Levels Of Inflammatory Mediators Research Articles

Effects of Lycopene as Monotherapy or Combined with Clobetasol on Spleen Index and Inflammatory Markers in Mouse Model of Imiquimod-Induced Psoriasis

Background: Lycopene has demonstrated favorable impacts on diverse health conditions, particularly those of an inflammatory nature. Objective: To evaluate the impact of topical application of lycopene on the spleens of mice with psoriasis induced by imiquimod (IMQ). Methods: The study employed a sample size of 48 mice, divided into six groups of eight mice each. The experimental protocol involved the application of IMQ to each of the five groups twice. The first application was administered for six days to induce psoriasis, followed by a second application for another six days while the tested medications were concurrently administered, with the exception of the first group, which served as the control group. Following the six-day induction phase, group 2 was treated exclusively with petrolatum jelly. On the other hand, groups 3-6 were subjected to different treatments, including clobetasol propionate, lycopene at concentrations of 0.125 mg/ml and 0.25 mg/ml, and a combination of 0.05% clobetasol and 0.25 mg/ml of lycopene. Each of the examined pharmaceutical substances was administered topically once daily for a duration of six days at the IMQ application site. Results: Lycopene at a concentration of 0.25 mg/ml resulted in a significant reduction in the spleen index and a restoration of the tissue levels of inflammatory mediators (TNF-α, IL-23, NF-κB, and IL-17) that were close to normal. Conclusion: The anti-inflammatory properties of lycopene can significantly aid in the normalization of spleens in patients who have developed psoriasis due to imiquimod.matory capabilities.

GP73 enhances the ox-LDL-induced inflammatory response in THP-1 derived macrophages via affecting NLRP3 inflammasome signaling

BackgroundAtherosclerosis is a chronic inflammatory disease with its molecular basis incompletely understood. Here, we determined whether the Golgi phosphoprotein 73 (GP73), a novel protein highly related to inflammation and disrupted lipid metabolism, was involved in the development of atherosclerosis. MethodsPublic microarray databases of human vascular samples were analyzed for expression patterns. Apolipoprotein-E-gene-deficient (ApoE−/−) mice (8-week-old) were randomly assigned to either a chow diet group or a high-fat diet group. The levels of serum GP73, lipid profiles and key inflammatory cytokines were determined by ELISA. The aortic root plaque was isolated and used for by Oil Red O staining. PMA-differentiated THP-1 macrophages were transfected with GP73 small interfering RNA (siRNA) or infected with adenovirus expressing GP73, and then stimulated with oxidized low density lipoprotein (ox-LDL). The expressions of pro-inflammatory cytokines and signal pathway key targets were determined by ELISA kit and Western blot respectively. In addition, ichloro-dihydro-fluorescein diacetate (DCFH-DA) was used to measure the intracellular ROS levels. ResultsThe expressions of GP73 and NLRP3 were substantially upregulated in human atherosclerotic lesions. There were significant linear correlations between GP73 and inflammatory cytokines expressions. High-fat diet-induced atherosclerosis and increased levels of plasma inflammatory mediators (IL-1β, IL-18, and TNF-α) were observed in ApoE−/− mice. Besides, the expressions of GP73 in the aorta and serum were significantly upregulated and positively correlated with the NLRP3 expression. In the THP-1 derived macrophages, ox-LDL treatment upregulated the expressions of GP73 and NLRP3 proteins and activated the inflammatory responses in a concentration-dependent and time-dependent manner. Silencing of GP73 attenuated the inflammatory response and rescued the decreased migration induced by ox-LDL, inhibiting the NLRP3 inflammasome signaling and the ROS and p-NF-κB activation. ConclusionsWe demonstrated that GP73 promoted the ox-LDL-induced inflammation in macrophages by affecting the NF-κB/NLRP3 inflammasome signaling, and may play a role in atherosclerosis.

