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1.
Commun Chem ; 7(1): 122, 2024 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-38831043

RESUMEN

The cell membrane not only serves as the boundary between the cell's interior and the external environment but also plays a crucial role in regulating fundamental cellular behaviours. Interfacial membranization of membraneless coacervates, formed through liquid-liquid phase separation (LLPS), represents a reliable approach to constructing hierarchical cell-like entities known as protocells. In this study, we demonstrate the capability to modulate the interfacial membrane fluidity and thickness of dextran-bound coacervate protocells by adjusting the molecular weight of dextran or utilizing dextranase-catalyzed hydrolysis. This modulation allows for rational control over colloidal stability, interfacial molecular transport and cell-protocell interactions. Our work opens a new avenue for surface engineering of coacervate protocells, enabling the establishment of cell-mimicking structures and behaviours.

2.
Cells ; 13(9)2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38727300

RESUMEN

Excessive extracellular matrix (ECM) deposition is a defining feature of cardiac fibrosis. Most notably, it is characterized by a significant change in the concentration and volume fraction of collagen I, a disproportionate deposition of collagen subtypes, and a disturbed ECM network arrangement, which directly affect the systolic and diastolic functions of the heart. Immune cells that reside within or infiltrate the myocardium, including macrophages, play important roles in fibroblast activation and consequent ECM remodeling. Through both direct and indirect connections to fibroblasts, monocyte-derived macrophages and resident cardiac macrophages play complex, bidirectional, regulatory roles in cardiac fibrosis. In this review, we discuss emerging interactions between fibroblasts and macrophages in physiology and pathologic conditions, providing insights for future research aimed at targeting macrophages to combat cardiac fibrosis.


Asunto(s)
Fibroblastos , Fibrosis , Macrófagos , Miocardio , Humanos , Macrófagos/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Animales , Miocardio/patología , Miocardio/metabolismo , Matriz Extracelular/metabolismo , Comunicación Celular
3.
World J Clin Cases ; 12(13): 2248-2253, 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38808355

RESUMEN

BACKGROUND: Cardiac arrest (CA) induced by electric shock is a rare occurrence, particularly in cases of prolonged CA. Currently, there is limited literature on similar incidents, and we present a relevant case report. CASE SUMMARY: A 27-year-old Asian male man, experiencing respiratory CA due to electric shock, was successfully restored to sinus rhythm after 50 min of cardiopulmonary resuscitation and 8 electrical defibrillation sessions. In the subsequent stages, the patient received multiple organ function protection measures, leading to a successful recovery and eventual discharge from the hospital. CONCLUSION: Prolonging resuscitation time can enhance the chances of survival for patients, this study provide valuable insights into the management of electric shock-induced CA.

4.
Cell Death Dis ; 15(5): 350, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38773070

RESUMEN

Seipin is one key mediator of lipid metabolism that is highly expressed in adipose tissues as well as in the brain. Lack of Seipin gene, Bscl2, leads to not only severe lipid metabolic disorders but also cognitive impairments and motor disabilities. Myelin, composed mainly of lipids, facilitates nerve transmission and is important for motor coordination and learning. Whether Seipin deficiency-leaded defects in learning and motor coordination is underlined by lipid dysregulation and its consequent myelin abnormalities remains to be elucidated. In the present study, we verified the expression of Seipin in oligodendrocytes (OLs) and their precursors, oligodendrocyte precursor cells (OPCs), and demonstrated that Seipin deficiency compromised OPC differentiation, which led to decreased OL numbers, myelin protein, myelinated fiber proportion and thickness of myelin. Deficiency of Seipin resulted in impaired spatial cognition and motor coordination in mice. Mechanistically, Seipin deficiency suppressed sphingolipid metabolism-related genes in OPCs and caused morphological abnormalities in lipid droplets (LDs), which markedly impeded OPC differentiation. Importantly, rosiglitazone, one agonist of PPAR-gamma, substantially restored phenotypes resulting from Seipin deficiency, such as aberrant LDs, reduced sphingolipids, obstructed OPC differentiation, and neurobehavioral defects. Collectively, the present study elucidated how Seipin deficiency-induced lipid dysregulation leads to neurobehavioral deficits via impairing myelination, which may pave the way for developing novel intervention strategy for treating metabolism-involved neurological disorders.


