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1.
Artículo en Inglés | MEDLINE | ID: mdl-38753239

RESUMEN

Nuclear reactors will face the problem of decommissioning at the end of their operating life due to the high radioactivity of reactor components and environmental safety considerations. The Heavy Water Research Reactor (HWRR) is the first large-scale research reactor to be decommissioned in China. The second phase of HWRR decommissioning involves the main components in the reactor block, so the radiation source terms and the radioactive waste level need to be evaluated before demolition and disposal. Based on the operating history, three-dimensional geometry, materials, and other information of the HWRR, the activity of radionuclides in the main components of HWRR is calculated and analyzed, and the MCNP/ORIGEN coupling scheme is utilized for theoretical analysis. The theoretical results indicate that 14C, 54Mn, 55Fe, 60Co, 63Ni, and 152Eu are the main radioactive nuclides. The total activity of radioactive nuclides was 2.36E + 15 Bq at the end of 2007, 4.27E + 13 Bq at the end of 2021, and 1.83E + 13 Bq at the end of 2025. Furthermore, local sampling and radiometric analyses based on the HPGe gamma-ray spectrometer are also performed to verify the theoretical results, the ratio of theoretical activity values to the measured activity of the experimental sample is within 2.5 times, so the theoretical results are conservative. According to the classification standards for radioactive waste, the inner shell, outer shell, cooling water tank, sand layer, and heavy concrete shielding layer are all low-level waste. These results and conclusions can serve as a reference for the second phase decommissioning of the HWRR and the subsequent disposal of radioactive waste.

2.
China CDC Wkly ; 6(11): 208-212, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38532747

RESUMEN

What is already known about this topic?: Addressing health disparities is a worldwide priority, with a well-established acknowledgment of the influence of childhood circumstances on these discrepancies. In China, particularly among the elderly, health inequalities are a notable concern. What is added by this report?: The inequality in healthy aging has increased from 2011 to 2020, both in general and concerning childhood factors. Nevertheless, the impact of early-life healthcare access and parental health behaviors on healthy aging gaps has reduced among older adults in better health within the top segment of healthy aging. What are the implications for public health practice?: Efforts towards reducing regional health disparities and improving healthcare access for children, along with promoting the health and well-being of parents, especially in economically disadvantaged households, are crucial policy considerations.

3.
Int J Surg ; 110(4): 2253-2262, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38320088

RESUMEN

BACKGROUND: Roux-en-Y reconstruction is a common anastomosis technique during gastrectomy in gastric cancer. There is a lack of studies on gallstones after Roux-en-Y reconstruction gastrectomy. This study investigated the incidence and potential risk factors associated with gallstones after Roux-en-Y reconstructive gastrectomy in gastric cancer. METHODS: The study analyzed data from gastric cancer who underwent radical gastrectomy and Roux-en-Y reconstruction at two hospitals between January 2014 and December 2020. The patients fall into distal and total gastrectomy groups based on the extent of gastrectomy. The cumulative event probability curve was plotted using the Kaplan-Meier, and differences in gallstone between groups were evaluated using the Log-Rank. Propensity score matching was applied to construct a balanced total versus distal gastrectomies cohort. A Cox regression was employed to analyze the risk factors for gallstones after Roux-en-Y reconstructive gastrectomy in gastric cancer. Further subgroup analysis was performed. RESULTS: Five hundred thirty-one patients were included in this study, 201 in the distal gastrectomy group and 330 in the total gastrectomy. During the follow-up, gallstones occurred in 170 cases after gastrectomy, of which 145 cases accounted for 85.29% of all stones in the first two years after surgery. Then, to reduce the impact of bias, a 1:1 propensity score matching analysis was performed on the two groups of patients. A total of 344 patients were evaluated, with each subgroup comprising 172 patients. In the matched population, the Cox regression analysis revealed that females, BMI ≥23 kg/m 2 , total gastrectomy, No.12 lymph node dissection, and adjuvant chemotherapy were risk factors for gallstones after Roux-en-Y reconstructive gastrectomy. Subgroup analysis showed that open surgery further increased the risk of gallstones after total gastrectomy. CONCLUSION: The incidence of gallstones increased significantly within 2years after Roux-en-Y reconstructive gastrectomy for gastric cancer. Patients with these risk factors should be followed closely after gastrectomy to avoid symptomatic gallstones.


