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1.
J Hepatocell Carcinoma ; 11: 1221-1233, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38957436

RESUMEN

Purpose: Long noncoding RNAs (lncRNAs) might be closely associated with hepatocellular carcinoma (HCC) progression and could serve as diagnostic and prognostic markers. This study aimed to investigate lncRNA-based diagnostic biomarkers for hepatitis B virus (HBV)-associated HCC. Materials and Methods: High-throughput transcriptome sequencing was conducted on the liver tissues of 15 patients with HBV-associated liver diseases (5 with chronic hepatitis B [CHB], 5 with liver cirrhosis [LC], and 5 with HCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze lncRNA expressions. Potential diagnostic performance for HBV-associated HCC screening was evaluated. Results: Through trend analysis and functional analysis, we found that 8 lncRNAs were gradually upregulated and 1 lncRNA was progressively downregulated by regulation of target mRNAs and downstream HCC-associated signaling pathways. The validation of dysregulated lncRNAs in peripheral blood mononuclear cells (PBMCs) and HCC tissues by qRT-PCR revealed that ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were significantly increased in HCC compared with CHB and cirrhosis. Moreover, differentially expressed lncRNAs were aberrantly elevated in Huh7, Hep3B, HepG2, and HepG2.215 cells compared with LX2 cells. Furthermore, ADAMTSL4-AS1, SOCS2-AS1, and AC067931 were identified as novel biomarkers for HBV-associated HCC. For distinguishing HCC from CHB, ADAMTSL4-AS1, AC067931, and SOCS2-AS1 combined with alpha-fetoprotein (AFP) had an area under the curve (AUC) of 0.945 (sensitivity, 83.9%; specificity, 89.8%). Similarly, for distinguishing HCC from LC, this combination had an AUC of 0.871 (sensitivity, 91.1%; specificity, 68.2%). Furthermore, this combination showed the highest diagnostic ability to distinguish HCC from CHB and LC (AUC, 0.905; sensitivity, 91.1%; specificity, 75.3%). In particular, this combination identified AFP-negative (AFP < 20 ng/mL) (AUC = 0.814), small (AUC = 0.909), and early stage (AUC = 0.863) tumors. Conclusion: ADAMTSL4-AS1, SOCS2-AS1, and AC067931 combined with AFP in PBMCs may serve as a noninvasive diagnostic biomarker for HBV-associated HCC, especially AFP-negative, small, and early stage HCC.

2.
BMC Cancer ; 24(1): 800, 2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38965506

RESUMEN

Drug resistance remains a significant challenge in the treatment of pancreatic cancer. The development of drug-resistant cell lines is crucial to understanding the underlying mechanisms of resistance and developing novel drugs to improve clinical outcomes. Here, a novel pancreatic cancer cell line, PDAC-X1, derived from Chinese patients has been established. PDAC-X1 was characterized by the immune phenotype, biology, genetics, molecular characteristics, and tumorigenicity. In vitro analysis revealed that PDAC-X1 cells exhibited epithelial morphology and cell markers (CK7 and CK19), expressed cancer-associated markers (E-cadherin, Vimentin, Ki-67, CEA, CA19-9), and produced pancreatic cancer-like organs in suspension culture. In vivo analysis showed that PDAC-X1 cells maintained tumorigenicity with a 100% tumor formation rate. This cell line exhibited a complex karyotype, dominated by subtriploid karyotypes. In addition, PDAC-X1 cells exhibited intrinsic multidrug resistance to multiple drugs, including gemcitabine, paclitaxel, 5-fluorouracil, and oxaliplatin. In conclusion, the PDAC-X1 cell line has been established and characterized, representing a useful and valuable preclinical model to study the underlying mechanisms of drug resistance and develop novel drug therapeutics to improve patient outcomes.


