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1.
Biomed Pharmacother ; 177: 116973, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38908204

RESUMO

Hepatocyte transplantation is an effective treatment for end-stage liver disease. However, due to the limited supply of human hepatocytes, porcine hepatocytes have garnered attention as a potential alternative source. Nonetheless, traditional primary porcine hepatocytes exhibit certain limitations in function maintenance and in vitro proliferation. This study has discovered that by using histone deacetylase inhibitors (HDACi), primary porcine hepatocytes can be successfully reprogrammed into liver progenitor cells with high proliferative potential. This method enables porcine hepatocytes to proliferate over an extended period in vitro and exhibit increased susceptibility in lentivirus-mediated gene modification. These liver progenitor cells can readily differentiate into mature hepatocytes and, upon microencapsulation transplantation into mice with acute liver failure, significantly improve the survival rate. This research provides new possibilities for the application of porcine hepatocytes in the treatment of end-stage liver disease.

2.
J Cancer Res Clin Oncol ; 150(6): 309, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890157

RESUMO

PURPOSE: Limited treatment options exist for unresectable intrahepatic cholangiocarcinoma (ICC), with systemic chemotherapy (SC) serving as the primary approach. This study aimed to assess the effectiveness of first-line hepatic arterial infusion chemotherapy (HAIC) in combination with lenvatinib and PD-(L)1 inhibitors (HLP) compared to SC combined with PD-(L)1 inhibitors (SCP) or SC alone in treating unresectable ICC. METHODS: Patient with unresectable ICC who underwent first-line treatment with HLP, SCP or SC from January 2016 to December 2022 were retrospectively analyzed. The study evaluated and compared efficacy and safety outcomes across the three treatment groups. RESULTS: The study comprised 42, 49, and 50 patients in the HLP, SCP, and SC groups, respectively. Median progression-free survival (PFS) times were 30.0, 10.2, and 6.5 months for HLP, SCP, and SC groups. While the SC group had a median overall survival (OS) time of 21.8 months, the HLP and SCP groups hadn't reached median OS. The HLP group demonstrated significantly superior PFS (p < 0.001) and OS (p = 0.014) compared to the others. Moreover, the HLP group exhibited the highest objective response rate (ORR) at 50.0% and the highest disease control rate (DCR) at 88.1%, surpassing the SC group (ORR, 6.0%; DCR, 52.0%) and SCP group (ORR, 18.4%; DCR, 73.5%) (p < 0.05). Generally, the HLP group reported fewer grades 3-4 adverse events (AEs) compared with others. CONCLUSION: In contrast to systemic chemotherapy with or without PD-(L)1 inhibitors, the triple combination therapy incorporating HAIC, lenvatinib, and PD-(L)1 inhibitors showcased favorable survival benefits and manageable adverse events for unresectable ICC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias dos Ductos Biliares , Colangiocarcinoma , Infusões Intra-Arteriais , Compostos de Fenilureia , Quinolinas , Humanos , Colangiocarcinoma/tratamento farmacológico , Colangiocarcinoma/patologia , Feminino , Masculino , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Quinolinas/efeitos adversos , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/efeitos adversos , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias dos Ductos Biliares/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adulto , Inibidores de Checkpoint Imunológico/administração & dosagem , Inibidores de Checkpoint Imunológico/efeitos adversos , Inibidores de Checkpoint Imunológico/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Idoso de 80 Anos ou mais , Artéria Hepática
3.
Sheng Wu Gong Cheng Xue Bao ; 40(3): 758-772, 2024 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-38545975

RESUMO

With the rapid development of synthetic biology, lots of synthetic biology technology achievements in various application fields have been commercialized, generating broad market prospects. The commercialization of products employing synthetic biology technology (hereinafter referred as synthetic biology products) has brought benefits to human beings, but it has also produced potential safety risks. At present, relevant laws and standards for regulation of biotechnology or genetically modified organisms have been adopted to regulate the safety risks of commercialization of synthetic biology products (CSBP). However, due to the complexity and uncertainty of synthetic biology, the safety risks of CSBP cannot be comprehensively regulated by these laws and standards. Therefore, it is of great significance to formulate specific supervision and management measures for regulating the safety risks of CSBP. This paper summarized the situation of CSBP in the fields of food, medical care, agriculture, environment, energy and materials, analyzed the safety risks existing in the CSBP, and sorted out current supervision situation of its safety risks in European countries, United States, as well as in China. We further proposed suggestions on the safety supervision and management measures on the safety risks of CSBP, including classified examination and approval, classified identification of products, and strict screening and approval of market entities before entering the market, and strengthening safety supervision and emergency treatment as well as accident responsibility investigation after entering the market. This whole-process safety regulation might provide support for the safety of CSBP and promote the healthy and long-term development of synthetic biology industry.


