Publications by authors named "Yingnan Zhao"

71 Publications

Variational Dynamic for Self-Supervised Exploration in Deep Reinforcement Learning.

IEEE Trans Neural Netw Learn Syst 2021 Dec 1;PP. Epub 2021 Dec 1.

Efficient exploration remains a challenging problem in reinforcement learning, especially for tasks where extrinsic rewards from environments are sparse or even totally disregarded. Significant advances based on intrinsic motivation show promising results in simple environments but often get stuck in environments with multimodal and stochastic dynamics. In this work, we propose a variational dynamic model based on the conditional variational inference to model the multimodality and stochasticity. We consider the environmental state-action transition as a conditional generative process by generating the next-state prediction under the condition of the current state, action, and latent variable, which provides a better understanding of the dynamics and leads to a better performance in exploration. We derive an upper bound of the negative log likelihood of the environmental transition and use such an upper bound as the intrinsic reward for exploration, which allows the agent to learn skills by self-supervised exploration without observing extrinsic rewards. We evaluate the proposed method on several image-based simulation tasks and a real robotic manipulating task. Our method outperforms several state-of-the-art environment model-based exploration approaches.
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http://dx.doi.org/10.1109/TNNLS.2021.3129160DOI Listing
December 2021

Application of the OMAHA System in the education of nursing students: A systematic review and narrative synthesis.

Nurse Educ Pract 2021 Nov 29;57:103221. Epub 2021 Sep 29.

School of Nursing, Jilin University, No.965 Xinjiang Street, Changchun 130021, Jilin, People's Republic of China. Electronic address:

Aim: The aim of this systematic review was to synthesize evidence on the application of the Omaha System in the education of nursing students and to provide advice for educators to apply the Omaha System to practice and research effectively and meaningfully.

Background: It is a necessary part of nursing education to provide students with informatics experience. The Omaha System is a standardized nursing terminology designed to enhance practice, documentation, and information management.

Design: A systematic review and narrative synthesis.

Methods: Studies from eight databases (PubMed, Web of Science, Embase, CINAHL, PsycINFO, China Biology Medicine disc, CNKI, Wanfang Data) were systematically retrieved. Twenty-three articles were found and synthesized.

Results: Existing studies showed that the Omaha System was mainly applied in student community practice as a tool for guiding practice and collecting information, and the practice data were used by educators to analyse the outcomes of nursing education. Recently, the Omaha System was introduced into the classroom environment and achieved positive results in terms of teaching. Students' feedback on the use of the Omaha System was generally positive.

Conclusions: The Omaha System can be an active teaching and learning tool for nursing education, and further research is needed to explore and realize its potential in the field of education.
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http://dx.doi.org/10.1016/j.nepr.2021.103221DOI Listing
November 2021

Farnesylthiosalicylic Acid-Loaded Albumin Nanoparticle Alleviates Renal Fibrosis by Inhibiting Ras/Raf1/p38 Signaling Pathway.

Int J Nanomedicine 2021 21;16:6441-6453. Epub 2021 Sep 21.

Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, People's Republic of China.

Background: Renal fibrosis is the common pathway in chronic kidney diseases progression to end-stage renal disease, but to date, no clinical drug for its treatment is approved. It has been demonstrated that the inhibitor of proto-oncogene Ras, farnesylthiosalicylic acid (FTS), shows therapeutic potential for renal fibrosis, but its application was hindered by the water-insolubility and low bioavailability. Hence, in this study, we improved these properties of FTS by encapsulating it into bovine serum albumin nanoparticles (AN-FTS) and tested its therapeutic effect in renal fibrosis.

Methods: AN-FTS was developed using a classic emulsification-solvent ultrasonication. The pharmacokinetics of DiD-loaded albumin nanoparticle were investigated in SD rats. The biodistribution and therapeutic efficacy of AN-FTS was assessed in a mouse model of renal fibrosis induced by unilateral ureteral obstruction (UUO).

Results: AN-FTS showed a uniform spherical shape with the size of 100.6 ± 1.12 nm and PDI < 0.25. In vitro, AN-FTS displayed stronger inhibitory effects on the activation of renal fibroblasts cells NRK-49F than free FTS. In vivo, AN-FTS showed significantly higher peak concentration and area under the concentration-time curve. After intravenous administration to UUO-induced renal fibrosis mice, AN-FTS accumulated preferentially in the fibrotic kidney, and alleviated renal fibrosis and inflammation significantly more than the free drug. Mechanistically, the improved anti-fibrosis effect of AN-FTS was associated with greater inhibition in renal epithelial-to-mesenchymal transformation process via Ras/Raf1/p38 signaling pathway.

Conclusion: The study reveals that AN-FTS is capable of delivering FTS to fibrotic kidney and showed superior therapeutic efficacy for renal fibrosis.
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http://dx.doi.org/10.2147/IJN.S318124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464329PMC
November 2021

Berberine exerts neuroprotective activities against cerebral ischemia/reperfusion injury through up-regulating PPAR-γ to suppress NF-κB-mediated pyroptosis.

Brain Res Bull 2021 Dec 11;177:22-30. Epub 2021 Sep 11.

Department of Neurology (Six), The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, PR China. Electronic address:

Objective: Berberine (BBR) is an anti-inflammatory alkaloid compound extracted from herbs. The purpose of this study is to probe the possible effect and the mechanism of BBR against cerebral ischemia/reperfusion (I/R) injury.

Methods: In vitro oxygen and glucose deprivation (OGD) model was established on neurons from rat hippocampus, which was then subjected to BBR, IVA337 (PPAR-γ agonist), or GW9662 (PPAR-γ antagonist) treatment, to identify their effects on neuronal pyroptosis. MTT assay was utilized to determine cell survival rates, TUNEL staining for observation of β-tubulin and MAP2 expressions, qRT-PCR for detection of mRNA expression of PPAR-γ, Western blot for assessment of protein expressions of PPAR-γ and pyroptosis-related proteins (AIM2, NLPR3, ASC, cleaved-Caspase-1, GSDMD, and GSDMD-N), and ELISA for examination of IL-18 and IL-1β expressions.

Results: OGD modeling induced neuron pyroptosis, as evidenced by increased expression levels of pyroptosis-related proteins as well as IL-1β and IL-18, and elevated cell apoptosis rate. In addition, OGD exposure led to PPAR-γ up-regulation and NF-κB activation. Overexpression of PPAR-γ ameliorated cell pyroptosis, while knockdown of PPAR-γ intensified neuron pyroptosis that could be reversed by BBR. Furthermore, either BBR could block the activation of NF-κB signaling pathway through PPAR-γ.

Conclusion: BBR protects rats from cerebral I/R injury by up-regulating PPAR-γ to restrain NF-κB-mediated pyroptosis.
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http://dx.doi.org/10.1016/j.brainresbull.2021.09.005DOI Listing
December 2021

Effectiveness of caregiver non-pharmacological interventions for behavioural and psychological symptoms of dementia: An updated meta-analysis.

