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1.
Stroke ; 54(9): 2442-2445, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37497674

RESUMO

BACKGROUND: Experimental studies have demonstrated the neuroprotection of ischemic postconditioning (IPostC) in acute ischemic stroke by attenuating ischemia-reperfusion injury. This study aimed to investigate the safety and tolerability of direct IPostC in both a dog model and patients with acute ischemic stroke treated with thrombectomy. METHODS: The study involved 2 parts. First, IPostC was induced by repeated balloon inflation and deflation in dogs, where a low-pressure balloon was navigated to the anterior spinal artery, and 4 cycles of 5-minute ischemia followed by 5-minute reperfusion were performed. Vascular injuries were assessed using angiography and vascular tissue specimens. Then, a 3+3 dose-escalation trial was conducted in patients with acute ischemic stroke following successful thrombectomy recanalization. Patients received direct IPostC with ischemia and reperfusion durations in progressive increments of 0, 1, 2, 3, 4, and 5 minutes ×4 cycles. Major adverse responses were defined as vessel perforation, rupture, dissection, reocclusion, severe vasospasm, thrombotic events, and rupture of the balloon. RESULTS: IPostC was investigated in 4 dogs. No vessel perforation or rupture, dissection, or vasospasm was observed under the angiography. Only 1 vessel experienced mild injury between the intima and the internal elastic membrane detected on a histopathologic slide. Then, 18 patients were recruited. The duration of IPostC was progressively escalated with no major response happened. No patient experienced agitation, discomfort, or other tolerability issues. Five patients (27.8%) experienced any intracranial hemorrhage after thrombectomy, and 1 (5.6%) was symptomatic. At 3-month follow-up, no patient died, and 9 patients (50%) achieved functional independence. CONCLUSIONS: Direct IPostC inducing by 4 cycles of 5-minute ischemia followed by 5-minute reperfusion is safe, feasible, and tolerable in patients with acute ischemic stroke treated with thrombectomy. Further investigations are needed to determine the safety and preliminary efficacy of direct IPostC. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05153655.


Assuntos
Isquemia Encefálica , Pós-Condicionamento Isquêmico , AVC Isquêmico , Traumatismo por Reperfusão , Acidente Vascular Cerebral , Animais , Cães , Traumatismo por Reperfusão/prevenção & controle , Hemorragias Intracranianas , Trombectomia/efeitos adversos , Acidente Vascular Cerebral/cirurgia , Isquemia Encefálica/cirurgia , Resultado do Tratamento
2.
Int J Mol Sci ; 23(19)2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36233122

RESUMO

Hydrogen sulfide (H2S), as an endogenous gaseous signaling molecule, plays an important role in the inflammatory process. Our previous study found that Cystathionine-γ-lyase (CTH) and H2S are correlated with the occurrence and development of Clinical Mastitis (CM) in Holstein cows. However, the functions and regulatory mechanisms of CTH/H2S are still unknown. In this study, the inflammatory mammary cell model based on the MAC-T cell line was established by Lipopolysaccharide (LPS)-induced manner to further explore the function and regulatory mechanism of CTH/H2S in cows with CM. In the inflammatory MAC-T cell, the CTH expression and H2S production were both repressed in an LPS-dose dependent manner, which demonstrated that CTH/H2S is related to the progression of inflammation. The inhibition of CTH/H2S using a selective CTH inhibitor, ß-cyano-l-Alanine (BCA), promoted LPS-induced inflammation response and the expression of inflammatory cytokines. However, this was reversed by the H2S donor NaHS, demonstrating that H2S can protect cells from inflammatory damage. Intriguingly, interleukin-8 (IL-8) showed an inverse expression pattern correlated with the H2S-mediated cell protection effect during the inflammation process, and the inhibition test using a selective IL-8 receptor antagonist, SB225002, showed that IL-8 signaling plays a critical role in mediating endogenous H2S synthesis, and CTH/H2S exerts its anti-inflammation via IL-8-mediated signaling. This study provided support for the prevention and treatment of CM and the development of a novel anti-inflammatory strategy.


