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1.
Front Bioeng Biotechnol ; 9: 768698, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34790654

RESUMO

Cancer is still one of the main causes of morbidity and death rate around the world, although diagnostic and therapeutic technologies are used to advance human disease treatment. Currently, surgical resection of solid tumors is the most effective and a prior remedial measure to treat cancer. Although medical treatment, technology, and science have advanced significantly, it is challenging to completely treat this lethal disease. Near-infrared (NIR) fluorescence, including the first near-infrared region (NIR-I, 650-900 nm) and the second near-infrared region (NIR-II, 1,000-1,700 nm), plays an important role in image-guided cancer surgeries due to its inherent advantages, such as great tissue penetration, minimal tissue absorption and emission light scattering, and low autofluorescence. By virtue of its high precision in identifying tumor tissue margins, there are growing number of NIR fluorescence-guided surgeries for various living animal models as well as patients in clinical therapy. Herein, this review introduces the basic construction and operation principles of fluorescence molecular imaging technology, and the representative application of NIR-I/II image-guided surgery in biomedical research studies are summarized. Ultimately, we discuss the present challenges and future perspectives in the field of fluorescence imaging for surgical navigation and also put forward our opinions on how to improve the efficiency of the surgical treatment.

2.
Cancer Manag Res ; 13: 8575-8583, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34815712

RESUMO

Purpose: Long non-coding RNA (lncRNA) DNAJC3 antisense RNA 1 (head to head) (DNAJC3-AS1) plays a key role in the progression of several cancers. However, its biological role in hepatocellular carcinoma (HCC) is still unclear. We aimed to investigate the role of DNAJC3-AS1 in the development of HCC and reveal the potential mechanisms. Materials and Methods: Expression analysis of DNAJC3-AS1 and microRNA-27b (miR-27b) at both mature and premature levels was determined by RT-qPCR. HCC patients were followed up for 5 years to analyze the prognostic value of DNAJC3-AS1 for HCC. The direct interaction between DNAJC3-AS1 and premature miR-27b was analyzed with RNA pull-down assay. Subcellular analysis of DNAJC3-AS1 was explored by subcellular fractionation assay. DNAJC3-AS1 overexpression and knockdown were carried out to analyze the role of DNAJC3-AS1 in miR-27b maturation. Cell proliferation was analyzed by BrdU assay. Results: DNAJC3-AS1 was overexpressed in HCC and predicts the poor survival. MiR-27b was downregulated at mature miRNA level, but upregulated at premature level. DNAJC3-AS1 directly interacted with premature miR-27b and was localized to both nuclear and cytoplasm. DNAJC3-AS1 overexpression upregulated premature miR-27b and downregulated mature miR-27b, while DNAJC3-AS1 knockdown led to the opposite results. DNAJC3-AS1 suppressed the role of miR-27b in inhibiting cell proliferation. Conclusion: DNAJC3-AS1 promotes HCC by sponging premature miR-27b and might be a biomarker and therapeutic target for HCC.

3.
Small ; : e2104295, 2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34716655

RESUMO

A promising anode material consisting of bimetallic thiophosphate Znx Co1- x PS3 and CoS2 with 2D/3D heterostructure is designed and prepared by an effective chemical transformation. Density functional theory calculations illustrate that the Zn2+ can effectively modulate the electrical ordering of Znx Co1- x PS3 on the nanoscale: the reduced charge distribution emerging around the Zn ions can enhance the local built-in electric field, which will accelerate the ions migration rate by Coulomb forces and provide tempting opportunities for manipulating Li+ storage behavior. Moreover, the merits of the large planar size enable Znx Co1- x PS3 to provide abundant anchoring sites for metallic CoS2 nanocubes, generating a 2D/3D heterostructure with a strong electric field. The resultant Znx Co1- x PS3 /CoS2 can offer the combined advantages of bimetallic alloying and heterostructure in lithium storage applications, leading to outstanding performance as an anode material for lithium-ion batteries. Consequently, a high capacity of 794 mA h g-1 can be retained after 100 cycles at 0.2 A g-1 . Even at 3.0 A g-1 , a satisfactory capacity of 465 mA h g-1 can be delivered. The appealing alloying-heterostructure and electrochemical performance of this bimetallic thiophosphate demonstrate its great promise for applications in practical rechargeable batteries.

