Plasma Levels Of Protein Research Articles

Associations of potential plasma biomarkers with suicide attempt history, current suicidal ideation and subsequent suicidal events in patients with depression: A discovery study

A growing body of evidences suggests that suicidal ideation (SI) and suicidal behaviors have biological bases. However, no biological marker is currently available to evaluate the suicide risk in individuals with SI or suicide attempt (SA). Moreover, the current risk assessment techniques poorly predict future suicidal events. The aim of this study was to examine the association of 39 new and already described peripheral cells and proteins (implicated in the immune system, oxidative stress and plasticity) with lifetime SA, past month SA, current SI, and future suicidal events (visit to the Emergency Department for SI or SA) in 266 treatment-seeking individuals with mood disorders. Equal parts of patients with and without past history of SA were recruited. All individuals at inclusion gave blood, were evaluated for SA recency, current SI, and were followed for two years afterwards. The 39 peripheral blood cellular and protein markers were entered separately for each outcome in Elastic Net models with 10-fold cross-validation, followed by single-analyte covariate-adjusted regression analyses for pre-selected analytes. Past month SA was associated with increased plasma levels of thrombospondin-2 and C-reactive protein, whereas current SI was associated with lower plasma serotonin levels. These associations were robust to adjustments for key covariates and corrections for multiple testing. The Cox proportional hazards regression showed that higher levels of thrombospondin-1 and of platelet-derived growth factor-AB predicted a future suicidal event. These two associations remained after adjustment for sex, age, and SA history, and outperformed the predictive value of past SA. Thrombospondins and platelet-derived growth factors have never been investigated in the context of suicide. Altogether, our results highlight the involvement in the suicidal process of platelet biological response and plasticity modifiers and also of inflammatory factors. They also suggest that SI and SA may have different biological correlates and that biomarkers associated with past SA or current SI do not automatically also predict future events.

Identification of blood protein biomarkers associated with prostate cancer risk using genetic prediction models: analysis of over 140,000 subjects.

Prostate cancer (PCa) brings huge public health burden in men. A growing number of conventional observational studies report associations of multiple circulating proteins with PCa risk. However, the existing findings may be subject to incoherent biases of conventional epidemiologic studies. To better characterize their associations, herein, we evaluated associations of genetically predicted concentrations of plasma proteins with PCa risk. We developed comprehensive genetic prediction models for protein levels in plasma. After testing 1308 proteins in 79 194 cases and 61 112 controls of European ancestry included in the consortia of BPC3, CAPS, CRUK, PEGASUS, and PRACTICAL, 24 proteins showed significant associations with PCa risk, including 16 previously reported proteins and eight novel proteins. Of them, 14 proteins showed negative associations and 10 showed positive associations with PCa risk. For 18 of the identified proteins, potential functional somatic changes of encoding genes were detected in PCa patients in The Cancer Genome Atlas (TCGA). Genes encoding these proteins were significantly involved in cancer-related pathways. We further identified drugs targeting the identified proteins, which may serve as candidates for drug repurposing for treating PCa. In conclusion, this study identifies novel protein biomarker candidates for PCa risk, which may provide new perspectives on the etiology of PCa and improve its therapeutic strategies.

Mollification of Lead Induced Liver Injury by Lycopersicon esculentum (Tomato) Extract

