Blood IL-6 Research Articles

Biomarkers to Differentiate Acute Chest Syndrome From Vaso-Occlusive Crisis in Children With Sickle Cell Disease.

Acute Chest Syndrome (ACS) is the leading cause of death in children with sickle cell disease (SCD) in the US-about half of the children who develop ACS present initially with pain. Here, we studied biomarkers to differentiate ACS from vaso-occlusive crises (VOC) in children with SCD who presented with pain to the emergency department (ED). We conducted a prospective cohort study of consecutive patients who presented to the ED with pain and were discharged with ACS or VOC between March, 2017 and February, 2020. We identified 7 patients with ACS and 19 patients with VOC. The two groups were comparable in age and sex. All patients with ACS had asthma versus 42% of the VOC group. The ACS group had lower weight and BMI z-scores. Patients with ACS compared to VOC had significantly higher respiratory rates, lower O2 saturation, and longer hospital stays. They also had higher white blood cell count, glucose level (> 99 mg/dL), anion gap (> 9 mEq/L), sPLA2 (> 7 pg/mL), IFN-γ (> 17.8 pg/mL), IL-10 (1.54 pg/mL), and IL-12 (> 0.5 pg/mL) levels. We identified biomarkers associated with ACS development in children with SCD presenting with pain that allow for earlier ACS interventions to reduce mortality and morbidity.

Association between vitamin D levels with IL-6 and IL-10 in umbilical cord blood of infants

A worldwide issue, vitamin D deficiency affects pregnant mothers and babies everywhere, including Indonesia. It involves the adaptive immune system by controlling the production of pro- and anti-inflammatory cytokines and the balance between humoral (Th2) and cell-mediated (Th1) immunity. The aim of this study was to investigate the relationship between vitamin D and the cytokines IL-6 and IL-10 in infants. It also examined the relationship between ferritin and IL-6/IL-10 in newborns. The study collected 114 umbilical cord blood samples from term-born mothers without clinical symptoms. IL-6 and IL-10 were among the cytokine profiles measured by the enzyme-linked immunosorbent assay (ELISA). SPSS was used for statistical analysis, and an in-silico investigation was carried out to examine the molecular relationships between vitamin D and IL-6/IL-10. Using the 20 ng/mL as the cut-off for vitamin D insufficiency suggested the insignificant association of vitamin D with IL-6 (p=0.42), IL-10 (p=0.76), and ferritin (p=0.47). When the umbilical cord vitamin D level was categorized into four quartiles, the association with the highest statistical significance (quartile 4 versus quartile 2) was observed for IL-6 (p<0.001), IL-10 (p<0.001), and ferritin (p<0.001). However, the linear regression did not suggest the significant correlations of vitamin D with IL-6 (p=0.40) and IL-10 (p=0.45). A significant correlation based on the linear regression was found between ferritin and IL-10 (p=0.03). Molecular docking studies demonstrated binding affinities of -8.04 kcal/mol for IL-6-vitamin D and -8.53 kcal/mol for IL-10-vitamin D complexes, with stable root mean square deviation throughout the simulations. This study contributes valuable insights into the clinical and computational analysis of the relationship of vitamin D with IL-6 or IL-10.

Swimming exercise regulates indices of skeletal muscle glucose metabolism and attenuates cardiac inflammatory cytokines activity via IL-6/TNF-α pathway in streptozotocin-induced diabetic rats

Diabetes mellitus (DM) manifests with impaired glucose metabolism that affects the musculoskeletal and cardiovascular systems. This study investigated the effects of swimming exercise on some indices of muscle glucose metabolism and cardiac inflammatory markers in diabetic rats induced with streptozotocin. Wistar rats of both sexes (150–200 g) were assigned into five groups of seven (7) rats. Group 1: Control (CON), Group 2: Diabetes only (DM), Group 3: Exercise only (EX), Group 4: Diabetes + Exercise (DM + EX), Group 5: Diabetes + Insulin (DM + IN). Type 1 DM was induced via intraperitoneal injection of streptozotocin (60 mg/kg). Insulin (6 IU/g) was administered (IP) to animals in group 5. Swimming exercise test was done for 27 days after which animals were euthanized. Blood samples were collected while hamstring muscles and heart were harvested and homogenized to assess biochemical parameters. The body weight, serum insulin level, muscle glucose metabolic indices (glycogen, Glut-4, CK-MB), and cardiac troponin-T were significantly (P < 0.05) decreased. In contrast, the random blood glucose, cardiac TNF-α, and IL-6 levels were increased (P < 0.05) in diabetic rats when compared with the control group. Swimming exercise regimen significantly (P < 0.05) reversed these anomalies by reducing blood glucose and cardiac inflammatory cytokines (TNF-α and IL-6) levels, improving serum insulin, muscle glycogen, and GLUT-4 expression in diabetic rats when compared to the DM group. The cardiac inflammatory cytokine levels in DM + EX were comparable to the DM + IN group. In conclusion, swimming exercise improves muscle glucose metabolism and protects the heart against cardiac inflammation in diabetic conditions.

