Validation of the COmprehensive Score for Financial Toxicity (COST) in Vietnamese patients with cancer.

INTRODUCTION: The COmprehensive Score for Financial Toxicity (COST) has proven to be a reliable tool for quantifying the impact of financial toxicity (FT) in patients with cancer in clinical and public health settings. However, the COST has not yet been validated in Vietnam. Therefore, we aimed to evaluate its reliability and validity among Vietnamese patients with cancer. METHODS: A cross-sectional study was conducted in a sample of 300 patients with cancer aged 27-95 years (mean: 58.5±11.2) in a tertiary hospital. The COST was translated into Vietnamese and English and adjusted to suit the local culture. Reliability was evaluated using Cronbach's alpha and McDonald's omega coefficients. The construct and convergent validities were also assessed. RESULTS: The COST demonstrated good internal consistency and reliability (Cronbach's alpha = 0.913; McDonald's omega = 0.915). The exploratory factor analysis revealed two factors that explained 64.9% of the variance. The adjusted fit indices indicated a good fit of the model (χ2 (39) = 67.78, p = 0.003; standardized root mean squared residual = 0.042; Tucker-Lewis index = 0.971; comparative fit index = 0.979; root mean square error of approximation = 0.061, 90% confidence interval = 0.035-0084). Higher COST scores were significantly correlated with higher health-related quality of life (EQ-5D-5L utility score: r = 0.21, p = 0.002; EQ VAS: r = 0.28, p < 0.001). Multivariate quantile regression analysis revealed that female sex, rural residence, and unstable job/unemployment were associated with lower COST scores. There was no statistically significant difference in other factors, including clinical factors (types of cancer, staging, and treatment modalities). CONCLUSIONS: The COST is reliable and valid, making it suitable for assessing FT severity in Vietnamese patients with cancer.

Beyond Medical Bills: High Prevalence of Financial Toxicity and Diverse Management Strategies Among Vietnamese Patients with Cancer.

Objectives: This study was conducted to measure financial toxicity (FT) among patients with cancer in Vietnam using the COmprehensive Score for financial Toxicity (COST) and to describe the cost management strategies employed by these patients. Methods: This comprehensive cross-sectional study enrolled 634 patients from 2 specialized oncology hospitals in Vietnam. Using COST cutoff scores, FT was classified as none/mild (≥26), moderate (14-25), or severe (≤13). Cost management strategies, or coping mechanisms, were classified into 4 groups: lifestyle changes, financial resource strategies, treatment modifications, and support seeking. Results: The prevalence of FT was 91.8%, with 51.7% of participants demonstrating severe and 40.1% exhibiting moderate FT. Severe FT was significantly associated with female sex, low education level, unstable employment, low household economic status, and advanced cancer stage. The most common coping strategies were as follows: among lifestyle changes, reducing spending on basic items and leisure activities (78.7%) and cutting back on essential household expenses (66.4%); among financial resource strategies, borrowing money from relatives or friends (49.1%) and withdrawing funds from retirement or savings accounts (32.1%); within treatment modifications, switching treatment facilities or doctors due to cost concerns (9.3%); and within support seeking, obtaining help from welfare or community organizations (18.8%). All strategies were significantly more likely to be used by patients with severe FT. Conclusions: FT was highly prevalent among patients with cancer. Most patients relied on lifestyle adjustments and coping strategies, underscoring the need for improved financial support systems to alleviate the economic burden associated with cancer care.

Validation of the Disaster Adaptation and Resilience Scale for Vulnerable Communities in Vietnam's Coastal Regions.

OBJECTIVES: This study validated the Vietnamese version of the Disaster Adaptation and Resilience Scale (DARS) for use in vulnerable communities in Vietnam. METHODS: This was a cross-sectional study involving 595 adults from 2 identified communities. The original DARS assessment tool was translated, and the validity and reliability of the Vietnamese version of DARS (V-DARS) were assessed. The internal consistency of the overall scale and its subscales was evaluated using Cronbach's alpha and McDonald's omega reliability coefficients. Confirmatory factor analysis (CFA) was employed to evaluate its construct validity, building upon the factor structure identified in exploratory factor analysis (EFA). Construct validity was assessed based on convergent and discriminant validity. RESULTS: Following the established criteria for EFA, 8 items were removed, resulting in a refined V-DARS structure comprising 35 items distributed across 5 distinct factors. Both alpha and omega reliability coefficients indicated strong internal consistency for the overall scale (α=0.963, ω=0.963) and for each of the 5 sub-scales (all>0.80). The CFA model also retained the 5-factor structure with 35 items. The model fit indices showed acceptable values (RMSEA: 0.072; CFI: 0.912; TLI: 0.904; chi-square test: <0.01). Additionally, the convergent and discriminant validity of the V-DARS were deemed appropriate and satisfactory for explaining the measurement structure. CONCLUSIONS: Our findings suggest that the V-DARS is a valid and reliable scale for use within vulnerable communities in Vietnam to assess adaptive responses to natural disasters. It may also be considered for use in other populations.

