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1.
Anal Chem ; 96(6): 2286-2291, 2024 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-38289025

RESUMEN

The link between inflammation and the evolution of cancer is well established. Visualizing and tracking both tumor proliferation and the associated inflammatory response within a living organism are vital for dissecting the nexus between these two processes and for crafting precise treatment modalities. We report the creation and synthesis of an advanced NIR chemiluminescence probe that stands out for its exceptional selectivity, extraordinary sensitivity at nanomolar concentrations, swift detection capabilities, and broad application prospects. Crucially, this probe has been successfully utilized to image endogenous ONOO- across different inflammation models, including abdominal inflammation triggered by LPS, subcutaneous inflammatory conditions, and tumors grafted onto mice. These findings highlight the significant promise of chemiluminescence imaging in enhancing our grasp of the intricate interplay between cancer and inflammation and in steering the development of potent, targeted therapeutic strategies.


Asunto(s)
Inflamación , Neoplasias , Animales , Ratones , Inflamación/diagnóstico por imagen , Luminiscencia , Neoplasias/diagnóstico por imagen , Colorantes Fluorescentes , Ácido Peroxinitroso
2.
J Exp Bot ; 2024 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-39126211

RESUMEN

The endoplasmic reticulum (ER) is crucial for maintaining cell homeostasis because it is the primary site for synthesizing secreted and transmembrane proteins and lipids. The unfolded protein response (UPR) is activated to restore ER homeostasis under ER stress. However, the relationship between lipids and the ER stress response in plants is not well understood. Arabidopsis Golgi anti-apoptotic proteins (GAAPs) are involved in resisting ER stress. To elucidate the function of GAAPs, PASTICCINO2 (PAS2), involved in very long-chain fatty acid (VLCFA) synthesis, was found to interact with GAAPs and IRE1. Single pas2 and gaap1/gaap2pas2 double mutants exhibited increased seedling damage and impaired UPR response under chronic ER stress. Site mutation combined with genetic analysis revealed that the role of PAS2 in resisting ER stress depended on its VLCFA synthesis domain. VLCFA contents were upregulated under ER stress, which required GAAPs. Exogenous VLCFAs partially restored the defect in UPR upregulation caused by PAS2 or GAAP mutations under chronic ER stress. These findings demonstrate that the association of PAS2 with GAAPs confers plant resistance to ER stress by regulating VLCFA synthesis and the UPR. This provides a basis for further studies on the connection between lipids and cell fate decisions under stress.

3.
Toxicol Appl Pharmacol ; 492: 117127, 2024 Oct 16.
Artículo en Inglés | MEDLINE | ID: mdl-39419123

RESUMEN

Acute lung injury (ALI) is a serious respiratory disease characterized by diffuse alveolar injury, and it has emerged as a major concern in clinical practice due to limited treatments. This study aimed to explore the pharmacological effects and regulatory mechanism of sappanone A (SA) on ALI. In vivo, mice were administered with SA followed by intratracheal injection of lipopolysaccharide (LPS) to establish an animal model of ALI. We observed that SA exerted comparable anti-inflammatory effects to dexamethasone, as evidenced by effectively mitigating histopathological abnormalities and suppressing the inflammatory response in the lung tissues of mice with ALI. RNA sequencing analysis revealed that SA significantly inhibited the activation of the nuclear factor kappa B (NF-κB) signaling pathway. In vitro, we found that SA protected BEAS-2B cells against LPS-induced cellular injury and reduced inflammatory cytokine generation. Furthermore, both in vivo and in vitro experiments demonstrated that SA effectively prevented LPS-induced oxidative stress and apoptosis. Consistent with the results of the RNA sequencing analysis, SA significantly inhibited the increased protein expressions of p105, p50, c-REL, as well as the ratios of p-p65/p65 and p-IκBα/IκBα in the lung tissues of mice with ALI and LPS-stimulated BEAS-2B cells. Additionally, SA inhibited the nuclear translocation of p65 in BEAS-2B cells stimulated with LPS. Importantly, specific blockade of the NF-κB signaling pathway using BAY11-7082 was identified to alleviate LPS-induced cellular injury in BEAS-2B cells. Collectively, these findings suggest that SA can ameliorate ALI, at least in part, through the inhibition of NF-κB signaling pathway activation.

