Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.829
Filtrar
1.
Int J Cancer ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33038280

RESUMO

Obesity is considered a chronic inflammatory state characterised by continued secretion of adipokines and cytokines. Experimental and epidemiological evidence indicates that circulating adipokines may be associated with the development of obesity-related cancers, but it is unclear if these associations are causal or confounded. We examined potential causal associations of specific adipokines [adiponectin, leptin, soluble leptin receptor (sOB-R), and plasminogen activator inhibitor-1 (PAI-1)] with five obesity-related cancers (colorectal, pancreatic, renal cell carcinoma, ovarian, and endometrial) using Mendelian randomization (MR) methods. We used summary-level data from large genetic consortia for 114 530 cancer cases and 245 284 controls. We constructed genetic instruments using 18 genetic variants for adiponectin, 2 for leptin, and 4 for both sOB-R and PAI-1 (P-value for inclusion<5 ˟ 10-8 ). Causal estimates were obtained using two-sample MR methods. In the inverse-variance weighted models, we found an inverse association between adiponectin and risk of colorectal cancer [odds ratio (OR) per 1 µg/mL increment in adiponectin concentration: 0.90 (95% confidence interval [CI]: 0.84-0.97); P: 0.01]; but, evidence of horizontal pleiotropy was detected and the association was not present when this was taken into consideration. No association was found for adiponectin and risks of pancreatic cancer, renal cell carcinoma, ovarian cancer, and endometrial cancer. Leptin, sOB-R and PAI-1 were also similarly unrelated to risk of obesity-related cancers. Despite the large sample size, our MR analyses do not support causal effects of circulating adiponectin, leptin, sOB-R, and PAI-1 concentrations on the development of five obesity-related cancers. This article is protected by copyright. All rights reserved.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33041238

RESUMO

BACKGROUND: Surgical mobilization of the maxillary segment affects nasal morphology. This study assessed the impact of the type of maxillary mobilization on the three-dimensional (3D) nasal morphometry. METHODS: Pre- and postsurgery cone beam computed tomography-derived facial image datasets of consecutive patients who underwent two-jaw orthognathic surgery were reviewed. Using preoperative 3D facial models as the positional reference of the skeletal framework, 12-month postoperative 3D facial models were classified into four types of maxillary mobilizations (advancement [n = 83], setback [n = 24], intrusion [n = 55], and extrusion [n = 52]) and four types of final maxillary positions (anterosuperior [n = 44], anteroinferior [n = 39], posterosuperior [n = 11], and posteroinferior [n = 13]). Six 3D soft tissue nasal morphometric parameters were measured, with excellent intra- and interexaminer reliability scores (ICC>0.897) for all the measurements. The 3D nasal change for each nasal parameter was computed as the difference between postoperative and preoperative measurement values. RESULTS: The intrusion maxillary mobilization resulted in a significantly (all p<0.05) larger 3D nasal change in terms of alar width, alar base width, and nostril angle parameters, and a smaller change in terms of the nasal tip height parameter than the extrusion maxillary mobilization; however, no significant (all p>0.05) difference was observed between advancement and setback maxillary mobilizations. The anterosuperior and posterosuperior maxillary positions had a significantly (all p<0.05) larger 3D nasal change in terms of the alar base width and nostril angle than the anteroinferior and posteroinferior maxillary positions. CONCLUSION: The type of maxillary mobilization affects the 3D nasal morphometry.

