccharide (LPS)-induced damage in macrophages. The present study investigated the protective effects exerted by the humanized anti-TLR4 mAb against LPS-induced acute kidney injury (AKI), as well as the underlying mechanisms. Female C57BL/6 mice were randomly divided into four groups (n=8 per group): i) Control; ii) LPS; iii) LPS + humanized anti-TLR4 mAb (1 µg/g); and iv) LPS + humanized anti-TLR4 mAb (10 µg/g). Serum creatinine, blood urea nitrogen, IL-6, TNFα and IL-1β levels were then examined, followed by renal pathology assessment, immunohistochemical staining, reverse transcription-quantitative PCR and western blotting to assess apoptosis/survival/inflammation-related molecules and kidney injury molecule (KIM)-1. The humanized anti-TLR4 mAb successfully ameliorated LPS-induced AKI and renal pathological damage. The humanized anti-TLR4 mAb also dose-dependently suppressed LPS-induced elevations in serum IL-6, TNFα and IL-1β, and decreased the renal expression levels of myeloid differentiation primary response 88 (MyD88), IKKα/β, IκB, p65 and KIM-1. Compared with the LPS group, renal Bax and KIM-1 expression levels were significantly downregulated, and Bcl-2 expression was notably upregulated by the humanized anti-TLR4 mAb. Moreover, the humanized anti-TLR4 mAb also significantly decreased the protein expression levels of MyD88, phosphorylated (p)-IKKα/β, p-IκB and p-p65 in the renal tissues compared with the LPS group. Therefore, the present study indicated that the anti-inflammatory effects of the humanized anti-TLR4 mAb against LPS-related AKI in mice were mediated via inhibition of the TLR4/NF-κB signaling pathway.

Relationship Between Blood Cytokine Levels, Psychological Comorbidity, and Widespreadness of Pain in Chronic Pelvic Pain.

Background: Low-grade inflammation has been implicated in the etiology of depression, long-term fatigue and chronic pain. TNFα and IL-6 are perhaps the most studied pro-inflammatory cytokines in the field of psychoneuroimmunology. The purpose of our study was to further investigate these relationships in patients with chronic pelvic pain specifically. Using plasma samples from a large, well-described cohort of patients with pelvic pain and healthy controls via the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network, we examined the relationship between TNFα and IL-6 and comorbid psychological symptoms. We also investigated the relationship between IL-8 and GM-CSF, and widespreadness of pain.Methods: We included baseline blood samples in the analyses, 261 patients (148 women) and 110 healthy controls (74 women). Fourteen pro- and anti-inflammatory or regulatory cytokines were analyzed in a Luminex® xMAP® high-sensitivity assay. We used regression models that accounted for known factors associated with the outcome variables to determine the relationship between cytokine levels and clinical measures.Results: There were no statistical differences in cytokine levels between patients and healthy controls when controlling for age. In patients, TNFα was significantly associated with levels of fatigue (p = 0.026), but not with pain intensity or depression. IL-6 was not significantly related to any of the outcome variables. Women with pelvic pain showed a negative relationship between IL-8 and widespreadness of pain, while men did not (p = 0.003). For both sexes, GM-CSF was positively related to widespreadness of pain (p = 0.039).Conclusion: Our results do not suggest low-grade systemic inflammation in chronic pelvic pain. Higher TNFα blood levels were related to higher fatigue ratings, while higher systemic GM-CSF levels predicted more widespread pain. Our study further suggests a potentially protective role of IL-8 with regard to with regard to the widepreadness of pain in the body, at least for women.

Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) and ADMSC-Derived Secretome Expedited Wound Healing in a Rodent Model - A Preliminary Study.

IntroductionThe biological role of mesenchymal stem cells (MSCs) in wound healing has been demonstrated. However, there were limited studies on the healing effect of secretome which consists of many biological factors secreted by MSCs. In this study, we aimed to compare the therapeutic effects of secretome with MSCs on facilitating wound healing.MethodsGreen fluorescent protein labelled adipose-derived MSCs (GFP-ADMSCs) or secretome was injected in the full-thickness skin excision model on SD rats. The wound healing process was evaluated by calculating the healing rate and the histological examinations on skin biopsy. The cell viability, proliferation and mobility of the rat dermal fibroblasts were compared after different treatments. The inflammatory response in macrophages was indicated by the level of nitric oxide (NO) and inflammatory cytokines through NO assay and ELISA.ResultsOn day 5 and day 14, both MSCs and secretome accelerated the wound healing, secretome further enhanced the process. GFP-MSCs were detected 10 days after transplantation. The level of IL-6 and TNF-α in blood was reduced after MSCs and secretome treatments. The expressions of VEGF and PCNA were increased after treatment, higher intensity of VEGF was observed in secretome-injected tissue. The concentrations of total protein and VEGF in secretome were 2.2 ± 0.5 mg/mL and 882.0 ± 72.7 pg/mL, respectively. The cell viability and proliferation of FR were promoted significantly after the treatment. The scratch test showed that secretome accelerated the wound healing speed. Secretome reduced the metabolism of macrophages remarkably, but it did not decrease the level of macrophage-secreted NO. The expression of the pro-inflammatory cytokines (IL-6, MCP-1 and TNF-α) was downregulated significantly.ConclusionOur study indicated both MSCs and MSCs-derived secretome enhanced the wound healing process in early phase. Secretome further promoted the healing effects through promoting the fibroblast proliferation and migration and suppressing the inflammatory response.