Asunto(s)
Anastomosis en-Y de Roux , Cálculos Biliares , Gastrectomía , Complicaciones Posoperatorias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Gastrectomía/efectos adversos , Gastrectomía/métodos , Femenino , Masculino , Persona de Mediana Edad , Cálculos Biliares/cirugía , Cálculos Biliares/epidemiología , Cálculos Biliares/etiología , Incidencia , Anastomosis en-Y de Roux/efectos adversos , Anciano , Factores de Riesgo , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Puntaje de Propensión , Estudios de Cohortes , Adulto
4.
Int J Anal Chem ; 2024: 5531430, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38250173

RESUMEN

Surface-enhanced Raman scattering (SERS) technology has unique advantages in the rapid detection of pesticides in plant-derived foods, leading to reduced detection limits and increased accuracy. Plant-derived Chinese herbal medicines have similar sources to plant-derived foods; however, due to the rough surfaces and complex compositions of herbal medicines, the detection of pesticide residues in this context continues to rely heavily on traditional methods, which are time consuming and laborious and are unable to meet market demands for portability. The application of flexible nanomaterials and SERS technology in this realm would allow rapid and accurate detection in a portable format. Therefore, in this review, we summarize the underlying principles and characteristics of SERS technology, with particular focus on applications of SERS for the analysis of pesticide residues in agricultural products. This paper summarizes recent research progress in the field from three main directions: sample pretreatment, SERS substrates, and data processing. The prospects and limitations of SERS technology are also discussed, in order to provide theoretical support for rapid detection of pesticide residues in Chinese herbal medicines.

5.
Food Chem ; 439: 138122, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38070231

RESUMEN

Food safety concerns about the authenticity of soy product freshness have increased due to high demand from public. Developing an accurate and convenient monitoring method for freshness authenticity is crucial for safeguarding food safety. From this motive, this study employed PtPd NPs to encapsulate tetraphenylethylene (TPE) for engineering an AIE-based fluorescent nanozyme (PtPd NPs@TPE) with oxidase-like activity, achieving the ratiometric fluorescence monitoring of putrescine (PUT) to judge the freshness authenticity of soy products. In this design, PUT acted as an antioxidant and inhibited the oxidation process of PtPd NPs@TPE to o-phenylenediamine (OPD), leading to the reduction of oxidative product 2,3-diaminophenothiazine (DAP) alone with the weaken of yellow fluorescence from DAP at 552 nm and bright of bule fluorescence from PtPd NPs@TPE at 442 nm. On this basis, a ratiometric fluorescence strategy integrated with smartphone-based sensor was developed for PUT with acceptable results to combat food freshness fraud of soy products.


Asunto(s)
Oxidorreductasas , Teléfono Inteligente , Fluorescencia , Oxidación-Reducción , Espectrometría de Fluorescencia/métodos , Colorantes Fluorescentes
6.
Eur J Med Chem ; 264: 116051, 2024 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-38104377

RESUMEN

Macrocyclic compounds, characterized by cyclic structures, often originate from either modified forms of unicyclic canonical molecules or natural products. Within the field of medicinal chemistry, there has been a growing fascination with drug-like macrocycles in recent years, primarily due to compelling evidence indicating that macrocyclization can significantly influence both the biological and physiochemical properties, as well as the selectivity, when compared to their acyclic counterparts. The approval of contemporary pharmaceutical agents like Lorlatinib underscore the notable clinical relevance of drug-like macrocycles. Nonetheless, the synthesis of these drug-like macrocycles poses substantial challenges, primarily stemming from the complexity of ring-closing reactions, which are inherently dependent on the size and geometry of the bridging linker, impacting overall yields. Nevertheless, macrocycles offer a promising avenue for expanding the synthetic toolkit in medicinal chemistry, enabling the creation of bioactive compounds. To shed light on the subject, we delve into the clinical prowess of established macrocyclic drugs, spanning various therapeutic areas, including oncology, and infectious diseases. Case studies of clinically approved macrocyclic agents illustrate their profound impact on patient care and disease management. As we embark on this journey through the world of macrocyclic pharmaceuticals, we aim to provide a comprehensive overview of their synthesis and clinical applications, shedding light on the pivotal role they play in modern medicine.