3.
Parkinsonism Relat Disord ; 80: 142-147, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33002721

RESUMO

BACKGROUND: Mutations in the F-box protein 7 (FBXO7) gene result in autosomal recessive parkinsonism. This usually manifests as early-onset parkinsonian-pyramidal syndrome but patients exhibit high phenotypic variability. Here we describe the findings of a Yemeni family with two novel FBXO7 mutations. METHODS: Clinical data and DNA were available for three siblings with early-onset parkinsonism together with their parents and three unaffected siblings. A targeted next generation sequencing panel was used to screen the proband for mutations in 14 genes known to cause a parkinsonian disorder. In addition, SNCA, PARK2, PINK1, and PARK7 were screened for copy number variants. RESULTS: The proband carried two novel compound heterozygous FBXO7 mutations: a missense mutation in exon 1 (p.G39R; c.115G > A) and a frameshift mutation in exon 5 (p.L280fs; c.838del). The mutations segregated with disease in the family with the exception of a potentially pre-symptomatic individual whose age was below the age of onset in two of their three affected siblings. P.G39R occurred at a highly conserved amino acid residue and both mutations were predicted to be deleterious in silico. In contrast to most reported families, the phenotype in this pedigree was consistent with clinically typical Parkinson's disease (PD) with a lack of pyramidal signs and good response to dopaminergic therapy. CONCLUSIONS: Our study expands the phenotype associated with FBXO7 to include early-onset PD and broadens the list of causative mutations. These data suggest that FBXO7 should be included in clinical genetic testing panels for PD, particularly in patients with early onset or a recessive inheritance pattern.

4.
Sleep Med ; 76: 36-42, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-33075612

RESUMO

OBJECTIVE: Our study aimed to investigate the association between sleep deprivation and parasomnias including nightmare and sleepwalking in Chinese adolescents. METHODS: A total of 19,229 high school students aged 10-20 in Fuzhou were invited to complete questionnaires regarding sleep duration, parasomnias including nightmare and sleepwalking, and emotional problems. Subjects with sleep deprivation (SD) defined as sleeping less than 8 h either on weekdays or on weekends were categorized as three groups: weekday SD, weekend SD and habitual SD. RESULTS: The prevalence of recurrent nightmare was significantly higher for subjects with SD (SD vs non sleep deprivation (NSD): 7.6% vs 3.7%). In all subjects, habitual SD was associated with the highest risk of recurrent nightmare [Odds ratio (OR) = 2.19, 95% Confidential interval (95% CI) = 1.73-2.75, P < 0.001], followed by weekday SD (OR = 2.06, 95% CI = 1.64-2.61, P < 0.001) and weekend SD (OR = 1.45, 95% CI = 1.01-2.08, P = 0.045). No significant association was found between sleepwalking and sleep deprivation. In further age-based (10-13/14-17 years) and sex-based subgroup analyses, the findings were consistent except that association between weekend SD and recurrent nightmare disappeared among subjects aged 14-17 or among girls. CONCLUSIONS: Our study found a significant association between recurrent nightmare and sleep deprivation either on weekdays or on weekends in adolescents, which was stronger with more deprivation episodes. No significant association was found between sleepwalking and sleep deprivation. Association between weekend SD and recurrent nightmare disappeared among subjects aged 14-17 or among girls.

5.
World J Clin Cases ; 8(19): 4505-4511, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33083411

RESUMO

BACKGROUND: Urinary tract lymphoepithelioma-like carcinoma is rarely seen. Although it is termed after lymphoepithelioma at the nasopharynx, it behaves more like high grade urothelial carcinoma by immunohistochemical features. Most published literatures focused on its rarity but few discussed results of long-term follow-ups. As no available guidelines are applicable, we postulated that principles should be similar to that of urothelial carcinoma at urinary tract. As of now, this work features the longest follow-up of this cancer at the upper urinary tract. CASE SUMMARY: A 63-year-old female had a chief complaint of intermittent left flank pain for 2 mo, along with accompanying symptoms including vomiting and body weight loss, about 7 kg over 2 mo. Laboratory data showed normocytic anemia, mildly poor renal function, and hyperparathyroidism. Urine analysis showed mild hematuria. Computed tomography showed a 4.2-cm-width irregular mass over left renal pelvic and enlarged lymph node at the left renal hilum. Whole-body bone scan was negative of active bone lesions. Biopsy from ureteroscopy showed urothelial carcinoma. Specimen from laparoscopic nephroureterectomy with bladder cuff resection showed lymphoepithelioma-like carcinoma with muscular invasion (pT3). She took adjuvant chemotherapies of 2 cycles and full courses of radiation therapy. No recurrence was observed with designed investigative programs. CONCLUSION: Locally advanced urinary tract lymphoepithelioma-like carcinoma could benefit from nephroureterectomy and bladder cuff excision in terms of recurrence-free survival.