Fermented calcium butyrate supplementation in post-peak laying hens improved ovarian function and tibia quality through the "gut-bone" axis.

The compromised egg quality and leg abnormality during the end of the laying cycle (after 40 weeks) have been leading to poor animal welfare and substantial economic losses. Therefore, the effects of fermented calcium (Ca) butyrate, produced by fermentation by Clostridium butyricum, on production, eggshell quality, and tibial property of hens were explored. A total of 192 Hy-line brown laying hens at 50-week-old were assigned to a basal diet or the basal diet with 300 mg/kg of the fermented Ca butyrate from 50 to 58 weeks of age. Each treatment had 6 replicates with 16 hens each. The diet supplemented with 300 mg/kg fermented Ca butyrate notably increased egg weight, ovarian follicle number, and eggshell strength (P = 0.072) as compared to the basal diet, which were associated with cytokine secretion, toll-like receptor signaling pathways, and intestinal immunity based on the RNA-seq data from the granulosa. Dietary Ca butyrate inclusion decreased the expression of ileal tumor necrosis factor-alpha and serum pro-inflammatory cytokine concentration, as well as increased the content of serum immunoglobulin A when compared to the basal diet (both P < 0.05). The birds that received fermented Ca butyrate diets exhibited higher villus height (P < 0.05) and upregulated expression of tight junction proteins, whereas it did not alter the composition of cecal microbiota (P > 0.05). In addition, the diet with fermented Ca butyrate reduced the number of osteoclasts in the proximal tibia and the level of C-terminal cross-linked telopeptide of type I collagen, a bone resorption marker (P < 0.05), whereas it tended to increase the concentration of the procollagen type I N-terminal propeptide that reflects bone formation marker in serum. Moreover, the layers fed fermented Ca butyrate diets possessed higher (P < 0.05) bone area and trabecular number of the proximal tibia, yield load, and ultimate load than those that consumed basal diets. Collectively, dietary fermented Ca butyrate supplementation in post-peak layer diets improved the ovarian function and tibia quality, which might be related to enhancing intestinal integrity and consequently decreasing inflammation mediated bone resorption.

Identification of Ecdysteroid Sinapate Esters with COX-2 Inhibitory Effects from Fibraurea recisa Using Molecular Networking and MS2LDA.

The roots of Fibraurea recisa are recognized as a rich source of protoberberine and aporphine alkaloids, but the non-alkaloidal metabolites in this plant are underexplored. The present study investigated the chemical composition of the plant roots using untargeted metabolomics-based molecular networking and MS2LDA motif annotation, revealing the presence of a characteristic fragment motif related to several sinapoyl-functionalized metabolites. Guided by the targeted motif, two new sinapic acid-ecdysteroid hybrids, named 3-O-sinapoyl makisterone A (1) and 2-O-sinapoyl makisterone A (2), were isolated. The structures of these compounds, including their absolute configuration, were elucidated by HR-ESIQTOFMS, MS2 fragmentation, NMR spectroscopy, and chemical degradation coupled with optical rotation measurements. Although neither compound inhibited nitric oxide (NO) production or inducible nitric oxide synthase (iNOS) protein expression on lipopolysaccharide-induced RAW 264 cells, 2 significantly suppressed cyclooxygenase 2 (COX-2) protein expression at 1-30 µM. Additionally, decreased expression of COX-2 protein was barely observed after treatment with methyl sinapate or makisterone A, the steroid skeleton of 1 and 2. These results indicated that the presence of the sinapoyl moiety at C-2 on the C28-ecdysteroid skeleton played a key role in the selectivity for the suppression of the COX-2 protein expression.

Sleep Quality and Poor Sleep-related Factors Among Healthcare Workers During the COVID-19 Pandemic in Vietnam.

