Elevated Serum Levels Research Articles

MPO-DNA Complexes and cf-DNA in Patients with Sepsis and Their Clinical Value.

Background/Objectives: Neutrophils, as the first line of defense in the immune response, produce neutrophil extracellular traps (NETs) upon activation, which are significant in the pathogenesis and organ damage in sepsis. This study aims to explore the clinical value of myeloperoxidase-DNA (MPO-DNA) and cell-free DNA (cf-DNA) in sepsis patients. Methods: Clinical data were collected from 106 sepsis patients, 25 non-sepsis patients, and 51 healthy controls. Sequential Organ Failure Assessment (SOFA) scores were calculated, and levels of MPO-DNA) complexes and cf-DNA were measured using specific kits. Correlation analyses assessed relationships between indicators, while logistic regression identified independent risk factors. Receiver operating characteristic (ROC) curves calculated the area under the curve (AUC) to evaluate the diagnostic value of the biomarkers. Results: Sepsis patients exhibited significantly elevated levels of MPO-DNA and cf-DNA compared to non-sepsis patients and healthy controls. In sepsis patients, MPO-DNA and cf-DNA levels correlated with inflammation, coagulation, and organ damage indicators, as well as procalcitonin (PCT) levels and SOFA scores. Both C-reactive protein (CRP) and cf-DNA were identified as independent risk factors for sepsis, demonstrating moderate diagnostic value. ROC analysis showed that the combination of MPO-DNA and CRP (AUC: 0.837) enhances the AUC value of CRP (0.777). Conclusions: In summary, elevated serum levels of MPO-DNA and cf-DNA in sepsis patients correlate with SOFA scores and PCT levels, providing reference value for sepsis diagnosis in clinical settings.

Phylogenetic position of the pigeon mite, Ornithonyssus sylviarum, with amplification of its immunogenetic biomarkers in Egypt

Ornithonyssus sylviarum (O. sylviarum) is an obligatory, blood-sucking ectoparasite widely distributed among poultry and other mammals, causing significant economic losses. This study represented the first report of molecular genotypic identification of O. sylviarum from pigeons, Columba livia domestica, in Egypt. PCR and sequencing of the 28S rRNA gene were conducted. The resulting mite sequences were subjected to BLAST analysis, revealing 90–100% similarity to O. sylviarum in all tested samples. The sequences were deposited in GenBank under the accession numbers PP049086 and PP033720. A phylogenetic tree was constructed to compare the obtained species with related species worldwide. Additionally, infected pigeons showed increased expression of IL-1, IL-10, IFN-γ, and TGF-β3 genes and elevated serum levels of stress biomarkers. The increased level of these cytokines indicates there was a disturbance in the immune status of the infected host with parasite compared with control healthy ones. This increases the susceptibility to infection with other pathogens.

COVID-19 Inflammatory Syndrome: Lessons from TNFRI and CRP about the Risk of Death in Severe Disease.

Background/Objectives: Cytokine storm in severe COVID-19 is responsible for irreversible tissue damage and death. Soluble mediators from the TNF superfamily, their correlation with clinical outcome, and the use of TNF receptors as a potent predictor for clinical outcome were evaluated. Methods: Severe COVID-19 patients had the levels of soluble mediators from the TNF superfamily quantified and categorized according to the clinical outcome (death versus survival). Statistical modeling was performed to predict clinical outcomes. Results: COVID-19 patients have elevated serum levels from the TNF superfamily. Regardless of sex and age, the sTNFRI levels were observed to be significantly higher in deceased patients from the first weeks following the onset of symptoms. We analyzed hematological parameters and inflammatory markers, and there was a difference between the groups for the following factors: erythrocytes, hemoglobin, hematocrit, leukocytes, neutrophils, band cells, lymphocytes, monocytes, CRP, IL-8, IFN-γ, IL-10, IL-6, IL-4, IL-2, leptin MIF sCD40L, and sTNFRI (p < 0.05). A post hoc analysis showed an inferential capacity over 70% for some hematological markers, CRP, and inflammatory mediators in deceased patients. sTNFRI was strongly associated with death, and the sTNFRI/sTNFRII ratio differed between outcomes (p < 0.001; power above 90%), highlighting the impact of these proteins on clinical results. The final logistic model, including sTNFRI/sTNFRII and CRP, indicated high sensitivity, specificity, accuracy, and an eight-fold higher odds ratio for an unfavorable outcome. Conclusions: The joint use of the sTNFRI/sTNFRII ratio with CRP proves to be a promising tool to assist in the clinical management of patients hospitalized for COVID-19.

