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As the aging population increases in China, the incidence of osteoporosis increases as well. Because of the progress in osteoporosis study, the pathogenesis of osteoporosis has increasingly drawn attention in the recent years. In the traditional concept, the cause of osteoporosis includes endocrine disturbance, metabolic disturbance, and mechanical factor. However, the concept of osteoimmunology has been suggested recently. It is considered that immune system and immune factor play an important role in the development of osteoporosis. Osteoimmunology is a field of research dedicating to the study of the interactions between the immune system, the hemopoietic system, and the bone. The cells in the immune system that regulate bone cells and the hemopoietic function are T lymphocytes. These cells secrete inflammatory cytokines and Wnt ligands that promote bone resorption and stimulate bone formation. In addition, T cells regulate bone homeostasis by cross talking with BM stromal cells and osteoblastic cells via CD40 ligand (CD40L) and other costimulatory molecules. This article describes the effect of immune factor on the development of osteoporosis. [ABSTRACT FROM AUTHOR]

Background/Aims: β-hydroxybutyrate (BHBA) is the major component of ketone bodies in ketosis. Dairy cows with ketosis often undergo oxidative stress. BHBA is related to the inflammation involved in other diseases of dairy cattle. However, whether BHBA can induce inflammatory injury in dairy cow hepatocytes and the potential mechanism of this induction are not clear. The NF-κB pathway plays a vital role in the inflammatory response. Methods: Therefore, this study evaluated the oxidative stress, pro-inflammatory factors and NF-κB pathway in cultured calf hepatocytes treated with different concentrations of BHBA, pyrrolidine dithiocarbamate (PDTC, an NF-κB pathway inhibitor) and N-acetylcysteine (NAC, antioxidant). Results: The results showed that BHBA could significantly increase the levels of oxidation indicators (MDA, NO and iNOS), whereas the levels of antioxidation indicators (GSH-Px, CAT and SOD) were markedly decreased in hepatocytes. The IKKβ activity and phospho-IκBα (p-IκBα) contents were increased in BHBA-treated hepatocytes. This increase was accompanied by the increased expression level and transcription activity of p65. The expression levels of NF-κB-regulated inflammatory cytokines, namely TNF-α, IL-6 and IL-1β, were markedly increased after BHBA treatment, while significantly decreased after NAC treatment. However, the p-IκBα level and the expression and activity of p65 and its target genes were markedly decreased in the PDTC + BHBA group compared with the BHBA (1.8 mM) group. Moreover, immunocytofluorescence of p65 showed a similar trend. Conclusion: The present data indicate that higher concentrations of BHBA can induce cattle hepatocyte inflammatory injury through the NF-κB signaling pathway, which may be activated by oxidative stress. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

This experiment was conducted to examine the effect of dietary copper supplementation on ghrelin mRNA expression level in the fundic gland of growing pigs. A total of 45 crossbred pigs were randomly assigned to three groups of 15 pigs, five replicates of three animals comprised each group. Pigs were allocated to diets that contained 5 mg/kg copper (as the control group), 125 mg/kg copper sulfate, or 125 mg/kg copper methionine. At the end of the experiment, five pigs were selected at random from each group, slaughtered, and collected the fundic gland for determination of ghrelin mRNA expression level. The results showed that average daily gain, average daily feed intake, absolute weight, serum growth hormone (GH) concentration, and ghrelin mRNA level were higher in pigs fed the diets with 125 mg/kg copper methionine and 125 mg/kg copper sulfate ( P < 0.05), than in pigs fed a diet with 5 mg/kg copper. These data suggest that high dietary copper (125 mg/kg) appears to increase feed intake and promote weight gain by enhancing the secretion of GH and ghrelin mRNA level in growing pigs. [ABSTRACT FROM AUTHOR]

Accumulation of neurotoxic bilirubin due to a transient neonatal or persistent inherited deficiency of bilirubin glucuronidation activity can cause irreversible brain damage and death. Strategies to inhibit bilirubin production and prevent neurotoxicity in neonatal and adult settings seem promising. We evaluated the impact of Bvra deficiency in neonatal and aged mice, in a background of unconjugated hyperbilirubinemia, by abolishing bilirubin production. We also investigated the disposal of biliverdin during fetal development. In Ugt1−/− mice, Bvra deficiency appeared sufficient to prevent lethality and to normalize bilirubin level in adults. Although biliverdin accumulated in Bvra-deficient fetuses, both Bvra−/− and Bvra−/−Ugt1−/− pups were healthy and reached adulthood having normal liver, brain, and spleen histology, albeit with increased iron levels in the latter. During aging, both Bvra−/− and Bvra−/−Ugt1−/− mice presented normal levels of relevant hematological and metabolic parameters. Interestingly, the oxidative status in erythrocytes from 9-months-old Bvra−/− and Bvra−/−Ugt1−/− mice was significantly reduced. In addition, triglycerides levels in these 9-months-old Bvra−/− mice were significantly higher than WT controls, while Bvra−/−Ugt1−/− tested normal. The normal parameters observed in Bvra−/−Ugt1−/− mice fed chow diet indicate that Bvra inhibition to treat unconjugated hyperbilirubinemia seems safe and effective. [ABSTRACT FROM AUTHOR]

