Adult Renal Dysfunction and Risk of Dementia or Cognitive Decline: Brain-Kidney Axis Hypothesis Based on a Systematic Review and Meta-Analysis.

OBJECTIVE: The brain-kidney axis was proposed to emphasize roles of kidney functioning in modulating neurodegeneration. We aimed to evaluate the associations of renal diseases and blood markers with risk of dementia or cognitive decline among non-demented adults. METHODS: The PubMed, EMBASE, and Cochrane library were searched until February 1st, 2022, to include longitudinal studies. Multivariate adjusted effects were pooled by random-effects models. The robust error meta-regression models were used for dose-response analyses. The credibility of meta-analyses was graded and an innovative index (Sdifference) was developed to evaluate the evidence tendency. RESULTS: A total of 41 longitudinal studies (6,480,136 participants, mean age range: 58.5-83.5 years) were included, of which 33 were for meta-analyses. Though with low level of evidence, five indicators of kidney were associated with increased risk of dementia or cognitive decline, including acute kidney injury (hazard ratio [HR] = 2.24, p = 0.0001), chronic kidney disease (HR = 1.29, p = 0.0001), higher serum creatinine (HR = 1.35, p = 0.0001), higher urine albumin creatine ratio (UACR, HR = 1.23, p = 0.0001), and lower estimated glomerular filtration rate (eGFR, HR = 1.18, p = 0.0001). A linear relationship was revealed for eGFR (p = 0.0217) or UACR (p = 0.0006). Heterogeneity is a main concern to jeopardize the evidence robustness, especially for eGFR (Sdifference = 0.05). CONCLUSION: Some renal indicators were associated with a higher risk of dementia, though the evidence base warrants further strengthening. Renal function management might serve as a promising target for dementia prediction and prevention.

MicroRNA-9501 inhibits breast cancer proliferation and metastasis through regulating Wnt/ß-catenin pathway.

OBJECTIVE: This research was designed to explore the expression characteristics of microRNA-9501 in breast cancer (BCa), and to further explore whether it can influence the development of BCa through the regulation of Wnt/ß-Catenin pathway. PATIENTS AND METHODS: QPCR was carried out to examine microRNA-9501 level in tumor tissue samples and paracancerous ones collected from 42 BCa patients, and the interplay between microRNA-9501 expression and the clinical indicators, as well as the prognosis of BCa patients were analyzed. In addition, we detected microRNA-9501 expression in BCa cell lines by qPCR. Subsequently, microRNA-9501 overexpression model was constructed in BCa cell lines MCF-7 and MDA-MB-231. Then, CCK-8, EdU, cell wound healing, as well as transwell assays, were carried out to evaluate the impact of microRNA-9501 on the biological functions of BCa cells. Finally, the Dual-Luciferase reporting test and tumor formation experiment in nude mice were conducted to further clarify the potential molecular mechanism. RESULTS: QPCR results indicated that microRNA-9501 level in tumor tissue specimens of BCa patients was remarkably higher than that in adjacent ones, and the difference was statistically significant. Compared with patients with high expression of microRNA-9501, patients with lowly-expressed microRNA-9501 had higher tumor stage, higher incidence of lymph node or distant metastasis, and lower overall survival rate. In addition, compared with control group, cells in microRNA-9501 overexpression group showed a significant decrease in proliferation rate, invasiveness, and migration ability. Meanwhile, luciferase reporting assay revealed that overexpression of ß-Catenin remarkably attenuated the luciferase activity of the vector containing wild-type microRNA-9501 sequences, further demonstrating that microRNA-9501 can be targeted by ß-Catenin. Meanwhile, qPCR revealed a negative association between ß-Catenin and microRNA-9501 in BCa tissues. Finally, tumor-bearing experiments in nude mice also demonstrated that microRNA-9501 may suppress the malignant growth of breast tumor. CONCLUSIONS: MicroRNA-9501 expression was found remarkably decreased in BCa tissues and cell lines, which was closely relevant to the pathological stage, metastasis incidence, and prognosis of BCa patients. In addition, microRNA-9501 may suppress the malignant progression of BCa via modulating Wnt/ß-Catenin path-way.

Effect of levocarnitine on cerebral ischemia-reperfusion rats via activating Nrf2/ARE signaling pathway.

