Search

Introduction: Periodontitis is the main indication for dental extraction and often leads to peri‐implantitis (PI). Alveolar ridge preservation (ARP) is an effective means of preserving ridge dimensions after extraction. However, whether PI prevalence is lower after ARP for extraction after periodontitis remains unclear. This study investigated PI after ARP in patients with periodontitis. Materials and Methods: This study explored the 138 dental implants of 113 patients. The reasons for extraction were categorized as periodontitis or nonperiodontitis. All implants were placed at sites treated using ARP. PI was diagnosed on the basis of radiographic bone loss of ≥3 mm, as determined through comparison of standardized bitewing radiographs obtained immediately after insertion with those obtained after at least 6 months. Chi‐square and two‐sample t testing and generalized estimating equations (GEE) logistic regression model were employed to identify risk factors for PI. Statistical significance was indicated by p < 0.05. Results: The overall PI prevalence was 24.6% (n = 34). The GEE univariate logistic regression demonstrated that implant sites and implant types were significantly associated with PI (premolar vs. molar: crude odds ratios [OR] = 5.27, 95% confidence intervals [CI] = 2.15–12.87, p = 0.0003; bone level vs. tissue level: crude OR = 5.08, 95% CI = 2.10–12.24; p = 0.003, respectively). After adjustment for confounding factors, the risks of PI were significantly associated with implant sites (premolar vs. molar: adjusted OR [AOR] = 4.62, 95% CI = 1.74–12.24; p = 0.002) and implant types (bone level vs. tissue level: AOR = 6.46, 95% CI = 1.67–25.02; p = 0.007). The reason for dental extraction—that is, periodontitis or nonperiodontitis—was not significantly associated with PI. Conclusion: ARP reduces the incidence of periodontitis‐related PI at extraction sites. To address the limitations of our study, consistent and prospective randomized controlled trials are warranted. [ABSTRACT FROM AUTHOR]

Dysnatremia and dyskalemia are common problems in acutely hospitalized elderly patients. These disorders are associated with an increased risk of mortality and functional complications that often occur concomitantly with acute kidney injury in addition to multiple comorbidities. In a single-center prospective observational study, we recruited 401 acute geriatric inpatients. In-hospital outcomes included all-cause mortality, length of stay, and changes in functional status as determined by the Activities of Daily Living (ADL) scale, Eastern Cooperative Oncology Group (ECOG) performance, and Clinical Frailty Scale (CFS). The prevalence of dysnatremia alone, dyskalemia alone, and dysnatremia plus dyskalemia during initial hospitalization were 28.4%, 14.7% and 32.4%, respectively. Patients with electrolyte imbalance exhibited higher mortality rates and longer hospital stays than those without electrolyte imbalance. Those with initial dysnatremia, or dysnatremia plus dyskalemia were associated with worse ADL scores, ECOG performance and CFS scores at discharge. Subgroup analyses showed that resolution of dysnatremia was related to reduced mortality risk and improved CFS score, whereas recovery of renal function was associated with decreased mortality and better ECOG and CFS ratings. Our data suggest that restoration of initial dysnatremia and acute kidney injury during acute geriatric care may benefit in-hospital survival and functional status at discharge. [ABSTRACT FROM AUTHOR]

Background: Older patients are at risk for acute kidney injury and chronic kidney disease. Age-related increases in DNA methylation at CpG islands have been linked to aging-related diseases like cancer and cardiovascular disease, but the exact causal relationship between methylation in renal aging and other kidney diseases remains unclear. This study aimed to elucidate the methylation status of peripheral blood mononuclear cells (PBMCs) in the Asian population. Using human whole blood DNA methylation analysis from the Taiwan Biobank, we included participants with both whole blood genome-wide methylation data and follow-up data on serum creatinine. We investigated hyper- and hypomethylated genes in comparison of participants with higher and lower estimated glomerular filtration (eGFR) decline rate in overall cohort as well as in comparison of old and young participants in subgroup of participants with higher eGFR decline rate. Common genes and signaling pathways in both comparative analyses were identified. Results: Among 1587 participants in the analysis, 187 participants had higher eGFR decline rate. According to the comparison of methylation in participants with different eGFR declines and at different ages, respectively, we identified common hypermethylated genes, including DNMT3A and GGACT, as well as hypomethylated genes such as ARL6IP5, CYB5D1, BCL6, RPRD2, ZNF451, and MIAT in both participants with higher eGFR decline and those of older age. We observed associations between the methylation status of signaling pathways and aging as well as renal function decline. These pathways notably included autophagy, p38 mitogen-activated protein kinases, and sirtuins, which were associated with autophagy process and cytokine production. Conclusions: Through methylation analysis of PBMCs, we identified genes and signaling pathways which could play crucial roles in the interplay of renal aging and renal function decline. These findings contribute to the development of novel biomarkers for identifying at-risk groups and even for therapeutic agent discovery. [ABSTRACT FROM AUTHOR]