Soil-salinisation has become an increasingly severe form of soil degradation due to climate variability and human disturbance in arid and semiarid areas. A cellular automata (CA) model was used by integrating a geographic information system (GIS) and remote sensing. Spatial and attribute data from Changling County were analysed to form a database in the GIS. Factors for soil-salinisation were confirmed. A soil salinity forecast formula was obtained by analysing the soil-salinisation system in Changling County. The CA model and database were integrated to simulate and forecast the soilsalinisation spatial-temporal distribution and its evolution. The results indicate the CA model is an effective decision-making support system for the prevention and control of soil-salinisation. [ABSTRACT FROM AUTHOR]

By observing the curative effect of autologous stem cells changes before and after the treatment, to explore the stem cell treatment of diabetes and its complications. 32 patients were type 2 diabetic patients with different complications. By intravenous injection of autologous stem cells, observe improving symptoms, signs and auxiliary examination of patients after three months. Evaluation index: glycated hemoglobin level; ankle brachial pressure index (ABI); limb electromyogram; 24h urine protein quantity. Diabetic complications of different systems and glycated hemoglobincan be effectively improved. Conclusion: This research and application of autologous bone marrow stem cell transplantation for treatment of type 2 diabetes chronic complications achieves certain results, non-toxic side effects occuring. Just only preliminary observes the clinical effect, a small sample size. We need to expand the sample and observation period further for the long-term efficacy and side effects. [ABSTRACT FROM AUTHOR]

Soft assembly of peptide and curcumin (Cur) molecules enables functional integration by finding dynamic equilibrium states through non-covalent interactions. Herein, we developed two soft assembly systems, curcumin-egg white peptides (Cur-EWP) aggregations (AGs) and Cur-EWP-casein-quaternary chitosan (Cur-EWP-CA-QC) nanoparticles (NPs) to comparatively investigate their therapeutic effects on ulcerative colitis in mice and elucidate their underlying mechanism. Results revealed that Cur-EWP AGs, despite gastrointestinal tract instability, exhibited a propensity for swift accumulation within the colorectal region, enriching mucus-associated and short-chain fatty acid (SCAF)-producing bacteria, restoring the intestinal barrier damage. Whereas, Cur-EWP-CA-QC NPs, benefiting from their remarkable stability and exceptional mucosal adsorption properties, not only enhanced permeability of Cur and EWP in the small intestine to activate the immune response and boost tight junction protein expression but also, in their unabsorbed state, regulated the intestinal flora, exerting potent anti-inflammatory activity. Soft assembly of peptides and hydrophobic nutraceuticals could synergize biological activities to modulate chronic diseases. • Soft assembly of egg white peptides (EWP) and Cur formed unstable aggregations. • Protein-polysaccharides complexes enhanced the soft assembly of Cur and EWP. • Soft assembly of EWP and Cur exert synergistic anti-inflammatory. • Cur and EWP soft assemblies prevent colitis by regulating intestinal flora. • Assembled Cur and EWP facilitated absorption to repair intestinal damage. [ABSTRACT FROM AUTHOR]

Diabetic peripheral neuropathy is a common complications of Type 2 Diabetes and its main pathological feature is myelin sheath damage of peripheral nerve that was induced by Schwann cells (SCs) apoptosis. Increasing evidence suggested that taurine might play a role in improving DPN because of its ability to prevent SCs apoptosis. In this study, we explore the effect of taurine on preventing SCs apoptosis and its underlying mechanism. Sprague Dawley rats were treated with streptozotocin to establish the diabetes model. Rats were randomly divided into control, diabetes, taurine treatment (as giving 0.5%, 1% and 2% taurine in drinking water) groups. RSC96 cell (a rat SCs line) was used for intervention experiments in vitro. Results showed that taurine significantly corrected morphology of damaged myelin sheath and inhibited SCs apoptosis in sciatic nerve of diabetic rats. Moreover, taurine prevented apoptosis of RSC96 cells exposed to high glucose. Mechanistically, taurine up-regulated NGF expression and phosphorylation levels of Akt and GSK3β, while, blocking activation of NGF and phosphorylation of Akt and GSK3β increased apoptosis of high glucose-exposed RSC96 cells with taurine supplement. These results revealed taurine improved the myelin sheath damage of sciatic nerve in diabetic rats by controlling SCs apoptosis via NGF/Akt/GSK3β signaling pathways, which provides some clues that taurine might be effective and feasible candidate for the treatment of DPN. [ABSTRACT FROM AUTHOR]

