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1.
Phys Rev Lett ; 131(20): 202502, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-38039451

RESUMO

Traditional photonuclear reactions primarily excite giant dipole resonances, making the measurement of isovector giant resonances with higher multipolarities a great challenge. In this Letter, the manipulation of collective excitations of different multipole transitions in even-even nuclei via vortex γ photons is investigated. We develop the calculation method for photonuclear cross sections induced by the vortex γ photon beam using the fully self-consistent random-phase approximation plus particle-vibration coupling (RPA+PVC) model based on Skyrme density functional. We find that the electromagnetic transitions with multipolarity J<|m_{γ}| are forbidden for vortex γ photons due to the angular momentum conservation, with m_{γ} being the projection of total angular momentum of γ photon on its propagation direction. For instance, this allows for probing the isovector giant quadrupole resonance without interference from dipole transitions using vortex γ photons with m_{γ}=2. Furthermore, the electromagnetic transition with J=|m_{γ}|+1 vanishes at a specific polar angle. Therefore, the giant resonances with specific multipolarity can be extracted via vortex γ photons. Moreover, the vortex properties of γ photons can be meticulously diagnosed by measuring the nuclear photon-absorption cross section. Our method opens new avenues for photonuclear excitations, generation of coherent γ photon laser and precise detection of vortex particles, and consequently, has significant impact on nuclear physics, nuclear astrophysics and strong laser physics.

2.
Bioorg Chem ; 130: 106199, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36370648

RESUMO

Due to the diverse H2O2 distribution in organelles, fluorescent probes were usually required to be prepared separately, which limited the convenience and practicability. Herein, we reported a flexible strategy to in-situ construct H2O2 fluorescent probes in different organelles. A tetrazine fused probe TP was developed with rapid click reaction capacity and sensitive H2O2 response. When treated with H2O2, the turn-on fluorescence was effectively quenched by the tetrazine part. Only after click reaction with dienophiles, the fluorescence resumed. In application, cells were firstly treated with triphenylphosphorus tagged norbornene (TPP-NB) to label mitochondria, which was followed by the introduction of probe TP to trigger click reaction. The in-situ constructed probe P1 served as a local H2O2 sensor. In a similar way, probe P2 was in-situ constructed in lysosomes via probe TP and morpholine tagged norbornene (MP-NB). With this on-demand modular assembling and double turn-on features, our strategy to construct fluorescent probes presented high flexibility and anti-interference performance, which was expected to inspired more applications in biological studies.


Assuntos
Corantes Fluorescentes , Peróxido de Hidrogênio , Humanos , Corantes Fluorescentes/metabolismo , Peróxido de Hidrogênio/metabolismo , Células HeLa , Lisossomos/metabolismo , Mitocôndrias , Norbornanos/metabolismo
3.
J Nanobiotechnology ; 21(1): 107, 2023 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-36964565

RESUMO

Due to the excellent biocompatible physicochemical performance, luminogens with aggregation-induced emission (AIEgens) characteristics have played a significant role in biomedical fluorescence imaging recently. However, screening AIEgens for special applications takes a lot of time and efforts by using conventional chemical synthesis route. Fortunately, artificial intelligence techniques that could predict the properties of AIEgen molecules would be helpful and valuable for novel AIEgens design and synthesis. In this work, we applied machine learning (ML) techniques to screen AIEgens with expected excitation and emission wavelength for biomedical deep fluorescence imaging. First, a database of various AIEgens collected from the literature was established. Then, by extracting key features using molecular descriptors and training various state-of-the-art ML models, a multi-modal molecular descriptors strategy has been proposed to extract the structure-property relationships of AIEgens and predict molecular absorption and emission wavelength peaks. Compared to the first principles calculations, the proposed strategy provided greater accuracy at a lower computational cost. Finally, three newly predicted AIEgens with desired absorption and emission wavelength peaks were synthesized successfully and applied for cellular fluorescence imaging and deep penetration imaging. All the results were consistent successfully with our expectations, which demonstrated the above ML has a great potential for screening AIEgens with suitable wavelengths, which could boost the design and development of novel organic fluorescent materials.


