The fate of immune complexes in membranous nephropathy.

The most characteristic feature of membranous nephropathy (MN) is the presence of subepithelial electron dense deposits and the consequential thickening of the glomerular basement membrane. There have been great advances in the understanding of the destiny of immune complexes in MN by the benefit of experimental models represented by Heymann nephritis. Subepithelial immune complexes are formed in situ by autoantibodies targeting native autoantigens or exogenous planted antigens such as the phospholipase A2 receptor (PLA2R) and cationic BSA respectively. The nascent immune complexes would not be pathogenic until they develop into immune deposits. Podocytes are the major source of autoantigens in idiopathic membranous nephropathy. They also participate in the modulation and removal of the immune complexes to a large extent. The balance between deposition and clearance is regulated by a wide range of factors such as the composition and physicochemical properties of the immune complexes and the complement system. Complement components such as C3 and C1q have been reported to be precipitated with the deposits whereas a complement regulatory protein CR1 expressed by podocytes is involved in the phagocytosis of immune complexes by podocytes. Podocytes regulate the dynamic change of immune complexes which is disturbed in membranous nephropathy. To elucidate the precise fate of the immune complexes is essential for developing more rational and novel therapies for membranous nephropathy.

ECM-Mimicking Strontium-Doped Nanofibrous Microspheres for Periodontal Tissue Regeneration in Osteoporosis.

Regenerating periodontal defects in osteoporosis patients presents a significant clinical challenge. Unlike the relatively straightforward regeneration of homogeneous bone tissue, periodontal regeneration requires the intricate reconstruction of the cementum-periodontal ligament-alveolar bone interface. Strontium (Sr)-doped biomaterials have been extensively utilized in bone tissue engineering due to their remarkable pro-osteogenic attributes. However, their application in periodontal tissue regeneration has been scarcely explored. In this study, we synthesized an innovative injectable Sr-BGN/GNM scaffold by integrating Sr-doped bioactive glass nanospheres (Sr-BGNs) into the nanofiber architecture of gelatin nanofiber microspheres (GNMs). This design, mimicking the natural bone extracellular matrix (ECM), enhanced the scaffold's mechanical properties and effectively controlled the sustained release of Sr ions (Sr2+), thereby promoting the proliferation, osteogenic differentiation, and ECM secretion of PDLSCs and BMSCs, as well as enhancing vascularization in endothelial cells. In vivo experiments further indicated that the Sr-BGNs/GNMs significantly promoted osteogenesis and angiogenesis. Moreover, the scaffold's tunable degradation kinetics optimized the prolonged release and pro-regenerative effects of Sr2+ in vivo, matching the pace of periodontal regeneration and thereby facilitating the regeneration of functional periodontal tissues under osteoporotic conditions. Therefore, Sr-BGNs/GNMs emerge as a promising candidate for advancing periodontal regeneration strategies.

A simple protocol to establish a conditionally immortalized mouse podocyte cell line.

Podocytes are specialized terminally differentiated cells in the glomerulus that are the primary target cells in many glomerular diseases. However, the current podocyte cell lines suffer from prolonged in vitro differentiation and limited survival time, which impede research progress. Therefore, it is necessary to establish a cell line that exhibits superior performance and characteristics. We propose a simple protocol to obtain an immortalized mouse podocyte cell (MPC) line from suckling mouse kidneys. Primary podocytes were cultured in vitro and infected with the SV40 tsA58 gene to obtain immortalized MPCs. The podocytes were characterized using Western blotting and quantitative real-time PCR. Podocyte injury was examined using the Cell Counting Kit-8 assay and flow cytometry. First, we successfully isolated an MPC line and identified 39 °C as the optimal differentiation temperature. Compared to undifferentiated MPCs, the expression of WT1 and synaptopodin was upregulated in differentiated MPCs. Second, the MPCs ceased proliferating at a nonpermissive temperature after day 4, and podocyte-specific proteins were expressed normally after at least 15 passages. Finally, podocyte injury models were induced to simulate podocyte injury in vitro. In summary, we provide a simple and popularized protocol to establish a conditionally immortalized MPC, which is a powerful tool for the study of podocytes.

Single cell landscape of parietal epithelial cells in healthy and diseased states.

