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1.
Small ; : e2404954, 2024 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-39314023

RESUMO

Heterostructure engineering offers a powerful approach to creating innovative electrocatalysts. By combining different materials, it can achieve synergistic effects that enhance both charge storage and electrocatalytic activity. In this work, it is capitalized on this concept by designing a 1D/3D CoWO4(OH)2·H2O/molybdenum disulfide (CTH/MoS2) heterostructure. It is achieved this by in situ depositing 3D MoS2 nanoflowers on 1D CTH nanorods. To explore the impact of precursor choice, various sulfur (S) sources is investigated. Interestingly, the S precursor influenced the dimensionality of the MoS2 component. For example, L-cysteine (L-cys), and glutathione (GSH) resulted in 0D morphologies, thiourea (TU) led to a 2D structure, and thioacetamide (TAA) yielded a desirable 3D architecture. Notably, the 1D/3D CTH/MoS2-TAA heterostructure exhibited exceptional performance in both supercapacitors (SCs) and quantum dot-sensitized solar cells (QDSSCs). This achievement can be attributed to several factors: the synergetic effect between 1D CTH and 3D MoS2, improved accessibility due to the multi-dimensional structure, and a tailored electronic structure facilitated by the Mott-Schottky (M-S) interaction arising from the different material Fermi levels. This interaction further enhances conductivity, ultimately leading to the observed high specific capacity in SCs (154.44 mAh g-1 at 3 mA cm-2) and remarkable photovoltaic efficiency in QDSSCs (6.48%).

2.
Front Pharmacol ; 15: 1421470, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050762

RESUMO

Background: Vasculogenic Mimicry (VM) can reduce the efficacy of anti-angiogenesis and promote distant metastasis in hepatocellular carcinoma (HCC). Our previous studies have found that Celastrus orbiculatus extract (COE) can inhibit the VM formation in HCC by reducing EphA2 expression. However the underlying mechanism related to EphA2 in VM formation is unclear. Purpose: This study aimed to confirm that EphA2 is one of the potential targets of COE, and to explore the effect of EphA2 in VM formation in hypoxia context in HCC. Methods: TCM Systems Pharmacology database and proteomics analysis were used to explore the key targets of COE in HCC treatment. CD31-PAS double staining and VE-CAD staining were used to indicate vasculogenic mimicry. The localization of EphA2 and VE-CAD was examined through fluorescent microscopy. CCK8 assay, cell invasion assay, and tube formation assay were used to indicate the formation of VM under hypoxic conditions. The regulatory relationship of EphA2 upstream and downstream molecules were evaluated through COIP and Western Blot. The nude mouse xenograft tumor models were used to observe the VM formation after knocking down or overexpressing EphA2. Results: EphA2 is identified to the target of COE, and the driving gene of HCC. In HCC surgical specimens, EphA2 expression is closely associated with the VM formation of HCC. COE-regulated EphA2 is involved in hypoxia-induced VM formation in HCC cells in vitro. EphA2 is regulated by HIF directly or indirectly by C-MYC. Overexpression of EphA2 can promote the VM formation of HCC in nude mice, while knocking down EphA2 can inhibit the VM formation. Conclusion: EphA2, as a target of COE, plays a crucial regulatory role in the formation of vasculogenic mimicry in HCC, involving upstream HIF/MYC transcriptional promotion and downstream PI3K/FAK/VE-CAD expression regulation.

3.
Dalton Trans ; 53(27): 11368-11379, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38896134

RESUMO

The design of multimodal cancer therapy was focused on reaching an efficient process and minimizing harmful effects on patients. In the present study, the Au-MnO2 nanostructures have been successfully constructed and produced as novel multipurpose photosensitive agents simultaneously for photodynamic therapy (PDT), photothermal therapy (PTT), and chemodynamic therapy (CDT). The prepared AuNPs were conjugated with MnO2 NPs by its participation in the thermal decomposition process of KMnO4 confirmed by X-ray diffraction (XRD), transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy (FT-IR). The 16.5 nm Au-MnO2 nanostructure exhibited an absorbance at 438 nm, which is beneficial for application in light induction therapy due to the NIR band, as well as its properties of generating reactive oxygen species (ROS) associated with the 808 nm laser light for PDT. The photothermal transduction efficiency was calculated and compared with that of the non-irradiated nanostructure, in which it was found that the 808 nm laser induced a high efficiency of 83%, 41.5%, and 37.5% for PDT, PTT, and CDT, respectively. The results of DPBF and TMB assays showed that the efficiency of PDT and PTT was higher than that of CDT. The nanostructure also confirmed the time-dependent peroxidase properties at different H2O2, TMB, and H2TMB concentrations, promising good potency in applying nanomedicine in clinical cancer therapy.