A Prospective Study of Novel Therapeutic Targets Interleukin 6, Tumor Necrosis Factor α, and Interferon γ as Predictive Biomarkers for the Development of Posttraumatic Epilepsy

BackgroundPosttraumatic epilepsy (PTE) is a serious and debilitating consequence of traumatic brain injury (TBI). Sometimes, the management of PTE becomes a challenging task on account of its resistance to existing antiepileptic drugs and often contributes to poor functional and psychosocial outcomes after TBI. We investigated the role of inflammatory markers interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and interferon γ (INF-γ) in predicting the development of PTE.MethodsA prospective analysis was performed of 254 patients who were admitted with head injury to our hospital, 35 of whom had posttraumatic epilepsy (32 males and 3 females); 30 adults (28 men, 2 women) with a similar demographic profile were selected randomly as control individuals. Blood levels of TNF-α, IL-6, and INF-γ were evaluated in all participants.ResultsIL-6 levels were significantly higher in the PTE group (121.36 pg/mL; standard deviation [SD], 89.23) than in the nonseizure group (65.30 pg/mL; SD, 74.75; P = 0.01), whereas there was no significant difference between the seizure group (11.42 pg/mL; SD, 7.84) and the nonseizure groups (10.58 pg/mL; SD, 7.84) in terms of TNF-α level (P = 0.343). The level of INF-γ in the seizure group tended to be higher (mean, 1.88 pg/mL, SD, 2.13 in seizure group vs. 1.10 pg/mL, SD, 1.45 in the nonseizure group); however, no statistically significant difference was detected among the 2 groups (P = 0.09).ConculsionsPosttraumatic epilepsy has a strong association with an increased level of IL-6 in the blood. INF-γ may or may not be associated with PTE. However, TNF-α was not associated with PTE.

Synergistic Mechanism of Interferon alpha-1b, Interleukin-2 and Thalidomide for Immune Regulation in Patients with Acute Myeloid Leukemia

To explore the synergistic immunomodulatory mechanism of interferon alpha-1b, interleukin-2 and thalidomide (ITI) regimen on patients with acute myeloid leukemia (AML). Sixty eight untreated de novo or relapsed or refractory or maintenance therapy patients with AML admitted in the Affiliated Cancer Hospital of Zhengzhou University and the other 11 medical units from March 2016 to May 2019 were treated with ITI regimen. Peripheral blood specimen per patient was collected into EDTA-K3 anticoagulation vacuum tube before the administration of ITI and 3 months after the treatment; peripheral blood lymphocyte subsets and perforin and Granzyme B expression were analyzed by using flow cytometry; the levels of VEGF, IFN-γ, TNF-α and IL-6 in the plasma were detected by using a cytometric bead array. Thirty-five healthy subjects from the hospital physical examination centre were selected as normal controls. The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of perforin and Granzyme B of NK cells in the peripheral blood of patients with hematological malignancies were lower than those of healthy controls. The level of VEGF, IL-6 and TNF-α in the peripheral plasma were higher than those of the healthy control group, and the difference was statistically significant. The level of IFN-γ was lower, and the difference was not statistically significant. The ratio of CD4+/CD8+ T cells, the percentage of NK cells, the expression of Granzyme B and Perforin of NK cells in peripheral blood were higher after the therapy of thalidomide combined with rhIFNα-1b for 3 months as compared with those before treatment of ITI, the level of the IFN-γ in peripheral plasma was higher while that of VEGF was lower, the difference was statistically significant; after treatment, the ratio of CD3+ CD4+ and CD3+ CD8+ lymphocytes and the level of TNF-α in peripheral blood were higher those that before treatment, IL-6 was lower, while the difference was not statistically significant. The ITI regimen can raise the ratio of CD4+/CD8+ T cells and the percentage of natural killer cells, also, can enhance the generation of perforin and granzyme B and the concentration of IFN-γ as well as inhibit the generation of VEGF, suggesting that these activities may enhance the antitumour capacity of patients with AML.