OBJECTIVES: The coronavirus disease 2019 (COVID-19) pandemic has increased the workload of healthcare workers (HCWs), impacting their health. This study aimed to assess sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and identify factors associated with poor sleep among HCWs in Vietnam during the COVID-19 pandemic. METHODS: In this cross-sectional study, 1000 frontline HCWs were recruited from various healthcare facilities in Vietnam between October 2021 and November 2021. Data were collected using a 3-part self-administered questionnaire, which covered demographics, sleep quality, and factors related to poor sleep. Poor sleep quality was defined as a total PSQI score of 5 or higher. RESULTS: Participants' mean age was 33.20±6.81 years (range, 20.0-61.0), and 63.0% were women. The median work experience was 8.54±6.30 years. Approximately 6.3% had chronic comorbidities, such as hypertension and diabetes mellitus. About 59.5% were directly responsible for patient care and treatment, while 7.1% worked in tracing and sampling. A total of 73.8% reported poor sleep quality. Multivariate logistic regression revealed significant associations between poor sleep quality and the presence of chronic comorbidities (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.17 to 5.24), being a frontline HCW directly involved in patient care and treatment (OR, 1.59; 95% CI, 1.16 to 2.16), increased working hours (OR, 1.84; 95% CI,1.37 to 2.48), and a higher frequency of encountering critically ill and dying patients (OR, 1.42; 95% CI, 1.03 to 1.95). CONCLUSIONS: The high prevalence of poor sleep among HCWs in Vietnam during the COVID-19 pandemic was similar to that in other countries. Working conditions should be adjusted to improve sleep quality among this population.

Mental health and its determinants among adolescents living in families with separated or divorced parents in an urban area of Vietnam.

BACKGROUND: We assessed the prevalence of stress, anxiety, and depression among adolescents living in families with separated or divorced parents in Hue City, Vietnam and identified factors associated with these conditions. METHODS: This cross-sectional study enrolled 309 adolescents, aged 12 to 17 years, living in families with separated or divorced parents in Hue City, Vietnam. The depression anxiety stress scale-21 (DASS-21) was used to measure stress, anxiety, and depression. Predictors of overall and individual mental health problems were identified using ordered and binary logistic regression, respectively. RESULTS: The DASS-21 scale revealed a 49.2% prevalence of stress, while anxiety and depression had s prevalence rates of 61.5%. Among participants, 42.4% experienced all 3 mental health issues. Several factors were identified as significant predictors of mental health problems, including poor to average economic status (adjusted odds ratio [aOR], 2.00; 95% confidence interval [CI], 1.21-3.31; p=0.007); being in high school (aOR, 5.02; 95% CI, 2.93-8.60; p<0.001); maternal occupation of teacher, healthcare professional, or official (aOR, 2.39; 95% CI, 1.13-5.03; p=0.022); longer duration of family separation or divorce (aOR, 1.24; 95% CI, 1.05-1.45; p=0.009); living with one's mother (aOR, 1.69; 95% CI, 1.03-2.76; p=0.04); alcohol consumption (aOR, 1.70; 95% CI, 0.99-2.92; p=0.050); and being bullied (aOR, 5.33; 95% CI, 1.10-25.69; p=0.037). Most of these factors were associated with stress, anxiety, and depression. Additionally, smoking was associated with stress. CONCLUSION: Adolescents with separated or divorced parents were at increased risk of stress, anxiety, and depression. The findings of this study provide important implications for prevention programs.

Protein Kinase D3 (PKD3) Requires Hsp90 for Stability and Promotion of Prostate Cancer Cell Migration.

Prostate cancer metastasis is a significant cause of mortality in men. PKD3 facilitates tumor growth and metastasis, however, its regulation is largely unclear. The Hsp90 chaperone stabilizes an array of signaling client proteins, thus is an enabler of the malignant phenotype. Here, using different prostate cancer cell lines, we report that Hsp90 ensures PKD3 conformational stability and function to promote cancer cell migration. We found that pharmacological inhibition of either PKDs or Hsp90 dose-dependently abrogated the migration of DU145 and PC3 metastatic prostate cancer cells. Hsp90 inhibition by ganetespib caused a dose-dependent depletion of PKD2, PKD3, and Akt, which are all involved in metastasis formation. Proximity ligation assay and immunoprecipitation experiments demonstrated a physical interaction between Hsp90 and PKD3. Inhibition of the chaperone-client interaction induced misfolding and proteasomal degradation of PKD3. PKD3 siRNA combined with ganetespib treatment demonstrated a specific involvement of PKD3 in DU145 and PC3 cell migration, which was entirely dependent on Hsp90. Finally, ectopic expression of PKD3 enhanced migration of non-metastatic LNCaP cells in an Hsp90-dependent manner. Altogether, our findings identify PKD3 as an Hsp90 client and uncover a potential mechanism of Hsp90 in prostate cancer metastasis. The molecular interaction revealed here may regulate other biological and pathological functions.

