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1.
Proc Natl Acad Sci U S A ; 121(19): e2313590121, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38683978

RESUMO

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules.


Assuntos
Fator Neurotrófico Derivado do Encéfalo , Exossomos , Músculo Esquelético , Exossomos/metabolismo , Animais , Músculo Esquelético/metabolismo , Músculo Esquelético/inervação , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Camundongos , Fibronectinas/metabolismo , Neurônios Motores/metabolismo , Interleucina-6/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Neurônios/metabolismo , Fatores de Crescimento Neural/metabolismo , Miocinas
2.
Nano Lett ; 23(23): 10971-10982, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-37991895

RESUMO

Nanoparticles have emerged as potential transporters of drugs targeting Alzheimer's disease (AD), but their design should consider the blood-brain barrier (BBB) integrity and neuroinflammation of the AD brain. This study presents that aging is a significant factor for the brain localization and retention of nanoparticles, which we engineered to bind with reactive astrocytes and activated microglia. We assembled 200 nm-diameter particles using a block copolymer of poly(lactic-co-glycolic acid) (PLGA) and CD44-binding hyaluronic acid (HA). The resulting PLGA-b-HA nanoparticles displayed increased binding to CD44-expressing reactive astrocytes and activated microglia. Upon intravascular injection, nanoparticles were localized to the hippocampi of both APP/PS1 AD model mice and their control littermates at 13-16 months of age due to enhanced transvascular transport through the leaky BBB. No particles were found in the hippocampi of young adult mice. These findings demonstrate the brain localization of nanoparticles due to aging-induced BBB breakdown regardless of AD pathology.


Assuntos
Doença de Alzheimer , Nanopartículas , Camundongos , Animais , Doença de Alzheimer/metabolismo , Camundongos Transgênicos , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/metabolismo
3.
BMC Pediatr ; 23(1): 408, 2023 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-37598160

RESUMO

BACKGROUND: Scarce evidence exists on pediatric colorectal polyp risk factors. This study explored the clinical manifestations, morphological and pathological characteristics of, and risk factors for pediatric colorectal polyps. METHODS: This retrospective case-control study included children who received colonoscopy, divided into a colorectal polyp group and a normal control group based on colonoscopy results. The risk factors for colorectal polyps in children were analyzed through logistic regression analysis. RESULTS: The mean age of children with polyps was 6.77 ± 3.44 years. Polyps were detected predominantly in males (72.9%); hematochezia was the primary clinical manifestation (80.25%). Most polyps were juvenile (88.9%) and solitary (87.7%); 50.6% were located in the rectosigmoid area. Univariate analysis showed that gender (P = 0.037), age (P < 0.001), family aggregation (P < 0.001), specific immunoglobulin E (sIgE) (P < 0.001), platelet count (P = 0.001), aspartate aminotransferase (AST) (P = 0.016), meat intake (P = 0.010), and vegetable intake (P < 0.001) were significantly associated with colorectal polyps. Age ≤ 6 years (3-6 years: OR: 26.601, 95% CI: 3.761-160.910; < 3 years: OR: 22.678, 95% CI: 1.873-274.535), positive family aggregation (OR: 3.540, 95% CI: 1.177-10.643), positive sIgE (OR:2.263, 95% CI: 1.076-4.761), and higher meat intake (OR:1.046, 95% CI: 1.029-1.063) were risk factors for pediatric colorectal polyps in logistic regression analysis. Higher vegetable intake (OR: 0.993, 95% CI: 0.986-1.000) was a protective factor against pediatric colorectal polyps. The area under the curve (AUC) of meat intake in the receiver operating characteristic (ROC) curve analysis for predicting colorectal polyps was 0.607; the best cut-off value was 92.14 g/d (P = 0.010, 95% CI: 0.527-0.687). The meat and vegetable intake combination AUC in predicting pediatric colorectal polyps was 0.781 (P < 0.001, 95% CI: 0.718-0.845). CONCLUSIONS: Juvenile, solitary, and located in the rectosigmoid region polyps are most common in children. Hematochezia is the main clinical manifestation. Most polyps were, but multiple and proximally located polyps were also detected. Age ≤ 6 years, especially 3-6 years, positive family aggregation, positive sIgE, and higher meat intake are risk factors for pediatric colorectal polyps. A higher vegetable intake is a protective factor.