4.
J Mater Chem B ; 9(39): 8246-8252, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34499075

RESUMO

Drug-induced acute liver injury (DIALI) is a common liver disease, affecting a number of people worldwide with increasing morbidity each year. Thus, it is vital to develop new tools for intervention and diagnosis. Peroxynitrite (ONOO-), a highly reactive species, plays an important role in the DIALI process. Thus, in situ molecular imaging of endogenous ONOO- levels is considerably significant for detecting ONOO-. In this work, we present two destroyed-type ratiometric fluorescent probes, AHC and AHMC, for ONOO- detection by using a molecular hybridization strategy. The probe AHMC was developed by introducing the ester structure to AHC directly to enhance its membrane penetrability for living cell imaging. Probe AHC exhibited good analytical performance toward ONOO- compared to other reactive species, with a low detection limit (≈1.8 nM) and a strong ratiometric fluorescence response (134-fold). In cell imaging experiments, AHMC showed outstanding selectivity, favourable biocompatibility and mitochondria-targeting ability, which not only was used to detect endogenous and exogenous ONOO- changes, but also enabled noninvasive visualization of ONOO- generation in a different drug-induced DIALI model. We hope that these ratiometric probes can be useful chemical tools for the in-depth research of drug-induced acute hepatotoxicity.

5.
Huan Jing Ke Xue ; 42(10): 4708-4716, 2021 Oct 08.
Artigo em Chinês | MEDLINE | ID: mdl-34581113

RESUMO

Environmental DNA(eDNA), a new tool for monitoring the biodiversity of aquatic ecosystems, is able to analyze characteristics of biodiversity from a microscopic perspective. Based on eDNA data collected from the Weihe River, diversity indexes, non-metric multidimensional scaling, cluster analysis, and correlation network analysis were employed to explore the diversity and community structure of zooplankton focusing on the niche differentiation of keystone species and environmental adaptability. The eDNA approach identified three types of zooplankton including Rotifera, Cladocera, and Copepoda, among which the dominant species was Brachionus calyciflorus. The zooplankton community shows significant differences in species composition, abundance, diversity and spatial distribution characteristics(P<0.01). The average values of the Chao1 index, ACE index, Shannon index, and Simpson index were 22.25, 22.38, 2.32, and 0.68, respectively. The downstream biodiversity is significantly higher than in the upstream area. Non-metric multidimensional scale analysis and hierarchical cluster analysis further showed that the zooplankton community structure shows distinct regional differences. The keystone species in the community have a high degree of connection with other species, with a high node degree, centrality, and modularity. The niche breadth(Bi) of the operational taxonomic units(OTUs) of the keystone species varied from 0.38 to 0.80. The medium niche species accounted for 63% of all keystone species. The average niche overlap index(Qik) was 0.72, and the degree of overlap was generally high. RDA analysis further identified that water environmental variables were closely related to changes in the zooplankton community structure and niche differentiation. For example, total nitrogen and water temperature were the main limiting factors, which play important roles in shaping the zooplankton community structure.


Assuntos
Cladóceros , Zooplâncton , Animais , Biodiversidade , Ecossistema , Rios , Estações do Ano , Zooplâncton/genética
6.
Neurology ; 97(21): 986-988, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34556564

RESUMO

BACKGROUND AND OBJECTIVES: To identify fetal familial cerebral cavernous malformation (CCM) and a novel variation. METHODS: A 37-year-old pregnant woman (G4P0) presented with right-handed numbness since 2 weeks at 31 weeks of gestation. Evaluation with brain MRI revealed multiple CCMs. As a result, fetal MRI, fetal whole exome sequencing, and maternal Sanger sequencing were performed. RESULTS: The mother's brain MRI demonstrated numerous CCMs involving the brain stem, cerebral hemispheres, and cerebellum. Fetal MRI showed a CCM located in the left frontal lobe in susceptibility-weighted imaging (SWI). The neuroimaging characteristics of the mother and the fetus suggested that their CCMs may be familial. Genetic analysis revealed a novel variation in KRIT1 (c.1A>G, p.0?), also called CCM1, in the mother and the baby. The mother delivered a daughter at 32 weeks of gestation with an Apgar score of 10 by cesarean section. DISCUSSION: This variation of the initial codon in the KRIT1 gene leads to a phenotype with an early-onset. To our knowledge, this is the first-ever reported case of fetal familial CCM and this novel variation. Brain MRI has excellent sensitivity and specificity, providing the best option for detecting CCMs, even in utero, primarily when SWI is used.