Syn-COM: A Multi-Level Predictive Synergy Framework for Innovative Drug Combinations.

Drug prediction and treatment using bioinformatics and large-scale modeling have emerged as pivotal research areas. This study proposes a novel multi-level collaboration framework named Syn-COM for feature extraction and data integration of diseases and drugs. The framework aims to explore optimal drug combinations and interactions by integrating molecular virtuality, similarity clustering, overlap area, and network distance. It uniquely combines the characteristics of Chinese herbal medicine with clinical experience and innovatively assesses drug interaction and correlation through a synergy matrix. Gouty arthritis (GA) was used as a case study to validate the framework's reliability, leading to the identification of an effective drug combination for GA treatment, comprising Tamaricis Cacumen (Si = 0.73), Cuscutae Semen (Si = 0.68), Artemisiae Annuae Herba (Si = 0.62), Schizonepetae Herba (Si = 0.73), Gleditsiae Spina (Si = 0.89), Prunellae Spica (Si = 0.75), and Achyranthis Bidentatae Radix (Si = 0.62). The efficacy of the identified drug combination was confirmed through animal experiments and traditional Chinese medicine (TCM) component analysis. Results demonstrated significant reductions in the blood inflammatory factors IL1A, IL6, and uric acid, as well as downregulation of TGFB1, PTGS2, and MMP3 expression (p < 0.05), along with improvements in ankle joint swelling in GA mice. This drug combination notably enhances therapeutic outcomes in GA by targeting key genes, underscoring the potential of integrating traditional medicine with modern bioinformatics for effective disease treatment.

Effects of Maltodextrin-Fructose Supplementation on Inflammatory Biomarkers and Lipidomic Profile Following Endurance Running: A Randomized Placebo-Controlled Cross-Over Trial.

Managing metabolism for optimal training, performance, and recovery in medium-to-high-level endurance runners involves enhancing energy systems through strategic nutrient intake. Optimal carbohydrate intake before, during, and after endurance running can enhance glycogen stores and maintain optimal blood glucose levels, influencing various physiological responses and adaptations, including transitory post-endurance inflammation. This randomized trial investigates the impact of a high-dose 2:1 maltodextrin-fructose supplementation to medium-to-high-level endurance runners immediately before, during, and after a 15 km run at 90% VO2max intensity on post-exercise inflammatory stress. We evaluated inflammatory biomarkers and lipidomic profiles before the endurance tests and up to 24 h after. We focused on the effects of high-dose 2:1 maltodextrin-fructose supplementation on white blood cell count, neutrophil number, IL-6, cortisol, and CRP levels, as well as polyunsaturated fatty acids, ω-3 index, and AA/EPA ratio. This supplementation significantly reduced inflammatory markers and metabolic stress. Additionally, it may enhance the post-activity increase in blood ω-3 fatty acid levels and reduce the increase in ω-6 levels, resulting in a lower trend of AA/EPA ratio at 24 h in the treated arm. Adequate carbohydrate supplementation may acutely mitigate inflammation during a one-hour endurance activity of moderate-to-high intensity. These effects could be beneficial for athletes engaging in frequent, high-intensity activities.

Wenjing decoction: Mechanism in the treatment of dysmenorrhea with blood stasis syndrome through network pharmacology and experimental verification

