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1.
Opt Express ; 31(2): 1154-1166, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36785156

RESUMEN

A highly sensitive differential Helmholtz photoacoustic sensor with active noise reduction was reported. Coupled to one cavity of the photoacoustic cell, an intensity-modulated excitation light would reflect multiple times to produce photoacoustic signal, and meanwhile cause the solid-state photoacoustic effect forming differential mode noise with the frequency same as the photoacoustic signal, which could not be suppressed by conventional differential technology. Wavelength modulation technology is a splendid method to restrain this effect, which is not suitable for light sources with not adjustable wavelength. To suppress this kind of noise, an intensity-modulated compensation light was coupled to another cavity, whose central wavelength was at the non-absorption line of the measured gas. The compensation light was of the same frequency, phase, and power as the excitation light, by which the solid-state photoacoustic effects were produced to form destructive interference called active noise reduction. The experiment results showed that the active noise reduction significantly improved the signal-to-noise ratio and signal-to-background ratio. Compared with the differential, the differential with active noise reduction improved signal-to- noise ratio by about 1.2 times and signal-to-background ratio by about 9.4 times. When low-power near-infrared lasers were employed as the two light sources, the minimum detection limits for acetylene and methane reached 21 and 200 ppb, respectively.

2.
Opt Express ; 30(16): 28984-28996, 2022 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-36299083

RESUMEN

A high-sensitivity differential Helmholtz photoacoustic cell based on multiple reflection was reported, and its performance parameters and gas replacement time were optimized by finite element simulation. To realize the long absorption path of the measured gas, the collimated excitation light was reflected multiple times on the gold-plated wall of the absorption cavity, and the wavelength modulation technology was used to reduce the multiple reflection noise. Additionally, the differential could suppress external co-phase noise and double the photoacoustic signal. When a laser with a central wavelength of 1653 nm was employed as the excitation light source, the minimum detection limit of 177 ppb (signal-to-noise ratio, SNR = 1) for methane was achieved within a detection time of 1 s, and the corresponding normalized noise equivalent absorption coefficient was 4.1×10-10 cm-1WHZ-1/2.

3.
Anticancer Drugs ; 33(1): 61-74, 2022 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-34620741

RESUMEN

Exosomes are critical mediators of intercellular communication in the tumor microenvironment. Exosomal circular RNAs (circRNAs) can act as biomarkers and play crucial roles in many cancers, including non-small cell lung cancer (NSCLC). The aim of this study was to explore the functions and regulatory mechanism of exosomal circ_0007385 in NSCLC. The expression levels of circ_0007385, microRNA-1253 (miR-1253), family with sequence similarity 83, member A (FAM83A) mRNA were determined by quantitative real-time PCR (qRT-PCR). Cell Counting Kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (Edu), and colony formation assays were utilized to determine cell proliferation ability. Sphere formation efficiency was determined by sphere formation assay. All protein levels were detected by western blot assay. Exosomes were detected using transmission electron microscopy analysis. Size distribution of exosomes was analyzed by nanoparticle tracking analysis. The interaction between miR-1253 and circ_0007385 or FAM83A was confirmed by dual-luciferase reporter, RNA immunoprecipitation (RIP) and RNA pull-down assays. Mice xenograft model was established to verify the function of circ_0007385 in vivo. Circ_0007385 was upregulated in NSCLC tissues and cells. Knockdown of circ_0007385 inhibited NSCLC cell proliferation and stemness, while exosomal circ_0007385 facilitated NSCLC cell proliferation and stemness. In addition, miR-1253 was a direct target of circ_0007385, and miR-1253 reversed the inhibitory effects of circ_0007385 on cell proliferation and stemness in NSCLC cells. Moreover, FAM83A was a direct target of miR-1253, and miR-1253 suppressed NSCLC cell proliferation and stemness by targeting FAM83A. Furthermore, circ_0007385 knockdown inhibited tumor growth in vivo. Exosomal circ_0007385 promoted NSCLC cell proliferation and stemness by regulating miR-1253/FAM83A axis.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , MicroARNs/metabolismo , ARN Circular/metabolismo , Animales , Apoptosis/fisiología , Línea Celular Tumoral , Proliferación Celular/fisiología , Exosomas/metabolismo , Técnicas de Silenciamiento del Gen , Humanos , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Proteínas de Neoplasias/metabolismo , Tamaño de la Partícula , Microambiente Tumoral/fisiología , Regulación hacia Arriba , Ensayos Antitumor por Modelo de Xenoinjerto
4.
Sensors (Basel) ; 22(1)2021 Dec 30.
Artículo en Inglés | MEDLINE | ID: mdl-35009823