6.
Nat Commun ; 11(1): 5062, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033254

RESUMO

Septins are GTP-binding proteins involved in diverse cellular processes including division and membrane remodeling. Septins form linear, palindromic heteromeric complexes that can assemble in filaments and higher-order structures. Structural studies revealed various septin architectures, but questions concerning assembly-dynamics and -pathways persist. Here we used high-speed atomic force microscopy (HS-AFM) and kinetic modeling which allowed us to determine that septin filament assembly was a diffusion-driven process, while formation of higher-order structures was complex and involved self-templating. Slightly acidic pH and increased monovalent ion concentrations favor filament-assembly, -alignment and -pairing. Filament-alignment and -pairing further favored diffusion-driven assembly. Pairing is mediated by the septin N-termini face, and may occur symmetrically or staggered, likely important for the formation of higher-order structures of different shapes. Multilayered structures are templated by the morphology of the underlying layers. The septin C-termini face, namely the C-terminal extension of Cdc12, may be involved in membrane binding.


Assuntos
Microscopia de Força Atômica , Septinas/metabolismo , Simulação por Computador , Difusão , Concentração de Íons de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Cinética , Lipídeos/química , Domínios Proteicos , Septinas/ultraestrutura , Eletricidade Estática
7.
Ann Palliat Med ; 9(5): 2524-2537, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33065778

RESUMO

BACKGROUND: The overall objective response rate (ORR) of published clinical trials in advanced gastroesophageal cancer patients who received anti-program-death-1 (anti-PD-1) or program-death-legend-1 (anti-PD-L1) therapy was only 10%. This ratio is far away from satisfying. It is necessary to identify patients who are more likely to benefit from the treatment. This study aimed to identify the factors with which the patients would have a higher response rate to anti-PD-1/anti-PD-L1 therapy. METHODS: The study was carried out according to the Cochrane handbook for systemic reviews of intervention. The comparisons were conducted according to the patients' characteristics to distinguish the factors with which the patients would have a higher response rate and better survival from the therapy. RESULTS: One thousand and nine hundred ninety-eight patients with advanced gastroesophageal cancer receiving anti-PD-1 or anti-PD-L-1 therapy were enrolled totally. Both the anti-PD-1 and anti-PD-L-1 therapy were significantly more efficacy in patients with high expression of PD-L1. Adenocarcinoma patients with high microsatellite instability (MSI-H) were more likely to benefit from anti-PD-1 therapy. Patients with a better Eastern Cooperative Oncology Group (ECOG) performance status had a significantly higher ORR and disease control rate (DCR). The treatment also had a better performance in improving the overall survival (OS) and progression-free survival (PFS) in patients with high expression of PD-L1. CONCLUSIONS: The expression level of PD-L1, MSI, and ECOG performance status could be the predictors of achieving clinical benefit from anti-PD-1/anti-PD-L1 therapy in advanced gastroesophageal cancer.

