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1.
Mol Ther ; 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429082

RESUMO

It is reported that microRNAs (miRNAs) play an important role in various human diseases. However, the mechanisms of miRNA in these diseases have not been fully understood. Therefore, detecting potential miRNA-disease associations has far-reaching significance for pathological development and the diagnosis and treatment of complex diseases. In this study, we propose a novel diffusion-based computational method DF-MDA for predicting miRNA-disease association based on the assumption that molecules are related to each other in human physiological processes. Specifically, we first construct a heterogeneous network by integrating various known associations among miRNAs, diseases, proteins, lncRNAs and drugs. Then, more representative features are extracted through a diffusion-based machine learning method. Finally, the Random Forest classifier is adopted to classify miRNA-disease associations. In the five-fold cross validation experiment, the proposed model obtained the average AUC of 0.9321 on the HMDD v3.0 dataset. To further verify the prediction performance of the proposed model, DF-MDA was applied in three significant human diseases, including Lymphoma, Lung Neoplasms and Colon Neoplasms. As a result, 47, 46 and 47 out of top 50 predictions were validated by independent databases. These experimental results demonstrated that DF-MDA is a reliable and efficient method for predicting potential miRNA-disease associations.

2.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430045

RESUMO

Plant-based nutritional supplementation has been shown to attenuate and reduce mortality in the processes of both acute and chronic disorders, including diabetes, obesity, cardiovascular disease, cancer, inflammatory diseases, and neurological and neurodegenerative disorders. Low-level systemic inflammation is an important contributor to these afflictions and diets enriched in phytochemicals can slow the progression. The goal of this study was to determine the impact of lipopolysaccharide (LPS)-induced inflammation on changes in glucose and insulin tolerance, performance enhancement, levels of urinary neopterin and concentrations of neurotransmitters in the striatum in mouse models. Both acute and chronic injections of LPS (2 mg/kg or 0.33 mg/kg/day, respectively) reduced glucose and insulin tolerance and elevated neopterin levels, which are indicative of systemic inflammatory responses. In addition, there were significant decreases in striatal neurotransmitter levels (dopamine and DOPAC), while serotonin (5-HT) levels were essentially unchanged. LPS resulted in impaired execution in the incremental loading test, which was reversed in mice on a supplemental plant-based diet, improving their immune function and maintaining skeletal muscle mitochondrial activity. In conclusion, plant-based nutritional supplementation attenuated the metabolic changes elicited by LPS injections, causing systemic inflammatory activity that contributed to both systemic and neurological alterations.

3.
BMC Musculoskelet Disord ; 22(1): 60, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33430847

RESUMO

BACKGROUND: Displaced patellar fractures are commonly treated with open reduction and fixation with several different types of tension-band (TB) constructs. The main objective of this study was to compare the prevalence of postoperative complications after surgical stabilization of comminuted patellar fractures with either a modified Kirschner-wire tension band (MKTB), a cannulated-screw tension band (CSTB), or a ring-pin tension band (RPTB). METHODS: We conducted a retrospective and consecutive cohort study of comminuted patellar fractures (n = 334) stabilized using a TB construct. Postoperative premature loss of reduction, infection, and skin breakdown were compared according to the type of TB constructs received (MKTB, CSTB, or RPTB). The rate of implant removal due to symptomatic hardware was also evaluated. RESULTS: Fixation failure rate was significantly different among the groups (P = 0.013), with failure rates of 4.7% observed in the MKTB group,14.5% in the CSTB group, and 4.9% in the RPTB group. Skin breakdown and infection were not significantly different among the groups (Ps > 0.05). Due to symptomatic hardware, 40.5% of the patients in the MKTB group, 22.9% in the CSTB group, and 24.3% in the RPTB group underwent implant removal (P = 0.004). After adjusting for age, gender, comorbidities, number of supplementary screws/K-wires, and use of cerclage cables, multivariate regression analysis revealed that CSTB contributed to a 2.08-times greater risk of fixation failure compared to RPTB, while MKTB and RPTB were similar in risk of failure. In addition, it was found that patients who underwent MKTB fixation were more than twice as likely to undergo implant removal for symptomatic hardware compared with RPTB (odds ratio = 2.11, 95% CI = 1.20 to 3.72; P = 0.010). CONCLUSIONS: RPTB have advantage over MKTB and CSTB fixation in terms of symptomatic hardware and premature failure, respectively. LEVEL OF EVIDENCE: Therapeutic Level III.

