Levels Of Inflammatory Markers Research Articles

Mefunidone Inhibits Inflammation, Oxidative Stress, and Epithelial-Mesenchymal Transition in Lens Epithelial Cells.

Inflammation, oxidative stress, and epithelial-mesenchymal transition (EMT) play crucial roles in forming posterior capsular opacification (PCO), particularly in fibrotic PCO. Here we investigated the protective effects of mefunidone (MFD), a novel compound with potent antifibrotic properties, which could be useful in preventing PCO. We utilized an extracapsular lens extraction (ECLE) surgery in mice to simulate the development of PCO in vivo. Treatment was performed immediately postsurgery through the intracameral injection of MFD solution. Expression levels of EMT and inflammatory markers were analyzed using Western blot, qRT-PCR, immunofluorescence, and hematoxylin and eosin staining. Additionally, the oxidative stress indicator malondialdehyde and glutathione expression were monitored to assess the oxidative stress response. In vitro experiments, TGF-β2, and H2O2 were used to treat lens epithelial cells to induce EMT and oxidative stress models, respectively. These models were employed to explore the effects of MFD and investigate its underlying mechanisms. Compared to the model group, the group treated with anterior chamber MFD injection effectively suppressed inflammation, oxidative stress, and fibrotic responses within the capsular bag after ECLE and partially inhibited the downregulation of the epithelial marker E-cadherin. To further elucidate the underlying mechanisms, we discovered that MFD treatment in vitro remarkably reduced inflammation, decreased the production of reactive oxygen species, and suppressed the phosphorylation of TGF-β/SMAD as well as MAPK/ERK, thereby inhibiting the occurrence of EMT. Our findings substantiate the efficacy of MFD in treating PCO and provide insights into its potential mechanisms of action.

Probiotic Supplements Benefit Psoriasis Therapy Rather Than Affecting Disease Risk: Evidence from NHANES Machine-Learning and Meta-Analysis Study.

This research aimed to evaluate the impact of probiotic supplementation on the severity of psoriasis symptoms and its association with the risk of developing the disease. We analyzed the association between probiotic usage and psoriasis among 21,942 participants from the 2009-2014 NHANES, employing advanced machine learning techniques for data analysis. A separate meta-analysis was conducted to assess the effects of probiotics on the severity, life quality, and some related inflammation factors. Dichotomous data were analyzed using odds ratios (ORs) corresponding to the 95% confidence interval (CI). Analysis of NHANES data did not reveal a statistically significant association between probiotic intake and the risk of psoriasis. However, the meta-analysis indicated that probiotic supplementation significantly lowers Psoriasis Area and Severity Index (PASI) scores both for change in PASI score and post-data change, and enhances PASI 75 (OR = 4.80, 95% CI = 2.92-7.89) and clearance responses (OR = 3.14, 95% CI = 1.99-4.96), as well as reduced levels of inflammatory markers. While the improvement of life quality was only observed in the post-treatment data. While probiotic supplements do not appear to reduce the risk of psoriasis, they have a significant positive effect on reducing disease severity. Registered on PROSPERO: Registration number CRD42023484417.

Serum inflammation biomarkers level in cystoid and diffuse diabetic macular edema.

To assess serum inflammatory biomarker levels in patients with different subtypes of diabetic macular edema (DME). We retrospectively analyzed 50 eyes from 37 treatment-naïve DME patients who underwent intravitreal injection therapy between June and December 2023. Based on the morphological characteristics of macular edema in optical coherence tomography (OCT), the eyes were categorized into the cystoid macular edema (CME) group (n = 25) and diffuse retinal thickening (DRT) group (n = 25). Additionally, 25 eyes with diabetes retinopathy but without DME served as the control group. Comprehensive clinical data were reviewed, including best-corrected visual acuity (BCVA), central macular thickness (CMT), macular cube volume (VOL) and hematological examination. The neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII) were calculated. NLR and SII levels were significantly higher in the CME group compared to the DRT group and control group (all P < 0.01). The optimal ROC cutoff value of NLR for CME was 2.27, with 88.0% sensitivity and 68.0% specificity. The optimal ROC cutoff value of SII for CME was 447.33, with 84.0% sensitivity and 60.0% specificity. After initial intravitreal injection therapy, BCVA and VOL significantly improved in each group (all P < 0.01). However, no significant correlation was found between systemic inflammatory marker levels and postoperative changes in BCVA, CMT and VOL (all P > 0.05). Our study suggests that elevated NLR and SII levels are significantly associated with CME. Elevated serum inflammatory biomarkers may indicate a higher incidence of CME in these patients.

