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1.
RSC Adv ; 12(18): 11262-11271, 2022 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-35425033

RESUMO

By controlling the species of the organic sulfur source, CdS samples were produced with different photocatalytic performances by a low-temperature solvothermal method. Different species of the organic sulfur source were chosen as the coordination agent to control the interactions in the crystal growth process. Among them, thioacetamide was the best coordination agent. The hydrophobic chain could be good for reducing the resistance of charge transfer, and increasing the rate of surface charge transfer and the lifetime of the photoexcited electrons. Benefiting from the hydrophobic chain, CdS shows an excellent photocatalytic hydrogen evolution rate of 943.54 µmol h-1 g-1 and a rhodamine B photocatalytic degradation rate of 99.1% in 60 min, which is superior to the photocatalysis of pure CdS prepared by many other methods.

2.
Aesthetic Plast Surg ; 2022 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-35237878

RESUMO

BACKGROUND: As the most principal complication following breast augmentation with silicone breast implants, capsular contracture is greatly influenced by surface texture. However, there have long been widespread debates on the function of smooth or textured surface implants in reducing capsular contracture. MATERIALS AND METHODS: Three commercially available silicone breast implants with smooth and textured surfaces were subjected to surface characterization, and in vitro and in vivo assessments were then implemented to investigate the effect of these different surfaces on the biological behaviors of fibroblasts and capsular formation in rat models. RESULTS: Surface characterization demonstrated that all three samples were hydrophobic with distinct roughness values. Comparing the interactions of fibroblasts or tissues with different surfaces, we observed that as surface roughness increased, the adhesion and cell spreading of fibroblasts, the level of echogenicity, the density of collagen and α-SMA-positive immunoreactivity decreased, while the proliferation of fibroblasts and capsule thickness increased. CONCLUSIONS: Our findings elucidated that the effect of silicone implant surface texture on fibroblasts' behaviors and capsular formation was associated with variations in surface roughness, and the number of myofibroblasts may have a more significant influence on the process of contracture than capsule thickness in the early stage of capsular formation. These results highlight that targeting myofibroblasts may be wielded in the prevention and treatment strategies of capsular contracture clinically. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

3.
Mil Med Res ; 9(1): 9, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35152910

RESUMO

BACKGROUND: Ultrasound-triggered microbubble destruction (UTMD) is a widely used noninvasive technology in both military and civilian medicine, which could enhance radiosensitivity of various tumors. However, little information is available regarding the effects of UTMD on radiotherapy for glioblastoma or the underlying mechanism. This study aimed to delineate the effect of UTMD on the radiosensitivity of glioblastoma and the potential involvement of autophagy. METHODS: GL261, U251 cells and orthotopic glioblastoma-bearing mice were treated with ionizing radiation (IR) or IR plus UTMD. Autophagy was observed by confocal microscopy and transmission electron microscopy. Western blotting and immunofluorescence analysis were used to detect progesterone receptor membrane component 1 (PGRMC1), light chain 3 beta 2 (LC3B2) and sequestosome 1 (SQSTM1/p62) levels. Lentiviral vectors or siRNAs transfection, and fluorescent probes staining were used to explore the underlying mechanism. RESULTS: UTMD enhanced the radiosensitivity of glioblastoma in vitro and in vivo (P < 0.01). UTMD inhibited autophagic flux by disrupting autophagosome-lysosome fusion without impairing lysosomal function or autophagosome synthesis in IR-treated glioblastoma cells. Suppression of autophagy by 3-methyladenine, bafilomycin A1 or ATG5 siRNA had no significant effect on UTMD-induced radiosensitization in glioblastoma cells (P < 0.05). Similar results were found when autophagy was induced by rapamycin or ATG5 overexpression (P > 0.05). Furthermore, UTMD inhibited PGRMC1 expression and binding with LC3B2 in IR-exposed glioblastoma cells (P < 0.01). PGRMC1 inhibitor AG-205 or PGRMC1 siRNA pretreatment enhanced UTMD-induced LC3B2 and p62 accumulation in IR-exposed glioblastoma cells, thereby promoting UTMD-mediated radiosensitization (P < 0.05). Moreover, PGRMC1 overexpression abolished UTMD-caused blockade of autophagic degradation, subsequently inhibiting UTMD-induced radiosensitization of glioblastoma cells. Finally, compared with IR plus UTMD group, PGRMC1 overexpression significantly increased tumor size [(3.8 ± 1.1) mm2 vs. (8.0 ± 1.9) mm2, P < 0.05] and decreased survival time [(67.2 ± 2.6) d vs. (40.0 ± 1.2) d, P = 0.0026] in glioblastoma-bearing mice. CONCLUSION: UTMD enhanced the radiosensitivity of glioblastoma partially by disrupting PGRMC1-mediated autophagy.