Aim: Autonomic dysfunction contributes to cardiovascular morbidity/mortality and can be evaluated with heart rate variability (HRV). This study is to evaluate the prognostic significance of HRV on renal function in non‐dialysis chronic kidney disease (CKD) patients. Methods: We enrolled 326 non‐dialysis CKD patients in this prospective observational study. The median follow‐up period was 2.02 years. Five‐minutes of electrocardiography recordings obtained at enrolment were reprocessed to assess HRV. Five frequency‐domain measures and one time‐domain measures were obtained. Rapid CKD progression was defined as annual estimated glomerular filtration rate (eGFR) loss over 30% per year or eGFR decline rate over 3 mL/min per 1.73 m2 per year. The prevalence of abnormal HRV, associated factors of HRV and impact of HRV on the risk of CKD progression were analyzed. Results: The abnormality of HRV increased along with the severity of CKD. In patients with stage 5 CKD, the proportion of abnormal ln(low frequency power) (LF), ln(high frequency power) (HF), lnLF/HF were 69.5, 52.8 and 50%, respectively. Associated factors of HRV included advanced CKD, diabetes mellitus, serum albumin, severe proteinuria, Beck Anxiety Inventory score, erythropoietin use, renin‐angiotensin system inhibitors and heart failure. Multivariate logistic regression model analysis revealed lower lnLF/HF, hypertension and severe proteinuria were the risk factors of rapid CKD progression. Conclusion: The prevalence of autonomic dysfunction measured by HRV among each stage CKD patients is different. Most patients in advanced CKD stage have reduced values of HRV parameters. The estimation of lnLF/HF also provided prognostic information on CKD progression in addition to classical risk factors. SUMMARY AT A GLANCE: This Taiwanese single centre study (n = 326) examined heart rate variability (a relatively simple measure of autonomic activity) in people with non‐dialysis chronic kidney disease (CKD) and found that abnormalities in this parameter (specifically low proportion of low‐frequency to high‐frequency power, a measure of sympathovagal balance) is an independent predictor of glomerular filtration rate (GFR) decline. [ABSTRACT FROM AUTHOR]

Aims: Diabetic nephropathy (DMN) is usually diagnosed clinically without pathology, and the prognosis of which compared to non-diabetic renal diseases has rarely been investigated especially in ethnic Chinese population. Here we reported the outcome of patients with biopsy-proved DMN compared to those with isolated crescentic glomerulonephritis (GN) or lupus nephritis (LN).Methods: This retrospective observational study included patients with DMN (n = 55), crescentic GN (n = 48) and LN (n = 82) from an original cohort of 987 adult patients who underwent kidney biopsy. The median follow-up period was 8.3 years. The Cox regression model was used to identify factors associated with the outcome measures of end-stage renal disease (ESRD) and all-cause mortality.Results: Patients with DMN and crescentic GN exhibited higher rates of ESRD than LN group (65.5%, 66.7% versus 32.9%, p < 0.001). After accounting for the competing risk of death, DMN versus LN, along with lower hemoglobin values, lower estimated glomerular filtration rates and severe proteinuria were independent predictors for ESRD. Patients with DMN and crescentic GN displayed higher mortality rates than LN patients following the development of ESRD (38.2% and 29.2% versus 9.8%, p < 0.001). Multivariate analysis showed old age (≧65 years) and lower serum albumin levels were independently associated with overall death.Conclusions: Patients with biopsy-proved DMN, but not crescentic GN, showed a greater risk of ESRD than LN counterparts. Given the grave renal prognosis of DMN, more meticulous follow-up is critical to ensure that best therapeutic strategies are used to avert progression to ESRD. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) can increase the risk of developing incident chronic kidney disease (CKD). The severity, frequency and duration of AKI are crucial predictors of poor renal outcome. A repair process after AKI can be adaptive and kidney recovers completely after a mild injury. However, severe injury will lead to a maladaptive repair, which frequently progresses to nephron loss, vascular rarefaction, chronic inflammation and fibrosis. Although different mechanisms underlying AKI‐CKD transition have been extensively discussed, no definite intervention has been proved effective to block or to retard the transition until recently. In CKD, renin‐angiotensin system (RAS) inhibitor has been proved effective to slow down disease progression. Furthermore, RAS needs to be highlighted again in AKI‐CKD transition because recent animal studies have shown the activation of intra‐renal RAS after AKI, and RAS blockade can reduce the ensuing CKD and mortality. In patients with the complete renal recovery after AKI, administration of RAS inhibitor is associated with reduced risk of subsequent CKD as well. In this article, we will demonstrate the role of RAS in AKI‐CKD transition comprehensively. We will then emphasize the promising effect of RAS inhibitor on CKD prevention in patients recovering from AKI based on evidence from the bench to clinical research. All of these discussions will contribute to the establishment of reliable monitoring and therapeutic strategies for patients with functional recovery from AKI who can be most easily ignored. Summary at a Glance: Renin‐angiotensin system (RAS) is activated after AKI and leads to AKI‐CKD continuum. RAS blockade can reduce the ensuing CKD and mortality. Using RAS blockade could be considered for the monitoring and therapeutic strategies after AKI. [ABSTRACT FROM AUTHOR]