(−)-Epigallocatechin-3-gallate (EGCG) ameliorates ovalbumin-induced asthma by inhibiting inflammation via the TNF-α/TNF-R1/NLRP3 signaling pathway

(−)-Epigallocatechin-3-gallate (EGCG) is a polyphenol in green tea with potential lung-protective effects. However, the effects of EGCG on airway inflammation in asthma remain unclear. The aim of this study was to investigate the effect and mechanism of EGCG on asthmatic airway inflammation. In this study, the therapeutic effects of EGCG on ovalbumin (OVA)-induced asthmatic mice were tested first. Second, the effects of EGCG on airway inflammation, airway hyperresponsiveness (AHR), airway mucus hypersecretion, cell apoptosis and differential genes were investigated. Finally, the relationships between the effects of EGCG on airway inflammation and the TNF-α/TNF-R1/NLRP3 signaling pathway in asthmatic mice were explored. The results showed that EGCG could attenuate AHR, alleviate the symptoms of alveolar wall thickening and inflammatory cell infiltration, decrease the levels of inflammatory cytokines and airway mucus markers, reduce apoptosis and reactive oxygen species (ROS) and increase the mitochondrial membrane potential (MMP) in primary lung cells in asthmatic mice. Additionally, EGCG significantly inhibited the activation of the TNF-α/TNF-R1/NLRP3 signaling pathway in the lung tissues of asthmatic mice. The lowest binding free energies of EGCG with TNF-α, TNF-R1 and NLRP3 were −11.6, −11.6 and −8.2 kcal/mol, respectively. Moreover, the equilibrium dissociation constant (KD) of EGCG and TNF-R1was 26.05 μmol/L. EGCG-mediated inhibition of TNF-α/TNF-R1/NLRP3 signaling pathway activation was blocked in LPS-induced BEAS-2B and RAW264.7 cells overexpressing TNF-α. Consequently, EGCG effectively attenuated AHR and inhibited airway inflammation and airway mucus hypersecretion in asthmatic mice, and these effects may be closely related to the TNF-α/TNF-R1/NLRP3 signaling pathway.

Pickled radish alleviates the progression of colitis in mice by reducing inflammation and repairing intestinal barrier

Scope: Pickled radish is a traditional fermented food known for its health benefits, however, evidence supporting its role in regulating gastrointestinal function is limited. This study aimed to investigate the beneficial effect of pickled radish on DSS-induced colitis in mice. Method and Results: Divide the mice into four groups: control, DSS model, low-dose (DSS+ 5 % pickled radish powder), and high-dose (DSS+ 10 % pickled radish powder). Colitis was induced by 3 % DSS administration in drinking water for eight days. Body weight loss, disease activity index (DAI), colon length, histology, and levels of inflammatory markers were measured to evaluate the effects of pickled radish on colitis. The results indicate that pickled radish significantly eased symptoms of colitis in mice induced by DSS, dose-dependently reducing DAI, reversed colon shortening, alleviating pathological damage to colon tissue and inflammatory response. Mechanistic investigation revealed that pickled radish upregulated the expression of tight junction-related genes (Zo-1, E-cadherin) and down-regulated inflammation-related genes (Il-1β, Il-6, TNF-α). Moreover, low-dose pickled radish significantly reversed the imbalance of gut microbiota and increased SCFAs. Conclusion: These findings suggest the potential of pickled radish in functional foods targeting the improvement of gastrointestinal health.

Possible Risk Factors Contributing to Atrial Fibrillation Occurrence in Heart Failure With Mildly Reduced Ejection Fraction.

