Serum Profiles Research Articles

Proteomic Profiling of COVID-19 Patients Sera: Differential Expression with Varying Disease Stage and Potential Biomarkers

Background/Objectives: SARS-CoV-2 is one of the viruses that caused worldwide health issues. This effect is mainly due to the wide range of disease prognoses it can cause. The aim of this study is to determine protein profiles that can be used as potential biomarkers for patients’ stratification, as well as potential targets for drug development. Methods: Eighty peripheral blood samples were collected from heathy as well as SARS-CoV-2 patients admitted at a major tertiary care center in Riyadh, Saudi Arabia. A label-free quantitative mass spectrometry-based proteomic analysis was conducted on the extracted sera. Protein–protein interactions and functional annotations of identified proteins were performed using the STRING. Results: In total, two-hundred-eighty-eight proteins were dysregulated among all four categories. Dysregulated proteins were mainly involved in the network map of SARS-CoV-2, immune responses, complement activation, and lipid transport. Compared to healthy subjects, the most common upregulated protein in all three categories were CRP, LGALS3BP, SAA2, as well as others involved in SARS-CoV-2 pathways such as ZAP70 and IGLL1. Notably, we found fifteen proteins that significantly discriminate between healthy/recovered subjects and moderate/under medication patients, among which are the SERPINA7, HSPD1 and TTC41P proteins. These proteins were also significantly downregulated in under medication versus moderate patients. Conclusions: Our results emphasize the possible association of specific proteins with the SARS-CoV-2 pathogenesis and their potential use as disease biomarkers and drug targets. Our study also gave insights about specific proteins that are likely increased upon infection but are likely restored post recovery.

Effect of black soldier fly (Hermetia illucens) larvae meal and oil on the performance, biochemical profile, intestinal health and gut microbial dynamics in laying hens

This study investigated the effect of incorporating black soldier fly (BSF) larvae meal and oil on laying hens' performance, egg quality, serum profile, intestinal structure, and gut health. A total of 378 Lohmann laying hens (age 48 wk) were randomly assigned to 6 treatments with 3 replicates of 21 hens each. Following 7 d acclimation, the trail was conducted for 8 weeks. The dietary groups include: basal corn-soybean meal diet (S) without BSF (BSO) oil (S+BSO 0), S with BSF oil (S+BSO 100), BSF meal (9 %) without BSF oil (BSF 9+BSO 0), BSF meal (9 %) with BSF oil (BSF 9+BSO 100), BSF meal (18 %) without BSF oil (BSF 18+BSO 0), and BSF meal (18 %) with BSF oil (BSF 18+BSO 100). The results showed that the BSF 18 + BSO 100 diet significantly reduced egg weight (P < 0.001) compared to other dietary treatments. The addition of BSF meal reduced feed intake (P < 0.001) and the Haugh units (P < 0.05) in hens fed 18 % BSF meal with and without BSO. The jejunum villus area, crypt depth, and intestinal wall thickness increased with the increase in the inclusion of BSF larvae meal (P < 0.001). The ileum villus height, crypt depth and intestinal wall thickness increased (P < 0.001) at 9 % BSF meal and then decreased at 18 % BSF meal with and without BSF oil. The bacteria genera Ruminococcus, Clostridiales, Bacteroidales, Ruminococcus torques, and Intestinimonas were positively associated with the dietary treatments, while Prevotellaceae UCG-001, Clostridium, and Faecalibacterium were negatively associated with the dietary treatments. The inclusion of BSF meal and oil enriched the functional network of several pathways, including ascorbate and aldarate metabolism, D-arginine and D-ornithine metabolism, and fatty acid metabolism, highlighting the positive effects of BSF larvae meal and oil on the chicken gut microbiota. In conclusion, BSF meal at 9 % with BSF oil and BSF meal at 18 % without BSF oil can be incorporated into the diet without impairing the performance and gut health of laying hens.

Changes in the serum proteome profile of patients with neuroborreliosis, foresters, and patients treated according to ILADS method

ObjectivesThe aim of study was to evaluate the changes in proteomic profile of human serum induced by the development of tick-borne neuroborreliosis (NB), before/after therapy, patients treated with prolonged multidrug therapy according to ILADS (International Lyme and Associated Diseases Society), and foresters frequently exposed to tick bites. MethodsA proteomics approach was used to analyze the expression of proteins in serum of patients and sex/age-matched healthy donors. The analysis was performed using SDS-PAGE/LC-MS/MS (Q-Exactive OrbiTrap mass spectrometer). ResultsObtained results indicated changes in the serum proteome of patients with NB putting attention to the proteins involved mainly in calcium transport/metabolism and signaling molecules that differ patients before and after classic therapy. Moreover, ILADS treated patients have different protein distribution than patients from other groups, what is the consequence of prolonged antibiotic therapy. In the case of foresters, the most important result is the increased β-secretase level. ConclusionsObtained results may contribute to a better understanding of the mechanism of the development of tick-borne diseases, as well as will allow create new opportunities for its rapid and more effective therapy. However, further studies, on larger patients groups, are needed to apply them in clinical practice.