Comparison of Perceptions About Patient Safety Culture Between Physicians and Nurses in Public Hospitals in Vietnam.

Introduction: Patient safety culture (PSC) is a vital component in ensuring high-quality and safe patient care. Assessment of physicians' and nurses' perceptions of existing hospital PSC is the first step to promoting PSC. This paper is aimed to assess physicians' and nurses' perceptions of PSC in 5 public general hospitals in Hanoi, Vietnam. Methods: This cross-sectional study surveyed 410 physicians and 824 nurses utilizing the validated Hospital Survey on Patient Safety Culture in an online format. Results: The composite positive physician's perception of PSC varied from 47.8 to 89.6% with the lowest composite score of patient safety for "staffing" (47.8%) and the highest composite score for "teamwork within units" (89.6%). The composite positive responses for perception among nurses varied from 51.3 to 94.2% with the lowest composite score of patient safety for "staffing" (51.3%) and the highest composite score for "teamwork within units" (94.2%). Conclusion: The mean scores for "supervisor/manager expectations"; "staffing", "management support for patient safety", "teamwork across units", "handoffs and transitions" among nurses were significantly higher than that among physicians (p<0.05). About two-thirds of physicians and nurses reported no event in the past 12 months (62.8 and 71.7%, respectively). The nurses reported significantly higher patient grades (every good and excellent) than physicians (75% vs 67.1%, p <0.001). Hospitals could develop and implement intervention programs to improve patient safety, including providing interventions on teamwork and communication, encouraging staff to notify incidents, and avoiding punitive responses.

Self-control as an important factor affecting the online learning readiness of Vietnamese medical and health students during the COVID-19 pandemic: a network analysis.

PURPOSE: The current study aimed to use network analysis to investigate medical and health students' readiness for online learning during the coronavirus disease 2019 (COVID-19) pandemic at the University of Medicine and Pharmacy, Hue University. METHODS: A questionnaire survey on the students' readiness for online learning was performed using a Google Form from May 13 to June 22, 2021. In total, 1,377 completed responses were eligible for analysis out of 1,411 participants. The network structure was estimated for readiness scales with 6 factors: computer skills, internet skills, online communication, motivation, self-control, and self-learning. Data were fitted using a Gaussian graphical model with the extended Bayesian information criterion. RESULTS: In 1,377 students, a network structure was identified with 6 nodes and no isolated nodes. The top 3 partial correlations were similar in networks for the overall sample and subgroups of gender and grade levels. The self-control node was the strongest for the connection to others, with the highest nodal strength. The change of nodal strength was greatest in online communication for both gender and grade levels. The correlation stability coefficient for nodal strength was achieved for all networks. CONCLUSION: These findings indicated that self-control was the most important factor in students' readiness network structures for online learning. Therefore, self-control needs to be encouraged during online learning to improve the effectiveness of achieving online learning outcomes for students.

Molecular networking-based discovery of anti-inflammatory chromene dimers from Melicope pteleifolia.

With the aid of a feature-based molecular networking strategy, five undescribed C2 and C1 symmetric chromene dimers, namely, melptelchromenes A-E, were isolated from the leaves of Melicope pteleifolia. Four asymmetric dimers were found to be racemates and were resolved by chiral phase HPLC analyses. Their structures, including absolute configurations, were elucidated by HRMS, NMR spectroscopy, and quantum mechanical calculations of ECD spectra and NMR chemical shifts. Melptelchromenes A-D possess a unique ethylidene linkage via two 2H-chromene cores, while melptelchromene E represents the first example of a dimeric chromene featuring a 1,3-diarylbutan-1-ol moiety. Of these compounds, 6,6'-linked dimeric chromenes showed nitric oxide inhibitory activities on lipopolysaccharide-induced RAW 264 cells, and (-)- and (+)-melptelchromene E were the two most potent compounds (IC50, 3.0 and 5.1 µM, respectively).

