110023 research outputs found
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Calreticulin nuclear translocalization alleviates CaM/CaMKII/CREB signaling pathway to enhance chemosensitivity in HDAC inhibitor-resistant hepatocellular carcinoma cells
No full text[[abstract]]Calreticulin (CRT) is located in the endoplasmic reticulum (ER), it helps proteins fold correctly inside the ER, and acts as a modulator of Ca2+ homeostasis. Aberrant expression of CRT is implicated in several cancer types, qualifying CRT as a potential therapeutic target. However, it remains unclear how CRT affects specific oncogenic pathways. In this study, we used histone deacetylase inhibitors (HDACis) to establish drug-resistant liver cancer cells and further analyzed the molecular mechanism of development of drug resistance in those cells. The 2D gel electrophoresis and RT-PCR data showed that CRT was downregulated in HDACis-resistant cells by comparing with HA22T parental cells. We previously elucidated the development of drug-resistance in HCC cells via activation of PP1-eIF2α pathway, but not via ER stress pathway. Here, we show that thapsigargin induced ER stress through mechanism other than ER stress downstream protein GRP78-PERK to regulate CRT expression in HDACis-R cells. Moreover, the expression level of CRT was not the main cause of apoptosis in HDACis-resistant cells. Mechanistic studies identified the apoptosis factors in the nucleus-the HDACis-mediated overexpression of CRT, CRT translocation to the cell nucleus, and reduced CaM/CaMKII/CREB pathway-that led to chemosensitivity in HDACis-R HCC cells
Detection of mosaicism for 46,X,i(Y)(q10) in the blood lymphocytes in a phenotypically normal male neonate with prenatally detected 45,X/46,XY at amniocentesis and cytogenetic discrepancy in various tissues
No full text[[abstract]]Objective: We present detection of mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes in a phenotypically normal male neonate with prenatally detected 45,X/46, XY at amniocentesis and cytogenetic discrepancy in various tissues.
Case report: A 35-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 45,X [8]/46,XY [15]. Simultaneous array comparative genomic hybridization (aCGH) on uncultured amniocytes revealed the result of arr (Y) × 0-1 with 25.493-Mb mosaic deletion of chromosome Yp11.31-q11.23. Prenatal ultrasound findings were unremarkable. The fetus had normal male external genitalia on fetal ultrasound. Following genetic counseling, the pregnancy was carried to 38 weeks of gestation, and a phenotypically normal male baby was delivered without any abnormalities of the male external genitalia. The cord blood had a karyotypes of 46,X,i(Y) (q10)[8]/45,X[3]/46,XY [29], and placenta had a karyotypes of 45,X [25]/46,X,i(Y) (q10)[7]/46,XY [8]. When follow-up at age two months, the neonate was normal in development. The peripheral blood had a karyotypes of 46,X,i(Y) (q10)[8]/45,X[5]/46,XY [27]. Interphase fluorescence in situ hybridization (FISH) analysis on 101 buccal mucosal cells showed normal X and Y signals in 101/101 cells.
Conclusion: Fetuses with 45,X/46, XY at amniocentesis can be associated with mosaicism for 46,X,i(Y) (q10) in the blood lymphocytes, cytogenetic discrepancy in various tissues and a favorable outcome
Reliability and Validity of a Chinese Version of the Cohen–Mansfield Agitation Inventory-Short Form in Assessing Agitated Behavior
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
嚴重特殊傳染性肺炎：新冠肺炎之居家照護
No full text[[abstract]]新冠肺炎已造成全球大流行，大量的病患不但考驗醫療體系的量能，也造成醫護人員沉重的負擔。新冠肺炎無症狀或輕症患者大多可採居家照護方式進行居家隔離，不需要到醫院治療。本文利用文獻查證說明新冠肺炎疾病特性、居家照護評估、照顧者及患者在居家環境上的準備、患者自我照顧注意事項，以期無症狀或輕症患者可於家中進行適當的自我隔離照護，對減少醫療量能負荷有所幫助。[[abstract]]Coronavirus disease 2019 (COVID-19) has become a global pandemic. High volumes of COVID-19 patients have not only tested the capacity of the medical system, but have placed a heavy burden on medical and nursing professionals as well. Most patients with asymptomatic or mild COVID-19 could be cared for at home as part of home isolation or quarantine rather than being sent to the hospital for treatment. The authors carried out a literature search focusing on COVID-19 disease characteristics, needs assessment for home-based care, environment preparation for home-based caregivers and patients, and guidance for patients' self-care. By highlighting the relative information, the authors hope that patients with asymptomatic or mild COVID-19 could be properly and safely cared for at home during home isolation or quarantine, which, in turn, could help alleviate the stress on medical care systems
Novel Aurora A Kinase Inhibitor Fangchinoline Enhances Cisplatin–DNA Adducts and Cisplatin Therapeutic Efficacy in OVCAR-3 Ovarian Cancer Cells-Derived Xenograft Model
