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1.
World J Gastroenterol ; 27(13): 1354-1361, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33833488

RESUMO

BACKGROUND: Rectal subepithelial lesions (SELs) are commonly seen in endoscopic examination, generally manifested as bumps with a smooth surface. Precise preoperative diagnoses for rectal SELs are difficult because abnormal tissues are not easily to be obtained by regular endoscopic forceps biopsy. Traditional guidance modalities of preoperative biopsy, including endoscopic ultrasound, computed tomography, and transabdominal ultrasound, are often unsatisfactory. An updated, safe, and effective biopsy guidance method is required. We herein report a new biopsy guidance modality-endorectal ultrasound (ERUS) combined with contrast-enhanced ultrasound (CEUS). CASE SUMMARY: A 32-year-old woman complained of a mass inside the rectovaginal space for 9 years, which became enlarged within 1 year. A rectal SEL detected by endoscopy was suspected to be a gastrointestinal stromal tumor or exophytic uterine fibroid. Pathological diagnosis was difficult because of unsuccessful transabdominal core needle biopsy with insufficient tissues, as well as vaginal hemorrhage. A second biopsy was suggested after multiple disciplinary treatment discussion, which referred to a transperineal core needle biopsy (CNB) guided by ERUS combined with CEUS. Adequate samples were procured and rectal gastrointestinal stromal tumor was proved to be the pathological diagnosis. Imatinib was recommended for first-line therapy by multiple disciplinary treatment discussion. After the tumor shrunk, resection of the rectal gastrointestinal stromal tumor was performed through the posterior vaginal wall. Adjuvant therapy was applied and no recurrence or metastasis has been found by the last follow-up on December 13, 2019. CONCLUSION: Transperineal CNB guided by ERUS and CEUS is a safe and effective preoperative biopsy of rectal SELs yet with some limitations.

2.
BMC Med Inform Decis Mak ; 21(Suppl 5): 95, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836745

RESUMO

BACKGROUND: Sepsis is a highly lethal and heterogeneous disease. Utilization of an unsupervised method may identify novel clinical phenotypes that lead to targeted therapies and improved care. METHODS: Our objective was to derive clinically relevant sepsis phenotypes from a multivariate panel of physiological data using subgraph-augmented nonnegative matrix factorization. We utilized data from the Medical Information Mart for Intensive Care III database of patients who were admitted to the intensive care unit with sepsis. The extracted data contained patient demographics, physiological records, sequential organ failure assessment scores, and comorbidities. We applied frequent subgraph mining to extract subgraphs from physiological time series and performed nonnegative matrix factorization over the subgraphs to derive patient clusters as phenotypes. Finally, we profiled these phenotypes based on demographics, physiological patterns, disease trajectories, comorbidities and outcomes, and performed functional validation of their clinical implications. RESULTS: We analyzed a cohort of 5782 patients, derived three novel phenotypes of distinct clinical characteristics and demonstrated their prognostic implications on patient outcome. Subgroup 1 included relatively less severe/deadly patients (30-day mortality, 17%) and was the smallest-in-size group (n = 1218, 21%). It was characterized by old age (mean age, 73 years), a male majority (male-to-female ratio, 59-to-41), and complex chronic conditions. Subgroup 2 included the most severe/deadliest patients (30-day mortality, 28%) and was the second-in-size group (n = 2036, 35%). It was characterized by a male majority (male-to-female ratio, 60-to-40), severe organ dysfunction or failure compounded by a wide range of comorbidities, and uniquely high incidences of coagulopathy and liver disease. Subgroup 3 included the least severe/deadly patients (30-day mortality, 10%) and was the largest group (n = 2528, 44%). It was characterized by low age (mean age, 60 years), a balanced gender ratio (male-to-female ratio, 50-to-50), the least complicated conditions, and a uniquely high incidence of neurologic disease. These phenotypes were validated to be prognostic factors of mortality for sepsis patients. CONCLUSIONS: Our results suggest that these phenotypes can be used to develop targeted therapies based on phenotypic heterogeneity and algorithms designed for monitoring, validating and intervening clinical decisions for sepsis patients.