Ageing Res Rev 2021 11 17;71:101448. Epub 2021 Aug 17.

School of Nursing, Jilin University, Changchun, China. Electronic address:

Background: The behavioural and psychological symptoms of dementia (BPSD) have significant negative effects on the health of both patients with dementia and their caregivers. However, the reported effectiveness of non-pharmacological interventions targeting caregivers of patients with dementia for BPSD is inconsistent.

Methods: We systematically searched the databases PubMed, PsycINFO, CINAHL, Embase, Cochrane Library and four Chinese databases from 2010 through April 2021. The Standardised mean difference (SMD) was calculated using random-effects models. Risk of bias in individual studies was assessed using Cochrane Collaboration's tool, and the certainty of evidence was assessed using the five GRADE criteria.

Results: Thirty-one randomised controlled trials (RCTs) involving 3501 dyads were included. The meta-analysis indicated that non-pharmacological interventions showed small but significant effects on both BPSD in patients with dementia (SMD = -0.14; 95% CI, -0.22 to -0.06; P = 0.001) and caregiver reactions to BPSD (SMD = -0.16; 95% CI, -0.25 to -0.07; P = 0.001). The effect sizes of BPSD in patients at follow-up (SMD = -0.24; 95% CI, -0.38 to -0.09; P = 0.002) were larger than those at post-test. Tailored interventions were associated with more substantial reductions in BPSD in patients (SMD = -0.24; 95% CI, -0.37 to -0.11; P < 0.001) than standardised interventions (SMD = -0.07; 95% CI, -0.18 to 0.04; P = 0.218).

Conclusions: Non-pharmacological interventions targeting caregivers have the potential to reduce BPSD in patients with dementia and improve caregiver negative reactions to BPSD. Moreover, tailored interventions seemed to be more effective in reducing BPSD, and more significant improvements in BPSD may be observed in long-term follow-up.
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http://dx.doi.org/10.1016/j.arr.2021.101448DOI Listing
November 2021

Comprehensive analysis of an immune-related ceRNA network in identifying a novel lncRNA signature as a prognostic biomarker for hepatocellular carcinoma.

Aging (Albany NY) 2021 07 8;13(13):17607-17628. Epub 2021 Jul 8.

Department of Hepatobiliary Surgery I, General Surgery Center, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

The function of competitive endogenous RNA (ceRNA) network in the immune regulation of hepatocellular carcinoma (HCC) is unclear. Our study aimed to construct an immune-related ceRNA network and develop an immune-related long noncoding RNA (lncRNA) signature to assess the prognosis of HCC patients and to optimize the treatment methods. We firstly constructed a ceRNA regulatory network for HCC using differentially expressed lncRNAs, mRNAs and microRNAs (miRNAs) from the Cancer Genome Atlas. A signature was constructed by 11 immune-related prognostic lncRNAs from the ceRNA network. The survival analysis and receiver operating characteristic analysis validated the reliability of the signature. Multivariate Cox regression analysis revealed that the signature could act an independent prognostic indicator. This signature also showed high association with immune cell infiltration and immune check blockades. LINC00491 was identified as the hub lncRNA in the signature. and evidence demonstrated that silencing of LINC00491 significantly inhibited HCC growth. Finally, 59 lncRNAs, 21 miRNAs, and 26 mRNAs were obtained to build the immune-related ceRNA network for HCC. In conclusion, our novel immune-related lncRNA prognostic signature and the immune-related ceRNA network might provide in-depth insights into tumor-immune interaction of HCC and promote better individual treatment strategies in HCC patients.
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http://dx.doi.org/10.18632/aging.203250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312417PMC
July 2021

Facile Synthesis of Water-Stable Multicolor Carbonized Polymer Dots from a Single Unconjugated Glucose for Engineering White Light-Emitting Diodes with a High Color Rendering Index.

ACS Appl Mater Interfaces 2021 Jun 18;13(25):30098-30105. Epub 2021 Jun 18.

Green Catalysis Center, and College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.

Tunable emission carbonized polymer dots (CPDs) are highly desirable for the preparation of optoelectronic devices, especially white light-emitting diodes (WLEDs). In most available studies, polychromatic CPDs are synthesized using aromatic molecules as precursors. However, few studies report the successful synthesis of polychromatic CPDs using two or more unconjugated precursors. In this work, we prepare multicolor fluorescent CPDs from a single unconjugated precursor, glucose, via a hydrothermal reaction. By controlling the particle size and degree of graphitization of the synthesized CPDs, their emission wavelength can be tuned in the range 440-625 nm (i.e., almost the entire visible region). Furthermore, the CPDs can be used to construct LEDs of varying colors, including WLEDs (CIE coordinates: 0.34, 0.36) with the correlated color temperature and color rendering index of 4997 K and 92.69, respectively. In brief, the strategy proposed in this study successfully converts unconjugated glucose into high-performance LEDs with great application potential.
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http://dx.doi.org/10.1021/acsami.1c07444DOI Listing
June 2021

Canagliflozin Facilitates Reverse Cholesterol Transport Through Activation of AMPK/ABC Transporter Pathway.

Drug Des Devel Ther 2021 18;15:2117-2128. Epub 2021 May 18.

Department of Pharmacy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People's Republic of China.

Background And Purpose: Cholesterol is an essential lipid and its homeostasis is a major factor for many diseases, such as hyperlipidemia, atherosclerosis, diabetes, and obesity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor canagliflozin (Cana) is a new kind of hypoglycemic agent, which decreases urinary glucose reabsorption and reduces hyperglycemia. Cana has been shown to regulate serum lipid, decrease serum triglyceride and increase serum high-density lipoprotein-cholesterol (HDL-C), and improve cardiovascular outcomes. But evidence of how Cana impacted the cholesterol metabolism remains elusive.

Methods: We treated Cana on mice with chow diet or western diet and then detected cholesterol metabolism in the liver and intestine. To explore the mechanism, we also treated hepG2 cells and Caco2 cells with different concentrations of Cana.

Results: In this study, we showed that Cana facilitated hepatic and intestinal cholesterol efflux. Mechanically, Cana via activating adenosine monophosphate-activated protein kinase (AMPK) increased the expression of ATP-binding cassette (ABC) transporters ABCG5 and ABCG8 in liver and intestine, increased biliary and fecal cholesterol excretion.

Conclusion: This research confirms that Cana regulates cholesterol efflux and improves blood and hepatic lipid; this may be a partial reason for improving cardiovascular disease.
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http://dx.doi.org/10.2147/DDDT.S306367DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8140894PMC
November 2021

Foamer-Derived Bulk Nitrogen Defects and Oxygen-Doped Porous Carbon Nitride with Greatly Extended Visible-Light Response and Efficient Photocatalytic Activity.

