Potential application of Klotho as a prognostic biomarker for patients with diabetic kidney disease: a meta-analysis of clinical studies.

Background: Diabetic kidney disease (DKD) is a serious diabetic complication and the performance of serum Klotho in DKD's prognostic evaluation is controversial. Objective: To assess the association of serum Klotho with adverse kidney and non-kidney clinical outcomes in patients with DKD. Design: Clinical studies regarding the relationship of serum Klotho with DKD were included. Study quality was assessed using the Newcastle-Ottawa scale. Subgroup and sensitive analyses were performed to search for the source of heterogeneity. Data sources and methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane library databases up to 27 September 2022. The associations of Klotho with albuminuria, such as the urinary albumin creatinine ratio (UACR), kidney outcomes such as persistent albuminuria, estimated glomerular filtration rate decline, and non-kidney outcomes such as diabetic retinopathy, cardiovascular morbidity, and mortality, were evaluated. The indicators, such as the correlation coefficient (r), odds ratio (OR), relative risk, and hazard ratio, were retrieved or calculated from the eligible studies. Results: In all, 17 studies involving 5682 participants fulfilled the inclusion criteria and were included in this meta-analysis. There was no significant association of serum Klotho with UACR in DKD patients [summary r, -0.28 (-0.55, 0.04)] with high heterogeneity. By contrast, a strong association was observed regarding serum Klotho with kidney outcomes [pooled OR, 1.60 (1.15, 2.23)], non-kidney outcomes [pooled OR, 2.78 (2.11, 3.66)], or combined kidney and non-kidney outcomes [pooled OR, 1.96 (1.45, 2.65)] with moderate heterogeneity. Subgroup analysis indicated that age, study design, and the estimated glomerular filtration rate may be the sources of heterogeneity. Conclusion: A decreased serum Klotho level is possibly associated with an increased risk of developing kidney and non-kidney clinical outcomes in DKD patients; thus, Klotho may be a possible biomarker to predict DKD clinical outcomes. Additional studies are needed to clarify and validate Klotho's prognostic value.

Upstream and downstream regulators of Klotho expression in chronic kidney disease.

Klotho is a critical protein that protects the kidney. Klotho is severely downregulated in chronic kidney disease (CKD), and its deficiency is implicated in the pathogenesis and progression of CKD. Conversely, an increase in Klotho levels results in improved kidney function and delays CKD progression, supporting the notion that modulating Klotho levels could represent a possible therapeutic strategy for CKD treatment. Nevertheless, the regulatory mechanisms responsible for the loss of Klotho remain elusive. Previous studies have demonstrated that oxidative stress, inflammation, and epigenetic modifications can modulate Klotho levels. These mechanisms result in a decrease in Klotho mRNA transcript levels and reduced translation, thus can be grouped together as upstream regulatory mechanisms. However, therapeutic strategies that aim to rescue Klotho levels by targeting these upstream mechanisms do not always result in increased Klotho, indicating the involvement of other regulatory mechanisms. Emerging evidence has shown that endoplasmic reticulum (ER) stress, the unfolded protein response, and ER-associated degradation also affect the modification, translocation, and degradation of Klotho, and thus are proposed to be downstream regulatory mechanisms. Here, we discuss the current understanding of upstream and downstream regulatory mechanisms of Klotho and examine potential therapeutic strategies to upregulate Klotho expression for CKD treatment.

Childhood maltreatment influences suicidal behavior: Rumination mediates and regulatory emotional self-efficacy moderates.

To investigate the mediating role of rumination in the association between childhood maltreatment and suicidal behavior, and the moderating role of regulatory emotional self-efficacy, university students (N = 1,458) from 5 universities in China completed questionnaires in classrooms. Path analyses showed emotional maltreatment had the greatest positive association with suicidal behavior and rumination compared with other types of childhood maltreatment. Rumination partly mediated the relationship between childhood maltreatment and suicidal behavior. High regulatory emotional self-efficacy moderated the relation between ruminating childhood maltreatment and suicidal behavior.

The controversy of klotho as a potential biomarker in chronic kidney disease.

