Elevated proinflammatory cytokines in response to mechanical stimulus are associated with reduced knee loading 2 years after anterior cruciate ligament reconstruction.

BACKGROUND: The aim of this study was to test the hypothesis that proinflammatory cytokines correlate with knee loading mechanics during gait following a mechanical walking stimulus in subjects 2 years after anterior cruciate ligament reconstruction. Elevated systemic levels of proinflammatory cytokines can be sustained for years after injury. Considering roughly 50% of these patients progress to Osteoarthritis 10-15 years after injury, a better understanding of the role of proinflammatory cytokines such as tumor necrosis factor-α and Interleukin-1ß on Osteoarthritis risk is needed. METHODS: Serum proinflammatory cytokines concentrations were measured in 21 subjects 2 years after unilateral ACLR from blood drawn at rest and 3.5 h after 30 min of walking. An optoelectronic system and a force plate measured subjects' knee kinetics. Correlations were tested between inflammatory marker response and knee extension and knee adduction moments. FINDINGS: Changes in proinflammatory cytokines due to mechanical stimulus were correlated (R = 0.86) and showed substantial variation between subjects in both cytokines at 3.5 h post-walk. Knee loading correlated with 3.5-h changes in tumor necrosis factor-α concentration (Knee extension moment: R = -0.5, Knee adduction moment: R = -0.5) and Interleukin-1ß concentration (Knee extension moment: R = -0.44). However, no significant changes in concentrations were observed in tumor necrosis factor-α and Interleukin-1ß when comparing baseline and post walking stimulus conditions. INTERPRETATION: The significant associations between changes in serum proinflammatory markers following a mechanical stimulus and gait metrics in subjects at risk for developing Osteoarthritis underscore the importance of investigating the interaction between biomarkers and biomechanical factors in Osteoarthritis development.

Exploring the impact of interleukins on sarcopenia development: A systematic review and meta-analysis.

BACKGROUND: The role of interleukins in sarcopenia development has been acknowledged, yet the specifics of their involvement remain to be fully understood. This study aimed to explore alterations in interleukin levels among sarcopenia patients. METHODS: Searches were conducted in Embase, Medline, and the Cochrane Library for literature published up to May 2023. Eligible observational studies with a diagnosis of sarcopenia were included. The Newcastle-Ottawa Scale was utilized for quality assessment. For data synthesis, a random-effects model was used, and the Mantel-Haenszel method was used for pooled estimates. RESULTS: Of the 7685 articles screened, 37 met the inclusion criteria. Statistically significant differences in the levels of IL-1ß, IL-6 and IL-10 were detected in sarcopenia patients. Specifically, IL-1ß (95 % CI: 0.33 [0.12, 0.54], P < 0.05), IL-6 (95 % CI: 0.91 [0.59, 1.24], P < 0.05), and IL-10 (95 % CI: 0.11 [0.07,0.15], P < 0.05) were detected. However, no significant associations were found between serum IL-4 (95 % CI: 0.36 [-0.18, 0.42], P = 0.44), IL-8 (95 % CI: -1.05 [-3.06, 0.95], P = 0.3), IL-12 (95 % CI: -3.92 [-8.32,0.48], P = 0.08) or IL-17 (95 % CI: 0.22 [-2.43, 2.88], P = 0.87) and sarcopenia. Subgroup analysis showed no significant difference in IL-6 (95 % CI: -0.03 [-0.72, 0.66], P = 0.93) and IL-10 (95 % CI: 0.1 [-0.44, 0.64], P = 0.72) among patients with European standard sarcopenia. CONCLUSIONS: Inflammation plays a role in sarcopenia, and the serum levels of IL-1ß, IL-6, and IL-10 are associated with sarcopenia. Further research is needed to clarify these associations. CLINICAL TRIALS REGISTRATION NUMBER: CRD42024506656.

Increased serum levels of proNGF, mature NGF and interleukins in burn-injured children.