Assuntos
Biotecnologia , Biologia Sintética , Humanos , Estados Unidos , Indústrias , China
4.
World J Gastroenterol ; 30(7): 774-778, 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38515953

RESUMO

This research aimed to examine the diagnostic accuracy and clinical significance of endoscopic ultrasonography (EUS) in the context of small rectal neuroendocrine neoplasms (NENs). A total of 108 patients with rectal subepithelial lesions (SELs) with a diameter of < 20 mm were included in the analysis. The diagnosis and depth assessment of EUS was compared to the histology findings. The prevalence of NENs in rectal SELs was 78.7% (85/108). The sensitivity of EUS in detecting rectal NENs was 98.9% (84/85), while the specificity was 52.2% (12/23). Overall, the diagnostic accuracy of EUS in identifying rectal NENs was 88.9% (96/108). The overall accuracy rate for EUS in assessing the depth of invasion in rectal NENs was 92.9% (78/84). Therefore, EUS demonstrates reasonable diagnostic accuracy in detecting small rectal NENs, with good sensitivity but inferior specificity. EUS may also assist physicians in assessing the depth of invasion in small rectal NENs before endoscopic excision.


Assuntos
Tumores Neuroendócrinos , Neoplasias Retais , Humanos , Endossonografia , Relevância Clínica , Tumores Neuroendócrinos/patologia , Neoplasias Retais/patologia , Reto/diagnóstico por imagem , Reto/patologia
5.
Sci Rep ; 14(1): 4580, 2024 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-38403657

RESUMO

Hypertension (HTN) affects over 1.2 billion individuals worldwide and is defined as systolic blood pressure (BP) ≥ 140 mmHg and diastolic BP ≥ 90 mmHg. Hypertension is also considered a high risk factor for cerebrovascular diseases, which may lead to vascular cognitive impairment (VCI). VCI is associated with executive dysfunction and is also a transitional stage between hypertension and vascular dementia. Hence, it is essential to establish a reliable approach to diagnosing the severity of VCI. In 28 HTN (51-83 yrs; 18 males, 10 females) and 28 healthy controls (HC) (51-75 yrs; 7 males, 21 females), we investigated which regions demonstrate alterations in the resting-state functional connectome due to vascular cognitive impairment in HTN by using the amplitude of the low-frequency fluctuations (ALFF), regional homogeneity (ReHo), graph theoretical analysis (GTA), and network-based statistic (NBS) methods. In the group comparison between ALFF/ReHo, HTN showed reduced spontaneous activity in the regions corresponding to vascular or metabolic dysfunction and enhanced brain activity, mainly in the primary somatosensory cortex and prefrontal areas. We also observed cognitive dysfunction in HTN, such as executive function, processing speed, and memory. Both the GTA and NBS analyses indicated that the HTN demonstrated complex local segregation, worse global integration, and weak functional connectivity. Our findings show that resting-state functional connectivity was altered, particularly in the frontal and parietal regions, by hypertensive individuals with potential vascular cognitive impairment.


Assuntos
Disfunção Cognitiva , Conectoma , Hipertensão , Masculino , Feminino , Humanos , Conectoma/métodos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Hipertensão/complicações , Mapeamento Encefálico
6.
Endocrine ; 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38386167