Assuntos
Sulfeto de Hidrogênio , Lipopolissacarídeos , Animais , Anti-Inflamatórios , Bovinos , Cistationina , Cistationina gama-Liase/metabolismo , Citocinas , Feminino , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/farmacologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-8 , Lipopolissacarídeos/toxicidade , Linfócitos T/metabolismo
3.
J Neuroinflammation ; 18(1): 133, 2021 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-34118948

RESUMO

BACKGROUND: Brain ischemia compromises natural killer (NK) cell-mediated immune defenses by acting on neurogenic and intracellular pathways. Less is known about the posttranscriptional mechanisms that regulate NK cell activation and cytotoxicity after ischemic stroke. METHODS: Using a NanoString nCounter® miRNA array panel, we explored the microRNA (miRNA) profile of splenic NK cells in mice subjected to middle cerebral artery occlusion. Differential gene expression and function/pathway analysis were applied to investigate the main functions of predicted miRNA target genes. miR-1224 inhibitor/mimics transfection and passive transfer of NK cells were performed to confirm the impact of miR-1224 in NK cells after brain ischemia. RESULTS: We observed striking dysregulation of several miRNAs in response to ischemia. Among those miRNAs, miR-1224 markedly increased 3 days after ischemic stroke. Transfection of miR-1224 mimics into NK cells resulted in suppression of NK cell activity, while an miR-1224 inhibitor enhanced NK cell activity and cytotoxicity, especially in the periphery. Passive transfer of NK cells treated with an miR-1224 inhibitor prevented the accumulation of a bacterial burden in the lungs after ischemic stroke, suggesting an enhanced immune defense of NK cells. The transcription factor Sp1, which controls cytokine/chemokine release by NK cells at the transcriptional level, is a predicted target of miR-1224. The inhibitory effect of miR-1224 on NK cell activity was blocked in Sp1 knockout mice. CONCLUSIONS: These findings indicate that miR-1224 may serve as a negative regulator of NK cell activation in an Sp1-dependent manner; this mechanism may be a novel target to prevent poststroke infection specifically in the periphery and preserve immune defense in the brain.


Assuntos
Encéfalo/metabolismo , AVC Isquêmico/metabolismo , Células Matadoras Naturais/metabolismo , Células Matadoras Naturais/patologia , MicroRNAs/metabolismo , Transdução de Sinais , Fator de Transcrição Sp1/metabolismo , Animais , Encéfalo/diagnóstico por imagem , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Infarto da Artéria Cerebral Média/diagnóstico por imagem , Infarto da Artéria Cerebral Média/metabolismo , AVC Isquêmico/diagnóstico por imagem , Células Matadoras Naturais/imunologia , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL
4.
Opt Express ; 28(21): 30701-30709, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33115065

RESUMO

In this paper, an on-chip silicon polarization beam splitter using a particle-swarm-optimized counter-tapered directional coupler is proposed, designed, and fabricated. The coupling length of the proposed device is only 5 µm. As the waveguide width variation ΔW increases from -20 to 20 nm, the simulated polarization extinction ratio larger than 18.67 dB and the corresponding insertion loss lower than 0.17 dB are achieved. Measured experimental results achieved insertion loss <0.50 dB, TE polarization extinction between 16.68 to 31.87 dB, TM polarization extinction between 17.78 to 31.13 dB, over the wavelength range 1525 to 1600 nm.

5.
Opt Lett ; 44(2): 403-406, 2019 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-30644911

RESUMO

An integrated flexible-grid 1×2 wavelength-selective switch based on reconfigurable add-drop silicon microring resonators using strip waveguides is designed and experimentally demonstrated. By flexibly tuning the resonance of microring resonators and path phase differences via the thermo-optic effect, the transmission spectra with adjustable bandwidths can be formed as desired at the output ports. Our experimental results reveal that the fabricated flexible-grid 1×2 wavelength-selective switch provides crosstalk lower than -10.39 dB. The 3-dB bandwidth varies from 0.38 nm to 1 nm, the in-band ripple is less than 0.52 dB, and the response time is about 17.6 µs.

