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1.
Cell ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39013470

RESUMO

Allogeneic chimeric antigen receptor (CAR)-T cells hold great promise for expanding the accessibility of CAR-T therapy, whereas the risks of allograft rejection have hampered its application. Here, we genetically engineered healthy-donor-derived, CD19-targeting CAR-T cells using CRISPR-Cas9 to address the issue of immune rejection and treated one patient with refractory immune-mediated necrotizing myopathy and two patients with diffuse cutaneous systemic sclerosis with these cells. This study was registered at ClinicalTrials.gov (NCT05859997). The infused cells persisted for over 3 months, achieving complete B cell depletion within 2 weeks of treatment. During the 6-month follow-up, we observed deep remission without cytokine release syndrome or other serious adverse events in all three patients, primarily shown by the significant improvement in the clinical response index scores for the two diseases, respectively, and supported by the observations of reversal of inflammation and fibrosis. Our results demonstrate the high safety and promising immune modulatory effect of the off-the-shelf CAR-T cells in treating severe refractory autoimmune diseases.

2.
RNA Biol ; 20(1): 311-322, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-37294214

RESUMO

The exon junction complex (EJC) plays key roles throughout the lifespan of RNA and is particularly relevant in the nervous system. We investigated the roles of two EJC members, the paralogs MAGOH and MAGOHB, with respect to brain tumour development. High MAGOH/MAGOHB expression was observed in 14 tumour types; glioblastoma (GBM) showed the greatest difference compared to normal tissue. Increased MAGOH/MAGOHB expression was associated with poor prognosis in glioma patients, while knockdown of MAGOH/MAGOHB affected different cancer phenotypes. Reduced MAGOH/MAGOHB expression in GBM cells caused alterations in the splicing profile, including re-splicing and skipping of multiple exons. The binding profiles of EJC proteins indicated that exons affected by MAGOH/MAGOHB knockdown accumulated fewer complexes on average, providing a possible explanation for their sensitivity to MAGOH/MAGOHB knockdown. Transcripts (genes) showing alterations in the splicing profile are mainly implicated in cell division, cell cycle, splicing, and translation. We propose that high MAGOH/MAGOHB levels are required to safeguard the splicing of genes in high demand in scenarios requiring increased cell proliferation (brain development and GBM growth), ensuring efficient cell division, cell cycle regulation, and gene expression (splicing and translation). Since differentiated neuronal cells do not require increased MAGOH/MAGOHB expression, targeting these paralogs is a potential option for treating GBM.


Assuntos
Genes cdc , Glioblastoma , Humanos , Splicing de RNA , Divisão Celular , Núcleo Celular/metabolismo , Glioblastoma/metabolismo , Proteínas Nucleares/metabolismo
3.
BMC Musculoskelet Disord ; 24(1): 598, 2023 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-37479999