Assuntos
Antineoplásicos , Ouro , Compostos de Manganês , Óxidos , Fotoquimioterapia , Fármacos Fotossensibilizantes , Terapia Fototérmica , Compostos de Manganês/química , Compostos de Manganês/farmacologia , Ouro/química , Ouro/farmacologia , Óxidos/química , Óxidos/farmacologia , Humanos , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Nanoestruturas/química , Sobrevivência Celular/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Neoplasias/terapia , Nanopartículas Metálicas/química , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular Tumoral
4.
Nutrients ; 16(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38794737

RESUMO

Functional ability decline occurs with age. This study aims to investigate the associations between the lifestyle factors-exercising, food consumption, and smoking-and the functional ability of the activities of daily living (ADL) by gender. The data were obtained from the Taiwan longitudinal study on aging, a national cohort study. The cross-sectional results demonstrated that the frequency of exercising was negatively associated with ADL in both men and women. Dairy products were positively associated with ADL in men. The longitudinal results illustrated that current and consistent exercising were negatively associated with changes in ADL scores over 4- and 8-year periods in both men and women. Seafood consumption was negatively associated with changes in the subsequent 4-year ADL scores. Past smoking was positively associated with changes in subsequent 4-year ADL scores in men, while current smoking was positively associated with changes in subsequent 8-year ADL scores in women. Therefore, consistent exercising, food consumption, and smoking were associated with ADL functional ability in elderly people, and the associations differed by gender. Elders exercising consistently had good ADL performance and maintained their ADL ability better, especially women. Seafood consumption decreased the risk of ADL decline, while smoking increased the risk of ADL decline.


Assuntos
Atividades Cotidianas , Envelhecimento , Exercício Físico , Estilo de Vida , Fumar , Humanos , Masculino , Feminino , Taiwan/epidemiologia , Estudos Longitudinais , Idoso , Envelhecimento/fisiologia , Estudos Transversais , Fumar/epidemiologia , Idoso de 80 Anos ou mais , Fatores de Risco , Dieta/estatística & dados numéricos , Fatores Sexuais , Alimentos Marinhos
5.
Adv Sci (Weinh) ; 11(24): e2309526, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38650119

RESUMO

Photocatalytic reduction of CO2 is a promising strategy to mitigate the effects of global warming by converting CO2 into valuable energy-dense products. Silver bismuth iodide (SBI) is an attractive material owing to its tunable bandgap and favorable band-edge positions for efficient CO2 photoreduction. In this study, SBI materials, including AgBi2I7, AgBiI4, Ag2BiI5, and Ag3BiI6 are first synthesized, through gas-solid reaction by controlling the stoichiometric ratio of reactants. The X-ray absorption near edge structure (XANES) and extended X-ray absorption fine structure (EXAFS) results revealed that the distance between Ag-I is proportional to the degree of Ag ions delocalization, which occupies the vacant sites. That greatly retards the charge recombination at vacant sites. In addition, the surface potential via photo-assisted Kelvin probe force measurements of various SBI catalysts shows that Ag3BiI6 exhibits the highest surface potential change due to the rich delocalized Ag ions. This results in effective charge carrier transport and prevention of charge recombination at vacant sites. Taking the above advantages, the averaged CO and CH4 production rates for Ag3BiI6 achieved 0.23 and 0.10 µmol g-1 h-1, respectively. The findings suggest that Ag3BiI6 has a high potential as a novel photocatalyst for CO2 reduction and sheds light on the possibility of solving environmental contamination and sustainable energy crises.

