Dl-3-n-Butylphthalide Protects against Memory Deficits in Vascular Dementia Rats by Attenuating Pyroptosis via TLR-4/NF-κB Signaling Pathway.

INTRODUCTION: Inflammation is closely associated with the pathogenesis of vascular dementia (VD). Dl-3-n-butylphthalide (NBP) is a small molecule compound extracted from the seeds of Chinese celery, which have anti-inflammatory properties in animal models of acute ischemia and patients with stroke. In this experiment, we studied the protective effects of NBP in a rat model of VD induced by permanent bilateral occlusion of the common carotid arteries and investigated the role of the TLR-4/NF-κB inflammatory signaling pathway in the pathology of VD. METHODS: The Morris water maze test was used to evaluate cognitive deficits in the VD rats. Western blot, immunohistochemistry, and PCR analyses were used to analyze the molecular basis of the inflammatory response. RESULTS: NBP significantly improved the learning and memory ability of VD rats. With regard to the protective mechanism, the results showed that NBP significantly downregulated the relative expression of Cleaved Cas-1/Cas-1 and Cleaved GSDMD/GSDMD. Moreover, NBP decreased the levels of the TLR-4 and NF-κB (P65) protein and phosphorylation of P65 in the hippocampus of VD rats via the TLR-4/NF-κB signaling pathway. CONCLUSION: These findings demonstrate that NBP protects against memory deficits in permanent bilateral common carotid artery occlusion-induced VD rats by attenuating pyroptosis via the TLR-4/NF-κB signaling pathway.

Identification of differentially expressed circulating exosomal lncRNAs in IgA nephropathy patients.

BACKGROUND: Although immunoglobulin A nephropathy (IgAN) is one of the foremost primary glomerular disease, treatment of IgAN is still in infancy. Non-invasive biomarkers are urgently needed for IgAN diagnosis. We investigate the difference in expression profiles of exosomal long non-coding-RNAs (lncRNAs) in plasma from IgAN patients compared with their healthy first-degree relatives, which may reveal novel non-invasive IgAN biomarkers. METHODS: We isolated exosomes from the plasma of both IgAN patients and their healthy first-degree relatives. High-throughput RNA sequencing and real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate lncRNA expression profiles. Pathway enrichment analysis was used to predict their nearest protein-coding genes. RESULTS: lncRNA-G21551 was significantly down-regulated in IgAN patients. Interestingly, the nearest protein-coding gene of lncRNA-G21551 was found to be encoding the low affinity receptor of the Fc segment of immunoglobulin G (FCGR3B). CONCLUSIONS: Exosomal lncRNA-G21551, with FCGR3B as the nearest protein-coding gene, was down-regulated in IgAN patients, indicating its potential to serve as a non-invasive biomarker for IgAN.

Systemic inflammation modulates the ability of serum ferritin to predict all-cause and cardiovascular mortality in peritoneal dialysis patients.

BACKGROUND: This study aimed to ascertain whether the correlation of high serum ferritin with mortality is affected by systemic inflammation and to investigate the optimal serum ferritin level for predicting death when inflammation is considered in peritoneal dialysis (PD) patients. METHODS: We classified 221 patients into four groups according to serum ferritin concentration (100 µg/L) and high-sensitivity CRP (hs-CRP) level (3 mg/L), and followed them regularly from the date of catheterization to Dec 31, 2016, at Sun Yat-Sen Memorial Hospital, China. Clinical and biochemical data were collected at baseline, and clinical outcomes such as all-cause and cardiovascular mortality were assessed. RESULTS: During a median follow-up of 35 months (3 ~ 109 months), 50 (22.6%) deaths occurred. Cardiovascular disease (46.0%) was the most common cause of death, followed by infection (10.0%). The Kaplan-Meier survival analysis and log-rank test revealed significantly worse survival accumulation among PD patients with higher serum ferritin (≥100 µg/L) under elevated hsCRP levels (> 3 mg/L) (P = 0.022). A multivariate Cox regression analysis revealed that an increased serum ferritin level was independently associated with a higher risk of all-cause and cardiovascular mortality in PD patients (HR = 3.114, P = 0.021; and HR = 9.382, P = 0.032) with hsCRP above 3 mg/L after adjusting for relevant confounding factors. CONCLUSION: Higher serum ferritin levels were associated with an increased risk of all-cause and cardiovascular mortality in patients undergoing PD only in the presence of elevated hsCRP levels. The correlation of serum ferritin with poor outcome should take into consideration systemic inflammation.