4.
Mol Med Rep ; 23(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33398370

RESUMO

MicroRNAs (miRs) exhibit oncogenic or tumor suppressive functions that contribute to the initiation and development of various types of human cancer. miR­149­3p has been reported to serve multiple roles in the regulation of proliferation, apoptosis and metastasis. However, the effects and detailed mechanism of miR­149­3p in oral squamous cell carcinoma (OSCC) remain unclear. In the present study, miR­149­3p mimic, mimic control, miR­149­3p inhibitor and inhibitor control were transiently transfected into Cal27 and SCC­9 cells. The viability, proliferation and apoptosis of OSCC cells were determined using Cell Counting Kit­8, colony formation and Annexin V assays, respectively. The mRNA expression levels of miR­149­3p and AKT2 were determined by reverse transcription­quantitative PCR. The protein expression levels of AKT2, cleaved caspase­3 and cleaved PARP were examined by western blot analysis. The binding of miR­149­3p to the AKT2 3'­untranslated region was evaluated by a dual luciferase reporter assay. In the present study, overexpression of miR­149­3p reduced the viability and proliferation of OSCC cells. By contrast, increased cell viability and proliferation was observed in miR­149­3p­deficient OSCC cells. Dual luciferase reporter assay indicated that miR­149­3p significantly decreased the luciferase activity of the wild­type AKT2 3'­untranslated region. Moreover, overexpression of miR­149­3p downregulated the mRNA and protein expression levels of AKT2, suggesting that miR­149­3p was a negative modulator of AKT2. Restoration of AKT2 efficiently reversed the miR­149­3p­mediated reduction in the proliferative capacity of OSCC cells. In addition, miR­149­3p enhanced the sensitivity of OSCC cells to the chemotherapeutic drug 5­fluorouracil. Taken together, the current findings revealed an inhibitory effect of miR­149­3p on the proliferation of OSCC cells through the post­transcriptional suppression of AKT2, and indicated a potential chemosensitizing function of miR­149­3p for the treatment of patients with OSCC.

6.
Oral Oncol ; 112: 105029, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33142225

RESUMO

INTRODUCTION: Primary radiotherapy (RT) and transoral surgery (TOS) are effective local therapy treatments for oropharyngeal squamous cell carcinoma (OPSCC), but their cost profiles differ. We compared the one-year costs of these competing treatments using a large claims-based database. METHODS: Eligible individuals were patients in the SEER-Medicare registry diagnosed with OPSCC between 2000 and 2011. Patients were categorized as receiving either primary RT +/- chemotherapy, or TOS +/- adjuvant RT or chemoradiotherapy (CRT), and all treatment costs from 1 month prior to diagnosis to 1 year after diagnosis were calculated. Univariable and multivariable linear regression models were used to determine predictors of payer expenditure. Patient-borne pharmacy costs were also analyzed. RESULTS: The cohort included 3497 patients (73% RT, 27% TOS), of whom 73% were locally advanced. The mean total 13 month costs for RT alone, CRT, TOS alone, TOS + RT and TOS + CRT were $39,083, $63,537, $25,468, $36,592, and $99,919, respectively, for early-stage patients. For locally advanced individuals, the mean costs were $45,049, $68,099, $40,626, $53,729, and $71,397, respectively. On multivariable analysis, the adjusted increase in total costs versus RT alone were $21,844, -$5431, $7984, and $28,581 for CRT, TOS alone, TOS + RT, and TOS + CRT, respectively. The difference between CRT and TOS + RT became non-significant for TOS patients undergoing transoral surgery plus neck dissection. Cisplatin was associated with significant less cost than cetuximab and taxane-based chemotherapy. CONCLUSION: In this population of elderly patients, transoral surgery was generally associated with less expensive treatment, with the addition of chemotherapy serving as the main driver of increased cost.