Background: Crigler-Najjar syndrome (CNs) presents as unconjugated hyperbilirubinemia, as a result of UGT1A1 deficiency, and can be categorized in a severe (type I) and mild (type II) phenotype. CNs type II patients usually benefit from phenobarbital treatment that induces residual UGT1A1 activity.Case Presentation: Here we present a CNs type II patient that is not responsive to phenobarbital treatment, which can be explained by two heterozygous mutations in the UGT1A1 gene. A 3 nucleotide insertion in the HNF-1α binding site in the proximal promoter previously reported in a Crigler-Najjar patient on one allele and a novel two nucleotide deletion in exon 1, resulting in a frameshift and a premature stop codon.Conclusion: In newly diagnosed CNs patients with unconjugated bilirubin levels consistent with CNs type II but that are unresponsive to phenobarbital treatment, disruption of the HNF-1α binding site in the proximal promoter should be considered as a probable cause. Upon confirming a mutation in the HNF-1α site, phenobarbital treatment should be stopped or at least be reconsidered because of its sedative effects and its teratogenic properties. [ABSTRACT FROM AUTHOR]

Objective: To systematically review the literature regarding the epidemiology of functional constipation and functional nonretentive fecal incontinence (FNRFI) in children. Secondary objectives were to assess the geographical, age, and sex distribution of functional constipation and FNRFI and to evaluate associated factors.Study Design: The Cochrane Library, PubMed, and Embase databases were searched from 2006 until September 2017. The following inclusion criteria were applied: (1) prospective studies of population-based samples; (2) reporting on the prevalence of functional constipation or FNRFI according to the Rome III/IV criteria; (3) in children aged 0-18 years; and (4) published in full manuscript form. A quality assessment of included studies was conducted. Random effect meta-analyses with meta-regression analyses of study characteristics were performed.Results: Thirty-seven studies were included, of which 35 reported on the prevalence of functional constipation and 15 of FNRFI. The reported prevalence of functional constipation ranged from 0.5% to 32.2%, with a pooled prevalence of 9.5% (95% CI 7.5-12.1). The prevalence of FRNFI ranged from 0.0% to 1.8%, with a pooled prevalence of 0.4% (95% CI 0.2-0.7). The prevalence of functional constipation was 8.6% in boys compared with 8.9% in girls (OR 0.99, 95% CI 0.9-1.4). Geographical location, dietary habits, and exposure to stressful life events were reported to be associated with the prevalence of functional constipation. Data on FNRFI were scarce and no associated factors were identified.Conclusion: Functional constipation is common in childhood and is associated with geographical location, lifestyle factors, and stressful life events. FNRFI is rare, and no associated factors were identified. [ABSTRACT FROM AUTHOR]

Diabetic neuropathy (DN) is a common neurological complication caused by diabetes mellitus (DM). Axonal degeneration is generally accepted to be the major pathological change in peripheral DN. Taurine has been evidenced to be neuroprotective in various aspects, but its effect on spinal cord axon injury (SCAI) in DN remains barely reported. This study showed that taurine significantly ameliorated axonal damage of spinal cord (SC), based on morphological and functional analyses, in a rat model of DN induced by streptozotocin (STZ). Taurine was also found to induce neurite outgrowth in cultured cerebral cortex neurons with high glucose exposure. Moreover, taurine up-regulated the expression of nerve growth factor (NGF) and neurite outgrowth relative protein GAP-43 in rat DN model and cultured cortical neurons/VSC4.1 cells. Besides, taurine increased the activating phosphorylation signals of TrkA, Akt, and mTOR. Mechanistically, the neuroprotection by taurine was related to the NGF–pAKT–mTOR axis, because either NGF-neutralizing antibody or Akt or mTOR inhibitors was found to attenuate its beneficial effects. Together, our results demonstrated that taurine promotes spinal cord axon repair in a model of SCAI in STZ-induced diabetic rats, mechanistically associating with the NGF-dependent activation of Akt/mTOR pathway. [ABSTRACT FROM AUTHOR]