Assuntos
Glioblastoma , Animais , Autofagia/genética , Glioblastoma/patologia , Glioblastoma/radioterapia , Humanos , Proteínas de Membrana , Camundongos , Microbolhas , Tolerância a Radiação/genética , Radiação Ionizante , Receptores de Progesterona
4.
Cell Death Dis ; 13(1): 41, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013118

RESUMO

Despite the great advances in target therapy, lung cancer remains the top cause of cancer-related death worldwide. G protein-coupled receptor neurokinin-1 (NK1R) is shown to play multiple roles in various cancers; however, the pathological roles and clinical implication in lung cancer are unclarified. Here we identified NK1R as a significantly upregulated GPCR in the transcriptome and tissue array of human lung cancer samples, associated with advanced clinical stages and poor prognosis. Notably, NK1R is co-expressed with epidermal growth factor receptor (EGFR) in NSCLC patients' tissues and co-localized in the tumor cells. NK1R can crosstalk with EGFR by interacting with EGFR, transactivating EGFR phosphorylation and regulating the intracellular signaling of ERK1/2 and Akt. Activation of NK1R promotes the proliferation, colony formation, EMT, MMP2/14 expression, and migration of lung cancer cells. The inhibition of NK1R by selective antagonist aprepitant repressed cell proliferation and migration in vitro. Knockdown of NK1R significantly slowed down the tumor growth in nude mice. The sensitivity of lung cancer cells to gefitinib/osimertinib is highly increased in the presence of the selective NK1R antagonist aprepitant. Our data suggest that NK1R plays an important role in lung cancer development through EGFR signaling and the crosstalk between NK1R and EGFR may provide a potential therapeutic target for lung cancer treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Receptores da Neurocinina-1/metabolismo , Animais , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/metabolismo , Humanos , Neoplasias Pulmonares/patologia , Camundongos , Antagonistas dos Receptores de Neurocinina-1/farmacologia , Fosforilação , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Receptores da Neurocinina-1/genética , Transdução de Sinais
5.
Med Phys ; 49(3): 1333-1343, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35018646

RESUMO

OBJECTIVES: In this study, Ultrasound Needle-an improved minimally invasive ultrasonic horn device was used to explore its potential of synergizing with urokinase in enhancing clots lysis in an in vitro intracranial hematoma model. MATERIALS AND METHODS: Ten milliliter bovine blood was incubated for 3 h at 37℃, and coagulated into clot to mimic intracranial hematoma in vitro. Ultrasound Needle was an improved ultrasonic horn with a fine tip (1.80 mm) and metallic sheath, and had a frequency of 29.62 kHz. The 10,000 IU urokinase was injected through the metallic sheath during the vibration of Ultrasound Needle tip to lyse the clots for 8 min under different working parameter settings (n = 8) to explore the influence of parameters Amplitude (%) and Duty (%) on clot lysis weight (W0 ). The maximum temperatures were measured by an infrared thermometer during the treatment process. The W0 of different treatment groups (US (Ultrasound Needle), US + NS (normal saline), UK (urokinase), US + UK, n = 8) were compared to verify the synergistic lysis effect of Ultrasound Needle combined with urokinase at optimal working parameters (40% Amplitude, 20% Duty; input power 4.20 W; axial tip-vibration amplitude 69.17 µm). Clots samples after treatment were fixed overnight for macroscopic examination. And fluorescent frozen sections and scanning electron microscopy examination were performed to show microscopic changes in clots and evaluate the cavitation effect of Ultrasound Needle on promoting drug diffusion within the clots. RESULTS: The clot lysis weight W0 increased with the parameters Amplitude (%) and Duty (%), reached a peak (2.435 ± 0.137 g) at 40% Amplitude and 20% Duty (input power 4.20 W), and then decreased. Higher Amplitude (%) and Duty (%) led to higher maximum temperature, and W0 was negatively correlated with the maximum temperature after the peak (r = -0.958). At the optimal parameter setting, the maximum temperature was 33.8 ± 0.9℃, and the W0 of the US + UK group was more than four times of UK alone group (2.435 ± 0.137 g vs. 0.607 ± 0.185 g). Fluorescent frozen sections confirmed that the ultrasound energy of Ultrasound Needle could mechanically damage the clot tissues and promote the intra-clots drug diffusion. Macroscopic examination showed that US + UK group caused larger clots lysis area than UK alone group (2.08 cm2 vs. 0.65 cm2 ). In addition, electron microscopy examination exhibited that the fibrin filaments of the clots in US + UK group were lysed more thoroughly compared to single treatment groups. CONCLUSIONS: Ultrasound Needle, an improved ultrasonic horn device, can mechanically damage the clot tissues and exhibit an excellent synergistic lysis effect with thrombolytic drugs. Therefore, Ultrasound Needle has great potential in providing a new minimally invasive strategy for rapid intracranial hematoma evacuation.