The stem and progenitor cells and the functional activity of liver from age-different Wistar rats

The liver has a big potential for self-healing, but the activity of regeneration decreases with age. Changes are occurring, including in the functional activity of various liver cell populations, the study of the characteristics of which can become the basis for the development of new therapeutic approaches to the liver diseases treatment at older people. The aim of this research was to study the level of stem and progenitor cells and the functional activity of the healthy liver from age- different rats. Material and methods. Experiments were carried out on Wistar rats aged 6 and 12 months. Ultrasound and histological examination of the liver from rats was used to assess morphological changes. The lipid profile of blood serum was evaluated by biochemical methods. Cytometric methods were used to study the surface and intracellular antigens of stem and progenitor cells isolated from the bone marrow, arterial blood and liver of rats. Results and discussion. In 12-month-old male Wistar rats, compared with 6-month-old rats, excessive formation of extracellular matrix components, disruption of tissue architecture, development of portal hypertension, as well as an increase in the concentration of cholesterol, triglycerides, high- and low-density lipoproteins were revealed. We identified age- related differences in the content of hematopoietic and mesenchymal stem cells, epithelial cells (CD45–CD326+) in the bone marrow, blood and liver of rats. In the liver parenchyma, the populations of hepatocyte precursors (CD45– CD326+CD133+), oval cells (CD45–CD326+CD133+CD90+). At the same time, the level of all cell populations in the liver parenchyma of rats expressing the intracellular marker Sox9 was higher in one-year-old animals compared to younger ones, regardless of the cell phenotype. Conclusions. In the liver of 12-month-old rats, compared to 6-month-old rats, the number of cells expressing Sox9, lymphocytes with an inflammatory phenotype increases, the number of stem cells and various populations of epithelial and endothelial cells decreases, which leads to a decrease in the regenerative capacity of the liver, disruption of the tissue architecture of the organ and changes in lipid metabolism. These changes largely determine the increased susceptibility with age to the development of chronic liver diseases.

Short-Term Zinc Supplementation Stimulates Visceral Adipose Catabolism and Inflammation in Mice

Background: Zinc (Zn), a fundamental trace element in human biology, exhibits pivotal roles in sustaining vital physiological processes and regulating metabolic homeostasis. Insufficient zinc intake has been linked to deleterious consequences on growth, reproductive functions, metabolic activities, and immune responses in both humans and animals. Oral zinc supplementation is usually performed to meet zinc requirement. Previous studies have shown that long-term supplementation of zinc in mice impaired AKT signaling and induced adipocyte hypertrophy in visceral adipose tissue. Methods: The presented study was conducted to investigate the role and mechanism of short-term zinc supplementation on lipids metabolism. Zinc sulfate was supplemented in the drinking water of C57/BL6J male mice at 30 ppm or 90 ppm for one week. Water consumption, food intake, and body weight were analyzed, adipose tissue and serum profile of metabolites were investigated, and the key genes related to lipid metabolism were analyzed. Results: Short-term zinc supplementation decreased visceral adipose tissue weight and adipocyte size compared to the control group, but no difference was observed in food intake, water consumption, and body weight between the two groups. Further studies revealed that short-term zinc supplementation significantly increased the serum insulin level while decreasing the serum NEFA content. In addition, zinc supplementation increased the expression of Atgl and Hsl in the visceral adipose tissue compared with the control mice. Furthermore, the phosphorylation level of HSL and protein level of PPARg in the epididymal adipose tissue increased by zinc supplementation compared with the control mice. In comparison, the protein level of FASN was down-regulated by short-term zinc supplementation in the epididymal adipose tissue, although the expression of lipogenic genes was not changed. The expression of F4/80 and Tnfa were increased in zinc-supplemented adipose tissue as compared with the control group. Conclusions: Our findings suggest that short-term zinc supplementation might reduce fat deposition by enhancing lipolysis in mice. Future studies could focus on the effect of intermittent zinc supplementation on fat reduction in both animal models and humans.

Comparative analysis of compartment-specific immunothrombotic biomarker profiles in bronchoalveolar lavage fluid and serum of patients with pneumonia-related acute respiratory distress syndrome: A preliminary cross-sectional study.