Introduction: Ridge deformities in implant sites are common challenges that clinicians face. Great benefits, including reduced treatment cost and time, can be achieved if simultaneous implant placement and guided bone regeneration are feasible. This case report presents an innovative approach using platelet‐rich fibrin (PRF) and autografts to correct an atrophic ridge in conjunction with implant placement. Case Presentation: A 48‐year‐old male patient lost a molar tooth due to severe chronic periodontitis. Because of severe and active infection, socket augmentation was not feasible at the time of tooth extraction, resulting in prominent bone loss in the buccal plate. After implant placement, an autograft was applied for ridge augmentation along with a PRF membrane serving as a barrier. There were no adverse events during healing. An implant prosthesis was delivered 8 months postoperatively. After 1 year of function, both clinical and radiographic examinations revealed promising and stable treatment outcomes. Conclusion: Within the limitations of this case report, application of a PRF membrane may be a feasible approach to serve as a barrier membrane when performing simultaneous implant placement and ridge augmentation procedures. [ABSTRACT FROM AUTHOR]

We investigated the association between antipsychotic medications and the risk of dental caries in patients with schizophrenia. We enroled a nationwide cohort of patients with newly diagnosed schizophrenia within 1 year of dental caries development. Exposure to antipsychotics and other medications was categorised according to their type and duration, and the association between exposure and dental caries was assessed through logistic regressions. Of the 3610 patients with newly diagnosed schizophrenia, 2149 (59.5%) exhibited an incidence of treated dental caries. Logistic regression analysis identified a younger age, female sex, high income, a 2-year history of dental caries, and exposure to first-generation antipsychotics, and antihypertensives as independent risk factors for treated dental caries in patients with schizophrenia. Hyposalivation, the adverse effect of first-generation antipsychotics and antihypertensives, was associated with an increased risk of treated dental caries. However, hypersalivation from first-generation antipsychotics for dental caries was associated with a protective factor. These findings suggest that clinicians should pay attention to the aforementioned risk factors for dental caries in patients with schizophrenia, particularly while prescribing first-generation antipsychotics and antihypertensives to such patients. [ABSTRACT FROM AUTHOR]

ABSTRACT Background: Periodontal disease often results in severely bony defects around the teeth and leads to eventual extraction. Remaining bone morphology often compromises ideally restoration-driven positions and deteriorates the success rates for dental implants. Purpose: The present investigation illustrates the clinical outcome of immediately installing an implant following orthodontic forced eruption and atraumatic extraction. Material and Methods: The subject of this study is a 40-year-old Asian female with a right mandibular first molar that had a deep probing depth on the mesial side and mobility. Via the aid of radiographic examination, the tooth that had an angular bony defect and apical lesion was diagnosed as having deep caries and chronic periodontitis with a poor prognosis. After consultation with the patient, we developed a treatment plan incorporating a forced eruption with immediate implantation, intended to augment the alveolar bone volume and increase the width of keratinized gingivae, in a nonsurgical manner. Results: Following 12 months of orthodontic treatment, the tooth was successfully moved occlusally in conjunction with an 8 mm vertical interdental bone augmentation. Because of sufficient volume of bone and satisfactory gingival dimensions, the implant showed adequate initial stability in the correct position to facilitate physiological and aesthetic prerequisites. After 6 months of ossteointegration, a customized impression coping was utilized to transfer the established emergence profile to a definitive cast for the fabrication of a customized abutment. The final prosthesis was made using a customized metal abutment and ceramometal crown. Conclusion: In the face of difficult clinical challenges, meticulous inspection and a comprehensive treatment plan were crucial. Interdisciplinary treatment through the careful integration of multiple specialists suggests the possibility of optimal results with high predictability. [ABSTRACT FROM AUTHOR]

