Stroke caregivers' perception on instant messaging application use for psychological intervention: a qualitative study.

In caring for patients with stroke, the leading cause of death and disability affecting over 80 million people worldwide, caregivers experience substantial psychological and physical burdens and difficulties in help-seeking owing to physical and time-constraints. Social distancing measures imposed during the coronavirus disease 2019 (COVID-19) pandemic further restricted them from using caregiver support services. While the use of telehealth emerged as a global prevailing trend during the COVID-19 pandemic, evidence for utilising instant messaging (IM) applications for psychological intervention is scanty. This study aimed to explore stroke caregivers' perceived potential utility of IM-delivered psychological intervention. Between January and August 2020, 36 adult family stroke caregivers in Hong Kong were recruited to individual telephone semi-structured interviews using purposive sampling. The interviews were audio-recorded, transcribed verbatim and analysed using an interpretive description approach. Three themes of caregivers' perceptions towards IM-delivered psychological intervention emerged: perceived high convenience and ease of use, perceived advantages that overcome existing barriers to services and message delivery tailored to individual needs. Our findings suggested that there is an imminent need among stroke caregivers for personalised psychological interventions and that IM is a potential modality for overcoming existing barriers in delivering accessible support to caregivers in real-time, real-world settings. Our study highlighted caregivers' acceptance and perceived benefits of IM-delivered psychological intervention and provided practical insights into the design of IM-delivered psychological interventions.

A Comparative Study of Titanium Cranioplasty for Extensive Calvarial Bone Defects: Three-Dimensionally Printed Titanium Implants Versus Premolded Titanium Mesh.

OBJECTIVE: This study compared the complications and symmetry outcomes between 3-dimensionally printed titanium implants and premolded titanium mesh in patients with extensive calvarial bone defects. METHODS: This retrospective analysis included patients with calvarial defects >50 cm2 undergoing cranioplasty who received either a 3-dimensionally printed titanium implant manufactured by selective laser melting techniques (N = 12) or a premolded titanium mesh customized onto a 3-dimensionally printed skull template (N = 23). Complications including intracranial infection, hardware extrusion, wound dehiscence, and cerebrospinal fluid leaks were investigated. Predictive factors affecting complications were investigated to identify the odds ratios in univariate and multivariate analyses. The symmetry was assessed by calculating the root mean square deviation, which showed the morphological deviation of the selected area compared with the mirrored image of the contralateral region. RESULTS: The overall complication rate was 26.1% (6/23 patients) in the premolded titanium group and 16.7% (2/12 patients) in the 3-dimensionally printed group. The reoperation rates did not differ significantly between the 2 groups (3-dimensionally printed group, 16.7%, versus premolded group, 21.7%). In multivariate analysis, only the number of previous cranial operation was significantly associated with the complication rate (odds ratio, 2.42; 95% confidence interval, 1.037-5.649; P = 0.041). The mean ± SD of the root mean square deviation was significantly smaller in the 3-dimensionally printed group (2.58 ± 0.93 versus 4.82 ± 1.31 mm, P < 0.001). CONCLUSIONS: The 3-dimensionally printed titanium implant manufactured by the selective laser melting technique showed comparable stability and improved symmetry outcomes compared with the conventional titanium mesh in the reconstruction of extensive calvarial defects.

Oncologic Safety and Efficacy of Cell-Assisted Lipotransfer for Breast Reconstruction in a Murine Model of Residual Breast Cancer.

BACKGROUND: Cell-assisted lipotransfer (CAL) is a novel technique for fat grafting that combines the grafting of autologous fat and adipose-derived stromal cells (ASCs) to enhance fat graft retention; however, its oncologic safety is controversial. METHODS: Herein, we investigated the oncologic safety of CAL for breast reconstruction using a murine model of residual breast cancer. Various concentrations of 4T1 cells (murine breast cancer cells) were injected into female mastectomized BALB/c mice to determine the appropriate concentration for injection. One week after injection, mice were divided into control (100 µL fat), low CAL (2.5 × 105 ASCs/100 µL fat), and high CAL (1.0 × 106 ASCs/100 µL fat) groups, and fat grafting was performed. The injection of 5.0 × 103 4T1 cells was appropriate to produce a murine model of residual breast cancer. RESULTS: The weight of the fat tumor mass was significantly higher in the high CAL group than in the other groups (p < 0.05). However, the estimated tumor weight was not significantly different between the groups. Additionally, the fat graft survival rate was significantly higher in the high CAL group than in the control and low CAL groups (p < 0.05). No significant difference was noted in the percentage of Ki-67-positive cells, suggesting that tumor proliferation was not significantly different between the groups. CONCLUSION: In summary, CAL significantly improved fat graft survival without affecting tumor size and proliferation in a murine model of residual breast cancer. These results highlight the oncologic safety of CAL for breast reconstruction. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Effectiveness of individualized 3D titanium-printed Orthognathic osteotomy guides and custom plates.