4.
Anal Chem ; 95(35): 13191-13200, 2023 09 05.
Artículo en Inglés | MEDLINE | ID: mdl-37610431

RESUMEN

Chemiluminescent probes have become increasingly popular in various research areas including precise tumor imaging and immunofluorescence analysis. Nevertheless, previously developed chemiluminescence probes are mainly limited to studying oxidation reaction-associated biological events. This study presents the first example of bioimaging applicable bicyclic dioxetane chemiluminescent probes with tunable emission wavelengths that range from 525 to 800 nm. These newly developed probes were able to detect the analytes of ß-Gal, H2O2, and superoxide with high specificity and a limit of detection of 77 mU L-1, 96, and 28 nM, respectively. The bioimaging application of the probes was verified in ovarian and liver cancer cells and macrophage cells, allowing the detection of the content of ß-Gal, H2O2, and superoxide inside the cells. The high specificity allowed us to image the xenografted tumor in mice. We expect that our probes will receive extensive applications in recording complex biomolecular events using noninvasive imaging techniques.


Asunto(s)
Peróxido de Hidrógeno , Superóxidos , Animales , Ratones , Diagnóstico por Imagen , Línea Celular , Xenoinjertos
5.
Hepatology ; 76(1): 94-111, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34735734

RESUMEN

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (HIR) injury, a common clinical complication of liver transplantation and resection, affects patient prognosis. Ring finger protein 5 (RNF5) is an E3 ubiquitin ligase that plays important roles in endoplasmic reticulum stress, unfolded protein reactions, and inflammatory responses; however, its role in HIR is unclear. APPROACH AND RESULTS: RNF5 expression was significantly down-regulated during HIR in mice and hepatocytes. Subsequently, RNF5 knockdown and overexpression of cell lines were subjected to hypoxia-reoxygenation challenge. Results showed that RNF5 knockdown significantly increased hepatocyte inflammation and apoptosis, whereas RNF5 overexpression had the opposite effect. Furthermore, hepatocyte-specific RNF5 knockout and transgenic mice were established and subjected to HIR, and RNF5 deficiency markedly aggravated liver damage and cell apoptosis and activated hepatic inflammatory responses, whereas hepatic RNF5 transgenic mice had the opposite effect compared with RNF5 knockout mice. Mechanistically, RNF5 interacted with phosphoglycerate mutase family member 5 (PGAM5) and mediated the degradation of PGAM5 through K48-linked ubiquitination, thereby inhibiting the activation of apoptosis-regulating kinase 1 (ASK1) and its downstream c-Jun N-terminal kinase (JNK)/p38. This eventually suppresses the inflammatory response and cell apoptosis in HIR. CONCLUSIONS: We revealed that RNF5 protected against HIR through its interaction with PGAM5 to inhibit the activation of ASK1 and the downstream JNK/p38 signaling cascade. Our findings indicate that the RNF5-PGAM5 axis may be a promising therapeutic target for HIR.


Asunto(s)
Proteínas de la Membrana , Fosfoproteínas Fosfatasas , Daño por Reperfusión , Ubiquitina-Proteína Ligasas , Animales , Apoptosis , Humanos , Hígado/metabolismo , Proteínas de la Membrana/metabolismo , Ratones , Fosfoproteínas Fosfatasas/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación
6.
Acta Pharmacol Sin ; 44(11): 2253-2264, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37311796

RESUMEN

Although STAT3 has been reported as a negative regulator of type I interferon (IFN) signaling, the effects of pharmacologically inhibiting STAT3 on innate antiviral immunity are not well known. Capsaicin, approved for the treatment of postherpetic neuralgia and diabetic peripheral nerve pain, is an agonist of transient receptor potential vanilloid subtype 1 (TRPV1), with additional recognized potencies in anticancer, anti-inflammatory, and metabolic diseases. We investigated the effects of capsaicin on viral replication and innate antiviral immune response and discovered that capsaicin dose-dependently inhibited the replication of VSV, EMCV, and H1N1. In VSV-infected mice, pretreatment with capsaicin improved the survival rate and suppressed inflammatory responses accompanied by attenuated VSV replication in the liver, lung, and spleen. The inhibition of viral replication by capsaicin was independent of TRPV1 and occurred mainly at postviral entry steps. We further revealed that capsaicin directly bound to STAT3 protein and selectively promoted its lysosomal degradation. As a result, the negative regulation of STAT3 on the type I IFN response was attenuated, and host resistance to viral infection was enhanced. Our results suggest that capsaicin is a promising small-molecule drug candidate, and offer a feasible pharmacological strategy for strengthening host resistance to viral infection.


