Complement 3 Research Articles

Relationship between CD274 gene polymorphism and systemic lupus erythematosus risk in a Chinese Han population.

Relationship between surface antigen differentiation cluster 274 (CD274) gene polymorphism and systemic lupus erythematosus (SLE) risk is limited. This study aims to discuss whether in a Chinese Han population, CD274 gene polymorphisms may relate to SLE susceptibility. Three hundred and ten SLE patients and 390 healthy controls were included in this case-control study. Using the Kompetitive Allele-Specific PCR (KASP) approach, five single nucleotide polymorphisms (SNPs), including rs2890658, rs4143815, rs822339, rs2282055, and rs2297137, were genotyped for CD274 gene polymorphisms. Correlation between the polymorphisms and clinical, laboratory features in SLE patients were discussed. Frequency of C allele was substantially lower in SLE patients than in healthy controls (p = .015), and CC genotype was significantly negatively related to developing SLE at locus rs4143815 (p = .013). At locus rs822339, frequency of GA genotype was higher than that of the healthy controls (p = .006). At locus rs2282055, frequency of GG genotype was lower than that of healthy controls (p = .024). According to subgroup analysis, the CD274 gene polymorphisms rs2890658, rs4143815, rs822339, rs2282055, and rs2297137 were partly linked to some clinical symptoms of SLE patients, such as Complement 4 (C4), C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR). CD274 gene polymorphisms may be susceptible to SLE in the Chinese Han people.

Serological characteristics and clinical implications of IgG subclasses in visceral leishmaniasis.

Visceral leishmaniasis (VL) represents the most severe form of Leishmaniasis infection, often resulting in fatality without timely treatment. Previous studies have found that immunosuppression increases the risk of VL disease progression and mortality, and the total immunoglobulin G (IgG) levels in peripheral blood vary before and after treatment. However, the distinct levels and roles of IgG subclasses in VL have not been documented yet. This study aims to elucidate the characteristics and clinical significance of IgG subclasses in VL. A total of 43 cases newly-diagnosed with VL were enrolled in the cohort. We measured the levels of IgG subclasses before and after standard treatment and conducted assessments of bone marrow features. In addition, we analysed other haematological indices and examined the variations in IgG subclasses, as well as their correlation with clinical and laboratory factors. The levels of total IgG, IgG1, and the ratios of both IgG1/IgG and IgG1/IgG2 decreased significantly after treatment, whereas the ratios of IgG2/ IgG showed an obvious increase. The VL patients without hyperglobulinemia displayed significant lower IgG1/IgG2 ratios, but higher IgG2/IgG ratios compared with those with hyperglobulinemia. In addition, VL patients with positive bone marrow amastigotes had significant higher IgG1/IgG and IgG1/IgG2 ratios, but lower IgG2/IgG ratios. IgG subclasses were correlated with abnormal blood test results, particularly immunological elements including IgM and Complement 4 (C4). IgG1 and IgG2 exhibited contrasting changes after treatment in VL patients. The features of bone marrow and laboratory tests indicated that IgG1 and IgG2 serve different roles in the progression of VL. The ratios of IgG subclasses may be more precise indicators to evaluate immune reaction in VL than traditional total IgG.

Impacts of pyraclostrobin on intestinal health and the intestinal microbiota in common carp (Cyprinus carpio L.)

Pyraclostrobin (PYR) is a strobilurin fungicide that is commonly used in agriculture, and its use in agriculture may lead to an increase in its residue in the aquatic environment and may have a deleterious influence on the intestinal health of aquatic creatures. Here, common carp were chronically exposed to PYR (0, 0.5, or 5.0 μg/L) for 30 d to determine its effect on the physical and immunological barrier and intestinal microbiota in the intestine. PYR exposure caused significant histological changes; altered the mRNA expression levels of occludin, claudin-2, and zonula occludens-1 (ZO-1); induced oxidative stress in the common carp intestine; and increased the serum D-lactate and diamine oxidase (DAO) levels. Moreover, PYR significantly increased the protein expression levels of tumour necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1β), and IL-6 while decreasing the level of transforming growth factor beta (TGF-β). Further studies revealed that PYR significantly reduced lysozyme (LZM) and acid phosphatase (ACP) activities as well as complement 3 (C3) and immunoglobulin M (IgM) levels. Furthermore, PYR decreased gut microbial diversity while increasing the abundance of pathogenic bacteria such as Aeromonas and Shewanella, causing an intestinal microbial disturbances in common carp. These results imply that PYR has a negative impact on fish intestinal health and may pose serious health risks to fish by disrupting the intestinal microbiota, physical barrier, and immunological barrier in common carp.

