Elevated Serum Levels Research Articles

Job’s syndrom. Case reports

Primary immunodeficiencies with impaired humoral link are genetically determined diseases characterized by impaired antibody formation. The article presents information about an orphan disease – hyperimmunoglobulinemia E syndrome (hyper-IgE), or Job’s syndrome, which is characterized by elevated IgE levels in the blood serum, recurrent infections and various clinical manifestations (specific abnormalities of connective tissue, skeleton, tooth enamel, neurological disorders, etc.). Historical aspects of Job’s syndrome are described, the importance of immunoglobulins E in the human immune system is shown. It is noted that genetic testing, including sequencing of the STAT3 and DOCK8 genes, plays a decisive role in confirming the diagnosis. Low prevalence of Job’s syndrome is the reason for late diagnosis. Clinical cases of Job’s syndrome, a variant of primary immunodeficiency confirmed genetically, are presented.

The HLA-B -21 M/T dimorphism associates with disease severity in COVID-19.

Host genetics shape immune responses and influence severity of infectious diseases. The HLA-B -21 M/T dimorphism tunes the functionality of natural killer (NK) cells expressing the inhibitory receptor NKG2A. NKG2A+ NK cells have been reported to recognize SARS-CoV-2-infected cells, but it remains unclear whether the HLA-B -21 M/T dimorphism associates with COVID-19 severity. Here, we investigated the influence of the HLA-B -21 M/T dimorphism in a cohort of 230 unvaccinated patients hospitalized with COVID-19 and requiring respiratory support. We found that HLA-B -21 M/M genotypes were more prevalent in patients with moderate compared to severe COVID-19 (6.0% vs. 0.9%). Comparison of age- and sex-matched sub-groups revealed that patients with M/M genotypes required mechanical respiratory support less frequently (OR = 0.13, 95% CI = 0.01-0.76, P = 0.013). Furthermore, patients with M/M genotypes showed a coordinately shifted signature of clinical laboratory parameters, coinciding with elevated serum levels of the anti-viral cytokine IFN-γ. These findings demonstrate that HLA-B variants associate with COVID-19 severity and suggest that the robust functionality of NKG2A+ NK cells in patients carrying the M/M genotype may contribute to protection from severe disease.

Elevated Serum Levels of Osteopontin in Patients with Psoriasis: Is It Associated with Ocular Comorbidities?

Introduction: Psoriasis is a chronic inflammatory disease affecting 2%-3% of the global population via immune-mediated mechanisms. Osteopontin plays a crucial role in T-helper 1 and T-helper 17-mediated illnesses, including psoriasis. Ocular complications in psoriasis have been reported and their assessment is of importance. Osteopontin is normally expressed constitutively in ocular structures and is linked to ocular homeostasis. Objective: This study aimed to clarify the role of osteopontin (OPN) in psoriasis (PS) and its correlation with disease severity and ocular manifestations. Methods: A case-control study involving 40 psoriatic patients and an equal number of age and sex-matched healthy subjects was conducted. We used the psoriasis area severity index (PASI) to assess disease severity and performed a comprehensive ophthalmological examination. Additionally, we measured serum osteopontin levels using Enzyme-Linked Immunosorbent Assay (ELISA) in both groups. Results: A significant elevation in serum OPN levels in psoriatic patients compared to controls was found (P=0.00). Furthermore, there was a highly significant positive correlation between serum OPN levels and patient age, disease duration, and PASI scores. Notably, a higher prevalence of ocular complications, including blepharitis, corneal affection, conjunctivitis, keratoconjunctivitis sicca, and cataract, in psoriatic patients compared to controls was observed. Importantly, significant associations between serum OPN levels and the presence of cataracts and intraocular pressure (IOP) were identified. Additionally, significant correlations between serum OPN levels and measures of visual acuity and ocular surface health were found. Conclusions: Osteopontin is considered a marker of psoriasis severity and is associated with ocular comorbidities in psoriasis.

Heat exposure promotes sarcopenia via gut microbiota-derived metabolites.