Ethnopharmacological relevanceTraditional Chinese Medicine (TCM) formula Wenjing Decoction (WJD) longstanding efficacy in enhancing blood circulation, resolving blood stasis, and mitigating dysmenorrhea symptoms. Despite its prevalent application, the specific mechanism underlying effect of WJD remains elusive. ObjectiveThe purpose of this study is to examine the material basis of Wenjing Decoction and explore the effect of WJD on rat models of dysmenorrhea with blood stasis syndrome and elucidate its mechanism. MethodsIn this study, we initially identified the chemical constituents of WJD using liquid chromatography-mass spectrometry (LC-MS). Subsequently, we employed network pharmacology to predict the mechanism of WJD in treating acute blood stasis dysmenorrhea. To further investigate the role of WJD, we established a rat model of acute blood stasis. We monitored changes in blood coagulation indexes, IL-6, TNF-α, NO, and COX-2 in rats before and after administration to confirm the successful establishment of the rat model and evaluate the therapeutic effect of WJD on dysmenorrhea and acute blood stasis. Finally, real-time fluorescence quantitative PCR (qPCR) and Western blot (WB) were utilized to investigate its mechanism. ResultsThrough LC-MS analysis, 69 chemical substances were identified in WJD. Network pharmacology study revealed that the mechanism of WJD in treating BSS may be associated with the PI3K/AKT/NF-κB pathway. Following administration, the WJD group showed gradual recovery of physical signs and coagulation index to a healthy level. Additionally, the levels of IL-6, TNF-α, and COX-2 decreased in a dose-dependent manner, whereas NO levels increased. Results from QPCR and WB detection indicated increased expression levels of p-PI3K, p-AKT, Bcl-2, and eNOS, and decreased expression levels of Bax, NFκBp65, ICAM1, and VCAM1. ConclusionThe results show that WJD significantly improves the characterization, dysmenorrhea index, and coagulation-related factors in BSS rats. Through network pharmacological prediction, real-time fluorescence quantitative PCR, and Western blot analysis, it is postulated that the beneficial effects of WJD on dysmenorrhea may be linked to the PI3K/AKT/NF-κB signaling pathway. These findings offer a theoretical foundation for the advancement and utilization of WJD.

Obstructive sleep apnea comorbid with insomnia symptoms and objective short sleep duration is associated with clinical and preclinical cardiometabolic risk factors: Clinical implications

BackgroundInsomnia with objective short sleep duration (ISSD) but not insomnia with normal sleep duration (INSD) is associated with cardiometabolic morbidity. It has been reported that sleep apnea comorbid with insomnia (COMISA) confers higher cardiovascular risk than each condition alone. We hypothesize that the association of COMISA with clinical (hypertension) and preclinical (inflammatory and metabolic) biomarkers is driven by the ISSD phenotype. MethodsA clinical sample of 101 adults with mild-to-moderate OSA (mmOSA) (5 ≤ AHI <30) and insomnia symptoms underwent polysomnography or home sleep apnea testing, blood pressure measures (BP), fasting blood glucose, insulin, CRP and IL-6 plasma levels. Insomnia was based on PSQI. Objective short sleep duration was based on the median total sleep time of the sample. Participants were classified into 2 groups based on objective sleep duration: mmOSA with ISSD vs. mmOSA with INSD. Analysis of covariance and logistic regression analysis were conducted controlling for confounders. ResultsSystolic and diastolic BP were elevated in the ISSD group compared to INSD group (p = 0.039 and p = 0.004, respectively). Also, the risk of hypertension was significantly higher in the ISSD (OR = 3.88, 95%CI = 1.26–11.95, p < 0.05) compared to INSD group. Plasma IL-6 concentrations and insulin resistance as indexed by glucose/insulin ratio were significantly higher in the ISSD group compared to INSD group (both p < 0.05). CRP levels were not different between the two groups. ConclusionIt appears that the additive adverse effects of COMISA on cardiometabolic risks are driven by the ISSD phenotype, a finding with potential implications for further phenotyping COMISA.

Cholesterol to saturated fat index (CSI), metabolic parameters and inflammatory factors among obese individuals

BackgroundThe role of dietary fat quality in promotion of cardiovascular diseases is studies before. However, the results are inconsistent. Recently, cholesterol to saturated fatty acid index (CSI) is suggested as a novel indicator of the atherogenicity and thrombogenicity potential of a diet. However, due to limited number of studies, in the current cross-sectional study, we aimed to evaluate the role of CSI in metabolic and inflammatory response among obese individuals.MethodsIn the current cross-sectional study 488 obese individuals aged 18–50 years old were involved in volunteer based invitation from outpatient obesity clinics. Subjects underwent anthropometric assays including weight, height, waist circumference (WC) and body composition and their fasting blood sample were obtained for biochemical assessments including blood sugar, serum lipids, hs-CRP and IL-6 concentrations by commercial kits. Physical activity was also assessed by short form of international physical activity questionnaire (IPAQ).ResultsAccording to our results, being at the top tetile of CSI was associated with higher anthropometric indices including weight, height, WC, FFM, and basal metabolic rate (BMR) compared with those at the lowest tertile (P < 0.05). Similarly, those at the highest category of CSI had significantly higher levels of serum glucose and hs-CRP both in crude and adjusted models in ANCOVA and in multinomial logistic regression models (P < 0.05).ConclusionIn the current study, for the first time, we identified the possible triggering role of dietary cholesterol to saturated fat index in increasing serum glucose and hs-CRP levels. due to cross-sectional design of the current study, causal inference is impossible. Further studies will help for better scientific justification.

A Retrospective Study of Brain-Heart Syndrome in Patients with Acute Cerebrovascular Diseases.

