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1.
Nat Commun ; 15(1): 8727, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39379410

RESUMEN

Water is essential to the formation of intracontinental granites, but its origin remains elusive. Here we address this scientific problem by analyzing D/H isotopes of apatites, hydrous minerals in Jurassic and Early Cretaceous granites and basalts from eastern North China Craton, where water was previously interpreted as derived from subducting slab. Results reveal extremely low δD values in pristine Early Cretaceous granitic (-203‰ to -127‰) and basaltic (-197‰ to -107‰) apatites, contrasting with relatively high δD values (-137‰ to -47‰) in Jurassic granites. Given the depth-dependent D/H isotopic fractionation during slab dehydration and high-water contents in coeval primitive mafic magmas, the Early Cretaceous magma water is attributed to the stagnant slab within the mantle transition zone. Secular change in the depth of water aligns with steepening of subducting Paleo-Pacific plate from Jurassic to Early Cretaceous, demonstrating the potential of apatite H isotopes in tracing water origin in granites and basalts.

2.
Curr Med Chem ; 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39297453

RESUMEN

In this manuscript, the resource distribution, pharmacological activity, pharma-cokinetics of sinomenine and the structure, synthesis, biological activity and mechanism of sinomenine derivatives reported from 2000 to December 2023 were reviewed. The lit-erature was retrieved through Web of Science, PubMed, Science Direct, SciFiner Scholar and other websites. Sinomenine belongs to isoquinoline alkaloids and was extracted from the Chinese herb Sinomenium acutum root. In Asian countries such as China and Japan, it is commonly prescribed as a treatment for rheumatoid arthritis. In addition, sinomenine also has sedative, analgesic, anti-inflammatory, immunosuppressive, neuroprotective, an-ti-drug dependence, anti-tumor and other biological activities. Sinomenine limited its ap-plication prospects because of its large dosage, poor epidermal permeability and short half-life. To overcome these defects, new sinomenine derivatives have been synthesized. Based on the comprehensive analysis of relevant literature at home and abroad, this paper reviews the recent progress in the study of sinomenine's pharmacological effects and structural modifications. Future research on sinomenine will focus on improving its thera-peutic effect, and developing new drug preparations and structural modifications. It is hoped that this review will help to better understand the research progress of sinomenine and provide constructive suggestions for further research of sinomenine.

3.
Nat Prod Res ; : 1-9, 2024 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-39308432

RESUMEN

Two new phenolic glycosides, Diplostephioside D (1) and Diplostephioside E (2) together with ten known phenols (3-12) were isolated from the dried roots of Iris domestica (L.) Goldblatt & Mabb. Among them, compounds 4-9 have not been reported previously from the family Iridaceae. The chemical structures were elucidated based on extensive spectroscopic experiments, including 1D and 2D NMR as well as HR-ESI-MS, and comparison with those reported in the literature. All of the isolated compounds were evaluated for their cytotoxic activity against HeLa cells. Compounds 1, 2, 4, 8 and 12 showed cytotoxic activities with IC50 values ranging from 13.52 ± 1.52 to 53.33 ± 1.40 µM.

4.
ACS Nano ; 18(32): 21459-21471, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39088247

RESUMEN

Hard carbon is considered as the most promising anode material for potassium-ion energy storage devices. Substantial progress has been made in exploring advanced hard carbons to solve the issues of sluggish kinetics and large volume changes caused by the large radius of K+. However, the relationship between their complicated microstructures and the K+ charge storage behavior is still not fully explored. Herein, a series of two-dimensional mesoporous carbon microcoins (2D-MCMs) with tunable microstructures in heteroatom content and graphitization degree are synthesized by a facile hard-template method and follow a temperature-controllable annealing process. It is found that high heteroatom content makes for surface-driven K+ storage behavior, which increases the capacity-contribution ratio from a high potential region, while a high graphitization degree makes for K+ intercalation behavior, which increases the capacity-contribution ratio from a low potential region. Electrochemical results from a three-electrode Swagelok cell demonstrate that a 2D-MCM anode with more capacity contribution from a low working region allows the porous carbon cathode to be operated in a much wider electrochemical window, thus storing more charge. As a result, potassium-ion capacitors based on the optimized 2D-MCM anode deliver a high energy density of 113 Wh kg-1 and an exhilarating power density of 51,000 W kg-1.