6.
ACS Appl Mater Interfaces ; 16(19): 24172-24190, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38688027

RESUMO

Of the most common, hypoxia, overexpressed glutathione (GSH), and insufficient H2O2 concentration in the tumor microenvironment (TME) are the main barriers to the advancment of reactive oxygen species (ROS) mediated Xdynamic therapies (X = photo, chemodynamic, chemo). Maximizing Fenton catalytic efficiency is crucial in chemodynamic therapy (CDT), yet endogenous H2O2 levels are not sufficient to attain better anticancer efficacy. Specifically, there is a need to amplify Fenton reactivity within tumors, leveraging the unique attributes of the TME. Herein, for the first time, we design RuxCu1-xO2-Ce6/CPT (RCpCCPT) anticancer nanoagent for TME-mediated synergistic therapy based on heterogeneous Ru-Cu peroxide nanodots (RuxCu1-xO2 NDs) and chlorine e6 (Ce6), loaded with ROS-responsive thioketal (TK) linked-camptothecin (CPT). The Ru-Cu peroxide NDs (RCp NDs, x = 0.50) possess the highest oxygen vacancy (OV) density, which grants them the potential to form massive Lewis's acid sites for peroxide adsorption, while the dispersibility and targetability of the NDs were improved via surface modification using hyaluronic acid (HA). In TME, RCpCCPT degrades, releasing H2O2, Ru2+/3+, and Cu+/2+ ions, which cooperatively facilitate hydroxyl radical (•OH) formation and deactivate antioxidant GSH enzymes through a cocatalytic loop, resulting in excellent tumor therapeutic efficacy. Furthermore, when combined with laser treatment, RCpCCPT produces singlet oxygen (1O2) for PDT, which induces cell apoptosis at tumor sites. Following ROS generation, the TK linkage is disrupted, releasing up to 92% of the CPT within 48 h. In vitro investigations showed that laser-treated RCpCCPT caused 81.5% cell death from PDT/CDT and chemotherapy (CT). RCpCCPT in cancer cells produces red-blue emission in images of cells taking them in, which allows for fluorescence image-guided Xdynamic treatment. The overall results show that RCp NDs and RCpCCPT are more biocompatible and have excellent Xdynamic therapeutic effectiveness in vitro and in vivo.


Assuntos
Cobre , Peróxido de Hidrogênio , Rutênio , Microambiente Tumoral , Peróxido de Hidrogênio/química , Peróxido de Hidrogênio/metabolismo , Peróxido de Hidrogênio/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Cobre/química , Cobre/farmacologia , Animais , Camundongos , Humanos , Rutênio/química , Rutênio/farmacologia , Nanopartículas/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Peróxidos/química , Peróxidos/farmacologia , Linhagem Celular Tumoral , Fotoquimioterapia , Portadores de Fármacos/química , Espécies Reativas de Oxigênio/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/patologia
7.
Anal Chim Acta ; 1298: 342410, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38462334

RESUMO

Ferroptosis is an emerging iron-dependent oxidative cell death type, and recently has been demonstrated to show close relation with Golgi apparatus (GA). Exploring the fluctuation of superoxide anion (O2•-) level in GA during ferroptosis is of great significance to profoundly study the biological functions of GA in ferroptosis. Here, we present a GA-targeting probe (N-GA) to monitor cellular O2•- during ferroptosis. N-GA employed a triflate group and a tetradecanoic amide unit as the recognition site for O2•- and GA-targeting unit, respectively. After the response of N-GA to O2•-, the triflate unit of N-GA converted into hydroxyl group with strong electron-donating ability, generating bright green fluorescence under UV light. N-GA exhibited excellent sensitivity and selectivity towards O2•-. Fluorescence imaging results showed that N-GA could be applied as a GA-targeting probe to monitor cellular O2•-. The stimulation of cells with PMA and rotenone could result in the massive generation of endogenous O2•- in GA. Erastin-induced ferroptosis can markedly induce the increase of O2•- level in GA. Similar to Fer-1 and DFO, dihydrolipoic acid (DHLA) and rutin were demonstrated to inhibit the enormous production of O2•- in GA of the living cells during ferroptosis.