Asunto(s)
Subtipo H1N1 del Virus de la Influenza A , Interferón Tipo I , Infecciones por Orthomyxoviridae , Ratones , Animales , Capsaicina/farmacología , Factor de Transcripción STAT3 , Transducción de Señal , Proteínas Portadoras , Replicación Viral
7.
Gerontology ; 69(4): 428-449, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36470214

RESUMEN

INTRODUCTION: Senile osteoporosis is one of the most common age-related diseases worldwide. Glucagon like peptide-2 (GLP-2), a naturally occurring gastrointestinal peptide, possesses therapeutic effects on bone loss in postmenopausal women and ovariectomized rats. However, the role of GLP-2 in senile osteoporosis and underlying mechanisms has not been explored. METHODS: GLP-2 was subcutaneously injected into the 6-month-old male senile osteoporosis model of senescence-accelerated mouse prone 6 (SAMP6) mice for 6 weeks. SAMP6 subjected to normal saline and senescence-accelerated mouse resistant 1 served as control groups. Micro-computed tomography was performed to evaluate the bone mass and microarchitecture of the mice. Osteoblastic and osteoclastic activities were determined by biochemical, quantitative real-time PCR, histological, and histomorphometric analyses combined with hematoxylin-eosin, toluidine blue, and tartrate-resistant acid phosphatase staining. We also examined the proteins and structure of intestinal tight junction using immunohistochemical assay as well as a transmission electron microscope. Serum inflammation marker levels were measured using ELISA. Additionally, anti-oxidative enzymes GPX-4 and SOD-2 and receptors of GLP-2 and vitamin D expression in the ileum and colon were detected under immunofluorescence staining. RESULTS: Six-week GLP-2 treatment attenuated bone loss in SAMP6 mice, as evidenced by increased bone mineral density, improved microarchitecture in femora, and enhanced osteogenic activities. In contrast, the activity of osteoclastic activity was not obviously inhibited. Moreover, GLP-2 ameliorated tight junction structure and protein expression in the intestinal barrier, which was accompanied by the reduction of TNF-α level. The expression of receptors of intestinal GLP-2 and vitamin D in the ileum was elevated. Furthermore, the oxidative stress in the intestines was improved by increasing the GPX-4 and SOD-2 signaling. CONCLUSION: Our findings suggest that GLP-2 could ameliorate age-associated bone loss, tight junction structure, and improved antioxidant enzyme activity in the gut in SAMP6 mice. Amelioration of gut barrier dysfunction may potentially contribute to improving bone formation and provide evidence for targeting the entero-bone axis in the treatment of senile osteoporosis.


Asunto(s)
Péptido 2 Similar al Glucagón , Osteoporosis , Ratones , Masculino , Femenino , Ratas , Animales , Microtomografía por Rayos X/métodos , Péptido 2 Similar al Glucagón/farmacología , Modelos Animales de Enfermedad , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Osteoporosis/patología , Envejecimiento , Vitamina D , Superóxido Dismutasa
8.
Molecules ; 28(14)2023 Jul 11.
Artículo en Inglés | MEDLINE | ID: mdl-37513215

RESUMEN

α-Ketoamide moieties, as privileged units, may represent a valuable option to develop compounds with favorable biological activities, such as low toxicity, promising PK and drug-like properties. An efficient silver-catalyzed decarboxylative acylation of α-oxocarboxylic acids with isocyanides was developed to derivatize the α-ketoamide functional group via a multicomponent reaction (MCR) cascade sequence in one pot. A series of α-ketoamides was synthesized with three components of isocyanides, aromatic α-oxocarboxylic acid analogues and water in moderate yields. Based on the research, the silver-catalyzed decarboxylative acylation confirmed that an oxygen atom of the amide moiety was derived from the water and air as a sole oxidant for the whole process.

