Total Sialic Acid Research Articles

Antioxidant Enzyme Activities, Total Sialic Acid, Vitamin, and Trace Element Status in the Patient with Osteoporosis and Osteopenia

Antioxidant Enzyme Activities, Total Sialic Acid, Vitamin, and Trace Element Status in the Patient with Osteoporosis and Osteopenia

Effect of green coffee on miR-133a, miR-155 and inflammatory biomarkers in obese individuals

ObjectivesMetabolic syndrome is a cluster of conditions that increases the risk of atherosclerotic cardiovascular diseases. The current study was a randomized, double blind, placebo-controlled study that aimed to determine the impact of green coffee (GC) in obese patients with metabolic syndrome through analysis of miRNA-155, miRNA-133a and the inflammatory biomarkers such as resistin, TNF-α, total sialic acid, homocysteine, high sensitivity C-reactive protein (hs-CRP), and the anti-inflammatory cytokine, adiponectin.MethodsOne hundred-sixty obese patients were randomly supplemented either with GC capsules (800 mg) or placebo daily for six months. Both groups were advised to take a balanced diet. Blood samples were collected at baseline and after six months of supplementation.ResultsGC supplementation for 6 months reduced BMI (p = 0.002), waist circumference (p = 0.038), blood glucose (p = 0.002), HbA1c% (p = 0.000), Insulin (p = 0.000), systolic blood pressure (p = 0.005), diastolic BP (p = 0.001) compared with placebo. GC significantly decreased total cholesterol (TC, p = 0.000), LDL-C (p = 0.001), triglycerides (TG, p = 0.002) and increased HDL-C (p = 0.008) compared with placebo group. In addition, GC significantly (p ≤ 0.005) reduced total sialic acid, homocysteine, resistin, TNF-α, hs-CRP and the oxidative stress marker malondialdehyde (MDA), but increased serum adiponectin (p = 0.000) compared to placebo group. There was a significant reduction in the gene expression of miR-133a (p = 0.000) in GC group as compared with baseline levels and with the control placebo group (p = 0.001) after 6 months.ConclusionGC administration modulated metabolic syndrome by decreasing BMI, high BP, blood glucose, dyslipidemia, miRNA-133a and inflammatory biomarkers that constitute risk factors for cardiovascular diseases.ClinicalTrials.gov registration No. is NCT05688917.Graphical

Association of Serum Proteases and Acute Phase Factors Levels with Survival Outcomes in Patients with Colorectal Cancer.

Colorectal cancer (CRC) represents a substantial burden on global healthcare, contributing to significant morbidity and mortality worldwide. Despite advances in screening methodologies, its incidence remains high, necessitating continued efforts in early detection and treatment. Neoplastic invasion and metastasis are primary determinants of CRC lethality, emphasizing the urgency of understanding underlying mechanisms to develop effective therapeutic strategies. This study aimed to explore the potential of serum biomarkers in predicting survival outcomes in CRC patients, with a focus on cathepsin B (CB), leukocytic elastase (LE), total sialic acid (TSA), lipid-associated sialic acid (LASA), antitrypsin activity (ATA), C-reactive protein (CRP), and cystatin C (CC). We recruited 185 CRC patients and 35 healthy controls, assessing demographic variables, tumor characteristics, and 7 serum biomarker levels, including (1) CB, (2) LE, (3) TSA, (4) LASA, (5) ATA, (6) CRP, and (7) CC. Statistical analyses included ANOVA with Tukey's post hoc tests and MANOVA for continuous variables. Student's t-test was used for dependent samples, while non-parametric tests like Mann-Whitney U and Wilcoxon signed-rank tests were applied for variables deviating from the normal distribution. Categorical variables were assessed using chi-square and Kruskal-Wallis tests. Spearman's rank correlation coefficient was utilized to examine variable correlations. Survival analysis employed the Kaplan-Meier method with a log-rank test for comparing survival times between groups. Significant associations were observed between CB (p = 0.04), LE (p = 0.01), and TSA (p = 0.008) levels and survival outcomes in CRC patients. Dukes' classification stages also showed a significant correlation with survival (p = 0.001). However, no significant associations were found for LASA, ATA, CRP, and CC. Multivariate analysis of LE, TSA, and ATA demonstrated a notable correlation with survival (p = 0.041), notwithstanding ATA's lack of significance in univariate analysis (p = 0.13). CB, LE, and TSA emerged as promising diagnostic markers with prognostic value in CRC, potentially aiding in early diagnosis and treatment planning. Further research is needed to validate these findings and explore additional prognostic indicators.

