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1.
J Control Release ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38641021

RESUMO

The bioaerogel microparticles have been recently developed for respiratory drug delivery and attract fast increasing interests. These highly porous microparticles have ultralow density and hence possess much reduced aerodynamic diameter, which favour them with greatly enhanced dispersibility and improved aerosolisation behaviour. The adjustable particle geometric dimensions by varying preparation methods and controlling operation parameters make it possible to fabricate bioaerogel microparticles with accurate sizes for efficient delivery to the targeted regions of respiratory tract (i.e. intranasal and pulmonary). Additionally, the technical process can provide bioaerogel microparticles with the opportunities of accommodating polar, weak polar and non-polar drugs at sufficient amount to satisfy clinical needs, and the adsorbed drugs are primarily in the amorphous form that potentially can facilitate drug dissolution and improve bioavailability. Finally, the nature of biopolymers can further offer additional advantageous characteristics of improved mucoadhesion, sustained drug release and subsequently elongated time for continuous treatment on-site. These fascinating features strongly support bioaerogel microparticles to become a novel platform for effective delivery of a wide range of drugs to the targeted respiratory regions, with increased drug residence time on-site, sustained drug release, constant treatment for local and systemic diseases and anticipated better-quality of therapeutic effects.

2.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(2): 433-440, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38645856

RESUMO

Objective: Port-wine stains are a kind of dermatological disease of congenital capillary malformation. Based on the biological characteristics of port-wine stains and the advantages of microneedle transdermal administration, we intend to construct a nanodrug co-loaded with rapamycin (RPM), an anti-angiogenesis drug, and photochlor (HPPH), a photosensitizer, and integrate the nanodrug with dissolvable microneedles (MN) to achieve anti-angiogenesis and photodynamic combination therapy for port-wine stains. Methods: First, RPM and HPPH co-loaded nanoparticles (RPM-HPPH NP) were prepared by the emulsification solvent-volatilization method, and its ability to generate reactive oxygen species (ROS) was investigated under 660 nm laser irradiation. Mouse hemangioendothelioma endothelial cells (EOMA) were used as the subjects of the study. The cellular uptake behaviors were examined by fluorescence microscopy and flow cytometry. The cytotoxicity effects of RPM-HPPH NP with or without 660 nm laser irradiation on EOMA cells were examined by MTT assays (with free RPM serving as the control). Then, hyaluronic acid (HA) dissolvable microneedles loaded with RPM-HPPH NP (RPM-HPPH NP@HA MN) were obtained by compounding the nanodrug with HA dissolvable microneedle system through the molding method. The morphological characteristics and mechanical properties of RPM-HPPH NP@HA MN were investigated by scanning electron microscope and electronic universal testing machine. The penetration ability of RPM-HPPH NP@HA MN on the skin of nude mice was evaluated by trypan blue staining and H&E staining experiment. Results: The RPM-HPPH NP prepared in the study had a particle size of 150 nm and generated large amounts of ROS under laser irradiation. At the cellular level, RPM-HPPH NP was taken up by EOMA cells in a time-dependent manner. The cytotoxicity of RPM-HPPH NP was higher than that of free RPM with or without laser irradiation. Under laser irradiation, RPM-HPPH NP exhibited stronger cytotoxic effects and the difference was statistically significant (P<0.05). The height of the needle tip of RPM-HPPH NP@HA MN was 600 µm and the mechanical property of a single needle was 0.75048 N. Trypan blue staining and HE staining showed that pressing on the microneedles could produce pores on the skin surface and penetration of the stratum corneum. Conclusion: RPM-HPPH NP@HA MN can deliver RPM-HPPH NP percutaneously to the lesion tissue and realize the synergistic treatment of port-wine stains with anti-angiogenic therapy and photodynamic therapy, providing a new strategy for the construction of nanodrug-loaded microneedle delivery system and the clinical treatment of port-wine stains.


