C3 Levels Research Articles

Memory B cells and their transcriptomic profiles associated with belimumab resistance in systemic lupus erythematosus in the maintenance phase

The factors contributing to the treatment efficacy of belimumab in patients with systemic lupus erythematosus (SLE) in the maintenance phase are unknown. Here, we collected blood samples from patients with SLE (n=44) treated with belimumab before and three and six months after treatment. RNA-Seq of whole blood was performed, and gene expression was quantified. Immune cell type enrichment analysis estimated immune cell subtype proportions and gene expression in each subtype. The Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) < 4 at six months was set as the primary efficacy criterion. Non-responders exhibited upregulated B cell proliferation signals before treatment, associated with an increased number of memory B cells. A higher proportion of memory B cells before treatment predicted poor response (p=5.1×10-4). This was also associated with changes in disease activity and glucocorticoid dose at six months compared with baseline. Belimumab did not affect memory B cell proportion during the treatment time course, in contrast to naïve B cells. Higher memory B cell proportion was associated with higher type-I interferon (IFN) scores and lower white blood cell and complement C4 levels. Transcriptomic analysis of memory B cells in non-responders revealed significant upregulation of immunoglobulin genes (Ig). Memory B cells and high Ig expression in them were identified as a treatment-resistant factor of belimumab in SLE patients. Lower C4 and white blood cell counts may serve as clinical markers of higher memory B cells.

Complement 3 and 4 impact in osteoarthritis.

Aim: To investigate the association between serum complement 3 and 4 (C3 and C4) levels and clinical characteristics in osteoarthritis (OA) patients.Methods: This retrospective study included 361 OA patients divided into groups based on complement levels. Clinical data and laboratory test results, including C3, C4, ESR and CRP levels, were analyzed using non-parametric tests, Spearman correlation and multivariate regression.Results: The AC-OA group had lower PA, C3, C4, ESR, CRP and IgA levels compared with controls. C3 levels were positively correlated with ESR (r=0.260, p<0.001) and CRP (r=0.243, p<0.001). C4 levels also correlated with ESR (r=0.175, p=0.001) and CRP (r=0.263, p<0.001) and were significantly associated with the number of affected joints.Conclusion: Serum C4 levels are effective indicators of disease activity in OA, particularly in terms of joint involvement and CRP levels, while C3 levels showed no significant association. These findings suggest a potential role for C4 in predicting OA activity.

The Role of Immune Defense in Serratia marcescens Nosocomial Infections

Developing resistance mechanisms leads to various nosocomial infections caused by opportunistic bacteria. Serratia marcescens are well known to be opportunistic and are equipped with an armory of virulence factors against host immune response. The study aims to detect the immune defense in patients infected with multidrug-resistant S. marcescens. The study includes 132 clinical samples, including burn, wound, otitis media, and urinary tract infection (UTI) at several hospitals in Baghdad, Iraq. All isolates are identified by cultivation on MacConkey agar, nutrient agar, and blood agar, followed by biochemical tests and assessment with the VITEK 2 compact system. The isolates are tested for antibiotic susceptibility tests, interleukin-12 (IL12) levels, neutrophil ability to phagocytosis, and complement C3 and C4 levels. Out of 120 positive cultures, six isolates are identified as S. marcescens. The urine samples are the most isolated source and a higher level of antibiotic resistance was noticed in ampicillin and cefotaxime (100%), whereas a lower level is in imipenem. Stimulation (p ꞊ 0.005) provided a significant increase in IL-12 production. The infection with the S. marcescens stimulated the neutrophil’s phagocytosis process compared with the control. The interplay role of virulence factors in S. marcescens influences its pathogenesis, antibiotic resistance, and immune response, particularly involving neutrophils and IL-12. Understanding these interactions is crucial for developing effective therapeutic strategies.

Chinese herbal medicines and its active ingredient wogonin can improve immune inflammation in psoriatic arthritis.