BACKGROUND: Computer-aided design/manufacturing (CAD/CAM) technology was developed to improve surgical accuracy and minimize errors in surgical planning and orthognathic surgery. However, its accurate implementation during surgery remains a challenge. Hence, we compared the accuracy and stability of conventional orthognathic surgery and the novel modalities, such as virtual simulation and three-dimensional (3D) titanium-printed customized surgical osteotomy guides and plates. METHODS: This prospective study included 12 patients who were willing to undergo orthognathic surgery. The study group consisted of patients who underwent orthognathic two-jaw surgery using 3D-printed patient-specific plates processed by selective laser melting and an osteotomy guide; orthognathic surgery was also performed by the surgeon directly bending the ready-made plate in the control group. Based on the preoperative computed tomography images and intraoral 3D scan data, a 3D virtual surgery plan was implemented in the virtual simulation module, and the surgical guide and bone fixation plate were fabricated. The accuracy and stability were evaluated by comparing the results of the preoperative virtual simulation (T0) to those at 7 days (T1) and 6 months (T2) post-surgery. RESULT: The accuracy (ΔT1‒T0) and stability (ΔT2‒T1) measurements, using 11 anatomical references, both demonstrated more accurate results in the study group. The mean difference of accuracy for the study group (0.485 ± 0.280 mm) was significantly lower than in the control group (1.213 ± 0.716 mm) (P < 0.01). The mean operation time (6.83 ± 0.72 h) in the control group was longer than in the study group (5.76 ± 0.43 h) (P < 0.05). CONCLUSION: This prospective clinical study demonstrated the accuracy, stability, and effectiveness of using virtual preoperative simulation and patient-customized osteotomy guides and plates for orthognathic surgery.

Lipid metabolic reprogramming by hypoxia-inducible factor-1 in the hypoxic tumour microenvironment.

Cancer cells rewire metabolic processes to adapt to the nutrient- and oxygen-deprived tumour microenvironment, thereby promoting their proliferation and metastasis. Previous research has shown that modifying glucose metabolism, the Warburg effect, makes glycolytic cancer cells more invasive and aggressive. Lipid metabolism has also been receiving attention because lipids function as energy sources and signalling molecules. Because obesity is a risk factor for various cancer types, targeting lipid metabolism may be a promising cancer therapy. Here, we review the lipid metabolic reprogramming in cancer cells mediated by hypoxia-inducible factor-1 (HIF-1). HIF-1 is the master transcription factor for tumour growth and metastasis by transactivating genes related to proliferation, survival, angiogenesis, invasion, and metabolism. The glucose metabolic shift (the Warburg effect) is mediated by HIF-1. Recent research on HIF-1-related lipid metabolic reprogramming in cancer has confirmed that HIF-1 also modifies lipid accumulation, ß-oxidation, and lipolysis in cancer, triggering its progression. Therefore, targeting lipid metabolic alterations by HIF-1 has therapeutic potential for cancer. We summarize the role of the lipid metabolic shift mediated by HIF-1 in cancer and its putative applications for cancer therapy.

Risk factors for depressive symptoms by age group among human immunodeficiency virus-infected adults in Korea.

