Elevated Levels Of IL-6 Research Articles

Interaction between serum inflammatory cytokines and brain-derived neurotrophic factor in cognitive function among first-episode schizophrenia patients

BACKGROUND The pathogenesis of cognitive impairment in schizophrenia (SCZ) remains unclear. Accumulating studies showed that inflammatory-immune dysregulation and altered brain derived neurotrophic factor (BDNF) levels play a crucial role in the psychopathology of SCZ. However, their association with cognitive dysfunction in first-episode SCZ patients has not been thoroughly investigated. AIM To explore the interaction effects between cognitive function and inflammatory cytokines and BDNF in first-episode SCZ. METHODS The current study is a cross-sectional case-control investigation that recruited 84 patients with first-episode SCZ (SCZ group) and 80 healthy controls (HCs group) at the Huzhou Third Municipal Hospital between August 2021 and September 2023. ELISA was employed to measure the serum levels of interleukin (IL)-1β, IL-4, IL-6, IL-10, and BDNF. The Chinese brief cognitive test (C-BCT) and the positive and negative syndrome scales were measured the severity of cognitive impairment and psychiatric symptoms. RESULTS Compared to the HC group, the SCZ group exhibited elevated IL-1β and IL-6 levels, decreased BDNF levels, and reduced C-BCT scores (all P < 0.001). In SCZ, BDNF was negatively correlated with IL-6 (r = -0.324, P < 0.05). Information processing speed was negatively correlated with IL-6 (r = -0.315, P < 0.05) and positively with BDNF (r = 0.290, P < 0.05); attention, working memory, comprehensive ability, and executive function were negatively correlated with IL-1β and IL-6 (all P < 0.05) and positively with BDNF (all P < 0.05). Multiple regression analysis showed IL-6 influenced C-BCT dimensions (β = -0.218 to -0.327, all P < 0.05); attention and executive ability were influenced by IL-1β (β = -0.199 to -0.261, all P < 0.05) ; comprehensive executive ability was influenced by BDNF (β = 0.209, P < 0.05) . CONCLUSION Our findings suggested that interrelationships between immune dysfunction and neurotrophic deficiency might underlie the pathological mechanisms of cognitive impairments in first-episode SCZ patients.

Changes in serum concentration of perioperative inflammatory cytokines following the timing of surgery among mild–moderate traumatic brain injury patients and factors associated

BackgroundThe safe timing window for surgery during the acute phase of inflammation due to traumatic brain injury (TBI) has not been studied extensively. We aimed to elucidate the relationship between the timing of surgery and changes in perioperative serum levels of inflammatory cytokines and factors associated to optimize TBI management in low-middle-income countries.MethodsA prospective cohort study was conducted among TBI Patients with depressed skull fractures with a GCS > 8 operated at different timing from injury and followed up peri-operatively. We collected the clinical-radiological data, as well as pre-and postoperative venous samples from participants; we then did Luminex Assay to quantify the serum levels of pro/anti-inflammatory cytokines using the kits of 96-well human cytokine “27-Plex-Assay (#M500KCAF0Y®).” We performed the analysis with STATA version 17 and R_studio applying both descriptive and inferential methods.ResultsWe enrolled 82 TBI patients with a median (IQR) age of 25.5 (20–34) years, and the majority were male (85.4%). There were 48.8% victims of assaults, and 73.2% had a post-resuscitation admission GCS of 14–15. There were 38 (46.3%) who were operated within 48 h of injury versus 44 (53.7%) after 48 h. Serum levels of TNF-α were significantly higher after surgeries done >48 h compared to those done ≤48 h (p = 0.0327); whereas, the difference in post-operative mean serum levels of IL-10 was significantly increased in patients who developed later SSI compared to those who did not (11.56 versus −0.58 pg./mL, p = 0.0489). In multivariate analysis, the history of post-traumatic seizure (PTS) was associated with a postoperative increase in TNF-α (p = 0.01), the hemoglobin of 10–12 with a postoperative decrease of IL-4 (p = 0.05); the presence of focal neurological deficit was associated with a significant postoperative increased of TNF-α, IL-6, and IL-4 (p = 0.05). The presence of extra-axial hemorrhage was associated with a postoperative increase of IL-10 (p = 0.05).ConclusionDelayed surgical intervention beyond 48 h post-injury in mild–moderate TBI patients results in a significantly increased postoperative inflammatory response, as evidenced by elevated serum levels of TNF-α and IL-6. Neurological deficits, PTS, reduced hemoglobin rate, and extra-axial intracranial hemorrhage are factors associated with this heightened response.