In China, Chinese herbal medicines (CHMs) have been widely used in the treatment of psoriatic arthritis (PsA), showing great therapeutic effects in clinical practice. However, due to the great heterogeneity of PsA and the diversity of CHM combination patterns, there is little high-level evidence-based medical research on the treatment of PsA with CHMs. This study aims to explore the beneficial effects of CHMs on the immune inflammation in PsA and its specific mechanism. The data mining method was performed to analyze the real-world data of 91 PsA clinical cases. Network pharmacology, molecular docking, and cellular experiments were used to explore the mechanism of CHMs and its active ingredient wogonin in improving PsA immune inflammation. Data mining results showed that in PsA, immune inflammation was disturbed and relevant indexes were significantly correlated. After CHM treatment, the level of HCRP, C4, IL-12, IL-17, IL-23, TNF-α, TGF-β1, P65, P50, and IKBα was markedly improved, which was highly correlated with the application of CHMs. In addition, the core prescription containing 10 CHMs was screened, and the action mechanisms of the active ingredient wogonin on the immune inflammation in PsA were identified with network pharmacology and molecular docking. Cell experiments revealed that wogonin reduced M5-induced HaCaT cell viability and TNF-α and IL-1β expressions by blocking the PI3K/AKT pathway in a dose-dependent manner. Our findings strongly confirmed the enormous promise of CHMs as a therapy for PsA and may provide support for developing drugs and targets for PsA treatment.

Characteristics and therapeutic profile of the patients with upper cervical spinal cord ependymoma from the medulla oblongata to C4: A cohort of 108 cases.

Upper cervical spinal ependymomas (uCSE) is routinely identified as intramedullary ependymomas located from the oblongata medulla to C4 level. Our study aimed to report the outcomes and treatment profiles of uCSE from our cohort of uCSE patients. This retrospective observational study included 108 patients with upper cervical spinal ependymomas (uCSE) who underwent surgery at Huashan Hospital from 2008 to 2022. Demographic and clinical data were collected to identify risk factors may associated with post-operative spinal cord function, quality of life and respiratory function. The mean age of included patients was 44.30 ± 12.71 years old. The most common uCSE was ependymoma (103 of 108, 95.37 %), followed by subependymoma (3 of 108, 2.78 %) and anaplastic Ependymoma (2 of 108, 1.85 %). Age (P = 0.003), sex (P = 0.004), duration of symptoms (P = 0.010), pre-operative bladder functions (P = 0.012), post-operative pneumonia (P = 0.013) and Carbon Dioxide Retention (CDR) (P = 0.004) could independently correlate with Iiving quality of uCSE patients. Post-operative spinal cord function was associated with pneumonia immediately after operation (P = 0.017). In addition, post-operative pneumonia correlated with tumor location (P = 0.048), pre-operative McCormick scores (P = 0.008)/ motor functions (P = 0.022)/ NRS scores (P = 0.020), and tracheotomy immediately after operation (P < 0.001). Tracheotomy immediately after operation was associated with tumor location (P = 0.023), unsteady walking (P = 0.033), pre-operative NRS scores (P = 0.029), post-operative pneumonia (P < 0.001) and CDR (P < 0.001). Within uCSE patients, post-operative quality of life is associated with pre-operative spinal cord function and symptom duration, which emphasizing the importance of early intervention. Their post-operative respiratory dysfunctions also correlated with post-operative spinal cord function and quality of life.

Astragaloside IV can mitigate heat stress-induced tissue damage through modulation of the Keap1-Nrf2 signaling pathway in grass carp (Ctenopharyngodon idella).

This study investigated the potential protective effect of AS-IV against heat stress-induced tissue damage in grass carp (Ctenopharyngodon idella). Grass carp were injected intraperitoneally with 0, 2, 4, and 8 mg/kg of AS-IV for three consecutive days, and then subjected to heat stress (35 ± 0.5°C); thereafter, histopathological analyses of the liver and spleen were performed at 0, 6, 24, and 48 h, respectively. The results indicated that sustained heat stress resulted in hemorrhage, vacuolization, increased hepatic blood sinusoidal space, inflammatory cell infiltration in the liver, and decreased number of melanomacrophage centers in the spleen; conversely, 4 and 8 mg/kg AS-IV attenuated the pathological symptoms induced by heat stress and mitigated tissue damage in the liver and spleen of grass carp. The possible mechanism is that AS-IV promotes Nrf2 signaling through the downregulation of keap1a and keap1b, thereby activating the Keap1-Nrf2 signaling pathway, leading to changes in the levels of protection-related genes in the liver (GSH-Px and CAT levels were elevated while MDA levels were decreased, and gsh-px, cat, cu-zn sod, and hsp70 mRNA levels were upregulated while il-6 mRNA levels were downregulated) and spleen (GSH-Px, CAT, SOD, and GSH levels were increased while MDA levels were decreased, and il-6 mRNA levels were downregulated), which, in turn, improves the antioxidant ability of grass carp. Additionally, an appropriate dose of AS-IV transiently increased complement C3 levels after sustained heat stress, thereby improving the immunity of grass carp under heat stress. In conclusion, AS-IV can mitigate tissue damage induced in response to heat stress by modulating the redox homeostasis of grass carp and can be practically implemented in aquaculture sector.