RESUMEN

The concentration of trace gases in the atmospheric environment is extremely low, but it has a great impact on the living environment of organisms. Photoacoustic spectroscopy has attracted extensive attention in the field of trace gas detection because of its high sensitivity, good selectivity, and fast response. As the core of a photoacoustic detection setup, the photoacoustic cell has a significant impact on detection performance. To improve detection sensitivity, a sphere-tube coupled photoacoustic cell (STPAC) was developed, which was mainly composed of a diffuse-reflective sphere and an acoustic resonance tube. Modulated light was reflected multiple times in the sphere to increase optical path, and photoacoustic (PA) signals were further amplified by the tube. Based on STPAC, a PA gas detection setup was built with a laser diode (LD) at 450 nm as the light source. The experimental results showed that the minimum detection limit (noise equivalent concentration, NEC) of NO2 was ~0.7 parts per billion (ppb). Compared with the T-type PA cell (TPAC) in which the modulated light passed through the sphere, the signal-to-noise ratio of STPAC was increased by an order of magnitude at the same concentration of the NO2 sample.


Asunto(s)
Gases , Dióxido de Nitrógeno , Acústica , Relación Señal-Ruido , Análisis Espectral
5.
Chin J Cancer Res ; 33(5): 616-626, 2021 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-34815635

RESUMEN

OBJECTIVE: Chidamide is an oral histone deacetylase subtype-selective inhibitor approved for relapsed or refractory peripheral T-cell lymphoma (PTCL). This phase 1b study evaluated the safety, pharmacokinetics, and preliminary efficacy of chidamide in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) for treatment-naïve PTCL patients. METHODS: This study was an open-label, multicenter trial composed of dose escalation and dose expansion. Patients received CHOP for six 21-d cycles and chidamide on d 1, 4, 8 and 11 in each cycle. Four dose levels of chidamide (20, 25, 30 and 35 mg) were evaluated. The primary objective was to evaluate the safety and tolerability of the combination regimen. RESULTS: A total of 30 patients were evaluated in this study: 15 in the dose-escalation part and 15 in the dose-expansion part. In the dose-escalation study, three patients were enrolled in the 35 mg chidamide cohort. One had dose-limiting toxicity with grade 3 vascular access complications, and one had grade 2 neutropenia with a sustained temperature >38 °C. Dose escalation was stopped at this chidamide dose level. The most common (≥10%) grade 3 or 4 adverse events (AEs) were leukopenia (90.0%), neutropenia (83.3%), vomiting (13.3%), thrombocytopenia (10.0%) and febrile neutropenia (10.0%). No significant changes in chidamide pharmacokinetic properties were observed before and after combination treatment. The objective response rate for the 28 patients evaluable for preliminary efficacy was 89.3% (25/28), with 16 (57.1%) achieving complete response or unconfirmed complete response. The estimated median progression-free survival was 14.0 months. In summary, we chose chidamide 30 mg as the recommended dose for phase 2. CONCLUSIONS: The addition of chidamide to standard CHOP chemotherapy was tolerable with promising preliminary efficacy in previously untreated PTCL patients, which supports further clinical studies with this combination regimen for the frontline treatment of PTCL.