Rapid total sialic acid monitoring during cell culture process using a machine learning model based soft sensor.

Total sialic acid content (TSA) in biotherapeutic proteins is often a critical quality attribute as it impacts the drug efficacy. Traditional wet chemical assays to quantify TSA in biotherapeutic proteins during cell culture typically takes several hours or longer due to the complexity of the assay which involves isolation of sialic acid from the protein of interest, followed by sample preparation and chromatographic based separation for analysis. Here, we developed a machine learning model-based technology to rapidly predict TSA during cell culture by using typically measured process parameters. The technology features a user interface, where the users only have to upload cell culture process parameters as input variables and TSA values are instantly displayed on a dashboard platform based on the model predictions. In this study, multiple machine learning algorithms were assessed on our dataset, with the Random Forest model being identified as the most promising model. Feature importance analysis from the Random Forest model revealed that attributes like viable cell density (VCD), glutamate, ammonium, phosphate, and basal medium type are critical for predictions. Notably, while the model demonstrated strong predictability by Day 14 of observation, challenges remain in forecasting TSA values at the edges of the calibration range. This research not only emphasizes the transformative power of machine learning and soft sensors in bioprocessing but also introduces a rapid and efficient tool for sialic acid prediction, signaling significant advancements in bioprocessing. Future endeavors may focus on data augmentation to further enhance model precision and exploration of process control capabilities.

High-magnitude cyclic stretch induces protein sialylation and RNA de-sialylation at the alveolar epithelial membrane

Sialylated glycans such as sialoglycoproteins, sialoglycolipids and sialoglycoRNA are ubiquitous in the glycocalyx of cells where they play a key role in barrier function, mechanosensation, infection, immune cell traffcking, and inflammation. These functions are particularly relevant at the blood-gas barrier of the lung. The alveolar epithelial glycocalyx is furthermore unique in that it is constantly exposed to cyclic stretch because of normal breathing. Yet, the abundance, regulation and function of sialylated glycans in the alveolar epithelial glycocalyx remains unknown. Here, we focused on the effects of mechanical stretch on the abundance and de novo formation of sialoglyco-proteins and -RNA as major constituents of the alveolar epithelial sialome. Human primary alveolar epithelial cells (hPAEpiC) were exposed to high magnitude cyclic stretch (18% CS) at 0.25 Hz for 24-48 hours to mimic biomechanical forces at the alveolar epithelium during high tidal volume ventilation. Total sialic acids in sialoglycoproteins were labeled with biotin by periodate oxidation and aldehyde ligation (pAL), and total sialic acids in sialoglycoRNA were quantified by 1, 2-diamino-4,5-methylene dioxybenzene ( DMB) assay. De novo formed sialic acids were labeled with biotin using N-azidoacetyl-mannosamine (Ac4ManNAz). Biotinylated siaolglyco-proteins and -RNAs were detected with streptavidin by Western and Northern blots, respectively, and quantified densitometrically. Stretch-dependent changes in the genes regulating sialic acid biosynthesis were assessed by RNA sequencing. High magnitude cyclic stretch increased the sialylation of proteins of different sizes (35-190 kDa) in the hPAEpiC glycocalyx. MGE showed this increase to be attributable to an increased de novo synthesis of sialic acids. On the other hand, high magnitude cyclic stretch reduced the sialylation of hPAEpiC sialoglycoRNA with no alteration in de novo synthesis, suggesting shedding, release or loss of sialoglycoRNA. RNA seq of hPAEpiC revealed that cyclic stretch upregulated the gene GNE (which encodes the enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase), the master regulator of sialic acid biosynthesis. Here, we demonstrate cyclic stretch-induced sialylation of proteins and de-sialylation of RNA in the alveolar epithelial glycocalyx. Given that sialic acids promote the adhesion of both infectious pathogens and immune cells, these effects may contribute to the pathogenesis of ventilator-associated pneumonia and ventilator-induced lung injury. This work is supported by the German Research Foundation, CRC 1449 subproject B01 to MO & WMK. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