3.
Cytokine ; : 155509, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33840587

RESUMO

BACKGROUND: LncRNA PVT1 was reported to be elevated in septic myocardial tissue. The underlying mechanism by which PVT1 aggravated sepsis induced myocardial injury needs further investigation. METHODS: Mice was subjected to LPS injection to mimic in vivo sepsis model. HE staining was applied to observe tissue injury. Cardiac function of mice was determined by echocardiography. Bone marrow derived macrophage (BMDM) was used to confirm the regulatory effect of PVT1 in macrophage polarization. Western blotting or qRT-PCR were performed to evaluate protein or mRNA levels, respectively. ELISA was conducted to determine cytokine levels. Interaction between PVT1 and miR-29a, miR-29a and HMGB1 were accessed by dual luciferase assay. RESULTS: Expression of PVT1 was elevated in myocardial tissue and heart infiltrating macrophages of sepsis mice. PVT1 knockdown alleviated LPS induced myocardial injury and attenuated M1 macrophage polarization. The mechanic study suggested that PVT1 targeted miR-29a, thus elevated expression of HMGB1, which was repressed by miR-29a targeting. The effect of PVT1 on M1 macrophage polarization was dependent on targeting miR-29a. CONCLUSION: PVT1 promoted M1 polarization and aggravated LPS induced myocardial injury via miR-29a/HMGB1 axis.

4.
Appl Opt ; 60(10): B141-B150, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33798159

RESUMO

A volume holographic (VHG) grating-based multi-plane differential confocal microscopy (DCM) is proposed for axial scan-free imaging. Also, we briefly reviewed our previous works on volume holographic-based confocal imaging. We show that without degrading imaging performance, it is possible to simultaneously obtain two depth-resolved optically sectioned images with improved axial resolution using multi-plane DCM. The performance of our multi-plane DCM was evaluated by measuring the surface profile of a silicon micro-hole array with depths separation around 10 µm. The axial sensitivity of the system is around 25 nm. Our system has the advantages of multi-plane imaging with high axial sensitivity and high optical sectioning ability. Our method can be used for reflective surface profiling and multi-plane fluorescence imaging. The present methods may find important applications in surface metrology for label-free biological samples, as well as industrial applications.

5.
J Matern Fetal Neonatal Med ; : 1-9, 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792471

RESUMO

OBJECTIVES: To evaluate the performance of noninvasive prenatal screening (NIPS) for the fetal common aneuploidy screening in twin pregnancies. METHODS: The data of 5469 women with twin pregnancies were collected in this retrospective observational study between January 2017 and December 2018. Patients underwent NIPS as first-line screening or after standard serum screening for fetal aneuploidy. The performance of NIPS was examined, and a regression analysis was performed to investigate testing failure in cases of low fetal fraction. RESULTS: In this study, 2231 (40.8%) patients opted for NIPS as the primary prenatal screening test, and 3238 (59.2%) opted for serum screening, including 440 patients who opted for NIPS after serum screening. Among the 2671 pregnancies with available NIPS outcomes, 11 cases of aneuploidy were identified, seven of trisomy 21 and four of sex chromosome aneuploidy (SCA). The sensitivity and specificity for trisomy 21 were 100% (95% CI, 56.1-100.0%) and 100% (95% CI, 99.8-100.0%), respectively. The positive predictive value (PPV) for SCA was 40.0% (95% CI, 13.7-72.6%). No false negatives were found, with a negative predictive value (NPV) of 100% (95% CI, 99.8-100.0%) in total. In 32 pregnancies who failed NIPS test without available NIPS outcomes due to low fetal fraction, the regression analysis demonstrated that increasing BMI and assisted reproductive technology treatment were significant independent predictors. CONCLUSIONS: NIPS is a high-performing routine primary prenatal screening test in twin pregnancies, with a high PPV and low false positive rate for detecting trisomy 21. It is also useful to identify common sex chromosome aneuploidies in twin pregnancies, with similar performance to that reported in singleton pregnancy.