Aim Matrix metalloproteinase ( MMP)-8 is a protease that degrades numerous extracellular molecules and has been implicated in the pathogenesis of periodontitis. Polymorphism in the MMP-8 could affect the susceptibility to disease. Our aim was to evaluate the association between periodontitis and MMP-8 -799 C> T polymorphism. Material and methods Genomic DNA was obtained from 361 chronic periodontitis patients ( CP), 96 aggressive periodontitis patients ( AgP), and 106 periodontally healthy controls ( HC). MMP-8 -799 C> T polymorphism was determined using the polymerase chain reaction-restriction fragment length polymorphism ( PCR- RFLP). Results The frequencies of genotypes in diseased groups were similar but were significantly different from those in the HC. Multivariate logistic regression analysis with adjustment for age, gender and smoking indicated that increased risks of AgP and CP were associated with the -799 T allele (in AgP, adjusted OR = 1.99, p = 0.04; in CP, adjusted OR = 1.87, p = 0.007). To avoid the confounded effect of smoking on MMP-8 polymorphism to periodontitis, the analysis was conducted on non-smokers and the associations were significant. Conclusions These results suggested that non-smoking Taiwanese with the MMP-8 -799 T allele were associated with the risks of both CP and AgP. Further studies in other ethnic populations are necessary. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) and periodontitis are suggested to be closely linked based on microbial dysbiosis, but limited subgingival bacteria have been proven in the pathogenesis of RA. We enrolled 30 RA patients and 25 controls and divided them into three groups with matched age, gender, and diabetes statuses: group AM (all of the matched participants), group PD (periodontally diseased), and group PH (periodontally healthy). Their subgingival microbial composition was determined by V3–V4 16S rRNA gene sequencing. Significant differences in subgingival microbial clustering between the RA patients and controls were observed in groups AM and PD. Among the taxa enriched in RA, Aminipila butyrica and Peptococcus simiae were the only two species displaying positive correlation to the level of anti-citrullinated protein antibodies (ACPAs) in both of the groups. Surprisingly, the median of relative abundances of A. butyrica and P. simiae were 0% in the controls of group PD. Furthermore, a gene encoding arginine deiminase with the capability to produce citrulline was addressed in the complete genome sequence of A. butyrica. This is the first study to elucidate the important roles of A. butyrica and P. simiae as periodontal bacteria leading to RA possibly through the induction of ACPA production. [ABSTRACT FROM AUTHOR]

Background: Renal ischemia–reperfusion (I/R) injury is a major cause of acute kidney injury (AKI), which is associated with high morbidity and mortality. AKI is a serious and costly medical condition. Effective therapy for AKI is an unmet clinical need, and molecular mechanisms underlying the interactions between an injured kidney and distant organs remain unclear. Therefore, novel therapeutic strategies should be developed. Methods: We directed the differentiation of human induced pluripotent stem (iPS) cells into endothelial progenitor cells (iEPCs), which were then applied for treating mouse AKI. The mouse model of AKI was induced by I/R injury. Results: We discovered that intravenously infused iEPCs were recruited to the injured kidney, expressed the mature endothelial cell marker CD31, and replaced injured endothelial cells. Moreover, infused iEPCs produced abundant proangiogenic proteins, which entered into circulation. In AKI mice, blood urea nitrogen and plasma creatinine levels increased 2 days after I/R injury and reduced after the infusion of iEPCs. Tubular injury, cell apoptosis, and peritubular capillary rarefaction in injured kidneys were attenuated accordingly. In the AKI mice, iEPC therapy also ameliorated apoptosis of cardiomyocytes and cardiac dysfunction, as indicated by echocardiography. The therapy also ameliorated an increase in serum brain natriuretic peptide. Regarding the relevant mechanisms, indoxyl sulfate and interleukin-1β synergistically induced apoptosis of cardiomyocytes. Systemic iEPC therapy downregulated the proapoptotic protein caspase-3 and upregulated the anti-apoptotic protein Bcl-2 in the hearts of the AKI mice, possibly through the reduction of indoxyl sulfate and interleukin-1β. Conclusions: Therapy using human iPS cell-derived iEPCs provided a protective effect against ischemic AKI and remote cardiac dysfunction through the repair of endothelial cells and the attenuation of cardiomyocyte apoptosis. [ABSTRACT FROM AUTHOR]