5.
Biomed Pharmacother ; 178: 117239, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39098180

RESUMEN

Ulcerative colitis (UC) is a chronic non-specific inflammatory disease involving the mucosa and submucosa of the rectum and colon. Lindera aggregate (Sims) Kosterm is a traditional Chinese herb used for thousands of years in the treatment of gastrointestinal diseases. Previously, we have demonstrated that the extracts of Lindera aggregate have good anti-UC effects, but their pharmacodynamic active components have not been fully clarified. Therefore, we explored the therapeutic effect of Linderanine C (LDC), a characteristic component of Lindera aggregata, on UC and its mechanism in this study. Firstly, we found that LDC could significantly reduce the disease activity index of UC and improve shortened colon and pathological changes in vivo. Colon tissue transcriptomics suggested that the anti-UC effect of LDC might be related to its anti-inflammatory activity. Cellular experiments revealed that LDC could inhibit the expression of the M1 cell marker CD86 in RAW264.7 cells, reduce the production of inflammatory mediators such as IL-6 and TNF-α, and have good anti-inflammatory activity in vitro. Cellular transcriptomics reveal the potential involvement of the MAPK signaling pathway in the anti-inflammatory effect of LDC. The co-culture assay confirmed that LDC could significantly reduce inflammation-mediated intestinal epithelial cell injury. In conclusion, LDC was able to inhibit macrophage M1 polarization and reduce inflammatory mediator production by inhibiting the MAPK signaling pathway, effectively improving UC.


Asunto(s)
Antiinflamatorios , Colitis Ulcerosa , Sistema de Señalización de MAP Quinasas , Macrófagos , Animales , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/patología , Colitis Ulcerosa/metabolismo , Ratones , Células RAW 264.7 , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Antiinflamatorios/farmacología , Colon/efectos de los fármacos , Colon/patología , Colon/metabolismo , Ratones Endogámicos C57BL , Humanos , Polaridad Celular/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Modelos Animales de Enfermedad
6.
Arch Osteoporos ; 19(1): 56, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38954143

RESUMEN

This study examined low bone mineral density (BMD) prevalence and associated factors among Chinese people living with HIV (PLWH), uncovering a persistent high BMD risk in older individuals, even after adjusting for age and body mass index (BMI). Notably, lopinavir/ritonavir (LPV/r) therapy was linked to reduced BMD, highlighting the imperative need for regular BMD monitoring and interventions in older PLWH. PURPOSE: HIV infection and antiretroviral therapy (ART) have been shown to contribute to lower BMD, resulting in an increased susceptibility to osteopenia and osteoporosis. However, there is limited knowledge about the prevalence of reduced BMD and its associated factors among Chinese PLWH. In this cross-sectional study, we aimed to investigate the prevalence and factors associated with low BMD among PLWH in China. METHODS: We retrospectively enrolled PLWH and non-HIV volunteers who underwent dual-energy X-ray absorptiometry (DXA) scans to measure bone density. Demographic information, laboratory test results, ART regimens, and treatment duration were collected. Univariate and multiple regression analyses were performed to identify factors influencing abnormal bone mass in PLWH. RESULTS: A total of 829 individuals were included in this study, comprising the HIV group (n = 706) and the non-HIV group (n = 123). The prevalence of low BMD among all PLWH was found to be 13.88% (98 out of 706). However, among PLWH aged 50 years and above, the prevalence increased to 65.32% (81 out of 124). In contrast, control subjects in the same age group had a prevalence of 38.21% (47 out of 123). After adjusting for age and BMI, older PLWH still demonstrated a higher prevalence of low BMD compared to the non-HIV group (68.24% vs 34.94%, P < 0.001). Multivariate analysis revealed that older age was strongly associated with a higher risk of low BMD among PLWH, with an odds ratio (OR) of 6.28 for every 10-year increase in age in the ART-naïve population (95% confidence intervals [CIs], 3.12-12.65; P < 0.001) and OR of 4.83 in the ART-experienced population (3.20-7.29, P < 0.001). Within the ART-experienced group, current LPV/r treatment was associated with an increased risk of low BMD (OR = 3.55, 1.24-10.14, P < 0.05), along with lower BMI (OR = 0.84, 0.75-0.95, P < 0.05), and elevated alkaline phosphatase (OR = 1.02, 1.01-1.03, P < 0.01). CONCLUSION: The prevalence of low BMD is higher among PLWH aged 50 years and above compared to non-HIV individuals. The use of LPV/r for ART is associated with reduced BMD. These findings emphasize the importance of regular monitoring of BMD in older PLWH and the need for appropriate interventions to mitigate the risks of osteopenia and osteoporosis in this population.


