Blood IL-6 Research Articles

The therapeutic potential of mesenchymal stem cells in COVID-19: Present and future

Introduction: Coronavirus disease 2019 (COVID-19) was first reported in 2019 and has since become a health concern due to its rapid spread and high mortality rate. With the discovery of vaccines, there has been a reduction in disease occurrence, transmission, mortality, and morbidity in a population. However, with the emergence of newvariants, the available vaccines show varying efficiencies depending on the population and variants, while the present drugs may lose their effectiveness, hence the urgent need to explore effective therapies. Mesenchymal stemcells (MSCs) have been widely studied for their anti-inflammatory and immunomodulatory effects as COVID-19treatment and shown their potential to improve the condition of COVID-19 patients. This systematic review aims to assess the therapeutic potential of MSCs as anti-inflammatory and immunomodulatory agent in COVID-19. Materials and Methods: A literature search is performed on PubMed, ScienceDirect, ProQuest, and Google Scholar and potentially relevant studies to review, based on the inclusion and exclusion criteria we have determined.We identified 14,090 publications from our search and excluded duplicates as well as irrelevant studies from title,abstract, and full-text screening. Data extraction and analysis were then performed in the 20 eligible studies. Results and Discussion: Results show that MSCs improve immune system dysregulation throughimmunomodulatory and anti-inflammatory effects, through reducing blood C-reactive protein (CRP) and IL-6 levels. Conclusion: We conclude that MSC is one of the promising treatments in COVID-19 regardless of variants. Graphical Abstract

A randomized phase II study of full dose gemcitabine versus reduced dose gemcitabine and nab-paclitaxel in vulnerable patients with non-resectable pancreatic cancer (DPCG-01)

BackgroundAccording to current evidence, the best treatment for fit patients with non-resectable pancreatic cancer (PC) is combination chemotherapy, whereas frail patients are recommended gemcitabine (Gem) monotherapy. Randomized controlled trials in colorectal cancer and a post-hoc analysis of gemcitabine and nab-paclitaxel (GemNab) in PC suggest, however, that reduced dose of combination chemotherapy may be feasible and more efficient compared to monotherapy in frail patients. The aim of this study is to investigate whether reduced dose GemNab is superior to full dose Gem in patients with resectable PC, who are not candidates for full dose combination chemotherapy in first line.MethodsThe Danish Pancreas Cancer Group (DPCG)-01 trial is a national multicenter prospective randomized phase II trial. A total of 100 patients in ECOG performance status 0–2 with non-resectable PC, not candidate for full dose combination chemotherapy in first line, but eligible for full dose Gem, will be included. Patients are randomized 1:1 to either full dose Gem or GemNab in 80% of recommended dose.The primary endpoint is progression-free survival. Secondary endpoints are overall survival, overall response rate, quality of life, toxicity and rate of hospitalizations during treatment. The correlation between blood inflammatory markers, including YKL-40 and IL-6, circulating tumor DNA, and tissue biomarkers of resistance to chemotherapy and outcome will be explored. Finally, the study will include measures of frailty (G8, modified G8, and chair-stand-test) to assess whether scoring would enable a personalized allocation to different treatments or indicates a possibility for interventions.DiscussionSingle-drug treatment with Gem has for frail patients with non-resectable PC been the main treatment option for more than thirty years, but the impact on outcome is modest. If improved results and sustained tolerability with reduced dose combination chemotherapy can be shown, this could change the future practice for this increasing group of patients.Trial registrationClinicalTrials.gov Identifier: NCT05841420.Secondary Identifying No: N-20210068.EudraCT No: 2021–005067-52.Protocol version: 1.5, 16-MAY-2023.

#4153 OUTCOMES OF COVID-19 INFECTION AMONG MAINTENANCE HEMODIALYSIS PATIENTS – EXPERIENCE FROM THE FIRST COVID-19 HOSPITAL IN SERBIA

