Interleukin-6 Levels Research Articles

Elevated serum circulating cell-free mitochondrial DNA in amyotrophic lateral sclerosis.

The substantial role of inflammation in amyotrophic lateral sclerosis (ALS) is gaining support from recent research. Studies indicate that circulating cell-free mitochondrial DNA (ccf-mtDNA) can activate the immune system and is associated with neurodegenerative diseases. This research was designed to quantify ccf-mtDNA levels in the serum of ALS patients. The medical records of ALS patients were reviewed. Serum ccf-mtDNA levels of patients with ALS (n = 62) and age-matched healthy controls (n = 46) were measured and compared. Additionally, serum interleukin-6 (IL-6) levels were measured using an enzyme-linked immunosorbent assay in 26 ALS patients. Correlations between variables were analyzed. Serum ccf-mtDNA was notably higher in the patients with ALS. When stratified by genotype, the superoxide dismutase 1 (SOD1) mutation group showed the greatest increase in ccf-mtDNA levels relative to other ALS patients. Among all 108 individuals, a cut-off set at 1.1 × 105 mtDNA copies on a receiver-operating characteristic curve identified patients with ALS with 80.7% sensitivity and 50.0% specificity; the area under the curve was 0.69 (p < 0.001). Furthermore, serum ccf-mtDNA levels correlated negatively with the progression rate of ALS (ΔFS; rs = -0.26, p = 0.044), but not the ALSFRS-R score (rs = 0.06, p = 0.625). Importantly, the correlation between ccf-mtDNA and ΔFS was more pronounced in the SOD1 mutation group (rs = -0.62, p = 0.018). Lastly, a significant positive association was observed between serum ccf-mtDNA levels and IL-6 levels in ALS (r s= 0.41, p = 0.038). Our study found increased serum ccf-mtDNA in ALS patients, suggesting a link to inflammatory processes and disease mechanism. Moreover, ccf-mtDNA could be an indicator for ALS progression, especially in those with the SOD1 mutation.

The Relationship Between NLRP3 Inflammasome and Its Downstream Inflammatory Factors in Obstructive Sleep Apnea Patients with Carotid Atherosclerosis Under Cigarette Exposure

Aim: To study the relationship between NLRP3 (nucleotide oligomerization domain [NOD]-, leucine-rich repeats [LRR]-, and pyrin domain-containing protein 3) inflammasome and its downstream inflammatory factors in obstructive sleep apnea (OSA) patients with carotid atherosclerosis (CAS) under cigarette exposure, further exploring the risk factors of CAS in OSA patients. Methods: A total of 109 adult males who underwent polysomnography and carotid artery ultrasonography in our hospital from October 2019 to December 2021 were selected. According to the detection results, they were divided into the OSA group, the CAS group, and the OSA combined CAS group; additionally, 29 healthy subjects who underwent a physical examination were also included. According to whether they were smoking, the groups were further divided into smoking and non-smoking groups. The age, body mass index (BMI), blood pressure, apnea-hypopnea index (AHI), lowest blood oxygen saturation (LSaO2), carotid intima-media thickness (CIMT), levels of blood sugar, blood low-density lipoprotein cholesterol (LDLc), and serum NLRP3, interleukin-1β (IL-1β), and interleukin-18 (IL-18) of all subjects were recorded. Results: The OSA combined CAS group had higher LDLc levels and AHI and lower LSaO2 than the OSA group and CAS group. The levels of serum NLRP3, IL-1β, and IL-18 in the OSA group were higher than those in the normal control group (P &lt; 0.05); and those in the OSA combined CAS group were higher than the OSA group and CAS group (P &lt; 0.05), regardless of cigarette exposure. Considering cigarette exposure, serum NLRP3, IL-1β, and IL-18 levels were higher in the OSA, CAS, and OSA combined CAS smoking groups than those in the non-smoking group (P &lt; 0.05). Under cigarette exposure, AHI, LDLc, NLRP3, IL-1β, and IL-18 were significantly positively correlated (P &lt; 0.05), and LSaO2 was negatively correlated with CAS in OSA (P &lt; 0.05). AHI, LSaO2, LDLc, NLRP3, and IL-1β are the risk factors for OSA combined with CAS. Conclusion: LSaO2, AHI, LDLc, NLRP3, and IL-1β are the important risk factors for OSA combined with CAS under cigarette exposure, and their levels can be used to predict the occurrence of CAS in OSA.