To investigate the clinical characteristics, risk factors and outcomes of brain-heart syndrome (BHS) in patients with acute cerebrovascular diseases (ACVDs). A retrospective analysis was conducted of 100 patients who were admitted to our hospital with ACVDs between January 2023 and December 2023. The demographic, clinical, laboratory and imaging data of the patients were collected, and the presence and severity of BHS were evaluated. The neurological and cardiac outcomes of the patients at discharge and at 12-month follow-up were also assessed. Out of the 100 patients, 38% had BHS, classified as mild (18%), moderate (12%) and severe (8%). The most prevalent ACVDs were cerebral infarction (58%), cerebral haemorrhage (32%) and subarachnoid haemorrhage (10%). Cardiac complications included arrhythmia (26%), myocardial ischaemia (18%) and heart failure (10%). Patients with BHS had higher results for blood pressure, heart rate, white blood cell count, C-reactive protein, IL-6, D-dimer and troponin, more severe neurological deficits, higher mortality and poorer functional outcomes. Multivariable analysis identified age, hypertension, diabetes, coronary artery disease, prior cardiovascular events, cerebral haemorrhage, brainstem infarction and hypothalamic or insular lesions as independent risk factors for BHS. Brain-heart syndrome is a frequent, severe complication in patients with ACVD, linked with multiple risk factors and poor prognosis. Prompt diagnosis and treatment are crucial for improving patient outcomes.

Association of Interleukin-6 gene (rs1800795) variant with waist-hip-ratio and Insulin resistance: A cross-sectional study in adult women

Obesity is a major contributing factor to metabolic disorders and public health problems worldwide. The goal of the current study was to determine if the Interleukin-6 gene rs1800795 variant is linked to waist-hip-ratio (WHR) and insulin resistance (IR) in North Indian adult women. The WHO guidelines were followed by 37 women who had a WHR &gt;0.85 and 35 women who had a WHR &lt;0.85, out of the 72 women who took part in the study. Every adult woman underwent anthropometric measures. Fasting blood glucose, serum Insulin, lipid levels, and IL-6 levels were measured, and IR was computed. The RFLP technique was used to polymorphise the IL-6 gene (174 G&gt;C) variant. The study group's Insulin, HOMA-IR, BMI, lipid profile, TC/HDL ratio, HDL/LDL ratio, and serum IL-6 level were shown to differ significantly from the control. The percentage frequency of the IL-6 mutant genotype GC+CC (89.19%) and mutant allele C (75.68%) was higher in the study group (WHR &gt;0.85). According to the findings, WHR, TC, TG, and HOMA-IR were substantially correlated (all p &lt;0.05) with the mutant genotype GC+CC of the IL-6 174 G&gt;C gene. This study indicates that the IL-6 rs1800795 gene (174 G&gt;C) variant was substantially linked with metabolic risk variables, such as WHR and HOMA-IR.

Effects of dexmedetomidine on early postoperative cognitive function and postoperative inflammatory response: a systematic review and network meta-analysis.

Dexmedetomidine (DEX) has demonstrated potential as an effective agent for enhancing early postoperative cognitive function. However, there is ongoing debate regarding its optimal dosage and impact on early postoperative inflammatory response. This study aimed to assess and prioritize the effects of varying doses of DEX on early postoperative cognitive function and inflammatory response, in order to identify the most effective intervention dosage. Randomised controlled trials (RCTs) and retrospective cohort studies (RCS) from PubMed, Embase, and Cochrane Library up to January 28, 2024, were included. The Mini-Mental State Examination (MMSE) was utilized to assess the impact of varying doses of DEX on cognitive function during the early postoperative period as the primary outcome, peripheral blood levels of IL-6 and TNF-α were considered as secondary outcomes. Meta-analysis and Bayesian Network Meta-Analysis (NMA) were conducted using R. Funnel plots were generated using Stata 15.0. A total of 29 studies involving 2,807 patients and 25 different doses of DEX were included. DEX was given at a loading dose of 0.3-1.0 μg/kg followed by a maintenance dose of 0.1-0.5 μg/kg/h, or at a uniform intraoperative dose of 0.4-0.7 μg/kg/h. Network meta-analysis revealed most doses of DEX were significantly more effective than normal saline (NS) in improving postoperative MMSE scores (on days 1, 3, and 7) and lowering IL-6 and TNF-α levels. Probability results showed that a 1 μg/kg loading dose followed by a 0.6 μg/kg/h maintenance dose was the best dosing regimen for improving MMSE scores on postoperative days 1 (97.3%), 3 (100%), and 7 (99.9%), as well as for reducing postoperative blood IL-6 levels (1.3%). On the other hand, 0.3 μg/kg followed by 0.2 μg/kg/h was the optimal dosing regimen for reducing postoperative blood TNF-α levels (6.6%). Compared with NS, intraoperative intravenous DEX improved early postoperative cognitive function and postoperative inflammatory response in patients undergoing elective surgery. In particular, a 1 μg/kg loading dose and a 0.6 μg/kg/h maintenance dose resulted in the best improvement in postoperative MMSE scores and blood IL-6 levels, while a 0.3 μg/kg loading dose followed by a 0.2 μg/kg/h maintenance dose is the optimal regimen for lowering postoperative blood TNF-α levels.Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=433932, identifier CRD42023433932.