9.
Hepatology ; 73(2): 738-758, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32343849

RESUMEN

BACKGROUND AND AIMS: Hepatic ischemia-reperfusion (I/R) injury, which mainly involves inflammatory responses and apoptosis, is a common cause of organ dysfunction in liver transplantation (LT). As a critical mediator of inflammation and apoptosis in various cell types, the role of tripartite motif-containing (TRIM) 27 in hepatic I/R injury remains worthy of study. APPROACH AND RESULTS: This study systemically evaluated the putative role of TRIM27/transforming growth factor ß-activated kinase 1 (TAK1)/JNK (c-Jun N-terminal kinase)/p38 signaling in hepatic I/R injury. TRIM27 expression was significantly down-regulated in liver tissue from LT patients, mice subjected to hepatic I/R surgery, and hepatocytes challenged by hypoxia/reoxygenation (H/R) treatment. Subsequently, using global Trim27 knockout mice (Trim27-KO mice) and hepatocyte-specific Trim27 transgenic mice (Trim27-HTG mice), TRIM27 functions to ameliorate liver damage, reduce the inflammatory response, and prevent cell apoptosis. In parallel in vitro studies, activating TRIM27 also prevented H/R-induced hepatocyte inflammation and apoptosis. Mechanistically, TRIM27 constitutively interacted with the critical components, TAK1 and TAK1 binding protein 2/3 (TAB2/3), and promoted the degradation of TAB2/3, leading to inactivation of TAK1 and the subsequent suppression of downstream JNK/p38 signaling. CONCLUSIONS: TRIM27 is a key regulator of hepatic I/R injury by mediating the degradation of TAB2/3 and suppression of downstream TAK1-JNK/p38 signaling. TRIM27 may be a promising approach to protect the liver against I/R-mediated hepatocellular damage in transplant recipients.


Asunto(s)
Proteínas de Unión al ADN/metabolismo , Trasplante de Hígado/efectos adversos , Hígado/irrigación sanguínea , Proteínas Nucleares/metabolismo , Daño por Reperfusión/patología , Ubiquitina-Proteína Ligasas/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Animales , Biopsia , Línea Celular , Proteínas de Unión al ADN/genética , Modelos Animales de Enfermedad , Humanos , Hígado/patología , Quinasas Quinasa Quinasa PAM/metabolismo , Masculino , Ratones , Ratones Noqueados , Proteolisis , RNA-Seq , Daño por Reperfusión/etiología , Ubiquitina-Proteína Ligasas/genética
10.
J Exp Bot ; 73(8): 2601-2617, 2022 04 18.
Artículo en Inglés | MEDLINE | ID: mdl-35034107

RESUMEN

Maintaining proteostasis in the endoplasmic reticulum (ER) is critical for cell viability and plant survival under adverse conditions. The unfolded protein response (UPR) pathways interact with reactive oxygen species (ROS) to precisely trigger adaptive outputs or cell death under ER stress with varying degrees. However, little information is known about the relationship between UPR signalling and ROS regulation. Here, Arabidopsis GOLGI ANTI-APOPTOTIC PROTEIN1 (GAAP1)-GAAP4 were found to play redundant positive roles under ER stress. Genetic analysis showed that GAAP4 played a role in INOSITOL-REQUIRING ENZYME (IRE1)-dependent and -independent pathways. In addition, GAAPs played negative roles to activate the adaptive UPR under conditions of stress. Quantitative biochemical analysis showed that mutations in GAAP genes decreased the oxidised glutathione content and altered the pattern of ROS and glutathione in early ER stress. When plants were challenged with unmitigated ER stress, mutations in GAAP advanced ROS accumulation, which was associated with a decline in adaptive UPR. These data indicated that GAAPs resist cell death by regulating glutathione content to inhibit ROS accumulation and maintain UPR during ER stress. They provide a basis for further analysis of the regulation of cell fate decision under ER stress.