FEATURES OF THE METABOLISM OF SIALOGLYCOPROTEINS IN THE TISSUES OF THE LIVER, STOMACH AND SMALL INTESTINE OF RATS UNDER IMMOBILIZATION STRESS

Introduction. Immobilization stress leads to the intensification of free-radical reactions leading to the destruction of sialoglycoproteins of the gastroduodenal zone. The aim of the study. To evaluate the features of the metabolism of sialoglycoproteins in the tissues of the liver, stomach and small intestine of rats under immobilization stress. Methods. Total sialic acids (TSA) and levels of sialidase activity (SA) were determined in the serum, liver, stomach, and small intestine tissues of rats by standard testing systems in dynamics on the 21st, 35th, 60th and 90th days of observation. Results. The blood serum of laboratory rats showed a maximum increase in total sialic acids and sialidases by 35 days of stress exposure, while in the liver, on the contrary, a decrease in the above-mentioned indicators. In the mucous overlays of the stomach and small intestine, the number of TSA increased throughout the dynamics of observation, and the activity of sialidase decreased by day 21 and increased in the following days of the experiment. In the wall of the stomach and small intestine of experimental rodents, the level of TSA increased by the 35th day of observation. Conclusion. During immobilization stress in the exchange of sialoglycoproteins, a compensatory predominance of anabolic processes in liver tissues was noted against the background of the prevalence of catabolism in the mucosal layer of the stomach and small intestine on days 21, 35 of observation, changes in the walls of the above organs are less pronounced and manifest themselves at a later date.

Changes in the Serum and Tissue Levels of Free and Conjugated Sialic Acids, Neu5Ac, Neu5Gc, and KDN in Mice after the Oral Administration of Edible Bird’s Nests: An LC–MS/MS Quantitative Analysis

Edible bird’s nests have a variety of biological activities, the main components of which are sialic acids. Sialic acids are a group of nine-carbon N-acetylated derivatives of neuraminic acid containing a keto group at position C2 and play important roles in many biological processes. To verify whether the oral administration of edible bird’s nests would change the content and distribution of sialic acid components in vivo, a liquid chromatography–mass spectrometry method for the quantitative analysis of sialic acid levels in serum and tissues was developed. In the negative ion mode, the mobile phases consist of 0.1% formic acid in water (A) and acetonitrile (v/v) (B). Isocratic elution was performed with 60% B for 0−15 min. The chromatographic separation was performed on a Morphling HILIC Amide column (2.1 mm × 150 mm, 5 μm) at a flow rate of 0.5 mL min−1. The results showed that the correlation coefficients of the typical calibration curves were all higher than 0.995, exhibiting good linearity. The levels of free and conjugated forms of N-glycolylneuraminic acid (Neu5Gc), N-acetylneuraminic acid (Neu5Ac), and 2-keto-3-deoxy-D-glycero-D-galactonononic acid (KDN) in the serum and different tissues were simultaneously detected after the oral administration of the edible bird’s nests at a daily dose of 300 and 700 mg Kg−1 for seven days in mice. Our study found that the oral administration of edible bird’s nests can significantly increase the concentration of total sialic acids (Neu5Gc + Neu5Ac + KDN) in serum and spleen and lungs tissues, which may be related to the anti-inflammatory and immune function of edible bird’s nest, but further studies are needed to verify this. Neu5Ac was the dominant sialic acid in brain tissue, and Neu5Gc was the dominant sialic acid in serum and other tissues, including heart, liver, spleen, lungs, and kidney. Moreover, we found that the forms of Neu5Ac and Neu5Gc were mainly conjugated in all groups except liver tissue. In conclusion, the method we established had good linearity and accuracy; it allowed the analytes to be effectively separated from the matrix and endogenous substances in serum or tissues, so it could effectively detect the distribution and concentration of free and conjugated forms of sialic acids in serum and tissues, which was beneficial to the research and exploitation of edible bird’s nests and sialic acids.