Association between phase angle and inflammatory blood biomarkers in community-dwelling older adults: Itabashi Longitudinal Study on Aging

Background & AimBioelectrical impedance analysis–derived phase angle (PhA) reflects the disruption of the cell membrane and intra- and extracellular fluid imbalances caused by chronic inflammation. This study examined the association between PhA and inflammatory markers in community-dwelling older adults. MethodsA sex-stratified logistic regression analysis was conducted, with elevated C-reactive protein (CRP; ≥3.0 mg/L) and interleukin-6 (IL-6; >4.0 pg/mL) levels as the outcomes and whole-body and local PhAs as the exposures. The same analysis was conducted with further stratification for age, overweight status, history of inflammation-related non-communicable diseases, and dietary inflammatory index. The ability to identify inflammation in whole-body and local PhAs was assessed using a receiver operating characteristic (ROC) curve. ResultsThis study included 1,664 participants (age: 76 [73–80] years; 855 women). In men, significant odds ratios (ORs) at the 95% confidence interval (95% CI) were observed for abnormal CRP and IL-6 levels for both whole-body and leg PhAs in the third quartile compared with the lowest quartile (OR [95% CI] for abnormal CRP levels: 0.36 [0.18, 0.68] for whole-body PhA, 0.51 [0.27, 0.95] for leg PhA; OR [95% CI] for abnormal IL-6 levels: 0.36 [0.15, 0.81] for whole-body PhA, 0.33 [0.12, 0.78] for leg PhA). The areas under the ROC curves (95% CI) for identifying abnormal IL-6 were mild in men (0.62 [0.54, 0.70] for whole-body PhA and 0.62 [0.55, 0.70] for leg PhA). In men without a history of inflammation-related non-communicable diseases, it was 0.72 (0.59, 0.85) for whole-body PhA and 0.68 (0.54, 0.81) for leg PhA. In women, the PhA was not significantly associated with inflammatory markers. ConclusionPhA is associated with inflammation in community-dwelling older men, but may need to be combined with other information to identify inflammation.

Review of the potential value of serum interleukin levels as prognostic biomarkers of liver failure.

Liver failure (LF) is prevalent in China and is characterized by complex pathogenesis, challenging clinical management, poor prognosis, and rising incidence and mortality rates. The immune status is an important factor affecting LF prognosis. Interleukins (Ils) are a type of cytokine that act and interact with multiple cells, including immune cells. These signaling molecules play important roles in intercellular information transmission, including the regulation of immune cells; mediation of the activation, proliferation, and differentiation of T and B cells; and orchestration of the inflammatory response. To date, many studies have explored the correlation between IL expression and liver disease prognosis, but few studies have evaluated Ils as the prognostic biomarkers of LF. This article reviews the potential use of Ils as the prognostic biomarkers of LF. Particularly, it evaluates the predictive values of IL-21, IL-22, and IL-31, the three often overlooked yet promising prognostic biomarkers, in predicting susceptibility to LF. Harnessing biomarkers for early prognostic insights can facilitate tailored treatment strategies and enhance patient survival. Thus, this article focuses on the identification of IL-21, IL-22, and IL-33 as biomarkers in preclinical and clinical studies on LF and reviews their role as biomarkers in the pathogenesis and diagnosis of LF.

Clinical characteristics and risk factors associated with diverse manifestations of COVID-19 in patients aged 85 years and older.

The goal of this study is to assess the clinical attributes exhibited by patients aged 85 years and older who present different manifestations of COVID-19, and to examine the factors influencing the classification of the disease severity. This retrospective study was conducted at a single center, encompassing an analysis of clinical data obtained from patients with COVID-19 admitted to a general geriatric hospital in Hangzhou, Zhejiang, China, during the period from December 20, 2022, to February 1, 2023. The study focused on 91 eligible patients whose disease severity was compared based on the imaging findings. A total of 91 patients aged 85 years and older, with a median age of 92, including 46 males, 10 exhibiting mild symptoms, 48 moderate cases, and 33 severe cases met the inclusion criteria. Notably, disease severity displayed a significant correlation with age (p < 0.011). All patients presented with complicated chronic underlying conditions and a history of prolonged medication use. Rheumatic immune diseases (p = 0.040) and endocrine medications, primarily hypoglycemic agents (p = 0.034), exhibited statistical significance. Additionally, markers such as lactate dehydrogenase (LDH) (p = 0.030), interleukin 6 (IL-6) (p = 0.014), and D-dimer (p = 0.007) revealed significant associations with disease severity. Chest computed tomography scans predominantly revealed inflammatory features (n = 81, 89.0%). Notably, patients classified as having mild or moderate conditions exhibited eventual improvement, while 13 patients (39.4%) among the severe cases succumbed to the disease. The classification of disease among patients aged 85 years or older old is correlated with advanced age, concurrent rheumatic immune diseases, and prolonged administration of endocrine medications. Furthermore, patients with elevated levels of LDH, IL-6, and D-dimer demonstrated a higher propensity for developing severe diseases.