Asunto(s)
Diferenciación Celular , Disfunción Cognitiva , Subunidades gamma de la Proteína de Unión al GTP , Vaina de Mielina , Células Precursoras de Oligodendrocitos , Animales , Subunidades gamma de la Proteína de Unión al GTP/metabolismo , Subunidades gamma de la Proteína de Unión al GTP/genética , Ratones , Células Precursoras de Oligodendrocitos/metabolismo , Vaina de Mielina/metabolismo , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Disfunción Cognitiva/genética , Metabolismo de los Lípidos , Oligodendroglía/metabolismo , Oligodendroglía/patología , Ratones Endogámicos C57BL , PPAR gamma/metabolismo , PPAR gamma/genética , Ratones Noqueados , Masculino , Rosiglitazona/farmacología
5.
Ther Adv Med Oncol ; 16: 17588359241242613, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38606163

RESUMEN

Background: BRCA2 plays a key role in homologous recombination. However, information regarding its mutations in Chinese patients with breast cancer remains limited. Objectives: This study aimed to assess the clinicopathological characteristics of BRCA2 mutation breast cancer and explore the mutation's effect on hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative breast cancer survival in China. Design: This hospital-based cohort study prospectively included 629 women with breast cancer diagnosed from 2008 to 2023 at Zhejiang Cancer Hospital in China. Methods: We compared the clinicopathological characteristics and metastatic patterns and analysed the invasive disease-free survival (iDFS), distant relapse-free survival (DRFS) and first-line progression-free survival (PFS1) of patients with HR-positive/HER2-negative breast cancer according to BRCA2 mutations. Results: Among the 629 patients, 78 had BRCA2 mutations (12.4%) and 551 did not (87.6%). The mean age at diagnosis was lower in the BRCA2 mutation breast cancer group than in the non-mutation breast cancer group (38.91 versus 41.94 years, p = 0.016). BRCA2 mutation breast cancers were more likely to be lymph node-positive than non-mutation breast cancers (73.0% versus 56.6%, p = 0.037). The pathological grade was higher in 47.1% of BRCA2 mutation breast cancers than in 29.6% of non-mutation breast cancers (p = 0.014). The proportions of patients with BRCA2 mutations who developed contralateral breast cancer (19.2% versus 8.8%, p = 0.004), breast cancer in the family (53.8% versus 38.3%, p = 0.009) and ovarian cancer in the family (7.6% versus 2.4%, p = 0.022) were higher than those of patients without the mutation. The median follow-up time was 92.78 months. Multivariate analysis showed that BRCA2 mutation was not associated with poorer iDFS [hazard ratio = 0.9, 95% confidence interval (CI) = 0.64-1.27, p = 0.56] and poorer distant relapse-free survival (DRFS) (hazard ratio = 1.09, 95% CI = 0.61-1.93, p = 0.76). There was no significant difference between the two groups with regard to metastatic patterns in the advanced disease setting. In the first-line metastatic breast cancer setting, PFS1 expression was broadly similar between the two groups irrespective of chemotherapy or endocrine therapy. Conclusion: HR-positive/HER2-negative breast cancer with BRCA2 mutations differs from those without mutations in clinical behaviour and reflects more aggressive tumour behaviour. Our results indicate that BRCA2 mutations have no significant effect on the survival of Chinese women with HR-positive/HER2-negative breast cancer.

6.
Medicine (Baltimore) ; 103(15): e37770, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38608089

RESUMEN

RATIONALE: Gitelman syndrome (GS), also known as familial hypokalemia and hypomagnesemia, is a rare autosomal recessive inherited disease caused by primary renal desalinization caused by impaired reabsorption of sodium and chloride ions in the distal renal tubules. We report a case of clinical and genetic characteristics of GS accompanied with Graves disease and adrenocorticotrophic hormone (ACTH)-independent adrenocortical adenoma. PATIENT CONCERNS: The patient is a 45 year old female, was admitted to our hospital, due to a left adrenal gland occupying lesion as the chief complaint. DIAGNOSIS: The patient was finally diagnosed as GS with Graves disease and adrenocortical adenoma. INTERVENTIONS: Potassium magnesium aspartate (1788 mg/d, taken orally 3 times a day (supplement a few times a day, intake method, treatment duration). Contains 217.2 mg of potassium and 70.8 mg of magnesium, and potassium chloride (4.5 g/d, taken orally 3 times a day (supplement a few times a day, intake method, and treatment duration); Potassium 2356 mg), spironolactone (20 mg/d, taken orally once a day (supplement a few times a day, intake method, treatment duration). After 3 months of treatment, the patient's blood potassium fluctuated between 3.3-3.6 mmol/L, and blood magnesium fluctuated between 0.5-0.7 mmol/L, indicating a relief of fatigue symptoms. OUTCOMES: On the day 6 of hospitalization, the symptoms of dizziness, limb fatigue, fatigue and pain were completely relieved on patient. In the follow-up of the following year, no recurrence of the condition was found. LESSONS: The novel c.1444-10(IVS11)G > A variation may be a splicing mutation. The compound heterozygous mutations of the SLC12A3 gene may be the pathogenic cause of this GS pedigree.