7.
BMC Complement Med Ther ; 21(1): 206, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34372842

RESUMO

BACKGROUND: Alzheimer's disease (AD) is one of the most common neurodegenerative disorders, but there is still no effective way to stop or slow its progression. Our previous studies demonstrated that extract of Cynomorium songaricum (ECS), a Chinese herbal medicine, had neuroprotective effects in AD models in vivo. However, the pharmacological mechanism of ECS in AD is still unclear. METHODS: To study the mechanisms of action of the effects of ECS on AD, we used Aß25-35- and H2O2-exposed HT22 cells to mimic specific stages of AD in vitro. The mitochondrial membrane potential (MMP), intracellular ATP, intracellular reactive oxygen species (ROS), and expression levels of mitochondrial dynamics-related proteins in each group were examined. Furthermore, we explored the mechanisms by which ECS reduces the phosphorylation of Drp1 at Ser637 and the changes in the concentrations of intracellular calcium ions in the two models after FK506 intervention. RESULTS: The results showed that ECS significantly enhanced the MMP (P < 0.05), increased intracellular ATP levels (P < 0.05) and decreased intracellular ROS levels in the Aß- and H2O2-induced cell models (P < 0.05). Additionally, ECS regulated the expression levels of mitochondrial dynamics-related proteins by reducing the phosphorylation of Drp1 at Ser637 (P < 0.05) and decreasing the expression of Fis1 in the H2O2-induced models (P < 0.05). Further study indicated that ECS reduced the overload of intracellular calcium (P < 0.05). CONCLUSION: Our study results suggest that ECS protects the mitochondrial ultrastructure, ameliorates mitochondrial dysfunction, and maintains mitochondrial dynamics in AD models.

8.
Adv Sci (Weinh) ; 8(18): e2100120, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34323391

RESUMO

Rationally designed carbon materials with superstructures are promising candidates in applications such as electrocatalysis. However, the synthesis of highly porous carbon superstructures with macropores and carbon defects from a simple crystalline solid remains challenging. In this work, superstructured macroporous carbon rods composed of defective graphitic nanosheets are synthesized by direct carbonization of crystalline poly tannic acid (PTA) rods as precursors. During carbonization, PTA rods with a highly ordered lamellar structure induce a spatially confined two-step localized contraction that takes place in different dimensions and directions in each step. The unexpected contraction behavior results in the sponge-like macroporous carbon superstructure with large surface area, high porosity, and abundant defects, thus showing a superior electrocatalytic performance with high activity and selectivity for oxygen reduction reaction. The study provides new understandings in the design of functional carbon materials with distinctive structures and applications.

9.
Chem Sci ; 12(9): 3245-3252, 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-34164093

RESUMO

Electronic interactions can radically enhance the performance of supported metal catalysts and are critical for fundamentally understanding the nature of catalysts. However, at the microscopic level, the details of such interactions tuning the electronic properties of the sites on the metal particle's surface and metal-support interface remain obscure. Herein, we found polarized electronic metal-support interaction (pEMSI) in oxide-supported Pd nanoparticles (NPs) describing the enhanced accumulation of electrons at the surface of NPs (superficial Pd δ-) with positive Pd atoms distributed on the interface (interfacial Pd δ+). More superficial Pd δ- species mean stronger pEMSI resulting from the synergistic effect of moderate Pd-oxide interaction, high structural fluxionality and electron transport activity of Pd NPs. The surface Pd δ- species are responsible for improved catalytic performance for H2 evolution from metal hydrides and formates. These extensive insights into the nature of supported-metal NPs may open new avenues for regulating a metal particle's electronic structure precisely and exploiting high-performance catalysts.