OBJECTIVE: Levocarnitine plays a crucial role in the metabolism of organisms. The aim of this study was to explore the impact of Levocarnitine on cerebral ischemia-reperfusion (I/R) rats and the underlying mechanism. MATERIALS AND METHODS: Cerebral I/R model was first successfully established. Two groups were set up, including drug group (I/R + Levocarnitine group) and control group (I/R group). The influences of Levocarnitine on brain injury and oxidative stress in cerebral I/R rats were evaluated. Furthermore, the impacts of Levocarnitine on the nuclear factor E2-related factor 2 (Nrf2)/antioxidant responsive element (ARE) signaling pathway and neuronal apoptosis in rats were detected. RESULTS: Compared with I/R group, I/R + Levocarnitine group exhibited markedly lowered neurological deficit score and cerebral infarct volume. However, superoxide dismutase (SOD) and notably decreased malondialdehyde (MDA) were significantly up-regulated in I/R + Levocarnitine group. This suggested that Levocarnitine could relieve cerebral nerve injury and oxidative stress in cerebral I/R rats. Additionally, in I/R + Levocarnitine group, the protein expressions of Nrf2, heme oxygenase-1 (HO-1), and B-cell lymphoma 2 (Bcl-2) were significantly up-regulated, whereas cleaved Caspase-3 (c-Caspase-3) was notably down-regulated. Furthermore, neuronal apoptosis in cerebral I/R rats was remarkably inhibited. CONCLUSIONS: Levocarnitine alleviates brain injury and neuronal apoptosis in cerebral I/R rats by activating the Nrf2/ARE signaling pathway.

Study on diagnostic value of P1NP and ß-CTX in bone metastasis of patients with breast cancer and the correlation between them.

OBJECTIVE: This study aimed to investigate the diagnostic value of the total amino-terminal propeptide of type 1 procollagen (P1NP) and C-terminal telopeptide of ß-I collagen (ß-CTX) in bone metastasis of patients with breast cancer and the correlation between them. PATIENTS AND METHODS: The medical records of 73 patients were retrospectively analyzed. These patients with breast cancer were treated in Oncology, General Surgery, and Orthopedic Departments in The Third People's Hospital of Qingdao from March 2014 to April 2017, including 40 patients with bone metastasis (bone metastasis group) and 33 patients with no bone metastasis (non-bone metastasis group). Other 40 healthy people who received physical examination in the same period were selected as the control group. The expression of P1NP and ß-CTX in plasma were detected by the Enzyme-linked immunosorbent assay, and the correlation between them was analyzed. RESULTS: There were significant differences in P1NP and ß-CTX concentrations among the three groups (p<0.05). The concentrations of P1NP in the control group and the non-bone metastasis group were significantly lower than that in the bone metastasis group (p<0.05); the concentrations of ß-CTX in the control group and the non-bone metastasis group were significantly lower than that in the bone metastasis group (p<0.05). P1NP: AUC=0.852, sensitivity: 72.5%, specificity: 93.9%, CUT OFF=66.44. ß-CTX: AUC=0.883, sensitivity: 85.0%, specificity: 84.8%, CUT OFF=69.8. Joint detection: AUC=0.952, sensitivity: 84.8%, specificity: 99.5%, CUT OFF=99.5. The results of the concentrations of P1NP and ß-CTX in the bone metastasis group detected by the Pearson correlation analysis showed that their concentrations were positively correlated in the bone metastasis group (r=0.764, p<0.05). CONCLUSIONS: P1NP and ß-CTX in plasma have a high diagnostic value for bone metastasis of breast cancer and have important significance in the diagnosis of bone metastasis and disease monitoring.

Study on ceramide modulates EAAT-2 participation in the immunoinflammatory response in schizophrenia.