6.
Neurosci Bull ; 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33761112

RESUMO

Nerve agents are used in civil wars and terrorist attacks, posing a threat to public safety. Acute exposure to nerve agents such as soman (GD) causes serious brain damage, leading to death due to intense seizures induced by acetylcholinesterase inhibition and neuronal injury resulting from increased excitatory amino-acid levels and neuroinflammation. However, data on the anticonvulsant and neuroprotective efficacies of currently-used countermeasures are limited. Here, we evaluated the potential effects of transient receptor vanilloid 4 (TRPV4) in the treatment of soman-induced status epilepticus (SE) and secondary brain injury. We demonstrated that TRPV4 expression was markedly up-regulated in rat hippocampus after soman-induced seizures. Administration of the TRPV4 antagonist GSK2193874 prior to soman exposure significantly decreased the mortality rate in rats and reduced SE intensity. TRPV4-knockout mice also showed lower incidence of seizures and higher survival rates than wild-type mice following soman exposure. Further in vivo and in vitro experiments demonstrated that blocking TRPV4 prevented NMDA receptor-mediated glutamate excitotoxicity. The protein levels of the NLRP3 inflammasome complex and its downstream cytokines IL-1ß and IL-18 increased in soman-exposed rat hippocampus. However, TRPV4 inhibition or deletion markedly reversed the activation of the NLRP3 inflammasome pathway. In conclusion, our study suggests that the blockade of TRPV4 protects against soman exposure and reduces brain injury following SE by decreasing NMDA receptor-mediated excitotoxicity and NLRP3-mediated neuroinflammation. To our knowledge, this is the first study regarding the "dual-switch" function of TRPV4 in the treatment of soman intoxication.

7.
J Biomed Opt ; 26(3)2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33715316

RESUMO

Guest editors Toyohiko Yatagai, Osamu Matoba, Yoshihisa Aizu, Yasuhiro Awatsuji, and Yuan Luo introduce the articles in the Special Series on Biomedical Imaging and Sensing.

8.
Artif Intell Med ; 112: 102006, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33581826

RESUMO

High-resolution manometry (HRM) is the primary method for diagnosing esophageal motility disorders and its interpretation and classification are based on variables (features) from data of each swallow. Modeling and learning the semantics directly from raw swallow data could not only help automate the feature extraction, but also alleviate the bias from pre-defined features. With more than 32-thousand raw swallow data, a generative model using the approach of variational auto-encoder (VAE) was developed, which, to our knowledge, is the first deep-learning-based unsupervised model on raw esophageal manometry data. The VAE model was reformulated to include different types of loss motivated by domain knowledge and tuned with different hyper-parameters. Training of the VAE model was found sensitive on the learning rate and hence the evidence lower bound objective (ELBO) was further scaled by the data dimension. Case studies showed that the dimensionality of latent space have a big impact on the learned semantics. In particular, cases with 4-dimensional latent variables were found to encode various physiologically meaningful contraction patterns, including strength, propagation pattern as well as sphincter relaxation. Cases with so-called hybrid L2 loss seemed to better capture the coherence of contraction/relaxation transition. Discriminating capability was further evaluated using simple linear discriminative analysis (LDA) on predicting swallow type and swallow pressurization, which yields clustering patterns consistent with clinical impression. The current work on modeling and understanding swallow-level data will guide the development of study-level models for automatic diagnosis as the next stage.