Asunto(s)
Productos Biológicos , Compuestos Macrocíclicos , Humanos , Compuestos Macrocíclicos/química , Lactamas Macrocíclicas , Química Farmacéutica , Preparaciones Farmacéuticas
7.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5345-5355, 2023 Oct.
Artículo en Chino | MEDLINE | ID: mdl-38114124

RESUMEN

The study investigated the effect of Buyang Huanwu Decoction(BYHWD) on endogenous biomarkers in the urine of rats with chronic inflammation induced by lipopolysaccharide(LPS) using ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS), aiming to elucidate the molecular mechanism underlying the therapeutic effect of BYHWD on chronic inflammation from a metabolomics perspective. Male SD rats were randomly divided into a normal group, a model group, and low-, medium-, and high-dose BYHWD groups(7.5, 15, and 30 g·kg~(-1)). The model group and BYHWD groups received tail intravenous injection of LPS(200 µg·kg~(-1)) on the first day of each week, followed by oral administration of BYHWD once a day for four consecutive weeks. Urine samples were collected at the end of the administration period, and UPLC-Q-TOF-MS was used to analyze the metabolic profiles of the rat urine in each group. Multivariate statistical analysis methods such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to analyze the effect of BYHWD on endogenous metabolites. One-way ANOVA and variable importance for the projection(VIP) were used to screen for potential biomarkers related to chronic inflammation. The identified biomarkers were subjected to pathway and enrichment analysis using MetaboAnalyst 5.0. A total of 25 potential biomarkers were screened and identified in the rat urine in this experiment. Compared with the normal group, the model group showed significant increases in the levels of 14 substances(P<0.05) and significant decreases in the levels of 11 substances(P<0.05). BYHWD was able to effectively reverse the trend of most endogenous biomarkers. Compared with the model group, BYHWD significantly down-regulated 13 biomarkers(P<0.05) and up-regulated 10 biomarkers(P<0.05). The metabolic products were mainly related to the biosynthesis of pantothenic acid and coenzyme A, tryptophan metabolism, retinol metabolism, and propionate metabolism. BYHWD has therapeutic effect on chronic inflammation induced by LPS, which may be related to its ability to improve the levels of endogenous metabolites, enhance the body's anti-inflammatory and antioxidant capabilities, and restore normal metabolic activity.


Asunto(s)
Lipopolisacáridos , Metabolómica , Ratas , Masculino , Animales , Cromatografía Líquida de Alta Presión/métodos , Ratas Sprague-Dawley , Metabolómica/métodos , Inflamación/tratamiento farmacológico , Biomarcadores/orina
8.
Front Pharmacol ; 14: 1244563, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38143491