Assuntos
Pólipos do Colo , Masculino , Criança , Humanos , Pré-Escolar , Estudos de Casos e Controles , Estudos Retrospectivos , Pólipos do Colo/diagnóstico , Pólipos do Colo/epidemiologia , Pólipos do Colo/etiologia , China/epidemiologia , Imunoglobulina E , Fatores de Risco
4.
Ecotoxicol Environ Saf ; 254: 114701, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36871353

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are produced during combustion of organic matter, such as during cigarette smoking, and they exist widely in the environment. Exposure to 3,4-benzo[a]pyrene (BaP), as the most widely studied PAHs, relates to many cardiovascular diseases. However, the underlying mechanism of its involvement remains largely unclear. In this study, we developed a myocardial ischemia-reperfusion (I/R) injury mouse model and an oxygen and glucose deprivation-reoxygenation H9C2 cell model to evaluate the effect of BaP in I/R injury. After BaP exposure, the expression of autophagy-related proteins, the abundance of NLRP3 inflammasomes, and the degree of pyroptosis were measured. Our results show that BaP aggravates myocardial pyroptosis in a autophagy-dependent manner. In addition, we found that BaP activates the p53-BNIP3 pathway via the aryl hydrocarbon receptor to decrease autophagosome clearance. Our findings present new insights into the mechanisms underlying cardiotoxicity and reveal that the p53-BNIP3 pathway, which is involved in autophagy regulation, is a potential therapeutic target for BaP-induced myocardial I/R injury. Because PAHs are omnipresent in daily life, the toxic effects of these harmful substances should not be underestimated.


Assuntos
Traumatismo por Reperfusão Miocárdica , Camundongos , Animais , Traumatismo por Reperfusão Miocárdica/metabolismo , Piroptose , Benzo(a)pireno/toxicidade , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína Supressora de Tumor p53 , Autofagia
5.
Opt Express ; 29(9): 14016-14024, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33985127

RESUMO

Realizing vector spatiotemporal solitons that are stable in high dimensions is a long-standing goal in the study of nonlinear optical physics. Here, a scheme is proposed to generate three-dimensional (3D) vector spatiotemporal solitons in a cold atomic system with linear and nonlinear parity-time (PT) potentials by utilizing electromagnetically induced transparency (EIT). We investigate the existence and stability of these vector 3D semilunar solitons (SSs) and vortex solitons (VSs) supported by the linear and nonlinear PT potentials. The results show that these solitons have extremely low generation power and very slow propagation velocity and can stably propagate with constant total energy in this system. The frontal head-on collisions of two vector solitons feature quasi-elastic collisions. The dynamics characteristics of these solitons depend on the linear and nonlinear PT-symmetric potential parameters, in particular, the imaginary part of PT potentials. Our study provides a new route for manipulating high-dimensional nonlinear vector optical signals via the controlled optical linear and nonlinear potentials in cold atomic gases.

6.
Microb Pathog ; 147: 104292, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32505653

RESUMO

BACKGROUND AND AIMS: Helicobacter pylori (H. pylori) infection can occur in early childhood, without eradication therapies such infection can persist throughout life and cause many different diseases. This study investigated the metabolic characteristics and explored the underlying mechanism of children with H. pylori infection, and identified potential biomarkers for evaluating the efficacy of H. pylori eradication therapies. METHODS: We performed 1H NMR-based metabonomics coupled with multivariate analysis to investigate the metabolic profiling of serum samples between Children with and without H. pylori infection. In the same manner, we compared the alternations of metabolites in H. pylori-infected children before and after H. pylori eradication therapies. RESULTS: 21 metabolites from serum in H. pylori-infected and H. pylori-uninfected children were identified, which were mainly involved in energy, amino acid, lipid and microbial metabolism. We found that the serum levels of trimethylamine N-oxide and alanine were significantly higher in H. pylori-infected children compared to uninfected sera, whereas lactate was significantly lower. We also found that the levels of trimethylamine N-oxide and creatine in H. pylori-infected children was significantly decreased after H. pylori eradication therapies, whereas lactate and low-density lipoprotein/very low-density lipoprotein was significantly increased. CONCLUSIONS: This is the first study using 1H NMR-based metabolomics approach to explore the effects of H. pylori infection in children. Our results demonstrated that the disturbances of metabolism in energy, amino acids, lipids and microbiota could play an important role in the pathogenesis of gastrointestinal and extragastric diseases caused by H. pylori infection. Trimethylamine N-oxide and lactate might serve as potential serum biomarkers for evaluating the efficacy of H. pylori eradication therapies.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Microbiota , Criança , Pré-Escolar , Humanos , Metabolômica , Espectroscopia de Prótons por Ressonância Magnética
7.
J Cell Biochem ; 120(6): 10484-10494, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30614051