The unprecedented rise in global ambient temperatures in the last decade has significantly impacted human health, yet how heat exposure affects the development of sarcopenia remains enigmatic. Here, we demonstrate that chronic heat exposure induces skeletal muscle volume loss, leading to muscle strength and functional decline in mice. The microbiota composition of heat-exposed mice was analyzed using 16S ribosomal DNA analysis. Liquid chromatography-mass spectrometry (LC-MS) was used to explore the effects of heat exposure on the blood metabolome and to further analyze the correlation between blood metabolism and gut microbiota. Transplantation of microbiota from heat-exposed mice to germ-free mice was sufficient to increase adverse effects on skeletal muscle function in the host. Mechanistically, using an untargeted metabolomics strategy, we reveal that altered gut microbiota due to high temperatures is associated with elevated serum levels of homocitrulline. Homocitrulline causes mitochondrial dysfunction in myocytes by exacerbating ferroptosis levels. And Nrf2 activator (Oltipraz) supplementation alleviates muscle atrophy and dysfunction induced by heat exposure. Our findings reveal the detrimental effects of heat exposure on muscle function and provide new strategies for treating sarcopenia.

Wire injury induced moderate aortic valve stenosis in mice is accompanied by a chronic systemic inflammatory reaction

Abstract Background Patients with aortic valve stenosis (AS) have elevated serum levels of inflammation markers, and blood cytokine levels correlate with ventricular recovery after transcatheter aortic valve replacement. While presence of inflammatory processes in stenotic aortic valves is acknowledged, no systematic characterization of the systemic immune reaction upon AS has been performed, yet. Purpose Hypothesis of this study was that AS induces a systemic inflammatory reaction linked with local processes in the heart. Methods AS was induced by wire injury (WI) or sham surgery was performed in 3-4 months old male C57Bl/6J mice. AS severity, left ventricular (LV) function and hypertrophy indices were assessed with echocardiography (echo). After four weeks, explanted organs were weighted, and flow cytometry identified total leukocyte numbers in blood, heart, and peripheral immune organs (spleen, liver, lymph nodes) and uptake of Cy5-labelled perfluorocarbon nanoemulsions by whole blood leukocytes. Costimulatory molecules (flow cytometry, RT-qPCR) and cytokines (RT-qPCR, Multiplex Immunoassay) were analysed in heart, peripheral immune organs and blood. Results R-values were positive for spleen weight correlation with AS severity, cardiac function and mass suggesting cardiac hypertrophy to preserve heart function. Myocardial myeloid and T cell r-values were positive or negative, respectively, for correlation with spleen and liver weight, hinting at T cell recruitment from peripheral stores. Immune cell numbers in peripheral lymph nodes and spleen showed negative r-values for correlation with heart hypertrophy indices; number of liver myeloid cells correlated negatively with LV wall thickness (monocytes=-0.8571, p=0.0238) suggesting immune cell recruitment to hypertrophic hearts. Cytokine mRNA levels trended mainly towards increase in heart and regional lymph nodes and reduction in spleen and liver after WI. Correlation with echo was more homogeneous after WI, with r-values mainly positive, except of T cell activation markers, for aortic valves, but negative for myocardium, hinting at mechanisms preserving heart function. Correlating unchanged cytokine protein levels in myocardium and plasma with echo, r-values were mostly positive for myocardium, and were more positive than in sham for plasma. Echo and costimulatory molecule correlation showed a more homogeneous pattern in WI, with mostly positive r-values in myocardium and periphery, while most r-values were negative in sham. Together with reduced PFC-uptake by lymphatic cells, this hints at systemic immune cell activation in AS. Conclusion The results suggest that number and activation state of leukocytes in peripheral organs are directly linked to cardiac processes in AS. Considering the pathological value of inflammation, it is crucial to in future studies find out if modulation of the systemic inflammatory reaction relieves severity of AS and prevents development of heart failure.

Health Benefits of Yerba Mate Consumption on Cardiovascular Health

Background: Yerba mate is a Paraguayan kind of herbal tea prepared from the dried and roasted leaves of trees called Ilex paraguariensis St. Hill. It is known for high content of polyphenols, methylxanthines and saponins. According to the studies products rich in those nutrients may have a positive influence on the humans cardiovascular health. Materials and methods: We reviewed publications obtained from PubMed and Google Scholar. Articles were selected based on keywords such “yerba mate’’, “Ilex paraguariensis’’, “cardiovascular diseases’’. For the final analysis, qualified articles were published from 2005 to 2024. Results: Confirming positive impact on serum lipid levels individuals using mate tea. Long – term positive influence on blood pressure. Moreover subjects with obesity took advantages of Yerba beverage by decreasing waist-to-hip ratio. Patients with diabetes were observed to have a significant reduction in fasting plasma glucose level and HbA1c concentration. Conclusions: Most of the cited researches support the hypothesis of benefits coming from drinking mate infusions for patients with elevated lipid serum levels, obesity, high blood pressure and type 2 diabetes mellitus. All of mentioned health issues can lead to the cardiovascular problems therefore using mate infusions can prevent CVDs. Taking everything into consideration, medical professionals might recommend Yerba mate tea for their patients especially as a replacement of a coffee.