6.
Lancet Oncol ; 20(6): 806-815, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31036468

RESUMEN

BACKGROUND: Tucidinostat (formerly known as chidamide) is an oral subtype-selective histone deacetylase inhibitor. In an exploratory study, the combination of tucidinostat with exemestane showed preliminary signs of encouraging anti-tumour activity in patients with advanced hormone receptor-positive breast cancer. To build on these findings, we aimed to assess the efficacy and safety of this combination in a randomised trial in a larger population of postmenopausal patients with advanced, hormone receptor-positive breast cancer. METHODS: We did the randomised, double-blind, placebo-controlled, phase 3 ACE trial at 22 specialist cancer centres in China. Eligible patients were postmenopausal women (aged ≥60 years or aged <60 years if their serum follicle-stimulating hormone and oestradiol concentrations were within postmenopausal ranges) with hormone receptor-positive, HER2-negative breast cancer, whose disease had relapsed or progressed after at least one endocrine therapy (either in advanced or metastatic or adjuvant setting), and who had at least one measurable lesion, adequate organ function, Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and adequate haematological and biochemical parameters. Endocrine therapy did not have to be the most recent therapy before randomisation, but recurrence or progression after the most recent therapy was a prerequisite. Patients were randomly assigned (2:1) by a dynamic randomisation scheme via an interactive web-response system to receive 30 mg oral tucidinostat or placebo twice weekly. All patients in both groups also received 25 mg oral exemestane daily. Randomisation was stratified according to the presence of visceral metastases (yes vs no). Patients, investigators, study site staff, and the sponsor were masked to treatment assignment. The primary endpoint was investigator-assessed progression-free survival. Efficacy analyses were done in the full analysis set population, comprising all patients who received at least one dose of any study treatment, and safety analyses were done in all patients who received at least one dose of any study treatment and for whom at least one safety case report form was available. This study is registered with ClinicalTrials.gov, number NCT02482753. The study has reached the required number of events for final analysis of the primary endpoint. The trial is no longer enrolling patients, but follow-up for investigation of overall survival is ongoing. FINDINGS: Between July 20, 2015, and June 26, 2017, 365 patients were enrolled and randomly assigned, 244 to the tucidinostat group and 121 to the placebo group. The median duration of follow-up was 13·9 months (IQR 9·8-17·5). Investigator-assessed median progression-free survival was 7·4 months (95% CI 5·5-9·2) in the tucidinostat group and 3·8 months (3·7-5·5) in the placebo group (HR 0·75 [95% CI 0·58-0·98]; p=0·033). The most common grade 3 or 4 adverse events in either group were neutropenia (124 [51%] of 244 patients in the tucidinostat group vs three [2%] of 121 patients in the placebo group), thrombocytopenia (67 [27%] vs three [2%]), and leucopenia (46 [19%] vs three [2%]). Serious adverse events of any cause occurred in 51 (21%) of 244 patients in the tucidinostat group and seven (6%) of 121 patients in the placebo group. No treatment-related deaths were reported. INTERPRETATION: Tucidinostat plus exemestane improved progression-free survival compared with placebo plus exemestane in patients with advanced, hormone receptor-positive, HER2-negative breast cancer that progressed after previous endocrine therapy. Grade 3-4 haematological adverse events were more common in the tucidinostat plus exemestane group than in the placebo plus exemestane group. Tucidinostat plus exemestane could represent a new treatment option for these patients. FUNDING: Chipscreen Biosciences.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Terapia Recuperativa , Aminopiridinas/administración & dosificación , Androstadienos/administración & dosificación , Benzamidas/administración & dosificación , Neoplasias Óseas/metabolismo , Neoplasias Óseas/secundario , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Método Doble Ciego , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundario , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/metabolismo , Recurrencia Local de Neoplasia/patología , Posmenopausia , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Tasa de Supervivencia , Resultado del Tratamiento
7.
Anticancer Drugs ; 30(9): 909-916, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-30998512

RESUMEN

As a novel orally active multitarget small molecule inhibitor, CS2164 has shown broad antitumor activities against several human tumor xenograft models in immune-compromised mice. However, the ability of CS2164 to modulate antitumor immunity in an immune-competent mouse tumor model remains undefined, although antiangiogenic treatment has been reported to affect immune cell infiltration and remodel the tumor immune microenvironment. In the present study, the subcutaneous and ascites hepatocellular carcinoma (HCC) models in syngeneic Balb/c mice established by inoculation of an H22 hepatoma cell line were utilized to investigate the antitumor and immunomodulatory effects of CS2164. Although the antitumor effects of CS2164 were validated in both subcutaneous and ascites HCC models in syngeneic mice, CS2164 treatment consistently modulated immune cell populations, both in the periphery and in tumor microenvironments, with upregulation of CD4 and CD8 T cells in the spleen, but downregulation of immunosuppressive populations including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages in the spleen and tumor tissues. Furthermore, CS2164 increased the relative gene expression and protein production of several proinflammatory cytokines in tumor-related ascites. These results indicate that CS2164 exerts an antitumor effect associated with its immunomodulatory activities in mouse HCC models, and may also provide evidence for the immunotherapy potentiation of CS2164 in future cancer treatment.