Changes and Roles of IL-6, hsCRP, and proCT in Patients with Chronic Periodontitis in Head and Neck Cancer Pre/Post Radiotherapy

Background: Head and neck cancer (HNC) patients frequently undergo radiotherapy as a standalone treatment or in combination with chemotherapy. Radiotherapy is associated with adverse effects, including detrimental impacts on periodontal health, which increase the risk of periodontitis. Objective: To investigate the clinical significance of interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), and procalcitonin (proCT) as prognostic indicators. Methods: 150 participants were divided into three groups: (n=50, HNC post-RT) patients with head and neck cancer who had radiation treatment six months ago (n=50, HNC pre-RT), and individuals with periodontal health as the control group (n=50). Probing pocket depth (PPD), clinical attachment loss (CAL), gingival bleeding index (GBI), plaque index (PI), and hyposalivation were meticulously recorded. To quantify serum concentrations of IL-6, hs-CRP, and proCT, an electrochemiluminescence immunoassay (eCLIA) was used. Results: Serum levels of IL-6, hsCRP, and proCT were significantly elevated in two groups of patients with chronic periodontitis with head and neck cancer post-radiotherapy (CP+HNC post-RT) and patients with chronic periodontitis with HNC pre-radiotherapy (CP+HNC pre-RT) compared to a control group. ROC analysis demonstrated the diagnostic accuracy of IL-6, hsCRP, and proCT for both clinical cases. Furthermore, all clinical periodontal index scores (CAL, PPD, PI, and GBI) were significantly elevated compared to a control group. Conclusions: HNC post-RT patients presented significantly higher serum IL-6, hs-CRP, proCT, and periodontal score levels than HNC pre-RT.

Possible association of elevated CSF IL-6 levels with anxiety and frustration in psychiatric disorders.

Neuroinflammation is an important causal factor for a variety of psychiatric disorders. We previously reported increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and major depressive disorder. The present study aimed to examine the possible association of interleukin-6 levels with anxiety and frustration, negative valence symptoms shared in various psychiatric disorders. We included 129 patients with psychiatric disorders and 70 controls. CSF and plasma interleukin-6 levels were measured by immunoassay kits, and psychological symptoms were assessed with the State-Trait Anxiety Inventory, and the Basic Psychological Need Satisfaction and Frustration Scale. To examine regional cerebral blood flow, patients underwent arterial spin labeling analysis using magnetic resonance imaging. Cerebrospinal fluid interleukin-6 levels were significantly correlated with State-Trait Anxiety Inventory-trait anxiety (r = 0.25, P = 0.046) and Basic Psychological Need Satisfaction and Frustration Scale-autonomy frustration scores (r = 0.29, P = 0.018). Patients with abnormally high cerebrospinal fluid interleukin-6 levels (defined >97.5 percentile of the controls) had higher scores for trait anxiety (P = 0.035) and autonomy frustration (P = 0.026), and significantly increased regional cerebral blood flow in the left superior temporal gyrus, bilateral nucleus accumbens, and cerebellum than the remaining patients. Patients with elevated cerebrospinal fluid interleukin-6 constitute a subpopulation of psychiatric disorders associated with anxiety and autonomy frustration, which may be related to altered functions in specific brain areas.

Altered Cytokine Secretory Fingerprint of the Adipocytes Derived from Stem Cells of Morbidly Obese Patients-A Preliminary Study.