Assuntos
Inteligência Artificial , Imagem Óptica , Imagem Óptica/métodos , Fluorescência , Aprendizado de Máquina , Corantes Fluorescentes/química
4.
Appl Opt ; 62(32): 8558-8566, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-38037969

RESUMO

A design of a multiband terahertz (THz) metamaterial biosensor for early cancer detection is proposed. The THz biosensor composed of several arc-shaped connecting parts operates at three different frequencies, and the absorptivity of the three resonant frequencies exceeds 99% in free space. In this work, we analyzed the absorption spectrum and polarization independence under different design parameters, improved the performance of the sensor by adjusting the absorption characteristics of the sensor, and gave the calculation results. Additionally, we studied the influence of the refractive index and thickness of different samples on the sensor, and theoretically calculated the sensitivity of the sensor to basal cells, breast cells, cervical cells, and their corresponding cancer cells. The result shows that the maximum sensitivity of the sensor can reach 642.5 GHz/RIU, which is much higher than the reported biosensors. Therefore, the proposed THz sensor has great potential in early detection and early warning of cancer.


Assuntos
Neoplasias , Radiação Terahertz , Humanos , Refratometria , Detecção Precoce de Câncer , Refração Ocular
5.
Biochem Biophys Res Commun ; 596: 6-13, 2022 03 12.
Artigo em Inglês | MEDLINE | ID: mdl-35104663

RESUMO

Root hairs are cylindrical extensions of root epidermal cells that are important for the acquisition of water and minerals, interactions between plant and microbes. The deposition of cell wall materials in the tip enables root hairs to maintain elongation constantly. To date, our knowledge of the regulators that connect the architecture of cell wall and the root hair development remains very limited. Here, we demonstrated that COBL9 and COBL7, two genes of COBRA-Like family in Arabidopsis as well as their counterparts in rice, OsBC1L1 and OsBC1L8, regulate root hair growth. Single mutant cobl9, double mutants cobl7 cobl9 and double mutants osbc1l1 osbc1l8 all displayed prematurely terminated root hair elongation, though at varying levels. COBL7-YFP and COBL9-YFP accumulate prominently in the growing tips of newly emerged root hairs. Furthermore, cobl9, cobl7 cobl9 and osbc1l1 osbc1l8 mutants were defective in the enrichment of cellulose in the tips of the growing root hairs. We also discovered that overexpression of COBL9 could promote root hair elongation and salinity tolerance. Taken together, these results provide compelling evidence that the polarized COBL7 and COBL9 in the tip of the emerging root hairs have conserved roles in regulating root hair development and stress adaptation in dicots and monocots.


Assuntos
Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Celulose/metabolismo , Meristema/metabolismo , Raízes de Plantas/metabolismo , Arabidopsis/genética , Arabidopsis/crescimento & desenvolvimento , Proteínas de Arabidopsis/genética , Parede Celular/genética , Parede Celular/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Regulação da Expressão Gênica de Plantas , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Meristema/genética , Meristema/crescimento & desenvolvimento , Microscopia Confocal , Mutação , Raízes de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tolerância ao Sal/genética
6.
J Neuroinflammation ; 19(1): 52, 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35180864

RESUMO

BACKGROUND: Multiple sclerosis (MS) is one of the most common autoimmune disorders characterized by the infiltration of immune cells into the brain and demyelination. The unwanted immunosuppressive side effect of therapeutically successful natalizumab led us to focus on the choroid plexus (CP), a key site for the first wave of immune cell infiltration in experimental autoimmune encephalomyelitis (EAE), for the control of immune cells trafficking. Adenosine A2A receptor (A2AR) is emerging as a potential pharmacological target to control EAE pathogenesis. However, the cellular basis for the A2AR-mediated protection remains undetermined. METHODS: In the EAE model, we assessed A2AR expression and leukocyte trafficking determinants in the CP by immunohistochemistry and qPCR analyses. We determined the effect of the A2AR antagonist KW6002 treatment at days 8-12 or 8-14 post-immunization on T cell infiltration across the CP and EAE pathology. We determined the critical role of the CP-A2AR on T cell infiltration and EAE pathology by focal knock-down of CP-A2AR via intracerebroventricular injection of CRE-TAT recombinase into the A2ARflox/flox mice. In the cultured CP epithelium, we also evaluated the effect of overexpression of A2ARs or the A2AR agonist CGS21680 treatment on the CP permeability and lymphocytes migration. RESULTS: We found the specific upregulation of A2AR in the CP associated with enhanced CP gateway activity peaked at day 12 post-immunization in EAE mice. Furthermore, the KW6002 treatment at days 8-12 or 8-14 post-immunization reduced T cell trafficking across the CP and attenuated EAE pathology. Importantly, focal CP-A2AR knock-down attenuated the pathogenic infiltration of Th17+ cells across the CP via inhibiting the CCR6-CCL20 axis through NFκB/STAT3 pathway and protected against EAE pathology. Lastly, activation of A2AR in the cultured epithelium by A2AR overexpression or CGS21680 treatment increased the permeability of the CP epithelium and facilitated lymphocytes migration. CONCLUSION: These findings define the CP niche as one of the primary sites of A2AR action, whereby A2AR antagonists confer protection against EAE pathology. Thus, pharmacological targeting of the CP-A2AR represents a novel therapeutic strategy for MS by controlling immune cell trafficking across CP.