Clinical Predictors of Steroid Resistance in Childhood Nephrotic Syndrome.

We aimed to evaluate the clinical parameters, histopathological findings of nephrotic syndrome (NS) patients, and independent factors predicting steroid resistance in a single tertiary center. One hundred and sixty-two children (57 girls and 105 boys) with NS who were followed between 1998 and 2018 were analyzed in this retrospective cohort. The median (interquartile range; range) age and follow-up time were 4.9 (5.7; 0.1-16.8) and 5.5 (5.4; 0.1-20.3) years. A total of 82.7% of the patients were steroid-sensitive nephrotic syndrome (SSNS) and 17.3% were steroid-resistant nephrotic syndrome (SRNS). The median age at first presentation was lower in the SSNS group (P = .002). The most common histopathological findings were focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Hypertension and macroscopic and microscopic hematuria were higher in the SRNS group (P < .001). The age and microscopic hematuria were independent risk factors for steroid resistance (P = .019 and P = .002, respectively). Complement 3 (C3) was evaluated in 148 patients and found low in 7 patients who were subsequently diagnosed as membranoproliferative glomerulonephritis. There is still no better clinical predictor for steroid response than late age of onset and microscopic hematuria. Hypertension may also give a hint for potential steroid resistance.

Impact of different ANCA serotypes on the long-term outcome of ANCA-associated vasculitis patients

Objectives To investigate the clinical features and long-term outcomes of Chinese anti-neutrophil cytoplasmic antibodies (ANCAs)-associated vasculitis (AAV) patients with different ANCA serotypes. Methods Two hundred and twenty-four AAV patients from January 2010 to June 2021 were divided into myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA groups. Clinical and long-term outcomes were compared. Results In this study, the average follow-up was 46.4 months (range 0.3–188.4 months). One hundred and seventy-seven (79.0%) patients were MPO–ANCA-positive and 47 were PR3–ANCA-positive; the mean age of MPO–ANCA positive patients at diagnosis was elder than that of PR3–ANCA positive patients (67.0 vs. 60.0 years, p = .004). Among PR3–ANCA-positive patients, ear, nose and throat symptoms were more common (p = .014). Between two ANCA serotypes, there were no differences in complement 3 (C3), Birmingham vasculitis activity score (BVAS), five-factor score (FFS) or other organ involvements. For all AAV patients, the overall survival rates at one, three and five years were 80.0%, 67.0% and 56.4%, respectively. The cumulative relapse-free rates of one, three and five years were 89.5%, 76.4% and 68.4%, respectively. The survival of AAV patients was unaffected by the ANCA serotype (p = .23). The ANCA serotype also had no effect on either disease relapse (p = .20) or remission rates (p = .10). In our study, PR3–ANCA patients showed a better long-term survival, as the 5-year survival rate and the 5-year relapse-free survival rate of PR3–ANCA patients were 60.7% and 76.9%, while that of MPO–ANCA patients were 55.2% and 65.8%, respectively. Rather than ANCA serotype, younger patients with milder kidney involvement and lower disease assessment scores (BVAS and FFS) might be more relevant to better prognosis. Conclusions The likelihood of induced remission, patient survival or disease recurrence is all unaffected by ANCA serotypes. A better prognosis is seen in younger patients with milder kidney involvement and lower BVAS/FFS scores.

