Obesity is one of the most important public health issues worldwide. Moreover, an extreme phenotype, morbid obesity (MO) has insidiously become a global problem. Therefore, we aimed to document the ...prevalence trend and to unveil the epidemiological characteristics of MO in Taiwan.
Nationally representative samples aged 19 years and above from three consecutive waves of Nutrition and Health survey in Taiwan: 1993-1996, 2005-2008, and 2013-2014 (n = 3,071; 1,673; and 1,440; respectively) were analyzed for prevalence trend. And 39 MO (BMI ≥35 kg/m2) cases from the two recent surveys compared with 156 age, gender, and survey-matched normal weight controls (BMI: 18.5-24 kg/m2) for epidemiological characteristics study. The reduced rank regression analysis was used to find dietary pattern associated with MO.
The prevalence of overweight and obesity together (BMI ≥24 kg/m2) was stabilized in the recent two surveys, but that of MO (0.4%, 0.6%, to 1.4%) and obesity (BMI ≥27 kg/m2) (11.8%, 17.9%, to 22.0%) increased sharply. MO cases tended to have lower levels of education, personal income, and physical activity. Furthermore, their dietary pattern featured with a higher consumption frequency of red meat, processed animal products, and sweets/sweetened beverage, but lower frequencies of fresh fruits, nuts, breakfast cereal, and dairy products.
This study documents a polarization phenomenon with smaller proportion of overweight people at the center and higher proportions of normal weight and obesity subjects at two extremes. MO was associated with low socioeconomic status and poor dietary pattern. The obesogenic dietary pattern became more prevalent in later time.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the associations of body mass index (BMI) with all-cause, cardiovascular disease (CVD), and expanded CVD mortality in the elderly.
Observational cohort study.
Annual physical examination ...program for the elderly from 2006 to 2010.
We included 77,541 Taipei residents aged ≥ 65 years (39,365 men and 38,176 women).
BMI was categorized as underweight (BMI<18.5), normal weight (18.5 ≤ BMI<25), overweight (25 ≤ BMI<30), grade 1 obesity (30 ≤ BMI<35), or grade 2-3 obesity (BMI ≥ 35). Mortality was ascertained by national death files.
Underweight (hazard ratios HRs of all-cause, CVD, and expanded CVD mortality: 1.92, 1.74, and 1.77, respectively), grade 2-3 obesity (HRs: 1.59, 2.36, and 2.22, respectively), older age, male sex, smoking, and high fasting blood sugar were significant predictors of mortality. Meanwhile, being married/cohabitating, higher education, alcohol consumption, more regular exercise, and high total cholesterol were inversely associated with mortality. Multivariate stratified subgroup analyses verified smokers (HRs of all-cause, CVD, and expanded CVD mortality: 3.25, 10.71, and 7.86, respectively, for grade 2-3 obesity), the high triglyceride group (HRs: 5.82, 10.99, and 14.22, respectively for underweight), and patients with 3-4 factors related to metabolic syndrome (HRs: 4.86, 12.72, and 11.42, respectively, for underweight) were associated with mortality.
The associations of BMI with all-cause, CVD, expanded CVD mortality in the elderly are represented by U-shaped curves, suggesting unilateral promotions or interventions in weight reduction in the elderly may be inappropriate. Heterogeneous effects of grades 1 and 2-3 obesity on mortality were observed and should be treated as different levels of obesity.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The studies concerning clinical implications of TET2 mutation in patients with primary acute myeloid leukemia (AML) are scarce. We analyzed TET2 mutation in 486 adult patients with primary AML. TET2 ...mutation occurred in 13.2% of our patients and was closely associated with older age, higher white blood cell and blast counts, lower platelet numbers, normal karyotype, intermediate-risk cytogenetics, isolated trisomy 8, NPM1 mutation, and ASXL1 mutation but mutually exclusive with IDH mutation. TET2 mutation is an unfavorable prognostic factor in patients with intermediate-risk cytogenetics, and its negative impact was further enhanced when the mutation was combined with FLT3-ITD, NPM1-wild, or unfavorable genotypes (other than NPM1+/FLT3-ITD− or CEBPA+). A scoring system integrating TET2 mutation with FLT3-ITD, NPM1, and CEBPA mutations could well separate AML patients with intermediate-risk cytogenetics into 4 groups with different prognoses (P < .0001). Sequential analysis revealed that TET2 mutation detected at diagnosis was frequently lost at relapse; rarely, the mutation was acquired at relapse in those without TET2 mutation at diagnosis. In conclusion, TET2 mutation is associated with poor prognosis in AML patients with intermediate-risk cytogenetics, especially when it is combined with other adverse molecular markers. TET2 mutation appeared to be unstable during disease evolution.