No full text[[abstract]]Aurora A kinase (Aurora A) is a serine/threonine kinase regulating control of multiple events during cell-cycle progression. Playing roles in promoting proliferation and inhibiting cell death in cancer cells leads Aurora A to become a target for cancer therapy. It is overexpressed and associated with a poor prognosis in ovarian cancer. Improving cisplatin therapy outcomes remains an important issue for advanced-stage ovarian cancer treatment, and Aurora A inhibitors may improve it. In the present study, we identified natural compounds with higher docking scores than the known Aurora A ligand through structure-based virtual screening, including the natural compound fangchinoline, which has been associated with anticancer activities but not yet investigated in ovarian cancer. The binding and inhibition of Aurora A by fangchinoline were verified using cellular thermal shift and enzyme activity assays. Fangchinoline reduced viability and proliferation in ovarian cancer cell lines. Combination fangchinoline and cisplatin treatment enhanced cisplatin-DNA adduct levels, and the combination index revealed synergistic effects on cell viability. An in vivo study showed that fangchinoline significantly enhanced cisplatin therapeutic effects in OVCAR-3 ovarian cancer-bearing mice. Fangchinoline may inhibit tumor growth and enhance cisplatin therapy in ovarian cancer. This study reveals a novel Aurora A inhibitor, fangchinoline, as a potentially viable adjuvant for ovarian cancer therapy
Predicting Anticancer Drug Resistance Mediated by Mutations
No full text[[abstract]]Cancer drug resistance presents a challenge for precision medicine. Drug-resistant mutations are always emerging. In this study, we explored the relationship between drug-resistant mutations and drug resistance from the perspective of protein structure. By combining data from previously identified drug-resistant mutations and information of protein structure and function, we used machine learning-based methods to build models to predict cancer drug resistance mutations. The performance of our combined model achieved an accuracy of 86%, a Matthews correlation coefficient score of 0.57, and an F1 score of 0.66. We have constructed a fast, reliable method that predicts and investigates cancer drug resistance in a protein structure. Nonetheless, more information is needed concerning drug resistance and, in particular, clarification is needed about the relationships between the drug and the drug resistance mutations in proteins. Highly accurate predictions regarding drug resistance mutations can be helpful for developing new strategies with personalized cancer treatments. Our novel concept, which combines protein structure information, has the potential to elucidate physiological mechanisms of cancer drug resistance
Norketamine, the main metabolite of ketamine, induces mitochondria-dependent and ER stress-triggered apoptotic death in urothelial cells via a Ca2+-regulated ERK1/2-activating pathway
No full text[[abstract]]Ketamine-associated cystitis is characterized by suburothelial inflammation and urothelial cell death. Norketamine (NK), the main metabolite of ketamine, is abundant in urine following ketamine exposure. NK has been speculated to exert toxic effects in urothelial cells, similarly to ketamine. However, the molecular mechanisms contributing to NK-induced urothelial cytotoxicity are almost unclear. Here, we aimed to investigate the toxic effects of NK and the potential mechanisms underlying NK-induced urothelial cell injury. In this study, NK exposure significantly reduced cell viability and induced apoptosis in human urinary bladder epithelial-derived RT4 cells that NK (0.01-0.5 mM) exhibited greater cytotoxicity than ketamine (0.1-3 mM). Signals of mitochondrial dysfunction, including mitochondrial membrane potential (MMP) loss and cytosolic cytochrome c release, were found to be involved in NK-induced cell apoptosis and death. NK exposure of cells also triggered the expression of endoplasmic reticulum (ER) stress-related proteins including GRP78, CHOP, XBP-1, ATF-4 and -6, caspase-12, PERK, eIF-2α, and IRE-1. Pretreatment with 4-phenylbutyric acid (an ER stress inhibitor) markedly prevented the expression of ER stress-related proteins and apoptotic events in NK-exposed cells. Additionally, NK exposure significantly activated JNK, ERK1/2, and p38 signaling and increased intracellular calcium concentrations ([Ca2+]i). Pretreatment of cells with both PD98059 (an ERK1/2 inhibitor) and BAPTA/AM (a cell-permeable Ca2+ chelator), but not SP600125 (a JNK inhibitor) and SB203580 (a p38 inhibitor), effectively suppressed NK-induced mitochondrial dysfunction, ER stress-related signals, and apoptotic events. The elevation of [Ca2+]i in NK-exposed cells could be obviously inhibited by BAPTA/AM, but not PD98059. Taken together, these findings suggest that NK exposure exerts urothelial cytotoxicity via a [Ca2+]i-regulated ERK1/2 activation, which is involved in downstream mediation of the mitochondria-dependent and ER stress-triggered apoptotic pathway, consequently resulting in urothelial cell death. Our findings suggest that regulating [Ca2+]i/ERK signaling pathways may be a promising strategy for treatment of NK-induced urothelial cystitis
Quercetin induces oral tongue squamous cell carcinoma cell apoptosis via the JNK activation-regulated ERK/GSK-3 alpha/beta-mediated mitochondria-dependent apoptotic signaling pathway
No full text[[abstract]]Tongue squamous cell carcinoma (SCC) is a most common type of oral cancer. Due to its highly invasive nature and poor survival rate, the development of effective pharmacological therapeutic agents is urgently required. Quercetin (3,3',4',5,7‑pentahydroxyflavone) is a polyphenolic flavonoid found in plants and is an active component of Chinese herbal medicine. The present study investigated the pharmacological effects and possible mechanisms of quercetin on apoptosis of the tongue SCC‑derived SAS cell line. Following treatment with quercetin, cell viability was assessed via the MTT assay. Apoptotic and necrotic cells, mitochondrial transmembrane potential and caspase‑3/7 activity were analyzed via flow cytometric analyses. A caspase‑3 activity assay kit was used to detect the expression of caspase‑3 activity. Western blot analysis was performed to examine the expression levels of proteins associated with the MAPKs, AMPKα, GSK3‑α/β and caspase‑related signaling pathways. The results revealed that quercetin induced morphological alterations and decreased the viability of SAS cells. Quercetin also increased apoptosis‑related Annexin V‑FITC fluorescence and caspase‑3 activity, and induced mitochondria‑dependent apoptotic signals, including a decrease in mitochondrial transmembrane potential and Bcl‑2 protein expression, and an increase in cytosolic cytochrome c, Bax, Bak, cleaved caspase‑3, cleaved caspase‑7 and cleaved poly (ADP‑ribose) polymerase protein expression. Furthermore, quercetin significantly increased the protein expression levels of phosphorylated (p)‑ERK, p‑JNK1/2 and p‑GSK3‑α/β, but not p‑p38 or p‑AMPKα in SAS cells. Pretreatment with the pharmacological JNK inhibitor SP600125 effectively reduced the quercetin‑induced apoptosis‑related signals, as well as p‑ERK1/2 and p‑GSK3‑α/β protein expression. Both ERK1/2 and GSK3‑α/β inhibitors, PD98059 and LiCl, respectively, could significantly prevent the quercetin‑induced phosphorylation of ERK1/2 and GSK3‑α/β, but not JNK activation. Taken together, these results suggested that quercetin may induce tongue SCC cell apoptosis via the JNK‑activation‑regulated ERK1/2 and GSK3‑α/β‑mediated mitochondria‑dependent apoptotic signaling pathway
Circular economy for reduction of environmental impact of COVID-19 face mask waste
No full text[[abstract]]COVID-19 pandemic has posed severe threats to the society globally. World Health Organization (WHO) guidelines suggest that people wear face masks as a precautionary measure daily. This has resulted in the generation of massive amounts of mask-associated waste in the environment. Owing to the criticality of the epidemic, there has not been a large-scale investigation on where to discard masks, making this situation daunting. As the pandemic continues, the use of masks continues to increase; repeated use and disposal of masks has become an imperative issue. Most disposable masks comprise chemical fibers in the filter layer. Without proper treatment and disposal, these large amounts of chemical waste will eventually flow into rivers or oceans, leading to serious pollution. Therefore, to reduce the negative effects on the marine environment, it is crucial that we produce reusable masks and reduce disposable wearing habits. This study aimed to resolve this challenge using textile materials created by recycling fish-scale waste. Functional and comfortable masks manufactured without chemical additives to achieve multiple functions can increase the willingness to wear and be reused. Hence, product use can be prolonged, and the use of disposable masks can be curtailed. The product manufactured herein is biodegradable in nature, thus conforming to the green sustainable initiative
Distributed Denial-of-Service (DDoS) Attacks and Defense Mechanisms in Various Web-Enabled Computing Platforms: Issues, Challenges, and Future Research Directions
No full text[[abstract]]The demand for Internet security has escalated in the last two decades because the rapid proliferation in the number of Internet users has presented attackers with new detrimental opportunities. One of the simple yet powerful attack, lurking around the Internet today, is the Distributed Denial-of-Service (DDoS) attack. The expeditious surge in the collaborative environments, like IoT, cloud computing and SDN, have provided attackers with countless new avenues to benefit from the distributed nature of DDoS attacks. The attackers protect their anonymity by infecting distributed devices and utilizing them to create a bot army to constitute a large-scale attack. Thus, the development of an effective as well as efficient DDoS defense mechanism becomes an immediate goal. In this exposition, we present a DDoS threat analysis along with a few novel ground-breaking defense mechanisms proposed by various researchers for numerous domains. Further, we talk about popular performance metrics that evaluate the defense schemes. In the end, we list prevalent DDoS attack tools and open challenges