Context: Adipose-derived mesenchymal stem cells (ADMSCs) are progenitor cells that shape the tissue's biological properties. Objective: To examine the adipocytes differentiated from the ADMSCs of lean and obese individuals with/without a metabolic syndrome (MetSx) cytokine secretory profile, as to date, little is known on this topic. Methods: Interleukin, chemokine and growth factor levels in the culture medium were determined using the Human Cytokine kit. Results: We observed a characteristic secretory fingerprint displayed by the cells from the MetSx group and identified a set of putative markers (IL-1β, IL-6, IL-7, IL-10, IL-12, IL-13, VEGF, FGF, GM-CSF, TNF-α, IFN-γ) of the condition. Surprisingly, the concentrations of most of the molecules (except for IL-6, IFN-γ, IP-10, VEGF) decreased when compared with the cells from the lean group. We postulate that the difference stemmed from the fact that in vivo cytokines were mostly secreted by the activated monocytes/macrophages and not adipocytes per se. This may also suggest that the aforementioned upregulated cytokines (IL-6, IFN-γ, IP-10, VEGF) might have been the ones that attracted monocytes and triggered the vicious cycle of tissue inflammation. Conclusions: Our study indicated that the adipocytes newly derived from the ADMSCs of obese patients with metabolic syndrome displayed a secretory fingerprint that may be characteristic to the early stages of the condition.

Costunolide, an effective agent against oxidative damage, apoptosis and autophagy in the ovarian torsion/detorsion model

Aim This study assessed the efficacy of costunolide (COST) against oxidative tissue damage in the ovarian torsion/detorsion (TD) model. Methodology Animals were randomly assigned to sham, ovarian TD, COST 5 mg/kg + ovarian TD, and COST 10 mg/kg + ovarian TD groups. COST’s effectiveness was determined by assessing oxidative stress markers, interleukin levels, and histopathological examinations. Results Oxidative stress markers were elevated in the ovarian TD group compared to the sham group. COST treatment represented a decline compared to the TD group. Besides, the antioxidant activity was significantly higher in the ovarian TD group than in the sham group. COST treatment improved the antioxidant parameters compared to the TD group. Inflammatory parameters, such as tumour necrosis factor- alpha (TNF-α) and interleukin 1-beta (IL-1β) were higher in the ovarian TD group than the sham group. Conclusion COST treatment suppressed the proinflammatory cytokine expression compared to the TD group. Histopathological data supported these findings.

Iron chelating, antioxidant, and anti-inflammatory properties of brazilin from Caesalpinia sappan Linn

BackgroundIron overload and inflammation are severe conditions that can lead to various chronic diseases. However, the current iron chelator drugs have their limitations. The phytochemical compounds from herbals, such as brazilin, the major active compound in Caesalpinia sappan Linn., have significant therapeutic potential in various chronic diseases. Our study was designed to examine the effect of brazilin on iron chelating properties, antioxidant activity in hepatocytes, and anti-inflammatory potential in macrophages. MethodsThis study focused on the isolation, purification, and evaluation of brazilin, the principal bioactive constituent found in C. sappan wood. Brazilin was extracted via methanol maceration followed by column chromatography purification. The purified compound was characterized using high-performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) spectroscopy, and mass spectrometry (MS). The antioxidant potential of brazilin was assessed by in vitro assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2′-azinobis-(3-ethylbenzthiazolin-6-sulfonic acid (ABTS), and ferric-reducing antioxidant power (FRAP). Furthermore, its cellular antioxidant activity was evaluated using hydrogen peroxide-induced oxidative stress in the hepatocellular carcinoma cell line (Huh-7). The iron-chelating capacity of brazilin was determined spectrophotometrically, and Job's plot method was used to elucidated the stoichiometry of the iron-brazilin complex formation. The anti-inflammatory properties of brazilin were investigated in lipopolysaccharide (LPS)-stimulated macrophages (RAW 264.7). Nitric oxide (NO) inhibition was quantified using the Griess reagent, while the expression levels of pro-inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), were evaluated by RT-qPCR. ResultsThe results demonstrated that brazilin exhibited potent antioxidant activity in vitro and hepatocytes in a concentration-dependent manner. It also showed anti-inflammatory activity, in which NO production was significantly reduced and IL-6 and TNF-α expression in LPS-induced macrophages were repressed. Furthermore, it can bind ferric and ferrous ions. Brazilin acts as a bidentate iron chelator that forms a complex with iron in a 2:1 ratio, and two water molecules are used as additional chelators in this complex. ConclusionsOur findings have significant implications. Brazilin can potentially alleviate the harmful effects of iron-induced oxidative stress and inflammatory disorders.