The baseline levels and risk factors for high-sensitive C-reactive protein in Chinese healthy population.

BACKGROUND: Recent studies show that C-reactive protein (CRP) is not only a biomarker but also a pathogenic mediator contributing to the development of inflammation and ageing-related diseases. However, serum levels of CRP in the healthy ageing population remained unclear, which was investigated in the present study. METHODS: Serum levels of high sensitive C-reactive protein (hs-CRP), glucose (Glu), triglyceride (TG), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), superoxide dismutase (SOD), serum creatinine (SCr), serum uric acid (SUA) were measured in 6060healthy subjects (3672 male and 2388 female, mean age:45.9 years) who received routine physical examination at Sun Yat-sen Memorial Hospital, Guangzhou, China. RESULTS: In total of 6060 healthy people, serum levels of hs-CRP were significantly increased with ageing (P < 0.05), particularly in those with age over 45-year-old (1.31[0.69-2.75] vs 1.05[0.53-2.16]mg/L, P < 0.001). Interestingly, levels of serum hs-CRP were significantly higher in male than female population (1.24[0.65-2.57] vs 1.07[0.53-2.29]mg/L, P < 0.001). Correlation analysis also revealed that serum levels of hs-CRP positively correlated with age and SUA, but inversely correlated with serum levels of HDL-c and SOD (all P < 0.05). CONCLUSIONS: Baseline levels of serum hs-CRP are increased with ageing and are significantly higher in male than female healthy population. In addition, elevated serum levels of hs-CRP are also associated with increased SUA but decreased HDL-c and SOD. Thus, serum levels of hs-CRP may be an indicator associated with ageing in healthy Chinese population.

The incidence, risk factors and in-hospital mortality of acute kidney injury in patients after abdominal aortic aneurysm repair surgery.

BACKGROUND: Acute kidney injury (AKI) is a severe complication associated with abdominal aortic aneurysm (AAA) repair. In this study, we evaluated the incidence, risk factors and in-hospital mortality of AKI in patients after the AAA repair surgery. METHODS: A total of 314 Chinese AAA patients who underwent endovascular aneurysm repair (EVAR) or open aneurysm repair (OPEN) were enrolled in this study. AKI was diagnosed according to the 2012 KDIGO criteria. Logistic regression modeling was used to explore risk factors of AKI, while risk factors associated with in-hospital mortality in AKI patients were investigated using Cox proportional hazards model and Kaplan-Meier analysis, respectively. Multicollinearity analysis was performed to identify the collinearity between the variables before logistic regression analysis and Cox proportional hazards analysis. RESULTS: Among 314 patients, 94 (29.9%) developed AKI after AAA repair surgery. Severity of AKI and ruptured AAA were independently associated with an increase in in-hospital mortality in AKI patients after AAA repair. Kaplan-Meier analysis identified severity of AKI as being negatively associated with hospital survival in AKI patients. Risk factors associated with AKI included cardiovascular disease (OR 3.169, 95% confidence interval (CI) 1.538 to 6.527, P = 0.002), decreased eGFR (OR 0.965, 95%CI 0.954 to 0.977, P < 0.001), ruptured AAA (OR 2.717, 95%CI 1.320 to 5.592, P = 0.007), renal artery involvement (OR 2.903, 95%CI 1.219 to 6.912, P = 0.016) and OPEN (OR 2.094, 95%CI 1.048 to 4.183, P = 0.036). Further subgroup analysis identified OPEN as an important risk factor of AKI in ruptured AAA patients but not in ruptured AAA patients. The incidence of AKI was significantly lower in EVAR than in OPEN (27.1% vs. 42.8%) and, similarly lower in nonruptured AAA than in ruptured AAA (26.2% vs. 48.1%). CONCLUSION: One-third of AAA patients developed AKI after repair surgery. Severity of AKI was associated with reduced survival rate in AAA patients who developed postoperative AKI. Decreased preoperative creatinine clearance, cardiovascular disease, ruptured AAA and OPEN were independent risk factors for postoperative AKI in all 314 AAA patients. Although a lower rate of incident AKI was observed in EVAR compared with OPEN, subgroup analysis of ruptured AAA versus nonruptured AAA showed that EVAR was an independent protective factor for AKI only in ruptured AAA patients but not in nonruptured AAA patients.