Asunto(s)
Arabidopsis , Estrés del Retículo Endoplásmico , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Arabidopsis/metabolismo , Muerte Celular , Estrés del Retículo Endoplásmico/fisiología , Glutatión/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Respuesta de Proteína Desplegada
11.
Biomacromolecules ; 23(12): 5330-5339, 2022 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-36454623

RESUMEN

To alleviate the dilemma of drug administration in Alzheimer's disease (AD) patients, it is of great significance to develop a new drug delivery system. In this study, a subcutaneously implanted microneedle (MN) device with a swellable gelatin methacryloyl (GelMA) needle body and a dissolvable polyvinyl alcohol (PVA) backing layer was designed. The backing layer quickly dissolved once the MN was introduced into the subcutaneous, and the hydrogel needles were implanted in the subcutaneous to enable prolonged drug release. Compared with oral administration, the MN system offers the benefits of a high administration rate, a fast onset of effect, and a longer duration of action. By detecting the concentration of acetylcholine (ACH) and Aß 1-42, it was found that MN administration exhibited a stronger therapeutic effect. The biological safety of the MN system was also assessed, and no obvious signs of hemolysis, cytotoxicity, and inflammatory reaction were observed. Together, these findings suggested that the MN system is a convenient, efficient, and safe method of delivering donepezil hydrochloride (DPH) and may provide AD patients with a novel medicine administration option.


Asunto(s)
Enfermedad de Alzheimer , Humanos , Donepezilo/farmacología , Donepezilo/uso terapéutico , Enfermedad de Alzheimer/tratamiento farmacológico , Agujas , Sistemas de Liberación de Medicamentos , Alcohol Polivinílico , Administración Cutánea
12.
Hepatobiliary Pancreat Dis Int ; 21(2): 106-112, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34583911

RESUMEN

Mammalian target of rapamycin (mTOR) inhibitor as an attractive drug target with promising antitumor effects has been widely investigated. High quality clinical trial has been conducted in liver transplant (LT) recipients in Western countries. However, the pertinent studies in Eastern world are paucity. Therefore, we designed a clinical trial to test whether sirolimus can improve recurrence-free survival (RFS) in hepatocellular carcinoma (HCC) patients beyond the Milan criteria after LT. This is an open-labeled, single-arm, prospective, multicenter, and real-world study aiming to evaluate the clinical outcomes of early switch to sirolimus-based regimens in HCC patients after LT. Patients with a histologically proven HCC and beyond the Milan criteria will be enrolled. The initial immunosuppressant regimens are center-specific for the first 4-6 weeks. The following regimens integrated sirolimus into the regimens as a combination therapy with reduced calcineurin inhibitors based on the condition of patients and centers. The study is planned for 4 years in total with a 2-year enrollment period and a 2-year follow-up. We predict that sirolimus conversion regimen will provide survival benefits for patients particular in the key indicator RFS as well as better quality of life. If the trial is conducted successfully, we will have a continued monitoring over a longer follow-up time to estimate indicator of overall survival. We hope that the outcome will provide better evidence for clinical decision-making and revising treatment guidelines based on Chinese population data. Trial register: Trial registered at http://www.chictr.org.cn: ChiCTR2100042869.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/cirugía , Humanos , Inmunosupresores/efectos adversos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/cirugía , Trasplante de Hígado/métodos , Estudios Multicéntricos como Asunto , Recurrencia Local de Neoplasia/tratamiento farmacológico , Estudios Prospectivos , Calidad de Vida , Sirolimus/efectos adversos , Resultado del Tratamiento
13.
Org Biomol Chem ; 18(34): 6732-6737, 2020 09 14.
Artículo en Inglés | MEDLINE | ID: mdl-32832956

RESUMEN

A nitrate-promoted Pd-catalysed mild cross-dehydrogenative C(sp2)-H bond oxidation of oximes or azobenzenes with diverse carboxylic acids has been developed. In contrast to the previous catalytic systems, this protocol features mild conditions (close to room temperature for most cases) and a broad substrate scope (up to 64 examples), thus constituting a versatile method to directly prepare diverse O-aryl esters. Moreover, the superiority of the nitrate additive in this mild transformation was further determined by experimental and computational evidence.