9.
Endocr Connect ; 10(3): 325-335, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33617465

RESUMO

Exercise has been recommended as an important strategy to improve glucose metabolism in obesity. Adipose tissue fibrosis is associated with inflammation and is implicated in glucose metabolism disturbance and insulin resistance in obesity. However, the effect of exercise on the progression of adipose tissue fibrosis is still unknown. The aim of the present study was to investigate whether exercise retarded the progression of adipose tissue fibrosis and ameliorated glucose homeostasis in diet-induced obese mice. To do so, obesity and adipose tissue fibrosis in mice were induced by high-fat diet feeding for 12 weeks and the mice subsequently received high-fat diet and exercise intervention for another 12 weeks. Exercise alleviated high-fat diet-induced glucose intolerance and insulin resistance. Continued high-fat diet feeding exacerbated collagen deposition and further increased fibrosis-related gene expression in adipose tissue. Exercise attenuated or reversed these changes. Additionally, PPARγ, which has been shown to inhibit adipose tissue fibrosis, was observed to be increased following exercise. Moreover, exercise decreased the expression of HIF-1α in adipose fibrosis, and adipose tissue inflammation was inhibited. In conclusion, our data indicate that exercise attenuates and even reverses the progression of adipose tissue fibrosis, providing a plausible mechanism for its beneficial effects on glucose metabolism in obesity.

10.
Ticks Tick Borne Dis ; 12(3): 101679, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33578256

RESUMO

Ticks and tick-borne rickettsial diseases have been gaining greater attention in China over the past decade. However, most published studies to date have occurred in Northern China, with limited investigations occurring in China's southern provinces. As part of larger surveillance efforts, a cross-sectional survey was conducted in six sites at Guangdong, Guangxi and Yunnan investigating rickettsial infection in ticks. A total of 581 ticks were collected from hosts and screened via PCR, targeting rrs, gltA, ompB, sca4, and ompA gene fragments. Two of 12 Haemaphysalis formosensis ticks were infected with novel Rickettsia strain GD01, which was closest phylogenetically (97.3-98.9 % identity) to Rickettsia tamurae strain AT-1, but not within the same clade. Another detected strain (GD02) shared similar identity, 99-100 % across four gene targets, to recently detected Candidatus Rickettsia longicornii isolate ROK-HL727, with an overall prevalence of 12.5 % (71/569). The presence of such pathogens calls for increased public health attention and active surveillance in patients reporting recent tick bites.

11.
Artigo em Inglês | MEDLINE | ID: mdl-33566082

RESUMO

INTRODUCTION: The Consortium for Clinical Characterization of COVID-19 by EHR (4CE) is an international collaboration addressing COVID-19 with federated analyses of electronic health record (EHR) data. OBJECTIVE: We sought to develop and validate a computable phenotype for COVID-19 severity. METHODS: Twelve 4CE sites participated. First we developed an EHR-based severity phenotype consisting of six code classes, and we validated it on patient hospitalization data from the 12 4CE clinical sites against the outcomes of ICU admission and/or death. We also piloted an alternative machine-learning approach and compared selected predictors of severity to the 4CE phenotype at one site. RESULTS: The full 4CE severity phenotype had pooled sensitivity of 0.73 and specificity 0.83 for the combined outcome of ICU admission and/or death. The sensitivity of individual code categories for acuity had high variability - up to 0.65 across sites. At one pilot site, the expert-derived phenotype had mean AUC 0.903 (95% CI: 0.886, 0.921), compared to AUC 0.956 (95% CI: 0.952, 0.959) for the machine-learning approach. Billing codes were poor proxies of ICU admission, with as low as 49% precision and recall compared to chart review. DISCUSSION: We developed a severity phenotype using 6 code classes that proved resilient to coding variability across international institutions. In contrast, machine-learning approaches may overfit hospital-specific orders. Manual chart review revealed discrepancies even in the gold-standard outcomes, possibly due to heterogeneous pandemic conditions. CONCLUSION: We developed an EHR-based severity phenotype for COVID-19 in hospitalized patients and validated it at 12 international sites.