RESUMO

BACKGROUND: There have been few studies on the role of autophagy in pancreatic neuroendocrine tumours (PNETs). SQSTM1/p62 (also called Sequestosome 1) is a potential autophagy regulator, and its biological roles and clinical significance in PNETs remain poorly understood. PURPOSE: The purpose of this study was to evaluate the clinical significance of SQSTM1/p62 in human PNET specimens and to evaluate its potential value as a therapeutic target by studying its biological function in PNET cell lines. METHODS: SQSTM1/p62 protein expression was assessed in 106 PNET patient specimens by immunohistochemistry, and the relationship between SQSTM1/p62 protein expression and the clinicopathological features of PNETs in patients was analysed. The proliferation, invasion and apoptosis of SQSTM1/p62-knockdown QGP-1 and INS-1 cells were assessed by the MTT assay, a Transwell assay and flow cytometry. Cell autophagy was assessed by western blotting and mCherry-GFP-LC3B. RESULTS: The protein expression of SQSTM1/p62 in PNET patient specimens was significantly correlated with tumour recurrence (p = 0.005) and worse prognosis (log rank p = 0.020). Downregulation of the SQSTM1/p62 gene inhibited tumour cell proliferation and migration and induced PNET cell death. Downregulation of SQSTM1/p62 activated autophagy in PNET cell lines but blocked autophagic flow. Knockdown of the SQSTM1/p62 gene inhibited mTOR phosphorylation. CONCLUSION: The SQSTM1/P62 protein could be an independent prognostic marker for PNET patients. Downregulating SQSTM1/P62 can inhibit PNET progression, inhibit mTOR phosphorylation and block autophagic flow.

7.
J Clin Med ; 13(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38337362

RESUMO

Background: Adjuvant chemotherapy for breast cancer might impact cognitive function and brain structure. Methods: In this study, we investigated the cerebral microstructural changes in breast cancer survivors after adjuvant chemotherapy and the correlation with cognitive function with both cross-sectional and longitudinal study designs. All participants underwent structural MRI. In total, we recruited 67 prechemotherapy patients (BB), 67 postchemotherapy patients (BA), and 77 healthy controls (BH). For the follow-up study, 28 participants in the BH and 28 in the BB groups returned for imaging and assessment (BHF, BBF). Voxel-based morphometry analysis was performed to evaluate differences in brain volume; vertex-based shape analysis was used to assess the shape alterations of subcortical regions. Moreover, multiple regression was applied to assess the association between the changes in neuropsychological assessment and brain volume. Results: The results showed brain volume reduction in the temporal and parietal gyrus in BB and BA patients. Among each group, we also found significant shape alterations in the caudate and thalamus. Volume reductions in the temporal regions and shape changes in the caudate and hippocampus were also observed in patients from time point 1 to time point 2 (postchemotherapy). An association between brain volume and cognitive performance was also found in the limbic system. Conclusions: Based on our findings, we can provide a better understanding of the cerebral structural changes in breast cancer survivors, establish a subsequent prediction model, and serve as a reference for subsequent treatment.

8.
Front Neurol ; 15: 1332984, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38385045

RESUMO

Objective: Breast cancer was the most prevalent type of cancer and had the highest incidence rate among women worldwide. The wide use of adjuvant chemotherapy might have a detrimental effect on the human brain and result in chemotherapy-related cognitive impairment (CICI) among breast cancer patients. Furthermore, prior to chemotherapy, patients reported cancer-related cognitive impairment (CRCI), which might be due to physiological factors or mood symptoms. The present longitudinal study aimed to investigate microstructural and macroscale white matter alterations by generalized q-sampling imaging (GQI). Methods: The participants were categorized into a pre-chemotherapy group (BB) if they were diagnosed with primary breast cancer and an age-matched noncancer control group (HC). Some participants returned for follow-up assessment. In the present follow up study, 28 matched pairs of BB/BBF (follow up after chemotherapy) individuals and 28 matched pairs of HC/HCF (follow up) individuals were included. We then used GQI and graph theoretical analysis (GTA) to detect microstructural alterations in the whole brain. In addition, we evaluated the relationship between longitudinal changes in GQI indices and neuropsychological tests as well as psychiatric comorbidity. Findings: The results showed that disruption of white matter integrity occurred in the default mode network (DMN) of patients after chemotherapy, such as in the corpus callosum (CC) and middle frontal gyrus (MFG). Furthermore, weaker connections between brain regions and lower segregation ability were observed in the post-chemotherapy group. Significant correlations were observed between neuropsychological tests and white matter tracts of the CC, MFG, posterior limb of the internal capsule (PLIC) and superior longitudinal fasciculus (SLF). Conclusion: The results provided evidence of white matter alterations in breast cancer patients, and they may serve as potential imaging markers of cognitive changes. In the future, the study may be beneficial to create and evaluate strategies designed to maintain or improve cognitive function in breast cancer patients undergoing chemotherapy.

