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1.
Cancer Res ; 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38581448

RESUMO

Single-cell RNA-sequencing (scRNA-seq) greatly advanced the understanding of intratumoral heterogeneity by identifying distinct cancer cell subpopulations. However, translating biological differences into treatment strategies is challenging due to a lack of tools to facilitate efficient drug discovery that tackles heterogeneous tumors. Developing such approaches requires accurate prediction of drug response at the single-cell level to offer therapeutic options to specific cell subpopulations. Here, we developed a transparent computational framework (nicknamed scIDUC) to predict therapeutic efficacies on an individual-cell basis by integrating single-cell transcriptomic profiles with large, data-rich pan-cancer cell line screening datasets. This method achieved high accuracy in separating cells into their correct cellular drug response statuses. In three distinct prospective tests covering different diseases (rhabdomyosarcoma, pancreatic ductal adenocarcinoma, and castration-resistant prostate cancer), the predicted results using scIDUC were accurate and mirrored biological expectations. In the first two tests, the framework identified drugs for cell subpopulations that were resistant to standard-of-care (SOC) therapies due to intrinsic resistance or tumor microenvironmental effects, and the results showed high consistency with experimental findings from the original studies. In the third test using newly generated SOC therapy resistant cell lines, scIDUC identified efficacious drugs for the resistant line, and the predictions were validated with in vitro experiments. Together, this study demonstrates the potential of scIDUC to quickly translate scRNA-seq data into drug responses for individual cells, displaying the potential as a tool to improve treatment of heterogenous tumors.

2.
Glob Chang Biol ; 30(3): e17224, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38459661

RESUMO

Wood density is a fundamental property related to tree biomechanics and hydraulic function while playing a crucial role in assessing vegetation carbon stocks by linking volumetric retrieval and a mass estimate. This study provides a high-resolution map of the global distribution of tree wood density at the 0.01° (~1 km) spatial resolution, derived from four decision trees machine learning models using a global database of 28,822 tree-level wood density measurements. An ensemble of four top-performing models combined with eight cross-validation strategies shows great consistency, providing wood density patterns with pronounced spatial heterogeneity. The global pattern shows lower wood density values in northern and northwestern Europe, Canadian forest regions and slightly higher values in Siberia forests, western United States, and southern China. In contrast, tropical regions, especially wet tropical areas, exhibit high wood density. Climatic predictors explain 49%-63% of spatial variations, followed by vegetation characteristics (25%-31%) and edaphic properties (11%-16%). Notably, leaf type (evergreen vs. deciduous) and leaf habit type (broadleaved vs. needleleaved) are the most dominant individual features among all selected predictive covariates. Wood density tends to be higher for angiosperm broadleaf trees compared to gymnosperm needleleaf trees, particularly for evergreen species. The distributions of wood density categorized by leaf types and leaf habit types have good agreement with the features observed in wood density measurements. This global map quantifying wood density distribution can help improve accurate predictions of forest carbon stocks, providing deeper insights into ecosystem functioning and carbon cycling such as forest vulnerability to hydraulic and thermal stresses in the context of future climate change.


Assuntos
Ecossistema , Madeira , Canadá , Florestas , Folhas de Planta , Carbono
3.
Biol Direct ; 19(1): 19, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38429756