Asunto(s)
Absorciometría de Fotón , Densidad Ósea , Infecciones por VIH , Osteoporosis , Humanos , Estudios Transversales , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Prevalencia , Adulto , China/epidemiología , Estudios Retrospectivos , Osteoporosis/epidemiología , Factores de Riesgo , Anciano , Enfermedades Óseas Metabólicas/epidemiología
7.
Chem Commun (Camb) ; 60(64): 8423-8426, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39028305

RESUMEN

Nanowhisker-like Cu3(HHTP)2 composed of neat arrays grown on a copper foam is rationally designed and prepared using Cu(OH)2 nanowire arrays as a self-sacrifice template. Benefiting from the good conductivity of Cu3(HHTP)2 and an ordered array structure, the optimized Cu3(HHTP)2@CF-3 electrode exhibits high area capacity, good rate performance and cyclic stability.

8.
Int J Biol Macromol ; 276(Pt 1): 134117, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39084989

RESUMEN

The degradation of Belamcanda chinensis (L.) DC. polysaccharides was carried out by five concentrations of trifluoroacetic acid (TFA) (1-5 mol/L), and their physicochemical properties, degradation kinetics and anticomplementary activity were investigated. The findings revealed a notable reduction in the molecular weight of BCP, from an initial value of 2.622 × 105 g/mol to a final value of 6.255 × 104 g/mol, and the water solubility index increased from 90.66 ± 0.42 % to 97.78 ± 0.43 %. The degraded polysaccharides of B. chinensis exhibited a comparable monosaccharide composition comprising Man, GalA, Glc, Gal, and Ara. As the concentration of TFA increased, the degradation rate constant increased from 1.468 × 10-3 to 5.943 × 10-3, and the process followed the first-order degradation kinetic model (R2 > 0.97) and the random fracture model (R2 > 0.96). Furthermore, the five degraded polysaccharides still exhibit good thermal stability. In vitro experiments showed that DBCP-3 exhibited more potent anticomplementary activity than the original polysaccharides and positive drugs, which was strongly correlated with its Mw (r = 0.6-0.8), inhibiting complement activation by blocking C2 and C4. These results indicated that TFA degradation has a positive effect on polysaccharides, of which DBCP-3 is expected to treat diseases involving hyperactivation of the complement system.


Asunto(s)
Peso Molecular , Polisacáridos , Ácido Trifluoroacético , Polisacáridos/química , Polisacáridos/farmacología , Ácido Trifluoroacético/química , Cinética , Monosacáridos/análisis , Monosacáridos/química , Animales , Solubilidad , Caryophyllaceae/química , Activación de Complemento/efectos de los fármacos
9.
J Ethnopharmacol ; 333: 118498, 2024 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-38944357

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Lindera aggregata (Sims) Kosterm is a common traditional herb that has multiple bioactivities. Radix Linderae (LR), the dry roots of Lindera aggregata (Sims) Kosterm, is a traditional Chinese herbal medicine with antioxidant, anti-inflammatory and immunomodulatory properties, first found in Kaibao Era. Norboldine (Nor) is an alkaloid extracted from LR and is one of the primary active ingredients of LR. However, the pharmacological functions and mechanism of Nor in Alzheimer's disease (AD) are still unknown. AIM OF THE STUDY: This study aims to investigate the effect and mechanism of Nor therapy in improving the cognitive impairment and pathological features of 3 × Tg mice. MATERIALS AND METHODS: 3 × Tg mice were treated with two concentrations of Nor for one month and then the memory and cognitive abilities of mice were assessed by novel object recognition experiment and Morris water maze. The impact of Nor on the pathology of ADwere examined in PC12 cells and animal tissues using western blotting and immunofluorescence. Finally, western blotting was used to verify the anti-apoptotic effect of Nor by activating AMPK/GSK3ß/Nrf2 signaling pathway at animal and cellular levels. RESULTS: In this study, we showed that Nor treatment improved the capacity of the learning and memory of 3 × Tg mice and alleviated AD pathology such as Aß deposition. In addition, Nor restored the abnormalities of mitochondrial membrane potential, significantly reduced the production of intracellular ROS and neuronal cell apoptosis. Mechanistically, we combined network pharmacology and experimental verification to show that Nor may exert antioxidant stress and anti-apoptotic through the AMPK/GSK3ß/Nrf2 signaling pathway. CONCLUSION: Our data provide some evidence that Nor exerts a neuroprotective effect through the AMPK/GSK3ß/Nrf2 pathway, thereby improving cognitive impairment in AD model mice. Natural products derived from traditional Chinese medicines are becoming increasingly popular in the process of new drug development and discovery, and our findings provide new perspectives for the discovery of improved treatment strategies for AD.