RESUMO

Abdominal aortic aneurysm (AAA) is an unpredictable but lethal disease that poses a therapeutic dilemma. Circular RNAs (circRNAs), whose functional roles as transcriptional regulators and microRNA (miRNA) sponges have been shown in former studies, are potential biomarkers for many diseases. AAA in male C57BL/6 J mice was induced by coadministration of angiotensin II (Ang II) and 3,4-benzopyrene (BaP). The circRNA expression profiling was performed using two samples from the control group and two samples from the AAA group. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to confirm the reliability of the microarray results. Among the 14 236 detected circRNAs, 413 showed obvious expression changes (fold change ≥ 2; P < 0.05) between the BaP/Ang II-induced AAA group and control group. Of the 413 that showed significant changes, 271 were upregulated, while the other 142 were downregulated. The expression levels of 10 circRNAs were validated by qRT-PCR. The interactions of the differentially expressed circRNAs with miRNAs were predicted. Immunofluorescence showed prominent vascular smooth muscle cell apoptosis in abdominal aortic tissues in the BaP/Ang II group. Furthermore, a circRNA-miRNA coexpression network based on six apoptosis-related circRNAs was built. The genes regulated by the network mapped to several pathways, including apoptosis, the IL-17 signaling pathway, and vascular endothelial growth factor signaling pathway, all of which are related to AAA formation. This study performed circRNA expression profiling in AAA and the results specifically predicted the regulatory role of circRNAs in AAA pathogenesis.


Assuntos
Aneurisma da Aorta Abdominal/genética , RNA Circular , Angiotensina II/toxicidade , Animais , Aneurisma da Aorta Abdominal/induzido quimicamente , Aneurisma da Aorta Abdominal/patologia , Benzo(a)pireno/toxicidade , Modelos Animais de Doenças , Ontologia Genética , Redes Reguladoras de Genes , Masculino , Camundongos Endogâmicos C57BL , MicroRNAs , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/patologia , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Transcriptoma
8.
Heart Fail Rev ; 24(3): 335-342, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30610455

RESUMO

Cardiac resynchronization therapy (CRT) has been established to improve prognosis for patients with heart failure and SR. Whether the benefit observed with CRT on survival was similar in AF patients receiving atrio-ventricular junction ablation (AVJA) or not and patients in SR remains uncertain. The primary purpose of this study was to comprehensively evaluate the impact of CRT on the outcome of survival in atrial fibrillation (AF) patients with or without AVJA and patients in sinus rhythm (SR). Medline, Embase, and the Cochrane Library were searched for inception through June 31, 2018. Two reviewers independently evaluated and extracted data from 4 studies, including a total of 7896 CRT recipients, composed of 554 AF with AVJA (CRT+AF+AVJA), 1071 AF without AVJA (CRT+AF-AVJA), and 6244 SR (CRT+SR). The benefit on survival was comparable between CRT+AF+AVJA and CRT+SR (HR = 1.00; 95% CI, 0.73-1.40). CRT+AF+AVJA and CRT+SR both were associated with significantly higher survival compared with CRT+AF-AVJA, with hazard ratio of 0.64 (95% CI, 0.46-0.91) and 0.63 (95% CI, 0.53-0.75), respectively. The survival benefit was similar for patients with CRT+AF+AVJA and CRT+SR, while it was 36-37% high as compared to CRT+AF-AVJA. Whether aggressive intervention with AVJA in AF should be routinely combined with CRT despite rate-slowing drug treatment is helpful deserves further studies.