10.
J Voice ; 2021 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-34090740

RESUMO

BACKGROUND: Pepsinogen A (PGA)/pepsin A is often used as a diagnostic marker of extra-gastroesophageal reflux. We aimed to explore whether its positivity in upper aerodigestive tract (UADT) was specific enough to diagnose reflux. METHODS: PGA/pepsin A protein levels were examined in 10 types of tissues and 10 types of body fluid by immunological staining, western blot or Elisa, using three different commercially available brands simultaneously. Liquid chromatography-tandem mass spectrometry parallel reaction monitoring (LC-MS/MS PRM) served as a gold reference for the detection of PGA/pepsin A proteins. PGA gene expression was analyzed by reverse transcriptase sequencing methods for tissue samples. Specifically, 24 hour pH monitoring technique was conducted for patients who donated saliva samples. RESULTS: Eight out of ten types of human tissue samples (stomach, esophagus, lung, kidney, colon, parotid gland, nasal turbinate and nasal polyps) were confirmed positive for PGA/pepsin A gene and protein by genetic and PRM technique, respectively. Two out of ten types of body fluid samples (gastric fluid, urine) were confirmed positive for PGA/pepsin A protein by PRM technique. The consistence rates of PGA/pepsin A positivity among three commercial antibody brands and Elisa kit were poor, and Elisa results of salivary did not match with 24-hour pH monitoring. CONCLUSIONS: Multiple tissues and body fluid could be detected baseline expression levels of PGA/pepsin A gene and protein. However, those commercially available PGA/pepsin A antibodies achieved poor sensitivity and specificity, therefore, relying on the detection of PGA/pepsin A in UADT by single antibodies to diagnose extra-gastroesophageal reflux without a specific positive cut-off value is unreliable.

11.
Opt Express ; 29(11): 16781-16803, 2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34154233

RESUMO

We use a model to investigate both the temporal and spectral characteristics of a signal lightwave which has been spectrally broadened through phase modulation with a maximal-length sequence (MLS), which is a common type of pseudo-random bit sequence. The enhancement of the stimulated Brillouin scattering (SBS) threshold of the modulated lightwave in a fiber system is evaluated by numerically simulating the coupled three-wave SBS interaction equations. We find that SBS can build up on a nanosecond-level time scale in a short fiber, which can reduce the SBS suppressing capability of MLS modulation waveforms with GHz-level clock rate, if the sub-sequence ("run") lengths with the same symbol (zero or one) of the MLS extend over several nanoseconds. To ensure the SBS buildup is perturbed and thus suppressed also during these long sub-sequences, we introduce a low-pass filter to average the signal over several bits so that the modulation waveform changes gradually even during long runs and amplify the RF modulation waveforms to the level required for sufficient spectral broadening and carrier suppression of the optical signal. We find that the SBS suppression depends non-monotonically on the parameters of the filtered and amplified MLS waveform such as pattern length, modulation depth, and the ratio of low-pass filter cutoff frequency to clock rate for maximum SBS mitigation. We optimize the SBS suppression through numerical simulations and discuss it in terms of the temporal and spectral characteristics of the lightwave and modulation waveform using derived analytical expressions and numerical simulations. The simulations indicate that the normalized SBS threshold reaches a maximum for a RMS modulation depth of 0.56π and a ratio of filter cutoff frequency to clock rate of 0.54 and that MLS9 is superior to other investigated patterns.

12.
Eur J Nucl Med Mol Imaging ; 48(13): 4426-4436, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34131804

RESUMO

PURPOSE: H3K27M-mutant associated brainstem glioma (BSG) carries a very poor prognosis. We aimed to predict H3K27M mutation status by amide proton transfer-weighted (APTw) imaging and radiomic features. METHODS: Eighty-one BSG patients with APTw imaging at 3T MR and known H3K27M status were retrospectively studied. APTw values (mean, median, and max) and radiomic features within manually delineated 3D tumor masks were extracted. Comparison of APTw measures between H3K27M-mutant and wildtype groups was conducted by two-sample Student's T/Mann-Whitney U test and receiver operating characteristic curve (ROC) analysis. H3K27M-mutant prediction using APTw-derived radiomics was conducted using a machine learning algorithm (support vector machine) in randomly selected train (n = 64) and test (n = 17) sets. Sensitivity analysis with additional random splits of train and test sets, 2D tumor masks, and other classifiers were conducted. Finally, a prospective cohort including 29 BSG patients was acquired for validation of the radiomics algorithm. RESULTS: BSG patients with H3K27M-mutant were younger and had higher max APTw values than those with wildtype. APTw-derived radiomic measures reflecting tumor heterogeneity could predict H3K27M mutation status with an accuracy of 0.88, sensitivity of 0.92, and specificity of 0.80 in the test set. Sensitivity analysis confirmed the predictive ability (accuracy range: 0.71-0.94). In the independent prospective validation cohort, the algorithm reached an accuracy of 0.86, sensitivity of 0.88, and specificity of 0.85 for predicting H3K27M-mutation status. CONCLUSION: BSG patients with H3K27M-mutant had higher max APTw values than those with wildtype. APTw-derived radiomics could accurately predict a H3K27M-mutant status in BSG patients.