Single Nucleotide Polymorphism of IL-18 (Rs 1946519) in Recurrent Aborted Iraqi Women and Its Association with Toxoplasmosis

Background: We aimed to shed light on the risks of elevated levels of IL-18 in aborted women with toxoplasmosis by evaluating the risk or protective function of alleles or genotypes for single nucleotide polymorphism (SNP) of IL-18 (rs 1946519), which might be related to the susceptibility to toxoplasmosis. Methods: IL-18 levels in patient and control blood samples were determined using ELISA, and the SNP IL-18 (ra 1946519) was subjected to the high-resolution method. Results: Compared to healthy pregnant women (HP), the IL-18 serum levels of recurrent abortion with toxoplasmosis (RAWT), recurrent abortion without toxoplasmosis (RAWOT), and healthy non-pregnant (HNP) women decreased with significant differences. Additionally, a strong association between patients and controls was found in the SNP IL-18 data. RAWT and RAWOT with the genotypes AA and AC had significantly lower IL-18 serum levels than women HP, according to the distribution of IL-18 serum levels by SNP. Conclusion: The serum level of IL-18 varied by genotype in patients with substantial differences compared to controls, while the SNP of IL-18 has been linked as a risk factor in toxoplasmosis-infected recurrent abortion women.

Study the Relationship of IFN-γ (+874A/ T) Polymorphism, and Some Cytokines with Breast Cancer in a Population from Baghdad City, Iraq

Background: Breast cancer is still a complicated and common health issue that affects millions of people globally. Aim: the current investigation aimed to study the relationship of IFN-γ (+874 A/T) genetic polymorphism, and some cytokines to breast cancer women in a population from Baghdad city/ Iraq. Materials and Methods: In this study, (80) females with an age of (20-60) years were employed; they were attending Oncology Teaching Hospital, Medical City, Baghdad. All these females were notified regarding the purpose of these investigations and agreed to its protocol. 80 healthy women were taken into the current study for comparison purposes. Results: The findings demonstrated that C3 levels showed a significant (P≤0.05) elevation in patients compared to healthy females. C4 levels demonstrated significantly (P≤0.05) elevation in patients that compared to healthy females. IL-6 levels significantly (P <0.05) increased in patients compared with control group (4.15±0.65 pg/ml). IL-17 concentration in serum of patients showed a significant (P <0.05) increased in patients compared with healthy ones. T and A alleles of IFN-γ T / A +874 locus had distinct results when repeated distribution was used to compare women who had breast cancer to healthy individuals. In the patient BC sample, the T allele was 42.4%, while the allele T in the control group was 71.4%. While the allele A in the sample of BC patients, which is 57.6%, compared to the allele A in control group, which was 28.6%. Conclusions: This study suggests that elevated IL-6 and IL-17 levels, along with specific IFN-γ gene polymorphisms, could serve as potential biomarkers for breast cancer risk and prognosis.

Effects of supplemental feeding of Chinese herbal mixtures to perinatal sows on reproductive performance, immunity, and breast milk quality of sows

