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1.
Front Oncol ; 14: 1357612, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628664

RESUMO

Paragangliomas (PGLs) are rare neuroendocrine tumors which overproduce catecholamines (CAs). They are extra-adrenal, catecholamine-secreting tumors occurring outside the adrenal glands. Gastric PGLs originating from extra-adrenal paraganglia are exceptionally rare, and their presentation in geriatric patients further adds to the complexity of diagnosis and management. A 72-year-old male patient presented with enduring left upper abdominal pain and anemia persisting for over a year, and hypertension for six months. Physical examination revealed epigastric discomfort and pallor. Computed tomography scans revealed enlarged lymph nodes in the lesser curvature of the stomach and thickening of the gastric antrum wall with concavity. The patient underwent three cycles of neoadjuvant therapy before radical gastrectomy for gastric cancer. These imaging findings were confirmed during surgery and intraoperative blood pressure was in fluctuation. After the successful resection of the tumor, postoperative pathology confirmed paraganglioma. During postoperative examination, it was observed that the patient's CAs and their metabolites had returned to within the normal range. Combined with the existing ten literatures, we retrospective report the clinical and pathological characteristics and treatment strategies of the rare gastric paraganglioma.

2.
Nutr Cancer ; : 1-14, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38655678

RESUMO

OBJECTIVE: This study (CRD42023464989) aimed to explore the effects of pre-operation immunonutrition on safety and immune related factors in colorectal cancer patients undergoing surgery. METHODS: We systematically searched PubMed, Embase, and Wanfang databases to collect all clinical randomized controlled trials of the application of pre-operation immunonutrition for patients with colorectal cancer, published until July 2023. The primary outcomes were safety and immune related factors. RESULTS: A total of 16 studies were finally included. Preoperative immunonutrition could reduce the postoperative infection rate (risk ratio (RR) = 0.56, 95% confidence interval (CI): 0.36, 0.88; p = .01), and wound infection rate (RR = 0.44, 95% CI: 0.27, 0.70; p < .001) in patients with colorectal cancer. For length of stay (mean difference (MD) = -1.10, 95% CI: -2.70, 0.49; p = .17), it was similar between groups. Meanwhile, patients in the pre-operation immune nutrition group also had significantly increased infiltrative lymphocytes CD16+ (MD = 0.04, 95% CI: 0.02, 0.06; p < .001), and CD56+ (MD = 0.05, 95% CI: 0.03, 0.06; p < .001) cells in the tumor tissues, compared to the control group. CONCLUSION: Immunonutrition intervention has the potential to reduce postoperative infectious complications and improve tumor infiltrative lymphocytes in patients with colorectal cancer undergoing surgery.

3.
Eur J Oncol Nurs ; 70: 102546, 2024 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-38513455

RESUMO

OBJECTIVES: To investigate relationships between various symptoms occurring 1-2 and 5-6 days following days after thoracoscopic surgery, to identify core symptoms, and to monitor changes in core symptoms over time following lung cancer thoracoscopic surgery. METHODS: We evaluated symptoms using the Anderson Symptom Scale (Chinese version) and the Lung Cancer-Specific Symptoms Template in 214 lung cancer patients hospitalized in the Department of Thoracic Surgery of a provincial hospital in Jiangsu Province from March 2023 to September 2023. Data was collected at 1-2 days and 5-6 days postoperatively. Symptom networks were constructed for each time point, and centrality indicators were analyzed to identify core symptoms while controlling for influencing factors. RESULTS: According to the network analysis, fatigue (rs = 26.00、rc = 0.05、rb = 1.02) had the highest strength, closeness, and betweenness in the symptom network 1-2 days after lung cancer surgery. At 5-6 days after surgery, shortness of breath (rs = 27.00) emerged as the symptom with the highest strength, fatigue (rc = 0.04) had the highest closeness, and cough (rb = 1.08) ranked highest in betweenness within the symptom network. CONCLUSION: Fatigue stands out as the most core symptom in the network 1-2 days after lung cancer surgery. Shortness of breath, fatigue and cough are the most core symptoms in the symptom network 5-6 days after surgery. Therefore, clinical staff can improve the postoperative symptom experience of lung cancer patients by developing symptom management programmes tailored to these core symptoms.