Abstract Background and Aims Patients on maintenance hemodialysis (HD) might be particularly vulnerable to severe COVID-19 due to their older age and numerous comorbidities. Furthermore, their specific treatment regimen substantially exposes them to the risk of infection. The abrupt onset of the novel coronavirus disease (COVID-19) pandemic required prompt action and immediate reorganization of healthcare services while maintaining the necessary standard of treatment for chronic patients. In this study, we aimed to analyze clinical features and risk factors for poor outcomes in maintenance HD patients with COVID-19. Method We analyzed data for 226 maintenance HD patients (67.7% male, age range 25 – 90 years, time on dialysis 6 – 278 months) who contracted COVID-19 in their original dialysis units and were therefore transferred for further HD treatment to the first hospital in Serbia transformed to exclusively admit COVID-19 patients at the onset of the epidemic. According to the local protocol, all patients were hospitalized while being dialyzed. Data were collected from clinical charts and patient histories for the period between March 19, 2020, and March 19, 2022, and analysed with SPSS software, version 22 (IBM Corporation, New York, USA). Results A total of 1384 HD treatments were performed in 226 patients (6.12±4.50, range 1 – 34 per patient). Most patients (98.7%) had at least one comorbidity: hypertension (68.1%), diabetes (26.1%), cardiovascular disease (16.4%), cerebrovascular disease (7.5%), malignancy (9.3%), chronic respiratory disease (4.0%) or autoimmune disease (1.8%). The average number of comorbidities was 1.9±1.0 (range 0 – 4). Only 2.2% of all patients were vaccinated. Most patients (78.0%) had bilateral pneumonia upon admission, 15.3% had normal pulmonary X-ray, 5.1% had unilateral pneumonia and 1.7% had ARDS. 34% of the patients required mechanical ventilation. Fifty-seven patients (25.2%) received corticosteroid therapy, 5.3% were treated with chloroquine, 2.7% received antiviral therapy and 1.8% were administered IL6 antagonist. The overall mortality rate was 39.4%. Patients who died were significantly older (67.6±12.4 vs 63.2±12.7; p = 0.012), more often had cardiovascular disease (p = 0.046) and bilateral pneumonia (p<0.001), had worse CT severity score (13.0±5.1 vs 9.2±5.0; p<0.001) and required invasive mechanical ventilation (p<0.001) and had fewer HD treatments performed during hospitalization (5.1±4.8 vs 6.8±4.2; p = 0.007). They also had significantly higher white blood cells count (8.3±5.3 vs 5.6±2.9; p<0.001), serum urea (24.9±12.0 vs 21.1±8.4 mmol/L; p = 0.01), LDH (119.8±95.5 vs 63.9±72.9 IU/L; p<0.001), CRP (157.8±239.1 vs 61.1±94.8 mg/dL; p = 0.008), IL-6 (14.9±36.0 vs 2.8±7.3 pg/mL; p = 0.004), and Ddimer (372.3±294.1 vs 240.7±101.5 ng/mL; p<0.001). Multiple logistic regression showed a significant association between mortality and older age (OR 1.11, 95% CI 1.04-1.18, p = 0.001), need for mechanical ventilation (OR 43.1, 95% CI 9.5-198.6; p<0.001), higher CT severity score (OR 1.16, 95% CI 1.07 – 1.25; p<0.001), fewer HD procedures performed (OR 0.80, 95% CI 0.69-0.93; p = 0.003), and higher D-dimer levels (OR 1.00, 95% CI 1.00 - 1.01; p = 0.012). Conclusion Maintenance HD patients are considered a high-risk population for contracting COVID-19 and developing a severe form of the disease. Older age, higher CT severity score

Efficacy and safety of locally applied vancomycin powder injection for the prevention of prosthetic joint infection

Purpose: To determine the efficacy and safety of locally-applied vancomycin powder injection as precaution against prosthetic joint infection (PJI).
 Methods: A total of ninety subjects on admission in Department of Limb and Joint Surgery, PLA Medical Center, who underwent surgery for arthroplasty of knee and hip, were selected for this study. They were divided into two groups comprising control group (n = 45) given routine preventive antibiotic therapy as well as treatment group (n = 45) which received routine prophylactic antibiotics in combination with vancomycin therapy. PJI and the incidence of adverse reactions within 3 months after surgery were recorded. Body temperature of the patients was recorded with a thermometer. The number of neutrophils was measured by flow cytometry, while the expression levels of IL-6 and hs-CRP in peripheral blood were determined using enzyme-linked immunosorbent assay (ELISA) preoperatively and at 24, 72 and 168 h post- therapy.
 Results: At 90 days post-therapy, there was obviously significant reduction in the degree of PJI in the vancomycin-treated subjects compared with control group (p > 0.05). Moreover, within 3 days, normothermia, lowered neutrophil population and downregulated expressions of Il-6 and hs-CRP were seen in the vancomycin group, when compared to control subjects (p < 0.05). However, there was no significant difference in the incidence of adverse reactions between the treatment and control groups after therapy (p > 0.05).
 Conclusion: Topical application of vancomycin powder injection is safe, and regulates the body temperature of PJI patients in the short-term after surgery. Moreover, it decreases the levels of inflammatory indices. However, further clinical trials should be carried out prior to application in clinical practice.

A high-concentrate diet induces mitochondrial dysfunction by activating the MAPK signaling pathway in the mammary gland of dairy cows

