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1.
FASEB J ; 37(9): e22996, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37566526

RESUMO

Myocardial ischemia/reperfusion injury (MIRI) is a prevalent condition associated with numerous critical clinical conditions. miR-322 has been implicated in MIRI through poorly understood mechanisms. Our preliminary analysis indicated potential interaction of CREB-binding protein (CBP), a transcriptional coactivator and acetyltransferase, with HIF-1α/ß-catenin, which might regulate miR-322 expression. We, therefore, hypothesized that CBP/HIF-1α/ß-catenin/miR-322 axis might play a role in MIRI. Rat cardiomyocytes subjected to oxygen-glucose deprivation /reperfusion (OGD/R) and Langendorff perfused heart model were used to model MIRI in vitro and in vivo, respectively. We used various techniques such as CCK-8 assay, transferase dUTP nick end labeling staining, western blotting, RT-qPCR, chromatin immunoprecipitation (ChIP), dual-luciferase assay, co-immunoprecipitation (Co-IP), hematoxylin and eosin staining, and TTC staining to assess cell viability, apoptosis, and the levels of CBP, HIF-1α, ß-catenin, miR-322, and acetylation. Our results indicate that OGD/R in cardiomyocytes decreased CBP/HIF-1α/ß-catenin/miR-322 expression, increased cell apoptosis and cytokines, and reduced cell viability. However, overexpression of CBP or miR-322 suppressed OGD/R-induced cell injury, while knockdown of HIF-1α/ß-catenin further exacerbated the damage. HIF-1α/ß-catenin bound to miR-322 promoter to promote its expression, while CBP acetylated HIF-1α/ß-catenin for stabilization. Overexpression of CBP attenuated MIRI in rats by acetylating HIF-1α/ß-catenin to stabilize their expression, resulting in stronger binding of HIF-1α/ß-catenin with the miR-322 promoter and subsequent increased miR-322 levels. Therefore, activating CBP/HIF-1α/ß-catenin/miR-322 signaling may be a potential approach to treat MIRI.


Assuntos
MicroRNAs , Traumatismo por Reperfusão Miocárdica , Animais , Ratos , Apoptose , beta Catenina/genética , beta Catenina/metabolismo , Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo
2.
Pharmacol Res ; 204: 107208, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38729587

RESUMO

Cancer cell line is commonly used for discovery and development of anti-cancer drugs. It is generally considered that drug response remains constant for a certain cell line due to the identity of genetics thus protein patterns. Here, we demonstrated that cancer cells continued dividing even after reaching confluence, in that the proteomics was changed continuously and dramatically with strong relevance to cell division, cell adhesion and cell metabolism, indicating time-dependent intrinsically reprogramming of cells during expansion. Of note, the inhibition effect of most anti-cancer drugs was strikingly attenuated in culture cells along with cell expansion, with the strongest change at the third day when cells were still expanding. Profiling of an FDA-approved drug library revealed that attenuation of response with cell expansion is common for most drugs, an exception was TAK165 that was a selective inhibitor of mitochondrial respiratory chain complex I. Finally, we screened a panel of natural products and identified four pentacyclic triterpenes as selective inhibitors of cancer cells under prolonged growth. Taken together, our findings underscore that caution should be taken in evaluation of anti-cancer drugs using culture cells, and provide agents selectively targeting overgrowth cancer cells.