4.
J Cardiothorac Surg ; 19(1): 31, 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38287440

RESUMO

BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a unique, rarely metastatic tumor composed of myofibroblasts and fibrous spindle cells with inflammatory cell infiltration that can affect any organ in the human body. By reviewing the relevant literature on PubMed, we found that this is the first case report of IMT with both gastric and cardiac involvement. CASE PRESENTATION: A 57-year-old male patient was admitted to the hospital with complaints of malaise, poor appetite, and epigastric pain with black stools. We found a mass in the patient's stomach and left atrium by contrast-enhanced computed tomography, 18 F-fluorodeoxyglucose positron emission tomography/computed tomography, and other tests. The patient underwent laparoscopic Billroth II subtotal gastrectomy and Braun's gastrointestinal reconstruction under general anesthesia. On the 46th day following stomach surgery, the cardiac tumor was removed under general anesthesia. The patient has treated with doxorubicin 70 mg of D1 chemotherapy two months after cardiac surgery. Postoperative pathological immunohistochemistry of the mass confirmed the diagnosis of an IMT. His review three months after the cardiac surgery suggested the progression of the left atrial mass, but he declined further treatment and finally died one month after the review. CONCLUSIONS: As a unique class of tumors that rarely metastasize, IMTs have an unknown etiology and pathogenesis, and distant metastasis is primarily observed in patients with negative activin receptor-like kinase (ALK) expression. The preferred treatment for IMT is complete surgical resection, and the effectiveness of adjuvant therapy for patients with distant metastases is still being determined. The clinical presentation of IMT lacks specificity and is often related to the location of tumor growth, which poses a diagnostic challenge. Pathological immunohistochemistry is the only way to confirm the diagnosis at present. Our case report reminds clinicians that a category of ALK-negative IMT with a tendency toward distant metastasis should not be ignored.


Assuntos
Neoplasias Cardíacas , Laparoscopia , Masculino , Humanos , Pessoa de Meia-Idade , Quinase do Linfoma Anaplásico , Estômago , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirurgia
5.
Acta Biomater ; 173: 247-260, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37939818

RESUMO

Intimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. To develop a vascular adventitial drug delivery system to treat intimal hyperplasia post vascular injuries, we loaded miR-145-5p-agomir (miR-145) into an injectable and in-situ self-assembling RAD peptide hydrogel. In vitro data showed that the miR-145 could be well incorporated into the RAD peptide hydrogels and released in a slow and controlled manner. The released miR-145 could transfect SMCs successfully, and the transfected SMCs exhibited a reduced migration capacity and higher expressions of SMC contractile biomarkers as compared to the non-transfected SMCs. In vivo data showed that the retention of the miR-145 was greatly elongated by the RAD peptide hydrogels. In addition, the application of the miR-145-loaded RAD peptide hydrogels surrounding injured arteries decreased the proliferative SMCs, promoted the regeneration of endothelium, reduced the macrophage infiltration, inhibited the neointimal formation and prevented adverse ECM remodeling via downregulation of KLF4 expression. The RAD peptide hydrogels loaded with miR-145 can successfully inhibit intimal hyperplasia after vascular injuries and thus hold great potential as an innovative extravascular drug delivery approach to treat vascular diseases. STATEMENT OF SIGNIFICANCE: Intimal hyperplasia is a common lesion that can be observed in diverse vascular diseases. Drug-eluting stents and drug-coated balloons, which can release anti-proliferative agents to inhibit smooth muscle cell (SMC) proliferation, are developed to prevent intimal hyperplasia. However, these intervention devices still cannot achieve satisfactory clinical outcomes. In contrast to endovascular drug delivery, vascular adventitial drug delivery is a new strategy. Our work here demonstrates that the RAD peptide hydrogels loaded with miR-145-5p-agomir (miR-145) can successfully reverse intimal hyperplasia after vascular injuries and thus hold great potential as an innovative vascular adventitial drug delivery approach to treat vascular diseases. Our work proposes a possible paradigm shift from endovascular drug delivery to extravascular drug delivery for vascular disorder treatment.