Assuntos
Encefalomielite Autoimune Experimental , Adenosina/farmacologia , Adenosina/uso terapêutico , Animais , Plexo Corióideo/metabolismo , Encefalomielite Autoimune Experimental/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Receptor A2A de Adenosina/metabolismo , Receptor A2A de Adenosina/uso terapêutico
7.
Acta Pharmacol Sin ; 43(10): 2651-2665, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35217814

RESUMO

Canagliflozin is an antidiabetic medicine that inhibits sodium-glucose cotransporter 2 (SGLT2) in proximal tubules. Recently, it was reported to have several noncanonical effects other than SGLT2 inhibiting. However, the effects of canagliflozin on skeletal muscle regeneration remain largely unexplored. Thus, in vivo muscle contractile properties recovery in mice ischemic lower limbs following gliflozins treatment was evaluated. The C2C12 myoblast differentiation after gliflozins treatment was also assessed in vitro. As a result, both in vivo and in vitro data indicate that canagliflozin impairs intrinsic myogenic regeneration, thus hindering ischemic limb muscle contractile properties, fatigue resistance recovery, and tissue regeneration. Mitochondrial structure and activity are both disrupted by canagliflozin in myoblasts. Single-cell RNA sequencing of ischemic tibialis anterior reveals a decrease in leucyl-tRNA synthetase 2 (LARS2) in muscle stem cells attributable to canagliflozin. Further investigation explicates the noncanonical function of LARS2, which plays pivotal roles in regulating myoblast differentiation and muscle regeneration by affecting mitochondrial structure and activity. Enhanced expression of LARS2 restores the differentiation of canagliflozin-treated myoblasts, and accelerates ischemic skeletal muscle regeneration in canagliflozin-treated mice. Our data suggest that canagliflozin directly impairs ischemic skeletal muscle recovery in mice by downregulating LARS2 expression in muscle stem cells, and that LARS2 may be a promising therapeutic target for injured skeletal muscle regeneration.


Assuntos
Aminoacil-tRNA Sintetases , Inibidores do Transportador 2 de Sódio-Glicose , Aminoacil-tRNA Sintetases/metabolismo , Aminoacil-tRNA Sintetases/farmacologia , Animais , Canagliflozina/metabolismo , Canagliflozina/farmacologia , Canagliflozina/uso terapêutico , Diferenciação Celular , Glucose/metabolismo , Hipoglicemiantes/metabolismo , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Isquemia/tratamento farmacológico , Isquemia/metabolismo , Camundongos , Músculo Esquelético/metabolismo , Sódio/metabolismo , Sódio/farmacologia , Transportador 2 de Glucose-Sódio/metabolismo , Transportador 2 de Glucose-Sódio/farmacologia , Inibidores do Transportador 2 de Sódio-Glicose/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
8.
Psychol Health Med ; 27(9): 1877-1883, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33715523

RESUMO

The pandemic of Coronavirus Disease 2019(COVID-19) could be sources of anxiety among pregnant women and health care workers, which might affect the decision making on the mode of delivery. The aim of this study was to explore whether the cesarean section rates had significantly increased after the outbreak of COVID-19. We analyzed the labor data with cesarean rates in a tertiary maternity center during COVID-19 epidemic months from January to March in 2020, compared with pre-epidemic parallel months in 2019 by using Z-score test for proportions. Even though none of the staff or patient suffered with COVID-19 in the hospital, we found the cesarean section rates slightly increased in a non-infected population after the outbreak of COVID-19. Obstetricians should beware of the possible effects of COVID-19 on the mode of delivery.