Assuntos
Nanopartículas , Agulhas , Mancha Vinho do Porto , Sirolimo , Animais , Camundongos , Nanopartículas/química , Mancha Vinho do Porto/tratamento farmacológico , Sirolimo/administração & dosagem , Fármacos Fotossensibilizantes/administração & dosagem , Administração Cutânea , Fotoquimioterapia/métodos , Espécies Reativas de Oxigênio/metabolismo , Células Endoteliais/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Inibidores da Angiogênese/administração & dosagem , Hemangioendotelioma/tratamento farmacológico
3.
bioRxiv ; 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38529501

RESUMO

Inducible pluripotent stem cells (iPSCs) derived from patient samples have significantly enhanced our ability to model neurological diseases. Comparative studies of dopaminergic (DA) neurons differentiated from iPSCs derived from siblings with Gaucher disease discordant for parkinsonism provides a valuable avenue to explore genetic modifiers contributing to GBA1-associated parkinsonism in disease-relevant cells. However, such studies are often complicated by the inherent heterogeneity in differentiation efficiency among iPSC lines derived from different individuals. To address this technical challenge, we devised a selection strategy to enrich dopaminergic (DA) neurons expressing tyrosine hydroxylase (TH). A neomycin resistance gene (neo) was inserted at the C-terminus of the TH gene following a T2A self-cleavage peptide, placing its expression under the control of the TH promoter. This allows for TH+ DA neuron enrichment through geneticin selection. This method enabled us to generate comparable, high-purity DA neuron cultures from iPSC lines derived from three sisters that we followed for over a decade: one sibling is a healthy individual, and the other two have Gaucher disease (GD) with GBA1 genotype N370S/c.203delC+R257X (p.N409S/c.203delC+p.R296X). Notably, the younger sister with GD later developed Parkinson disease (PD). A comprehensive analysis of these high-purity DA neurons revealed that although GD DA neurons exhibited decreased levels of glucocerebrosidase (GCase), there was no substantial difference in GCase protein levels or lipid substrate accumulation between DA neurons from the GD and GD/PD sisters, suggesting that the PD discordance is related to of other genetic modifiers.

4.
J Pharm Biomed Anal ; 243: 116064, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38492509

RESUMO

To analyze the metabolites (blood, urine and feces) in normal rats after intragastric administration of the decoction of Phellodendri Amurensis Cortex (PAC) and to map the metabolic profile of PAC in vivo of rat; meanwhile, to evaluate the anti-rheumatoid arthritis (RA) effect of PAC by blood metabolomics technique and to explore its mechanism. Performing on UPLC-Q-TOF-MS technology with a Waters ACQUITY UPLC BEH-C18 column (100 mm × 2.1 mm, 1.7 µm), the mobile phase was acetonitrile-0.1% formic acid aqueous solution (gradient elution). Prior to and following the administration of the decoction of PAC, the samples of blood, urine, and fecal were collected from the rats, in the positive ion mode, pharmacogenic metabolites in each biological sample were identified according to the accurate mass, fragment ions, retention time, metabolic reaction type, comparison of reference substance and retrieval of Pub Med database; The adjuvant-type arthritis (AA) rat model was established, and blood metabonomics method was used to study the improvement effect of rheumatoid arthritis after drug intervention with PAC, and its mechanism was preliminarily explored through analysis of metabolic pathway. A total of 72 exogenous components were identified, including 17 prototype components and 55 metabolites; 14 biomarkers were screened by blood metabolomics techniques combined with multivariate statistical analysis, and PAC significantly improved symptoms of rheumatoid arthritis in rats, and the metabolic pathway analysis mainly involves 5 metabolic pathways. The components in the aqueous decoction of PAC mainly undergo phase I metabolic reactions in rats, such as oxidation, reduction, dehydrogenation, demethylation, and phase II metabolic reactions, such as acetylation, glucuronidation, methylation; PAC has anti-rheumatoid arthritis effects, and its mechanism of action may be related to biosynthesis of aminoacyl-tRNA, metabolism of phenylalanine, metabolism of tryptophan, degradation of valine, leucine and isoleucine and biosynthesis of pantothenic acid and coenzyme A, providing a scientific basis for the study of the pharmacodynamic substances and the action mechanism of PAC against RA.


Assuntos
Artrite Reumatoide , Medicamentos de Ervas Chinesas , Phellodendron , Ratos , Animais , Phellodendron/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Metaboloma , Artrite Reumatoide/tratamento farmacológico
5.
In Vitro Cell Dev Biol Anim ; 60(3): 287-299, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38485818