Assuntos
Fibrinolíticos , Hematoma , Terapia por Ultrassom , Ativador de Plasminogênio Tipo Uroquinase , Animais , Bovinos , Fibrinolíticos/uso terapêutico , Hematoma/tratamento farmacológico , Terapia Trombolítica , Ativador de Plasminogênio Tipo Uroquinase/uso terapêutico
6.
Theranostics ; 12(1): 307-323, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34987647

RESUMO

Background: Oxygen supplementation in myocardial infarction (MI) remains controversial. Inflammation is widely believed to play a central role in myocardial repair. A better understanding of these processes may lead to the design of novel strategies complementary to MI treatment. Methods: To investigate the role of hypoxia in inflammation and myocardial repair after acute MI, we placed MI mice in a tolerable mild hypoxia (10% O2) chamber for 7 days and then transferred the mice to ambient air for another 3 weeks. Results: We found that the cumulative survival rate of the MI mice under hypoxia was significantly higher than that under oxygen supplementation. Hypoxia promoted postinfarction myocardial repair. Importantly, we found that hypoxia modulated the phenotypic transition of blood monocytes from pro-inflammatory to pro-reparative in a timely manner, leading to the subsequent discontinuation of inflammation in myocardial tissues and promotion of myocardial repair post-MI. Specifically, cultured bone marrow-derived macrophages (BMDMs) primed by hypoxia in vitro exhibited improved reparative capacities and differed from M1 and M2 macrophages through the AMPKα2 signaling pathway. The deletion of AMPKα2 in monocytes/macrophages prevented the phenotypic transition induced by hypoxia and could not promote myocardial repair after MI when transplanted into the myocardium. Conclusions: Taken together, our work demonstrates that hypoxia promotes postinfarction myocardial repair by modulating the blood monocyte/macrophage phenotypic transition from pro-inflammatory to pro-reparative in a timely manner through the AMPKα2 signaling pathway. Hypoxia priming might be an attractive translational strategy for MI treatment by amplifying immune cells during early inflammation and subsequent resolution and repair.


Assuntos
Hipóxia/metabolismo , Inflamação/metabolismo , Infarto do Miocárdio/metabolismo , Miocárdio , Animais , Camundongos , Camundongos Endogâmicos C57BL , Miocárdio/metabolismo , Miocárdio/patologia , Remodelação Ventricular
7.
Med Phys ; 49(3): 1357-1367, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35092698