The aim of this study was to investigate the impact of supplementary feeding with Chinese herbal mixtures on perinatal sows, focusing on their reproductive performance, immunity and breast milk quality. Sixty healthy pregnant sows (Large white, 4 parities) were randomly allocated into five treatment groups (n = 12 per group): the control group received a basal diet, the TRT1 group received a basal diet supplemented with 2 kg/t Bazhen powder (BZP), while the TRT2, TRT3, and TRT4 groups received a basal diet supplemented with 1 kg/t, 2 kg/t, and 3 kg/t Qi-Zhu-Gui-Shao soothing liver and replenishing blood powder (QZGSP), respectively. The trial lasted for a duration of 5 weeks, commencing from day 100 of gestation and concluding on day 21 postpartum. The results showed that supplemental feeding of 2 kg/t and 3 kg/t QZGSP to periparturient sows significantly improved reproductive performance to different degrees, as evidenced by the shortened farrowing intervals and increased average daily feed intake and milk yield. Supplemental feeding of 2 kg/t and/or 3 kg/t QZGSP significantly elevated levels of IL-4, IL-10, IgG, and IgA in sow serum while reduced levels of TNF-α and IL-1β in sow serum. In addition, supplemental feeding of 2 kg/t and 3 kg/t QZGSP to perinatal sows significantly increased the protein and fat content in colostrum and milk. Analysis of 16S rRNA gene amplicon sequencing data in colostrum and milk microbiota revealed that supplemental feeding of QZGSP to perinatal sows is influenced the composition of colostrum and milk composition in sows. Specifically, at the genus level, a decrease in the relative abundance of Escherichia-Shigella, Staphylococcus and Streptococcus was observed in the TRT3 and/or TRT4 groups on day 0 of lactation. The findings from this study indicate that supplemental feeding of 2 kg/t and 3 kg/t QZGSP significantly improved the reproductive performance, immunity and milk quality in sows. Therefore, QZGSP is a beneficial feed additive for perinatal sows.

Physical exercise, systemic inflammation and adult-onset asthma: a 12-year follow-up study

Physical exercise in treatment of asthma is scarcely studied with no clear exercise guidelines for asthmatics. We aimed to investigate the associations between physical exercise frequency, systemic inflammation and asthma control. This has not been previously studied in adult-onset asthma. This study is part of Seinäjoki Adult Asthma Study (SAAS), where 203 patients with adult-onset asthma were evaluated in 2012-2013. Exercise frequency was recorded with a structured lifestyle questionnaire. Study population was divided into two categories by exercise frequency: Low frequency group exercised ≤2 times/week and high frequency group >2 times/week. Blood inflammatory markers were measured and IL-6 > 1.55 pg/ml and hs-CRP > 4.12 mg/l indicated systemic inflammation. High exercise frequency group had lower levels of hs-CRP (p = 0.007), IL-6 (p = 0.015), suPAR (p = 0.008) and adipsin (p = 0.031) and higher levels of adiponectin (p = 0.010) than low exercise frequency group. In logistic multivariate regression models higher exercise frequency lowered odds for elevated hs-CRP (OR = 0.37, 95% CI 0.15-0.94) and IL-6 levels (OR = 0.43, 95% CI 0.20-0.91), after adjusting for possible confounding factors. There was no difference in lung function tests, asthma control test or airways questionnaire 20 scores between the exercise frequency groups. However, differences were found in single symptom questions; high exercise frequency group had less symptoms during light housework and laughing but experienced more limitation of activity in self-reports. Higher exercise frequency is associated with lower level of systemic inflammation in patients with adult-onset asthma but no clear association was found to asthma outcomes. Exercise frequency may be associated with lesser amount of some individual asthma symptoms.

Diagnostic value of nasal sinus computed tomography/magnetic resonance imaging examination and serum cytokines in unilateral benign sphenoid sinus lesions

ObjectivesDue to the unique anatomical location of the sphenoid sinus and the extremely limited operational space during endoscopic nasal surgeries, even minor procedural errors can lead to severe complications. Hence, comprehensive preoperative assessment is crucial. It was to retrospectively analyze the diagnostic value of nasal sinus computed tomography (CT), magnetic resonance imaging (MRI), and serum interleukin (IL) cytokine levels for unilateral benign sphenoid sinus lesions (UBSSLs). Materials and methodsClinical data from 85 suspected UBSSL patients were collected. Surgical pathology served as the gold standard for evaluation, assessing the diagnostic value of nasal sinus CT, MRI, and serum IL-4, IL-9, and IL-17 levels. ResultsSurgical pathology confirmed 53 cases of UBSSLs. Relative to non-UBSSL patients, those with unilateral benign lesions showed greatly elevated serum levels of IL-4, IL-9, and IL-17 (P < 0.05). The detection rate of UBSSL using the combined CT + MRI approach was significantly higher than that of CT or MRI alone. Similarly, the combined detection rate of IL-4, IL-9, and IL-17 was significantly higher than that of IL-4, IL-9, or IL-17 individually. The detection rate of CT + MRI (88.68%) was higher than that of the IL-4+IL-9+IL-17 combination (75.47%) (P < 0.05). The areas under the receiver operating characteristic curves for diagnosing UBSSL using serum IL combinations, sinus CT + MRI, and IL combinations + CT + MRI were 0.812, 0.840, and 0.905, respectively. Moreover, the accuracy and sensitivity of the IL combinations + CT + MRI approach were higher than those of either the serum IL combinations or sinus CT + MRI alone. ConclusionElevated IL-4, IL-9, and IL-17 were associated with UBSSLs, and their combination with nasal sinus CT/MRI can enhance the diagnostic accuracy of this condition.