Assuntos
MicroRNAs , Lesões do Sistema Vascular , Humanos , Lesões do Sistema Vascular/terapia , Lesões do Sistema Vascular/metabolismo , Lesões do Sistema Vascular/patologia , Hiperplasia/metabolismo , Hiperplasia/patologia , Músculo Liso Vascular/metabolismo , Hidrogéis/farmacologia , Hidrogéis/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células , Células Cultivadas
6.
Anal Chem ; 95(41): 15153-15161, 2023 10 17.
Artigo em Inglês | MEDLINE | ID: mdl-37800909

RESUMO

The metabolic cross-talk between tumor and immune cells plays key roles in immune cell function and immune checkpoint blockade therapy. However, the characterization of tumor immunometabolism and its spatiotemporal alterations during immune response in a complex tumor microenvironment is challenging. Here, a 3D tumor-immune cell coculture spheroid model was developed to mimic tumor-immune interactions, combined with mass spectrometry imaging-based spatially resolved metabolomics to visualize tumor immunometabolic alterations during immune response. The inhibition of T cells was simulated by coculturing breast tumor spheroids with Jurkat T cells, and the reactivation of T cells can be monitored through diminishing cancer PD-L1 expressions by berberine. This system enables simultaneously screening and imaging discriminatory metabolites that are altered during T cell-mediated antitumor immune response and characterizing the distributions of berberine and its metabolites in tumor spheroids. We discovered that the transport and catabolism of glutamine were significantly reprogrammed during the antitumor immune response at both metabolite and enzyme levels, corresponding to its indispensable roles in energy metabolism and building new biomass. The combination of spatially resolved metabolomics with the 3D tumor-immune cell coculture spheroid visually reveals metabolic interactions between tumor and immune cells and possibly helps decipher the role of immunometabolic alterations in tumor immunotherapy.


Assuntos
Berberina , Neoplasias , Humanos , Técnicas de Cocultura , Neoplasias/patologia , Esferoides Celulares/patologia , Imunidade , Microambiente Tumoral
7.
J Neurointerv Surg ; 15(2): 157-162, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35135848

RESUMO

BACKGROUND: Pipeline embolization device (PED) deployment combined with coil therapy for large complex intracranial aneurysms is effective and considered superior to PED deployment alone. However, the optimal strategy for use of coils remains unclear. We used patient-specific aneurysm models and finite element analysis to determine the ideal packing density of coils after PED placement. METHODS: Finite element analysis was used to provide a higher-fidelity model for accurate post-treatment computational fluid dynamics analysis to simulate the real therapeutic process of PED and all coils. We then calculated and analyzed the reduction ratio of velocity to identify the hemodynamic change during PED deployment and each coil embolization. RESULTS: Sixteen consecutive patients underwent PED plus coil procedures to treat internal carotid artery intracranial aneurysms. After PED deployment, the intra-aneurysmal flow velocity significantly decreased (15.3 vs 10.0 cm/s; p<0.001). When the first coil was inserted, the flow velocity in the aneurysm further decreased and the reduction was significant (10.0 vs 5.3 cm/s; p<0.001). Analysis of covariance showed that the effect of the reduction ratio of velocity of the second coil was significantly lower than that of the first coil (p<0.001)-that is, when the packing density increased to 7.06%, the addition of coils produced no further hemodynamic effect. CONCLUSION: Adjunct coiling could improve the post-PED hemodynamic environment in treated intracranial aneurysms. However, dense packing is not necessary because the intra-aneurysmal hemodynamics tend to stabilize as the packing density reaches an average of 7.06% or after insertion of the second coil.


Assuntos
Doenças das Artérias Carótidas , Embolização Terapêutica , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/terapia , Prótese Vascular , Hemodinâmica , Doenças das Artérias Carótidas/terapia , Embolização Terapêutica/métodos , Resultado do Tratamento
8.
CNS Neurosci Ther ; 28(11): 1790-1799, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35855611