Background: Cancer cells promote glycolysis, which supports rapid cell growth and proliferation. Phosphofructokinase-fructose bisphosphatases (PFKFBs), a family of bidirectional glycolytic enzymes, play key roles in the regulation of glycolysis in many types of cancer. However, their roles in oral squamous cell carcinoma (OSCC), the most common type of oral cancer, are still unknown. Methods: We compared the gene expression levels of PFKFB family members and analyzed their clinical significance in oral cancer patients, whose clinical data were obtained the Cancer Genome Atlas database. Moreover, real-time quantitative polymerase chain reaction, western blotting, assays for cell viability, cell cycle, cell migration and viability of cell spheroid were performed in scramble and PFKFB-silenced cells. Results: We discovered that PFKFB3 expression in tumor tissues was slightly higher than that in tumor adjacent normal tissues but that PFKFB4 expression was significantly higher in the tumor tissues of oral cancer patients. High PFKFB3 and PFKFB4 expression had different effects on the prognosis of oral cancer patients with different clinicopathological outcomes. Our data showed that PFKFB3 and PFKFB4 play different roles; PFKFB3 is involved in cell viability, G2/M cell cycle progression, invasion, and migration, whereas PFKFB4 is involved in the drug resistance and cancer stemness of OSCC cells. Furthermore, oral cancer patients with co-expressions of PFKFB3/cell cycle or EMT markers and PFKFB4/stemness markers had poor prognosis. Conclusions: PFKFB3 and PFKFB4 play different biological roles in OSCC cells, which implying that they might be potential prognostic biomarkers for OSCC patients with certain clinicopathological outcomes. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate changes in alveolar bone width around dental implants and identify the anterior nasal spine (ANS), posterior nasal spine (PNS), and floor of the nasal cavity that can be used as reference landmarks for standardizing the orientation of different cone‐beam computed tomography (CBCT) scans. Materials and methods: We enrolled two groups that comprised 30 implants. Two CBCT scans from the same patient after implant surgery in the first group were obtained to determine differences in the relative distance and angle between the ANS and apex of the dental implant. Then we compared the second group of patients' presurgical and postsurgical CBCT images to evaluate changes in alveolar bone width after dental implant surgery by the aforementioned bony landmarks. Results: In the first group, no statistically significant differences were detected in the mean distance between the ANS, PNS and implant tip in different directions. In the second group, bone width increased at 1 mm (p = 0.020) and decreased at 4 mm (p < 0.001) and 7 mm (p < 0.001) below the alveolar bone crest after implant surgery. Conclusions: Within the limitations of the present study, the ANS, PNS, and floor of the nasal cavity can be useful in standardizing the orientation of CBCT scans and alveolar bone remodeling after implant surgery varied depending on the height and direction from the alveolar bone crest based on the three landmarks. [ABSTRACT FROM AUTHOR]

Acute kidney injury (AKI) is an independent risk factor for ensuing chronic kidney disease (CKD). Animal studies have demonstrated that renin-angiotensin system (RAS) inhibitor can reduce ensuing CKD after functional recovery from AKI. Here we study the association between ensuing CKD and use of RAS inhibitor including angiotensin converting enzyme inhibitor or angiotensin II type 1a receptor blocker starting after renal functional recovery in our prospectively collected observational AKI cohort. Adult patients who had cardiac surgery-associated AKI (CSA-AKI) are studied. Patients with CKD, unrecovered AKI, and use of RAS inhibitor before surgery are excluded. Among 587 eligible patients, 94 patients are users of RAS inhibitor which is started and continued after complete renal recovery during median follow-up period of 2.99 years. The users of RAS inhibitor show significantly lower rate of ensuing CKD (users vs. non-users, 26.6% vs. 42.2%) and longer median CKD-free survival time (users vs. non-users, 1079 days vs. 520 days). Multivariate Cox regression analyses further demonstrate that use of RAS inhibitor is independently associated with lower risk of ensuing CKD (hazard ratio = 0.46, P < 0.001). We conclude that use of RAS inhibitor in CSA-AKI patients after renal functional recovery is associated with lower risk of ensuing CKD development. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Spironolactone prevents chronic kidney disease caused by ischemic acute kidney injury," by B. C Jonatan and colleagues.