Effects of Plasma Therapy on Laboratory Factors and Clinical Improvement of COVID-19 Patients

Objectives: Over 50 million confirmed cases and 1.5 million fatalities worldwide have been linked to the COVID-19 pandemic. Researchers have used convalescent plasma (CP) from recovered patients, which includes neutralizing antibodies, to develop therapeutics for virus neutralization and prevention. This study assessed the effectiveness of CP using several clinical and laboratory variables. Methods: The intervention group received two doses of CP on the day of hospitalization, while the control group received standard care. Clinical and analytical data were documented and evaluated before plasma therapy and on the third and fifth days after therapy. The results were measured in the patient’s blood using the ELISA method. Results: The present study showed that the ICU hospitalization times for the control and CP groups were similar, with a slightly lower mortality rate in the CP group (6.2% vs. 8.2%, p &gt; 0.05). There was no significant association between COVID-19 and clinical factors such as blood pressure, heart rate (HR), respiration rate (RR), and temperature. The blood serum urea, serum LDH, ALT, PTT, PLT, and IL-6 were significantly higher in the CP group than in the control group (p &lt;0.05). Our results indicated that there was no difference in blood pH, PO2 , HCO3 , ESR, WBC counts, serum troponin, Na, AST, CRP, D-dimer, and PT between patients in the CP and control groups. Conclusion: Overall, in certain instances, CP therapy may help individuals with COVID-19 recover. In general, additional research is required to determine the efficacy of plasma treatment in COVID-19 patient care.

Effects of continuous negative pressure suction combined with autologous platelet-rich gel on the levels of CRP, IL-6, wound healing and length of stay in clients with diabetic foot

ObjectiveContinuous passive pressure suction and APG gel therapy effect diabetic foot IL-6, CRP, wound healing, and hospitalization. MethodsClinicopathological data from 102 diabetic foot ulcer patients treated at our institution between March 2018 and May 2022 was examined. Tables generated 51 joint and controlling teams randomly. The observation team received passive pressure suction and APG gel whereas the controlled team received conventional treatment. Teams monitored therapy outcomes, adverse responses, wound healing, hospital stay, and costs. Both teams compared blood uric acid, cystatin C, homocysteine, and serum IL-6, IL-10, and CRP before and after medication. ResultsThe joint team had higher hospitalization costs, shorter stays, and faster wound healing than the controlled team. Diaparity was significant (P < 0.05). The united team worked 100 %, unlike the controlling team. This difference was significant (P < 0.05). Both teams showed significant decreases in CRP, IL-6, and IL-10 levels after therapy (P < 0.05). After therapy, both the combined and controlled teams had substantial differences in blood CRP, IL-6, and IL-10 levels (P < 0.05). Both teams had significantly decreased uric acid, cystatin C, and homocysteine after treatment. The combined team showed significantly decreased uric acid, cystatin C, homocysteine levels following therapy compared to the control team (P < 0.05). ConclusionThe joint team experienced considerably fewer adverse events (3.92 % vs. 17.65 %) than the controls team (P < 0.05). Permanent passive pressure suction and APG gel therapy lower inflammatory response, blood uric acid, cystatin C, and homocysteine, speeding wound healing, reducing side effects.

A novel mouse model of hepatocyte-specific apoptosis-induced myeloid cell-dominant sterile liver injury and repair response.