Klotho is an identified longevity gene with beneficial pleiotropic effects on the kidney. Evidence shows that a decline in serum Klotho level occurs in early chronic kidney disease (CKD) and continues as CKD progresses. Klotho deficiency is associated with poor clinical outcomes and CKD mineral bone disorders (CKD-MBD). Klotho has been postulated as a candidate biomarker in the evaluation of CKD. However, the evidence for the clinical significance of the relationship between Klotho and kidney function, CKD stage, adverse kidney and/or non-kidney outcomes, and CKD-MBD remains inconsistent and in some areas, contradictory. Therefore, there is uncertainty as to whether Klotho is a potential biomarker in CKD; a general consensus regarding the clinical significance of Klotho in CKD has not been reached, and there is limited evidence synthesis in this area. To address this, we have systematically assessed the areas of controversy, focusing on the inconsistencies in the evidence base. We used a PICOM strategy to search for relevant studies and the Newcastle-Ottawa Scale scoring to evaluate included publications. We reviewed the inconsistent clinical findings based on the relationship of Klotho with CKD stage, kidney and/or non-kidney adverse outcomes, and CKD-MBD in human studies. Subsequently, we assessed the underlying sources of the controversies and highlighted future directions to resolve these inconsistencies and clarify whether Klotho has a role as a biomarker in clinical practice in CKD.

Prognostic value of PaO2/FiO2, SOFA and D-dimer in elderly patients with sepsis.

OBJECTIVE: To investigate the prognostic value for predicting mortality of partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2), the Sequential Organ Failure Assessment (SOFA) score and D-dimer in elderly patients with sepsis. METHODS: This retrospective cohort study enrolled elderly patients with sepsis admitted to the intensive care unit (ICU) between January 2019 and October 2020. Patients were divided into a survival group and a non-survival group. Biomarkers, SOFA, Acute Physiology and Chronic Health Evaluation II and Glasgow Coma Scale scores were recorded within 24 h after admission to the ICU. RESULTS: A total of 135 elderly patients with sepsis were enrolled in the study: 89 were in the survival group and 46 were in the non-survival group at 28 days. Univariate and multivariate regression analyses demonstrated that PaO2/FiO2, SOFA and D-dimer were independently associated with 28-day mortality. The predictive performance for mortality of the combination of PaO2/FiO2, SOFA score and D-dimer (area under the receiver operating characteristic curve of 0.926) was higher than the values for the individual factors (0.761, 0.745 and 0.878, respectively). CONCLUSION: The combination of PaO2/FiO2, SOFA score and D-dimer represents a promising tool and biomarker for predicting 28-day mortality of the elderly patients with sepsis.

Multicenter analysis and a rapid screening model to predict early novel coronavirus pneumonia using a random forest algorithm.

ABSTRACT: Early determination of coronavirus disease 2019 (COVID-19) pneumonia from numerous suspected cases is critical for the early isolation and treatment of patients.The purpose of the study was to develop and validate a rapid screening model to predict early COVID-19 pneumonia from suspected cases using a random forest algorithm in China.A total of 914 initially suspected COVID-19 pneumonia in multiple centers were prospectively included. The computer-assisted embedding method was used to screen the variables. The random forest algorithm was adopted to build a rapid screening model based on the training set. The screening model was evaluated by the confusion matrix and receiver operating characteristic (ROC) analysis in the validation.The rapid screening model was set up based on 4 epidemiological features, 3 clinical manifestations, decreased white blood cell count and lymphocytes, and imaging changes on chest X-ray or computed tomography. The area under the ROC curve was 0.956, and the model had a sensitivity of 83.82% and a specificity of 89.57%. The confusion matrix revealed that the prospective screening model had an accuracy of 87.0% for predicting early COVID-19 pneumonia.Here, we developed and validated a rapid screening model that could predict early COVID-19 pneumonia with high sensitivity and specificity. The use of this model to screen for COVID-19 pneumonia have epidemiological and clinical significance.

The relationship between different types of caries and periodontal disease severity in middle-aged and elderly people: findings from the 4th National Oral Health Survey of China.