Objective: Lead is a highly toxic, non-biodegradable heavy metal usually found in the environment largely as a pollutant of water, soil or air. Chronic lead exposure has adverse effects on human health. Lycopersicon esculentum has many phytochemicals that may ameliorate organ injury due to lead toxicity in humans. This study answered the question “Is aqueous extract of Lycopersicon esculentum (tomato) beneficent to lead toxicity induced liver injury?”
 Methodology: The study had five groups with fifteen animals each. The control was group CN. The lead toxicity group (PbT) had 30 mg/kg/day of lead acetate crystals, the concomitant extract group (CE) had concurrent administration of lead acetate and aqueous extract of L. esculentum (at 400 mg/kg). The post lead toxicity low dose extract. (PLE) had sequential administration of lead acetate and aq. extract L. esculentum (at 400 mg/kg). The post lead toxicity high dose extract. (PHE) had sequential administration of lead acetate and aq. extract L. esculentum (at 800 mg/kg). Both the lead acetate and extract were administered orally for twenty one days. At specific periods, blood samples were collected for biochemical analyses and organs harvested for histopathological evaluation.
 Result: The total plasma protein levels of the extract groups (CE, PLE and PHE) were significantly higher than that of the PbT group. The PbT group had markedly elevated plasma liver enzymes. Oxidative stress was only evident in the PbT group but not in the extract groups as suggested by the significantly depressed anti-oxidant activities and elevated lipid peroxidation. A cystic lesion was observed in one of the liver specimens from the PbT group. Histopathological findings included fatty infiltration of the liver in the PbT group and presence of multinucleated hepatocytes in the extract groups. The latter feature suggested the ability of aqueous extract of L. esculentum to ameliorate the lead (Pb) toxicity induced liver damage.
 Conclusion: Concurrent and post-exposure administration of aqueous extract of tomato fruit (L. esculentum) mollified the liver injury caused by lead toxicity.

Evaluation of Large-Scale Proteomics for Prediction of Cardiovascular Events

Whether protein risk scores derived from a single plasma sample could be useful for risk assessment for atherosclerotic cardiovascular disease (ASCVD), in conjunction with clinical risk factors and polygenic risk scores, is uncertain. To develop protein risk scores for ASCVD risk prediction and compare them to clinical risk factors and polygenic risk scores in primary and secondary event populations. The primary analysis was a retrospective study of primary events among 13 540 individuals in Iceland (aged 40-75 years) with proteomics data and no history of major ASCVD events at recruitment (study duration, August 23, 2000 until October 26, 2006; follow-up through 2018). We also analyzed a secondary event population from a randomized, double-blind lipid-lowering clinical trial (2013-2016), consisting of individuals with stable ASCVD receiving statin therapy and for whom proteomic data were available for 6791 individuals. Protein risk scores (based on 4963 plasma protein levels and developed in a training set in the primary event population); polygenic risk scores for coronary artery disease and stroke; and clinical risk factors that included age, sex, statin use, hypertension treatment, type 2 diabetes, body mass index, and smoking status at the time of plasma sampling. Outcomes were composites of myocardial infarction, stroke, and coronary heart disease death or cardiovascular death. Performance was evaluated using Cox survival models and measures of discrimination and reclassification that accounted for the competing risk of non-ASCVD death. In the primary event population test set (4018 individuals [59.0% women]; 465 events; median follow-up, 15.8 years), the protein risk score had a hazard ratio (HR) of 1.93 per SD (95% CI, 1.75 to 2.13). Addition of protein risk score and polygenic risk scores significantly increased the C index when added to a clinical risk factor model (C index change, 0.022 [95% CI, 0.007 to 0.038]). Addition of the protein risk score alone to a clinical risk factor model also led to a significantly increased C index (difference, 0.014 [95% CI, 0.002 to 0.028]). Among White individuals in the secondary event population (6307 participants; 432 events; median follow-up, 2.2 years), the protein risk score had an HR of 1.62 per SD (95% CI, 1.48 to 1.79) and significantly increased C index when added to a clinical risk factor model (C index change, 0.026 [95% CI, 0.011 to 0.042]). The protein risk score was significantly associated with major adverse cardiovascular events among individuals of African and Asian ancestries in the secondary event population. A protein risk score was significantly associated with ASCVD events in primary and secondary event populations. When added to clinical risk factors, the protein risk score and polygenic risk score both provided statistically significant but modest improvement in discrimination.

