Objective: This study examines how older residents’ social support and perceived empowerment are associated with their quality of life (QOL) in long-term care (LTC) facilities in Shanghai, China, ...controlling for their health-related conditions, facility type, and other socio-demographic characteristics. Method: Using a convenient sampling approach, we selected nine LTC facilities in Shanghai, China. We surveyed 515 older residents from these facilities. Results: Older participants in this study rate their QOL, social support, and perceived empowerment as moderate, and these variables are positively associated with their QOL. Older residents who live in government-owned and private-run LTC facilities are more likely to have a higher level of perceived QOL compared with those living in government-run facilities. Discussion: There is an urgent need to increase staff awareness and capacity to empower older residents, and to engage them in their care plan and delivery. LTC facilities could provide more opportunities for older residents’ social networking within and outside LTC facilities. Improvement of older residents’ QOL is critical in the future development of resident-centered care models in LTC facilities.
Fungi fibrinolytic compound 1 (FGFC1) is a rare marine-derived compound that can enhance fibrinolysis both in vitro and in vivo. The fibrinolytic activity characterization of FGFC1 mediated by ...plasminogen (Glu-/Lys-) and a single-chain urokinase-type plasminogen activator (pro-uPA) was further evaluated. The binding sites and mode of binding between FGFC1 and plasminogen were investigated by means of a combination of in vitro experiments and molecular docking. A 2.2-fold enhancement of fibrinolytic activity was achieved at 0.096 mM FGFC1, whereas the inhibition of fibrinolytic activity occurred when the FGFC1 concentration was above 0.24 mM. The inhibition of fibrinolytic activity of FGFC1 by 6-aminohexanoic acid (EACA) and tranexamic acid (TXA) together with the docking results revealed that the lysine-binding sites (LBSs) play a crucial role in the process of FGFC1 binding to plasminogen. The action mechanism of FGFC1 binding to plasminogen was inferred, and FGFC1 was able to induce plasminogen to exhibit an open conformation by binding through the LBSs. The molecular docking results showed that docking of ligands (EACA, FGFC1) with receptors (KR1-KR5) mainly occurred through hydrophilic and hydrophobic interactions. In addition, the binding affinity values of EACA to KR1-KR5 were -5.2, -4.3, -3.7, -4.5, and -4.3 kcal/moL, respectively, and those of FGFC1 to KR1-KR5 were -7.4, -9.0, -6.3, -8.3, and -6.7 kcal/moL, respectively. The findings demonstrate that both EACA and FGFC1 bound to KR1-KR5 with moderately high affinity. This study could provide a theoretical basis for the clinical pharmacology of FGFC1 and establish a foundation for practical applications of FGFC1.
Background
Macrophages play important roles in diabetes and sepsis-related intestinal injury. Accumulating evidence suggests that microRNAs (miRNAs) act as the fundamental link between macrophage ...polarization and tissue injury. However, the underlying mechanisms of miRNAs in regulating macrophage polarization–related intestinal injury under diabetes and sepsis conditions remain unclear.
Methods
The cecal ligation and puncture (CLP)–induced sepsis models were established in male wild-type (WT) and diabetic mice. Clodronate liposome was used to deplete macrophage. H&E staining, inflammatory cytokines tumor necrosis factor–α (TNF-α), interleukin-1β (IL-1β), and IL-6, and intestinal mucosal barrier function markers occludin, ZO-1, lipopolysaccharide (LPS), and intestinal fatty acid binding protein (iFABP) were used to assess elevated intestinal damage. miRNA array, RNA-seq, and bioinformatic analysis were performed to detect the miRNA and messenger RNA (mRNA) expression and the potential regulation mechanism.
In vitro
, RAW264.7 cells were cultured in the absence or presence of high glucose and LPS, miR-3061 mimics, and Snail small interfering RNA stimulation, respectively, for further mechanism studies. Luciferase reporter assay was used to confirm the interplay between miRNA and its target genes.