The Changes of Lymphocytes and Immune Molecules in Irradiated Mice by Different Doses of Radiation.

The effects of different radiation doses on T and B lymphocyte functional subsets and the changes of immune cells and immune molecules were observed in mice at different times post-irradiation to provide a theoretical basis for the changes of immune cells affected by radiation. In this study, the changes of T and B immune cells and immune-related molecules were observed at 1, 3, 7, 14, and 21 d after single irradiation of 2 Gy, 4 Gy, and 6 Gy. The results showed that white blood cells (WBC), lymphocytes (LYMPH), and lymphocyte percentage (LYMPH%) in peripheral blood of mice were significantly reduced and reached the lowest point 3 d after irradiation. Flow cytometry results showed that the percentages of CD3+T and CD8+/CD3+T lymphocytes in spleen and thymus were significantly decreased, and the percentages of CD19+B lymphocytes in spleen and CD4+/CD3+T lymphocytes in thymus were also decreased. However, the percentages of splenic NK cells, CD4+/CD3+T cells, and CD4+/CD8+ ratios in spleen and thymus were increased. Most of the indicators fell to the lowest or highest point 3 d after irradiation, indicating that immune function was suppressed at this time. From 7 to 21 d after irradiation, most immune cells gradually recovered. Single irradiation of 2 Gy, 4 Gy, and 6 Gy increased the contents of IL-1β, IL-2, IL-6, IL-17, TNF-α, TGF-β, and IFN-γ in serum of mice and decreased the contents of anti-inflammatory factors IL-4 and IL-10. The serum levels of immunoglobulin IgA, IgG, IgM and complement C3, C4 were significantly increased after irradiation. Our study showed that a single dose of 2 Gy, 4 Gy, and 6 Gy induced immunosuppression in mice, and maximum immunosuppression was achieved 3 d after irradiation. At this time, CD19+B lymphocytes were the most sensitive, followed by CD3+T lymphocytes, and NK cells were the most resistant. The radiosensitivity of CD8+/CD3+T lymphocytes was slightly higher than that of CD4+/CD3+T lymphocytes.

Effect of the Jiedu Tongluo Shengjin formulation on plasma immunoglobulin G (IgG) levels in patients with primary Sjögren’s syndrome

This study assessed the effect of Jiedu Tongluo Shengjin formulation on plasma IgG levels in pSS patients. 89 pSS patients were randomized into treatment (45 cases; 1 drop-out) and control (44 cases) groups using the random number table method. The control group received hydroxychloroquine sulfate and a placebo dose of Jiedu Tongluo Shengjin. The treatment group received hydroxychloroquine sulfate and the original Jiedu Tongluo Shengjin formulation. The treatment group showed significant decreases in SS disease activity index, TCM syndrome score, plasma IgG, and ESR, and significant increases in tear film break-up time, tear flow rate, salivary flow rate, C3, and C4 levels (p&lt;0.05). No significant changes were observed in the control group (p&gt;0.05). Jiedu Tongluo Shengjin effectively reduced eye and mouth dryness in pSS patients by improving inflammation and immune status.