We identified factors associated with depressive symptoms according to age group. We used data from a city-wide, cross-sectional survey conducted by the Seoul Metropolitan Government in 2014. Multivariable logistic regression analyses were performed to explore factors related to depressive symptoms. Depressive symptoms were assessed using a single item from the Korea National Health and Nutrition Examination Survey. Of the 370 subjects, 37.3% had depressive symptoms during the past 12 months. Compared to an age of ≥50 years, being 20-39 (adjusted odds ratio, 2.45; 95% confidence interval, 1.26-4.75) or 40-49 years (2.58; 1.32-5.06) of age was positively associated with depressive symptoms. In addition, a history of acquired immune deficiency syndrome-defining opportunistic disease (3.29; 1.09-9.92) and perceived discrimination (1.93; 1.16-3.20) in subjects aged 20-39 years, and poor subjective health (4.97; 1.42-17.32) in subjects aged 40-49 years, were associated with depressive symptoms, but no factor exhibited a significant association in subjects aged ≥ 50 years. In conclusion, a screening program that considers the factors identified in this study to prioritize patients with depression should be implemented.

Work hours and overtime of nurses working in Cambodian hospitals.

AIM: To examine the nature and prevalence of Cambodian nurses' work hours and overtime and related factors BACKGROUND: The chronic shortage of nursing workforce is a major cause of overtime among nurses. INTRODUCTION: Nursing shortage and working overtime among nurses negatively affect nurse and patient outcomes, but nurses' work hours and overtime in Cambodia have not been comprehensively examined. METHODS: A multicenter cross-sectional study was conducted in four Cambodian hospitals. Data were collected from 253 nurses providing direct nursing care using a questionnaire. The STROBE checklist was used for reporting this study. RESULTS: More than a fifth of staff nurses worked more than 48 h, which is the legal work hour limit in Cambodia. Two major reasons for working mandatory or voluntary overtime, on-call or 24-h on-call were (a) not wanting to let down colleagues and (b) able to get all work done. The number of patients cared for was related to whether or not nurses worked 48 h or more. CONCLUSION: Overtime work and adverse nurse scheduling are common in Cambodia. IMPLICATIONS FOR NURSING AND HEALTH POLICY: Nurse managers and healthcare institutes in Cambodia need to monitor Cambodian nurses' work hours, which are often beyond the legal work hour limit. Moreover, it is important to understand why nurses work overtime and develop health policies, strategies, and programs that can help promote patient and nurse safety and retain qualified nursing staff. The 24-h on-call practice needs to be regulated according to the labor policy in healthcare institutes to prevent adverse nurse and patient outcomes.

Qualitative Study of Chinese Stroke Caregivers' Caregiving Experience During the COVID-19 Pandemic.

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has led to disruptions in health care service delivery worldwide, inevitably affecting stroke survivors requiring ongoing rehabilitation and chronic illness management. To date, no published research has been found on stroke caregiving during the COVID-19 pandemic. This study aimed to explore Hong Kong stroke caregivers' caregiving experiences in the midst of this difficult time. METHODS: Individual semistructured interviews were conducted with 25 Chinese adult primary stroke caregivers from May to June 2020 via telephone. Interviews were transcribed verbatim and analyzed using an interpretive description approach and constant comparison strategy. RESULTS: Five themes of the stroke caregiving experience during the COVID-19 pandemic emerged: care service adversities, additional caregiving workload and strain, threatened relationship between caregiver and stroke survivors, threats to caregivers' physical and psychological well-being, and needs for continuing caregiving roles. Our findings suggested that caregivers have worsened physical and psychological well-being because of increases in care burden with simultaneously reduced formal and informal support. The relationship between caregiver and stroke survivor was subsequently affected, placing some survivors at heightened risk of abuse. CONCLUSIONS: Our study provides valuable findings about stroke caregiving experiences and needs during the pandemic. Delivery of psychological support, telemedicine, and household hygiene resources would be useful to mitigate caregivers' psychological distress during the COVID-19 pandemic.

Histone demethylase PHF2 activates CREB and promotes memory consolidation.