• Adeno-associated virus (AAV)-mediated gene therapy can correct Abcb4 deficiency (PFIC3) in mice. • By restoring phospholipid transport to bile, cholestasis and liver damage were strongly reduced. • Stable transgene expression resulted in long-term correction of the phenotype (26 weeks). • Hepatic transgene persistence was achieved by sufficiently reducing hepatocyte proliferation. Progressive familial intrahepatic cholestasis type 3 (PFIC3), for which there are limited therapeutic options, often leads to end-stage liver disease before adulthood due to impaired ABCB4-dependent phospholipid transport to bile. Using adeno-associated virus serotype 8 (AAV8)-mediated gene therapy, we aimed to restore the phospholipid content in bile to levels that prevent liver damage, thereby enabling stable hepatic ABCB4 expression and long-term correction of the phenotype in a murine model of PFIC3. Ten-week-old Abcb4 −/− mice received a single dose of AAV8-h ABCB4 (n = 10) or AAV8-GFP (n = 7) under control of a liver specific promoter via tail vein injection. Animals were sacrificed either 10 or 26 weeks after vector administration to assess transgene persistence, after being challenged with a 0.1% cholate diet for 2 weeks. Periodic evaluation of plasma cholestatic markers was performed and bile duct cannulation enabled analysis of biliary phospholipids. Liver fibrosis and the Ki67 proliferation index were assessed by immunohistochemistry. Stable transgene expression was achieved in all animals that received AAV8-h ABCB4 up to 26 weeks after administration. AAV8-h ABCB4 expression restored biliary phospholipid excretion, increasing the phospholipid and cholesterol content in bile to levels that ameliorate liver damage. This resulted in normalization of the plasma cholestatic markers, alkaline phosphatase and bilirubin. In addition, AAV8-h ABCB4 prevented progressive liver fibrosis and reduced hepatocyte proliferation for the duration of the study. Liver-directed gene therapy provides stable hepatic ABCB4 expression and long-term correction of the phenotype in a murine model of PFIC3. Translational studies that verify the clinical feasibility of this approach are warranted. Progressive familial intrahepatic cholestasis type 3 (PFIC3) is a severe genetic liver disease that results from impaired transport of lipids to bile, which makes the bile toxic to liver cells. Because therapeutic options are currently limited, this study aims to evaluate gene therapy to correct the underlying genetic defect in a mouse model of this disease. By introducing a functional copy of the missing gene in liver cells of mice, we were able to restore lipid transport to bile and strongly reduce damage to the liver. The proliferation of liver cells was also reduced, which contributes to long-term correction of the phenotype. Further studies are required to evaluate whether this approach can be applied to patients with PFIC3. [ABSTRACT FROM AUTHOR]

[Display omitted] • Precursor template Z-HA NPs induced EWDP self-assembly into well-defined structures. • Bioactivity and self-assembly properties of EWDP was simultaneously leverage. • The self-assembled EWDP reinforced the Cur' physio-chemical stability. • The self-assembled EWDP exert synergistic antioxidant activity with Cur. • The self-assembled EWDP enhance the bioaccessibility of Cur by boosting solubility. Natural multicomponent peptides with abundant bioactivity, varied sizes, and tunable interaction potential are available for rational designing novel self-assembled delivery carriers. Herein, we exploited zein-hyaluronic acid nanoparticles (Z-HA NPs) with a predetermined ordered structure as precursor templates to induce the self-assembly of egg white-derived peptides (EWDP) to generate stable spherical architectures for the enhancement of curcumin (Cur). The resulting Z-EWDP-HA NPs encapsulated hydrophobic Cur through robust hydrogen bonding and hydrophobic interactions with high encapsulation efficiency (97.38% at pH 7.0). The NPs presented superior Cur aqueous solubility, redispersibility, and photothermal stability. More importantly, the self-assembled EWDP could exert synergistic antioxidant activity with Cur and enhance the bioaccessibility of Cur. Meanwhile, the favorable biocompatibility and membrane affinity of EWDP further prolonged residence and time-controlled release feature of Cur in the small intestine. Precursor template-induced multicomponent peptides' self-assembly provides an efficient and controllable strategy for co-enhanced bioactivity and self-assembly capacity of peptides, which could dramatically broaden the functionalization of multicomponent peptides hydrolyzed from natural food proteins. [ABSTRACT FROM AUTHOR]

To construct an evaluation index system for public health emergency preparedness in tertiary general hospitals in China. Methods Based on a literature review, theoretical analysis, expert panel meetings, and the Delphi method, the analytic hierarchy process was used to construct the evaluation index system for emergency preparedness capacity. Results The response rates of the two rounds of questionnaires were 100%, the authority degree of experts was 0.879, and the Kendall coordination coefficients were 0.172 and 0.621 (P < 0.001), respectively. Finally, seven first-level indicators, 20 second -level indicators, and 74 third-level indicators were formed. The first-level indicators and their weights were: command and management (weight 0.209), emergency information communication (weight 0.123), emergency safety (weight 0.092), pre-check and triage (weight 0.209), emergency response (weight 0.034), emergency human resources (weight 0.123), and emergency equipment and materials (weight 0.209). Conclusions The evaluation index system for public health emergency preparedness capacity in tertiary general hospitals constructed in this study has good scientific and practical applicability. It can provide a basis for investigating, standardizing, and improving the public health emergency preparedness capacity in tertiary general hospitals, and it can also provide a basis for improving the index system of public health emergency capacity in hospitals. [ABSTRACT FROM AUTHOR]