Asunto(s)
Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Factores Inmunológicos/farmacología , Neoplasias Hepáticas/tratamiento farmacológico , Naftalenos/farmacología , Quinolinas/farmacología , Inhibidores de la Angiogénesis/farmacología , Animales , Apoptosis/efectos de los fármacos , Ascitis/tratamiento farmacológico , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD8-positivos/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Inmunoterapia/métodos , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Microambiente Tumoral/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto/métodos
8.
Phys Chem Chem Phys ; 21(32): 17801-17810, 2019 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-31372610

RESUMEN

The carbonization of transition metals in molten salts was performed to study the effect of electrochemical polarization and molten salt medium on the carbonization process. The carbonization of niobium (Nb) has been systemically investigated in Ar atmosphere and molten salts. The effect of particle size and structure of the starting materials, molten salt medium, and electric field on the formation of NbC was studied to reveal the dynamic barriers in the carbonization process. A native oxide layer and/or niobate derivatives generated on the Nb particles are the main barriers for the mass transfer of carbon and Nb towards each other. The results showed that molten salts can accelerate the formation of NbC by enhancing the diffusion of carbon, and the kinetic barrier can be effectively eliminated by supplying negative polarization to the cathode in molten salts to remove the oxide barriers, thereby enhancing carbonization. Besides Nb, tungsten (W), molybdenum (Mo), titanium (Ti), and tantalum (Ta) can also be carbonized in molten salts with the assistance of an applied electric field.

9.
Chin J Cancer Res ; 30(6): 605-612, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30700929

RESUMEN

OBJECTIVE: The recurrence or progression under endocrine therapy in hormone receptor-positive (HR+) advanced breast cancer (ABC) remained a critical clinical challenge. Chidamide is an oral subtype-selective histone deacetylase (HDAC) inhibitor with multiple functions in tumor growth inhibition and microenvironment modulation via epigenetic reprogramming. The purpose of this study was to evaluate the safety, pharmacokinetics (PK), and preliminary efficacy of chidamide in combination with exemestane in HR+ ABC patients. METHODS: Eligible patients were postmenopausal women with HR+ ABC recurrent or progressed to at least one endocrine therapy. Blood samples were obtained in the run-in period and the first day of combination treatment for PK analysis. In combination treatment, patients were given exemestane 25 mg daily and chidamide 30 mg twice a week (BIW) until progression of disease or intolerable toxicities. A treatment cycle was defined as 4 weeks. Safety, PK parameters, and preliminary efficacy were evaluated. RESULTS: A total of 20 patients were enrolled between July and December, 2015. The median number of treatments cycle was 5.2 (20.8 weeks) with 2 patients still on treatment at the data cut-off date of October, 2017. The treatment-related adverse events (AE) ≥ grade 3 in more than 2 patients were neutropenia (35%), thrombocytopenia (30%), and leucopenia (20%). The plasma exposure of exemestane was consistent in the presence or absence of chidamide. A slight increase in chidamide exposure was noted in the presence of exemestane, probably due to the inter- and intra-patient variations. The best response in 16 evaluable patients was assessed by Response Evaluation Criteria in Solid Tumors (RECIST), including 4 patients with partial response, 10 patients with stable disease. The median progression-free survival (PFS) was 7.6 months. CONCLUSIONS: The combination of chidamide with exemestane was generally well tolerated with promising preliminary efficacy in HR+ ABC patients. The overall results from this study encourage further pivotal trial in this patient population.

10.
Mol Cancer ; 16(1): 148, 2017 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-28851377

RESUMEN

PURPOSE: The present review aimed to assess the role of exosomal miRNAs in cancer-associated fibroblasts (CAFs), normal fibroblasts (NFs), and cancer cells. The roles of exosomal miRNAs and miRNA dysregulation in CAF formation and activation were summarized. METHODS: All relevant publications were retrieved from the PubMed database, with key words such as CAFs, CAF, stromal fibroblasts, cancer-associated fibroblasts, miRNA, exosomal, exosome, and similar terms. RESULTS: Recent studies have revealed that CAFs, NFs, and cancer cells can secrete exosomal miRNAs to affect each other. Dysregulation of miRNAs and exosomal miRNAs influence the formation and activation of CAFs. Furthermore, miRNA dysregulation in CAFs is considered to be associated with a secretory phenotype change, tumor invasion, tumor migration and metastasis, drug resistance, and poor prognosis. CONCLUSIONS: Finding of exosomal miRNA secretion provides novel insights into communication among CAFs, NFs, and cancer cells. MicroRNA dysregulation is also involved in the whole processes of CAF formation and function. Dysregulation of miRNAs in CAFs can affect the secretory phenotype of the latter cells.