The plasma EBV DNA load with IL-6 and VEGF levels as predictive and prognostic biomarker in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is often diagnosed at a very advanced stage due to its location and non-specific initial symptoms. Moreover, no clinically useful serological marker has been established so far for early detection of NPC. In this study, we have investigated the clinical significance of plasma Epstein–Barr virus DNA load along with interleukin-6 (IL-6) and vascular endothelial growth factor (VEGF) levels to evaluate if these three all together can be useful as a strong serological marker for early detection and prediction of treatment response in patients with NPC. Plasma EBV DNA load, IL-6 level, VEGF expressions were measured in 24 patients with NPC at presentation and various time points during and after treatment. There was a positive correlation between high plasma EBV DNA load with higher IL-6 and VEGF expression, which was closely associated with therapeutic response as well. Persistent or recurrent plasma EBV load with higher IL-6 and VEGF levels can potentially predict disease progression and may be useful to select patients for additional therapy and longer follow-up.

Interleukin 6 plasma levels are associated with progression of coronary plaques

BackgroundInflammation plays a pivotal role in atherogenesis and is a causal risk factor for atherosclerotic cardiovascular disease. Non-invasive coronary CT angiography (CCTA) enables evaluation of coronary plaque phenotype. This study...

Expiratory muscle strength training reduces oxidative stress and systemic inflammation in men with obstructive sleep apnea syndrome: a double-blinded, randomized parallel trial

Abstract Study Objectives This study aimed to evaluate and compare the effects of high and low-intensity expiratory muscle strength training (EMST) on disease severity, systemic inflammation, oxidative stress, respiratory muscle strength, exercise capacity, symptoms, daytime sleepiness, fatigue severity, and sleep quality in male patients with obstructive sleep apnea syndrome (OSAS). Methods Thirty-one male patients diagnosed with moderate OSAS were included in this double-blind, randomized, parallel study. Patients were randomized into two groups: High-EMST and Low-EMST groups. EMST was used at home 7 days/week, once a day, for 25 breaths, 12 weeks. Respiratory muscle strength was measured using a mouth pressure device. Disease severity (Apnea–Hypopnea Index [AHI]) and, respiratory sleep events by polysomnography, total oxidant level(TOS), total antioxidant level(TAS), oxidative stress index (OSI), C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and interleukin-10 (IL-10) levels by blood serum were evaluated. Results The percentage of AHI change in the high-EMST group(50.8%) was significantly higher than in the low-EMST group(6.3%; p = .002, d = 1.31). In general, as MEP increased by one unit, AHI decreased by 0.149 points (b = −0.149; CR = −3.065; p = .002), and as AHI increased by one unit, ODI increased by 0.746 points (b = 0.746; CR = 10.604; p &amp;lt; .001). TOS, OSI, TNF-α and IL-6 levels decreased at similar rates in both groups. Conclusions EMST significantly reduces systemic inflammation and oxidative stress while improving expiratory muscle strength in male patients with moderate OSAS. High-EMST is more effective in enhancing the severity of disease than low-EMST. EMST is a practical, effective, and promising treatment for pulmonary rehabilitation in patients with moderate OSAS. Clinical Trials Effect of EMST systemic inflammation and oxidative stress in patients with moderate OSAS, https://clinicaltrials.gov/study/NCT05242406, with the number NCT05242406.

Behçet's disease modifies the gingival inflammatory response.

Behçet's disease (BD) pathogenesis involves severe outcomes such as blindness, central nervous system manifestations, and deep venous thrombosis that impacts systemic and local inflammatory changes. We tested the hypothesis that BD negatively affects gingival health and increases the severity of gingivitis. The study included 37 BD patients with gingivitis without any sign of periodontitis. Systemically healthy 19 patients with gingivitis (G) and 20 periodontally and systemically healthy individuals (C) were recruited as controls. BD patients were further grouped as stable and unstable based on their responses to BD treatment. Clinical periodontal parameters were measured to determine the impact of BD on gingival health. Serum and saliva levels of ELA-2 (neutrophil elastase-2), SLPI (secretory leukocyte protease inhibitor), α1-AT (alpha1-anti-trypsin), VEGF (vascular endothelial growth factor), IL-6 (interleukin-6), IL-8 (interleukin-8), and TNF-α (tumor necrosis factor alpha) were analyzed using multiplex immunoassay to measure the systemic and local inflammatory impact of BD. Plaque index (PI), probing pocket depth (PPD), and bleeding on probing (BOP) were significantly higher in the BD group than in the controls (p<0.05). IL-6 was higher in both serum and saliva in the BD group than in the G group (p<0.05). ELA-2 levels in saliva were higher in the stable BD group than in the controls, while TNF-α and SLPI were statistically significantly higher in BD than in the control (p<0.05). Salivary α1-AT level was statistically lower in the BD group compared to the control group. Our study suggested that the gingival inflammatory profile was impaired in patients with BD.