6.
Arch Orthop Trauma Surg ; 139(11): 1617-1624, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31372713

RESUMO

PURPOSE: To identify the efficacy of isolated trochleoplasty (TP) as an independent treatment for severe trochlear dysplasia compared with TP combined with medial patellofemoral ligament (MPFL) reconstruction. METHODS: Search of current literature using terms (trochleoplasty and medial patellofemoral ligament reconstruction) in the electronic search engines PubMed and Embase, and Medline databases was performed on February 25, 2018, and it yielded 515 abstracts for review. At the end of the search, six articles met specific inclusion criteria and were included in this review. Means were calculated for population size, age and follow-up time. The Kujala score was analyzed as the primary clinical outcome parameter in the meta-analysis. Pooled estimates were calculated for postoperative complications. RESULTS: Six studies with a total of 192 knees (168 patients) were included in this analysis. The isolated TP group comprised of 3 articles with a total of 111 knees, and the TP combined with MPFL group comprised of 3 articles with a total of 81 knees. At the final follow-up, the preoperative Kujala score increased significantly by 21.39 (95% CI 18.94, 23.84; P < 0.00001) points in the isolated TP group and by 24.91 (95% CI 15.47, 34.36; P < 0.00001) points in the TP combined with MPFL group. The rates of subjective patellar instability including subluxation and anterior knee pain were 1.03% and8.45% respectively. Meanwhile, the rate of objective patellar redislocation was 2.06% in isolated TP group and 0% in TP combined with MFPL group. A total of 8.24% returned to the operating room for additional procedures in the isolated TP group and 7.04% in the TP combined with MPFL group. CONCLUSION: Trochleoplasty is a useful and reliable surgical technique to improve patellofemoral instability in patients with a dysplastic trochlea. However, it as isolated treatment for patients has lower outcome and higher residual instability compared with combined MPFL and trochleoplasty.


Assuntos
Instabilidade Articular , Articulação do Joelho/cirurgia , Ligamentos Articulares/cirurgia , Procedimentos Ortopédicos , Luxação Patelar/cirurgia , Humanos , Instabilidade Articular/epidemiologia , Instabilidade Articular/etiologia , Procedimentos Ortopédicos/efeitos adversos , Procedimentos Ortopédicos/métodos , Procedimentos Ortopédicos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Reoperação/estatística & dados numéricos
7.
Clin Exp Hypertens ; 40(3): 213-217, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29420090

RESUMO

OBJECTIVES: (1) To investigate the expression patterns of MΦ1 and MΦ2 phenotype markers of peripheral blood monocyte (PBMC)-derived macrophages in atherosclerosis patients and healthy controls, as well as the expression correlation among these genes. (2) To elucidate whether a high level of liver X receptor α (LXRα) expression is associated with anti-inflammatory MΦ2-type polarization. DESIGN: Peripheral blood monocytes (PBMCs) were obtained from 28 patients with carotid artery plaques and 10 normal persons, who did not have carotid artery plaques. M1 and M2 phenotype markers were analyzed after cellular differentiation into macrophages. Human macrophages derived from healthy donors were transfected with plasmid DNA encoding LXRα and control null-plasmids. Gene expression levels were quantified after further differentiation. RESULTS: Three genes (LXRα, CD68, and CD36) were expressed at a significantly lower rate in the atherosclerotic group than normal patients. There were correlations between the expression of LXRα, CD68, and peroxisome proliferator-activated receptor (PPARγ), and between CD163, CD36 and scavenger receptor class A (SRA1). Macrophages over-expressing LXRα exhibited enhanced expression level of MΦ2-type genes and decreased expression level of MΦ1-type genes. CONCLUSIONS: PBMCs from healthy persons were predisposed to the MΦ2 differentiation phenotype, which exhibits elevated cholesterol uptake and anti-inflammatory properties. LXRα over-expression polarizes macrophages towards the anti-inflammatory MΦ2 phenotype.