Preventive effect of imperatorin against doxorubicin-induced cardiotoxicity through suppression of NLRP3 inflammasome activation.

Cardiotoxicity is one of the major obstacles to anthracycline chemotherapy. Anthracycline cardiotoxicity is closely associated with inflammation. Imperatorin (IMP), a furocoumarin ingredient extracted from Angelica dahurica, might have potential activity in preventing anthracycline cardiotoxicity due to its anti-cancer, anti-inflammatory, anti-oxidant, cardioprotective properties. This study aims to reveal the effect of IMP on doxorubicin (DOX)-induced cardiotoxicity and its underlying mechanism. We established a rat model of DOX-induced cardiotoxicity by intraperitoneal injection with DOX (1.25mg/kg twice weekly for 6weeks), and found that both IMP (25mg/kg and 12.5mg/kg) and dexrazoxane 12.5mg/kg relieved DOX-induced reductions in heart weight, change in cardiac histopathology, and elevated serum levels of LDH, AST and CK-MB. Moreover, DOX upregulated mRNA levels of NLRP3, CASP1, GSDMD, ASC, IL-1β and IL-18, elevated protein expressions of NLRP3, ASC, GSDMD-FL, GSDMD-N, pro‑caspase‑1, caspase‑1 p20, pro‑IL‑1β and IL‑1β in heart tissues, as well as increased serum levels of pro-inflammatory cytokines including IL-1β and IL-18, however both of IMP and dexrazoxane suppressed these alterations. In addition, we carried out neonatal rat cardiomyocytes experiments to confirm the results of the in vivo study. Consistently, pretreatment with IMP 25µg/mL relieved DOX (1μg/mL)-induced cardiomyocytes injury, including decreased cell viability and reduced supernatant LDH. IMP inhibited DOX-induced activation of NLRP3 inflammasome in cardiomyocytes. In conclusion, IMP had a protective effect against DOX-induced cardiotoxicity via repressing the activation of NLRP3 inflammasome. These findings suggest that IMP may be a promising alternative or adjunctive drug for the prevention of anthracycline cardiotoxicity.

Fermented Moringa oleifera seed-cassava inclusion improves protein and selected biochemical indices in alloxan-induced diabetes in animal model

Despite the availability of many pharmacological interventions for diabetes management, current evidence shows an alarming rising trend in the occurrence of undesirable complications, confirming that other complementary approaches are required. This study evaluated the nutraceutical properties of fermented Moringa oleifera seed-Cassava (FMOC) inclusion on selected biochemical parameters in rats induced with diabetes. Portions of cassava was substituted with moringa seed at 100:0 (control), 80:20 (not fermented:T1), 80:20 (fermented;T2) and 70:30% (fermented:T3). Fermentation was achieved using a starter culture containing Lactic acid bacteria for 36 h. Thirty-six (36) male albino rats were randomly divided into six groups (n=6/group). Groups B-F were rendered diabetic using alloxan (150 mg/kg. bw; IP) while group A served as the normal control. The effects of FMOC on proximate and selected biochemical indices of diabetic rats were evaluated. Results showed that protein increased significantly (p<0.05) (2.43}0.1 to 20.44} 02 g/100g) in the fermented sample as against non fermented control. All test diets (especially T2) counteracted the diabetic effects in rats by lowering (P<0.05) the elevated serum levels of glucose (249.0 to 105.6 mg/dl), Cholesterol (6.73 to 4.13mmol/L), TAG (2.43 to 1.99mmo/L), LDL (3.72 to 2.66mmol/L), Urea (35.3 to 23.2mmol/L) and malondialdehyde (2.34 to 1.29mg/dl) compared with diabetic group. It also improved (P<0.05) glutathione (2.69-3.76mg/dl) and catalase enzyme activity (1.52-2.90 U/mg). No significant effect was recorded for HDL (P>0.05). Histological outcomes of pancreas corroborated these findings. A food–based approach incorporating fermented M. oleifera seed could be considered an effective strategy to manage the complications that might arise from diabetes.