14.
J Transl Med ; 17(1): 117, 2019 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-30961629

RESUMEN

BACKGROUND: Extrahepatic metastasis is the independent risk factor of poor survival of primary hepatic carcinoma (PHC), and most occurs in the chest and abdomen. Currently, there is still no available method to predict thoracoabdominal extrahepatic metastasis in PHC. In this study, a novel nomogram model was developed and validated for prediction of thoracoabdominal extrahepatic metastasis in PHC, thereby conducted individualized risk management for pretreatment different risk population. METHODS: The nomogram model was developed in a primary study that consisted of 330 consecutive pretreatment patients with PHC. Large-scale datasets were extracted from clinical practice. The nomogram was based on the predictors optimized by data dimension reduction through Lasso regression. The prediction performance was measured by the area under the receiver operating characteristic (AUROC), and calibrated to decrease the overfit bias. Individualized risk management was conducted by weighing the net benefit of different risk population via decision curve analysis. The prediction performance was internally and independently validated, respectively. An independent-validation study using a separate set of 107 consecutive patients. RESULTS: Four predictors from 55 high-dimensional clinical datasets, including size, portal vein tumor thrombus, infection, and carbohydrate antigen 125, were incorporated to develop a nomogram model. The nomogram demonstrated valuable prediction performance with AUROC of 0.830 (0.803 in internal-validation, and 0.773 in independent-validation, respectively), and fine calibration. Individual risk probability was visually scored. Weighing the net benefit, threshold probability was classified for three-independent risk population, which was < 19.9%, 19.9-71.8% and > 71.8%, respectively. According to this classification, pretreatment risk management was based on a treatment-flowchart for individualized clinical decision-making. CONCLUSIONS: The proposed nomogram is a useful tool for pretreatment risk management of thoracoabdominal extrahepatic metastasis in PHC for the first time, and may handily facilitate timely individualized clinical decision-making for different risk population.


Asunto(s)
Neoplasias Hepáticas/patología , Modelos Biológicos , Nomogramas , Gestión de Riesgos , Algoritmos , Calibración , Toma de Decisiones Clínicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pronóstico , Curva ROC , Factores de Riesgo
15.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4293-4299, 2019 Oct.
Artículo en Zh | MEDLINE | ID: mdl-31872712

RESUMEN

Based on the characteristics of biological supramolecules and the law of " imprinting template",the research status and common problems in " maintaining medicinal properties after carbonisatus" in traditional Chinese medicine( TCM) were analyzed,and the further countermeasures were put forward. According to the historical evolution of " maintaining medicinal properties after carbonisatus" in TCM processing,the origin of its common problems was clarified by using the theory of biosupramolecular chemistry. TCM is a megacomplex biological supramolecular system,so TCM processing is just the processing of megacomplex biological supramolecular system,and its essence is a TCM pharmaceutical technology with chemical changes in host and guest of biological supramolecular system with or without adjuvant material under high temperature and humidity. In this study on pharmaceutical technology,host molecule was destructed in the process of carbonizing,but guest molecule was retained. The changing law of the host and guest molecule was controlled by the " imprinting template",which was reflected in the degree of change in the drug properties and efficacy of the decoction pieces. Supramolecular chemistry ran through the whole process,and the " imprinting template" of charcoal medicine was characterized by the supramolecular topological structure characteristics and imprinting behavior. After being combined with the quantitative mathematical model of heating degree in processing,it can realize the accurate processing of " maintaining medicinal properties after carbonisatus" from the source,quantitatively control the quality of carbonic herbs,and formulate stable and controllable quality standards.


Asunto(s)
Medicamentos Herbarios Chinos , Medicina Tradicional China , Registros , Estándares de Referencia , Tecnología
16.
Nephrology (Carlton) ; 20(5): 321-8, 2015 May.
Artículo en Inglés | MEDLINE | ID: mdl-25597434