Effects of laminarin on growth performance and resistance against Pseudomonas plecoglossicida of large yellow croaker （Larimichthys crocea）

Laminarin (LAM) is widely used as an immunopotentiator in aquaculture, but its protective mechanism is still unclear. In this study, the effects of LAM on the growth performance and resistance against Pseudomonas plecoglossicida of large yellow croaker were studied in vitro and in vivo. The 42 d-feeding trial in large yellow croaker showed that dietary LAM could obviously promote the fish growth by improving the weight gain rate (WGR), specific growth rate (SGR), and feed conversion rate (FCR). Dietary LAM could also improve the survival rate of large yellow croakers subjected to P. plecoglossicida infection, and 500 mg/kg LAM produced the highest relative percent survival (RPS) of 35.00 %. LAM improved fish antioxidant level by enhancing serum total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity, and reducing malondialdehyde (MDA) content. In addition, LAM also improved fish innate immunity by increasing serum acid phosphatase (ACP) and alkaline phosphatase (AKP) activities and complement 3 (C3) content under P. plecoglossicida infection. What is more, on 9 d post P. plecoglossicida challenge, LAM could significantly decrease the bacteria load in head kidneys, spleens and livers of fish, and the lowest bacterial load was found in 500 mg/kg LAM group. In vitro, LAM exerted a protective role against inactivated P. plecoglossicida-triggered inflammatory injury in primary head kidney macrophages (PKM) of large yellow croaker by recovering cell viability, suppressing NO production, and reversing pro-inflammatory cytokine expression (IL-1β, IL-6, and IL-8). All these findings therefore will provide insights into the protection mechanism of LAM in fish, facilitating its application in prevention and control of fish bacteriosis.

Serum 25(OH)D levels are associated with disease activity and renal involvement in initial-onset childhood systemic lupus erythematosus.

Vitamin D deficiency is common in patients with systemic lupus erythematosus (SLE) and may affect their disease activity and severity. This study aims to assess the vitamin D status in patients with initial-onset SLE during childhood and its association with the clinical and laboratory markers of disease activity. This is a retrospective study that includes 168 patients with initial-onset SLE during childhood and 109 healthy children as controls. Clinical and laboratory data were recorded. The area under the curve (AUC) method was used to evaluate the efficacy of double-stranded deoxyribonucleic acid (dsDNA), lower 25(OH)D and complement 3 (C3) alone and in combination to diagnose the presence of renal damage in children with SLE. Compared with the controls (25.53 ± 7.02 ng/ml), patients with initial-onset SLE during childhood have lower serum 25(OH)D levels (18.63 ± 5.32 ng/ml) (P < 0.05). Among patients with initial-onset SLE during childhood, SLEDAI-2K scores are significantly higher in the vitamin D insufficiency (median = 14.5) and vitamin D deficiency (median = 14.0) groups than in the vitamin D sufficiency group (median = 9.0) (P < 0.05). Patients with initial-onset SLE during childhood with lower 25(OH)D levels are more likely to have lupus nephritis (LN) and a higher SDI score (P < 0.05). Compared with patients with other types of LN (16.69 ± 3.90 ng/ml), patients with type V LN have lower levels of 25(OH)D (12.27 ± 3.53 ng/ml) (P < 0.05). The AUC was 0.803 when dsDNA antibody, 25(OH)D level and C3 were used in combination to diagnose LN in patients with SLE. Vitamin D deficiency and insufficiency are closely related to an increase in SLEDAI and SDI scores. Significant decrease in vitamin D level is a risk factor for LN.

Cerebrospinal Fluid Complement 4 Levels Were Associated with Alzheimer's Disease Pathology and Cognition in Non-Demented Elderly.

Numerous studies have shown that the complement system plays an important role in Alzheimer's disease (AD). However, whether complement 4 (C4) protein in cerebrospinal fluid (CSF) was associated with AD pathology, especially in the early stage of AD, is still unclear. We aimed to explore the association of CSF C4 with AD pathology and cognition in the preclinical AD. The study included a total of 287 participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. Based on the A/T scheme, they were divided into four groups to access the changes of CSF C4 in the preclinical AD. Linear regression models were used to test the associations between CSF C4 and AD core biomarkers, namely Aβ42, P-tau, and T-tau. The level of CSF C4 decreased in the A + T- group compared with the A-T- group (p = 0.04) and it increased in the A-T+ group compared to the A + T- group (p = 0.01). In pooled samples, C4 was significantly associated with AD core biomarkers (all p < 0.05), but only in the A + group after stratification according to the A/T scheme. Furthermore, CSF C4 levels at baseline were associated with longitudinal cognitive changes. Our results showed that CSF C4 levels changed dynamically in the preclinical AD, and that the responses of CSF C4 to brain Aβ pathology, tau pathology and neurodegeneration were found only in the presence of amyloid plaques, both of which indicates the complex link between C4 and AD.