Subacute rumen acidosis can lead to mastitis in dairy cows. Mitochondrial dysfunction is closely related to the inflammatory response. This experiment was conducted to investigate the effects of a high-concentrate diet on mammary gland inflammation and mitochondrial damage in dairy cows. Twelve Holstein dairy cows in mid-lactation were randomly divided into 2 groups and fed a 40% concentrate (low concentrate, LC) diet or a 60% concentrate (high concentrate, HC) diet. Cows were fed individually, and the experiment lasted for 3 wk. After the experiment, mammary gland tissue, blood, and rumen fluid were collected. Compared with the LC diet, the HC diet significantly decreased rumen pH; the pH was <5.6 for more than 3 h. The HC diet also increased the concentration of LPS in the blood (7.17 ± 1.25 µg/mL vs. 12.12 ± 1.26 µg/mL), which indicated that feeding the HC diet successfully induced subacute rumen acidosis. The HC diet also increased the concentration of Ca2+ (34.80 ± 4.23 µg/g vs. 46.87 ± 7.24 µg/g) in the mammary gland and upregulated the expression of inflammatory factors IL-6 (1,128.31 ± 147.53 pg/g vs. 1,538.42 ± 241.38 pg/g), IL-1β (69.67 ± 5.86 pg/g vs. 90.13 ± 4.78 pg/g), and tumor necrosis factor-α (91.99 ± 10.43 pg/g vs. 131.75 ± 17.89 pg/g) in mammary venous blood. The HC diet also increased the activity of myeloperoxidase (0.41 ± 0.05 U/g vs. 0.71 ± 0.11 U/g) and decreased the content of ATP (0.47 ± 0.10 µg/mL vs. 0.32 ± 0.11 µg/mL) in the mammary gland. In addition, phosphorylation of JNK (1.00 ± 0.21 vs. 2.84 ± 0.75), ERK (1.00 ± 0.20 vs. 1.53 ± 0.31), and p38 (1.00 ± 0.13 vs. 1.47 ± 0.41) and protein expression of IL-6 (1.00 ± 0.22 vs. 2.21 ± 0.27) and IL-8 (1.00 ± 0.17 vs. 1.96 ± 0.26) were enhanced in cows of the HC group, indicating that the mitogen-activated protein kinase (MAPK) signaling pathway was activated. Compared with the LC diet, the HC diet reduced the protein expression of mitochondrial biogenesis-related proteins PGC-1α (1.00 ± 0.17 vs. 0.55 ± 0.12), NRF1 (1.00 ± 0.17 vs. 0.60 ± 0.10), TFAM (1.00 ± 0.10 vs. 0.73 ± 0.09), and SIRTI (1.00 ± 0.44 vs. 0.40 ± 0.10). The HC diet promoted mitochondrial fission and inhibited mitochondrial fusion by reducing protein expression of MFN1 (1.00 ± 0.31 vs. 0.49 ± 0.09), MFN2 (1.00 ± 0.19 vs. 0.69 ± 0.13), and OPA1 (1.00 ± 0.08 vs. 0.72 ± 0.07), and by increasing that of DRP1 (1.00 ± 0.09 vs. 1.39 ± 0.10), MFF (1.00 ± 0.15 vs. 1.89 ± 0.12), and TTC1/FIS1 (1.00 ± 0.08 vs. 1.76 ± 0.14), leading to mitochondrial dysfunction. The HC diet increased mitochondrial permeability by upregulating the protein expression of VDAC1 (1.00 ± 0.42 vs. 1.90 ± 0.44), ANT (1.00 ± 0.22 vs. 1.27 ± 0.17), and CYPD (1.00 ± 0.41 vs. 1.82 ± 0.43). Taken together, these results indicated that feeding the HC diet induced mitochondrial damage via the MAPK signaling pathway in the mammary gland of dairy cows.

Preterm birth prediction in pregnant women over than 35 years. Observational analytical cohort study.

Introduction. Premature birth can occur at any age; however, it is important to note that the risk of preterm birth can vary based on several factors, including the mother’s medical history, general health, and lifestyle. There is thought to be a relationship between maternal age and the risk of preterm birth, although the exact nature of this relationship may vary. At the same time, it is considered for ages over 35, an increased risk factor for the evolution of pregnancies with complications. Pregnant women over 35 face a higher risk of premature birth. This increased risk may be associated with age-related factors such as underlying health conditions, higher rates of multiple pregnancies (due to fertility treatments), and potential placental dysfunction. Material and methods. In the given study, the biomarkers IL-6, IL-8, IL-10, IL-12, SDF-1α and VEGF in amniotic fluid (AF) and maternal blood were investigated, considering the above as predictive of premature birth outcome. At the same time, the oxidative stress status of maternal blood and amniotic fluid collected in the second trimester of pregnancy was identified. Results. In the research, we obtained statistically significant increases in the biomarkers AAT-isopropyl, G-GTP, HPL-isopropyl from the amniotic fluid taken from pregnant women over 35 years of age in the second trimester of pregnancy in those pregnant women who had a preterm birth. In the serum of pregnant women with premature birth, an increase in the concentration of carnosine-histidine peptides, G-GTP, GR and SH (thiol) groups was identified, and the decrease in the values of SDF 1α, HPL – hexane and IL-12 were statistically significant in the serum pregnant women compared to that of the amniotic fluid. Identifying the values of biochemical mediators during pregnancy can be a method of predictive diagnosis Conclusions. Our study shows the relationship between some concentrations of oxidative stress biomarkers (AAT-isopropyl, HPL-isopropyl and G-GTP, IL-12) in amniotic fluid, and values of (Carnosine Histidine Peptide, GR and SH and SDF-1α) in the serum of pregnant women, in the second trimester of pregnancy.