Asunto(s)
Alcaloides , Enfermedad de Alzheimer , Disfunción Cognitiva , Lindera , Extractos Vegetales , Transducción de Señal , Animales , Masculino , Ratones , Ratas , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Apoptosis/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Cognitiva/metabolismo , Modelos Animales de Enfermedad , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Ratones Transgénicos , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Factor 2 Relacionado con NF-E2/metabolismo , Células PC12 , Transducción de Señal/efectos de los fármacos , Lindera/química , Extractos Vegetales/administración & dosificación , Alcaloides/administración & dosificación
10.
Eur J Med Chem ; 272: 116464, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38704940

RESUMEN

Diabetes mellitus is a chronic metabolic disorder characterized by high blood glucose levels, which can cause many diseases, including osteoporosis, fractures, arthritis, and foot complications. The inhibitors of dipeptidyl peptidase-4 (DPP-4), an enzyme involved in glucose metabolism regulation, are essential for managing Type 2 Diabetes Mellitus (T2DM). The inhibition of DPP-4 has become a promising treatment approach for T2DM because it can increase levels of active glucagon-like peptide-1 (GLP-1), leading to improved insulin secretion in response to glucose and reduced release of glucagon. The review commences by elucidating the role of DPP-4 in glucose homeostasis and its significance in T2DM pathophysiology. Furthermore, it presents the mechanism of action, preclinical pharmacodynamics, clinical efficacy, and toxicity profiles of small-molecule DPP-4 inhibitors across various clinical stages. This comprehensive review provides valuable insights into the synthesis and clinical application of DPP-4 inhibitors, serving as an invaluable resource for researchers, clinicians, and pharmaceutical professionals interested in diabetes therapeutics and drug development.


Asunto(s)
Diabetes Mellitus Tipo 2 , Dipeptidil Peptidasa 4 , Inhibidores de la Dipeptidil-Peptidasa IV , Inhibidores de la Dipeptidil-Peptidasa IV/farmacología , Inhibidores de la Dipeptidil-Peptidasa IV/síntesis química , Inhibidores de la Dipeptidil-Peptidasa IV/química , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Dipeptidil Peptidasa 4/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/síntesis química , Hipoglucemiantes/química , Hipoglucemiantes/uso terapéutico , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/síntesis química , Animales , Estructura Molecular , Relación Estructura-Actividad
11.
Front Oncol ; 14: 1372548, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606112

RESUMEN

Introduction: This systematic review and meta-analysis aimed to examine the risk of second primary cancers (SPCs) among retinoblastoma (Rb) patients, both hereditary and nonhereditary. Previous studies have reported on the long-term risk of SPCs in these patient populations, but a comprehensive synthesis of the existing evidence is lacking. Methods: A systematic search was conducted in PubMed, EMBASE, and Cochrane Library from inception to 12 March 2023, supplemented by manual screening. Eligible studies were identified, and data were extracted. The primary outcome measure was the standardized incidence ratios (SIRs) of SPCs in Rb patients. Summary estimates were calculated using random or fixed effects models. The quality of included studies was assessed using the Newcastle-Ottawa Scale. Results: Ten studies, including nine high-quality studies, were included in this review. The summary estimate of SIR for SPCs among hereditary Rb patients was 17.55 (95% CI=13.10-23.51), while the pooled estimate of SIR for SPCs among nonhereditary Rb patients was 1.36 (95% CI=0.90-2.04). Significant differences in SIRs for different SPC types were observed (P=0.028), including nasal cavity tumor (SIR=591.06, 95% CI=162.79-2146.01), bone tumor (SIR=442.91, 95% CI=191.63-1023.68), soft tissue sarcoma (SIR=202.93, 95% CI=114.10-360.93), CNS (SIR=12.84, 95% CI=8.80-18.74), and female breast cancer (SIR=3.68, 95% CI=2.52-5.37). Chemotherapy and radiation therapy were associated with an increased risk of SPCs among hereditary Rb patients. Discussion: The findings of this review indicate that hereditary Rb patients have a significantly elevated risk of developing SPCs, whereas nonhereditary Rb patients do not show the same risk. Furthermore, significant differences were observed in the SIRs of different SPC types. Treatment techniques, specifically chemotherapy and radiation therapy, were associated with an increased risk of SPCs among hereditary Rb patients. These findings highlight the importance of radiation protection for Rb patients and the need for further research and tailored management strategies for this high-risk population.