Histopathology and levels of proteins in plasma associate with survival after colorectal cancer diagnosis

BackgroundThe TNM system is used to assess prognosis after colorectal cancer (CRC) diagnosis. Other prognostic factors reported include histopathological assessments of the tumour, tumour mutations and proteins in the blood. As some of these factors are strongly correlated, it is important to evaluate the independent effects they may have on survival.MethodsTumour samples from 2162 CRC patients were visually assessed for amount of tumour stroma, severity of lymphocytic infiltrate at the tumour margins and the presence of lymphoid follicles. Somatic mutations in the tumour were assessed for 2134 individuals. Pre-surgical levels of 4963 plasma proteins were measured in 128 individuals. The associations between these features and prognosis were inspected by a Cox Proportional Hazards Model (CPH).ResultsLevels of stroma, lymphocytic infiltration and presence of lymphoid follicles all associate with prognosis, along with high tumour mutation burden, high microsatellite instability and TP53 and BRAF mutations. The somatic mutations are correlated with the histopathology and none of the somatic mutations associate with survival in a multivariate analysis. Amount of stroma and lymphocytic infiltration associate with local invasion of tumours. Elevated levels of two plasma proteins, CA-125 and PPP1R1A, associate with a worse prognosis.ConclusionsTumour stroma and lymphocytic infiltration variables are strongly associated with prognosis of CRC and capture the prognostic effects of tumour mutation status. CA-125 and PPP1R1A may be useful prognostic biomarkers in CRC.

Hypotension during transsphenoidal pituitary surgery associated with increase in plasma levels of brain injury markers.

Patients undergoing pituitary surgery may experience short- and long-term postoperative morbidity. Intraoperative factors such as hypotension might be a contributing factor. Our aim was to investigate the association between intraoperative hypotension and postoperative plasma levels of tau, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as markers of perioperative brain injury. Between June 2016 and October 2017, 35 patients from the Gothenburg Pituitary Tumor Study were included. For tau, NfL, and GFAP, concentrations were measured in plasma samples collected before and immediately following surgery, and on postoperative days 1 and 5. The difference between the highest postoperative value and the value before surgery was used for analysis (∆taupeak , ∆NfLpeak , ∆GFAPpeak ). Intraoperative hypotension was defined as the area under the curve of an absolute threshold below 70 mmHg (AUC70) and a relative threshold below 20% (AUC20%) of the baseline mean arterial blood pressure. Plasma tau and GFAP were highest immediately following surgery and on day 1, while NfL was highest on day 5. There was a positive correlation between AUC20% and both ∆taupeak (r2 = .20, p < .001) and ∆NfLpeak (r2 = .26, p < .001). No association was found between AUC20% and GFAP or between AUC70 and ∆taupeak , ∆NfLpeak or ∆GFAPpeak . Intraoperative relative, but not absolute, hypotension was associated with increased postoperative plasma tau and NfL concentrations. Patients undergoing pituitary surgery may be vulnerable to relative hypotension, but this needs to be validated in future prospective studies.

Diagnostic potential of plasma biomarkers and exhaled volatile organic compounds in predicting the different stages of acute mesenteric ischaemia: protocol for a multicentre prospective observational study (TACTIC study)

IntroductionAcute mesenteric ischaemia (AMI) is a life-threatening condition with short-term mortality of up to 80%. The diagnosis of AMI has remained troublesome due to the non-specific clinical presentation, symptoms and...

The association of monomeric C-reactive protein plasma level with the increase in plaques number and height in patients with low-grade carotid stenoses and HSCRP level

The association of monomeric C-reactive protein plasma level with the increase in plaques number and height in patients with low-grade carotid stenoses and HSCRP level

Transient anti-cytokine autoantibodies superimpose the hyperinflammatory response in Kawasaki disease and multisystem inflammatory syndrome in children: a comparative cohort study on correlates of disease

Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders. Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n=216) and MIS-C (n=56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls. ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P=0·02) and anti-IL-22 (P=0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P=0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P=0·02); and sCD25 (P=0·009), angiopoietin-2 (P=0·001), soluble IL-33-receptor (ST2, P=0·01) and CXCL10 (P=0·02) with ICU admission in MIS-C. Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation. The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication.