Vitamin U alleviates AFB1-induced hepatotoxicity in pregnant and lactating mice by regulating the Nrf2/Hmox1 pathway

This study investigated the protective effect of Vitamin U on liver injury induced by aflatoxin B1 (AFB1) in maternal mice. 25 pregnant ICR mice were randomly divided into five groups: the AFB1 group (AF, 0.3 mg AFB1/kg b.w.), the Vitamin U group (U, 50 mg Vitamin U/kg b.w.), the AFB1 + Vitamin U group (AU, 50 mg Vitamin U /kg b.w. + 0.3 mg AFB1/kg b.w.), the control group (DMSO), and the MOCK group (distilled water). They were administered substances by gavage every day for 28 days. Results indicated that exposure to AFB1 increased the liver index and caused histological disruptions. Elevated serum levels of ALT and ALP were observed, along with a significant increase in liver MDA content and a decrease in GSH-Px and T-SOD levels. Moreover, the Keap1 and Hmox1 gene was downregulated with statistical significance, while the IL1β and TNFα gene were significantly upregulated. Vitamin U was demonstrated by the organized structure of liver cells in tissue slices, effectively reducing liver cell necrosis. This intervention was associated with a significant decrease in serum ALT and ALP activities, as well as a significant decrease in liver MDA content. Additionally, there were significant increases in liver T-SOD and GSH-Px levels, along with upregulation of mRNA and protein expression of Nfr2, Hmox1 and Keap1, and downregulation of mRNA expression of the IL1β gene. In summary, Vitamin U mitigated oxidative stress-induced liver injury by modulating the Nrf2/Hmox1 signaling pathway and inflammatory factors affected by AFB1.

Relationships among Dioxin-like Mitochondria Inhibitor Substances (MIS)-Mediated Mitochondria Dysfunction, Obesity, and Lung Function in a Korean Cohort.

Mitochondrial dysfunction is closely linked to obesity and diabetes, with declining lung function in aging increasing diabetes risk, potentially due to elevated serum levels of dioxin-like mitochondria inhibitor substances (MIS) from prolonged exposure to environmental pollutants. However, the mechanisms connecting MIS, mitochondria, lung function, and metabolic disorder remain unclear. In this study, we analyzed data from 1371 adults aged 40-69 years in the 2008 Korean Genome Epidemiologic Study (KoGES) Ansung cohort. We indirectly estimated dioxin-like MIS levels by measuring intracellular ATP (MISATP) and reactive oxygen species (MISROS) in cultured cells treated with the serum of participants. Using correlation analysis and structural equation modeling (SEM), we explored the relationships among MIS, mitochondrial function, body mass index (BMI), and lung function (FEV1 and FVC). Our findings revealed that MISATP was associated with BMI in females and with FVC in males, while MISROS correlated with both BMI and FVC in males, not in females. Significant associations between BMI and FVC were found in the highest MIS subgroup in both sexes. SEM analyses demonstrated that MIS negatively influenced mitochondrial function, which in turn affected BMI and lung function. Age-related declines in lung function were also linked to mitochondrial dysfunction. This study underscores the potential of MIS assays as alternatives for assessing mitochondrial function and highlights the importance of mitochondrial health in metabolic disorders and lung function.

The Role of Adipokines between Genders in the Pathogenesis of Osteoarthritis

Osteoarthritis (OA) is a chronic, progressive, degenerative joint disease characterized by joint pain, stiffness, and limited movement. It presents significant intra- and inter-individual variability—in particular, between genders. Recent research has increasingly focused on the role of adipokines—especially leptin, adiponectin, and resistin—in the development of OA. Adipokines, peptide hormones primarily secreted by adipose tissue, are involved in crucial physiological processes related to metabolism and immunity. They can also impact bone and cartilage turnover by interacting with joint cells such as osteoblasts, osteoclasts, chondrocytes, and mesenchymal stem cells, thereby linking inflammation with bone cartilage homeostasis. This review aims to elucidate the structure and functions of various adipokines, their serum and synovial levels, and their association with clinical presentation and radiographic progression in OA patients, with a focus on differences between sexes. A narrative literature review was conducted using three databases specifically analyzing sex differences. OA patients generally show elevated serum and synovial levels of leptin, chemerin, and visfatin, as well as high plasma levels of resistin and visfatin. In contrast, synovial levels of adiponectin and omentin are reduced in OA patients compared to healthy individuals, with an inverse relationship to disease severity, suggesting a potential protective role. Resistin and leptin were positively correlated with pain severity and radiographic progression, while adiponectin’s role in OA remains controversial. Regarding sex differences, male OA patients exhibited higher serum levels of leptin, chemerin, and omentin compared to healthy controls, with a positive correlation to the BMI and estrogen levels, potentially explaining the sexual dimorphism observed in this condition. Studies on visfatin and lipocalin did not reveal significant differences in synovial or serum levels between the sexes. The role of resistin remains controversial. Adipokines influence the joint microenvironment and contribute to the progression of osteoarthritis (OA). However, the precise biological mechanisms are not yet fully understood due to the complex interactions between the metabolic, mechanical, and immune systems. Further research is needed to clarify their roles in OA and to identify targeted therapies for managing this degenerative disease.