Asunto(s)
Adenoma Corticosuprarrenal , Síndrome de Gitelman , Enfermedad de Graves , Femenino , Humanos , Persona de Mediana Edad , Síndrome de Gitelman/complicaciones , Síndrome de Gitelman/diagnóstico , Síndrome de Gitelman/genética , Magnesio , Enfermedad de Graves/complicaciones , Enfermedad de Graves/genética , Fatiga , Potasio , Miembro 3 de la Familia de Transportadores de Soluto 12
7.
J Mol Model ; 30(5): 135, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627284

RESUMEN

CONTEXT: Based on first principles, the structure, elasticity, mechanics, electronics, and optical properties of cubic K2Pb2O3 were studied. The structural parameters calculated by this method are close to the previous theoretical results. The elastic constant, bulk modulus, shear modulus, Young's modulus, Poisson's ratio, and mechanical stability are studied, and it is shown that cubic K2Pb2O3 is mechanically stable, isotropic, and brittleness. The electrical conductivity and chemical bonding of cubic K2Pb2O3 were analyzed based on the calculated band structure, density of states (DOS), and bond populations. The dispersion of optical functions, including the dielectric function, refractive index, extinction coefficient, reflectivity, absorption coefficient, and loss function, is displayed and analyzed. METHODS: All computations have been carried out based on density functional theory (DFT) as implemented in the CASTEP code. The norm conservation pseudopotential method is used to exchange correlation functionals within the generalized gradient approximation (GGA).

8.
Environ Sci Pollut Res Int ; 31(16): 24619-24633, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38446295

RESUMEN

Much research demonstrates the positive effects of financial inclusion and digital finance on expansion. Supply chains that can be relied upon are essential to national productivity and economic development. This study uses panel data from 2007 to 2022 covering 27 provinces in China to study the results of widespread access to digital financial services and supply chain management on regional economic growth using the instrumental variable approach (fixed effect model). In contrast to earlier research, this study employs an alternative measure of access to digital financial services utilization and digitalization. The data demonstrates that digital financial inclusion and supply chain management have a major impact on the development of the provincial economies in China. Based on the results of this research, we suggest increasing digital financial inclusion and bolstering human capital development to stimulate economic expansion. This essay makes a theoretical advancement in studying digital technology's widespread adoption of financial services by providing a comprehensive critical review and a fresh angle on the nuts and bolts of digital money and universal banking. Boosting institutional quality and governance are two more paths that authorities can take to stimulate economic expansion in the China area, and the results show how important these measures are for achieving this goal.


Asunto(s)
Desarrollo Económico , Instituciones de Salud , Humanos , China
9.
Cancer Cell Int ; 24(1): 114, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38528618

RESUMEN

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of digestive system tumor related death in the world. Unfortunately, effective chemopreventive agent is lack for patients with ESCC in clinical practice, which leads to the extremely high mortality rate. METHODS: A library of prescribed drugs was screened for finding critical anti-tumor properties in ESCC cells. The phosphoproteomics, kinase array, pulldown assay and drug affinity responsive target stabilization assay (DARTS) were applied to explore mechanisms and searched for synergistic targets. Established models of PDX in mice were used to determine the therapeutic effect of domperidone. RESULTS: After screening a library of prescribed drugs, we discovered that domperidone has anti-tumor properties. Domperidone, acting as a gastroprokinetic agent, has been widely used in clinic for gastrointestinal motility disorders. Despite limited research, there are indications that domperidone may have anti-tumor properties. In this study, we determined that domperidone significantly inhibited ESCC proliferation in vitro and in vivo. We employed phosphoproteomics to reveal p-ERK, and p-SMAD3 down-regulation upon domperidone treatment. Then, the results of kinase assay and pulldown assay further validated that domperidone directly combined with MEK1/2 and CDK4, leading to the inhibition of their kinase activity. Furthermore, our results revealed that MEK/ERK and CDK4/SMAD3 signal pathway were major pathways in domperidone against ESCC. CONCLUSION: Collectively, these findings suggest that domperidone serves as an effective "multi-target" inhibitor of MEK1/2 and CDK4, offering potential benefits for the chemoprevention of ESCC.