Asunto(s)
Fibroblastos Asociados al Cáncer , Exosomas , MicroARNs , Animales , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones
11.
Cancer Sci ; 108(3): 469-477, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28004478

RESUMEN

Although inhibitors targeting tumor angiogenic pathway have provided improvement for clinical treatment in patients with various solid tumors, the still very limited anti-cancer efficacy and acquired drug resistance demand new agents that may offer better clinical benefits. In the effort to find a small molecule potentially targeting several key pathways for tumor development, we designed, discovered and evaluated a novel multi-kinase inhibitor, CS2164. CS2164 inhibited the angiogenesis-related kinases (VEGFR2, VEGFR1, VEGFR3, PDGFRα and c-Kit), mitosis-related kinase Aurora B and chronic inflammation-related kinase CSF-1R in a high potency manner with the IC50 at a single-digit nanomolar range. Consequently, CS2164 displayed anti-angiogenic activities through suppression of VEGFR/PDGFR phosphorylation, inhibition of ligand-dependent cell proliferation and capillary tube formation, and prevention of vasculature formation in tumor tissues. CS2164 also showed induction of G2/M cell cycle arrest and suppression of cell proliferation in tumor tissues through the inhibition of Aurora B-mediated H3 phosphorylation. Furthermore, CS2164 demonstrated the inhibitory effect on CSF-1R phosphorylation that led to the suppression of ligand-stimulated monocyte-to-macrophage differentiation and reduced CSF-1R+ cells in tumor tissues. The in vivo animal efficacy studies revealed that CS2164 induced remarkable regression or complete inhibition of tumor growth at well-tolerated oral doses in several human tumor xenograft models. Collectively, these results indicate that CS2164 is a highly selective multi-kinase inhibitor with potent anti-tumor activities against tumor angiogenesis, mitosis and chronic inflammation, which may provide the rationale for further clinical assessment of CS2164 as a therapeutic agent in the treatment of cancer.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Inhibidores de la Angiogénesis/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Puntos de Control de la Fase M del Ciclo Celular/efectos de los fármacos , Mitosis/efectos de los fármacos , Neovascularización Patológica/tratamiento farmacológico , Fenilendiaminas/uso terapéutico , Quinolinas/uso terapéutico , Células 3T3 , Animales , Aurora Quinasa B/antagonistas & inhibidores , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Histonas/metabolismo , Humanos , Inflamación/tratamiento farmacológico , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Simulación del Acoplamiento Molecular , Naftalenos , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-kit/antagonistas & inhibidores , Receptor alfa de Factor de Crecimiento Derivado de Plaquetas/antagonistas & inhibidores , Receptores de Factor Estimulante de Colonias de Granulocitos y Macrófagos/antagonistas & inhibidores , Receptores de Factores de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Immunopharmacol Immunotoxicol ; 39(3): 124-130, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28303727