Systematic Evaluation of Regiochemistry and Lipidation of Aryl Trehalose Mincle Agonists.

The Macrophage-Inducible C-type Lectin receptor (Mincle) plays a critical role in innate immune recognition and pathology, and therefore represents a promising target for vaccine adjuvants. Innovative trehalose-based Mincle agonists with improved pharmacology and potency may prove useful in the development of Th17-mediated adaptive immune responses. Herein, we report on in vitro and in silico investigations of specific Mincle ligand-receptor interactions required for the effective receptor engagement and activation of Th17-polarizing cytokines. Specifically, we employed a library of trehalose benzoate scaffolds, varying the degree of aryl lipidation and regiochemistry that produce inflammatory cytokines in a Mincle-dependent fashion. In vitro interleukin-6 (IL-6) cytokine production by human peripheral blood mononuclear cells (hPBMCs) indicated that the lipid regiochemistry is key to potency and maximum cytokine output, with the tri-substituted compounds inducing higher levels of IL-6 in hPBMCs than the di-substituted derivatives. Additionally, IL-6 production trended higher after stimulation with compounds that contained lipids ranging from five to eight carbons long, compared to shorter (below five) or longer (above eight) carbon chains, across all the substitution patterns. An analysis of the additional cytokines produced by hPBMCs revealed that compound 4d, tri-substituted and five carbons long, induced significantly greater levels of interleukin-1β (IL-1β), tumor necrosis factor- α (TNF-α), interleukin-23 (IL-23), and interferon- γ (IFN-γ) than the other compounds tested in this study. An in silico assessment of 4d highlighted the capability of this analogue to bind to the human Mincle carbohydrate recognition domain (CRD) efficiently. Together, these data highlight important structure-activity findings regarding Mincle-specific cytokine induction, generating a lead adjuvant candidate for future formulations and immunological evaluations.

Effect of chronic periodontitis on the endothelial glycocalyx of rat penile corpus cavernosum.

Chronic periodontitis may induce erectile dysfunction (ED), however, the specific mechanism involved is unclear. The endothelial glycocalyx (eGlx) is a structure that can regulate endothelial nitric oxide synthase (eNOS) phosphorylation on the cavity surface of vessels. To investigate whether chronic periodontitis leads to ED by affecting the eGlx. Twenty-four 4-week-old male Sprague‒Dawley rats were randomly divided into four groups (n=6): the control group, chronic periodontitis group, chronic periodontitis + heparin group (subcutaneous heparin 200 U/kg/day, 7 days), and control + heparin group. Four weeks after the induction of periodontitis in the rats, the maximum intra-cavernous pressure/mean arterial pressure (ICPmax/MAP), serum C-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), nitric oxide (NO), heparin sulfate (HS), syndecan-1 (SDC-1), heparanase (HPSE), eNOS, and phosphor-eNOS (p-eNOS) concentration were measured, and the eGlx of the penile corpus cavernosum was observed by transmission electron microscopy (TEM). Chronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF-α, and IL-6 levels, reducing the p-eNOS/eNOS ratio and the NO concentration in the penile corpus cavernosum, and resulting in the inhibition of the erectile function. Serum CRP, TNF-α, and IL-6 levels and HPSE expression in penile cavernous tissue were significantly greater in the chronic periodontitis group than in the control group and the chronic periodontitis + heparin group (P<0.05). The average thickness of the eGlx muscle in the penile corpus cavernosum in the chronic periodontitis group was significantly lower than those in the control group and chronic periodontitis + heparin group (P<0.05). The HS concentration, SDC-1 expression, p-eNOS/eNOS, NO concentration, and ICPmax/MAP in the chronic periodontitis group were significantly lower than those in the control group and chronic periodontitis+ heparin group (P<0.01). The eGlx on penile cavernosum vessels may be a new therapeutic target for the treatment of ED. This study revealed that chronic periodontitis promotes the decomposition of vascular eGlx in the rat penile corpus cavernosum, however, it is not clear whether chronic periodontitis inhibits the synthesis of eGlx. Chronic periodontitis can degrade eGlx on the rat penile corpus cavernosum by increasing serum CRP, TNF-α, and IL-6 levels, reducing the p-eNOS/eNOS ratio and the NO concentration in penile cavernous tissue, and resulting in the inhibition of the erectile function. Heparin inhibited eGlx decomposition and improved erectile function in rats with chronic periodontitis.