RESUMEN

AIM: Despite the perceived importance of frailty, few studies focus on its impact on rural patients undergoing chronic dialysis. Comparison of different self-report questionnaires in assessing frailty among these patients has not been attempted before. METHODS: A prospectively enrolled chronic dialysis cohort from a rural centre was recruited for analysis. Six types of self-report questionnaires were administered to these patients. Clinical and dialysis-related laboratory parameters were collected. Correlation analyses between questionnaire results and dialysis complications were performed, and variables demonstrating significant correlations were entered into multivariate regression models to determine their independent associations. RESULTS: Six types of questionnaire (Strawbridge questionnaire, Edmonton Frail Scale, simple FRAIL scale, Groningen Frail Indicator, G8 questionnaire, and Tilburg Frail Indicator) were provided to rural patients undergoing chronic dialysis. Scores from each questionnaire showed significant association with each other, except the G8 questionnaire. Scores from the simple FRAIL scale correlated significantly with age (P = 0.02), female gender (P = 0.03), higher Liu's comorbidity index (P = 0.02), lower serum albumin (P = 0.03) and creatinine levels (P < 0.01), and higher ferritin levels (P = 0.02). The other five questionnaires did not show consistently significant relationships with important dialysis-related complications. Multivariate linear regression analysis identified an independently negative association between serum albumin and the simple FRAIL scale results (P = 0.01). CONCLUSION: This is the first study establishing the utility of different self-report questionnaires for assessing frailty in chronic dialysis patients. The simple FRAIL scale scores might demonstrate a closer relationship with dialysis-related complications.


Asunto(s)
Evaluación Geriátrica , Indicadores de Salud , Fallo Renal Crónico/complicaciones , Diálisis Renal/efectos adversos , Servicios de Salud Rural , Autoinforme , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Anciano Frágil , Humanos , Fallo Renal Crónico/terapia , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad , Factores Socioeconómicos
17.
World J Clin Cases ; 12(23): 5410-5415, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39156099

RESUMEN

BACKGROUND: Small cell lung cancer (SCLC) exhibits a pronounced tendency for metastasis and relapse, and the acquisition of resistance to chemotherapy and radiotherapy, leading to complexity in treatment outcomes. It is crucial to tackle these challenges by advancing targeted therapeutic approaches in ongoing research endeavors. Variant RET fusions have been reported in several solid tumors, but are rarely reported in SCLC. CASE SUMMARY: We present the first case of a KIF5B-RET fusion in a 65-year-old male patient with SCLC. To date, the patient has received the 4th line chemotherapy with anlotinib for one year and has shown a sustained favorable partial response. According to the results of next generation sequencing, this SCLC patient harbors the KIF5B-RET fusion, suggesting that RET fusion could serve as a promising molecular target for SCLC treatment. Next-generation sequencing (NGS) plays a critical role in comprehensively assessing the genotype and phenotype of cancer. CONCLUSION: NGS can provide SCLC patients with personalized and targeted therapy options, thereby improving their likelihood of survival.

18.
Arch Gerontol Geriatr ; 124: 105462, 2024 09.
Artículo en Inglés | MEDLINE | ID: mdl-38692155

RESUMEN

BACKGROUND: The study aimed to investigate the effect of Glucagon-like peptide-2 (GLP-2) on muscle aging in vivo and in vitro. METHODS: Six-week-old C57BL/6J mice were administered with D-galactose (200 mg/kg/day, intraperitoneally) for 8weeks, followed by daily subcutaneous injections of GLP-2 (300 or 600 µg/kg/day) for 4weeks. Skeletal muscle function and mass were evaluated using relative grip strength and muscle weight. The sizes and types of muscle fibers and apoptosis were assessed through histological analysis, immunofluorescence staining, and TUNEL staining, respectively. C2C12 myotubes were treated with D-galactose (40 mg/mL) and GLP-2. Protein expression of differentiation-related myogenic differentiation factor D (MyoD), myogenin (MyoG), and myosin heavy chain (Myhc), degradation-related Muscle RING finger 1 (MuRF-1), and muscle atrophy F-box (MAFbx)/Atrogin-1, and apoptosis-related B-cell leukemia/lymphoma 2 (Bcl-2) and Bax, were assessed using western blots. The Pi3k inhibitor LY294002 was applied to investigate whether GLP-2 regulated myogenesis and myotube aging via IGF-1/Pi3k/Akt/FoxO3a signaling pathway. RESULTS: The results demonstrated that GLP-2 significantly reversed the decline in muscles weight, relative grip strength, diameter, and cross-sectional area of muscle fibers induced by D-galactose in mice. Apart from suppressing the expressions of MuRF-1 and Atrogin-1 in the muscles and C2C12 myotubes, GLP-2 significantly increased the expressions of MyoD, MyoG, and Myhc compared to the D-galactose. GLP-2 significantly suppressed cell apoptosis. Western blot analysis indicated that the regulation of GLP-2 may be attributed to the activation of theIGF-1/Pi3k/Akt/FoxO3a phosphorylation pathway. CONCLUSIONS: This study suggested that GLP-2 ameliorated D-galactose induced muscle aging by IGF-1/Pi3k/Akt/FoxO3a pathway.