Assuntos
COVID-19 , Trabalho de Parto , COVID-19/epidemiologia , Cesárea , Estudos Transversais , Feminino , Humanos , Pandemias , Gravidez
9.
J Cell Mol Med ; 25(20): 9496-9512, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34564947

RESUMO

Store-operated Ca2+ entry (SOCE) machinery, including Orai channels, TRPCs, and STIM1, is key to cellular calcium homeostasis. The following characteristics of mitochondria are involved in the physiological and pathological regulation of cells: mitochondria mediate calcium uptake through calcium uniporters; mitochondria are regulated by mitochondrial dynamic related proteins (OPA1, MFN1/2, and DRP1) and form mitochondrial networks through continuous fission and fusion; mitochondria supply NADH to the electron transport chain through the Krebs cycle to produce ATP; under stress, mitochondria will produce excessive reactive oxygen species to regulate mitochondria-endoplasmic reticulum interactions and the related signalling pathways. Both SOCE and mitochondria play critical roles in mediating cardiac hypertrophy, diabetic cardiomyopathy, and cardiac ischaemia-reperfusion injury. All the mitochondrial characteristics mentioned above are determinants of SOCE activity, and vice versa. Ca2+ signalling dictates the reciprocal regulation between mitochondria and SOCE under the specific pathological conditions of cardiomyocytes. The coupling of mitochondria and SOCE is essential for various pathophysiological processes in the heart. Herein, we review the research focussing on the reciprocal regulation between mitochondria and SOCE and provide potential interplay patterns in cardiac diseases.


Assuntos
Sinalização do Cálcio , Cálcio/metabolismo , Mitocôndrias Cardíacas/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Biomarcadores , Canais de Cálcio/metabolismo , Cardiomiopatias Diabéticas/diagnóstico , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/metabolismo , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Humanos , Dinâmica Mitocondrial , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Transdução de Sinais , Molécula 1 de Interação Estromal/genética , Molécula 1 de Interação Estromal/metabolismo
10.
Biochem Biophys Res Commun ; 576: 40-47, 2021 10 22.
Artigo em Inglês | MEDLINE | ID: mdl-34478918

RESUMO

Stomata that are bordered by pairs of guard cells are specialized for regulating gas exchange and transpiration in plants. The stomatal morphology of grass is unique, characterized by two dumbbell-shaped guard cells flanked by two lateral subsidiary cells. This morphology and developmental pattern enable grass stomata to respond to environmental signals efficiently. In this study, we demonstrated that knockout either OsBC1L1 or OsBC1L8, two close homologs of OsBC1L family causes no discernible defects in rice stomatal development, however, the double knockout mutant osbc1l1 osbc1l8 exhibits excess stomatal production and stomatal clustering. OsBC1L1 overexpression also causes abnormal stomatal patterning in rice. Moreover, osbc1l1 osbc1l8 has many defective stomata complexes with only one subsidiary cell. The expression of OsSPCH2 and OsFAMA, two genes key to stomatal development is both down-regulated in osbc1l1 osbc1l8. In contrast, overexpressing OsBC1L1 suppresses only the expression of OsSPCH2. Both OsBC1L1 and OsBC1L8 could be detected to be localized at the cell plate and plasma membrane during cell division of guard mother cells and subsidiary mother cells. Taken together, these results suggest that OsBC1L1 and OsBC1L8 play essential roles in the development of rice stomatal complex likely through their involvement in cell reproduction.