Association of prenatal obesity and cord blood cytokine levels with allergic diseases in children: A 10-year follow-up cohort study

Background and aimAlthough studies have associated elevated prenatal obesity with increased risk of various diseases in offspring, little is known regarding the immune system. The aim of this study was to evaluate the relationship between prenatal obesity and levels of cytokines in umbilical cord blood and development of allergic disease during the first 10 years of life in an offspring. MethodsA cohort of term infants born at the ShaoXing Women and Children Hospitals in China in 2011 was enrolled in this study. Flow cytometry was performed to measure levels of various cord blood cytokines, namely IL1β, IL2, IL10, IL6, IL8, IL17, IL12, TNF-α and IFN-γ. Next, logistic regression was used to explore the association of prenatal BMI with the development of allergic disease. The relationship between levels of each cord blood cytokine with prenatal BMI, and allergic disease development was tested using linear and logistic regression analyses, respectively. ResultsAfter 10 years of follow-up, higher prenatal BMI was significantly associated with development of allergic disease in children (HR = 2.45, 95% CI:1.08–5.57, P = 0.033). We also adjusted for maternal age, education and infant gender, and found that prenatal BMI was significantly associated with higher levels of IL12 (P = 0.023) and IL1β (P = 0.049) in cord blood. Moreover, we adjusted for maternal age, education, allergic dermatitis, gestation age and infant gender, and found that increase in each unit (1.26 pg/ml) in IL17 was associated with a 55.5% higher risk of allergic disease in 10-year-old children (HR = 1.55, 95%Cl: 0.99–2.45, P = 0.056). Meanwhile, after adjusting for maternal age, education level, gestation age, prenatal BMI, gestational weight gain, infant gender and birthweight, we found that for every unit increase in IL10, IL6 and IL1β, the risk of overweight/obesity in children after 10-year follow-up increased by 18.7% (HR = 1.19, 95%Cl: 1.01–1.40, P = 0.042), 13.9% (HR = 1.14, 95%Cl: 1.02–1.27, P = 0.021) and 41.3% (HR = 1.41, 95%Cl: 1.02–1.95, P = 0.036), respectively. ConclusionsPrenatal obesity was positively correlated with allergic diseases in offspring. Cord blood cytokine may play mediating roles in the associations of prenatal obesity with offspring allergic diseases.

An exploratory clinical trial on intra-lumbar injection of B7H3-specific allogeneic universal CAR-T cells in patients with recurrent high-grade gliomas.

2043 Background: No standard-of-care treatment was established for recurrent high-grade gliomas (rHGGs) yet. Intrathecal infusion of autologous chimeric antigen receptor-T (CAR-T) cells has displayed potent anti-tumor activity in one patient (Brown et al. N Engl J Med 2016). We evaluated the safety, efficacy, pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of B7H3-specific allogeneic universal CAR-T (B7H3 UCAR-T) cells in patients with rHGGs. Methods: Eligible patients who had received standard treatment for newly-diagnosed high-grade gliomas but failed were treated with 2.5×107 B7H3 UCAR-T cells via intra-lumbar injection every month. Eligibility criteria included histologic and/or cytologic rHGGs, B7H3-positive antigen expression rate of &gt;50% in tumor tissue and Karnofsky performance status (KPS) ≥ 40. The primary endpoint was treatment-related adverse events (TAEs); secondary endpoints include overall survival (OS) and objective response rate (ORR); exploratory endpoints were PK and PD characteristics of B7H3 UCAR-T cells. Results: In the 7 patients enrolled, 4 (57.1%) were female, 5 (71.4%) glioblastoma (WHO Grade IV) and 2 (28.6%) diffuse midline glioma (WHO Grade IV), and the mean age was 40.4 years. The most common reported TAEs were increased cerebrospinal fluid (CSF) IL-6 (7/7, 100%), headache (7/7, 100%), increased blood IL-6 (6/7, 86%) and fever (6/7, 86%). No adverse events of grade 3 or greater related to B7H3 UCAR-T cells were reported. All the adverse events recovered or relieved after treatment. No typical or severe systemic cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS) or graft versus host disease (GvHD) were observed during the study period. Based on Immunotherapy Response Assessment in Neuro-Oncology (iRANO), 3 of 7 patients had response to therapy (42.9%; 95% CI: 15.8 to 75.0) and 7 of 7 patients were stable disease (100%; 95% CI: 64.6 to 100). As of cutoff date (January 30, 2023), two patients died. The median OS was not reached (95% CI: 12.9 to could not be estimated). The median follow-up for OS was 15.6 months (95% CI: 14.7 to 16.1). OS rate at 12 months was 85.7% (95% CI: 48.7 to 97.4). The CAR DNA copy numbers increased 1 day after each administration and persist at least 1 month in cerebrospinal fluid. IL-6 concentrations in CSF and peripheral blood increased after each administration while the change and concentration values in peripheral blood were much lower than those in CSF. Conclusions: In patients with rHGGs, B7H3 UCAR-T cells was not associated with any toxic effects of grade 3 or higher. B7H3 UCAR-T cells resulted in a significantly longer overall survival and a higher objective response rate than history data. B7H3 UCAR-T cells persist well in patients. Clinical trial information: ChiCTR2100047968 .