Levels of chemokines and other inflammatory mediators in patients with mild cognitive impairment undergoing rehabilitation

Alzheimer's disease is the most common neurodegenerative disease in old age. In some cases, it is preceded by mild cognitive impairment (MCI). One of the important components in the pathogenesis of neurodegeneration is chronic neuroinflammation (inflammatory activation of microglia and astrocytes in the brain). Systemic inflammatory response and immune dysregulation may contribute to neuroinflammation. The purpose of this study was to investigate the level of chemokines and other inflammatory mediators in patients with MCI who underwent medical rehabilitation, and to study its associations with the severity of cognitive impairment. The study group included 48 patients with MCI undergoing rehabilitation. Rehabilitation included cognitive therapy, psychotherapy and tasks for unaided performance. Repeated examination was conducted 6 months after the completion of rehabilitation. The control group included 46 healthy volunteers. Multiplex assay was used to determine serum cytokine and chemokine concentrations. Student's t-test was used to assess the significance of differences. Assessment of cognitive functions was performed using international neuropsychological scales. In patients with MCI, we have found an increase in the levels of several cytokines and chemokines (TNFα, CXCL10/IP10, MDC) that regulate systemic inflammation, cellular and humoral mechanisms of adaptive immunity. After the rehabilitation course their levels returned to normal. It was also found that decrease in CCL7 level in the patients before the rehabilitation course is associated with the severity of cognitive impairment. The findings contribute to understanding the role of chemokines in the pathogenesis of MCI, and indicate that their levels can be potential biomarkers of the severity of cognitive impairment. For translation of the findings into clinical practice, their validation in larger studies is needed, as well as assessing the associations between chemokine levels and the severity of cognitive impairment in MCI over long-term follow-up.

Low-dose radiation therapy suppresses viral pneumonia by enhancing broad-spectrum anti-inflammatory responses via transforming growth factor-β production.

Low-dose radiation therapy (LDRT) can suppress intractable inflammation, such as that in rheumatoid arthritis, and is used for treating more than 10,000 rheumatoid arthritis patients annually in Europe. Several recent clinical trials have reported that LDRT can effectively reduce the severity of coronavirus disease (COVID-19) and other cases of viral pneumonia. However, the therapeutic mechanism of LDRT remains unelucidated. Therefore, in the current study, we aimed to investigate the molecular mechanism underlying immunological alterations in influenza pneumonia after LDRT. Mice were irradiated to the whole lung 1 day post-infection. The changes in levels of inflammatory mediators (cytokines and chemokines) and immune cell populations in the bronchoalveolar lavage (BALF), lungs, and serum were examined. LDRT-treated mice displayed markedly increased survival rates and reduced lung edema and airway and vascular inflammation in the lung; however, the viral titers in the lungs were unaffected. Levels of primary inflammatory cytokines were reduced after LDRT, and transforming growth factor-β (TGF-β) levels increased significantly on day 1 following LDRT. Levels of chemokines increased from day 3 following LDRT. Additionally, M2 macrophage polarization or recruitment was increased following LDRT. We found that LDRT-induced TGF-β reduced the levels of cytokines and polarized M2 cells and blocked immune cell infiltration, including neutrophils, in BALF. LDRT-induced early TGF-β production was shown to be a key regulator involved in broad-spectrum anti-inflammatory activity in virus-infected lungs. Therefore, LDRT or TGF-β may be an alternative therapy for viral pneumonia.

Sleep duration and inflammatory mediator levels associated with long-term prognosis in temporomandibular disorders.

Sleep disturbance is a systemic symptom and at the same time a major modulating factor of temporomandibular disorders (TMD). Inflammation is known as a underlying mechanism involved in both poor sleep and increased pain. The relationship between long-term clinical characteristics and hematologic biomarkers of hypothalamic-pituitary-adrenal axis activity and inflammation in TMD patients according to sleep duration was investigated to verify the possible role of sleep disturbance and systemic inflammation in TMD. Inflammatory and stress mediator levels of venous blood samples were investigated in 63 female TMD patients along with comorbidity levels including stress, somatization, autonomic symptoms and sleep quality based on structured questionnaires. Differences in long-term clinical characteristics and hematologic variables following conservative treatment were analysed according to total sleep time as normal, short and long sleep groups. Also, clinical and hematologic indices related to favourable treatment response were sought out. Significantly less patients in the long sleep group reported pain on voluntary mandibular movement (p = .042) while depression (p = .043) and somatization levels (p = .002) were significantly higher in the short sleep group. Norepinephrine levels of the long sleep group were significantly lower than other groups. Decrease in pain intensity with treatment was smallest in the short sleep group. Erythrocyte sedimentation rate was associated with significant pain improvement at 3 months post-treatment and interleukin-1β, -4, and -8 levels could predict favourable treatment response. Short sleep is associated with more comorbidities and unfavourable long-term treatment response in TMD which may be mediated by systemic inflammation. Effective management of sleep is necessary for successful TMD management.