Analysis of the Blood Levels of NK and NKT Cells in Patients with Severe SARS-CoV-2 Infection.

Clinical features of SARS-CoV-2 infection vary, ranging from asymptomatic cases to pneumonia, and other serious complications. Some populations have been observed to be at higher risk for severe disease and death compared to other ethnical groups. To evaluate two parameters of the innate immune system, that play a significant role in viral immunity. In samples of peripheral blood from sixteen patients with severe COVID-19, ten with asymptomatic to mild illness, and fifteen healthy subjects, the percentage of NK and NKT cells, the expression of different NK cell receptors and the blood levels of pro-inflammatory cytokines were tested. We observed that patients with severe COVID-19 showed significantly lower frequencies of both CD56dim and CD56bright NK cells compared to patients with mild illness or healthy controls. Furthermore, patients with severe manifestation of COVID-19 exhibited an aberrant expression of the natural cytotoxicity receptors NKp30, NKp44 and NKp46. Similarly, NK cells from these patients showed statistically significant differences in the expression of various killer immunoglobulin-like receptors (KIRs) in the two main cell subsets (CD56bright, CD56dim) compared to controls or patients with mild disease. Moreover, patients with severe illness displayed decreased frequency of NKT cells (defined as CD3+CD56+) and elevated blood levels of the cytokines IL-6 and IL-8. This study suggests that the abnormal features of NK and NKT cells observed in patients with severe SARS-CoV-2 infection may play an important role in the outcome of this infectious disease in various population groups.

An Integrated Approach to Develop a Potent Vaccine Candidate Construct Against Prostate Cancer by Utilizing Machine Learning and Bioinformatics.

Prostate cancer is the most common malignancy among males. Prostaglandin G/H synthase (PGHS) is an essential enzyme in the synthesis of prostaglandins, and its activation has been linked to many malignancies, including colorectal cancer. Due to the limited effectiveness and specificity of existing prostate cancer therapies, this study was designed to formulate improved treatment techniques. Several immunoinformatic, reverse vaccinology, and molecular modeling methodologies were used to discover B- and T-cell epitopes for the glioblastoma multiforme tumor PGH2_HUMAN. This research evaluated Prostaglandin G/H synthase 2 protein as a potential vaccine candidate against the malignancy. The multi-epitope vaccine architecture is engineered to activate the immune system, with each epitope docked to its respective HLAs. Further, MD simulations analysis was performed to validate the findings. A multi-epitope subunit vaccine candidate was developed by concatenating the chosen B- and T-cell epitopes. Results yield a codon adaptive index (CAI) of 0.93 and a GC content of 56.77%. Thus, it conforms to a biological requirement for effective protein expression, suggesting competent vaccine efficacy inside the Escherichia coli system. Significant interleukin and cytokine responses were seen, characterized by elevated levels of IL-2 and IFN-γ in the immune system's response to the immunization. Molecular docking demonstrated an efficient binding affinity of -278 kcal/mol, with hydrogen bonding to several residues. Furthermore, the system total root mean square deviation (RMSD) reached 3.23 Å, with a maximum of up to 5.0 Å at the 100 ns time point but remains stable till 400 ns time intervals followed by stable root mean square fluctuation (RMSF) and radius of gyration values. The hydrogen bond cloud residues are the critical sites that significantly influence the binding energies of MMPBSA and MMGBSA via substantial van der Waals interactions. It has been determined that these in silico analyses will further augment the comprehension necessary for advancing the creation of targeted therapies for chemotherapeutic cancer treatments.