Biomolecular Dynamics of Nitric Oxide Metabolites and HIF1α in HPV Infection.

Viral infections cause oxygen deprivation, leading to hypoxia or anoxia in certain tissues. The limitation of mitochondrial respiration is one of the major events during hypoxia that induces alternative metabolic activities and increased levels of certain biomolecules such as nitric oxide (NO) metabolites. In this study, we aimed to investigate the role of NO metabolites and hypoxia in HPV infection. We included 36 patients with palmoplantar warts and 36 healthy subjects and performed serum determinations of NO metabolites (direct nitrite, total nitrite, nitrate, and 3-nitrotyrosine) and HIF1α, a marker of hypoxia. We found elevated serum levels in NO metabolites and HIF1α, and decreased direct nitrite/nitrate ratios in patients with warts versus controls. Additionally, we identified statistically significant positive correlations between NO metabolites and HIF1α levels, except for 3-nitrotyrosine. Our findings show that HPV infection causes hypoxia and alterations in NO metabolism and suggest a link between wart development and cellular stress. Our research could provide new insights for a comprehensive understanding of the pathogenesis of cutaneous HPV infections.

Association of Hemogram Parameters with Body Mass Index in Knee Osteoarthritis

Objective: This study aims to investigate the relationship between hemogram parameters, which are low-cost, easy, routinely applied low-grade inflammation indicators, and severity of knee osteoarthritis (KOA) and obesity. Materials and Methods: This study involved 140 KOA patients aged 45 to 85 who underwent knee radiographs, weight and height measurements, and routine laboratory tests. Recorded data included demographic information (gender, age), body mass index (BMI), routine hemogram, and laboratory parameters. Patients were categorized into two groups based on their Kellgren-Lawrence (KL) scores (mild: KL 1-3, severe: KL 4) and four groups according to their BMI (BMI 35). Results: The findings revealed significantly elevated levels of serum Neutrophil-to-Lymphocyte Ratio (NLR) and C-reactive protein (CRP) in severe KOA compared to mild KOA (P30 in mild KOA groups, while mean blood NLR was notably higher in patients with BMI=30-35 in severe KOA groups. Conclusions: These results suggest that NLR and NMR could provide a new perspective on the relationship between obesity and mild KOA in clinical practice, presenting a cost-effective and easily applicable alternative for determining disease prognosis and progression.

Abstract B006: The role of tumor specific IGFBP-3 in the onset and progression of skeletal muscle wasting in a murine model of pancreatic cancer

Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer- related death and is highly associated with skeletal muscle wasting (SMW) that leads to treatment intolerance and reduced survival. Research substantiates the role of increased levels of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) in PDAC-related SMW. Canonically, supraphysiological levels of IGFBP-3 block insulin-like growth factor-1 (IGF-1) binding, thus downregulating the activation of its downstream targets Akt and mTOR. Non-canonical signaling via TGF-βRI results in aberrant FoxO1 signaling, which upregulates the ubiquitin proteasome pathway (UPP) and induces autophagy. Dysregulated UPP and autophagy activation have been shown to promote muscle degradation. Recent findings from our lab implicate canonical and non-canonical signaling of tumor associated IGFBP-3 in increased protein catabolism and decreased anabolism, resulting in SMW in a syngeneic murine model of PDAC. We tested the hypothesis that genetic ablation of IGFBP-3 in PDAC tumor cells attenuates SMW via regulation of Akt and FoxO1, leading to decreases in UPP and autophagy in skeletal muscle.Methods: C57BL/6J female mice (6-8 weeks) were randomized to one of three groups: 1) no tumor control (NTC) (n=10), 2) KCKO-Luc parental cells (PDAC) (n=14), or 3) IGFBP-3-/- KCKO-Luc (n=14). Tumor cells were injected orthotopically. Tumor and lean mass were assessed longitudinally via dual energy x-ray absorptiometry (DEXA). At sacrifice, quadriceps muscles were collected for protein and transcriptional analysis, Tibialis Anterior (TA) muscles for histology and serum for ELISA. TA frozen sections were stained with Oil Red O (ORO) to highlight intramuscular adipogenesis.Results: PDAC mice experience significantly reduced survival (T1/2=56 days) compared to IGFBP-3-/- mice that maintained 100% survival at day 100 (p&amp;lt;0.0001). IGFBP-3-/- mice lost significantly less lean mass from baseline to day 56 compared to PDAC mice (p&amp;lt;0.0001). PDAC mice exhibited 3-fold elevated serum levels of IGFBP-3 compared to NTC and IGFBP-3-/- mice (p&amp;lt;0.01). Transcriptionally, PDAC mice displayed increased expression of igfbp3, tgfbr1, and UPP associated genes fbxo32, and trim63 compared to NTC and IGFBP-3-/- mice. Further, the ratio of pAkt (Ser473), pS6 (Ser235/236), and pFoxO1 (Ser253) to total protein levels were significantly reduced in PDAC mice (p&amp;lt;0.05 vs NTC and IGFBP-3-/-). Additionally, protein levels of ULK1 and the ratio of LC3bII over LC3bI, markers of autophagy, are elevated in PDAC mice compared to NTC and IGFBP-3-/- mice (p&amp;lt;0.05). Lastly, there is a significant increase in ORO positive staining in PDAC mice compared to NTC and IGFBP-3-/- mice (p&amp;lt;0.0001).Conclusion: These findings suggest that PDAC-related SMW is driven by tumor derived IGFBP-3, which acts as an endocrine factor on skeletal muscle cells to inhibit protein synthesis and activate FoxO1 signaling to upregulate the UPP and autophagy. Lastly, we identify skeletal muscle adipogenesis as a biomarker for autophagy upregulation and SMW. Citation Format: Zachary R Sechrist, Calvin L Cole. The role of tumor specific IGFBP-3 in the onset and progression of skeletal muscle wasting in a murine model of pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B006.

Elevated serum levels of C-terminal agrin fragment in acetylcholine receptor antibody-positive myasthenia gravis

Agrin is essential for neuromuscular junction (NMJ) formation and maintenance. The C-terminal agrin fragment (CAF), generated by neurotrypsin-mediated cleavage of agrin, has been gaining attention as a potential biomarker for sarcopenia. We investigated serum CAF levels in myasthenia gravis (MG), a NMJ disorder. Compared to healthy controls, serum CAF levels were significantly elevated in acetylcholine receptor antibody-positive MG (AChR-MG) patients, but not in muscle-specific kinase antibody-positive MG patients. In AChR-MG, baseline and post-treatment CAF levels inversely correlated with post-treatment MG activities of daily living scores, suggesting that elevated CAF levels may reflect protective mechanisms against AChR-MG pathogenesis, such as improved NMJ regeneration.

Progranulin mediates the onset of pristane induced systemic lupus erythematosus

BackgroundsProgranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE.MethodsWild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed.ResultsFollowing exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection.ConclusionThe results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.

Differential expression of plasma cytokines in sepsis patients and their clinical implications.

Sepsis, which is characterized by acute systemic inflammation and is associated with high rates of morbidity and mortality, presents a significant challenge in health care. Some scholars have found that the sequential organ failure assessment (SOFA) and quick SOFA scores are not ideal for predicting severe sepsis and mortality. Microbial culture takes a long time (2-3 d) and provides no information for early diagnosis and treatment. Therefore, new diagnostic methods for sepsis need to be explored. To assess cytokine levels in the plasma of sepsis patients and identify potential biomarkers for diagnosing sepsis. Ten sepsis patients admitted to the emergency department within 24 h of onset were enrolled as the observation group, whereas ten noninfected patients served as the control group. Of the 10 noninfected patients, 9 hypertension combined with cerebral infarction, 1 patients with vertiginous syndrome. Plasma Cytokines were measured using the Bio-Plex Pro™ Human Chemokine Panel 40-plex. Differentially expressed cytokines in plasma of sepsis and nonsepsis patients were analyzed using Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Interleukin (IL)-16, granulocyte-macrophage granulocyte-macrophage colony-stimulating factor (GM-CSF), CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 plasma levels were significantly increased in sepsis patients. GO analysis revealed that these cytokines were mainly associated with cellular structures such as intermediates, nuclear plaques, adhesion plaques, lateral plasma membranes, and cell matrix junctions. These genes were involved in various molecular functions, such as cytokine activity, receptor ligand activity, and signal receptor activator activity, contributing to various biological functions, such as leukocyte chemotaxis, migration, and chemotaxis. KEGG analysis indicated involvement in cytokine cytokine receptor interactions, chemokine signaling pathways, virus-protein interactions with cytokines and cytokine receptors, and the tumor necrosis factor signaling pathway. Elevated serum levels of IL-16, GM-CSF, CX3CL1, CXCL9, CXCL16, CCL25, and CCL23 in sepsis patients suggest their potential as diagnostic biomarkers for sepsis.