OBJECTIVE: Burns are among the most common injuries in children. In burns of more than 20% of the total body surface area, a systemic inflammatory response involving several chemical mediators occurs. Among them, nerve growth factor (NGF) regulates the inflammatory response related to wound healing and promotes keratinocyte proliferation and angiogenesis. The aim of our study was to investigate the physiological response to injury in children with moderate-severe burns, assaying proNGF, mature NGF (mNGF), interleukins (IL)-1ß, and Il-10 serum levels. PATIENTS AND METHODS: This is a prospective observational study, including twelve children hospitalized for moderate-severe burns at the Gemelli Hospital (Rome). Their laboratory features were compared to those of patients with obstructive hydrocephalus who underwent surgery. RESULTS: Our results showed an increase in proNGF and mNGF serum levels. In burn patients, proNGF levels increased before mNGF, and serum concentrations of both were not correlated with burn extension and depth. The most significant levels of mNGF and proNGF were reported in scalds involving the face. Serum IL-1ß and IL-10 peak levels were reached with a time-course pattern similar to proNGF. CONCLUSIONS: Our preliminary results validate the hypothesis that serum levels of proNGF and mNGF may represent inflammatory biomarkers useful for monitoring burn patients and defining new strategies for their treatment.

Cytokine and Microbiome Changes in Adolescents with Anorexia Nervosa at Admission, Discharge, and One-Year Follow-Up.

Anorexia nervosa (AN) is a severe eating disorder that predominantly affects females and typically manifests during adolescence. There is increasing evidence that serum cytokine levels are altered in individuals with AN. Previous research has largely focused on adult patients, assuming a low-grade pro-inflammatory state. The serum levels of the cytokine tumour necrosis factor-alpha (TNF-α), interleukin (IL)-1ß, IL-6 and IL-15, which are pro-inflammatory, were examined in 63 female adolescents with AN and 41 age-matched healthy controls (HC). We included three time points (admission, discharge, and 1-year follow-up) and investigated the clinical data to assess whether the gut microbiota was associated with cytokine alterations. Relative to the HC group, serum levels of IL-1ß and IL-6 were significantly lower during the acute phase (admission) of AN. IL-1ß expression was normalised to control levels after weight recovery. TNF-α levels were not significantly different between the AN and HC groups. IL-15 levels were significantly elevated in patients with AN at all time points. We found associations between cytokines and bodyweight, illness duration, depressive symptoms, and the microbiome. In contrast to most findings for adults, we observed lower levels of the pro-inflammatory cytokines IL-1ß and IL-6 in adolescent patients, whereas the level of IL-15 was consistently increased. Thus, the presence of inflammatory dysregulation suggests a varied rather than uniform pro-inflammatory state.

Ghrelin attenuates the inflammatory response induced by experimental endotoxemia in mice.

OBJECTIVE: Aim: The aim of this research is to assess the anti-inflammatory effect of ghrelin in mice models of polymicrobial sepsis. PATIENTS AND METHODS: Materials and Methods: 35 male albino Swiss mice, ages 8-12 weeks, weighing 23-33g, were randomly separated into five groups n = 7; normal group was fed their usual diets until time of sampling, the sham group subjected to Anaesthesia and laparotomy, sepsis group subjected to cecal ligation and puncture, vehicle group was given an equivalent volume of intraperitoneal saline injections immediately after cecal ligation and puncture, and the ghrelin group was treated with 80 µg/kg of ghrelin intraperitoneal injections immediately following cecal ligation and puncture. Twenty hours after cecal ligation and puncture, mice were sacrificed; myocardial tissue and serum samples were collected. Serum IL-1ß, NF-κB, and TLR4 levels were measured, and inflammatory response's effects on cardiac tissue were evaluated. RESULTS: Results: The mean serum IL-1ß, NF-κB, and TLR4 levels were markedly elevated in the sepsis and vehicle groups than in the normal and sham groups. The mean serum levels of IL-1ß, NF-κB, and TLR4 were considerably lower in the ghrelin-treated group than in the vehicle and sepsis groups. Myocardium tissue of the normal and sham groups showed normal architecture. The sepsis and vehicle groups had a severe myocardial injury. The histological characteristics of ghrelin-treated mice differed slightly from those of the normal and sham groups. CONCLUSION: Conclusions: Our study concluded that ghrelin exerts anti-inflammatory effects in polymicrobial sepsis, as indicated by a considerable decrease in the IL-1ß, NF-κB and TLR4 serum levels.

Expression of FoxO3a in sepsis mice and its association with lymphocyte apoptosis.