RESUMEN

CONTEXT: Shikonin is a kind of naphthoquinone compound found mainly in Lithospermum erythrorhizon Sieb,et Zucc. Previous studies have shown that Shikonin has anti-tumor, anti-inflammatory and extensive pharmacological effects. According to new studies, Shikonin could also modulate the immune system function, but the effect to NK (nature killer) cells is yet unknown. OBJECTIVE: To investigate the effect and mechanism of Shikonin on NK cells proliferation and cytotoxicity to colon cancer cell line (Caco-2). METHODS: The proliferation and cytotoxicity of NK cells cultured with Shikonin were detected with CCK-8 assay. The expressions of perforin, GranB and IFN-γ were examined with FCM. The content of TNF-alpha was disclosed with ELISA kit. p-ERK1/2 and p-Akt expression of NK cells were detected with western blot. RESULTS: With CCK-8 assay, it is found that Shikonin could significantly enhance NK cells proliferation and cytotoxicity to colon cancer cells. With FCM assay, it is found that Shikonin could improve the expression of perforin and GranB in a dose-dependent manner. Shikonin had no effect on TNF-alpha and IFN-γ expression. In mechanism, the study shows that Shikonin could enhance the expression of p-ERK1/2 and p-Akt. CONCLUSIONS: Shikonin enhances NK cells proliferation and cytotoxicity via the improvement of perforin, GranB, p-ERK1/2 and p-Akt expression.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/inmunología , Inmunidad Celular/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Naftoquinonas/farmacología , Células CACO-2 , Neoplasias del Colon/patología , Humanos , Células Asesinas Naturales , Sistema de Señalización de MAP Quinasas/inmunología , Proteína Quinasa 1 Activada por Mitógenos/inmunología , Proteína Quinasa 3 Activada por Mitógenos/inmunología , Proteínas Proto-Oncogénicas c-akt/inmunología
13.
J Diabetes ; 16(2): e13484, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37853916

RESUMEN

BACKGROUND: To evaluate the glycemic control effects of vhiglitazar (carfloglitazar), a novel peroxisome proliferator-activated receptor pan-agonist, in patients with type 2 diabetes mellitus (T2DM) with metabolic syndrome (MetS) or insulin resistance (IR) using pooled data analysis of two phase III clinical trials. METHODS: Data were collected from two randomized phase III clinical trials in China, comparing chiglitazar to placebo or sitagliptin in T2DM patients. The MetS was defined by the Adult Treatment Panel III MetS criteria, and IR was defined by homeostatic model assessment for insulin resistance (HOMA-IR) ≥4.31 (male) or 4.51 (female). The main end point of this analysis was glycemic control in the different arms within each subgroup. RESULTS: In the MetS subgroup, changes in glycated hemoglobin (HbA1c) from baseline at week 24 in the chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg arms were -1.44%, -1.68%, and -1.37%, respectively; p < .05 was obtained when chiglitazar 48 mg was compared with sitagliptin. In the IR subgroup, the changes in HbA1c were -1.58%, -1.56%, and -1.26% in chiglitazar 32 mg, chiglitazar 48 mg, and sitagliptin 100 mg arms, respectively; p < .05 was obtained when chiglitazar 32 mg was compared with sitaligptin. The two doses of chiglitazar demonstrated a greater reduction in fasting plasma glucose and 2 h postprandial plasma glucose than sitagliptin in the pooled population and in the MetS and IR subgroups. CONCLUSIONS: Chiglitazar shows promising efficacy for glycemic control in patients with T2DM associated with MetS or IR. Further prospective trials are required to validate these findings.


Asunto(s)
Carbazoles , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Síndrome Metabólico , Propionatos , Adulto , Humanos , Masculino , Femenino , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Síndrome Metabólico/complicaciones , Síndrome Metabólico/tratamiento farmacológico , Hemoglobina Glucada , Glucemia/metabolismo , Control Glucémico , Hipoglucemiantes/uso terapéutico , Fosfato de Sitagliptina/uso terapéutico
14.
Photoacoustics ; 36: 100591, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38322617

RESUMEN

Atmospheric aerosols play a pivotal role in the earth-atmospheric system. Analyzing their optical properties, specifically absorption and scattering coefficients, is essential for comprehending the impact of aerosols on climate. When different optical properties of aerosols are individually measured using multiple devices, cumulative errors in the detection results inevitably occur. To address this challenge, based on photoacoustic spectroscopy (PAS) and integrating sphere (IS) scattering enhancement, a compact gas cell (PASIS-Cell) was developed. The PASIS-Cell comprises a dual-T-type photoacoustic cell (DTPAC) and an IS. IS is coupled with DTPAC through a transparent quartz tube, thereby enhancing the scattering signal without compromising the acoustic characteristics of DTPAC. Concurrently, DTPAC can realize high-performance photoacoustic detection of absorption signal. Experimental results demonstrate that PASIS-Cell can simultaneously invert atmospheric aerosol absorption and scattering coefficients, with a minimum detection limit of less than 1 Mm-1, showcasing its potential in the analysis of aerosol optical properties.