RESUMEN

Background: Recent studies have shown that bile acids are essential in irritable bowel syndrome (IBS) pathology, and cholecystectomy has direct effects on bile acid metabolism. However, whether cholecystectomy increases the risk of IBS remains unclear. We aimed to investigate the association between cholecystectomy and IBS risk in the UK Biobank (UKB). Methods: This study is a prospective analysis of 413,472 participants who were free of IBS, inflammatory bowel disease, cancer, or common benign digestive tract diseases. We identified incidents of IBS through self-reporting or links to primary healthcare and hospitalization data. We evaluated hazard ratios (HRs) adjusted for sociodemographic characteristics, health behaviours, comorbidities, and medications. Results: During a median follow-up period of 12.7 years, we observed 15,503 new cases of IBS. Participants with a history of cholecystectomy had a 46% higher risk of IBS than those without (HR = 1.46, 95% CI: 1.32-1.60), and further subtype analysis showed that the risk of IBS with diarrhoea was significantly higher than the risk of IBS without diarrhoea (HR = 1.71, 95% CI: 1.30-2.25 vs. HR = 1.42, 95% CI: 1.28-1.58). The overall covariate-adjusted HRs for IBS were similar between the group with both cholecystectomy and gallstones (HR = 1.45, 95% CI: 1.32-1.58) and the group with cholecystectomy without gallstones (HR = 1.50, 95% CI: 1.36-1.67) when the group without both cholecystectomy and gallstones was used as a reference. The overall covariate-adjusted HR was not significantly different in the group without cholecystectomy with gallstones (HR = 1.18, 95% CI: 0.95-1.47). The positive association of cholecystectomy with IBS risk did not change when stratifying the data based on age, sex, BMI, smoking, alcohol consumption, healthy diet, quality sleep, physical activity, type 2 diabetes, hypertension, hyperlipidaemia, mental illness, NSAID intake, or acid inhibitor intake. Sensitivity analyses, including propensity score matching analysis and lagging the exposure for two or four years, indicated that the effects were robust. Conclusion: Cholecystectomy was associated with a higher risk of IBS, especially IBS with diarrhoea. Additional prospective randomized controlled and experimental studies are warranted to further validate the association and to explore the relevant biological mechanisms.

9.
Eur J Med Chem ; 262: 115928, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37944387

RESUMEN

Gastrointestinal (GI) cancers encompass a group of malignancies affecting the digestive system, including the stomach, esophagus, liver, colon, rectum and pancreas. These cancers represent a significant global health burden, necessitating effective treatment strategies. Small-molecule drugs have emerged as crucial therapeutic options in the fight against GI cancers due to their oral bioavailability, targeted mechanisms of action, and well-established safety profiles. The review then elucidates the clinical applications and synthetic methods of clinically approved small-molecule drugs for the treatment of GI cancer, shedding light on their mechanisms of action and their potential in mitigating GI cancer progression. The review also discusses future prospects and the evolving landscape of small-molecule drug development in GI oncology, highlighting the potential for personalized medicine. In summary, this review provides valuable insights into cutting-edge strategies for harnessing clinically approved small-molecule drugs to combat GI cancer effectively.


Asunto(s)
Neoplasias Gastrointestinales , Humanos , Neoplasias Gastrointestinales/tratamiento farmacológico , Neoplasias Gastrointestinales/patología , Resultado del Tratamiento
10.
Eur J Med Chem ; 262: 115919, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37922830

RESUMEN

Hepatitis, a global public health concern, presents a significant burden on healthcare systems worldwide. Particularly, hepatitis B and C are viral infections that can lead to severe liver damage, cirrhosis, and even hepatocellular carcinoma (HCC). The urgency to combat these diseases has driven researchers to explore existing small-molecule drugs as potential therapeutics. This comprehensive review provides a systematic overview of synthetic routes to key antiviral agents used to manage hepatitis. Furthermore, it elucidates the mechanisms of action of these drugs, shedding light on their interference with viral replication and liver disease progression. The review also discusses the clinical applications of these drugs, including their use in combination therapies and various patient populations. By evaluating the synthetic pathways and clinical utility of these drugs, this review not only consolidates current knowledge but also highlights potential future directions for research and drug development in the fight against hepatitis, ultimately contributing to improved patient outcomes and reduced global disease burden.