Purpose: Epithelial-to-mesenchymal transition (EMT) is an important cause of high mortality in breast cancer. Twist1 is one of the EMT transcription factors (EMT-TFs) with a noticeably short half-life, which is regulated by proteasome degradation pathways. Recent studies have found that USP13 stabilizes several specific oncogenic proteins. As yet, however, the relationship between Twist1 and USP13 has not been investigated. Methods: Co-Immunoprecipitation, GST-pulldown, Western blot, qRT-PCR and immunofluorescence assays were used to investigate the role of USP13 in de-ubiquitination of Twist1. Chromatin immunoprecipitation and Luciferase reporter assays were used to investigate the role of Twist1 in inhibiting USP13 reporter transcription. Scratch wound healing, cell migration and invasion assays, and a mouse lung metastases assay were used to investigate the roles of USP13 and Twist1 in promoting breast cancer metastasis. Results: We found that Twist1 can be de-ubiquitinated by USP13. In addition, we found that the protein levels of Twist1 dose-dependently increased with USP13 overexpression, while USP13 knockdown resulted in a decreased expression of endogenous Twist1. We also found that USP13 can directly interact with Twist1 and specifically cleave the K48-linked polyubiquitin chains of Twist1 induced by FBXL14. We found that the effect of USP13 in promoting the migration and invasion capacities of breast cancer cells can at least partly be achieved through its regulation of Twist1, while Twist1 can inhibit the transcriptional activity of USP13. Conclusions: Our data indicate that an interplay between Twist1 and USP13 can form a negative physiological feedback loop. Our findings show that USP13 may play an essential role in breast cancer metastasis by regulating Twist1 and, as such, provide a potential target for the clinical treatment of breast cancer. [ABSTRACT FROM AUTHOR]

The mechanisms of Bisphenol A (BPA) induced learning and memory impairment have still not been fully elucidated. MicroRNAs (miRNAs) are endogenous non-coding small RNA molecules involved in the process of toxicant-induced neurotoxicity. To investigate the role of miRNAs in BPA-induced learning and memory impairment, we analyzed the impacts of BPA on miRNA expression profile by high-throughput sequencing in mice hippocampus. Results showed that mice treated with BPA displayed impairments of spatial learning and memory and changes in the expression of miRNAs in the hippocampus. Seventeen miRNAs were significantly differentially expressed after BPA exposure, of these, 13 and 4 miRNAs were up- and downregulated, respectively. Bioinformatic analysis of Gene Ontology (GO) and pathway suggests that BPA exposure significantly triggered transcriptional changes of miRNAs associated with learning and memory; the top five affected pathways involved in impairment of learning and memory are: 1) Long-term depression (LTD); 2) Thyroid hormone synthesis; 3) GnRH signaling pathway; 4) Long-term potentiation (LTP); 5) Serotonergic synapse. Eight BPA-responsive differentially expressed miRNAs regulating LTP and LTD were further screened to validate the miRNA sequencing data using Real-Time PCR. The deregulation expression levels of proteins of five target genes (CaMKII, MEK1/2, IP3R, AMPAR1 and PLCβ4) were investigated via western blot, for further verifying the results of gene target analysis. Our results showed that LTP and LTD related miRNAs and their targets could contribute to BPA-induced impairment of learning and memory. This study provides valuable information for novel miRNA biomarkers to detect changes in impairment of learning and memory induced by BPA exposure. [ABSTRACT FROM AUTHOR]

Mycobacterium tuberculosis is capable of escaping the clearance of immune system mainly due to its complex constituents of cell wall. Certain studies show that glycoproteins are involved in immune evasion and act as virulence factors. Peptidoglycan deacetylase Rv1096 is a member of mannosylated proteins. Previously, we reported Rv1096 protein contributed to the resistance of Mycobacterium smegmatis (M. smegmatis) to lysozyme, but more characterization of this protein is required where further intracellular function is unknown. Here, Rv1096 was heterologously over-expressed in the fast-growing and nonpathogenic M. smegmatis (named as M. smegmatis /Rv1096). We observed the morphological alterations in M. smegmatis /Rv1096 including an elongated rod-like shape and increased amounts of Z-rings, which implied that Rv1096 facilitated the cell growth and division. Moreover, a series of assays concerning the interaction between M. smegmatis /Rv1096 and host were carried out. The results showed that M. smegmatis /Rv1096 evaded the killing of macrophages due to the inhibition of phagosome-lysosome fusion, nicotinamide adenine dinucleotide phosphate oxidase activity and reactive oxygen species production. The secretion of interleukin-12 and tumor necrosis factor-α was also impaired by Rv1096. In addition, five putative interaction partners of Rv1096 were identified, which possibly cooperated with Rv1096 in cell division and immune regulation. These results suggested that Rv1096 had effects on mycobacterial division and might act as a virulence factor to mediate the immune evasion in macrophage during mycobacterial infection. • Mycobacterial deacetylase Rv1096 had effects on mycobacterial cell division. • Rv1096 protein promoted mycobacterial persistent survival in macrophages as a potential virulence factor. • Rv1096 might interact with its partners to facilitate mycobacterial cell division and survival in macrophages. [ABSTRACT FROM AUTHOR]