10.
Discov Med ; 36(182): 527-537, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38531793

RESUMEN

BACKGROUND: The clinical outcomes of chemotherapy (CT) for the treatment of metastatic triple-negative (TN) and hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) have proven to be disappointing. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway, a tumor-promoting signaling cascade frequently mutated in breast cancer (BC), has been implicated in chemoresistance. In this study, our objective is to investigate the efficacy and safety of combining everolimus with chemotherapy in mBC patients exhibiting mutations in the PI3K/AKT/mTOR pathway. METHODS: We conducted a retrospective analysis to characterize the efficacy, safety, and their association with clinical and molecular characteristics of metastatic lesions in 14 patients with HER2- mBC. These patients harbored at least one altered member of the PI3K/AKT/mTOR signaling pathway and were treated with a combination of a chemotherapy agent and the mTOR inhibitor everolimus (CT+EVE). RESULTS: The majority of patients belonged to the triple-negative (TN) subtype (9/14, 64.3%), having already undergone 2 lines of chemotherapy (CT) in the metastatic setting (11, 78.6%). These patients carried altered phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and were administered a vinorelbine-containing regimen (10, 71.4%). The objective response rate (ORR) was 42.9%, with a disease control rate of 92.9%. The median progression-free survival (PFS) and overall survival (OS) were 5.9 (95% confidence interval (CI): 4.9-13.6) months and 14.3 (95% CI: 8.5-not reached (NR)) months, respectively. Patients with fewer prior treatment lines tended to exhibit longer PFS. OS, PFS, and ORR were comparable between hormone receptor-positive (HR+) and triple-negative breast cancer (TNBC) patients, but numerical improvements were noted in patients with a single PI3K pathway alteration compared to those with more than one alteration. Genomic alterations that surfaced upon progression on CT+EVE included cyclin dependent kinase 4 (CDK4) and epidermal growth factor receptor (EGFR) amplification, as well as neurofibromin 1 (NF1) mutation, suggesting potential mechanisms of acquired resistance. An analysis of adverse events indicated manageable toxicities. CONCLUSIONS: The findings of this study suggest both activity and safety for the combination of chemotherapy and the mTOR inhibitor everolimus (CT+EVE) in patients with HER2- mBC who have alterations in the PI3K pathway, particularly those who have received fewer prior chemotherapy. However, it is crucial to note that large-scale, randomized control studies are warranted to more comprehensively characterize the efficacy and safety of this combination therapy.


Asunto(s)
Neoplasias de la Mama , Everolimus , Humanos , Femenino , Everolimus/uso terapéutico , Neoplasias de la Mama/patología , Proteínas Proto-Oncogénicas c-akt/uso terapéutico , Fosfatidilinositol 3-Quinasas , Estudios Retrospectivos , Receptor ErbB-2/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Serina-Treonina Quinasas TOR
11.
Small Methods ; : e2301724, 2024 Mar 26.
Artículo en Francés | MEDLINE | ID: mdl-38530063

RESUMEN

Liquid-liquid phase separation (LLPS) is responsible for the emergence of intracellular membrane-less organelles and the development of coacervate protocells. Benefitting from the advantages of simplicity, precision, programmability, and noninvasiveness, light has become an effective tool to regulate the assembly dynamics of LLPS, and mediate various biochemical processes associated with LLPS. In this review, recent advances in optically controlling membrane-less organelles within living organisms are summarized, thereby modulating a series of biological processes including irreversible protein aggregation pathologies, transcription activation, metabolic flux, genomic rearrangements, and enzymatic reactions. Among these, the intracellular systems (i.e., optoDroplet, Corelet, PixELL, CasDrop, and other optogenetic systems) that enable the photo-mediated control over biomolecular condensation are highlighted. The design of photoactive complex coacervate protocells in laboratory settings by utilizing photochromic molecules such as azobenzene and diarylethene is further discussed. This review is expected to provide in-depth insights into phase separation-associated biochemical processes, bio-metabolism, and diseases.