RESUMO

The study aimed to investigate the effect of ginsenoside Rg1 on intervertebral disc degeneration (IVDD) in rats and IL-1ß-induced nucleus pulposus (NP) cells, and explore its underlying mechanism. Forty IVDD rat models were divided into the IVDD group, low-dose (L-Rg1) group (intraperitoneal injection of 20 mg/kg/d ginsenoside Rg1), medium-dose (M-Rg1) group (intraperitoneal injection of 40 mg/kg/d ginsenoside Rg1), and high-dose (H-Rg1) group (intraperitoneal injection of 80 mg/kg/d ginsenoside Rg1). The pathological change was observed by HE and safranin O-fast green staining. The expression of IL-1ß, IL-6, TNF-α, MMP3, aggrecan, and collagen II was detected. The expression of NF-κB p65 in IVD tissues was detected. Rat NP cells were induced by IL-1ß to simulate IVDD environment and divided into the control group, IL-1ß group, and 20, 50, and 100 µmol/L Rg1 groups. The cell proliferation activity, the apoptosis, and the expression of IL-6, TNF-α, MMP3, aggrecan, collagen II, and NF-κB pathway-related protein were detected. In IVDD rats, ginsenoside Rg1 improved the pathology of IVD tissues; suppressed the expression of IL-1ß, IL-6, TNF-α, aggrecan, and collagen II; and inhibited the expression of p-p65/p65 and nuclear translocation of p65, to alleviate the IVDD progression. In the IL-1ß-induced NP cells, ginsenoside Rg1 also improved the cell proliferation and inhibited the apoptosis and the expression of IL-6, TNF-α, aggrecan, collagen II, p-p65/p65, and IκK in a dose-dependent manner. Ginsenoside Rg1 alleviated IVDD in rats and inhibited apoptosis, inflammatory response, and ECM degradation in IL-1ß-induced NP cells. And Rg1 may exert its effect via inhibiting the activation of NF-κB signaling pathway.


Assuntos
Ginsenosídeos , Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Doenças dos Roedores , Ratos , Animais , NF-kappa B/metabolismo , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Metaloproteinase 3 da Matriz/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-6/metabolismo , Agrecanas/genética , Transdução de Sinais , Colágeno/farmacologia , Inflamação/patologia , Apoptose , Disco Intervertebral/metabolismo , Disco Intervertebral/patologia , Doenças dos Roedores/metabolismo , Doenças dos Roedores/patologia
6.
ACS Biomater Sci Eng ; 10(4): 1921-1945, 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457377

RESUMO

The development of static hydrogels as an optimal choice for bone tissue engineering (BTE) remains a difficult challenge primarily due to the intricate nature of bone healing processes, continuous physiological functions, and pathological changes. Hence, there is an urgent need to exploit smart hydrogels with programmable properties that can effectively enhance bone regeneration. Increasing evidence suggests that photoresponsive hydrogels are promising bioscaffolds for BTE due to their advantages such as controlled drug release, cell fate modulation, and the photothermal effect. Here, we review the current advances in photoresponsive hydrogels. The mechanism of photoresponsiveness and its advanced applications in bone repair are also elucidated. Future research would focus on the development of more efficient, safer, and smarter photoresponsive hydrogels for BTE. This review is aimed at offering comprehensive guidance on the trends of photoresponsive hydrogels and shedding light on their potential clinical application in BTE.


Assuntos
Hidrogéis , Engenharia Tecidual , Hidrogéis/uso terapêutico , Osso e Ossos , Regeneração Óssea , Cicatrização
7.
J Intern Med ; 295(5): 620-633, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38343089

RESUMO

BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in haemodialysis (HD) patients and is associated with an increased risk of death. Roxadustat and recombinant human erythropoietin (rHuEPO, abbreviated as EPO) are the main treatment strategies for renal anaemia in HD patients, but it has not been clear whether there is a difference in their effect on LVH. METHODS: In this multi-centre, prospective, randomized trial of 12-month duration, study participants were randomized in a 1:1 ratio to the roxadustat group or the EPO group. The doses of both treatment regimens were adjusted so that the patients had a haemoglobin level of 10.0-12.0 g per dL. The primary study endpoint was the change from baseline to 12 months in the left ventricular mass index (LVMI, g/m2) measured by echocardiography. RESULTS: In total, 114 patients were enrolled. The mean age was 50 years, and the median dialysis duration was 33 months. Sixty-one patients were men, and 24 were diabetic. LVMI decreased from 116.18 ± 27.84 to 110.70 ± 25.74 g/m2 in the roxadustat group. However, it increased from 109.35 ± 23.41 to 114.99 ± 28.46 g/m2 in the EPO group, with a significant difference in the change in LVMI between the two groups [-5.48 (-11.60 to 0.65) vs. 5.65 (0.74 to 10.55), p < 0.05]. Changes in left ventricular mass, end-diastolic volume and 6-min walk test seemed superior in the roxadustat group. There were no significant differences in other cardiac geometry, biochemical parameters and major adverse cardiovascular events between the two groups. CONCLUSIONS: Compared to EPO, roxadustat is more helpful in the regression of LVH in HD patients.