12.
Molecules ; 29(7)2024 Mar 23.
Artículo en Inglés | MEDLINE | ID: mdl-38611728

RESUMEN

The epidermal growth factor receptor (EGFR) plays a pivotal role in cancer therapeutics, with small-molecule EGFR inhibitors emerging as significant agents in combating this disease. This review explores the synthesis and clinical utilization of EGFR inhibitors, starting with the indispensable role of EGFR in oncogenesis and emphasizing the intricate molecular aspects of the EGFR-signaling pathway. It subsequently provides information on the structural characteristics of representative small-molecule EGFR inhibitors in the clinic. The synthetic methods and associated challenges pertaining to these compounds are thoroughly examined, along with innovative strategies to overcome these obstacles. Furthermore, the review discusses the clinical applications of FDA-approved EGFR inhibitors such as erlotinib, gefitinib, afatinib, and osimertinib across various cancer types and their corresponding clinical outcomes. Additionally, it addresses the emergence of resistance mechanisms and potential counterstrategies. Taken together, this review aims to provide valuable insights for researchers, clinicians, and pharmaceutical scientists interested in comprehending the current landscape of small-molecule EGFR inhibitors.


Asunto(s)
Carcinogénesis , Transformación Celular Neoplásica , Humanos , Afatinib , Receptores ErbB , Clorhidrato de Erlotinib
13.
Materials (Basel) ; 17(8)2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38673080

RESUMEN

The utilization of calcined coal gangue (CCG) and limestone for the preparation of blended cement is an efficient approach to address the issue of coal gangue disposal. However, the compressive strength development of blended cement is slow, particularly at high substitution levels of CCG. Therefore, this study aimed to promote the hydration and mechanical properties of the calcined coal gangue-limestone blended cements by increasing the curing temperature. In this study, the samples were cured at two different temperatures, namely 20 and 40 °C. The four groups of samples contained 15 wt.%, 30 wt.%, 45 wt.% and 60 wt.% cement substitutions using CCG and limestone (2:1 mass ratio). The compressive strength, hydration and microstructure were investigated at the ages of 1 to 28 d. X-ray diffraction (XRD) and thermogravimetry (TG) were used to study the hydration behavior of samples. Mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM) were used to determine the microstructure of the samples. The results indicate that an increase in curing temperature significantly promotes the compressive strength of the calcined coal gangue-limestone blended cements from 1 to 28 d. The microstructural analysis indicates that increasing the curing temperature not only promotes cement hydration but also facilitates the reaction of CCG, which precipitated more hydrates such as C-A-S-H gel, Hc and Mc. These hydrates are conducive to refining the pore structures and densifying the microstructure, which sufficiently explains the enhanced compressive strength of the calcined coal gangue-limestone blended cements.

14.
Nat Prod Res ; : 1-9, 2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38656956

RESUMEN

Two new triterpenoid saponins (oleanolic acid 2ß-hydroxyl-3-O-ß-D-glucuronopyranoside-6'-O-buthyl ester (1) and oleanolic acid 2ß-hydroxyl-3-O-[ß-D-glucuronopyranosyl-6'-O-methylester]-28-O-ß-D-glucopyranoside (2)) and two new goodyerosides (4-methylenefuran-2(5H)-one (6'-O-vanilloyl)-ß-D-glucopyranoside (3), 3-hydroxy-2(5H)-furanone, 4-(6'-O-vanilloyl)-ß-D-glucopyranoside (4)), together with seven known compounds (5-11) were isolated from the whole plant of Tournefortia sibirica L. The chemical structures of the compounds were determined by spectroscopic analysis (1D and 2D NMR) and HR-ESI-MS. Compounds 1, 6 and 9 showed significant cytotoxicity towards A549, SK-Hep1 and HeLa cells, with IC50 values ranging from 1.68 ± 0.09 to 6.87 ± 0.13 µM.