Network analysis of psychological factors related to academic pressure faced by medical students in the central and highland regions of Vietnam.

Medical students experience extensive pressure during their undergraduate courses. Given the complex associations between psychological factors in association with academic pressure. We investigated the study with objectives: To examine psychological factors related to academic pressure by analysing interactions between 'study motivation', 'study environment', 'study conditions', 'teacher quality', 'training programme', 'management system', 'evaluation', and 'extracurricular activities' using a network analysis approach. A total of 878 medical students majoring in general medicine from the first, third, and fifth years of a six-year course at the largest medical university in central and highland regions of Vietnam were involved in this cross-sectional study. The approach used was convenient cluster sampling with a self-administered questionnaire by the participants. Network analysis for pairwise correlations between psychological factors was estimated . Important factors in the network analysis were calculated using centrality indices including node strength (S), closeness (C), and betweenness (B). The higher score of S, C, and B indicate the more importance of the node. The results obtained from the network analysis of eight psychological factors showed that 'teaching quality' was mostly connected with other factors overall, while the 'training programme' was seen in both genders and freshman students. 'Study conditions' and 'training programme' were mostly connected with other factors in junior and senior students, respectively. The strong pairwise correlation was confirmed: management system and evaluation activity, followed by study environment and study conditions, and teaching quality and training programme. Additionally, nodes with high centrality were shown to be 'management system' (S = 0.97, C = 0.019, B = 1), and 'training programme' (S = 0.96, C = 0.021, B = 4). Our study findings indicate that satisfaction with the training programme amongst eight psychological factors is the most important factor affecting academic pressure among medical students. The training programme is linked with teaching quality, whereas the management system is correlated with evaluation activity.

Attention Deficit Hyperactivity Disorder (ADHD) and Associated Factors Among First-Year Elementary School Students.

PURPOSE: Attention deficit hyperactivity disorder (ADHD) is a mental health disorder commonly in children. This study aimed to examine the prevalence of ADHD and risk factors among first-year pupils in Vietnam's urban city. PATIENTS AND METHODS: A cross-sectional study was conducted in four randomly selected primary schools. Information on 525 pupils in grade 1 (ages 6 to 7 years) was collected from 525 parents/caregivers and 28 teachers. We used the Vanderbilt Assessment Scales with two separate versions for parents and teachers to screen children with ADHD symptoms. RESULTS: Among the total of 525 pupils, 24 (4.6%) were found to have ADHD symptom types (boy: 6.5%; girl: 2.1%). The combined ADHD type accounted for the highest proportion of 3.4%, followed by predominantly inattentive and predominantly hyperactivity type. ADHD prevalence rated by teachers was higher than those rated by parents. High agreement between parents and teachers was reported (κ > 0.6). The risk of ADHD increased in male participants (aOR=4.90, 95% CI 1.51-15.85), those having a first-degree relative with ADHD (aOR=85.2, 95% CI 1.66-4371.8), in-utero exposure to tobacco smoke (aOR=4.78, 95% CI 1.31-17.44), and prenatal alcohol drinking (aOR=8.87, 95% CI 2.29-34.42). CONCLUSION: These findings suggest the importance of ADHD screening for pupils attending elementary schools, particularly those with a family history of ADHD. Public health programs should reduce prenatal exposure to the potential risk factors of ADHD (smoking and alcohol consumption).

Measurement of Health-Related Quality of Life Among Colorectal Cancer Patients Using the Vietnamese Value Set of the EQ-5D-5L.