Cyclophilins modify their profile depending on the organ or tissue in a murine inflammatory model

Inflammation is the leading subjacent cause of many chronic diseases. Despite several studies in the last decades, the molecular mechanism involving its pathophysiology is not fully known. Recently, the implication of cyclophilins in inflammatory-based diseases has been demonstrated. However, the main role of cyclophilins in these processes remains elusive. Hence, a mouse model of systemic inflammation was used to better understand the relationship between cyclophilins and their tissue distribution. To induce inflammation, mice were fed with high-fat diet for 10 weeks. In these conditions, serum levels of interleukins 2 and 6, tumour necrosis factor-α, interferon-ϒ, and the monocyte chemoattractant protein 1 were elevated, evidencing a systemic inflammatory state. Then, in this inflammatory model, cyclophilins and CD147 profiles in the aorta, liver, and kidney were studied. The results demonstrate that, upon inflammatory conditions, cyclophilins A and C expression levels were increased in the aorta. Cyclophilins A and D were augmented in the liver, meanwhile, cyclophilins B and C were diminished. In the kidney, cyclophilins B and C levels were elevated. Furthermore, CD147 receptor was also increased in the aorta, liver, and kidney. In addition, when cyclophilin A was modulated, serum levels of inflammatory mediators were decreased, indicating a reduction in systemic inflammation. Besides, the expression levels of cyclophilin A and CD147 were also reduced in the aorta and liver, when cyclophilin A was modulated. Therefore, these results suggest that each cyclophilin has a different profile depending on the tissue, under inflammatory conditions.

The inhibitory potential of chemical constituents of Ficus carica targeting interleukin-6 (IL-6) mediated inflammation.

Inflammation is an innate reaction of the body of an individual when subjected to the noxious factors repeatedly. Pharmacological approaches focused at disrupting cytokine signaling networks have become significant therapeutic alternatives for the treatment of inflammatory illnesses, cancer and autoimmune disorders. High levels of inflammatory mediators, particularly interleukin IL-1, IL-6, IL-18, IL-12, and tumor necrosis factor alpha leads to a cytokine storm in the body. Among all the released cytokines in a patient suffering from inflammatory disorder, IL-6 mediator has a pivotal role in this inflammatory cascade which progresses to a cytokine storm. Therefore, the blockage of the IL-6 inflammatory mediator could be a promising treatment option for the patients with hyper inflammatory conditions. The phytochemicals could provide the new lead compounds against the IL-6 mediator. Ficus carica has been the ideal plant of research and investigation due to its commercial, economic and medical importance. The anti-inflammatory properties of F. carica were further investigated by in silico and in vivo approaches. The docking scores of Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin are -9.231, -8.921, -8.840, and -8.335 Kcal/mole respectively. The free energy of binding and stability of the docked complexes of these top four phytochemicals with the IL-6 were further analyzed by Molecular Mechanics-Generalized Born Surface Area and Molecular Dynamic simulations, respectively. The in vivo anti-inflammatory carrageenan-induced rat paw edema model was used for the validation of in silico results. The maximum percentage paw edema inhibition with petroleum ether and ethyl acetate was 70.32% and 45.05%, respectively. The in vivo anti-inflammatory activity confirms the anti-inflammatory potential of F. carica. Therefore, it is predicted that Cyanidin-3,5-diglucoside, Kaempferol-7-O-rutinoside, Cyanidin-3-rhamnoglucoside, and Rutin have the potential to inhibit the IL-6 mediator which will aid in mitigating the cytokine storm in patients with acute inflammations.

Disturbed microbiota-metabolites-immune interaction network is associated with olfactory dysfunction in patients with chronic rhinosinusitis.