This study investigated forkhead box O3a (FoxO3a) expression in peripheral blood of sepsis mice and its correlation with lymphocyte apoptosis. Sixty male C57 mice were randomly assigned to sham, model, and intervention groups. Sepsis was induced via cecal ligation in the model and intervention groups, while sham mice underwent similar procedures excluding cecal ligation. Apoptosis proteins in lymphocytes were assessed by Western blotting, reactive oxygen species (ROS) levels by 2,7-Dichlorodi-hydrofluorescein diacetate (DCFH-DA), and serum interleukin-1ß (IL-1ß) and IL-10 content. The model group exhibited elevated mortality, increased lymphocyte apoptosis, higher Caspase3 expression, and lower Bcl-2/Bax ratio compared to sham and intervention groups. Additionally, the model group displayed decreased serum IL-10, elevated IL-1ß, heightened lymphocytic ROS, reduced FoxO3a expression, and increased levels of p-FoxO3a, p-PI3K, and p-Akt compared to sham. In sepsis mice, inhibited FoxO3a signaling in lymphocytes leads to enhanced apoptosis, elevated ROS, and immune cell dysfunction, contributing to increased mortality.

[Ameliorative effect of rare ginsenosides on reproductive injury induced by cyclophosphamide in female rats: based on metabonomics].

Objective: To investigate the effect of rare ginsenosides (RGS) on reproductive injury induced by cyclophosphamide (CP) in female rats. Methods: Twenty-four female rats were divided into four groups [normal control (NC), RGS, CP, and CP+RGS group] with 6 rats in each group. CP group (the model group) and CP+RGS group (the treatment group) were intraperitoneally injected with CP 30 mg/kg for 5 days for modeling, and CP+RGS group was given RGS intragastric intervention. General growth status of rats in each group was observed, the organ index was calculated, and the pathological changes of ovary, uterus, liver and kidney were observed by hematoxylin-eosin staining. Serum levels of estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), pro-inflammatory factors interleukin (IL) 6, IL-1ß, tumor necrosis factor-α were detected. The urine samples were collected after RGS treatment for metabonomics analysis. Metabolomic profiling based on ultra performance liquid chromatography (UPLC) coupled with mass spectrometry (MS) was used to analyze and determine the urine metabolites of rats in each group. Results: Compared with NC group, the ovary index of CP group [(0.054±0.015) %] was significantly decreased (P<0.05), the uterus index [(0.293±0.036) %] and estradiol level [(62.9±6.4) pmol/L] were significantly decreased (all P<0.01), serum levels of FSH, LH, IL-6 and IL-1ß [(20.4±1.0) U/L, (29.0±3.0) U/L, (185.4±28.6) ng/L, (72.9±2.0) ng/L, respectively] were significantly increased (all P<0.01). Compared with CP group, the ovary index in CP+RGS group [(0.075±0.010) %] was significantly increased (P<0.05), serum estradiol level [(122.1±16.2) pmol/L] was significantly increased (P<0.01), serum FSH, IL-1ß and IL-6 levels [(16.7±1.0) U/L, (111.8±17.4) ng/L, (60.1±2.2) ng/L, respectively] were significantly decreased (all P<0.01). Metabonomics analysis results showed that, a total of 352 metabolites were detected in urine, of which 12 were found to be potential markers associated with reproductive injury according to the screening standard. After treatment with RGS, differential metabolites were improved in the direction of NC group. Pathway enrichment suggests that the therapeutic effect of RGS was related to multiple metabolic pathways, including purine metabolism and taurine and hypotaurine metabolism. Conclusion: RGS might reduce inflammation and thus ameliorate the damage caused by CP to the reproductive system of female rats by affecting purine metabolism and other pathways.

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

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

Preventive and therapeutic vascular photobiomodulation decreases the inflammatory markers and enhances the muscle repair process in an animal model.