Results
Compared with WT CLP mice, the diabetic CLP mice showed severe intestinal damage characterized by significant increases in Chui’s scores, expression of inflammatory cytokines (TNF-α, IL-1β, and IL-6), serum LPS and iFABP concentration, and significant reductions in tight junction protein occludin and ZO-1 levels. Macrophage depletion reversed the intestinal damage caused by CLP. The bioinformatic analysis revealed that miR-3061/Snail1 might be a potential regulation axis of macrophage polarization. Furthermore, high glucose and LPS stimulation increased M1 macrophage and reduced the levels of miR-3061, which was negatively associated with Snail1 in RAW264.7 cells. Mechanistic studies demonstrated that miR-3061 regulated macrophage polarization by targeting the Snail1 mRNA 3′‐untranslated region. Moreover, miR-3061 overexpression suppressed Snail1 expression and inhibited M1 macrophage and inflammatory cytokines.
Conclusion
This study elucidated that diabetes exacerbated sepsis-induced intestinal injury by promoting M1 macrophage polarization and further demonstrated that the miR-3061/Sani1 axis may be the potential target of macrophage polarization.
Primary health care (PHC) is usually the initial point of contact for individuals seeking to access health care and providers of PHC play a crucial role in the healthcare model. However, few studies ...have assessed the knowledge, ability, and skills (capacity) of PHC providers in delivering care. This study aimed to identify the capacity of PHC providers in countries of the Southeast and East Asian Nursing Education and Research Network (SEANERN).
A multi-national cross-sectional survey was performed among SEANERN countries. A 1-5 Likert scale was used to measure eight components of knowledge, ability, and skill of PHC providers. Descriptive statistics were employed, and radar charts were used to depict the levels of the three dimensions (knowledge, skill and ability) and eight components.
Totally, 606 valid questionnaires from PHC providers were returned from seven countries of SEANERN (China, Myanmar, Indonesia, Thailand, Vietnam, Cambodia, and Malaysia), with a responsive rate of 97.6% (606/621). For the three dimensions the ranges of total mean scores were distributed as follows: knowledge dimension: 2.78~3.11; skill dimension: 2.66~3.16; ability dimension: 2.67~3.06. Furthermore, radar charts revealed that the transition of PHC provider's knowledge into skill and from skill into ability decreased gradually. Their competencies in four areas, including safe water and sanitation, nutritional promotion, endemic diseases prevention, and essential provision of drugs, were especially low.
The general capacity perceived by PHC providers themselves seems relatively low and imbalanced. To address the problem, SEANERN, through the collaboration of the members, can facilitate the appropriate education and training of PHC providers by developing feasible, practical and culturally appropriate training plans.
Background:
During the progression of atherosclerosis (AS), the vascular endothelial and smooth muscle cells are reciprocally regulated by extracellular vesicles (EVs). EVs have different effects on ...pathological and physiological processes due to the different cargoes contained in EVs.
Purpose:
To study the effects of endothelial cells-derived EVs on normal and inflammatory conditions. To investigate the effects of curcumin and curcumin derivatives (Nicotinic-curcumin) on endothelial EVs.
Methods:
EVs were isolated from human umbilical vein endothelial cells (HUVECs) by ultracentrifugation. To examined the effect of normal and LPS-induced endothelial cells-derived EVs on the proliferation of human aortic smooth muscle cells (HASMCs), the CCK-8 assay was performed. Transwell and wound healing assays were conducted to assess cell migration. The effects of EVs on lipid accumulation following treatment with oxidized low-density lipoprotein (Ox-LDL) were evaluated with the oil red O staining assay and HPLC. The number of EVs was calculated using the nanoparticle tracking analysis (NTA) and BCA. The expression levels of Rab27a and Rab27b that regulate the EVs secretion were measured by Western blotting assay. The differential expression of miRNAs in endothelial EVs and LPS-induced endothelial EVs was analyzed using miRNA-Sequencing (miRNA-Seq) and RT-PCR.