34 Successive Bouts of Exercise Influences the Inflammatory Cytokine Response in Thoroughbred Horses Regardless of Recovery Aid Supplementation

Abstract In equine sports, the rate of recovery after an exhaustive exercise session greatly affects the ability of the animal to perform subsequently, especially if the next exercise session occurs quickly. Carnitine participates in fatty acid delivery to the mitochondria and may facilitate muscle recovery post-exercise. The objective of the study was to determine the effects of a commercially available carnitine supplement (Renew, Platinum Performance, Buellton, CA) on adult The ability of Thoroughbred horses (16 geldings, 2 mares, 6.69 ± 0.49 years, 524.81 ± 10.07 kg, 5.66 ± 0.12 BCS) to perform successive bouts of exhaustive exercise. All horses participated in a moderate workload conditioning program for 6-weeks before testing. Horses received a ration of applesauce (30 mL, CON, n = 8) or ration of applesauce containing 19.6 g of the product (30 mL, AID, n = 8) 1 h before performing an incremental standardized exercise test (iSET) to exhaustion (day 1). Heart rate (HR) and gait biomechanics were recorded throughout the duration of the iSET. Blood was collected at 0, 10 min, 1, 4 and 6 h relative to exercise for the measurement of lactate and interleukin (IL) 1b, 8 and 10 mRNA content. for the measurement of lactate and interleukin (IL) 1b, IL8 and IL10 mRNA content. The AID was administered again at 1 h post-iSET after collection of the blood sample. All horses were rested for 24 h before repeating the iSET (day 3) with performance data and sample collection. The AID did not affect time to maximum HR, time to reach V200 or total gallop time during the iSET on day 1 or day 3. The rate of HR decline post iSET was slower (P &amp;lt; 0.05) for all horses on day 3 compared with day 1. Blood lactate concentration was not affected by AID or day. The right front limb posterior fetlock angle at full stance phase increased (P &amp;lt; 0.05) with speed for both CON and AID supplemented horses on day 1. Horses receiving AID demonstrated an increase (P &amp;lt; 0.05) in this measure at day 3 while no significant differences (P &amp;gt; 0.05) in posterior angle were detected in CON. Administration of AID did not affect whole blood IL1b, IL8 or IL10 mRNA content on day 1 or day 3. Consolidation of the data demonstrates increased (P &amp;lt; 0.05) expression of IL1b and IL8 mRNA during post-exercise recovery time on day 1 that was absent on day 3. Expression of IL10 was altered (P &amp;lt; 0.05) over time post-exercise on both days. Results of the experiment demonstrate that successive bouts of exercise affect the inflammatory response to exhaustion. Although AID did not affect IL gene expression, it did promote retention of flexion at the fetlock joint suggesting that carnitine products may facilitate recovery from strenuous exercise.

Epstein-Barr virus predominance and immunological abnormalities in oral squamous cell carcinoma

BACKGROUND: Both benign and harmful head and neck disorders have been associated with the Epstein-Barr virus (EBV). Many studies have connected EBV to oral squamous cell carcinoma (OSCC). Oral squamous cell carcinoma is the most prevalent type of cancer. Fresh tissue samples from patients with OSCC were tested for the presence of Epstein-Barr virus. OBJECTIVE: To determine the frequency of EBV and IL10 expression in OSCC patients. MATERIALS AND METHODS: Fifty individuals with OSCC and 25 with clinically healthy oral mucosa were studied. In situ hybridization was used for the detection of EBV. Serum IL-10 levels were also evaluated in patients and controls using a human IL-10 ELISA Kit. RESULTS: EBV was detected in 4 healthy patients, 6 with moderately differentiated OSCC, 10 with poorly differentiated OSCC, and 19 with undifferentiated OSCC. These differences were statistically significant (p&lt;0.05). IL-10 expression was more common in OSCC diagnostic groups than healthy controls, and the difference in blood IL-10 levels between patients and controls was statistically significant (p&lt;0.01). CONCLUSION: The prevalence of EBV in OSCC suggests its possible role in oral cavity malignancy. On the other hand, IL-10 is expressed at higher levels in OSCC biopsies; such elevated concentrations may promote viral spread.

Folate deprivation induced neuroinflammation impairs cognition

Nutritional status is associated with many neurocognitive diseases. Folate is one of the micronutrients, and its deficiency is associated with clinical outcomes of neurological diseases. Nevertheless, molecular mechanism behind the folate deficiency induced neurological disorders are not well-known. We have hypothesized that folate-deficiency is a cardinal determinant responsible for manifestation of cognitive impairment through inflammation mediated neurodegenerative pathologies. Objective of the current study was to assess whether folate deficiency is associated with cognitive dysfunction or is merely an epiphenomenon and to identify the underlying mechanisms. We developed folate insufficient zebrafish model through intra-peritoneal treatment of methotrexate. T-maze test was carried to assess the spatial learning and memory of the fish. Higher latency of the folate-deprived zebrafishes in the T-maze test is a reflection of altered cognition. This result is supported by declined levels of dopamine and serotonin, neurotransmitters linked with learning and memory. Elevated IL-6 and CRP in peripheral blood, along with increased expression of NF-ĸB in brain indicates manifestation of neuroinflammation. Indeed, together with upregulation of maptb gene it can be implied that folate deficiency acts as a risk factor for neurodegeneration in the form of tauopathies. Furthermore, diminished localisation of synaptopodin, a protein linked to neural plasticity, suggests that neuroinflammation caused by folate deprivation hampers the plasticity of brain. Histological analysis of brain revealed the development of histopathological features including spongiform degeneration and neuronal loss in folate deprived condition. We thus conclude that folate deficiency results in NF-ĸB activation, which through multiple processes mediated by neuroinflammation could lead to cognitive decline.