Immunothrombosis has emerged as a potential mechanistic link underlying the development and progression of acute respiratory distress syndrome (ARDS), but understanding its specific profile in patients, both locally and systemically, is limited. The objective of this study was to characterize and compare the immunothrombotic signatures in patients diagnosed with pneumonia-related ARDS (p-ARDS) at both the pulmonary and systemic levels and to evaluate their clinical relevance. The study included 23 consecutive patients diagnosed with p-ARDS admitted to the intensive care unit at a tertiary university hospital from July 2022 to May 2023, alongside 40 concurrently hospitalized patients with common pneumonia as controls. Paired bronchoalveolar lavage fluid (BALF) and serum samples were collected from the participants for the analysis of 15 biomarkers to assess and quantify the pulmonary and systemic immunothrombotic signatures. The study results revealed significant pulmonary inflammation and systemic endothelial injury in p-ARDS patients compared to pneumonia controls. These observations were maintained after adjustment for severity of illness (Acute Physiology and Chronic Health Evaluation II scores). In terms of clinical relevance, inflammatory biomarkers (interleukin [IL]-6, IL-8) in BALF were found to correlate with PaO2/FiO2 ratio, while serum levels of a disintegrin and metalloproteinase with thrombospondin type 1 motif 13 (ADAMTS-13) and thrombomodulin showed associations with Sequential Organ Failure Assessment and Disseminated Intravascular Coagulation scores. In conclusion, this preliminary investigation identified compartment-specific variations in the immunothrombotic signature between patients with p-ARDS and those with pneumonia alone, with inflammatory responses predominantly localized in the alveolar compartments and coagulation/endothelial injury biomarkers more pronounced in peripheral blood.

Blood cytokines in children with erosive gastritis

Aim: To evaluate the cytokine profile of blood serum in children with erosive gastritis depending on the activity of the inflammatory process, bacterial invasion of H. pylori and family predisposition to peptic ulcer disease. Gastroscopy was performed with the collection of biopsy material from the gastric mucosa in 168 children aged 7-17 years with gastroenterological complaints. Subsequently, a morphological examination of biopsy specimens confirmed the diagnosis of gastritis in all examined patients and determined H. pylori invasion. The content of cytokines in the blood serum (IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IL-1β, IFNα, TNFα) was determined using the enzyme immunoassay method. When analyzing cytokine levels in schoolchildren infected with H. pylori, there were no differences in cytokine concentrations (p 0.05). While in uninfected children in the presence of erosive changes, a decrease in IL-2 content was noted (p = 0.026). In individuals with a family history of peptic ulcer disease with erosive gastritis, an increase in the content of IL-8 was observed (p = 0.006), which is known to play an important role in maintaining innate immunity. Whereas, in the absence of a family predisposition, schoolchildren with erosive gastritis showed a decrease in IL-2 (p = 0.027), which is similar to the level of IL-2 in schoolchildren with erosive gastritis without H. pylori infection. IL-2 is considered an activator of the antitumor response and this property is being actively studied in patients with gastric cancer. In the context of these data, it can be assumed that in individuals with erosive gastritis, even without a family predisposition and H. pylori infection, inhibition of IL-2 synthesis is observed. What causes this influence is an open question. Thus, the variety of components of the cytokine profile involved in the regulation of the inflammatory process and the influencing negative factors create difficulties in assessing and, even more so, predicting the role and significance of changes in the content of a particular cytokine in the blood serum in children with erosive gastritis.

Lipidomic profiling of serum and liver tissue reveals hepatoprotective mechanism of taxifolin in rats with CCl4-induced subacute hepatic injury based on LC-MS/MS

Currently, the hepatoprotective activity of taxifolin, a flavonoid isolated from Pseudotsuga taxifolia, has been reported in many animal models. However, whether the protective effect of taxifolin on the liver is related to its effect on lipidomics is unclear. Based on the significant therapeutic effect of taxifolin on CCl4 induced subacute hepatic injury, we observed the intervention of taxifolin by lipidomics. The results demonstrate that taxifolin can effectively reverse the damage caused by CCl4, which including hepatocyte vacuolization and necrosis. Lipomic profiling based on liquid chromatography-mass spectrometry showed that taxifolin was able to restore lipidomic changes caused by CCl4, including the levels of lysophosphatidylserine (LPS), phosphatidylcholine (PC), coenzyme (Co), phosphatidylglyceride (PG), phosphatidylserine (PS), dimethylphosphatidylethanolamine (dMePE), ceramide (Cer), sphingosine (So), triglycerides (TG), and monogalactosyl diacylglycerol (MGDG) in the rat liver, and phosphatidylcarbinol (PMe) and phosphatidylethanolamine (PE), plant sphingosine (phSM), glucose ceramide (CerG1), TG, and diglycerides (DG) in serum. Spearman's correlation analysis showed that CerG1, phSM, PE, and PMe in serum, and Cer, dMePE, PG, PS, So, TG, and MGDG in liver were positively correlated with serum levels of aspartate transaminase, alanine transaminase, and liver index; while TG, DG in serum, and Co, LPS, PC in liver were negatively correlated with the parameters. In total, 43 and 34 lipid molecules were altered by taxifolin treatment in the liver and serum, respectively, mainly including glycerophosphoglycerols, glycerophosphocholines, glycerophosphoethanolamines, and linoleic acids and derivatives. Our findings help to provide novel insights into the mechanism of the hepatoprotective effect of taxifolin from a lipidomics approach.