Photobiomodulation therapy (PBM) has shown positive effects when applied locally to modulate the inflammatory process and facilitate muscle repair. However, the available literature on the mechanisms of action of vascular photobiomodulation (VPBM), a non-invasive method of vascular irradiation, specifically in the context of local muscle repair, is limited. Thus, this study aimed to assess the impact of vascular photobiomodulation (VPBM) using a low-level laser (LLL) on the inflammatory response and the process of skeletal muscle repair whether administered prior to or following cryoinjury-induced acute muscle damage in the tibialis anterior (TA) muscles. Wistar rats (n = 85) were organized into the following experimental groups: (1) Control (n = 5); (2) Non-Injury + VPBM (n = 20); (3) Injured (n = 20); (4) Pre-VPBM + Injury (n = 20); (5) Injury + Post-VPBM (n = 20). VPBM was administered over the vein/artery at the base of the animals' tails (wavelength: 780 nm; power: 40 mW; application area: 0.04 cm2; energy density: 80 J/cm2). Euthanasia of the animals was carried out at 1, 2, 5, and 7 days after inducing the injuries. Tibialis anterior (TA) muscles were collected for both qualitative and quantitative histological analysis using H&E staining and for assessing protein expression of TNF-α, MCP-1, IL-1ß, and IL-6 via ELISA. Blood samples were collected and analyzed using an automatic hematological analyzer and a leukocyte differential counter. Data were subjected to statistical analysis (ANOVA/Tukey). The results revealed that applying VPBM prior to injury led to an increase in circulating neutrophils (granulocytes) after 1 day and a subsequent increase in monocytes after 2 and 5 days, compared to the Non-Injury + VPBM and Injured groups. Notably, an increase in erythrocytes and hemoglobin concentration was observed in the Non-Injury + VPBM group on days 1 and 2 in comparison to the Injured group. In terms of histological aspects, only the Prior VPBM + Injured group exhibited a reduction in the number of inflammatory cells after 1, 5, and 7 days, along with an increase in blood vessels at 5 days. Both the Prior VPBM + Injured and Injured + VPBM after groups displayed a decrease in myonecrosis at 1, 2, and 7 days, an increase in newly-formed and immature fibers after 5 and 7 days, and neovascularization after 1, 2, and 7 days. Regarding protein expression, there was an increase in MCP-1 after 1 and 5 days, TNF-α, IL-6, and IL-1ß after 1, 2, and 5 days in the Injured + VPBM after group when compared to the other experimental groups. The Prior VPBM + Injured group exhibited increased MCP-1 production after 2 days, in comparison to the Non-Injury + VPBM and Control groups. Notably, on day 7, the Injured group continued to show elevated MCP-1 protein expression when compared to the VPBM groups. In conclusion, VPBM effectively modulated hematological parameters, circulating leukocytes, the protein expression of the chemokine MCP-1, and the proinflammatory cytokines TNF-α and IL-1ß, ultimately influencing the inflammatory process. This modulation resulted in a reduction of myonecrosis, restoration of tissue architecture, increased formation of newly and immature muscle fibers, and enhanced neovascularization, with more pronounced effects when VPBM was applied prior to the muscle injury.

Comprehensive assessment of circulatory miRNAs as potential diagnostic markers in HCV recurrence post liver transplantation.

HCV recurrence after liver transplantation is one of the causal agents for graft rejection. This study aims to profile non-invasive biomarkers in patients with HCC who had liver transplants. One hundred participants were categorized into three groups (20 control, 32 recurrent HCV (RHCV), and 48 non-RHCV). The expression of six miRNAs (hsa-miR-124-3p, hsa-miR-155-5p, hsa-miR-205-5p, hsa-miR-499a-5p, hsa-miR-574-3p, and hsa-miR-103a-3p) and two mRNAs IL-1ß, STAT1 were quantified. RHCV group has higher levels of hsa-miR-574-3p and hsa-miR-155-5p and lesser levels of hsa-miR-499a-5p than control groups (p = 0.024, 0.0001, 0.002; respectively). RHCV and non-RHCV groups revealed a significant reduction in levels of IL-1ß and STAT1 mRNA compared to the control (p = 0.011, 0.014; respectively). According to ROC analysis, miR-155-5p can differentiate among the patients' groups, while miR-574-3p, IL-1ß, and STAT1 mRNA can discriminate between RHCV and control groups. In conclusion, RHCV patients have dysregulated expression of five transcripts compared to non-RHCV and control groups.

Expression pattern of the bone morphogenetic protein-4 and its relationship with inflammation, vascular injury in patients suffered the arterial occlusive diseases. / åŠ¨è„‰é˜»å¡žæ€§ç–¾ç— æ‚£è€ è¡€æµ†éª¨å½¢æ€å‘ç”Ÿè›‹ç™½-4çš„è¡¨è¾¾å˜åŒ–åŠå ¶ä¸Žç‚Žç—‡å’Œè¡€ç®¡æŸä¼¤çš„ç›¸å ³æ€§.