OBJECTIVE: Abnormal immunoinflammatory responses play important roles in the pathogenesis of schizophrenia, but the underlying molecular mechanisms are still unclear. MATERIALS AND METHODS: In this study, the ceramide agonist daunorubicin (DNR) was injected into the lateral ventricles to induce ceramide accumulation. The behavioral tests were used to observe schizophrenia-like behavioral changes. Changes in the mRNA levels of the proinflammatory cytokines and the protein levels of the glutamate transporter excitatory amino acid transporter-2 (EAAT-2) were detected. After inhibition of nuclear factor-κB (NF-κB), the above indices were detected again. Nissl staining was used to assess neuronal damage. RESULTS: After intracerebroventricular injection of DNR, ceramide significantly accumulated in the hippocampus, and behavioral tests revealed negative schizophrenia symptoms accompanied by induced learning and memory dysfunction. Furthermore, the hippocampus demonstrated increased mRNA levels of the proinflammatory cytokines including interleukin-1ß (IL-1ß), IL-6, and tumor necrosis factor-α (TNF-α) and significantly decreased EAAT-2 protein levels. Nissl staining revealed neuronal damage after ceramide accumulation. The NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) reduced the behavioral abnormalities caused by ceramide accumulation, downregulated CONCLUSIONS: The experimental results suggest that ceramide reduces EAAT-2 expression through the NF-κB/TNF-α pathway and causes neuronal excitotoxicity in the pathogenesis of schizophrenia, leading to neuronal damage.

Protective effects of deferasirox and N-acetyl-L-cysteine on iron overload-injured bone marrow

Using an iron overload mouse model, we explored the protective effect of deferasirox (DFX) and N-acetyl-L-cysteine (NAC) on injured bone marrow hematopoietic stem/progenitor cells (HSPC) induced by iron overload. Mice were intraperitoneally injected with 25 mg iron dextran every 3 days for 4 weeks to establish an iron overload (Fe) model. DFX or NAC were co-administered with iron dextran in two groups of mice (Fe+DFX and Fe+NAC), and the function of HSPCs was then examined. Iron overload markedly decreased the number of murine HSPCs in bone marrow. Subsequent colony-forming cell assays showed that iron overload also decreased the colony forming capacity of HSPCs, the effect of which could be reversed by DFX and NAC. The bone marrow hematopoiesis damage caused by iron overload could be alleviated by DFX and NAC.

The role of human epididymis protein 4 in the diagnosis of epithelial ovarian cancer

Purpose: Epithelial ovarian cancer is one of the most lethal female genital tract cancers. Early diagnosis of EOC would benefit the patients a lot. Human epididymis protein 4 (HE4) has been regarded as a new powerful biomarker in diagnosis of EOC; we hope to obtain system knowledge of HE4 and understand the role of HE4 in diagnosis of epithelial ovarian cancer (EOC). Methods: We searched Pubmed, Embase, Medline, and Chinese National Knowledge Infrastructure (CNKI) for articles that included HE4's origin, characteristics, detection methods, clinical efficacy alone or combined with CA125, the risk of malignancy index, and the risk of ovarian malignancy algorithm. The diagnostic performance for the EOC and the role in the recurrence and procession in EOC were also discussed. Results: We got 83 most related articles and found that there were significantly difference existing among the studies, such as the clinical characteristics of patients, the methodology for measuring HE4, the different cut-offs for HE4 and so on. Conclusion: HE4 is a promising biomarker for the early diagnosis of EOC. However, each lab should establish its own reference internal of HE4 (AU)

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Jade-1: its structure, regulation and functions in the renal cancer.

Jade-1 is originally identified by the yeast two-hybrid system as a protein partner of von Hippel-Lindau (pVHL) tumor suppressor, a well-known renal tumor suppressor. In cellular signaling pathways, many upstream Jade-1 regulators, such as pVHL, CK1α, PC1, and NPHP4, can control its activity by stabilization, phosphorylation, and nuclear translocation. Numerous downstream effectors, including ß-catenin, AKT, p21, and Bcl-2, are well modulated by Jade-1, which mainly regulates cell proliferation and apoptosis. Jade-1 is also deemed to be a candidate of transcriptional co-activator associated with histone acetyltransferase (HAT) activity. This review focuses on the anticancer role of Jade-1 in clear cell renal carcinoma and the inhibitory effect of Jade-1 on cystic renal diseases. This review aims to provide a basis of disease prevention or therapy.

The role of human epididymis protein 4 in the diagnosis of epithelial ovarian cancer.