Serum Level of Cadherin-P (CDH3) Is a Novel Predictor of Cardiovascular Events Related to Atherosclerosis in a 3-Year Follow-Up Study

Background: Placental cadherin (CDH3) is an adhesion molecule expressed in many malignant tumors. The role of serum CDH3 in atherosclerosis is unclear. Methods: This 3-year follow-up study measured atherosclerosis and serum CDH3 in 218 angiography inpatients. Coronary stenosis was assessed as the Gensini score. The brachiocephalic and femoral plaques were quantified by ultrasound. Microarray serum profiling was conducted in selected samples. CDH3 in the serum was measured using an indirect ELISA. The odds ratio (OR), ROC analysis, and logistic regressions were used to evaluate the associations between CDH3 content, atherosclerotic lesions, and various serum biomarkers. Results: Serum CDH3 was associated with the severity of atherosclerosis and diastolic blood pressure. The levels of CDH3 were able to discriminate patients with total subclinical and hemodynamically significant atherosclerotic lesions in all circulation pools (coronary, brachiocephalic, and femoral). Elevated serum CDH3 appeared to be a risk factor for cardiovascular outcomes after 3-year follow up with OR = 1.81 (95% CI: 1.07–3.72; p = 0.022). Endothelin-1 and NOx were associated with the content of CDH3 in the serum, suggesting the involvement of certain signal transduction pathways that may participate in plaque formation. Conclusions: CDH3 was associated with cardiovascular outcomes adjusted for coronary plaque presence, indicating a role of CDH3 in plaque biology.

Contemporaneous Inflammatory, Angiogenic, Fibrogenic, and Angiostatic Cytokine Profiles of the Time-to-Tumor Development by Cancer Cells to Orchestrate Tumor Neovascularization, Progression, and Metastasis.

Cytokines can promote various cancer processes, such as angiogenesis, epithelial to mesenchymal transition (EMT), invasion, and tumor progression, and maintain cancer stem-cell-like (CSCs) cells. The mechanism(s) that continuously promote(s) tumors to progress in the TME still need(s) to be investigated. The data in the present study analyzed the inflammatory, angiogenic, fibrogenic, and angiostatic cytokine profiles in the host serum during tumor development in a mouse model of human pancreatic cancer. Pancreatic MiaPaCa-2-eGFP cancer cells were subcutaneously implanted in RAG2xCγ double mutant mice. Blood samples were collected before cancer cell implantation and every week until the end point of the study. The extracted serum from the blood of each mouse at different time points during tumor development was analyzed using a Bio-Plex microarray analysis and a Bio-Plex 200 system for proinflammatory (IL-1β, IL-10, IFN-γ, and TNF-α) and angiogenic and fibrogenic (IL-15, IL-18, basic FGF, LIF, M-CSF, MIG, MIP-2, PDGF-BB, and VEGF) cytokines. Here, we find that during cancer cell colonization for tumor development, host angiogenic, fibrogenic, and proinflammatory cytokine profiling in the tumor-bearing mice has been shown to significantly reduce host angiostatic and proinflammatory cytokines that restrain tumor development and increase those for tumor growth. The proinflammatory cytokines IL-15, IL-18, and IL-1β profiles reveal a significant host serum increase after day 35 when the tumor began to progress in growth. In contrast, the angiostatic cytokine profiles of TNFα, MIG, M-CSF, IL-10, and IFNγ in the host serum revealed a dramatic and significant decrease after day 5 post-implantation of cancer cells. OP treatment of tumor-bearing mice on day 35 maintained high levels of angiostatic and fibrogenic cytokines. The data suggest an entirely new regulation by cancer cells for tumor development. The findings identify for the first time how pancreatic cancer cells use host cytokine profiling to orchestrate the initiation of tumor development.

Evaluation of the Anti-Inflammatory/Immunomodulatory Effect of Teucrium montanum L. Extract in Collagen-Induced Arthritis in Rats.

The anti-inflammatory/immunomodulatory effects of Teucrium montanum L. (TM), a plant distributed in the Mediterranean region, have been insufficiently examined. The effects of the TM ethanol extract were tested in a rat collagen-induced arthritis (CIA) model of rheumatoid arthritis. LC-MS was used for the phytochemical analysis of the TM extract. Dark Agouti rats were immunized with bovine type II collagen (CII) in incomplete Freund's adjuvant for CIA, and treated with 100 or 200 mg/kg of TM extract daily via oral administration. Clinical and histopathological evaluations and a flow cytometric analysis of the phenotypic and functional characteristics of splenocytes and draining lymph node cells were performed. The cytokines in the paw tissue culture supernatants and anti-CII antibodies in serum were determined by ELISA. The TM extract, with the dominant components verbascoside and luteolin 7-O-rutinoside, reduced the arthritic score and ankle joint inflammation in CIA rats, promoted the antioxidant profile in serum, and lowered pro-inflammatory TNF-α, IL-6 and IL-1β production. It suppressed the activation status of CD11b+ cells by lowering CD86, MHCII and TLR-4 expression, and promoted the Th17/T regulatory cell (Tregs) balance towards Tregs. A lower frequency of B cells was accompanied by a lower level of anti-CII antibodies in treated rats. These findings imply the favorable effect of TM extract on the clinical presentation of CIA, suggesting its anti-inflammatory/immunomodulatory action and potential therapeutic effect.