RESUMO

BACKGROUND: In this study, to provide a theoretical basis for understanding the clinical characteristics of epiphyseal fractures in children and improving their management, we explored and analyzed the proportions of different types of epiphyseal fractures in children and evaluated the causes of injury and epidemiological characteristics. METHODS: We retrospectively analyzed children younger than 18 years with fresh epiphyseal fractures who were admitted to our hospital from July 2015 to February 2020. Demographic information, injury mechanisms, fracture characteristics, fracture classification and surgical information were collected. RESULTS: A total of 1124 pediatric patients (1147 epiphyseal fractures), including 789 boys and 335 girls, were included in this study. Epiphyseal fractures were classified as Salter-Harris type II (1002 cases), type IV (105 cases), type III (25 cases), Salter-Harris type I (14 cases), and Salter-Harris type V (1 case). The number of fracture sites peaked in the adolescent group (440 cases). The most three common sites of epiphyseal fractures were the distal radius (460 cases) in which Salter-Harris type II fractures were the most common (454 cases) and Salter-Harris type I (3 cases), Salter-Harris type IV (2 cases), Salter-Harris type III was the least common (1 case). Followed by phalanges of fingers (233 cases) in which Salter-Harris type II fractures were the most common (224 cases) and Salter-Harris type IV (4 cases), Salter-Harris type I (3 cases), Salter-Harris type III fractures were the least common (2 cases). Distal humerus (146 cases) in which Salter-Harris type II fractures were the most common (95 cases), followed by Salter-Harris type IV (49 cases), Salter-Harris type I fractures were the least common (2 cases). The most three important causes of fractures were falls (720 patients), car accident injuries (68 patients), and basketball falls (43 patients). Among the 1124 children with epiphyseal fractures, 1058 were treated mainly by surgery and the ratio of open and closed reduction was 1:5.3. Eighty-eight patients showed an interval > 72 h between the injury and the hospital visit. Among these 88 patients, the most common fracture type was distal radial epiphyseal fracture (32 cases), and all fractures were of Salter-Harris type II. CONCLUSIONS: The epidemiological characteristics of epiphyseal fractures in children indicate the need to strengthen health and safety education and protective measures to prevent the occurrence of these fractures in children. In addition, emergency surgeons and orthopedic surgeons in general hospitals should strengthen their basic knowledge of diagnosing and treating epiphyseal injuries in children to reduce missed diagnoses, misdiagnoses or malpractice.


Assuntos
Fraturas Ósseas , Fraturas Fechadas , Fraturas do Punho , Adolescente , Masculino , Feminino , Humanos , Criança , Estudos Retrospectivos , Dedos
4.
Int J Mol Sci ; 24(21)2023 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-37958543

RESUMO

Reactive oxygen species (ROS) are an important part of adaptation to biotic and abiotic stresses and regulate seed germination through positive or negative signaling. Seed adaptation to abiotic stress may be mediated by hydrogen peroxide (H2O2). The effects of the ROS scavenger N,N'-dimethylthiourea (DMTU) on maize seed germination through endogenous H2O2 regulation is unclear. In this study, we investigated the effects of different doses of DMTU on seed endogenous H2O2 and radicle development parameters using two maize varieties (ZD958 and DMY1). The inhibitory effect of DMTU on the germination rate and radicle growth was dose-dependent. The inhibitory effect of DMTU on radicle growth ceased after transferring maize seeds from DMTU to a water medium. Histochemical analyses showed that DMTU eliminated stable H2O2 accumulation in the radicle sheaths and radicles. The activity of antioxidant enzyme and the expression of antioxidant enzyme-related genes (ZmAPX2 and ZmCAT2) were reduced in maize seeds cultured with DMTU compared with normal culture conditions (0 mmol·dm-3 DMTU). We suggest the use of 200 mmol·dm-3 DMTU as an H2O2 scavenger to study the ROS equilibrium mechanisms during the germination of maize seeds, assisting in the future with the efficient development of plant growth regulators to enhance the seed germination performance of test maize varieties under abiotic stress.


Assuntos
Antioxidantes , Germinação , Espécies Reativas de Oxigênio/metabolismo , Antioxidantes/farmacologia , Sementes , Zea mays , Oxigênio/farmacologia , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo
5.
BMC Musculoskelet Disord ; 23(1): 892, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36183061