RESUMO

BACKGROUND: Ischemic stroke is a serious cerebrovascular disease with high morbidity and disability. Zinc accumulation has been shown to play a vital role in neuronal death and blood-brain barrier damage following ischemia in acute stage. However, almost nothing is known about whether zinc is involved in neurological recovery in ischemic prolonged period. This study investigates whether zinc promotes neurological recovery through astrocytes-induced angiogenesis during ischemic repair phase. METHODS: Sprague-Dawley rats were subjected to 2 h ischemia/14, 21, and 28 days reperfusion by middle cerebral artery occlusion, then administered ZnCl2 (10 mg/kg) via intraperitoneally daily from 7 days to tissue collection to observe brain tissue morphology, neurological function recovery by cortical width index, Adhesive removal test, and Forelimb placing test. Angiogenesis, astrocyte activation, and HIF-1α/VEGF pathway were assessed via Western blot, immunofluorescence, and BrdU method in vivo and in vitro. RESULTS: The results showed that zinc significantly alleviated brain atrophy and improved neurological function recovery during the cerebral ischemia repair stage. Zinc significantly increased the protein levels of HIF-1α, VEGF-A, and VEGF-R2 in astrocytes, and promoted angiogenesis during cerebral ischemia repair. In vitro and in vivo studies confirmed that zinc promoted angiogenesis via the astrocyte-mediated HIF-1α/VEGF signaling pathway. CONCLUSIONS: Zinc significantly improves neurological function recovery during the cerebral ischemia repair stage, providing new evidence supporting zinc as a potential therapeutic target for ischemic stroke by promoting astrocyte induced angiogenesis.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Astrócitos/metabolismo , Isquemia Encefálica/metabolismo , Bromodesoxiuridina/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/fisiologia , Acidente Vascular Cerebral/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Zinco/uso terapêutico
9.
Bioact Mater ; 18: 164-177, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35387168

RESUMO

A personalized medication regimen provides precise treatment for an individual and can be guided by pre-clinical drug screening. The economical and high-efficiency simulation of the liver tumor microenvironment (TME) in a drug-screening model has high value yet challenging to accomplish. Herein, we propose a simulation of the liver TME with suspended alginate-gelatin hydrogel capsules encapsulating patient-derived liver tumor multicellular clusters, and the culture of patient-derived tumor organoids(PDTOs) for personalized pre-clinical drug screening. The hydrogel capsule offers a 3D matrix environment with mechanical and biological properties similar to those of the liver in vivo. As a result, 18 of the 28 patient-derived multicellular clusters were successfully cultured as PDTOs. These PDTOs, along with hepatocyte growth factor (HGF) of non-cellular components, preserve stromal cells, including cancer-associated fibroblasts (CAFs) and vascular endothelial cells (VECs). They also maintain stable expression of molecular markers and tumor heterogeneity similar to those of the original liver tumors. Drugs, including cabazitaxel, oxaliplatin, and sorafenib, were tested in PDTOs. The sensitivity of PDTOs to these drugs differs between individuals. The sensitivity of one PDTO to oxaliplatin was validated using magnetic resonance imaging (MRI) and biochemical tests after oxaliplatin clinical treatment of the corresponding patient. Therefore, this approach is promising for economical, accurate, and high-throughput drug screening for personalized treatment.

10.
Neurology ; 98(16): e1670-e1678, 2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35228337

RESUMO

BACKGROUND AND OBJECTIVES: Brain arteriovenous malformation (bAVM) is a congenital disorder and a leading cause of hemorrhagic stroke. Germline genetic variants play an essential role in the pathogenesis of bAVM. However, the biological relevance of disease-associated genes identified in previous studies is elusive. In this study, we aim to systematically investigate the contribution of germline variants to bAVM and explore the critical molecular pathways underlying the pathogenesis of bAVM. METHODS: Probands with sporadic bAVM were consecutively recruited into this study from November 2015 to November 2018 and underwent exome sequencing. The controls were aggregated from individuals who were not known to have vascular malformation and underwent exome sequencing for clinical or research purposes. The retained control dataset included 4,609 individuals, including 251 individuals with parental samples sequenced. We first analyzed de novo variants in cases and controls and performed a pathway enrichment analysis. A gene-based rare variant association analysis was then performed to identify genes whose variants were significantly enriched in cases. RESULTS: We collected an exome-sequenced bAVM cohort consisting of 152 trios and 40 singletons. By first focusing on de novo variants, we observed a significant mutational burden of likely gene-disrupting variants in cases vs controls. By performing a pathway enrichment analysis of all nonsynonymous de novo variants identified in cases, we found the angiopoietin-like protein 8 (ANGPTL8) regulatory pathway to be significantly enriched in patients with bAVM. Through an exome-wide rare variant association analysis utilizing 4,394 in-house exome data as controls, we identified SLC19A3 as a disease-associated gene for bAVM. In addition, we found that the SLC19A3 variants in cases are preferably located at the N' side of the SLC19A3 protein. These findings implicate a phenotypic expansion of SLC19A3-related disorders with a domain-specific effect. DISCUSSION: This study provides insights into the biological basis of bAVM by identifying novel molecular pathways and candidate genes.