PURPOSE: Health-related quality of life (HRQoL) is an important construct in clinical settings, and it is crucial that it should be properly measured. As the EuroQol-5-dimensions-5 levels (EQ-5D-5L) is more effective for such measurement than the 3-level model, data on economic models, clinical studies, and public health evaluations previously collected through the EQ-5D-3L need to be revaluated using the EQ-5D-5L. This study evaluated colorectal cancer (CRC) patients' HRQoL scores using the Vietnamese EQ-5D-5L value set. PATIENTS AND METHODS: The cross-sectional study included CRC patients treated at a tertiary public hospital. HRQoL was assessed using the EQ-5D-5L, and HRQoL utility scores were calculated using the Vietnamese value set. Tobit regression examined factors associated with HRQoL. RESULTS: The analysis included 197 CRC patients. Ages ranged from 20 to 87 years (M = 57.64, SD = 13.5); 42.2% and 57.8% were diagnosed with cancer of the colon or rectum/anus, respectively. Mean EQ-5D-5L was 0.561 (range, -0.5115 to 1). Most participants experienced anxiety/depression (88%), followed by pain/discomfort (87%), mobility (71%), usual activity (69%), and self-care (67%). Advanced CRC stage (stage II: ß -0.303, se 0.08; stage III: ß -0.305, se 0.07; stage IV: ß -0.456, se 0.07) and surgery (ß -0.113, se 0.05) were negatively associated with EQ-5D-5L scores. Advanced education (high school: ß 0.273, se 0.07); college/vocational: ß 0.134se 0.05; university/higher: Coef 0.213, se 0.08;) and older age (age group 35-44: ß 0.253, se 0.10; 45-54: ß 0.327, se 0.09; 55-64: ß 0.355 se 0.09; 65+ ß 0.204, se 0.09) were positively associated with EQ-5D-5L scores. CONCLUSION: Patients in advanced CRC stages or undergoing surgery experienced lower HRQoL and higher prevalence of anxiety/depression and pain/discomfort. Older age and high educational attainment predicted high HRQoL. This study provides information on CRC patients' health utility based on various patient characteristics, which can be used in future economic evaluations.

The Direct and Indirect Costs of Colorectal Cancer in Vietnam: An Economic Analysis from a Social Perspective.

The incidence and mortality of colorectal cancer (CRC) has increased rapidly in Vietnam, but the economic burden of this disease has never been estimated. We estimate the direct and indirect cost of CRC patients in Vietnam in 2018 using a prevalence-based approach and human capital method. The total economic cost of CRC was VND 3041.88 billion (~$132.9 million), representing 0.055% of the 2018 gross domestic product. Notably, indirect costs comprised 83.58 % of the total cost, 82.61% of which is future income loss, because CRC occurs during productive years. The economic burden of CRC in Vietnam is substantial. The medical cost for CRC diagnosis and treatment is higher for younger patients and for those in advanced stages. Strategies to decrease the economic burden of CRC at the patient and national level, such as screening programs, should be developed and implemented in Vietnam.

Trends in prediabetes and diabetes prevalence and associated risk factors in Vietnamese adults.

OBJECTIVES: The prevalence of diabetes mellitus is rapidly increasing in Vietnam, particularly among adults aged over 45 years. This study estimated trends in diabetes and prediabetes prevalence and determined risk factors in Vietnamese adults (over 45 years). METHODS: A cross-sectional study was conducted based on data from an annual diabetes screening program among people aged 45-69 years in an urban city in central Vietnam (Da Nang). Joinpoint regression analyses were performed to calculate the annual percentage change and ptrend-values. Multinomial logistic regression analysis was used to determine risk factors. RESULTS: In total, 3,765 men and 9,149 women were included in this analysis. The age-adjusted prevalence of diabetes and prediabetes in 2017 was 11.4% and 52.9%, respectively. The prevalence of diabetes was higher in men (15.1%) than in women (10.3%), but that of prediabetes was similar in both genders (53.4% vs. 52.8%). The prevalence of prediabetes significantly increased during the study period, whereas no upward or downward trend for diabetes was observed. The prevalence of obesity, abdominal obesity, hypertension, and dyslipidemia showed no obvious trend. Obesity, a high waist-to-hip ratio, hypertension, more severe abdominal obesity, and dyslipidemia were significantly associated with a higher risk of diabetes and prediabetes. CONCLUSIONS: Diabetes and prediabetes were more prevalent among people aged over 45 years than in the general population. Da Nang has experienced a marked increase in the prevalence of prediabetes. These findings have significant implications regarding the need for nationwide public health interventions and management aiming at diabetes prevention and control.

Glomerular Collagen Deposition and Lipocalin-2 Expression Are Early Signs of Renal Injury in Prediabetic Obese Rats.