Abstract: Disseminated infections with hemophagocytic syndrome caused by non-tuberculous mycobacteria (NTM) are rare. A 60-year-old woman, who presented with fever, chills, anorexia, and right upper quadrant pain, was admitted to our hospital. Hepatosplenomegaly, pancytopenia, elevated liver aminotransferases, and hyperferritinemia were noted after admission. A gallium scan and chest computed tomography revealed multiple mediastinal lymphadenopathy. A bone marrow examination revealed hemophagocytosis. Bone marrow and liver biopsies showed non-caseating granulomatosis and cultures from bone marrow and liver all yielded Mycobacterium kansasii. The patient responded well to azithromycin, isoniazid, rifampin, and ethambutol. No immunocompromised conditions such as malignancy, autoimmune disease, or HIV infection were detected initially. However, a right femoral tumor with pathological fracture was found five months later during follow-up at the outpatient clinic. Bone biopsy showed granulocytic sarcoma. To our knowledge, this is the first reported case of life-threatening hemophagocytosis due to M. kansasii. Patients with disseminated NTM infections should be closely monitored if any immunocompromising condition develops. [Copyright &y& Elsevier]

Background. Metabolic syndrome (MS) is thought to be a risk marker for cardiovascular diseases in the general population and in patients with chronic kidney disease. This study investigated whether the presence of MS also modifies cardiovascular (CV) outcomes among non-diabetic patients undergoing long-term peritoneal dialysis (PD).Methods. We enrolled 280 patients from a medical centre in North Taiwan who began PD between January 1999 and December 2005 and followed them until December 2009. MS was defined by the modified National Cholesterol Educational Programme (Adult Treatment Panel III) criteria. All parameters and biochemical data were collected by chart review. Patient outcomes (overall and CV death, fatal or non-fatal CV events) were recorded during the follow-up period. Survival was analysed by the Kaplan–Meier method, and the influence of MS and its components on outcomes were analysed by Cox regression models.Results. The average follow-up period was 49.2 months. Non-diabetic patients with MS had worse outcomes than those without MS or at risk for MS, but better than their diabetic counterparts. By multivariate analysis, MS was independently associated with increased risk for CV death (hazard ratio, HR = 13.27) and fatal or non-fatal CV events (HR = 10.50). Among five MS components, hypertriglyceridaemia, low high-density lipoprotein levels and hyperglycaemia were significant risk factors for adverse CV outcomes.Conclusions. MS is a potent risk marker for adverse CV outcomes in non-diabetic patients on PD. Timely interventions targeting specific component of this syndrome may be required in this subset of patients. [ABSTRACT FROM PUBLISHER]