Evaluation of Interleukin-6 Levels in Patients with Type 2 Diabetes Mellitus

Background: It has been suggested that inflammatory processes play an important role in the pathogenesis of type 2 diabetes. Individuals who develop type 2 diabetes show signs of low-grade inflammation years before disease onset. This low-grade inflammation has been assumed to be implicated in the pathogenetic mechanisms that cause type 2 Diabetes Mellitus. Inflammatory mediators such as the IL-6 family of cytokines have been proposed to be involved in the events that lead to type 2 diabetes. IL-6 has immunoregulatory actions been proposed to affect glucose homeostasis and metabolism directly and indirectly by action on skeletal muscle cells, adipocytes, hepatocytes, pancreatic b-cells and neuroendocrine cells. Many studies have suggested the role of IL-6 in the pathogenesis of type 2 diabetes mellitus. However, no references have been observed in Bangladesh regarding IL-6 and its association with type 2 diabetes mellitus. It thus may highlight the importance of low-grade inflammation in the pathophysiology of type 2 diabetes mellitus. The purpose of this study was to evaluate type 2 diabetes patients' levels of interleukin-6. Materials and methods: A hospital-based cross-sectional observational study was carried out in the Department of Biochemistry Chittagong Medical College, Department of Endocrinology of Chittagong Medical College Hospital and Chattogram Diabetic Hospital. One hundred (100) type 2 diabetes mellitus patient was included in the study by nonprobability consecutive sampling. Important variables in this study were serum IL-6, BMI, waist circumference and duration of Diabetes Mellitus. Results: The mean serum IL-6 level was 10.08±0.39 pg/ml in patients with type 2 Diabetes Mellitus. Serum IL-6 was positively correlated (r 0.33, p &lt;0.01) with waist circumference and duration of diabetes mellitus (r 0.26, p &lt;0.05). The mean IL-6 was significantly different between BMI groups (F (2,97) =5.39, p=0.006) and was higher in the obese group (10.52±4.00) compared to the overweight and normal BMI (6.78±1.95) and overweight (8.08±3.15) group. Conclusion: It can be concluded that type 2 diabetes mellitus patients had increased serum levels of IL-6. It can give an insight into the possible role of sub clinical inflammation among patients with type 2 Diabetes Mellitus. IAHS Medical Journal Volume 6(2) December 2023; 53-57

DMRT3-mediated lncRNA OIP5-AS1 promotes the pyroptosis of bronchial epithelial cells by binding with EIF4A3 to enhance YAP mRNA stability.

Asthma is featured by persistent airway inflammation. Long noncoding RNAs (lncRNAs) are reported to play critical roles in asthma. However, the function of Opa interacting protein 5-antisense 1 (OIP5-AS1) in pyroptosis during the development of asthma remains unexplored. The blood samples of asthma patients (n = 32) as well as the baseline characteristics of asthma patients or healthy people were collected. An in vivo model of asthma was established using house dust mites (HDM). To mimic asthma in vitro, BEAS-2B cells were treated with HDM. Cell pyroptosis and apoptosis were examined by flow cytometry. The levels of interleukin-1 beta (IL-1β) and interleukin-18 (IL-18) were detected by enzyme-linked immunosorbent assay (ELISA). The binding among messenger RNAs (mRNAs) was assessed by chromatin immunoprecipitation (ChIP), dual luciferase report assay, RNA immunoprecipitation (RIP), co-immunoprecipitation (Co-IP), and RNA pull-down assay, respectively. The cellular localization was observed by fluorescence in situ hybridization (FISH) staining. The level of OIP5-AS1 was upregulated in asthma patients. HDM induced pyroptosis and increased the levels of IL-18, IL-1β, and lactate dehydrogenase (LDH) in BEAS-2B cells, which was obviously reversed by OIP5-AS1 knockdown. Consistently, the expressions of NOD-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), c-caspase 1, and pyroptosis-related gasdermin D-1 (GSDMD-1) in BEAS-2B cells were upregulated by HDM treatment, while these phenomena were partially abolished by silencing of OIP5-AS1. Moreover, HDM promoted the progression of asthma in vivo, which was rescued by the downregulation of OIP5-AS1. OIP5-AS1 silencing decreased HDM-induced cell pyroptosis by inactivation of NLRP3. More importantly, OIP5-AS1 promoted the mRNA stability of yes-associated protein (YAP) via binding with eukaryotic translation initiation factor 4A3 (EIF4A3), and OIP5-AS1 was transcriptionally upregulated by doublesex and mab-3 related transcription factor 3 (DMRT3). DMRT3-mediated OIP5-AS1 aggravated the progression of asthma by mediation of the EIF4A3/YAP axis, which might provide a new therapeutic strategy against asthma.