Pre-Treatment Serum Complement 3 Levels And Rituximab Response In Idiopathic Membranous Nephropathy

Objective: The efficacy of rituximab has been reported in patients with idiopathic membranous nephropathy (MN). We aimed to evaluate the relationship between biochemical tests at diagnosis, immunohistochemical profile, and rituximab response in patients with idiopathic MN unresponsive to other therapies in our center. Material and Methods: In this study, nine patients with idiopathic MN who received other immunosuppressive therapies between 2017-2022 and who underwent renal biopsy in our center were evaluated. Pre-treatment phospholipase A2 antibody levels were positive in 6 patients, and antibodies could not be analyzed in 3 patients. All patients received rituximab ≥2 grams after renin-angiotensin-aldosterone system (RAAS) blocker, cyclophosphamide, steroid, and calcineurin inhibitors. Results: Of the nine patients included in the study, 7 (78.2%) were male, and the mean age was 39.713.2 years. Four patients had complete remission (CR) with rituximab treatment, and five had partial remission (PR). Sclerotic glomeruli count, IgG, A, M, C1q, C3, C4d, fibrinogen, kappa and lambda staining, tubular atrophy, and interstitial fibrosis findings on renal biopsy were similar. However, the serum complement 3 (C3) level was significantly lower within normal limits (1.22  0.26 vs 1.560  0.56 p=0.016). The mean arterial pressure was significantly higher (96.22.5 mmHg vs 84.754.27 mmHg, p=0.018) in patients with partial remission compared to those with complete remission. Conclusion: A low baseline serum C3 level within normal limits before treatment in patients with idiopathic membranous nephropathy may help predicting unresponsiveness to other immunosuppressive therapies and partial response to rituximab treatment.

Insights into the interaction between stocking density and feeding rate in fish Megalobrama ambylcephala based on growth performance, innate immunity, antioxidant activity, and the GH-IGF1 axis

The interaction between stocking density and feeding rate was investigated in juvenile blunt snout bream (Megalobrama ambylcephala) (11.94 ± 0.04 g) based on growth performance and health status. A 2 × 4 factorial design was adopted, containing two stocking densities (10 and 20 fish/m3) and four feeding rates (3%, 4%, 5% and 6% body weight/day). After the 12-weeks feeding trial, high stocking density (20 fish/m3) significantly (P < 0.05) reduced weight gain rate (WGR), feed intake (FI), protein efficiency ratio (PER), nitrogen and energy retention efficiency (NRE and ERE), plasma immunoglobulin M (IgM) level, plasma lysozyme (LZM), myeloperoxidase (MPO) and alkaline phosphatase (AKP) activities, as well as hepatic superoxide dismutase (SOD) and catalase (CAT) activities, while the opposite was observed in feed conversion rate (FCR), condition factor (CF) and plasma complement 4 (C4) level. The highest feeding rate (6%) significantly (P < 0.05) increased WGR, FI, FCR, CF, the intraperitoneal fat ratio and the protein expression of growth hormone receptor, but significantly (P < 0.001) decreased PER, NRE and ERE. Moderate feeding rates (4%–5%) significantly (P < 0.05) increased body lipid and energy contents, the activities of SOD, CAT, glutathione peroxidase, LZM, MPO, AKP and acid phosphatase, the levels of complement 3 and 4 (C3 and C4), and the transcriptions and protein levels of growth hormone and insulin-like growth factor 1, while the opposite was noted in the malondialdehyde content. Furthermore, an interactive effect between stocking density and feeding rate was also noted in WGR, FI, plasma ACP, AKP and MPO activities, and liver malondialdehyde content. In summary, stocking density and feeding rate interactively affect the growth performance and health status of blunt snout bream. The optimum feeding rate of this species increased when cultured under high-density conditions.

Alterations of Plasma Biochemical and Immunological Parameters and Spatiotemporal Expression of TLR2 and TLR9 in Gibel Carp (Carassius auratus gibelio) after CyHV-2 Infection.