Asunto(s)
Carcinoma Hepatocelular , Hepatitis B , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Antivirales/farmacología , Antivirales/uso terapéutico , Hepatitis B/tratamiento farmacológico , Virus de la Hepatitis B
11.
J Agric Food Chem ; 71(43): 16381-16390, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37908144

RESUMEN

Considering the enormous demand for meat in people's daily lives, the development of efficient meat freshness assays is of great significance for safeguarding food safety. Here, a novel bimetallic nanozyme Fe@CeO2 with high peroxidase-like activity was first synthesized by embedding ferrocenecarboxylic acid (Fc) into hollow CeO2 nanospheres, which combined with xanthine oxidase (XOD) to develop a self-supplying H2O2-facilitated enzymatic cascade catalytic system of XOD + Fe@CeO2, yielding a meat freshness indicator hypoxanthine (Hx)-responsive colorimetric and photothermal dual-mode analytical platform for judging meat freshness upon the assistance of 3,3',5,5'-tetramethylbenzidine (TMB). Owing to the catalytic activity of XOD to convert Hx into H2O2, Fe@CeO2 rapidly dissociated it into •OH via a peroxidase activity-triggered Fenton-like reaction, emerging a typical enzymatic cascade catalytic reaction. As a result, the colorless TMB was oxidized to be the product of dark-blue oxTMB by •OH, with a chromogenic reaction-driven absorption enhancement at 652 nm, which endowed it with a significant photothermal effect under 660 nm laser irradiation. On this basis, an Hx concentration-dependent colorimetric and photothermal dual-mode signal cascade catalytic enhancement sensing platform was proposed by integrating with a Color Picker App-installed smartphone and a 660 nm laser-equipped handheld thermal imager, achieving the onsite quantitative, reliable, and visual detection of Hx in real meat samples for judging meat freshness with acceptable results. Notably, the colorimetric and photothermal dual-mode signal cascade catalytic enhancement improved not only the reliability but also the sensitivity of the assay, which provided new insights for efficient onsite visual monitoring of meat freshness to safeguard food safety.


Asunto(s)
Colorimetría , Peróxido de Hidrógeno , Humanos , Reproducibilidad de los Resultados , Carne , Peroxidasas , Hipoxantinas
12.
BMC Geriatr ; 23(1): 639, 2023 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-37817067

RESUMEN

Whilst early-life conditions have been understood to impact upon the health of older adults, further exploration of the field is required. There is a lack of consensus on conceptualising these conditions, and interpretation of experiences are socially and culturally dependent.To advance this important topic we invite authors to submit their research to the Collection on 'The impact of early-life/childhood circumstances or conditions on the health of older adults'.


Asunto(s)
Envejecimiento Saludable , Humanos , Anciano
13.
Eur J Med Chem ; 261: 115868, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37844346

RESUMEN

Lung cancer continues to pose a significant challenge as a prominent contributor to global cancer-related mortality. Despite the considerable strides made in therapeutic interventions within the past decade, a substantial population of patients diagnosed with non-small cell lung cancer (NSCLC) still face the grim reality of an incurable condition. In the realm of optimal management strategies for individuals afflicted with locally advanced, yet amenable to surgical resection, NSCLC, a therapeutic approach encompassing chemoradiation stands as a fundamental component. Significant strides have been made in the therapeutic landscape of NSCLC during the preceding two decades, facilitating an enhanced comprehension of the underlying disease biology, and mechanisms governing tumor progression, as well as advancements in early detection modalities and multimodal therapeutic interventions. Nevertheless, the overall rates of curative interventions and survival outcomes for NSCLC continue to exhibit a discouragingly low trajectory, particularly in the context of metastatic disease. Hence, the imperative for sustained research endeavors in the realm of novel pharmaceutical agents and combinatorial therapeutic approaches remains paramount, with the overarching objective of broadening the scope of clinical advantages conferred upon a wider demographic of patients, thereby fostering tangible improvements in outcomes pertaining to NSCLC. The primary objective of this review is to provide an all-encompassing examination encompassing the clinical application and synthetic routes of specific drugs, with the explicit aim of disseminating invaluable knowledge that can inform future research and development endeavors focused on NSCLC.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Terapia Combinada
14.
Eur J Med Chem ; 261: 115847, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37801826