A simple dietary intervention to reduce inflammation and oxidative stress in individuals with metabolic syndrome

Abstract Funding Acknowledgements Type of funding sources: None. Background Approximately 25% of the world's population have metabolic syndrome and those diagnosed have a two-fold risk of developing cardiovascular disease. Inflammation and oxidative stress are responsible for the pathogenesis of metabolic syndrome. Diets with a high intake of vegetables containing carotenoids, a type of antioxidants, are associated with reduced levels of inflammation and oxidative stress, yet interventions to increase vegetable intake have been difficult to adapt. We conducted a randomized controlled trial of a simple dietary antioxidant intervention to reduce the levels of inflammation and oxidative stress. Purpose To examine the effect of a simple dietary antioxidant intervention on levels of inflammation and oxidative stress in persons with metabolic syndrome. Methods A total of 93 individuals with metabolic syndrome (mean age 61 ± 12 years old, 71% female) were enrolled. The intervention group received an 11.5-ounce serving of 100% carotenoid-rich vegetable juice to consume once per day for 30 days. The control group maintained their normal dietary pattern for 30 days. Adherence to the intervention was measured with Veggie Meter®, a validated reflection spectroscopy approach to assess skin carotenoid levels. Inflammation and oxidative stress were measured by plasma levels of high-sensitivity C-reactive protein (CRP) and malondialdehyde (MDA) at baseline and one-month post intervention. Two-way repeated measures analysis of variance was used to compare the group means over time. Log-transformation was applied as necessary for the variables with skewed distribution. Results There was no significant interaction between treatment and time on skin carotenoid levels, (respectively, P=0.214). There was a statistically significant increase of skin carotenoid levels in the intervention group alone (220 vs 264 in pre and post intervention, respectively, P=0.002). Change in mean CRP levels did not differ between control and intervention groups (P=0.520). Similarly, change in mean MDA did not significantly differ between two groups (P = 0.450). Conclusion A simple and easy to adapt, 1-month dietary antioxidant intervention did not change levels of inflammation and oxidative stress in individuals with metabolic syndrome, potentially due to the short-term treatment. Future interventions with dietary antioxidants should be implemented for longer time periods to fully assess the impact on inflammation and oxidative stress.

Effect of galectin-3 on synovial inflammation in knee osteoarthritis via stimulating phosphatidylinositol-3-kinase/Akt pathway

Galectin-3 (Gal-3), a glycan-binding protein responsible for inflammation, has been reportedly implicated in inflammatory arthritis. This study aimed to determine clinical and pathological effects of Gal-3 on inflammation in knee osteoarthritis (OA). Gal-3 mRNA and protein levels in synoviocytes, synovium, synovial fluid, and plasma of knee OA patients were determined using real-time polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. Signaling mechanism underlying inflammatory effect of Gal-3 was further elucidated in human knee OA synoviocytes. Clinical study uncovered significant increases in plasma and synovial fluid Gal-3 levels in knee OA patients, particularly those with advanced-stage. In knee OA patients, plasma Gal-3 was significantly associated with radiographic severity and indicators of body composition, physical performance, and knee pain and disability. In the inflamed synovium of knee OA patients, further analysis depicted a marked up-regulation of Gal-3 mRNA expression, consistent with immunohistochemical analysis showing localization of Gal-3 protein in the lining and sublining layers of the inflamed synovium. An in vitro study unveiled that aberrant Gal-3 mRNA expression was regulated by tumor necrosis factor (TNF)-α in knee OA synoviocytes. Gal-3 significantly enhanced production of NO and IL-6, up-regulated mRNA expressions of IL-6, NF-κB, and MMP-13, and down-regulated mRNA expressions of ACAN and SOX-9 via stimulating Akt phosphorylation in knee OA synoviocytes. Gal-3 exerted an inflammatory action, which might emerge as a possible mediator of synovitis and cartilage degeneration in knee OA.