The biology and diversity of glomerular parietal epithelial cells (PECs) are important for understanding podocyte regeneration and crescent formation. Although protein markers have revealed the morphological heterogeneity of PECs, the molecular characteristics of PEC subpopulations remain largely unknown. Here, we performed a comprehensive analysis of PECs using single-cell RNA sequencing (scRNA-seq) data. Our analysis identified five distinct PEC subpopulations: PEC-A1, PEC-A2, PEC-A3, PEC-A4 and PEC-B. Among these subpopulations, PEC- A1 and PEC-A2 were characterized as podocyte progenitors while PEC-A4 represented tubular progenitors. Further dynamic signaling network analysis indicated that activation of PEC-A4 and the proliferation of PEC-A3 played pivotal roles in crescent formation. Analyses suggested that upstream signals released by podocytes, immune cells, endothelial cells and mesangial cells serve as pathogenic signals and may be promising intervention targets in crescentic glomerulonephritis. Pharmacological blockade of two such pathogenic signaling targets, proteins Mif and Csf1r, reduced hyperplasia of the PECs and crescent formation in anti-glomerular basement membrane glomerulonephritis murine models. Thus, our study demonstrates that scRNA-seq-based analysis provided valuable insights into the pathology and therapeutic strategies for crescentic glomerulonephritis.

Simultaneous Recovery of Nitrogen and Phosphorus from Sewage by Magnesium Ammonium Phosphate Method with Magnesium-Loaded Bentonite.

Excessive nitrogen (N) and phosphorus (P) result in serious eutrophication of water. In this study, magnesium modified acid bentonite was prepared by the impregnation method, and nitrogen and phosphorus were simultaneously removed by the magnesium ammonium phosphate method (MAP), which solved the problem of the poor adsorption capacity of bentonite. The morphology and structure of MgO-SBt were characterized by XRD, FT-IR, SEM, EDS, XPS, BET, etc. The results show that the acidified bentonite can increase the distance between bentonite layers, the layer spacing is expanded to 1.560 nm, and the specific surface area is expanded to 95.433 m2/g. After Mg modification, the characteristic peaks of MgO appear at 2θ of 42.95°, 62.31°, and 78.72°, indicating that MgO has been successfully loaded and that MgO bonded to the surface and interior pores of the acidified bentonite, boosting adsorption performance. When the dosage of MgO-SBt is 0.25 g/L, pH = 9, and N/P ratio is 5:1, the maximum adsorption capacity of MgO-SBt for N and P can reach 193.448 mg/g and 322.581 mg/g. In addition, the mechanism of the simultaneous adsorption of nitrogen and phosphorus by MgO-SBt was deeply characterized by the kinetic model, isothermal adsorption model, and thermodynamic model. The results showed that the simultaneous adsorption of nitrogen and phosphorus by MgO-SBt was chemisorption and a spontaneous exothermic process.

Course monitoring of membranous nephropathy: Both autoantibodies and podocytes require multidimensional attention.

A variety of podocyte antigens have been identified in human membranous nephropathy (MN), which is divided into various antigen-dominated subtypes, confirming the concept that MN is the common pattern of glomerular injury in multiple autoimmune responses. The detection of autoantibodies, which has been widely used in the clinical practice of MN, may lead to personalized precision medicine. However, given the potential risks of immunosuppressive therapy, more autoantibodies and biomarkers need to be identified to predict the prognosis and therapeutic response of MN more accurately. In this review, we attempted to summarize the autoantigens/autoantibodies and autoimmune mechanisms that can predict disease states based on the current understanding of MN pathogenesis, especially the podocyte injury manifestations. In conclusion, both the autoimmune response and podocyte injury require multidimensional attention in the disease course of MN.

Triose Kinase Controls the Lipogenic Potential of Fructose and Dietary Tolerance.

The surge in fructose consumption is a major factor behind the rapid rise of nonalcoholic fatty liver disease in modern society. Through flux and genetic analyses, we demonstrate that fructose is catabolized at a much higher rate than glucose, and triose kinase (TK) couples fructolysis with lipogenesis metabolically and transcriptionally. In the absence of TK, fructose oxidation is accelerated through the activation of aldehyde dehydrogenase (ALDH) and serine biosynthesis, accompanied by increased oxidative stress and fructose aversion. TK is also required by the endogenous fructolysis pathway to drive lipogenesis and hepatic triglyceride accumulation under high-fat diet and leptin-deficient conditions. Intriguingly, a nonsynonymous TK allele (rs2260655_A) segregated during human migration out of Africa behaves as TK null for its inability to rescue fructose toxicity and increase hepatic triglyceride accumulation. Therefore, we posit TK as a metabolic switch controlling the lipogenic potential of fructose and its dietary tolerance.