OBJECTIVES: Bone morphogenetic protein-4 (BMP4) has been proved to be an important regulatory factor for the pathological process of atherosclerosis (AS). However, there are few related clinical studies. This study aims to investigate the levels of plasma BMP4 in patients suffering from the arterial occlusive diseases (ACD) characterized by AS, and further to test the relationship between BMP4 and inflammation and vascular injury. METHODS: A total of 38 ACD patients (the ACD group) and 38 healthy people for the physical examination (the control group) were enrolled. The plasma in each subject from both groups was obtained to test the levels of BMP4, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-10, and vascular endothelial cadherin (VE-cadherin), and the relationship between BMP4 and the detected indicators above were further analyzed. RESULTS: Compared with the control group, the patients in the ACD group displayed significant elevations in the neutrophil to lymphocyte ratio [NLR, 1.63 (1.26, 1.91) vs 3.43 (2.16, 6.61)] and platelet to lymphocyte ratio [PLR, 6.37 (5.26, 7.74) vs 15.79 (7.97, 20.53)], while decrease in the lymphocyte to monocyte ratio [LMR, 5.67 (4.41, 7.14) vs 3.43 (2.07, 3.74)] (all P<0.05). Besides, the ACD patients displayed significant elevations in plasma BMP4 [581.26 (389.85, 735.64) pg/mL vs 653.97(510.95, 890.43) pg/mL], TNF-α [254.16 (182.96, 340.70) pg/mL vs 293.29(238.90, 383.44) pg/mL], and VE-cadherin [1.54 (1.08, 2.13) ng/mL vs 1.85 (1.30, 2.54) ng/mL], and decrease in IL-10 [175.89 (118.39, 219.25) pg/mL vs 135.92 (95.80, 178.04) pg/mL] (all P<0.05). While the levels of IL-1ß remained statistically comparable between the 2 groups (P=0.09). Furthermore, the plasma BMP4 levels were further revealed to be positively correlated with the levels of IL-1ß (r=0.35), TNF-α (r=0.31) and VE-cadherin (r=0.47), while they were negatively correlated with the levels of IL-10 (r=-0.37; all P<0.01). CONCLUSIONS: After ACD occurrence, the patients' plasma concentrations of BMP4 would be upregulated, which may serve as a candidate to indicate the levels of inflammation and vascular injury.

Acclimation to higher temperature and antioxidant supplemented diets improved rainbow trout (Oncorhynchus mykiss) resilience to heatwaves.

Coldwater species are challenged with increasing water temperatures and fluctuations over their upper thermal limits. This study evaluated the potential of acclimation to higher temperature and dietary antioxidants capacity to mitigate the adverse effects of heat shocks in rainbow trout. To this end, rainbow trout fingerlings were acclimated at optimal (14 °C) and high (20 °C) temperatures and fed on selenium (5 mg/kg) and polyphenol (2 g/kg) supplemented diets for 60 days and then were exposed to heat shocks by increasing water temperature up to 30 °C. Growth performance, survival rate, haemato-immunological parameters, and expression of HSP70α, HSP70ß, HSP90ß, and IL-1ß genes were measured to evaluate the hypothesises. The rainbow trout acclimated to 20 °C and fed on antioxidants supplemented diets showed a significantly higher aftershock survival rate. Moreover, fish acclimated to higher temperature showed higher red blood cell counts as well as serum total protein and albumin during the acclimation trial and heat shocks phase. Acclimation to higher temperature and feeding on antioxidants remarkably enhanced fish immune and antioxidant capacity in comparison to fish adapted to cold water and fed on the basal diet measured by improved respiratory burst and lysozyme activities and upregulation of IL-1ß expression during exposure of fish to heat shocks. Furthermore, fish acclimated to higher temperature, especially those fed on antioxidant supplemented diets, showed lower expression levels of HSPs genes during the heat shock phase, indicating that high heat shocks were less stressful for these fish in comparison to cold water acclimated fish. This finding was also supported by lower cortisol levels during heat shocks in fish acclimated to higher temperature. In conclusion, the results of this study indicated that acclimation to higher temperature and/or fed on diets supplemented by selenium and polyphenol, can help to mitigate the adverse effects of the heat shock in rainbow trout.

Myokine Secretion following an Aerobic Exercise Intervention in Individuals with Type 2 Diabetes with or without Exercise Resistance.

Type 2 diabetes (T2D) is characterized by muscle metabolic dysfunction that exercise can minimize, but some patients do not respond to an exercise intervention. Myokine secretion is intrinsically altered in patients with T2D, but the role of myokines in exercise resistance in this patient population has never been studied. We sought to determine if changes in myokine secretion were linked to the response to an exercise intervention in patients with T2D. The participants followed a 10-week aerobic exercise training intervention, and patients with T2D were grouped based on muscle mitochondrial function improvement (responders versus non-responders). We measured myokines in serum and cell-culture medium of myotubes derived from participants pre- and post-intervention and in response to an in vitro model of muscle contraction. We also quantified the expression of genes related to inflammation in the myotubes pre- and post-intervention. No significant differences were detected depending on T2D status or response to exercise in the biological markers measured, with the exception of modest differences in expression patterns for certain myokines (IL-1ß, IL-8, IL-10, and IL-15). Further investigation into the molecular mechanisms involving myokines may explain exercise resistance with T2D; however, the role in metabolic adaptations to exercise in T2D requires further investigation.