9.
Nat Commun ; 11(1): 5173, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33057068

RESUMO

In ovarian cancer (OC), IL-17-producing T cells (Th17s) predict improved survival, whereas regulatory T cells predict poorer survival. We previously developed a vaccine whereby patient-derived dendritic cells (DCs) are programmed to induce Th17 responses to the OC antigen folate receptor alpha (FRα). Here we report the results of a single-arm open-label phase I clinical trial designed to determine vaccine safety and tolerability (primary outcomes) and recurrence-free survival (secondary outcome). Immunogenicity is also evaluated. Recruitment is complete with a total of 19 Stage IIIC-IV OC patients in first remission after conventional therapy. DCs are generated using our Th17-inducing protocol and are pulsed with HLA class II epitopes from FRα. Mature antigen-loaded DCs are injected intradermally. All patients have completed study-related interventions. No grade 3 or higher adverse events are seen. Vaccination results in the development of Th1, Th17, and antibody responses to FRα in the majority of patients. Th1 and antibody responses are associated with prolonged recurrence-free survival. Antibody-dependent cell-mediated cytotoxic activity against FRα is also associated with prolonged RFS. Of 18 patients evaluable for efficacy, 39% (7/18) remain recurrence-free at the time of data censoring, with a median follow-up of 49.2 months. Thus, vaccination with Th17-inducing FRα-loaded DCs is safe, induces antigen-specific immunity, and is associated with prolonged remission.

10.
J Exp Clin Cancer Res ; 39(1): 209, 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33028359

RESUMO

BACKGROUND: Our previous study showed that calreticulin (CRT) promoted EGF-induced epithelial-mesenchymal transition (EMT) in pancreatic cancer (PC) via Integrin/EGFR-ERK/MAPK signaling. We next investigated the novel signal pathway and molecular mechanism involving the oncogenic role of CRT in PC. METHODS: We investigated the potential role and mechanism of CRT in regulating intracellular free Ca2+ dependent acute and chronic endoplasmic reticulum stress (ERS)-induced EMT in PC in vitro and vivo. RESULTS: Thapsigargin (TG) induced acute ERS via increasing intracellular free Ca2+ in PC cells, which was reversed by CRT silencing. Additionally, CRT silencing inhibited TG-induced EMT in vitro by reversing TG-induced changes of the key proteins in EMT signaling (ZO-1, E-cadherin and Slug) and ERK/MAPK signaling (pERK). TG-promoted cell invasion and migration was also rescued by CRT silencing but enhanced by IRE1α silencing (one of the key stressors in unfolded protein response). Meanwhile, CRT was co-immunoprecipitated and co-localized with IRE1α in vitro and its silencing led to the chronic ERS via upregulating IRE1α independent of IRE1-XBP1 axis. Moreover, CRT silencing inhibited IRE1α silencing-promoted EMT, including inhibiting the activation of EMT and ERK/MAPK signaling and the promotion of cell mobility. In vivo, CRT silencing decreased subcutaneous tumor size and distant liver metastasis following with the increase of IRE1α expression. A negative relationship between CRT and IRE1α was also observed in clinical PC samples, which coordinately promoted the advanced clinical stages and poor prognosis of PC patients. CONCLUSIONS: CRT promotes EMT in PC via mediating intracellular free Ca2+ dependent TG-induced acute ERS and IRE1α-mediated chronic ERS via Slug and ERK/MAPK signaling.

11.
Blood Adv ; 4(19): 4898-4911, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33035333

RESUMO

ZUMA-1 demonstrated a high rate of durable response and a manageable safety profile with axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with refractory large B-cell lymphoma. As previously reported, prespecified clinical covariates for secondary end point analysis were not clearly predictive of efficacy; these included Eastern Cooperative Oncology Group performance status (0 vs 1), age, disease subtype, disease stage, and International Prognostic Index score. We interrogated covariates included in the statistical analysis plan and an extensive panel of biomarkers according to an expanded translational biomarker plan. Univariable and multivariable analyses indicated that rapid CAR T-cell expansion commensurate with pretreatment tumor burden (influenced by product T-cell fitness), the number of CD8 and CCR7+CD45RA+ T cells infused, and host systemic inflammation, were the most significant determining factors for durable response. Key parameters differentially associated with clinical efficacy and toxicities, with both theoretical and practical implications for optimizing CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT02348216.