Alzheimer’s disease-associated complement gene variants influence plasma complement protein levels

BackgroundAlzheimer’s disease (AD) has been associated with immune dysregulation in biomarker and genome-wide association studies (GWAS). GWAS hits include the genes encoding complement regulators clusterin (CLU) and complement receptor 1 (CR1), recognised as key players in AD pathology, and complement proteins have been proposed as biomarkers.Main bodyTo address whether changes in plasma complement protein levels in AD relate to AD-associated complement gene variants we first measured relevant plasma complement proteins (clusterin, C1q, C1s, CR1, factor H) in a large cohort comprising early onset AD (EOAD; n = 912), late onset AD (LOAD; n = 492) and control (n = 504) donors. Clusterin and C1q were significantly increased (p < 0.001) and sCR1 and factor H reduced (p < 0.01) in AD plasma versus controls. ROC analyses were performed to assess utility of the measured complement biomarkers, alone or in combination with amyloid beta, in predicting AD. C1q was the most predictive single complement biomarker (AUC 0.655 LOAD, 0.601 EOAD); combining C1q with other complement or neurodegeneration makers through stepAIC-informed models improved predictive values slightly. Effects of GWS SNPs (rs6656401, rs6691117 in CR1; rs11136000, rs9331888 in CLU; rs3919533 in C1S) on protein concentrations were assessed by comparing protein levels in carriers of the minor vs major allele. To identify new associations between SNPs and changes in plasma protein levels, we performed a GWAS combining genotyping data in the cohort with complement protein levels as endophenotype. SNPs in CR1 (rs6656401), C1S (rs3919533) and CFH (rs6664877) reached significance and influenced plasma levels of the corresponding protein, whereas SNPs in CLU did not influence clusterin levels.ConclusionComplement dysregulation is evident in AD and may contribute to pathology. AD-associated SNPs in CR1, C1S and CFH impact plasma levels of the encoded proteins, suggesting a mechanism for impact on disease risk.

Stocking density affects immune and stress-related gene expression of Butter catfish (Ompok bimaculatus) fry in biofloc landscapes

Scientific research into fish wellness is critical, and the concerns about crowding-related stress due to increased stocking density are inevitable. Taking this into consideration, the study defines the physiological signature of Ompok bimaculatus (Butter catfish) in a biofloc system when subjected to varying levels of stocking density. Fish (mean weight = 1.21 g ± 0.08, n = 600) were randomly stocked in 40-L glass aquaria at stocking densities of 0.5 g/L (T1), 1 g/L (T2), 1.5 g/L (T3), and 2 g/L (T4) and fed a 35% protein diet. After the 90-day trial, the physio-biochemical, molecular, and tissue-level changes were assessed. An integrated biomarker response (IBR) analysis for the key stress indicators aided us in better understanding them. There was a significant difference in blood count between T1 and T4 (total erythrocyte count, hemoglobin, and packed cell volume). T1 had higher levels of globulin and total plasma protein, but T2 had higher levels of albumin. Only in T1 did the respiratory burst and lysozyme activity appear to be higher (p < 0.05). Increased stocking densities had a significant impact on the liver function enzymes, GOT and GPT (p < 0.05). In comparison to lower densities (T1 & T2), higher stocking density (T3 & T4) was found to raise glucose and cortisol levels (p < 0.05). Antioxidant enzymes such as catalase, glutathione-S-transferase, and malondialdehyde were found to be more pronounced in lower density tissues (T1). Furthermore, the IBR plots show that lower densities have better health than higher densities. At higher stocking densities, mRNA expression of HSP70, IL-1, and IL-20 increased (p < 0.05) in kidney and liver tissues. The Nrf-2 and Tlr-9 genes were also upregulated. Also, when stocking density was increased, tissue-level histo-architectural changes were more pronounced than when stocking density was kept low. The findings of this study show that the welfare of Butter catfish cultured at high density in biofloc systems suffers from severe stress, and therefore draw more attention to the development of a species-specific standard rearing methodology in the pursuit of a profitable aqua-farming enterprise.

Effects of olanzapine on anhedonia in schizophrenia: mediated by complement factor H.