Assuntos
Terapia de Ressincronização Cardíaca/mortalidade , Ablação por Cateter , Insuficiência Cardíaca/terapia , Síndrome do Nó Sinusal/terapia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial , Feminino , Insuficiência Cardíaca/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Metanálise em Rede , Estudos Observacionais como Assunto , Prognóstico , Síndrome do Nó Sinusal/mortalidade , Taxa de Sobrevida , Resultado do Tratamento
9.
Sensors (Basel) ; 18(7)2018 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-30037104

RESUMO

The dual-channel synthetic aperture radar (SAR) system is widely applied in the field of ground moving-target indication (GMTI). With the increase of the imaging resolution, the resulting substantial raw data samples increase the transmission and storage burden. We tackle the problem by adopting the joint sparsity model 1 (JSM-1) in distributed compressed sensing (DCS) to exploit the correlation between the two channels of the dual-channel SAR system. We propose a novel algorithm, namely the hierarchical variational Bayesian based distributed compressed sensing (HVB-DCS) algorithm for the JSM-1 model, which decouples the common component from the innovation components by applying variational Bayesian approximation. Using the proposed HVB-DCS algorithm in the dual-channel SAR based GMTI (SAR-GMTI) system, we can jointly reconstruct the dual-channel signals, and simultaneously detect the moving targets and stationary clutter, which enables sampling at a further lower rate in azimuth as well as improves the reconstruction accuracy. The simulation and experimental results show that the proposed HVB-DCS algorithm is capable of detecting multiple moving targets while suppressing the clutter at a much lower data rate in azimuth compared with the compressed sensing (CS) and range-Doppler (RD) algorithms.

10.
Pediatr Surg Int ; 33(5): 575-580, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28124113

RESUMO

BACKGROUND: Intestinal necrosis is the most serious complication of intussusception. The risk factors associated with intestinal necrosis in pediatric patients with intussusception have not been well characterized. OBJECTIVE: This study aimed to investigate the risk factors associated with intestinal necrosis in pediatric patients with failed non-surgical reduction for intussusception. METHODS: Hospitalized patients who failed the air-enema reduction for intussusception in the outpatient department and subsequently underwent surgery were retrospectively reviewed. All cases were categorized into two groups: intestinal necrosis group and non-intestinal necrosis group based on the surgical findings. Demographic and clinical features including the findings from the surgery were recorded and analyzed. Factors associated with intestinal necrosis were analyzed using univariate and multivariate unconditional logistic regression analyses. RESULTS: A total of 728 cases were included. Among them, 171 had intestinal necrosis at the time of surgery. The group with intestinal necrosis had a longer duration of symptom or length of illness (P = 0.000), and younger (P = 0.000) than the non-intestinal necrosis group. Complex/compound type of intussusceptions is more likely to have intestinal necrosis. Multivariate analysis showed that the presence of grossly bloody stool (OR = 2.12; 95% CI 1.19-3.76, P = 0.010) and duration of symptom (OR = 1.07; 95% CI 1.06-1.08, P = 0.000) were independent risk factors for intestinal necrosis in patients hospitalized for surgical reduction for intussusceptions. CONCLUSION: At time of admission, the presence of bloody stools and duration of symptom are the important risk factors for developing intestinal necrosis for those patients who failed non-surgical reduction. The length of illness has the highest sensitivity and specificity to correlate with intestinal necrosis. This finding may suggest that we should take the intussusception cases that have the longer duration of symptom directly to operation room for reduction.


Assuntos
Intestinos/patologia , Intussuscepção/complicações , Intussuscepção/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Intestinos/cirurgia , Intussuscepção/cirurgia , Modelos Logísticos , Masculino , Necrose , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Falha de Tratamento , Resultado do Tratamento
11.
Sensors (Basel) ; 17(4)2017 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-28425949

