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One key approach for anticancer therapy is drug combination. Drug combinations can help reduce doses and thereby decrease side effects. Furthermore, the likelihood of drug resistance is reduced. Distinct alterations in tumor metabolism have been described in past decades, but metabolism has yet to be targeted in clinical cancer therapy. Recently, we found evidence for synergism between dichloroacetate (DCA), a pyruvate dehydrogenase kinase inhibitor, and the HIF-1α inhibitor PX-478. In this study, we aimed to analyse this synergism in cell lines of different cancer types and to identify the underlying biochemical mechanisms.
The dose-dependent antiproliferative effects of the single drugs and their combination were assessed using SRB assays. FACS, Western blot and HPLC analyses were performed to investigate changes in reactive oxygen species levels, apoptosis and the cell cycle. Additionally, real-time metabolic analyses (Seahorse) were performed with DCA-treated MCF-7 cells.
The combination of DCA and PX-478 produced synergistic effects in all eight cancer cell lines tested, including colorectal, lung, breast, cervical, liver and brain cancer. Reactive oxygen species generation and apoptosis played important roles in this synergism. Furthermore, cell proliferation was inhibited by the combination treatment.
Here, we found that these tumor metabolism-targeting compounds exhibited a potent synergism across all tested cancer cell lines. Thus, we highly recommend the combination of these two compounds for progression to in vivo translational and clinical trials.
Here, we found that these tumor metabolism-targeting compounds exhibited a potent synergism across all tested cancer cell lines. Thus, we highly recommend the combination of these two compounds for progression to in vivo translational and clinical trials.
Informal caregivers of persons with dementia often experience elevated levels of caregiving burden. However, existing studies tend to use a variable-centered approach to explore it. This study aims to understand the caregiving burden of informal caregivers of persons with dementia in Singapore through a combination of variable-centered and person-centered analytical approaches, and explore the correlates of identified factors and latent classes of caregiving burden.
Zarit Burden Interview was used to gauge the caregiving burden of 282 primary informal caregivers of persons with dementia recruited through convenience sampling in Singapore. Factor analysis and latent class analysis were conducted to identify the latent factors and the latent classes of Zarit Burden Interview, followed by multiple linear regression and multinomial logistic regression to explore their significant correlates.
The analyses suggested a 17-item 3-factor structure for Zarit burden interview and three mutually exclusive caregivin generalizability of our findings among caregivers elsewhere and explore the type of support needed by caregivers, especially those experiencing high burden.
Cultivated tea is one of the most important economic and ecological trees distributed worldwide. Cultivated tea suffer from long-term targeted selection of traits and overexploitation of habitats by human beings, which may have changed its genetic structure. The chloroplast is an organelle with a conserved cyclic genomic structure, and it can help us better understand the evolutionary relationship of Camellia plants.
We conducted comparative and evolutionary analyses on cultivated tea and wild tea, and we detected the evolutionary characteristics of cultivated tea. The chloroplast genome sizes of cultivated tea were slightly different, ranging from 157,025 to 157,100bp. In addition, the cultivated species were more conserved than the wild species, in terms of the genome length, gene number, gene arrangement and GC content. However, comparing Camellia sinensis var. sinensis and Camellia sinensis var. assamica with their cultivars, the IR length variation was approximately 20bp and 30bp, respectively. The nea was mainly manifested in the nucleotide polymorphisms and sequence insertions. These results provided evidence regarding the influence of human activities on tea.
The cultivated species were more conserved than the wild species in terms of architecture and linear sequence order. The variation of the chloroplast genome in cultivated tea was mainly manifested in the nucleotide polymorphisms and sequence insertions. These results provided evidence regarding the influence of human activities on tea.
Healthcare-associated infections (HAIs) represent a major Public Health issue. Hospital-based prevalence studies are a common tool of HAI surveillance, but data quality problems and non-representativeness can undermine their reliability.
This study proposes three algorithms that, given a convenience sample and variables relevant for the outcome of the study, select a subsample with specific distributional characteristics, boosting either representativeness (Probability and Distance procedures) or risk factors' balance (Uniformity procedure). A "Quality Score" (QS) was also developed to grade sampled units according to data completeness and reliability. The methodologies were evaluated through bootstrapping on a convenience sample of 135 hospitals collected during the 2016 Italian Point Prevalence Survey (PPS) on HAIs.
The QS highlighted wide variations in data quality among hospitals (median QS 52.9 points, range 7.98-628, lower meaning better quality), with most problems ascribable to ward and hospitale collection.
Ubiquitin-conjugating enzyme E2W (UBE2W) is a protein-coding gene that has an important role in ubiquitination and may be vital in the repair of DNA damage. However, studies on the prognostic value of UBE2W and its correlation with tumor-infiltrating immune cells in multiple cancers have not been addressed.
We investigated UBE2W expression in the Oncomine database, the Tumor Immune Estimation Resource (TIMER), TNMplot database. Then, the clinical prognostic value of UBE2W was analyzed via online public databases. Meanwhile, we explored the correlation between UBE2W and DNA repair associate genes expression and DNA methyltransferase expression by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). By using the same method, the correlation between UBE2W and tumor-infiltrating immune cells was explored. Genomic Profiles of UBE2W in breast cancer (BRCA) were accessed in cBioPortal (v3.5.0). Functional proteins associated network was analyzed by STRING database (v11.0).