Clinical features and mortality in Chinese with lupus nephritis and neuropsychiatric lupus: A 124-patient study.

BACKGROUND: Few investigation has focused on the patients with lupus nephritis (LN) and neuropsychiatric systemic lupus erythematosus (NPSLE). This study was aimed to investigate the clinical features, mortality, and the predictors for mortality of this group of patients. MATERIALS AND METHODS: Medical records were retrospectively reviewed in Sun Yat-sen Memorial Hospital from 1996 to 2012. Data of demographic information, clinical manifestations, laboratory tests, SLE disease activity index 2000 (SLEDAI-2K) score, diagnosis, complications, treatment, and mortality was collected. RESULTS: A total of 124 patients were included in our study. Thirty-five (29.1%) patients had glomerular filtration rate <60 ml/min/1.73 m(2), while 24 (19.4%) experienced acute kidney injury (AKI). Thirteen of the 19 American College of Rheumatology defined NPSLE syndromes were identified. The most frequent manifestation was seizure disorder (56/124, 45.2%), followed by psychosis (37/124, 29.8%) and cerebrovascular disease (35/124, 28.2%). One hundred and five (84.7%) patients had SLEDAI-2K scores ≥15, the mean of which was 21.5 ± 6.2. The mortality during hospitalization was 12.9% (16/124) with NP involvement itself being the leading cause of death (7/16, 43.8%). Multivariate logistic regression confirmed that age <14 years at onset of NPSLE (odds ratios [OR]: 9.95, 95% confidence intervals [CI]: 1.43-69.36, P = 0.020), AKI (OR: 10.40, 95% CI: 2.33-46.48, P = 0.002) and pneumonia (OR: 4.52, 95% CI: 1.14-17.96, P = 0.032) were risk factors for mortality, while cyclophosphamide (CYC) treatment (OR: 0.09, 95% CI: 0.02-0.54, P = 0.008) was a protective factor. CONCLUSION: Most of SLE patients with LN and new-onset NPSLE are in an active disease state. NP manifestation itself was the leading cause of death during hospitalization. Childhood-onset NPSLE, AKI and pneumonia might be predictors of mortality, whereas CYC treatment might improve the prognosis.

The ratio of neutrophil to lymphocyte as a potential marker of clinicopathological activity for lupus nephritis.

INTRODUCTION: The ratio of neutrophil to lymphocyte (NLR) is a novel inflammatory factor that is elevated in systemic lupus erythematosus (SLE). However, the relationship between NLR and renal pathological manifestations in patients with lupus nephritis (LN) has not been investigated. METHODS: A retrospective study included 240 SLE patients, in which 186 patients with renal involvement and 124 LN patients underwent renal biopsy, 125 healthy volunteers and 125 chronic kidney disease (CKD) controls. Patients with SLE disease activity 2000 (SLEDAI-2 K) > 9 and ≤ 9 were defined as severely active and mildly active, respectively. Clinical parameters and renal pathological data were collected from medical records. The correlations between NLR and clinicopathological features were analyzed. RESULTS: The NLR of SLE group was significantly higher than that of the sex-age matched control groups. Patients with nephritis had higher NLR levels than those without nephritis (P = 0.044). Increased NLR was observed in severely active group compared to mildly active group (P = 0.020). NLR was significantly positively related with SLEDAI score, Renal SLEDAI score, C-reactive protein (CRP), 24-h urine protein, renal activity index (AI), cellular crescents and tubular atrophy, and negatively correlated with serum albumin. NLR was significantly decreased after treatment. Based on the receiver operating characteristic (ROC) curve, the best NLR cut-off value to predict severe activity of SLE and cellular crescents in renal pathology was 2.19 and 3.16, respectively. CONCLUSION: NLR may be a non-invasive and potential inflammatory marker in evaluating clinical and renal pathological activity in LN patients.