12.
J Appl Microbiol ; 135(5)2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38544327

RESUMEN

AIMS: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections poses a significant threat to human health, necessitating urgent development of new antimicrobial agents. Silver nanoparticles (AgNPs), which are among the most widely used engineered nanomaterials, have been extensively studied. However, the impact of AgNPs on CRKP and the potential for drug resistance development remain inadequately explored. METHODS AND RESULTS: In this study, broth dilution method was used to determine the minimum inhibitory concentration (MIC) was determined using the broth dilution method. Results indicated MIC values of 93.1 ± 193.3 µg ml-1 for AgNPs, 2.3 ± 5.1 µg ml-1 for AgNO3, and 25.1 ± 48.3 µg ml-1 for imipenem (IMI). The combined inhibitory effect of AgNPs and IMI on CRKP was assessed using the checkerboard method. Moreover, after 6-20 generations of continuous culture, the MIC value of AgNPs increased 2-fold. Compared to IMI, resistance of Kl. pneumoniae to AgNPs developed more slowly, with a higher fold increase in MIC observed after 20 generations. Whole-genome sequencing revealed four nonsynonymous single nucleotide polymorphism mutations in CRKP after 20 generations of AgNP treatment. CONCLUSION: We have demonstrated that AgNPs significantly inhibit CRKP isolates and enhance the antibacterial activity of imipenem against Kl. pneumoniae. Although the development of AgNP resistance is gradual, continued efforts are necessary for monitoring and studying the mechanisms of AgNP resistance.


Asunto(s)
Antibacterianos , Carbapenémicos , Imipenem , Klebsiella pneumoniae , Nanopartículas del Metal , Pruebas de Sensibilidad Microbiana , Plata , Imipenem/farmacología , Klebsiella pneumoniae/efectos de los fármacos , Klebsiella pneumoniae/genética , Plata/farmacología , Antibacterianos/farmacología , Carbapenémicos/farmacología , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/tratamiento farmacológico , Humanos , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/genética , Farmacorresistencia Bacteriana/genética
13.
J Org Chem ; 89(6): 4176-4184, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38436198

RESUMEN

A simple and efficient visible-light-promoted selenylation/cyclization of o-alkynyl benzylazides/o-propargyl arylazides have been realized for the practical synthesis of seleno-substituted isoquinolines and quinolines. This strategy provides the synthesis of valuable seleno-substituted isoquinoline and quinoline derivatives via the construction of one C(sp2)-Se bond and one C-N bond within one process.

14.
J Med Chem ; 67(5): 3860-3873, 2024 Mar 14.
Artículo en Inglés | MEDLINE | ID: mdl-38407934

RESUMEN

Unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs) are widely applied for surgical procedures and extracorporeal therapies, which, however, suffer bleeding risk. Protamine, the only clinically approved antidote, can completely neutralize UFH, but only partially neutralizes LMWHs, and also has a number of safety drawbacks. Here, we show that caltrop-like multicationic small molecules can completely neutralize both UFH and LMWHs. In vitro and ex vivo assays with plasma and whole blood and in vivo assays with mice and rats support that the lead compound is not only superior to protamine by displaying higher neutralization activity and broader therapeutic windows but also biocompatible. The effective neutralization dose and the maximum tolerated dose of the lead compound are determined to be 0.4 and 25 mg/kg in mice, respectively, suggesting good promise for further preclinical studies.


Asunto(s)
Heparina de Bajo-Peso-Molecular , Heparina , Ratas , Ratones , Animales , Heparina/uso terapéutico , Heparina de Bajo-Peso-Molecular/farmacología , Heparina de Bajo-Peso-Molecular/uso terapéutico , Antídotos/farmacología , Antídotos/uso terapéutico , Protaminas/farmacología , Bioensayo , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico
15.
Zhongguo Zhong Yao Za Zhi ; 49(2): 453-460, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38403321