• Cr (VI) induced mitophagy in A549 cells and in lung of BALB/c mice. • HMGA2 played an important role in Cr (VI)-induced mitophagy. • The mechanism for HMGA2 to promote mitophagy was the ability to bind to the protein of PARK2. Chromium (Cr) (VI) is a proven toxin, mutagen and carcinogen. Here, the role of high mobility group A2 (HMGA2) mediating Cr (VI)-induced mitophagy was investigated. Cr (VI)-treatment caused the formation of double membrane autophagic vesicles (AVs) engulfing mitochondria and increased the expression of PINK1, PARK2, LC3 as well as HMGA2 particularly in mitochondria in A549 cells. Silencing of HMGA2 by siRNA decreased expression of PINK1, PARK2 and LC3 II especially in mitochondria, while over-expression of HMGA2 increased the expression of them in A549 cells. It indicated that HMGA2 played a critical role in Cr (VI)-induced mitophagy. Most importantly, the results of co-immunoprecipitation showed for the first time that HMGA2 could bind to PARK2 in mitochondria to activate the mitophagy pathway. In BALB/c mice, Cr (VI) increased the expression of PINK1 and PARK2 in lung tissues. Furthermore, over-expression of HMGA2 in BALB/c mice by transfection of plasmid HMGA2 significantly increased the levels of PINK1, PARK2 and LC3 II in lung tissues. Collectively, our data demonstrated that HMGA2 plays an important role in Cr (VI)-induced mitophagy through direct interaction with PARK2 in A549 cells and lung tissue. [ABSTRACT FROM AUTHOR]

• Cr (VI) could induce aerobic glycolysis in A549 cells. • ER stress and autophagy are involved in Cr (VI)-induced glycolysis in A549 cells. • Aerobic glycolysis played an important role in attenuating Cr (VI)-induced apoptosis. • ATF4 is involved in Cr (VI)-induced aerobic glycolysis and its effect of attenuating apoptosis in A549 cells. Chromium (Cr) (VI) compounds are known to be serious toxic and carcinogenic, but the mechanism is not clear. In our previous study, we found that Cr (VI)-induced ER stress plays an important role in the crosstalk between apoptosis and autophagy, while autophagy was apoptosis-dependent and subsequently prevents apoptosis cell death to keep A549 cells resistant to Cr (VI)-induced toxicity. In this study, we found that Cr (VI) could induce aerobic glycolysis in A549 cells. Both ER stress inhibitor, phenylbutyric acid (4-PBA) and the inhibitor of autophagy, 3-MA, repressed Cr (VI)-induced glycolysis, indicating that both ER stress and autophagy were involved in Cr (VI)-induced glycolysis in A549 cells. Co-treatment of the inhibitor of aerobic glycolysis, 2-DG and Cr (VI) for 24 h increased Cr (VI)-induced cleaved caspase-3, caspase-9 and the number of apoptotic cells, demonstrating that aerobic glycolysis played an important role in attenuating Cr (VI)-induced apoptosis. Furthermore, knockdown of ATF4 by siATF4 significantly decreased Cr (VI)-induced aerobic glycolysis and apoptosis, suggesting that ATF4 was involved in Cr (VI)-induced aerobic glycolysis and its effect of attenuating apoptosis in A549 cells. Taken together, our results demonstrated that autophagy-dependent glycolysis played a role in attenuating Cr (VI)-induced apoptosis. ER stress was involved in facilitating glycolysis, whose induction was mediated by ATF4. These findings open a window for the development of therapeutic interventions to prevent Cr (VI)-induced toxicity. [ABSTRACT FROM AUTHOR]

• 2,5-hexanedione exposure induced neuropathy in treated animals. • The axon-miRNAs related to 2,5-hexanedione induced neuropathy. • Axon-related miRNAs mediate 2,5-hexanedione toxicity by regulating many pathways. Exposure to organic solvent in industry, including n-hexane is correlated with central-peripheral axonopathy, which is mediated by its active metabolite, 2,5-hexanedione (HD). However, the underlying mechanism is still largely unknown. Recently identified microRNAs (miRNAs) may play important roles in toxicant exposure and in the process of toxicant-induced neuropathys. To examine the role of miRNAs in HD-induced toxicity, neuropathic animal model was successfully built. miRNA microarray analysis revealed 105 differentially expressed miRNAs after HD exposure. Bioinformatics analysis showed that "Axon" and "Neurotrophin Signaling Pathway" was the top significant GO term and pathway, respectively. 7 miRNAs both related to "Axon" and "Neurotrophin Signaling Pathway" were screened out and further confirmed by Real-Time PCR. Correspondingly, the deregulation expression levels of proteins of four target genes (GSK3β, Map3k1, BDNF and MAP1B) were further confirmed via western blot, verifying the results of gene target analysis. Taken together, our results showed that the axon-related miRNAs to be associated with MAP1B or neurotrophin signal pathways changed in nerve tissues following HD exposure. These miRNAs may play important roles in HD-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Abstract Cadmium (Cd) is a highly ubiquitous detrimental metal in the environment. It is a well-known inducer of tumorigenesis, but the mechanism is not clear. In our previous study, we found that ROS-dependent Atg4B upregulation mediated Cd-induced autophagy and autophagy played an important role in Cd-induced proliferation and invasion in A549 cells. In this study, we found that Cd induced both apoptosis and autophagy in A549 cells, and apoptosis preceded autophagy. Z-VAD-FMK repressed Cd-induced LC3 and Beclin1, indicating that apoptosis was essential for Cd-induced autophagy. 3MA destroyed the recovery of mitochondrial membrane potential and increased Cd-induced CL-CASP9 and CL-CASP3 expression, suggesting that Cd-induced autophagy prevented A549 cells from apoptosis. Further study showed that Atg4B upregulation was mediated by mitochondrial dysfunction and conversely affected mitochondrial function by decreasing Bcl-2 protein expression and its localization in mitochondria, and played an important role in Cd-induced apoptosis. Moreover, Bcl-2 was involved in Cd-induced autophagy. Co-IP assay showed that Atg4B could directly bind to Bcl-2, and consequently promote disassociation of Bcl-2-Beclin1 and released autophagic protein Beclin1 to activate autophagic pathway. Taken together, our results demonstrated that the interaction of Atg4B and Bcl-2 might play an important role in Cd-induced crosstalk between apoptosis and autophagy through disassociation of Bcl-2-Beclin1. Cd-induced autophagy is apoptosis-dependent and prevents apoptotic cell death to ensure the growth and proliferation of A549 cells. Graphical abstract fx1 Highlights • CdCl 2 induced both apoptosis and autophagy in A549 cells, and apoptosis preceded autophagy. • Atg4B was involved in both CdCl 2 -induced apoptosis and autophagy. • Atg4B could bind to Bcl-2 and subsequently promote disassociation of Bcl-2-Beclin1, releasing Beclin1 to activate autophagic pathway. [ABSTRACT FROM AUTHOR]