Assuntos
Anemia , Eritropoetina , Falência Renal Crônica , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Estudos Prospectivos , Diálise Renal/efeitos adversos , Anemia/etiologia , Anemia/complicações , Eritropoetina/uso terapêutico , Hipertrofia Ventricular Esquerda/tratamento farmacológico , Hipertrofia Ventricular Esquerda/etiologia , Falência Renal Crônica/complicações , Falência Renal Crônica/terapia
8.
J Mater Chem B ; 12(9): 2354-2363, 2024 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-38344940

RESUMO

Hematopoietic stem cell (HSC) expansion offers a key strategy to address the source limitation and donor shortages of HSCs for the treatment of various blood disorders. Specific remodeling of the complex bone marrow microenvironment that contributes to efficient in vitro expansion of HSCs remains challenging. Here, inspired by the regions with different stiffness levels in the bone marrow niche, a three dimensional (3D) bone marrow-mimicking composite scaffold created based on gelatin-hyaluronic acid (Gel-HA) hydrogels and graphene foams (GFs) was engineered to support the in vitro expansion of HSCs. The composite scaffold was prepared by forming a photo-cross-linked Gel-HA hydrogel surrounding the GF. The "soft" Gel-HA hydrogel and "stiff" GF replicate the structure and stiffness of the vascular niche and endosteal niche in the bone marrow, respectively. Furthermore, HSCs cultured in the Gel-HA/GF scaffold proliferated well and retained the CD34+CD38- immunophenotype and pluripotency, suggesting that the Gel-HA/GF composite scaffold supported the in vitro expansion of HSCs, maintaining the primitive phenotype and the ability to differentiate into functional blood cells. Thus, the hydrogel/graphene composite scaffold offers a means of facilitating HSC expansion through structurally and mechanically mimicking bone marrow niches, demonstrating great promise for HSC transplantation.


Assuntos
Medula Óssea , Grafite , Grafite/farmacologia , Hidrogéis/química , Células-Tronco Hematopoéticas , Células da Medula Óssea
9.
Environ Sci Pollut Res Int ; 31(14): 21089-21106, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38379046

RESUMO

Interactions between crude oil and its downstream products are crucial but complex. The main purpose of this study is to examine the risk spillover relationships between the crude oil futures market and the petrochemical downstream futures market in the context of the COVID-19 epidemic in China. By combining the dynamic conditional correlation-generalized autoregressive conditional heteroskedasticity (DCC-GARCH) model and the Diebold-Yilmaz spillover index based on time-varying parameter-vector autoregression (TVP-VAR-DY), we investigate the dynamic correlations between Shanghai crude oil futures (INE) and the downstream futures in China's petrochemical industry chain. At the same time, we also incorporate the representative global crude oil futures (BRENT and WTI) in our study as a comparative analysis. Our results show a significant positive correlation between three crude oil futures and China's downstream future products, with a more pronounced link observed between INE and the downstream futures market. Moreover, the correlation between crude oil futures and various downstream products exhibits heterogeneity; that is, direct derivatives of crude oil show higher sensitivity to price fluctuations compared to products with longer production chains. Furthermore, the spillover results indicate that the international crude oil futures, particularly BRENT, primarily function as spillover transmitters, while INE mainly serves as the recipient. In the post-pandemic period, the international crude oil market still exhibits a high spillover effect, and the spillover effect of INE to polyvinyl chloride, pure terephthalic acid, and bitumen futures increased, reflecting market recovery in China to some extent. These results provide potential insights for policymakers, financial institutions, industry participants, and investors, emphasizing the importance of enhanced risk management, diversified investment strategies, and attention to market dynamics.