Assuntos
Antineoplásicos , Proliferação de Células , Proteômica , Humanos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Fatores de Tempo , Produtos Biológicos/farmacologia , Triterpenos Pentacíclicos/farmacologia
3.
BMC Vet Res ; 20(1): 191, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734611

RESUMO

BACKGROUND: Many proteins of African swine fever virus (ASFV, such as p72, p54, p30, CD2v, K205R) have been successfully expressed and characterized. However, there are few reports on the DP96R protein of ASFV, which is the virulence protein of ASFV and plays an important role in the process of host infection and invasion of ASFV. RESULTS: Firstly, the prokaryotic expression vector of DP96R gene was constructed, the prokaryotic system was used to induce the expression of DP96R protein, and monoclonal antibody was prepared by immunizing mice. Four monoclonal cells of DP96R protein were obtained by three ELISA screening and two sub-cloning; the titer of ascites antibody was up to 1:500,000, and the monoclonal antibody could specifically recognize DP96R protein. Finally, the subtypes of the four strains of monoclonal antibodies were identified and the minimum epitopes recognized by them were determined. CONCLUSION: Monoclonal antibody against ASFV DP96R protein was successfully prepared and identified, which lays a foundation for further exploration of the structure and function of DP96R protein and ASFV diagnostic technology.


Assuntos
Vírus da Febre Suína Africana , Anticorpos Monoclonais , Epitopos , Camundongos Endogâmicos BALB C , Proteínas Virais , Animais , Feminino , Camundongos , Febre Suína Africana/imunologia , Febre Suína Africana/virologia , Vírus da Febre Suína Africana/imunologia , Anticorpos Monoclonais/imunologia , Anticorpos Antivirais/imunologia , Epitopos/imunologia , Suínos , Proteínas Virais/imunologia
4.
J Infect Dis ; 2023 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-37996071

RESUMO

BACKGROUND: The emergence of rapidly evolving SARS-CoV-2 variants, coupled with waning vaccine-induced immunity, has contributed to the rise of vaccine breakthrough infections. It is crucial to understand how vaccine-induced protection is mediated. METHODS: We examined two prospective cohorts of mRNA-vaccinated-and-boosted individuals during the Omicron wave of infection in Singapore. RESULTS: We found that, individuals, who remain uninfected over the follow-up period, had a higher variant-specific IgA, but not IgG, antibody response at 1-month post booster vaccination, compared with individuals who became infected. CONCLUSIONS: We conclude that IgA may have a potential contributory role in protection against Omicron infection.

5.
J Cell Physiol ; 238(11): 2692-2709, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37796139

RESUMO

Oxidative stress has been considered to be closely related to spaceflight-induced bone loss; however, mechanism is elusive and there are no effective countermeasures. Using cultured rat calvarial osteoblasts exposed to microgravity simulated by a random positioning machine, this study addressed the hypotheses that microgravity-induced shortening of primary cilia leads to oxidative stress and that primary cilium protection prevents oxidative stress and osteogenesis loss. Microgravity was found to induce oxidative stress (as represented by increased levels of reactive oxygen species (ROS) and malondialdehyde production, and decreased activities of antioxidant enzymes), which was perfectly replicated in osteoblasts growing in NG with abrogated primary cilia (created by transfection of an interfering RNA), suggesting the possibility that shortening of primary cilia leads to oxidative stress. Oxidative stress was accompanied by mitochondrial dysfunction (represented by increased mitochondrial ROS and decreased mitochondrial membrane potential) and intracellular Ca2+ overload, and the latter was found to be caused by increased activity of Ca2+ channel transient receptor potential vanilloid 4 (TRPV4), as also evidenced by TRPV4 agonist GSK1016790A-elicited Ca2+ influx. Supplementation of HC-067047, a specific antagonist of TRPV4, attenuated microgravity-induced mitochondrial dysfunction, oxidative stress, and osteogenesis loss. Although TRPV4 was found localized in primary cilia and expressed at low levels in NG, microgravity-induced shortening of primary cilia led to increased TRPV4 levels and Ca2+ influx. When primary cilia were protected by miR-129-3p overexpression or supplementation with a natural flavonoid moslosooflavone, microgravity-induced increased TRPV4 expression, mitochondrial dysfunction, oxidative stress, and osteogenesis loss were all prevented. Our data revealed a new mechanism that primary cilia function as a controller for TRPV4 expression. Microgravity-induced injury on primary cilia leads to increased expression and overactive channel of TRPV4, causing intracellular Ca2+ overload and oxidative stress, and primary cilium protection could be an effective countermeasure against microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts.