15.
Artículo en Inglés | MEDLINE | ID: mdl-38751475

RESUMEN

Background: The ACE study previously demonstrated that tucidinostat (chidamide), a subtype-selective histone deacetylase (HDAC) inhibitor, plus exemestane significantly improved progression-free survival (PFS) in advanced hormone receptor-positive (HR+) breast cancer patients with a manageable safety profile. The analysis of long-term safety and overall survival (OS) is presented here. Methods: ACE is a randomized, double-blind, placebo-controlled, phase 3 trial comparing tucidinostat 30 mg/twice weekly plus exemestane 25 mg/day versus placebo plus exemestane 25 mg/day in postmenopausal patients with advanced, HR+ breast cancer. The primary endpoint was PFS, and OS was the secondary endpoint. Results: Of the 365 patients enrolled between July 2015, and June 2017, 244 were assigned to tucidinostat plus exemestane (tucidinostat group) and 121 to placebo plus exemestane group (placebo group). Baseline characteristics were well balanced between groups. The median follow-up from randomization to data cut-off (February 25, 2021) of this analysis was 26.5 months (range, 13.9-45.5 months). A total of 231 deaths (63.3%) from 365 patients occurred, including 155 deaths (63.5%) in the tucidinostat group and 76 deaths (62.8%) in the placebo group. The median OS was 30.3 months (95% CI, 26.7-36.7) in the tucidinostat group and 30.3 months (95% CI, 24.8-38.1) in the placebo group. The safety profiles of both tucidinostat and placebo groups remained consistent with those previously reported, and no new safety signals were observed with longer follow-up. Neutropenia of grade 3 or 4 occurred in 51.6% of the patients in the tucidinostat group and 2.5% of the patients in the placebo group. Adverse events (AEs) that led to treatment discontinuations from any cause occurred in 28 (11.5%) patients in the tucidinostat group and 4 (3.3%) in the placebo group. Conclusions: Although tucidinostat in combination with exemestane had produced a clinically meaningful and statistically significant improvement in the primary endpoint PFS, the ACE study did not show a prolongation of the secondary endpoint OS in the tucidinostat combination regimen. Ongoing studies have been considered in terms of potential identification of what patient subpopulations could benefit most from the tucidinostat combination regimens in advanced HR+ breast cancer.

16.
Front Bioeng Biotechnol ; 10: 906728, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35711634

RESUMEN

The study of brain science is vital to human health. The application of hyperspectral imaging in biomedical fields has grown dramatically in recent years due to their unique optical imaging method and multidimensional information acquisition. Hyperspectral imaging technology can acquire two-dimensional spatial information and one-dimensional spectral information of biological samples simultaneously, covering the ultraviolet, visible and infrared spectral ranges with high spectral resolution, which can provide diagnostic information about the physiological, morphological and biochemical components of tissues and organs. This technology also presents finer spectral features for brain imaging studies, and further provides more auxiliary information for cerebral disease research. This paper reviews the recent advance of hyperspectral imaging in cerebral diagnosis. Firstly, the experimental setup, image acquisition and pre-processing, and analysis methods of hyperspectral technology were introduced. Secondly, the latest research progress and applications of hyperspectral imaging in brain tissue metabolism, hemodynamics, and brain cancer diagnosis in recent years were summarized briefly. Finally, the limitations of the application of hyperspectral imaging in cerebral disease diagnosis field were analyzed, and the future development direction was proposed.

17.
Front Pharmacol ; 13: 932914, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36120308

RESUMEN

Histone deacetylase (HDAC) is one of the most characterized epigenetic modifiers, modulating chromatin structure and gene expression, which plays an important role in cell cycle, differentiation and apoptosis. Dysregulation of HDAC promotes cancer progression, thus inhibitors targeting HDACs have evidently shown therapeutic efficacy in multiple cancers. Tucidinostat (formerly known as chidamide), a novel subtype-selective HDAC inhibitor, inhibits Class I HDAC1, HDAC2, HDAC3, as well as Class IIb HDAC10. Tucidinostat is approved in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL), advanced breast cancer and R/R adult T-cell leukemia-lymphoma (ATLL). Compared with other HDAC inhibitors, tucidinostat shows notable antitumor activity, remarkable synergistic effect with immunotherapy, and manageable toxicity. Here, we comprehensively summarize recent advances in tucidinostat as both monotherapy and a regimen of combination therapy in both hematological and solid malignancies in clinic. Further studies will endeavor to identify more combination strategies with tucidinostat and to identify specific clinical biomarkers to predict the therapeutic effect.