15.
Eur J Med Chem ; 271: 116446, 2024 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-38678824

RESUMEN

The strategic integration of fluorine atoms into anti-infectious agents has become a cornerstone in the field of medicinal chemistry, owing to the unique influence of fluorine on the chemical and biological properties of pharmaceuticals. This review examines the synthetic methodologies that enable the incorporation of fluorine into anti-infectious drugs, and the resultant clinical applications of these fluorine-enriched compounds. With a focus on clinically approved medications, the discussion extends to the molecular mechanisms. It further outlines the specific effects of fluorination, which contribute to the heightened efficacy of anti-infective therapies. By presenting a comprehensive analysis of current drugs and their developmental pathways, this review underscores the continuing evolution and significance of fluorine in advancing anti-infectious treatment options. The insights offered extend valuable guidance for future drug design and the development of next-generation anti-infectious agents.


Asunto(s)
Flúor , Flúor/química , Humanos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/síntesis química , Industria Farmacéutica , Estructura Molecular , Animales
16.
J Colloid Interface Sci ; 665: 702-710, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38552585

RESUMEN

Lithium polysulfide (LiPSs) shuttle effect and difficulties with Li2S oxidation are hinder the marketization of lithium-sulfur batteries. We suggest using a bidirectional catalyst in the sulfur host to solve these problems. We produced a nitrogen-doped cobalt phosphide (N-CoP@NC) as a sulfur carrier in this work. The introduction of nitrogen into cobalt phosphide enhances the electron transmission speed and forms shorter Co-N bonds. As a result, new defect energy levels are introduced, leading to an increase in the charge number of Co central atoms, which abate the Li-S and SS bonds in Li2S and Li2S4, thereby promoting the oxidation of Li2S during charging, as well as the alteration process of LiPSs during charge and discharge. Additionally, the crystal flaws that result in increased Co-S bond formation help to boost polysulfides' adsorption ability. The Li-S batteries shows outstanding cyclability when paired with this electrocatalyst, demonstrating a minimal capacity degradation rate of only 0.07 % per cycle over 500 cycles at a rate of 0.5C. As a result, incorporating anion doping in the host emerges as a promising method for crafting materials tailored for Li-S batteries.

17.
Eur J Med Chem ; 267: 116185, 2024 Mar 05.
Artículo en Inglés | MEDLINE | ID: mdl-38295688

RESUMEN

Type 2 diabetes mellitus (T2DM) is a long-term metabolic disorder characterized by the body's resistance to insulin and inadequate production of insulin. Small molecule drugs to treat T2DM mainly control blood sugar levels by improving insulin sensitivity, increasing insulin secretion, or reducing liver glycogen production. With the deepening of research on the pathogenesis of diabetes, many drugs with new targets and mechanisms of action have been discovered. The targets of the drugs for T2DM are mainly dipeptidyl peptidase IV inhibitors (DPP4), sodium/glucose cotransporter 2 inhibitors (SGLT2), sulfonylurea receptor modulators (SUR), peroxisome proliferator-activated receptor γ agonists (PPARγ), etc. We are of the opinion that acquiring a comprehensive comprehension of the synthetic procedures employed in drug molecule production will serve as a source of inventive and pragmatic inspiration for the advancement of novel, more potent, and feasible synthetic methodologies. This review aims to outline the clinical applications and synthetic routes of some representative drugs to treat T2DM, which will drive the discovery of new, more effective T2DM drugs.


Asunto(s)
Diabetes Mellitus Tipo 2 , Inhibidores de la Dipeptidil-Peptidasa IV , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Hipoglucemiantes/farmacología , Hipoglucemiantes/uso terapéutico , Inhibidores de la Dipeptidil-Peptidasa IV/uso terapéutico , Insulina
18.
Eur J Med Chem ; 265: 116124, 2024 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-38183778

RESUMEN

In 2023, the U.S. Food and Drug Administration (FDA) granted approval to a total of 55 new drugs, comprising 29 new chemical entities (NCEs) and 25 new biological entities (NBEs). These drugs primarily focus on oncology, the central nervous system, anti-infection, hematology, cardiovascular, ophthalmology, immunomodulatory and other therapeutic areas. Out of the 55 drugs, 33 (60 %) underwent an accelerated review process and received approval, while 25 (45 %) were specifically approved for the treatment of rare diseases. The purpose of this review is to provide an overview of the clinical uses and production techniques of 29 newly FDA-approved NCEs in 2023. Our intention is to offer a comprehensive understanding of the synthetic approaches employed in the creation of these drug molecules, with the aim of inspiring the development of novel, efficient, and applicable synthetic methodologies.