Epidemiological investigations and experimental studies indicate that chronic arsenic exposure can reduce learning and memory function. However, the underlying mechanism of this effect remains largely unknown. Emerging evidence suggests that microRNA (miRNA) play an important role in toxicant exposure and a regulatory role in cognitive function. In this study, we observed that subchronic arsenic exposure induced impairment of learning and memory and significantly up-regulated miRNA-219 (miR-219) expression in the mouse hippocampus. Furthermore, the expression of CaMKII, an experimentally validated target of miR-219, was decreased in the mice exposed to arsenic. Suppression of miR-219 by adeno-associated viral (AAV)-delivered anti-miR-219 prevented the arsenic-induced impairment of learning and memory and relieved the pathological changes in the synaptic structure of the hippocampus. Furthermore, we observed that the NMDA receptor subunit 2 (NR2) and the memory-related proteins c-Fos and c-Jun were up-regulated by inhibition of miR-219 in the mouse hippocampus. Taken together, the results of this study indicate that inhibition of miR-219 regulates arsenic-induced damage in the structure of the hippocampus and impairment of learning and memory, possibly by targeting CaMKII. Suppression of miR-219 may be a potential strategy to ameliorate arsenic-induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Hexavalent chromium [Cr (VI)] is a proven human carcinogen which is widely used in steel manufacturing and painting. Here, the involvement of high mobility group A2 (HMGA2) in Cr (VI)-mediated glycolysis and oxidative phosphorylation (OXPHOS) was investigated. First, Cr (VI) treatment induced aerobic glycolysis by increasing the expression of GLUT1, HK II, PKM2 and LDHA enzymes, and reduced OXPHOS by decreasing mitochondrial mass, the expression of COX IV and ND1, and increasing Ca2+ content in mitochondria in A549 and HELF cells. And overexpression of HMGA2 induced aerobic glycolysis and decreased OXPHOS. Secondly, using endoplasmic reticulum (ER) stress inhibitor, 4-phenylbutyric acid (4-PBA) and knockdown of activating transcription factor 4 (ATF4) gene by siRNA, we demonstrated that ER stress and ATF4 elevation mediated Cr (VI)-induced glycolysis and inhibited OXPHOS. Furthermore, using tunicamycin (Tm), siHMGA2, transfection of HMGA2 and siATF4, we demonstrated that ER stress-enhanced interaction of HMGA2 and ATF4 resulted in Cr (VI)-induced glycolysis and inhibited OXPHOS. Additionally, ChIP assay revealed that HMGA2 protein could directly bind to the promoter sequence of ATF4 gene, which modulated Cr (VI)-induced ATF4 elevation. Finally, in lung tissues of BALB/c mice injected with HMGA2 plasmids, it is verified that HMGA2 involved in regulation of ATF4, glycolysis and OXPHOS in vivo. Combining, our data discovered that ER stress-enhanced the interaction of HMGA2 and ATF4 played an important role in Cr (VI)-mediated glycolysis and OXPHOS. These results imply a root cause for the carcinogenicity of Cr (VI), and could guide development of novel therapeutics for cancers. [Display omitted] • HMGA2 was involved in Cr (VI)-mediated glycolysis and oxidative phosphorylation (OXPHOS) in vivo and in vitro. • Endoplasmic reticulum stress and ATF4 elevation mediated Cr (VI)-induced glycolysis and inhibited OXPHOS. • Interaction of HMGA2 and ATF4 resulted in Cr (VI)- mediated glycolysis and OXPHOS. • HMGA2 protein could directly bind to the promoter sequence of ATF4 gene. [ABSTRACT FROM AUTHOR]