Assuntos
Neoplasias Encefálicas , Glioma , Amidas , Tronco Encefálico , Glioma/diagnóstico por imagem , Glioma/genética , Humanos , Imageamento por Ressonância Magnética , Prótons , Estudos Retrospectivos
13.
Proc Natl Acad Sci U S A ; 118(24)2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34099558

RESUMO

Cytosolic DNA activates cGAS (cytosolic DNA sensor cyclic AMP-GMP synthase)-STING (stimulator of interferon genes) signaling, which triggers interferon and inflammatory responses that help defend against microbial infection and cancer. However, aberrant cytosolic self-DNA in Aicardi-Goutière's syndrome and constituently active gain-of-function mutations in STING in STING-associated vasculopathy with onset in infancy (SAVI) patients lead to excessive type I interferons and proinflammatory cytokines, which cause difficult-to-treat and sometimes fatal autoimmune disease. Here, in silico docking identified a potent STING antagonist SN-011 that binds with higher affinity to the cyclic dinucleotide (CDN)-binding pocket of STING than endogenous 2'3'-cGAMP. SN-011 locks STING in an open inactive conformation, which inhibits interferon and inflammatory cytokine induction activated by 2'3'-cGAMP, herpes simplex virus type 1 infection, Trex1 deficiency, overexpression of cGAS-STING, or SAVI STING mutants. In Trex1 -/- mice, SN-011 was well tolerated, strongly inhibited hallmarks of inflammation and autoimmunity disease, and prevented death. Thus, a specific STING inhibitor that binds to the STING CDN-binding pocket is a promising lead compound for STING-driven disease.

14.
J Med Internet Res ; 23(6): e25259, 2021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34033579

RESUMO

BACKGROUND: Due to strict, nationwide, comprehensive COVID-19 protective measures, including home quarantine, all Chinese medical students began taking web-based classes beginning in the spring semester of 2020. Home quarantine, web-based classes, and the stress surrounding the COVID-19 pandemic may have triggered an increased incidence of mental health problems among medical students. Although there have been increasing amounts of literature on depression among medical students, studies focusing on positive psychological resources, such as resilience during the COVID-19 pandemic, still need to be expanded. OBJECTIVE: This study aims to assess depression among medical students who are taking web-based classes during the COVID-19 pandemic and to investigate the role of coping styles as mediators between resilience and depression. METHODS: A cross-sectional study of 666 medical students involving stratified sampling in Shenyang, Liaoning Province, China, was completed between March 20 and April 10, 2020. The participants responded to a self-administered, smartphone-based questionnaire, which included the Patient Health Questionnaire-9, Simplified Coping Style Questionnaire, and Ego Resilience 89 Scale. Hierarchical linear regression and structural equation modeling were used in this study. RESULTS: The prevalence of depression among the participants was 9.6% (64/666) in this study. The regression analysis revealed that grade (the year in which the medical student was in training) (P=.013), how well students adapted to web-based classes (P<.001), their levels of resilience (P=.04), and their coping styles were independent predictors for depression (P<.001). Resilience and positive coping styles were negatively related to depression (resilience: P=.04; positive coping styles: P<.001), and negative coping styles were positively related to depression (P<.001). The structural equation modeling analysis showed that the effect of resilience on depression was partially mediated by coping styles (P=.007). CONCLUSIONS: In this study, it was found that the prevalence of depression was slightly low and coping styles mediated the association between resilience and depression among medical students during the COVID-19 pandemic. These findings have significant implications for future studies. Future studies and interventions should aim to improve resilience and promote positive coping styles.


