110023 research outputs found
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T Cells Mediate Kidney Tubular Injury via Impaired PDHA1 and Autophagy in Type 1 Diabetes
No full text[[abstract]]Context: Nephropathy is a severe complication of type 1 diabetes (T1DM). However, the interaction between the PDHA1-regulated mechanism and CD4+ T cells in the early stage of kidney tubular injury remains unknown.
Objective: To evaluate the role of PDHA1 in the regulation of tubular cells and CD4+ T cells and further to study its interaction in tubular cell injury in T1DM.
Methods: Plasma and total RNA were collected from T cells of T1DM patients (n = 35) and healthy donors (n = 33) and evaluated for neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, PDHA1, and biomarkers of CD4+ T cells including T helper 1 cells (Th1) and regulatory T cells (Treg) markers. HK-2 cells cocultured with CD4+ T cells from T1DM patients or healthy donors (HDs) to evaluate the interaction with CD4+ T cells.
Results: Increased PDHA1 gene expression levels in CD4+ T cells were positively associated with the plasma level of NGAL in T1DM patients and HDs. Our data demonstrated that the Th1/Treg subsets skewed Th1 in T1DM. Knockdown of PDHA1 in kidney tubular cells decreased ATP/ROS production, NAD/NADH ratio, mitochondrial respiration, and cell apoptosis. Furthermore, PDHA1 depletion induced impaired autophagic flux. Coculture of tubular cells and T1DM T cells showed impaired CPT1A, upregulated FASN, and induced kidney injury.
Conclusion: Our findings indicate that Th1 cells induced tubular cell injury through dysregulated metabolic reprogramming and autophagy, thereby indicating a new therapeutic approach for kidney tubular injury in T1DM
Attitudes toward People with Schizophrenia among Undergraduate Nursing Students
No full text[[abstract]]Background:
Negative attitudes toward mental disorders are not only an interpersonal issue but also a concern of mental health care. Given that nursing students are future health care providers, it is pivotal to improve their attitudes toward individuals with mental disorders prior to their transition into clinical practice. However, research on nursing students’ attitudes in relation to schizophrenia in Taiwan remains unexplored.
Aim:
The aim of this article is to examine the correlates of attitudes toward individuals with schizophrenia among Taiwanese undergraduate nursing students.
Method:
A descriptive, correlational, and cross-sectional study was adopted. Self-reported questionnaires were conducted with a convenience sample of 306 Taiwanese undergraduate nursing students. Descriptive statistics, independent t tests, one-way analysis of variance, Pearson’s correlations, and a stepwise regression analysis were performed.
Results:
Nursing students expressed negative attitudes toward individuals with schizophrenia. Nursing students, who were female, had contact with individuals with mental disorders, and expressed greater empathy and personality traits held more favorable attitudes toward individuals with schizophrenia. The study found that empathy, personality traits, and academic year were the most crucial attributes contributing to attitudes of nursing students toward individuals with schizophrenia.
Conclusion:
Findings suggest that nursing education programs with empathy- and personality-tailored modules in mental health are pivotal to provide humanistic approaches with supportive attitudes regarding schizophrenia
Early Comprehensive Kidney Care in Dialysis-Requiring Acute Kidney Injury Survivors: A Populational Study
No full text[[abstract]]Background: For patients with Acute Kidney Injury (AKI), a strong and graded relationship exists between AKI severity and mortality. One of the most severe entities of AKI is Dialysis-Requiring Acute Kidney Injury (D-AKI), which is associated with high rates of mortality and end-stage renal disease (ESRD). For this high-risk population group, there is a lack of evidence regarding optimal post-AKI care. We propose that post-AKI care through the combined efforts of the nephrologist and the multidisciplinary care team may improve outcomes. Our aim here is to study for survivors of dialysis-requiring acute kidney injury, the effects of implementing early comprehensive kidney care.
Methods: This is a retrospective longitudinal cohort study of Taiwanese through analyzing the National Health Insurance Research Database (NHIRD). We included patients with acute dialysis during hospitalization from January 1, 2015 to December 31, 2018. Propensity match was done at 1:1, including estimated glomerular filtration rate (eGFR) based on CKD-EPI which was performed due to large initial disparities between these two cohorts.