BACKGROUND: The relationship between dental caries and periodontal disease is still controversial. The objective of this study was to explore the relationship between different types of caries and periodontal disease severity in middle-aged and elderly people in China. METHODS: The study population consisted of 4407 middle-aged and 4117 elderly subjects. Caries were divided into the following three types: type A, crown caries; type B, lesions involving both the crown and root, representing mixed-type caries; and type C, root caries. These three types together represent the overall caries situation, which we call type ABC. Caries were quantitated by decayed and filled teeth (DFT index). Periodontitis was evaluated by clinical attachment loss. RESULTS: Middle-aged people with periodontitis had a significant association with DFT type B (OR: 1.21, 95% CI 1.17-1.25) and type C (OR: 1.40, 95% CI 1.24-1.56). Elderly people with periodontitis had a significant association with DFT type C (OR: 1.28, 95% CI 1.21-1.35). CONCLUSIONS: In China, caries types B/C were positively correlated with periodontitis in the middle-aged group, and only caries type C was positively correlated with periodontitis in the elderly group.

A two-week single-group longitudinal test of a new sonic-powered toothbrush simulating the 'bass brushing technique' with tapered bristles on the brush head for reduction of dental plaque and gingivitis.

OBJECTIVE: To investigate the effect of a new powered toothbrush with tapered bristles on the brush head for the reduction of dental plaque and gingivitis. METHODS: This was a single-centre, single-group, longitudinal clinical trial. Thirty-two participants who were typical manual toothbrush users were recruited and assigned the sonic-powered brush. Interviews were arranged on the 1st , 4th , and 15th days which represented the baseline (T1 ), middle (T2 ) and final (T3 ) time points, respectively. At each visit, the plaque index (PlI), gingival index (GI), bleeding on probing (BOP) and probing depth (PD) were recorded for the Ramfjord index teeth, gingival crevicular fluid(GCF) samples were collected and the proportions of eight periodontal pathogenic bacteria were analysed. Repeated-measures analysis of variance (ANOVA) was used for comparisons at different time points. RESULTS: PlI was significantly reduced by 41.67% from T1 to T2 (p<0.001) and decreased by 18.57% from T2 to T3 (p=0.003). GI also varied significantly from T1 to T2 (p=0.018) and T1 to T3 (p=0.037). A 35.86% reduction in the BOP percentage occurred after using the sonic-powered toothbrush for 3 days (p=0.001). However, no significant difference was observed in the mean values of PD at different examination intervals (p=0.529). There was no significant difference in the proportions of bacteria between T1 and T3 (p>0.05). CONCLUSION: This research demonstrated the efficacy of the sonic-powered brush handle together with tapered bristles on the brush in reducing plaque and gingivitis within a short time period.

A rapid screening model for early predicting novel coronavirus pneumonia in Zhejiang Province of China: a multicenter study.

Novel coronavirus pneumonia (NCP) has been widely spread in China and several other countries. Early finding of this pneumonia from huge numbers of suspects gives clinicians a big challenge. The aim of the study was to develop a rapid screening model for early predicting NCP in a Zhejiang population, as well as its utility in other areas. A total of 880 participants who were initially suspected of NCP from January 17 to February 19 were included. Potential predictors were selected via stepwise logistic regression analysis. The model was established based on epidemiological features, clinical manifestations, white blood cell count, and pulmonary imaging changes, with the area under receiver operating characteristic (AUROC) curve of 0.920. At a cut-off value of 1.0, the model could determine NCP with a sensitivity of 85% and a specificity of 82.3%. We further developed a simplified model by combining the geographical regions and rounding the coefficients, with the AUROC of 0.909, as well as a model without epidemiological factors with the AUROC of 0.859. The study demonstrated that the screening model was a helpful and cost-effective tool for early predicting NCP and had great clinical significance given the high activity of NCP.

Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis.