RESUMEN

Application of chemotherapeutic agents to inhibit the HIV replication process has brought about a significant metamorphosis in the landscape of AIDS. Substantial declines in morbidity and mortality rates have been attained, accompanied by notable decreases in healthcare resource utilization. However, treatment modalities do not uniformly inhibit HIV replication in every patient, while the emergence of drug-resistant viral strains poses a substantial obstacle to subsequent therapeutic interventions. Furthermore, chronic administration of therapy may lead to the manifestation of toxicities. These challenges necessitate the exploration of novel pharmacological agents and innovative therapeutic approaches aimed at effectively managing the persistent viral replication characteristic of chronic infection. This review examines the role of clinically approved small-molecule drugs in the treatment of HIV/AIDS, which provides an in-depth analysis of the major classes of small-molecule drugs, including nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), integrase inhibitors, entry inhibitors, and pharmacokinetic enhancers. The review mainly discusses the application, synthetic routes, and mechanisms of action of small-molecule drugs employed in the treatment of HIV, as well as their use in combination with antiretroviral therapy, presenting viewpoints on forthcoming avenues in the development of novel anti-HIV drugs.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Inhibidores de Fusión de VIH , Infecciones por VIH , Humanos , Fármacos Anti-VIH/farmacología , Fármacos Anti-VIH/uso terapéutico , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Inhibidores de la Transcriptasa Inversa/farmacología , Infecciones por VIH/tratamiento farmacológico
15.
Eur J Med Chem ; 261: 115835, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37801827

RESUMEN

Lymphoma is a form of cancer that impacts the lymphatic system, which plays a crucial role in defending the body against infections and illnesses. It is characterized by the atypical proliferation of lymphocytes, a type of white blood cell, which can form tumors in the lymph nodes, bone marrow, spleen, etc. Lymphoma is usually treated using a combination of targeted therapy, chemotherapy, and radiation therapy. In recent years, there has been a growing interest in the development of new drugs to treat lymphoma, which has led to the discovery of several promising compounds. The primary targets for lymphoma treatment have been identified as Bruton's tyrosine kinase (BTK), phosphoinositide3-kinase (PI3K), histone deacetylase (HDAC), and DNA polymerase (POLA). This review aims to provide an overview of the clinical applications and synthesis of several notable drugs approved to treat lymphoma, to expedite the exploration of more potent novel medications for the management of lymphoma.


Asunto(s)
Linfoma , Humanos , Linfoma/tratamiento farmacológico , Agammaglobulinemia Tirosina Quinasa/metabolismo , Médula Ósea , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico
16.
Eur J Med Chem ; 261: 115848, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37793326

RESUMEN

Janus kinase (JAK) plays a crucial role in intracellular signaling pathways, particularly in cytokine-mediated signal transduction, making them attractive therapeutic targets for a wide range of diseases, including autoimmune disorders, myeloproliferative neoplasms, and inflammatory conditions. The review provides a comprehensive overview of the development and therapeutic potential of small-molecule inhibitors targeting JAK family of proteins in various clinical trials. It also discusses the mechanisms of action, specificity, and selectivity of these inhibitors, shedding light on the challenges associated with achieving target selectivity while minimizing off-target effects. Moreover, the review offers insights into the clinical applications of JAK inhibitors, summarizing the ongoing clinical trials and the Food and Drug Administration (FDA)-approved JAK inhibitors currently available for various diseases. Overall, this review provides a thorough examination of the synthesis and clinical use of typical small-molecule JAK inhibitors in different clinical stages and offers a bright future for the development of novel small-molecule JAK inhibitors.


Asunto(s)
Enfermedades Autoinmunes , Inhibidores de las Cinasas Janus , Trastornos Mieloproliferativos , Humanos , Quinasas Janus , Inhibidores de las Cinasas Janus/farmacología , Inhibidores de las Cinasas Janus/uso terapéutico , Trastornos Mieloproliferativos/tratamiento farmacológico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/metabolismo , Transducción de Señal
17.
Eur J Med Chem ; 261: 115827, 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-37757658