Heart failure (HF) is often accompanied by atrial fibrillation (AF), which significantly worsens the outcome of both diseases. Half of individuals with HF has AF, and HF occurs in more than one-third of individuals with AF. Thus, HF and AF are commonly encountered together and are closely interrelated with similar risk factors. The aim of this study was to investigate the impact of potential risk factors on the occurrence of paroxysmal/persistent AF in patients with heart failure with moderately reduced ejection fraction (HFmrEF). The study included 193 patients with HFmrEF and nonvalvular paroxysmal/persistent AF after successful cardioversion. As a control group the similar 76 patients without AF were examined. All patients underwent the examination, including electrocardiography (ECG), echocardiography, ambulatory blood pressure monitoring and Holter ECG monitoring. Levels of inflammatory markers, such as high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and the fibrotic marker transforming growth factor-β1 (TGF-β1) were measured using the enzyme-linked immunosorbent assay (ELISA) method. The obtained results were modeled using binary logistic regression using the odds ratio (OR). It was shown that frequent episodes of hypertensive crisis (HC) and increased body mass index (BMI) were possible risk factors for paroxysmal/persistent AF. An increased OR of diastolic and systolic parameters of the left ventricle was associated with significant atrial and ventricular remodeling. Statistically, higher OR of inflammatory markers levels, such as hs-CRP, IL-6 and TNF-α were associated with an increased risk of paroxysmal/persistent AF occurrence in HFmrEF patients compared to similar patients without AF. An increase of the fibrosis marker TGF-β1 OR was statistically significant in patients with persistent AF. It could be considered that frequency of HC, BMI, atrial and ventricular remodeling, as well as an increase of inflammation markers were possible risk factors for the occurrence of paroxysmal/persistent AF in HFmrEF patients. Moreover, fibrosis factor level significantly increased the likelihood of persistent AF in these patients.

Butyrate modulates gut microbiota and anti-inflammatory response in attenuating cisplatin-induced kidney injury.

In our previous research, we reported that administering probiotics Lactobacillus reuteri and Clostridium butyricum (LCs) before cisplatin treatment effectively modifies structures of the gut microbiota and restore ecological balance and significantly increases butyrate levels, a process closely associated with reducing cisplatin-induced nephrotoxicity. This study aims to investigate further whether the elevation of metabolite butyrate in the gut, promoted by probiotics LCs, can effectively mitigate the nephrotoxic effects of cisplatin and the progression of renal senescence in rats. Results show that butyrate administration significantly improved kidney function and decreased renal fibrosis in a dose-dependent manner compared to the cisplatin group. Its effects were associated with reductions in inflammatory responses, evidenced by decreased levels of key inflammatory markers, including KIM-1, MPO, NOX2, F4/80, and TGF-β1, alongside increased production of the anti-inflammatory cytokine IL-10. Furthermore, the butyrate intervention ameliorated cisplatin-induced gut microbiota dysbiosis, preserving the structure and diversity of healthy microbial communities. Specifically, we observed a decrease in the abundance of Escherichia_Shigella and Blautia, alongside an increase in the abundance of the butyrate-producing genus Roseburia. Notably, Escherichia_Shigella exhibited a positive correlation with the pro-inflammatory factor MPO, while displaying a negative correlation with the anti-inflammatory cytokine IL-10. Butyrate also attenuated the cisplatin-induced expression of senescence markers p21 and p16 in kidney tissue. It alleviated the cisplatin-increased senescence-associated beta-galactosidase activity and reactive oxygen species production in SV40 MES-13 cells. These results indicate that butyrate, derived from the gut microbiota, may exert a protective effect against cisplatin-induced kidney damage by regulating microbiota balance and anti-inflammatory effects.

Tyrosine hydroxylase-positive neurons in the rostral ventrolateral medulla mediate sympathetic activation in sepsis

AimSepsis results in high mortality and is associated with organ dysfunction caused by infection. The present study aimed to elucidate whether early-stage sympathetic activation is associated with the prognosis of sepsis and its possible mechanisms. MethodsPatients with sepsis and healthy controls were included. Sepsis in rats was induced by lipopolysaccharide. Dexmedetomidine, a α2-adrenergic receptor agonist, was used in patients and rats with sepsis to evaluate the role of the sympathetic nervous system in sepsis. Holter monitoring was used to detect heart rate variability, while plasma samples were obtained to measure levels of norepinephrine and inflammatory markers. Mean arterial pressure, heart rate, and renal sympathetic nerve activity were recorded. Immunofluorescence was used to detect the activation of neurons in the rostral ventrolateral medulla (RVLM). ResultsIn patients with sepsis, plasma levels of norepinephrine and interleukin-1β were higher compared with those in controls and positively correlated with acute physiology and chronic health evaluation (APACHEII). SDNN and SDANN were significantly reduced as well as negatively correlated with APACHEII. Meanwhile, rats with sepsis showed increased of sympathetic outflow and plasma levels of norepinephrine, with increased c-fos levels in the RVLM. Treatment with dexmedetomidine could improve prognosis. Lesion of tyrosine hydroxylase-positive neurons in the RVLM attenuated sympathetic activation and target organs damage in septic rats as well as improved survival. ConclusionThe results suggest that tyrosine hydroxylase-positive neurons in the RVLM might contribute to the prognosis of sepsis via activation of the sympathetic nervous system, while dexmedetomidine could ameliorate sepsis via inhibiting sympathetic activation.