The effect of haemostatic agents on early healing of the extraction socket.

AIM: This study aims to explore the effect of two commercially available haemostatic agents (i.e., collagen sponge and oxide cellulose) on early healing of the extraction socket. MATERIAL AND METHODS: In a murine model, bilateral maxillary first molars were extracted and the sockets were filled with or without haemostatic agents. Histology, histomorphometry and immunostaining assays were performed on samples harvested on postextraction day 1, 3, 7 and 14. In vitro studies were also designed to investigate the effect of agents on the dynamics of pH and viability of cells. RESULTS: Early socket healing was delayed by both agents but with different patterns. The migration of cells was impeded by oxide cellulose on postextraction day 1 compared with the collagen and the control group. The proliferation and osteogenic differentiation of cells were delayed by both materials. Moreover, apoptosis of periodontal ligament cells was present in the haemostatic agent groups. These effects are attributed to the compression to periodontal ligament by both agents, the acidic niche caused by oxide cellulose, and the intense foreign body reaction and inflammatory response caused by the agents. CONCLUSIONS: The placement of haemostatic agents delay the early extraction socket healing via different biological mechanism.

Screening the Expression Changes in MicroRNAs and Their Target Genes in Mature Cementoblasts Stimulated with Cyclic Tensile Stress.

Cementum is a thin layer of cementoblast-produced mineralized tissue covering the root surfaces of teeth. Mechanical forces, which are produced during masticatory activity, play a paramount role in stimulating cementoblastogenesis, which thereby facilitates the maintenance, remodeling and integrity of cementum. However, hitherto, the extent to which a post-transcriptional modulation mechanism is involved in this process has rarely been reported. In this study, a mature murine cementoblast cell line OCCM-30 cells (immortalized osteocalcin positive cementoblasts) was cultured and subjected to cyclic tensile stress (0.5 Hz, 2000 µstrain). We showed that the cyclic tensile stress could not only rearrange the cell alignment, but also influence the proliferation in an S-shaped manner. Furthermore, cyclic tensile stress could significantly promote cementoblastogenesis-related genes, proteins and mineralized nodules. From the miRNA array analyses, we found that 60 and 103 miRNAs were significantly altered 6 and 18 h after the stimulation using cyclic tensile stress, respectively. Based on a literature review and bioinformatics analyses, we found that miR-146b-5p and its target gene Smad4 play an important role in this procedure. The upregulation of miR-146b-5p and downregulation of Smad4 induced by the tensile stress were further confirmed by qRT-PCR. The direct binding of miR-146b-5p to the three prime untranslated region (3' UTR) of Smad4 was established using a dual-luciferase reporter assay. Taken together, these results suggest an important involvement of miR-146b-5p and its target gene Smad4 in the cementoblastogenesis of mature cementoblasts.

Enamel etching for bonding fixed orthodontic braces.