18.
J Phys Chem B ; 125(50): 13744-13751, 2021 Dec 23.
Artículo en Inglés | MEDLINE | ID: mdl-34894674

RESUMEN

The magnetohydrodynamic (MHD) effect was usually used to improve the mass transport during electrodeposition in a solution electrolyte. Herein, we reported the effect of a magnetic field on the electrode process of Al electrodeposition in a [Emim]Cl-AlCl3 ionic liquid composed of pure ions. Under a uniform and perpendicular magnetic field to the Cu electrode plane, electrochemical impedance spectroscopy (EIS) of the circuit, the cyclic voltammetry (CV) curves, and the different capacitances at the potential of zero charge (PZC) were measured, and the electrodeposition of aluminum was carried out at a constant current density. The results indicated that a vertical magnetic field significantly reduced the resistance (activation energy) for charge transfer of electrochemical reduction of Al2Cl7-; meanwhile, the capacitance of an electric double layer (EDL) and the density of the electrodeposited aluminum layer were increased.

19.
Waste Manag ; 135: 182-189, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34509770

RESUMEN

A low-cost and easy-available silicon (Si) feedstock is of great significance for developing high-performance lithium-ion battery (LIB) anode materials. Herein, we employ waste crystalline Si solar panels as silicon raw materials, and transform micro-sized Si (m-Si) into porous Si (p-Si) by an alloying/dealloying approach in molten salt where Li+ was first reduced and simultaneously alloyed with m-Si to generate Li-Si alloy at the cathode. Subsequently, the as-prepared Li-Si alloy served as the anode in the same molten salt to release Li+ into the molten salt, resulting in the production of p-Si by taking advantage of the volume expansion/contraction effect. In the whole process, Li+ was shuttled between the electrodes in molten LiCl-KCl, without consuming Li salt. The obtained p-Si was applied as an anode in a half-type LIBs that delivered a capacity of 2427.7 mAh g-1 at 1 A g-1 after 200 cycles with a capacity retention rate of 91.5% (1383.3 mAh g-1 after 500 cycles). Overall, this work offers a straightforward way to convent waste Si panels to high-performance Si anodes for LIBs, giving retired Si a second life and alleviating greenhouse gas emissions caused by Si production.


Asunto(s)
Litio , Silicio , Suministros de Energía Eléctrica , Electrodos , Porosidad
20.
Clin Pharmacol Drug Dev ; 10(7): 789-796, 2021 07.
Artículo en Inglés | MEDLINE | ID: mdl-33345463

RESUMEN

The effect of age on the pharmacokinetics and safety of chiglitazar was evaluated in patients < 65 and ≥ 65 years with type 2 diabetes mellitus (T2DM). A total of 20 T2DM patients (<65 vs ≥65 years 1:1) completed the study. Patients received multiple doses of 48 mg chiglitazar once daily for 7 days consecutively. After the first dosing, chiglitazar maximum plasma concentration (Cmax ) and area under the plasma concentration-time curve (AUC) in patients ≥ 65 years were similar to those observed in patients < 65 years, with the geometric mean ratio (GMR) for Cmax and AUC being 97.22% and 96.83%, respectively. No significant difference was observed in Cmax (GMR, 97.23%) in the steady state. Compared with the patients < 65 years, a slight increase (8%-13%) of AUC was observed in the patients ≥ 65 years after multiple doses. Chiglitazar was generally well tolerated following multiple doses in both age groups. In conclusion, there were no significant clinical influences on the pharmacokinetic properties and safety profiles of chiglitazar between patients with T2DM < 65 and ≥ 65 years, indicating that in the future it is not required to adjust the dosing regimen by age for T2DM patients ≥ 65 years.


Asunto(s)
Carbazoles/administración & dosificación , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/administración & dosificación , Propionatos/administración & dosificación , Factores de Edad , Anciano , Área Bajo la Curva , Carbazoles/efectos adversos , Carbazoles/farmacocinética , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Hipoglucemiantes/farmacocinética , Masculino , Persona de Mediana Edad , Receptores Activados del Proliferador del Peroxisoma/agonistas , Propionatos/efectos adversos , Propionatos/farmacocinética
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