ACS Appl Mater Interfaces 2021 May 17;13(20):23866-23876. Epub 2021 May 17.

Key Laboratory of Polyoxometalate Science of Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun 130024, China.

Constructing bulk defects and doping are feasible ways to essentially narrow the band gap and improve the light absorption of photocatalysts. Herein, inspired by bread foaming, the foaming agent azoformamide or azodicarbonamide (AC) was introduced during the thermal polymerization of urea. In the polymerization process, a large number of bubbles produced by AC decomposition seriously interfered with the polymerization of urea, resulting in the breaking of the hydrogen bonds and van der Waals interaction in carbon nitride, distortion of its structure, and partial oxidation, thus forming a series of porous carbon nitrides U/AC ( is the ratio of AC to urea; where = 0.25, 0.5, and 1) with bulk N defects and O doping. Its band gap was reduced to 1.91 eV and the absorption band edge was greatly extended to 650 nm. The optimal U/AC exhibits the highest visible light photocatalytic hydrogen production rate of about 44.7 μmol·h (10 mg catalysts) and shows superior photocatalytic performance for the oxidation of diphenylhydrazine to azobenzene, with conversion and selectivity of almost 100%, and is one of the most active defective carbon nitrides, especially under long-wavelength (λ ≥ 550 nm) light irradiation. It paves the way for the design of highly efficient and wide-spectral-response photocatalysts.
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http://dx.doi.org/10.1021/acsami.1c06235DOI Listing
May 2021

Sensory-based approaches in psychiatric care: A systematic mixed-methods review.

J Adv Nurs 2021 Oct 5;77(10):3991-4004. Epub 2021 May 5.

School of Nursing, Jilin University, Jilin, People's Republic of China.

Aims: Sensory-based approaches, including sensory room, sensory cart and specific sensory integration programs, feature various sensory stimulations to focus on a particular space or program. This systematic mixed-methods review describes the impact of sensory-based approaches in psychiatric care and summarizes the important components of sensory interventions.

Design: Systematic mixed-methods review was based on the guidelines by Pluye and Hong for comprehensively searching, appraising and synthesizing research evidence.

Data Sources: Data were collected from five databases: CINAHL, Embase, Pubmed, Web of Science and Cochrane before March 9, 2020.

Review Methods: Qualitative, quantitative, mixed-methods and original studies published in English on sensory-based approaches in psychiatric care were included. The studies were selected by screening titles, abstracts and full texts, and the quality of each study was assessed by two researchers independently. The data were analysed using thematic analysis.

Results: Sixteen studies were chosen for review. Through data integration, four subthemes with positive effects were formed: (1) calming of the patient's mood; (2) calming of the patient's body; (3) improvement of self-care ability; and (4) improvement of the nurse-patient relationship. The sensory-based approach may also lead to negative effects.

Conclusions: Several important components play important roles in the sensory-based approaches: (1) rich, culture-based, personalized sensory stimulation; (2) a quiet, safe, home-based physical environment; (3) a good one-to-one nurse-patient relationship; (4) and the cultivation of patient autonomy and self-management. Sensory-based approaches in a multicultural environment and home environment will be important topics of psychiatric care in the future.

Impact: There is a lack of synthesis of studies on results of sensory-based approaches in psychiatric care. Four components are important to sensory interventions. It is necessary for mental health service centres and home care for the patients with psychotic disorders to use sensory-based approaches for reference.
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http://dx.doi.org/10.1111/jan.14884DOI Listing
October 2021

Hepatocyte-specific deletion of Nlrp6 in mice exacerbates the development of non-alcoholic steatohepatitis.

Free Radic Biol Med 2021 06 20;169:110-121. Epub 2021 Apr 20.

Department of Pharmacy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, Sichuan Province, China; Laboratory of Clinical Pharmacy and Adverse Drug Reaction, National Clinical Research Center for Geriatrics,West China Hospital, Sichuan University, Chengdu, Sichuan Province, China. Electronic address:

Objective: Previous studies have established that deficiency in Nucleotide-binding and oligomerization domain (NOD)-like receptor family pyrin domain containing 6 (Nlrp6) changes the configuration of the gut microbiota, which leads to hepatic steatosis. Here, we aimed to determine the hepatic function of Nlrp6 in lipid metabolism and inflammation and its role in the development of non-alcoholic steatohepatitis (NASH).

Methods: Nlrp6 and hepatocyte-specific Nlrp6-knockout mice were fed a high-fat diet (HFD) or methionine-choline deficient (MCD) diet to induce fatty liver or steatohepatitis, respectively. Primary hepatocytes were isolated to further explore the underlying mechanisms in vitro. In addition, we used adenovirus to overexpress Nlrp6 in ob/ob mice to demonstrate its role in NASH.

Results: Hepatic Nlrp6 expression was downregulated in NASH patients and in obese mice. Hepatocyte-specific Nlrp6 deficiency promoted HFD- or MCD diet-induced lipid accumulation and inflammation, whereas Nlrp6 overexpression in ob/ob mice had beneficial effects. In vitro studies demonstrated that knockdown of Nlrp6 aggravated hepatic steatosis and inflammation in hepatocytes, but its overexpression markedly attenuated these abnormalities. Moreover, both in vitro and in vivo study demonstrated that Nlrp6 inhibited Cd36-mediated lipid uptake. Nlrp6 deficiency-enhanced fatty acid uptake was blocked by a Cd36 inhibitor in hepatocytes. Nlrp6 ablation increased the expression of proinflammatory cytokines, likely as a result of increased NF-κB phosphorylation and activation. Mechanistically, Nlrp6 promoted the degradation of transforming growth factor-β-activated kinase 1 (TAK1)-binding protein 2/3 (TAB2/3) via a lysosomal-dependent pathway, which suppressed NF-κB activation.

Conclusions: Nlrp6 may play a key role in the pathological process of NASH by inhibiting Cd36 and NF-κB pathways. It may be a potential therapeutic target for NASH.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.04.008DOI Listing
June 2021

Feeding-induced hepatokine, Manf, ameliorates diet-induced obesity by promoting adipose browning via p38 MAPK pathway.

J Exp Med 2021 06;218(6)

Department of Pharmacy, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.