BACKGROUND: The predictive value of soluble Klotho (sKlotho) for adverse outcomes in patients on maintenance hemodialysis (MHD) is controversial. In this study, we aimed to clarify the potential association of sKlotho levels with adverse outcomes in this patient population. MATERIALS: A total of 211 patients on MHD were identified and stratified according to the median sKlotho level. Patients were followed up for adverse outcomes including cardiovascular (CV) morbidity and all-cause mortality. RESULTS: During the 36-month follow-up, 75 patients [51 CV events (including 16 CV deaths) and 40 deaths] experienced adverse outcomes. After stratification according to median sKlotho level, patients with a lower sKlotho level had a greater risk of CV events (38.2% vs. 19.5%, p = 0.006), all-cause mortality (28.4% vs. 11.6%, p = 0.003), and combined adverse outcomes (51.0% vs. 24.2%, p < 0.001). Similar observations were made from analyses using Kaplan-Meier survival curves. Cox regression analysis showed that a low sKlotho level was strongly correlated with CV morbidity [1.942 (1.030-3.661), p = 0.040)], all-cause mortality [2.073 (1.023-4.203), p = 0.043], and combined adverse outcomes [1.818 (1.092-3.026), p = 0.021] in fully adjusted models. CONCLUSIONS: The sKlotho level was an independent predictive factor of adverse outcomes including CV morbidity and mortality in patients on MHD.

The prognostic value of soluble Klotho in patients with haemodialysis: a systematic review and meta-analysis.

AIM: The correlation between soluble Klotho (sKlotho) levels and clinical outcomes remains inconclusive for patients undergoing maintenance haemodialysis (MHD). We aimed to evaluate the potential predictive significance of sKlotho in this population by conducting a meta-analysis. METHODS: PubMed, Embase, Web of Science and Cochrane Library were comprehensively searched for studies concerning the association between sKlotho level and clinical outcomes including cardiovascular (CV) events and all-cause mortality. The pooled hazard ratios (HR) and 95% confidence intervals (CI) were generated using either random or fixed effects models. Sensitivity and subgroup analyses were used to explore heterogeneity sources. RESULTS: Eight prospective studies with 992 MHD participants were included and reduced sKlotho levels predicted more adverse outcomes in this meta-analysis. The pooled HRs and 95% CIs related to CV events, mortality, or composite outcomes were 1.73 (95% CI 1.08-2.76, p = 0.02), 2.34 (95% CI 1.34-2.07, p = 0.003) or 1.75 (95% CI 1.19-2.57, p = 0.005). Moderate heterogeneity was observed in the composite adverse outcomes (I 2 = 57%, p = 0.05). Age and sKlotho level were the main sources of heterogeneities in the subgroup analysis. CONCLUSION: Lower sKlotho levels were associated with more CV events and all-cause mortality, suggesting that sKlotho may have predictive value in CKD patients receiving haemodialysis.

The Prognostic Role of Klotho in Patients with Chronic Kidney Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: The prognostic role of Klotho in patients with chronic kidney disease is still controversial. Therefore, we performed this meta-analysis to assess the relationship between the low sKlotho level and the risk of adverse kidney outcomes. MATERIALS AND METHODS: We systematically searched medical databases, such as PubMed, Embase, and the Cochrane Library, for eligible publications regarding the relationship between the low sKlotho level and risk of adverse kidney outcomes. The quality of included studies was assessed by using the Newcastle-Ottawa Scale. Combined hazard ratios (HRs) and its 95% confidence intervals (CIs) were calculated using a random- or fixed-effect model. Subgroup analysis was conducted with stratification by age, estimated glomerular filtration rate (eGFR), follow-up interval, region, and study quality. All data was analyzed by RevMan 5.3 analysis software. RESULTS: Eight cohort studies with 3586 participants from 3818 studies were included in our final analysis. Levels of sKlotho were significantly correlated with the eGFR, with a summary correlation coefficient r and 95% CI of 0.469 (0.226, 0.658). Additionally, low sKlotho levels were strongly associated with increased adverse kidney outcomes, and the pooled HR and its 95% CI were 1.64 (1.19, 2.26; P = 0.002), despite publication bias and statistical heterogeneity (I 2 = 52%, P = 0.07). Furthermore, this positive correlation was still observed in all of the subgroup analyses. However, heterogeneity was present in subgroup analyses stratified by the eGFR and follow-up interval. CONCLUSION: Levels of sKlotho are positively correlated with the eGFR, and low sKlotho levels are significantly associated with an increased risk of poor kidney outcomes. Therefore, sKlotho could be used as a novel biomarker for early diagnosis and prognostic assessment for patients with chronic kidney disease. Studies with a larger sample size and longer follow-up period are warranted to validate our results.