Assuntos
Aterosclerose/genética , Diferenciação Celular/genética , Expressão Gênica , Receptores X do Fígado/genética , Macrófagos/metabolismo , Antígenos CD/genética , Antígenos de Diferenciação Mielomonocítica/genética , Antígenos CD36/genética , Estudos de Casos e Controles , Células Cultivadas , Humanos , Hipertensão/metabolismo , Inflamação/fisiopatologia , Leucócitos Mononucleares , Macrófagos/fisiologia , PPAR gama/genética , Fenótipo , Cultura Primária de Células , Receptores de Superfície Celular/genética , Receptores Depuradores Classe A/genética , Transfecção
8.
Am J Cancer Res ; 14(5): 2439-2452, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38859830

RESUMO

lncRNA PTCSC3, which stands for Papillary Thyroid Carcinoma Susceptibility Candidate 3, has been found to play a role in various cellular processes, including cell proliferation, apoptosis, and migration, acting as either an oncogene or a tumor suppressor depending on the context. This study investigates the influence of lncRNA PTCSC3, derived from human bone marrow mesenchymal stem cell (hBMSC), on the efficacy of erlotinib (Er)-resistant lung adenocarcinoma (LUAD) cells and elucidates underlying mechanism. The hBMSCs and LUAD (PC9 and A549) cells were employed to establish an Er-resistant LUAD cell model. It was observed that exposure to hBMSCs reduced the viability of A549-Er and PC9-Er cells and increased their rate of apoptosis. Further investigations revealed that in the presence of hBMSCs-containing medium, PTCSC3 expression was significantly upregulated, concomitantly with a suppression of the Wnt/ß-Catenin pathway. Conversely, silencing PTCSC3 led to enhanced A549-Er and PC9-Er activities, reduced cell apoptosis, and activated Wnt/ß-Catenin pathway. The effects of PTCSC3 modulation were also examined by transfecting LUAD cells with different PTCSC3 expression vectors and treating them with XAV939, a Wnt/ß-Catenin pathway inhibitor, which similarly decreased cell viability. In the rescue experiment, the effect of hBMSCs on LUAD cells could be counteracted by down-regulation of PTCSC3, and the effect of PTCSC3 down-regulation on cells was mitigated by XAV939. This study revealed that hBMSCs promote the up-regulation of PTCSC3 in LUAD cells, thus inhibiting Wnt/ß-Catenin pathway and reversing Er resistance, offering a potential novel strategy to enhance the efficacy of chemotherapy in LUAD.

9.
Medicine (Baltimore) ; 103(16): e37831, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38640322

RESUMO

Oral squamous cell carcinoma (OSCC) is a malignant tumor that occurs in oral cavity and is dominated by squamous cells. The relationship between CDK1, CCNA2, and OSCC is still unclear. The OSCC datasets GSE74530 and GSE85195 configuration files were downloaded from the Gene Expression Omnibus (GEO) database and were derived from platforms GPL570 and GPL6480. Differentially expressed genes (DEGs) were screened. The weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, construction and analysis of protein-protein interaction (PPI) network, Comparative Toxicogenomics Database analysis were performed. Gene expression heatmap was drawn. TargetScan was used to screen miRNAs that regulate central DEGs. A total of 1756 DEGs were identified. According to Gene Ontology (GO) analysis, they were predominantly enriched in processes related to organic acid catabolic metabolism, centromeric, and chromosomal region condensation, and oxidoreductase activity. In Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, the DEGs were mainly concentrated in metabolic pathways, P53 signaling pathway, and PPAR signaling pathway. Weighted gene co-expression network analysis was performed with a soft-thresholding power set at 9, leading to the identification of 6 core genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1). The gene expression heatmap revealed that core genes (CDK1, CCNA2) were highly expressed in OSCC samples. Comparative Toxicogenomics Database analysis demonstrated associations between the 6 genes (BUB1B, CCNB1, KIF20A, CCNA2, CDCA8, CDK1) and oral tumors, precancerous lesions, inflammation, immune system disorders, and tongue tumors. The associated miRNAs for CDK1 gene were hsa-miR-203a-3p.2, while for CCNA2 gene, they were hsa-miR-6766-3p, hsa-miR-4782-3p, and hsa-miR-219a-5p. CDK1 and CCNA2 are highly expressed in OSCC. The higher the expression of CDK1 and CCNA2, the worse the prognosis.