Activating beige adipocytes in white adipose tissue (WAT) to increase energy expenditure is a promising strategy to combat obesity. We identified that mesencephalic astrocyte-derived neurotrophic factor (Manf) is a feeding-induced hepatokine. Liver-specific Manf overexpression protected mice against high-fat diet-induced obesity and promoted browning of inguinal subcutaneous WAT (iWAT). Manf overexpression in liver was also associated with decreased adipose inflammation and improved insulin sensitivity and hepatic steatosis. Mechanistically, Manf could directly promote browning of white adipocytes via the p38 MAPK pathway. Blockade of p38 MAPK abolished Manf-induced browning. Consistently, liver-specific Manf knockout mice showed impaired iWAT browning and exacerbated diet-induced obesity, insulin resistance, and hepatic steatosis. Recombinant Manf reduced obesity and improved insulin resistance in both diet-induced and genetic obese mouse models. Finally, we showed that circulating Manf level was positively correlated with BMI in humans. This study reveals the crucial role of Manf in regulating thermogenesis in adipose tissue, representing a potential therapeutic target for obesity and related metabolic disorders.
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http://dx.doi.org/10.1084/jem.20201203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054200PMC
June 2021

Job satisfaction, resilience and social support in relation to nurses' turnover intention based on the theory of planned behaviour: A structural equation modelling approach.

Int J Nurs Pract 2021 Dec 15;27(6):e12941. Epub 2021 Apr 15.

School of Nursing, Jilin University, Jilin, China.

Background: Many national studies have shown that nurses have a high turnover rate. The key to maintaining the stability of nursing staff is to explore the factors that affect their turnover intention; however, no research has been performed to explore the influencing factors and mechanisms of nurses' turnover intention based on the Theory of Planned Behaviour.

Aim: Based on the Theory of Planned Behaviour, examining the relationships among resilience, job satisfaction, social support and turnover intention of nurses, a structural equation model was constructed to examine the mediating role of job satisfaction and social support between resilience and turnover intention.

Methods: In this descriptive cross-sectional study, a total of 350 questionnaires were distributed to participants from three tertiary hospitals in Changchun, Jilin Province, between December 2018 and March 2019.

Results: The final model fits well. Job satisfaction and social support directly influences turnover intention. Resilience indirectly influences turnover intention through job satisfaction and social support.

Conclusion: Turnover intention is a complex variable, which is directly and indirectly affected by many factors. In this study, a new structural equation model was proposed, which laid a foundation for future longitudinal studies.
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http://dx.doi.org/10.1111/ijn.12941DOI Listing
December 2021

Effectiveness of patient-targeted interventions to inform decision making and improve uptake of colorectal cancer genetic evaluation for at-risk individuals: A systematic review.

Int J Nurs Stud 2021 Jun 20;118:103928. Epub 2021 Mar 20.

Basic Nursing Department, School of Nursing, Jilin University, 965 Xinjiang Street, Changchun, Jilin 130021, China. Electronic address:

Background: Inherited colorectal cancer syndromes increase the risk of contracting colorectal and other cancers. International guidelines recommend the identification of individuals with hereditary colorectal cancer and the supervision of asymptomatic individuals with a family history. However, detection of hereditary colorectal cancer is suboptimal. The prevalence of genetic counselling and testing for individuals with high genetic risk is low.

Objective: To identify, characterize and summarize patient-targeted interventions on improving the uptake of colorectal cancer genetic evaluation for at-risk individuals and enhancing their informed decision making.

Design: Systematic review.

Data Sources: Six electronic databases (PubMed, CINAHL, Web of Science, Embase, PsycINFO, and Cochrane library) were searched to identify eligible clinical trials from each database's inception to March 25, 2020. The reference lists of the included studies and reviews were checked for additional articles.

Review Methods: Studies were screened and independently appraised by two reviewers using the standardized critical appraisal checklist for randomized controlled trials and quasi-experimental studies from the Joanna Briggs Institute. The results were tabulated and reported in descriptive format.

Results: Based on the inclusion criteria, 8 articles satisfied the inclusion criteria and were included. The studies examined patient-targeted intervention strategies related to risk assessment, education, and decision aids. Outcomes included (1) informed decisions regarding microsatellite instability testing, (2) informed decisions concerning genetic testing, (3) genetic counselling and testing. Most of the included studies revealed that interventions had positive effects on the uptake of colorectal cancer genetic evaluation for at-risk individuals and their informed decision making.

Conclusions: There were few studies included in this review, and the results were inconsistent. Based on this review, the conclusion cannot be made that interventions for risk assessment, education, and decision aids have positive effects on the uptake of colorectal cancer genetic evaluation for at-risk individuals and their informed decision making. However, to our knowledge, this is the first systematic review to summarize the effectiveness of patient-targeted interventions to inform decision making and improve uptake of colorectal cancer genetic evaluation for at-risk individuals. This review provides important evidence for related topics. Future studies with rigorous designs are recommended. Nurses have a crucial role in personalized health care. The involvement of nurses in collaboration with all the stakeholders in the development, implementation and evaluation of cancer genetic screening programs to improve genetic referral of individual at risk.
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http://dx.doi.org/10.1016/j.ijnurstu.2021.103928DOI Listing
June 2021

Blocking 5-LO pathway alleviates renal fibrosis by inhibiting the epithelial-mesenchymal transition.

Biomed Pharmacother 2021 Jun 12;138:111470. Epub 2021 Mar 12.

Laboratory of Clinical Pharmacy and Adverse Drug Reaction, West China Hospital of Sichuan University, Chengdu, China; Department of Pharmacy, West China Hospital of Sichuan University, Chengdu, China. Electronic address:

The enzyme 5-lipoxygenase (5-LO) converts arachidonic acid to leukotrienes, which mediate inflammation. The enzyme is known to contribute to organ fibrosis, but how it contributes to renal fibrosis is unclear. Here, we reported that fibrotic kidneys expressed high levels of 5-LO, and deleting the 5-LO gene mitigated renal fibrosis in mice subjected to unilateral ureteral obstruction (UUO), based on assays of collagen deposition, injury and inflammation. Mechanistically, the exogenous leukotrienes B and C, the downstream products of 5-LO, could induce the epithelial-mesenchymal transition (EMT) in kidney epithelial cell cultures, based on assays of E-cadherin, vimentin and snail expression. Studies in UUO mice confirmed that 5-LO deletion inhibited the EMT in the obstructed kidney. More importantly, 5-LO inhibitor zileuton loaded in CREKA-Lip, which could target to fibrotic kidney, markedly attenuated UUO-induced renal fibrosis and injury by inhibiting the EMT in the obstructed kidney. Our results suggested that 5-LO activity may contribute to renal fibrosis by promoting renal EMT, implying that the enzyme may be a useful therapeutic target.
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http://dx.doi.org/10.1016/j.biopha.2021.111470DOI Listing
June 2021

Mesencephalic astrocyte-derived neurotrophic factor alleviates alcohol induced hepatic steatosis via activating Stat3-mediated autophagy.

Biochem Biophys Res Commun 2021 04 10;550:197-203. Epub 2021 Mar 10.