Assuntos
Adaptação Psicológica , COVID-19/epidemiologia , Depressão/epidemiologia , Educação à Distância , Internet , Resiliência Psicológica , Estudantes de Medicina/psicologia , Inquéritos e Questionários , China/epidemiologia , Estudos Transversais , Depressão/psicologia , Feminino , Humanos , Masculino , Pandemias , Prevalência , Quarentena , Adulto Jovem
15.
Front Pharmacol ; 12: 690256, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054561

RESUMO

Mitochondrial dysfunction with oxidative damage plays the fundamental roles in the pathogenesis of Alzheimer's disease. In traditional Chinese medicine (TCM) practice, animal tissue-derived gelatins are often used as nootropic agents to treat cognitive deterioration and senile dementia. Tortoise plastron gelatin (TPG) and deer antler gelatin (DAG) are the two most commonly used gelatins for this purpose. This study sought to examine the effects of the two gelatins in preventing neuronal mitochondria from oxidative damage. PC12 cells, a cell line derived from rat pheochromocytoma, exposed to the neurotoxin Aß25-35 served as an in vitro model of Alzheimer's disease. The cells were separately pre-treated with TPG and DAG at various concentrations ranging from 6.26 µg/ml-200 µg/ml, followed by co-incubation with 20 µM Aß25-35 for different duration. Cell viability, mitochondrial membrane potential (MMP) and ultrastructure, intracellular ATP, reactive oxygen species (ROS) and calcium (Ca2+) level, the expression of mitochondrial dynamic proteins and biomarkers of apoptosis were measured. Pretreatment with TPG and DAG reversed the Aß-induced reduction of cell viability in a dose-dependent manner. Both TPG and DAG significantly increased MMP and ATP, alleviated the accumulation of damaged mitochondrial fragments, and normalized the aberrant expression of multiple mitochondrial dynamic proteins of the Aß-exposed cells. Both gelatins also suppressed intracellular ROS overproduction and Ca2+ overload, overexpression of cytochrome c and pro-apoptosis biomarkers induced by the Aß exposure. These results suggest that TPG and DAG may have the anti-dementia potential by preventing neuronal mitochondria from oxidative damage.

16.
Opt Express ; 29(9): 13778-13786, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33985106

RESUMO

A novel approach for ultrafast and temperature-insensitive strain interrogation using a polarization-maintaining photonic crystal fiber (PM-PCF) based Sagnac loop interferometer (SLI) and linear wavelength-to-time (WTT) mapping is proposed and experimentally demonstrated. The PM-PCF incorporated in the SLI is used as the sensing element to achieve stable strain sensing with ultra-low temperature-dependence due to its intrinsic thermal insensitivity, which can be used to eliminate the cross-sensitivity effect and increase the measurement accuracy. A dispersive element is employed to realize the WTT mapping and real-time strain interrogation is obtained by converting the strain-encoded wavelength shift to time shift in the temporal domain, which can be directly monitored by a real-time oscilloscope. The proposed system offers an ultrafast interrogation speed of 100 MHz and a strain sensitivity of -0.17 ps/µÎµ.

17.
Front Pharmacol ; 12: 665456, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33986688

RESUMO

Ischemic stroke is a common type of cerebrovascular event and also the leading cause of disability. Post-stroke cognitive impairment occurs frequently in stroke survivors. Shexiang Baoxin Pill (SBP) is a proprietary Chinese medicine, initially used to treat cardiovascular diseases. Herein, we aim to explore the effects of SBP on oxygen glucose deprivation and reoxygenation (OGD/R) in neuronal cells (CATH.a) and cerebral ischemia/reperfusion injury induced post-stroke cognitive impairment in middle cerebral artery occlusion (MCAO) rat model. MCAO rats received two doses of oral SBP treatment (28 or 56 mg/kg) after 1 h of operation and once daily for 2 weeks continuously. Behavioral tests, immunoblotting, and immunofluorescence were examined after 14 days. Current data suggest that SBP enhanced cell viability and downregulated apoptosis via activating the PI3K/Akt signaling pathway in CATH. a cells. Furthermore, 14 days of SBP treatment promoted the recovery of learning and locomotor function in the MCAO rats. SBP up-regulated the expression of p-Akt, p-GSK3ß, as well as the expression of NMDAR1, PSD-95, and AMPAR. Also, SBP down-regulated the expression of p-CaMKII. These results indicated that long-term SBP treatment might be a potential option for cognitive impairment induced by the ischemic stroke.