Background: Renal erythropoietin (EPO)-producing (REP) cells produce EPO through hypoxia-inducible factor (HIF) 2α-activated gene transcription. Insufficient EPO production leads to anemia in patients with chronic kidney disease. Although recombinant EPO is effective to improve anemia, no reliable REP cell lines limit further progress of research and development of novel treatment. Methods: We screened Epo mRNA expression in mouse fibroblast cell lines. Small interfering RNA specific for HIF1α or HIF2α was transfected to study Epo expression in C3H10T1/2 cells. The effect of transforming growth factor-β1 (TGF-β1) on HIF-EPO axis was studied in C3H10T1/2 cells and mice. Results: Similar to mouse REP pericytes, C3H10T1/2 cells differentiated to α-smooth muscle actin+ myofibroblasts after exposure to TGF-β1. Specific HIF knockdown demonstrated the role of HIF2α in hypoxia-induced Epo expression. Sustained TGF-β1 exposure increased neither DNA methyltransferase nor methylation of Epas1 and Epo genes. However, TGF-β1 repressed HIF2α-encoding Epas1 promptly through activating activin receptor-like kinase-5 (ALK5), thereby decreasing Epo induction by hypoxia and prolyl hydroxylase domain inhibitor roxadustat. In mice with pro-fibrotic injury induced by ureteral obstruction, upregulation of Tgfb1 was accompanied with downregulation of Epas1 and Epo in injured kidneys and myofibroblasts, which were reversed by ALK5 inhibitor SB431542. Conclusion: C3H10T1/2 cells possessed the property of HIF2α-dependent Epo expression in REP pericytes. TGF-β1 induced not only the transition to myofibroblasts but also a repressive effect on Epas1-Epo axis in C3H10T1/2 cells. The repressive effect of TGF-β1 on Epas1-Epo axis was confirmed in REP pericytes in vivo. Inhibition of TGF-β1-ALK5 signaling might provide a novel treatment to rescue EPO expression in REP pericytes of injured kidney. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to assess whether alveolar ridge preservation (ARP) can reduce the need of ridge augmentation at posterior tooth sites. Material and methods: This study enrolled patients who received dental implants at posterior tooth sites during 2013–2019. Demographic data and dental treatment histories were collected. Based on healing patterns after tooth extraction, patients were divided into ARP and spontaneous healing (SH) groups. Three surgical treatment plans were devised according to the alveolar bone volume on cone-beam computed tomography (CBCT). The three treatment plans were to perform implant alone, simultaneous guided bone regeneration (GBR) and implantation, and staged GBR before implantation. Statistical analyses were performed to determine relationships. Results: There were 92 implant records in the ARP group and 249 implant records in the SH group. A significant intergroup difference was observed regarding the frequency distribution of the treatment modality of staged GBR before implant (χ2 = 15.07, p = 0.0005). Based on the implant alone treatment modality and simple logistic regression, the SH pattern was related to staged GBR before implant (SH vs. ARP: crude odds ratio (OR) = 4.65, 95% confidence interval (CI) = 2.15–11.61, p = 0.0003). After adjusting confounding factors, the risk was still significant (adjusted OR = 5.02, 95% CI = 2.26–12.85, p = 0.0002). Conclusions: The study results suggested that ARP is more likely to lead to the treatment modality of implant alone and reduce the need for staged GBR before implantation. Clinical relevance: This study describes ARP capable of minimizing the need for staged GBR before implantation and shortening the treatment duration. [ABSTRACT FROM AUTHOR]

The origin and fate of renal myofibroblasts is not clear after acute kidney injury (AKI). Here, we demonstrate that myofibroblasts were activated from quiescent pericytes (qPericytes) and the cell numbers increased after ischemia/reperfusion injury-induced AKI (IRI-AKI). Myofibroblasts underwent apoptosis during renal recovery but one-fifth of them survived in the recovered kidneys on day 28 after IRI-AKI and their cell numbers increased again after day 56. Microarray data showed the distinctive gene expression patterns of qPericytes, activated pericytes (aPericytes, myofibroblasts), and inactivated pericytes (iPericytes) isolated from kidneys before, on day 7, and on day 28 after IRI-AKI. Hypermethylation of the Acta2 repressor Ybx2 during IRI-AKI resulted in epigenetic modification of iPericytes to promote the transition to chronic kidney disease (CKD) and aggravated fibrogenesis induced by a second AKI induced by adenine. Mechanistically, transforming growth factor-β1 decreased the binding of YBX2 to the promoter of Acta2 and induced Ybx2 hypermethylation, thereby increasing α-smooth muscle actin expression in aPericytes. Demethylation by 5-azacytidine recovered the microvascular stabilizing function of aPericytes, reversed the profibrotic property of iPericytes, prevented AKI-CKD transition, and attenuated fibrogenesis induced by a second adenine-AKI. In conclusion, intervention to erase hypermethylation of pericytes after AKI provides a strategy to stop the transition to CKD. [ABSTRACT FROM AUTHOR]

Renal erythropoietin-producing cells (REPCs) remain in the kidneys of patients with chronic kidney disease, but these cells do not produce sufficient erythropoietin in response to hypoxic stimuli. Treatment with HIF stabilizers rescues erythropoietin production in these cells, but the mechanisms underlying the decreased response of REPCs in fibrotic kidneys to anemic stimulation remain elusive. Here, we show that fibroblast-like FOXD1+ progenitor-derived kidney pericytes, which are characterized by the expression of α1 type I collagen and PDGFRβ, produce erythropoietin through HIF2α regulation but that production is repressed when these cells differentiate into myofibroblasts. DNA methyltransferases and erythropoietin hypermethylation are upregulated in myofibroblasts. Exposure of myofibroblasts to nanomolar concentrations of the demethylating agent 5-azacytidine increased basal expression and hypoxic induction of erythropoietin. Mechanistically, the profibrotic factor TGF-β1 induced hypermethylation and repression of erythropoietin in pericytes; these effects were prevented by 5-azacytidine treatment. These findings shed light on the molecular mechanisms underlying erythropoietin repression in kidney myofibroblasts and demonstrate that clinically relevant, nontoxic doses of 5-azacytidine can restore erythropoietin production and ameliorate anemia in the setting of kidney fibrosis in mice. [ABSTRACT FROM AUTHOR]