Long-term memory formation is attributed to experience-dependent gene expression. Dynamic changes in histone methylation are essential for the epigenetic regulation of memory consolidation-related genes. Here, we demonstrate that the plant homeodomain finger protein 2 (PHF2) histone demethylase is upregulated in the mouse hippocampus during the experience phase and plays an essential role in memory formation. PHF2 promotes the expression of memory-related genes by epigenetically reinforcing the TrkB-CREB signaling pathway. In behavioral tests, memory formation is enhanced by transgenic overexpression of PHF2 in mice, but is impaired by silencing PHF2 in the hippocampus. Electrophysiological studies reveal that PHF2 elevates field excitatory postsynaptic potential (fEPSP) and NMDA receptor-mediated evoked excitatory postsynaptic current (EPSC) in CA1 pyramidal neurons, suggesting that PHF2 promotes long-term potentiation. This study provides insight into the epigenetic regulation of learning and memory formation, which advances our knowledge to improve memory in patients with degenerative brain diseases.

How cancer cells remodel lipid metabolism: strategies targeting transcription factors.

Reprogramming of lipid metabolism has received increasing recognition as a hallmark of cancer cells because lipid dysregulation and the alteration of related enzyme profiles are closely correlated with oncogenic signals and malignant phenotypes, such as metastasis and therapeutic resistance. In this review, we describe recent findings that support the importance of lipids, as well as the transcription factors involved in cancer lipid metabolism. With recent advances in transcription factor analysis, including computer-modeling techniques, transcription factors are emerging as central players in cancer biology. Considering the limited number and the crucial role of transcription factors associated with lipid rewiring in cancers, transcription factor targeting is a promising potential strategy for cancer therapy.

Compact Fat Grafting: A Novel Method to Improve Graft Retention Through Modulation of Adipocyte Size.

BACKGROUND: The viable zone where adipocytes and/or adipose-derived stem cells survive is present at the surface of graft fat tissue; however, there is controversy regarding the zone thickness. Graft retention could be improved if more adipocytes are included in the zone. OBJECTIVES: We hypothesize that a temporary reduction in adipocyte size prior to grafting could increase the number of adipocytes in the viable zone. We reduced the adipocyte size by treatment with MLN4924, which controls lipid accumulation in adipocytes, and investigated the histological and microenvironmental changes in grafted fat. METHODS: Subcutaneous fat harvested from wild-type C57BL/6J mice was chopped into small pieces; treated with dimethyl sulfoxide (control group), 0.25 µM MLN4924, or 0.5 µM MLN4924 for 4 days; and grafted into recipient C57BL/6J mice at the supraperiosteal plane of the skull. RESULTS: The reduced adipocyte size in response to MLN4924 treatment was restored within 8 weeks after fat grafting. The MLN4924-treated groups exhibited substantially greater graft volume, lower tissue hypoxia, and higher production of M2 macrophages compared with the control group. CONCLUSIONS: Grafting with compact fat that had smaller adipocytes improved the microenvironment by modulating tissue hypoxia and macrophage polarization, leading to improved graft retention. Therefore, compact fat grafting may offer a new clinical strategy without the need for stem cell manipulation.

Factors influencing supportive care needs of multiple myeloma patients treated with chemotherapy.

PURPOSE: The present study is a descriptive survey conducted to identify factors influencing supportive care needs of patients with multiple myeloma treated with chemotherapy. METHODS: A structured questionnaire was provided to 141 patients with multiple myeloma who were treated as inpatients or outpatients at Seoul St. Mary's Hospital of the Catholic University of Korea. Data were analyzed with t test, ANOVA, Scheffe's test, correlational analysis, and linear regression analysis using SPSS version 21.0. RESULTS: The mean score of supportive care needs of patients with multiple myeloma was 1.51 out of 4 points. Of supportive care needs, information on future disease outcome scored the highest, with a mean score of 2.12, followed by easy and candid explanation by health care staff (2.11), and information on foods that are healthy for cancer patients (2.02). The mean score of disease-related knowledge was 0.52 of 1 point, and diagnostic test results scored the lowest among the subdomains of disease-related knowledge. The mean score of emotional state was 1.13 out of 3 points, mean anxiety score was 1.01 out of 3 points, and mean depression score was 1.26 out of 3 points. Anxiety and depression were identified as factors influencing supportive care needs of patients with multiple myeloma. CONCLUSIONS: The present study demonstrated that the supportive care needs of patients with multiple myeloma are associated with their emotional state. The supportive care needs of patients with multiple myeloma should be identified at an individual level, and should be addressed to reduce anxiety and depression.