Olfactory dysfunction (OD) is a debilitating symptom frequently reported by patients with chronic rhinosinusitis (CRS) and it is associated with a dysregulated sinonasal inflammation. However, little information is available about the effect of the inflammation-related nasal microbiota and related metabolites on the olfactory function in these patients. Therefore, the current study aimed to investigate the nasal microbiota-metabolites-immune interactions and their role in the pathogenesis of OD in CRS patients. 23 and 19 CRS patients with and without OD, respectively, were enrolled in the present study. The "Sniffin' Sticks" was used to measure the olfactory function, while the metagenomic shotgun sequencing and the untargeted metabolite profiling were performed to assess the differences in terms of the nasal microbiome and metabolome between the two groups. The levels of nasal mucus inflammatory mediators were investigated by a multiplex flow Cytometric Bead Array (CBA). A decreased diversity in the nasal microbiome from the OD group compared to the NOD group was evidenced. The metagenomic analysis revealed a significant enrichment of Acinetobacter johnsonii in the OD group, while Mycoplasma arginini, Aeromonas dhakensis, and Salmonella enterica were significantly less represented (LDA value > 3, p < 0.05). The nasal metabolome profiles were significantly different between the OD and NOD groups (P < 0.05). The purine metabolism was the most significantly enriched metabolic subpathway in OD patients compared with NOD patients (P < 0.001). The expressions of IL-5, IL-8, MIP-1α, MCP-1, and TNF were statistically and significantly increased in the OD group (P < 0.05). All these data, including the dysregulation of the nasal microbiota, differential metabolites, and elevated inflammatory mediators in OD patients demonstrated a clear interaction relationship. The disturbed nasal microbiota-metabolite-immune interaction networks may be implicated in the pathogenesis of OD in CRS patients and the underlying pathophysiological mechanisms need to be further investigated in future studies.

Expression profile of HERVs and inflammatory mediators detected in nasal mucosa as a predictive biomarker of COVID-19 severity.

Our research group and others demonstrated the implication of the human endogenous retroviruses (HERVs) in SARS-CoV-2 infection and their association with disease progression, suggesting HERVs as contributing factors in COVID-19 immunopathology. To identify early predictive biomarkers of the COVID-19 severity, we analyzed the expression of HERVs and inflammatory mediators in SARS-CoV-2-positive and -negative nasopharyngeal/oropharyngeal swabs with respect to biochemical parameters and clinical outcome. Residuals of swab samples (20 SARS-CoV-2-negative and 43 SARS-CoV-2-positive) were collected during the first wave of the pandemic and expression levels of HERVs and inflammatory mediators were analyzed by qRT-Real time PCR. The results obtained show that infection with SARS-CoV-2 resulted in a general increase in the expression of HERVs and mediators of the immune response. In particular, SARS-CoV-2 infection is associated with increased expression of HERV-K and HERV-W, IL-1β, IL-6, IL-17, TNF-α, MCP-1, INF-γ, TLR-3, and TLR-7, while lower levels of IL-10, IFN-α, IFN-β, and TLR-4 were found in individuals who underwent hospitalization. Moreover, higher expression of HERV-W, IL-1β, IL-6, IFN-α, and IFN-β reflected the respiratory outcome of patients during hospitalization. Interestingly, a machine learning model was able to classify hospitalized vs not hospitalized patients with good accuracy based on the expression levels of HERV-K, HERV-W, IL-6, TNF-a, TLR-3, TLR-7, and the N gene of SARS-CoV-2. These latest biomarkers also correlated with parameters of coagulation and inflammation. Overall, the present results suggest HERVs as contributing elements in COVID-19 and early genomic biomarkers to predict COVID-19 severity and disease outcome.

ALDH2 ameliorates ethanol-induced gastric ulcer through suppressing NLPR3 inflammasome activation and ferroptosis

Gastric ulcer (GU) is a prevalent and life-threating gastrointestinal disorder. Aldehyde dehydrogenase 2 (ALDH2) is a pivotal component of alcohol metabolism which has been supported to suppress oxidative stress-elicited DNA damage in gastric mucosa cells. Nonetheless, whether ALDH2 is also involved in GU remains indistinct. Firstly, HCl/ethanol-induced experimental rat GU model was successfully established. RT-qPCR and Western blot tested ALDH2 expression in rat tissues. Following the addition of ALDH2 activator Alda-1, gastric lesion area and index were measured. H&E staining detected the histopathology of gastric tissues. ELISA examined the levels of inflammatory mediators. Alcian blue staining evaluated mucus production of gastric mucosa. Oxidative stress levels were estimated by corresponding kits and Western blot. Western blot examined the expression of NLRP3 inflammasome- and ferroptosis-related proteins. Prussian blue staining and corresponding assay kits measured ferroptosis. In ethanol-treated GES-1 cells, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, iron content, ferroptosis, inflammation and oxidative stress were detected as aforementioned above. In addition to that, DCFH-DA staining examined ROS generation. The experimental data corroborated that ALDH2 expression was declined in the tissues of HCl/ethanol-treated rats. Alda-1 ameliorated HCl/ethanol-stimulated gastric mucosal damage, inflammatory response, oxidative stress, NLRP3 inflammasome activation and ferroptosis in rats. Also, the suppressive role of ALDH2 in inflammatory response and oxidative stress was reversed by ferroptosis activator erastin or NLRP3 activator nigericin in HCl/ethanol-challenged GES-1 cells. To be summarized, ALDH2 might play the protective role in the process of GU.