9.
Spine (Phila Pa 1976) ; 49(12): 884-891, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38112156

RESUMO

STUDY DESIGN: Retrospective study. OBJECTIVES: This study aimed to develop an initial deep-learning (DL) model based on computerized tomography (CT) scans for diagnosing lumbar spinal stenosis. SUMMARY OF BACKGROUND DATA: Magnetic resonance imaging is commonly used for diagnosing lumbar spinal stenosis due to its high soft tissue resolution, but CT is more portable, cost-effective, and has wider regional coverage. Using DL models to improve the accuracy of CT diagnosis can effectively reduce missed diagnoses and misdiagnoses in clinical practice. MATERIALS AND METHODS: Axial lumbar spine CT scans obtained between March 2022 and September 2023 were included. The data set was divided into a training set (62.3%), a validation set (22.9%), and a control set (14.8%). All data were labeled by two spine surgeons using the widely accepted grading system for lumbar spinal stenosis. The training and validation sets were used to annotate the regions of interest by the two spine surgeons. First, a region of interest detection model and a convolutional neural network classifier were trained using the training set. After training, the model was preliminarily evaluated using a validation set. Finally, the performance of the DL model was evaluated on the control set, and a comparison was made between the model and the classification performance of specialists with varying levels of experience. RESULTS: The central stenosis grading accuracies of DL Model Version 1 and DL Model Version 2 were 88% and 83%, respectively. The lateral recess grading accuracies of DL Model Version 1 and DL Model Version 2 were 75% and 71%, respectively. CONCLUSIONS: Our preliminarily developed DL system for assessing the degree of lumbar spinal stenosis in CT, including the central canal and lateral recess, has shown similar accuracy to experienced specialist physicians. This holds great value for further development and clinical application.


Assuntos
Aprendizado Profundo , Vértebras Lombares , Estenose Espinal , Tomografia Computadorizada por Raios X , Estenose Espinal/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Idoso , Masculino , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Adulto
10.
Opt Express ; 31(22): 36314-36326, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-38017786

RESUMO

The intensity coupling characteristics of Ne dual-isotope inflation and dual-longitudinal-mode operation ring lasers were investigated based on the Lamb theory. Considering the contribution of the Ne isotope system to the polarization of the gain medium and gain saturation effects, the frequency coupling effects were analyzed. Combined with the plasma dispersion function, the optical cavity length is 0.47 m, Ne20: Ne22= 0.53:0.47; the frequency spacing of the adjacent longitudinal mode is 640 MHz, and the intensity tuning curve of the ring laser is simulated. The alterations in the gain self-saturation and mutual saturation coefficients between the four frequencies generated via dual-longitudinal mode splitting are comprehensively discussed. Finally, a detection experiment for the intensity-tuning curve is designed to verify the theoretical analysis.

11.
Nanomaterials (Basel) ; 13(19)2023 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-37836326

RESUMO

Copper-doped zinc oxide films (Zn1-xCuxO) (x = 0, 2%, 4%, 6%) were fabricated on conductive substrates using the sol-gel process. The crystal structure, optical and resistive switching properties of Zn1-xCuxO films are studied and discussed. RRAM is made using Zn1-xCuxO as the resistive layer. The results show that the (002) peak intensity and grain size of Zn1-xCuxOfilms increase from 0 to 6%. In addition, PL spectroscopy shows that the oxygen vacancy defect density of Zn1-xCuxO films also increases with the increase in Cu. The improved resistive switching performance of the RRAM device can be attributed to the formation of conductive filaments and the destruction of more oxygen vacancies in the Zn1-xCuxO film. Consequently, the RRAM device exhibits a higher low resistance state to high resistance state ratio and an HRS state of higher resistance value.