Fenofibrate attenuates renal lipotoxicity in uninephrectomized mice with high-fat diet-induced obesity.

The objective of this study was to investigate the role of fenofibrate, a peroxisome proliferator-activated receptor-α agonist, in obesity-induced kidney damage (lipotoxicity) in mice with uninephrectomy. C57BL/6 mice underwent uninephrectomy and sham surgeries and were fed normocaloric or high-fat diets. After 10 weeks, obese mice were administered 0.02% fenofibrate for 10 weeks. Kidney function and morphology were evaluated, as well as levels of inflammatory and fibrotic mediators and lipid metabolism markers. High-fat diet-fed mice developed characteristic obesity and hyperlipidemia, with subsequent renal lipid accumulation and damage, including mesangial expansion, interstitial fibrosis, inflammation, and proteinuria. These changes were greater in obese uninephrectomy mice than in obese sham mice. Fenofibrate treatment prevented hyperlipidemia and glomerular lesions, lowered lipid accumulation, ameliorated renal dysfunction, and attenuated inflammation and renal fibrosis. Furthermore, fenofibrate treatment downregulated renal tissue expression of plasminogen activator inhibitor-1, monocyte chemoattractant protein-1, and local expression of fibroblast growth factor-21. Peroxisome proliferator-activated receptor-α activation by fenofibrate, with subsequent lipolysis, attenuated glomerular and tubulointerstitial lesions induced by renal lipotoxicity, thus protecting the kidneys of uninephrectomy mice from obesity-induced lesions. The study findings suggest a pathway in the pharmacological action of fenofibrate, providing insight into the mechanisms involved in kidney damage caused by obesity in kidney donors.

Allium cepa L. as a natural antioxidant: Its efficacy in combating heat stress-induced physiological alterations

Heat stress (HS) is a major physiological stressor that induces oxidative damage, inflammation, and metabolic disruptions, all of which cause harm to health. This study investigates the potential protective effects of Allium cepa L. (AC), against the physiological alterations brought on by HS. Twenty male rats were utilized in this study and divided into 4 groups: Control, HS, AC, and HS + AC. Rats were exposed to 38–39 °C for 2 h each day for three weeks to induce HS while 1.0 ml/100 g body weight of ethanolic extract of AC was administered orally for three weeks. Hematological parameters, inflammatory markers, and lipid profiles were analyzed using blood samples obtained through heart puncture.The findings demonstrated that HS significantly lowered levels of hemoglobin (HB), red blood cell (RBC) counts, and antioxidant enzyme activity. However, there was a significant rise in the levels of inflammatory markers, platelet counts, LDL-c triglyceride (TG), total cholesterol (TC), and white blood cell (WBC). Many of these alterations were reversed by AC supplementation, by increasing RBC counts, HB levels, and antioxidant enzyme activities while decreasing LDL-c, TG and TC, MDA, and TNF-α (tumor necrosis factor-α). However, the positive benefits of AC were partially diminished in the HS + AC group, perhaps due to the severe oxidative stress caused by heat stress (HS).This study highlights the probable potential of AC as a natural antioxidant in modifying heat stress-induced oxidative damage, hematological changes, and lipid metabolism disruptions; however, its protective effects are insufficient to mitigate heat stress. Therefore, further research is required to explore the other possible underlying mechanisms.

Strong Positive Correlations Between the Levels of Systemic Inflammation Markers and the Occurrence of Persistent Atrial Fibrillation.