RESUMEN

This study aimed to investigate the therapeutic effects of Morinda officinalis iridoid glycosides(MOIG) on paw edema and bone loss of rheumatoid arthritis(RA) rats, and analyze its potential mechanism based on ultra-high performance liguid chromatography-guadrupole time-of-flight tandem mass spectrometry(UPLC-Q-TOF-MS) serum metabolomics. RA rats were established by injecting bovin type Ⅱ collagen. The collagen-induced arthritis(CIA) rats were administered drug by gavage for 8 weeks, the arthritic score were used to evaluate the severity of paw edem, serum bone metabolism biochemical parameters were measured by ELISA kits, Masson staining was used to observe the bone microstructure of the femur in CIA rats. UPLC-Q-TOF-MS was used to analyze the alteration of serum metabolite of CIA rats, principal component analysis(PCA) and partial least squares-discriminant analysis(PLS-DA) were used to screen the potential biomarkers, KEGG database analysis were used to construct related metabolic pathways. The results demonstrated that the arthritic score, serum levels of IL-6 and parameters related with bone metabolism including OCN, CTX-Ⅰ, DPD and TRAP were significantly increased, and the ratio of OPG and RANKL was significantly decreased, the microstructure of bone tissue and cartilage were destructed in CIA rats, while MOIG treatments could significantly reduce arthritis score, mitigate the paw edema, reverse the changes of serum biochemical indicators related with bone metabolism, and improve the microstructure of bone tissue and cartilage of CIA rats. The non-targeted metabolomics results showed that 24 altered metabolites were identified in serum of CIA rats; compared with normal group, 13 significantly altered metabolites related to RA were identified in serum of CIA rats, mainly involving alanine, aspartate and glutamate metabolism; compared with CIA model group, MOIG treatment reversed the alteration of 15 differential metabolites, mainly involving into alanine, aspartate and glutamate metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism, valine, leucine and isoleucine biosynthesis. Therefore, MOIG significantly alleviated paw edema, improved the destruction of microstructure of bone and cartilage in CIA rats maybe through involving into the regulation of amino acid metabolism.


Asunto(s)
Artritis Reumatoide , Morinda , Ratas , Animales , Glicósidos Iridoides/química , Morinda/química , Cromatografía Líquida de Alta Presión , Ácido Aspártico , Metabolómica , Artritis Reumatoide/tratamiento farmacológico , Edema , Alanina/uso terapéutico , Glutamatos/uso terapéutico , Biomarcadores
16.
Nat Commun ; 15(1): 698, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38267435

RESUMEN

Creating different pore environments within a covalent organic framework (COF) will lead to useful multicompartment structure and multiple functions, which however has been scarcely achieved. Herein we report designed synthesis of three two-dimensional COFs with amphiphilic porosity by steric-hindrance-mediated precision hydrophilic-hydrophobic microphase separation. Dictated by the different steric effect of the substituents introduced to a monomer, dual-pore COFs with kgm net, in which all hydroxyls locate in trigonal micropores while hydrophobic sidechains exclusively distribute in hexagonal mesopores, have been constructed to form completely separated hydrophilic and hydrophobic nanochannels. The unique amphiphilic channels in the COFs enable the formation of Janus membranes via interface growth. This work has realized the creation of two types of channels with opposite properties in one COF, demonstrating the feasibility of introducing different properties/functions into different pores of heteropore COFs, which can be a useful strategy to develop multifunctional materials.

17.
Int J Biol Macromol ; 259(Pt 1): 129002, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38176501

RESUMEN

Tumor cell-targeting molecules play a vital role in cancer diagnosis, targeted therapy, and biomarker discovery. Aptamers are emerging as novel targeting molecules with unique advantages in cancer research. In this work, we have developed several DNA aptamers through cell-based systematic evolution of ligands by exponential enrichment (Cell-SELEX). The selected SYL-6 aptamer can bind to a variety of cancer cells with high signal. Tumor tissue imaging demonstrated that SYL-6-Cy5 fluorescent probe was able to recognize multiple clinical tumor tissues but not the normal tissues, which indicates great potential of SYL-6 for clinical tumor diagnosis. Meanwhile, we identified prohibitin 2 (PHB2) as the molecular target of SYL-6 using mass spectrometry, pull-down and RNA interference assays. Moreover, SYL-6 can be used as a delivery vehicle to carry with doxorubicin (Dox) chemotherapeutic agents for antitumor targeted chemotherapy. The constructed SYL-6-Dox can not only selectively kill tumor cells in vitro, but also inhibit tumor growth with reduced side effects in vivo. This work may provide a general tumor cell-targeting molecule and a potential biomarker for cancer diagnosis and targeted therapy.