Analyze interleukin-1β, interleukin-6, and tumor necrosis factor-α levels in dry eye and the therapeutic effect of cyclosporine A.

Dry eye is a common eye disease. Artificial tears supplements are widely used for the treatment of dry eyes. However, multiple adverse effects have been observed in patients receiving long-term treatment with artificial tears, which may affect the therapeutic effect. To analyze the characteristics of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) levels in patients with dry eye and the therapeutic effect of artificial tears combined with cyclosporine A. A total of 124 dry eye patients treated at The First People's Hospital of Xining from April 2020 to April 2022 were selected as the observation group, while 20 healthy individuals served as the control group during the same period. Levels of inflammatory markers, including IL-1β, IL-6, and TNF-α, were analyzed. The observation group was further divided into a study group and a control group, each consisting of 62 patients. The control group received artificial tears, whereas the study group received a combination of artificial tears and cyclosporine A. Inflammatory markers, Schirmer's test (SIT), tear break-up time (TBUT), corneal fluorescein staining (CFS), National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) scores, and adverse events (AEs) were compared between the two groups. The observation group exhibited significantly elevated serum levels of IL-1β, IL-6, and TNF-α in comparison to the healthy group. Following treatment, the study group demonstrated substantial reductions in IL-1β, IL-6, and TNF-α levels relative to the control group. Moreover, after treatment, the study group experienced a marked decrease in CFS scores and significant increases in both SIT and BUT levels when compared to the control group. Additionally, significant improvements were observed in the primary symptom of dry eye and secondary symptoms such as photophobia, foreign body sensation, fatigue, red eye, and burning sensation within the study group. Furthermore, post-treatment NEI-VFQ-25 scores across all dimensions exhibited significant enhancements in the study group compared to the control group (P < 0.05). It is noteworthy that significant AEs were reported in both groups throughout the treatment period. Cyclosporine A combined with artificial tears is effective in treating dry eye, yielding enhanced outcomes by improving SIT and TBUT levels, reducing CFS scores, and ameliorating vision-related quality of life.

Mechanisms behind elevated serum levels of plasminogen activator inhibitor-1 in frontotemporal lobar degeneration.

Mechanisms behind elevated serum levels of plasminogen activator inhibitor-1 in frontotemporal lobar degeneration.

Treatment with Gac Fruit Extract and Probiotics Reduces Serum Trimethylamine N-Oxide in Chronic Kidney Disease Rats.

Chronic kidney disease (CKD) affects more than 850 million people worldwide, contributing to morbidity and mortality, particularly through cardiovascular disease (CVD). The altered composition in CKD patients leads to increased production and absorption of uremic toxins such as trimethylamine (TMA) and its oxidized form, trimethylamine N-oxide (TMAO), which are associated with cardiovascular risks. This study investigated the potential of supplementary interventions with high-carotenoid-content gac fruit extract and probiotics to mitigate serum TMAO by modulating the gut microbiota. We conducted an animal study involving 48 male Wistar rats, divided into six groups: the control, CKD control, and four treatment groups receiving gac fruit extract, carotenoid extract, or combinations with Ligilactobacillus salivarius and Lactobacillus crispatus and Lactobacillus casei as a standard probiotic. CKD was induced in rats using cisplatin and they were supplemented with choline to enhance TMA production. The measures included serum creatinine, TMAO levels, gut microbiota composition, and the expression of fecal TMA lyase and intestinal zonula occluden-1 (ZO-1). CKD rats showed increased TMA production and elevated serum levels of TMAO. Treatment with gac fruit extract and selective probiotics significantly altered the composition of the gut microbiota by decreasing Actinobacteriota abundance and increasing the abundance of Bacteroides. This combination effectively promoted ZO-1 expression, reduced fecal TMA lyase, and subsequently lowered serum TMAO levels, demonstrating the therapeutic potential of these interventions. Our results highlight the benefits of gac fruit extract combined with probiotics for the effective reduction in serum TMAO levels in rats with CKD, supporting the further exploration of dietary and microbial interventions to improve outcomes in patients with CKD.