Determination of Malondialdehyde, Nitric Oxide, Reduced Glutathione, Sialic Acid and Ceruloplasmin Levels in Sheep Liver Tissue With Hydatic Cyst

Cystic echinococcosis is a prevalent helminth-zoonosis that poses a significant threat to human and animal health worldwide. Although it typically shows an asymptomatic clinical course, it has been reported to cause many damages and biochemical changes in tissues and organism. The aim of this study was to investigate the concentrations of nitric oxide (NO), reduced glutathione (GSH), malondialdehyde (MDA), ceruloplasmin (Cp), and total sialic acid (TSA) in sheep liver tissue affected by cystic echinococcosis. The study was carried out on sheep between 4-5 years of age brought to the slaughterhouse in the Igdir territory. The livers were examined post-mortem for cystic echinococcosis and cystic structures. Sheep liver tissues that tested positive for protoscolex were designated as the ‘infected group’, while healthy sheep liver tissues without lesions were assigned to the ‘control group’. The results showed significantly higher levels of NO, MDA, Cp and TSA in the infected group compared to the control group (p<0.05), while GSH levels were significantly lower (p<0.05). These findings indicate that cystic echinococcosis in sheep is closely associated with mechanisms of inflammation, oxidative stress, and tissue damage. Moreover, our study provides insights into the oxidative response of cystic echinococcosis in liver tissue and enhances our understanding of the disease’s pathogenesis.

Assessment of Glycoconjugates Levels as Liability in Oral Precancerous and Oral Cancer Patients By IJISRT

Background: Because glycoproteins are crucial for maintaining the integrity of cells, dysglycoproteinemia has long been associated with cancer patients. The objective is to assess and correlate the serum glycoprotein levels in patients with oral cancer and possibly malignant illnesses. RESOURCES AND METHODS: There are 75 participants in this study, divided into three groups. Group 1: mouth cancer comprises 25 participants who have received a diagnosis of mouth cancer confirmed by histopathology. Group 2: Oral precancer comprises 25 participants who have been diagnosed with oral possibly malignant based on a histopathological confirmation. Group 3: A controlled group of twenty-five healthy volunteers, matched for age and sex.  Outcomes: The individuals in the OPM and OC group had significantly greater mean serum levels of protein bound hexose, total sialic acid, and fucose as compared to control.

Evaluation of Systemic Inflammation Before and After Standard Anti-tuberculosis Treatment in Patients With Active Pulmonary Tuberculosis and Diabetes Mellitus.

Background Diabetes mellitus (DM) is a common comorbidity of active pulmonary tuberculosis (APTB) that increases the risk of treatment failure during anti-tuberculosis chemotherapy. Evaluating systemic inflammatory response could help determine differences in response to treatment between APTB patients and those with APTB and DM. Methodology To explore changes in systemic inflammation, measured by a set of inflammatory mediators in subjects with APTB and TBDM before and after six months of anti-tuberculosis chemotherapy, 30 APTB and nine TBDM subjects underwent cytokine testing, including interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta 1 (TGF-β1) by enzyme-linked immunosorbent assay, C-reactive protein by nephelometry, and sialic acid by colorimetric assay at baseline and following six months of standard anti-tuberculosis treatment. Sputum smear microscopy or molecular biology (Xpert MTB/RIF) was used for diagnosis, and sputum smear microscopy was performed monthly during the treatment of the patient with pulmonary tuberculosis to evaluate his evolution. Principal component analysis examined changes in the inflammatory status. Results Both groups showed negative sputum smear microscopy in the sixth month after starting anti-tuberculosis chemotherapy. TGF-β1 was found to be significantly higher in subjects with TBDM before treatment compared to APTB patients (p<0.001), and systemic inflammation continued only in TBDM subjects after treatment (accumulation and persistence of inflammatory mediators like IL-6, IL-8, IL-10, IFN-γ, TNF-α, TGF-β1, C-reactive protein, and sialic acid in blood). On the other hand, the mediators IFN-γ, C-reactive protein, and total sialic acid were found to be most influential in distinguishing pre- and post-treatment inflammatory response in subjects with APTB without DM. Conclusions Inflammatory mediators analyzed in combination, including IFN-γ, CRP, and total sialic acid, may be useful in evaluating the systemic inflammatory response in subjects with APTB and TBDM before and after anti-tuberculosis treatment. Determining these mediators revealed persistent systemic inflammation in TBDM subjects after six months of standard tuberculosis treatment, despite negative sputum smear microscopy results and good glycemic control. This suggests a need for inflammation-modulating therapies during tuberculosis control. Finally, monitoring sputum smear microscopy results alongside the determination of proposed inflammatory mediators (IFN-γ, CRP, and total sialic acid) are effective in evaluating the response to anti-tuberculosis treatment in APTB subjects without DM, warranting further investigation.