12.
Head Neck ; 2020 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-33026701

RESUMO

BACKGROUND: In remote thyroid surgery, a reliable intraoperative neuromonitoring (IONM) procedure is an important tool for reducing injury to recurrent laryngeal nerve (RLN). This study proposes an alternative or adjunct technique for performing full percutaneous (PC) IONM and confirms its feasibility in animal experiments. METHODS: This prospective porcine model study enrolled four piglets with eight nerve sides. Evoked electromyography (EMG) was stimulated from PC ball-tip probe, and recorded from EMG endotracheal tube (ETT) and from PC paired long-needle electrodes on the perichondrium of the lateral aspect of thyroid cartilage. RESULTS: In all RLNs and vagus nerves, typical laryngeal EMG waveforms were successfully evoked by PC probe stimulation and recorded by both ETT and PC needle electrodes. CONCLUSIONS: This study confirms the feasibility of the full PC IONM techniques in porcine model. However, further clinical studies are needed to compare the practicality of different remote-access approaches for thyroid surgery.

13.
BMC Vet Res ; 16(1): 395, 2020 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-33081761

RESUMO

BACKGROUND: A selection of haematological and serum biochemical profile was first presented from the 81 samples of Chinese water deer (Hydropotes inermis). The deer health assessment database was initially established, especially in relation to determining potential effects associated with diseases diagnosis. RESULTS: Blood samples were analyzed for different haematological parameters viz. white blood cells (WBC), red blood cells (RBC), haemoglobin (HGB), packed-cell volume (PCV), platelet count (PLT), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), mean corpuscular volume (MCV), mean red blood cells distribution width coefficient of variation (RDW) and different hematological parameters viz. total protein (TP), albumin (ALB), globulin (GLB), albumin to globulin ratio (A/G), total bilirubin (TBIL), alkaline phosphatase (ALP), γ-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), AST/ALT, creatinine, urea (BUN), uric acid, total cholesterol (TC), triglyceride, creatine kinase (CK), lactate dehydrogenase (LDH) and cortisol. The adult females had higher values than adult males in albumin, mean corpuscular volume, packed-cell volume, and hemoglobin content values. The deer from Shanghai had higher urea nitrogen values than those from Zhoushan. CONCLUSION: To our knowledge this is the first report about the haematological and serum biochemical parameters in Chinese water deer. We had initially established a profile of Chinese water deer on haematological and serum biochemical parameters based on 81 samples we had collected. The findings can serve as a primary reference for health monitoring and disease prevention in this species.

14.
Mycoses ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037734

RESUMO

BACKGROUND: The rare occurrence of cryptococcosis caused by Cryptococcus gattii sensu lato (C. gattii s.l.) leads to the difficulties in studying the molecular epidemiology of this globally emerging disease. OBJECTIVES: To establish the molecular epidemiological profile of C. gattii s.l. in Taiwan, and understand the genetic relationship between locally endemic and global isolates. METHODS: A nationwide survey on environmental C. gattii s.l. in Taiwan was conducted from 2017 to 2019. The geographic distribution and molecular epidemiology based on multilocus sequence typing (MLST) data of the environmental isolates were compared with 18 previously collected clinical isolates. Phylogenetic analysis was performed to elucidate the genetic relationship between the global isolates and the isolates endemic to Taiwan. RESULTS: From a total of 622 environmental samples, 104 (16.7%) were positive for C. gattii s.l.. Seven sequence types were identified among the environmental isolates. The genetic population structure showed that the environmental and clinical isolates were closely linked by sequence types and geographical locations. Phylogenetic analysis revealed the association between the C. gattii s.l. isolates in Taiwan and those from South America and South Asia. The recombination test suggested that, in Taiwan, the C. gattii sensu stricto (C. gattii s.s). isolates undergo clonal reproduction and sexual recombination, whereas C. deuterogattii isolates were clonal. CONCLUSIONS: The molecular epidemiology of environmental C. gattii s.l. isolates is closely linked to the clinical isolates. Phylogenetic analysis of the environmental isolates provides an insight into the mechanisms underlying reproduction and dispersal of C. gattii s.l. in Taiwan.