RESUMO

PURPOSE: To investigate the factors influencing and long-term effects of manual myotomy (MM) occurring during physiotherapy for congenital muscular torticollis (CMT). METHODS: We retrospectively collected the clinical data of children with CMT receiving physiotherapy between 2008 and 2018. The children were divided into manual myotomy (MM) and non-manual myotomy (NMM) groups according to whether MM occurred during treatment. We assessed physiotherapy outcomes in children with CMT using craniofacial asymmetry parameters and the Cheng-Tang rating score. By measuring the ear-eye distance, ear-nose distance, eye-mouth distance, ear-mouth distance, half-head circumference, and half-head top at two sides to evaluate craniofacial asymmetry. Based on the Cheng-Tang assessment criteria, we recorded the range of rotation, range of lateral flexion, the status of the contracted muscle, the hardness of the mass, the extent of head tilting during activities and sleeping, the status of daily activities, face size, type of head shape, cranial changes, and subjective head tilting to assess the effectiveness of treatment. Clinical data and outcome indicators (craniofacial asymmetry parameters and Cheng-Tang rating score) were compared. RESULTS: The MM group had a significantly higher total Cheng-Tang rating score than the NMM group (P < 0.05). Age at initial physiotherapy session was the risk factor for MM during physiotherapy. CONCLUSION: Children with CMT developing MM during physiotherapy generally have a good outcome, although we do not recommend MM as a goal of treatment. Physiotherapists should understand this phenomenon, assess relevant factors to predict risk, and carefully observe treatment to prevent possible complications.


Assuntos
Fibroma , Miotomia , Torcicolo , Criança , Humanos , Lactente , Músculos do Pescoço , Modalidades de Fisioterapia , Estudos Retrospectivos , Torcicolo/complicações , Torcicolo/congênito , Torcicolo/cirurgia , Resultado do Tratamento
6.
Cancer Sci ; 112(8): 3150-3162, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34097336

RESUMO

Glioma is one of the most commonly diagnosed intracranial malignancies. The molecular mechanism underlying the development of glioma is still largely unknown. In this study, we present the first report concerning the function and mechanism of cyclin-dependent kinase-like 3 (CDKL3) in the development and prognosis of glioma. It is shown that CDKL3 was upregulated in glioma tissues and could independently predict poor prognosis of patients. Silencing CDKL3 in glioma cells could inhibit cell proliferation and migration and induce cell apoptosis and cell cycle arrest, whereas the overexpression of CDKL3 promoted cell proliferation. The in vivo experiments also indicated that knockdown of CDKL3 significantly suppressed tumor growth of glioma. Gene expression profiling of CDKL3 knockdown U87 cells identified RRM2 as a potential target of CDKL3, which was proved to have direct interaction with CDKL3. Given similar effects on glioma development with CDKL3, knockdown of RRM2 could rescue the effects of CDKL3 overexpression on glioma cells. Moreover, knockdown of CDKL3 or RRM2 suppressed the activity of JNK signaling, whereas CDKL3 overexpression produced the opposite effect. In conclusion, our results identified CDKL3 as a promotor for glioma, probably through the regulation of RRM2 and activation of the JNK signalling pathway, highlighting the significance of CDKL3 as a promising therapeutic target of glioma.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Ribonucleosídeo Difosfato Redutase/genética , Regulação para Cima , Animais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma/genética , Glioma/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , Camundongos , Transplante de Neoplasias , Prognóstico , Ribonucleosídeo Difosfato Redutase/metabolismo , Análise de Sobrevida
7.
Cell Biol Int ; 45(5): 1030-1037, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33404163

RESUMO

Antimetastatic effect of Metformin has been documented in epithelial ovarian cancer (EOC). Presently, we investigated the regulatory mechanism of Metformin in EOC metastasis. First, Girdin was significantly enhanced in EOC tumorous tissues and cell lines. Seconded, knockdown of Girdin significantly suppressed EOC cell viability, migration, and invasion, while upregulation of Girdin produced the opposite effects in vitro and facilitated lung metastasis in EOC cell xenograft in vivo. In addition, we confirmed that the inhibitory effect of Metformin on Girdin expression. Mechanistically, the oncogenic effects of Girdin could be reversed by LY294002 (an AKT pathway inhibitor) and Metformin. These results suggested that Metformin attenuated EOC metastasis through Girdin and targeting Girdin may be a promising therapeutic strategy for EOC in the future.