In this study, a retrospective analysis was conducted to investigate the associations between systemic inflammation markers and persistent atrial fibrillation (pAF), intending to identify potential biomarkers for early detection of pAF.In the analysis, a total of 207 patients were included, with 109 in the pAF group and 98 in the non-pAF group. The associations between three systemic inflammation markers were investigated, namely, the systemic immune inflammation index (SII), system inflammation response index (SIRI), and aggregate index of systemic inflammation (AISI), and pAF.The proportion of pAF showed a gradual increase with increasing logSII, logSIRI, and logAISI tertiles. Compared with those in the lowest tertiles, those in the highest logSII and logSIRI tertiles had 3.196- and 2.884-fold higher risks of developing pAF, respectively. Nonetheless, no significant correlation between logAISI and pAF risk was observed in the highest tertile of logAISI. The restricted cubic spline analysis revealed a nonlinear relationship between the elevation of systemic inflammation markers and the risk of pAF, with logSII ≥ 2.56, logSIRI ≥ -0.10, and logAISI ≥ 2.28 identified as significant predictors. The receiver operating characteristic analysis of logSII, logSIRI, and logAISI showed AUC values of 0.629, 0.721, and 0.646, respectively. It also presented favorable sensitivity and specificity of these systemic inflammation markers in detecting the presence of pAF.To conclude, our cross-sectional study shows significant positive correlations between the SII, SIRI, and AISI with the incidence of pAF.

Female mice exhibit similar long-term plasticity and microglial properties between the dorsal and ventral hippocampal poles

The hippocampus is a heterogenous structure that exhibits functional segregation along its longitudinal axis. We recently showed that in male mice, microglia, the brain’s resident immune cells, differ between the dorsal (DH) and ventral (VH) hippocampus, impacting long-term potentiation (LTP) mainly through the CX3CL1-CX3CR1 signaling. Here, we assessed the specific features of the hippocampal poles in female mice, demonstrating a similar LTP amplitude in VH and DH in both control and Cx3cr1 knock-out mice. In addition, the expression levels of Cx3cr1 and Cx3cl1 mRNA do not differ between the two poles in control mice. These data support the critical role of the CX3CL1-CX3CR1 signaling in setting the physiological amount of plasticity, equally between poles in females. Although BDNF is higher in DH compared to VH, the expression levels of inflammatory markers involved in plasticity and of phagocytosis markers in microglia are comparable between the two poles. In accordance, microglia soma and arborization area/perimeter, and microglial ultrastructure are similar across regions, with the exception of microglial density, cells arborization solidity and circularity that are higher in DH. Understanding the molecular processes underlying microglial sex differences and their potential implications for plasticity in specific brain regions is of major importance in physiological and pathological conditions.

A prebiotic intervention improves mood in everyday life in healthy women but not in men: Exploratory results from a larger double-blind placebo controlled cross-over study

Prebiotic dietary fiber (PDF) may reduce feelings of stress or improve mood in healthy individuals. Yet gut intervention studies that focus on mood in daily life are lacking and few studies include extensive biological sample analyses to gain mechanistic insights. As part of a larger randomized placebo-controlled crossover study including healthy individuals, we explored the effects of 12 weeks of PDF (acacia gum and carrot powder) on everyday mood, as measured with ecological momentary assessment (EMA). Microbiome composition and levels of microbial metabolites, endocrine, and inflammatory markers were determined prior to and after both intervention phases. Fifty-four participants completed the study. The intervention significantly increased daily positive affect (PA) and reduced daily negative affect (NA) in female but not male participants. The intervention-induced reduction in NA was associated with an increase in microbial diversity in female participants. The intervention did not significantly affect levels of fecal short chain fatty acids, cortisol, and inflammatory markers. This is one of the first studies to show that a dietary fiber intervention can positively alter mood as it is experienced in everyday life. Overall, our findings may stimulate more targeted gut-microbiome interventions and detection of its mental health effects in real life.

Comparison of [18F]FAPI-42 and [18F]FDG PET/CT in the evaluation of systemic vasculitis.