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is the main subtype of esophageal cancer. Current therapeutic effect is far from satisfaction. Hence, identifying susceptible genes and potential targets is necessary for therapy of ESCC patients. METHODS: Plant homeodomain (PHD)-finger domain protein 5 A (PHF5A) expression in ESCC tissues was examined by immunohistochemistry. RNA interference was used for in vitro loss-of-function experiments. In vivo assay was performed using xenograft mice model by subcutaneous injection. Besides, microarray assay and co-immunoprecipitation experiments were used to study the potential downstream molecules of PHF5A in ESCC. The molecular mechanism between PHF5A and vascular endothelial growth factor A (VEGFA) was explored by a series of ubiquitination related assays. RESULTS: We found that PHF5A was highly expressed in ESCC tissues compared to normal tissues and that was correlated with poor prognosis of ESCC. Loss-of-function experiments revealed that PHF5A silence remarkably inhibited cell proliferation, migration, and induced apoptosis as well as cell cycle arrest. Consistently, in vivo assay demonstrated that PHF5A deficiency was able to attenuate tumor growth. Furthermore, molecular studies showed that PHF5A silencing promoted VEGFA ubiquitination by interacting with MDM2, thereby regulating VEGFA protein expression. Subsequently, in rescue experiments, our data suggested that ESCC cell viability and migration promoted by PHF5A were dependent on intact VEGFA. Finally, PI3K/AKT signaling rescue was able to alleviate shPHF5A-mediated cell apoptosis and cell cycle arrest. CONCLUSION: PHF5A is a tumor promoter in ESCC, which is dependent on VEGFA and PI3K/AKT signaling. PHF5A might serve as a potential therapeutic target for ESCC treatment.


Assuntos
Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Fator A de Crescimento do Endotélio Vascular , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patologia , Carcinoma de Células Escamosas do Esôfago/genética , Carcinoma de Células Escamosas do Esôfago/metabolismo , Carcinoma de Células Escamosas do Esôfago/patologia , Regulação Neoplásica da Expressão Gênica , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas de Ligação a RNA/genética , Transativadores/genética , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
4.
Transpl Immunol ; 84: 102018, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38452983

RESUMO

BACKGROUND: Renal ischemia/reperfusion injury (RIRI) is an inevitable consequence of kidney transplantation and has a negative impact on both short-term and long-term graft survival. The identification of key markers in RIRI to improve the prognosis of patients would be highly advantageous. METHODS: Gene expression profile data of GSE27274 were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were analyzed using the Limma package. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment of DEGs were performed. Support vector machine-recursive feature elimination and least absolute shrinkage and selection operator regression modeling were both performed to identify potential biomarkers. The GSE148420 dataset, quantitative reverse transcriptase-PCR, and western blotting results of kidney tissue samples were used to validate the bioinformatic analysis. Lastly, exploring differences between different groups through gene set enrichment analysis and using DsigDB database to identify potential therapeutic drugs targeting hub genes. RESULTS: A total of 160 upregulated and 180 downregulated DEGs were identified. Functional enrichment analysis identified significant enrichment in processes involving peroxisomes. As a subunit of Polycomb Repressive Complex 1(PRC1), chromobox 6(Cbx6) was identified as a potential biomarker with an area under the receiver operating characteristic curve of 0.875 (95% confidence interval 0.624-1.000) in the validation cohort, and it was highly expressed in the RIRI group (p < 0.05). In the high expression group Cbx6 was more enriched in the toll-like receptor signaling pathway. We predicted 15 potential drugs targeting hub genes of RIRI. CONCLUSIONS: We identified Cbx6 as a potential biomarker for RIRI and 15 potential drugs for the treatment of RIRI, which might shed a light on the treatment of RIRI.