Imbalance of Peripheral Temperature, Sympathovagal, and Cytokine Profile in Long COVID.

A persistent state of inflammation has been reported during the COVID-19 pandemic. This study aimed to assess short-term heart rate variability (HRV), peripheral body temperature, and serum cytokine levels in patients with long COVID. We evaluated 202 patients with long COVID symptoms categorized them according to the duration of their COVID symptoms (≤120 days, n = 81; >120 days, n = 121), in addition to 95 healthy individuals selected as controls. All HRV variables differed significantly between the control group and patients with long COVID in the ≤120 days group (p < 0.05), and participants in the long COVID ≤120 days group had higher temperatures than those in the long COVID >120 days group in all regions analysed (p < 0.05). Cytokine analysis showed higher levels of interleukin 17 (IL-17) and interleukin 2 (IL-2), and lower levels of interleukin 4 (IL-4) (p < 0.05). Our results suggest a reduction in parasympathetic activation during long COVID and an increase in body temperature due to possible endothelial damage caused by the maintenance of elevated levels of inflammatory mediators. Furthermore, high serum levels of IL-17 and IL-2 and low levels of IL-4 appear to constitute a long-term profile of COVID-19 cytokines, and these markers are potential targets for long COVID-treatment and prevention strategies.

Ocimum sanctum L water extract: In-situ green synthesis of zinc oxide nanoparticles for treatment of rheumatoid arthritis: Preclinical study

Background and objectiveRheumatoid arthritis is a chronic progressive autoimmune disorder, characterised by destruction of cartilage and under line bones. Though exact etiology of rheumatoid arthritis (RA) remains unknown. It is believed that alteration in control of cellular or molecular responses is involved in the chronic inflammation. Earlier in RA patients it was observed the circulating RA specific biomarkers and immunoglobulin deposits in the synovial joints. Zinc Oxide Nanoparticles (ZnO NPs) is used as an anti-inflammatory and anticancer agent, however there is nil/very less scientific data shows the anti-arthritic activity of green synthesis ZnO nanoparticles (Ocimum sanctum water extract in-situ synthesis of ZnO NPs having active compound Caffeic acid and Rosmerinic acid). Hence, the present activity was planned to assess the anti-arthritic activity of ZnO NPs in CIA rats. MethodsArthritis in rats were induced by subcutaneous injection of collagen type II (CII) (200 µl) at the base of tail on day 0 followed by booster dose on day 14. ZnO NPs were given (2 mg/kg b.wt./day) orally for 20 days. At the end of the study serum, joint homogenate was used to assess the level of biomarkers (RF, a-CCP, a-CII and CRP) and inflammatory mediators. In addition, m-RNA expression of various genes such as Nuclear factor-kB (NF-kB), inflammatory mediators like tumour necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) etc. were assayed in joint tissue. Finally all these biochemical and molecular results were confirmed by microscopic study of joint tissue. ResultsZnO NPs, treated rats showed decrease in inflammation and clinical severity. This was related with decrease in the level of biomarkers (like RF, a-CCP and CRP), inflammatory mediators (TNF-α, COX-2) and activity of transcription factor NF-kB. All these findings were positively correlated with microscopic analysis of joint tissue that showed reduced inflammation and bone erosion in treated group. ConclusionThis study validates the anti-arthritic activity of ZnO NPs as it mitigates the arthritis related symptoms in CIA rats.