Expression of Tenascin-C Is Upregulated in the Early Stages of Radiation Pneumonitis/Fibrosis in a Novel Mouse Model.

The lung is a major dose-limiting organ for radiation therapy (RT) for cancer in the thoracic region, and the clarification of radiation-induced lung damage (RILD) is important. However, there have been few reports containing a detailed comparison of radiographic images with the pathological findings of radiation pneumonitis (RP)/radiation fibrosis (RF). We recently reported the upregulated expression of tenascin-C (TNC), an inflammation-associated extracellular matrix molecule, in surgically resected lung tissue, and elevated serum levels were elevated in a RILD patient. Therefore, we have developed a novel mouse model of partial lung irradiation and studied it with special attention paid to the computed tomography (CT) images and immunohistological findings. The right lungs of mice (BALB/c) were irradiated locally at 30 Gy/1fr, and the following two groups were created. In Group 1, sequential CT was performed to confirm the time-dependent changes in RILD. In Group 2, the CT images and histopathological findings of the lung were compared. RP findings were detected histologically at 16 weeks after irradiation; they were also observed on the CT images from 20 weeks. The immunostaining of TNC was observed before the appearance of RP on the CT images. The findings suggest that TNC could be an inflammatory marker preceding lung fibrosis.

Effects of black mulberry leaf extract on liver health and metabolic parameters in rats with high-fat diet-induced liver changes

AimNon-alcoholic fatty liver disease (NAFLD) lacks a definitive treatment. Previous research indicates that fruits and vegetables may alleviate inflammatory markers and improve NAFLD outcomes. This study investigates the effects of black mulberry leaf extract on NAFLD induced by a high-fat diet in rats. MethodsMale rats were randomized into control and high-fat diet groups. After four months on a high-fat diet, rats received black mulberry leaf extract at doses of 150, 300, and 600 mg/kg for eight weeks. Evaluations included weight, blood sugar, total cholesterol, triglycerides, and liver enzyme activities (AST, ALT). ResultsThe high-fat diet resulted in increased weight (P < 0.0001), fasting plasma glucose (FPG) (P < 0.0001), triglycerides (P = 0.031), and total cholesterol (P < 0.0001), along with elevated serum levels of AST (P < 0.0001) and ALT (P = 0.009). Administration of black mulberry leaf extract significantly reduced weight (P = 0.008), FPG (P < 0.0001), total cholesterol (P = 0.0001), and ALT (P = 0.0001) and AST (P = 0.0001) levels in a dose-dependent manner at doses of 600 mg, 300 mg, and 150 mg per day. ConclusionBlack mulberry leaf extract exhibits therapeutic potential in managing NAFLD. Further studies are warranted to comprehensively assess its impacts.

Associations between exposure to brominated flame retardants and periodontitis in U.S. adults

BackgroundIncreasing evidence has shown that environmental factors play a crucial role in the pathogenesis of periodontitis. Humans are simultaneously exposed to a variety of environmental brominated flame retardants (BFRs). However, the relationship between BFRs in periodontitis remains unclear. This study aimed to investigate the overall association between BFRs and periodontitis in a nationally representative US population and to further identify important chemicals. MethodsData from 3322 NHANES participants from 2009 to 2016 were used. Serum BFRs were registered, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE100, PBDE-153, PBDE-154, PBDE-183, PBDE-209 and PBB-153. Survey weighted generalized logistic regression models, restricted cubic splines (RCS) were conducted to assess single BFRs exposure with periodontitis. Meanwhile, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to evaluate the overall association of BFRs mixtures with periodontitis and to identify significant chemicals. ResultsA total of 3322 participants were included in the study, of whom 1795 had periodontitis. After adjusting for potential confounders, multiple logistic regression analysis revealed significant positive associations between serum levels of PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153 and the risk of periodontitis (all P < 0.05). A dose-response relationship was observed for many of these BFRs, with higher quantiles associated with an increased risk of periodontitis. WQS regression identified PBDE-183 (38.60%), PBDE-153 (21.20%), PBDE-209 (14.40%), and PBDE-99 (11.90%) as the BFRs with the largest weights contributing to the overall mixture effect on periodontitis risk. BKMR analysis further supported the positive association between serum BFRs and periodontitis, with most individual BFRs showing a positive trend, except for PBDE-153. Restricted cubic spline analysis revealed a generally increasing probability of periodontitis with increasing concentrations of BFRs, albeit with some nonlinear patterns for certain compounds. ConclusionIn conclusion, this study provides compelling evidence of a significant association between exposure to brominated flame retardants (BFRs) and an increased risk of periodontitis in a nationally representative sample of U.S. adults. Elevated serum levels of several BFRs, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153, were found to be positively associated with periodontitis, exhibiting a dose-response relationship.