RESUMO

We consider the joint sparsity Model 1 (JSM-1) in a decentralized scenario, where a number of sensors are connected through a network and there is no fusion center. A novel algorithm, named distributed compact sensing matrix pursuit (DCSMP), is proposed to exploit the computational and communication capabilities of the sensor nodes. In contrast to the conventional distributed compressed sensing algorithms adopting a random sensing matrix, the proposed algorithm focuses on the deterministic sensing matrices built directly on the real acquisition systems. The proposed DCSMP algorithm can be divided into two independent parts, the common and innovation support set estimation processes. The goal of the common support set estimation process is to obtain an estimated common support set by fusing the candidate support set information from an individual node and its neighboring nodes. In the following innovation support set estimation process, the measurement vector is projected into a subspace that is perpendicular to the subspace spanned by the columns indexed by the estimated common support set, to remove the impact of the estimated common support set. We can then search the innovation support set using an orthogonal matching pursuit (OMP) algorithm based on the projected measurement vector and projected sensing matrix. In the proposed DCSMP algorithm, the process of estimating the common component/support set is decoupled with that of estimating the innovation component/support set. Thus, the inaccurately estimated common support set will have no impact on estimating the innovation support set. It is proven that under the condition the estimated common support set contains the true common support set, the proposed algorithm can find the true innovation set correctly. Moreover, since the innovation support set estimation process is independent of the common support set estimation process, there is no requirement for the cardinality of both sets; thus, the proposed DCSMP algorithm is capable of tackling the unknown sparsity problem successfully.

12.
BMC Complement Altern Med ; 16(1): 297, 2016 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-27543143

RESUMO

BACKGROUND: Memory loss is the most prominent symptoms of brain aging, but there is currently no evidence-based treatment strategy. Acupuncture has been widely used in China and the effectiveness for improving learning and memory has been mentioned in previous studies. We conducted this systematic review and meta-analysis to evaluate the effectiveness of acupuncture for improving learning and memory in animal experiments. METHODS: We searched Pubmed, Embase, Ovid Medline(R), the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical Database (VIP) and Wanfang data Information Site to collect studies published up to December 2015. Study quality for each included article was evaluated according to the CAMARADES 10-item checklist. Outcome measure is Morris water maze. A meta-analysis was conducted according to the Cochrane systematic review method by using RevMan 5.3 software. RESULTS: Forty-two studies involving 944 animals were included. The quality score of the studies ranged from 2 to 8, with a mean of 5.3. Meta-analysis results showed that 24 studies reported significant effect of acupuncture for decreasing escape latency (-3.00, 95 % CI: -3.78 ~ -2.23, P < 0.00001), 14 studies reported significant effect of acupuncture for increasing frequency of cross platform (2.57, 95 % CI: 1.92 ~ 3.22, P < 0.00001), and 7 studies reported significant effect of acupuncture for increasing time in target quadrant (2.00, 95 % CI: 1.10 ~ 2.91, P < 0.00001) compared with the control group. CONCLUSIONS: These findings show acupuncture has a potential role in improving learning and memory ability in animal models, suggesting it as a candidate therapy for memory loss of aged brain.


Assuntos
Terapia por Acupuntura , Aprendizagem em Labirinto/fisiologia , Memória/fisiologia , Animais
13.
Plant J ; 77(1): 1-15, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24164574

RESUMO

Arabidopsis AGL13 is a member of the AGL6 clade of the MADS box gene family. GUS activity was specifically detected from the initiation to maturation of both pollen and ovules in AGL13:GUS Arabidopsis. The sterility of the flower with defective pollen and ovules was found in AGL13 RNAi knockdown and AGL13 + SRDX dominant-negative mutants. These results indicate that AGL13 acts as an activator in regulation of early initiation and further development of pollen and ovules. The production of similar floral organ defects in the severe AGL13 + SRDX and SEP2 + SRDX plants and the similar enhancement of AG nuclear localization efficiency by AGL13 and SEP3 proteins suggest a similar function for AGL13 and E functional SEP proteins. Additional fluorescence resonance energy transfer (FRET) analysis indicated that, similar to SEP proteins, AGL13 is able to interact with AG to form quartet-like complexes (AGL13-AG)2 and interact with AG-AP3-PI to form a higher-order heterotetrameric complex (AGL13-AG-AP3-PI). Through these complexes, AGL13 and AG could regulate the expression of similar downstream genes involved in pollen morphogenesis, anther cell layer formation and the ovule development. AGL13 also regulates AG/AP3/PI expression by positive regulatory feedback loops and suppresses its own expression through negative regulatory feedback loops by activating AGL6, which acts as a repressor of AGL13. Our data suggest that AGL13 is likely a putative ancestor for the E functional genes which specifies male and female gametophyte morphogenesis in plants during evolution.