Assuntos
Cílios , Osteoblastos , Osteogênese , Estresse Oxidativo , Canais de Cátion TRPV , Ausência de Peso , Animais , Ratos , Cílios/metabolismo , Osteoblastos/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Canais de Cátion TRPV/agonistas , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/metabolismo , Células Cultivadas , Morfolinas/farmacologia , Pirróis/farmacologia , Gravitação
6.
J Med Virol ; 95(1): e28258, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36305052

RESUMO

Waning antibody levels against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the emergence of variants of concern highlight the need for booster vaccinations. This is particularly important for the elderly population, who are at a higher risk of developing severe coronavirus disease 2019 (COVID-19) disease. While studies have shown increased antibody responses following booster vaccination, understanding the changes in T and B cell compartments induced by a third vaccine dose remains limited. We analyzed the humoral and cellular responses in subjects who received either a homologous messenger RNA(mRNA) booster vaccine (BNT162b2 + BNT162b2 + BNT162b2; ''BBB") or a heterologous mRNA booster vaccine (BNT162b2 + BNT162b2 + mRNA-1273; ''BBM") at Day 0 (prebooster), Day 7, and Day 28 (postbooster). Compared with BBB, elderly individuals (≥60 years old) who received the BBM vaccination regimen display higher levels of neutralizing antibodies against the Wuhan and Delta strains along with a higher boost in immunoglobulin G memory B cells, particularly against the Omicron variant. Circulating T helper type 1(Th1), Th2, Th17, and T follicular helper responses were also increased in elderly individuals given the BBM regimen. While mRNA vaccines increase antibody, T cell, and B cell responses against SARS-CoV-2 1 month after receiving the third dose booster, the efficacy of the booster vaccine strategies may vary depending on age group and regimen combination.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Humanos , Pessoa de Meia-Idade , SARS-CoV-2/genética , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas de mRNA , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinação
7.
Cancer Cell Int ; 23(1): 229, 2023 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794491

RESUMO

BACKGROUND: Mutations in the KEAP1-NFE2L2 signaling pathway were linked to increased tumorigenesis and aggressiveness. Interestingly, not all hotspot mutations on NFE2L2 were damaging; some even were activating. However, there was conflicting evidence about the association between NFE2L2 mutation and Nrf2-activating mutation and responsiveness to immune checkpoint inhibitors (ICIs) in non-small cell lung cancer (NSCLC) and other multiple cancers. METHODS: The study with the largest sample size (n = 49,533) explored the landscape of NFE2L2 mutations and their impact response/resistance to ICIs using public cohorts. In addition, the in-house WXPH cohort was used to validate the efficacy of immunotherapy in the NFE2L2 mutated patients with NSCLC. RESULTS: In two pan-cancer cohorts, Nrf2-activating mutation was associated with higher TMB value compared to wild-type. We identified a significant association between Nrf2-activating mutation and shorter overall survival in pan-cancer patients and NSCLC patients but not in those undergoing ICIs treatment. Similar findings were obtained in cancer patients carrying the NFE2L2 mutation. Furthermore, in NSCLC and other cancer cohorts, patients with NFE2L2 mutation demonstrated more objective responses to ICIs than patients with wild type. Our in-house WXPH cohort further confirmed the efficacy of immunotherapy in the NFE2L2 mutated patients with NSCLC. Lastly, decreased inflammatory signaling pathways and immune-depleted immunological microenvironments were enriched in Nrf2-activating mutation patients with NSCLC. CONCLUSIONS: Our study found that patients with Nrf2-activating mutation had improved immunotherapy outcomes than patients with wild type in NSCLC and other tumor cohorts, implying that Nrf2-activating mutation defined a distinct subset of pan-cancers and might have implications as a biomarker for guiding ICI treatment, especially NSCLC.