Assuntos
Oryza/crescimento & desenvolvimento , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Oryza/genética , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Folhas de Planta/metabolismo , Estômatos de Plantas/genética , Estômatos de Plantas/crescimento & desenvolvimento , Estômatos de Plantas/metabolismo
11.
BMC Musculoskelet Disord ; 22(1): 1051, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34930205

RESUMO

BACKGROUND: Kashin-Beck disease (KBD) is a chronic, deforming, endemic osteochondropathy that begins in patients as young as 2-3 years of age. The pathogenesis of KBD remains unclear, although selenium (Se) deficiency and T-2 toxin food contamination are both linked to the disease. In the present study, we evaluated transforming growth factor-ß receptor (TGF-ßR I and II) levels in clinical samples of KBD and in pre-clinical disease models. METHODS: Human specimens were obtained from the hand phalanges of eight donors with KBD and eight control donors. Animal models of the disease were established using Sprague-Dawley rats, which were fed an Se-deficient diet for 4 weeks and later administered the T-2 toxin. Cartilage cellularity and morphology were examined by hematoxylin and eosin staining. Expression and localization of TGF-ßRI and II were evaluated using immunohistochemical staining and western blotting. RESULTS: In the KBD samples, chondral necrosis was detected based on cartilage cell disappearance and alkalinity loss in the matrix ground substance. In the necrotic areas, TGF-ßRI and II staining were strong. Positive percentages of TGF-ßRI and II staining were higher in the cartilage samples of KBD donors than in those of control donors. TGF-ßRI and II staining was also increased in cartilage samples from rats administered T-2 toxin or fed on Se-deficient plus T-2 toxin diets. CONCLUSION: TGF-ßRI and II may be involved in the pathophysiology of KBD. This study provides new insights into the pathways that contribute to KBD development.


Assuntos
Doença de Kashin-Bek/genética , Receptor do Fator de Crescimento Transformador beta Tipo II/genética , Receptor do Fator de Crescimento Transformador beta Tipo I/genética , Animais , China/epidemiologia , Humanos , Ratos , Ratos Sprague-Dawley
12.
BMC Surg ; 21(1): 124, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33750366

RESUMO

BACKGROUND: To explore the clinical characteristics, diagnosis and treatment of obturator hernia. METHODS: Eighty-six patients who were diagnosed as obturator hernia by abdominal CT in the Department of Gastrointestinal Surgery of our hospital between 2009 and 2019 were enrolled in this study. Patient characteristics, surgical method, postoperative complications and mortalities were retrospectively reviewed. RESULTS: Thirty days mortality rate of 5.5% and 46.1% were observed in surgery group and non-surgery group, respectively. Surgery was performed as an emergency procedure in 59 cases and elective procedure in 14 cases depending on different hernia contents, intestinal necrosis and signs of peritonitis. In the emergency surgery group, segmental intestinal resection with anastomosis was performed in 24 patients (24/59, 40.7%). There were 4 deaths (4/59, 6.8%) in this group, all of which occurred in patients undergoing SI resections. In contrast, no bowel resection, postoperative complications, or death occurred in the elective surgery group. 3-year recurrence rates of 5.1% (3/59) and 7.1% (1/14) were observed in the emergency surgery and the elective surgery group, respectively. CONCLUSIONS: CT examination plays an important role in improving the diagnostic rate of obturator hernia. Timely surgical treatment is the key to improve the efficacy of obturator hernia and prevent the deterioration of the condition. In addition, intestinal resection and postoperative complications may be the important factors leading to postoperative death.


Assuntos
Hérnia do Obturador , Idoso , Idoso de 80 Anos ou mais , Feminino , Hérnia do Obturador/diagnóstico por imagem , Hérnia do Obturador/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centro Cirúrgico Hospitalar , Tomografia Computadorizada por Raios X , Resultado do Tratamento
13.
Arch Gynecol Obstet ; 301(3): 721-727, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32114673

RESUMO

PURPOSE: To investigate whether there are left-right asymmetries in tubal endometriosis and the factors affecting this predisposition. METHODS: Women who underwent salpingectomy for gynecological diseases and were diagnosed with tubal endometriosis between January 2002 and July 2019 were included in the study. The frequencies of left and right tubal endometriosis were compared with the expected 50% using a binominal test. The demographic characteristics and presence of ovarian endometrioid cysts, adenomyosis, and hydrosalpinx were also analyzed. RESULTS: During the study period of more than 17 years, 305 women were diagnosed with tubal endometriosis. The distribution of tubal endometriosis in the left or right fallopian tubes was analyzed. Tubal endometriosis was found in the left fallopian tube in 168 (55.08%) women, in the right fallopian tube in 93 (30.49%), and bilaterally in 44 (14.43%). Left unilateral tubal endometriosis was found most frequently (64.37%, 168/261), and its incidence was significantly higher than 50% (P < 0.001, binominal test). Furthermore, the frequency of left ovarian endometrioid cysts (58.82%) was higher than that of right ovarian endometrioid cysts (41.18%) (P < 0.001, binominal test). CONCLUSION: Our study confirms that tubal endometriosis is a left-side asymmetric disease, and this predisposition is highly consistent with ovarian endometrioid cysts, which supports the transplantation theory of the origin of endometriosis.