The role of fibroblast activation protein (FAP)-targeted imaging in systemic vasculitis is currently unclear. We aimed to evaluate the clinical value of fluorine-18-labeled FAP inhibitor 42 ([18F]FAPI-42) in patients with systemic vasculitis and to compare with [18F]fluorodeoxyglucose (FDG) imaging. Patients with systemic vasculitis who underwent dual-tracer PET/CT([18F]FDG and [18F]FAPI) imaging from September 2020 to March 2022 were retrospectively analyzed. Positive lesions are defined as vascular/extravascular lesions with increased tracer uptake above surrounding background, which cannot be attributed to the physiologic biodistribution of the radiotracer. The vascular/extravascular lesion detection rate and semiquantitative values (SUVmax, TBRblood and TBRliver) of [18F]FAPI and [18F]FDG were compared, and the correlation between the extent and range of tracer uptake and levels of inflammatory markers was investigated. Thirty patients (13 males and 17 females; mean age, 52.5 ± 17.2 years) with systemic vasculitis were included (17 large vessel vasculitis, 10 anti-neutrophil cytoplasmic antibody-associated vasculitis, 2 Behcet's disease and 1 polyarteritis nodosa). [18F]FDG PET/CT had positive findings in 93.3% (28/30) of patients, while [18F]FAPI PET/CT had positive findings in all patients (100%, P = 0.500). Compared with [18F]FDG PET/CT, [18F]FAPI PET/CT detected more lesions (161/168 vs. 145/168, P = 0.005), and more extensive vascular involvement in 60% (18/30) of patients. Although SUVmax did not differ significantly between [18F]FAPI and [18F]FDG (median, 5.94 vs. 5.46, P = 0.517), [18F]FAPI had higher TBRliver (median, 9.59 vs. 3.15, P < 0.001) and TBRblood (median, 5.45 vs. 4.20, P = 0.006). The total number of positive lesions in FAPI PET/CT show a moderate correlation with erythrocyte sedimentation rate (rs =0.478, P = 0.008) and C-reactive protein (rs =0.486, P = 0.006). After treatment, follow-up FAPI PET/CT of 6 patients showed decreased SUVmax, TBR and number of detected lesions, paralleling the clinical remission. [18F]FAPI PET/CT imaging is a promising imaging modality for the diagnosis and therapeutic monitoring of systemic vasculitis.

Evaluation of Inflammatory Status in COVID-19 Patients with Chronic Kidney Disease: A Comparative Analysis Based on Creatinine Clearance Levels

Background and Objectives: Patients with chronic kidney disease (CKD) are at increased risk of severe COVID-19 outcomes due to their compromised immune systems and chronic inflammatory state. This study aimed to evaluate and compare the inflammatory status of COVID-19 patients with CKD, stratified by creatinine clearance (CrCl) levels: CrCl &lt; 30 mL/min, CrCl 30–60 mL/min, and CrCl &gt; 60 mL/min. Multiple inflammatory scores combining laboratory parameters were assessed, including novel scores and established indices. Methods: In this retrospective cohort study, 223 patients admitted with confirmed COVID-19 were included and divided into three groups based on CrCl levels: CrCl &lt; 30 (n = 41), CrCl 30–60 (n = 78), and CrCl &gt; 60 (n = 104). Laboratory parameters including C-reactive protein (CRP), interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), ferritin, platelet count, absolute neutrophil count (ANC), absolute lymphocyte count (ALC), and serum albumin were collected. Multiple inflammatory scores were calculated, including inflammation scores (IS1–IS4), the systemic inflammatory index (SII), the C-reactive protein-to-albumin ratio (CAR), the lymphocyte-to-C-reactive protein ratio (LCR), and the prognostic nutritional index (PNI). Statistical analyses were performed to compare inflammatory scores among groups and assess correlations with clinical outcomes. Results: The CrCl &lt; 30 group exhibited significantly higher levels of inflammatory markers and inflammatory scores compared with the other groups (p &lt; 0.001). Among the additional scores, CAR and SII were significantly elevated in patients with lower CrCl levels, while LCR and PNI were decreased. CAR showed a strong positive correlation with COVID-19 severity (r = 0.65, p &lt; 0.001), and PNI was inversely correlated with mortality (r = −0.58, p &lt; 0.001). Multivariate regression analysis indicated that lower CrCl levels, higher IS3 and CAR, and lower PNI were independent predictors of severe COVID-19 outcomes. Conclusions: CKD patients with lower CrCl levels have an amplified inflammatory response during COVID-19 infection, as evidenced by elevated inflammatory scores. The additional inflammatory scores, particularly CAR and PNI, may serve as valuable tools for risk stratification and management of COVID-19 in CKD patients. Early identification of patients with high CAR and low PNI could improve clinical outcomes through timely therapeutic interventions.