TRPM7 contributes to pyroptosis and its involvement in status epilepticus

BackgroundPyroptosis, a novel form of programmed cell death, has been implicated in neurodegeneration diseases. However, its role in status epilepticus (SE)—a condition characterized by prolonged or repeated seizures—remains inadequately understood.MethodsSE were induced by intraperitoneal injection of pilocarpine (PILO). Neuronal excitability was assessed through electroencephalogram (EEG) recordings and patch clamp. Chromatin immunoprecipitation (ChIP) assay was applied to verify the interaction of phosphorylated signal transducer and activator of transcription 3 (p-STAT3) protein with the promoters of Nlrp3 (the gene encoding NOD-like receptor family pyrin domain containing 3) and Trpm7 (transient receptor potential melastatin 7). To further investigate the role of TRPM7 in SE, AAV-sh-TRPM7-EGFP transfected mice and TRPM7 conditional knockout (TRPM7-CKO) mice were utilized.ResultsOur findings revealed elevated levels of IL-18 and IL-1β levels in primary epilepsy patients, along with increased expression level of the TRPM7 in SE models. Knockdown of TRPM7 alleviated neuronal damage and pyroptosis, reversing PILO-treated neuronal hyperexcitability. We demonstrated that p-STAT3 binds to the promoters of both Trpm7 and Nlrp3, modulating their transcriptions in SE. Importantly, inhibition of TRPM7 with NS8593, and inflammasome inhibition with MCC950, alleviated neuronal hyperexcitability and pyroptosis in SE. A new compound, SDUY-225, formulated based on the structure of NS8593 mitigated neuronal damage, pyroptosis, and hyperexcitability.ConclusionsTRPM7 contributes to pyroptosis in SE, establishing a positive feedback loop involving the p-STAT3/TRPM7/Zn2+/p-STAT3 signaling pathway. Findings in this study raise the possibility that targeting TRPM7 and NLRP3 represents a promising therapeutic approach for SE.

Differential TLR2 and TLR4 mediated inflammatory and apoptotic responses in asymptomatic and symptomatic Leptospira interrogans infections in canine uterine tissue

Leptospirosis is major zoonotic disease with global implications, affecting both domestic animals and humans. It is caused by Leptospira interrogans (L. interrogans), which can damage multiple organs, including the kidneys, liver, testes, and uterus. Despite this, L. interrogans can also persist asymptomatically in tissues, akin to nonpathogenic strains. The mechanisms driving asymptomatic infections remain poorly understood. This study investigated the role of L. interrogans in asymptomatic infection within the uterine tissue of canines, focusing on the differential expression of Toll-like receptors (TLRs)2 and 4 and their roles in inflammatory and apoptotic pathways. We hypothesized that TLR2 and TLR4 coexpression is crucial for eliciting inflammation and apoptosis, whereas TLR4 alone might be insufficient. Our findings revealed that in symptomatic infections, both TLR2 and TLR4 are coexpressed, leading to markedly elevated levels of the proinflammatory cytokines IL-10, IL-1β, TNF-α, and IL-6. This enhanced inflammatory response is further evidenced by increased CD4 expression, indicating robust T helper cell activation. In contrast, asymptomatic infections are characterized by exclusive TLR4 expression, with inflammatory markers remaining at baseline levels. Additionally, we observed that L. interrogans induces apoptosis in symptomatic animals through TLR2 and TLR4 mediated activation of Caspase 8 and Caspase 3. These findings illustrate that L. interrogans drives both inflammation and apoptosis via the combination of TLR2 and TLR4 actions. When only TLR4 is activated, the immune response is insufficient, resulting in an asymptomatic disease course. This study provides novel insights into the differential roles of TLR receptors in leptospirosis, offering potential directions for targeted therapeutic strategies.

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.

Secretory leukocyte protease inhibitor influences periarticular joint inflammation in B. burgdorferi -infected mice.