N-3 Fatty Acid Supplementation After Burn Supports Wound Healing and Prevents Systemic Inflammation. An Experimental Study in Rats

Objective: Burn may cause hypersensitivity towards infection, systemic inflammatory response syndrome, respiratory distress syndrome and multiple organ failure. Anti-inflammatory and resistance towards infection effects of omega-3 (n-3) fatty acids was shown before. But their effect on systemic inflammation and wound healing after burn was not investigated. &#x0D; Methods: Seventy Wistar albino rats were used in the study. Fourteen rats without burn composed the control group. Cutaneous burn was created on remaining 56 rats which received 50 mg/kg/day intraperitoneal ringer lactat solution in two equal amounts. Twenty-eight rats with burn received injections of n-3 1 mg/kg/day throughout the study. Rats in control group were sacrificed on day 4 and rats in treatment groups were sacrificed on days 4 and 8. Leukocyte and mast cell infiltration, epidermal and collagen thickness measurements were used in histological evaluation. White blood cell, hematocrite, total protein, albumin, fibronectin, TNFα, IL1β and IL6 levels were measured for biochemical evaluations. &#x0D; Results: Elevation of leukocyte and mast cell infiltration was lower and collagen thickness was higher in n-3 receiving group on day 4. There was no difference in leukocyte infiltration on the 8th day whereas mast cell infiltration was lower and collagen thickness was higher in n-3 receiving group. Epidermal thickness was higher in n-3 receiving group on both evaluation days. White blood cell counts were higher in 8th day than 4th day groups. Total protein on 8th, IL-6 on 4th, and albumin levels on both days was lower than control.&#x0D; Conclusion: N-3 fatty acids used after burn enhances wound healing and prevents systemic inflammation.

Alpha-Mangostin ameliorates acute kidney injury via modifying levels of circulating TNF-α and IL-6 in glycerol-induced rhabdomyolysis animal model.

Alpha mangostin (AM), isolated from G. mangostana, showed beneficial effects in several disorders due to its antioxidant and anti-inflammatory properties. Acute kidney injury (AKI) due to different etiologies can develop into severe complications, resulting in high mortality rates. In this work, AM is tested for its ability to alleviate AKI in glycerol-induced AKI rat model, where 30 Male Sprague-Dawley rats were assigned to a healthy group, glycerol-treated group and AM-treated group. Glycerol- and AM groups received a single dose of glycerol (per IM, 50% glycerol in saline, 8 ml/kg), whereas control group was injected with saline. AM treatment (a single daily dose, per IP, 175mg/kg) was accomplished for three days. Animals were executed to collect blood samples and kidney tissue for biochemical and histological examination. It was found that glycerol induced increase in serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, serum magnesium, TNF-α and IL-6. It also induced renal edema and hypocalcemia along with histopathological renal damage. AM treatment improved renal histological features and alleviated increase in serum creatinine, BUN, serum magnesium, TNF-α and IL-6 levels, as well as renal edema and lipid peroxidation but did not affect serum calcium levels. This suggests AM as a potential therapeutic agent for treating AKI mainly via its antioxidant and anti-inflammatory properties.

Blood biomarkers and Ki-67 proliferation marker in breast cancer

Metastasis is the leading cause of death in patients with breast cancer (BC). It is known that the lesion of regional lymph nodes by tumor cells is more common in tumors with higher proliferative activity. Moreover, there is literature evidence on effects of cytokines and proteins upon the migration potential of the tumor. The aim of our work was to study the correlation between the concentrations of cytokines, proteins, and expression of Ki-67 proliferation marker in breast cancer with histology of non-specific invasive carcinoma.On the basis of pathological findings, 16 patients had metastases in regional lymph nodes (group I), and 18 patients had no detectable metastases (group II). Solid-phase enzyme immunoassay was used to determine concentrations of 14 cytokines in the supernatants of immunocompetent blood cells, i.e., IL-2, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1β, IL-1ra, TNFα, IFNγ, G-CSF, GM-CSF, VEGF and MCP-1, and concentrations of 6 proteins were determined in blood serum: estrogen and progesterone receptors, cadherin-E (CDH1), plasminogen activator type 1 (PAI-1), mucin 1 (MUC1), heat shock protein 90αA1 (HSP90αA1). Immunohistochemical study of Ki-67 expression was performed in paraffin sections of tumors using monoclonal antibodies.The study showed that Ki-67 expression in tumor tissues and blood concentrations of IL-6, IL-8, IL-1β and TNFα were higher in group I patients. On the contrary, blood concentrations of CDH1 and PAI-1 were higher in group II patients. It was found that Ki-67 showed both inverse correlations with CDH1 and PAI1, and direct correlations with IL-8 and TNFα. CDH1 had a direct correlation with PAI1, and inverse correlations with IL-6, IL-1β and TNFα. The studied cytokines showed direct correlations with each other. The analysis of ROC curves showed good quality and optimal values of the cut-off points for Ki-67 expression, cytokine and protein concentrations, thus allowing best prediction for detectable lymphatic metastasis.On the basis of these results, a quotient was proposed, which represents a ratio of CDH1 contents to the sum of IL-1β and TNFα concentrations in blood samples, which can help identification of the patients with breast cancer at risk for lymphatic metastasis.