Assuntos
COVID-19 , Petróleo , Humanos , China , Indústrias , Pandemias
10.
Front Pharmacol ; 15: 1325544, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38420201

RESUMO

Introduction: The synergistic treatment of chemotherapy and photodynamic therapy (PDT) has remarkable potential in cancer therapy. However, challenges remain, such as unstable chemotherapeutic drug release, suboptimal targeting, and reduced efficacy of PDT under hypoxic conditions commonly found in solid tumors. Methods: To address these issues, we use camptothecin (CPT) and pheophorbide a (Pa) incorporated through the functional thioketal, which serves as the reactive oxygen species (ROS)-responsive trigger, to construct a ROS-responsive prodrug (CPT-TK-Pa). Subsequently, we co-loaded it with a platinum nanozyme (PtNP) in distearylphosphatidylethanolamine-polyethylene glycol (DSPE-PEG) to obtain the ROS-responsive prodrug nanoparticle (CPT-TK-Pa/Pt NP). Results and Discussion: Specifically, the incorporated PtNP within CPT-TK-Pa/Pt NP positively catalyzes the conversion of hydrogen peroxide (H2O2) to oxygen, thereby ameliorating the hypoxic state of the tumor. This enhanced oxygen generation could replenish the oxygen that is consumed by Pa during 660 nm exposure, enabling controlled CPT release and amplifying the photodynamic response. In vitro investigations reveal the potency of CPT-TK-Pa/Pt NPs in inhibiting colon tumor cells. Given its ROS-responsive release mechanism and enhanced PDT efficacy, CPT-TK-Pa/Pt NP has the potential to be a promising candidate for cancer therapy.

11.
Nano Lett ; 24(10): 3005-3013, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38416810

RESUMO

Most aggregation-induced emission (AIE) luminogens exhibit high brightness, excellent photostability, and good biocompatibility, but these AIE-active agents, which kill two birds with one stone to result in applications in both stimulated emission depletion (STED) super-resolution imaging and photodynamic therapy (PDT), have not been reported yet but are urgently needed. To meet the requirements of STED nanoscopy and PDT, D-A-π-A-D type DTPABT-HP is designed by tuning conjugated π spacers. It exhibits red-shifted emission, high PLQY of 32.04%, and impressive 1O2 generation (9.24 fold compared to RB) in nanoparticles (NPs). Then, DTPABT-HP NPs are applied in cell imaging via STED nanoscopy, especially visualizing the dynamic changes of lysosomes in the PDT process at ultrahigh resolution. After that, in vivo PDT was also conducted by DTPABT-HP NPs, resulting in significantly inhibited tumor growth, with an inhibition rate of 86%. The work here is beneficial to the design of multifunctional agents and the deep understanding of their phototheranostic mechanism in biological research.


Assuntos
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Fármacos Fotossensibilizantes/uso terapêutico , Diagnóstico por Imagem , Neoplasias/tratamento farmacológico , Fotoquimioterapia/métodos
12.
Sci Transl Med ; 16(730): eadf9735, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38232138

RESUMO

Genetic variation at the transmembrane protein 106B gene (TMEM106B) has been linked to risk of frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) through an unknown mechanism. We found that presence of the TMEM106B rs3173615 protective genotype was associated with longer survival after symptom onset in a postmortem FTLD-TDP cohort, suggesting a slower disease course. The seminal discovery that filaments derived from TMEM106B is a common feature in aging and, across a range of neurodegenerative disorders, suggests that genetic variants in TMEM106B could modulate disease risk and progression through modulating TMEM106B aggregation. To explore this possibility and assess the pathological relevance of TMEM106B accumulation, we generated a new antibody targeting the TMEM106B filament core sequence. Analysis of postmortem samples revealed that the TMEM106B rs3173615 risk allele was associated with higher TMEM106B core accumulation in patients with FTLD-TDP. In contrast, minimal TMEM106B core deposition was detected in carriers of the protective allele. Although the abundance of monomeric full-length TMEM106B was unchanged, carriers of the protective genotype exhibited an increase in dimeric full-length TMEM106B. Increased TMEM106B core deposition was also associated with enhanced TDP-43 dysfunction, and interactome data suggested a role for TMEM106B core filaments in impaired RNA transport, local translation, and endolysosomal function in FTLD-TDP. Overall, these findings suggest that prevention of TMEM106B core accumulation is central to the mechanism by which the TMEM106B protective haplotype reduces disease risk and slows progression.