15.
J Orthop Surg (Hong Kong) ; 28(3): 2309499020961564, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33054547
16.
J Chin Med Assoc ; 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33055527

RESUMO

BACKGROUND: Acromegaly is associated with cardiovascular alterations. Up to 50% acromegalic patients suffered from treatment failure after multiple modalities. We investigated correlation between cardiovascular function and control of growth hormone (GH) in acromegalic patients following transsphenoidal adenomectomy (TSA). METHODS: We recruited acromegalic patients who had undergone TSA between 2006 and 2014 in this cross-sectional study. Patients were assigned to group 1, controlled acromegaly (GH <1.0 ng/mL and normalized insulin-like growth factor-1 [IGF-1]); group 2, partially controlled acromegaly (either GH >1.0 ng/mL or non-normalized IGF-1); or group 3, uncontrolled acromegaly (GH >1.0 ng/mL and non-normalized IGF-1). Echocardiography evaluated the left ventricular mass index, left ventricular ejection fraction, and the early transmitral filling velocity (E)-to-late transmitral filling velocity (A) and the E-to-the early diastolic mitral annular velocity (E') ratios. Carotid tonometry evaluated the intima-media thickness of the carotid artery, carotid femoral pulse wave velocity, augmentation index, aortic characteristic impedance (Zc), and pulse pressure amplification. RESULTS: Thirty-three patients participated in this study. Fourteen of the 33 patients were males (42%). Mean age at diagnosis was 50.33 years (SD: 18.45). Compared to patients in group 1, patients in group 3 had younger age and shorter years after operation, without statistical significance. Cumulative GH levels were progressively higher from group 1 to group 3, without statistical significance. The groups did not differ with respect to cardiovascular structure and function evaluated by echocardiography and carotid tonometry. Only Zc value had a difference that was of borderline significance (group 1: 109.13 ± 32.99; group 2: 129.30 ± 32.27; group 3: 159.56 ± 77.4 dynes x s/cm; ANOVA p = 0.088; p = 0.086 for group 1 vs. group 3). CONCLUSION: In the patients with acromegaly who had undergone TSA, cardiac structure and vascular stiffness did not differ among the groups with different levels of GH control.

17.
Clin Cancer Res ; 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33008815

RESUMO

BACKGROUND: Rearrangements involving the MYC protooncogene are common in newly diagnosed multiple myeloma (MM), but their prognostic significance is still unclear. The purpose of this study was to assess the impact of MYC rearrangement on clinical characteristics, treatment response, and survival in newly diagnosed MM. PATIENTS AND METHODS: This is a retrospective study including 1342 patients seen in Mayo Clinic in Rochester, MN, from January 2006 to January 2018, and who had cytogenetic testing by fluorescence in-situ hybridization at diagnosis, including MYC testing using the break apart FISH probe (8q24.1). RESULTS: A rearrangement involving MYC was found in 8% of patients, and was associated with elevated ß2-microglobulin, ≥50% bone marrow plasma cells, IgA MM, and the co-occurrence of trisomies. There were no differences in overall response rates between patients with and without MYC rearrangement when induction chemotherapy was proteasome inhibitor (PI)-based, immunomodulatory drug (IMiD)-based or PI+IMiD-based. Overall survival was shorter in patients with MYC rearrangement compared to patients without MYC rearrangement (5.3 vs. 8.0 years, P<0.001). MYC rearrangement was associated with increased risk of death on multivariate analysis when high-risk cytogenetic abnormalities, ISS stage III, and ≥70 years of age were included (risk ratio: 1.5, P=0.007). CONCLUSION: MYC rearrangement is associated with high disease burden and is an independent adverse prognostic factor in newly diagnosed MM.