RESUMO

OBJECTIVES: To explore the feasibility, efficacy, and safety of ultrasound-targeted microbubbles destruction (UTMD) assisted dual delivery of beta-amyloid (Aß) antibody loaded by microbubbles (MBAß ) and neural stem cells (NSCs) on Alzheimer's disease (AD). METHODS: Twenty-seven APP/PS1 double transgenic mice (Tg mice) and 33 wild-type mice were used. Wild-type mice were insonated by diagnostic ultrasound with microbubbles (MB) for 5 min to observe the blood brain barrier (BBB) opening. The survival situation of engrafted NSCs crossing the opened BBB mediated by UTMD in Tg mice was evaluated by in vivo imaging system. We further explored the combination therapy effects of UTMD mediated Aß antibody and NSCs dual delivery. Tg mice in each group were exposed to diagnostic ultrasound for 5 min once a week for four times, with MB, MBAß , and/or NSCs administration according to groups. Cognition and memory functions were explored by Morris water maze test, Aß plaques deposition was evaluated by immunohistochemical, and brain-derived neurotrophic factor (BDNF) and synaptophysin (SYN) expression were detected by western blot and immunofluorescence. RESULTS: BBB was opened mediated by diagnostic ultrasound with MB, and the duration of opening was about 10 h. The transplanted NSCs survived in Tg mice for no more than 72 h. Compared with control group, the Tg mice in combined delivery of NSCs and Aß antibody by UTMD group improved memory function and spatial learning with shorter latency to find the platform, longer distance traveled, and longer time spent in targeted quadrant, and more crossing times (p < 0.05). Besides, the combination delivery group promoted the clearance of Aß plaques compared with control group both in hippocampus (p < 0.01) and cortex (p < 0.05). Moreover, the expression of BDNF in combination delivery group was significantly higher than that in control group and ultrasound-mediated MB group (p < 0.05). No significant change of SYN was observed in each group. CONCLUSION: UTMD assisted dual delivery of Aß antibody and NSCs crossing the BBB into AD mice brain could help to clear Aß plaques, increase the expression of BDNF, and restore the impaired neural function. This finding may offer potential insight into treatment of AD.


Assuntos
Doença de Alzheimer , Células-Tronco Neurais , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/terapia , Peptídeos beta-Amiloides/metabolismo , Animais , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Microbolhas , Células-Tronco Neurais/metabolismo
8.
Biomed Res Int ; 2021: 6624101, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34285917

RESUMO

AIMS: Although several studies have indicated that valproate (VPA) and oxcarbazepine (OXC) cause reproductive endocrine disorders and sexual dysfunction, there remains some controversy regarding these issues in males with epilepsy. This study is aimed at evaluating the effects of VPA and OXC on sexual function, sperm quality, and sex hormones in young males with epilepsy. METHODS: Males with newly diagnosed epilepsy treated with VPA and OXC were recruited, and sexual function questionnaires (International Index of Erectile Function-5 (IIEF-5)), sperm quality, and sex hormone levels were assessed before treatment and at 6 months after treatment with VPA or OXC monotherapy. RESULTS: Forty-four young males with epilepsy (23 treated with VPA, 21 treated with OXC) and 30 age-matched healthy individuals were recruited for our study. The sexual function, sperm quality, marriage rate, and fertility rate of these young males with epilepsy were lower than those of healthy controls. Sperm quality were significantly reduced in young male patients after 6 months of VPA administration. The level of follicle stimulating hormone (FSH) was increased in patients after OXC treatment. Meanwhile, sexual function and sperm quality were not affected. CONCLUSION: Sexual function and sperm quality were reduced in young males with epilepsy. VPA may exert a negative effect on sperm quality, whereas OXC has no harmful effect on sexual function and sperm quality in young males with epilepsy.


Assuntos
Epilepsia/fisiopatologia , Hormônios Esteroides Gonadais/metabolismo , Oxcarbazepina/farmacologia , Espermatozoides/fisiologia , Ácido Valproico/farmacologia , Adulto , Estudos de Casos e Controles , Humanos , Masculino , Espermatozoides/efeitos dos fármacos , Inquéritos e Questionários
9.
Front Oncol ; 11: 685694, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34307151

RESUMO

BACKGROUND: Sorafenib is the first molecular-targeted drug for the treatment of advanced hepatocellular carcinoma (HCC). However, its treatment efficiency decreases after a short period of time because of the development of drug resistance. This study investigates the role of key genes in regulating sorafenib-resistance and elucidates the mechanism of drug resistance in hepatocellular carcinoma. METHODS: The HCC HepG2 cells were used to generate a sorafenib-resistant cell model by culturing the cells in gradually increasing concentration of sorafenib. RNA microarray was applied to profile gene expression and screen key genes associated with sorafenib resistance. Specific targets were knockdown in sorafenib-resistant HepG2 cells for functional studies. The HCC model was established in ACI rats using Morris hepatoma3924A cells to validate selected genes associated with sorafenib resistance in vivo. RESULTS: The HepG2 sorafenib-resistant cell model was successfully established. The IC50 of sorafenib was 9.988µM in HepG2 sorafenib-resistant cells. A total of 35 up-regulated genes were detected by expression profile chip. High-content screening technology was used and a potential drug-resistance related gene RPL28 was filtered out. After knocking down RPL28 in HepG2 sorafenib-resistant cells, the results of cell proliferation and apoptosis illustrated that RPL28 is the key gene involving in drug resistance. Furthermore, it was found that both RNA and protein expression of RPL28 increased in HepG2 sorafenib-resistant specimens of Morris Hepatoma rats. In addition, the expression of proliferative protein Ki-67 increased in sorafenib-resistant cells. CONCLUSION: Our study suggested that RPL28 is a key gene inducing sorafenib resistance in HCC and could be a potential target for the treatment of drug-resistant HCC.