Assuntos
Proteína Quinase CDC2 , Carcinoma de Células Escamosas , Ciclina A2 , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Proteína Quinase CDC2/genética , Proteína Quinase CDC2/metabolismo , Biologia Computacional , Ciclina A2/genética , Ciclina A2/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/genética , Redes Reguladoras de Genes , Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/genética , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
10.
Aging (Albany NY) ; 162024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38568110

RESUMO

OBJECTIVE: Adenoid cystic carcinoma (ACC) is a tumor type derived from glands. However, relationship between CCNA2 and KIF23, and adenoid cystic carcinoma remains unclear. METHODS: GSE36820 and GSE88804 profiles for ACC were obtained from the Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) were identified, and Weighted Gene Co-expression Network Analysis (WGCNA) was conducted. Subsequently, the construction and analysis of protein-protein interaction (PPI) network, functional enrichment analysis, and Gene Set Enrichment Analysis (GSEA) were performed. A gene expression heat map was generated to visually depict the expression difference of core genes between adenoid cystic carcinoma and normal samples. TargetScan was employed to identify miRNAs that regulated central DEGs. Western blotting (WB) was conducted for cell verification. RESULTS: A total of 885 DEGs were identified. GO and KEGG analyses revealed their main enrichment in responses to chemical stimuli, cell proliferation, tissue development, and regulation of cell proliferation. The GO and KEGG results indicated significant enrichment in aldosterone-regulated sodium reabsorption, the cell cycle, and the PPAR signaling pathway. Notably, core genes (CCNA2 and KIF23) were found to be highly expressed in Adenoid Cystic Carcinoma samples and expressed at low levels in normal samples. WB validated the overexpression of CCNA2 and KIF23 in the Adenoid Cystic Carcinoma group, confirming the protein-level changes associated with cell cycle, metastasis, apoptosis, and inflammatory factors in Adenoid Cystic Carcinoma groups with gene overexpression and knockout. CONCLUSIONS: CCNA2 and KIF23 exhibit high expression levels in ACC, suggesting their potential role as molecular targets for this malignancy.

11.
ArXiv ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38947937

RESUMO

Tails used as inertial appendages induce body rotations of animals and robots-a phenomenon that is governed largely by the ratio of the body and tail moments of inertia. However, vertebrate tails have more degrees of freedom (e.g., number of joints, rotational axes) than most current theoretical models and robotic tails. To understand how morphology affects inertial appendage function, we developed an optimization-based approach that finds the maximally effective tail trajectory and measures error from a target trajectory. For tails of equal total length and mass, increasing the number of equal-length joints increased the complexity of maximally effective tail motions. When we optimized the relative lengths of tail bones while keeping the total tail length, mass, and number of joints the same, this optimization-based approach found that the lengths match the pattern found in the tail bones of mammals specialized for inertial maneuvering. In both experiments, adding joints enhanced the performance of the inertial appendage, but with diminishing returns, largely due to the total control effort constraint. This optimization-based simulation can compare the maximum performance of diverse inertial appendages that dynamically vary in moment of inertia in 3D space, predict inertial capabilities from skeletal data, and inform the design of robotic inertial appendages.

12.
Animals (Basel) ; 14(9)2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38731279

RESUMO

The type II Na/Pi co-transporter (NaPi2b), encoded by the solute carrier (SLC) transporter 34A2 (SLC34A2), is responsible for calcium (Ca) and phosphorus (P) homeostasis. Unbalanced Ca/P metabolism induces mastitis in dairy cows. However, the specific role of SLC34A2 in regulating this imbalance in Holstein cows with clinical mastitis (CM) remains unclear. The aim of this study was to investigate the role of SLC34A2 and identify differentially expressed proteins (DEPs) that interact with SLC34A2 and are associated with Ca/P metabolism in dairy cows with CM. Immunohistochemical and immunofluorescence staining results showed that SLC34A2 was located primarily in the mammary epithelial cells of the mammary alveoli in both the control (healthy cows, Con/C) and CM groups. Compared to the Con/C group, the relative expression of the SLC34A2 gene and protein were significantly downregulated in the CM group. We identified 12 important DEPs included in 11 GO terms and two pathways interacting with SLC34A2 using data-independent acquisition proteomics. The PPI (protein-and-protein interaction) network results suggested that these DEPs were associated with ion metabolism and homeostasis, especially SLC34A2. These results demonstrate that SLC34A2 downregulation is negatively correlated with the occurrence and development of CM in Holstein cows, providing a basis for exploring the function and regulatory mechanism of SLC34A2 in Ca/P metabolism and homeostasis in Holstein cows with CM.