PURPOSE: Epithelial ovarian cancer is one of the most lethal female genital tract cancers. Early diagnosis of EOC would benefit the patients a lot. Human epididymis protein 4 (HE4) has been regarded as a new powerful biomarker in diagnosis of EOC; we hope to obtain system knowledge of HE4 and understand the role of HE4 in diagnosis of epithelial ovarian cancer (EOC). METHODS: We searched Pubmed, Embase, Medline, and Chinese National Knowledge Infrastructure (CNKI) for articles that included HE4's origin, characteristics, detection methods, clinical efficacy alone or combined with CA125, the risk of malignancy index, and the risk of ovarian malignancy algorithm. The diagnostic performance for the EOC and the role in the recurrence and procession in EOC were also discussed. RESULTS: We got 83 most related articles and found that there were significantly difference existing among the studies, such as the clinical characteristics of patients, the methodology for measuring HE4, the different cut-offs for HE4 and so on. CONCLUSION: HE4 is a promising biomarker for the early diagnosis of EOC. However, each lab should establish its own reference internal of HE4.

Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

Analysis of key genes and modules during the courses of traumatic brain injury with microarray technology.

Gene expression data acquired at different times after traumatic brain injury (TBI) were analyzed to identify differentially expressed genes (DEGs). Interaction network analysis and functional enrichment analysis were performed to extract valuable information, which may benefit diagnosis and treatment of TBI. Microarray data were downloaded from Gene Expression Omnibus and pre-treated with MATLAB. DEGs were screened out with the SAM method. Interaction networks of the DEGs were established, followed by module analysis and functional enrichment analysis to obtain insight into the molecular mechanisms. A total of 39 samples at six time points (30 min, 4, 8, 24 , 72 h, and 21 days) were analyzed and generated 377 DEGs. Eight modules were identified from the networks and network ontology analysis revealed that cell surface receptor-linked signaling pathway, response to wounding and signaling pathway were significantly overrepresented. Altered risk genes and modules in TBI were uncovered through comparing the gene expression data acquired at various time points. These genes or modules could be potential biomarkers for diagnosis and treatment of TBI.

Tracing the evolution of physics on the backbone of citation networks.

Many innovations are inspired by past ideas in a nontrivial way. Tracing these origins and identifying scientific branches is crucial for research inspirations. In this paper, we use citation relations to identify the descendant chart, i.e., the family tree of research papers. Unlike other spanning trees that focus on cost or distance minimization, we make use of the nature of citations and identify the most important parent for each publication, leading to a treelike backbone of the citation network. Measures are introduced to validate the backbone as the descendant chart. We show that citation backbones can well characterize the hierarchical and fractal structure of scientific development, and lead to an accurate classification of fields and subfields.

Solitary intracerebral chondroma without meningeal attachment: a case report with review of the literature.

Intracranial chondromas are rare, benign cartilaginous tumours that account for < 0.3% of primary intracranial tumours. They usually originate from the basal synchondrosis and are extradural though, extremely rarely, they can be intracerebral. Here the case of a 45-year old female is presented with a solitary intracerebral chondroma located in the right frontal lobe with no meningeal attachment. The epidemiology, aetiology, clinical behaviour, radiological features, histological features and treatment of the case are discussed with a review of previous cases reported in the literature.

Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells.

Anion exchanger-1 (AE1), an erythroid-specific membrane protein, mediates the Cl(-)/HCO(-)(3) exchange across the plasma membrane and regulates intracellular pH. We have found that AE1 was unexpectedly expressed in gastric cancer cells and participated in the tumorigenesis of the cancer. Here, we focus on the induction of AE1 expression and its role in gastric carcinogenesis as well as in the differentiation of K562 cells. The results show that expression of AE1 is not related to genetic mutation or the mRNA level, but rather, that it is modulated by miR-24. miR-24 decreases the expression of AE1 through binding to the 3'UTR of AE1 mRNA. Transfection of an miR-24 into gastric cancer cells reduced the elevation of the AE1 protein, which resulted in return of AE1-sequestrated p16 to the nucleus, thereby inhibiting proliferation of the cells. Furthermore, the miR-24 inhibitor cooperated with hemin to induce the expression of AE1 in K562 cells and differentiation of the cells, which is consistent with results obtained from the cells cultured at pH 7.6 or from forced stable expression of AE1. These findings establish a novel regulation of miR-24-related AE1 expression in gastric carcinogenesis and erythropoiesis.