Sinomenine: A Protential Biomaterial for Its Antitumor Effect in H22 Hepatoma-Bearing Mice and Its Mechanisms

Sinomenine (SIN) is a natural isoquinoline alkaloid extracted from the Chinese medicinal plant Sinomenium acutum with promising antitumor properties. Although its antitumor effect and mechanism have been studied, its effects on the structure and function of tumor cell membranes remain unclear. This study aimed to evaluate the antitumor effect of SIN on H22 hepatoma-bearing mice and its mechanism of action on tumor cell membranes, and the tumor inhibition rate and life extension rate were examined. Flow cytometry was used to evaluate the dose-dependent induction of apoptosis in H22 cells. The main components of tumor cell membrane, including total protein, cholesterol and sialic acid (SA) were characterized. The ultrastructure of cell membrane was observed using transmission electron microscopy (TEM). Furthermore, SIN’s effect on the function of cell membranes was studied by analyzing fluidity, sealing, and ion pump activity. The results demonstrated that SIN effectively inhibited the growth of liver cancer cells in vivo and prolonged the lifespan of H22 hepatoma-bearing mice. SIN induced apoptosis of H22 cells in a dose-dependent manner, significantly reduced total protein, cholesterol, and SA contents in H22 cell membranes, and significantly decreased the fluidity, sealing, Na+/K+-ATPase and Ca2+/Mg2+-ATPase activities of H22 cell membranes with increasing doses. Overall, these findings suggested that SIN reduced the main component contents of H22 cell membranes, leading to changes in structure and function of cell membrane, ultimately resulting in tumor cell apoptosis and inhibition of tumor growth. The findings indicated that SIN has great potential as a biomaterial for anti-liver cancer drugs, and provides new ideas and methods for developing antitumor drugs through membrane pharmacology.

Sialic acid in human milk and infant formulas in China: concentration, distribution and type.

This study compared the concentrations, types and distributions of sialic acid (SA) in human milk at different stages of the postnatal period with those in a range of infant formulas. Breast milk from mothers of healthy, full-term and exclusively breastfed infants was collected on the 2nd (n 246), 7th (n 135), 30th (n 85) and 90th (n 48) day after birth. The SA profiles of human milk, including their distribution, were analysed and compared with twenty-four different infant formulas. Outcome of this observational study was the result of natural exposure. Only SA of type Neu5Ac was detected in human milk. Total SA concentrations were highest in colostrum and reduced significantly over the next 3 months. Approximately 68·7–76·1 % of all SA in human milk were bound to oligosaccharides. Two types of SA, Neu5Ac and Neu5Gc, have been detected in infant formulas. Most SA was present in infant formulas combined with protein. Breastfed infants could receive more SA than formula-fed infants with the same energy intake. Overall, human milk is a preferable source of SA than infant formulas in terms of total SA content, dynamics, distribution and type. These SA profiles in the natural state are worth to be considered by the production of formulas because they may have a great effect on infant nutrition and development.