Feeding rats with high-fat diet (HFD) with a single streptozotocin (STZ) injection induced obesity, slightly elevated fasting blood glucose and impaired glucose and insulin tolerance, and caused cardiac hypertrophy and mild diastolic dysfunction as published before by Koncsos et al. in 2016. Here we aimed to explore the renal consequences in the same groups of rats. Male Long-Evans rats were fed normal chow (CON; n = 9) or HFD containing 40% lard and were administered STZ at 20 mg/kg (i.p.) at week four (prediabetic rats, PRED, n = 9). At week 21 blood and urine samples were taken and kidney and liver samples were collected for histology, immunohistochemistry and for analysis of gene expression. HFD and STZ increased body weight and visceral adiposity and plasma leptin concentration. Despite hyperleptinemia, plasma C-reactive protein concentration decreased in PRED rats. Immunohistochemistry revealed elevated collagen IV protein expression in the glomeruli, and Lcn2 mRNA expression increased, while Il-1ß mRNA expression decreased in both the renal cortex and medulla in PRED vs. CON rats. Kidney histology, urinary protein excretion, plasma creatinine, glomerular Feret diameter, desmin protein expression, and cortical and medullary mRNA expression of TGF-ß1, Nrf2, and PPARγ were similar in CON and PRED rats. Reduced AMPKα phosphorylation of the autophagy regulator Akt was the first sign of liver damage, while plasma lipid and liver enzyme concentrations were similar. In conclusion, glomerular collagen deposition and increased lipocalin-2 expression were the early signs of kidney injury, while most biomarkers of inflammation, oxidative stress and fibrosis were negative in the kidneys of obese, prediabetic rats with mild heart and liver injury.

Hsp90 Stabilizes SIRT1 Orthologs in Mammalian Cells and C. elegans.

Sirtuin 1 (SIRT1) othologs are ubiquitous NAD⁺-dependent deacetylases that act as nutrient sensors and modulate metabolism and stress responses in diverse organisms. Both mammalian SIRT1 and Caenorhabditis elegans SIR-2.1 have been implicated in dietary restriction, longevity, and healthspan. Hsp90 is an evolutionarily conserved molecular chaperone that stabilizes a plethora of signaling 'client' proteins and regulates fundamental biological processes. Here we report that Hsp90 is required for conformational stabilization of SIRT1 and SIR-2.1. We find that inhibition of Hsp90 by geldanamycin (GA) induces the depletion of mammalian SIRT1 protein in a concentration and time dependent manner in COS-7 and HepG2 cells. In contrast to SIRT1, SIRT2 level remains unchanged by GA treatment, reflecting a specific Hsp90 SIRT1 interaction. Hsp90 inhibition leads to the destabilization and proteasomal degradation of SIRT1. Moreover, we observe a GA-sensitive physical interaction between SIRT1 and Hsp90 by immunoprecipitation. We also demonstrate that hsp-90 gene silencing also induces SIR-2.1 protein depletion and proteasomal degradation in C. elegans. Our findings identify metazoan SIRT1 orthologs as Hsp90 clients and reveal a novel crosstalk between the proteostasis and nutrient signaling networks, which may have implications in various age related diseases.

RNA interference links oxidative stress to the inhibition of heat stress adaptation.

UNLABELLED: Increased oxidative stress is associated with various diseases and aging, while adaptation to heat stress is an important determinant of survival and contributes to longevity. However, the impact of oxidative stress on heat resistance remains largely unclear. AIM: In this study we investigated how oxidative stress impinges on heat stress responses. RESULTS: We report that hydrogen-peroxide (H(2)O(2)) pretreatment inhibits both acquired thermotolerance and heat-induced Hsp70 expression in mammalian cells, as well as acquired thermotolerance in the nematode Caenorhabditis elegans, via RNA interference. Moreover, we demonstrate that elimination of RNA interference by silencing key enzymes in microRNA biogenesis, dcr-1 or pash-1, restores the diminished intrinsic thermotolerance of aged and H(2)O(2)-elimination compromised (catalase-2 and peroxiredoxin-2 deficient) worms. INNOVATION AND CONCLUSION: These results uncover a novel post-transcriptional element in the regulation of heat stress adaptation under oxidative conditions that may have implications in disease susceptibility and aging.

The heat shock connection of metabolic stress and dietary restriction.

Molecular chaperones and the heat shock response guard and modulate protein conformation, protect proteins from misfolding and aggregation, and maintain signalling and organellar networks. Overnutrition and the metabolic syndrome represent a pro-aging condition, and dietary restriction is the most robust environmental intervention that induces longevity from yeast to mammals. In recent years a considerable effort has been made to elucidate the signaling pathways involved in metabolic signaling. Here we review the current understanding on the connection between metabolic stress, dietary restriction and the heat shock response and highlight results showing chaperone induction as a promising therapeutic strategy to promote healthy aging and to prevent metabolic disorders.