Department of Pharmacy and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Laboratory of Clinical Pharmacy and Adverse Drug Reaction, West China Hospital, Sichuan University, China. Electronic address:

Alcoholic fatty liver disease (AFLD) is induced by alcohol consumption and may progress to more severe liver diseases such as alcoholic steatohepatitis, fibrosis and cirrhosis, and even hepatocellular carcinoma. Mesencephalic astrocyte-derived neurotrophic factor (MANF) participates in maintaining lipid homeostasis. However, the role of MANF in the pathogenesis of AFLD remains unclear. We established an AFLD mouse model following the US National Institute on Alcohol Abuse and Alcoholism procedure. Both mRNA and protein levels of MANF were significantly increased in the chronic binge alcohol feeding model. Liver-specific knockout of MANF aggravated hepatic lipid accumulation. Similarly, liver-specific overexpression of MANF alleviated AFLD in mouse livers. MANF affected hepatic lipid metabolism by modulating autophagy. The levels of LC3-II and Atg5-Atg12 were decreased in mouse livers with MANF liver-specific knockout and increased with MANF liver-specific overexpression. Furthermore, MANF changed the phosphorylation of Stat3 and its nuclear localization. MANF may have a protective role in the development of AFLD.
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http://dx.doi.org/10.1016/j.bbrc.2021.02.123DOI Listing
April 2021

Sirtuin 6 supra-physiological overexpression in hypothalamic pro-opiomelanocortin neurons promotes obesity via the hypothalamus-adipose axis.

FASEB J 2021 03;35(3):e21408

Laboratory of Clinical Pharmacy and Adverse Drug Reaction, West China Hospital of Sichuan University, Chengdu, China.

Sirtuin 6 (Sirt6), a member of the Sirtuin family, has important roles in maintaining glucose and lipid metabolism. Our previous studies demonstrated that the deletion of Sirt6 in pro-opiomelanocortin (POMC)-expressing cells by the loxP-Cre system resulted in severe obesity and hepatic steatosis. However, whether overexpression of Sirt6 in hypothalamic POMC neurons could ameliorate diet-induced obesity is still unknown. Thus, we generated mice specifically overexpressing Sirt6 in hypothalamic POMC neurons (PSOE) by stereotaxic injection of Cre-dependent adeno-associated viruses into the arcuate nucleus of Pomc-Cre mice. PSOE mice showed increased adiposity and decreased energy expenditure. Furthermore, thermogenesis of BAT and lipolysis of WAT were both impaired, caused by reduced sympathetic nerve innervation and activity in adipose tissues. Mechanistically, Sirt6 overexpression decreasing STAT3 acetylation, thus lowering POMC expression in the hypothalamus underlined the observed phenotypes in PSOE mice. These results demonstrate that Sirt6 overexpression specifically in the hypothalamic POMC neurons exacerbates diet-induced obesity and metabolic disorders via the hypothalamus-adipose axis.
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http://dx.doi.org/10.1096/fj.202002607DOI Listing
March 2021

Glucagon-like peptide 1 analogue prevents cholesterol gallstone formation by modulating intestinal farnesoid X receptor activity.

Metabolism 2021 05 11;118:154728. Epub 2021 Feb 11.

Laboratory of Clinical Pharmacy and Adverse Drug Reaction, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China; Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, China. Electronic address:

Background & Aims: Cholesterol gallstone disease (CGD) is a common gastrointestinal disease. Liraglutide, an analogue of glucagon-like peptide 1, has been approved to treat type 2 diabetes. Clinical studies have suggested a potential role of liraglutide in CGD.

Methods: Mice were subcutaneously injected with liraglutide, then fed a lithogenic diet. Bile duct cannulation was performed to collect bile output in mice. Intestinal-specific ablation or pharmacological inhibition of farnesoid X receptor (FXR) was used to study its functions in CGD.

Results: Liraglutide could protect mice against CGD. Liraglutide treatment increased the biliary concentration of cholesterol, phospholipids and bile acids and thereby decreased the cholesterol saturation index. The resistance to CGD conferred by liraglutide is likely a result of increased bile acid synthesis and efficient bile acid transport. The expression of a key bile acid synthetic enzyme, Cyp7a1, was significantly increased in liraglutide-treated mice. The increased expression of Cyp7a1 resulted from a relieved suppression signal of Fgf15 from the ileum. Mechanistically, liraglutide treatment altered bile acid composition and suppressed FXR activity in the ileum. Genetic ablation or pharmacological inhibition of FXR in the intestine protected mice against CGD. More importantly, intestinal FXR was required for liraglutide-mediated regulation of hepatic expression of Cyp7a1.

Conclusion: Liraglutide improved CGD by increasing bile acid secretion and decreasing cholesterol saturation index. Liraglutide attenuates the negative feedback inhibition of bile acids through inhibiting intestinal FXR activity. Our results suggest that liraglutide may represent a novel way for treating or preventing cholesterol gallstones in individuals with high risk of CGD.
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http://dx.doi.org/10.1016/j.metabol.2021.154728DOI Listing
May 2021

Modifiable factors associated with behavioural and psychological symptoms of dementia among patients residing at home: The impacts of patient, caregiver and environmental variables.

Geriatr Nurs 2021 Mar-Apr;42(2):358-365. Epub 2021 Feb 6.

School of Nursing, Jilin University, Changchun, People's Republic of China. Electronic address:

The present study aimed to explore the modifiable factors of behavioural and psychological symptoms of dementia (BPSD) among patients residing at home in terms of patient, caregiver and environmental factors. A cross-sectional survey of 193 patients with dementia residing at home and their caregivers who visited the memory clinic of the Department of Neurology in a tertiary (the highest level) hospital in China from November 2018 to May 2019 was performed. Exacerbated BPSD were associated with patient (old age, high education level, increased dementia severity, and the use of psychotropic drugs), caregiver (low positive aspects and high expressed emotion) and environmental (poor home environment) factors. The use of psychotropic drugs by the patient, positive aspects and expressed emotions of the caregiver, and home environment were modifiable factors that provided evidence for the direction of intervention for BPSD among patients residing at home.
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http://dx.doi.org/10.1016/j.gerinurse.2021.01.008DOI Listing
September 2021

Targeting Interstitial Myofibroblast-Expressed Integrin αvβ3 Alleviates Renal Fibrosis.

Mol Pharm 2021 03 5;18(3):1373-1385. Epub 2021 Feb 5.

Laboratory of Clinical Pharmacy and Adverse Drug Reaction, West China Hospital of Sichuan University, Chengdu 610041, China.