7.
Reprod Biomed Online ; 42(1): 237-247, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33168492

RESUMO

Studies suggest that the presence of endometriosis may lead to impaired ovarian reserve, while results evaluating the changes in antral follicle count (AFC) in endometriosis remain controversial. A systematic search returned 15 studies, of which nine compared AFC between patients with and without endometriosis, five articles reported differences in AFC between affected and unaffected ovaries in patients with unilateral ovarian endometriosis and one reported both of the above two situations. Overall results showed a significant decrease in AFC and anti-Müllerian hormone (AMH) and increase in serum FSH concentrations in patients with endometriosis when compared with controls. Additionally, the AFC for the ovary with the endometrioma was also significantly lower than that of the contralateral ovary in patients with unilateral ovarian endometriosis. Moreover, it appears that the AFC in patients with endometriosis where the ovaries are not affected or in early stage were not significantly different in the control group. These findings demonstrate that endometriosis is associated with reduced AFC and AMH and elevated serum concentrations of FSH, suggesting a reduction in ovarian reserve in patients with endometriosis, especially in those with ovarian endometrioma and advanced stage.

8.
Fitoterapia ; 148: 104793, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33276011

RESUMO

Phytochemical investigation on the nonpolar extracts of P. acidus leaves afforded three new cleistanthane diterpenoids, named phyllanacidins A-C (1-3), in addition to three known ones (4-6). Among them, compounds 2 and 3 represent the first examples of 17-nor cleistanthane diterpenoids. Their structures including absolute configurations were elucidated on the basis of extensive spectroscopic data and single crystal X-ray diffraction analysis. All the isolated cleistanthane diterpenoids were evaluated for their cytotoxic activities against five human cancer cell lines. Compounds 4-6 exhibited moderate cytotoxicity with IC50 values ranging from 16.11 to 30.82 µM.

9.
Gastrointest Endosc ; 93(1): 154-162.e5, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32531402

RESUMO

BACKGROUND AND AIMS: Most patients with pancreatic cancer are diagnosed at a late stage and are not candidates for surgical resection. Many have jaundice requiring biliary drainage, which can be accomplished using ERCP or percutaneous transhepatic biliary drainage (PTBD). To date, no studies have evaluated the impact of ERCP or PTBD on survival among patients with unresectable pancreatic cancer. The aims of our study were to compare overall survival between patients with unresectable pancreatic cancer receiving ERCP with those receiving PTBD, to compare overall survival between patients who received a biliary intervention (ERCP or PTBD) versus those who received no biliary intervention, and to compare secondary outcomes, such as length of hospital stay and costs, between ERCP and PTBD. METHODS: We conducted a retrospective cohort study using the Surveillance, Epidemiology, and End Results-Medicare database. Patients with known pancreatic cancer were included if they had a pancreatic head mass and/or evidence of biliary obstruction. We used a time-varying Cox proportional hazards model to estimate overall survival of patients receiving ERCP versus PTBD and overall survival among patients who received a biliary intervention versus no biliary drainage. Secondary outcomes included length of hospital stay, costs, and admissions within 30 days. RESULTS: Of 14,808 patients with unresectable pancreatic cancer, 8898 patients (60.0%) underwent biliary drainage and 5910 patients (39.9%) received no biliary intervention. ERCP accounted for most biliary interventions (8271, 93.0%), whereas 623 patients (7.0%) underwent PTBD. In multivariable analysis, ERCP was associated with reduced mortality compared with PTBD (adjusted hazard ratio [aHR], .67; 95% confidence interval [CI], .60-.75). When ERCP or PTBD was compared with no biliary intervention, both procedures were associated with a survival benefit (aHR, .51 [95% CI, .49-.54] and .53 [95% CI, .48-.59], respectively). Compared with patients receiving PTBD, those who underwent ERCP had shorter mean length of hospital stay (7.0 ± 5.7 days vs 9.6 ± 6.6 days, respectively; P < .001) and lower hospital charges ($54,899.25 vs $75,246.00, P < .001) but no significant difference in hospitalization or 30-day readmissions. CONCLUSIONS: ERCP is associated with reduced mortality compared with PTBD in pancreatic cancer patients, highlighting the critical role of ERCP in the management of biliary obstruction from pancreatic cancer.