Mid- to long-term clinical outcomes of modified technique skip-level titanium plate fixation in cervical laminoplasty compared to continuous fixation

PurposeTo compare the efficacy and safety of skip titanium plates combined with adjacent spinous process suture suspension versus continuous titanium plate fixation in cervical laminoplasty.MethodsA retrospective analysis of 125 patients (62 men, 63 women, average age 60.9 ± 10.4 years) with multilevel cervical spondylotic myelopathy who had cervical laminoplasty with Arch titanium plate fixation from January 2012 to March 2024 in our hospital was done. Patients were stratified into two cohorts based on the fixation technique: Group A (n = 64): Modified technique of skip-level titanium plate fixation (Arch titanium plates at C4 and C6 levels combined with adjacent spinous process suture suspension)Group B (n = 61): Continuous plating (Arch titanium plates applied sequentially from C3 to C7).The comparative analysis focused on perioperative parameters (operative duration, intraoperative blood loss, length of hospital stay), economic factors (hospital costs), and various clinical indicators.ResultsThe average follow up period was (73.0 ± 38.4) months. Both groups showed no significant differences in gender, age, and disease duration (P > 0.05). Group A had lower hospitalization costs, intraoperative blood loss, operation time, and postoperative hospital stay compared to Group B (P < 0.05). Postoperatively, both groups had significant improvements in JOA scores and NDI (P < 0.005), but there were no significant differences in postoperative scores and improvement rates between the two groups (P > 0.05). At 3 months postoperatively and at the last follow-up, the C2-7 Cobb angle and cervical curvature index decreased compared to preoperative values (P < 0.05), with a significant difference in the C2-7 Cobb angle at the last follow-up (P < 0.05). The sagittal diameter of the spinal canal from C3 to C7 significantly increased (P < 0.05), but there were no significant differences in the improvement of C3, C5, and C7 between the two groups (P > 0.05). At 3 months postoperatively, the opening angles of the C4 and C6 laminae in Group A were smaller than those in Group B (P < 0.05), but there were no significant differences at the last follow-up (P > 0.05). The healing of the C4 and C6 laminae in Group B was superior to that in Group A (P < 0.05), but there were no differences in healing at the last follow-up (P > 0.05). The incidence of axial symptoms was similar (10.9% in Group A and 14.8% in Group B, P = 0.523).ConclusionsDuring C3-7 laminoplasty, the clinical efficacy of the method combining mini titanium plate fixation (at C4 and C6) with suture fixation is comparable to that of continuous fixation. Moreover, it has an advantage in cost control.

Efficacy of complement inhibition with pegcetacoplan in children with C3 glomerulopathy.

C3 glomerulopathy (C3G) is a rare kidney disease due to a dysregulation of the alternative complement pathway, orphan of specific treatment. Pegcetacoplan is an inhibitor of the third complement component C3, currently on a phase III registration protocol in C3G. Here we describe our experience with the off-label use of pegcetacoplan in pediatric patients with C3G. This retrospective, observational study evaluated the efficacy and safety of pegcetacoplan in five pediatric patients, not eligible in the registration protocol, over a 12-week treatment period. The drug was given subcutaneously, twice a week for the first month, then weekly. The change in urinary protein-to-urinary creatinine ratio (mean of three samples) was the primary endpoint. We also evaluated the changes in serum C3, albumin, sC5-b9, creatinine, and urinary erythrocytes (number/µL). At baseline, median proteinuria/creatininuria ratio (mean of three samples) was 4.97mg/mg (3.53-7.69), and after 12weeks of treatment with pegcetacoplan, it decreased to less than 30% of baseline (p = 0.043) as did erythrocyturia (p = 0.043). C3 levels increased more than 600% of baseline (p = 0.043), whereas the levels of sC5-b9 decreased to normal range (p = 0.043). Three of four patients with impaired kidney function showed an improvement in eGFR. No adverse event was recorded. In C3G patients, pegcetacoplan therapy improves clinical and laboratory features during a 12-week treatment. The present study, although small and with a limited follow-up, supports the use of complement-targeted therapy in C3G. Further studies with a larger number of patients and longer follow-up are needed.