5.
Heliyon ; 10(6): e27530, 2024 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-38501018

RESUMO

Background: Ulcerative colitis (UC) is a chronic non-specific inflammatory disease with intestinal tract as the main site. The pathogenic of UC has not yet been clarified, and multiple mechanisms can lead to the pathogenesis of UC. Traditional Chinese medicine (TCM) offers an opportunity for UC treatment. TCM has become the preferred treatment for UC with characteristics of multiple targets, multiple pathways and high safety. This review attempted to summarize the characteristics of TCM (compound prescriptions, single Chinese herbs, and active ingredients) for UC treatment and discussed their pathogenesis based on analyzing the UC-related gut microbiota, signaling pathway and cytokine. In order to provide more systematic and diverse reference for TCM in the prevention and treatment of UC, and provide theoretical reference for clinical treatment of UC. Materials and methods: The information was acquired from different databases, including Web of Science, PubMed, CNKI, Wanfang, and VIP databases. We then focused on the recent research progress in UC treatment by TCM. Finally, the deficiencies and future perspectives are proposed. Results: Modern pharmacological studies have shown that the compound prescriptions (strengthening spleen, clearing heat and removing dampness, clearing heat and removing toxin), single Chinese herbs (replenishing Qi, clearing heat, tonifying blood, etc.), and active ingredients (alkaloids, polysaccharides, flavonoids, polyphenols, terpenes, etc.) have an efficiency in UC treatment by regulating gut microbiota, signaling pathway and cytokine. Conclusions: TCM can achieve its purpose of UC prevention and treatment by acting in multiple ways, and TCM deserves further research and development in this field.

6.
NPJ Precis Oncol ; 8(1): 74, 2024 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-38521810

RESUMO

Rab27A is a small GTPase-mediating exosome secretion, which participates in tumorigenesis of multiple cancer types. Understanding the biological role of Rab27A in non-small cell lung cancer (NSCLC) is of great importance for oncological research and clinical treatment. In this study, we investigate the function and internal mechanism of Rab27A in NSCLC. Results show that Rab27A is overexpressed in NSCLC, and regulates the tumor proliferation, migration, invasion, and cell motility in vitro and in vivo, and is negatively regulated by miR-124. Further research reveals that upregulated Rab27A can induce the production of IFNα in the medium by mediating exosome secretion. Then IFNα activates TYK2/STAT/HSPA5 signaling to promote NSCLC cell proliferation and metastasis. This process can be suppressed by TYK2 inhibitor Cerdulatinib. These results suggest that Rab27A is involved in the pathogenesis of NSCLC by regulating exosome secretion and downstream signaling, and inhibitors targeting this axis may become a promising strategy in future clinical practice.

7.
J Colloid Interface Sci ; 662: 377-390, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359502

RESUMO

Developing highly efficient photocatalysts based on conjugated microporous polymers (CMPs) are often impeded by the intrinsically large exciton binding energy and sluggish charge transfer kinetics that result from their vulnerable driving force. Herein, a family of pyrene-based nitrogen-implanted CMPs were constructed, where the nitrogen gradient was regulated. Accordingly, the built-in electric field endowed by the nitrogen gradient dramatically accelerates the dissociation of exciton into free carriers, thereby enhancing charge separation efficiency. As a result, PyCMP-3N generated by polymerization of 1,3,6,8-tetrakis(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrene and 2,4,6-tris(4-bromophenyl)-1,3,5-triazine featured an optimized built-in electric field and exhibited the highest photocatalytic removal efficiency of uranium (VI) (99.5 %). Our proposed strategy not only provides inspiration for constructing the built-in electric field by controlling nitrogen concentration gradients, but also offers an in-depth understanding the crucial role of built-in electric field in exciton dissociation and charge transfer, efficiently promoting CMPs photocatalysis.

8.
ACS Chem Biol ; 19(3): 654-659, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38331720

RESUMO

Extracellular soluble proteins are key agents in the development of various diseases. However, strategies to remove therapeutically relevant extracellular targets are still scarce. Here, we establish dendronized DNA chimera (DENTAC) as an efficient approach for targeted degradation of the extracellular protein of interest (ePOI). DENTAC consists of a DNA dendron against cell-surface scavenger receptors (SRs), a protein ligand, and a connecting linker, which harnesses SRs as a lysosome-trafficking receptor to mediate the lysosomal degradation of the ePOI. We interrogate and optimize structure-activity relationships of DENTAC. Using neutravidin as a model ePOI, we show that both branch number and DNA length in the DNA dendron are important determinants for efficient lysosomal delivery and degradation of the protein. We demonstrate three branches and 10 nucleotide-length polythymidine as the optimal DNA dendron components to construct DENTAC. We further exemplify the anticancer application of DENTAC by targeting matrix metalloproteinase-9 (MMP-9), where we find linker property as another factor important for DENTAC performance. We reveal that MMP-9-targeting DENTAC effectively restrain cancer cell proliferation, migration, and invasion. This study thus provides a potent strategy to delete extracellular proteins that are commonly difficult to target.