Assuntos
Proteínas de Arabidopsis/genética , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas , Modelos Biológicos , Arabidopsis/citologia , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/metabolismo , Flores/citologia , Flores/genética , Flores/crescimento & desenvolvimento , Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Genes Reporter , Proteínas de Domínio MADS/genética , Proteínas de Domínio MADS/metabolismo , Mutação , Especificidade de Órgãos , Óvulo Vegetal/citologia , Óvulo Vegetal/genética , Óvulo Vegetal/crescimento & desenvolvimento , Fenótipo , Plantas Geneticamente Modificadas , Pólen/citologia , Pólen/genética , Pólen/crescimento & desenvolvimento , Multimerização Proteica , Interferência de RNA
14.
Nano Converg ; 11(1): 18, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689075

RESUMO

Ischemia-reperfusion injury (IRI) poses significant challenges across various organ systems, including the heart, brain, and kidneys. Exosomes have shown great potentials and applications in mitigating IRI-induced cell and tissue damage through modulating inflammatory responses, enhancing angiogenesis, and promoting tissue repair. Despite these advances, a more systematic understanding of exosomes from different sources and their biotransport is critical for optimizing therapeutic efficacy and accelerating the clinical adoption of exosomes for IRI therapies. Therefore, this review article overviews the administration routes of exosomes from different sources, such as mesenchymal stem cells and other somatic cells, in the context of IRI treatment. Furthermore, this article covers how the delivered exosomes modulate molecular pathways of recipient cells, aiding in the prevention of cell death and the promotions of regeneration in IRI models. In the end, this article discusses the ongoing research efforts and propose future research directions of exosome-based therapies.

15.
Int Immunopharmacol ; 126: 111241, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37984253

RESUMO

BACKGROUND: Sepsis is a systemic inflammatory syndrome that can lead to multiple organ dysfunction and life-threatening complications. Sepsis-induced myocardial dysfunction (SIMD) has been confirmed to be present in half of patients with septic shock, increasing their mortality rate to 70-90%. The pathogenesis of SIMD is complex, and no specific clinical treatment has yet been developed. Caloric restriction mimetics (CRM), compounds that simulate the biochemical and functional properties of CR, can improve cardiovascular injury by activating autophagy. This study investigated the effect of a new type of CRM which can induce hypoxia, the SGLT nonspecific inhibitor phlorizin on SIMD. MATERIALS AND METHODS: In vivo, phlorizin was administered at 1 mg/kg/day intragastrically for 28 days. In vitro, AC16 was treated with 120 µM phlorizin for 48 h. Echocardiography was used to assess cardiac function. Myocardial injury markers were detected in serum and cell supernatant. Western blotting was employed to detect changed proteins associated with apoptosis and autophagy. Immunofluorescence, immunohistochemistry, co-immunoprecipitation, molecular docking, and other methods were also used to illustrate cellular changes. RESULTS: In vivo, phlorizin significantly improved the survival rate and cardiac function after sepsis injury, reduced markers of myocardial injury, inhibited myocardial apoptosis and oxidative stress, and promoted autophagy. In vitro, phlorizin alleviated the apoptosis of AC16, as well as inhibited oxidative stress and apoptotic enzyme activity. Phlorizin acts on autophagy at multiple sites through low energy (activation of AMPK) and hypoxia (release of Beclin-1 by Hif-1α/Bnip3 axis), promoting the formation and degradation of autophagosomes. CONCLUSION: We indicated for the first time that phlorizin could inhibit glucose uptake via GLUT-1 and conforms to the metabolic characteristics of CRM, it can induce the hypoxic transcriptional paradigm. In addition, it inhibits apoptosis and improves SIMD by promoting autophagy generation and unobstructing autophagy flux. Moreover, it affects autophagy by releasing Beclin-1 through the Hif-1α/Bnip3 axis.