Nucleotide sequence variants, gene expression and serum profile of immune and antioxidant markers associated with bacterial diarrhea susceptibility in Barki lambs

BackgroundDespite the fact that diarrhea is more accurately described as a clinical symptom than a disease. Diarrhea is one of the most important issues in ovine medicine, particularly in lambs, and because of high morbidity and mortality rate, sluggish growth performance, and veterinary costs, it is believed to be a major source of economic loss. Salmonella and enterotoxigenic Escherichia coli are the most common and commercially significant agents responsible for diarrhea.ObjectiveThe objective of this study was to monitor the nucleotide sequence variations, gene expression, serum inflammatory and oxidative stress biomarkers in diarrheic lambs. Another aim was to identify different pathotypes and virulence genes of Salmonella and E. coli causing diarrhea.MethodologyBlood samples were taken from 50 Barki who were diarrheal and 50 who appeared to be healthy, and then divided in 3 portions, with EDTA added to the first part for CBC, DNA and RNA extraction. The second sample received 5000 I.U. of heparin calcium, and a clean plain tube was used for the third component. The second and third sections were centrifuged to extract serum and plasma until the biochemical and immunological analysis was completed. Fecal samples were collected for bacteriological examination, and the bacteria were identified by PCR analysis. PCR-DNA sequencing was conducted for immune (SELL, JAK2, SLC11A1, IL10, FEZF1, NCF4, LITAF, SBD2, NFKB, TNF-α, IL1B, IL6, LGALS, and CATH1), antioxidant (SOD1, CAT, GPX1, GST, Nrf2, Keap1, HMOX1, and NQO1), and GIT health (CALB1, GT, and MUC2) genes in healthy and diarrheic lambs.ResultsVirulent genetic markers of pathogenic characteristics of E. coli (astA, Vt2e (Stx2e), CFA/I, groES and luxS) and Salmonella (invA, SopB, bcfC and avrA) were detected in all diarrheic lambs. PCR-DNA sequencing of immune, antioxidant and intestinal health genes found eleven single nucleotide polymorphisms (SNPs) linked to either diarrhea resistance or susceptibility in Barki lambs. Transcript levels of immune, antioxidant, and GIT health (CALB1, GT, and MUC2) genes varied between healthy and diarrheic lambs. Nucleotide sequence variation of the genes under inquiry between reference sequences in GenBank and those of the animals under investigation verified all identified SNPs. Significant (P = 0.001) erythrocytosis, neutrophilic leukocytosis, with lymphocytopenia were observed in diarrheic lambs. Significant (P = 0.001) increases in serum IL-1α, IL-1β, IL-6, TNF-α (90.5 ± 1.7, 101.8 ± 1.7, 72.3 ± 6.6, 71.26 ± 4.89 Pg/ml, respectively), serum Fb, Cp, Hp, SAA (230.7 ± 12.4 mg/dl, 6.5 ± 0.07 mg/dl, 2.5 ± 0.09 g/dl, 7.4 ± 0.4 mg/L, respectively), free radicals (MDA, NO), cortisol (6.91 ± 0.18 μg/dl) and growth hormone, with significant (P = 0.001) decreases in serum IL-10 (81.71 ± 1.05 Pg/ml), antioxidants (CAT, GPx), insulin, triiodothyronine (T3) and thyroxine (T4) in diarrheic lambs.ConclusionsThe study's findings provided credence to the theory that marker-assisted selection (MAS) could be used to predict and prevent diarrhea in Barki sheep by selecting lambs based on SNPs in genes linked to inflammation, antioxidants, and intestinal health. In order to establish an efficient management protocol and determine the most susceptible risk period for disease occurrence, gene expression profiles of the genes under investigation, pro-inflammatory cytokines and acute phase proteins may also be utilized as proxy biomarkers for lamb enteritis.

Unique Gut Microbiome and Metabolic Profiles in Chinese Workers Exposed to Dust: Insights from a Case-Control Study.