Assuntos
Dendrímeros , Metaloproteinase 9 da Matriz , Proteólise , Dendrímeros/farmacologia , Proliferação de Células , DNA
9.
Int J Biol Macromol ; 262(Pt 1): 129974, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38331068

RESUMO

Mitochondria in breast cancer play a critical role in survival and adaptation to dynamic environments. Thus, targeting mitochondria emerges as a promising therapeutic strategy for breast cancer. However, the adaptive unfolded protein response in mitochondria (UPRmt) due to mitochondrial unspecific distribution might contribute to diminished therapeutic outcomes. Herein, mitochondrial targeting liposome agents (CTPP-Lipid) are constructed and adopted for delivering the copper ion (CuET-DSF), which is especially sensitive for mitochondria-abundant breast tumors. In brief, the CTPP-Lipid@CuET achieves the goal of Cu2+ overloading by mitochondria targeting delivery. This rapidly increases ROS production, disrupts mitochondrial structure, and avoids the adaptive UPRmt formation, finally leading to apoptosis of breast cancer cells. In general, the Cu2+ overloading at mitochondria by CTPP-Lipid@CuET is a potential strategy for antitumor therapy, providing new insights into breast tumor therapy.


Assuntos
Neoplasias da Mama , Lipossomos , Humanos , Feminino , Cobre/farmacologia , Neoplasias da Mama/tratamento farmacológico , Resposta a Proteínas não Dobradas , Lipídeos
10.
Adv Mater ; : e2314021, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38359076

RESUMO

Photoactivatable molecules, with high-precision spatialtemporal control, have largely promoted bioimaging and phototherapy applications of fluorescent dyes. Here, the first photoactivatable sensor (BI) is described that can be triggered by broad excitation light (405-660 nm), which further undergoes intersystem crossing and H-atom transfer processes to forming superoxide anion radicals (O2 -• ) and carbon radicals. Particularly, the photoinduced gain of carbon-centered radicals (BI•) allows for radical-radical coupling to afford the combined crosslink product (BI─BI), which would be oxidized in the presence of O2 -• to produce an extended conjugate system with near infrared emission (820 nm). Besides, the photochemically generated product (Cy─BI) possesses ultra-high photothermal conversion efficiency up to 90.9%, which optimized phototherapy potential. What's more, Western Blot assay reveals that both BI and the photoproduct Cy─BI can efficiently inhibit the expression of CHK1, and the irradiation of BI and Cy─BI further induces apoptosis and ultimately enhances the phototherapeutic effects. Thus, the combination of cell cycle block inducing apoptosis, photodynamic therapy and photothermal therapy treatments significantly suppress solid tumor in vivo antitumor efficacy explorations. This is a novel finding in developing photoactivatable molecules, as well as the broad applicability of photoimaging and phototherapy in tumor-related areas.

11.
Pharmacol Ther ; 256: 108610, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38367868

RESUMO

Accumulating evidence indicates that epigenetic events undergo deregulation in various cancer types, playing crucial roles in tumor development. Among the epigenetic factors involved in the epigenetic remodeling of chromatin, the chromodomain helicase DNA-binding protein (CHD) family frequently exhibits gain- or loss-of-function mutations in distinct cancer types. Therefore, targeting CHD remodelers holds the potential for antitumor treatment. In this review, we discuss epigenetic regulations of cancer development. We emphasize proteins in the CHD family, delving deeply into the intricate mechanisms governing their functions. Additionally, we provide an overview of current therapeutic strategies targeting CHD family members in preclinical trials. We further discuss the promising approaches that have demonstrated early signs of success in cancer treatment.