Evaluation of the Diagnostic Utility of Selected Serum Adipokines and Cytokines in Subjects with MASLD-A Pilot Study.

Excess adipose tissue, particularly of the visceral type, triggering chronic low-grade inflammation and altering its secretory profile, is a contributing factor to the initiation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the levels of selected adipokines and cytokines in individuals with normal weight and obesity, assessing their potential for diagnosing MASLD and establishing a cutoff point for body fat content associated with hepatic steatosis development. The research involved 99 participants categorized by body mass index and MASLD presence, undergoing body composition analysis, liver elastography, biochemical tests, and evaluation of adipokines and cytokines in serum. The results indicated elevated IL-6 (interleukin 6) serum levels in individuals with obesity with MASLD compared to the normal-weight group without MASLD. The multivariate regression analysis demonstrated a connection between hepatic steatosis and total adipose tissue content, VAT (visceral adipose tissue), VAT/SAT (subcutaneous adipose tissue) ratio, HOMA-IR (homeostasis model assessment of insulin resistance), IL-6, Il-1ß (interleukin 1ß), and MMP-2 (matrix metalloproteinase 2). Among the adipokines and cytokines examined in this study, interleukin 6 was the strongest predictor of MASLD regardless of gender. In addition, an association between the development of hepatic steatosis and higher serum IL-1ß levels and higher adipose tissue was observed in women. However, further studies on a larger group of patients are needed to consider the use of these cytokines as markers of MASLD. The HOMA-IR index demonstrated potential diagnostic utility in identifying hepatic steatosis.

Salivary interleukin-17A and interleukin-18 levels in patients with celiac disease and periodontitis.

Background: An increased level of interleukin-17A and interleukin-18 in the serum and intestinal mucosa of celiac disease patients reflecting the severity of villous atrophy and inflammation was documented. Thus, the objective of this study was to evaluate the concentrations of salivary-17A, interleukin-1 beta, and interleukin-18 in patients with celiac disease who are on a gluten-free diet, both with and without periodontitis, and to compare these levels with those in healthy individuals. Methods: The study involved 23 participants with serologically confirmed celiac disease (CD) and 23 control subjects. The CD patients had been following a gluten-free diet (GFD) for a minimum of 1 year and had no other autoimmune disorders. The research involved collecting demographic data, conducting periodontal examinations, gathering unstimulated whole saliva, and performing enzyme-linked immunosorbent assays to measure salivary interleukin-17A, interleukin-1 beta, and interleukin-18 levels. Spearman's correlation analysis was utilized to explore the relationships between CD markers in patients on a GFD and their periodontal clinical findings. Results: The periodontal findings indicated significantly lower values in celiac disease patients adhering to a gluten-free diet compared to control subjects (p = 0.001). No significant differences were found in salivary IL-17A, IL-18, and IL-1B levels between celiac disease patients and control subjects. Nevertheless, the levels of all interleukins were elevated in periodontitis patients in both the celiac and control groups. The IL-1 Beta level was significantly higher in periodontitis patients compared to non-periodontitis patients in the control group (p = 0.035). Significant negative correlations were observed between serum IgA levels and plaque index (r = -0.460, p = 0.010), as well as gingival index (r = -0.396, p = 0.030) in CD patients on a gluten-free diet. Conclusion: Celiac disease patients on gluten-free diet exhibited better periodontal health compared to control subjects. However, increased levels of salivary IL-17A, IL-18 and IL-1B levels were associated with periodontitis. Additionally, serum IgA level was significantly inversely associated with periodontitis clinical manifestations and with salivary inflammatory mediators in CD patients on GFD.

[Regulation of electroacupuncture on non-canonical pathway of hepatocellular pyroptosis in rats with nonalcoholic fatty liver disease].