Assuntos
Ferroptose , Superóxidos , Corantes Fluorescentes/toxicidade , Ferro , Complexo de Golgi/metabolismo
8.
Heliyon ; 10(1): e23184, 2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38163209

RESUMO

Papillary renal cell carcinoma (PRCC) is a highly heterogeneous cancer, and PRCC patients with advanced/metastatic subgroup showed obviously shorter survival compared to other kinds of renal cell carcinomas. However, the molecular mechanism and prognostic predictors of PRCC remain unclear and are worth deep studying. The aim of this study is to identify novel molecular classification and construct a reliable prognostic model for PRCC. The expression data were retrieved from TCGA, GEO, GTEx and TARGET databases. CRISPR data was obtained from Depmap database. The key genes were selected by the intersection of CRISPR-Cas9 screening genes, differentially expressed genes, and genes with prognostic capacity in PRCC. The molecular classification was identified based on the key genes. Drug sensitivity, tumor microenvironment, somatic mutation, and survival were compared among the novel classification. A prognostic model utilizing multiple machine learning algorithms based on the key genes was developed and tested by independent external validation set. Our study identified three clusters (C1, C2 and C3) in PRCC based on 41 key genes. C2 had obviously higher expression of the key genes and lower survival than C1 and C3. Significant differences in drug sensitivity, tumor microenvironment, and mutation landscape have been observed among the three clusters. By utilizing 21 combinations of 9 machine learning algorithms, 9 out of 41 genes were chosen to construct a robust prognostic signature, which exhibited good prognostic ability. SERPINH1 was identified as a critical gene for its strong prognostic ability in PRCC by univariate and multiple Cox regression analyses. Quantitative real-time PCR and Western blot demonstrated that SERPINH1 mRNA and protein were highly expressed in PRCC cells compared with normal human renal cells. This study exhibited a new molecular classification and prognostic signature for PRCC, which may provide a potential biomarker and therapy target for PRCC patients.

9.
Pharmaceuticals (Basel) ; 17(1)2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38256960

RESUMO

The use of tocilizumab against the interleukin-6 receptor (IL-6R) has been demonstrated as inhibiting the progression of diverse cancers in vitro and in vivo. Nonetheless, evidence regarding the anti-tumor effects of tocilizumab on human colorectal carcinoma (CRC) corresponding to IL-6R expression levels remains scarce. To investigate the influence of IL-6R expression, SW480 and HT-29 cells inoculated subcutaneously into NU/NU mice were used as human CRC xenograft models with anti-IL-6R antibody (tocilizumab) therapy. The IL-6R expression levels, histology of CRC growth/invasiveness, and tumor growth-related signaling pathway were estimated by H&E and immunohistochemical staining. SW480 tumor cells with higher IL-6R expression levels showed better responsiveness in tocilizumab therapy than in the treated HT-29 group. Likewise, therapeutic effects of tocilizumab on the proliferative ability with mitotic index and Ki-67 expressions, invasiveness with MMP-9 proteinase expressions, and ERK 1/2 and STAT3 signaling transduction in the SW480 treatment group were superior to the HT-29 treatment group. In light of our results, IL-6R is the key indicator for the efficacy of tocilizumab treatment in CRC xenografts. From the perspective of precision medicine, tumor response to anti-IL-6R antibody therapy could be predicted on the basis of IL-6R expression levels. In this manner, tocilizumab may serve as a targeted and promising anti-CRC therapy.

10.
Emerg Microbes Infect ; 13(1): 2300466, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38164719

RESUMO

During its global epidemic, Zika virus (ZIKV) attracted widespread attention due to its link with various severe neurological symptoms and potential harm to male fertility. However, the understanding of how ZIKV invades and persists in the male reproductive system is limited due to the lack of immunocompetent small animal models. In this study, immunocompetent murine models were generated by using anti-IFNAR antibody blocked C57BL/6 male mice and human STAT2 (hSTAT2) knock in (KI) male mice. After infection, viral RNA could persist in the testes even after the disappearance of viremia. We also found a population of ZIKV-susceptible S100A4+ monocytes/macrophages that were recruited into testes from peripheral blood and played a crucial role for ZIKV infection in the testis. By using single-cell RNA sequencing, we also proved that S100A4+ monocytes/macrophages had a great impact on the microenvironment of ZIKV-infected testes, thus promoting ZIKV-induced testicular lesions. In conclusion, this study proposed a novel mechanism of long-term ZIKV infection in the male reproductive system.