Assuntos
Cromatina , Neoplasias , Humanos , DNA Helicases/genética , DNA Helicases/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Mutação , Proteínas de Ligação a DNA/metabolismo , Montagem e Desmontagem da Cromatina , Epigênese Genética
12.
Adv Mater ; : e2311733, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38339920

RESUMO

Immunotherapy has received widespread attention for its effective and long-term tumor-eliminating ability. However, for immunogenic "cold" tumors, such as prostate cancer (PCa), the low immunogenicity of the tumor itself is a serious obstacle to efficacy. Here, this work reports a strategy to enhance PCa immunogenicity by triggering cascade self-enhanced ferroptosis in tumor cells, turning the tumor from "cold" to "hot". This work develops a transformable self-assembled peptide TEP-FFG-CRApY with alkaline phosphatase (ALP) responsiveness and glutathione peroxidase 4 (GPX4) protein targeting. TEP-FFG-CRApY self-assembles into nanoparticles under aqueous conditions and transforms into nanofibers in response to ALP during endosome/lysosome uptake into tumor cells, promoting lysosomal membrane permeabilization (LMP). On the one hand, the released TEP-FFG-CRAY nanofibers target GPX4 and selectively degrade the GPX4 protein under the light irradiation, inducing ferroptosis; on the other hand, the large amount of leaked Fe2+ further cascade to amplify the ferroptosis through the Fenton reaction. TEP-FFG-CRApY-induced immunogenic ferroptosis improves tumor cell immunogenicity by promoting the maturation of dendritic cells (DCs) and increasing intratumor T-cell infiltration. More importantly, recovered T cells further enhance ferroptosis by secreting large amounts of interferon-gamma (IFN-γ). This work provides a novel strategy for the molecular design of synergistic molecularly targeted therapy for immunogenic "cold" tumors.

13.
Nanoscale Adv ; 6(5): 1423-1435, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38419880

RESUMO

Drug delivery systems based on nanoparticles still face challenges of low efficacy and an inability to track treatment effects in tumor therapy due to biological barriers. This limitation hinders clinicians' ability to determine treatment effects and proper drug dosages, thus, ultimately impeding the further application and transformation of nanoplatforms. To address this challenge, an all-in-one nanoplatform for therapy and imaging is proposed. The nanoplatform is constructed by using nanoparticles through the co-encapsulation of the photothermal therapeutic agent IR780, the passively targeted drug OA@Fe3O4, and the chemotherapeutic drug paclitaxel. Under the guidance of magnetic navigation, the nanoparticles can enhance local enrichment of the drug, while the luminescence properties of IR780 enable drug tracking at the same time. Remarkably, the nanoparticles exhibit improved photothermal-chemotherapy synergy under magnetic targeting guidance, demonstrating antitumor effects in both in vitro and in vivo experiments. It is demonstrated that the use of these polymeric nanoparticles has significant potential for future biomedical applications and clinical decisions.

14.
J Am Geriatr Soc ; 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38319006

RESUMO

BACKGROUND: Sexual function is an important yet understudied aspect of overall health and well-being in older adults. We aimed to examine sexual function and its correlates among people 50 years and older in China. METHODS: We enrolled people aged 50 years and older recruited from four regions in China between September 2021 and July 2022 in a multicenter cross-sectional study. Data were collected through an investigator-administered questionnaire about demographic characteristics, health characteristics, and sexual function status. Logistic regression was used to assess correlates of lower sexual function (the highest quintile of the sex-specific population distribution of Natsal-SF scores [i.e., lower functioning compared with the remaining]). RESULTS: A total of 465 women and 832 men who were sexually active in the past year were included in the analysis (mean age: 60.4 ± 7.2) [Correction added after first online publication on 12 Feb 2024. The word "years" has been changed to "year" in this sentence.]. Over a quarter of all participants were dissatisfied with their sex life. Notably, 92 women and 167 men were categorized as having a lower sexual function. Age (in men only), living in urban areas, general health status, being underweight or overweight (in men only), and having depressive symptoms were associated with lower sexual function. Among all participants, 43.1% of men and 54.0% of women experienced sexual response problems lasting 3 months or more. Less than one-third of all participants had sought help or advice for sex life in the past year. CONCLUSIONS: Sexual dysfunction and sexual dissatisfaction are prevalent among older adults in China and are associated with self-assessed poor health. More efforts are needed to better understand sexual health needs and tailor service provision.