Galectin-12 Regulates Immune Responses in the Skin through Sebaceous Glands

Sebaceous glands are holocrine glands that produce sebum, which primarily contains lipids that help maintain the barrier function of the skin. Dysregulated lipid production contributes to the progression of some diseases characterized by dry skin, including atopic dermatitis. Although the lipid production of sebaceous glands has been well studied, few studies have assessed their role in skin immune responses. We found that sebaceous glands and sebocytes expressed interleukin (IL)-4 receptor and produced high levels of Th2-associated inflammatory mediators following IL-4 treatment, suggesting immunomodulatory effects. Galectin-12 is a lipogenic factor expressed in sebocytes that affects their differentiation and proliferation. Using galectin-12-knockdown sebocytes, we demonstrated that galectin-12 regulated immune response in cells exposed to IL-4 and promoted CCL26 expression by upregulating PPARγ. Moreover, galectin-12 suppresses the expression of endoplasmic reticulum (ER) stress-response molecules and CCL26 upregulation by IL-4 was reversed following sebocyte treatment with inducers of ER stress, suggesting that galectin-12 controls IL-4 signaling by suppressing ER stress. Using galectin-12-knockout mice, we demonstrated that galectin-12 positively regulated the IL-4-induced enlargement of sebaceous glands and development of an atopic dermatitis-like phenotype. Thus, galectin-12 regulates the skin immune response through promoting PPARγ expression and suppressing ER stress in sebaceous glands.

A randomized, double-blind pilot study of analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen following dental implant placement surgery.

Introduction: Post-surgical pain following dental implant placement surgery is typically managed with non-opioid analgesics, including non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen. However, the comparative analgesic efficacy of over-the-counter doses of non-steroidal anti-inflammatory drugs and acetaminophen in implant patients is unknown. Therefore, we compared the analgesic and anti-inflammatory effects of naproxen sodium and acetaminophen after surgical placement of one or two dental implants. Methods: Adult patients were treated with naproxen sodium (440mg loading dose +220mg q8h, n = 15) or acetaminophen (1,000mg q6h-max daily dose 3,000mg, n = 15) for 3days after implant placement in a randomized, double-blind design. Pain was assessed on a 0-10 scale every 20min for 6h after study medication treatment. Tramadol (50mg) was available as a rescue medication. Plasma and gingival crevicular fluid (GCF) were collected prior to the surgery and 0, 1, 2, 4, 6, 24, and 72h after surgery for quantification of interleukin (IL)-6, IL-8, and IL-1β levels. Results: Pain scores were significantly lower in patients treated with naproxen sodium compared to those treated with acetaminophen. Inflammatory mediator levels in plasma and gingival crevicular fluid increased after surgery and returned to near baseline levels by 72h. Plasma IL-6 levels were significantly lower 6h after surgery in patients treated with naproxen sodium compared to acetaminophen. No differences in inflammatory mediator concentrations in gingival crevicular fluid were observed between the treatment groups. The number of implants placed and body mass index (BMI) influenced inflammatory mediator concentrations in plasma and gingival crevicular fluid, respectively. Discussion: Naproxen sodium was more effective than acetaminophen in reducing post-operative pain and systemic inflammation following surgical placement of one or two dental implants. Further studies are needed to determine whether these findings are applicable to more complex implant cases and how they affect clinical outcomes following implant placement. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT04694300.

Postoperative serum interleukin-6 levels correlate with survival in stage I-III colorectal cancer

AimsThe preoperative serum levels of inflammatory mediators, including C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6), have been demonstrated to be correlated with patient outcomes in colorectal cancer (CRC); however, the prognostic role of these levels has been less well-studied in postoperative settings.Materials and methodsA total of 122 stage I-III CRC patients were retrospectively enrolled. Serum levels of CRP, PCT and IL-6 were measured after surgery, and their prognostic value was evaluated. Kaplan-Meier analysis was used to determine the differences in disease-free survival (DFS) and overall survival (OS) between patients with different levels of these mediators, and the Cox proportional hazards model was used to estimate the risk factors.ResultsIn contrast to CRP and PCT, only the level of IL-6 was significant in predicting DFS (P = 0.01) but not OS (P = 0.07). A total of 66.39% (81/122) of patients were assigned to the low IL-6 group and no significant differences were found in the collected clinicopathological parameters among the low or high IL-6 subgroups. The level of IL-6 was negatively correlated with postoperative (1 w) (R=-0.24, P = 0.02) absolute lymphocyte counts. Patients with low levels of IL-6 had better DFS (log rank = 6.10, P = 0.01) but not OS (log rank = 2.28, P = 0.13). Finally, the level of IL-6 was an independent risk factor for DFS (HR: 1.81, 95% CI: 1.03–3.15, P = 0.04).ConclusionsCompared to CRP and PCT, the level of IL-6 was observed to be the only significant factor in predicting the prognosis of stage I-III CRC patients after surgery, and a low level of IL-6 was associated with good DFS.