Assuntos
Carcinoma Epitelial do Ovário/metabolismo , Proteínas dos Microfilamentos/genética , Metástase Neoplásica/tratamento farmacológico , Proteínas de Transporte Vesicular/genética , Adulto , Animais , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Transição Epitelial-Mesenquimal , Feminino , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Metformina/metabolismo , Metformina/farmacologia , Camundongos Nus , Proteínas dos Microfilamentos/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Metástase Neoplásica/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Transcriptoma/genética , Proteínas de Transporte Vesicular/efeitos dos fármacos , Proteínas de Transporte Vesicular/metabolismo
8.
Neuropathology ; 41(5): 371-375, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34374134

RESUMO

Calcifying pseudoneoplasms of the neuraxis (CAPNON) are rare, slow-growing, benign lesions occurring throughout the neuroaxis that are frequently misdiagnosed and overlooked by clinicians. Here, we report a case of a 56-year-old woman who presented with a history of recurrent headache for the previous six years. Magnetic resonance imaging (MRI) revealed a 2.3-cm-sized solid mass in the right frontal lobe that was surrounded by marked edematous areas. The lesion demonstrated dense calcification and avid enhancement. The lesion was initially diagnosed as oligodendroglioma, and then found to be CAPNON based on histopathology of a surgically resected tissue. Genetic analysis revealed a nonsense mutation in the CUL4B gene. The patient's condition appeared to reflect a reactive, rather than neoplastic, process. Clinicians should be prepared to detect such pseudotumors histopathologically in order to avoid unnecessary differential tests of neoplastic or infectious diseases, as well as potentially harmful therapies.


Assuntos
Calcinose , Oligodendroglioma , Sistema Nervoso Central , Proteínas Culina , Feminino , Humanos , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade
9.
Nano Lett ; 20(9): 6824-6830, 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32816495

RESUMO

Light-emitting diodes (LEDs) based on III-V/II-VI materials have delivered a compelling performance in the mid-infrared (mid-IR) region, which enabled wide-ranging applications in sensing, including environmental monitoring, defense, and medical diagnostics. Continued efforts are underway to realize on-chip sensors via heterogeneous integration of mid-IR emitters on a silicon photonic chip, but the uptake of such an approach is limited by the high costs and interfacial strains, associated with the processes of heterogeneous integrations. Here, the black phosphorus (BP)-based van der Waals (vdW) heterostructures are exploited as room-temperature LEDs. The demonstrated devices emit linearly polarized light, and the spectra cover the technologically important mid-IR atmospheric window. Additionally, the BP LEDs exhibit fast modulation speed and exceptional operation stability. The measured peak extrinsic quantum efficiency is comparable to the III-V/II-VI mid-IR LEDs. By leveraging the integrability of vdW heterostructures, we further demonstrate a silicon photonic waveguide-integrated BP LED.

10.
J Environ Manage ; 294: 112946, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34153632

RESUMO

The economic and environmental aspects of energy production have become important due to the increasing complexity energy sector and envoirnmental pollution, warranting to test the connection between financial imbalances, energy prices and carbon emission. The study aims to test the impact of vertical fiscal imbalances (VFI) on energy prices and carbon emission trends by considering the dual-perspectives of environmental regulation and industrial structure. The empirical outcomes indicated that vertical fiscal imbalances limited the environmental quality of Pakistan. Furthermore, VFI also caused environmental degradation by affecting industrial structure. VFI inhibits the intensity of environmental regulation, promotes the upgrade of industrial structures, both of which cause additional carbon emissions. The study suggest to energy ministries and energy regulation offices to revisit the machinism of energy prices determination and revised machanisim should provide a user-friendly assessment to understand the actual costs associated with the rising concern of environmental pollution. By this, envoirnmental protection maximization and optimal energy conservation is expacted to increase. Based on empirical findings, the study extends the suggestion that vertical fiscal imbalances should be considered an active indicator by the key policy makers and other stakeholders for energy prices determination and environmental quality upgradation.