Results:
Treatment with endothelial EVs reduced the proliferation and migration of HASMCs as well as lipid accumulation in HASMCs. However, treatment with LPS-induced endothelial EVs did not inhibit the migration of HASMCs or lipid accumulation, instead it promoted the proliferation of HASMCs. Treatment with the two types of EVs induced differential expression of several miRNAs, including miR-92a-3p, miR-126-5p, miR-125a-3p, miR-143-3p, etc. Moreover, 1 μg/mL LPS induction greatly increased secretion of endothelial EVs. Treatment with curcumin and nicotinic-curcumin reduced endothelial EVs secretion, possibly by inhibiting inflammation.
Conclusion:
Endothelial EVs may confer beneficial effects on atherosclerosis by regulating vascular smooth muscle cell (VSMCs), whereas pro-inflammatory factors may disrupt this effect.
Intracranial aneurysm (IA) is a bulging of blood vessels around the brain that is often asymptomatic but may cause severe complications and death if ruptured. Macrophage-mediated immune responses can ...contribute to the development of IA. During homeostasis and inflammation, circulating monocytes can infiltrate the vasculature, where they develop into macrophages, and modulate immune responses. Based on the expression of CD14 and CD16, total circulating monocytes can be distinguished into three main subsets, including the CD14+CD16− classical monocytes, the CD14+CD16+ intermediate monocytes, and the CD14loCD16++ non-classical monocytes. In this study, we found that frequencies of CD14+CD16− classical monocytes were significantly lower in IA patients than in healthy controls, while the frequencies of CD14+CD16+ intermediate monocytes and CD14loCD16++ non-classical monocytes were significantly higher in IA patients than in healthy controls. The frequencies of CD14+CD16+ intermediate monocytes were further elevated in IA-ruptured patients compared to those in IA-unruptured patients. Compared to classical monocytes, intermediate monocytes and non-classical monocytes presented higher TNF-α and IL-1β expression. When cocultured with autologous naive CD4 T cells, intermediate and non-classical monocytes preferentially promoted the expression of TBX21 and RORC over the expression of FOXP3 in CD4 T cells. Inhibition of TNF-α and IL-1β slightly reduced TBX21 expression and markedly reduced RORC expression, and at the same time significantly increased FOXP3 expression in CD4 T cells. Overall, this study demonstrated that the monocytes were dysregulated in IA patients in a manner that favored the development of proinflammatory responses.
Nasopharyngeal carcinoma, a malignant tumor prevalent in southeast Asia and north Africa, still lacks effective treatment. Esketamine, an N-methyl-D-aspartatic acid (NMDA) receptor (NMDAR) ...antagonist, is widely used in clinical anesthesia. Emerging evidence suggests that esketamine plays an important role in inhibiting tumor cell activity. However, the underlying mechanisms of esketamine on nasopharyngeal carcinoma remain unknown. In this study, we found that esketamine inhibited the proliferation and migration of nasopharyngeal carcinoma cells. Mechanically, transcriptome sequencing and subsequent verification experiments revealed that esketamine promoted the apoptosis of nasopharyngeal carcinoma cells through endoplasmic reticulum stress PERK/ATF4/CHOP signaling pathway mediated by NMDAR. Additionally, when combined with esketamine, the inhibitory effect of cisplatin on the proliferation of nasopharyngeal carcinoma cells was significantly enhanced. These findings provide new insights into future anti-nasopharyngeal carcinoma clinical strategies via targeting the NMDAR/PERK/CHOP axis alone or in combination with cisplatin.
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•Esketamine inhibits the proliferation and migration of NPC cells.•Esketamine induced apoptosis of nasopharyngeal carcinoma cells.•Esketamine induced apoptosis of NPC cells by PERK/ATF4/CHOP pathway through NMDAR.•Esketamine enhanced the antitumor activity of cisplatin.