High serum immunoglobulin D levels in systemic lupus erythematosus: more to be found?

INTRODUCTION: Many studies have shown that serum immunoglobulin D (IgD) is usually increased in autoimmune diseases. The potential role of IgD in systemic lupus erythematosus (SLE) is still unclear. Our study aimed to compare the serum IgD levels of SLE with different population and to evaluate the relationship between serum IgD and SLE. METHODS: Fifty SLE patients, 40 non-SLE chronic kidney disease (CKD) patients, and 50 healthy volunteers were enrolled in this study. Serum IgD levels were analyzed by ELISA assay and compared between groups. The correlation of serum IgD and SLE disease were evaluated. The ability of serum IgD to predict SLE was analyzed by graphing receiver operating characteristic curves. RESULTS: Serum IgD levels were significantly higher in SLE patients compared to non-SLE CKD and healthy controls (7436.1 ± 5862.1 vs. 4517.8 ± 5255.2 vs. 4180.4 ± 4881 ng/mL, p = 0.01, p = 0.002, respectively), and in patients with high SLE Disease Activity Index (SLEDAI) scores compared with those with low scores (8572.9 ± 5968.7 vs. 5020.4 ± 4972.5 ng/mL, p = 0.044). High level of inflammatory cytokines and decreased circulating basophil counts were found in SLE patients (p < 0.05). No correlations was identified between serum IgD levels and SLEDAI scores (p > 0.05). Serum IgD was noninferior to IgG or IgE in discriminating SLE with an area under the curve of 0.672 (95% CI, 0.59-0.75). CONCLUSIONS: Serum IgD levels are significantly elevated in SLE patients with high SLEDAI scores. Simultaneous occurrence of increased inflammatory cytokines and decreased basophil counts highlights the potential role of IgD-targets interaction in SLE pathogenesis. Key points • Total serum IgD levels were elevated in SLE patients. • High IgD levels were significantly higher in SLE patients with high SLEDAI scores. • The ability of serum IgD was equivalent to IgG or IgE in discriminating SLE from CKD and healthy adult.

Case Report: Recurrent Deposition in Renal Allografts: A Rare Case of Fibronectin Glomerulopathy Overlooked in Native Kidneys.

Fibronectin glomerulopathy (FNG) is a rare inherited kidney disease characterized by extensive deposition of fibronectin in the glomeruli, especially in the mesangial and subendothelial regions. The disease progresses slowly and eventually leads to kidney failure in 15-20 years. Here, we report an interesting case. The patient presented with proteinuria and was diagnosed with immune complex-mediated glomerulonephritis, and lupus nephritis was suspected. This patient progressed to end-stage renal disease after 18 years and received an allogeneic kidney transplant. However, proteinuria recurred 27 months after kidney transplantation. The renal biopsy found extensive deposition in glomeruli, and the patient was diagnosed with FNG using mass spectrometry analysis and confirmed by immunohistochemistry in both the native and transplanted kidneys. Gene sequencing revealed that a missense mutation in the fibronectin 1 (FN1) gene caused reduced binding to heparin, endothelial cells, and podocytes and impaired stress fiber formation. The patient had stable renal function but persistent nephrotic proteinuria after 6 months of follow-up. Given the persistence of abnormal circulating fibronectin levels, FNG can relapse following renal transplantation. The circulating fibronectin deposits on grafts, and renal function progressively deteriorates after recurrence. Therefore, whether renal transplantation is an acceptable treatment for FNG is still debatable.

Corrigendum: Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy.

[This corrects the article DOI: 10.3389/fimmu.2022.978315.].

Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response to renin-angiotensin system inhibitors in patients with IgA nephropathy.