This study aimed to identify distinct gut microbiome and serum metabolic features in workers exposed to dust compared to healthy controls. A case-control study was conducted with dust-exposed workers without silicosis and age-matched healthy controls. Gut microbiome composition was analyzed using 16S rRNA sequencing, and serum and fecal metabolomic profiles were assessed by LC-MS. Dust-exposed workers showed higher levels of Blautia and Trichoderma and lower levels of Anaplasma, Aspergillus, Plasmodiophoromycetes, and Escherichia coli-Shigella. Metabolites such as indole-3-acetate and gentamicin C1a were downregulated, while adenine, 2-phenylacetamide, and 4-pyridoxic acid were upregulated. Blautia spp. were linked to altered metabolites in dust-exposed workers, suggesting microbiome-metabolite interactions that may affect silicosis progression. However, the small sample size and cross-sectional design limit generalizability, and further longitudinal studies are needed.

Exploring the protective role of green tea extract against cardiovascular alterations induced by chronic REM sleep deprivation via modulation of inflammation and oxidative stress

BackgroundChronic Rapid eye movement (REM) sleep deprivation has been associated with various cardiovascular alterations, including disruptions in antioxidant defense mechanisms, lipid metabolism, and inflammatory responses. This study investigates the therapeutic potential of green tea extract (GTE) in mitigating these adverse effects.MethodsA total of 24 male Wistar albino rats were used in this study and divided into the control group (n = 8), Chronic-REM Sleep Deprivation (CRSD) Group (n = 8) and Chronic-REM SD + Green Tea 200 (CRSD + GTE200) Group (n = 8). After 21 days, a comprehensive analysis of paraoxonase (PON1), arylesterase (ARE), malondialdehyde (MDA), glutathione (GSH), nitric oxide (NOx), proinflammatory cytokines, and lipid profiles in aortic tissue, heart tissue, and serum was conducted in a sleep-deprived rat model.ResultsChronic REM sleep deprivation led to a significant reduction in PON1 and ARE levels in aortic (p = 0.046, p = 0.035 respectively) and heart tissues (p = 0.020, p = 0.019 respectively), indicative of compromised antioxidant defenses. MDA levels increased, and NOx levels decreased, suggesting oxidative stress and impaired vascular function. Lipid profile alterations, including increased triglycerides and total cholesterol, were observed in serum. Elevated levels of inflammatory cytokines (IL-6 and TNF-alpha) further indicated an inflammatory response (p = 0.007, p = 0.018 respectively). GTE administration demonstrated a protective role, restoring antioxidant enzyme levels, suppressing lipid peroxidation, and improving NOx levels.ConclusionThese findings suggest the therapeutic potential of GTE in alleviating the cardiovascular impairments of chronic REM sleep deprivation, emphasizing its candidacy for further clinical exploration as a natural intervention in sleep-related disorders and associated cardiovascular risks.

Serum Biochemical Profile, Intestinal and Liver Histomorphometry of Captive Broad-Snouted Caiman (Caiman latirostris) Fed With a Diet Enriched With Soybean (Glycine max).

The impact of plant-based diets on crocodilians is unclear. Serum profiles and histomorphometry provide valuable insights into their nutritional and physiological status. This study aims to elucidate the impact of three levels of soybean meal substitution combined chicken by-product minced on the growth and health of broad-snouted caiman (Caiman latirostris). The research assesses the effects of diets supplemented with soybean meal on the blood biochemical profile, intestinal histomorphometry, and hepatic parameters of C. latirostris, providing essential information for understanding on the implications of dietary changes in this species. Forty-eight 6-month-old broad-snouted caimans were assigned to three dietary groups (0%, 25%, 40% soybean meal). Over a period of 90 days, data on growth, food consumption, serum biochemical analysis, intestinal and hepatic morphometry were recorded. The results showed that diets containing higher levels of soybean meal did not significantly affect growth, feed intake or serum profiles of total protein, albumin and cholesterol. However, changes in intestinal morphology were observed, with longer and wider villi in the animals feed with diets with soybean meal, indicating a gradual adaptation to new feeding diets. The presence of soybean meal reduced serum glucose and triglyceride profiles and hepatic lipid accumulation without affecting macronutrient digestion and absorption, considered beneficial for the caiman's health. This study provides valuable insights into the inclusion of soybean meal in the diet of Caiman latirostris and its effects on the intestines, liver, and physiology. It also highlights the importance of considering nutritional management as a key tool in improving the well-being and health of crocodilians in captivity.

Synergistic Benefits of Dietary Silymarin and Selenium on Growth, Immune Functions, Antioxidants, and Gut/Liver Health of Thinlip Mullet (Liza ramada) Juveniles