The Role of WNT3A Protein and Gene Variants in Allergic Rhinitis: A Case-Control Study.

Allergic rhinitis (AR) is a prevalent inflammatory disorder of the upper respiratory tract, driven by allergen exposure. Understanding mechanisms and identifying biomarkers for AR could significantly impact diagnosis and treatment. This study aimed to investigate the association between serum Wingless-Type MMTV Integration Site Family, Member 3A (WNT3A) protein levels, WNT3A polymorphisms, and AR. A cohort of 92 AR patients and 86 healthy controls was recruited. Serum WNT3A levels were measured by enzyme-linked immunosorbent assay (ELISA). WNT3A gene polymorphisms (rs752107 and rs3121310) were analyzed using Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) method. The study revealed significantly higher serum WNT3A levels in AR patients compared to controls (p < 0.0001). The impact of WNT3A in the differential diagnosis of AR was determined to be moderate, with an area under the curve (AUC) value of 0.67 (95% Confidence Interval: 0.59-0.75) based on the receiver operating characteristic (ROC) curve analysis. The rs3121310 polymorphism showed a significant association with the GA genotype more prevalent in controls (p < 0.05). However, no significant relationship was observed between rs3121310 genotypes and clinical parameters of the patients. These findings suggest a role for WNT3A in AR pathogenesis, given the elevated serum levels in patients. Larger cohort studies are needed to validate these findings and explore serum WNT3A levels as a biomarker for AR diagnosis and treatment monitoring.

Neurobiological Effects of Lipoid Proteinosis: A Study on Phosphorylated Tau, S100B, NSE, NEFL, and GFAP

Background: Lipoid Proteinosis (LP), also termed Urbach-Wiethe disease, is an enigmatic genodermato-sis marked by the systemic deposition of hyaline material. With its etiology rooted in ECM1 mutations, LP’s neuropathological spectrum has been hypothesized to involve an array of neurodegenerative biomarkers, underscoring a potential for substantial neurobiological implications. This study endeav-ored to elucidate the serum concentrations of neurodegenerative biomarkers—phosphorylated Tau (pMAPT), S100B, Neuron-Specific Enolase (NSE), Neurofilament Light Chain (NEFL), and Glial Fibrillary Acidic Protein (GFAP)—in LP patients, seeking to establish their diagnostic utility for the condition. Materials and Methods: Fifteen LP patients and 15 matched healthy controls were enrolled. Serum levels of the biomarkers were quantified using ELISA, and their predictive power was assessed through binary logistic regression and Receiver Operating Characteristic (ROC) analysis. Results: Elevated serum levels of NSE, NEFL, and GFAP were observed in LP subjects relative to healthy counterparts, reaching statistical significance (p&amp;lt;0.05). In contrast, pMAPT and S100B levels did not differ appreciably. GFAP is considered a predictive marker for LP with an area under the curve (AUC) value of 0.813 and a 95% confidence interval (CI) of 0.658-0.968 (p=0.003). Conclusions: The study underscores a distinctive neurodegenerative profile in LP, with NSE, NEFL, and GFAP concentrations significantly amplified. These biomarkers, particularly GFAP, may represent novel indicators for LP, offering prospective biomarker-based diagnostic strategies. The insights garnered herein pave the way for advanced understanding and clinical management of LP, delineating a novel avenue for future high-impact research.