Associations Between COVID-19 Misinformation Exposure and Belief With COVID-19 Knowledge and Preventive Behaviors: Cross-Sectional Online Study.

BACKGROUND: Online misinformation proliferation during the COVID-19 pandemic has become a major public health concern. OBJECTIVE: We aimed to assess the prevalence of COVID-19 misinformation exposure and beliefs, associated factors including psychological distress with misinformation exposure, and the associations between COVID-19 knowledge and number of preventive behaviors. METHODS: A cross-sectional online survey was conducted with 1049 South Korean adults in April 2020. Respondents were asked about receiving COVID-19 misinformation using 12 items identified by the World Health Organization. Logistic regression was used to compute adjusted odds ratios (aORs) for the association of receiving misinformation with sociodemographic characteristics, source of information, COVID-19 misinformation belief, and psychological distress, as well as the associations of COVID-19 misinformation belief with COVID-19 knowledge and the number of COVID-19 preventive behaviors among those who received the misinformation. All data were weighted according to the Korea census data in 2018. RESULTS: Overall, 67.78% (n=711) of respondents reported exposure to at least one COVID-19 misinformation item. Misinformation exposure was associated with younger age, higher education levels, and lower income. Sources of information associated with misinformation exposure were social networking services (aOR 1.67, 95% CI 1.20-2.32) and instant messaging (aOR 1.79, 1.27-2.51). Misinformation exposure was also associated with psychological distress including anxiety (aOR 1.80, 1.24-2.61), depressive (aOR 1.47, 1.09-2.00), and posttraumatic stress disorder symptoms (aOR 1.97, 1.42-2.73), as well as misinformation belief (aOR 7.33, 5.17-10.38). Misinformation belief was associated with poorer COVID-19 knowledge (high: aOR 0.62, 0.45-0.84) and fewer preventive behaviors (≥7 behaviors: aOR 0.54, 0.39-0.74). CONCLUSIONS: COVID-19 misinformation exposure was associated with misinformation belief, while misinformation belief was associated with fewer preventive behaviors. Given the potential of misinformation to undermine global efforts in COVID-19 disease control, up-to-date public health strategies are required to counter the proliferation of misinformation.

Targeted Downregulation of kdm4a Ameliorates Tau-engendered Defects in Drosophila melanogaster.

BACKGROUND: Tauopathies, a class of neurodegenerative diseases that includes Alzheimer's disease (AD), are characterized by the deposition of neurofibrillary tangles composed of hyperphosphorylated tau protein in the human brain. As abnormal alterations in histone acetylation and methylation show a cause and effect relationship with AD, we investigated the role of several Jumonji domain-containing histone demethylase (JHDM) genes, which have yet to be studied in AD pathology. METHODS: To examine alterations of several JHDM genes in AD pathology, we performed bioinformatics analyses of JHDM gene expression profiles in brain tissue samples from deceased AD patients. Furthermore, to investigate the possible relationship between alterations in JHDM gene expression profiles and AD pathology in vivo, we examined whether tissue-specific downregulation of JHDM Drosophila homologs (kdm) can affect tauR406W-induced neurotoxicity using transgenic flies containing the UAS-Gal4 binary system. RESULTS: The expression levels of JHDM1A, JHDM2A/2B, and JHDM3A/3B were significantly higher in postmortem brain tissue from patients with AD than from non-demented controls, whereas JHDM1B mRNA levels were downregulated in the brains of patients with AD. Using transgenic flies, we revealed that knockdown of kdm2 (homolog to human JHDM1), kdm3 (homolog to human JHDM2), kdm4a (homolog to human JHDM3A), or kdm4b (homolog to human JHDM3B) genes in the eye ameliorated the tauR406W-engendered defects, resulting in less severe phenotypes. However, kdm4a knockdown in the central nervous system uniquely ameliorated tauR406W-induced locomotion defects by restoring heterochromatin. CONCLUSION: Our results suggest that downregulation of kdm4a expression may be a potential therapeutic target in AD.

Professional socialisation of nursing students in a collectivist culture: a qualitative study.