10.
BMC Neurol ; 21(1): 251, 2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34187396

RESUMO

BACKGROUND: Epilepsy is a severe chronic neurologic disease with a prevalence of 0.7% worldwide; anti-seizure medications (ASMs) are the mainstay of epilepsy treatment. The effects of sociodemographic factors on the characteristics of initial treatment in patients with newly diagnosed focal epilepsy in Western China are unknown. This study was conducted to explore sociodemographic factors associated with initial treatment characteristics. METHODS: Patients with focal epilepsy on continuous ASM treatment who visited to our epilepsy center at Sichuan Provincial People's Hospital between January 2018 and December 2019 were recruited. Data on initial treatment status and sociodemographic variables were obtained from the patients with a questionnaire designed by our researchers. We examined whether sociodemographic factors were associated with epileptic patients' access to neurologists and prescriptions of individual ASMs. RESULTS: A total of 569 patients completed this study. We found that patients with a higher education level, aged < 16 years, and with a higher household disposable income were more likely to receive treatment from a neurologist than their counterparts. Patients with a lower personal income level and who were treated at a junior hospital were more likely to receive prescriptions for carbamazepine, and those who were younger than 16 years were less likely to receive prescriptions for carbamazepine and oxcarbazepine. Patients with a higher education level, with a higher household disposable income level, who were younger than 16 years, and who were treated at a senior hospital were more likely to receive prescriptions for levetiracetam than their counterparts. Adult, female patients with focal epilepsy treated at a senior hospital were more likely to receive prescriptions for lamotrigine. CONCLUSIONS: This observation suggests that sociodemographic characteristics are associated with access to neurologists and prescriptions of individual antiepileptic drugs. These data may help public health officials establish guidelines for doctors and distribute resources according to the needs of different patient groups.


Assuntos
Anticonvulsivantes , Epilepsias Parciais , Adolescente , Adulto , Anticonvulsivantes/administração & dosagem , Anticonvulsivantes/uso terapêutico , China , Epilepsias Parciais/tratamento farmacológico , Epilepsias Parciais/epidemiologia , Feminino , Humanos , Masculino , Fatores Socioeconômicos , Adulto Jovem
11.
Mol Cell ; 81(15): 3187-3204.e7, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34157307

RESUMO

OTULIN coordinates with LUBAC to edit linear polyubiquitin chains in embryonic development, autoimmunity, and inflammatory diseases. However, the mechanism by which angiogenesis, especially that of endothelial cells (ECs), is regulated by linear ubiquitination remains unclear. Here, we reveal that constitutive or EC-specific deletion of Otulin resulted in arteriovenous malformations and embryonic lethality. LUBAC conjugates linear ubiquitin chains onto Activin receptor-like kinase 1 (ALK1), which is responsible for angiogenesis defects, inhibiting ALK1 enzyme activity and Smad1/5 activation. Conversely, OTULIN deubiquitinates ALK1 to promote Smad1/5 activation. Consistently, embryonic survival of Otulin-deficient mice was prolonged by BMP9 pretreatment or EC-specific ALK1Q200D (constitutively active) knockin. Moreover, mutant ALK1 from type 2 hereditary hemorrhagic telangiectasia (HHT2) patients exhibited excessive linear ubiquitination and increased HOIP binding. As such, a HOIP inhibitor restricted the excessive angiogenesis of ECs derived from ALK1G309S-expressing HHT2 patients. These results show that OTULIN and LUBAC govern ALK1 activity to balance EC angiogenesis.