10.
Front Oncol ; 10: 567160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33262942

RESUMO

Objectives: To investigate the development and validation of a radiomics nomogram based on PET/CT for guiding personalized targeted therapy in patients with lung adenocarcinoma mutation(s) in the EGFR gene. Methods: A cohort of 109 (77/32 in training/validation cohort) consecutive lung adenocarcinoma patients with an EGFR mutation was enrolled in this study. A total of 1672 radiomic features were extracted from PET and CT images, respectively. The least absolute shrinkage and selection operator (LASSO) Cox regression was used to select the radiomic features and construct the radiomics nomogram for the estimation of overall survival (OS), which was then assessed with respect to calibration and clinical usefulness. Patients with an EGFR mutation were divided into high- and low- risk groups according to their nomogram score. The treatment strategy for high- and low-risk groups was analyzed using Kaplan-Meier analysis and a log-rank test. Results: The C-index of the radiomics nomogram for the prediction of OS in lung adenocarcinoma in patients with an EGFR mutation was 0.840 and 0.803 in the training and validation cohorts, respectively. Distant metastasis [(Hazard ratio, HR),1.80], metabolic tumor volume (MTV, HR, 1.62), and rad score (HR, 17.23) were the independent risk factors for patients with an EGFR mutation. The calibration curve showed that the predicted survival time was remarkably close to the actual time. Decision curve analysis demonstrated that the radiomics nomogram was clinically useful. Targeted therapy for patients with high-risk EGFR mutations attained a greater benefit than other therapies (p < 0.0001), whereas the prognoses of the two therapies were similar in the low-risk group (p = 0.85). Conclusions: Development and validation of a radiomics nomogram based on PET/CT radiomic features combined with clinicopathological factors may guide targeted therapy for patients with lung adenocarcinoma with EGFR mutations. This is conducive to the advancement of precision medicine.

11.
Gastroenterol Res Pract ; 2020: 6131485, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33299406

RESUMO

Aim: This study is aimed at investigating predictive and prognostic factors of synchronous colorectal lung-limited metastasis (SCLLM) based on The Surveillance, Epidemiology, and End Results (SEER) database. Methods: A multivariate logistic regression model was constructed to identify independent predictors of SCLLM. A multivariate Cox proportional hazards regression model was used to distinguish independent prognostic factors. Results: This study enrolled 168,007 colorectal cancer (CRC) patients without metastatic diseases and 1,298 cases with SCLLM. Eight features, involving race, tumor location, pathological grade, histological type, T stage, N stage, and tumor size as well as CEA, could be used as the independent predictors. As the nomogram shown, the T4 stage contributed the most to SCLLM, followed by the N2 stage, elevated CEA, and rectal cancer. A multivariate regression analysis discriminated 9 independent prognostic factors, including age, race, marital status, pathological grade, T stage, colectomy/proctectomy, chemotherapy, CEA, and TD. The prognostic nomogram illustrated that nonresection/NOS played as the poorest prognostic factor, followed by nonchemotherapy, ≥75-year old and T4 stage. The cumulative survival curves revealed the influence of each prognostic factor on survival after controlling the other variables. Conclusions: This study identified independent predictors and prognostic factors for SCLLM based on a large database of the United States. The predictors and prognostic factors can provide supporting evidence for the prevention and treatment of SCLLM.

12.
Front Oncol ; 10: 592996, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304850

RESUMO

Acute promyelocytic leukemia (APL) has become a highly curable disease after four decades of endeavors. Thanks to the efforts of investigators throughout the world, the chemo-free concept has become a reality for both low- and high-risk patients. All-trans retinoic acid (ATRA) plus arsenic trioxide (ATO) without chemotherapy has become a first-line treatment for newly diagnosed APL and has been adopted in guidelines or expert recommendations from the NCCN and ELN and in China. Though the regimen has achieved great success, challenges still exist. The rate of early death still has not diminished significantly and is a major obstacle to curing all patients. Leukocytosis is the most important factor for ED, and completely abandoning chemotherapy is dangerous for certain patients in practice. To narrow the gap between guidelines and practice, this review aims to examine the history of the chemo-free model for the treatment of APL in the arsenic-alone era (1974-2002) and the arsenic plus ATRA era (2002-present) and provide practical considerations regarding early death.

