Showing papers by "Xiaoyan Jiang published in 2020"

Associations of sleep quality and sleep duration with frailty and pre-frailty in an elderly population Rugao longevity and ageing study.

Abstract: Previous studies suggest that poor sleep quality or abnormal sleep duration may be associated with frailty. Here we test the associations of sleep disturbances with both frailty and pre-frailty in an elderly population. Participants included 1726 community-dwelling elders aged 70–87 years. Pittsburgh Sleep Quality Index (PSQI) was used to assess sleep disturbances. Frailty was defined using phenotype criteria. Logistic regression models were used to estimate odds ratio of the associations. The average PSQI score was 5.4 (SD, 3.1). Overall 43.6% of the participants had poor sleep quality (PSQI> 5), 8.2% had night sleep time ≤ 5 h, and 27.8% had night sleep time ≥ 9 h. The prevalence of frailty and pre-frailty was 9.2 and 52.8%, respectively. The proportions of PSQI> 5 increased with the severity of frailty status (robust: pre-frail: frail, 34.5%: 48%: 56.1%, P 5) was associated with higher odds of frailty (OR = 1.78, 95% CI 1.19–2.66) and pre-frailty (OR = 1.51, 95% CI 1.20–1.90). Sleep latency, sleep disturbance, and daytime dysfunction components of PSQI measurements were also associated with frailty and pre-frailty. In addition, sleep time 9 h/night was associated with higher odds of frailty and pre-frailty. We provided preliminary evidences that poor sleep quality and prolonged sleep duration were associated with being frailty and pre-frailty in an elderly population aged 70–87 years. The associations need to be validated in other elderly populations.

Depressive symptoms are associated with incident frailty in a Chinese population: the Rugao Longevity and Aging Study.

Abstract: This study aimed at investigating whether depression symptoms are associated with prevalent and incident physical frailty in Chinese older population. We analyzed data of 1168 older Chinese adults aged 70 and above in the aging arm of the Rugao Longevity and Aging Study (RuLAS). Depressive symptoms (Geriatric Depression Scale ≥ 6) were assessed by the Geriatric Depression Scale. Frailty was defined using Fried phenotype criteria at baseline and 3-year survey. At baseline, 8.9% of the participants had depression symptoms. The prevalence of pre-frailty and frailty were 34.5% and 5.9%, respectively. The percentages of depressive symptoms increase from robust (5.3%) to pre-frail (11.2%), and then to frail (31.9%) groups. After adjustments of multiple covariates, depressive symptoms were associated with both prevalent pre-frailty (OR = 1.75, 95% CI 1.08–2.84) and prevalent frailty (OR = 5.64, 95% CI 2.85–11.14) at baseline. At 3-year survey, 9.3% participants reported the development of frailty. After multiple adjustments, depressive symptoms were associated with a 2.79-fold (95% CI 1.09–7.10) increased risk of 3-year incident frailty. Depressive symptoms are associated with prevalent and incident frailty in Chinese older population. Together with the observations of the European populations, depressive symptoms may be a candidate risk factor of frailty.

Cholesterol grafted cationic lipopolymers: Potential siRNA carriers for selective chronic myeloid leukemia therapy.

Abstract: Synthetic siRNA technology has emerged as a promising approach for molecular therapy of cancer but, despite its potential for post-transcriptional gene silencing, there is an urgent need to develop efficient delivery systems particularly for difficult-to-transfect, anchorage-independent cells. In this study, we designed highly hydrophobic cationic lipopolymers by grafting cholesterol (Chol) onto low-molecular weight (0.6, 1.2, and 2.0 kDa) polyethylenimines (PEIs) to enable specific siRNA therapy to chronic myeloid leukemia (CML) cells. The siRNA binding by PEI-Chol led to nano-sized (100-200 nm diameter) polyplexes with enhanced ζ-potential (+20 to +35 mV) and ability to protect the loaded siRNA completely in fresh serum. The siRNA delivery to CML (K562) cells was proportional to degree of substitution and, unexpectedly, inversely proportional to molecular size of the polymeric backbone. Chol grafting with as little as ~1.0 Chol/PEI on 0.6 and 1.2 kDa PEIs enabled silencing of the reporter Green Fluorescent Protein gene as well as the endogenous BCR-Abl oncogene in K562 cells. The PEI-Chol mediated delivery of siRNAs specific for BCR-Abl and KSP genes significantly arrested the growth the cells which was significantly reflected in colony formation potency of K562 cells. BCR-Able siRNA mediated therapeutic efficacy was also observed in significantly increased caspase activity and apoptosis of K562 cells. Thus, Chol-grafted low-molecular weight PEIs appear to be unique siRNA carriers to realize the molecular therapy in CML cells.

Frailty and incident depressive symptoms in a Chinese sample: the Rugao Longevity and Ageing Study.