Prevalence of canine renal insufficiency: A decade-long retrospective study in and around Patna, Bihar

This retrospective study investigates the prevalence and epidemiological factors associated with renal insufficiency in dogs within Patna, Bihar, India. Out of 5,700 dogs with various illnesses, 317 were diagnosed with renal insufficiency, identified by serum creatinine levels exceeding 5 mg/dL. The study assessed the incidence of renal insufficiency across different demographics, including age, sex, breed, and season. The highest incidence was observed in dogs aged 8-10 years, with males showing a higher prevalence than females. Pomeranians (32.18%), Labrador Retrievers (25.55%), and German Shepherds (20.82%) were the most affected breeds. Seasonally, the post-monsoon period (September-November) exhibited the highest incidence (37.85%) of renal disorders. Laboratory investigations revealed significant haematological and biochemical alterations in affected dogs, including lower haemoglobin, total erythrocyte count, and packed cell volume, alongside elevated serum levels of blood urea nitrogen (BUN), creatinine, potassium, and phosphorus. Ultrasonography indicated decreased renal size and increased echogenicity in dogs with renal insufficiency. The study concludes that renal insufficiency in dogs is most prevalent in older males and certain breeds, particularly during the post-monsoon season. Regular monitoring of serum BUN and creatinine levels is recommended for early diagnosis and management of this condition.

7002 Building Poor Bone, A Rare Presentation Of Skeletal Fluorosis

Abstract Disclosure: C. Pham: None. J.S. Lopresti: None. Skeletal fluorosis is a rare disease associated with osteosclerosis and fractures. Case: 26 year old male presented with a history of multiple traumatic fractures but no childhood or family history of fractures. Initial labs revealed a corrected calcium of 8.1 mg/dL (8.5-10.3), ALP 1,504 U/L (40-129), PTH 131 pg/ml (15-65), 25-OH D 14 ng/ml (30-100), PO4 3.7 mg/dl (2.5-4.5) and normal creatinine. X-Rays demonstrated osteosclerosis and cortical expansion of bone and nuclear bone scan demonstrated diffuse increased uptake. Further history revealed huffing of computer inhalants (10 cans daily) for years. Due to these findings, urine fluoride 16.88 mg/L (0.20-3.20 mg/L) and serum fluoride 0.40 mg/L (<0.05 mg/L) were obtained and vitamin D was started. 4 months later, his vitamin D level improved to 21 while calcium levels normalized despite ongoing inhalant use. ALP (878) and PTH (92) continued to be elevated albeit at improved levels. Conclusion: Exposure to fluoride leads to a rare condition called skeletal fluorosis causing accelerated osteogenesis and bone turnover leading to weak bone. Symptoms include bony pain, fractures, and osteosclerosis on radiographs. Differential diagnosis includes other conditions associated with osteosclerosis such as Paget’s disease and myelofibrosis. However, diffuse osteosclerosis and vertebral osteophytosis are noted only in skeletal fluorosis compared to other potential causes, though our patient did not have a CT spine done to assess for osteophytes. Biochemical studies can include hypocalcemia and hyperparathyroidism. It is thought that low calcium intake contributes to the hyperparathyroidism. Elevated serum and urine fluoride levels are also diagnostic and can persist for months after cessation of fluoride intake. Sodium fluoride has been posited as a treatment for osteoporosis due to its tremendous ability to build bone; however, the quality of bone made is poor leading to unacceptable fracture rates. Skeletal fluorosis should be suspected in any patient with history of diffuse osteosclerosis and hyperparathyroidism; and vitamin D supplementation should be initiated. In our case, hypocalcemia and PTH levels were improved despite active inhalant use after vitamin D supplementation. This suggests that Vitamin D deficiency and fluoride may be two independent driving factors in hyperparathyroidism in patients with fluorosis. Increased calcium absorption with vitamin D provides therapeutic benefit in both cases. Presentation: 6/1/2024