BACKGROUND: Acid etching of tooth surfaces to promote the bonding of orthodontic attachments to the enamel has been a routine procedure in orthodontic treatment since the 1960s. Various types of orthodontic etchants and etching techniques have been introduced in the past five decades. Although a large amount of information on this topic has been published, there is a significant lack of consensus regarding the clinical effects of different dental etchants and etching techniques. OBJECTIVES: To compare the effects of different dental etchants and different etching techniques for the bonding of fixed orthodontic appliances. SEARCH METHODS: We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 8 March 2013), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 2), MEDLINE via OVID (to 8 March 2013), EMBASE via OVID (to 8 March 2013), Chinese Biomedical Literature Database (to 12 March 2011), the WHO International Clinical Trials Registry Platform (to 8 March 2013) and the National Institutes of Health Clinical Trials Registry (to 8 March 2013). A handsearching group updated the handsearching of journals, carried out as part of the Cochrane Worldwide Handsearching Programme, to the most current issue. There were no restrictions regarding language or date of publication. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing different etching materials, or different etching techniques using the same etchants, for the bonding of fixed orthodontic brackets to incisors, canines and premolars in children and adults. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and assessed the risk of bias of included studies independently and in duplicate. We resolved disagreements by discussion among the review team. We contacted the corresponding authors of the included studies to obtain additional information, if necessary. MAIN RESULTS: We included 13 studies randomizing 417 participants with 7184 teeth/brackets. We assessed two studies (15%) as being at low risk of bias, 10 studies (77%) as being at high risk of bias and one study (8%) as being at unclear risk of bias. Self etching primers (SEPs) versus conventional etchantsEleven studies compared the effects of SEPs with conventional etchants. Only five of these studies (three of split-mouth design and two of parallel design) reported data at the participant level, with the remaining studies reporting at the tooth level, thus ignoring clustering/the paired nature of the data. A meta-analysis of these five studies, with follow-up ranging from 5 to 37 months, provided low-quality evidence that was insufficient to determine whether or not there is a difference in bond failure rate between SEPs and convention etchants (risk ratio 1.14; 95% confidence interval (CI) 0.75 to 1.73; 221 participants). The uncertainty in the CI includes both no effect and appreciable benefit and harm. Subgroup analysis did not show a difference between split-mouth and parallel studies.There were no data available to allow assessment of the outcomes: decalcification, participant satisfaction and cost-effectiveness. One study reported decalcification, but only at the tooth level. SEPs versus SEPsTwo studies compared two different SEPs. Both studies reported bond failure rate, with one of the studies also reporting decalcification. However, as both studies reported outcomes only at the tooth level, there were no data available to evaluate the superiority of any of the SEPs over the others investigated with regards to any of the outcomes of this review.We did not find any eligible studies evaluating different etching materials (e.g. phosphoric acid, polyacrylic acid, maleic acid), concentrations or etching times. AUTHORS' CONCLUSIONS: We found low-quality evidence that was insufficient to conclude whether or not there is a difference in bond failure rate between SEPs and conventional etching systems when bonding fixed orthodontic appliances over a 5- to 37-month follow-up. Insufficient data were also available to allow any conclusions to be formed regarding the superiority of SEPs or conventional etching for the outcomes: decalcification, participant satisfaction and cost-effectiveness, or regarding the superiority of different etching materials, concentrations or etching times, or of any one SEP over another. Further well-designed RCTs on this topic are needed to provide more evidence in order to answer these clinical questions.

Effect of parathyroid hormone on experimental tooth movement in rats.

INTRODUCTION: The aim of this study was to investigate the effect of parathyroid hormone injection on experimental tooth movement in rats. METHODS: Sixty male Wistar rats were randomly divided into 2 groups. Their maxillary right first molars were moved mesially with nickel-titanium closed-coil springs. The experimental group received daily subcutaneous injections of parathyroid hormone at a dose of 4 µg per 100 g of body weight for 12 days, and the control group received vehicle injections. The results were evaluated by intraoral measurements and by hematoxylin and eosin, tartrate-resistant acid phosphatase, and immunohistochemistry staining. RESULTS: The tooth movement and osteoclast numbers were significantly increased in the parathyroid hormone group compared with the control group. The expressions of receptor activator of nuclear factor kappa B ligand and insulin-like growth factor-I were significantly stimulated in the parathyroid hormone group. CONCLUSIONS: The data suggest that short-term parathyroid hormone injection might be a potential method for accelerating orthodontic tooth movement by increasing the alveolar bone turnover rate.

Distalization of the mandibular dentition of an adult with a skeletal Class III malocclusion.

This case report describes the orthodontic treatment of an 18-year-old woman with a skeletal Class III malocclusion and a midline deviation. The treatment plan consisted of distalizing the mandibular dentition asymmetrically and producing space for retraction of the mandibular anterior teeth. Short Class III elastics, an open-coil spring, and the mulitloop edgewise archwire technique were used, combining the entire maxillary dentition as integrated anchorage. The active treatment period was 26 months. Normal overbite and overjet were obtained, and facial balance was improved.

Craniofacial morphology characteristics of operated unilateral complete cleft lip and palate patients in mixed dentition.

OBJECTIVE: The objective of this study was to analyze craniofacial morphologic characteristics at the stage of mixed dentition in Chinese children who had received surgery for unilateral complete cleft lip and palate (UCCLP) compared with the healthy population. MATERIAL AND METHODS: Lateral cephalometric radiographs were taken for 2 groups of individuals: (1) 48 UCCLP patients who had been operated on before 2 years of age, and (2) 60 noncleft peers as controls. RESULTS: The operated UCCLP groups differed from the control group as follows: reduced cranial base length, less maxillary length, more retrognathic maxilla, retusion of the entire maxilla, more incongruous intermaxillary relation, more concave skeletal profile, and more lingually inclined maxillary and mandibular incisors. CONCLUSIONS: The operated UCCLP children at the mixed dentition stage showed serious craniofacial deformities and the craniofacial growth was influenced (especially in maxilla).