Assuntos
Infecção por Zika virus , Zika virus , Humanos , Masculino , Camundongos , Animais , Zika virus/genética , Testículo , Monócitos , Camundongos Endogâmicos C57BL , Macrófagos , Modelos Animais de Doenças , Proteína A4 de Ligação a Cálcio da Família S100
11.
Mol Pharm ; 21(2): 801-812, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38217878

RESUMO

Cancer is a significant global public health concern, ranking as the leading cause of mortality worldwide. This study thoroughly explores boron-doped carbon dots (B-CDs) through a simple/rapid microwave-assisted approach and their versatile applications in cancer therapy. The result was highly uniform particles with an average diameter of approximately 4 nm. B-CDs exhibited notable properties, including strong fluorescence with a quantum yield of 33%. Colloid stability tests revealed their robustness within a pH range of 6-12, NaCl concentrations up to 0.5 M, and temperatures ranging from 30 to 60 °C. The study also delved into the kinetics of naproxen release from B-CDs as a drug delivery system. The loading efficacy of naproxen exceeded 55.56%. Under varying pH conditions, the release of naproxen from B-CDs conformed to the Peppas-Sahlin model, demonstrating the potential of Naproxen-loaded CDs for cancer drug delivery. In vitro cytotoxicity assessments, conducted using the CCK-8 Assay and flow cytometry, consistently indicated low toxicity with average cell viability exceeding 80%. An in vivo toxicity test on female mice administered 20 mg/kg of B-CDs for 31 days revealed reversible histological changes in the liver and kidneys, while the pancreas remained unaffected. Importantly, B-CDs did not impact the mice's physical behavior, body weight, or survival. In vivo experiments targeting benzo(a)pyrene-induced fibrosarcoma demonstrated the efficacy of B-CDs as naproxen carriers in the treatment of cancer. This in vivo study provides a thorough comprehension of B-CDs synthesis and toxicity and their potential applications in cancer therapy and drug delivery systems.


Assuntos
Antineoplásicos , Pontos Quânticos , Feminino , Animais , Camundongos , Pontos Quânticos/química , Boro , Naproxeno/uso terapêutico , Carbono/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico
12.
Pain Pract ; 24(1): 82-90, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37615236

RESUMO

PURPOSE: Accurate predictions of postoperative pain intensity are necessary for customizing analgesia plans. Insomnia is a risk factor for severe postoperative pain. Moreover, heart rate variability (HRV) can provide information on the sympathetic-parasympathetic balance in response to noxious stimuli. We developed a prediction model that uses the insomnia severity index (ISI), HRV, and other demographic factors to predict the odds of higher postoperative pain. METHODS: We recruited gynecological surgery patients classified as American Society of Anesthesiologists class 1-3. An ISI questionnaire was completed 1 day before surgery. HRV was calculated offline using intraoperative electrocardiogram data. Pain severity at the postanesthesia care unit (PACU) was assessed with the 0-10 numerical rating scale (NRS). The primary outcome was the model's predictive ability for moderate-to-severe postoperative pain. The secondary outcome was the relationship between individual risk factors and opioid consumption in the PACU. RESULTS: Our study enrolled 169 women. Higher ISI scores (p = 0.001), higher parasympathetic activity (rMSSD, pNN50, HF; p < 0.001, p < 0.001, p < 0.001), loss of fractal dynamics (SD2, alpha 1; p = 0.012, p = 0.039) in HRV analysis before the end of surgery were associated with higher NRS scores, while laparoscopic surgery (p = 0.031) was associated with lower NRS scores. We constructed a multiple logistic model (area under the curve = 0.852) to predict higher NRS scores at PACU arrival. The five selected predictors were age (OR: 0.94; p = 0.020), ISI score (OR: 1.14; p = 0.002), surgery type (laparoscopic or open; OR: 0.12; p < 0.001), total power (OR: 2.02; p < 0.001), and alpha 1 (OR: 0.03; p < 0.001). CONCLUSION: We employed a multiple logistic regression model to determine the likelihood of moderate-to-severe postoperative pain upon arrival at the PACU. Physicians could personalize analgesic regimens based on a deeper comprehension of the factors that contribute to postoperative pain.