Blood-based protein biomarkers and red blood cell aggregation in pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is highly malignant with a low 5-year survival rate. Blood biomarkers may be of value for the noninvasive diagnosis of pancreatic cancer. This study assessed blood-based biomarkers and disturbances in red blood cell aggregation associated with pancreatic cancer. We studied 61 patients who underwent pancreatic resection. Of these 61 patients, 46 patients had PDAC, and 15 patients had inflammatory tumours. Serum VEGF, hypoxia-inducible factor (HIF-1α), elastin-derived peptides (EDPs), total sialic acid (TSA) and resistin levels were measured. Red blood cell aggregation was assessed by a laser-assisted optical rotational cell analyser. VEGF (p < 0.000001), HIF-1α (p = 0.000002), resistin (p = 0.000349), EDP (p = 0.000089) and TSA (p = 0.000013) levels were significantly higher in the PDAC group than in the inflammatory tumour group. The aggregation index (AI), syllectogram amplitude (AMP) and threshold shear rate (γthr) were significantly higher in the PDAC group, whereas the aggregation half-time (t1/2) was lower than in the inflammatory tumour group. Multivariate analyses revealed that VEGF, TSA and EDP levels were variables that predicted PDAC. VEGF levels were the most powerful predictor of PDAC independent of CA 19-9 levels. The cut-off points for VEGF, TSA and EDP levels were 134.56 pg/ml, 109.11 mg/dl and 36.4 ng/ml, respectively, with sensitivities of 97.8%, 87% and 69.6%, respectively, and specificities of 86.7%, 86.7% and 93.3%, respectively. This study indicated that there are significant differences in blood-based biomarkers for differentiating between PDAC and inflammatory tumours of the pancreas. We also confirmed that PDAC is associated with the excessive aggregation of RBCs.

Evaluation of Total and Lipid-Bound Sialic Acids, Trace and Macro Elements, and Some Biochemical Parameters in Dogs with Babesiosis

The present study was designed to investigate the changes at the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), trace and macroelements, and some biochemical parameters in dogs naturally infected with babesiosis. While babesiosis group consisted of seven dogs which were diagnosed with babesiosis clinically and parasitologically (ELISA), control group consisted of seven healthy dogs. Serum TSA and LSA levels in blood samples were measured spectrophotometrically by Sydow and Katapodis methods, respectively. Some biochemical parameters and macroelement measurements were performed using a modular autoanalyzer device. Trace mineral measurements were performed by ICP-MS technique. Compared to the healthy group, dogs with babesiosis had considerably higher TSA and LSA levels. Serum AST, ALP, LDH and CK enzyme activities and CRP, glucose, globulin, total bilirubin, urea, uric acid, creatinine and BUN levels of the babesiosis group significantly increased, while total protein level significantly decreased. The changes in ALT enzyme activity and triglyceride, cholesterol, HDL, LDL, HDL-CDL and ferritin levels were not statistically significant. Zinc, copper, magnesium, sodium, and potassium levels of the babesiosis group decreased significantly, while iron and chlorine levels increased significantly (p

Effects of rotating electric fields on blood metabolic indicators: an experimental study

BACKGROUND: Stress is an integral part of life in both humans and animals. Up to 70% of the Russian population have reported a certain degree of stress associated with approximately 80% of diseases. This heavy burden of stress explains a significant body of research on the issue of stress and its associations with health indicators. AIM: To study the effects of rotating electric fields on blood metabolic parameters in experimental animals with different levels of resistance to stress. MATERIALS AND METHODS: A total of 54 non-inbred white male rats comprised the sample. We measured serum levels of 11-hydroxycorticosteroids, glucose, C-reactive protein, total sialic acids and the activity of hepatospecific enzymes, such as aspartate transferase, alanine transferase, and alkaline phosphatase at the 10th and the 20th day of exposure to a man-made rotating electric field and in the non-exposed control group. By the level of resistance to stress all rats were divided into stress-resistant, stress-unresistant and ambivalent groups using the "open field" method. RESULTS: On the 10th day of exposure, the levels of 11-hydroxycorticosteroids, glucose, C-reactive protein, total sialic acids increased in all three groups of animals. The activity of aspartate transferase, alanine transferase, and alkaline phosphatase also increased in all rats. On the 20th day, the studied parameters remained elevated compared to the control group. The most pronounced changes were observed in the group of stress-unresistant individuals. CONCLUSION: Our results demonstrate significant effects of rotating electric fields on blood metabolic indicators in rats. The degree of change depends on individual level of stress resistance.