13.
Onco Targets Ther ; 17: 131-144, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38405176

RESUMO

Objective: This work aimed to explore the prognostic risk factors of lung cancer (LC) patients and establish a line chart prediction model. Methods: A total of 322 LC patients were taken as the study subjects. They were randomly divided into a training set (n = 202) and a validation set (n = 120). Basic information and laboratory indicators were collected, and the progression-free survival (PFS) and overall survival (OS) were followed up. Single-factor and cyclooxygenase (COX) multivariate analyses were performed on the training set to construct a Nomogram prediction model, which was validated with 120 patients in the validation set, and Harrell's consistency was analyzed. Results: Single-factor analysis revealed significant differences in PFS (P<0.05) between genders, body mass index (BMI), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), squamous cell carcinoma antigen (SCCA), treatment methods, treatment response evaluation, smoking status, presence of pericardial effusion, and programmed death ligand 1 (PD-L1) at 0 and 1-50%. Significant differences in OS (P<0.05) were observed for age, tumor location, treatment methods, White blood cells (WBC), uric acid (UA), CA125, pro-gastrin-releasing peptide (ProGRP), SCCA, cytokeratin fragment 21 (CYFRA21), and smoking status. COX analysis identified male gender, progressive disease (PD) as treatment response, and SCCA > 1.6 as risk factors for LC PFS. The consistency indices of the line chart models for predicting PFS and OS were 0.782 and 0.772, respectively. Conclusion: Male gender, treatment response of PD, and SCCA > 1.6 are independent risk factors affecting the survival of LC patients. The PFS line chart model demonstrates good concordance.

14.
Brain Res ; 1838: 148988, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38729332

RESUMO

Poly (ADP-ribose) polymerase (PARP) inhibitors have potent anti-inflammatory effects, including the suppression of brain microglial activation. Veliparib, a well-known PARP1/2 inhibitor, exhibits particularly high brain penetration, but its effects on stroke outcome is unknown. Here, the effects of veliparib on the short-term outcome of intracerebral hemorrhage (ICH), the most lethal type of stroke, were investigated. Collagenase-induced mice ICH model was applied, and the T2-weighted magnetic resonance imaging was performed to evaluate lesion volume. Motor function and hematoma volume were also measured. We further performed immunofluorescence, enzyme linked immunosorbent assay, flow cytometry, and blood-brain barrier assessment to explore the potential mechanisms. Our results demonstrated veliparib reduced the ICH lesion volume dose-dependently and at a dosage of 5 mg/kg, veliparib significantly improved mouse motor function and promoted hematoma resolution at days 3 and 7 post-ICH. Veliparib inhibited glial activation and downregulated the production of pro-inflammatory cytokines. Veliparib significantly decreased microglia counts and inhibited peripheral immune cell infiltration into the brain on day 3 after ICH. Veliparib improved blood-brain barrier integrity at day 3 after ICH. These findings demonstrate that veliparib improves ICH outcome by inhibiting inflammatory responses and may represent a promising novel therapy for ICH.