12.
J Med Internet Res ; 23(3): e22219, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33600347

RESUMO

Coincident with the tsunami of COVID-19-related publications, there has been a surge of studies using real-world data, including those obtained from the electronic health record (EHR). Unfortunately, several of these high-profile publications were retracted because of concerns regarding the soundness and quality of the studies and the EHR data they purported to analyze. These retractions highlight that although a small community of EHR informatics experts can readily identify strengths and flaws in EHR-derived studies, many medical editorial teams and otherwise sophisticated medical readers lack the framework to fully critically appraise these studies. In addition, conventional statistical analyses cannot overcome the need for an understanding of the opportunities and limitations of EHR-derived studies. We distill here from the broader informatics literature six key considerations that are crucial for appraising studies utilizing EHR data: data completeness, data collection and handling (eg, transformation), data type (ie, codified, textual), robustness of methods against EHR variability (within and across institutions, countries, and time), transparency of data and analytic code, and the multidisciplinary approach. These considerations will inform researchers, clinicians, and other stakeholders as to the recommended best practices in reviewing manuscripts, grants, and other outputs from EHR-data derived studies, and thereby promote and foster rigor, quality, and reliability of this rapidly growing field.


Assuntos
/epidemiologia , Coleta de Dados/métodos , Registros Eletrônicos de Saúde , Coleta de Dados/normas , Humanos , Revisão da Pesquisa por Pares/normas , Editoração/normas , Reprodutibilidade dos Testes , /isolamento & purificação
13.
J Med Internet Res ; 23(2): e26302, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33529155

RESUMO

BACKGROUND: The emergence of SARS-CoV-2 (ie, COVID-19) has given rise to a global pandemic affecting 215 countries and over 40 million people as of October 2020. Meanwhile, we are also experiencing an infodemic induced by the overabundance of information, some accurate and some inaccurate, spreading rapidly across social media platforms. Social media has arguably shifted the information acquisition and dissemination of a considerably large population of internet users toward higher interactivities. OBJECTIVE: This study aimed to investigate COVID-19-related health beliefs on one of the mainstream social media platforms, Twitter, as well as potential impacting factors associated with fluctuations in health beliefs on social media. METHODS: We used COVID-19-related posts from the mainstream social media platform Twitter to monitor health beliefs. A total of 92,687,660 tweets corresponding to 8,967,986 unique users from January 6 to June 21, 2020, were retrieved. To quantify health beliefs, we employed the health belief model (HBM) with four core constructs: perceived susceptibility, perceived severity, perceived benefits, and perceived barriers. We utilized natural language processing and machine learning techniques to automate the process of judging the conformity of each tweet with each of the four HBM constructs. A total of 5000 tweets were manually annotated for training the machine learning architectures. RESULTS: The machine learning classifiers yielded areas under the receiver operating characteristic curves over 0.86 for the classification of all four HBM constructs. Our analyses revealed a basic reproduction number R0 of 7.62 for trends in the number of Twitter users posting health belief-related content over the study period. The fluctuations in the number of health belief-related tweets could reflect dynamics in case and death statistics, systematic interventions, and public events. Specifically, we observed that scientific events, such as scientific publications, and nonscientific events, such as politicians' speeches, were comparable in their ability to influence health belief trends on social media through a Kruskal-Wallis test (P=.78 and P=.92 for perceived benefits and perceived barriers, respectively). CONCLUSIONS: As an analogy of the classic epidemiology model where an infection is considered to be spreading in a population with an R0 greater than 1, we found that the number of users tweeting about COVID-19 health beliefs was amplifying in an epidemic manner and could partially intensify the infodemic. It is "unhealthy" that both scientific and nonscientific events constitute no disparity in impacting the health belief trends on Twitter, since nonscientific events, such as politicians' speeches, might not be endorsed by substantial evidence and could sometimes be misleading.