Assuntos
Demência Frontotemporal , Humanos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Demência Frontotemporal/genética , Demência Frontotemporal/metabolismo , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Polimorfismo de Nucleotídeo Único/genética
13.
Bioelectrochemistry ; 157: 108652, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38271768

RESUMO

Doxorubicin (DOX) is a clinical chemotherapeutic drug and patients usually suffer from dose-dependent cytotoxic and side effects during chemotherapy process with DOX. Therefore, developing a reliable strategy for DOX analysis in biological samples for dosage guidance during chemotherapy process is of great significance. Herein, a sensitive and selective electrochemical biosensor for DOX detection was designed based on gold nanoparticles (AuNPs) and DNA tetrahedron (TDN) nanoprobe bifunctional glassy carbon electrode that could detect DOX in human serum and cell lysate samples. AuNPs not only could enhance electron transfer efficiency and detection sensitivity, but also could improve the biocompatibility of electrode. TDN nanoprobes were employed as specific DOX bind sites that could bind abundant DOX through intercalative characteristics to contribute to sensitive and selective detection. Under the optimal conditions, the proposed TDN nanoprobes-based DOX biosensor exhibited a wide linear range that ranged from 1.0 nM to 50 µM and a low detection limit that was 0.3 nM. Moreover, the proposed DOX biosensor displayed nice selectivity, reproducibility and stability, and was successfully applied for DOX detection in human serum and cell lysate samples. These promising results maybe pave a way for DOX dosage guidance and therapeutic efficacy optimization in clinic.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Humanos , Ouro , Reprodutibilidade dos Testes , Técnicas Eletroquímicas/métodos , Doxorrubicina/análise , DNA , Técnicas Biossensoriais/métodos , Limite de Detecção
14.
Heliyon ; 10(1): e23829, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38192816

RESUMO

ANP32B, a member of the acidic leucine-rich nuclear phosphoprotein 32 family member B, is aberrantly expressed in various cancers, including colorectal cancer. However, the function and mechanism of action of ANP32B in colorectal cancer remain unclear. The present study therefore analyzed the expression of ANP32B and its activity in colorectal cancer patient samples and colorectal cancer cell lines. ANP32B expression was found to be significantly upregulated in colorectal cancer patient samples and cell lines. Upregulation of ANP32B enhanced colorectal cancer cell proliferation and migration, whereas downregulation of ANP32B suppressed colorectal cancer cell proliferation. RNA sequencing analysis of differentially expressed genes in ANP32B silenced colorectal cancer cells showed that histone PARylation factor 1 (HPF1), which protects against DNA damage by interacting with the anti-tumor target PARP1, was significantly downregulated. Luciferase promoter assays testing the regulatory association between ANP32B and HPF1 showed that ANP32B interacted with the HPF1 promoter. Analysis of colorectal cancer samples from The Cancer Genome Atlas showed that ANP32B and HPF1 expression were positively correlated, and recovery assays showed that ANP32B promoted colorectal cancer progression by up-regulating HPF1. Overexpression of ANP32B also reduced the sensitivity of colorectal cancer cells to PARP1 inhibitor, consistent with the oncogenic role of ANP32B. ANP32B may alter the sensitivity of colorectal cancer cells to PARP1 inhibitor via a mechanism associated with the HPF1 gene. In summary, these findings showed that ANP32B acted as a tumor promoter, potentiating both colorectal cancer malignancy and drug resistance. Targeting the ANP32B/HPF1 axis may have benefit for patients with colorectal cancer.

15.
Bioact Mater ; 34: 326-337, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38274294

RESUMO

Atherosclerosis is a significant contributor to global cardiovascular disease. Reducing the formation of atherosclerotic plaque effectively can lead to a decrease in cardiovascular diseases. Therefore, controlling macrophage function is crucial. This study presents the creation of a bifunctional nanoparticle that is specific to macrophages to achieve intracellular and extracellular synergistic therapy for restoring macrophage functions. The nanoparticle is conjugated with anti-CD47 antibody to modulate extracellular CD47-SIRPα phagocytic signaling axis on the outer surface of macrophages and encapsulates the NLRP3 inhibitor (CY-09) to regulate intracellular inflammation response of macrophages. The results showed that the nanoparticles accumulate in the atherosclerotic plaque, alter macrophage phagocytosis, inhibit NLRP3 inflammasome activation, and decrease the plaque burden in Apoe-/- mice whilst ensuring safety. Examination of single-cell RNA sequencing indicates that this multifunctional nanoparticle decreases the expression of genes linked to inflammation and manages inflammatory pathways in the plaque lesion. This study proposes a synergistic therapeutic approach that utilizes a bifunctional nanoparticle, conjugated with anti-CD47, to regulate the microenvironment of plaques.