Disparate distribution of activating and inhibitory killer cell immunoglobulin-like receptor genes in patients with systemic lupus erythematosus.

The genes of killer cell immunoglobulin-like receptors (KIRs), which are involved in the activation of T cells and natural killer cells, are highly variable. In recent years, the role of KIRs in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of the polymorphism of KIR genes with the susceptibility to systemic lupus erythematosus (SLE). The polymorphism of KIR genes of 93 patients with SLE together with 123 healthy donors as the control group was determined by polymerase chain reaction with sequence-specific primers. Twenty-seven novel gene combinations were found. Genotypic frequencies of KIR2DL2 (p < 0.001) and KIR2DS1 (p < 0.001) were much higher in patients with SLE than in control subjects. Individuals with two and more than two activating KIR genes were found more frequently in patients than in control subjects (80.7% versus 66.7%, p = 0.022). The results suggest that a genetic disturbance between activating and inhibitory KIR genes may be one of the key factors underlying the pathogenesis of SLE.

Hydrolysis and photolysis of diacylhydrazines-type insect growth regulator JS-118 in aqueous solutions under abiotic conditions.

JS-118 is a diacylhydrazines-type insect growth regulator which is now used extensively in China. The hydrolysis and photolysis of the pesticide JS-118 in aqueous solutions have been assessed under natural and controlled conditions in this project. Hydrolysis experimental results show that JS-118 is quite stable in aqueous solutions in dark, with no significant variations be observed in degradation under various conditions. Abiotic hydrolysis is relatively unimportant compared to photolysis. The rate of photodecomposition of JS-118 in aqueous solutions follows first-order kinetics both in UV radiation and natural sunlight. The degradation rates are faster under UV light than sunlight, with the half-lives (t (1/2) = ln2/k) of 6.00-10.85 min and 6.63-10.16 day, respectively. Under UV light, two major photoproducts are detected, and tentatively identified according to HPLC-MS spectral information as N-t-butyl-N-(3,5-dimethylbenzoyl) and 3,7-dimethyl-benzoatedihydrofuran. The corresponding photolysis pathways of JS-118 are also proposed. The results obtained indicate that direct photoreaction is an important dissipation pathway of JS-118 in natural water systems.

Models of financial markets with extensive participation incentives.

We consider models of financial markets in which all parties involved find incentives to participate. Strategies are evaluated directly by their virtual wealth. By tuning the price sensitivity and market impact, a phase diagram with several attractor behaviors resembling those of real markets emerge, reflecting the roles played by the arbitrageurs and trendsetters, and including a phase with irregular price trends and positive sums. The positive sumness of the players' wealth provides participation incentives for them. Evolution and the bid-ask spread provide mechanisms for the gain in wealth of both the players and market makers. New players survive in the market if the evolutionary rate is sufficiently slow. We test the applicability of the model on real Hang Seng Index data over 20 years. Comparisons with other models show that our model has a superior average performance when applied to real financial data.

Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies.

Many patients who require allogeneic hematopoietic stem cell transplantation (allo-HSCT) lack a human leukocyte antigen (HLA)-matched donor. Here, we report a protocol for haploidentical allo-HSCT that combines granulocyte-colony stimulating factor primed bone marrow (G-BM) and peripheral blood stem cells (PBSC) without in vitro T-cell depletion (TCD). In this study, 171 patients, including 86 in high-risk group, underwent transplantation from haploidentical family donors. All patients achieved sustained, full donor chimerism. One hundred and eleven patients were alive in remission at a median of 682 (253-1502) days. The cumulative incidence of grade III-IV acute graft-versus-host disease (GVHD) was 23% and that of extensive chronic GVHD, 47%; these were not influenced by HLA disparity. Patients younger than 15 years had less grade III-IV acute GVHD than older patients (P=0.044). The 2-year probability of relapse was 12% for standard-risk disease and 39% for high-risk disease. The 2-year probability of leukemia-free survival (LFS) was 68% for standard-risk patients and 42% for high-risk patients (P=0.0009). Grade III-IV acute GVHD was associated with better LFS (P=0.0017). The results require confirmation and show that G-BM combined with PBSC from haploidentical family donors, without in vitro TCD, may be used as a good source of stem cells for allo-HSCT.