Renal fibrosis is the final manifestation of various chronic kidney diseases. Interstitial myofibroblasts, which are reported to highly express integrin αvβ3, are the effector cells in renal fibrogenesis. Since current therapies do not efficiently target these cells, there is no effective therapeutic method for preventing or mitigating the disease. Here, we modified sterically stable PEGylated liposomes with the pentapeptide cRGDfC (RGD-Lip), which has a high affinity for αvβ3, to specifically deliver drug to renal interstitial myofibroblasts. Our results showed that attaching cRGDfC to liposomes significantly increased their uptake by activated renal fibroblasts NRK-49F cells, and this effect was greatly abolished by adding excess-free cRGDfC or a knockdown of αvβ3. Systemic administration of RGD-Lip gave rise to significant accumulation in a fibrotic kidney, which is ascribed to the specific recognition with integrin αvβ3 on interstitial myofibroblasts. When loaded with celastrol, RGD-guided liposomes dramatically depressed the proliferation and activation of NRK-49F cells . Additionally, celastrol-loaded RGD-Lip markedly attenuated renal fibrosis, injury, and inflammation induced by unilateral ureteral obstruction (UUO) in mice, without inducing significant systemic toxicity. Thus, this liposomal system shows great promise for delivering therapeutic agents to interstitial myofibroblasts for renal fibrosis treatment with minimal side effects.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01182DOI Listing
March 2021

Inhibition of the sodium-glucose co-transporter SGLT2 by canagliflozin ameliorates diet-induced obesity by increasing intra-adipose sympathetic innervation.

Br J Pharmacol 2021 04 1;178(8):1756-1771. Epub 2021 Mar 1.

Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Background And Purpose: Inhibition of the sodium-glucose cotransporter 2 (SGLT2) induces hypoglycaemia by increasing urinary glucose excretion and increasing the use of fat. However, the underlying mechanism is poorly understood. This study was aimed to determine the effects of canagliflozin, a selective SGLT2 inhibitor, on diet-induced obesity and the underlying mechanism(s).

Experimental Approach: Adult C57BL/6J male mice were fed with a standard chow diet or high-fat diet supplemented with vehicle or canagliflozin. Whole body energy expenditure was monitored by metabolic cages, noradrenaline levels were measured by HPLC, glucose uptake was measured by PET/CT, and mRNA and protein expression were measured by RT-PCR and western blotting analysis.

Key Results: Mice treated with canagliflozin were resistant to high-fat diet-induced obesity and its metabolic consequences. Canagliflozin treatment decreased fat mass and increased energy expenditure via increasing thermogenesis and lipolysis in adipose tissue. Mechanistically, SGLT2 inhibition by canagliflozin elevated adipose sympathetic innervation and fat mobilization via a β -adrenoceptor-cAMP-PKA signalling pathway. Finally, we showed that canagliflozin improved insulin resistance and hepatic steatosis in mice fed with a high-fat diet.

Conclusions And Implications: Chronic inhibition of SGLT2 increased energy consumption by increasing intra-adipose sympathetic innervation to counteract diet-induced obesity. The present study reveals a new therapeutic function for SGLT2 inhibitors in regulating energy homeostasis.
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http://dx.doi.org/10.1111/bph.15381DOI Listing
April 2021

Facilely controllable synthesis of copper-benzothiadiazole complexes solvothermal reactions: exploring the customized synthetic approach by experiments.

Dalton Trans 2021 Feb;50(5):1816-1823

Green Catalysis Center, College of Chemistry, Zhengzhou University, Henan 450001, China.

It is very challenging to transform small organic molecules into customized coordination polymer (CP) because the functionalities with desired properties are greatly influenced by several elements, including the assembly modes of the organic linkers and metal nodes, organic linker functionalization, and defects. Therefore, deep cognition for the molecular-level engineering of CP chemistry is very important. Herein, we obtained five new copper-benzothiadiazole complexes via a controllable synthesis approach: [CuII(L1)(CH3CN)]2 (C1), [CuIBr(L1)]n (C2), [CuI3Br3(L2)2]n (C3), [CuICl(L3)]2 (C4), and [CuIICl2(L3)2] (C5). In the exploration, we successfully modulated the structure of the organic linker and the valence state of the metal nodes as well as the assembly modes of the organic linkers and metal nodes through the facilely controllable solvothermal reaction. The results from our experiments also indicated that the fusing process was driven by a CuII/CuI catalytic cycle. In this pathway, oxygen is the final electron acceptor and the solvent DMSO acts as a co-oxidant. In C2 and C3, the ever-expanding macrocycles were constructed from CuX clusters and organic chromophore linkers, forming interesting 1D chain structures, while the supramolecular macrocycles were assembled through hydrogen bonding expanding to a 3D network of C5. Interestingly, C1-C4 exhibit chromophore-based fluorescence, but are not phosphorescence.
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http://dx.doi.org/10.1039/d0dt03817bDOI Listing
February 2021

The role of teamwork in the implicit rationing of nursing care: A systematic mixed-methods review.

J Nurs Manag 2021 Jul 29;29(5):890-904. Epub 2020 Dec 29.

School of Nursing, Jilin University, Changchun, China.

Aim: To systematically evaluate the role of teamwork in implicit rationing care and how to improve teamwork.

Background: The implicit rationing of nursing leads to adverse effects for both patients and nurses. Therefore, how to reduce it has attracted increasing research attention. How teamwork may be an important factor in reducing implicit rationing care has become a focus of research.

Methods: Data between May 2000 and May 2020 were collected from five databases. The study was guided by the framework of a mixed studies review.

Results: Seventeen studies were chosen for review regarding efficient teamwork to reduce implicit rationing care. The following seven subthemes with positive effects that improve teamwork and reduce implicit rationing care were formed: (a) improving knowledge and skills; (b) promoting effective communication; (c) building mutual trust; (d) reducing turnover intention; (e) reasonable staffing; (f) division of responsibilities; and (g) cultivating team consciousness.

Conclusions: Teamwork can decrease implicit care and is influenced by many factors, but the intervention is singular. In the future, teamwork can be further improved to reduce implicit care.

Implications For Nursing Management: With more intervention research in the future, leadership and team-oriented roles can be used to complete all the care needed.
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http://dx.doi.org/10.1111/jonm.13231DOI Listing
July 2021

Construction of the 1D Covalent Organic Framework/2D g-CN Heterojunction with High Apparent Quantum Efficiency at 500 nm.

ACS Appl Mater Interfaces 2020 Nov 6;12(46):51555-51562. Epub 2020 Nov 6.

Key Laboratory of Polyoxometalate Science of the Ministry of Education, Faculty of Chemistry, Northeast Normal University, Changchun 130024, P. R. China.