Helicobacter pylori infection promotes liver injury through an exosome-mediated mechanism

Helicobacter pylori infection has been thought to be associated with liver diseases, although the exact mechanisms remain elusive. This study identified H. pylori-induced liver inflammation and tissue damage in infected mice and examined the exosome-mediated mechanism underlying H. pylori infection's impact on liver injury. Exosomes were isolated from H. pylori-infected gastric epithelial GES-1 cells (Hp-GES-EVs), and the crucial virulence factor CagA was identified within these exosomes. Fluorescent labeling demonstrated that Hp-GES-EVs can be absorbed by liver cells. Treatment with Hp-GES-EVs enhanced the proliferation, migration, and invasion of Hep G2 and Hep 3B cells. Additionally, exposure to Hp-GES-EVs activated NF-κB and PI3K/AKT signaling pathways, which provides a reasonable explanation for the liver inflammation and neoplastic traits. Using a mouse model established via tail vein injection of Hp-GES-EVs, exosome-driven liver injury was evidenced by slight hepatocellular erosion around the central hepatic vein and elevated serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and IL-6. Administering the exosome inhibitor GW4869 via intraperitoneal injection in mice resulted in a reduction of liver damage caused by H. pylori infection. These findings illuminate the exosome-mediated pathogenesis of H. pylori-induced liver injury and offer valuable insights into the extra-gastrointestinal manifestations of H. pylori infection.

Impact of physical activity and diet in the treatment of hypothyroidism: A systematic review

Introduction and Objective: Thyroid diseases constitute a significant health challenge of the 21st century. Due to the growing awareness of the accompanying symptoms and the impact of the proper functioning of the thyroid gland on the overall condition of the body, patients show increasing interest in therapeutic methods. The main aim of the article is to present the impact of physical activity and proper diet on the management of patients with hypothyroidism. Review and Methods: Review and summary of studies and meta-analysis of studies available in open-source format on Google Scholar, Web of Science and PubMed. Abbreviated Description of the State of Knowledge: Hypothyroidism is a clinical condition characterized by the insufficient production of thyroid hormones by the thyroid gland. This hormonal deficiency leads to a generalized decrease in metabolic processes. Clinically, hypothyroidism is diagnosed based on elevated serum levels of thyroid-stimulating hormone (TSH) and decreased levels of free thyroxine (T4). Prevalent symptoms include fatigue, constipation, weight gain, cold intolerance, depression and dry skin. Effective management typically involves hormone replacement therapy with synthetic thyroxine. Summary: Hypothyroidism is a complex disease influenced by many factors. A multidisciplinary approach is recommended in its treatment, including pharmacological treatment, diet and appropriately selected physical activity. Early diagnosis and treatment are essential to improve the physical and mental condition of patients.

Increased of IL-18 levels are associated with periodontitis: a systematic review and meta-analysis

BackgroundThe presence of a polymicrobial dysbiotic film in direct and constant contact with periodontal tissues initiates the host immune response. Interleukin 18 (IL-18) triggers up-regulates the production of other proinflammatory cytokines (TNF-α, IL-1β, IL-6), creating a vicious cycle that expands the inflammatory and destructive process in the periodontal tissue. A systematic review and meta-analysis was carried out with the main propose to investigate IL-18 expression in different biological samples from subjects with chronic periodontitis.MethodsThe protocol followed PRISMA guidelines and was registered in Open Science Framework (OSF):https://doi.org/10.17605/OSF.IO/BS9GM. A digital search was conducted in the databases PubMed, ScienceDirect, Google Scholar, Web of Science and Dentistry & Oral Sciences Source databases were consulted from March 15th, 2005 to February 10th, 2023. Study quality was assessed using the JBI tool for cross-sectional studies and clinical trials. A meta-analysis was performed using a random/fixed effects model to evaluate the concentration of IL-18 in serum, plasma, saliva, gingival tissue and GCF of exposure group compared to control group.ResultsThe search strategy provided a total of 3,156 articles, of which 18 investigations met the inclusion criteria and 15 articles were quantitatively analyzed. The total number of patients studied was 1,275 (682 cases and 593 controls). The meta-analysis revealed significantly elevated IL-18 levels of serum, saliva and GCF of subjects with chronic periodontitis compared to healthy subjects (Serum: SMD = 62.73, 95%CI: 25.43-100.03, Z = 3.29, p = 0.001*; Saliva: SMD = 243.63, 95%CI: 8.68-478.59, Z = 2.03, p = 0.042*; GCF: SMD = 150.26, 95%CI: 56.86-243.66, Z = 3.15, p = 0.02*).ConclusionIL-18 levels in serum, saliva and GCF could have the potential to be used as complementary diagnostic tools to the clinical and radiographic parameters in subjects with periodontitis.