Apoptosis, inflammation, and wound healing are critical pathophysiological events associated with various liver diseases. Currently, there is a lack of in vivo approaches to study hepatocyte apoptosis-induced liver injury and repair. To address this critical knowledge gap, we developed a unique genetically modified mouse model, namely, 3-Transgene (Tg) with inducible Hepatocyte-Specific Apoptosis Phenotype (3xTg-iHAP) in this study. The 3xTg-iHAP mice possess three transgenes including Alb-Cre, Rosa26-rtTA, and tetO-Fasl on a B6 background. These mice are phenotypically normal, viable, and fertile. After subcutaneous administration of a single dose of doxycycline (5 mg/kg, Dox) to 3xTg-iHAP mice, we observed a complete histological spectrum of sterile liver wound-healing responses: asymptomatic hepatocyte apoptosis at 8 h, necrotic liver injury and sterile inflammation at 48 h, followed by hepatocyte mitosis and regeneration within 7 days. During the injury phase, the mice exhibited an increase in the biomarkers of alanine aminotransferase (ALT), chemokine (C-X-C motif) ligand 1 (CXCL1), and IL-6 in peripheral blood, as well as α-smooth muscle actin (α-SMA) protein in liver tissues. Conversely, the mice displayed a decrease in these markers in the recovery phase. Remarkably, this model shows that the sterile liver injury following elevated hepatocyte apoptosis is associated with an increase in myeloid cells in the liver. Within 7 days post-Dox administration, the liver of Dox-treated 3xTg-iHAP mice displays a normal histological structure, indicating the completion of wound healing. Together, we established a novel mouse model of injury and regeneration induced by hepatocyte apoptosis. This tool provides a robust in vivo platform for studying the pathophysiology of sterile liver inflammation, regeneration, and new therapeutic interventions for liver diseases.NEW & NOTEWORTHY Bu et al. present a triple-transgenic mouse model, namely, 3xTg-iHAP mice that are engineered to explore hepatocyte apoptosis-triggered sterile liver injury and regeneration. This model demonstrates a full spectrum of liver wound-healing responses from asymptomatic apoptosis to injury, myeloid cell-dominant sterile inflammation, and repair after induction of hepatocyte-specific apoptosis. The robust nature of this model makes it an invaluable in vivo tool for studying sterile liver inflammation, regeneration, and new therapeutic strategies.

Plants and their uses in dermatological recipes of the Receptarium of Burkhard III von Hallwyl from 16th century Switzerland – Data mining a historical text and preliminary in vitro screening

Ethnopharmacological relevanceHistorical texts on materia medica can be an attractive source of ethnopharmacological information. Various research groups have investigated corresponding resources from Europe and the Mediterranean region, pursuing different objectives. Regardless of the method used, the indexing of textual information and its conversion into data sets useful for further investigations represents a significant challenge. Aim of the studyFirst, this study aims to systematically catalogue pharmaco-botanical information in the Receptarium of Burkhard von Hallwyl (RBH) in order to identify candidate plants in a targeted manner. Secondly, the potential of RBH as a resource for pharmacological investigations will be assessed by means of a preliminary in vitro screening. Materials and methodsWe developed a relational database for the systematic recording of parameters composing the medical recipes contained in the historical text. Focusing on dermatological recipes, we explored the mentioned plants and their uses by drawing on specific literature. The botanical identities (candidate species) suggested in the literature for the historical plant names were rated based on their plausibility of being the correct attribution. The historical uses were interpreted by consulting medical-historical and modern clinical literature. For the subsequent in vitro screening, we selected candidate species used in recipes directed at the treatment of inflammatory or infectious skin disorders and wounds. Plants were collected in Switzerland and their hydroethanolic crude extracts tested for possible cytotoxic effects and for their potential to modulate the release of IL-6 and TNF in PS-stimulated whole blood and PBMCs. ResultsThe historical text analysis points up the challenges associated with the assessment of historical plant names. Often two or more plant species are available as candidates for each of the 161 historical plant names counted in the 200 dermatological recipes in RBH. On the other hand, our method enabled to draw conclusions about the diseases underlying the 56 medical applications mentioned in the text. On this basis, 11 candidate species were selected for in vitro screening, four of which were used in RBH in herbal simple recipes and seven in a herbal compound formulation. None of the extracts tested showed a noteworthy effect on cell viability except for the sample of Sanicula europaea L. Extracts were tested at 50 μg/mL in the whole blood assay, where especially Vincetoxicum hirundinaria Medik. or Solanum nigrum L. showed inhibitory or stimulatory activities. In the PBMC assay, the root of Vincetoxicum hirundinaria revealed a distinct inhibitory effect on IL-6 release (IC50 of 3.6 μg/mL). ConclusionsUsing the example of RBH, this study illustrates a possible ethnopharmacological path from unlocking the historical text and its subsequent analysis, through the selection and collection of plant candidates to their in vitro investigation. Fully documenting our approach to the analysis of historical texts, we hope to contribute to the discussion on solutions for the digital indexing of premodern information on the use of plants or other natural products.