OBJECTIVE: To observe the effect and mechanism of electroacupuncture (EA) on non-canonical pathway of hepatocellular pyroptosis in nonalcoholic fatty liver disease (NAFLD). METHODS: Sixty male SD rats were randomly divided into a normal diet group (n=15) and a high fat modeling group (n=45). The rats in the high fat modeling group were fed with customized high fat diet for 8 weeks to establish NAFLD model. Thirty successfully modeled rats were selected and randomly divided into a model group (n=10), an EA group (n=10) and a non-acupoint with shallow needling group (n=10), and 10 rats were randomly selected from the normal diet group as the control group additionally. In the EA group, EA was applied at bilateral "Fenglong" (ST 40) and "Ganshu" (BL 18), with disperse-dense wave, in frequency of 4 Hz/20 Hz and in intensity of 3 mA. In the non-acupoint with shallow needling group, shallow needling was delivered at points 5 mm from bilateral "Fenglong" (ST 40) and "Ganshu" (BL 18), the EA stimulation parameters were same as the EA group. The intervention was given once a day, 20 min a time, 5 days a week for 4 weeks in the two groups. After intervention, the liver morphology was observed by oil red "O" staining, the serum levels of lipopolysaccharide (LPS), interleukin (IL)-1ß, IL-18 and tumor necrosis factor-α (TNF-α) were detected by ELISA, the protein expression of gasdermin D (GSDMD), GSDMD-N, cysteine aspartic acid specific protease-11 (Caspase-11), IL-1ß, IL-18 and TNF-α in liver tissue were detected by Western blot, the mRNA expression of GSDMD, Caspase-11, IL-1ß, IL-18 and TNF-α in liver tissue was detected by real-time PCR in rats of each group. RESULTS: In the model group, vacuoles in different size were found in the hepatocellular cytoplasm, and the fat droplets were in schistose accumulation. Compared with the model group, the hepatocellular fat droplets and the degree of hepatic steatosis were reduced in the EA group and the non-acupoint with shallow needling group. Compared with the control group, the serum levels of LPS, IL-1ß, IL-18 and TNF-α were increased (P<0.01), the protein and mRNA expression of GSDMD, Caspase-11, IL-1ß, IL-18, TNF-α as well as the protein expression of GSDMD-N in the liver tissue were increased (P<0.01) in the model group. Compared with the model group, the serum levels of LPS, IL-1ß, IL-18 and TNF-α were decreased (P<0.01), the protein and mRNA expression of GSDMD, IL-1ß, IL-18 and TNF-α in the liver tissue were decreased (P<0.01), the protein expression of GSDMD-N and the mRNA expression of Caspase-11 in the liver tissue were decreased (P<0.01) in the EA group and the non-acupoint with shallow needling group. Compared with the model group, the protein expression of Caspase-11 in the liver tissue was decreased (P<0.01) in the EA group. Compared with the non-acupoint with shallow needling group, the serum levels of LPS, IL-1ß, IL-18 and TNF-α were decreased (P<0.01), the protein and mRNA expression of GSDMD, Caspase-11, IL-1ß and IL-18 in the liver tissue were decreased (P<0.01), the protein expression of GSDMD-N and the mRNA expression of TNF-α in the liver tissue were decreased (P<0.01) in the EA group. CONCLUSION: EA can inhibit hepatocellular pyroptosis in NAFLD rats, and its mechanism may be related to reducing the serum level of LPS, and down-regulating the expression of the non-canonical pathway related factors i.e. GSDMD, GSDMD-N, Caspase-11, IL-1ß, IL-18 and TNF-α.

Interaction of obesity and proteins associated with the NLRP3 inflammasome following mild traumatic brain injury.

The NOD-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome has been associated with worse outcomes from severe traumatic brain injury (TBI). The NLRP3 inflammasome is also strongly associated with other pro-inflammatory conditions, such as obesity. Little is known about the potential effect of mild TBI (mTBI) on the NLRP3 inflammasome and the extent to which modifying factors, such as obesity, may augment the inflammatory response to mTBI. The purpose of this study was to evaluate the association of NLRP3 inflammasome proteins with obese body mass index (BMI ≥ 30) within 24 h of mTBI after presenting to a level 1 trauma center emergency department. This is a secondary analysis of prospectively enrolled patients with mTBI who presented to the emergency department of one U.S. Level 1 trauma center from 2013 to 2018 (n = 243). A series of regression models were built to evaluate the association of NLRP3 proteins obtained from blood plasma within 24 h of injury and BMI as well as the potential interaction effect of higher BMI with NLRP3 proteins (n = 243). A logistic regression model revealed a significant association between IL-18 (p < 0.001) in mTBI patients with obese BMI compared to mTBI patients with non-obese BMI (< 30). Moderation analyses revealed statistically significant interaction effects between apoptotic speck-like protein (ASC), caspase-1, IL-18, IL-1ß and obese BMI which worsened symptom burden, quality of life, and physical function at 2 weeks and 6 months post-injury. Higher acute concentrations of IL-1ß in the overall cohort predicted higher symptoms at 6-months and worse physical function at 2-weeks and 6-months. Higher acute concentrations of IL-18 in the overall cohort predicted worse physical function at 6-months. In this single center mTBI cohort, obese BMI interacted with higher acute concentrations of NLRP3 inflammasome proteins and worsened short- and long-term clinical outcomes.