Assuntos
Autofagia , Miócitos Cardíacos , Florizina , Sepse , Florizina/farmacologia , Hipóxia , Miócitos Cardíacos/efeitos dos fármacos , Sepse/complicações , Masculino , Animais , Camundongos , Camundongos Endogâmicos C57BL , Restrição Calórica , Coração/efeitos dos fármacos , Cardiotônicos/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Apoptose
16.
Int Immunopharmacol ; 140: 112921, 2024 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-39133953

RESUMO

Effective treatment of myocardial ischemia-reperfusion (MIR) injury remains an unmet clinical need. Cardiomyocyte apoptosis is common at this stage and poses a significant risk. Corylin, a flavonoid compound extracted from Psoralea corylifolia L., has been shown to have anti-inflammatory, anticancer, and antiatherosclerotic properties. However, whether and how corylin affects MIR injury remain unclear. In this study, we explored the mechanism of corylin as a potent therapeutic agent for MI/R injury, using a left anterior descending (LAD) coronary artery ligation and oxygen-glucose deprivation and reperfusion (OGD/R) model in vivo and in vitro. TUNEL, Annexin-V/PI double staining,Ki67 immunohistochemistry, western blot analysis, and immunofluorescence were used to validate cell apoptosis level and Raf-1/ASK1 complex activity. The interaction between corylin and Raf-1/ASK1 complex was detected using molecular docking, corylin-Raf-1 binding assays, and coimmunoprecipitation (Co-IP). Moreover, TTC staining, echocardiography, HE staining, Masson trichrome staining and serological testing were performed to assess the cardioprotective effects of corylin in vivo. These findings showed that corylin reduces MIR injury-induced cardiomyocyte apoptosis and improves cardiac function. Mechanistically, corylin can interact with Raf-1 and promote the formation of the Raf-1/ASK1 complex, thus inhibiting cardiomyocyte apoptosis. In conclusion, our results demonstrate that corylin ameliorated cardiac dysfunction after MIR injury by reducing myocardial apoptosis.


Assuntos
Apoptose , MAP Quinase Quinase Quinase 5 , Traumatismo por Reperfusão Miocárdica , Miócitos Cardíacos , Proteínas Proto-Oncogênicas c-raf , Apoptose/efeitos dos fármacos , Animais , Proteínas Proto-Oncogênicas c-raf/metabolismo , Traumatismo por Reperfusão Miocárdica/tratamento farmacológico , Traumatismo por Reperfusão Miocárdica/metabolismo , Traumatismo por Reperfusão Miocárdica/patologia , Masculino , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Camundongos Endogâmicos C57BL , Camundongos , Humanos , Psoralea/química , Modelos Animais de Doenças
17.
Heliyon ; 10(1): e23537, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38169833

RESUMO

Introduction: Transcutaneous electrical acupoint stimulation (TEAS) has been proposed for postoperative urinary retention (POUR). This meta-analysis evaluated the effect of TEAS in preventing POUR. Methods: Databases were searched until February 6, 2023. Randomized controlled trials (RCTs) about TEAS for preventing POUR were included. The primary concern was the incidence of POUR, with post-void residual urine volume as a secondary outcome. Results: Fourteen studies with 2865 participants were identified. TEAS reduced the incidence of POUR (RR = 0.44, 95%CI = 0.33 to 0.58, P < 0.00001) and decreased the post-void residual urine volume (MD = -75.41 mL, 95%CI = -118.76 to -32.06, P = 0.0007). The preventive effect on POUR was found in patients receiving anorectal, gynecologic, orthopedic and biliary surgery, but not urinary surgery. Dilatational- and continuous-wave TEAS had a great outcome in preventing POUR. Intraoperative TEAS, preoperative and intraoperative TEAS, and postoperative TEAS were beneficial, and TEAS was more beneficial when compared with sham TEAS and blank control. It is nevertheless difficult to rule out publication bias. Conclusions: TEAS could prevent POUR. Due to insufficient evidence, multicenter, large-sample and high-quality RCTs should be conducted. (Registration:INPLASY202320095).

18.
Adv Sci (Weinh) ; 11(11): e2306826, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38161217

RESUMO

Motivated by the unexplored potential of in vitro neural systems for computing and by the corresponding need of versatile, scalable interfaces for multimodal interaction, an accurate, modular, fully customizable, and portable recording/stimulation solution that can be easily fabricated, robustly operated, and broadly disseminated is presented. This approach entails a reconfigurable platform that works across multiple industry standards and that enables a complete signal chain, from neural substrates sampled through micro-electrode arrays (MEAs) to data acquisition, downstream analysis, and cloud storage. Built-in modularity supports the seamless integration of electrical/optical stimulation and fluidic interfaces. Custom MEA fabrication leverages maskless photolithography, favoring the rapid prototyping of a variety of configurations, spatial topologies, and constitutive materials. Through a dedicated analysis and management software suite, the utility and robustness of this system are demonstrated across neural cultures and applications, including embryonic stem cell-derived and primary neurons, organotypic brain slices, 3D engineered tissue mimics, concurrent calcium imaging, and long-term recording. Overall, this technology, termed "mind in vitro" to underscore the computing inspiration, provides an end-to-end solution that can be widely deployed due to its affordable (>10× cost reduction) and open-source nature, catering to the expanding needs of both conventional and unconventional electrophysiology.