BACKGROUND: Beyond the formal curriculum of skill attainment, nursing students are able to undergo the professional socialisation process in clinical contexts and establish their identity as healthcare providers. However, the cultural context that affects the socialisation process in clinical placements is less discussed. We aimed to explore nursing students' learning and professional socialisation during clinical placements by considering the socio-cultural contexts in South Korea. METHODS: A grounded theory approach was used for this research. Four rounds of in-depth and intensive interviews were carried out, with the recruitment of 16 nursing students, four nurses and two university lecturers in South Korea (29 interviews in total). A constructivist grounded theory framework was adopted to analyse the interview data. NVivo 11 was used to manage the interview data for analysis. RESULTS: The researchers identified the process of learning and professional socialisation under three core themes: 1) Struggling at the bottom of the hierarchy, 2) Acceptance and conformity, and 3) The need for 'nunchi' (in Korean, it means to study the atmosphere and discover the embedded intention of others' behaviour). The results offered insights into the challenges encountered by nursing students on clinical placements and how students attempt to adapt and conform to the difficulties encountered in clinical education to maximise their learning and for their professional socialisation. The significance of the hidden curriculum was discussed. CONCLUSIONS: While experiential learning is a great opportunity for students to build on their coping skills and professional socialisation, a lack of support can result in failure to manage the hidden curriculum and theoretical and practical skills. Nursing educators therefore need to orientate students to the professional culture prior to beginning clinical placements.

Phosphate supplementation for hypophosphatemia during continuous renal replacement therapy in adults.

BACKGROUND: Hypophosphatemia is common during continuous renal replacement therapy (CRRT) in critically ill patients and can cause generalized muscle weakness, prolonged respiratory failure, and myocardial dysfunction. This study aimed to investigate the efficacy and safety of adding phosphate to the dialysate and replacement solutions to treat hypophosphatemia occurring in intensive CRRT in critically ill patients. METHODS: We retrospectively analyzed 73 patients treated with intensive CRRT (effluent flow ≥35 ml/kg/hr) in the intensive care unit. The control group (group 1, n = 22) received no phosphate supplementation. The treatment groups received dialysate and replacement solution phosphate supplementation at 2.0 mmol/L (group 2, n = 26) or 3.0 mmol/L (group 3, n = 25). RESULTS: The CRRT-induced hypophosphatemia incidence was 59.0%. Correction of hypophosphatemia with phosphate supplementation changed the mean serum phosphorus levels to 1.24 ± 0.37 and 1.44 ± 0.31 mmol/L in groups 2 and 3, respectively (p = .02). The time required for correction was 1.65 ± 0.80 and 1.39 ± 1.43 days for groups 2 and 3, respectively and was significantly longer in group 2 (p = .02). After supplementation, hypophosphatemia, and hyperphosphatemia both occurred in 7% of group 2. Group 3 developed no hypophosphatemia, but 20% developed hyperphosphatemia. The serum phosphate levels in hyperphosphatemia cases returned to normal within 2.0 days (group 2) and 1.0 day (group 3) after stopping phosphate supplementation. CONCLUSION: Phosphate supplementation effectively corrected CRRT-induced hypophosphatemia in critically ill patients with an acute kidney injury. The use of 2 mmol/L phosphate is appropriate in patients with CRRT-induced hypophosphatemia, but a different concentration could be required to prevent hypophosphatemia at the start of CRRT.

CST3 and GDF15 ameliorate renal fibrosis by inhibiting fibroblast growth and activation.

The final strategies to care patients with end-stage renal fibrosis rely on dialysis and kidney transplantation. Because such treatments are invasive and cause health problems eventually, it is necessary to develop new therapeutic strategies for delaying the disease progress. We here searched for cytokines showing an anti-fibrotic activity in cell-based experiments. Cystatin C (CST3) and Growth differentiation factor 15 (GDF15) were identified to have anti-fibrotic activities in a cytokine array screening. In primary fibroblasts isolated from the mouse kidneys subjected to ureteral obstruction-induced fibrosis, each cytokine induced apoptotic cell death and reduced collagen production. These anti-fibrotic effects were further augmented by co-administration of both cytokines. Mechanistically, CST3 and GDF15 were found to block the TGF-ß receptor and the N-Myc signaling pathways, respectively. In mice with unilateral ureter obstruction, each cytokine and the combination of two cytokines effectively reduced the fibrotic burden in the subjected kidneys. Therefore, we propose that CST3 and GDF15 could be potential candidates for biopharmaceutics to ameliorate renal fibrosis.