Anhedonia is a trans-diagnostic symptom in schizophrenia and MDD. Our recent work indicated that increased plasma level of complement factor H (CFH) is associated with anhedonia in major depressive disorder. This study hypothesized that CFH is likely to be a biomarker of anhedonia in schizophrenia. A 12-week prospective study is performed to observe the effects of olanzapine on anhedonia and CFH. We used the Chinese version of Snaith-Hamilton Pleasure Scale (SHAPS) to evaluate anhedonic phenotype in patients with schizophrenia. Plasma levels of C-reactive protein (CRP), C3, C4 and CFH were measured. Of the recruited 152 samples, patients with anhedonia were found in 99/152 (65.13%). Patients with anhedonia had notably higher PANSS negative subscores, SHAPS total score and higher level of plasma CFH than those without anhedonia (Ps<0.05). Stepwise multivariate linear regression analysis showed that increasing level of plasma CFH was a risk factor for SHAPS total score (β = 0.18, p = 0.03). Of the 99 patients with anhedonia, 74 completed the 12-week follow-up. We observed significantly reduced scores of PANSS, SHAPS and decreased plasma CFH level, when the patients completed this study. The change of SHAPS total score is positively correlated with the level of CFH decrease (p = 0.02). Our results implied that plasma CFH levels may be a biomarker for anhedonia in schizophrenia, and the effect of olanzapine on treating anhedonia is through decreasing plasma CFH levels.

An Exciting Performance of Established and Novel Biomarkers in Diagnosing Periprosthetic Joint Infections: A Single-center Retrospective Cohort Study.

Significant progress has been made in recent years in the diagnosis of periprosthetic joint infections (PJI). However, the lack of a gold standard test for the diagnosis of PJI remains a challenge.The aim of this study was to evaluate the diagnostic values of the albumin/fibrinogen ratio (AFR), the C-reactive protein/albumin ratio (CAR), and the levels of fibrinogen (FIB) and albumin (ALB) in the diagnosis of PJI. The medical records of 158 patients who had undergone hip or knee revisions from January 2018 to May 2022 were retrospectively analyzed. Of these patients, 79 were diagnosed with PJI, while 79 were diagnosed with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of C-reactive protein (CRP), ALB, and FIB; the erythrocyte sedimentation rate (ESR); and the AFR and CAR in the two groups were recorded and analyzed. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator; the diagnostic value for each indicator was calculated as the area under the curve (AUC). The ESR, CRP, FIB, and CAR values in the PJI group were significantly higher than those in the AL group, and the ALB and AFR values were significantly lower than those in the AL group (p < 0.001). The AUC values of AFR and fibrinogen were 0.851 and 0.848, respectively, which were slightly higher than those of CRP (0.826) and ESR (0.846). The AUC of CAR was 0.831 which was slightly lower than that of CRP (0.846). ALB had an AUC of 0.727. The optimal threshold, sensitivity, and specificity, respectively, were 10.05, 84.81%, and 82.28% for AFR; 4.03 μg/mL, 77.22%, and 86.08% for FIB; 0.23, 72.15%, and 82.28% for CAR; and 37.30 g/L, 65.82%, and 73.42% for ALB. AFR, CAR, and FIB are good new auxiliary diagnostic indicators of PJI, while ALB is of fair value for the diagnosis of PJI.

‘Immune-inflammatory markers & clinical characteristics for outcomes in hospitalized SARS-CoV-2 infected patients of Pakistan: a retrospective analysis’