Assuntos
Endometriose/diagnóstico , Endometriose/epidemiologia , Adulto , Feminino , Humanos , Estudos Retrospectivos , Adulto Jovem
14.
J Cell Physiol ; 234(11): 21166-21181, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31032939

RESUMO

Lipofectamine 2000 (Lipo2000) delivery system is commonly used for short interfering RNA (siRNA) transfection, whereas the cellular responses have attracted little attention. The purpose of this study is to evaluate the effect of siRNA transfection using Lipo2000 on cellular functions and the possible underlying mechanism. Primary human umbilical vein endothelial cells (HUVECs) and adult human coronary artery endothelial cell line (HCAECs) were treated with different concentrations of a Lipo2000/negative control siRNA (NC siRNA) complex or Lipo2000 for specific durations. The cell proliferation, apoptosis rate, and protein expression of claudin5 (CLDN5) and ETS-related gene (ERG) were analyzed as indicators of cellular function. The effects of the Lipo2000/NC siRNA complex on cellular autophagy and endoplasmic reticulum (ER) unfolded protein response (UPR) were investigated by western blot and real-time polymerase chain reaction analyses; autophagy was also evaluated by transmission electron microscopy. The Lipo2000/NC siRNA complex inhibited proliferation, downregulated various proteins, and increased the apoptosis in both HUVECs and HCAECs. Both autophagy and UPR were observed in HUVECs treated with the Lipo2000/NC siRNA complex, ER stress-induced autophagy acted as a cellular protective factor against apoptosis, as inhibition of autophagy by chemical inhibitors increased the cell apoptosis rate. Chemical chaperones failed to prevent the Lipo2000/siRNA complex-induced UPR. However, knockdown of protein kinase RNA-like ER kinase and inositol-requiring protein 1, instead of activating transcription factor-6, partially ameliorated the UPR and reversed the protein level of CLDN5 and ERG downregulated by Lipo2000/NC siRNA complex. This study provides the first evidence that the Lipo2000-mediated transport of siRNA leads to an increase in UPR and ER stress-related apoptosis in endothelial cells.


Assuntos
Células Endoteliais/efeitos dos fármacos , Lipídeos/farmacologia , RNA Interferente Pequeno/farmacologia , Resposta a Proteínas não Dobradas/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Transfecção
15.
Mol Reprod Dev ; 86(9): 1094-1105, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31215738

RESUMO

Asthenozoospermia is a common cause of male infertility, but in most cases its etiology is unknown. The exocytic cell vesicles called seminal extracellular vesicles in the human seminal fluid have been reported to play a pivotal role in promoting the motility of spermatozoa, and functional disorder of seminal extracellular vesicles may cause male infertility. To determine whether abnormal seminal extracellular vesicles are involved in asthenozoospermia, the differential abundance proteins between normozoospermic (NSEV) and asthenozoospermic seminal extracellular vesicles (ASEV) samples were analyzed by iTRAQ coupled with two-dimensional liquid chromatography-tandem mass spectrometry. A total of 3,699 proteins were identified in the seminal extracellular vesicles (false discovery rate <0.01). Overall, 11 proteins were significantly upregulated (>1.2) in ASEV and 80 were significantly downregulated (<0.833). Functional bioinformatic analysis showed that these proteins with differential abundance were mainly associated with transport, metabolism, and signal pathways. The changes of OPTN, SMYD2, EIF2B2, TRPV6, ACE, PRSS8, and PPAP2A in ASEV were verified by western blot analysis, and we found that the abundance of TRPV6 markedly reduced in the seminal extracellular vesicles and ejaculated spermatozoa of asthenozoospermic patients, which indicated trpv6 was important in sperm motility. This study provides deeper insight into the involvement of seminal extracellular vesicles in asthenozoospermia and should aid the search for novel biomarkers of male infertility.