Bone extraction and division can enhance the accuracy of diagnoses based on whole-body bone SPECT data. This study developed a method for using conventional SPECT for automatic recognition of the vertebral column. A novel feature of the proposed approach is a novel "bone graph" image description method that represents the connectivity between these image regions to facilitate manipulation of morphological relationships in the skeleton before surgery. By tracking the paths shown on the bone graph, skeletal structures can be identified by performing morphological operations. The performance of the method was evaluated quantitatively and qualitatively by two experienced nuclear medicine physicians. Datasets for whole-body bone SPECT scans in 46 lung cancer patients with bone metastasis were obtained with Tc-99m MDP. The algorithm successfully segmented vertebrae in the thoracolumbar spine. The quantitative assessment shows that the segmentation method achieved an average TP, FP, and FN rates of 95.1%, 9.1%, and 4.9%. The qualitative evaluation shows an average acceptance rate of 83%, where the data for the acceptable and unacceptable groups had a Cronbach's alpha value of 0.718, which indicated reasonable internal consistency and reliability. [ABSTRACT FROM AUTHOR]

Pericytes are the major source of scar-producing myofibroblasts following kidney injury; however, the mechanisms of this transition are unclear. To clarify this, we examined Collagen 1 (α1)-green fluorescent protein (GFP) reporter mice (pericytes and myofibroblasts express GFP) following ureteral obstruction or ischemia-reperfusion injury and focused on the role of platelet-derived growth factor (PDGF)-receptor (PDGFR) signaling in these two different injury models. Pericyte proliferation was noted after injury with reactivation of α-smooth muscle actin expression, a marker of the myofibroblast phenotype. PDGF expression increased in injured tubules, endothelium, and macrophages after injury, whereas PDGFR subunits α and β were expressed exclusively in interstitial GFP-labeled pericytes and myofibroblasts. When PDGFRα or PDGFRβ activation was inhibited by receptor-specific antibody following injury, proliferation and differentiation of pericytes decreased. The antibodies also blunted the injury-induced transcription of PDGF, transforming growth factor β1, and chemokine CCL2. They also reduced macrophage infiltration and fibrosis. Imatinib, a PDGFR tyrosine kinase inhibitor, attenuated pericyte proliferation and kidney fibrosis in both fibrogenic models. Thus, PDGFR signaling is involved in pericyte activation, proliferation, and differentiation into myofibroblasts during progressive kidney injury. Hence, pericytes may be a novel target to prevent kidney fibrosis by means of PDGFR signaling blockade. [ABSTRACT FROM AUTHOR]

The aim of this study was to use a cone-beam computed tomography (CBCT) to assess changes in alveolar bone width around dental implants at native and reconstructed bone sites before and after implant surgery. A total of 99 implant sites from 54 patients with at least two CBCT scans before and after implant surgery during 2010–2019 were assessed in this study. Demographic data, dental treatments and CBCT scans were collected. Horizontal alveolar bone widths around implants at three levels (subcrestal width 1 mm (CW1), subcrestal width 4 mm (CW4), and subcrestal width 7 mm (CW7)) were measured. A p-value of < 0.05 indicated statistically significant differences. The initial bone widths (mean ± standard deviation (SD)) at CW1, CW4, and CW7 were 6.98 ± 2.24, 9.97 ± 2.64, and 11.33 ± 3.00 mm, respectively, and the postsurgery widths were 6.83 ± 2.02, 9.58 ± 2.55, and 11.19 ± 2.90 mm, respectively. The change in bone width was 0.15 ± 1.74 mm at CW1, 0.39 ± 1.12 mm at CW4 (p = 0.0008), and 0.14 ± 1.05 mm at CW7. A statistically significant change in bone width was observed at only the CW4 level. Compared with those at the native bone sites, the changes in bone width around implants at reconstructed sites did not differ significantly. A significant alveolar bone width resorption was found only at the middle third on CBCT scans. No significant changes in bone width around implants were detected between native and reconstructed bone sites. [ABSTRACT FROM AUTHOR]