Cyprinid herpesvirus II (CyHV-2), a highly contagious pathogen of gibel carp (Carassius auratus gibelio), causes herpesviral hematopoietic necrosis disease (HVHND) and enormous financial losses. However, there is limited information available regarding the changes in plasma biochemical and immunological parameters and the response characteristics of Toll-like receptor 2 (TLR2) and Toll-like receptor 9 (TLR9) in gibel carp after CyHV-2 infection. To address this knowledge gap, a sub-lethal CyHV-2 infection was conducted in gibel carp, and the sample was collected daily from 1 to 7 days post infection. The plasma biochemical analyses showed significant decreases in the content of glucose, total cholesterol (TCHO), and total protein (TP), along with marked increases in the level of uric acid, urea, creatinine (CREA), Complement 3 (C3), immunoglobulin D (IgD), and immunoglobulin M (IgM) as well as in the activity of alanine aminotransferase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), and lactate dehydrogenase (LDH) in the infected group. Compared with the control group, the concentration of cortisol, triglyceride (TG), and Complement 4 (C4) had no noticeable alterations in the infected group. Real-time quantitative PCR analysis showed significant upregulation of TLR2 and TLR9 mRNA expression in the spleen, kidney, brain, liver, intestine, and gill post CyHV-2 infection. Interestingly, a time- and tissue-dependent expression profile has been comparatively observed for TLR2 and TLR9 in the above tissues of gibel carp after CyHV-2 infection, suggesting distinct roles between TLR2 and TLR9 in antiviral response to CyHV-2 infection. Overall, our results demonstrated that CyHV-2 infection led to the disruption of the physiological metabolic process and damage to the liver and kidney, and induced different spatiotemporal expression patterns of TLR2 and TLR9, ultimately stimulating antiviral response via innate and adaptive immune system. These findings may provide a deeper understanding of the host immunity response to CyHV-2 infection and offer novel perspectives for the prevention and treatment and therapeutic drug development against CyHV-2.

Cerebral Microstructural and Microvascular Changes in Non-Neuropsychiatric Systemic Lupus Erythematosus: A Study Using Diffusion Kurtosis Imaging and 3D Pseudo-Continuous Arterial Spin Labeling.

The purpose of this study was to observe cerebral microstructure and microcirculation features, as well as changes in white matter (WM) and gray matter (GM) among patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). We compared 36 female patients with non-NPSLE and 20 age- and gender-matched healthy controls (HCs) who underwent 3.0T MRI imaging with diffusion kurtosis imaging (DKI) and 3D pseudo-continuous Arterial Spin Labeling (pCASL). Mean kurtosis (MK), mean kurtosis tensor (MKT), and cerebral blood flow (CBF) values were obtained from 25 brain regions, including WM and GM. We analyzed the correlation between imaging indicators and clinical data. When compared with HCs, patients with non-NPSLE had reduced MK and MKT values in regional WM, deep GM, and the left frontal lobe cortical GM, and increased CBF in the right parietal lobe WM and right semioval center (SOC). The MK and MKT values were weakly correlated with CBF in some regions, including WM and GM. Complement 3 (C3) and Complement 4 (C4) showed a weak positive correlation with MK and MKT in some regions, including WM and deep GM, while platelet (PLT) was positively correlated with MKT in the left frontal lobe WM; dsDNA antibody was correlated negatively with MK in the right occipital lobe WM; and erythrocyte sedimentation rate (ESR) was correlated negatively with CBF in the left SOC. Our findings revealed the presence of brain microstructural and microvascular abnormalities in non-NPSLE patients, indicating microstructural damage in the cortical GM, which was less commonly reported. We found DKI and pCASL useful in detecting early brain lesions, and MK was a more sensitive and beneficial indicator.