Relationship between the genetic polymorphisms of vicR and vicK Streptococcus mutans genes and early childhood caries in two-year-old children.

BACKGROUND: The VicRK two-component signalling system regulates virulence and cariogenicity in Streptococcus mutans (S. mutans). The purpose of this study was to explore the genetic polymorphisms of the vicR and vicK genes, which are associated with dental caries in children with S. mutans. METHODS: In this study, 121 (from each group) clinical S. mutans strains were isolated from caries-free children and children with high-severity caries to sequence the vicR and vicK genes. Genomic DNA was extracted from S. mutans strains and amplified using PCR. The PCR products were purified and sequenced. A chi-squared test and ABI Variant Reporter software were used to analyse the sequencing results. RESULTS: The 242 clinically isolated S. mutans strains contained the full-length vicR and vicK genes. No nucleotide sequence insertions or deletions were observed in the two genes. Four silent point mutations were identified in the vicR genes, and no missense mutations could be detected. Forty-one mutations were identified in the vicK genes. In addition to 32 silent mutations, 9 missense mutations at the 173, 337, 470, 1051, 1132, 1258, 1260, 1277, and 1348 bp positions were found. The distribution frequencies of the missense mutations were not significantly different between the groups, except for the C470T mutation. The frequency of the C470T missense mutation was higher in the high-severity caries group than in the caries-free group. CONCLUSIONS: vicR sequences are highly conserved in S. mutans clinical isolates. The locus 470 missense mutation of the vicK gene may be related to caries in children with S. mutans.

Comparison of microsatellite status detection methods in colorectal carcinoma.

There are two commonly accepted methods for detecting microsatellite status. One is to detect amplified microsatellite loci by polymerase chain reaction (PCR) and the other is to detect mismatch repair gene (MMR) protein expression by immunohistochemistry (IHC). PCR detection is considered to be accurate in clinical operations while IHC is widely used due to ease of operation and lesser expense. In order to compare IHC with PCR in detecting microsatellite status in colorectal carcinoma, a total of 569 samples of colorectal carcinoma resection were collected in the Department of Pathology, Nanjing Drum Tower Hospital, between June 2014 and June 2017. In all samples, IHC and PCR was used to detect microsatellite status and the consistency of results between the two methods was compared. We found that 48 cases of microsatellite instability (MSI) were detected by PCR including 37 cases of microsatellite instability high (MSI-H), 11 cases of microsatellite instability low (MSI-L), and 521 cases of MSS. MSI accounted for 8.44% of all cases and MSI-H accounted for 6.50%. IHC results of the 569 patients showed that 69 cases were deficient mismatch repair (dMMR) and 500 cases were proficient mismatch repair (pMMR). dMMR accounted for 12.13% of all cases. Loss expression of PMS2 protein was the most common while MSH6 was rare. The coincidence rate of the two methods for detecting microsatellite states was 91.92%. IHC and the PCR method had high consistency in microsatellite status. Compared with PCR, the IHC method is more economical and more convenient for clinical operations. When the 4 repair proteins were without deficiency detected by IHC, it could be diagnosed as MSS/MSI-L and further PCR was not necessary. When any repair protein was found to be deficient, PCR detection was needed to determine whether MSI existed. Our conclusion will save a lot of time and costs in clinical work.

DNA methylation mechanism of intracellular zinc deficiency-induced injury in primary hippocampal neurons in the rat brain.