8.
Clin Infect Dis ; 75(12): 2088-2096, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-35543372

RESUMO

BACKGROUND: Waning antibody levels post-vaccination and the emergence of variants of concern (VOCs) capable of evading protective immunity have raised the need for booster vaccinations. However, which combination of coronavirus disease 2019 (COVID-19) vaccines offers the strongest immune response against the Omicron variant is unknown. METHODS: This randomized, participant-blinded, controlled trial assessed the reactogenicity and immunogenicity of different COVID-19 vaccine booster combinations. A total of 100 BNT162b2-vaccinated individuals were enrolled and randomized 1:1 to either homologous (BNT162b2 + BNT162b2 + BNT162b2; "BBB") or heterologous messenger RNA (mRNA) (BNT162b2 + BNT162b2 + mRNA-1273; "BBM") booster vaccine. The primary end point was the level of neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) wild-type and VOCs at day 28. RESULTS: A total of 51 participants were allocated to BBB and 49 to BBM; 50 and 48, respectively, were analyzed for safety and immunogenicity outcomes. At day 28 post-boost, mean SARS-CoV-2 spike antibody titers were lower with BBB (22 382 IU/mL; 95% confidence interval [CI], 18 210 to 27 517) vs BBM (29 751 IU/mL; 95% CI, 25 281 to 35 011; P = .034) as was the median level of neutralizing antibodies: BBB 99.0% (interquartile range [IQR], 97.9% to 99.3%) vs BBM 99.3% (IQR, 98.8% to 99.5%; P = .021). On subgroup analysis, significant higher mean spike antibody titer, median surrogate neutralizing antibody level against all VOCs, and live Omicron neutralization titer were observed only in older adults receiving BBM. Both vaccines were well tolerated. CONCLUSIONS: Heterologous mRNA-1273 booster vaccination compared with homologous BNT123b2 induced a stronger neutralizing response against the Omicron variant in older individuals. CLINICAL TRIALS REGISTRATION: NCT05142319.


Assuntos
Vacina BNT162 , COVID-19 , Humanos , Idoso , SARS-CoV-2 , Formação de Anticorpos , Vacina de mRNA-1273 contra 2019-nCoV , Vacinação , Anticorpos Neutralizantes , Anticorpos Antivirais
9.
J Neuroinflammation ; 19(1): 21, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-35073927

RESUMO

BACKGROUND: Understanding the pathophysiology of central nervous system tuberculosis (CNS-TB) is hampered by the lack of a good pre-clinical model that mirrors the human CNS-TB infection. We developed a murine CNS-TB model that demonstrates neurobehavioral changes with similar immunopathology with human CNS-TB. METHODS: We injected two Mycobacterium tuberculosis (M.tb) strains, H37Rv and CDC1551, respectively, into two mouse strains, C3HeB/FeJ and Nos2-/- mice, either into the third ventricle or intravenous. We compared the neurological symptoms, histopathological changes and levels of adhesion molecules, chemokines, and inflammatory cytokines in the brain induced by the infections through different routes in different strains. RESULTS: Intra-cerebroventricular infection of Nos2-/- mice with M.tb led to development of neurological signs and more severe brain granulomas compared to C3HeB/FeJ mice. Compared with CDC1551 M.tb, H37Rv M.tb infection resulted in a higher neurobehavioral score and earlier mortality. Intra-cerebroventricular infection caused necrotic neutrophil-dominated pyogranulomas in the brain relative to intravenous infection which resulted in disseminated granulomas and mycobacteraemia. Histologically, intra-cerebroventricular infection of Nos2-/- mice with M.tb resembled human CNS-TB brain biopsy specimens. H37Rv intra-cerebroventricular infected mice demonstrated higher brain concentrations of inflammatory cytokines, chemokines and adhesion molecule ICAM-1 than H37Rv intravenous-infected mice. CONCLUSIONS: Intra-cerebroventricular infection of Nos2-/- mice with H37Rv creates a murine CNS-TB model that resembled human CNS-TB immunopathology, exhibiting the worst neurobehavioral score with a high and early mortality reflecting disease severity and its associated neurological morbidity. Our murine CNS-TB model serves as a pre-clinical platform to dissect host-pathogen interactions and evaluate therapeutic agents for CNS-TB.