Background: Renin-angiotensin system inhibitors (RASi) are the first choice and basic therapy for the treatment of IgA nephropathy (IgAN) with proteinuria. However, approximately 40% of patients have no response to RASi treatment. The aim of this study was to screen potential biomarkers for predicting the treatment response of RASi in patients with IgAN. Methods: We included IgAN patients who were treatment-naive. They received supportive treatment, including a maximum tolerant dose of RASi for 3 months. According to the degree of decrease in proteinuria after 3 months of follow-up, these patients were divided into a sensitive group and a resistant group. The plasma of the two groups of patients was collected, and the exosomes were extracted for high-throughput sequencing. The screening of hub genes was performed using a weighted gene co-expression network (WGCNA) and filtering differentially expressed genes (DEGs). We randomly selected 20 patients in the sensitive group and 20 patients in the resistant group for hub gene validation by real-time quantitative polymerase chain reaction (qRT-PCR). A receiver operating characteristic (ROC) curve was used to evaluate hub genes that predicted the efficacy of the RASi response among the 40 validation patients. Results: After screening 370 IgAN patients according to the inclusion and exclusion criteria and the RASi treatment response evaluation, there were 38 patients in the sensitive group and 32 patients in the resistant group. IRAK1, ABCD1 and PLXNB3 were identified as hub genes by analyzing the high-throughput sequencing of the plasma exosomes of the two groups through WGCNA and DEGs screening. The sequencing data were consistent with the validation data showing that these three hub genes were upregulated in the resistant group compared with the sensitive group. The ROC curve indicated that IRAK1 was a good biomarker to predict the therapeutic response of RASi in patients with IgAN. Conclusions: Plasma exosomal IRAK1 can be a potential biomarker for predicting the treatment response of RASi in patients with IgAN.

Pittsburgh Sleep Quality Index score predicts all-cause mortality in Chinese dialysis patients.

BACKGROUND: The relationship between Pittsburgh Sleep Quality Index (PSQI) score and survival of dialysis patients has not been well studied. The aim of this study was to explore the association between PSQI score and all-cause mortality in dialysis patients. METHODS: Fifty-one hemodialysis and 58 peritoneal dialysis patients were enrolled in this study. PSQI score > 5 and ≤ 5 indicated "poor sleepers" and "good sleepers", respectively. The primary outcome was all-cause mortality. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were performed. RESULTS: The median PSQI score was 7.0 (4.0-10.0). Sixty-seven (61.5%) patients had poor sleep quality (SQ). Compared with good sleepers, poor sleepers had significantly lower levels of hemoglobin [74.0 (61.0, 85.0) vs. 78.0 (68.0, 97.0), P = 0.03] and serum bicarbonate (18.0 ± 4.5 vs. 20.0 ± 3.7, P = 0.022). The follow-up time was 69.1 ± 29.9 months. By multivariate Cox proportional hazards analysis, PSQI total score was the independent risk factor of all-cause mortality [hazard ratio (HR) 1.20, 95% confidence interval (CI) 1.05-1.36, P = 0.007]. Restricted cubic spline (RCS) analysis showed that 7 was the cutoff value at which the effect of PSQI score on mortality changed. Patients with a PSQI score > 7 had a 2.96-fold increased risk of all-cause mortality (HR 2.96, 95% CI 1.15-7.61, P = 0.025). CONCLUSIONS: PSQI score can be used as a predictor of all-cause mortality in dialysis patients, and those with PSQI > 7 were associated with increased odds of mortality.

MicroRNA-140-5p Mediates Renal Fibrosis Through TGF-ß1/Smad Signaling Pathway by Directly Targeting TGFBR1.

Renal tubulointerstitial fibrosis is usually the final outcome of various end-stage renal diseases. Recent studies have reported that microRNAs (miRNAs) play an important role in renal fibrosis. However, the biological function of microRNAs in renal fibrosis is complicated and remains unclear. In this study, our results show that miR-140-5p expression is significantly down-regulated in mice with unilateral ureteral obstruction and human proximal tubule epithelial cells (HK2) treated with TGF-ß1. The knockdown of miR-140-5p upregulates the expression levels of collagen I, collagen IV, and α-SMA, decreases E-cadherin expression, and increases Smad-2/3 phosphorylation. In contrast, the overexpression of miR-140-5p decreases the expression levels of collagen I, collagen IV, and α-SMA, enhances E-cadherin expression, and inhibits the phosphorylation of Smad-2/3 in HK2 cells treated with TGF-ß1. The dual-luciferase reporter assay revealed that TGFBR1 is a direct target gene of miR-140-5p. The enforced expression of miR-140-5p significantly inhibited the expression of TGFBR1 in HK2 cells. Furthermore, the knockdown of TGFBR1 has a similar effect of miR-140-5p overexpression on blocking the TGF-ß1/smad signal pathway activation. In contrast, the overexpression of TGFBR1 reverses the effect of miR-140-5p inhibition on the activation of the TGF-ß1/smad signal pathway. This study demonstrates that miR-140-5p regulates the TGF-ß1/smad signaling pathway by suppressing the expression of TGFBR1. Therefore, miR-140-5p may have a therapeutic potential for preventing fibrotic kidney diseases through inhibiting the TGF-ß1/Smad signaling pathway by directly targeting TGFBR1.