OBJECTIVE: To explore Zn2+ deficiency-induced neuronal injury in relation to DNA methylation, providing valuable data and basic information for clarifying the mechanism of Zn2+ deficiency-induced neuronal injury. METHODS: Cultured hippocampal neurons were exposed to the cell membrane-permeant Zn2+ chelator N,N,N',N'-Tetrakis (2-pyridylmethyl) ethylenediamine (TPEN) (2 µM), and to TPEN (2 µM) plus ZnSO4 (5 µM) for 24 hours. We analyzed intracellular Zn2+ levels, neuronal viability, and protein/mRNA levels for DNA (cytosine-5) methyltransferase 1 (DNMT1), DNA (cytosine-5-) methyltransferase 3 alpha (DNMT3a), methyl CpG binding protein 2 (MeCP2), Brain-derived neurotrophic factor (BDNF), and growth arrest and DNA-damage-inducible, beta (GADD45b) in the treated neurons. RESULTS: We found that exposure of hippocampal neurons to TPEN (2 µM) for 24 hours significantly reduced intracellular Zn2+ concentration and neuronal viability. Furthermore, DNMT3a, DNMT1, BDNF, and GADD45b protein levels in TPEN-treated neurons were significantly downregulated, whereas MeCP2 levels were, as expected, upregulated. In addition, DNMT3a and DNMT1 mRNA levels in TPEN-treated neurons were downregulated, while MeCP2, GADD45b, and BDNF mRNA were largely upregulated. Addition of ZnSO4 (5 µM) almost completely reversed the TPEN-induced alterations. CONCLUSION: Our data suggest that free Zn2+ deficiency-induced hippocampal neuronal injury correlates with free Zn2+ deficiency-induced changes in methylation-related protein gene expression including DNMT3a/DNMT1/MeCP2 and GADD45b, as well as BDNF gene expression.

Plasma s-Klotho is related to kidney function and predicts adverse renal outcomes in patients with advanced chronic kidney disease.

To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3-5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross-sectional study to investigate correlations between s-Klotho and estimated glomerular filtration rate (eGFR) and other parameters. Patients were then followed prospectively for 20.1±10.1 months according to s-Klotho median level until serum creatinine doubled, or initiation of renal replacement therapy, or death. s-Klotho levels inpatients with CKD were significantly lower than that in the control group. For patients with CKD, there were no differences in age distribution among subgroups. However, s-Klotho level differed significantly across CKD stages, and it was lower in the advanced CKD group compared with the moderate CKD group. Correlation analysis revealed that s-Klotho was positively associated with eGFR, but inversely associated with FGF23. During the follow-up of 20.1±10.1 months, patients with higher s-Klotho levels showed a reduced risk of kidney adverse outcomes, including serum creatinine doubling and initiation of renal replacement therapy. Cox regression analysis revealed that low s-Klotho was an independent risk factor for CKD progression. s-Klotho level was closely correlated with kidney function, further, low s-Klotho level could predict adverse kidney disease outcomes in patients with progressive CKD.

Fibroblast growth factor 2 protects against renal ischaemia/reperfusion injury by attenuating mitochondrial damage and proinflammatory signalling.

Ischaemia-reperfusion injury (I/RI) is a common cause of acute kidney injury (AKI). The molecular basis underlying I/RI-induced renal pathogenesis and measures to prevent or reverse this pathologic process remains to be resolved. Basic fibroblast growth factor (FGF2) is reported to have protective roles of myocardial infarction as well as in several other I/R related disorders. Herein we present evidence that FGF2 exhibits robust protective effect against renal histological and functional damages in a rat I/RI model. FGF2 treatment greatly alleviated I/R-induced acute renal dysfunction and largely blunted I/R-induced elevation in serum creatinine and blood urea nitrogen, and also the number of TUNEL-positive tubular cells in the kidney. Mechanistically, FGF2 substantially ameliorated renal I/RI by mitigating several mitochondria damaging parameters including pro-apoptotic alteration of Bcl2/Bax expression, caspase-3 activation, loss of mitochondrial membrane potential and KATP channel integrity. Of note, the protective effect of FGF2 was significantly compromised by the KATP channel blocker 5-HD. Interestingly, I/RI alone resulted in mild activation of FGFR, whereas FGF2 treatment led to more robust receptor activation. More significantly, post-I/RI administration of FGF2 also exhibited robust protection against I/RI by reducing cell apoptosis, inhibiting the release of damage-associated molecular pattern molecule HMBG1 and activation of its downstream inflammatory cytokines such as IL-1α, IL-6 and TNF α. Taken together, our data suggest that FGF2 offers effective protection against I/RI and improves animal survival by attenuating mitochondrial damage and HMGB1-mediated inflammatory response. Therefore, FGF2 has the potential to be used for the prevention and treatment of I/RI-induced AKI.