The protective effect of caffeic acid phenethyl ester on cadmium-induced liver toxicity: A histopathological and biochemical study

In this study, the changes caused by caffeic acid phenethyl ester (CAPE) in the histopathological and biochemical parameters in the oxidant / antioxidant balance in mice with experimental cadmium toxicity were investigated. A total of 40 female Swiss albino mice were used, with 10 mice in each group. The mice were divided into four groups (Group I - Control group, Group II - CAPE group, Group III - Cadmium group, Group IV - Cadmium + CAPE group). Plasma paraoxonase (PON) activity, high-density lipoprotein (HDL), low-density lipoprotein (LDL), total sialic acid (TSA), total antioxidant capacity (TAC), total oxidant capacity (TOC), and oxidative stress index (OSI) were analyzed on mice’s blood samples. The results showed that cadmium intoxication triggered oxidative stress in the mice. It also lowered their PON activity alongside TAC and HDL levels (P&amp;lt;0.001, P&amp;lt;0.01, and P&amp;lt;0.01, respectively) and increased their TSA, LDL, TOC, and OSI levels (P&amp;lt;0.05, P&amp;lt;0.01, P&amp;lt;0.01, and P&amp;lt;0.01, respectively). The histopathological examination of the liver tissues revealed focal apoptotic regions, sinusoidal occlusion, and irregularity in the cadmium group and no significant change in the other groups. These results indicated that CAPE can significantly prevent biochemical and histopathological changes due to cadmium damage.

A-246 Desialylation Profiles of Monocytes and Macrophages Upon LPS Stimulation

Abstract Background Cell surface expresses a dense layer of glycans terminated with sialic acids (Sias), known as sialylation, which often represent different cellular statuses. Meanwhile, the removal of Sias from the glycans catalyzed by sialidase (desialylation) is also involved in many biological processes. Previous studies have established that lipopolysaccharide (LPS) can induce the expression of endogenous sialidases in monocytes and macrophages, leading to desialylation of the LPS receptor TLR4. This desialylation of TLR4 has been shown to impact the LPS/TLR4 signaling pathway. In this study, we conduct a profiling of desialylation in THP-1 monocytes and THP-1 macrophages in response to LPS stimulation. This will provide insights on the intricate connection between sialylation, desialylation, and LPS-induced signaling. Methods The activity of sialidases was assessed by utilizing 4-methylumbelliferyl-N-acetylneuraminic acid (4-MU-NANA) and ganglioside GM3 as substrates. The total sialic acid in the THP1 was quantified using liquid chromatography tandem mass spectrometry (LC-MS/MS). Flow cytometry was used to analyze the exposure of galactose on THP-1 monocytes and macrophages after LPS stimulation (100 ng/mL LPS for 24 h), using PNA-FITC staining. The expression level of Neu1 and Neu3 sialidases in cell lysates of THP-1 monocytes and macrophages were assessed by western blot technique after LPS stimulation. ELISA was used to measure the levels of sialidases in the cell supernatant of THP-1 monocytes and macrophages upon LPS stimulation. Result We found a significant reduction in total sialic acid levels in both THP-1 monocytes and macrophages upon LPS stimulation. This was further confirmed by the significant increase in total sialidase activities which measured by both 4-MU-Neu5Ac and GM3 substrates in THP-1 monocytes and macrophages upon LPS stimulation. Surprisingly, we also found that sialidase activities significantly increased in the cell supernatant of both THP-1 monocytes and macrophages, indicting sialidases secretion upon LPS stimulation. Western blot analysis further confirmed the high expression and secretion of both Neu1 and Neu3 sialidases from THP-1 monocytes and macrophages after LPS stimulation. Conclusion The present study conducted the first systematic profiling of desialylation and sialidase expression in monocytes and macrophages upon LPS stimulation. This results demonstrate that endogenous sialidase expression and secretion play a role in the LPS/TLR4 signaling pathway and subsequent cellular processes and functions in the context of inflammation and immune response.

Impact of estrogen on IgG glycosylation and serum protein glycosylation in a murine model of healthy postmenopause.