Assuntos
Malformações Arteriovenosas Intracranianas , Malformações do Sistema Nervoso , Hormônios Peptídicos , Proteína 8 Semelhante a Angiopoietina , Proteínas Semelhantes a Angiopoietina/genética , Encéfalo/patologia , Exoma/genética , Predisposição Genética para Doença/genética , Humanos , Malformações Arteriovenosas Intracranianas/genética , Malformações Arteriovenosas Intracranianas/patologia , Proteínas de Membrana Transportadoras/genética , Mutação , Hormônios Peptídicos/genética , Sequenciamento do Exoma
11.
Cell Tissue Bank ; 23(4): 739-752, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35066739

RESUMO

Human umbilical cord mesenchymal stem cells (hUC-MSCs) have considerable potential in cell therapy. Cryopreservation represents the gold standard in cell storage, but its effect on hUC-MSCs is still not well understood. The aim of this study was to investigate the effect of one year of cryopreservation and thawing on the biological characteristics of hUC-MSCs from the same donors. Fresh hUC-MSCs were cryopreserved in commercial freezing medium (serum-free CellBanker 2) at passage 2. After one year of cryopreservation, the hUC-MSCs were thawed and subcultured to passage 4. The comparison was performed in terms of followings: cell count, viability, morphology, proliferation capacity, differentiation potential and chromosomal stability. The total cell count and viability of hUC-MSCs before and after one year of cryopreservation were 1 × 107 and 96.34% and 0.943 × 107 and 93.81%, respectively. Cryopreserved and fresh hUC-MSCs displayed a similar cell doubling times, expressed the markers CD73, CD90, CD105 and were negative for the markers CD34, CD45, and HLA-DR. Karyotypes were found to be normal after one year of cryopreservation. The trilineage differentiation properties were maintained after cryopreservation. However, when compared to freshly isolated hUC-MSCs from the same donor, cryopreserved hUC-MSCs exhibited decreased expression of osteogenesis- and chondrogenesis-related genes including Runx2, Sox9, and Col1a1, and increased expression of adipogenesis-related genes. These results demonstrated that cryopreservation did not affect cell morphology, surface marker expression, cell viability, proliferative capacity, or chromosomal stability. However, the osteogenic and chondrogenic differentiation capacities of cryopreserved hUC-MSCs were slightly reduced compared with those of fresh cells from the same donor.


Assuntos
Células-Tronco Mesenquimais , Humanos , Condrogênese , Criopreservação/métodos , Cordão Umbilical , Instabilidade Cromossômica
12.
J Neurointerv Surg ; 13(6): 568-573, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32848021

RESUMO

BACKGROUND: Brain arteriovenous malformation (BAVM) is a main cause of cerebral hemorrhage and hemorrhagic stroke in adolescents. Morphologically, a BAVM is an abnormal connection between cerebrovascular arteries and veins. The genetic etiology of BAVMs has not been fully elucidated. In this study, we aim to investigate potential recessive genetic variants in BAVMs by interrogation of rare compound heterozygous variants. METHODS: We performed whole exome sequencing (WES) on 112 BAVM trios and analyzed the data for rare and deleterious compound heterozygous mutations associated with the disease. RESULTS: We identified 16 genes with compound heterozygous variants that were recurrent in more than one trio. Two genes (LRP2, MUC5B) were recurrently mutated in three trios. LRP2 has been previously associated with BAVM pathogenesis. Fourteen genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2, DNAH14, DNAH5, FCGBP, HERC2, HMCN1, MYH1, NHSL1, PLEC, RP1L1) were recurrently mutated in two trios, and five of these genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2) have been reported to play a role in angiogenesis or vascular diseases. Additionally, abnormal expression of the MYLK protein is related to spinal arteriovenous malformations. CONCLUSION: Our study indicates that rare recessive compound heterozygous variants may underlie cases of BAVM. These findings improve our understanding of BAVM pathology and indicate genes for functional validation.