Abstract: Background To explore the cross-sectional and longitudinal associations between frailty and incident depressive symptoms in a Chinese elderly sample Methods We analysed data of 1264 older Chinese elders aged 70-87 years in the Rugao Longevity and Ageing Study The frailty phenotype was assessed using the Fried criteria and depression symptoms was measured by the Geriatric Depression Scale Results At baseline, 106% of participants had depressive symptoms and 90% had frailty In cross-sectional analysis, both pre-frailty (odds ratio (OR) = 218, 95% CI 135-351) and frailty (OR = 464, 95% CI 249-866) were associated with depressive symptoms In longitudinal analyses, frailty (OR = 212, 95% CI 117-383), instead of pre-frailty, was associated with 15-year incident depressive symptoms in a full-adjusted model among participants free of baseline depressive symptoms In the components of frailty, lower grip strength was associated with increased risk of depressive symptoms onset (OR = 156, 95% CI 106-229) Conclusions Frailty and lower grip strength were associated with incident depressive symptoms in a Chinese elderly sample Interventions designed to prevent depressive symptoms may be useful by utilising physical aspects of the elderly population

Frailty index is associated with increased risk of elevated BNP in an elderly population: the Rugao Longevity and Ageing Study

Abstract: To explore whether frailty, defined by frailty index (FI), is associated with the risk of elevated B-type natriuretic peptide (BNP), a surrogate endpoint of cardiovascular events. Data of 1382 community-dwelling elders who had no documented cardiovascular diseases aged 70–84 years from the ageing arm of the Rugao Longevity and Ageing Study was used. Traditional risk factor index (TI) was constructed using eight established cardiovascular-related risk factors. FI was constructed using 36 health deficits. Elevated BNP was defined as BNP ≥ 100pg/mL. Cardiovascular events include incident major cardiovascular events and cardiovascular death. During a 3-year follow-up period, 97 participants had cardiovascular events. TI was not associated with the risk of elevated BNP, but was associated with cardiovascular events (HR = 1.16, 95% CI 1.01–1.34). Frailty index was not only associated with cardiovascular events (HR = 1.32, 95% CI 1.06–1.64), but also associated with elevated BNP with an OR of 1.22 (95% CI 1.02–1.47) for each 0.1 increment. Further, both frailty (OR = 1.93, 95% CI 1.67–3.17) and pre-frailty (OR = 1.54, 95% CI 1.06–2.25) were associated with increased risk of elevated BNP. FI is associated with increased risks of both cardiovascular events and surrogated endpoint of cardiovascular disease—elevated BNP. Frailty may be a non-traditional risk factor of cardiovascular diseases and frailty index may be a measurement for early identifying high risk elderly individuals of cardiovascular abnormities.

Genetic Variants of Homocysteine Metabolism, Homocysteine, and Frailty - Rugao Longevity and Ageing Study.

Abstract: Recently, elevated homocysteine was reported to be associated with frailty in cross-sectional studies. However, whether homocysteine is causally associated with frailty is unknown. Here, we explore the inter-relationships between five non-synonymous genetic variants of homocysteine metabolic four genes, plasma homocysteine levels, and frailty. Data of 1480 individuals aged 70–87 years from the ageing arm of Rugao Longevity and Ageing Study were used. Five variants of the four homocysteine metabolic enzyme genes were genotyped. Frailty was defined using Fried’s phenotype criteria. The percentage of high homocysteine (>15μmol/L) is 33.3%. Two functional variants that decrease methylenetetrahydrofolate reductase (MTHFR) activities, C677T (Ala222Val, rs1801133) and A1298C (Glu429Ala, rs1801131), were significantly associated with increased homocysteine levels (β=−1.16, p=0.01; and β=1.46, p<0.001, respectively). In addition, homocysteine increase gradually from CC-CC, CC-AC, CT-AC, CT-AA, CC-AA, to TT-AA genotypes of the C677T-A1298C combinations. The five polymorphisms in the homocysteine metabolic gene was not associated with frailty. However, homocysteine was significantly associated with frailty with an OR of 2.27 (95% 1.36–3.78) for high homocysteine after adjusting for multiple confounding factors. Elevated homocysteine is not a causal factor but a biomarker that manifests greater possibility of frailty in high risk elderly individuals for prevention.

Analysis of risk factors of stage IV gastric cancer from the SEER database

Abstract: IntroductionGastric cancer is the fourth most common cancer in the world. By the time the patients are diagnosed with stage IV gastric cancer, many patients already have distant metastases. There i...