The emergence of severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) variants has altered the trajectory of the COVID‐19 pandemic and raised some uncertainty on the long‐term efficiency of ...vaccine strategy. The development of new therapeutics against a wide range of SARS‐CoV‐2 variants is imperative. We, here, have designed an inhalable siRNA, C6G25S, which covers 99.8% of current SARS‐CoV‐2 variants and is capable of inhibiting dominant strains, including Alpha, Delta, Gamma, and Epsilon, at picomolar ranges of IC50 in vitro. Moreover, C6G25S could completely inhibit the production of infectious virions in lungs by prophylactic treatment, and decrease 96.2% of virions by cotreatment in K18‐hACE2‐transgenic mice, accompanied by a significant prevention of virus‐associated extensive pulmonary alveolar damage, vascular thrombi, and immune cell infiltrations. Our data suggest that C6G25S provides an alternative and effective approach to combating the COVID‐19 pandemic.
Synopsis
C6G25S is a fully modified siRNA specifically targeting the highly‐conserve region of SARS‐CoV‐2 genome. It has been developed as an inhalable and broad‐spectrum therapeutic that is highly stable and effective via direct respiratory administration.
A broadly active siRNA covers 99.8% of SARS‐CoV‐2 variants, including highly infective Delta and Omicron.
C6G25S completely inhibited the Delta variant in lungs of infected mice by prophylactic treatment and decreased 93% of virions by co‐treatment.
First study that use fully modified siRNA for inhalation and achieved promising therapeutic effect without a special delivery system.
C6G25S is a safe, effective, and feasible therapeutic approach that could reach the market in a short time.
C6G25S is a fully modified siRNA specifically targeting the highly‐conserve region of SARS‐CoV‐2 genome. It has been developed as an inhalable and broad‐spectrum therapeutic that is highly stable and effective via direct respiratory administration.
Although hypertension is common among older adults, the optimal blood pressure (BP) for survival in older adults remains unclear. We attempt to use a large cohort to assess the relationship between ...BP and mortality and to gain insight into what level of BP is required for optimal survival in older adults.A total of 77,389 community-dwelling adults, aged ≥65 years, were followed between 2006 and 2010. Mortality was determined using matching cohort identifications with national death files. Cox proportional hazards regression models were used to evaluate the relationship of BP with all-cause, cardiovascular disease (CVD), and expanded-CVD mortalities.The mortality risks of the stage 2-3 hypertension group were substantial (all-cause mortality: hazard ratio HR: 1.23; 95% confidence interval CI: 1.10-1.37; CVDs mortality: HR: 1.31; 95% CI: 1.05-1.64; expanded-CVDs mortality: HR: 1.40; 95% CI: 1.15-1.71). The cardiovascular and expanded-cardiovascular mortality risks were lowest when systolic blood pressures were 120 to 129 mm Hg, and increased significantly when systolic blood pressures (SBPs) were ≥160 mm Hg or diastolic BPs were ≥90 mm Hg. A J-curve phenomenon for SBP on CVD and expanded-CVD mortality was observed. The impacts of stage 2-3 hypertension on mortality risks were significantly increased among women. The mortality risks of hypertension were not attenuated with older age.This study provides insight for identifying the optimal BP for survival in older adults, and extends the knowledge of the impacts of hypertension on mortality risks among women and the older adults.