Toxicity of TPhP on the gills and intestines of zebrafish from the perspectives of histopathology, oxidative stress and immune response

As an organophosphate ester (OPE), triphenyl phosphate (TPhP) has been frequently detected in aquatic environments, and its environmental risk has been widely studied. The gills and intestines are the most important part of the mucosal immune barrier in fish as the first line of defense against the invasion of harmful substances. TPhP is more abundant in the gill and intestine of fish. However, knowledge of the toxic effects and potential mechanisms of TPhP on the intestine and gill is limited. Herein, the adverse effects of TPhP (0.01, 0.1 and 1 mg/L) on the gills and intestines of zebrafish after 75 days of exposure were investigated from the perspectives of histology, oxidative stress and immune level. The histological results of exposed zebrafish showed that TPhP caused significant damage to gills and intestines. TPhP significantly increased the activities of the antioxidant enzymes catalase (CAT) and glutathione s-transferase (GST), inducing oxidative damage to lipids, proteins, and DNA. Meanwhile, the immune function of the gills and intestines was significantly influenced by TPhP, as evidenced by the upregulation of the expression of interleukin-1β (IL-1β) and interleukin-6 (IL-6), upregulation of the content of complement 3 (C3) and complement 4 (C4), and downregulation of the activity of lysozyme (LZM) and the content of immunoglobulin M (IgM). Oxidative stress and the immune response were more severe in the gills. These findings indicate that TPhP, a typical OPE, caused tissue damage in aquatic organisms by inducing oxidative stress and immune damage and has strong environmental toxicity.

The Effect of Dietary Lipid Supplementation on the Serum Biochemistry, Antioxidant Responses, Initial Immunity, and mTOR Pathway of Juvenile Tilapia (Oreochromis niloticus)

The objectives of this study were to investigate the effect of different dietary lipid levels on the serum biochemistry, antioxidant responses, initial immunity, and mTOR pathway of juvenile genetic improvement-farmed tilapia (GIFT, Oreochromis niloticus). Six groups of the juveniles (initial body weight 20.66 ± 1.33 g) in triplicate were fed for 90 days using six iso-nitrogen diets with different lipid levels (0.35%, 3.35%, 6.35%, 9.35%, 12.35%, and 15.35%). The main results were as follows: Compared with the control group (0.35%), the diets with different lipid supplementation significantly improved (p &lt; 0.05) the contents of total protein (TP), albumin (ALB), globulin (GLB), glucose (GLU), triglyceride (TG), total cholesterol (T-CHO), high-density lipoprotein (HDL), low-density lipoprotein (LDL), total antioxidant capacity (T-AOC), malondialdehyde (MDA), complement 3 (C3), and immunoglobulin M (IgM), the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), lysozyme (LYZ), and alkaline phosphatase (ALP), the expression level of phosphatidylinositol-3-kinase (PI3K), Akt protein kinase B (Akt), and mammalian target of rapamycin (mTOR) genes in juvenile tilapia. However, diets with different lipid supplementation significantly reduced (p &lt; 0.05) the expression level of tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) genes of juvenile tilapia. In conclusion, the with different lipid supplementation could significantly affect the serum biochemistry, antioxidant responses, initial immunity, and mTOR pathway of juvenile tilapia.

Inhibition of acute complement responses towards bolus-injected nanoparticles using targeted short-circulating regulatory proteins.

Effective inhibition of the complement system is needed to prevent the accelerated clearance of nanomaterials by complement cascade and inflammatory responses. Here we show that a fusion construct consisting of human complement receptor 2 (CR2) (which recognizes nanosurface-deposited complement 3 (C3)) and complement receptor 1 (CR1) (which blocks C3 convertases) inhibits complement activation with picomolar to low nanomolar efficacy on many types of nanomaterial. We demonstrate that only a small percentage of nanoparticles are randomly opsonized with C3 both in vitro and in vivo, and CR2-CR1 immediately homes in on this subpopulation. Despite rapid in vivo clearance, the co-injection of CR2-CR1 in rats, or its mouse orthologue CR2-Crry in mice, with superparamagnetic iron oxide nanoparticles nearly completely blocks complement opsonization and unwanted granulocyte/monocyte uptake. Furthermore, the inhibitor completely prevents lethargy caused by bolus-injected nanoparticles, without inducing long-lasting complement suppression. These findings suggest the potential of the targeted complement regulators for clinical evaluation.