12.
Medicine (Baltimore) ; 102(36): e34839, 2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37682202

RESUMO

Serum carbohydrate antigen 125 (CA125) is associated with the prognosis of various malignancies, including ovarian and pancreatic cancer. The relationship between preoperative serum CA125 level and the survival of patients with intrahepatic cholangiocarcinoma (ICC) has not been fully studied. The aim of this study was to explore the prognostic value of CA125 in ICC after hepatectomy. We retrospectively reviewed the clinicopathological data of 178 ICC patients who underwent hepatic resection. Receiver operating characteristic analyses were performed to estimate the relationships of serum CA125, α-fetoprotein, carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 with the prognosis of ICC. The predictive value of CA125 for the prognosis of ICC patients was demonstrated by univariate analyses and Cox proportional hazards models. CA125 was correlated with tumor size, differentiation, capsulation, tumor node-metastasis stage, recurrence, and CEA. Univariate analysis indicated that CA125, sex, tumor number, tumor size, differentiation, surgical resection margin, tumor node metastasis stage, and CEA were risk factors for both the overall survival and the disease-free survival of ICC patients. Cox proportional hazards models showed that preoperative elevated CA125, a tumor size > 5 cm, and an R1 surgical resection margin were independent prognostic predictors of overall survival and disease-free survival. CA125 also had strong predictive value for the prognosis of different ICC subgroups, including patients without lymph node metastasis and with elevated carbohydrate antigen 19-9 levels. Preoperative elevated serum CA125 level is a noninvasive, simple, and reliable indicator of the prognosis of ICC patients after hepatectomy.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Prognóstico , Hepatectomia , Estudos Retrospectivos , Antígeno Carcinoembrionário , Margens de Excisão , Colangiocarcinoma/cirurgia , Antígeno Ca-125 , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Carboidratos
13.
Proc Natl Acad Sci U S A ; 120(33): e2302799120, 2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37549264

RESUMO

Members of the nucleobase/ascorbic acid transporter (NAT) gene family are found in all kingdoms of life. In mammals, the concentrative uptake of ascorbic acid (vitamin C) by members of the NAT family is driven by the Na+ gradient, while the uptake of nucleobases in bacteria is powered by the H+ gradient. Here, we report the structure and function of PurTCp, a NAT family member from Colwellia psychrerythraea. The structure of PurTCp was determined to 2.80 Å resolution by X-ray crystallography. PurTCp forms a homodimer, and each protomer has 14 transmembrane segments folded into a transport domain (core domain) and a scaffold domain (gate domain). A purine base is present in the structure and defines the location of the substrate binding site. Functional studies reveal that PurTCp transports purines but not pyrimidines and that purine binding and transport is dependent on the pH. Mutation of a conserved aspartate residue close to the substrate binding site reveals the critical role of this residue in H+-dependent transport of purines. Comparison of the PurTCp structure with transporters of the same structural fold suggests that rigid-body motions of the substrate-binding domain are central for substrate translocation across the membrane.


Assuntos
Ácido Ascórbico , Purinas , Animais , Transporte Biológico , Purinas/metabolismo , Mutação , Sítios de Ligação , Ácido Ascórbico/metabolismo , Mamíferos/metabolismo
14.
BMC Musculoskelet Disord ; 24(1): 667, 2023 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-37612739

RESUMO

PURPOSE: This study aims to evaluate complications, clinical outcomes, and radiographic results following Coflex implantation. METHODS: We retrospectively studied 66 patients who had decompressive surgery combined with Coflex implantation to treat lumbar spinal stenosis. All imaging data were collected and examined for imaging changes. Clinical outcomes, included Oswestry Disability Index (ODI), back and leg visual analog scale (VAS) scores, were evaluated before surgery, six months after surgery and at the last follow-up. The number of complications occurring after five years of follow-up was counted. All reoperation cases were meticulously recorded. RESULTS: 66 patients were followed up for 5-14 years. The VAS and ODI scores were significantly improved compared with baseline. Heterotopic Ossification (HO) was detectable in 59 (89.4%). 26 (39.4%) patients had osteolysis at the contact site of Coflex with the spinous process. Coflex loosening was detected in 39 (60%) patients. Spinous process anastomosis was found in 34 (51.5%) patients. There was a statistically significant difference in the VAS score of back pain between patients with and without spinous process anastomosis. Nine cases of lumbar spinal restenosis were observed, and prosthesis fracture was observed in one case. CONCLUSION: Our study identified various imaging changes after Coflex implantation, and majority of them did not affect clinical outcomes. The majority of patients had HO, but osteolysis and Coflex loosening were relatively rare. The VAS score for back pain of these patients was higher if they have spinous process anastomosis. After five-year follow-up, we found lumbar spinal restenosis and prosthesis fracture cases.