Inhibition of neddylation facilitates cell migration through enhanced phosphorylation of caveolin-1 in PC3 and U373MG cells.

BACKGROUND: Protein neddylation is a post-translational modification by a covalent conjugation with the neural precursor cell expressed, developmentally downregulated 8 (NEDD8). Although this process has been reported to participate in diverse cellular signaling, little is known about its role in cancer cell migration. Given a recent proteomics report showing that NEDD8 is downregulated in prostate cancer tissues versus normal prostate tissues, we tested the possibility that neddylation plays a role in cancer evolution, and then tried to identify target proteins of the neddylation. METHODS: The neddylation process was inhibited by transfecting cancer cells with NEDD8-targeting siRNAs or by treating the cells with a NAE1 inhibitor MLN4924. Cell migration was evaluated by an in vitro wound-healing assay and a Transwell migration assay. His/NEDD8-conjugated proteins were pulled down with nickel-affinity beads under a denaturing condition, and identified by Western blotting. All data were processed using the Microsoft Excel program and analyzed statistically by two-sided, unpaired Student's t-test. RESULTS: Caveolin-1, which plays a critical role in cell migration, was identified to be conjugated with NEDD8. When the neddylation was inhibited, the phosphorylation of caveolin-1 at Tyr14 was augmented in PC3 and U373MG cells, thereby leading to increased cell migration. Such consequences by neddylation inhibition were abolished in the presence of a Src family kinase inhibitor PP2. CONCLUSIONS: NEDD8 seems to inhibit the Src-mediated phosphorylation of caveolin-1 by modifying the structure of caveolin-1 protein, which blocks the migration of cancer cells. Although the neddylation process is currently regarded as an emerging target for cancer therapy, our results suggest the possibility that the inhibition of neddylation could facilitate cancer invasion or metastasis at least in some types of cancers.

Sirtuin 1 modulates cellular responses to hypoxia by deacetylating hypoxia-inducible factor 1alpha.

To survive in hypoxic environments, organisms must be able to cope with redox imbalance and oxygen deficiency. The SIRT1 deacetylase and the HIF-1alpha transcription factor act as redox and oxygen sensors, respectively. Here, we found that SIRT1 binds to HIF-1alpha and deacetylates it at Lys674, which is acetylated by PCAF. By doing so, SIRT1 inactivated HIF-1alpha by blocking p300 recruitment and consequently repressed HIF-1 target genes. During hypoxia, SIRT1 was downregulated due to decreased NAD(+) levels, which allowed the acetylation and activation of HIF-1alpha. Conversely, when the redox change was attenuated by blocking glycolysis, SIRT1 was upregulated, leading to the deacetylation and inactivation of HIF-1alpha even in hypoxia. In addition, we confirmed the SIRT1-HIF-1alpha interaction in hypoxic mouse tissues and observed in vivo that SIRT1 has negative effects on tumor growth and angiogenesis. Our results suggest that crosstalk between oxygen- and redox-responsive signal transducers occurs through the SIRT1-HIF-1alpha interaction.

Retrospective cohort study on Korean adolescents' sleep, depression, school adjustment, and life satisfaction.

Sleep patterns have an important role in the physical and psychological health of adolescents. In this study, we investigated the effects of sleep duration on depression, school adjustment, and life satisfaction of adolescents. A retrospective cohort study was conducted using secondary data on first and second grade students in middle schools from the Korean Children and Youth Panel Survey. Those who responded to all items about sleep were selected, and those who were within 30 min of sleep duration difference across 1 year were selected. Participants who had no change in variables of personal factors, parental factors, and family environment across 1 year were selected (n = 421). Longer total sleep duration and shorter weekend oversleeping had effects on lower depression, higher school adjustment, and greater life satisfaction after adjusting for personal factors, parental factors, and family environment. Therefore, we propose that school nurses assess adolescents' sleep patterns and counsel and educate adolescents and their parents about the influence of sleep patterns on adolescents.