Efficacy and Optimal Dose of Coenzyme Q10 Supplementation on Inflammation-Related Biomarkers: A GRADE-Assessed Systematic Review and Updated Meta-Analysis of Randomized Controlled Trials.

Coenzyme Q10 (CoQ10) has become a popular nutritional supplement due to its wide range of beneficial biological effects. Previous meta-analyses show that the attenuation of CoQ10 on inflammatory biomarkers remains controversial. This meta-analysis aims to assess the efficacy and optimal dose of CoQ10 supplementation on inflammatory indicators in the general population. Databases are searched up to December 2022 resulting in 6713 articles, of which 31 are retrieved for full-text assessment and included 1517 subjects. Double-blind randomized controlled trials (RCTs) of CoQ10 supplementation are eligible if they contain C reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). CoQ10 supplementation can significantly reduce the levels of circulating CRP (SMD: -0.40, 95% CI: [-0.67 to -0.13], p = 0.003), IL-6 (SMD: -0.67, 95% CI: [-1.01 to -0.33], p < 0.001), and TNF-α (SMD: -1.06, 95% CI: [-1.59 to -0.52], p < 0.001) and increase the concentration of circulating CoQ10. This meta-analysis provides evidence for CoQ10 supplementation to reduce the level of inflammatory mediators in the general population and proposes that daily supplementation of 300-400mg CoQ10 show superior inhibition of inflammatory factors.

Anti-Arthritic Activity of Annona Reticulata Leaves Methanolic Extract on Adjuvant Induced Arthritis in Rats

The research is expected to assess the effect of Annona Reticulata Methanolic leaves Extract (ARME) on progression of adjuvant induced arthritis in Wistar rats. ARME was obtained through bioactivity guided fraction by 5-Lipooxygenase inhibitory activity. ARME was administrated at 100 and 200mg/kg body weight via oral route for a period of 35 days to the experimental models. On day 8, via a single intra-plantar injection of 0.1mL suspension of heat killed Mycobacterium tuberculosis (100μg/animal) Arthritis was induced, in incomplete Freund’s adjuvant of left foot pads of Wistar rats (female). The paw volume was observed by recording the hematological and biochemical parameters, hind limb paw volume, pathological and radiography changes to evaluate the effect of the extract. On day 35, levels of pro-inflammatory cytokines (TNF-a, IL-1Β) and inflammatory mediators (PGE2, LTB4) was measured in serum samples. On the day of sacrifice, the liver was collected to record the stabilizing ability of lipid peroxide, activities of enzymatic antioxidants catalase, Superoxide Dismutase (SOD) and non-enzymatic antioxidants reduced glutathione (GSH) levels. ARME treated groups; 100 and 200mg/kg and prednisolone 10mg/kg significantly decreased hind paw volume, reduced serum levels of TNF-a, IL-1Β, PGE2 and LTB4, reduced MDA levels and increased levels of catalase, SOD and GSH in the liver. The promising results of serum biochemistry, haematology, histopathology and radiographic changes suggest that the administration of ARME was able to effectively modulate the inflammatory response and conquer the advancement of arthritis in the experimental animal model. Results obtained from the acute oral toxicity limit test establish that ARME (LD50&gt;2000mg/kg) was safe in accordance to the OECD guideline 423. These findings may help to overcome some hurdles in the treatment of rheumatoid arthritis.

Inflammatory panel cytokines are elevated in the neocortex of late-stage Alzheimer’s disease but not Lewy body dementias