Vitamin (D) levels in children of families with a case of rheumatic fever or rheumatic heart disease

Background The most prevalent acquired heart illnesses in children are rheumatic fever (RF) and rheumatic heart disease (RHD). Differential regulation of innate immune cell subsets by vitamin D has been shown to effect cell maturation, metabolism, antigen presentation as well as cytokine and chemokine response and production. Aim The aim of this work was to evaluate vitamin D levels in children with acute RF and its relation to serum immunoglobulin levels. Patients and methods This cross-sectional study was conducted at Tanta University Hospital, Pediatric cardiology unit, outpatient clinic, and clinical pathology unit in two groups: group 1 which included 49 children who were subdivided into: group 1a: which included 10 RF or RHD patients and group 1b: included 39 children (brothers or sisters of rheumatic patients). Group 2 (control group): included 40 apparently healthy children of matched age and sex. All patients were subjected to full history taking, echocardiographic examination and laboratory investigations (Vitamin D3, erythrocyte sedimentation rate, antistreptolysin O titre, C-reactive protein (CRP), Calcium (Ca), phosphorus, immunoglobulins G (IgG), complement 3 (C3), and complement 4 (C4). Results There is a statistically significant decrease Ca, C4, and vit D3 levels in patient group compared with the control group. Vitamin D level was positively correlated with C4 levels. There is no statistically significant change was recorded regarding Ph, immunoglobulins G, or C3. Conclusion Children with RHD and children in families with RF or RHD are risky for vitamin D deficiency.

Cassava Foliage Effects on Antioxidant Capacity, Growth, Immunity, and Ruminal Microbial Metabolism in Hainan Black Goats.

Cassava (Manihot esculenta Crantz) foliage is a byproduct of cassava production characterized by high biomass and nutrient content. In this study, we investigated the effects of cassava foliage on antioxidant capacity, growth performance, and immunity status in goats, as well as rumen fermentation and microbial metabolism. Twenty-five Hainan black goats were randomly divided into five groups (n = 5 per group) and accepted five treatments: 0% (T1), 25% (T2), 50% (T3), 75% (T4), and 100% (T5) of the cassava foliage silage replaced king grass, respectively. The feeding experiment lasted for 70 d (including 10 d adaptation period and 60 d treatment period). Feeding a diet containing 50% cassava foliage resulted in beneficial effects for goat growth and health, as reflected by the higher average daily feed intake (ADFI), average daily gain (ADG) and better feed conversion rate (FCR), as well as by the reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine (CRE), and triglycerides (TG). Meanwhile, cassava foliage improved antioxidant activity by increasing the level of glutathion peroxidase (GSH-Px), superoxide dismutase (SOD), and total antioxidant capacity (T-AOC) and lowering malondialdehyde (MDA). Moreover, feeding cassava foliage was also beneficial to immunity status by enhancing complement 3 (C3), complement 4 (C4), immunoglobulin A (IgA), immunoglobulin G (IgG), and immunoglobulin M (IgM). Furthermore, the addition of dietary cassava foliage also altered rumen fermentation, rumen bacterial community composition, and metabolism. The abundance of Butyrivibrio_2 and Prevotella_1 was elevated, as were the concentrations of beneficial metabolites such as butyric acid; there was a concomitant decline in metabolites that hindered nutrient metabolism and harmed host health. In summary, goats fed a diet containing 50% cassava foliage silage demonstrated a greater abundance of Butyrivibrio_2, which enhanced the production of butyric acid; these changes led to greater antioxidant capacity, growth performance, and immunity in the goats.

Lc-pPG-612-OmpU-CTB: A promising oral vaccine for protecting Carassius auratus against Vibrio mimicus infection.