Impact of Rs657152 Gene Polymorphisms on Inflammatory Markers in COVID-19 Patients With Type 2 Diabetes Mellitus

COVID-19 has significantly affected people with pre-existing conditions, particularly those suffering from type 2 diabetes mellitus (T2DM), as it increases the risk of complications and mortality. The dysregulated inflammatory response in T2DM patients is a critical factor contributing to severe disease progression in these individuals. Recent research suggests that genetic variations, such as Rs657152 polymorphisms, could influence inflammatory markers and immune responses in T2DM patients infected with COVID-19. Understanding this genetic relationship is crucial for improving treatment strategies and predicting outcomes in this high-risk group. The present was designed to evaluate the correlation of Rs657152 gene polymorphisms with inflammatory markers in COVID-19 patients with T2DM. This study enrolled 91 participants, including 31 healthy individuals, 30 COVID-19 patients with T2DM, and 30 non-diabetic COVID-19 patients. Inflammatory markers (CRP, IL-6, D-dimer, and ferritin) were measured, and Rs657152 polymorphisms were genotyped. Statistical analysis was conducted using SPSS version 23. COVID-19 patients with T2DM showed significantly higher BMI, greater severity of COVID-19, and increased levels of inflammatory markers compared to non-diabetic patients. A significant correlation was observed between the Rs657152 polymorphisms and elevated levels of IL-6, D-dimer, and ferritin in T2DM patients (P&lt;0.05). The polymorphisms of the Rs657152 gene may exacerbate the inflammatory response in COVID-19 patients with T2DM, contributing to increased severity of the disease.

Rosmarinic Acid Ameliorates Dermatophagoides farinae Extract-Induced Atopic Dermatitis-like Skin Inflammation by Activating the Nrf2/HO-1 Signaling Pathway

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. AD pathogenesis is associated with increased oxidative stress, impairment of the skin barrier, and activation of the immune response. Rosmarinic acid (RA), a caffeic acid ester, is known for its anti-inflammatory and antioxidant properties. However, the effects of RA on Dermatophagoides farinae extract (DfE)-induced AD-like skin inflammation, as well as its ability to regulate oxidative stress through the Nrf2/HO-1 pathway in TNF-α/IFN-γ-treated keratinocytes, remain unclear. We investigated RA activity in a DfE-induced AD-like skin inflammation mouse model and IFN-γ/TNF-α-stimulated keratinocytes. We found that RA attenuates DfE-induced inflammation by decreasing dermatitis scores and serum inflammatory marker levels and mast cell infiltration. Additionally, RA significantly suppressed IFN-γ/TNF-α-induced chemokine production in keratinocytes and reduced Th cytokine levels in concanavalin A-stimulated splenocytes. Importantly, RA also increased Nrf2/HO-1 expression in TNF-α/IFN-γ-treated keratinocytes. In conclusion, this study demonstrated that RA effectively alleviates DfE-induced AD-like skin lesions by reducing the levels of inflammatory cytokines and chemokines. Furthermore, RA promotes Nrf2/HO-1 signaling in keratinocytes, which may help mitigate DfE-induced oxidative stress, thereby alleviating AD-like skin inflammation. These findings highlight the potential of RA as a therapeutic agent for treating AD and other skin inflammation.

Efficacy of dupilumab in the treatment of COPD with type 2 inflammation: a real-world study

BackgroundThe real-world study on efficacy and safety of dupilumab in chronic obstructive pulmonary disease (COPD)with type 2 inflammation are scarce. Our objective was to assess the impact of dupilumab in such patients within a real-world setting. MethodsSeventeen patients with COPD and type 2 inflammation, who underwent triple inhaled therapy in conjunction with dupilumab from January 2020 to October 2023, comprised the research group. Similarly, another 17 patients with COPD and type 2 inflammation, who received only triple inhaled therapy, were included in the control group. After a six-month treatment period, pulmonary function tests, type 2 inflammatory marker levels, and quality of life assessments were compared between the two groups to evaluate the effectiveness of dupilumab in combination with triple inhaled therapy for COPD with type 2 inflammation. ResultsFollowing treatment, the research group exhibited significant improvements in forced expiratory volume in one second (FEV1) and forced expiratory flow between 25% and 75% of forced vital capacity (FVC) compared to the control group (P < 0.05). Notably, the FEV1 and FVC values of the research group were also notably superior to those of the control group post-treatment (P < 0.05). Additionally, the research group demonstrated a statistically significant enhancement in COPD Assessment Test scores after treatment (P < 0.05). ConclusionThe combination of dupilumab with triple inhaled therapy has been shown to enhance pulmonary function, decrease immunoglobulin E levels, manage airway inflammation, and elevate the quality of life of patients with COPD and type 2 inflammation.