Pleuropulmonary Manifestations in Patients with Systemic Lupus Erythematosus

Objective — to assess the prevalence of non-infectious pleuropulmonary manifestations in patients with systemic lupus erythematosus (SLE), as well as the demographic, clinical and laboratory characteristics of such patients. Materials and methods. A total of 435 patients with SLE (87.5 % female; median age 37 (26—49) years) were enrolled in a cross-sectional study, including 200 with pleuropulmonary manifestations and 235 without them. Patients were evaluated for demographic details, clinical SLE manifestations, SLE Disease Activity Index 2000 (SLEDAI-2K), SLICC/ACR Damage Index (DI). Laboratory evaluations included complete blood count with erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), high-sensitivity CRP (hs-CRP), interleukin-6 (IL-6), IL-10, complement C3 and C4 levels, specific autoantibodies. Procalcitonin and presepsin serum levels were measured to exclude infections. Results and discussion. At least one pleuropulmonary manifestation occurred in 46 % of patients, with pleurisy being the most frequent (24 %). Respiratory involvement was associated with male sex, longer disease duration, and older age at disease onset. Patients with respiratory complications had higher SLEDAI-2K and SLICC/ACR DI scores than those without pleuropulmonary involvement. Patients with pleuropulmonary manifestations more frequently exhibited lymphadenopathy, nephritis, pericarditis, other cardiac manifestations, fever, weight loss, anemia, and thrombocytopenia; conversely, cutaneous manifestations occurred less frequently in patients with pleuropulmonary involvement. Patients with respiratory involvement were found to have higher levels of ESR, CRP, hs-CRP, and IL-6. A higher frequency of positive anti-La/SSB, antiphospholipid, and anti-chromatin antibodies was observed in patients with pleuropulmonary manifestations compared to those without them.In multivariate logistic analysis, respiratory involvement was positively associated with older age (odds ratio (OR) 1.03 (95 % confidence interval (CI) 1.01—1.05), p = 0.004), higher SLEDAI-2K (OR 1.05 (95 % CI 1.01— 1.09), p = 0.030) and SLICC/ACR DI scores (OR 11.34 (95 % CI 1.03—1.74), p = 0.027), presence of lymphadenopathy (OR 2.27 (95 % CI 1.33—3.88), p = 0.003), pericarditis (OR 4.40 (95 % CI 2.29—8.46), p &lt; 0.001), other cardiac manifestations (OR 10.1 (95 % CI 5.65—17.9), p &lt; 0.001), and systemic symptoms (OR 2.14 (95 % CI 1.24—3.70), p = 0.007). Cutaneous manifestations were, on the other hand, negatively associated with the occurrence of pleuropulmonary symptoms (OR 0.27 (95 % CI 0.15—0.50), p &lt; 0.001). Conclusions. Pleuropulmonary manifestations are frequent in SLE, particularly pleuritis. Respiratory involvement is associated with male sex, older age, longer disease duration, and occurs mainly in patients with active and severe lupus, often with previous or concomitant major organ involvement other than lungs. Patients with pleuropulmonary involvement have higher levels of inflammatory markers and higher frequency of positive anti-La/SSB, antiphospholipid, and anti-chromatin antibodies.

Biocatalytic Clusterzyme Patches Restore Lung Function via Immunomodulation and Mitochondria Protection.

Currently, pulmonary complications such as lung infections during the perioperative period are still the main cause of prolonged hospitalization and death in patients with lung injury due to the lack of effective drugs. Clusterzyme, a kind of artificial enzyme with a high enzyme-like activity and safety profile, exhibits good effects on reducing oxidative stress and immunomodulation. Here, we present the functionalized patches that is administered on the lung airways and rescues the injured organ via clusterzymes. The long-term antioxidant capacity of the patches significantly ameliorated lipopolysaccharide-induced lung function impairment with a significant reduction in lung goblet cell metaplasia and oxidative stress. The inflammatory factors such as cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α levels decreased by 50%, while the mtDNA copy number increased by 50% and ATP production increased by 100%. Mice lung function was significantly improved, suggesting that the patches can rescue lung injury by modulating oxidative stress and immune responses as well as protecting the mitochondria, providing an avenue for effective intervention of lung injury.