Assuntos
Dióxido de Carbono , Desenvolvimento Econômico , Dióxido de Carbono/análise , Poluição Ambiental/análise , Indústrias , Paquistão
11.
Med Sci Monit ; 26: e919029, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32023237

RESUMO

BACKGROUND Cardiovascular complications, such as diabetic cardiomyopathy (DCM), are the leading cause of death in diabetic patients. Shengmai Powder (SMP) was found to have cardioprotective effects. MATERIAL AND METHODS Based on the systematic pharmacological methodology, this research determined the genes of DCM and the known targets of SMP, predicted potential compounds and targets of SMP, constructed networks for DCM and SMP, and performed network analysis. RESULTS Five network were constructed: (1) the DCM gene PPI network; (2) the Compound-compound target network of SMP; (3) the SMP-DCM PPI network; (4) the Compound-known target network of SMP; (5) and the SMP known target-DCM PPI network. Several DCM and treatment related targets, clusters, signaling pathways, and biological processes were found. CONCLUSIONS SMP is able to regulate glycometabolism-related, lipid metabolism-related, inflammatory response-related, oxidative stress-related signaling pathways, and biological processes and targets, which suggests that SMP may have a therapeutic effect on DCM.


Assuntos
Cardiotônicos/uso terapêutico , Cardiomiopatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Redes Reguladoras de Genes , Cardiotônicos/farmacologia , Análise por Conglomerados , Cardiomiopatias Diabéticas/genética , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Pós
12.
BMC Med Inform Decis Mak ; 20(Suppl 3): 128, 2020 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646472

RESUMO

BACKGROUND: Nowadays, the latent power of technology, which can offer innovative resolutions to disease diagnosis, has awakened high-level anticipation in the community of patients as well as professionals. An easy-to-use mobile app is developed by us, which is purposefully intended for those patients with glaucoma. METHODS: A mobile App has been invented for smartphones for the convenient use wherever and whenever. The corresponding experiments carried out by public retinal image database and real captured clinical data reveal the ideal classification accuracy of the App. Also, user feedback evaluation is also carried out in terms of performance test as well as and users' experience. RESULTS: For clinical test using Yanbao App, we found 274 patients for the identification with 648 retinal images to be evaluated by glaucoma classification. Of the 243 glaucoma patients, 191 were screened out with an accuracy of 0.7860 (sensitivity); the number of non-glaucoma patients was 310 of 405, and the accuracy reached 0.7654 (specificity).` The total Accuracy amounted to 0.7731, and the result is close to the test performance obtained on public dataset ORIGA and DRISHTI-GS1. CONCLUSIONS: Yanbao App can be applied as an innovative approach exploiting mobile technology to enhance the clinicians' efficiency and a balanced medical resources as well as a provided better tiered medical service system.


Assuntos
Glaucoma , Aplicativos Móveis , Bases de Dados Factuais , Glaucoma/diagnóstico , Humanos , Smartphone
13.
Cell Physiol Biochem ; 49(5): 1755-1765, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30231239

RESUMO

BACKGROUND/AIMS: Increasing evidence has shown that miR-216b plays an important role in human cancer progression. However, little is known about the function of miR-216b in renal cell carcinoma. METHODS: The expression levels of miR-216b in renal cell carcinoma tissues and cell lines were examined by qRT-PCR. The biological role of miR-216b in renal cell carcinoma proliferation and/or metastasis was examined in vitro and in vivo. The target of miR-216b was identified by a dual-luciferase reporter assay. The expression level of KRAS protein was measured by western blotting. RESULTS: The expression of miR-216b was downregulated in clear cell renal cell carcinoma (ccRCC) cell lines and specimens compared to the adjacent normal tissues. Furthermore, miR-216b can bind to the 3'untranslated region (UTR) of KRAS and inhibit the expression of KRAS through translational repression. The in vitro study revealed that miR-216b attenuated ccRCC cell proliferation and invasion. Furthermore, in vivo study also showed that miR-216b suppressed tumor growth. MiR-216b exerted its tumor suppressor function through inhibiting the KRAS-related MAPK/ERK and PI3K/AKT pathways. CONCLUSION: Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in ccRCC.