Assuntos
Distúrbios do Início e da Manutenção do Sono , Qualidade do Sono , Humanos , Feminino , Frequência Cardíaca/fisiologia , Distúrbios do Início e da Manutenção do Sono/tratamento farmacológico , Analgésicos , Analgésicos Opioides/uso terapêutico , Dor Pós-Operatória/diagnóstico , Dor Pós-Operatória/epidemiologia , Dor Pós-Operatória/tratamento farmacológico
13.
Foods ; 12(22)2023 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-38002159

RESUMO

Emerging evidence has demonstrated that using a new manufacturing technology to produce γ-aminobutyric acid (GABA)-fortified oolong (GO) tea could relieve human stress and exert versatile physiological benefits. The purpose of this human study was to investigate the therapeutic effects of daily GO tea consumption on improvements in blood pressure, relaxation-related brain waves, and quality of life (QOL) over a period of 28 consecutive days. Total polyphenols, major catechins, and free amino acids were analyzed via an HPLC assay. Changes in heart rate, blood pressure, α brain waves (index of relaxation), and the eight-item QOL score were investigated on days 0, 7, 14, 21, and 28. The chemical analysis results showed that GO tea contained the most abundant amino acids and GABA, contributing to the relaxation activity. Among all study participants, the daily consumption of GO tea could reduce systolic blood pressure on day 21 and diastolic blood pressure on day 28 (p < 0.05 for both). For participants with pre-hypertension, GO tea could effectively reduce heart rate and systolic and diastolic blood pressure on day 28 (p < 0.05). At the end of the study, incremental changes in alpha brain waves and QOL scores were also demonstrated (p < 0.05 for both). This study suggests that GO tea might potentially serve as a natural source for alternative therapy to improve blood pressure, stress relief, and QOL.

14.
ACS Appl Mater Interfaces ; 15(48): 55258-55275, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38013418

RESUMO

In recent studies, iron-containing Fenton nanocatalysts have demonstrated significant promise for clinical use due to their effective antitumor activity and low cytotoxicity. A new approach was reported in this work utilizing cation exchange synthesis to fabricate FeMnOx nanoparticles (NPs) that boost Fenton reactions and responses to the tumor microenvironment (TME) for chemodynamic therapy (CDT) and chemotherapy (CT). Within the TME, the redox metal pair of Fe2+/Mn2+ helps break down endogenous hydrogen peroxide (H2O2) into very harmful hydroxyl radicals (•OH) while simultaneously deactivating glutathione (GSH) to boost CDT performance. To further enhance the therapeutic potential, FeMnOx NPs were encapsulated with thioketal-linked camptothecin (CPT-TK-COOH), a reactive oxygen species (ROS)-responsive prodrug, achieving a high CPT-loading capacity of up to 51.1%. Upon ROS generation through the Fenton reaction, the prodrug TK linkage was disrupted, releasing 80% of the CPT payload within 48 h. Notably, FeMnOx@CPT exhibited excellent dual-modal imaging capabilities, enabling magnetic resonance and fluorescence imaging for image-guided therapy. In vitro studies showed the cytocompatibility of FeMnOx NPs using MDA-Mb-231 and 4T1 cells, but in the presence of H2O2, they induced significant cytotoxicity, resulting in 80% cell death through CDT and CT effects. Upon intravenous administration, FeMnOx@CPT displayed remarkable tumor accumulation, which enhanced tumor suppression in xenografts through improved CDT and CT effects. Moreover, no significant adverse effects were observed in the FeMnOx NP-treated animals. In the current study, the FeMnOx@CPT anticancer platform, with its boosted •OH-producing capability and ROS-cleavable drug release, has been validated utilizing in vitro and animal studies, suggesting its capacity as a viable strategy for clinical trials.


Assuntos
Nanopartículas , Neoplasias , Pró-Fármacos , Humanos , Animais , Espécies Reativas de Oxigênio , Peróxido de Hidrogênio , Microambiente Tumoral , Administração Intravenosa , Glutationa , Linhagem Celular Tumoral , Neoplasias/tratamento farmacológico
15.
Orphanet J Rare Dis ; 18(1): 340, 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37904148

RESUMO

BACKGROUND: Multiple epiphyseal dysplasia (MED) is a rare congenital bone dysplasia. Patients with MED develop secondary hip osteoarthritis as early as the third to the fourth decade. Currently, there is no consensus on the prevention of the progressive hip osteoarthritis secondary to MED. The Bernese periacetabular osteotomy (PAO) is a joint-preserving surgery to reshape acetabulum and extend femoral head coverage. However, there is no documentary evidence for the effect of the procedure on MED hips. PATIENTS AND METHODS: We analyzed the preliminary outcomes following the Bernese PAO in 6 MED hips. The average age at the time of surgery was 14.3 years (range from 11.4 to 17.2 years). For our study interest of time efficiency, radiographic parameters were analyzed preoperatively and 1 year postoperatively. The hip function was evaluated by the Harris Hip Score (HHS) before and after surgery. RESULTS: The mean follow-up time was 1.7 years. The mean lateral center-edge angle increased from 3.8° to 47.1° (p = 0.02), anterior center-edge angle increased from 7.3° to 35.1° (p = 0.02), and acetabulum index decreased from 27.8° to 14.6° (p = 0.04). The femoral head coverage ratio increased from 66.8% to 100% (p = 0.02). The post-operative anteroposterior pelvic radiograph demonstrated all preoperative broken Shenton lines were reversed. The mean HHS improved from 67.3 to 86.7 (p = 0.05). CONCLUSION: Bernese PAO is a feasible treatment for hip disorders in MED patients. It reshapes acetabular and femoral morphology efficiently. In our study, the preliminary results showed the procedure not only improved radiographic outcomes but also hip function.