Assuntos
Astenozoospermia/metabolismo , Vesículas Extracelulares/metabolismo , Proteômica , Sêmen/metabolismo , Proteínas de Plasma Seminal/metabolismo , Adulto , Astenozoospermia/patologia , Vesículas Extracelulares/patologia , Humanos , Masculino
17.
Heart Surg Forum ; 22(3): E180-E182, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-31237539

RESUMO

BACKGROUND: Cor biloculare, two-chambered heart due to the absence of atrial and ventricular septa, is a rare congenital heart anomaly. For Cor biloculare and other cardiac defects with single ventricle physiology, Glenn anastomosis has been developed as a palliative procedure. Thrombosis secondary to Glenn anastomosis in the patient with Cor biloculare could pose a serious threat to the survival, and has never been reported before. CASE REPORT: We report the case of a 27-year-old patient, with past history of Glenn anastomosis that was performed 7 years ago for the palliation of Cor biloculare. She presented with pulmonary embolism and ischemic stroke simultaneously at 7 days after Cesarean section. Due to her critical status, systemic anticoagulation with low-molecular-weight heparin was started immediately, followed by lifelong warfarin therapy. Pulmonary embolism regressed and neurological symptoms were considerably diminished after the anticoagulation treatment. CONCLUSION: This case illuminates the potential risk of thrombotic events in this patient cohort and demonstrates that anticoagulation therapy is an effective, secure, and appropriate for the management of this disease.


Assuntos
Isquemia Encefálica/etiologia , Técnica de Fontan/efeitos adversos , Cardiopatias Congênitas/cirurgia , Transtornos Puerperais/etiologia , Embolia Pulmonar/etiologia , Acidente Vascular Cerebral/etiologia , Adulto , Anticoagulantes/uso terapêutico , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Cesárea , Feminino , Cardiopatias Congênitas/complicações , Humanos , Transtornos Puerperais/diagnóstico , Transtornos Puerperais/terapia , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/terapia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia
18.
Am J Orthod Dentofacial Orthop ; 156(6): 823-831, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31784016

RESUMO

INTRODUCTION: An accurate prediction in the soft tissue changes is of great importance for orthodontic treatment planning. Previous studies on the accuracy of the Dolphin visual treatment objective (VTO) in predicting treatment results were mainly focused on orthognathic treatment. The accuracy of Dolphin VTO prediction for orthodontic treatment is, however, poorly understood. The aim of this study was to evaluate the accuracy of Dolphin VTO prediction in soft tissue changes after orthodontic treatment by comparing the changes between predicted and actual values. METHODS: A total of 157 patients were screened for eligibility, and 34 young adult patients (8 males, 26 females; mean age 24.8 ± 3.9 years) were finally included in the study based on the inclusion and exclusion criteria. The landmarks and parameters of the Holdaway soft tissue analysis were used for the cephalometric analyses. The cephalometric tracings of the actual treatment result and the Dolphin predicted treatment outcome were superimposed to calculate the prediction errors. Paired t test was used to compare the statistical differences between the predicted and actual treatment outcomes of the parameters used in the Holdaway soft tissue analysis. RESULTS: There were significant differences between the predicted and actual values in parameters of the Holdaway soft tissue analysis (P < 0.05). The prediction of the landmarks in the lips region (ie, subnasale, soft tissue A-point, upper lip, lower lip, and soft tissue B-point) was inclined to be overestimated horizontally and underestimated vertically, whereas the prediction of the landmarks belonging to the chin region (ie, soft tissue pogonion, soft tissue gnathion, and soft tissue menton) was inclined to be underestimated horizontally and overestimated vertically. The most accurate prediction was found in the soft tissue A-point, whereas the least accurate one was found in the soft tissue in the chin region. The prediction was relatively more accurate in the vertical direction than in the horizontal direction. CONCLUSIONS: The Dolphin VTO prediction in soft tissue changes after the orthodontic treatment in patients with bimaxillary protrusion is the most accurate for the soft tissue A-point and the least accurate for the soft tissue chin region.