ABSTRACTObjectiveAccumulating evidence suggests the role of immune-inflammatory markers in early risk stratification and prognostication of COVID-19 patients. We aimed to evaluate their association with severity and the development of diagnostic scores with optimal thresholds in critical patients.Setting and participantsThis retrospective case study includes hospitalized COVID-19 patients from March 2019 to March, 2022, in the developing area teaching hospital in Pakistan. Polymerase chain reaction (PCR) positive patients, n = 467 were investigated for clinical outcomes, comorbidities and disease prognosis. The plasma levels of Interleukin-6 (IL-6), Lactate dehydrogenase (LDH), C-reactive protein (CRP), Procalcitonin (PCT), ferritin and Complete blood count markers were measured.ResultsMajority were males (58.8%) and patients with comorbidities had more severe disease. Hypertension and diabetes mellitus were the commonest comorbidities. Shortness of breath, myalgia and cough were the main symptoms. The hematological markers NLR, as well as the plasma levels of immune-inflammatory variables, IL-6, LDH, Procalcitonin, Erythrocyte sedimentation rate, Ferritin were markedly raised in severe and critical patients (p < 0.0001 for these markers). ROC analysis supports IL-6 as the most accurate marker with high prognostic relevance with proposed cut-off threshold (43 pg/ml), determining >90% of patients in terms of COVID-19 severity (AUC = 0.93, 91.7%, se; 90.3%sp). Furthermore, positive correlation with all other markers including NLR with cut-off = 2.99 (AUC = 0.87, se = 89.8%, sp = 88.4%), CRP with cut-offs at 42.9 mg/l, (AUC = 0.883, se = 89.3% and sp = 78.6%), LDH cut-off at 267μg/L, evidenced in >80% patients (AUC = 0.834 se = 84% and sp = 80%). Additionally, ESR and ferritin have the corresponding AUC 0.81 and 0.813 with cut-off at 55 mm/hr and 370, respectively.ConclusionInvestigating the immune-inflammatory markers can assist physicians in providing prompt treatment and ICU admission in terms of COVID-19 severity. As a result, which may reduce the overall mortality of COVID-19 patients.

Exploring dysregulated immune response genes and endothelial dysfunction biomarkers as predictors of severe COVID-19

Identifying individuals and factors associated with severe cases of COVID-19 is crucial as the pandemic continues to spread globally. Effective biomarkers for predicting severe cases are essential for optimizing clinical management, therapy, and preventing unfavorable outcomes. This exploratory observational study aimed to investigate the expression of dysregulated immune response genes (ARG1, NOS2, ITGA4, and SELPLG) in total leukocytes, plasmatic levels of P-selectin and PSGL-1, and their clinical associations in patients with mild and severe COVID-19. Data from 117 confirmed COVID-19 patients (severe = 58, mild = 59) were collected upon admission. Gene expression was measured using RT-qPCR, and plasma protein levels assessed with ELISA assay. The severe COVID-19 patient group had a higher median age of 62.0 (p = 0.0001), a higher proportion of black individuals (86.2%, p < 0.0001), and more males (65.5%, p = 0.007). The neutrophil–lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were significantly higher in the severe COVID-19 patient group (p < 0.0001), indicating ongoing systemic inflammation. Severe COVID-19 patients also exhibited increased expression of ARG1 (p < 0.05) and SELPLG (p < 0.0001) genes, as well as higher concentrations of soluble P-selectin (p < 0.005) and PSGL-1 (p < 0.05) proteins. Multivariate analysis revealed that NLR, PLR, the expression of SELPLG and sPSGL-1 were independent predictors of COVID-19 severity. In conclusion, this study suggests that biomarkers of endothelial dysfunction and dysregulated leukocyte responses are associated with COVID-19 severity, serving as promising predictive tools for optimizing clinical management and patient monitoring.

Hepatic Health and Humoral Immunological Parameters of Common Carp (Cyprinus carpio) Fed Lactic Acid-supplemented Diets

Background: Organic acids and their salts are known as appropriate substitutes in feed for improving the health, growth, and performance of fish. Objectives: The present study was conducted to determine the effects of dietary lactic acid supplementation on immunological factors, hepatic enzyme activity, and plasma proteins in common carp, Cyprinus carpio. The fish were fed the diets mentioned above for 56 days, then their growth performance, humoral immunity, and plasma hepatic enzymes were assessed. Methods: A total of 180 fish (mean weight=25 g) were randomly distributed in twelve tanks (150 L water in each tank) as four treatments, fed diets containing 0, 2.5, 5, and 10 g/kg lactic acid (T0, T1, T2, and T3, respectively). Results: At the end of the feeding trial, T2 showed significantly higher growth performance than T0. Plasma total protein, albumin, and globulin levels of T1-T3 were significantly higher than that of T0. However, plasma protein levels decreased significantly by elevation in dietary lactic acid concentration (10 g/kg). No significant differences were observed in plasma aspartate aminotransferase (AST) and alkaline phosphatase (ALP) activity among the treatments, although alanine aminotransferase (ALT) activity decreased significantly in fish-fed dietary lactic acid supplementation (T1-T3) compared with the control group (T0). All humoral immunity parameters (lysozyme, complement, immunoglobulin, and bactericidal activity) increased significantly in T1-T3 treatments compared to the T0 group. Conclusion: Overall, dietary lactic acid supplementation improves growth performance, humoral immunological parameters, and hepatic health. According to the results, dietary lactic acid (2.5-5 g/kg) is recommended for preparing common carp feed.