Immunomodulatory Effects of Mesenchymal Stem Cell Secretome in Systemic Lupus Erythematosus: A Meta-Analysis

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by immune system dysregulation and multi-organ damage. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option due to their immunomodulatory properties, primarily mediated through their secretome (MSCS). This meta-analysis aimed to evaluate the efficacy and safety of MSCS in SLE patients. Methods: A systematic search of PubMed, Embase, and Web of Science was conducted for studies published between 2013 and 2024 investigating the effects of MSCS in SLE. Randomized controlled trials (RCTs) comparing MSCS with placebo or standard care were included. The primary outcome was SLE disease activity, assessed using the SLE Disease Activity Index (SLEDAI). Secondary outcomes included immunological markers (e.g., anti-dsDNA antibodies, complement levels), quality of life, and adverse events. Data were pooled using a random-effects model. Results: Nine RCTs (n=485 patients) met the inclusion criteria. MSCS therapy significantly reduced SLEDAI scores compared to controls (standardized mean difference [SMD] -0.78, 95% CI -1.25 to -0.31, p=0.001). Significant improvements were also observed in anti-dsDNA antibody levels (SMD -0.62, 95% CI -1.01 to -0.23, p=0.002) and complement C3 levels (SMD 0.55, 95% CI 0.21 to 0.89, p=0.002). MSCS was generally well-tolerated, with no serious adverse events reported. Conclusion: This meta-analysis demonstrates that MSCS therapy has significant immunomodulatory effects in SLE, leading to improved disease activity and immunological profiles. Larger, well-designed RCTs with longer follow-up periods are needed to confirm these findings and assess the long-term efficacy and safety of MSCS in SLE.

Analysis of expression and its clinical significance of the ADAMTS-2 in systemic lupus erythematosus.

ADAMTS-2 is a procollagen N-proteinase that plays an important role in inflammation regulation. The objective of our research is to explore the expression of ADAMTS-2 in Systemic Lupus Erythematosus (SLE), and analyze its relationship with clinical features of SLE, and evaluate the potential value of ADAMTS-2 as a diagnostic biomarker in SLE. ADAMTS-2 expression in PBMCs was detected by RT-qPCR in SLE patients, RA patients, and healthy controls (HC). The diagnostic value of ADAMTS-2 for SLE was evaluated by ROC curve, and the correlation between ADAMTS-2 and the clinical characteristics of SLE was analyzed by Spearman's rank correlation coefficient. The expression profiles of GSE8650 and GSE82221 were downloaded from the GEO database. We performed GSEA to further understand the functions of ADAMTS-2 in SLE. CIBERSORT was utilized for immune cell infiltration analysis. RT-qPCR results validated that the expression of ADAMTS-2 in PBMCs was significantly increased in SLE patients than RA patients and HC. ROC anaylsis suggested that ADAMTS-2 has significant value in distinguishing new-onset SLE patients from RA patients and HC (AUC = 0.805, p < 0.0001). The expression of ADAMTS-2 was negatively correlated with C3, WBC, PLT, neutrophil, and monocyte level. PBMCs samples with high ADAMTS-2 expression were enriched in TNFA_SIGNALING_VIA_NFKB pathway. We found that ADAMTS-2 was positively correlated with neutrophils, M0 macrophages and M2 macrophages. ADAMTS-2 may be a potential biomarker of SLE patients and closely related to the occurrence and development of SLE. ADAMTS-2 is expected to be a new target for SLE treatment. Key Points • ADAMTS-2 is a potential biomarker of disease activity in SLE patients that develop a flare. • Samples with high ADAMTS-2 expression are enriched in TNFA_SIGNALING_VIA_NFKB pathway in SLE. • ADAMTS-2 expression is positively correlated with neutrophils, M0 macrophages and M2 macrophages.

Association of C4 Null Alleles and Persistently Low C4 in Asian Indian Patients With Systemic Lupus Erythematosus.

The association between heterozygous C4 deficiency and systemic lupus erythematosus (SLE) is unclear. There is a lack of data in South Asian Indians on any possible association of C4A and C4B null alleles with lupus. We aimed to study the prevalence of C4A and C4B null alleles in a cohort of SLE patients with persistently low C4 levels compared to healthy controls (HC). Patients with SLE and HC were recruited for this prospective observational study. C4 (C4AQ and C4BQ) polymorphisms were tested using a touch-down polymerase chain reaction protocol. One hundred and three SLE patients and 103 HC were included in the study. Persistently low C4 levels were observed in 25 (23.6%) of SLE. The frequency of C4A and C4B null alleles was similarly distributed across SLE and HC (4% and 3.8%, respectively). Univariate analysis showed a low age, higher proportion of elevated dsDNA, and higher positive anti-SSA (Sjogren's syndrome-related antigen A) antibodies at presentation were associated in SLE patients with the null allele group on comparison without the null allele group. However, these associations did not persist in the multivariate analysis. In conclusion, C4 null allele frequency was similar in SLE and HC. No characteristic associations were observed in SLE with C4 null alleles was observed. Therefore, C4 null allele is an unlikely explanation for persistently low C4 in South Indian Asian patients with lupus.