Assuntos
/psicologia , Análise de Dados , Educação em Saúde/estatística & dados numéricos , Aprendizado de Máquina , Processamento de Linguagem Natural , Opinião Pública , Mídias Sociais/estatística & dados numéricos , /epidemiologia , Humanos , Pandemias
14.
J Med Entomol ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399212

RESUMO

Spotted fever group rickettsiae, mainly maintained and transmitted by ticks, are important etiological agents of (re)emerging zoonotic diseases worldwide. It is of great significance to investigate spotted fever group rickettsiae in ticks in different areas for the prevention and control of rickettsioses. In this study, a total of 305 ticks were collected from wild and domestic animals in Chongqing, Guizhou, Yunnan, and Guangxi provinces of southwestern China during 2017-2019 and examined for the presence of spotted fever group rickettsiae by PCR with primers targeting the partial gltA, ompA, rrs, and htrA genes. Results showed that two spotted fever group rickettsiae species, including the pathogenic Candidatus Rickettsia jingxinensis (Rickettsiales: Rickettsiaceae) and a potential novel species Rickettsia sp. sw (Rickettsiales: Rickettsiaceae), were identified. The Ca. R. jingxinensis sequences were recovered from Rhipicephalus microplus (Ixodida: Ixodidae) and Haemaphysalis longicornis (Ixodida: Ixodidae) ticks and phylogenetically clustered with previous Ca. R. jingxinensis, Ca. R. longicornii (Rickettsiales: Rickettsiaceae), and Rickettsia sp. XY118 (Rickettsiales: Rickettsiaceae) strains. Rickettsia sp. sw was detected in Amblyomma geoemydae (Ixodida: Ixodidae) and Rh. microplus. Interestingly, as far as we know, this was the first report of Rickettsia (Rickettsiales: Rickettsiaceae) in A. geoemydae. Phylogenetic analyses indicated that this potential novel species was closely related to R. aeschlimannii (Rickettsiales: Rickettsiaceae) with gltA and ompA genes and grouped in a cluster composed of R. montanensis (Rickettsiales: Rickettsiaceae), R. raoultii (Rickettsiales: Rickettsiaceae), R. aeschlimannii, R. massiliae (Rickettsiales: Rickettsiaceae), and R. rhipicephali (Rickettsiales: Rickettsiaceae) with htrA, while formed a separate clade with rrs. The pathogenicity of Rickettsia sp. sw should be further confirmed. These results expand the knowledge of the geographical distribution and vector distribution of spotted fever group rickettsiae in China and are useful for assessing the potential public health risk.

15.
Nanoscale Res Lett ; 16(1): 19, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33512585

RESUMO

High-quality Sn(IV)-doped CdS nanowires were synthesized by a thermal evaporation route. Both XRD and Raman scattering spectrum confirmed the doping effect. The room temperature photoluminescence (PL) demonstrated that both near bandgap emission and discrete trapped-state emission appeared simultaneously and significantly, which were attributed to the strong exciton trapping by impurities and electron-phonon coupling during the light transportation. The PL intensity ratio of near bandgap emission to trapped-state emission could be tune via doped Sn(IV) concentration in the CdS nanowires. It is interesting that the trapped-state emission shows well separated peaks with the assistance of 1LO, 2LO, 4LO phonons, demonstrating the boosting electron-phonon coupling in these doped CdS nanowires. The influence of Sn(IV) dopant is further revealed by PL lifetime decay profile. The optical micro-cavity also plays an important role on this emission process. Our results will be helpful to the understanding of doping modulated carrier interaction, trapping and recombination in one-dimensional (1D) nanostructures.