Abstract This study investigates the synergistic impact of silymarin (SI) levels combined with inorganic selenium (sodium selenite: Se) on growth, feed utilization, biochemical parameters, antioxidants, innate immunity, intestinal and liver histology, and gene expression of thinlip mullet (Liza ramada) juveniles. The experimental design involved thinlip mullets initially weighing 3.5±0.13 g, distributed in a completely randomized design with 30 fish per hapa (0.5 × 0.5 × 1 m), and conducted in triplicate over 60 days. Seven experimental diets were employed, including a control (without SI and Se supplementation), a negative control (with only Se supplementation), and four treatments with varying levels of silymarin (250, 450, 650, 850 mg/kg) alongside selenium (0.5 mg/kg diet). The growth performance results highlighted significant enhancements in final body weight, weight gain, and specific growth rate, particularly in the SI 850 mg/kg + Se treatment. Survival rates, feed intake, and feed conversion ratios showed positive trends across the SI-Se supplemented groups. Biochemical profiles of serum exhibited that the control diet induced elevated concentrations of glucose, cholesterol, alanine aminotransferase, aspartate aminotransferase, and urea, while Se or SI supplementation significantly mitigated these levels, with the lowest concentrations observed in the SI-Se supplemented groups. Moreover, SI supplementation increased serum protein content. Antioxidant enzyme activities, represented by superoxide dismutase (SOD), catalase (CAT), and catalase (GPx), demonstrated notable improvements in the SI-Se fortified groups, with significantly elevated GPx activity compared to the Se-supplemented and control groups. Immune system responses, including lysozyme, bactericidal, nitro-blue tetrazolium (NBT%), and serum alternative complement pathway (ACH50) activities, were highest in the SI-Se augmented groups. SI and Se in L. ramada reduce liver pro-inflammatory gene expression (IL-1 β, hepcidin) vs. control group. Histological examinations of the intestine and liver depicted structural enhancements, especially at moderate and high levels of SI with Se supplementation. The results indicate improved intestinal villi morphology and hepatic architecture, supporting the positive influence of dietary treatments on the health of thinlip mullet juveniles. In conclusion, the combined supplementation of SI at 850 mg/kg diet and Se at 0.5 mg/kg diet positively influenced the growth, biochemical profiles, antioxidant status, immune responses, gene expression, and histological integrity of thinlip mullet juveniles, providing valuable insights for optimizing aquafeed formulations.

Impact of triflumezopyrim (insecticide) on blood and serum biochemistry of freshwater fish, subadult Labeo rohita (Hamilton, 1822)

The impact of insecticides on water bodies can be evaluated by studying the physiology and health of fish. These chemicals pose a significant and direct risk to aquatic ecosystems and hence aquatic animals like fish. Therefore, this study was designed to investigate the toxic effects of sub-lethal concentrations of triflumezopyrim, a novel synthetic insecticide commonly used in crop protection, on the biochemical and hematological parameters of freshwater sub-adult Labeo rohita L. Here, fish were subjected to sub-lethal doses of triflumezopyrim at various concentrations (1.41 ppm, 3.27 ppm, and 4.97 ppm) for 21 days. In addition, fish were grown in an insecticide-free control group to determine the toxic effects of the insecticides. The obtained data on various biochemical and hematological parameters of the fish were analyzed using state-of-the-art statistics. Our findings suggest that triflumezopyrim exposure has a significant effect on blood variables. However, variable response, such as mean corpuscular volume, hemoglobin concentration, neutrophils, and eosinophils were unaffected by insecticide treatment, regardless of the dose. Our interhematological parameter analysis revealed varying interrelationships at various insecticide doses. Similarly, triflumezopyrim exposure significantly affected the response of serum biomarker profiles i.e., the difference in mean treatment pairs (control and three doses of triflumezopyrim) had a significant effect on the response of most serum profile parameters.

Biomarker Profiles in Serum and CSF for Early Diagnosis of Selected Neurodegenerative Diseases

Biomarker research and justification for neurodegenerative illnesses have seen enormous efforts over the last ten years. Bio-fluid-based biomarkers have been believed to provide a better and easier approach to detecting biomarkers for diagnosing nervous system pathologies. Objectives: To evaluate the diagnostic potential of certain biomarkers in serum and cerebrospinal fluid to diagnose Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease at an initial stage. Methods: 280 participants were taken and distributed into four groups, comprising, 70 patients with early-stage Alzheimer’s disease, 70 with early-stage Parkinson’s disease, 70 with early-stage Huntington’s disease, and 70 age-matched healthy controls. Blood and cerebrospinal fluid samples were drawn and medical history was taken from the patients. Serum and cerebrospinal fluid levels of amyloid-beta (Aβ42), total tau (t-tau), phosphorylated tau (p-tau), alpha-synuclein, huntingtin protein, and neuro-filament light chain were evaluated using enzyme-linked immunosorbent assays. Results: Alzheimer’s disease patients showed reduced serum Aβ42 (80.4 ± 15.6 pg/mL) and elevated t-tau (140.5 ± 18.2 pg/mL). Parkinson’s disease patients had raised serum alpha-synuclein (12.5 ± 2.3 ng/mL) and neuro-filament light chain. Huntington’s disease patients showed significant increases in serum huntingtin protein (8.2 ± 2.0 ng/mL). These profiles indicate efficacy in early diagnosis. Conclusions: It was concluded that Aβ42 and tau effectively detect Alzheimer’s disease, while Parkinson’s disease patients can be effectively diagnosed with Serum and cerebrospinal fluid levels of the neuro-filament light chain. Similarly, huntingtin protein and neuro-filament light chain are sensitive enough to detect Huntington’s disease at its early stages.