Anti-C1q antibodies in IgG4-related disease are common and associated with renal involvement and cutaneous small-vessel vasculitis.

To evaluate the prevalence and clinical associations of anti-C1q antibodies in IgG4-related disease (IgG4-RD), focusing on renal involvement and cutaneous small-vessel vasculitis (CSVV). We enrolled patients who met the revised 2020 Comprehensive Diagnostic Criteria and/or the 2019 ACR/EULAR Classification Criteria for IgG4-RD. Variables included demographics, organ involvement, clinical phenotypes, disease activity, serum biomarkers, follow-up duration, remission, and relapses. Anti-C1q antibodies were measured using a quantitative enzyme-linked immunosorbent assay (cut-off <10 U/ml). Seventy patients with a mean age of 52.1 years were included. 34 (48.6%) were male. Anti-C1q antibodies were positive in 74.3%, with a median level of 19.8 U/ml. Patients with active disease had higher anti-C1q antibody levels than inactive patients (p= 0.03). Renal involvement was more frequent in anti-C1q positive patients (p= 0.01). Six patients (8.6%) had CSVV, and all had positive anti-C1q levels. All exhibited palpable purpura and one patient had urticarial-like lesions. These patients had multi-organ involvement, and most had high IgG, IgG1, IgG4, and hypocomplementemia. Skin biopsies in three patients showed leukocytoclastic vasculitis with lymphocytic and eosinophilic infiltrates. Anti-C1q antibody levels correlated negatively with levels of C3 and C4, and positively with levels of IgG1, IgG4, and serum free light chains. Anti-C1q positivity did not predict relapse-free survival. This study is the first to evaluate anti-C1q antibodies in IgG4-RD, finding a high prevalence, particularly in patients with renal involvement and CSVV. The results support the hypothesis that immune complex-mediated complement activation contributes to IgG4-RD pathogenesis.

Effects of periodontal disease on the proteomic profile of the periodontal ligament.

Periodontal disease affects over 1 billion people globally. This study investigated how periodontitis affects the protein profile of the periodontal ligament (PDL) in rats. Eight Holtzman rats were divided into the control and experimental periodontitis groups. The PDL was isolated using laser capture microdissection, and protein extracts were analyzed by mass spectrometry. Data analysis utilized specialized software, and Gene Ontology enrichment analysis identified significant protein functions. The data are available via ProteomeXchange with identifier PXD055817. Proteins such as SerpinB1, C5, and Lgals3 were validated through immunohistochemistry, and their gene expression was examined in an in vitro human PDL cell line. This study identified 1326 proteins, with 156 unique to the control group, 294 unique to the periodontitis group, and 876 common to both groups. Enrichment analysis revealed that proteins associated with the regulation of enzyme activity and RNA binding were significantly represented in the periodontitis group. There were increased levels of SerpinB1, C5, and Lgals3 in the periodontitis group based on proteomic and immunohistochemical analyses. Furthermore, these targets showed increased gene expression in stimulated human PDL cells. This study provides insights into the periodontitis-related alterations in the protein composition of the PDL and PDL cells, identifying both novel and previously known disease-associated proteins. SIGNIFICANCE: The periodontal ligament plays a crucial role in oral functions by providing structural support to the tooth. Due to the presence of undifferentiated mesenchymal cells, research into its regenerative capacity is ongoing. Pathological conditions can affect these functions and protein composition. Currently, there is a lack of comprehensive research specifically focusing on evaluating the periodontal ligament in both healthy and diseased states. This pioneering study screened for protein alterations and the mechanisms related to periodontitis. The possibility of using proteomic analysis to evaluate the protein alterations that occur in periodontitis-a disease with a high global incidence-could provide therapeutic targets and new biomarkers for future clinical studies.