Highly heterogeneous glutenite reservoirs with large amounts of gravel and weak interfaces pose a great challenge to predicting the trajectory of hydraulic fractures during the fracturing process. ...Based on the phase field method, a fully coupled numerical model of hydraulic fracturing is established. This paper is devoted to investigating the variation in the overall expansion pattern of hydraulic fractures in reservoirs considering randomly distributed gravel and weak interfaces. The numerical results demonstrate that the existence of gravel and a weak interface could alter the extending paths of the hydraulic fractures as well as the value of critical bifurcation injection rate. As the fracture energy of the weak interface is large enough, the hydraulic fracture tends to cross the gravel and the weak interface between the rock matrix and the gravel, forming a planar fracture. Deflection and branching of the hydraulic fracture are more likely to occur in reservoirs containing large gravels. The presented results extend the understanding of fractures propagating in heterogeneous reservoirs.
Spiritual care competence of nurses is crucial to satisfy the spiritual needs of the clients, but the dearth of conceptual frameworks has hindered the clarification of the construct, especially for ...nurses in the People's Republic of China. This article developed a 3*3*3 matrix framework to clarify the components of spiritual care competence for Chinese nurses through the synthesis of existing empirical and theoretical work, which includes three aspects (awareness, understanding, and application) on three levels (intrapersonal, interpersonal, and transpersonal) of three contents of spirituality (namely, worldview, connectedness, and transcendence). The proposed framework can be used as a model to promote spiritual care competence of nurses in China. Adoption of the framework to guide studies would allow for the design of interventions for the attainment of this competence.
Sepsis in patients is a great threat to human health due to its high incidence rate, its rapid and unpredictable progression, as well as it is difficult to treat, and it has poor prognosis. ...Ferroptosis is a newly discovered type of cell death characterized by the iron-dependent peroxide aggregation. Furthermore, ferroptosis is different from other forms of cell death, namely apoptosis, necrosis, pyroptosis and autophagy. Our study investigated the role of ferroptosis-related genes in sepsis.
The GSE65682 dataset from the Gene Expression Omnibus (GEO) database was used to screen ferroptosis-related genes associated with sepsis, and the GSE134347 dataset for the external validation of selected hub genes. The univariate Cox regression analysis, Kaplan-Meier (K-M) survival analysis and weighted gene co-expression network analysis (WGCNA) were used to identify hub genes. Evaluation of the immune cell infiltration in sepsis was used to explain the immune heterogeneity among the cell subtypes. Gene set variation analysis (GSVA) and transcriptional regulatory analysis of selected hub genes further elucidated the probable mechanism of ferroptosis-related genes associated with prognosis in sepsis. Finally, we constructed a competing endogenous RNA (ceRNA) network model.
A total of 479 RNA-seq data points were used for analysis, including 365 samples from patients who survived sepsis and 114 samples from patients who succumbed to sepsis from the available GSE65682 dataset. Consequently, the univariate Cox regression analysis and consensus clustering analysis divide all 479 sepsis samples into two clusters of “survivals” vs. “non-survivals”. Following complex analysis were identified as the most important ferroptosis-related genes. Indeed, the WGCNA and K-M analyses associated the expression patterns of NEDD4L and SIAH2 hub genes as the best prognosis for the survival of sepsis (p < 0.05). The expression trend was also consistent with the survival trend of the NEDD4L and SIAH2 hub genes by the external validation of GSE134347 (p < 0.05). Immune cell infiltration analysis indicated that the types and numbers of different immune cells vary among different subtypes and NEDD4L and SIAH2 hub genes. For example, NEDD4L and SIAH2 gene expression had a positive correlation with M0 macrophages and a negative correlation with neutrophils (p > 0.05). Finally, analysis of two hub genes and transcription factors (TFs) showed that 71 TFs were predicted to be related to NEDD4L while 64 TFs to SIAH2 by the Cistrome DB online database.
We suggest that NEDD4L and SIAH2 hub genes are involved in the ferroptosis-associated sepsis. The pattern of NEDD4L and SIAH2 expression in patients undergoing sepsis may have prognostic potential for the severity of sepsis and eventually for patients' survival.
•Identify two molecular subtypes related to ferroptosis in sepsis using bioinformatics methods.•Screen NEDD4L and SIAH2 as prognostic ferroptosis-related genes in sepsis.•Provide a new idea for the study of the prognostic mechanism of sepsis.•Improve the diagnosis and treatment of sepsis.
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