Lyme disease, caused by Borrelia burgdorferi , is the most common tick-borne infection in the United States. Arthritis is a major clinical manifestation of infection, and synovial tissue damage has been attributed to the excessive pro-inflammatory responses. The secretory leukocyte protease inhibitor (SLPI) promotes tissue repair and exerts anti-inflammatory effects. The role of SLPI in the development of Lyme arthritis in C57BL/6 mice, which can be infected with B. burgdorferi , but only develop mild joint inflammation, was therefore examined. SLPI -deficient C57BL/6 mice challenged with B. burgdorferi had a higher infection load in the tibiotarsal joints and marked periarticular swelling, compared to infected wild type control mice. The ankle joint tissues of B. burgdorferi- infected SLPI -deficient mice contained significantly higher percentages of infiltrating neutrophils and macrophages. B. burgdorferi -infected SLPI -deficient mice also exhibited elevated serum levels of IL-6, neutrophil elastase, and MMP-8. Moreover, using a recently developed BASEHIT ( BA cterial S election to E lucidate H ost-microbe I nteractions in high T hroughput) library, we found that SLPI directly interacts with B. burgdorferi . These data demonstrate the importance of SLPI in suppressing periarticular joint inflammation in Lyme disease.

In silicon desinging of RANKL-targeting vaccine for protection of osteoporosis based on the epitope of Denosumab

BackgroundLife quality of osteoporosis patients is affected significantly due to the severely complications of fracture and pain. RANKL, indicated as the key mediator of osteoporosis, plays a pathogenic role of osteoclasts induction. To target this program, two medications, bisphosphonate and Denosumab, were developed and achieved remarkable advantages in clinics. Unfortunately, fracture-related side-effects always emerge unavoidably, after either long-term administration of bisphosphonates or Denosumab withdrawing. To address these challenges, vaccine-based approach has been adopted to achieve sustainable protection through induction and maintenance of effective antibodies in mild level over decades. MethodsA Denosumab binding peptide was firstly identified as the basic component of vaccine. This peptide was then fused with diphtheria toxin T domain, a widely used adjuvant protein. Its capabilities to penetrate the autologous tolerance and induce the immune responses was then demonstrated with in-silicon evaluation. Finally, the efficacy of the DR3 vaccine was assessed through immunization on the human RANKL transgenic mice model of osteoporosis. ResultsThe DTT-RANKL(220–245)3 vaccine, termed as DR3, were predicted as highly antigenic and non-allergenicity. This molecule was comprised of 46.5 % of helix, 8.5 % strand and 45.1 % coil, the optimized Z-value of the tertiary structure was 6.39, and the favored area in the Ramachandran plot was 96.1 % after refinement. Molecular docking showed a tight binding of DR3 vaccine to TLR2 (−9.2 kcal/mol) and TLR4 (−9.5 kcal/mol). In addition, the immune stimulation indicated robust responses post administration of DR3 vaccine, including high level production of of antibodies and cytokines, activated T and B lymphocytes, and the long-last immune memory. In agree with the simulation, vaccinated mice generated high titers anti-hRANKL antibodies and elevated levels of IL-4 and IL-10 at 7th week post immunization. ConclusionDR3 vaccine was aroused to benefit the prevention and treatment of osteoporosis, and other bone-resorptive diseases potentially.

Mechanism of Pyroptosis in Postoperative Cognitive Dysfunction Rats and α7-nicotinic Receptor Agonist Regulating NLRP3 Inflammasome Activation

Background: This study investigates the efficacy of α7-nicotinic acetylcholine receptor (α7nAChR) agonists in mitigating postoperative cognitive dysfunction (POCD) in a rat model. This investigation aimed to elucidate the therapeutic potential of α7nAChR agonists in modulating neuroinflammatory pathways to improve cognitive outcomes post-surgery. Objective: Serum levels of pro-inflammatory cytokines IL-1β and IL-18 were measured as markers of systemic inflammation, while the expression levels of NLRP3 mRNA were quantified to evaluate pyroptosis and NLRP3 inflammasome activation. Methods: Adult male Sprague-Dawley rats were divided into control (no surgery), POCD (surgeryinduced), and POCD treated with an α7nAChR agonist. Cognitive function was assessed using the Morris Water Maze (MWM) and Novel Object Recognition (NOR) tests. Results: The results showed a notable cognitive impairment in the group with POCD, as shown by increased escape latency noted in the MWM test and decreased discrimination index in the NOR test, while controls had no change. However, treatment with the α7nAChR agonist led to a significant improvement in cognitive performance among the POCD rats such that it closely matched those of the controls. Furthermore, the POCD group exhibited elevated serum levels of IL-1β and IL-18 and increased expression of pyroptosis-related markers, indicating enhanced neuroinflammation and inflammasome activation. Conclusion: These findings highlighted the therapeutic efficacy of α7nAChR agonists in mitigating neuroinflammation and improving cognitive outcomes post-surgery. Our study supports the potential of targeting the cholinergic anti-inflammatory pathway, emphasizing clinical evaluation of α7nAChR agonists in postoperative patients.