The reasonable construction of heterojunction photocatalysts with clear nanostructures and a good interface contact especially the one-dimensional/two-dimensional (1D/2D) composite heterojunction with unique morphology is considered one of the most effective strategies for designing highly efficient photocatalysts. Herein, a series of the 1D β-keto-enamine-based covalent organic framework (COF)/2D g-CN composite materials COF-CN (1:; where 1: represents the mass ratio of COF and g-CN, = 2.5, 5, 10, 15, 20) is prepared through the in situ reaction of 2,4,6-triformylphloroglucinol (Tp) and benzidine (BD) in stripped g-CN suspension. A series of characterizations, such as X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), and transmission electron microscopy (TEM), have verified their 1D/2D heterojunction structure. With the introduction of 1D COF nanobelts, the absorption of the composite is largely extended to 560 nm. Photocatalytic experiments reveal that the composite COF/CN shows evidently superior photocatalytic performance than individual COF and g-CN. The optimized COF-CN (1:10) exhibits a H production rate of 12.8 mmol g·h under visible-light (λ ≥ 420 nm) irradiation, which is about 62 and 284 times higher than those of COF and g-CN, respectively. The apparent quantum efficiency (AQE) of COF-CN (1:10) is about 15.09% under 500 nm light irradiation, which is one of the highest among previous COF- or g-CN-based materials. This work provides important strategies for designing and constructing high-efficiency heterojunction photocatalysts with multidimensional features.
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http://dx.doi.org/10.1021/acsami.0c15780DOI Listing
November 2020

SB431542-Loaded Liposomes Alleviate Liver Fibrosis by Suppressing TGF-β Signaling.

Mol Pharm 2020 11 22;17(11):4152-4162. Epub 2020 Oct 22.

Laboratory of Clinical Pharmacy and Adverse Drug Reaction, West China Hospital of Sichuan University, Chengdu 610041, China.

Liver fibrosis is a common outcome of most chronic liver diseases, but there is no clinically approved drug for its treatment. Previous studies have reported the potential of SB431542 as an inhibitor of TGF-β signaling in the treatment of liver fibrosis, but it shows poor water solubility and low bioavailability. Here, we improve these characteristics of SB431542 by loading it into liposomes (SB-Lips) with two FDA-approved excipients: soya phosphatidyl S100 and Solutol HS15. , SB-Lips had stronger inhibitory effects on the proliferation and activation of hepatic stellate cells LX-2 than free SB. After an intravenous injection in a CCl-induced liver fibrosis mouse model, SB-Lips accumulated preferentially in the liver, its area under the concentration-time curve was significantly higher than that of free SB431542, and it alleviated hepatic fibrosis significantly more than free drug, which was associated with greater inhibition of TGF-β signaling. Furthermore, SB-Lips did not cause significant injury to other organs. These results suggest that our liposomal system is safe and effective for delivering SB431542 to fibrotic liver.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c00633DOI Listing
November 2020

Informal dementia caregivers' experiences and perceptions about mealtime care: A qualitative evidence synthesis.

J Adv Nurs 2020 Dec 30;76(12):3317-3328. Epub 2020 Sep 30.

School of Nursing, Jilin University, Changchun, Jilin, People's Republic of China.

Aims: To systematically identify, evaluate and synthesize the available qualitative evidence on the mealtime care experiences of informal caregivers of people with dementia.

Design: A qualitative evidence synthesis using the Thomas and Harden method.

Data Sources: All qualitative and mixed-method studies in English and Chinese were retrieved from PubMed, Web of Science, Embase, Cochrane, CINAHL, CNKI, WanFang, and Vip from the inception of each database until November 2019.

Review Methods: Two researchers independently selected the studies using qualitative assessment and review instruments for quality evaluation and thematic synthesis for the data analysis.

Results: Ten studies were chosen for this review. The analytical themes identified included injecting a new element, moving forward in the challenge and external supports facilitating better coping.

Conclusion: Community nurses should effectively use resources to provide food-related information and services to families with dementia. Future research should combine informal caregiver experiences and clinical skills to develop high-quality interventions to improve the quality of mealtimes.

Impact: The findings established that informal caregivers experienced not only changes in their roles and concerns but also emotional changes. Informal caregivers develop different coping strategies to adapt to feeding issues without professional support. Although informal caregivers attach great importance to mealtimes and nutrition issues, they experience a lack of information and support services. Community nurses can provide more economical, practical, and accessible information resources based on informal caregivers' perceptions of mealtime care. Future interventions need to be more aware of the importance of dyad or family-centred support services.
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http://dx.doi.org/10.1111/jan.14550DOI Listing
December 2020

The diabetes medication canagliflozin promotes mitochondrial remodelling of adipocyte via the AMPK-Sirt1-Pgc-1α signalling pathway.

Adipocyte 2020 12;9(1):484-494

Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University . Chengdu China.

The diabetes medication canagliflozin (Cana) is a sodium glucose cotransporter 2 (SGLT2) inhibitor acting by increasing urinary glucose excretion and thus reducing hyperglycaemia. Cana treatment also reduces body weight. However, it remains unclear whether Cana could directly work on adipose tissue. In the present study, the pharmacological effects of Cana and the associated mechanism were investigated in adipocytes and mice. Stromal-vascular fractions (SVFs) were isolated from subcutaneous adipose tissue and differentiated into mature adipocytes. Our results show that Cana treatment directly increased cellular energy expenditure of adipocytes by inducing mitochondrial biogenesis independently of SGLT2 inhibition. Along with mitochondrial biogenesis, Cana also increased mitochondrial oxidative phosphorylation, fatty acid oxidation and thermogenesis. Mechanistically, Cana promoted mitochondrial biogenesis and function via an Adenosine monophosphate-activated protein kinase (AMPK) - silent information regulator 1 (Sirt1) - peroxisome proliferator-activated receptor γ coactivator-1α (Pgc-1α) signalling pathway. Consistently, study demonstrated that Cana increased AMPK phosphorylation and the expression of Sirt1 and Pgc-1α. The present study reveals a new therapeutic function for Cana in regulating energy homoeostasis.

Abbreviations: Ucp-1, uncoupling protein 1; cAMP, cyclic adenosine monophosphate; PKA, cAMP-dependent protein kinase A; SGLT, sodium glucose cotransporter; Cana, canagliflozin; T2DM: type 2 diabetes; Veh, vehicle; Pgc-1α, peroxisome proliferator-activated receptor γ coactivator-1α; SVFs, stromal-vascular fractions; FBS, bovine serum; Ad, adenovirus; mtDNA, mitochondrial DNA; COX2, cytochrome oxidase subunit 2; RT-PCR, real-time PCR; SDS-PAGE, sodium dodecyl sulphate-polyacrylamide gel electrophoresis; Prdm16, PR domain zinc finger protein 16; Cidea, cell death inducing DFFA-like effector A; Pgc-1β, peroxisome proliferator-activated receptor γ coactivator-1β; NRF1, nuclear respiratory factor 1; Tfam, mitochondrial transcription factor A; OXPHOS, oxidative phosphorylation; FAO, fatty acid oxidation; AMPK, Adenosine monophosphate-activated protein kinase; p-AMPK, phosphorylated AMPK; Sirt1, silent information regulator 1; mTOR, mammalian target of rapamycin; WAT, white adipose tissue; Fabp4, fatty acid binding protein 4; Lpl, lipoprotein lipase; Slc5a2, solute carrier family 5 member 2; ERRα, oestrogen related receptor α; Uqcrc2, ubiquinol-cytochrome c reductase core protein 2; Uqcrfs1, ubiquinol-cytochrome c reductase, Rieske iron-sulphur polypeptide 1; Cox4, cytochrome c oxidase subunit 4; Pparα, peroxisome proliferator activated receptor α; NAD, nicotinamide adenine dinucleotide; Dio2, iodothyronine deiodinase 2; Tmem26, transmembrane protein 26; Hoxa9, homeobox A9; FCCP, carbonyl cyanide 4-(trifluoromethoxy) phenylhydrazone; Rot/AA, rotenone/antimycin A; OCR, oxygen consumption rate; Pparγ, peroxisome proliferator activated receptor γ; C/ebp, CCAAT/enhancer binding protein; LKB1, liver kinase B1; AUC, area under the cure; Vd, apparent volume of distribution.
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http://dx.doi.org/10.1080/21623945.2020.1807850DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7469612PMC
December 2020