Potential of CME@ZIF-8 MOF Nanoformulation: Smart Delivery of Silymarin for Enhanced Performance and Mechanism in Albino Rats.

Silymarin, an antioxidant, is locally used for kidney and heart ailments. However, its limited water solubility and less oral bioavailability limit its therapeutic efficiency. The present study investigated the enhancement of solubility and bioavailability of silymarin by loading it in Cordia myxa plant extract-coated zeolitic imidazole framework (CME@ZIF-8) against carbon tetrachloride (CCl4)-induced nephrotoxicity and cardiac toxicity in albino rats. The synthesized PEG-coated silymarin drug-loaded CME@ZIF-8 MOFs (PEG-Sily@CME@ZIF-8) were characterized by scanning electron microscopy, transmission electron microscopy, high-resolution transmission electron microscopy, energy dispersive X-ray spectroscopy, UV-visible spectroscopy, X-ray diffraction, Fourier transform infrared spectroscopy, thermogravimetric analysis, and zeta potential. The average crystal size of CME@ZIF-8 and PEG-Sily@CME@ZIF-8 was 12.69 and 16.81 nm, respectively. The silymarin drug loading percentage in PEG-Sily@CME@ZIF-8 was 33.05% (w/w). In the animal model with CCl4 treatment, different parameters like serum profile, enzymatic level, genotoxicity, and histopathology were assessed. Treatment with PEG-Sily@CME@ZIF-8 with different doses of 500, 1000, and 1500 μg/kg body weight efficiently ameliorated the alterations in the antioxidant defenses, biochemical parameters, and histopathological alterations and DNA damage in comparison to silymarin drug in a CCl4-induced toxicity rat model via alleviating the cellular abnormalities and attenuation of normal antioxidant enzymes levels. Moreover, the molecular mechanism of drug-silymarin interaction with the target protein was investigated. It involves the binding pockets of silymarin molecules with VEGFR, TNF-α, NLRP3, AT1R, NOX1, RIPK1, Caspase-3, CHOP, and MMP-9 proteins, elucidating the silymarin-protein interactions by the formation of hydrogen bonds and hydrophobic interactions. This study suggests that the nanodrug PEG-Sily@CME@ZIF-8 MOFs protect the kidneys and heart possibly by mitigating oxidative stress more efficiently than the conventional drug silymarin.

Biochemical Modulators of Tight Junctions (TJs): Occludin, Claudin-2 and Zonulin as Biomarkers of Intestinal Barrier Leakage in the Diagnosis and Assessment of Inflammatory Bowel Disease Progression.

Considering the increasing worldwide prevalence of inflammatory bowel disease (IBD), the early diagnosis of this disease is extremely important. However, non-invasive diagnostic methods remain limited, while invasive techniques are the most commonly used in daily practice. Therefore, there is a serious need to find new non-invasive biomarkers of IBD. The serum profiles of occludin, claudin-2, and zonulin were assessed in IBD patients using the ELISA method. The levels of the analyzed biomarkers were measured before and after a year of anti-inflammatory treatment, which was a tumor necrosis factor α (TNF-α) inhibitor (adalimumab) in patients with ulcerative colitis (UC) and conventional therapy in patients with Crohn's disease (CD). In IBD patients, the serum level of occludin (p < 0.001) decreased compared to healthy individuals, while the level of claudin-2 (p < 0.001) increased. Additionally, zonulin (p < 0.01) concentration increased in CD patients compared to the control group. The highest diagnostic ability was presented by occludin measurements with the area under the curve (AUC) of 0.959 (95% CI 0.907-1) in UC and 0.948 (95% CI 0.879-1) in CD. Claudin-2 also demonstrated very good ability in diagnosing UC and CD with AUC values of 0.864 (95% CI 0.776-0.952) and 0.896 (95% CI 0.792-0.999), respectively. The ability of zonulin to diagnose CD was estimated as good with an AUC of 0.74 (95% CI 0.598-0.881). Moreover, a significant correlation was identified between C-reactive protein (CRP), claudin-2 (r = -0.37; p < 0.05), and zonulin (r = -0.44; p < 0.05) in UC patients. Treatment with adalimumab improved the level of occludin, claudin-2, and zonulin in UC patients, while anti-inflammatory conventional therapy decreased the concentration of zonulin in CD. Occludin and claudin-2 measurements present significant utility in diagnosing both UC and CD, while zonulin assessments may be useful in CD diagnosis. Additionally, claudin-2 and zonulin measurements may be helpful in evaluating the intensity of the inflammatory process. Anti-TNF-α treatment improved the value of occludin, claudin-2, and zonulin, indicating its beneficial effect on the integrity of tight junctions in UC.