Assuntos
Mycobacterium tuberculosis , Tuberculose do Sistema Nervoso Central , Tuberculose , Animais , Modelos Animais de Doenças , Humanos , Camundongos , Camundongos Endogâmicos , Mycobacterium tuberculosis/fisiologia , Óxido Nítrico Sintase Tipo II , Tuberculose do Sistema Nervoso Central/patologia
10.
Sensors (Basel) ; 22(23)2022 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-36502148

RESUMO

Pyroelectric infrared (PIR) sensors are low-cost, low-power, and highly reliable sensors that have been widely used in smart environments. Indoor localization systems may be wearable or non-wearable, where the latter are also known as device-free localization systems. Since binary PIR sensors detect only the presence of a subject's motion in their field of view (FOV) without other information about the actual location, information from overlapping FOVs of multiple sensors can be useful for localization. This study introduces the PIRILS (pyroelectric infrared indoor localization system), in which the sensing signal processing algorithms are augmented by deep learning algorithms that are designed based on the operational characteristics of the PIR sensor. Expanding to the detection of multiple targets, the PIRILS develops a quantized scheme that exploits the behavior of an artificial neural network (ANN) model to demonstrate localization performance in tracking multiple targets. To further improve the localization performance, the PIRILS incorporates a data augmentation strategy that enhances the training data diversity of the target's motion. Experimental results indicate system stability, improved positioning accuracy, and expanded applicability, thus providing an improved indoor multi-target localization framework.


Assuntos
Algoritmos , Inteligência Artificial , Redes Neurais de Computação , Processamento de Sinais Assistido por Computador , Movimento (Física)
11.
Heart Vessels ; 36(10): 1525-1535, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33830315

RESUMO

The mutation MYBPC3-E334K is a culprit mutation of hypertrophic cardiomyopathy (HCM). The pathogenicity of MYBPC3-E334K is conflicting in ClinVar because of the limited segregation data and the relatively high frequency in gnomAD (0.03% overall, with 0.3% in East Asians and 0.8% in Japanese). The main aim is to clarify the clinical importance and phenotype-genotype correlations in subjects with or without MYBPC3-E334K alone. The prevalence of MYBPC3-E334K was sequenced in 1017 HCM unrelated probands. The clinical features, morphology phenotypes, and electrical phenotypes were further analyzed according to the phenotype and genotype status in families with single-mutation MYBPC3-E334K. Nine of 1017 (0.88%) unrelated HCM probands were detected harboring MYBPC3-E334K, and three of them harbored a second variant in sarcomere protein gene. Family study and co-segregation analyses indicated that patients with single-mutation MYBPC3-E334K showed autosomal dominant mode of inheritance with incomplete penetrance. The overall disease penetrance was 52.6%, and the disease penetrance was higher in males than in females (100% in men vs 25% in women, p = 0.003). The mean age at diagnosis of males was approximately 25 years younger than females (36.57 ± 18.65 vs 62.33 ± 12.10, p = 0.062). The variant MYBPC3-E334K was classified as a likely pathogenic variant, and a second sarcomere variant did not reveal obvious cumulative effects. The patients harboring single-mutation MYBPC3-E334K had incomplete penetrance, and males demonstrated higher penetrance and early onset HCM than females. A second sarcomere variant did not reveal obvious cumulative effects.


Assuntos
Cardiomiopatia Hipertrófica , Proteínas de Transporte/genética , Adolescente , Adulto , Idoso , Cardiomiopatia Hipertrófica/diagnóstico , Cardiomiopatia Hipertrófica/genética , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fenótipo , Adulto Jovem
12.
Sensors (Basel) ; 21(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34577386

RESUMO

Pyroelectric Infrared (PIR) sensors are low-cost, low-power, and highly reliable sensors that have been widely used in smart environments. Indoor localization systems can be categorized as wearable and non-wearable systems, where the latter are also known as device-free localization systems. Since the binary PIR sensor detects only the presence of a human motion in its field of view (FOV) without any other information about the actual location, utilizing the information of overlapping FOV of multiple sensors can be useful for localization. In this study, a PIR detector and sensing signal processing algorithms were designed based on the characteristics of the PIR sensor. We applied the designed PIR detector as a sensor node to create a non-wearable cooperative indoor human localization system. To improve the system performance, signal processing algorithms and refinement schemes (i.e., the Kalman filter, a Transferable Belief Model, and a TBM-based hybrid approach (TBM + Kalman filter)) were applied and compared. Experimental results indicated system stability and improved positioning accuracy, thus providing an indoor cooperative localization framework for PIR sensor networks.


Assuntos
Algoritmos , Processamento de Sinais Assistido por Computador , Humanos , Movimento (Física)
13.
Zhongguo Zhong Yao Za Zhi ; 46(3): 670-677, 2021 Feb.
Artigo em Zh | MEDLINE | ID: mdl-33645034

RESUMO

This study aims to investigate the potential mechanism of curcumin in mediating interleukin-6(IL-6)/signal transducer and activator of transcription 3(STAT3) signaling pathway to repair intestinal mucosal injury induced by 5-fluorouracil(5-FU) chemotherapy for colon cancer. SD rats were intraperitoneally injected with 60 mg·kg~(-1)·d~(-1) 5-FU for 4 days to establish a model of intestinal mucosal injury. Then the rats were randomly divided into model group(equal volume of normal saline), curcumin low, medium and high dose groups(50, 100, 200 mg·kg~(-1)), and normal SD rats were used as control group(equal volume of normal saline). Each group received gavage administration for 4 consecutive days, and the changes of body weight and feces were recorded every day. After administration, blood was collected from the heart, and jejunum tissues were collected. The levels of serum interleukin-1ß(IL-1ß) and tumor necrosis factor-α(TNF-α) were detected by ELISA, and at the same time, the concentration of Evans blue(EB) in jejunum was measured. Hematoxylin-eosin(HE) staining was used to observe the pathological state of jejunum, and the length of jejunum villi and the depth of crypt were measured. The positive expression levels of claudin, occludin and ZO-1 were detected by immunohistochemistry. Western blot was used to detect the protein expression of IL-6, p-STAT3, E-cadherin, vimentin and N-cadherin in jejunum tissues. The results showed that, curcumin significantly increased body weight and fecal weight(P<0.05 or P<0.01), decreased fecal score, EB concentration, IL-1ß and TNF-α levels(P<0.05 or P<0.01) in rats. In addition, curcumin maintained the integrity of mucosal surface and villi structure of jejunum to a large extent, and reduced pathological changes in a dose-dependent manner. Meanwhile, curcumin could increase the positive expression of occludin, claudin and ZO-1(P<0.05 or P<0.01), repair intestinal barrier function, downregulate the protein expression of IL-6, p-STAT3, vimentin and N-cadherin in jejunum tissues(P<0.05 or P<0.01), and upregulate the protein expression of E-cadherin(P<0.05). Therefore, curcumin could repair the intestinal mucosal injury induced by 5-FU chemotherapy for colon cancer, and the mechanism may be related to the inhibition of IL-6/STAT3 signal and the inhibition of epithelial-mesenchymal transition(EMT) process.


Assuntos
Neoplasias do Colo , Curcumina , Animais , Neoplasias do Colo/tratamento farmacológico , Fluoruracila/toxicidade , Interleucina-6/genética , Mucosa Intestinal/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais
14.
Chemistry ; 26(10): 2285-2292, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31868267

RESUMO

It is known that the low lifetime of photogenerated carriers is the main drawback of elemental photocatalysts. Therefore, a facile and versatile one-step strategy to simultaneously achieve the oxygen covalent functionalization of amorphous red phosphorus (RP) and in situ modification of CdCO3 is reported. This strategy endows RP with enhanced charge carrier separation ability and photocatalytic activity by coupling band-gap engineering and heterojunction construction. The as-prepared nCdCO3 /SO-RP (n=0.1, 0.25, 0.5, 1.0) composites exhibited excellent photocatalytic H2 evolution activity (up to 516.3 µmol g-1 h) from visible-light-driven water splitting (λ>400 nm), which is about 17.6 times higher than that of pristine RP. By experimental and theoretical investigations, the roles of surface oxygen covalent functionalization, that is, prolonging the lifetime of photogenerated carriers and inducing the negative shift of the conduction band potential, were studied in detail. Moreover, the charge transfer mechanism of these composites has also been proposed. In addition, these composites are stable and can be reused at least for three times without significant activity loss. This work may provide a good example of how to promote the activity of elemental photocatalysts by decorating their atomic structure.

15.
Am J Physiol Cell Physiol ; 317(2): C253-C261, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30649914

RESUMO

Myocardial ischemia-reperfusion (I/R) is a common and lethal disease that threatens people's life worldwide. The underlying mechanisms are under intensive study and yet remain unclear. Here, we explored the function of miR-322/503 in myocardial I/R injury. We used isolated rat perfused heart as an in vivo model and H9c2 cells subjected with the oxygen and glucose deprivation followed by reperfusion as in vitro model to study myocardial I/R injury. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to measure the infarct size, and terminal deoxynucleotidyl transferase dUTP-mediated nick-end label (TUNEL) staining was used to examine apoptosis. Quantitative RT-PCR and Western blot were used to determine expression levels of miR-322/503, Smad ubiquitin regulatory factor 2 (Smurf2), enhancer of zeste homolog 2 (EZH2), p-Akt, and p-GSK3ß. Overexpression of miR-322/503 decreased infarct size, inhibited cell apoptosis, and promoted cell proliferation through upregualtion of p-Akt and p-GSK3ß. Thus the expression of miR-322/503 was reduced during I/R process. On the molecular level, miR-322/503 directly bound Smurf2 mRNA and suppressed its translation. Smurf2 ubiquitinated EZH2 and degraded EZH2, which could activate Akt/GSK3ß signaling. Our study demonstrates that miR-322/503 plays a beneficial role in myocardial I/R injury. By inhibition of Smurf2 translation, miR-322/503 induces EZH2 expression and activates Akt/GSK3ß pathway, thereby protecting cells from ischemia reperfusion injury.


Assuntos
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , MicroRNAs/metabolismo , Infarto do Miocárdio/prevenção & controle , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miócitos Cardíacos/enzimologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Animais , Apoptose , Sítios de Ligação , Hipóxia Celular , Linhagem Celular , Proliferação de Células , Modelos Animais de Doenças , Glucose/deficiência , Preparação de Coração Isolado , Masculino , MicroRNAs/genética , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/genética , Traumatismo por Reperfusão Miocárdica/patologia , Miócitos Cardíacos/patologia , Fosforilação , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Ubiquitina-Proteína Ligases/genética
16.
Org Biomol Chem ; 17(25): 6293-6304, 2019 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-31204752

RESUMO

The intramolecular oxa-Michael addition giving tetrahydropyrans has been examined experimentally using both acidic and basic catalysis. With acidic catalysis, the diequatorial product is exclusively obtained in a kinetically controlled reaction in all cases. Under basic conditions at low temperature, the reaction is again under kinetic control, but formation of the axial-equatorial isomer is generally favoured with an (E)-Michael acceptor, although isomerisation to the diequatorial isomer is observed at higher temperatures. Computationally, it is found that the acid catalysed reaction has a late transition state and the kinetic favouring of the diequatorial isomer has a steric explanation. In contrast, under strongly basic conditions, an early transition state is found. Electrostatic effects are likely to be the main contributor to the stereoselectivity for the (E)-isomer and steric interactions for the (Z)-isomer.

18.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4095-4100, 2019 Oct.
Artigo em Zh | MEDLINE | ID: mdl-31872682

RESUMO

The study is aimed to effectively obtain the planting area of traditional Chinese medicine resources. The herbs used as the material for traditional Chinese medicine are mostly planted in natural environment suitable mountainous areas. The UAV low altitude remote sensing data were used as the samples and the GF-2 remote sensing images were applied for the data source to extract the planting area of Salvia miltiorrhiza and Artemisia argyi in Luoning county combined with field investigation. Remote sensing satellite data of standard processing obtain specific remote sensing data coverage. The UAV data were pre-processed to visually interpret the species and distribution of traditional Chinese medicine resources in the sample quadrat. Support vector machine( SVM) was used to classify and estimate the area of traditional Chinese medicine resources in Luoning county,confusion matrix was used to determine the accuracy of spatial distribution of traditional Chinese medicine resources. The result showed that the application of UAV of low altitude remote sensing technology and remote sensing image of satellite in the extraction of S. miltiorrhiza and other varieties planting area was feasible,it also provides a scientific reference for poverty alleviation policies of the traditional Chinese medicine Industry in local areas.Meanwhile,research on remote sensing classification of Chinese medicinal materials based on multi-source and multi-phase high-resolution remote sensing images is actively carried out to explore more effective methods for information extraction of Chinese medicinal materials.


Assuntos
Altitude , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Tecnologia de Sensoriamento Remoto , Recursos Naturais , Máquina de Vetores de Suporte
20.
Pain Med ; 16(11): 2162-70, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26744887

RESUMO

OBJECTIVES: Postherpetic neuralgia (PHN) is one of the most intractable pain disorders, especially in elderly patients. There is evidence that repetitive transcranial magnetic stimulation (rTMS) reduces neuropathic pain; however, its effectiveness for PHN is unknown. This study investigated the efficacy of high-frequency rTMS in patients with PHN. DESIGN: A total of 40 patients were randomly assigned to receive 10 sessions of real or sham rTMS of the primary motor cortex. Each stimulation session consisted of a series of 300 five-second pulses with a frequency of 10 Hz and an interval of 3 seconds between each train, giving a total of 1500 pulses per session. The primary outcome was pain intensity measured before stimulation from first intervention (T0) to the final stimulation (T10), and 1 and 3 months after final stimulation (T11 and T12). Other outcomes measured included scores on the short form McGill pain questionnaire, self-rating depression scale, quality of life (QOL), sleep quality, the patient global impression of change, medication regulation, and reported adverse events. RESULTS: The real rTMS group demonstrated greater reduction of visual analogue scale (VAS) than the sham group at each time point except for T0 (P = 0.399) and T1 (P = 0.091). Mean VAS reduction in the real rTMS group was 16.89% for duration of disease longer than 6 months. These analgesic effects were associated with long-term improvement in rating-scale items related to QOL. CONCLUSION: The results suggest that rTMS is an effective and safe therapy in patients with PHN.


Assuntos
Córtex Motor/fisiopatologia , Neuralgia Pós-Herpética/terapia , Neuralgia/terapia , Estimulação Magnética Transcraniana , Adulto , Idoso , Idoso de 80 Anos ou mais , Humanos , Masculino , Pessoa de Meia-Idade , Neuralgia Pós-Herpética/diagnóstico , Medição da Dor , Qualidade de Vida , Estimulação Magnética Transcraniana/métodos , Resultado do Tratamento
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