Asunto(s)
Aptámeros de Nucleótidos , Neoplasias , Humanos , Aptámeros de Nucleótidos/metabolismo , Prohibitinas , Doxorrubicina/farmacología , Neoplasias/tratamiento farmacológico , Biomarcadores , Técnica SELEX de Producción de Aptámeros/métodos , Línea Celular Tumoral
18.
J Med Chem ; 67(3): 2176-2187, 2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38284525

RESUMEN

Long-acting neuromuscular blocks followed by rapid reversal may provide prolonged surgeries with improved conditions by omitting repetitive or continuous administration of the neuromuscular blocking agent (NMBA), eliminating residual neuromuscular block and minimizing postoperative recovery, which, however, is not clinically available. Here, we demonstrate that imidazolium-based macrocycles (IMCs) and acyclic cucurbit[n]urils (ACBs) can form such partners by functioning as long-acting NMBAs and rapid reversal agents through a pseudo[2]catenation mechanism based on stable complexation with Ka values of over 109 M-1. In vivo experiments with rats reveal that, at the dose of 2- and 3-fold ED90, one IMC attains a duration of action corresponding to 158 or 442 min for human adults, covering most of prolonged surgeries. The block can be reversed by one ACB with recovery time significantly shorter than that achieved by sugammadex for reversing the block of rocuronium, the clinically most widely used intermediate-acting NMBA.


Asunto(s)
Catenanos , Bloqueo Neuromuscular , gamma-Ciclodextrinas , Adulto , Humanos , Animales , Ratas , Sugammadex/farmacología , Rocuronio
19.
Chem Asian J ; 19(6): e202301103, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38288641

RESUMEN

The development of effective and stable non-precious catalysts for hydrogenation of ester to diols remains a challenge. Herein, the catalytic hydrogenation of ethyl lactate (EL) to 1,2-propanediol (1,2-PDO) with supported Co catalysts derived from layered double hydroxides (LDHs) is investigated. Catalytic tests reveal that LDH-derived Co catalysts exhibit the best catalytic performance with 98 % of EL conversion and >99 % of 1,2-PDO selectivity at mild conditions, compared with other Co catalysts (supported on Al2O3, and TiO2) and LDH-derived Cu catalysts. Due to the strong interaction among Co and Al matrix, the main composition is metallic Co0 and CoO after reduction at 600 °C. Besides, the catalyst shows good recyclability in the liquid phase hydrogenation. The superior catalytic performance can be attributed to the synergistic effect between Co0 and CoO, in which H2 molecule is activated on Co0 and EL is strongly adsorbed on CoO via hydroxyl groups.

20.
Lab Chip ; 24(4): 776-786, 2024 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-38197467

RESUMEN

Thread-based microfluidic colorimetric sensors have been deemed a potential tool that may be incorporated into textiles for non-invasive sweat analysis. Nevertheless, their poor performance significantly limits their practical uses in sweat glucose detection down to 20 µM. Herein, a microfluidic glucose sensing device containing a salt-responsive thread is developed for the highly sensitive detection of glucose in human sweat. By grafting a zwitterionic polymer brush-which could react to ionic strength by changing the conformation of the polymer chains from the collapsing state to the stretching state-onto the cotton thread, the salt-responsive thread was created. Compared to the pristine cotton thread, the modified thread has better ion-capture capabilities, a more noticeable swelling effect, and a higher ability to absorb water. These enable a significant enrichment of glucose when the saline solution passes through it. The salt-responsive thread was employed to construct a thread/paper-based microfluidic sensing device for the monitoring of glucose in artificial sweat, exhibiting a sensitivity of -0.255 µM-1 and a detection limit of 14.7 µM. In comparison to the pristine cotton thread-based device, the performance is significantly superior. Using a hydrophobic fabric and salt-responsive threads, a glucose-sensing headband was prepared for on-body sweat glucose monitoring. With the use of a smartphone-based image analysis system, the headband can detect the concentration of glucose in a volunteer's perspiration. Using the thread-based salt-responsive zwitterionic polymer brush might offer a novel approach to creating wearable sweat sensors with extremely high sensitivity.


Asunto(s)
Técnicas Biosensibles , Sudor , Humanos , Sudor/química , Microfluídica , Automonitorización de la Glucosa Sanguínea , Glucemia/análisis , Glucosa/análisis , Polímeros
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