Assuntos
Receptores de Activinas Tipo II/genética , Receptores de Activinas Tipo II/metabolismo , Endopeptidases/genética , Complexos Multiproteicos/metabolismo , Neovascularização Patológica/genética , Poliubiquitina/metabolismo , Adulto , Animais , Endopeptidases/metabolismo , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Feminino , Fator 2 de Diferenciação de Crescimento/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos Mutantes , Mutação , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica/genética , Proteína Smad1/genética , Proteína Smad1/metabolismo , Proteína Smad5/genética , Proteína Smad5/metabolismo , Telangiectasia Hemorrágica Hereditária , Ubiquitina-Proteína Ligases/metabolismo
12.
Ultrasound Med Biol ; 47(9): 2692-2701, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34130882

RESUMO

Failure of coronary recanalization within 12 h or no flow in the myocardium after percutaneous coronary intervention is associated with high mortality from myocardial infarction, and insufficient angiogenesis in the border zone results in the expansion of infarct area. In this study, we examined the effects of ultrasound-targeted microbubble destruction (UTMD) on angiogenesis and left ventricular dysfunction in a mouse model of myocardial infarction. Fifty-four mice with MI were treated with no UTMD, ultrasound (US) alone or UTMD four times (days 1, 3, 5 and 7), and another 18 mice underwent sham operation and therapy. Therapeutic US was generated with a linear transducer connected to a commercial diagnostic US system (VINNO70). UTMD was performed with the VINNO70 at a peak negative pressure of 0.8 MPa and lipid microbubbles. Transthoracic echocardiography was performed on the first and seventh days. The results indicated that UTMD decreased the infarct size ratio from 78.1 ± 5.3% (untreated) to 43.3 ± 6.4%, accelerated angiogenesis and ameliorated left ventricular dysfunction. The ejection fraction increased from 25.05 ± 8.52% (untreated) to 42.83 ± 9.44% (UTMD). Compared with that in other groups, expression of vascular endothelial growth factor and endothelial nitric oxide synthase and release of nitric oxide were significantly upregulated after UTMD treatment, indicating angiogenesis. Therefore, UTMD is a potential physical approach in the treatment of myocardial infarction.


Assuntos
Infarto do Miocárdio , Disfunção Ventricular Esquerda , Animais , Camundongos , Microbolhas , Infarto do Miocárdio/complicações , Infarto do Miocárdio/terapia , Miocárdio , Fator A de Crescimento do Endotélio Vascular , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/terapia
13.
Neural Regen Res ; 16(10): 2064-2070, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33642395

RESUMO

Compared with other stem cells, human induced pluripotent stem cells-derived neural progenitor cells (iPSC-NPCs) are more similar to cortical neurons in morphology and immunohistochemistry. Thus, they have greater potential for promoting the survival and growth of neurons and alleviating the proliferation of astrocytes. Transplantation of stem cell exosomes and stem cells themselves have both been shown to effectively repair nerve injury. However, there is no study on the protective effects of exosomes derived from iPSC-NPCs on oxygen and glucose deprived neurons. In this study, we established an oxygen-glucose deprivation model in embryonic cortical neurons of the rat by culturing the neurons in an atmosphere of 95% N2 and 5% CO2 for 1 hour and then treated them with iPSC-NPC-derived exosomes for 30 minutes. Our results showed that iPSC-NPC-derived exosomes increased the survival of oxygen- and glucose-deprived neurons and the level of brain-derived neurotrophic factor in the culture medium. Additionally, it attenuated oxygen and glucose deprivation-induced changes in the expression of the PTEN/AKT signaling pathway as well as synaptic plasticity-related proteins in the neurons. Further, it increased the length of the longest neurite in the oxygen- and glucose-deprived neurons. These findings validate the hypothesis that exosomes from iPSC-NPCs exhibit a neuroprotective effect on oxygen- and glucose-deprived neurons by regulating the PTEN/AKT signaling pathway and neurite outgrowth. This study was approved by the Animal Ethics Committee of Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, China (approval No. SRRSH20191010) on October 10, 2019.