15.
Vaccine X ; 16: 100434, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38304877

RESUMO

Background: Mpox, one of the most serious threats to global health, is now being seen in small but rising numbers in Beijing, China. Our study aimed to investigate healthcare workers' (HCWs) knowledge of Mpox and to explore reasons associated with their hesitancy to vaccinate against Mpox in Beijing, China. Methods: A cross-sectional study was conducted among HCWs in Beijing from July 24 to August 2, 2023, through an online questionnaire. Participants answered questions about sociodemographic characteristics, Mpox information sources, Mpox knowledge, perception of vaccines, and attitudes toward Mpox vaccination. We used Chi-squared test to compare difference in Mpox vaccination hesitancy between different groups. Multivariable logistic regression models were applied to analyze correlates of vaccination hesitancy among HCWs. Results: A total of 2331 HCWs completed the questionnaire, with an effective response rate of 92.45 % (2155/2331). Most of the HCWs in this study worked at tertiary hospitals (89.65 %), with a mean age of 36.69 ± 9.08 years. Among the 2155 participants, 52.99 % had over ten years of working experience, and 16.66 % were from high-risk departments relevant to Mpox treatment. Approximately 84.41 % knew about Mpox before this study, 80.79 % exhibited a high level of knowledge about Mpox, whereas 42.37 % were hesitant to be vaccinated against Mpox. Moreover, the hesitancy rate of HCWs in high-risk departments (47.91 %) was higher than in lower-risk departments (41.26 %). Higher educational level (aOR = 1.75, 95 %CI: 1.17-2.62), longer working years (1.71, 1.32-2.22), working at high-risk departments (1.34, 1.05-1.71), and lower level of knowledge about Mpox (1.78, 1.13-2.85) appeared as the most significant determinants of Mpox vaccination hesitancy among HCWs who knew about Mpox. For the HCWs who did not know about Mpox, longer working years (1.96, 1.02-3.78) were significant factors associated with their hesitancy. The predominant reason for hesitancy toward Mpox vaccination among HCWs encompassed apprehensions about vaccine side effects. Conclusion: HCWs had good knowledge of Mpox, whereas their Mpox vaccination hesitancy was also relatively high in Beijing, China. Increasing HCWs' vaccination confidence and knowledge level about Mpox, especially for those working in high-risk departments, may be an essential way of reducing their hesitancy.

16.
J Cancer Sci Clin Ther ; 7(4): 253-258, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344217

RESUMO

We recently reported a computational method (IDACombo) designed to predict the efficacy of cancer drug combinations using monotherapy response data and the assumptions of independent drug action. Given the strong agreement between IDACombo predictions and measured drug combination efficacy in vitro and in clinical trials, we believe IDACombo can be of immediate use to researchers who are working to develop novel drug combinations. While we previously released our method as an R package, we have now created an R Shiny application to allow researchers without programming experience to easily utilize this method. The app provides a graphical interface which enables users to easily generate efficacy predictions with IDACombo using provided data from several high-throughput cell line screens or using custom, user-provided data.