Asunto(s)
Aprobación de Drogas , Inmunomodulación , Estados Unidos , United States Food and Drug Administration , Preparaciones Farmacéuticas
19.
Acta Pharmacol Sin ; 45(4): 803-814, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38172305

RESUMEN

Overactivation of the NLRP3 inflammasomes induces production of pro-inflammatory cytokines and drives pathological processes. Pharmacological inhibition of NLRP3 is an explicit strategy for the treatment of inflammatory diseases. Thus far no drug specifically targeting NLRP3 has been approved by the FDA for clinical use. This study was aimed to discover novel NLRP3 inhibitors that could suppress NLRP3-mediated pyroptosis. We screened 95 natural products from our in-house library for their inhibitory activity on IL-1ß secretion in LPS + ATP-challenged BMDMs, found that Britannin exerted the most potent inhibitory effect with an IC50 value of 3.630 µM. We showed that Britannin (1, 5, 10 µM) dose-dependently inhibited secretion of the cleaved Caspase-1 (p20) and the mature IL-1ß, and suppressed NLRP3-mediated pyroptosis in both murine and human macrophages. We demonstrated that Britannin specifically inhibited the activation step of NLRP3 inflammasome in BMDMs via interrupting the assembly step, especially the interaction between NLRP3 and NEK7. We revealed that Britannin directly bound to NLRP3 NACHT domain at Arg335 and Gly271. Moreover, Britannin suppressed NLRP3 activation in an ATPase-independent way, suggesting it as a lead compound for design and development of novel NLRP3 inhibitors. In mouse models of MSU-induced gouty arthritis and LPS-induced acute lung injury (ALI), administration of Britannin (20 mg/kg, i.p.) significantly alleviated NLRP3-mediated inflammation; the therapeutic effects of Britannin were dismissed by NLRP3 knockout. In conclusion, Britannin is an effective natural NLRP3 inhibitor and a potential lead compound for the development of drugs targeting NLRP3.


Asunto(s)
Inflamasomas , Lactonas , Proteína con Dominio Pirina 3 de la Familia NLR , Sesquiterpenos , Animales , Humanos , Ratones , Inflamasomas/agonistas , Interleucina-1beta/metabolismo , Lactonas/farmacología , Lactonas/uso terapéutico , Lipopolisacáridos/farmacología , Macrófagos , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/antagonistas & inhibidores , Sesquiterpenos/farmacología , Sesquiterpenos/uso terapéutico
20.
Technol Health Care ; 32(1): 1-8, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37270822

RESUMEN

BACKGROUND: Juxta-papillary duodenal diverticula (JPDD) are common but are usually asymptomatic, and they are often diagnosed by coincidence. OBJECTIVE: To analyse the anatomy and classification of JPDD and its relationship with biliary and pancreatic disorders, and to explore the diagnostic value of multi-slice spiral computed tomography (MSCT) in patients with JPDD. METHODS: The imaging data of patients with JPDD, which was obtained via abdominal computed tomography examination and confirmed via gastroscopy and/or upper gastrointestinal barium enema, in our hospital from 1 January 2019 to 31 December 2020 were retrospectively analysed. All patients were scanned using MSCT, and the imaging findings, classification and grading were analysed. RESULTS: A total of 119 duodenal diverticula were detected in 96 patients, including 73 single diverticula and 23 multiple diverticula. The imaging findings were mainly cystic lesions of the inner wall of the duodenum protruding to the outside of the cavity. The thin layer showed a narrow neck connected with the duodenal cavity, and the shape and size of the diverticula were different: 67 central-type cases and 29 peripheral-type cases. There were 50 cases of type I, 33 cases of type II, 19 cases of type III and six cases of type IV. Furthermore, there were seven small, 87 medium and 14 large diverticula. The differences in the location and size of the JPDD in MSCT grading were statistically significant (P< 0.05). CONCLUSION: The MSCT method has an important diagnostic value for the classification of JPDD, and MSCT images are helpful in the clinical evaluation of patients with JPDD and the selection of treatment options.


Asunto(s)
Divertículo , Enfermedades Duodenales , Humanos , Estudios Retrospectivos , Enfermedades Duodenales/diagnóstico por imagen , Divertículo/diagnóstico por imagen , Divertículo/patología , Tomografía Computarizada por Rayos X , Tomografía Computarizada Espiral
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