Corticosteroids combined with doublet or single-agent immunosuppressive therapy for active proliferative lupus nephritis.

OBJECTIVES: We performed a meta-analysis to assess whether corticosteroids (C) plus (+) doublet immunosuppressive therapy (IT) is superior to the classical combination of C with single-agent IT in active proliferative lupus nephritis (LN). METHOD: Randomized trials evaluating the benefits and risks of C+doublet versus single-agent IT in active proliferative LN were obtained by searching PubMed, EMBASE, and Cochrane Central Register. The primary outcome was overall response rate (ORR). The secondary outcomes were the change from baseline in Systemic Lupus Erythematosus Disease Activity Index (SLE-DAI) score, negative conversion ratio of anti-double-stranded DNA (anti-dsDNA), and adverse events. The PROSPERO registry number is CRD42017068491. RESULTS: Eleven trials with 1855 patients were included. Compared with C+single-agent IT, C+doublet IT had a significantly higher ORR (relative risk [RR], 1.22; 95% confidence interval [CI], 1.09 to 1.35; P < 0.01). In a subgroup analysis, C+doublet IT without biologics had a significantly higher ORR than C+single-agent IT (RR, 1.30; 95% CI, 1.13 to 1.50; P < 0.01), while C+doublet IT including biologics improved ORR only for refractory severe LN (RR, 1.46; 95% CI, 1.09 to 1.96; P = 0.012). A larger change from baseline in SLE-DAI scores (standardized mean difference, - 0.49; 95% CI, - 0.68 to - 0.30; P < 0.01) and a higher negative conversion ratio of anti-dsDNA (RR, 1.34; 95% CI, 1.06 to 1.69; P = 0.014) were observed with C+doublet IT than with C+single-agent IT. The rates of adverse events were similar between the two regimens. CONCLUSIONS: Compared with single-agent IT, the combination of C and doublet IT without biologics improved clinical outcomes in active proliferative LN. Key Points • Compared with corticosteroids + single-agent immunosuppressive therapy, corticosteroids + doublet immunosuppressive therapy without biologics had a significantly higher overall response rate in active proliferative lupus nephritis. • Compared with corticosteroids + single-agent immunosuppressive therapy, corticosteroids + doublet immunosuppressive therapy including biologics improved overall response rate only for refractory severe lupus nephritis. • A larger change from baseline in SLE-DAI scores and a higher negative conversion ratio of anti-dsDNA were observed with corticosteroids + doublet immunosuppressive therapy than with corticosteroids + single-agent immunosuppressive therapy.

Low level of circulating basophil counts in biopsy-proven active lupus nephritis.

Basophils have been shown to be important players in promoting lupus nephritis (LN). However, the relationship between circulating basophil counts and renal pathology activity of LN remains unclear. In this retrospective study, 159 clinical and pathology samples from patients with biopsy-proven LN were analyzed. The renal activity and classification were evaluated according to renal pathology. The correlations between circulating basophil counts and renal pathology activity index were assessed. Overall, circulating basophil counts correlated with total systemic lupus erythematosus disease activity index (SLEDAI) score (r = - 0.31), renal SLEDAI score (r = - 0.35), activity index (AI) score(r = - 0.40), and renal histologic activity parameters (p < 0.05, respectively). Compared with systemic lupus erythematosus (SLE) non-LN patients, the LN group had lower basophil counts (0.007 ± 0.007 vs. 0.011 ± 0.010 × 109/L, p = 0.04). Subgroup analyses revealed that the circulating basophil counts in group B (AI > 8) were significantly lower than that in group A (AI ≤ 8) (0.004 ± 0.006 vs. 0.009 ± 0.009 × 109/L, p < 0.001). The difference was still significant when eliminating the influence of SLEDAI. Significant differences were found in circulating basophil counts among LN pathology classification groups (p < 0.01). Groups of classes III, IV, and V were more likely to have lower circulating basophil counts when compared with group of class I/II (p < 0.05). These findings suggest a potential role of circulating basophil counts as a convenient and helpful marker for renal activity of LN.