Asunto(s)
Proteína Forkhead Box O3 , Galactosa , Péptido 2 Similar al Glucagón , Factor I del Crecimiento Similar a la Insulina , Ratones Endogámicos C57BL , Músculo Esquelético , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Animales , Ratones , Proteína Forkhead Box O3/metabolismo , Transducción de Señal/efectos de los fármacos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Péptido 2 Similar al Glucagón/farmacología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Envejecimiento/efectos de los fármacos , Apoptosis/efectos de los fármacos , Masculino , Fibras Musculares Esqueléticas/efectos de los fármacos , Fibras Musculares Esqueléticas/metabolismo , Fibras Musculares Esqueléticas/patología
19.
Int Immunopharmacol ; 131: 111861, 2024 Apr 20.
Artículo en Inglés | MEDLINE | ID: mdl-38484665

RESUMEN

Glutathione (GSH) depletion, mitochondrial damage, and oxidative stress have been implicated in the pathogenesis of acetaminophen (APAP) hepatotoxicity. Here, we demonstrated that the expression of histone deacetylase 6 (HDAC6) is highly elevated, whereas malate dehydrogenase 1 (MDH1) is downregulated in liver tissues and AML-12 cells induced by APAP. The therapeutic benefits of LT-630, a novel HDAC6 inhibitor on APAP-induced liver injury, were also substantiated. On this basis, we demonstrated that LT-630 improved the protein expression and acetylation level of MDH1. Furthermore, after overexpression of MDH1, an upregulated NADPH/NADP+ ratio and GSH level and decreased cell apoptosis were observed in APAP-stimulated AML-12 cells. Importantly, MDH1 siRNA clearly reversed the protection of LT-630 on APAP-stimulated AML-12 cells. In conclusion, LT-630 could ameliorate liver injury by modulating MDH1-mediated oxidative stress induced by APAP.


Asunto(s)
Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Enfermedad Hepática Inducida por Sustancias y Drogas , Histona Desacetilasa 6 , Leucemia Mieloide Aguda , Animales , Humanos , Ratones , Acetaminofén , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/metabolismo , Glutatión/metabolismo , Histona Desacetilasa 6/antagonistas & inhibidores , Leucemia Mieloide Aguda/metabolismo , Hígado/patología , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos
20.
Eur J Pharm Biopharm ; 185: 5-12, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36739099

RESUMEN

Melasma is a common hyperpigmented skin condition that occurs on the face and other areas prone to light exposure, seriously affecting people's quality of life. Microneedle, a new type of transdermal drug delivery device, can significantly improve skin permeability. In this study, we designed and fabricated a polymer microneedle roller (PMR) using a mold hot pressing method, and established a mouse model of melasma induced by ultraviolet radiation. The dynamometer and insertion test of MNs into parafilm and skin of mice indicates that the MNs have sufficient mechanical properties to insert parafilm and skin of mice. The two methods (apply hydroquinone cream (HQC) directly and pre-treat with PMR before applying HQC) were used to treat melasma. From the results of skin surface observation, determination of superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in skin and liver tissues, histological observation, and skin Optical coherence tomography (OCT), we confirmed both the two methods had a therapeutic effect while the PMR pretreatment group exhibited a better therapeutic effect. In addition, there were statistical differences between the UV group (P < 0.05). Together these results indicated that the MNs may be promising in future clinical applications in improving the UV irradiation-induced pigmentation like melisma.


Asunto(s)
Melanosis , Polímeros , Ratones , Animales , Hidroquinonas/uso terapéutico , Parafina/uso terapéutico , Calidad de Vida , Rayos Ultravioleta , Melanosis/tratamiento farmacológico , Melanosis/patología
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