BackgroundChronically dysregulated neuroinflammation has been implicated in neurodegenerative dementias, with separate studies reporting increased brain levels of inflammatory mediators and gliosis in Alzheimer’s disease (AD) as well as in Lewy body dementias (LBD). However, it is unclear whether the nature and extent of neuroinflammatory responses in LBD are comparable to those in AD. In this study, we performed head-to-head measurements of a panel of cytokines in the post-mortem neocortex of AD versus the two major clinical subtypes of LBD, namely, dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD).MethodsPost-mortem tissues from the mid-temporal cortex (Brodmann area 21) of a cohort of neuropathologically well-defined AD, PDD and DLB patients were processed and measured for a comprehensive range of cytokines (IL-1α, IL-1Ra, IL-8, IL-10, IL-12p70, IL-13, IFN-γ, GM-CSF and FGF-2) using a multiplex immunoassay platform. Associations between inflammation markers and neuropathological measures of neuritic plaques, neurofibrillary tangles as well as Lewy bodies were also performed.ResultsWe found IL-1α, IFN-γ, GM-CSF and IL-13 to be elevated in the mid-temporal cortex of AD patients. In contrast, none of the measured cytokines were significantly altered in either DLB or PDD. Similar cytokine changes were observed in two other neocortical areas of AD patients. Furthermore, increases of IL-1α, IFN-γ, GM-CSF, IL-10 and IL-13 associated with moderate-to-severe neurofibrillary tangle burden, but not with neuritic plaques or Lewy bodies. Our findings of elevated neocortical pro- and anti-inflammatory cytokines in AD, but not in DLB or PDD, suggest that neuroinflammatory responses are strongly linked to neurofibrillary tangle burden, which is higher in AD compared to LBD. In conclusion, neuroinflammation may not play a prominent role in the pathophysiology of late-stage LBD.

A DNA methylation based measure outperforms circulating CRP as a marker of chronic inflammation and partly reflects the monocytic response to long-term inflammatory exposure: ACanadian Longitudinal Study on Aging analysis.

A key hallmark in the age-related dysfunction of physiological systems is disruption related to the regulation of inflammation, often resulting in a chronic, low-grade inflammatory state (i.e., inflammaging). In order to understand the causes of overall system decline, methods to quantify the life-long exposure or damage related to chronic inflammation are critical. Here, we characterize a comprehensive epigenetic inflammation score (EIS) based on DNA methylation loci (CpGs) that are associated with circulating levels of C-reactive protein (CRP). In a cohort of 1446 older adults, we show that associations to age and health-related traits such as smoking history, chronic conditions, and established measures of accelerated aging were stronger for EIS than CRP, while the risk of longitudinal outcomes such as outpatient or inpatient visits and increased frailty were relatively similar. To determine whether variation in EIS actually reflects the cellular response to chronic inflammation we exposed THP1 myelo-monocytic cells to low levels of inflammatory mediators for 14 days, finding that EIS increased in response to both CRP (p = 0.011) and TNF (p = 0.068). Interestingly, a refined version of EIS based only on those CpGs that changed in vitro was more strongly associated with many of the aforementioned traits as compared to EIS. In conclusion, our study demonstrates that EIS outperforms circulating CRP with regard to its association to health-traits that are synonymous with chronic inflammation and accelerated aging, and substantiates its potential role as a clinically relevant tool for stratifying patient risk of adverse outcomes prior to treatment or following illness.

Quantitative analysis of culturable bacteria, levels of endotoxins, inflammatory mediators and substance P in teeth with symptomatic irreversible pulpitis and in teeth with vital normal pulp tissues.

To comparatively analyse the levels of culturable bacteria, endotoxins (LPS), tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and substance P in teeth with symptomatic irreversible pulpitis (SIP) and vital normal pulp (VNP) tissues. Thirty-two patients were included (20 teeth with SIP and 12 teeth with VNP tissues) in this cross-sectional study. Samples were collected from the full length of the root canals (microbial analysis) and periapical tissues (2 mm beyond the apex for immunological analysis), using sterile absorbent paper points. The levels of culturable bacteria (culture method), endotoxins (LAL Pyrogent 5000), TNF-α, IL-1β and substance P (ELISA) were assessed. The Mann-Whitney test was used for comparisons between the levels of CFU/mL, LPS, TNF-α, IL-1β and substance P in the SIP and VNP groups. The statistical analysis was performed with the significance level set at 5%. Culturable bacteria were recovered from all teeth with SIP. On the other hand, no positive cultures were observed in the VNP tissues group (p > .05). The levels of LPS were approximately four times higher in teeth with SIP than in teeth with VNP tissues (p < .05). Higher levels of TNF-α and substance P were detected in teeth with SIP (p < .05). On the other hand, no difference in the levels of IL-1β was detected between the two groups (p > .05). Teeth with symptomatic irreversible pulpitis present higher levels of culturable bacteria, endotoxins, TNF-α and substance P than those with vital normal pulp tissues. On the other hand, the levels of IL-1β were similar in teeth from both groups suggesting reduced implications of this inflammatory mediator in the early stages of infection.