UBE2W was abnormally expressed and significantly correlated with mismatch repair (MMR) gene mutation levels, DNA methyltransferase, and BRCA1/2 expression in breast cancer. High expression of UBE2W may promote the tumor immunosuppression and metastasis, induce endocrine therapy resistance and deteriorate outcomes of patients with breast cancer. These findings suggest that UBE2W could be a potential biomarker of prognosis and tumor-infiltrating immune cells. Besides, RBX1 may be a new E3 that was regulated by UBE2W.
Ubiquitin E2 UBE2W is a potential prognostic biomarker and is correlated with immune infiltration in BRCA.
Ubiquitin E2 UBE2W is a potential prognostic biomarker and is correlated with immune infiltration in BRCA.
Evidence was previously provided for sex-related differences in the human gut microbiota composition, and sex-specific discrepancy in hormonal profiles was proposed as a main determinant of these differences. On the basis of these findings, the assumption was made on the role of microbiota in the sexual dimorphism of human diseases. To date, sex differences in fecal microbiota were demonstrated primarily at lower taxonomic levels, whereas phylum-level differences between sexes were reported in few studies only. In the present population-based cross-sectional research, sex differences in the phylum-level human gut microbiota composition were identified in a large (total n = 2301) sample of relatively healthy individuals from Ukraine.
Relative abundances of Firmicutes and Actinobacteria, as determined by qRT-PCR, were found to be significantly increased, while that of Bacteroidetes was significantly decreased in females compared to males. The Firmicutes to Bacteroidetes (F/B) ratio was significantly increasnvestigation is needed to draw strong conclusions regarding the mechanistic basis for sex-specific differences in the gut microbiota composition and regarding the role of these differences in the initiation and progression of human chronic diseases.
Self-sampling for human papillomavirus (HPV) testing is a feasible option to improve the cervical screening coverage. However, an ideal triage method for HPV-positive self-samples does not yet exist. The aim of this study was to explore the utility of HPV genotyping and p16
immunostaining (p16) in triaging HPV-positive self-samples, focusing on HPV-positive, cytology-negative (HPCN) women.
A total of 73,699 women were screened in a cervical screening project in China via SeqHPV assay on self-samples. HPV-positive women were called-back and collected cervical sample for p16 immunostaining and liquid-based cytology, those who met any result of HPV16/18+ or visual inspection with acetic acid (VIA) + or p16+ were referred for colposcopy, and HPCN women with adequate data on p16 and pathology were analyzed. A triage strategy was considered acceptable if the negative predictive value (NPV) for cervical intraepithelial neoplasia 3 or worse (CIN3+) was 98% or more, combined with an improvement of sensitivity anective than HPV genotypes alone in the triage of HPCN women.
Genotyping for HPV16/33 could be utilized to optimize the management of HPCN women. Moreover, p16 immunostaining, either alone or combined with extended genotypes, is more effective than HPV genotypes alone in the triage of HPCN women.
In adult patients with pulmonary arterial hypertension (PAH), right ventricular (RV) failure may worsen rapidly, resulting in a poor prognosis. In this population, non-invasive assessment of RV function is challenging. RV stroke work index (RVSWI) measured by right heart catheterization (RHC) represents a promising index for RV function. The aim of the present study was to comprehensively evaluate non-invasive measures to calculate RVSWI derived by echocardiography (RVSWI
) using RHC (RVSWI
) as a reference in adult PAH patients.
Retrospectively, 54 consecutive treatment naïve patients with PAH (65 ± 13years, 36 women) were analyzed. Echocardiography and RHC were performed within a median of 1day [IQR 0-1days]. RVSWI
was calculated as (mean pulmonary arterial pressure (mPAP)-mean right atrial pressure (mRAP)) x stroke volume index (SVI)
. this website Four methods for RVSWI
were evaluated RVSWI
= Tricuspid regurgitant maximum pressure gradient (TR
) x SVI
, RVSWI
= (TR
-mRAP
) x SVI
, RVSWI
= TR meang*mL*m
, RVSWI
42 ± 286 (5 ± 25%) mmHg*mL*m
and for RVSWI
214 ± 273 (23 ± 27%) mmHg*mL*m
.
The correlation with RVSWI
was moderate to strong for all echocardiographic measures, whereas only RVSWI
displayed high concordance of absolute values. The results, however, suggest that RVSWI
or RVSWI
could be the preferable echocardiographic methods. Prospective studies are warranted to evaluate the clinical utility of such measures in relation to treatment response, risk stratification and prognosis in patients with PAH.
The correlation with RVSWIRHC was moderate to strong for all echocardiographic measures, whereas only RVSWIECHO-3 displayed high concordance of absolute values. The results, however, suggest that RVSWIECHO-1 or RVSWIECHO-3 could be the preferable echocardiographic methods. Prospective studies are warranted to evaluate the clinical utility of such measures in relation to treatment response, risk stratification and prognosis in patients with PAH.
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