7975 TLR4 Signaling Modulates Reproductive and Metabolic Outcomes in a Mouse Model of Polycystic Ovary Syndrome

Abstract Disclosure: K.D. Wiggins: None. Z. Del Mundo: None. J.A. Ayala Angulo: None. M. Lopez: None. C. Garcia: None. C. Nguyen: None. J. De La Torre: None. A. Saba: None. D. Trinh: None. D. Nicholas: None. Polycystic Ovarian Syndrome (PCOS), characterized by disruptions in both reproductive and metabolic functions, is associated with abnormal immune system activity and chronic inflammation. Although the precise mechanistic drivers of chronic inflammation in PCOS are not fully elucidated, elevated serum levels of lipopolysaccharide (LPS) have been observed. We propose that Toll-like receptor 4 (TLR4) signaling, influenced by dysregulated LPS levels, is a central driver of chronic inflammation affecting both reproductive and metabolic pathways. To investigate this hypothesis, we subcutaneously implanted a nonsteroidal aromatase inhibitor, Letrozole (LET), in pubertal TLR4 knockout mice (TLR4KO) and C57BL/6J (wild type) mice. Our five-week LET treatment revealed that TLR4KO mice successfully entered all phases of the estrous cycle, with normalized Luteinizing Hormone (LH) and increased Follicle Stimulating Hormone (FSH) levels. These findings highlight TLR4's role in shaping cycling patterns and regulating fundamental hormonal pathways vital for reproductive health. Despite the genetic manipulation of the inflammatory pathway leading to a reduction in overall body weight gain, it had no discernible impact on the overall body composition of fat and lean mass. Additionally, our study found that dysregulation of blood glucose levels over time was independent of reduced body weight. TLR4KO mice demonstrated inefficient glucose clearance compared to wild-type mice, hinting at potential increases in insulin resistance, imbalances in adipose tissue inflammation, or possible alterations in the gut microbiota. Our study underscores the significance of disrupting the pro-inflammatory TLR4 pathway in shaping the reproductive and metabolic phenotypes in Letrozole-induced PCOS. The investigation into TLR4 becomes pivotal for comprehending the role of chronic inflammation in PCOS development or progression, offering valuable insights into potential therapeutic targets. Presentation: 6/2/2024

Comparison between statistical and machine learning methods to detect the hematological indices with the greatest influence on elevated serum levels of low-density lipoprotein cholesterol

IntroductionElevated levels of low-density lipoprotein-cholesterol (LDL-C) is a significant risk factor for the development of cardiovascular diseases (CVD)s. Furthermore, studies have revealed an association between indices of the complete blood count (CBC) and dyslipidemia. We aimed to investigate the relationship between CBC parameters and serum levels of LDL. MethodIn a prospective study involving 9704 participants aged 35–65 years, comprehensive screening was conducted to estimate LDL-C levels and CBC indicators. The association between these biomarkers and high LDL-C (LDL-C≥130 mg/dL (3.25 mmol/L)) was investigated using various analytical methods, including Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Neural Network (NN), and Support Vector Machine (SVM) methodologies. ResultThe present study found that age, hemoglobin (HGB), hematocrit (HCT), platelet count (PLT), lymphocyte (LYM), PLT-LYM ratio (PLR), PLT-High-Density Lipoprotein (HDL) ratio (PHR), HGB-LYM ratio (HLR), red blood cell count (RBC), Neutrophil-HDL ratio (NHR), and PLT-RBC ratio (PRR) were all statistically significant between the two groups (p<0.05). Another important finding was that red cell distribution width (RDW) was a significant predictor for higher LDL levels in women. Furthermore, in men, RDW-PLT ratio (RPR) and PHR were the most important indicators for assessing the elevated LDL levels. ConclusionThe study found that sex increases LDL-C odds in females by 52.9 %, while age and HCT increase it by 4.1 % and 5.5 %, respectively. RPR and PHR were the most influential variables for both genders. Elevated RPR and PHR were negatively correlated with increased LDL levels in men, and RDW levels was a statistically significant factor for women. Moreover, RDW was a significant factor in women for high levels of HDL-C.The study revealed that females have higher LDL-C levels (16 % compared to 14 % of males), with significant differences across variables like age, HGB, HCT, PLT, RLR, PHR, RBC, LYM, NHR, RPR, and key factors like RDW and SII.