Airway microbiota and immune mediator relationships differ in obesity and asthma

Asthma and obesity are both complex conditions characterized by chronic inflammation, and obesity-related severe asthma has been associated with differences in the microbiome. However, whether the airway microbiome and microbiota-immune response relationships differ between obese persons with or without nonsevere asthma is unestablished. We compared the airway microbiome and microbiota-immune mediator relationships between obese and nonobese subjects, with and without mild-moderate asthma. We performed cross-sectional analyses of the airway (induced sputum) microbiome and cytokine profiles from blood and sputum using 16S ribosomal RNA gene and internal transcribed spacer region sequencing to profile bacteria and fungi, and multiplex immunoassays. Analysis tools included QIIME 2, linear discriminant analysis effect size (aka LEfSe), Piphillin, and Sparse inverse covariance estimation for ecological association inference (aka SPIEC-EASI). Obesity, irrespective of asthma status, was associated with significant differences in sputum bacterial community structure and composition (unweighted UniFrac permutational analysis of variance, P= .02), including a higher relative abundance of Prevotella, Gemella, and Streptococcus species. Among subjects with asthma, additional differences in sputum bacterial composition and fungal richness were identified between obese and nonobese individuals. Correlation network analyses demonstrated differences between obese and nonobese asthma in relationships between cytokine mediators, and these together with specific airway bacteria involving blood PAI-1, sputum IL-1β, GM-CSF, IL-8, TNF-α, and several Prevotella species. Obesity itself is associated with an altered sputum microbiome, which further differs in those with mild-moderate asthma. The distinct differences in airway microbiota and immune marker relationships in obese asthma suggest potential involvement of airway microbes that may affect mechanisms or outcomes of obese asthma.

Changes and Significance of Interleukin 17 Expression in Patients After Renal Transplantation

The purpose of this study was to investigate the expression and significance of interleukin (IL)-17 in acute rejection after renal transplantation. From September 2019 to December 2021, patients and healthy volunteers who underwent renal allograft transplantation and renal biopsy in our hospital were selected and divided into 4 groups: the stable group (stable) showed no obvious abnormality in renal transplantation pathology; the pathologic diagnosis of acute rejection was the rejection group; the pathologic diagnosis of renal transplantation was immunosuppressive poisoning in the drug group; and the normal group (control) was healthy volunteers. The expression of IL-17 was detected by reverse transcription-polymerase chain reaction, quantitative enzyme-linked immunosorbent assay, and immunohistochemistry. Analysis of the area under the curve and sensitivity and specificity of IL-17 for the diagnosis of acute rejection after raw transplantation was done using receiver operating characteristic curves. Compared with those in the normal group and the stable group, the expression of IL-17 DNA in the blood, the value of IL-17 in the blood, and the integrated optical density value of IL-17 in the transplanted kidney were significantly higher in the rejection group (P < .05). There were no statistically significant differences in the expression of blood IL-17 DNA, the value of blood IL-17, or the integrated optical density value of transplanted kidney IL-17 between the normal group and the stable group (P > .05). IL-17 is involved in acute rejection after renal transplantation. Increased expression of IL-17 is seen in the blood and kidneys of patients with acute rejection after renal transplantation. The detection of IL-17 may provide a theoretical basis for diagnosing and treating acute rejection in human kidney transplantation.

Association between response to anti-PD-1 treatment and blood soluble PD-L1 and IL-8 changes in patients with NSCLC

In this study, we explored the dynamic changes in blood sPD-L1 and its clinical value during anti-PD-1 immunotherapy in non-small cell lung cancer (NSCLC) patients. First, we established a sandwich ELISA for functional sPD-L1 that can bind to PD-1 and has biological functions. By monitoring functional sPD-L1 in 39 NSCLC patients treated with anti-PD-1 antibodies, we found a positive correlation between baseline sPD-L1 and tissue PD-L1 (P = 0.0376, r = 0.3581), with patients with lymph node metastasis having higher sPD-L1 levels (P = 0.0037) than those without lymph node metastasis. Although baseline functional sPD-L1 and PFS did not correlate significantly in this study, changes in sPD-L1 in patients with different clinical responses showed different trends. Blood sPD-L1 increased in 93% of patients after two cycles of anti-PD-1 treatment (P = 0.0054); sPD-L1 in nonresponsive patients continued to increase (P = 0.0181), but sPD-L1 started to decline in responsive patients. Blood IL-8 levels were associated with tumor load, and when combined with IL-8, the evaluation accuracy of sPD-L1 improved to 86.4%. This study preliminarily shows that the combination of sPD-L1 and IL-8 is a convenient and effective method for monitoring and evaluating the effectiveness of anti-PD-1 immunotherapy in NSCLC patients.