Anti-inflammatory effect of Faloak (Sterculia quadrifida R. Br) stem bark on TNF-α, IL-1ß, and IL-6 in DENV-3-infected Wistar rats.

Background: Dengue infection can trigger an immunological response that results in an inflammatory reaction, which acts as a defensive mechanism to protect the host. Dengue infection leads to an elevation in the release of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6). These three cytokines have been shown to correlate with the development of thrombocytopenia and plasma leakage, which is related to the severity of the disease. Aim: This study aims to investigate the effect of faloak (Sterculia quadrifida R. Br) stem bark on TNF-α, IL-1ß, and IL-6 levels in Wistar rats infected with dengue, specifically DENV-3. Methods: A group of 27 male Wistar rats (Rattus norvegicus) aged 2-3 months and weighting 200-300 g were divided into three distinct groups: healthy, dengue, and treatment (dengue infection and extract) groups. The rats in both the dengue and treatment groups were administered an injection of DENV-3 with a titer of 105 pfu at a dosage of 0.8 cc via the intraperitoneal route. The propagation of DENV-3 was initiated using C6/36 cells, and it underwent four passages. The extract was administered orally via a nasogastric tube at a dosage of 1,500 mg/kg body weight once daily for 7 days. The healthy group underwent blood sampling on the first day, whereas the dengue and therapy groups underwent blood sampling on the fifth and eighth, respectively. Results: Compared with the healthy group, TNF-α levels in the dengue and treatment groups showed significant differences on day 5 post-infection. The post hoc analysis revealed a statistically significant difference between the dengue-treatment and dengue-healthy groups. The IL-1ß levels in the dengue and healthy groups significantly differed on days 5 and 8 post-infection compared to the healthy group. The treatment group had less of a decrease in IL-6 levels on days 5 and 8 than the dengue group. However, no statistically significant differences were observed. Conclusion: The stem bark of S. quadrifida shows potential as an anti-inflammatory agent in dengue infections, particularly in its ability to decrease levels of TNF-α and IL-1ß.

Pro Inflammatory Cytokines Profiles of Patients With Long COVID Differ Between Variant Epochs.

BACKGROUND: Over 30% of patients with COVID-19 have persistent symptoms that last beyond 30 days and referred to as Long COVID. Long COVID has been associated with a persistent elevation in peripheral cytokines including interleukin-6, interleukin-1ß, and tumor necrosis factor-α. This study reports cytokine profiles of patients in our clinic across SARS-COV-2 variant epochs. METHODS: The clinical cytokine panel was analyzed in patients with Long COVID during periods that were stratified according to variant epoch. The 4 variant epochs were defined as: (1) wild-type through alpha, (2) alpha/beta/gamma, (3) delta, and (4) omicron variants. RESULTS: A total of 390 patients had the clinical cytokine panel performed; the median age was 48 years (IQR 38-59) and 62% were female. Distribution by variant was wild-type and alpha, 50% (n = 196); alpha/beta/gamma, 7.9% (n = 31); delta, 18% (n = 72); and omicron, 23% (n = 91). Time to cytokine panel testing was significantly longer for the earlier epochs. Tumor necrosis factor-α (P < .001) and interleukin 1ß (P < .001) were significantly more elevated in the earlier epochs (median of 558 days in wild-type through Alpha epoch vs 263 days in omicron epoch, P < .001)). Nucleocapsid antibodies were consistently detected across epochs. DISCUSSION: When stratified by variant epoch, patients with early epoch Long COVID had persistently elevated peripheral pro-inflammatory cytokine levels when compared to later epoch Long COVID. Patients with Long COVID have similar clusters of symptoms across epochs, suggesting that the underlying pathology is independent of the peripheral cytokine signature.