Assuntos
Fraturas Ósseas , Osteólise , Humanos , Seguimentos , Estudos Retrospectivos , Implantação de Prótese , Reoperação
15.
FASEB J ; 37(9): e22996, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37566526

RESUMO

Myocardial ischemia/reperfusion injury (MIRI) is a prevalent condition associated with numerous critical clinical conditions. miR-322 has been implicated in MIRI through poorly understood mechanisms. Our preliminary analysis indicated potential interaction of CREB-binding protein (CBP), a transcriptional coactivator and acetyltransferase, with HIF-1α/ß-catenin, which might regulate miR-322 expression. We, therefore, hypothesized that CBP/HIF-1α/ß-catenin/miR-322 axis might play a role in MIRI. Rat cardiomyocytes subjected to oxygen-glucose deprivation /reperfusion (OGD/R) and Langendorff perfused heart model were used to model MIRI in vitro and in vivo, respectively. We used various techniques such as CCK-8 assay, transferase dUTP nick end labeling staining, western blotting, RT-qPCR, chromatin immunoprecipitation (ChIP), dual-luciferase assay, co-immunoprecipitation (Co-IP), hematoxylin and eosin staining, and TTC staining to assess cell viability, apoptosis, and the levels of CBP, HIF-1α, ß-catenin, miR-322, and acetylation. Our results indicate that OGD/R in cardiomyocytes decreased CBP/HIF-1α/ß-catenin/miR-322 expression, increased cell apoptosis and cytokines, and reduced cell viability. However, overexpression of CBP or miR-322 suppressed OGD/R-induced cell injury, while knockdown of HIF-1α/ß-catenin further exacerbated the damage. HIF-1α/ß-catenin bound to miR-322 promoter to promote its expression, while CBP acetylated HIF-1α/ß-catenin for stabilization. Overexpression of CBP attenuated MIRI in rats by acetylating HIF-1α/ß-catenin to stabilize their expression, resulting in stronger binding of HIF-1α/ß-catenin with the miR-322 promoter and subsequent increased miR-322 levels. Therefore, activating CBP/HIF-1α/ß-catenin/miR-322 signaling may be a potential approach to treat MIRI.


Assuntos
MicroRNAs , Traumatismo por Reperfusão Miocárdica , Animais , Ratos , Apoptose , beta Catenina/genética , beta Catenina/metabolismo , Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo
16.
PLoS Genet ; 19(7): e1010786, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37459304

RESUMO

Human ear morphology, a complex anatomical structure represented by a multidimensional set of correlated and heritable phenotypes, has a poorly understood genetic architecture. In this study, we quantitatively assessed 136 ear morphology traits using deep learning analysis of digital face images in 14,921 individuals from five different cohorts in Europe, Asia, and Latin America. Through GWAS meta-analysis and C-GWASs, a recently introduced method to effectively combine GWASs of many traits, we identified 16 genetic loci involved in various ear phenotypes, eight of which have not been previously associated with human ear features. Our findings suggest that ear morphology shares genetic determinants with other surface ectoderm-derived traits such as facial variation, mono eyebrow, and male pattern baldness. Our results enhance the genetic understanding of human ear morphology and shed light on the shared genetic contributors of different surface ectoderm-derived phenotypes. Additionally, gene editing experiments in mice have demonstrated that knocking out the newly ear-associated gene (Intu) and a previously ear-associated gene (Tbx15) causes deviating mouse ear morphology.


Assuntos
Loci Gênicos , Estudo de Associação Genômica Ampla , Humanos , Masculino , Animais , Camundongos , Estudo de Associação Genômica Ampla/métodos , Fenótipo , Ásia , Polimorfismo de Nucleotídeo Único/genética
17.
Front Psychiatry ; 14: 1161246, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37363171

RESUMO

Objective: Previous studies have discussed the impact of chemotherapy on the brain microstructure. There is no evidence of the impact regarding cancer-related psychiatric comorbidity on cancer survivors. We aimed to evaluate the impact of both chemotherapy and mental health problem on brain microstructural alterations and consequent cognitive dysfunction in breast cancer survivors. Methods: In this cross-sectional study conducted in a tertiary center, data from 125 female breast cancer survivors who had not received chemotherapy (BB = 65; 49.86 ± 8.23 years) and had received chemotherapy (BA = 60; 49.82 ± 7.89 years) as well as from 71 age-matched healthy controls (47.18 ± 8.08 years) was collected. Chemotherapeutic agents used were docetaxel and epirubicin. We used neuropsychological testing and questionnaire to evaluate psychiatric comorbidity, cognitive dysfunction as well as generalized sampling imaging (GQI) and graph theoretical analysis (GTA) to detect microstructural alterations in the brain. Findings: Cross-comparison between groups revealed that neurotoxicity caused by chemotherapy and cancer-related psychiatric comorbidity may affect the corpus callosum and middle frontal gyrus. In addition, GQI indices were correlated with the testing scores of cognitive function, quality of life, anxiety, and depression. Furthermore, weaker connections between brain regions and lower segregated ability were found in the post-treatment group. Conclusion: This study suggests that chemotherapy and cancer-related mental health problem both play an important role in the development of white matter alterations and cognitive dysfunction.