Assuntos
Luxação do Quadril , Osteoartrite do Quadril , Osteocondrodisplasias , Humanos , Criança , Adolescente , Osteoartrite do Quadril/etiologia , Osteoartrite do Quadril/cirurgia , Estudos Retrospectivos , Acetábulo/cirurgia , Acetábulo/anormalidades , Osteotomia/efeitos adversos , Osteotomia/métodos , Resultado do Tratamento , Luxação do Quadril/etiologia , Luxação do Quadril/cirurgia
16.
BMC Infect Dis ; 23(1): 584, 2023 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-37674103

RESUMO

OBJECTIVE: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity. RESULTS: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor. CONCLUSION: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access. SYSTEMATIC REVIEW REGISTRATION: Registered on PROSPERO, Identifier: CRD42022297754.


Assuntos
Síndrome da Imunodeficiência Adquirida , Coinfecção , Tuberculose , Humanos , Vacina BCG , Coinfecção/epidemiologia , Prevalência , Fatores de Risco , Tuberculose/epidemiologia , China/epidemiologia
17.
Epigenetics Chromatin ; 16(1): 35, 2023 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-37749610

RESUMO

BACKGROUND: Blood-based tests have public appeal in screening cancers due to their minimally invasive nature, ability to integrate with other routine blood tests, and high compliance. This study aimed to investigate whether certain epigenetic modulation of peripheral blood mononuclear cells (PBMCs) could be a biomarker of colorectal cancer (CRC). RESULTS: Western blotting of histones in the PBMCs from 40 colorectal cancer patients and 40 healthy controls was performed to identify the crotonylation sites of proteins. The correlation of crotonylation with tumor staging and diagnostic efficacy were analyzed. Crotonylation of H2BK12 (H2BK12cr) was identified significantly upregulated in the PBMCs of CRC patients compared to healthy controls, and were closely related to distant metastasis (P = 0.0478) and late TNM stage (P = 0.0201). Receiver operator characteristic curve (ROC) analysis demonstrated that the area under curve (AUC) of H2BK12cr was 0.8488, the sensitivity was 70%, and the specificity was 92.5%. The H2BK12cr parameter significantly increased the diagnostic effectiveness of CRC compared with the commercial carcinoembryonic antigen assays. CONCLUSIONS: The H2BK12cr level in PBMCs of CRC patients has a potential to be a biomarker for distinguishing CRC patients from healthy controls with the advantages of easy operation and high diagnostic efficacy.


Assuntos
Neoplasias Colorretais , Histonas , Humanos , Leucócitos Mononucleares , Biomarcadores , Epigenômica , Neoplasias Colorretais/diagnóstico
18.
J Exp Bot ; 74(21): 6790-6803, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37610886

RESUMO

It is often expected that Zn decreases Cd accumulation in plants due to competition for the same transporters. Here, we found that increasing Zn supply markedly increased the root-to-shoot translocation of Cd in rice. RNA sequencing showed that high Zn up-regulated expression of genes involved in glutathione biosynthesis and metabolism and the Zn/Cd transporter gene OsHMA2, but down-regulated expression of genes related to Zn uptake. Knockout of the iron or Zn transporter genes OsIRT1, OsIRT2, or OsZIP9 did not affect the Zn promotional effect on Cd translocation. Knockout of the manganese/Cd transporter gene OsNRAMP5 greatly reduced Cd uptake but did not affect the Zn promotional effect. Variation in the tonoplast transporter gene OsHMA3 affected Cd translocation but did not change the Zn promotional effect. Knockout of the Zn/Cd transporter gene OsHMA2 not only decreased Cd and Zn translocation, but also abolished the Zn promotional effect. Increased expression of OsHMA2 under high Zn conditions supports the hypothesis that this transporter participates in the promotional effect of Zn on Cd translocation. The results also show that OsIRT1, OsIRT2, and OsZIP9 made only small contributions to Cd uptake under low Zn conditions but not under high Zn conditions, whereas the dominant role of OsNRAMP5 in Cd uptake diminished under low Zn conditions.