Body mass index, waist circumference, insulin, and leptin plasma levels differentiate between clozapine-responsive and clozapine-resistant schizophrenia.

Between 25% and 50% of patients suffering from treatment-resistant schizophrenia fail to achieve a clinical response with clozapine. The rapid identification and treatment of this subgroup of patients represents a challenge for healthcare practice. To evaluate the relationship between metabolic alterations and the clinical response to clozapine. A multicenter, observational, case-control study was performed. Patients diagnosed with schizophrenia treated with clozapine were eligible (minimum dose 400 mg/d for at least 8 weeks and/or clozapine plasma levels ⩾ 350 µg/mL). According to the Positive and Negative Syndrome Scale (PANSS) total score, patients were classified as clozapine-responsive (CR) (<80 points) or clozapine non-responsive (CNR) (⩾80 points). Groups were compared based on demographic and treatment-related characteristics, together with body mass index (BMI), waist circumference, insulin, leptin, and C-reactive protein plasma levels. Plasma levels of clozapine and its main metabolite, nor-clozapine, were measured in all the participants. In addition, the potential relationship between PANSS scores and leptin or insulin plasma levels was assessed. A total of 46 patients were included: 25 CR and 21 CNR. BMI and waist circumference, fasting insulin and leptin plasma levels were lower in the CNR group, while C-reactive protein was not different. Moreover, significant negative correlations were observed between PANSS positive and general psychopathology subscores, on one hand, and insulin and leptin plasma levels, on the other hand, as well as between PANSS negative subscores and leptin plasma levels. Our results suggest that the lack of metabolic effect induced by clozapine is associated with the lack of clinical response.

Analysis of inflammatory protein profiles in the circulation of COVID-19 patients identifies patients with severe disease phenotypes

BackgroundThe coronavirus disease (COVID-19) caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) can present with a broad range of clinical manifestations, ranging from asymptomatic to severe multiple organ failure. The severity of the disease can vary depending on factors such as age, sex, ethnicity, and pre-existing medical conditions. Despite multiple efforts to identify reliable prognostic factors and biomarkers, the predictive capacity of these markers for clinical outcomes remains poor. Circulating proteins, which reflect the active mechanisms in an individual, can be easily measured in clinical practice and therefore may be useful as biomarkers for COVID-19 disease severity. In this study, we sought to identify protein biomarkers and endotypes for COVID-19 severity and evaluate their reproducibility in an independent cohort. MethodsWe investigated a cohort of 153 Greek patients with confirmed SARS-CoV-2 infection in which plasma protein levels were measured using the Olink Explore 1536 panel, which consists of 1472 proteins. We compared the protein profiles from severe and moderate COVID-19 patients to identify proteins associated with disease severity. To evaluate the reproducibility of our findings, we compared the protein profiles of 174 patients with comparable COVID-19 severities in a US COVID-19 cohort to identify proteins consistently correlated with COVID-19 severity in both groups. ResultsWe identified 218 differentially regulated proteins associated with severity, 20 proteins were also replicated in an external cohort which we used for validation. Moreover, we performed unsupervised clustering of patients based on 97 proteins with the highest log2 fold changes in order to identify COVID-19 endotypes. Clustering of patients based on differentially regulated proteins revealed the presence of three clinical endotypes. While endotypes 2 and 3 were enriched for severe COVID-19 patients, endotypes 3 represented the most severe form of the disease. ConclusionsThese results suggest that identified circulating proteins may be useful for identifying COVID-19 patients with worse outcomes, and this potential utility may extend to other populations. Trial registrationNCT04357366.