Association of Apical Periodontitis with Glycated Hemoglobin Levels and Systemic Inflammatory Markers in Patients with Type 2 Diabetes: A Cross-Sectional Study

IntroductionThis cross-sectional study, as a preliminary part of an ongoing project, aimed to investigate the effect of apical peridontitis (AP) on glycated hemoglobin (HbA1c) and systemic inflammatory markers in diabetic individuals. MethodsA total of 280 individuals (140 with type 2 diabetes mellitus [T2DM] and 140 healthy) with and without AP were enrolled. Sixty-four age-, gender-, and body mass index–matched participants each in T2DM with AP group (DAP), T2DM without apical periodontitis (D), systemically healthy controls with apical periodontitis (CAP), and without apical periodontitis (C) groups were evaluated. Radiologic and clinical oral examination was performed for confirming the diagnosis of AP and periapical index scoring (PAI). Blood analyses were carried out for interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, high-sensitivity C-reactive protein (hsCRP), and HbA1c assessment. ResultsSignificantly higher levels of IL-1β, TNF-α, and hsCRP were observed in patients with AP in both diabetes and control groups (P < .05). In the diabetes group, AP contributed to significantly raised levels of HbA1c compared with T2DM group patients without AP. After controlling for possible confounders, partial corelation coefficients revealed positive corelation of presence of AP as well as size of the periapical lesion with HbA1c and serum levels of inflammatory markers in both diabetic and healthy individuals. Multivariate linear regression analysis revealed both presence of AP (P < .05) as well as the size of lesion (P < .001) were found to significantly predict the HbA1c levels as well as the levels of IL-1β, IL-6, TNF-α, and hsCRP in both diabetic and non-diabetic individuals. ConclusionsThese findings suggest that both presence of AP and size of periapical lesion was associated with glycemic control and systemic inflammatory burden in patients with T2DM.

Shen Qi Wan regulates OPN/CD44/PI3K pathway to improve airway inflammation in COPD: Network pharmacology, bioinformatics, and experimental validation

BackgroundChronic obstructive pulmonary disease (COPD) is one of the most common respiratory diseases with undefined pathogenesis and unsatisfactory therapeutic options. Shenqi Wan (SQW), a traditional Chinese medicinal compound, has demonstrated certain preventive and therapeutic effects on COPD. However, the underlying molecular mechanisms remain incompletely understood. In this study, we used weighted gene co-expression network analysis (WGCNA) and machine learning to identify biomarkers for COPD, combined with network pharmacology and experimental validation to evaluate how SQW reduces airway inflammation in COPD. MethodsTargets of SQW in treating COPD and its network regulation mechanism were predicted via network pharmacology. Meanwhile, potential biomarkers were predicted using WGCNA and machine learning algorithms and validated in COPD patients. The relationship between the core pathway and key target was analyzed by ingenuity pathway analysis (IPA) to reveal the regulatory mechanism of SQW. We evaluated the efficacy of SQW treatment in LPS/MS-induced COPD mice by evaluating lung function, histopathological parameters, and levels of inflammatory markers and oxidative stress. The distribution and expression of OPN/CD44/PI3K loop-related proteins were examined through immunofluorescence staining and Western Blotting. In vitro, we added LPS to BEAS-2B cells to mimic the inflammatory microenvironment and transfected the cells with OPN overexpression plasmid to observe the improvement induced by SQW. ResultsGO and KEGG analyses demonstrated that SQW inhibited inflammation and oxidative stress via the PI3K/Akt pathway, thereby improving COPD. Machine learning algorithms identified OPN as a potential biomarker, with elevated expression observed in the lung tissue of COPD patients. IPA indicated that OPN may modulate the CD44-mediated activation of the PI3K/AKT pathway, forming a positive feedback regulatory mechanism. SQW ameliorated lung function and pathological injury in mice; further, it reduced inflammation, oxidative stress, and OPN/CD44/PI3K positive feedback loop-related protein expression in both mice and cells. After OPN overexpression, the levels of inflammatory factors and ROS were significantly increased, and the OPN/CD44/PI3K signal was further activated, weakening the ameliorative effect of the SQW drug-containing serum. ConclusionOverall, SQW contributed to ameliorating COPD by reducing airway inflammation and oxidative stress through inhibiting the OPN/CD44/PI3K positive feedback loop.