RESUMEN

Myeloid leukemia denotes a hematologic malignancy characterized by aberrant proliferation and impaired differentiation of blood progenitor cells within the bone marrow. Despite the availability of several treatment options, the clinical outlook for individuals afflicted with myeloid leukemia continues to be unfavorable, making it a challenging disease to manage. Over the past, substantial endeavors have been dedicated to the identification of novel targets and the advancement of enhanced therapeutic modalities to ameliorate the management of this disease, resulting in the discovery of many clinically approved small-molecule drugs for myeloid leukemia, including histone deacetylase inhibitors, hypomethylating agents, and tyrosine kinase inhibitors. This comprehensive review succinctly presents an up-to-date assessment of the application and synthetic routes of clinically sanctioned small-molecule drugs employed in the treatment of myeloid leukemia. Additionally, it provides a concise exploration of the pertinent challenges and prospects encompassing drug resistance and toxicity. Overall, this review effectively underscores the considerable promise exhibited by clinically endorsed small-molecule drugs in the therapeutic realm of myeloid leukemia, while concurrently shedding light on the prospective avenues that may shape the future landscape of drug development within this domain.


Asunto(s)
Leucemia Mieloide Aguda , Leucemia Mieloide , Humanos , Estudios Prospectivos , Médula Ósea , Leucemia Mieloide Aguda/tratamiento farmacológico
18.
Food Chem ; 429: 136961, 2023 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-37499507

RESUMEN

To combat food freshness fraud, it is urgent to develop a method which could realize the detection of biogenic amines (BAs) present in food. In our study, we developed a colorimetric and ratiometric fluorescence dual-mode sensor which integrated with silver metallization-based response system of AIE liposome + OPD + RSM + Ag+ toward BAs in foods for fighting freshness fraud. With the hydrolysis from the alkaline of BAs to resorcinol monoacetate (RSM), the production resorcinol (RS) could metallize silver ion (Ag+) to silver atoms (Ag0) which could lead to a BAs concentration-dependent decrease of the oxidation product 2,3-diaminophenothiazine (DAP) of Ag+ to o-phenylenediamine (OPD). As a result, the dual-mode sensor has a low detection limit and wide linear range in the spiked detection of soy products, pork and milk samples for BAs. Thus, providing a reliable method for food safety and forestalling food freshness fraud.


Asunto(s)
Liposomas , Plata , Aminas Biogénicas/análisis , Inocuidad de los Alimentos
19.
Insects ; 14(5)2023 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-37233056

RESUMEN

Tetranychus urticae Koch is a worldwide agricultural pest mite that feeds on more than 1100 kinds of crops. The mite has developed a high level of tolerance to high temperatures, but the physiological mechanism underlying the outstanding adaptability of this pest to high temperatures remains unclear. To clarify the physiological mechanisms of T. urticae in response to short-term heat stress, four temperatures (36, 39, 42, and 45 °C) and three short-term heat durations (2, 4, and 6 h) were conducted to test the effects on protein content, the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), and the total antioxidant capacity (T-AOC). The results showed that protein content, antioxidant enzyme activity, and T-AOC in T. urticae were significantly induced by heat stress. These results suggest that heat stress induces oxidative stress and that antioxidant enzymes play an important role in reducing oxidative damage in T. urticae. The data of this study will provide a basis for further research on the molecular mechanisms of thermostability and ecological adaptability of T. urticae.

20.
Econ Hum Biol ; 49: 101236, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36867949

RESUMEN

Using 2002-2018 German Socio-Economic Panel (GSOEP) data for German adults aged 18 + , this study measures changes in the body mass index (BMI) distribution and obesity inequality to estimate the relation between the latter and subjective well-being. In addition to documenting a significant association between the various measures of obesity inequality and subjective well-being, especially among women, we show a significant increase in obesity inequality, particularly among females and those with low education and/or low income. This rising inequality points to the need to combat obesity through initiatives targeted at specific sociodemographic groups.


Asunto(s)
Obesidad , Pobreza , Adulto , Humanos , Femenino , Factores Socioeconómicos , Obesidad/epidemiología , Alemania/epidemiología , Escolaridad , Índice de Masa Corporal
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