16.
PLoS Genet ; 17(1): e1009233, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33476325

RESUMO

Runx1 is highly expressed in osteoblasts, however, its function in osteogenesis is unclear. We generated mesenchymal progenitor-specific (Runx1f/fTwist2-Cre) and osteoblast-specific (Runx1f/fCol1α1-Cre) conditional knockout (Runx1 CKO) mice. The mutant CKO mice with normal skeletal development displayed a severe osteoporosis phenotype at postnatal and adult stages. Runx1 CKO resulted in decreased osteogenesis and increased adipogenesis. RNA-sequencing analysis, Western blot, and qPCR validation of Runx1 CKO samples showed that Runx1 regulates BMP signaling pathway and Wnt/ß-catenin signaling pathway. ChIP assay revealed direct binding of Runx1 to the promoter regions of Bmp7, Alk3, and Atf4, and promoter mapping demonstrated that Runx1 upregulates their promoter activity through the binding regions. Bmp7 overexpression rescued Alk3, Runx2, and Atf4 expression in Runx1-deficient BMSCs. Runx2 expression was decreased while Runx1 was not changed in Alk3 deficient osteoblasts. Atf4 overexpression in Runx1-deficient BMSCs did not rescue expression of Runx1, Bmp7, and Alk3. Smad1/5/8 activity was vitally reduced in Runx1 CKO cells, indicating Runx1 positively regulates the Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 signaling pathway. Notably, Runx1 overexpression in Runx2-/- osteoblasts rescued expression of Atf4, OCN, and ALP to compensate Runx2 function. Runx1 CKO mice at various osteoblast differentiation stages reduced Wnt signaling and caused high expression of C/ebpα and Pparγ and largely increased adipogenesis. Co-culture of Runx1-deficient and wild-type cells demonstrated that Runx1 regulates osteoblast-adipocyte lineage commitment both cell-autonomously and non-autonomously. Notably, Runx1 overexpression rescued bone loss in OVX-induced osteoporosis. This study focused on the role of Runx1 in different cell populations with regards to BMP and Wnt signaling pathways and in the interacting network underlying bone homeostasis as well as adipogenesis, and has provided new insight and advancement of knowledge in skeletal development. Collectively, Runx1 maintains adult bone homeostasis from bone loss though up-regulating Bmp7/Alk3/Smad1/5/8/Runx2/ATF4 and WNT/ß-Catenin signaling pathways, and targeting Runx1 potentially leads to novel therapeutics for osteoporosis.

17.
Environ Int ; 147: 106361, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33401173

RESUMO

Corona virus disease 2019 has spread worldwide, and appropriate drug design and screening activities are required to overcome the associated pandemic. Using computational simulation, blockade mechanism of SARS-CoV-2 spike receptor binding domain (S RBD) and human angiotensin converting enzyme 2 (hACE2) was clarified based on interactions between RBD and hesperidin. Interactions between anti-SARS-CoV-2 drugs and therapy were investigated based on the binding energy and druggability of the compounds, and they exhibited negative correlations; the compounds were classified into eight common types of structures with highest activity. An anti-SARS-CoV-2 drug screening strategy based on blocking S RBD/hACE2 binding was established according to the first key change (interactions between hesperidin and S RBD/hACE2) vs the second key change (interactions between anti-SARS-CoV-2 drugs and RBD/hACE2) trends. Our findings provide valuable information on the mechanism of RBD/hACE2 binding and on the associated screening strategies for anti-SARS-CoV-2 drugs based on blocking mechanisms of pockets.


Assuntos
Preparações Farmacêuticas , Humanos , Peptidil Dipeptidase A , Glicoproteína da Espícula de Coronavírus
18.
Int J Biol Macromol ; 168: 526-536, 2021 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-33310104

RESUMO

Phototherapy holds promise in cancer treatment for its prominent antitumor efficacy and low systematic toxicity compared with traditional chemotherapy. However, the higher risk of tumor metastasis caused by the severe hypoxic state during phototherapy is a threat in practical use. Here, in order to tackle this challenge, we developed a delivery system via loading the photosensitizer indocyanine green (ICG) into the low molecular weight heparin (LMWH) modified liposomes (LMWH-ICG-Lip) to realize the synergistic effects between photosensitizer and drug vehicle, achieving better phototherapeutic efficacy and meanwhile alleviating the potential risk of tumor metastasis caused by phototherapy. In this system, besides elongating the photosensitizers' circulation time and enhancing their accumulating efficacy to tumor tissues, LMWH itself also exhibited anti-metastasis efficacy via inhibiting adhesion of platelets to tumor cells and decreasing migration and invasion capability of tumor cells. In vivo efficacy evaluation was conducted on orthotopic 4T1 breast cancer model, and the system of LMWH-ICG-Lip could alleviate metastasis potential of residual tumor cells after irradiation, and elicit optimistic antitumor and anti-metastasis efficacy for phototherapy.