The glycosylation of immunoglobulin (Ig) G regulates IgG interaction capability with Fc gamma receptors found in all immune cells. In pathogenic conditions, estrogen can impact IgG levels and glycosylation. Following menopause, when estrogen levels decline affecting the immune system and potentially leading to a heightened susceptibility of immune activation. In this study, we aim to determine if estrogen levels can regulate IgG glycosylation in postmenopausal healthy situations. Mice were ovariectomized to simulate an estrogen-deficient postmenopausal status and then treated with 17-beta-estradiol (E2) at different doses and different administration strategies. Using a highly sensitive liquid chromatography-tandem mass spectrometry (MS/MS) glycoproteomic method, we demonstrated that E2 treatment increased the degree of glycosylation on IgG-Fc with both galactosylation and sialylation in the position required for interaction with Fc gamma receptors. We also observed that only long-term estrogen deficiency reduces IgG levels and that estrogen status had no impact on total IgG sialylation on both Fab and Fc domains or general glycoprotein sialylation evaluated by ELISA. Furthermore, E2 status did not affect the total sialic acid content of total cells in lymphoid organs and neither B cells nor plasma cells. The study concluded that E2 treatment does not affect total serum glycoprotein sialylation but alters IgG glycosylation, including IgG sialylation, implying that estrogen functions as an intrinsic modulator of IgG sialylation and could thereby be one pathway by which estrogen modulates immunity.

Protective effects of resveratrol against fumonisin B1-induced liver toxicity in mice.

The aim of this study was to investigate the effects of resveratrol against fumonisin B1 (FB1)-induced liver toxicity, as, to the best of our knowledge, these effects have not been investigated yet, even though the toxic effects and mechanisms of FB1 and the antioxidative effects of resveratrol are well known. 40 BALB/c mice were divided into control, FB1, resveratrol, and FB1+resveratrol groups. Control received saline for 14 days. The FB1 group received 2.25 mg/kg FB1 every other day for 14 days. The resveratrol group received 10 mg/kg resveratrol for 14 days. The FB1+resveratrol group received 2.25 mg/kg FB1 every other day and 10 mg/kg resveratrol every day for 14 days. All administrations were peritoneal. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), total sialic acid (TSA) levels were analysed in serum samples, while total antioxidant status (TAS) and total oxidant status (TOS) were measured in the liver. Additionally, the liver tissue was examined for histopathological changes. AST, ALT, and TSA were significantly higher in the FB1 group than control. Resveratrol countered FB1 effects for all parameters, including TOS and TAS. Liver histology showed FB1-induced hyperaemia, infiltrations, and megalokaryosis in some hepatocytes. No pathological findings were detected in the control, resveratrol, or FB1+resveratrol group. Our findings confirm resveratrol's protective effect against liver damage and oxidative stress caused by FB1. In addition, they suggest that increased serum TSA levels can be used as a biomarker of FB1-induced hepatotoxicity.

Potential noninvasive biomarkers for the malignant transformation of oral leukoplakia: A systematic review and meta-analysis.

The rising cancer incidence in patients with oral leukoplakia (OL) highlights the importance of identifying potential biomarkers for high-risk individuals and lesions because these biomarkers are useful in developing personalized management strategies for OL patients. This study systematically searched and analyzed the literature on potential saliva and serum biomarkers for OL malignant transformation. PubMed and Scopus were searched for studies published up to April 2022. The primary outcome of this study was the difference in biomarker concentrations in saliva or serum samples from healthy control (HC), OL and oral cancer (OC) populations. Cohen's d with 95% credible interval was calculated and pooled using the inverse variance heterogeneity method. A total of seven saliva biomarkers were analyzed in this paper, including interleukin-1alpha, interleukin-6 (IL-6), interleukin-6-8, tumor necrosis factor alpha (TNF-α), copper, zinc, and lactate dehydrogenase. IL-6 and TNF-α exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. A total of 13 serum biomarkers were analyzed, including IL-6, TNF-α, C-reactive protein, total cholesterol, triglycerides, high-density lipoproteins, low-density lipoproteins, albumin, protein, β2-microglobulin, fucose, lipid-bound sialic acid (LSA), and total sialic acid (TSA). LSA and TSA exhibited statistically significant deviations in comparisons between HC versus OL and OL versus OC. IL-6 and TNF-α in saliva have strong predictive values for OL deterioration, and LSA and TSA concentration levels in serum also have the potential to serve as biomarkers for OL deterioration.