18.
Pathol Res Pract ; 222: 153455, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33962176

RESUMO

BACKGROUND: Esophageal carcinoma has poor prognosis and novel therapies for esophageal carcinoma are urgently needed. Quercetin is a natural flavonoid compound that can be found in many foods. In this study, we investigated the effects of quercetin on invasion and angiogenesis of esophageal cancer cells. METHODS: Human esophageal cancer cell line Eca109 was treated with 5 µg/mL or 10 µg/mL of quercetin. Colony formation assay was performed. Cell migration and invasion were evaluated by wound healing and transwell assays, respectively. Human umbilical vein/vascular endothelium cells (CLR-1730) were treated with Eca109 conditioned medium, and the effects of quercetin on CLR-1730 were evaluated by wound healing and tube formation assays. Protein levels of VEGF-A, MMP9, and MMP2 were determined by Western blotting. RESULTS: The ability of colony forming in Eca109 was reduced with the administration of 10 µg/mL quercetin, but there was no difference between the 5 µg/mL quercetin group and control. The migration distance and the number of invasive cells were significantly reduced in the 10 µg/mL quercetin group. At the lower level of quercetin at 5 µg/mL, only the invasion of cells was significantly inhibited. In endothelial cells treated with Eca109 conditioned medium, cell migration and tube forming ability were suppressed. The decreased protein levels of VEGF-A, MMP9, and MMP2 were observed at the 10 µg/mL quercetin group. CONCLUSION: Quercetin suppressed the invasion and angiogenesis of esophageal cancer cells, and the effects were associated with the decreased expression of VEGF-A, MMP2, and MMP9.

19.
Cell Death Dis ; 12(5): 457, 2021 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-33963173

RESUMO

Colorectal cancer (CRC) is one of the most aggressive and lethal cancers. The role of autophagy in the pathobiology of CRC is intricate, with opposing functions manifested in different cellular contexts. The Yes-associated protein (YAP), a transcriptional coactivator inactivated by the Hippo tumor-suppressor pathway, functions as an oncoprotein in a variety of cancers. In this study, we found that YAP could negatively regulate autophagy in CRC cells, and consequently, promote tumor progression of CRC in vitro and in vivo. Mechanistically, YAP interacts with TEAD forming a complex to upregulate the transcription of the apoptosis-inhibitory protein Bcl-2, which may subsequently facilitate cell survival by suppressing autophagy-related cell death; silencing Bcl-2 expression could alleviate YAP-induced autophagy inhibition without affecting YAP expression. Collectively, our data provide evidence for YAP/Bcl-2 as a potential therapeutic target for drug exploration against CRC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Neoplasias Colorretais/genética , Genes bcl-2/genética , Animais , Autofagia , Neoplasias Colorretais/patologia , Progressão da Doença , Humanos , Camundongos , Camundongos Nus , Transfecção , Regulação para Cima
20.
JCI Insight ; 6(11)2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33945508

RESUMO

The epithelial cell-derived cytokines IL-25, IL-33, and thymic stromal lymphopoietin (TSLP) initiate type 2 inflammation in allergic diseases, including asthma. However, the signaling pathway regulating these cytokines expression remains elusive. Since microRNAs are pivotal regulators of gene expression, we profiled microRNA expression in bronchial epithelial brushings from type 2-low and type 2-high asthma patients. miR-206 was the most highly expressed epithelial microRNA in type 2-high asthma relative to type 2-low asthma but was downregulated in both subsets compared with healthy controls. CD39, an ectonucleotidase degrading ATP, was a target of miR-206 and upregulated in asthma. Allergen-induced acute extracellular ATP accumulation led to miR-206 downregulation and CD39 upregulation in human bronchial epithelial cells, forming a feedback loop to eliminate excessive ATP. Airway ATP levels were markedly elevated and strongly correlated with IL-25 and TSLP expression in asthma patients. Intriguingly, airway miR-206 antagonism increased Cd39 expression; reduced ATP accumulation; suppressed IL-25, IL-33, and Tslp expression and group 2 innate lymphoid cell expansion; and alleviated type 2 inflammation in a mouse model of allergic airway inflammation. In contrast, airway miR-206 overexpression had opposite effects. Overall, epithelial miR-206 upregulates airway IL-25 and TSLP expression by targeting the CD39-extracellular ATP axis, which represents a potentially novel therapeutic target in type 2-high asthma.

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