16.
Nurs Open ; 11(1): e2072, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38268256

RESUMO

AIM: To explore the impact of the Omicron variant on maternal and neonatal outcomes. DESIGN: Cross-sectional cohort study of women giving live birth in a single hospital in Shanghai in December 2022. METHODS: Demographic characteristics, maternal and neonatal outcomes and laboratory testing results were retrieved from medical records. Propensity score matching was used to match COVID-19-positive and -negative women. Differential analysis was used to assess associations between COVID-19 and in-hospital maternal and neonatal outcomes. RESULTS: A total of 1508 women were included, comprising 729 natural births, 741 caesarean sections and 38 forceps deliveries. After 1:1 matching, 310 clients were included for analysis with each 155 in COVID-19-positive and -negative groups. Higher maternal fever was found in all modes of delivery, and higher preterm birth and lower pH value of blood gas of the umbilical artery in the vaginal delivery subgroup (p < 0.05). Other maternal and neonatal outcomes showed no significant difference between COVID-19-positive and -negative clients.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Recém-Nascido , Gravidez , Humanos , Feminino , Estudos Transversais , Nascimento Prematuro/epidemiologia , SARS-CoV-2 , China/epidemiologia , Estudos de Coortes , Complicações Infecciosas na Gravidez/epidemiologia
17.
Heart Surg Forum ; 27(1): E006-E013, 2024 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-38286647

RESUMO

Primary heart tumors are rare, with atrial myxomas being the most common type. Atrial myxomas can lead to embolisms, heart obstruction, and systemic symptoms. Herein, we report a case of 72-year-old woman who presented with a left atrial myxoma at the atrial septal defect occluder, a new acute cerebral infarction, and MINOCA (myocardial infarction with no obstructive coronary atherosclerosis). Left atrial myxoma is a common primary cardiac tumor; however, left atrial myxomas arising after percutaneous atrial septal defect occlusion are rare. Additionally, the patient presented with a new case of multiple systemic emboli. The patient underwent surgical resection of a left atrial myxoma, occluder, and left atrium, and atrial septal repair, and was discharged with good recovery for outpatient follow-up. The possibility of a cardiac tumor, especially an atrial myxoma, which can lead to a series of complications, should be considered at the closure site after percutaneous atrial septal closure. Therefore, active surgical treatment and long-term follow-up are warranted in such cases.


Assuntos
Embolia , Neoplasias Cardíacas , Comunicação Interatrial , Embolia Intracraniana , Mixoma , Dispositivo para Oclusão Septal , Feminino , Humanos , Idoso , Dispositivo para Oclusão Septal/efeitos adversos , Embolia Intracraniana/diagnóstico , Embolia Intracraniana/etiologia , Embolia Intracraniana/cirurgia , MINOCA , Comunicação Interatrial/complicações , Comunicação Interatrial/diagnóstico , Comunicação Interatrial/cirurgia , Embolia/diagnóstico , Embolia/etiologia , Embolia/cirurgia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirurgia , Mixoma/complicações , Mixoma/diagnóstico , Mixoma/cirurgia , Cateterismo Cardíaco/efeitos adversos
18.
Int J Biol Macromol ; 261(Pt 1): 129751, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38280702

RESUMO

Porous hydrogels as scaffolds have great potential in tissue engineering. However, there are still challenges in preparing porous hydrogels with tunable pore size and controlled porosity. Here, we successfully established a photoinduced gas-foaming method of porous hydrogels with controlled macro-micro-nano multiscale. A diazirine (DZ)-modified gelatin (GelDZ) biomaterial was prepared by introducing photocrosslinked DZ group into gelatin. Upon exposure to 365 nm UV light, DZ could be converted to the active group carbene, which could randomly insert into OH, NH, or CH bonds to form covalent crosslinks. GelDZ generated N2 by photodegradation and formed gas-induced porous hydrogels by intermolecular crosslinking without initiator. The loose porous structure of the hydrogel can promote the infiltration of host cells and blood vessels, which was conducive to tissue repair. The interfacial crosslinking of photoactivated GelDZ with tissue proteins imparted adhesion properties to the hydrogel. GelDZ also possessed photoreduction ability, which can reduce silver ions from metal precursors to silver nanoparticles (Ag NPs) in situ, and showed great antibacterial activity due to the sustained release of Ag NPs. GelDZ-Ag NPs prepared by in situ photoreaction can effectively inhibit wound infection and promote skin wound healing, providing a new strategy for designing porous hydrogel in tissue engineering.