Predictive Value and Potential of Targeting Complement Factor C3 in Patients with Renal Injury in Preeclampsia.

The activation of the complement system is accompanied by the occurrence and development of preeclampsia, as well as kidney diseases. Here, the role of complement C3 [C3] in renal injury in preeclampsia was explored, and its potential application as an early diagnostic biomarker or drug target to ameliorate kidney injury induced by preeclampsia was preliminarily evaluated. A total of 48 subjects were included in the present study, and the complement C3 levels and renal function were analyzed. Patients with preeclampsia with severe features [sPe] had poorer renal function compared with the patients with preeclampsia. Urinary C3 levels could be used to distinguish between healthy controls, patients with preeclampsia, and patients with sPe. Increased renal inflammation and oxidative stress were notably increased in the preeclampsia mice with impaired renal function and attenuation of C3 activity using a C3 receptor antagonist, which reduced Pe-like symptoms and renal impairment, decreased serum blood urea nitrogen, creatinine, and urinary albumin levels, and decreased expression of the oxidative stress marker malondialdehyde, whilst increasing superoxide dismutase activity. In addition, activation of the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 ([HO-1) pathway was involved in the inhibition of complement C3 in the kidney. Higher urinary C3 levels could be used to predict kidney damage as it was found that the activation of the Nrf2/HO-1 pathway attenuated C3 levels, and this resulted in increased renal impairment in preeclampsia.

Dynamic Complement Protein Changes in Aqueous Humor and Plasma of Patients With Retinal Vein Occlusion During Ranibizumab Treatment.

To assess dynamic changes of complement protein in aqueous humor (AH) and plasma of retinal vein occlusion (RVO) patients during ranibizumab treatment, and to explore the differential expression of complement proteins in branch retinal vein occlusion (BRVO) and central retinal vein occlusion (CRVO). This prospective, consecutive case series study collected AH and plasma samples from 27 RVO patients at baseline, 1 and 2 months after ranibizumab treatment, including 19 BRVO and 8 CRVO patients. The concentrations of 13 complement proteins and vascular endothelial growth factor A (VEGF-A) were measured using Luminex® × MAP® technology. During ranibizumab treatment, a reduction in the levels of C1q (p < 0.001), C2 (p = 0.030), C4 (p = 0.001), C4b (p = 0.026), C3b/iC3b (p < 0.001), C5 (p = 0.007), C5a (p = 0.005), CFD (p = 0.022), CFH (p < 0.001), and CFI (p < 0.001) in AH was observed. No significant changes were observed in the plasma levels of all measured factors. At baseline, CRVO had higher levels of C4 (p = 0.003), C4b (p < 0.001), C3b/iC3b (p < 0.001), C5 (p = 0.020), C5a (p = 0.007), CFD (p = 0.002), CFH (p < 0.001), and CFI (p < 0.001) in AH compared to BRVO. Ranibizumab treatment reduced the intraocular but not circulating activation of classical and alternative complement pathways in RVO patients. Differences in intraocular complement proteins were observed between BRVO and CRVO patients, which may reflect different pathogenesis.

Quantitation of Plasma Proteins to Predict Taxane-Induced Peripheral Neuropathy.

Taxane-induced peripheral neuropathy (TIPN) is a dose-limiting toxicity of paclitaxel in patients with cancer. TIPN prediction is challenging although patients with higher systemic paclitaxel exposure have higher TIPN risk. This study aimed to identify protein predictors of TIPN and paclitaxel pharmacokinetics (PK). This is a retrospective analysis of a prospective study of females with early-stage breast cancer receiving weekly paclitaxel. TIPN was assessed using the sensory subscale of the European Organisation for Research and Treatment of Cancer QLQ-Chemotherapy-Induced Peripheral Neuropathy (CIPN)20 (CIPN8). A blood sample was collected within 10 minutes before the end of the first paclitaxel infusion to measure plasma proteins using liquid chromatography-mass spectrometry and to estimate maximum systemic paclitaxel concentration (Cmax). A second sample was collected approximately 24 hours after the first infusion to estimate paclitaxel time above threshold (Tc>0.05). Linear mixed-effect and regression models were used to identify proteins predictive of TIPN and paclitaxel PK parameters, respectively, using a Bonferroni-adjusted α = .0006. Data from 36 participants were included in the analysis testing associations of 83 proteins with TIPN or PK. Higher levels of complement C3 were associated with more severe TIPN trajectories (P = .0002). No proteins were associated with either Cmax or Tc>0.05 (all P > .0006). Complement C3 concentration at the end of initial paclitaxel infusion may be useful for identifying patients with breast cancer and potentially other tumor types who could benefit from TIPN prevention strategies to improve long-term treatment outcomes.