18.
Front Neuroinform ; 17: 956600, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36873565

RESUMO

Background: Understanding neural connections facilitates the neuroscience and cognitive behavioral research. There are many nerve fiber intersections in the brain that need to be observed, and the size is between 30 and 50 nanometers. Improving image resolution has become an important issue for mapping the neural connections non-invasively. Generalized q-sampling imaging (GQI) was used to reveal the fiber geometry of straight and crossing. In this work, we attempted to achieve super-resolution with a deep learning method on diffusion weighted imaging (DWI). Materials and methods: A three-dimensional super-resolution convolutional neural network (3D SRCNN) was utilized to achieve super-resolution on DWI. Then, generalized fractional anisotropy (GFA), normalized quantitative anisotropy (NQA), and the isotropic value of the orientation distribution function (ISO) mapping were reconstructed using GQI with super-resolution DWI. We also reconstructed the orientation distribution function (ODF) of brain fibers using GQI. Results: With the proposed super-resolution method, the reconstructed DWI was closer to the target image than the interpolation method. The peak signal-to-noise ratio (PSNR) and structural similarity index measure (SSIM) were also significantly improved. The diffusion index mapping reconstructed by GQI also had higher performance. The ventricles and white matter regions were much clearer. Conclusion: This super-resolution method can assist in postprocessing low-resolution images. With SRCNN, high-resolution images can be effectively and accurately generated. The method can clearly reconstruct the intersection structure in the brain connectome and has the potential to accurately describe the fiber geometry on a subvoxel scale.

19.
J Affect Disord ; 330: 239-244, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-36870453

RESUMO

BACKGROUND: Structural and functional brain changes have been found to be associated with altered emotion and cognition in patients with bipolar disorder (BD). Widespread microstructural white matter abnormalities have been observed using traditional structural imaging in BD. q-Ball imaging (QBI) and graph theoretical analysis (GTA) improve the specificity and sensitivity and high accuracy of fiber tracking. We applied QBI and GTA to investigate and compare the structural connectivity alterations and network alterations in patients with and without BD. METHODS: Sixty-two patients with BD and 62 healthy controls (HCs) completed a MR scan. We evaluated the group differences in generalized fractional anisotropy (GFA) and normalized quantitative anisotropy (NQA) values by voxel-based statistical analysis with QBI. We also evaluated the group differences in topological parameters of GTA and subnetwork interconnections in network-based statistical analysis (NBS). RESULTS: The QBI indices in the BD group were significantly lower than those in the HC group in the corpus callosum, cingulate gyrus, and caudate. The GTA indices indicated that the BD group demonstrated less global integration and higher local segregation than the HC group, but they retained small-world properties. NBS evaluation showed that the majority of the more connected subnetworks in BD occurred in thalamo-temporal/parietal connectivity. CONCLUSION: Our findings supported white matter integrity with network alterations in BD.


Assuntos
Transtorno Bipolar , Conectoma , Substância Branca , Humanos , Transtorno Bipolar/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Corpo Caloso , Imageamento por Ressonância Magnética/métodos
20.
J Autism Dev Disord ; 53(2): 648-655, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33474660

RESUMO

Little research has examined burn injury in the pediatric population with autism spectrum disorder (ASD). We used data from Taiwan's National Health Insurance Research Database to identify 15,844 participants aged <18 years with ASD and 130,860 participants without ASD. Our results revealed that the hazard ratios differed across three age ranges. The ASD group had a lower risk of burn injury than the non-ASD group when they were less than 6 years of age, a higher risk from 6 years to 12 years of age, and no difference when they were older than 12 years of age. More research is required to study the characteristics and causes of burn injury in the pediatric population with ASD.


Assuntos
Transtorno do Espectro Autista , Queimaduras , Criança , Humanos , Adolescente , Transtorno do Espectro Autista/epidemiologia , Transtorno do Espectro Autista/etiologia , Risco , Queimaduras/epidemiologia , Queimaduras/complicações , Modelos de Riscos Proporcionais , Bases de Dados Factuais
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