Assuntos
Benzimidazóis , Hemorragia Cerebral , Hematoma , Inibidores de Poli(ADP-Ribose) Polimerases , Animais , Benzimidazóis/farmacologia , Hemorragia Cerebral/tratamento farmacológico , Camundongos , Hematoma/tratamento farmacológico , Masculino , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inflamação/tratamento farmacológico , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo , Modelos Animais de Doenças , Fármacos Neuroprotetores/farmacologia , Camundongos Endogâmicos C57BL , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Citocinas/metabolismo
15.
Sci Rep ; 14(1): 5709, 2024 03 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459090

RESUMO

There is increasing evidence of abnormal neurodevelopmental outcomes in preterm infants with low-grade intraventricular hemorrhage (IVH). The purpose of the study was to explore whether brain microstructure and volume are associated with neuro-behavioral outcomes at 40 weeks corrected gestational age in preterm infants with low-grade IVH. MR imaging at term-equivalent age (TEA) was performed in 25 preterm infants with mild IVH (Papile grading I/II) and 40 control subjects without IVH. These subjects all had neonatal behavioral neurological assessment (NBNA) at 40 weeks' corrected age. Microstructure and volume evaluation of the brain were performed by using diffusion kurtosis imaging (DKI) and Synthetic MRI. Correlations among microstructure parameters, volume, and developmental outcomes were explored by using Spearman's correlation. In preterm infants with low-grade IVH, the volume of brain parenchymal fraction (BPF) was reduced. In addition, mean kurtosis (MK), fractional anisotropy (FA), radial kurtosis (RK), axial kurtosis (AK) in several major brain regions were reduced, while mean diffusivity (MD) was increased (P < 0.05). BPF, RK in the cerebellum, MK in the genu of the corpus callosum, and MK in the thalamus of preterm infants with low-grade IVH were associated with lower NBNA scores (r = 0.831, 0.836, 0.728, 0.772, P < 0.05). DKI and Synthetic MRI can quantitatively evaluate the microstructure alterations and brain volumes in preterm infants with low-grade IVH, which provides clinicians with a more comprehensive and accurate neurobehavioral assessment of preterm infants with low-grade IVH.


Assuntos
Doenças do Prematuro , Recém-Nascido Prematuro , Lactente , Humanos , Recém-Nascido , Encéfalo/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/complicações , Imagem de Tensor de Difusão/métodos , Imageamento por Ressonância Magnética , Doenças do Prematuro/diagnóstico por imagem
16.
Nat Med ; 30(5): 1395-1405, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693247

RESUMO

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.


Assuntos
Paralisia Cerebral , Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Heterogeneidade Genética , Humanos , Paralisia Cerebral/genética , Feminino , Masculino , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Exoma/genética , Lactente , Testes Genéticos , Estudos de Coortes , Predisposição Genética para Doença , Recém-Nascido
17.
ACS Omega ; 8(33): 30665-30680, 2023 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-37636917

RESUMO

High-pressure valves are an essential infrastructure for hydrogen refueling stations, and the issue of safety and reliability of their operation affects the efficiency of the entire hydrogen delivery system. Hydrogen ball valves are subjected to high-frequency, rapid reciprocating opening and closing for a long time, and the sealing surface between the valve seat and the ball has an uneven wear distribution problem. In this paper, a theoretical derivation of the seat wear volume and wear depth during the hydrogen ball valve adhesive wear process is presented, and a simulation model based on transient dynamics theory is established to carry out a nonlinear finite element analysis of the dynamic contact and frictional wear of the sealing structure during the opening and closing process of the hydrogen ball valve. In order to effectively reduce the wear unevenness of the sealing surface of the ball valve, a new type of valve seat sealing surface with an unequal-width structure is proposed. Comparing the sealing pressure and seat sealing surface wear depth of the ball valve before and after the improvement, the improved ball valve sealing performance is reliable, while the seat sealing surface wear distribution is more uniform.