14.
Med Phys ; 48(7): 3927-3935, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33774845

RESUMO

PURPOSE: Ultrasound-targeted microbubble destruction (UTMD) has been widely applied to enhance chemotherapy of tumors, yet few studies have focused on the metastatic potential induced by UTMD. This study aimed to explore the metastasis of VX2 tumors after treatment with UTMD and chemotherapy. METHODS: Forty-four New Zealand rabbits bearing subcutaneous VX2 tumors were enrolled for the treatment of UTMD with chemotherapy. For UTMD, the tumors were insonated using two pulsing protocols of diagnostic ultrasound (DUS, VINNO and ECARE) with a mechanical index (MI) of 0.29-0.33, tone burst of 8.0 cycles, and frequencies of 3-4 MHz. A total dose of 2 ml SonoVue® was injected intermittently during 10-min UTMD exposure. The combination therapy was treated using doxorubicin (DOX, 2 mg/kg) and DUS, while the tumors treated using DOX only served as the control. Tumor size was measured using the tumor volume formula. Survival time was observed until animal death or the end of the study (120 days). Specific organs (lung, liver, kidney, and brain) were removed for metastatic evaluation. RESULTS: There were no statistical differences in overall metastasis classification and individual organ metastases among all groups (P > 0.05). The tumor growth rate only showed inhibition on the 5th day (P < 0.01). The survival time did not demonstrate any significant difference between UTMD and chemotherapy only (P > 0.05). CONCLUSIONS: UTMD using long-pulse DUS with commercial microbubbles did not pose a risk of metastasis enhancement in DOX chemotherapy.


Assuntos
Neoplasias Hepáticas , Microbolhas , Animais , Terapia Combinada , Coelhos , Ultrassonografia
15.
Ageing Res Rev ; 67: 101303, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33609777

RESUMO

OTU domain-containing ubiquitin aldehyde-binding proteins Otubain1 (OTUB1) and Otubain2 (OTUB2) were initially identified as OTU deubiquitinases (DUBs). Recently, Otubains have emerged as essential regulators of diverse physiological processes, such as immune signaling and DNA damage response. Dysregulation of those processes is likely to increase the risk in multiple aspects of aging-related diseases, including cancers, neurodegenerative disorders, chronic kidney diseases, bone dysplasia and pulmonary fibrosis. Consistently, Otubains are aberrantly expressed in cancers and have been identified to be both tumor suppressors and tumor promoters in different types of cancers. Therefore, the regulatory mechanism of the activity and expression of Otubains is very important for better understanding of Otubains-associated biological networks and human diseases. This review provides a comprehensive description of functions and regulatory axis of Otubains, highlighting experimental evidences indicating Otubains as potential therapeutic targets against aging-related disorders.


Assuntos
Cisteína Endopeptidases , Proteostase , Cisteína Endopeptidases/metabolismo , Humanos , Transdução de Sinais
16.
Res High Educ ; 62(7): 915-941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33612921

RESUMO

Most U.S. universities have made explicit commitments to educating economically diverse student bodies; however, the higher education system is highly stratified. In this paper, we seek to understand stratification in the wake of the Great Recession by examining enrollment among students from differing income backgrounds by institutional type. Two theoretical frameworks suggest different conclusions. A Disaster Capitalism framework suggests that in places where the recession was most severe, enrollment by income would become more stratified than in places where the downturn was less severe. In contrast, Effectively Maintained Inequality would suggest that enrollments were already effectively stratified by income and would not necessarily be sensitive to exposure to an economic shock. Employing fixed effects modeling and novel data based on the tax records of 30 million Americans, we examine income composition by institutional type from 2004 to 2012. We find that although stratification by institutional type worsened during the recession and subsequent recovery, patterns of economic stratification were not more intense for institutions that enrolled students from states hardest hit by the recession. We conclude that these patterns are consistent with an Effectively Maintained Inequality framework. During the recession, the top quintiles continued to enjoy their longstanding disproportionate enrollment in the most selective institutions. For the bottom quintiles, the longstanding marginalization from 4-year college going persisted through the recession. These stratification patterns, however, were not more pronounced in places hardest hit by the recession.