Isolation and Evaluation of Potential Use of Prebiotics-Utilizing Butyrate-Producing Bacteria in Nibea coibor.

Butyrate-producing bacteria (BPB) benefit the health of aquatic animals. This current study aimed to isolate BPB from the intestines of Nibea coibor and assess their probiotic potential. The results showed that nine isolates were obtained in vitro from the gut of N. coibor, including six Clostridium butyricum, two Proteocatella sphenisci, and one Fusobacterium varium. The representative bacteria, C. butyricum CG-3 and P. sphenisci DG-1, which produce high butyrate levels, were further studied for short-chain fatty acid (SCFA) production and antibiotic susceptibility. The effects of BPB singly (CB: basal diet + CG-3 and PS: basal diet + DG-1, at 107 CFU/g) or in combination with galactooligosaccharides (GOS) (0.5%) and inulin (0.5%) (CBIG) or D-sorbitol (0.5%) (PSGS) on the growth and health status of N. coibor were investigated. Results showed an increase in growth parameters in the CB, CBIG, and PSGS groups, except for the PS group. Alterations in intestinal microbiota (including diversity, abundance, and function) were observed in four experimental groups (CB, CBIG, PS, and PSGS groups). SCFA contents increased in treated groups; butyrate production was positively related to bacterial abundance. Compared to control, levels of complement C3, complement C4, immunoglobulin M (IgM), transforming growth factor-β (TGF-β), interleukin (IL)-10, IL-1β, and lysozyme (LZM) increased, while malondialdehyde (MDA) decreased in treated groups. Contents of IL-6 (PS and PSGS groups), tumor necrosis factor-alpha (TNF-α) (CB, PS, and PSGS groups), total antioxidant capacity (T-AOC) (CB and PS groups), total superoxide dismutase (T-SOD) (PS group), catalase (CAT) (CB and PSGS groups), and activities of amylase (PS and PSGS groups), trypsin (CB group), and lipase (CBIG group) were increased. Our results suggested the potential use of C. butyricum CG-1 or P. sphenisci DG-1 singly or in combination with prebiotics improved growth and health conditions in N. coibor.

Effectiveness of a Novel PLA2R1 Knock-In Rat Model in Repairing Renal Function Damage.

Phospholipase A2 receptor 1 (PLA2R1) exists in many animals and plays an important role in membranous nephropathy. In this study, we aimed to evaluate a PLA2R1 knock-in rat model with repaired kidney function to study the molecular mechanisms of membranous nephropathy. We constructed the PLA2R1 knockout [PLA2R1(-)] model and PLA2R1 knock in [PLA2R1(+)] model in rats. Consistent complement C3 and IgA expression was confirmed through colocalization studies. Urinary biochemical indicators were performed using Automatic Biochemistry Analyzer. The complement C3, IgG, and Nephrin were detected by immunofluorescence assay. The expression levels of complement C3, IgA, and PLA2R1 were detected by western blot. The differential expression proteins (DEPs) between control and PLA2R1(+) models were detected by liquid chromatography with tandem mass spectrometry. The PLA2R1(-) model showed proteinuria, complement C3 aggregation, and IgA and IgG deposition in the glomerulus. Comparing with the PLA2R1(-) model, the PLA2R1(+) model, the deposition of complement C3 and IgA in the glomerulus did not completely disappear, and IgG expression weakened. Moreover, the absolute value of urinary protein was much lower in the PLA2R1(+) model than in the PLA2R1(-) model, and some of the humanized PLA2R1 gene fragments repaired some of the kidney functions. Humanized PLA2R1-insertion in rats can repair part of the renal function and reduce proteinuria, which will help in studying the molecular mechanisms of membranous nephropathy, as well as the entire membranous nephropathy-related system and complement activation signaling pathway.