18.
J Chin Med Assoc ; 2020 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-33009207

RESUMO

BACKGROUND: Gene therapy is the advance therapeutics for supplying or replaceing the genetic material in patients with inherited disorders. Recent clinical studies have made some progress in a wide range of applications, including monogenic disorders, neurodegenerative diseases, malignant tumors, and congenital diseases. Heart diseases, especially myocardial ischemia, remain one of the leading causes of mortality worldwide and usually result in irreparable cardiomyocyte damage and severe heart failure. METHODS: Most advances in induced pluripotent stem cell (iPSC) technologies for promoting regenerative medicine and stem cell research. However, the driver molecules of myocardial-lineage differentiation and the functional reconstruction capacity of iPSC-derived cardiomyocytes are still an open question. Nanomedicine-based gene delivery provided an crucial platform to carry on the biogenomic materials for equipping functionalities and engineering the living organ environment. Nanodiamond (ND), a carbon-based nanomaterial, has been discovered and shown the high biocompatible and less toxicity for transporting protein, drug, and genomic plasmids. RESULTS: Here, we applied nanodiamond (ND) as a gene delvery vehicle to carry microRNA (miR-181a), and then tranfected into iPS to promote cardiomyocyte-lineage differentiation. Notably. MiR-181a plays a key role in iPS-dervied cardiomyocyte differentiation which directly target Hox-A11, leading to elevated MyoD expression and enhanced cardiomyocyte differentiation. CONCLUSION: Our study demonstrated that miR-181a promotes iPSC differentiation into functional cardiomyocytes. Delivery of NANO-DIAMOND-miR-181a may host clinical potential to enhance the differentiation and recovery of the cardiogenic function in injured cardiomyocytes.

19.
J Biopharm Stat ; : 1-17, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33001745

RESUMO

In ophthalmologic or otolaryngologic studies, bilateral correlated data often arise when observations involving paired organs (e.g., eyes, ears) are measured from each subject. Based on Donner's model , in this paper, we focus on investigating the relationship between the disease probability and covariates (such as ages, weights, gender, and so on) via the logistic regression for the analysis of bilateral correlated data. We first propose a new minorization-maximization (MM) algorithm and a fast quadratic lower bound (QLB) algorithm to calculate the maximum likelihood estimates of the vector of regression coefficients, and then develop three large-sample tests (i.e., the likelihood ratio test, Wald test, and score test) to test if covariates have a significant impact on the disease probability. Simulation studies are conducted to evaluate the performance of the proposed fast QLB algorithm and three testing methods. A real ophthalmologic data set in Iran is used to illustrate the proposed methods.

20.
Int J Mol Sci ; 21(19)2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33003599

RESUMO

Discoidin domain receptor 1 (Drd1) is a collagen-binding membrane protein, but its role in osteoblasts during osteogenesis remains undefined. We generated inducible osteoblast-specific Ddr1 knockout (OKOΔDdr1) mice; their stature at birth, body weight and body length were significantly decreased compared with those of control Ddr1f/f-4OHT mice. We hypothesize that Ddr1 regulates osteogenesis of osteoblasts. Micro-CT showed that compared to 4-week-old Ddr1f/f-4OHT mice, OKOΔDdr1 mice presented significant decreases in cancellous bone volume and trabecular number and significant increases in trabecular separation. The cortical bone volume was decreased in OKOΔDdr1 mice, resulting in decreased mechanical properties of femurs compared with those of Ddr1f/f-4OHT mice. In femurs of 4-week-old OKOΔDdr1 mice, H&E staining showed fewer osteocytes and decreased cortical bone thickness than Ddr1f/f-4OHT. Osteoblast differentiation markers, including BMP2, Runx2, alkaline phosphatase (ALP), Col-I and OC, were decreased compared with those of control mice. Ddr1 knockdown in osteoblasts resulted in decreased mineralization, ALP activity, phosphorylated p38 and protein levels of BMP2, Runx2, ALP, Col-I and OC during osteogenesis. Overexpression and knockdown of Ddr1 in osteoblasts demonstrated that DDR1 mediates the expression and activity of Runx2 and the downstream osteogenesis markers during osteogenesis through regulation of p38 phosphorylation.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA