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1.
Nature ; 630(8016): 340-345, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38778106

RESUMEN

Two-dimensional (2D) semiconductors have shown great potential for monolithic three-dimensional (M3D) integration due to their dangling-bonds-free surface and the ability to integrate to various substrates without the conventional constraint of lattice matching1-10. However, with atomically thin body thickness, 2D semiconductors are not compatible with various high-energy processes in microelectronics11-13, where the M3D integration of multiple 2D circuit tiers is challenging. Here we report an alternative low-temperature M3D integration approach by van der Waals (vdW) lamination of entire prefabricated circuit tiers, where the processing temperature is controlled to 120 °C. By further repeating the vdW lamination process tier by tier, an M3D integrated system is achieved with 10 circuit tiers in the vertical direction, overcoming previous thermal budget limitations. Detailed electrical characterization demonstrates the bottom 2D transistor is not impacted after repetitively laminating vdW circuit tiers on top. Furthermore, by vertically connecting devices within different tiers through vdW inter-tier vias, various logic and heterogeneous structures are realized with desired system functions. Our demonstration provides a low-temperature route towards fabricating M3D circuits with increased numbers of tiers.

2.
Nano Lett ; 24(2): 770-776, 2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38180314

RESUMEN

van der Waals heterostructures (vdWHs) based on two-dimensional (2D) semiconductors have attracted considerable attention. However, the reported vdWHs are largely based on vertical device structure with large overlapping area, while the realization of lateral heterostructures contacted through 2D edges remains challenging and is majorly limited by the difficulties of manipulating the lateral distance of 2D materials at nanometer scale (during transfer process). Here, we demonstrate a simple interfacial sliding approach for realizing an edge-by-edge lateral contact. By stretching a vertical vdWH, two 2D flakes could gradually slide apart or toward each other. Therefore, by applying proper strain, the initial vertical vdWH could be converted into a lateral heterojunction with intimately contacted 2D edges. The lateral contact structure is supported by both microscope characterization and in situ electrical measurements, exhibiting carrier tunneling behavior. Finally, this approach can be extended to 3D thin films, as demonstrated by the lateral 2D/3D and 3D/3D Schottky junction.

3.
Nano Lett ; 24(25): 7724-7731, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38864413

RESUMEN

Perovskite monocrystalline films are regarded as desirable candidates for the integration of high-performance optoelectronics due to their unique photophysical properties. However, the heterogeneous integration of a perovskite monocrystalline film with other semiconductors is fundamentally limited by the lattice mismatch, which hinders direct epitaxy. Herein, the van der Waals (vdW) integration strategy for 3D perovskites is developed, where perovskite monocrystalline films are epitaxially grown on the mother substrate, followed by its peeling off and transferring to arbitrary semiconductors, forming monocrystalline heterojunctions. The as-achieved CsPbBr3-Nb-doped SrTiO3 (Nb:STO) vdW p-n heterojunction exhibited comparable performance to their directly epitaxial counterpart, demonstrating the feasibility of vdW integration for 3D perovskites. Furthermore, the vdW integration could be extended to silicon substrates, rendering the CsPbBr3-n-Si and CsPbCl3-p-Si p-n heterojunction with apparent rectification behaviors and photoresponse. The vdW integration significantly enriches the selections of semiconductors hybridizing with perovskites and provides opportunities for monocrystalline perovskite optoelectronics with complex configurations and multiple functionalities.

4.
J Med Virol ; 95(10): e29186, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37855656

RESUMEN

To the best of our knowledge, no previous study has quantitatively estimated the dynamics and cumulative susceptibility to influenza infections after the widespread lifting of COVID-19 public health measures. We constructed an imitated stochastic susceptible-infected-removed model using particle-filtered Markov Chain Monte Carlo sampling to estimate the time-dependent reproduction number of influenza based on influenza surveillance data in southern China, northern China, and the United States during the 2022-2023 season. We compared these estimates to those from 2011 to 2019 seasons without strong social distancing interventions to determine cumulative susceptibility during COVID-19 restrictions. Compared to the 2011-2019 seasons without a strong intervention with social measures, the 2022-2023 influenza season length was 45.0%, 47.1%, and 57.1% shorter in southern China, northern China, and the United States, respectively, corresponding to an 140.1%, 74.8%, and 50.9% increase in scale of influenza infections, and a 60.3%, 72.9%, and 45.1% increase in population susceptibility to influenza. Large and high-intensity influenza epidemics occurred in China and the United States in 2022-2023. Population susceptibility increased in 2019-2022, especially in China. We recommend promoting influenza vaccination, taking personal prevention actions on at-risk populations, and monitoring changes in the dynamic levels of influenza and other respiratory infections to prevent potential outbreaks in the coming influenza season.


Asunto(s)
COVID-19 , Gripe Humana , Humanos , Estados Unidos/epidemiología , Gripe Humana/epidemiología , Gripe Humana/prevención & control , COVID-19/epidemiología , Estaciones del Año , Pandemias , China/epidemiología
5.
BMC Pulm Med ; 23(1): 183, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37231402

RESUMEN

BACKGROUND: To investigate the changes and clinical significance of vascular endothelial injury markers in type 2 diabetes mellitus (T2DM) complicated with pulmonary embolism (PE). METHODS: This prospective study enrolled patients with T2DM hospitalized in one hospital from January 2021 to June 2022. Soluble thrombomodulin (sTM) (ELISA), von Willebrand factor (vWF) (ELISA), and circulating endothelial cells (CECs) (flow cytometry) were measured. PE was diagnosed by computed tomography pulmonary angiography (CTPA). RESULTS: Thirty participants were enrolled in each group. The plasma levels of sTM (151.22 ± 120.57 vs. 532.93 ± 243.82 vs. 1016.51 ± 218.00 pg/mL, P < 0.001) and vWF (9.63 ± 2.73 vs. 11.50 ± 2.17 vs. 18.02 ± 3.40 ng/mL, P < 0.001) and the percentage of CECs (0.17 ± 0.46 vs. 0.30 ± 0.08 vs. 0.56 ± 0.18%, P < 0.001) gradually increased from the control group to the T2DM group to the T2DM + PE group. sTM (OR = 1.002, 95%CI: 1.002-1.025, P = 0.022) and vWF (OR = 1.168, 95%CI: 1.168-2.916, P = 0.009) were associated with T2DM + PE. sTM > 676.68 pg/mL for the diagnosis of T2DM + PE achieved an AUC of 0.973, while vWF > 13.75 ng/mL achieved an AUC of 0.954. The combination of sTM and vWF above their cutoff points achieved an AUC of 0.993, with 100% sensitivity and 96.7% specificity. CONCLUSIONS: Patients with T2DM show endothelial injury and dysfunction, which were worse in patients with T2DM and PE. High sTM and vWF levels have certain clinical predictive values for screening T2DM accompanied by PE.


Asunto(s)
Diabetes Mellitus Tipo 2 , Embolia Pulmonar , Humanos , Células Endoteliales , Diabetes Mellitus Tipo 2/complicaciones , Factor de von Willebrand/análisis , Estudios Prospectivos , Endotelio Vascular/química , Biomarcadores
6.
Zhongguo Zhong Yao Za Zhi ; 48(7): 1962-1975, 2023 Apr.
Artículo en Zh | MEDLINE | ID: mdl-37282973

RESUMEN

In this study, an overview of systematic reviews/Meta-analysis(SR/MA) of Chinese herbal injections for sepsis was performed to provide references for clinical practice and promote the quality improvement of clinical evidence. Eight Chinese and English databases such as CNKI, Medline, and EMbase were electronically searched for SR/MA of Chinese herbal injections for sepsis from database inception to June 2022. AMSTAR 2, PRISMA 2020, and GRADE system, combined with Recommendations for Clinical Evidence Grading on Traditional Chinese Medicine Based on Evidence Body, were applied to evaluate the methodological quality, reporting quality, and evidence quality of the included articles. Twenty-seven articles of SR/MA were included, containing four Chinese herbal injections(Xuebijing Injection, Shenfu Injection, Shenmai Injection, and Shengmai Injection). AMSTAR 2 checklist showed that the methodological quality of the SR/MA ranged from moderate to very low. Item 2(prior study design) was the critical item with poor scores, and the non-critical items with poor scores were items 3(explain the selection of the study designs), items 10(report on the sources of funding), and items 16(conflicts of interest stated). In terms of PRISMA 2020, items in eight topics with complete reporting of missing>50%, including search strategy, certainty assessment, results of syntheses, certainty of evidence, registration and protocol, support, competing interests, availability of data, code and other materials. The included SR/MA involved 30 outcome indicators. Evidence quality of mortality, APACHE Ⅱ, and safety, the top three outcome indicators, was evaluated, and all of them were graded as the medium level. The lack of random allocation sequence, allocation concealment mechanism, blinding, and trial sample size was the main reason for the reduction of the evidence level. The available evidence shows that Chinese herbal injections can serve as an effective and safe adjunctive treatment for sepsis, which can reduce mortality, inhibit inflammation, improve coagulation function, and regulate immune function, tissue perfusion, and oxygenation in patients with sepsis. However, the quality of SR/MA was suboptimal, and more high-quality SR/MA is needed to provide evidence to support the efficacy and safety of Chinese herbal injections in the treatment of sepsis.


Asunto(s)
Medicina Tradicional China , Sepsis , Humanos , Inyecciones , Proyectos de Investigación , Sepsis/tratamiento farmacológico
7.
Pharm Biol ; 60(1): 1365-1373, 2022 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35881053

RESUMEN

CONTEXT: α2-Macroglobulin (α2-M) is believed to be a potential anti-irradiation agent, but related mechanisms remains unclear. OBJECTIVE: We investigated the irradiation protective effect of α2-M. MATERIALS AND METHODS: A total of 10 Gy dose of irradiation was used to damage human skin fibroblasts. The influence of α2-M (100 µg/mL) on the proliferation, migration, invasion and apoptosis of fibroblasts was observed using Cell Counting Kit-8 (CCK8), wound healing, transwell, and flow cytometry. Malondialdehyde, superoxide dismutase and catalase was measured using related ELISA kits. The levels of mitochondrial membrane potential and calcium were detected using flow cytometry. The expression of transient receptor potential melastatin 2 (TRPM2) was investigated through western blotting and immunofluorescence staining. RESULTS: High purity of α2-M was isolated from Cohn fraction IV. α2-M significantly increased cell proliferation, migration, invasion, but suppressed cell apoptosis after irradiation. The promotion of cell proliferation, migration and invasion by α2-M exceeded over 50% compared group irradiation. The increased cell ratio in the S phase and decreased cell ratio in the G2 phase induced by irradiation were remarkably reversed by α2-M. α2-M markedly suppressed the increased oxidative stress level caused by irradiation. The mitochondrial damage induced by irradiation was improved by α2-M through inhibiting mitochondrial membrane potential loss, calcium and TRPM2 expression. DISCUSSION AND CONCLUSIONS: α2-M significantly promoted the decreased fibroblast viability and improved the mitochondria dysfunction caused by irradiation. α2-M might present anti-radiation effect through alleviating mitochondrial dysfunction caused by irradiation. This study could provide a novel understanding about the improvement of α2-M on irradiation-induced injury.


Asunto(s)
alfa 2-Macroglobulinas Asociadas al Embarazo , Canales Catiónicos TRPM , Apoptosis , Calcio/metabolismo , Femenino , Fibroblastos/metabolismo , Humanos , Potencial de la Membrana Mitocondrial , Mitocondrias/metabolismo , Embarazo , alfa 2-Macroglobulinas Asociadas al Embarazo/metabolismo , alfa 2-Macroglobulinas Asociadas al Embarazo/farmacología , Canales Catiónicos TRPM/metabolismo
8.
Clin Infect Dis ; 73(6): e1314-e1320, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-33772573

RESUMEN

BACKGROUND: The relative contributions of asymptomatic, presymptomatic, and symptomatic transmission of severe acute respiratory syndrome coronavirus 2 have not been clearly measured, although control measures may differ in response to the risk of spread posed by different types of cases. METHODS: We collected detailed information on transmission events and symptom status based on laboratory-confirmed patient data and contact tracing data from 4 provinces and 1 municipality in China. We estimated the variation in risk of transmission over time and the severity of secondary infections by symptomatic status of the infector. RESULTS: There were 393 symptomatic index cases with 3136 close contacts and 185 asymptomatic index cases with 1078 close contacts included in the study. The secondary attack rates among close contacts of symptomatic and asymptomatic index cases were 4.1% (128 of 3136) and 1.1% (12 of 1078), respectively, corresponding to a higher transmission risk from symptomatic cases than from asymptomatic cases (odds ratio, 3.79; 95% confidence interval, 2.06-6.95). Approximately 25% (32 of 128) and 50% (6 of 12) of the infected close contacts were asymptomatic from symptomatic and asymptomatic index cases, respectively, while more than one third (38%) of the infections in the close contacts of symptomatic cases were attributable to exposure to the index cases before symptom onset. CONCLUSIONS: Asymptomatic and presymptomatic transmissions play an important role in spreading infection, although asymptomatic cases pose a lower risk of transmission than symptomatic cases. Early case detection and effective test-and-trace measures are important to reduce transmission.


Asunto(s)
COVID-19 , SARS-CoV-2 , China/epidemiología , Trazado de Contacto , Humanos , Incidencia
9.
Emerg Infect Dis ; 27(9): 2288-2293, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-34423766

RESUMEN

We estimated the symptomatic, PCR-confirmed secondary attack rate (SAR) for 2,382 close contacts of 476 symptomatic persons with coronavirus disease in Yichang, Hubei Province, China, identified during January 23-February 25, 2020. The SAR among all close contacts was 6.5%; among close contacts who lived with an index case-patient, the SAR was 10.8%; among close-contact spouses of index case-patients, the SAR was 15.9%. The SAR varied by close contact age, from 3.0% for those <18 years of age to 12.5% for those >60 years of age. Multilevel logistic regression showed that factors significantly associated with increased SAR were living together, being a spouse, and being >60 years of age. Multilevel regression did not support SAR differing significantly by whether the most recent contact occurred before or after the index case-patient's onset of illness (p = 0.66). The relatively high SAR for coronavirus disease suggests relatively high virus transmissibility.


Asunto(s)
COVID-19 , SARS-CoV-2 , Adolescente , Niño , China/epidemiología , Humanos , Incidencia , Modelos Logísticos
10.
Lancet ; 396(10243): 63-70, 2020 07 04.
Artículo en Inglés | MEDLINE | ID: mdl-32505220

RESUMEN

COVID-19 was declared a pandemic by WHO on March 11, 2020, the first non-influenza pandemic, affecting more than 200 countries and areas, with more than 5·9 million cases by May 31, 2020. Countries have developed strategies to deal with the COVID-19 pandemic that fit their epidemiological situations, capacities, and values. We describe China's strategies for prevention and control of COVID-19 (containment and suppression) and their application, from the perspective of the COVID-19 experience to date in China. Although China has contained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and nearly stopped indigenous transmission, a strong suppression effort must continue to prevent re-establishment of community transmission from importation-related cases. We believe that case finding and management, with identification and quarantine of close contacts, are vitally important containment measures and are essential in China's pathway forward. We describe the next steps planned in China that follow the containment effort. We believe that sharing countries' experiences will help the global community manage the COVID-19 pandemic by identifying what works in the struggle against SARS-CoV-2.


Asunto(s)
Manejo de Caso/organización & administración , Trazado de Contacto , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/prevención & control , Pandemias/prevención & control , Neumonía Viral/epidemiología , Neumonía Viral/prevención & control , Betacoronavirus , COVID-19 , China/epidemiología , Infecciones por Coronavirus/transmisión , Transmisión de Enfermedad Infecciosa/prevención & control , Humanos , Neumonía Viral/transmisión , Cuarentena , SARS-CoV-2
11.
Angew Chem Int Ed Engl ; 60(10): 5370-5376, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33259085

RESUMEN

We describe a cerium-catalyzed aerobic oxidative ring expansion for the expedient construction of synthetically challenging macrolactones under visible-light conditions. Cyanoanthracene has been employed as co-catalyst to accelerate the turnover of the cerium cycle leading to a fast conversion within 20 min of irradiation. Taking advantage of the high efficiency and operationally simple conditions, a collection of over 100 macrolactones equipped with ring systems ranging from 9- to 19-membered macrocycles have been prepared from simple building blocks. Moreover, the enabling potential of this strategy to simplify the generation of molecular complexity has been demonstrated through the concise synthesis of sonnerlactone.

12.
Phys Chem Chem Phys ; 20(19): 13340-13347, 2018 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-29717734

RESUMEN

Twin boundaries (TBs) play an essential role in enhancing the mechanical, electronic and transport properties of polycrystalline materials. However, the mechanisms are not well understood. In particular, we considered that they may play an important role in boron rich boron carbide (BvrBC), which exhibits promising properties such as low density, super hardness, high abrasion resistance, and excellent neutron absorption. Here, we apply first-principles-based simulations to identify the atomic structures of TBs in BvrBC and their roles for the inelastic response to applied stresses. In addition to symmetric TBs in BvrBC, we identified a new type of asymmetric twin that constitutes the phase boundaries between boron rich boron carbide (B13C2) and BvrBC (B14C). The predicted mechanical response of these asymmetric twins indicates a significant reduction of the ideal shear strength compared to single crystals B13C2 and B14C, suggesting that the asymmetric twins facilitate the disintegration of icosahedral clusters under applied stress, which in turn leads to amorphous band formation and brittle failure. These results provide a mechanistic basis towards understating the roles of TBs in BvrBC and related superhard ceramics.

13.
Med Sci Monit ; 24: 7340-7347, 2018 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-30317248

RESUMEN

BACKGROUND Renal cell carcinoma (RCC) is one of the common malignant tumors in the urinary system, which endangers human health for a long time. The past decade, the molecular biology of renal cell carcinoma has made considerable progress, so that we have a more profound understanding of renal cell carcinoma. Molecular biological mechanism of renal cell carcinoma remains to be explored. Evidence indicates that long non-coding RNAs (lncRNAs) may be important players in human cancer progression, including RCC. In this study, we found that a newly discovered pseudogene-derived lncRNA named DUXAP8, a 2107-bp RNA, was remarkably upregulated in RCC. MATERIAL AND METHODS Expression of lncRNA DUXAP8 was determined by a qRT-PCR assay in RCC tissues. The proliferation and invasion of RCC cell were measured by a cell proliferation assay and a Transwell invasion assay. Expression of miR-126 was detected by real-time PCR. Interactions between lncRNA DUXAP8 and miR-126 were measured by a luciferase reporter assay and an RNA-pull down assay. In vivo experiments were used to detect tumor formation. RESULTS Together, our study not only identifies lncRNA DUXAP8 as a negative regulator of renal cancer with potential clinical value, but also reveals a regulatory mechanism by long non-coding RNAs to control tumor development. CONCLUSIONS Results from this study provide evidence that lncRNA DUXAP8 enhances renal cell carcinoma progression via downregulating of miR-126, which offers a new approach for the treatment of RCC.


Asunto(s)
Carcinoma de Células Renales/genética , Neoplasias Renales/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Apoptosis/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , MicroARNs/metabolismo
14.
Small ; 13(47)2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-29106073

RESUMEN

2D halide semiconductors, a new family of 2D materials in addition to transition metal dichalcogenides, present ultralow dark current and high light conversion yield, which hold great potential in photoconductive detectors. Herein, a facile aqueous solution method is developed for the preparation of large-scale 2D lead dihalide nanosheets (PbF2-x Ix ). High-performance UV photodetectors are successfully implemented based on 2D PbF2-x Ix nanosheets. By modulating the components of halogens, the bandgap of PbF2-x Ix nanosheets can be tuned to meet varied detection spectra. The photoresponse dependence on incident power density, wavelength, detection environment, and temperature are systematically studied to investigate their detection mechanism. For PbI2 photodetectors, they are dominantly driven by a photoconduction mechanism and show a fast response speed and a low noise current density. A high normalized detectivity of 1.5 × 1012 Jones and an ION /IOFF ratio up to 103 are reached. On the other hand, PbFI photodetectors demonstrate a photogating mechanism mediated by trap states showing high responsivity. The novel 2D halide materials with wide bandgaps, superior detection performance, and facile synthesis process can enrich the Van der Waals solids family and hold great potential for a wide variety of applications in advanced optoelectronics.

15.
Nano Lett ; 15(12): 7963-9, 2015 Dec 09.
Artículo en Inglés | MEDLINE | ID: mdl-26529584

RESUMEN

Organolead triiodide perovskite (CH3NH3PbI3) as a light-sensitive material has attracted extensive attention in optoelectronics. The reported perovskite photodetectors (PDs) mainly focus on the individual, which limits their spatial imaging applications. Uniform perovskite networks combining transparency and device performance were synthesized on poly(ethylene terephthalate) (PET) by controlling perovskite crystallization. Photodetector arrays based on above network were fabricated to demonstrate the potential for image mapping. The trade-off between the PD performance and transparency was systematically investigated and the optimal device was obtained from 30 wt % precursor concentration. The switching ratio, normalized detectivity, and equivalent dark current derived shot noise as the critical parameters of PD arrays reached 300, 1.02 × 10(12) Jones, and 4.73 × 10(-15)A Hz(-1/2), respectively. Furthermore, the PD arrays could clearly detect spatial light intensity distribution, thus demonstrating its preliminary imaging function. The perovskite network PD arrays fabricated on PET substrates could also conduct superior flexibility under wide angle and large number of bending. For the common problem of perovskite optoelectronics in stability, the perovskite networks sheathed with hydrophobic polymers greatly enhanced the device stability due to the improved interface contacts, surface passivation, and moisture isolation. Taking into consideration transparency, flexibility, imaging and stability, the present PD arrays were expected to be widely applied in visualized portable optoelectronic system.

16.
Tumour Biol ; 36(4): 2993-9, 2015 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-25510664

RESUMEN

Epidermal growth factor inhibitors (EGFRIs), the first targeted cancer therapy, are currently an essential treatment for many advance-stage epithelial cancers. These agents have the superior ability to target cancers cells and better safety profile compared to conventional chemotherapies. However, all responding patients eventually developed acquired resistance to EGFRIs and the mechanisms of acquired resistance invariably develops. In the current study, we reported the tumor xenografts of the human A431 squamous cell carcinoma, after 25-week consecutive therapy with EGFR inhibitor (gefitinib) that developed resistance as a result of c-Kit overexpression. Moreover, combined therapeutic inhibition of EGFR and c-Kit may abrogate this acquired mechanism of drug resistance due to an enhanced apoptotic effect in gefitinib-resistant xenograft model. Taken together, the results suggest that at least in the A431 xenograft model displaying acquired resistance to gefitinib can emerge in vivo, at least in part, by mechanisms involving the c-Kit overexpression.


Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Receptores ErbB/genética , Neoplasias Pulmonares/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-kit/genética , Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Receptores ErbB/antagonistas & inhibidores , Gefitinib , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/administración & dosificación , Proteínas Proto-Oncogénicas c-kit/biosíntesis , Quinazolinas/administración & dosificación , Transducción de Señal/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
17.
J Pharmacol Sci ; 129(1): 65-71, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-26390965

RESUMEN

The purpose of this paper is to investigate the possible mechanisms of resistance to chemotherapy in melanoma from the perspective of molecular biology and to discuss the strategies to overcome them. Cisplatin, a DNA-damaging compound that triggers apoptotic cell death, is commonly used in the treatment of malignant melanoma. However, most patients develop mechanisms of acquired resistance and about 25% of them do not achieve tumor regression at all, due to intrinsic resistance to therapy. In the current study, we reported the tumor xenografts of the human A375 melanoma, after 40-weeks' consecutive therapy with cisplatin that developed resistance as a result of EphB4 overexpression. Moreover, the expression of phospho-AKT and phospho-ERK were significantly increased in cisplatin-resistant tumors. In addition, combined of cisplatin with EphB4 selective inhibitor could abrogate this acquired mechanism of drug resistance due to an enhanced apoptotic effect in cisplatin-resistant xenografts. In summary, these results help to understand the mechanisms of acquired resistance to chemotherapy and provide important information for clinical treatment strategies.


Asunto(s)
Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Cisplatino/farmacología , Cisplatino/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/genética , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Melanoma/tratamiento farmacológico , Melanoma/patología , Receptor EphB4/antagonistas & inhibidores , Receptor EphB4/genética , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Animales , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Modelos Animales de Enfermedad , Xenoinjertos , Humanos , Melanoma/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Terapia Molecular Dirigida , Trasplante de Neoplasias , Receptor EphB4/fisiología , Neoplasias Cutáneas/genética
18.
J Pharmacol Sci ; 125(3): 255-63, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-25048016

RESUMEN

Polysaccharides isolated from Scutellaria barbata (PSB) have been reported to have anti-tumor effects. To investigate the underlying mechanism, a highly invasive, metastatic and phospho-c-Met overexpression lung carcinoma cell, 95-D cell line was used. The results showed that in vitro, PSB not only could inhibit the proliferation of 95-D cell line (IC(50) = 35.2 µg/mL), but also down-regulated the expression of phospho-c-Met and its downstream signaling molecules including phospho-Erk and phospho-Akt. In vivo, PSB inhibited tumor growth in the 95-D subcutaneous xenograft model in a dose-dependent manner; after once-daily intraperitoneal injection for 3 weeks, tumor growth inhibition T/C ratio for 100 and 200 mg/kg treatments was 42.72% and 13.6%, respectively. In the end of the in vivo study, tumor tissues were harvested for further evaluation of the phosphorylation level of c-Met, AKT, and ERK. Ex vivo results demonstrated that the phosphorylation of c-Met and its downstream signaling molecules were also significantly inhibited by PSB. Immunohistochemistry analysis showed dose-dependent inhibition of tumor cell proliferation (Ki67) and reduction of microvessel density (CD31). In summary, the results indicated that PSB exerted anti-tumor growth activity on human lung cancer 95-D in vitro and in vivo by directly regulating the c-Met signaling pathway and the anti-tumor effects were mainly based on its anti-proliferation and anti-angiogenesis action.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antineoplásicos Fitogénicos/uso terapéutico , Carcinoma/tratamiento farmacológico , Carcinoma/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Fitoterapia , Extractos Vegetales/química , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Proteínas Proto-Oncogénicas c-met/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Animales , Carcinoma/irrigación sanguínea , Carcinoma/patología , Línea Celular Tumoral , Transformación Celular Neoplásica/efectos de los fármacos , Modelos Animales de Enfermedad , Xenoinjertos , Humanos , Neoplasias Pulmonares/irrigación sanguínea , Neoplasias Pulmonares/patología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/genética , Ratones Endogámicos BALB C , Ratones Desnudos , Trasplante de Neoplasias , Proteína Oncogénica v-akt/metabolismo , Scutellaria
19.
Molecules ; 19(7): 8740-51, 2014 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-24968330

RESUMEN

During our systematic study on the anticancer activities of Scutellaria barbata, scutebarbatine A (SBT-A), one of the major alkaloids in S. barbata, was found to have antitumor effects on A549 cells. Thus, we designed the present study to investigate in detail the antitumor effects of SBT-A. The cytotoxic effect of SBT-A on A549 in vitro were determined by an MTT assay and evaluated by IC50 values. Furthermore, results of Hoechst 33258 and Annexin V/PI staining assays demonstrated that SBT-A had significant antitumor effects on A549 cells via apoptosis, in a concentration-dependent manner. What's more, the mechanism was explored by western blotting, and our study revealed that SBT-A can up-regulate the expressions of cytochrome c, caspase-3 and 9, and down-regulate the levels of Bcl-2 in A549 cells. Finally, the antitumor effects of SBT-A were evaluated in vivo by using transplanted tumor nude mice, and the results confirmed that SBT-A has a notable antitumor effect on A549 cancer via mitochondria-mediated apoptosis. Collectively, our results demonstrated that SBT-A showed significant antitumor effects on A549 cells in vivo and in vitro via mitochondria-mediated apoptosis by up-regulating expressions of caspase-3 and 9, and down-regulating Bcl-2.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Naftoles/farmacología , Niacina/farmacología , Animales , Apoptosis , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Forma de la Célula , Humanos , Ratones Desnudos , Carga Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto
20.
Front Immunol ; 15: 1373876, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715602

RESUMEN

Objective: The objective of this study was to investigate the impact of electro-acupuncture (EA) on sepsis-related intestinal injury and its relationship with macrophage polarization. Methods: A sepsis model was established using cecal ligation and puncture (CLP) to assess the effectiveness of EA. The extent of pathological injury was evaluated using Chiu's score, the expression of ZO-1 and Ocludin, and the impact on macrophage polarization was examined through flow cytometry and immunofluorescence staining. The expression of spermidine, one type of polyamine, and ornithine decarboxylase (ODC) was measured using ELISA and PCR. Once the efficacy was determined, a polyamine depletion model was created, and the role of polyamines was reassessed by evaluating efficacy and observing macrophage polarization. Results: EA treatment reduced the Chiu's score and increased the expression of ZO-1 and Ocludin in the intestinal tissue of septic mice. It inhibited the secretion of IL-1ß and TNF-α, promoted the polarization of M2-type macrophages, increased the secretion of IL-10, and upregulated the expression of Arg-1, spermidine, and ODC. However, after depleting polyamines, the beneficial effects of EA on alleviating intestinal tissue damage and modulating macrophage polarization disappeared. Conclusion: The mechanism underlying the alleviation of intestinal injury associated with CLP-induced sepsis by EA involves with the promotion of M2-type macrophage polarization mediated by spermidine expression.


Asunto(s)
Modelos Animales de Enfermedad , Electroacupuntura , Macrófagos , Poliaminas , Sepsis , Animales , Sepsis/terapia , Sepsis/metabolismo , Sepsis/inmunología , Ratones , Macrófagos/inmunología , Macrófagos/metabolismo , Electroacupuntura/métodos , Poliaminas/metabolismo , Masculino , Activación de Macrófagos , Intestinos/patología , Intestinos/inmunología , Ratones Endogámicos C57BL , Citocinas/metabolismo
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