Predicting severe COVID-19 using readily available admission indicators: SpO2/FiO2 ratio, comorbidity index, and gender.

The focus of this study was to identify risk factors for severe and critical COVID-19, evaluate local respiratory immune responses to SARS-CoV-2 infection, and develop a prognostic tool for COVID-19 severity using accessible early indicators. Using nasopharyngeal swab samples from hospitalized patients with COVID-19 of varying severity during the first wave of the pandemic from March to May 2020 in Louisiana, we evaluated the association between COVID-19 severity and viral load, respiratory immune mediators, and demographic/clinical factors. We found that the SpO2/FiO2 ratio at triage, total comorbidity burden (represented by Charlson Comorbidity Index), and gender were significantly associated with COVID-19 severity. Using these early significant indicators, we developed a prognostic tool for COVID-19 severity that is simple and convenient. Additionally, our study demonstrated that elevated levels of respiratory immune mediators, including IL-10, IL-6, MCP-1, and MCP-3, were significantly associated with COVID-19 severity. We also found that viral load at the time of admission was associated with disease severity. Our findings highlight the feasibility and importance of evaluating the humoral component of local mucosal immune responses and viral load at the infected site using convenient nasopharyngeal swab samples, which could be an effective method to understand the relationship between viral infection and immune responses at the early stages of infection. Our proposed prognostic tool has the potential to be useful for COVID-19 management in clinical settings, as it utilizes accessible and easy-to-collect variables at the time of admission.

The Microbiome Modifies Manifestations of Hemophagocytic Lymphohistiocytosis in Perforin-Deficient Mice.

Primary hemophagocytic lymphohistiocytosis (HLH) is a life-threatening hyperinflammatory syndrome caused by inborn errors of cytotoxicity. Patients with biallelic PRF1 null mutations (encoding perforin) usually develop excessive immune cell activation, hypercytokinemia, and life-threateningimmunopathology in the first 6 months of life, often without an apparent infectious trigger. In contrast, perforin-deficient (PKO) mice only develop HLH after systemic infection with lymphocytic choriomeningitis virus (LCMV). We hypothesized that restricted microbe-immune cell interactions due to specific pathogen-free (SPF) housing might explain the need for this specific viral trigger in PKO mice. To investigate the influence of a "wild" microbiome in PKO mice, we fostered PKO newborns with Wildling microbiota ('PKO-Wildlings') and monitored them for signs of HLH. PKO-Wildlings survived long-term without spontaneous disease. Also, systemic infection with vaccinia virus did not reach the threshold of immune activation required to trigger HLH in PKO-Wildlings. Interestingly, after infection with LCMV, PKO-Wildlings developed an altered HLH pattern. This included lower IFN-γ serum levels along with improved IFN-γ-driven anemia, but more elevated levels of IL-17 and increased liver inflammation compared with PKO-SPF mice. Thus, wild microbiota alone is not sufficient to trigger HLH in PKO mice, but host-microbe interactions shape inflammatory cytokine patterns, thereby influencing manifestations of HLH immunopathology.

Deranged cytokine levels are linked to cancer-related cognitive impairment in lymphoma patients receiving R-CHOP chemotherapy

Cancer-related cognitive impairment (CRCI) is a significant issue commonly observed following chemotherapy treatment. The study aimed to investigate the changes in cognitive function and their association with IL-6, IL-1β, and IL-10 levels before and after R-CHOP chemotherapy over six cycles. Seventy chemotherapy naïve, newly diagnosed lymphoma patients were enrolled. Cognitive functions and inflammatory cytokines were assessed at baseline (TP1), after 3rd cycle (TP2), and after 6th cycle (TP3). Patients, with mean age of 44.17 ± 13.67 years, showed significantly increased levels of IL-6 and IL-1β and decreased IL-10 levels over time (p < .001). On the Montreal Cognitive Assessment (MoCA), scores of domains such as executive functioning (p = .002), attention (p < .001), language (p < .001), recall (p = .005), and orientation (p < .001) significantly decreased post six cycles of R-CHOP chemotherapy. Correlation analysis at TP2 indicated a positive association between elevated IL-6 levels with a decrease in MoCA scores indicating a decline in cognitive function (ρ = 0.68, p < .001). At TP3, no association of MoCA scores with IL-6 and IL-1β was observed. Decreased IL-10 levels showed a weak association with decreased MoCA scores at TP2 and TP3 ( ρ = 0.2, p = .09; for TP3, ρ = 0.16, p = .17), but this was not significant. In summary, the findings of the present study highlight significant cognitive decline and changes in inflammatory cytokine levels following six cycles of R-CHOP. Objective cognitive assessments may be done to detect CRCI in patients treated with R-CHOP.