Assuntos
Encéfalo , Neurônios , Eletrodos , Encéfalo/fisiologia , Neurônios/fisiologia , Estimulação Elétrica , Fenômenos Eletrofisiológicos/fisiologia
19.
Front Aging Neurosci ; 15: 1287122, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38149170

RESUMO

Background: It has been well documented that atrophy of hippocampus and hippocampal subfields is closely linked to cognitive decline in normal aging and patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). However, evidence is still sparce regarding the atrophy of hippocampus and hippocampal subfields in normal aging adults who later developed MCI or AD. Objective: To examine whether atrophy of hippocampus and hippocampal subfields has occurred in normal aging before a diagnosis of MCI or AD. Methods: We analyzed structural magnetic resonance imaging (MRI) data of cognitively normal (CN, n = 144), MCI (n = 90), and AD (n = 145) participants obtained from the Alzheimer's Disease Neuroimaging Initiative. The CN participants were categorized into early dementia converters (CN-C) and non-converters (CN-NC) based on their scores of clinical dementia rating after an average of 36.2 months (range: 6-105 months). We extracted the whole hippocampus and hippocampal subfields for each participant using FreeSurfer, and analyzed the differences in volumes of hippocampus and hippocampal subfields between groups. We then examined the associations between volume of hippocampal subfields and delayed recall scores in each group separately. Results: Hippocampus and most of the hippocampal subfields demonstrated significant atrophy during the progression of AD. The CN-C and CN-NC groups differed in the left hippocampus-amygdala transition area (HATA). Furthermore, the volume of presubiculum was significantly correlated with delayed recall scores in the CN-NC and AD groups, but not in the CN-C and MCI groups. Conclusion: Hippocampal subfield atrophy (i.e., left HATA) had occurred in cognitively normal elderly individuals before clinical symptoms were recognized. Significant associations of presubiculum with delayed recall scores in the CN-NC and AD groups highlight the essential role of the hippocampal subfields in both early dementia detection and AD progression.

20.
J Alzheimers Dis ; 93(2): 791-801, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37092228

RESUMO

BACKGROUND: Hippocampal atrophy is a significant brain marker of pathology in Alzheimer's disease (AD). The hippocampal parenchymal fraction (HPF) was recently developed to better assess the hippocampal volumetric integrity, and it has been shown to be a sensitive measure of hippocampal atrophy in AD. OBJECTIVE: To investigate the clinical relevance of hippocampal volumetric integrity as measured by the HPF and the coupling between the HPF and brain atrophy during AD progression. METHODS: We included data from 143 cognitively normal (CN), 101 mild cognitive impairment (MCI), and 125 AD participants. We examined group differences in the HPF, associations between HPF and cognitive ability, and coupling between the HPF and cortical grey matter volume in the CN, MCI, and AD groups. RESULTS: We observed progressive decreases in HPF from CN to MCI and from MCI to AD, and increases in the asymmetry of HPF, with the lowest asymmetry index (AI) in the CN group and the highest AI in the AD group. There was a significant association between HPF and cognitive ability across participants. The coupling between HPF and cortical regions was observed in bilateral hippocampus, parahippocampal gyrus, temporal, frontal, and occipital regions, thalamus, and amygdala in CN, MCI, and AD groups, with a greater involvement of temporal, occipital, frontal, and subcortical regions in MCI and AD patients, especially in AD patients. CONCLUSION: This study provides novel evidence for the neuroanatomical basis of cognitive decline and brain atrophy during AD progression, which may have important clinical implications for the prognosis of AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Imageamento por Ressonância Magnética , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/patologia , Doença de Alzheimer/patologia , Atrofia/patologia
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