13.
Front Med (Lausanne) ; 7: 556818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304910

RESUMO

Background: Coronavirus disease (COVID-19) has swept around the globe and led to a worldwide catastrophe. Studies examining the disease progression of patients with non-severe disease on admission are scarce but of profound importance in the early identification of patients at a high risk of deterioration. Objectives: To elucidate the differences in clinical characteristics between patients with progressive and non-progressive COVID-19 and to determine the risk factors for disease progression. Study design: Clinical data of 365 patients with non-severe COVID-19 from 1 January 2020 to 18 March 2020 were retrospectively collected. Patients were stratified into progressive and non-progressive disease groups. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for disease progression. Results: Compared with patients with non-progressive disease, those who progressed to severe COVID-19 were older and had significantly decreased lymphocyte and eosinophil counts; increased neutrophil and platelet counts; lower albumin levels; higher levels of lactate dehydrogenase, C-reactive protein (CRP), creatinine, creatinine kinase, and urea nitrogen; and longer prothrombin times. Hypertension, fever, fatigue, anorexia, bacterial coinfection, bilateral patchy shadowing, antibiotic and corticosteroid administration, and oxygen support had a significantly higher incidence among patients with progressive disease. A significantly longer duration of hospital stay was also observed in patients with progressive disease. Bilateral patchy shadowing (OR = 4.82, 95% CI: 1.33-17.50; P = 0.017) and elevated levels of creatinine (OR =6.24, 95% CI: 1.42-27.40; P = 0.015), and CRP (OR = 7.28, 95% CI: 2.56-20.74; P < 0.001) were independent predictors for disease progression. Conclusion: The clinical characteristics of patients with progressive and non-progressive COVID-19 were significantly different. Bilateral patchy shadowing and increased levels of creatinine, and CRP were independent predictors of disease progression.

14.
Medicine (Baltimore) ; 99(49): e23385, 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33285724

RESUMO

BACKGROUND: Sepsis has become a global healthcare problem and continues to be one of the leading causes of death due to infection. In essence, early recognition and diagnosis of sepsis is needed to inhibit the transition into septic shock, which is correlated with higher mortality. Many studies have suggested antimicrobial de-escalation as one of the strategies to replace the empirical broad-spectrum antimicrobial treatment using a narrower antimicrobial therapy, especially among patients with sepsis. However, antimicrobial de-escalation therapeutic effects in sepsis remains unclear. We therefore performed the present study in an attempt to assess efficacy and safety of antimicrobial de-escalation therapy in patients with sepsis. METHODS: We will carry out a systematic literature search to establish the potentially eligible trials from electronic databases, including EMBASE (1980 to October 16, 2020), MEDLINE via PubMed (1966 to October 16, 2020), Web of Science (1965 to October 16, 2020), Cochrane Library (CENTRAL; 2020, Issue 10), WanFang databases (last searched October 16, 2020), and China National Knowledge Infrastructure (CNKI; last searched October 16, 2020). For this study, the language restrictions are English or Chinese. Two authors independently examined quality based on the Cochrane Risk of Bias Tool V.2.0 and extracted data. Data obtained from the study will be synthesised using applicable statistical methods. RESULTS: The results of the present study will systematically assess efficacy and safety of antimicrobial de-escalation therapy among patients with sepsis. CONCLUSION: The results of the present study will help to establish the efficacy and safety of antimicrobial de-escalation to treat patients with sepsis. It can also help to identify the most efficient and safe therapeutically-relevant method. ETHICS AND DISSEMINATION: The present study is a meta-analysis and the pooled results are based on published evidence. Therefore, ethics approval is not necessary. OSF REGISTRATION NUMBER: October 22, 2020.osf.io/93wym. (https://osf.io/93wym/).