Association between inflammatory markers and anemia in patients with diabetic foot ulcer.

Aim: Anemia of inflammation (AI) is common among patients with diabetic foot ulcers (DFU). This study aimed to investigate the specific relationship between inflammation indicators and anemia in patients with DFU.Materials & methods: This cross-sectional study was carried out among patients with DFU between 2018 and 2023. Clinical data were gathered before treatment. Restricted cubic spline regression was employed to investigate the non-linear associations between inflammation and anemia.Results: A total of 395 patients with Wagner grades 2-4 were enrolled in the study. About 63.54% of the patients with DFU had anemia which was primarily presented with normocytic hypopigmentation anemia. Elevated IL-6 levels (39.10-369pg/ml) were significantly associated with an increased likelihood of anemia (OR=4.84; 95% CI: 1.97-11.90). Similarly, high CRP levels (48.56-385mg/l) were linked to a higher prevalence of anemia (OR=5.01; 95% CI: 2.35-10.68). Furthermore, a nonlinear relationship was observed between CRP levels and anemia, suggesting that CRP values exceeding 53.889mg/l may trigger anemia in patients with diabetic foot ulcers.Conclusion: Inflammation is identified as an independent risk factor for AI in patients with DFU. The inflammation indicators (CRP and IL-6) and anemia exhibit an L-shaped nonlinear correlation in patients with DFU.

Metabolomic Analysis and Biochemical Profiling of Cadmium-Induced Metabolic Impairment and Its Amelioration by Resveratrol.

Exposure to heavy metals, particularly cadmium (Cd), poses significant health risks because of their toxic effects and potential for bioaccumulation in living organisms. This study examined the biochemical and metabolomic changes induced by Cd exposure in an animal model via advanced liquid chromatography with tandem mass spectrometry (LC-MS/MS) and biochemical assays to reveal significant disruptions in lipid and amino acid metabolism as well as alterations in key metabolic pathways. Cd exposure led to significant weight loss, hyperglycemia, and insulin resistance, indicating its role in metabolic disorders such as diabetes. The accumulation of Cd in the liver and kidneys, identified via ICP-OES, corresponded with elevated levels of liver (ALT, AST) and kidney (BUN, creatinine) biomarkers, suggesting organ-specific toxicity. At the metabolic level, Cd exposure caused the accumulation of lipid metabolites such as ceramides and sphingolipids, which are associated with insulin resistance and broader metabolic impairments. Amino acid metabolism was also significantly disrupted, with increased concentrations of key amino acids such as phenylalanine, tryptophan, and arginine affecting pathways such as the urea cycle and Krebs cycle. These metabolic disturbances are linked to oxidative stress, systemic inflammation, and impaired glucose regulation, as evidenced by elevated CRP and IL-6 levels. The protective effects of resveratrol (RSV) were clearly demonstrated in this study. RSV treatment ameliorated Cd-induced biochemical and metabolic alterations, as shown by improved glycemic control, restored lipid profiles, and normalized amino acid concentrations. Additionally, RSV significantly reduced inflammatory markers and improved liver and kidney function, highlighting its antioxidant properties and potential as a therapeutic agent against Cd toxicity. However, RSV did not significantly reduce Cd accumulation in organs, indicating that its protective effects are related to mitigating oxidative damage and metabolic disruption rather than promoting Cd excretion. This study enhances our understanding of the molecular mechanisms underlying Cd-induced metabolic impairments and highlights the therapeutic potential of RSV in combating Cd toxicity. These findings underscore the need for further research into heavy metal exposure and its mitigation to protect human health, particularly in areas of environmental contamination.