Clinical Significance of the Levels of Peripheral Blood Tregs and Cytokines IL-35, TGF-β and IL-10 in Hemophilia A Patients with FⅧ Inhibitor

To explore the levels of regulatory T cells (Tregs) and cytokines IL-35, TGF-β and IL-10 in peripheral blood of hemophilia A(HA) patients with FⅧ inhibitor and their clinical significance. 43 HA patients admitted to the Hematology Department of the Affiliated Hospital of North China University of Science and Technology from October 2019 to December 2020 were selected, including 6 cases with FⅧ inhibitor and 37 cases without FⅧ inhibitor. In addition, 20 healthy males who underwent physical examinations were selected as healthy controls. Flow cytometry was used to detect the levels of CD4 + CD25 + CD127 - Tregs in peripheral blood of the HA patients and healthy controls, and ELISA assay was used to detect the expression levels of IL-35, TGF-β and IL-10 in serum, and their differences between different groups were compared. Compared with the healthy control group, the level of Tregs in HA patients was decreased, and the level of Tregs in the FⅧ inhibitor positive group was the lowest, the difference was statistically significant (P <0.05). There was no significant difference in the expression level of Tregs in HA patients of different severity levels. The serum IL-35, TGF-β, and IL-10 levels in both FⅧ inhibitor negative and positive groups were significantly lower than those in healthy control group, and those in FⅧ inhibitor positive group were significantly lower than those in FⅧ inhibitor negative group (all P <0.05). The decrease of Tregs, IL-35, TGF-β, and IL-10 levels in HA patients may be related to the formation of FⅧ inhibitors.

Laboratory blood markers in COVID-19 and their connection to Viral variant

Morality rates in COVID-19 are dependent on timely diagnosis. Therefore, studying the relationship between laboratory markers and the severity of disease is important. The first wave of COVID-19 associated with the spread of the original strain of SARS-CoV-2, showed higher mortality rates caused by cytokine storm. As the viral variant changed, a change in the disease course towards a less pronounced inflammatory reaction was observed. These changes affected major players of inflammation, cytokines. However, cytokines are not the only markers in the inflammatory response. The purpose of this work was to determine the significance of laboratory markers in inflammation: WBC, C-reactive protein, ferritin, fibrinogen, and D-dimer. The study included 227 patients with acute COVID-19 in the first 5–7 days from the onset of the disease from January 2021 to March 2022. When compared with reference, all groups were characterized by reduced absolute values of lymphocytes. Correlation analysis between the absolute value of lymphocytes and plasma cytokine concentrations also revealed statistically significant strong relationships with the level of the chemokine CCL22/MDC. Given that CCL22/MDC is an important component of lymphopoiesis, its low concentrations may indicate dysregulation of this process in COVID-19. In addition, we noted a positive correlation between the level of C-reactive protein and IL-6 in peripheral blood. IL-6 is a proinflammatory cytokine, and its elevated levels have been associated with the development of severe COVID-19. One of its functions is the induction of C-reactive protein, and this trend persists regardless of which variant causes COVID-19. We also noted positive correlations between the concentrations of fibrinogen and IL-18, ferritin and IL-6, IL-18. Both of these proteins are involved in inflammation along with cytokines. The literature provides data on the significance of these markers for determining the severity of COVID-19. There is evidence of a synergistic effect of ferritin and IL-18 against viral pathogens. Of interest was the negative correlation between plasma D-dimer levels and IFNα. At the same time, data on the role of the latter in thrombus formation processes are increasingly appearing in the literature.

CE9A215 (inotodiol), a lanostane-type oxysterol, mitigates LPS-induced sepsis through multifaceted mechanisms

Dysregulated host response against infection triggers sepsis that leads to multiple organ dysfunction due to uncontrolled inflammatory responses. Despite marked progress in understanding of sepsis, numerous clinical trials for treatment of sepsis have proven daunting and a new therapeutic approach is highly needed. CE9A215 (inotodiol), a fungal secondary metabolite, has been researched for its pharmacological activities and has shown potent anti-allergic effects. In this study, we evaluated the anti-inflammatory activities of CE9A215 upon lipopolysaccharide (LPS) stimulation in vivo and in vitro for the first time. CE9A215 decreased the production of interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and IL-1β in a concentration-dependent manner in LPS-stimulated RAW264.7 cells. Intriguingly, in human mast cell line LUVA, CE9A215 significantly lowered IL-4 and IL-10, and this effect could be beneficial for the clearance of bacterial infection. In addition, administration of CE9A215 improved the survival rate of LPS-stimulated mice and inhibited the pro-inflammatory cytokines, IL-6, TNF-α, and IL-1β in blood. Moreover, CE9A215 enhanced the expression levels of plasma phospholipid transfer protein (PLTP), apolipoprotein E (ApoE), and ATP-binding cassette transporter (ABCA1) in LPS-stimulated RAW246.7 cells. Liver PLTP level increased significantly in the CE9A215-administered group compared with the control group, which implies that CE9A215 promotes LPS clearance and neutralization by reverse transport of LPS by increasing the expressions of PLTP, ApoE, and ABCA1. Our results highlight CE9A215's potential as a novel therapeutic option for the treatment of sepsis.