Assuntos
Antibacterianos/uso terapêutico , Sepse/tratamento farmacológico , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Resistência Microbiana a Medicamentos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Sepse/mortalidade
15.
Nat Commun ; 11(1): 6364, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311474

RESUMO

RIPK1 is a death-domain (DD) containing kinase involved in regulating apoptosis, necroptosis and inflammation. RIPK1 activation is known to be regulated by its DD-mediated interaction and ubiquitination, though underlying mechanisms remain incompletely understood. Here we show that K627 in human RIPK1-DD and its equivalent K612 in murine RIPK1-DD is a key ubiquitination site that regulates the overall ubiquitination pattern of RIPK1 and its DD-mediated interactions with other DD-containing proteins. K627R/K612R mutation inhibits the activation of RIPK1 and blocks both apoptosis and necroptosis mediated by TNFR1 signaling. However, Ripk1K612R/K612R mutation sensitizes cells to necroptosis and caspase-1 activation in response to TLRs signaling. Ripk1K612R/K612R mice are viable, but develop age-dependent reduction of RIPK1 expression, spontaneous intestinal inflammation and splenomegaly, which can be rescued by antibiotic treatment and partially by Ripk3 deficiency. Furthermore, we show that the interaction of RIPK1 with FADD contributes to suppressing the activation of RIPK3 mediated by TLRs signaling. Our study demonstrates the distinct roles of K612 ubiquitination in mRIPK1/K627 ubiquitination in hRIPK1 in regulating its pro-death kinase activity in response to TNFα and pro-survival activity in response to TLRs signaling.


Assuntos
Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Receptores Tipo I de Fatores de Necrose Tumoral/genética , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Transdução de Sinais/fisiologia , Ubiquitinação , Animais , Apoptose , Células HEK293 , Humanos , Inflamação/metabolismo , Inflamação/patologia , Camundongos , Camundongos Knockout , Mutação , Necroptose/fisiologia , Fosforilação , Esplenomegalia/patologia , Transcriptoma , Fator de Necrose Tumoral alfa/metabolismo
16.
Leuk Res ; 100: 106480, 2020 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-33285315

RESUMO

Central nervous system (CNS) involvement in patients with acute myeloid leukemia (AML) varies, ranging from 0.6%-46%. Leukocyte immunoglobulin-like receptor B4 (LILRB4) has been shown to be critical in orchestration of infiltration of AML cells into the CNS in animal models, however it is unknown if an association exists between LILRB4 and CNS involvement (CNS+) in human patients with AML. LILRB4 was measured by flow cytometry in a heterogeneous population of fifty-six AML patients. Patients were then followed clinically for the development of CNS + . LILRB4 was positive in 91 % of patients with CNS + compared to 38 % without CNS involvement (p < 0.002). In logistic analysis: age, BMI, serum albumin and positive LILRB4 were predictive for CNS+ [OR, 95 % CI, p-value]: 0.95, 0.92-0.99, p < 0.01; 0.85, 0.73-0.998, p < 0.05; 0.23, 0.066-0.78, p < 0.02; 16.46, 1.93-140.2, p < 0.02, respectively. This finding of the association of LILRB4 with CNS + in combination with earlier findings suggests that LILRB4 has a mechanistic role in infiltration of the CNS and may provide insight into the pathogenesis of AML seeding the CNS. Moreover, this proof of concept and the findings in the present study may lead to the development of innovative and novel therapies to improve the lives of patients with AML.

17.
Asia Pac J Clin Nutr ; 29(4): 782-788, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33377372

RESUMO

BACKGROUND AND OBJECTIVES: Urinary iodine is an essential index of iodine nutrition evaluation. To establish the number of repeated spot urine collections necessary to reflect individual iodine status over 2 months and assess its feasibility to serve as an independent indicator of individual iodine status. METHODS AND STUDY DESIGN: We performed a longitudinal, 2-months study from May to June in 2015 of 23 apparently healthy Chinese women aged 18 to 44 (32±9) y. Spot urine samples were collected on any two days of the week, and 24-h urine samples were collected once every 6 days. RESULTS: 368 spot urine and 230 24-h urine samples were analysed. The median urinary iodine concentration (UIC) was 140.5 (75.2, 246.9) µg/L. The estimated 24-h urinary iodine excretion (24-h UIE) values from spot urine samples and measured 24-h UIE values from 24-h urine samples were 348±240 µg/24h and 330±216 µg/24h (p=0.003), respectively. Irrespective of the urinary iodine method, the intra- individual coefficient of variation (CV%) was lower than the inter-individual CV%. Bland-Altman analysis revealed differences between spot urine and 24-h urine. When the precision ranges with 95% confidence were ±15%, ±20%, ±25% or 30%, the number of an individual's spot urine samples required were 30, 16, 11 or 8, respectively. CONCLUSIONS: Repeated spot urine is not a feasible way to assess recent individual iodine intake. The development of a multi-indicator system could provide an acceptable individual evaluation index of iodine status.