Klotho mitigates cyclosporine A (CsA)-induced epithelial-mesenchymal transition (EMT) and renal fibrosis in rats.

PURPOSE: Klotho deficiency is implicated in various kidney diseases, including renal fibrosis. The aim of this study was to investigate the effect of Klotho administration on epithelial-mesenchymal transition (EMT) and renal fibrosis induced by cyclosporine A (CsA) in rats. METHODS: CsA-induced renal fibrosis was established by oral administration of CsA (30 mg/kg) to rats on a low-salt diet for 28 days. Klotho was administered to rats by intraperitoneal injection. Renal pathological changes were evaluated by hematoxylin and eosin and Masson's trichrome staining. The EMT response was assessed by measuring the level of TGF-ß1, E-cadherin and α-SMA by immunohistochemistry and Western blot. RESULTS: Administration of CsA for 28 days induced renal damage, decreased Klotho expression and activated the EMT response (demonstrated as increased TGF-ß1 and α-SMA expression accompanied by decreased in E-cadherin expression). Treatment with Klotho significantly ameliorated pathological lesions of the kidney by modulating the expression of EMT-associated proteins in the kidney. CONCLUSIONS: Klotho inhibits CsA-induced EMT and renal fibrosis in rats. Klotho may serve as a therapeutic agent to minimize CsA-induced renal fibrosis.

Nerve growth factor-induced Akt/mTOR activation protects the ischemic heart via restoring autophagic flux and attenuating ubiquitinated protein accumulation.

The dysregulation of autophagy is related to a variety of cardiovascular diseases, such as myocardial ischemia/reperfusion (I/R). Nerve growth factor (NGF) has been shown to have therapeutic potential in ischaemic heart injury. In this study, we demonstrate that NGF administration can accelerate autophagic flux and attenuate protein ubiquitination in myocardial I/R heart. Our results showed that NGF could restored heart function and decreased the apoptosis of cardiomyocytes which induced by myocardial I/R injury. The protective effect of NGF is associated with the inhibition of autophagy related proteins. On another hand, NGF enhances the clearance of ubiquitinated protein and increases the survival of myocardial cell in vivo and in vitro. Additionally, NGF could activate the PI3K/AKT and mTOR signaling pathways. These results suggested that the cardioprotective effect of NGF is related to the restoration of autophagic flux and attenuation of protein ubiquitination via the activation of PI3K/AKT and mTOR pathway.

[A Method to Measure the Velocity of Fragments of Large Equivalence Explosion Field Based on Explosion Flame Spectral Analysis].

The deflagration fire lasting for a long time and covering a large area in the process of large equivalent explosion makes it difficult to obtain velocity parameters of fragments in the near-field. In order to solve the problem, it is proposed in this paper a photoelectric transceiver integrated method which utilize laser screen as the sensing area. The analysis of three different types of warhead explosion flame spectral distribution of radiation shows that 0.3 to 1.0 µm within the band is at relatively low intensity. On the basis of this, the optical system applies the principle of determining the fixed distance by measuring the time and the reflector technology, which consists of single longitudinal mode laser, cylindrical Fresnel lens, narrow-band filters and high-speed optical sensors, etc. The system has its advantage, such as transceiver, compact structure and combination of narrowband filter and single longitudinal mode laser, which can stop the spectrum of fire from suppressing the interference of background light effectively. Large amounts of experiments in different models and equivalent have been conducted to measure the velocity of difference kinds of warheads, obtaining higher signal-to-noise ratio of the waveform signal after a series of signal de-noising and recognition through NI company data acquisition and recording system. The experimental results show that this method can complete the accurately test velocity of fragments around center of the explosion. Specifically, the minimum size of fragments can be measured is 4 mm while the speed can be obtained is up to 1 200 m x s(-1) and the capture rate is better than 95% comparing with test results of target plate. At the same time, the system adopts Fresnel lenses-transparent to form a rectangular screen, which makes the distribution of rectangular light uniform in vertical direction, and the light intensity uniformity in horizontal direction is more than 80%. Consequently, the system can distinguish preliminarily the correspondence between the velocity and the sizes of prefabricated fragments.