Results: After the propensity match, each cohort had 4,988 patients. The mean eGFR based on CKD-EPI was 27.5 ml/min/1.73 m2, and the mean follow-up period was 1.4 years.The hazard ratio for chronic dialysis or ESRD was 0.55 (95% CI, 0.49-0.62; p < 0.001). The hazard ratio for all-cause mortality was 0.79 (95% CI, 0.57-0.88; p < 0.001). Both outcomes favored early comprehensive kidney care.
Conclusions: For survivors of dialysis-requiring acute kidney injury, early comprehensive kidney care significantly lowered risks of chronic dialysis and all-cause mortality
Reliability and validity of a Chinese version of the Cohen-Mansfield agitation inventory-short form in assessing agitated behaviour.
No full text[[abstract]]Background: Patients with dementia often present agitated behaviors. The Cohen-Mansfield Agitation Inventory-short form (CMAI-SF) is one of the most widely used instruments to evaluate agitated behaviors that affect patients' quality of life and impose burden on caregivers. However, there is no simplified Chinese version of the CMAI-SF (C-CMAI-SF) in clinical settings.
Purpose: This study aimed to develop a Chinese version of the C-CMAI-SF and examine its validity and reliability.
Methods: This cross-sectional study included three phases. In Phase I, the original CMAI-SF was translated to Chinese. In Phase II, experts were invited to examine the content validity index (CVI). Phase III was conducted to test the validity and reliability of the C-CMAI-SF.
Results: The scale showed good validity and reliability with a scale-level CVI of 0.89, Cronbach's alpha (measure of internal consistency) of 0.874, and test-retest correlation coefficient of 0.902 (for 257 individuals). Using factor analysis, three factors were identified. Regarding concurrent validity, the C-CMAI-SF score was correlated with the Neuropsychiatric Inventory (agitation aggression subscale) and the Cornell Scale for Depression in Dementia (agitation subscale).
Conclusions: The study demonstrated that the C-CMAI-SF is a valid and reliable instrument for evaluating agitated behaviors in people with dementia.
Relevance to clinical practice: The C-CMAI-SF is an easy and quick tool used to identify and evaluate agitated behaviors in busy clinical settings
5,8-Dihydroxy-4 ′, 7-dimethoxyflavone Attenuates TNF-α Induced Expression of Vascular Cell Adhesion Molecule-1 through EGFR/PKCα/PI3K/Akt/Sp1-Dependent Induction of Heme Oxygenase-1 in Human Cardiac Fibroblasts
No full text[[abstract]]Recently, we found that 5,8-dihydroxy-4',7-dimethoxyflavone (DDF) upregulated the expression of heme oxygenase (HO)-1 via p38 mitogen-activated protein kinase/nuclear factor-erythroid factor 2-related factor 2 (MAPK/Nrf2) pathway in human cardiac fibroblasts (HCFs). However, the alternative processes by which DDF induces the upregulation of HO-1 expression are unknown. Activation of epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase/protein kinase B (PI3K/Akt), and protein kinase C (PKC)α may initiate specificity protein (Sp)1 activity, which has been reported to induce expression of antioxidant molecules. Thus, we explored whether these components are engaged in DDF-induced HO-1 upregulation in HCFs. Western blotting, promoter-reporter analyses, and real-time polymerase chain reactions were adopted to measure HO-1 and vascular cell adhesion molecule (VCAM)-1 expressions in HCFs. Respective small interfering (si)RNAs and pharmacological inhibitors were employed to investigate the signaling components engaged in DDF-induced HO-1 upregulation. The chromatin immunoprecipitation assay was conducted to detect the binding interaction of Sp1 and antioxidant response elements (ARE) on the promoter of HO-1. An adhesion assay of THP-1 monocyte was undertaken to examine the functional effect of HO-1 on tumor necrosis factor (TNF)-α-induced VCAM-1 expression. DDF stimulated the EGFR/PKCα/PI3K/Akt pathway leading to activation of Sp1 in HCFs. The roles of these protein kinases in HO-1 induction were ensured by transfection with their respective siRNAs. Chromatin immunoprecipitation assays revealed the interaction between Sp1 and the binding site of proximal ARE on the HO-1 promoter, which was abolished by glutathione, AG1478, G?6976, LY294002, or mithramycin A. HO-1 expression enhanced by DDF abolished the monocyte adherence to HCFs and VCAM-1 expression induced by TNF-α. Pretreatment with an inhibitor of HO-1: zinc protoporphyrin IX reversed these inhibitory effects of HO-1. We concluded that DDF-induced HO-1 expression was mediated via an EGFR/PKCα/PI3K/Akt-dependent Sp1 pathway and attenuated the responses of inflammation in HCFs