Jiawei Bai-Hu-decoction ameliorated heat stroke-induced brain injury by inhibiting TLR4/NF-κB signal and mitophagy of glial cell

Ethnopharmacological relevanceJiawei Bai-Hu-Decoction (JWBHD), a prescription formulated with seven traditional Chinese medicinal material has demonstrated clinical efficacy in mitigating brain injury among heat stroke (HS) patients. Aim of the studyThis study aimed to evaluate the therapeutic efficacy of JWBHD on rat model of HS and to explore its therapeutic mechanisms by integrating network pharmacology and pharmacodynamic methodologies, which major components were analyzed by using UPLC-MS/MS. Materials and methodsThe network pharmacology analysis was firstly conducted to predict the potential active ingredients and therapeutic targets of JWBHD. The anti-HS effectiveness of JWBHD was then evaluated on rats experienced HS. Rat brain tissues were harvested for a comprehensive array of experiments, including Western blot, PCR, H&E staining, Nissl staining, ELISA, transmission electron microscope, flow cytometry and immunofluorescence to validate the protective effects of JWBHD against HS-induced brain damage. Furthermore, the inhibitory effects of JWBHD on TLR4/NF-κB signal and mitophagy of glial were further verified on HS-challenged F98 cell line. Finally, the chemical compositions of the water extract of JWBHD were analyzed by using UPLC-MS/MS. ResultsNetwork pharmacology has identified fifty core targets and numerous HS-related signaling pathways as potential therapeutic targets of JWBHD. Analysis of protein-protein interaction (PPI) and GO suggests that JWBHD may suppress HS-induced inflammatory signals. In experiments conducted on HS-rats, JWBHD significantly reduced the core temperature, restored blood pressure and alleviated neurological defect. Furthermore, JWBHD downregulated the counts of white blood cells and monocytes, decreased the levels of inflammatory cytokines such as IL-1β, IL-6 and TNF-α in peripheral blood, and suppressed the expression of TLR4 and NF-κB in the cerebral cortex of HS-rats. Besides, JWBHD inhibited the apoptosis of cortical cells and mitigated the damage to the cerebral cortex in HS group. Conversely, overactive mitophagy was observed in the cerebral cortex of HS-rats. However, JWBHD restored the mitochondrial membrane potential and downregulated expressions of mitophagic proteins including Pink1, Parkin, LC3B and Tom20. JWBHD reduced the co-localization of Pink1 and GFAP, a specific marker of astrocytes in the cerebral cortex of HS-rats. In addition, the inhibitory effect of JWBHD on TLR4/NF-κB signaling and overactive mitophagy were further confirmed in F98 cells. Finally, UPLC-MS/MS analysis showed that the main components of JWBHD include isoliquiritigenin, liquiritin, dipotassium glycyrrhizinate, ginsenoside Rb1, ginsenoside Re, etc. ConclusionsJWBHD protected rats from HS and prevented HS-induced damage in the cerebral cortex by suppressing TLR4/NF-κB signaling and mitophagy of glial.

Sinomenine hydrochloride improves DSS-induced colitis in mice through inhibition of the TLR2/NF-κB signaling pathway

BackgroundSinomenine hydrochloride (SH) has anti-inflammatory and immunosuppressive effects, and its effectiveness in inflammatory diseases, such as rheumatoid arthritis, has been demonstrated. However, whether SH has a therapeutic effect on dextran sodium sulfate (DSS)-induced ulcerative colitis (UC) in mice and its mechanism of action have not been clarified. This study aimed to investigate the therapeutic effects and mechanism of action of SH on UC. MethodsTwenty-four mice were randomly divided into control, model, SH low-dose (SH-L, 20mg/kg), and SH high-dose (SH-H, 60mg/kg) groups with six mice in each group. Disease activity index (DAI), colonic mucosal damage index, and colonic histopathology scores were calculated. The expression levels of related proteins, genes, and downstream inflammatory factors in the Toll-like receptor 2/NF-κB (TLR2/NF-κB) signaling pathway were quantified. ResultsSH inhibited weight loss, decreased DAI and histopathological scores, decreased the expression levels of TLR2, MyD88, P-P65, P65 proteins, and TLR2 genes, and also suppressed the expression of inflammatory factors TNF-α, IL-1 β, and IL-6 in the peripheral blood of mice. ConclusionThe therapeutic effect of SH on DSS-induced UC in mice may be related to the inhibition of the TLR2/NF-κB signaling pathway.