18.
IUBMB Life ; 73(2): 341-348, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33368968

RESUMO

Glioma alone accounts for 30% of various kinds of primary brain tumors and is the highest cause of mortality associated with intracranial malignant cancers. In the present study, Suzuki-coupling products of remimazolan were synthesized and investigated for anti-neoplastic property against glioma cells. RFMSP treatment for 48 hr suppressed viabilities of U-118MG and U87MG cells in dose dependent manner. Exposure of primary astrocytes to RFMSP at 2-20 µM concentration range minimally affected viabilities. RFMSP treatment at 5 µM doses raised apoptotic cell count to 53.8 ± 2.3% and 48.2 ± 1.8%, respectively in U-118MG and U87MG cells. Treatment of the cells with RFMSP induced nuclear condensation and subsequent fragmentation. In RFMSP treated U-118MG and U87MG cells, NF-κB p65 expression was markedly suppressed compared to the control cells. Additionally, RFMSP treatment decreased the ratio of nuclear to total NF-κB p65 level in both the cell lines. Treatment of U-118MG and U87MG cells with 5 µM RFMSP for 48 hr caused a marked down-regulation in survivin and XIAP levels. Treatment with RFMSP promoted Bax expression and suppressed Bcl-2 level. The caspase-9 and -3 activation was markedly induced by RFMSP treatment in U-118MG and U87MG cells compared to the control cells. In summary, the RFMSP synthesized by Suzuki-coupling of RFMSP inhibited glioma cell survival via DNA damage mediated apoptosis. The anti-glioma potential of RFMSP involved down-regulation of NF-κB expression, targeted survivin & XIAP levels and induced caspase activation in glioma cells. Therefore, RFMSP may be studied further as therapeutic agent for the treatment of glioma.


Assuntos
Apoptose , Benzodiazepinas/farmacologia , Neoplasias Encefálicas/tratamento farmacológico , Proliferação de Células , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/tratamento farmacológico , NF-kappa B/antagonistas & inibidores , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Ciclo Celular , Movimento Celular , Regulação para Baixo , Glioma/metabolismo , Glioma/patologia , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , Células Tumorais Cultivadas
19.
Front Endocrinol (Lausanne) ; 12: 774608, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35046894

RESUMO

Objective: Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and its pathogenesis is still unclear. Studies have shown that circular RNAs (circRNAs) can regulate blood glucose levels by targeting mRNAs, but the role of circRNAs in GDM is still unknown. Therefore, a joint microarray analysis of circRNAs and their target mRNAs in GDM patients and healthy pregnant women was carried out. Methods: In this study, microarray analyses of mRNA and circRNA in 6 GDM patients and 6 healthy controls were conducted to identify the differentially expressed mRNA and circRNA in GDM patients, and some of the discovered mRNAs and circRNAs were further validated in additional 56 samples by quantitative realtime PCR (qRT-PCR) and droplet digital PCR (ddPCR). Results: Gene ontology and pathway analyses showed that the differentially expressed genes were significantly enriched in T cell immune-related pathways. Cross matching of the differentially expressed mRNAs and circRNAs in the top 10 KEGG pathways identified 4 genes (CBLB, ITPR3, NFKBIA, and ICAM1) and 4 corresponding circRNAs (circ-CBLB, circ-ITPR3, circ-NFKBIA, and circ-ICAM1), and these candidates were subsequently verified in larger samples. These differentially expressed circRNAs and their linear transcript mRNAs were all related to the T cell receptor signaling pathway, and PCR results confirmed the initial microarray results. Moreover, circRNA/miRNA/mRNA interactions and circRNA-binding proteins were predicted, and circ-CBLB, circ-ITPR3, and circ-ICAM1 may serve as GDM-related miRNA sponges and regulate the expression of CBLB, ITPR3, NFKBIA, and ICAM1 in cellular immune pathways. Conclusion: Upregulation of T cell receptor signaling pathway components may represent the major pathological mechanism underlying GDM, thus providing a potential approach for the prevention and treatment of GDM.


Assuntos
Diabetes Gestacional/metabolismo , Receptores de Antígenos de Linfócitos T/metabolismo , Transdução de Sinais , Feminino , Ontologia Genética , Humanos , Análise em Microsséries , Gravidez , RNA Circular/metabolismo , RNA Mensageiro/metabolismo , Regulação para Cima
20.
Front Surg ; 8: 798640, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35155552

RESUMO

Uterine surgery is a common predisposing factor for uterine rupture, while an invasive mole that leads to uterine rupture is a rare clinical occurrence. Here, we report a case of a 31-year-old childless woman who underwent abortion after 53 days of pregnancy. She still experienced abdominal pain and scanty vaginal bleeding after the abortion. Her levels of human chorionic gonadotropin (HCG) were high, while ultrasound and MRI results revealed an enlarged uterus and a mass in the myometrium. During preparation for treatment, the gynecologist ruptured the uterus of the patient, leaving her shocked. Eventually the patient's uterus was removed the uterus and pathologically diagnosed as result is the an invasive mole.

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