Vibrio mimicus (V. mimicus) is known to cause severe bacterial diseases with high mortality rates in fish, resulting in significant economic losses in the global aquaculture industry. Therefore, the objective of this study was to develop a safe and effective vaccine for protecting Carassius auratus (C. auratus) against V. mimicus infection. Recombinant Lactobacillus casei (L. casei) strains, Lc-pPG-612-OmpU and Lc-pPG-612-OmpU-CTB (surface-displayed), were constructed using a L. casei strain (ATCC 393) as an antigen delivery carrier and the cholera toxin B subunit (CTB) as an adjuvant. The two recombinant strains of L. casei were administered to C. auratus via oral immunization, and the protective efficacy of the oral vaccines was assessed. The results demonstrated that oral immunization with the two strains significantly increased the levels of nonspecific immune indicators in C. auratus, including alkaline phosphatase (AKP), lysozyme (LYS), acid phosphatase (ACP), complement 3 (C3), complement 4 (C4), lectin, and superoxide dismutase (SOD). Moreover, the experiment groups exhibited significant increases in specific immunoglobulin M (IgM) antibodies against OmpU, as well as the transcription of immune-related genes (ie., IL-1β, TNF-α, IL-10, and TGF-β), when compared to the control groups. Following infection of C. auratus with V. mimicus, the mortality rate of the recombinant L. casei-treated fish was observed to be lower compared to the control group. This finding suggests that recombinant L. casei demonstrates effective protection against V. mimicus infection in C. auratus. Furthermore, the addition of the immune adjuvant CTB was found to induce a more robust adaptive and innate immune response in C. auratus, resulting in reduced mortality after infection with V. mimicus.

Long-term crowding stress induces chronic inflammatory response and declines the immunity of grass carp (Ctenopharyngodon idella)

This study is aimed to explore the mechanism of overcrowding stress on the immunity of grass carp Ctenopharyngodon idella. Fish were reared for 120 days at 10 kg/m3 (low stocking density, LSD), 15 kg/m3 (medium stocking density, MSD) and 20 kg/m3 (high stocking density, HSD). The results showed that HSD significantly increased the serum cortisol level, implying that fish reared at higher density were subjected to physiological stress. HSD led to a remarkable decline in serum lysozyme activity. The conspicuous decrease of serum complement 3 (C3) and immunoglobulin M (IgM) contents also appeared in the HSD group. The serum antioxidant enzymes activity included total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), glutathione peroxidase (GPx), and catalase (CAT) of fish reared at HSD group were clearly decreased. The serum glutathione (GSH) concentration of fish reared at HSD group was notably reduced. The malondialdehyde (MDA) level was obviously increased in HSD group. Long-term crowding stress gave rise to the constitution of melano-macrophage centers in spleen. The transcriptional levels of TLR4/NF-κB signaling pathway were notably up-regulated except for iκbα and mTOR pathway related genes were prominently down-regulated in fish reared at HSD group. The notably up-regulated pro-inflammatory cytokines (tnf-α, ifnγ2, il1-β, and il-8) except for il-6 and prominently down-regulated anti-inflammatory cytokines (il-10, il4/13a, il4/13b, tgf-β1 and tgf-β2) appeared in HSD group. All of the above results revealed that long-term overcrowding stress induced unbalanced inflammatory response via TLR4/NF-κB and mTOR signaling pathway and decreased the immunity in grass carp.

High level of serum complement 3 is a risk factor for vascular stenosis progression in TA patients receiving tocilizumab: a prospective observational study

BackgroundThe IL-6R antibody tocilizumab has been proven effective in treating Takayasu arteritis (TA). However, some patients show silent vascular stenosis progression (VSP) despite treatment with tocilizumab. The aim of the study was to explore the related risk factors of VSP in patients treated with tocilizumab.MethodsPatients receiving tocilizumab were enrolled from the prospective living ongoing East China Takayasu Arteritis cohort. Their medical information was uniformly recorded with a homogenized evaluation method. Magnetic resonant angiography or computed tomographic angiography was employed to monitor VSP during the follow-up period, and Cox regression analysis was performed to explore the related risk factors.ResultsThirty-eight patients were enrolled, among whom 18 (47.4%) experienced VSP, and seven and three patients experienced new and worsened vascular ischemic symptoms and events (VISE) during follow-up, respectively. The median period for VSP occurrence was 6.9 months during follow-up. Patients with VSP showed higher levels of baseline complement 3 (C3) than those in the patients without VSP. Multivariate Cox regression analysis revealed baseline C3 level (hazard ratio [HR] = 7.05, 95% confidence interval: 1.50–33.07, p = 0.013) was independently associated with VSP, with a cut-off value of 1.22 g/L.Conclusions47.4% of TA patients treated with tocilizumab would suffer VSP. A high C3 level is a risk factor for VSP in TA patients receiving tocilizumab, which may facilitate the option of tocilizumab in the future.