Assuntos
Cádmio , Oryza , Cádmio/metabolismo , Zinco/metabolismo , Oryza/genética , Oryza/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Transporte Biológico , Translocação Genética , Raízes de Plantas/genética , Raízes de Plantas/metabolismo
19.
Polymers (Basel) ; 15(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37447509

RESUMO

Curcumin (Cur) is a beneficial phytochemical with numerous health advantages. However, its limited solubility in oil and poor stability hinder its potential for biomedical applications. In this study, we employed a mixture of food-grade Tween 60, a polymeric surfactant, and Span 60 to adjust the hydrophilic lipophilic balance number (HLBt) and prepared nanoemulsions (NEs) of coconut oil (Cc oil) as carriers for Cur. The effects of HLBt values, surfactant-to-oil ratio, and oil ratio on the physicochemical characteristics of the food-grade oil-NEs were investigated using dynamic light scattering, transmission electron microscopy, differential scanning calorimetry, fluorescence polarization spectroscopy, and viscometry. Increasing the addition ratio of Tween 60 in the NEs, thereby increasing the HLBt, resulted in a reduction in NE size and an improvement in their storage stability. The temperature and size of the phase transition region of the NEs decreased with increasing HLBt. NEs with higher HLBt exhibited a disordering effect on the intra-NE molecular packing of Cc oil. NEs with high HLBt displayed low viscosity and demonstrated nearly Newtonian fluid behavior, while those with lower HLBt exhibited pseudoplastic fluid behavior. Cur was effectively encapsulated into the Cc oil-NEs, with higher encapsulation efficiency observed in NEs with higher HLBt values. Furthermore, the Cur remaining activity was significantly enhanced through encapsulation within stable NEs. The biocompatibility of the Cc oil-NEs was also demonstrated in vitro. In summary, this study highlights the preparation of stable NEs of Cc oil by adjusting the HLBt using Tween 60, facilitating effective encapsulation of Cur. These findings provide valuable insights for the development of Cur carriers with improved solubility, stability, and bioavailability.

20.
Curr Issues Mol Biol ; 45(6): 4908-4922, 2023 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-37367061

RESUMO

BACKGROUND/AIM: Colorectal cancer (CRC) is the third most common cancer with a high mortality rate worldwide. Although gallic acid and hesperidin exert anticancer activity, synergistic effects of gallic acid and hesperidin against CRC remain elusive. This study aims to investigate the therapeutic mechanism of a novel combination of gallic acid and hesperidin against CRC cell growth, including cell viability, cell-cycle-associated proteins, spheroid formation, and stemness. METHODS: Gallic acid and hesperidin derived from Hakka pomelo tea (HPT) were detected by colorimetric methods and high-performance liquid chromatography using ethyl acetate as an extraction medium. CRC cell lines (HT-29 and HCT-116) treated with the combined extract were investigated in our study for cell viability (trypan blue or soft agar colony formation assay), cell cycle (propidium iodide staining), cell-cycle-associated proteins (immunoblotting), and stem cell markers (immunohistochemistry staining). RESULTS: Compared with other extraction methods, HPT extraction using an ethyl acetate medium exerts the most potent effect on inhibiting HT-29 cell growth in a dose-dependent manner. Furthermore, the treatment with combined extract had a higher inhibitory effect on CRC cell viability than gallic acid or hesperidin alone. The underlying mechanism was involved in G1-phase arrest and Cip1/p21 upregulation that could attenuate HCT-116 cell proliferation (Ki-67), stemness (CD-133), and spheroid growth in a 3D formation assay mimicking in vivo tumorigenesis. CONCLUSION: Gallic acid and hesperidin exert synergistic effects on cell growth, spheroids, and stemness of CRC and may serve as a potential chemopreventive agent. Further testing for the safety and effectiveness of the combined extract in large-scale randomized trials is required.

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