Protective Effects of Jujubosides on 6-OHDA-Induced Neurotoxicity in SH-SY5Y and SK-N-SH Cells
No full text[[abstract]]6-hydroxydopamine (7-OHDA) is used to induce oxidative damage in neuronal cells, which can serve as an experimental model of Parkinson’s disease (PD). Jujuboside A and B confer free radical scavenging effects but have never been examined for their neuroprctive effects, especially in PD; therefore, in this study, we aimed to investigate the feasibility of jujubosides as protectors of neurons against 6-OHDA and the underlying mechanisms. 6-OHDA-induced neurotoxicity in the human neuronal cell lines SH-SY5Y and SK-N-SH, was used to evaluate the protective effects of jujubosides. These findings indicated that jujuboside A and B were both capable of rescuing the 6-OHDA-induced loss of cell viability, activation of apoptosis, elevation of reactive oxygen species, and downregulation of the expression levels of superoxide dismutase, catalase, and glutathione peroxidase. In addition, jujuboside A and B can reverse a 6-OHDA-elevated Bax/Bcl-2 ratio, downregulate phosphorylated PI3K and AKT, and activate caspase-3, -7, and -9. These findings showed that jujubosides were capable of protecting both SH-SY5Y and SK-N-SH neuronal cells from 6-OHDA-induced toxicity via the rebalancing of the redox system, together with the resetting of the PI3K/AKT apoptotic signaling cascade. In conclusion, jujuboside may be a potential drug for PD prevention.
The Contribution of PDCD6 Polymorphisms to Oral Cancer Risk
No full text[[abstract]]Background/Aim: Programmed cell death 6 (PDCD6) is up-regulated and highly expressed in early apoptotic cells. In several types of cancer, such as cervical, breast and lung cancers, the association of PDCD6 genotypes have been investigated. However, the contribution of PDCD6 variant genotypes to oral cancer has never been examined. The current study aimed to evaluate the contribution of the PDCD6 rs4957014 and rs3756712 genotypes to the risk of oral cancer in Taiwan.
Patients and Methods: The contribution of PDCD6 genotypes to oral cancer risk was examined among 958 patients with lung cancer and 958 age- and sex-matched healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).
Results: The data showed that the hetero-variant GT and homo-variant GG genotypes of PDCD6 rs4957014 were associated with a decreased risk of oral cancer [odds ratio (OR)=0.81 and 0.39, 95% confidence interval (CI)=0.67-0.97 and 0.27-0.56, respectively]. The recessive and dominant models also showed that G carriers have protective effects (OR=0.43 and 0.72, 95% CI=0.30-0.61 and 0.61-0.87, respectively). The analysis of allelic frequency distributions showed that the G allele of PDCD6 rs4957014 was associated with reduced oral cancer risk (OR=0.71, 95% CI=0.62-0.82). There was no significant association between any PDCD6 rs3756712 genotype and oral cancer risk. In addition, the GG genotype at PDCD6 rs4957014 significantly decreased the risk of oral cancer among both males (adjusted OR=0.31, 95%CI=0.24-0.56) and females (adjusted OR=0.44, 95% CI=0.22-0.91). Furthermore, the GG genotype at PDCD6 rs4957014 significantly decreased the risk of oral cancer among smokers (adjusted OR=0.35, 95% CI=0.22-0.58), alcohol drinkers (adjusted OR=0.33, 95% CI=0.18-0.49), non-betel quid chewers (adjusted OR=0.33, 95% CI=0.17-0.81), betel quid chewers (adjusted OR=0.34, 95% CI=0.21-0.59), but not among never-smokers and non-alcohol drinkers.