Assuntos
Fístula Arteriovenosa/genética , Sequenciamento do Exoma/métodos , Exoma/genética , Variação Genética/genética , Malformações Arteriovenosas Intracranianas/genética , Adolescente , Adulto , Fístula Arteriovenosa/epidemiologia , China/epidemiologia , Proteínas do Olho/genética , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/epidemiologia , Masculino , Adulto Jovem
13.
Med Sci Monit ; 26: e921184, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-32221273

RESUMO

BACKGROUND Retinal degeneration causes irreversible blindness. Human retinal progenitor cells (hRPCs) have the potential to treat retinal diseases. The vitreous cavity is a relatively immune-privileged site that is suitable for stem cell transplantation in the treatment of retinal diseases. This study aimed to evaluate the therapeutic efficacy and safety of intravitreal injection of hRPCs in retinal degeneration therapy. MATERIAL AND METHODS hRPCs were primary-cultured and injected into the vitreous cavity of RCS rats. To determine whether hRPCs formed teratomas in immune-deficient mice, hRPCs at different passages were transplanted into BALB/c-nu mice. The visual function was detected by electroretinography recording. Changes in the outer nuclear layer (ONL) were analyzed by histological testing and cell counting. The protective mechanism was further assessed by cytokine antibody array. RESULTS Intravitreal transplantation of hRPCs maintained retinal function and preserved retinal morphology. Importantly, grafted cells in the vitreous cavity were well tolerated, with no adverse effects. Teratoma was not formed in BALB/c-nu mice after hRPCs transplantation. The number of hRPCs-injected eyes and thickness of ONL in the hRPCs-treated group were higher than those in the untreated group and HBSS injection group. The cytokine antibody array revealed that hRPCs expressed GDF-15, PDGF-AA, EGF, and NT-4. CONCLUSIONS Our findings show that intravitreal injection of hRPCs is effective and safe in protecting photoreceptor cells in RCS rats, but were no longer effective at 12 weeks after transplantation. Moreover, hRPCs released multiple neurotrophic factors that may be involved in treating retinal disease.


Assuntos
Retina/citologia , Degeneração Retiniana/terapia , Transplante de Células-Tronco/métodos , Células-Tronco/fisiologia , Animais , Autorrenovação Celular , Células Cultivadas , Modelos Animais de Doenças , Feto/citologia , Humanos , Injeções Intravítreas , Camundongos , Cultura Primária de Células , Ratos , Retina/patologia , Degeneração Retiniana/patologia
14.
J Neurointerv Surg ; 12(2): 221-226, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31401562

RESUMO

BACKGROUND: Genetic risk factors play an important role in the pathogenesis of familial intracranial aneurysms (FIAs); however, the molecular mechanisms remain largely unknown. OBJECTIVE: To investigate potential FIA-causing genetic variants by rare variant interrogation and a family-based genomics approach in a large family with an extensive multigenerational pedigree with FIAs. METHOD: Exome sequencing (ES) was performed in a dominant likely family with intracranial aneurysms (IAs). Variants were analyzed by an in-house developed pipeline and prioritized using various filtering strategies, including population frequency, variant type, and predicted variant pathogenicity. Sanger sequencing was also performed to evaluate the segregation of the variants with the phenotype. RESULTS: Based on the ES data obtained from five individuals from a family with 7/21 living members affected with IAs, a total of 14 variants were prioritized as candidate variants. Familial segregation analysis revealed that NFX1 c.2519T>C (p.Leu840Pro) segregated in accordance with Mendelian expectations with the phenotype within the family-that is, present in all IA-affected cases and absent from all unaffected members of the second generation. This missense variant is absent from public databases (1000genome, ExAC, gnomAD, ESP5400), and has damaging predictions by bioinformatics tools (Gerp ++ score = 5.88, CADD score = 16.43, MutationTaster score = 1, LRT score = 0). In addition, 840Leu in NFX1 is robustly conserved in mammals and maps in a region before the RING-type zinc finger domain. CONCLUSION: NFX1 c.2519T>C (p.Leu840Pro) may contribute to the pathogenetics of a subset of FIAs.