Potential of Pterocarpus erinaceus Aqueous Stem Bark Extract to Prevent Oxidative Kidney Damage in Diabetic Rats

Diabetes is a chronic, metabolic disease characterized by elevated levels of blood glucose, which over time leads to serious damage to the heart, blood vessels, eyes, kidneys and nerves. This present study investigated the potential of Pterocarpus erinaceus aqueous stem bark extract to prevent oxidative kidney damage in diabetic rats. Thirty six (36) male wistar rats of 100 to 200g were used. The rats were divided into six groups (A-F). Diabetes mellitus was induced in groups B-F by injecting alloxan at the dose of 150 mg/kg body weight. After 72hours, diabetes was confirmed. Vitamin C 25 mg/kg b.wt was used as standard treatment for group C and aqueous extract of Pterocarpus erinaceus stem bark at doses of 100, 200 and 400 mg/kg b.wt were administered to groups D, E and F respectively. All treatments were given orally, daily for 14 days. Phytochemical screening of the extract, Blood glucose level and oral glucose tolerance test were determined. At the end of the experiment, the serum, kidney tissue and kidney homogenate were obtained for the determination of kidney function parameters, histology, lipid peroxidation, antioxidant and inflammation markers. Phytochemical results shows the presence of phenols, tannins, saponins, alkaloids, glycosides, cardiac glycosides and flavonoides. Diabetic rats administered with Pterocarpus erinaceus aqueous stem bark extract showed significant (P&lt;0.05) decrease in, blood glucose, creatinine, blood urea nitrogen (BUN), potassium, MDA, TNF-alpha, IL-6 and TGF-β when compared with diabetic control rats. Also a non significant (P&gt;0.05) decrease in uric acid, albumin, and an increase in sodium, GSH when compared with the diabetic control group. A significant (P&lt;0.05) increase was observed in SOD, CAT, GPx, and GST when compared with diabetic control rats. The kidney histology shows well protected kidney. These results obtained shows that aqueous extract of Pterocarpus erinaceus stem bark exhibited significant antihyperglycemic, improvement in kidney function, antioxidant and anti inflammatory markers and prevented kidney tissue damage in alloxan-induced diabetic rats. This might be useful in the management diabetes mellitus patients.

Akkermansia muciniphila Ameliorates Lung Injury in Smoke-Induced COPD Mice by IL-17 and Autophagy

Objective. Smoking is a primary hazard factor for chronic obstructive pulmonary disease (COPD), which induced a decrease in intestinal Akkermansia muciniphila abundance and Th17 imbalance in COPD. This study analyzed the changes of gut microbiota metabolism and Akkermansia abundance in patients with smoking-related COPD and explored the potential function of Akkermansia muciniphila in smoke-induced COPD mice. Methods. Gut microbiota diversity and metabolic profile were analyzed by 16S rRNA sequence and metabolomics in COPD patients. The IL-1β, IL-17, TNF-α, and IL-6 levels were tested by ELISA. Lung tissue damage was observed by HE staining. The expression of cleave-caspase 3, trophoblast antigen 2 (TROP2), and LC3 in lung tissues were analyzed by IHC or IF. The p-mTOR, mTOR, p62, and LC3 expression in lung tissues were tested by western blot. Results. The levels of IL-17, IL-1β, TNF-α, and IL-6 in the peripheral blood of COPD patients increased significantly. The number and alpha diversity of gut microbiota were decreased in COPD patients. The abundance of Akkermansia muciniphila in gut of COPD patients was decreased, and the metabolic phenotype and retinol metabolism were changed. In the retinol metabolism, the retinol and retinal were significantly changed. Akkermansia muciniphila could improve the alveolar structure and inflammatory cell infiltration in lung tissue, reduce the IL-17, TNF-α, and IL-6 levels in peripheral blood, promote the p-mTOR expression, and inhibit the expression of autophagy-related proteins in smoke-induced COPD mice. Conclusion. The number and alpha diversity of gut microbiota were decreased in patients with smoking-related COPD, accompanied by decreased abundance of Akkermansia muciniphila, and altered retinol metabolism function. Gut Akkermansia muciniphila ameliorated lung injury in smoke-induced COPD mice by inflammation and autophagy.

Experimental study on the effect of chlorhexidine gluconate (CG)-induced atrial fibrillation on renal water and sodium metabolism

To construct an animal model of atrial fibrillation and observe the effect of acute atrial fibrillation on renal water and sodium metabolism in mice. A total of 20 C57 mice were randomly assigned to 2 groups (n = 10/group): control group (CON) and atrial fibrillation group (AF). The mice model of atrial fibrillation was induced by chlorhexidine gluconate (CG) in combination with transesophageal atrial spacing. The urine of the two groups of mice was collected, and then we calculate the urine volume and urine sodium content. The expression of TGF-β and type III collagen in the atrial myocardium of the two groups was detected by immunohistochemistry and Western Blot. The levels of CRP and IL-6 in blood were observed by ELISA, and the NF-κB, TGF-β, collagen type III, AQP2, AQP3, AQP4, ENaC-β, ENaC-γ, SGK1 and NKCC proteins in the kidneys of the two groups of mice was observed by Western Blot. Compared with CON, the expression of TGF-β and type III collagen in the atrial myocardium of the mice in AF were increased, the levels of CRP and IL-6 in the blood in AF were increased, and the renal NF-κB, TGF-β, type III collagen AQP2, AQP3, ENaC-β, ENaC-γ, SGK1 and NKCC protein expression in AF were up-regulated. The level of urine volume and urine sodium content in AF were significantly reduced. In the acute attack of atrial fibrillation, the formation of renal inflammatory response and fibrosis is activated, and the renal water and sodium metabolism is hindered, which is related to the up-regulated of the expressions of renal NKCC, ENaC and AQPs.