18.
Front Neurol ; 14: 1280181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38283684

RESUMO

Background: The retrograde semi-retrieval technique (RESET) has been described as a modified technique for endovascular thrombectomy (EVT) whose safety and efficacy for intracranial atherosclerosis stenosis (ICAS) patients remain uncertain. This article presents our single-center experience, comparing RESET vs. non-RESET in ICAS patients. Materials and methods: We analyzed 327 consecutive ICAS patients who underwent EVT at Tianjin Huanhu Hospital from January 2018 and December 2022. Patients were categorized into two groups: RESET and non-RESET. The primary outcome was the first-pass effect (FPE). Secondary outcomes included successful reperfusion, functional independence at 90 days, mortality, and symptomatic intracranial hemorrhage (sICH). Results: RESET was significantly associated with FPE [adjusted odds ratio (aOR) 2.00, 95% confidence interval (CI) 1.03-3.87, p = 0.040]. RESET was not significantly associated with successful reperfusion (aOR 1.5, CI 0.55-4.06, p = 0.425), an mRS of 0-2 at 90 days (aOR 1.36, CI 0.83-2.21, p = 0.223), sICH (aOR 0.39, CI 0.12-1.23, p = 0.108), and mortality (aOR 0.49, CI 0.16-1.44, p = 0.193). After propensity score matching, the results were consistent with the primary analysis. Conclusion: Compared to non-RESET, patients treated with RESET showed increased FPE incidence and significantly decreased puncture-to-reperfusion time. RESET was proven to be safe and effective in enhancing reperfusion for LVO patients receiving EVT with underlying ICAS.

19.
Acad Radiol ; 30 Suppl 2: S93-S103, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37236897

RESUMO

RATIONALE AND OBJECTIVES: To develop the nomogram utilizing the American College of Radiology BI-RADS descriptors, clinical features, and apparent diffusion coefficient (ADC) to differentiate benign from malignant breast lesions. MATERIALS AND METHODS: A total of 341 lesions (161 malignant and 180 benign) were included. Clinical data and imaging features were reviewed. Univariable and multivariable logistic regression analyses were performed to determine the independent variables. ADC as a continuous or classified into binary form with a cutoff value of 1.30 × 10-3 mm2/s, incorporated other independent predictors to construct two nomograms, respectively. Receiver operating curve and calibration plot was employed to test the models' discriminative ability. The diagnostic performance between the developed model and the Kaiser score (KS) was also compared. RESULTS: In both models, high patient age, the presence of root sign, time-intensity curves (TICs) types (plateau and washout), heterogenous internal enhancement, the presence of peritumoral edema, and ADC were independently associated with malignancy. The AUCs of two multivariable models (AUC, 0.957; 95% CI: 0.929-0.976 and AUC, 0.958; 95% CI: 0.931-0.976) were significantly higher than that of the KS (AUC, 0.919, 95% CI: 0.885-0.946; both P < 0.001). At the same sensitivity of 95.7%, our models showed an increase in specificity by 5.56% (P = 0.076) and 6.11% (P = 0.035), respectively, as compared to the KS. CONCLUSION: The models incorporating MRI features (root sign, TIC, margins, internal enhancement, and presence of edema), quantitative ADC value, and patient age showed improved diagnostic performance and might have avoided more unnecessary biopsies in comparison with the KS, although further external validation is required.


Assuntos
Neoplasias da Mama , Imageamento por Ressonância Magnética Multiparamétrica , Humanos , Feminino , Diagnóstico Diferencial , Meios de Contraste , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Estudos Retrospectivos , Sensibilidade e Especificidade
20.
Animals (Basel) ; 13(12)2023 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-37370534

RESUMO

Increased poll gland secretion is a major characteristic and indicator of estrus in male Bactrian camels; however, research on these poll glands and their secretion is extremely rare. In this study, we determine the chemical composition of poll gland secretions and identify the key functional substances that regulate seasonal estrus in male camels. A GC/LC-MS dual platform was used to analyze ventral hair (control) and neck mane samples containing poll gland secretions from male Bactrian camels during estrus. Multidimensional and single-dimensional analyses were used to screen differentially expressed metabolites (DEMs) between groups. Functional prediction of enriched metabolites was performed using a Human Metabolome Database comparison and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis, which were then compared with a behavioral analysis of male Bactrian camels in estrus. A total of 1172 DEMs and 34 differential metabolic pathways were identified. One metabolite group was found to relate to steroid synthesis and metabolism, and another metabolite group was associated with neural metabolism. Therefore, we speculate that steroids and neurochemicals jointly regulate estrous behavior in male Bactrian camels, thus providing theoretical insights into the development and function of poll glands in Bactrian camels.

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