[Display omitted] • Cd increased glycolysis and decreased oxidative phosphorylation in vivo and in vitro. • Cd-induced metabolic reprogramming underlies the mechanism of its effect on cell migration. • HMGA2 played an important role in Cd-induced metabolic reprogramming. • Autophagy was required in the effect of HMGA2-induced metabolic reprogramming. • HMGA2/autophagy-mediated metabolic reprogramming promoted Cd-induced migration. High mobility group A2 (HMGA2) is closely related to the occurrence, development and prognosis of tumors. But the mechanism is unclear. Metabolic reprogramming is a dominant way to meet anabolic and energy requirements of tumor cells for their survival, growth and proliferation. Here, we investigated the role of metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis mediated by HMGA2/autophagy axis in cadmium (Cd, CdCl 2)-induced migration. First, we found that Cd induced glycolysis and reduced OXPHOS in vivo (0.5 and 1 mg/kg, i.p. or 0.8 and 1.6 μM, i.t.) and in vitro (2 μM in A549 cells and 0.05 μM in HELF cells). Then, genetic knockdown of HMGA2 restored Cd-reduced mitochondrial mass and OXPHOS and inhibited Cd-increased glycolysis, indicating that HMGA2 was involved in Cd-induced metabolic reprogramming. 2-Deoxy- d -glucose (2DG, 5 mM), the inhibitor of glycolysis decreased Cd/HMGA2-induced cell migration and restored Cd/HMGA2-decreased OXPHOS and mitochondrial mass. Inhibition of autophagy by 3-Methyladenine (3MA, 3 mM) elucidated an essential role of autophagy in HMGA2-induced glycolysis, migration, and HMGA2-reduced OXPHOS. Overall, our study demonstrated that autophagy was required for HMGA2-mediated metabolic reprogramming, which was critical for Cd-induced migration. Targeting HMGA2 and autophagy-dependent reprogrammed metabolism may be an effective way to inhibit Cd-induced cell migration. [ABSTRACT FROM AUTHOR]

Introduction: Anxiety disorders are the most common mental disorder, experienced by more than a quarter of the population. This study examines total outpatient curative care expenditures (CCE) for anxiety disorders and changes in their composition based on the System of Health Accounts 2011 (SHA 2011)., Methods: This study used multi-stage stratified random from a total of 9,318,513 outpatient sample data by 920 healthcare organizations, a total of 109,703 cases of anxiety disorders from 53 sample organizations (5.76%) from 2015 to 2020. Univariate analysis, multifactor analysis and structural equation modeling (SEM) were used to explore the influential factors affecting outpatient CCE for anxiety disorders., Results: Anxiety disorder outpatient CCE from 2015 to 2020 continued to increase from CNY 99.39million in 2015 to CNY 233.84 million in 2020, mainly concentrated in western medicine costs, 15-64 years, general hospital, generalized anxiety disorder and public financing. The results of univariate analysis showed statistically significant differences in all subgroups, and the results of multivariate analysis and SEM showed that the choice to purchase western drugs, purchase prepared Chinese drugs, choice to have a checkup, urban employees' basic medical insurance, and 0-14 years old were associated with high anxiety disorder outpatient CCE., Conclusion: Initiatives to improve the essential drug system, reduce the out-of-pocket (OOP) ratio, and strengthen primary health care to effectively reduce the medical burden on patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Shi, Zhao, Wan, Chai and Ma.)

Problem: The phenomenon of emergence delirium in pediatric patients undergoing general anesthesia has garnered increasing attention in the academic community. While formal non-pharmaceutical interventions have demonstrated efficacy in mitigating this phenomenon, the diversity of intervention types and their varying degrees of effectiveness necessitate further discussion. A scoping review was conducted to identify and explicate the categorization, content elements, and outcomes measures of non-pharmacological interventions utilized to forestall the onset of emergence delirium in children undergoing general anesthesia., Eligibility Criteria: This review was conducted in accordance with the Arksey and O'Malley's methodology framework and PRISMA-ScR. It encompassed experimental and quasi-experimental studies that involved any non-pharmacological interventions during the perioperative period to prevent emergence delirium in children aged 0 to 18 years undergoing general anesthesia for elective surgery., Sample: Thirty-two articles met the inclusion criteria, of which 29 were randomized controlled trials. The total sample size of the population was 4633., Results: The scoping review revealed 10 non-pharmacological interventions, that included distraction intervention, visual preconditioning, virtual reality, parental participation, maternal voice, light drinking, acupuncture, auditory stimulation, monochromic light and breathing training. Emergence delirium, preoperative anxiety, and postoperative pain were the primary outcomes, and four assessment instruments were employed to measure the extent and incidence of emergence delirium., Conclusion: Numerous non-pharmacological interventions have been employed to prevent emergence delirium. Nevertheless, the effectiveness of some interventions is not yet evident., Implications: The utilization of visual preconditioning and distraction interventions appears to be an emerging area of interest., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)