17.
Int J Biol Macromol ; 261(Pt 1): 129809, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38290633

RESUMO

Diabetes is one of the foremost chronic non-communicable diseases worldwide, which significantly impacts people's quality of life. This study aimed to investigate the hypoglycemic effects of γ-polyglutamic acid (γ-PGA) on STZ-induced type II diabetes mice and its potential mechanisms. The results indicated that γ-PGA intervention contributed to reducing fasting blood glucose levels in diabetic mice, regulating lipid metabolism in type II diabetes mice, and improving insulin resistance. Additionally, γ-PGA could alleviate liver inflammation, enhancing the activity of hepatic antioxidant enzymes. Investigation into the insulin signaling pathway revealed that γ-PGA significantly increased the expression of INSR, IRS-1, Akt, PI3K in diabetic mice, thereby enhancing insulin sensitivity and improving insulin resistance to regulate glucose metabolism. High-throughput sequencing of mouse gut microbiota using 16S rRNA showed that γ-PGA increased the abundance and evenness of beneficial bacteria in the intestines of type II diabetic mice, inhibited the growth of harmful bacteria, and may exerted hypoglycemic effects by modulating and improving relevant metabolic pathways associated with diabetes symptoms. This study provides new insights into the treatment of type II diabetes and highlights the significant potential of γ-PGA in treating type II diabetes.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Ácido Poliglutâmico/análogos & derivados , Humanos , Camundongos , Animais , Hipoglicemiantes/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , RNA Ribossômico 16S , Qualidade de Vida , Insulina/metabolismo , Glicemia/metabolismo
18.
Natl Sci Rev ; 11(2): nwad286, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38213521

RESUMO

Kidney transplantation is the gold standard for the treatment of end-stage renal diseases (ESRDs). However, the scarcity of donor kidneys has caused more and more ESRD patients to be stuck on the waiting list for transplant surgery. Improving the survival rate for renal grafts is an alternative solution to the shortage of donor kidneys. Therefore, real-time monitoring of the surgical process is crucial to the success of kidney transplantation, but efficient methods and techniques are lacking. Herein, a fluorescence technology based on bright, photostable and long-circulating aggregation-induced emission (AIE) active NIR-II nano-contrast agent DIPT-ICF nanoparticles for the whole-process monitoring and evaluation of renal transplantation has been reported. In the aggregated state, DIPT-ICF exhibits superior photophysical properties compared with the commercial dyes IR-26 and IR-1061. Besides, the long-circulating characteristic of the AIE nano-contrast agent helps to achieve renal angiography in kidney retrieval surgery, donor kidney quality evaluation, diagnosing vascular and ureteral complications, and assessment of renal graft reperfusion beyond renovascular reconstruction, which considerably outperforms the clinically approved indocyanine green (ICG).

19.
Vaccine X ; 16: 100439, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38283624

RESUMO

Background: During a vaccination plateau phase, traditional vaccination promotion strategies such as the mobilization of government and community appear to have limited impact on expanding the coverage. New strategies to promote vaccination are needed especially in older adults. Our study aimed to assess college students' intention to encourage coronavirus disease 2019 (COVID-19) vaccination among their grandparents and its correlates. Methods: A cross-sectional survey was conducted in China from May to June 2022. We collected information on socio-demographics of college students and their grandparents, constructs of health belief model (HBM) and theory of planned behavior (TPB) for college students, and college students' intention to encourage COVID-19 vaccination among their grandparents. Multilevel logistic regression models were performed to assess correlates of intention. Results: We enrolled 2681 college students who reported information for 6302 grandparents. 2272 students (84.7 %) intended to encourage COVID-19 vaccination for 4744 (75.3 %) grandparents. Intention was associated with having received a booster dose of COVID-19 vaccine (AOR 3.28, 95 % CI 1.68-6.42), having ever lived with their grandparents (2.07, 1.46-2.93), and having grandparents who regularly went outdoors (2.85, 1.70-4.76). HBM and TPB models showed that college students who had higher levels of perceived susceptibility (1.79, 1.12-2.87), perceived severity (1.52, 1.12-2.06) of COVID-19 among their grandparents, and higher levels of subjective norms (2.88, 1.61-5.15) were more likely to have the intention. Conclusion: College students' intention to encourage COVID-19 vaccination among their grandparents was high. It may be potentially viable to engage college students in promoting COVID-19 and other routine vaccination among older adults.