19.
J Natl Compr Canc Netw ; 19(4): 385-392, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33378738

RESUMO

BACKGROUND: The incidence of oral squamous cell carcinoma (OSCC) is increasing, with an estimated 369,000 new patients each year worldwide. Surgery is the primary treatment modality for early-stage OSCC, but there is scant evidence to prove the value of elective neck dissection (END) for relatively small early-stage OSCC. This study aimed to identify factors predicting survival for patients with clinical stage T1N0M0 (cT1N0M0) OSCC and whether up-front END improved survival. PATIENTS AND METHODS: Patients with cT1N0M0 OSCC who underwent tumor resection with or without END were identified and extracted from the SEER database. Kaplan-Meier survival analysis was used to assess overall survival and disease-specific survival. Prognostic factors were determined using Cox regression analysis. RESULTS: A total of 5,752 patients with cT1N0M0 OSCC were extracted, of whom 2,194 (38.1%) underwent tumor resection surgery with concurrent END and 3,558 (61.9%) underwent only tumor resection. In a multivariate Cox analysis, a relatively advanced age (>62 years) and relatively high pathologic grade were the significant negative predictors, but married status (hazard ratio, 0.709; P=.006) and undergoing END (hazard ratio, 0.708; P<.001) were identified as significant independent positive factors. CONCLUSIONS: Patients with cT1N0M0 OSCC gain significant overall and disease-specific survival benefit from END.

20.
Vector Borne Zoonotic Dis ; 21(3): 162-171, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33347789

RESUMO

Background: Tick-borne bacteria and protozoa can cause a variety of human and animal diseases in China. It is of great importance to monitor the prevalence and dynamic variation of these pathogens in ticks in ever-changing natural and social environment. Materials and Methods: Ticks were collected from Heilongjiang and Jilin provinces of northeastern China during 2018-2019 followed by morphological identification. The presence of Rickettsia spp., Anaplasma spp., Ehrlichia spp., Borrelia spp., Babesia spp., and Theileria spp. was examined by PCR and Sanger sequencing. The obtained sequences were subjected to phylogenetic analysis through Mega 7.0. Statistical analysis was performed using SPSS 24.0. Results: A total of 250 ticks from 5 species of 3 genera were collected. Ixodes and Haemaphysalis ticks carried more species of pathogens than Dermacentor, and the pathogens detected in Haemaphysalis japonica varied significantly among different sampling sites. The infection rates of Rickettsia spp., Anaplasma spp., Ehrlichia spp., Borrelia spp., Babesia spp., and Theileria spp. were 41.2%, 0, 2.0%, 7.2%, 1.2%, and 7.2%, respectively. Twelve pathogens were identified, among which Rickettsia raoultii (29.6%), Candidatus Rickettsia tarasevichiae (9.2%), and Theileria equi (4.4%) were the three most common ones. Rickettsia had its dominant vector, that is, R. raoultii had high infection rates in Dermacentor nuttalli and Dermacentor silvarum, Ca. R. tarasevichiae in Ixodes persulcatus, and Rickettsia heilongjiangensis in H. japonica. Interestingly, unclassified species were observed, including a Rickettsia sp., an Ehrlichia sp., a Borrelia sp., and a Babesia sp. Coinfections with different pathogens were identified in 9.2% of all tested ticks, with I. persulcatus most likely to be coinfected (23.8%) and Rickettsia spp. and Borrelia spp. as the most common combination (16.7%). Conclusions: The results of this study reflect high diversity and complexity of pathogens in ticks, which are useful for designing more targeted and effective control measures for tick-borne diseases in China.

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