Gastric cancer (GC) is the second most frequent cause of cancer-related deaths worldwide. MicroRNAs are single-stranded RNA molecules of 21-23 nucleotides that regulate target gene expression through ...specific base-pairing interactions between miRNA and untranslated regions of targeted mRNAs. In this study, we generated a multistep approach for the integrated analysis of miRNA and mRNA expression. First, both miRNA and mRNA expression profiling datasets in gastric cancer from the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) identified 79 and 1042 differentially expressed miRNAs and mRNAs, respectively, in gastric cancer. Second, inverse correlations between miRNA and mRNA expression levels identified 3206 miRNA-mRNA pairs combined with 79 dysregulated miRNAs and their 774 target mRNAs predicted by three prediction tools, miRanda, PITA, and RNAhybrid. Additionally, miR-204, which was found to be down-regulated in gastric cancer, was ectopically over-expressed in the AGS gastric cancer cell line and all down-regulated targets were identified by RNA sequencing (RNA-seq) analysis. Over-expression of miR-204 reduced the gastric cancer cell proliferation and suppressed the expression of three targets which were validated by qRT-PCR and luciferase assays. For the first time, we identified that
,
, and
are putative targets of miR-204 and elucidated that miR-204 acted as potential tumor suppressor and, therefore, are useful as a promising therapeutic target for gastric cancer.
Lockdown is an effective nonpharmaceutical intervention to reduce coronavirus disease 2019 (COVID-19) transmission, but it restricts daily activity. We aimed to investigate the impact of lockdown on ...pediatric body weight and body mass index (BMI).
The systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Four online databases (EMBASE, Medline, the Cochrane Library and CINAHL) were searched.
The pooled results showed that lockdown was associated with significant body weight gain (MD 2.67, 95% CI 2.12-3.23;
< 0.00001). The BMI of children with comorbidities or obesity did not change significantly. The BMI of general population was significantly higher during lockdown than before the pandemic (MD 0.94, 95% CI 0.32-1.56;
= 0.003). However, heterogeneity was high (I
= 84%). Among changes in weight classification, increases in the rates of obesity (OR 1.23, 95% CI 1.10-1.37;
= 0.0002) and overweight (OR 1.17, 95% CI 1.06-1.29;
= 0.001) were reported.
Our meta-analysis showed significant increases in body weight and BMI during lockdown among school-age children and adolescents. The prevalence of obesity and overweight also increased. The COVID-19 pandemic worsened the burden of childhood obesity.
Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the ...anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A major challenge to end the pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is to develop a broadly protective vaccine that elicits long-term immunity. As the key ...immunogen, the viral surface spike (S) protein is frequently mutated, and conserved epitopes are shielded by glycans. Here, we revealed that S protein glycosylation has site-differential effects on viral infectivity. We found that S protein generated by lung epithelial cells has glycoforms associated with increased infectivity. Compared to the fully glycosylated S protein, immunization of S protein with N-glycans trimmed to the mono-GlcNAc-decorated state (S
) elicited stronger immune responses and better protection for human angiotensin-converting enzyme 2 (hACE2) transgenic mice against variants of concern (VOCs). In addition, a broadly neutralizing monoclonal antibody was identified from S
-immunized mice that could neutralize wild-type SARS-CoV-2 and VOCs with subpicomolar potency. Together, these results demonstrate that removal of glycan shields to better expose the conserved sequences has the potential to be an effective and simple approach for developing a broadly protective SARS-CoV-2 vaccine.
We demonstrate directed translocation of ClO4− anions from cationic to neutral binding site along the synthetized BPym‐OH dye molecule that exhibits coupled excited‐state intramolecular ...proton‐transfer (ESIPT) and charge‐transfer (CT) reaction (PCCT). The results of steady‐state and time‐resolved spectroscopy together with computer simulation and modeling show that in low polar toluene the excited‐state redistribution of electronic charge enhanced by ESIPT generates the driving force, which is much stronger than by CT reaction itself and provides more informative gigantic shifts of fluorescence spectra signaling on ultrafast ion motion. The associated with ion translocation red‐shifted fluorescence band (at 750 nm, extending to near‐IR region) appears at the time ~83 ps as a result of electrochromic modulation of PCCT reaction. It occurs at substantial delay to PCCT that displayed fluorescence band at 640 nm and risetime of <200 fs. Thus, it becomes possible to visualize the manifestations of light‐triggered ion translocation and of its driving force by fluorescence techniques and to separate them in time and energy domains.
The light‐triggered translocation of ClO4− anion from cationic to neutral‐binding site along BPym‐OH dye is visualized by emission. The combination of time‐resolved fluorescence and molecular dynamic simulation allows its description in time and energy domains. This reaction generates dramatically red‐shifted fluorescence extending to near‐IR that appears at ~83 ps, resulting from electrochromic modulation of coupled proton‐electron transfer.
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