Soft-tissue characteristics of operated unilateral complete cleft lip and palate patients in mixed dentition.

PURPOSE: The purpose of the study was to provide quantitative information about the facial soft-tissue characteristics of operated unilateral complete cleft lip and palate (UCCLP) children compared with healthy children during mixed dentition. METHODS: Lateral cephalometric radiographs of 48 children with UCCLP who had been operated on before the age of 2 years were analyzed and compared with those of a control group of 60 healthy children with the same age, sex, and ethnic characteristics. RESULTS: The children with operated UCCLP differed from the control group by having a more concave profile, flatter nasal tip, more retrognathic basis nasi, shorter upper lip, thicker upper and lower lip, reduced upper-lip projection, and increased lower-lip projection. CONCLUSIONS: The facial soft-tissue morphology in operated UCCLP patients differed from normal controls of the same age, sex, and ethnic group. It may be necessary for children with UCCLP operated before 2 years of age to have some preventive treatment.

Secondary bone grafting for alveolar cleft in children with cleft lip or cleft lip and palate.

BACKGROUND: Secondary alveolar bone grafting has been widely used to reconstruct alveolar cleft. However, there is still some controversy. OBJECTIVES: To compare the effectiveness and safety of different secondary bone grafting methods. SEARCH STRATEGY: The final electronic and handsearches were carried out on 11 February 2011, and included the Cochrane Oral Health Group's Trials Register, Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Chinese Biomedical Literature Database and WHO International Clinical Trials Registry Platform. All the Chinese professional journals in the oral and dental field were handsearched and conference proceedings consulted. There was no language or time restriction. SELECTION CRITERIA: Only randomized clinical trials were selected. Patients with the diagnosis of cleft lip and alveolar process only, unilateral cleft lip and palate and bilateral cleft lip and palate involving the alveolar process and greater than 5 years of age were included. DATA COLLECTION AND ANALYSIS: Two review authors extracted data and assessed the quality of included studies independently. Disagreement between the two review authors was resolved by discussion in the review team. The first authors of the included studies were contacted for additional information, if necessary. MAIN RESULTS: Two of 582 potential studies met the inclusion criteria and were included. One trial compared alveolar bone grafting using artificial materials (InFuse bone graft substitute impregnated with BMP-2) with a traditional iliac graft. The other trial investigated the application of fibrin glue to the bone graft. Both trials were small with 21 and 27 patients and were assessed as being at high risk of bias. Any apparent differences between the interventions for outcomes in either study must therefore be treated with great caution and are not highlighted here. AUTHORS' CONCLUSIONS: Due to the high level of risk of bias in the two included trials there is insufficient evidence to conclude that one intervention is superior to another.

Correlation between dental maturity and cervical vertebral maturity.

OBJECTIVE: The aim of this study was to investigate the association between dental and skeletal maturity. STUDY DESIGN: Digital panoramic radiographs and lateral skull cephalograms of 302 patients (134 boys and 168 girls, ranging from 8 to 16 years of age) were examined. Dental maturity was assessed by calcification stages of the mandibular canines, first and second premolars, and second molars, whereas skeletal maturity was estimated by the cervical vertebral maturation (CVM) stages. The Spearman rank-order correlation coefficient was used to measure the association between CVM stage and dental calcification stage of individual teeth. RESULTS: The mean chronologic age of girls was significantly lower than that of boys in each CVM stage. The Spearman rank-order correlation coefficients between dental maturity and cervical vertebral maturity ranged from 0.391 to 0.582 for girls and from 0.464 to 0.496 for boys (P < 0.05). In girls, the mandibular second molar had the highest and the canine the lowest correlation. In boys, the canine had the highest and the first premolar the lowest correlation. CONCLUSIONS: Tooth calcification stage was significantly correlated with cervical vertebral maturation stage. The development of the mandibular second molar in females and that of the mandibular canine in males had the strongest correlations with cervical vertebral maturity. Therefore, it is practical to consider the relationship between dental and skeletal maturity when planning orthodontic treatment.