Puncta intended: connecting the dots between autophagy and cell stress networks

Abstract: Proteome profiling and global protein-interaction approaches have significantly improved our knowledge of the protein interactomes of autophagy and other cellular stress-response pathways. New discoveries regarding protein complexes, interaction partners, interaction domains, and biological roles of players that are part of these pathways are emerging. The fourth Vancouver Autophagy Symposium showcased research that expands our understanding of the protein interaction networks and molecular mechanisms underlying autophagy and other cellular stress responses in the context of distinct stressors. In the keynote presentation, Dr. Wade Harper described his team's recent discovery of a novel reticulophagy receptor for selective autophagic degradation of the endoplasmic reticulum, and discussed molecular mechanisms involved in ribophagy and non-autophagic ribosomal turnover. In other presentations, both omic and targeted approaches were used to reveal molecular players of other cellular stress responses including amyloid body and stress granule formation, anastasis, and extracellular vesicle biogenesis. Additional topics included the roles of autophagy in disease pathogenesis, autophagy regulatory mechanisms, and crosstalk between autophagy and cellular metabolism in anti-tumor immunity. The relationship between autophagy and other cell stress responses remains a relatively unexplored area in the field, with future investigations required to understand how the various processes are coordinated and connected in cells and tissues.Abbreviations: A-bodies: amyloid bodies; ACM: amyloid-converting motif; AMFR/gp78: autocrine motility factor receptor; ATG: autophagy-related; ATG4B: autophagy related 4B cysteine peptidase; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CAR T: chimeric antigen receptor T; CASP3: caspase 3; CCPG1: cell cycle progression 1; CAR: chimeric antigen receptor; CML: chronic myeloid leukemia; CCOCs: clear cell ovarian cancers; CVB3: coxsackievirus B3; CRISPR-Cas9: clustered regularly interspaced short palindromic repeats-CRISPR associated protein 9; DDXs: DEAD-box helicases; EIF2S1/EIF-2alpha: eukaryotic translation initiation factor 2 subunit alpha; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; ER: endoplasmic reticulum; EV: extracellular vesicle; FAO: fatty acid oxidation; GABARAP: GABA type A receptor-associated protein; ILK: integrin linked kinase; ISR: integrated stress response; MTOR: mechanistic target of rapamycin kinase; MPECs: memory precursory effector T cells; MAVS: mitochondrial antiviral signaling protein; NBR1: NBR1 autophagy cargo receptor; PI4KB/PI4KIIIβ: phosphatidylinositol 4-kinase beta; PLEKHM1: pleckstrin homology and RUN domain containing M1; RB1CC1: RB1 inducible coiled-coil 1; RTN3: reticulon 3; rIGSRNAs: ribosomal intergenic noncoding RNAs; RPL29: ribosomal protein L29; RPS3: ribosomal protein S3; S. cerevisiae: Saccharomyces cerevisiae; sEV: small extracellular vesicles; S. pombe: Schizosaccharomyces pombe; SQSTM1: sequestosome 1; SF3B1: splicing factor 3b subunit 1; SILAC-MS: stable isotope labeling with amino acids in cell culture-mass spectrometry; SNAP29: synaptosome associated protein 29; TEX264: testis expressed 264, ER-phagy receptor; TNBC: triple-negative breast cancer; ULK1: unc-51 like autophagy activating kinase 1; VAS: Vancouver Autophagy Symposium.

[Research Advances on the Biological Characteristics of Hematological Malignant Cells Immunologically Regulated by Exosome--Review].

Abstract: The minimal residual disease (MRD) is the origin element that caused the relapse and drug resistance of hematological malignancies, the immune cells play a great role to clear MRD. A variety of immune cells have anti-tumor effects. However, tumor cells antagonize anti-tumor effects by reprogramming of constituents associated with tumor environment. Many different cell types, including immune cells, mesenchymal cells and tumor cells in tumor microenvironment release exosomes. The latest researches indicate that "cargo" and surface ligands carried by exosomes secreted by hematological malignant cells not only can affect the function of natural killer cell (migration, activation, proliferation, secretion and NKG2D expression), macrophage (migration and secretion) and dendritic cell (maturation and presentation), but also regulate the expression of PD-L1 and CCR2, CCL2 secretion and transformation of monocytes. The altered function of immune cells will eventually have effect on the progression of hematological malignancies.

Associations of TNF-α -308 G>A and TNF-β 252 A>G with Physical Function and BNP-Rugao Longevity and Ageing Study.

Abstract: To explore the associations of TNF-α −308 G>A (rs1800629) and TNF-β 252 A>G (rs909253) with physical function and plasma B-type natriuretic peptide (BNP). Data of 1747 community-dwelling elders from the ageing arm of the Rugao Longevity and Ageing Study was used. Physical function was measured by handgrip strength, Timed Up and Go (TUG) test and 5-meter walking test (5MWT). AA genotype of the TNF-α −308 G>A was associated with higher mean time of TUG test and 5MWT (multivariable adjusted β=5.75 and 5.70, respectively, p G polymorphism, GG genotype was associated with higher mean time of TUG test and 5MWT (multivariable adjusted β=1.55 and 0.83, respectively, p G was associated with physical function measurements, plasma BNP level, and odds of elevated BNP in an elderly population. TNF-β 252 A>G also interacted with elevated BNP to be associated with greater odds of physical function measurements.

Combination therapy for treating blood cancer

Abstract: Provided herein are combination therapies for treating blood cancer, in particular, acute myeloid leukemia, by concurrently targeting Axl and BCL-2.