20.
Lancet Healthy Longev ; 5(1): e17-e30, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38183996

RESUMO

BACKGROUND: Sexually active older adults are often more susceptible to HIV and other sexually transmitted infections (STIs) due to various health conditions (especially a weakened immune system) and low use of condoms. We aimed to assess the global, regional, and national burdens and trends of HIV and other STIs in older adults from 1990 to 2019. METHODS: We retrieved data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 on the incidence and disability-adjusted life-years (DALYs) of HIV and other STIs (syphilis, chlamydia, gonorrhoea, trichomoniasis, and genital herpes) for older adults aged 60-89 years in 204 countries and territories from 1990 to 2019. Estimated annual percentage changes in the age-standardised incidence and DALY rates of HIV and other STIs, by age, sex, and Socio-demographic Index (SDI), were calculated to quantify the temporal trends. Spearman correlation analysis was used to examine the relationship between age-standardised rates and SDI. FINDINGS: In 2019, among older adults globally, there were an estimated 77 327 (95% uncertainty interval 59 443 to 97 648) new cases of HIV (age-standardised incidence rate 7·6 [5·9 to 9·6] per 100 000 population) and 26 414 267 (19 777 666 to 34 860 678) new cases of other STIs (2607·1 [1952·1 to 3440·8] per 100 000). The age-standardised incidence rate decreased by an average of 2·02% per year (95% CI -2·38 to -1·66) for HIV and remained stable for other STIs (-0·02% [-0·06 to 0·01]) from 1990 to 2019. The number of DALYs globally in 2019 was 1 905 099 (95% UI 1 670 056 to 2 242 807) for HIV and 132 033 (95% UI 83 512 to 225 630) for the other STIs. The age-standardised DALY rate remained stable from 1990 to 2019, with an average change of 0·97% (95% CI -0·54 to 2·50) per year globally for HIV but decreased by an annual average of 1·55% (95% CI -1·66 to -1·43) for other STIs. Despite the global decrease in the age-standardised incidence rate of HIV in older people from 1990 to 2019, many regions showed increases, with the largest increases seen in eastern Europe (average annual change 17·84% [14·16 to 21·63], central Asia (14·26% [11·35 to 17·25]), and high-income Asia Pacific (7·52% [6·54 to 8·51]). Regionally, the age-standardised incidence and DALY rates of HIV and other STIs decreased with increases in the SDI. INTERPRETATION: Although the incidence and DALY rates of HIV and STIs either declined or remained stable from 1990 to 2019, there were regional and demographic disparities. Health-care providers should be aware of the effects of ageing societies and other societal factors on the risk of HIV and other STIs in older adults, and develop age-appropriate interventions. The disparities in the allocation of health-care resources for older adults among regions of different SDIs should be addressed. FUNDING: Natural Science Foundation of China, Fujian Province's Third Batch of Flexible Introduction of High-Level Medical Talent Teams, Science and Technology Innovation Team (Tianshan Innovation Team) Project of Xinjiang Uighur Autonomous Region, Cure Alzheimer's Fund, Helse Sør-Øst, the Research Council of Norway, Molecule/VitaDAO, NordForsk Foundation, Akershus University Hospital, the Civitan Norges Forskningsfond for Alzheimers Sykdom, the Czech Republic-Norway KAPPA programme, and the Rosa Sløyfe/Norwegian Cancer Society & Norwegian Breast Cancer Society.


Assuntos
Neoplasias da Mama , Gonorreia , Infecções por HIV , Herpes Genital , Infecções Sexualmente Transmissíveis , Humanos , Idoso , Feminino , Carga Global da Doença , Infecções Sexualmente Transmissíveis/epidemiologia , Infecções por HIV/epidemiologia
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