Assuntos
Carcinoma de Células Renais/fisiopatologia , Regulação para Baixo , Neoplasias Renais/fisiopatologia , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/genética , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas p21(ras)/antagonistas & inibidores , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/uso terapêutico , Transdução de Sinais
14.
Langmuir ; 33(28): 7147-7151, 2017 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-28650162

RESUMO

Liquid crystals formed by the self-assembly of small molecules are very promising smart materials because of their unique properties, such as self-assembled multivalency, biocompatibility, and fast response to external stimuli. Here we report an iridescent liquid-crystal system composed of water layers, which is sandwiched by two bilayer membranes. Such membranes are composed of a self-assembled nonionic surfactant, which is called hexadecylglyceryl maleate (HGM), and only a small amount of ionic surfactants. It is found that the iridescent color of the liquid crystal system is very sensitive to the concentration of ionic surfactants, even if a trace of change of the ionic surfactants' concentration will induce the color change of liquid-crystal system. The result shows that with the increase in ionic surfactant concentration, the flat bilayer membrane tends to be curved to form some edge-dislocation defects. The appearance of such defects in the lamellar system leads to the decrease in spacing distance between adjacent bilayer membranes. This is because some vacant spaces emerged inevitably during this process. The ionic surfactant-sensitive HGM system also shows the thermal response. It is because the phase-separation results in the increase in local concentration of SDS in the bilayer membrane, which has the same effect as increasing the SDS concentration in the whole system.

15.
Neurosciences (Riyadh) ; 20(3): 280-4, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26166599

RESUMO

The combination of vascular anomalies with gliomas is rarely seen in the CNS, and is defined as "angioglioma". However, the definition, category, and histopathogenesis of angiogliomas remain controversial. Here, we present an unusual case of spinal hemangioblastoma (HB) combined with pilocytic astrocytoma (PA). Spinal MRI revealed lesions extending from T9 to T12 segments, in a "sandwich-like" fashion. After resection of the tumor, histopathologic study confirmed the diagnosis of HB as well as PA. A comprehensive review of the literature was further conducted. We describe a case of spinal HB combined with PA, in addition we discuss the clinicopathological relationship between HB and PA under these conditions, which may facilitate the understanding of the histogenesis of an angioglioma and guide its diagnosis and treatment.


Assuntos
Astrocitoma/diagnóstico , Hemangioblastoma/diagnóstico , Neoplasias da Coluna Vertebral/diagnóstico , Astrocitoma/cirurgia , Hemangioblastoma/cirurgia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias da Coluna Vertebral/cirurgia
16.
Biochem Biophys Res Commun ; 446(4): 1261-7, 2014 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-24690174

RESUMO

Previous studies from this laboratory indicated that microRNA-21 (miR-21) contributes to chemoresistance of glioblastoma multiforme (GBM) cells to teniposide, a type II topoisomerase inhibitor. We also showed that LRRFIP1 is a target of miR-21. In this study, we found that higher baseline LRRFIP1 expression in human GBM tissue (n=60) is associated with better prognosis upon later treatment with teniposide. Experiments in cultured U373MG cells showed enhanced toxicity of teniposide against U373MG cells transfected with a vector that resulted in LRRFIP1 overexpression (vs. cells transfected with control vector). Experiments in nude mice demonstrated better response of LRRFIP1 overexpressing xenografts to teniposide. These findings indicate that high baseline LRRFIP1 expression in GBM is associated with better response to teniposide, and encourage exploring LRRFIP1 as a target for GBM treatment.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Glioblastoma/tratamento farmacológico , Proteínas de Ligação a RNA/genética , Teniposídeo/uso terapêutico , Inibidores da Topoisomerase II/uso terapêutico , Regulação para Cima , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Glioblastoma/diagnóstico , Glioblastoma/genética , Humanos , Camundongos , Camundongos Nus , MicroRNAs/genética , Prognóstico , Transfecção
17.
Proc Natl Acad Sci U S A ; 108(16): 6543-8, 2011 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-21464306