Immunotherapy with dendritic cells and cytokine-induced killer cells for MDA-MB-231 breast cancer stem cells in nude mice.

OBJECTIVE: To compare the effects and safety of immunotherapy using different methods to load DC-CIK cells for MDA-MB-231 breast cancer stem cells. METHODS: A breast cancer model was established in BALB/c nude mice using breast cancer stem cells. All mice were randomly divided into six groups, and each group had three nude mice: the blank control group, the DC-CIK group (group D), the MDA-MB-231 CSC whole-cell lysate DC-CIK group (group L-D), the MDA-MB-231 CSC RNA DC-CIK group (group R-D), the THP DC-CIK group (group T-D) and group THP. Nude mice in groups D, L-D, R-D and T-D were injected with CSCs; 4 days later, the mice were inoculated with 1 × 10(6) DC-CIK cells via the tail vein. This injection was repeated 2 times a week for three weeks. The mice in groups THP and T-D were injected with a 5 mg/Kg dose of THP chemotherapeutic agents via the tail vein the day before DC-CIK injection, which was repeated one time a week for three weeks. Nude mice in the blank control group were injected with normal saline. The weights and sizes of the tumors were measured after the mice were euthanized. The expression of c-Myc, a key proto-oncogene associated with the Akt signaling pathway, was detected with RT-PCR. RESULTS: The tumor growth rates in each group were as follows: group L-D < group R-D < group D < group T-D < blank control group < group THP. The nude mice in groups L-D, R-D and D were normal, active and had a healthy appetite. The mice in groups T-D and THP were lethargic, less active and showed loss of appetite, and their caudal vein was easy to stimulate. The mice in the blank control group were sacrificed during the third week or when their tumors developed ulceration. Compared with the blank control group, c-Myc gene expression was reduced in the tumors of the five experimental groups. CONCLUSION: The results showed that DC-CIK cells stimulated by different methods were highly effect against MDA-MB-231 breast cancer stem cells in nude mice in all groups, especially in group L-D. DC-CIK immunotherapy may provide a new strategy for the clinical treatment of breast cancer.

Basophil count, a marker for disease activity in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disease, with frequent flares amid remissions. Basophils contribute to the immunopathogenesis of SLE. This retrospective clinical study evaluated blood basophil count as a potential marker of SLE activity. This study included 213 patients with SLE, 70 with non-SLE chronic kidney disease (CKD), and 100 healthy volunteers. SLE disease activity was scored using the SLE Disease Activity Index (SLEDAI). Baseline and post-immunosuppressant bioparameters were compared in patients with active SLE, with second samples taken at total SLEDAI ≤4. Blood basophil counts and other conventional biomarkers were compared among the groups. Among the 213 SLE patients (192 women, 21 men; mean age 33.0 ± 12.0 years), 149 had active disease. Basophil counts were significantly lower in patients with SLE than in patients with non-SLE CKD and healthy controls (0.009 ± 0.010 vs. 0.025 ± 0.015 vs. 0.022 ± 0.010 × 10(9)/L, p <0.001), and lower in patients with active than inactive SLE (0.008 ± 0.009 vs. 0.014 ± 0.012 × 10(9)/L, p <0.001). Basophil counts in SLE patients were significantly higher after than before immunosuppressive treatment (0.021 ± 0.017 vs. 0.008 ± 0.008 × 10(9)/L, p <0.001) and correlated with total SLEDAI score (r = -0.30, p <0.001). Receiver operator curve analysis showed that basophil counts were similar to conventional markers (leukocytes, platelets, and double-stranded (ds) DNA IgG) in differentiating active from inactive SLE. These findings indicate that blood basophil counts may be a useful biomarker in evaluating SLE activity.