19.
Cell Death Dis ; 11(12): 1057, 2020 12 12.
Artigo em Inglês | MEDLINE | ID: mdl-33311489

RESUMO

Cisplatin (CP) is an effective chemotherapeutic agent widely used in the treatment of various solid tumours. However, CP nephrotoxicity is an important limitation for CP use; currently, there is no method to ameliorate cisplatin-induced acute kidney injury (AKI). Recently, we identified a specific role of proline-serine-threonine phosphatase-interacting protein 2 (PSTPIP2) in cisplatin-induced AKI. PSTPIP2 was reported to play an important role in a variety of diseases. However, the functions of PSTPIP2 in experimental models of cisplatin-induced AKI have not been extensively studied. The present study demonstrated that cisplatin downregulated the expression of PSTPIP2 in the kidney tissue. Administration of AAV-PSTPIP2 or epithelial cell-specific overexpression of PSTPIP2 reduced cisplatin-induced kidney dysfunction and inhibited apoptosis of renal tubular epithelial cells. Small interfering RNA-based knockdown of PSTPIP2 expression abolished PSTPIP2 regulation of epithelial cell apoptosis in vitro. Histone acetylation may impact gene expression at the epigenetic level, and histone deacetylase (HDAC) inhibitors were reported to prevent cisplatin-induced nephrotoxicity. The UCSC database was used to predict that acetylation of histone H3 at lysine 27 (H3K27ac) induces binding to the PSTPIP2 promoter, and this prediction was validated by a ChIP assay. Interestingly, an HDAC-specific inhibitor (TSA) was sufficient to potently upregulate PSTPIP2 in epithelial cells. Histone acetylation-mediated silencing of PSTPIP2 may contribute to cisplatin nephrotoxicity. PSTPIP2 may serve as a potential therapeutic target in the prevention of cisplatin nephrotoxicity.

20.
Am J Phys Anthropol ; 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33305836

RESUMO

OBJECTIVES: Violence affected daily life in prehistoric societies, especially at conflict zones where different peoples fought over resources and for other reasons. In this study, cranial trauma was analyzed to discuss the pattern of violence experienced by three Bronze to early Iron Age populations (1,000-100 BCE) that belonged to the Subeixi culture. These populations lived in the Turpan Basin, a conflict zone in the middle of the Eurasian Steppe. METHODS: The injuries on 129 complete crania unearthed from the Subeixi cemeteries were examined for crude prevalence rate (CPR), trauma type, time of occurrence, possible weapon, and direction of the blow. Thirty-three injuries identified from poorly preserved crania were also included in the analyses except for the CPR. Data was also compared between the samples and with four other populations that had violence-related backgrounds. RESULTS: Overall, 16.3% (21/129) of the individuals showed violence-induced traumatic lesions. Results also indicated that most of the injuries were perimortem (81.6%), and that women and children were more involved in conflict than the other comparative populations. Wounds from weapons accounted for 42.1% of the identified cranial injuries. Distribution analysis suggested no dominant handedness of the attackers, and that blows came from all directions including the top (17.1%). Wounds caused by arrowheads and a special type of battle-ax popular in middle and eastern Eurasian Steppe were also recognized. DISCUSSION: A comprehensive analysis of the skeletal evidence, historical records, and archeological background would suggest that the raiding to be the most possible conflict pattern reflected by the samples. The attackers were likely to have been nomadic invaders from the steppe (such as the Xiongnu from historical records), who attacked the residents in the basin more likely for their resources rather than territory or labor force.

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