Conclusion: The G allele carriers of PDCD6 rs4957014 may have protective effects on oral cancer risk and serve as a practical marker for early detection of oral cancer in Taiwan
An Efficient Identity-based Aggregate Signcryption Scheme with Blockchain for IoT-enabled Maritime Transportation System
No full text[[abstract]]Maritime transportation has ushered in a period of vigorous development and has been the most critical mode of transport in international trade. Maritime communication is also becoming increasingly complex. This trend needs the IoT-enabled Maritime Transportation System (IMTS) to enhance its ability of privacy-preserving, performance continuously, and add the function of joint management. Although many aggregate signcryption (ASC) schemes have been presented to satisfy this requirement, they still suffer from performance deficiencies or security weaknesses. To address these issues, we design a more practical “Perception-Network-Application” IoT-enabled MTS (PNA-IMTS) network structure. Then, we propose an efficient Identity-based aggregate signcryption scheme with blockchain (B-ID-ASC) for PNA-IMTS based on this network model. The security analysis shows that the B-ID-ASC scheme is capable of providing confidentiality and unforgeability. It also can resist existing known attacks (impersonation attack, modification attack, man-in-the-middle attack). The performance analysis indicates that our B-ID-ASC scheme, having lower computation and communication costs than current ASC schemes, is more applicable for PNA-IMTS
Orchestration of APT malware evasive manoeuvers employed for eluding anti-virus and sandbox defense
No full text[[abstract]]The modern day cyber attacks are highly targeted and incorporate advanced tactics, techniques and procedures for greater stealth, impact and success. These attacks are also known as Advanced Persistent Threats(APT) because of their evasive and stealth nature along with longer foothold on the victim’s digital infrastructure. The malware involved in APT attacks are sophisticated and developed with the intention of sabotaging the victim’s digital infrastructure or performing espionage. They are capable of targeting multiple operating environments starting from desktop and server operating systems (Windows, Linux and MacOS), Mobile platforms (Android, iOS), Embedded platforms (IoT Devices), to Industrial control systems (ICS/SCADA Devices). The evolution of evasive tactics and techniques employed in such advanced malware leads to extensive research efforts to develop mechanisms that can counter these evasion techniques. The research primarily aims to demonstrate that evasive manoeuvers are currently over-weighing the security countermeasures deployed by the prevalent security solutions. This paper will first explain the evasion mechanism in a systematic manner employed in modern APT malware and aims to implement a novel Evasive Manoeuvers Re-Engineering Framework(EMRF).EMRF aims to establish and demonstrate combinations of evasive manoeuvers with much known APT malware samples to elude security solutions. The payload variants, i.e., executable, dynamic link library, and shell-code, were experimented through a research-based framework EMRF to demonstrate 36% to 96% of evasive behavior countering the majority of defender engines. The EMRF system with its dynamic user defined evasion manoeuvers is able to transform non-zero-day payloads more potent by evading majority of the modern security solutions. This research clearly demonstrates the attacker’s ability to deliver non-zero-day payloads easily rather than investing resources and time in discovering zero-day exploits and developing zero-day payloads. This important observation can potentially disrupt the Advanced Persistent Threat Defenses incorporated in modern day security solution where focus is mainly on to detect zero-day payloads and exploits. Exhibiting the threat landscape poised due to APT, the paper utilizes a dataset of 4403 APT malware samples to extract and orchestrate the prevalence of evasive manoeuvers like stealth, covert communication, and anti-analysis mechanisms. This paper will contribute towards advanced malware analysis as an avenue to analyzing intrusion, evasion, and deception to prevent detection and verification, an association of responsibility, and determination of intent