Assuntos
Face , Má Oclusão , Ortodontia Corretiva , Adulto , Cefalometria , Queixo , Face/anatomia & histologia , Feminino , Previsões , Humanos , Lábio , Masculino , Software , Adulto Jovem
19.
J Cell Mol Med ; 22(3): 1755-1768, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29168316

RESUMO

Outer dense fibers (ODFs), as unique accessory structures in mammalian sperm, are considered to play a role in the protection of the sperm tail against shear forces. However, the role and relevant mechanisms of ODFs in modulating sperm motility and its pathological involvement in asthenozoospermia were unknown. Here, we found that the percentage of ODF defects was higher in asthenozoospermic samples than that in control samples and was significantly correlated with the percentage of axoneme defects and non-motile sperm. Furthermore, the expression levels of ODF major components (Odf1, 2, 3, 4) were frequently down-regulated in asthenozoospermic samples. Intriguingly, the positive relationship between ODF size and sperm motility existed across species. The conditional disruption of Odf2 expression in mice led to reduced sperm motility and the characteristics of asthenozoospermia. Meanwhile, the expression of acetylated α-tubulin was decreased in sperm from both Odf2 conditional knockout (cKO) mice and asthenozoospermic men. Immunofluorescence and biochemistry analyses showed that Odf2 could bind to acetylated α-tubulin and protect the acetylation level of α-tubulin in HEK293T cells in a cold environment. Finally, we found that lithium elevated the expression levels of Odf family proteins and acetylated α-tubulin, elongated the midpiece length and increased the percentage of rapidly moving sperm in mice. Our results demonstrate that ODFs are beneficial for sperm motility via stabilization of the axoneme and that hypo-expression of Odf family proteins is involved in the pathogenesis of asthenozoospermia. The lithium administration assay will provide valuable insights into the development of new treatments for asthenozoospermia.


Assuntos
Axonema/metabolismo , Proteínas de Choque Térmico/genética , Motilidade dos Espermatozoides/genética , Cauda do Espermatozoide/metabolismo , Espermatozoides/metabolismo , Animais , Astenozoospermia/genética , Astenozoospermia/metabolismo , Células HEK293 , Proteínas de Choque Térmico/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Células NIH 3T3 , Ratos Sprague-Dawley
20.
Cell Physiol Biochem ; 45(5): 1975-1985, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29529599

RESUMO

BACKGROUND/AIMS: Long noncoding RNAs (lncRNAs) have recently emerged as novel and potentially promising therapeutic targets in various cancers. However, the expression pattern and biological function of lncRNAs in glioma remain largely elusive. In the present study, we investigated the functional role of an lncRNA, small nucleolar RNA host gene 16 (SNHG16), in glioma. METHODS: The expression levels of SNHG16 and miR-4518 were measured using qRT-PCR. The relationship between the levels of SNHG16 and clinicopathologic features were statically analyzed. The levels of proteins were detected using western blot. Bioinformatics analysis and luciferase reporter assays were applied to the analysis of the relationship between SNHG16, miR-4518 and PRMT5. Cell viability and apoptosis were measured using MTT and apoptosis ELISA assay, respectively. RESULTS: SNHG16 was highly expressed in glioma tissues and cell lines, which was related to poorer clinicopathologic features and shorter survival time. Knockdown of SNHG16 inhibits the viability and induces apoptosis of glioma cells. Further investigation revealed that SNHG16 could up-regulate the expression of miR-4518 targeted gene PRMT5 via acting as an endogenous sponge of miR-4518. Moreover, SNHG16 also affects the expression of Bcl-2 family proteins and the activation of PI3K/Akt signaling pathway. CONCLUSION: Our study revealed a novel SNHG16-miR-4518-PRMT5 pathway regulatory axis in glioma pathogenesis. SNHG16 could be used as a potential therapeutic target in the treatment of glioma.


Assuntos
Neoplasias Encefálicas/patologia , Glioma/patologia , MicroRNAs/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , RNA Longo não Codificante/metabolismo , Regiões 3' não Traduzidas , Idoso , Antagomirs/metabolismo , Apoptose , Sequência de Bases , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/mortalidade , Linhagem Celular Tumoral , Proliferação de Células , Intervalo Livre de Doença , Feminino , Glioma/genética , Glioma/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinases/metabolismo , Proteína-Arginina N-Metiltransferases/antagonistas & inibidores , Proteína-Arginina N-Metiltransferases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Interferência de RNA , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/genética , RNA Interferente Pequeno/metabolismo , Alinhamento de Sequência , Transdução de Sinais , Regulação para Cima
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