RESUMO

Perrault syndrome is a genetically heterogeneous recessive disorder characterized by ovarian dysgenesis and sensorineural hearing loss. In a nonconsanguineous family with five affected siblings, linkage analysis and genomic sequencing revealed the genetic basis of Perrault syndrome to be compound heterozygosity for mutations in the mitochondrial histidyl tRNA synthetase HARS2 at two highly conserved amino acids, L200V and V368L. The nucleotide substitution creating HARS2 p.L200V also created an alternate splice leading to deletion of 12 codons from the HARS2 message. Affected family members thus carried three mutant HARS2 transcripts. Aminoacylation activity of HARS2 p.V368L and HARS2 p.L200V was reduced and the deletion mutant was not stably expressed in mammalian mitochondria. In yeast, lethality of deletion of the single essential histydyl tRNA synthetase HTS1 was fully rescued by wild-type HTS1 and by HTS1 p.L198V (orthologous to HARS2 p.L200V), partially rescued by HTS1 p.V381L (orthologous to HARS2 p.V368L), and not rescued by the deletion mutant. In Caenorhabditis elegans, reduced expression by RNAi of the single essential histydyl tRNA synthetase hars-1 severely compromised fertility. Together, these data suggest that Perrault syndrome in this family was caused by reduction of HARS2 activity. These results implicate aberrations of mitochondrial translation in mammalian gonadal dysgenesis. More generally, the relationship between HARS2 and Perrault syndrome illustrates how causality may be demonstrated for extremely rare inherited mutations in essential, highly conserved genes.


Assuntos
Aminoacil-tRNA Sintetases/metabolismo , Proteínas Mitocondriais/metabolismo , Mutação de Sentido Incorreto , Processamento Alternativo/genética , Substituição de Aminoácidos , Aminoacil-tRNA Sintetases/genética , Animais , Caenorhabditis elegans/enzimologia , Caenorhabditis elegans/genética , Disgenesia Gonadal 46 XX/enzimologia , Disgenesia Gonadal 46 XX/genética , Perda Auditiva Neurossensorial/enzimologia , Perda Auditiva Neurossensorial/genética , Histidina-tRNA Ligase/genética , Histidina-tRNA Ligase/metabolismo , Humanos , Masculino , Proteínas Mitocondriais/genética , Saccharomyces cerevisiae/enzimologia , Saccharomyces cerevisiae/genética
18.
Artigo em Inglês | MEDLINE | ID: mdl-39019066

RESUMO

This study introduces a novel machine learning (ML) method utilizing a stacked auto-encoder network to predict stiffness degradation in photovoltaic (PV) modules with pre-existing cracks. The input data for the training process was derived from numerical simulations, ensuring a comprehensive representation of module behavior under various conditions. The findings highlight the robust predictive capability of the model, as evidenced by its impressive R2 value of 0.961 and notably low root mean square error (RMSE) of 4.02%. These metrics significantly outperform those of other conventional methods, including the convolutional neural network (CNN) with R2 of 0.905 and RMSE of 9.43%, the space vector machine (SVM) with R2 of 0.827 and RMSE of 17.93%, and the random forest (RF) with R2 of 0.899 and RMSE of 11.02%. Moreover, the findings suggest that the predictive dynamics of degradation are affected by the varying weight functions of different input parameters, such as climate temperature, grain size, material effort, and pre-crack size, as the degradation level changes. Furthermore, a geometric analysis reveals model deficiencies where significant overestimations correlate with thicker glass components, while pronounced underestimations are predominantly associated with thinner layers of polycrystalline silicon wafer and Ethylene Vinyl Acetate in the module. As a case study, it demonstrated that to maintain a constant degradation level between 1.30 and 1.32 in a PV module with components featuring consistent geometric attributes, the input parameters must be kept within specific ranges: climate temperature ranging from 33 to 57°C, grain size ranging from 36 to 81 µm, material effort ranging from 0.74 to 0.81, and pre-crack size ranging from 24 to 32 µm. Therefore, this underscores that the ML model not only predicts degradation but also delineates the parameter space required to achieve a consistent output value.