Coping strategies mediate the association between family functioning and posttraumatic growth in family caregivers of people with dementia.

Aging Ment Health 2021 09 7;25(9):1684-1691. Epub 2020 Jul 7.

School of Nursing, Jilin University, Jilin, People's Republic of China.

Objectives: This study aimed to examine the mediating effect of coping strategies on the relationship between family functioning and posttraumatic growth in family caregivers of people with dementia (PwD).

Methods: A total of 124 family caregivers of PwD from a memory clinic were investigated from July to October 2017. Family functioning, coping strategies, and posttraumatic growth of family caregivers of PwD were measured. Data were processed using descriptive statistics, correlation analysis, regression analysis, and structural equation modelling.

Results: Posttraumatic growth was observed in family caregivers of PwD. The caregiver's gender, relationship with the patient, and difficulty balancing financial income and expenditures in the past month, as well as disease severity of PwD, are significant predictors of posttraumatic growth. There were significantly positive correlations among posttraumatic growth, family functioning and positive coping strategies (<0.01). Positive coping strategies exert a complete mediating effect between family functioning and posttraumatic growth ( = 0.49,  < 0.05).

Conclusions: A model of the posttraumatic growth of family caregivers of PwD can be established, and the relevant mechanisms can be explored. Healthcare providers should pay attention to the family functioning of caregivers and take effective measures to provide them with positive coping strategies to promote their posttraumatic growth.
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http://dx.doi.org/10.1080/13607863.2020.1786800DOI Listing
September 2021

Sirt6 Alleviated Liver Fibrosis by Deacetylating Conserved Lysine 54 on Smad2 in Hepatic Stellate Cells.

Hepatology 2021 03 10;73(3):1140-1157. Epub 2020 Nov 10.

Department of Pharmacy, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.

Backgrounds And Aims: Activation of hepatic stellate cells (HSCs) is a central driver of fibrosis. This study aimed to elucidate the role of the deacetylase sirtuin 6 (Sirt6) in HSC activation and liver fibrosis.

Approach And Results: Gain-of-function and loss-of-function models were used to study the function of Sirt6 in HSC activation. Mass spectrometry was used to determine the specific acetylation site. The lecithin retinol acyltransferase-driven cyclization recombination recombinase construct (CreERT2) mouse line was created to generate HSC-specific conditional Sirt6-knockout mice (Sirt6 ). We found that Sirt6 is most abundantly expressed in HSCs as compared with other liver cell types. The expression of Sirt6 was decreased in activated HSCs and fibrotic livers of mice and humans. Sirt6 knockdown and Sirt6 overexpression increased and decreased fibrogenic gene expression, respectively, in HSCs. Mechanistically, Sirt6 inhibited the phosphorylation and nuclear localization of mothers against decapentaplegic homolog (Smad) 2. Further study demonstrated that Sirt6 could directly interact with Smad2, deacetylate Smad2, and decrease the transcription of transforming growth factor β/Smad2 signaling. Mass spectrometry revealed that Sirt6 deacetylated conserved lysine 54 on Smad2. Mutation of lysine 54 to Arginine in Smad2 abolished the regulatory effect of Sirt6. In vivo, specific ablation of Sirt6 in HSCs exacerbated hepatocyte injury and cholestasis-induced liver fibrosis in mice. With targeted delivery of the Sirt6 agonist MDL-800, its concentration was 9.28-fold higher in HSCs as compared with other liver cells and alleviated hepatic fibrosis.

Conclusions: Sirt6 plays a key role in HSC activation and liver fibrosis by deacetylating the profibrogenic transcription factor Smad2. Sirt6 may be a potential therapeutic target for liver fibrosis.
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http://dx.doi.org/10.1002/hep.31418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8048913PMC
March 2021

Health literacy and exercise interventions on clinical outcomes in Chinese patients with diabetes: a propensity score-matched comparison.

BMJ Open Diabetes Res Care 2020 06;8(1)

Department of Epidemiology, School of Public Health and Key Laboratory of Public Health Safety (National Ministry of Education), Fudan University, Shanghai, China

Introduction: Patients with diabetes in China have low health literacy, which likely leads to poor clinical outcomes. This study aimed to assess the effectiveness of health literacy and exercise interventions on clinical measurements in Chinese adults with type 2 diabetes mellitus (T2DM).

Research Design And Methods: A cluster randomized controlled trial was conducted from February 2015 through April 2017 in Shanghai, China. 799 patients with T2DM aged 18 years or older recruited from eight Community Healthcare Centers were randomized into one control arm and three intervention arms receiving 1-year health literacy intervention, exercise intervention or both as the comprehensive intervention. Propensity score matching was employed to minimize potential imbalance in randomization. The intervention-attributable effects on main clinical outcomes were estimated using a difference-in-difference regression approach.

Results: After propensity score matching, 634 patients were included in the analysis. The three intervention groups had decreased hemoglobin A1c (A1c) level after 12 months of intervention. The largest adjusted decrease was observed in the health literacy group (-0.95%, 95% CI: -1.30 to -0.59), followed by the exercise group (-0.81%, 95% CI: -1.17 to -0.45). However, A1c was observed to increase in the health literacy and the comprehensive groups from 12 to 24 months. No obvious changes were observed for other measurements including high-density and low-density lipoprotein cholesterols, and systolic and diastolic blood pressures.

Conclusions: Health literacy and exercise-focused interventions improve glycemic control in Chinese patients with diabetes after 12 months of intervention, and the health literacy intervention shows the greatest effect. Our results suggest that the interventions may have the potential to improve diabetes self-management and reduce diabetes burden in China.

Trial Registration Number: ISRCTN76130594.
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http://dx.doi.org/10.1136/bmjdrc-2020-001179DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264995PMC
June 2020
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