Serum TNFα and IL-17A levels may predict increased depressive symptoms: findings from the Shika Study cohort project in Japan

BackgroundLow-grade systemic inflammation may be a key player in the immune activation that has been reported for mental health deterioration. We hypothesised that elevated serum levels of inflammatory cytokines increase neuroinflammation and exacerbate depressive symptoms.MethodsThe participants were part of a cohort study for whom data was available for both 2015 and 2019. In 2015, blood samples were collected from 232 participants. Their depressive symptoms were assessed both 2015 and 2019 using the Centre for Epidemiologic Studies Depression Scale (CES-D) (n = 33). The multiplex immunoassay system (Luminex® 200) was used to measure the serum concentrations of IL-6, IL-10, IL-12, IL-17A and TNFα. Data were analysed using linear models with the level of significance considered to be p < 0.05.ResultsAfter controlling for age, BMI, smoking and alcohol consumption, in 2015 the serum concentrations of IL-17A and TNFα in 2015 were significantly positively associated with the CES-D scores of women (standardised β (B) = .027, p < 0.01 and B = 0.26, p < 0.01, respectively). The serum concentrations of IL-17A and TNFα of men were significantly positively associated with the CES-D scores of 2019 (B = 0.62, p = 0.02 and B = 0.59, p = 0.02, respectively).ConclusionsIn this cross-sectional study, we found a significant positive correlation between the depressive symptoms and serum TNFα and IL-17A levels of women. In addition, our longitudinal findings suggest the possibility that TNFα and IL-17A could elevate the depressive symptoms of men.

BML-111 Modulates and Alleviates p38/MAPK Signaling Pathway and Th1/Th2/Th17 Cytokine Response in Murine Psoriasis-Like Dermatitis.

Psoriasis is a prevalent cutaneous inflammatory disorder characterized by elevated keratinocyte inflammation. 5(S)-6(R)-7-trihydroxyheptanoic-acid-methyl-ester (BML-111), an established analogue of lipoxin A4, is known for its potent anti-inflammatory properties. However, the precise role of BML-111 within a murine psoriasis-like dermatitis model requires further clarification. This research aims to investigate the modulatory effects of BML-111 on inflammatory responses, the p38/mitogen-activated protein kinase (MAPK) signaling cascade, and T helper type 1 (Th1), Th2, and Th17 cell responses within the context of a murine psoriasis-like dermatitis model. A psoriasis-like dermatitis model was established by applying 5% imiquimod (IMQ) cream to the backs of C57BL/6 mice, which were pretreated intraperitoneally with or without BML-111 prior to IMQ application. Hematoxylin-eosin staining was utilized to detect the pathological alterations of the murine dorsal skin tissue. Furthermore, the psoriasis area and severity index (PASI) scoring system was used to assess the dynamic cutaneous alterations in the mice. The levels of tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin (IL)-1β, IL-6, IL-4, and IL-17A in the murine serum samples were quantified by means of enzyme-linked immunosorbent assays (ELISA). Western blotting was conducted to detect the proteins of TNF-α, IL-1β, IL-6, phospho-p38 (p-p38), and p38 in murine skin tissues. Lastly, a flow cytometry analysis was executed to evaluate the expression of peripheral blood Th1/Th2/Th17 cell subsets. BML-111 attenuated IMQ-induced pathological changes in skin tissue of psoriasis-like dermatitis mice. BML-111 treatment substantially reduced TNF-α, IL-1β, IL-6, IFN-γ and IL-17A levels and elevated IL-4 levels in serum and skin lesion tissues of IMQ-induced mice (p < 0.01, p < 0.01, p < 0.01, p < 0.05, p < 0.05, p < 0.05, respectively). The ratio of Th1/Th17 cells in the peripheral blood of BML-111-treated mice was substantially diminished and the ratio of Th2 cells was substantially augmented (p < 0.05, p < 0.01, p < 0.001, respectively). Mechanistically, p-p38 protein level was substantially reduced in the skin tissues of BML-111-treated mice (p < 0.05). While, dehydrocorydaline (DHC, a p38/MAPK pathway agonists) reversed the reduction of p-p38 protein level induced by BML-111 treatment in psoriasis-like mice (p < 0.05). BML-111 modulates the p38/MAPK signaling pathway and Th1/Th2/Th17 cytokine response, and alleviates psoriasis-like dermatitis in mice.