19.
Curr Med Chem ; 31(12): 1561-1577, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-37594166

RESUMO

INTRODUCTION: The role of lipid metabolism in lung adenocarcinoma (LUAD) is not completely researched. Lipid metabolism reprogramming is a characteristic of malignancies and contributes to carcinogenesis and progression. The transcriptome and scRNA- seq data and clinical information were downloaded from the public databases. METHODS: Lipid metabolism pathways were collected from the MSigDB database, and molecular subtypes were classified based on lipid metabolism features via consensus clustering. The bidirectional crosstalk between immune cells and malignant cells was analyzed. Differences in lipid metabolism at the single-cell level and their correlation with the tumor microenvironment (TME) were also studied. LUAD patients were classified into two subtypes, showing distinct mutation and lipid metabolism features based on lipid metabolism characteristics. Meanwhile, significant differences in the overall survival, clinical characteristics, and immune landscape were observed between the two subtypes. We also found that clust1 had higher oxidative stress status. There were 116 differentially expressed genes between the two subtypes, which were significantly associated with cell cycle progression. We identified 4001 immune cells, including 483 malignant cells and 3518 normal cells, and found active intercellular communication and significant differences in lipid metabolism characteristics between the malignant cells and normal cells. Furthermore, several lipid metabolism pathways were found to be associated with TME factors, including hypoxia and angiogenesis. RESULT: The current findings indicated that lipid metabolism was involved in the development and cellular heterogeneity of LUAD and revealed widespread reprogramming across multiple cellular elements in the TME of LUAD. CONCLUSION: This characterization improved the current understanding of tumor biology and enabled the identification of novel targets for immunotherapy.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Humanos , Metabolismo dos Lipídeos , Adenocarcinoma de Pulmão/genética , Carcinogênese , Transcriptoma , Neoplasias Pulmonares/genética , Microambiente Tumoral , Prognóstico
20.
Front Immunol ; 15: 1397716, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38873605

RESUMO

Background: To evaluate the methodological quality, report quality, and evidence quality of meta-analysis (MA) and systematic review (SR) on the efficacy of probiotics in the treatment of rheumatoid arthritis (RA). Methods: Databases were used to identify eligible SRs/MAs until February 12, 2024. The methodological quality of the studies was assessed using AMSTAR-2 tool, the quality of the literature reports was scored using PRISMA checklists, and the quality of the evidence was graded using GRADE system. Results: Seven reviews including 21 outcomes were included. Methodological quality of the included reviews was of general low, and the entries with poor scores were 2, 4, and 7. By PRISMA checklists, there were some reporting deficiencies, and quality problems were mainly reflected in the reporting registration and protocol, comprehensive search strategy and additional analysis. GRADE results elevated the quality of evidence to be low or very low overall. Conclusions: Probiotics may have a therapeutic effect on RA, based on the evidence provided by the SRs/MAs in this overview. Nevertheless, there is still a lack of conclusive evidence due to methodological limitations in the included research. To make trustworthy judgments regarding the efficacy of probiotics in the treatment of RA, more large-scale, high-quality randomized controlled trials are still required.


Assuntos
Artrite Reumatoide , Probióticos , Revisões Sistemáticas como Assunto , Probióticos/uso terapêutico , Artrite Reumatoide/terapia , Humanos , Resultado do Tratamento , Metanálise como Assunto
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