Assuntos
Nanopartículas Metálicas , Infecção dos Ferimentos , Humanos , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Gelatina/farmacologia , Gelatina/química , Porosidade , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Hidrogéis/farmacologia , Hidrogéis/química , Antibacterianos/farmacologia , Cicatrização
19.
Technol Health Care ; 32(1): 411-421, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37694323

RESUMO

BACKGROUND: Chinese chest pain centers (CPCs) have been expanding and maturing for the past decade, but patient wait times for pre-hospital care remain long. OBJECTIVE: To demonstrate that the remote electrocardiogram (ECG) monitoring system can ensure more efficient treatment for patients with ST-elevation myocardial infarction (STEMI) in CPCs, we compared patients with high-risk chest pain who used remote ECG monitoring systems to those who used conventional ECGs in retrospective cohort study. METHODS: Based on the inclusion and exclusion criteria, 290 patients who visited our CPC between June 2019 and March 2022 with acute chest pain and a diagnosis of STEMI as well as patients who had undergone an emergency primary percutaneous coronary intervention were selected. Among them, 73 patients with STEMI had employed remote real-time dynamic 12-lead ECG monitoring devices, while 217 patients with STEMI (i.e., the controls) had used conventional ECG monitoring. The effectiveness of treatment procedures for the two groups was investigated. As statistical measures, the symptom onset-to-wire times, first medical contact (FMC)-to-wire times, door-to-wire times, major adverse cardiac events in hospital, and the troponin T levels were analyzed. RESULTS: Compared with the control group, the patients with remote real-time dynamic 12-lead ECG monitoring devices showed shorter times for both symptom onset-to-wire (234.8 ± 95.8 min vs. 317.6 ± 129.6 min, P= 0.0321) and from symptom onset-to-FMC (170.5 ± 86.3 min vs. 245.3 ± 115.6 min, P= 0.0287); this group also had a lower 30-day mortality rate (2.73% vs. 4.14%, P= 0.003). The differences between the two groups were statistically significant (P< 0.05). CONCLUSION: With remote real-time dynamic 12-lead ECG monitoring equipment, myocardial ischemia can be treated more quickly, leading to fewer possible cardiac events and a better prognosis.


Assuntos
Serviços Médicos de Emergência , Infarto do Miocárdio , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/terapia , Estudos Retrospectivos , Clínicas de Dor , Dor no Peito/diagnóstico , Dor no Peito/etiologia , Eletrocardiografia/métodos
20.
Eur Radiol ; 34(1): 569-578, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37548692

RESUMO

OBJECTIVE: Microwave ablation (MWA) has emerged as a minimally invasive technology for papillary thyroid microcarcinoma (PTMC), but it has not been widely applied to treat T1bN0M0 PTC with high-level evidence. This study was designed to compare the real-world efficacy and safety of MWA or surgery for treating T1bN0M0 PTC. METHODS: From December 2019 to April 2021, 123 continuous unifocal T1bN0M0 PTC patients without lymph node metastasis (LNM) or distant metastasis (DM) were included from 10 hospitals. Patients were allocated into the MWA or surgery group based on their willingness. The main outcomes were local tumour progression (LTP), new thyroid cancer, LNM, and DM. The secondary outcomes included changes in tumour size and volume, complications, and cosmetic results. Subgroup analyses were conducted to identify influencing factors. RESULTS: Fifty-two patients chose MWA, and 71 patients chose surgery. Patients had similar demographic information and tumour characteristics in the two groups. The follow-up durations after MWA and surgery were 10.6 ± 4.2 and 10.4 ± 3.4 months, respectively. The LNM rate was 5.8% in the MWA group and 1.4% in the surgery group (p = 0.177). No LTP, new thyroid cancer, or distant metastasis (DM) occurred in either group. Five (9.6%) of the 52 patients in the MWA group and 8 (11.3%) of the 71 patients in the surgery group had complications (p = 0.27). Better cosmetic results were found in the MWA group (p < 0.01). CONCLUSION: MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. CLINICAL RELEVANCE STATEMENT: MWA achieved comparable short-time treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC. KEY POINTS: • MWA achieved comparable short-term treatment efficacy with surgery. MWA might be an optional choice for surgery for low-risk T1bN0M0 PTC but concerns about LNM need to be studied further. • The complication rate in the surgery group was higher than that in the MWA group without a significant difference. • There was no statistically significant difference in the LNM rate between the MWA and surgery groups.


Assuntos
Micro-Ondas , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Câncer Papilífero da Tireoide/patologia , Micro-Ondas/uso terapêutico , Estudos Prospectivos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Metástase Linfática , Ultrassonografia de Intervenção , Estudos Retrospectivos
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