Assuntos
Povo Asiático/genética , Exoma/genética , Variação Genética/genética , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/genética , Proteínas Repressoras/genética , Adulto , Povo Asiático/etnologia , Biologia Computacional/métodos , Feminino , Humanos , Aneurisma Intracraniano/etnologia , Masculino , Pessoa de Meia-Idade , Linhagem , Fenótipo
15.
Gene ; 691: 1-7, 2019 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-30599237

RESUMO

Triglycerides account for 99% of milk fat and play a central role in determining dairy product quality. Many factors influence triglyceride synthesis and milk fat secretion. MicroRNAs have been verified to be involved in numerous biological processes, but little is known about their roles in milk fat biosynthesis. In this study, we aim to explore whether miR-454 could regulate triglyceride synthesis in bovine mammary epithelial cells (BMECs) by targeting PPAR-γ. A luciferase reporter assay showed that the predicted target site was correct and that miR-454 and PPAR-γ had a direct interaction. In addition, miR-454 mimics and inhibitors were transfected into BMECs. The results showed that both the mRNA and protein levels of PPAR-γ were negatively correlated with miR-454 expression. Fat droplet accumulation and triglyceride production were also inversely correlated with miR-454 expression. Our results indicate that miR-454 regulates triglyceride synthesis by directly targeting the PPAR-γ 3' UTR in BMECs, suggesting that miR-454 could potentially be a new factor to elevate dairy product quality.


Assuntos
Glândulas Mamárias Animais/metabolismo , MicroRNAs/genética , PPAR gama/genética , Triglicerídeos/metabolismo , Regiões 3' não Traduzidas , Animais , Bovinos , Células Cultivadas , Células Epiteliais/citologia , Células Epiteliais/metabolismo , Feminino , Regulação da Expressão Gênica , Glândulas Mamárias Animais/citologia , Leite/química , PPAR gama/metabolismo
16.
Neurosci Lett ; 657: 62-68, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-28774569

RESUMO

Retinal progenitor cell is a promising candidate in the treatment of retinal pigmentosa diseases. The limiting factors of stem cell transplantation are the proliferation and differentiation capacities of hRPCs, which may be governed by culture conditions. Previous studies have proved that the secretome of human Umbilical Cord Mesenchymal stem cells (hUCMSCs) and human Adipose derived stem cells (hADSCs), including more active cytokines and neurotrophic factors, have the paracrine potential of enhancing proliferation and differentiation in several cell types. The aim of this study was to investigate whether hRPCs could effectively proliferate, adhere and differentiate towards specific retinal cell types by treating with the condition medium (CM) of hUCMSCs (hUCMSCCM) or hADSCs (hADSCCM). Here, we show that hUCMSCCM or hADSCCM enhances the proliferation rate of the S and G2 phase cells, with an upregulation of Ki67 expression. Moreover, the upregulation expression of NF, Recoverin and Rhodopsin indicates that specialized retinal cells including ganglion cells and photoreceptors are favored over hRPCs differentiation due to hUCMSCCM or hADSCCM. Under FBS induced differentiation conditions, hRPCs treated with hUCMSCCM or hADSCCM increase the expression of retinal neuron and photoreceptor specific markers. These results suggest that hUCMSCCM and hADSCCM can stimulate the hRPC proliferation, promote its adherence and support hRPC neuronal and photoreceptor differentiation. These findings may provide a new strategy to improve the viability of hRPCs and photoreceptor differentiation capacities.


Assuntos
Adesão Celular/fisiologia , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Meios de Cultivo Condicionados , Células-Tronco Mesenquimais/fisiologia , Células-Tronco Neurais/fisiologia , Neurônios Retinianos/fisiologia , Bancos de Tecidos , Células Cultivadas , Humanos
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