Periodontitis adversely affects lipoprotein subfractions – results from the cohort study SHIP-TREND: Periodontitis adversely affects lipoprotein subfractions

AimWe aimed to investigate the medium-term associations of periodontitis and the number of missing teeth with serum lipoproteins and their plasma subfractions using follow-up data from the population-based Study of Health in Pomerania (SHIP-TREND). MethodsA total of 2,058 participants with 7-year follow-up data underwent periodontal examinations, serum lipid panel tests, and proton nuclear magnetic resonance (1H-NMR) spectroscopy of plasma lipoproteins and their subfractions. Generalized models with gamma distribution and loglink were used to analyze associations between periodontal variables and lipoproteins and their subfractions, adjusting for confounders using propensity score weighting. ResultsPeriodontal variables were consistently associated with elevated follow-up serum levels of triglycerides, total cholesterol, and low-density lipoprotein cholesterol levels. When plasma lipoprotein subfractions were evaluated, periodontal variables were associated with elevated levels of triglycerides and cholesterol-enriched apolipoprotein B-containing lipoprotein particles, particularly small dense low-density lipoprotein, very-low-density lipoprotein and intermediate density lipoprotein. In addition, altered high-density lipoprotein particle composition was observed, suggesting potential functional changes. ConclusionThis study provides evidence for causal effects of periodontitis on conventional serum lipids and plasma lipoprotein subfractions. As the underlying biological mechanisms are not fully understood, further research is needed.

Unusual presentation of fetal ventriculomegaly: a case report

Fetal ventriculomegaly (VM) is a relatively common finding during prenatal examinations and occurs in approximately 0.2% of live births. Although there are various causes, obstructive VM due to cerebellar hemorrhage is exceedingly rare. A 33-year-old primigravida presented at 32 weeks of gestation with VM. At 36 weeks of age, a male infant was delivered via cesarean section. Postnatal imaging revealed severe bilateral hydrocephalus and space-occupying lesions in the cerebellum. Initial concerns about a potential germ cell tumor were raised due to elevated alpha-fetoprotein levels in both serum and cerebrospinal fluid. An external ventricular drain was placed to manage obstructive hydrocephalus. When the baby was 1 month old, surgical exploration revealed an old blood clot without any evidence of a tumor. Histopathological examination confirmed an old hemorrhage with no malignant cells. This case underscores the diagnostic challenges in distinguishing between hemorrhages and tumors in the context of fetal VM. Despite elevated alpha-fetoprotein levels, no tumors were identified. The underlying cause of cerebellar hemorrhage remains unclear despite extensive workups. Nevertheless, this case report details multifaceted diagnostic efforts to address the rare occurrence of cerebellar hemorrhage related to fetal VM, leading to a comprehensive case presentation.

Serum lipid and lipoprotein profiles and their association with intraocular pressure in primary open-angle glaucoma: an observational cross-sectional study in the Chinese population

BackgroundGlaucoma is a leading cause of vision impairment and permanent blindness. Primary open-angle glaucoma (POAG) is a prominent type of primary glaucoma; however, its cause is difficult to determine. This study aimed to analyze the serum lipid profile of Chinese POAG patients and assess its correlation with intraocular pressure (IOP).MethodsThe study included 1,139, 1,248, and 356 Chinese individuals with POAG, primary angle closure glaucoma (PACG), and controls, respectively. Peripheral whole blood samples were collected at the time of diagnosis. Enzymatic colorimetry was used to determine serum levels of different lipids: high-density lipoproteins (HDL), low-density lipoproteins (LDL), triglycerides, cholesterol, and very low-density lipoproteins (VLDL). Additionally, immunoturbidimetry was used to quantify serum levels of apolipoproteins A (APOA), B (APOB), E (APOE), and lipoprotein A [Lp(a)], while intraocular pressure (IOP) was measured in all patients with POAG.ResultsAfter adjusting for age and sex, patients with POAG exhibited elevated serum levels of VLDL, APOA, and APOE but mitigated cholesterol levels compared with the control participants. Significantly lower serum triglyceride, VLDL, and Lp(a) levels were found in patients with PACG than in control participants. Serum cholesterol (P = 0.019; β = -0.75, 95% confidence interval [CI]: -1.38 – -0.12) and HDL levels (P < 0.001; β = -2.91, 95% CI: -4.58 – -1.25) were inversely linked to IOP in patients with POAG, after adjusting for age, sex, and ocular metrics. In addition, serum Lp(a) levels were correlated with the average IOP (P = 0.023; β = -0.0039, 95% CI: -0.0073 – -0.006) and night peak (P = 0.027; β = -0.0061, 95% CI: -0.0113 – -0.0008) in patients with POAG.ConclusionsSignificantly different serum lipid and lipoprotein profiles were observed in POAG and PACG patients. This study highlighted the differences in serum lipid and lipoprotein levels among Chinese POAG patients and their relationship with IOP and IOP fluctuation. Serum lipid and lipoprotein profiles should be considered while evaluating glaucoma risk.