Asunto(s)
Carcinoma Ductal Pancreático , Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Neoplasias Pancreáticas , Humanos , Línea Celular Tumoral , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Animales , Ratones , Resistencia a Múltiples Medicamentos/genética , Ensayos Antitumor por Modelo de Xenoinjerto , Masculino , Femenino , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Gemcitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Desoxicitidina/uso terapéutico
3.
Int J Phytoremediation ; : 1-10, 2024 Jul 08.
Artículo en Inglés | MEDLINE | ID: mdl-38973396

RESUMEN

Vesicular sequestration is a potential strategy for enhancing plant tolerance to cadmium (Cd) and arsenic (As). In this study, the ectopic overexpression of yeast-derived ScSMF2 in Arabidopsis thaliana was found to enhance the accumulation and tolerance of Cd and As in transgenic plants. ScSMF2 was localized on vacuole membranes and formed puncta structures in plant cells when agro-infiltrated for transient expression. Transgenic Arabidopsis showed less retardation on root elongation and shoot weight and more accumulation of Cd, As (III) and As (V) when cultured on medium containing Cd or As. Overexpression of ScSMF2 promoted accumulation of Cd and arsenic in transgenic Arabidopsis, which were over twice higher than in WT plants when cultured in soil. This study provides insights into the mechanisms involved in the vesicular sequestration of heavy metals in plant and presents a potential strategy for enhancing the phytoremediation capacity of plants toward heavy metals.


Ectopic overexpression of the yeast Mn2+ transporter SMF2 in Arabidopsis thaliana substantially boosts the accumulation and tolerance to Cd and As in plants. This augmentation is attributed to the enhanced efficacy of intracellular vesicle sequestration, thereby bolstering the capacity of plants to sequester and detoxify these toxic heavy metals. This investigation introduces a potential approach for cultivating plants with improved phytoremediation capabilities, thereby advancing eco-friendly and sustainable remediation initiatives against heavy metal pollution.

4.
ACS Sens ; 9(6): 3272-3281, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38836565

RESUMEN

Hepatic fibrosis, the insidious progression of chronic liver scarring leading to life-threatening cirrhosis and hepatocellular carcinoma, necessitates the urgent development of noninvasive and precise diagnostic methodologies. Denatured collagen emerges as a critical biomarker in the pathogenesis of hepatic fibrosis. Herein, we have for the first time developed 3D-printed collagen capture chips for highly specific surface-enhanced Raman scattering (SERS) detection of denatured type I and type IV collagen in blood, facilitating the early diagnosis of hepatic fibrosis. Employing a novel blend of denatured collagen-targeting peptide-modified silver nanoparticle probes (Ag@DCTP) and polyethylene glycol diacrylate (PEGDA), we engineered a robust ink for the 3D fabrication of these collagen capture chips. The chips are further equipped with specialized SERS peptide probes, Ag@ICTP@R1 (S-I) and Ag@IVCTP@R2 (S-IV), tailored for the targeted detection of type I and IV collagen, respectively. The SERS chip platform demonstrated exceptional specificity and sensitivity in capturing and detecting denatured type I and IV collagen, achieving detection limits of 3.5 ng/mL for type I and 3.2 ng/mL for type IV collagen within a 10-400 ng/mL range. When tested on serum samples from hepatic fibrosis mouse models across a spectrum of fibrosis stages (S0-S4), the chips consistently measured denatured type I collagen and detected a progressive increase in type IV collagen concentration, which correlated with the severity of fibrosis. This novel strategy establishes a benchmark for the multiplexed detection of collagen biomarkers, enhancing our capacity to assess the stages of hepatic fibrosis.


Asunto(s)
Colágeno Tipo IV , Colágeno Tipo I , Cirrosis Hepática , Impresión Tridimensional , Plata , Espectrometría Raman , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Espectrometría Raman/métodos , Colágeno Tipo I/sangre , Colágeno Tipo I/química , Animales , Ratones , Colágeno Tipo IV/sangre , Colágeno Tipo IV/química , Plata/química , Nanopartículas del Metal/química , Desnaturalización Proteica , Humanos , Polietilenglicoles/química
5.
J Control Release ; 371: 484-497, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38851537

RESUMEN

The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.


Asunto(s)
Benzofuranos , Sistemas de Liberación de Medicamentos , Liposomas , Células Madre Mesenquimatosas , Daño por Reperfusión , Animales , Daño por Reperfusión/terapia , Masculino , Benzofuranos/administración & dosificación , Isquemia Encefálica/terapia , Materiales Biomiméticos/química , Materiales Biomiméticos/administración & dosificación , Ratones , Ratones Endogámicos C57BL , Trasplante de Células Madre Mesenquimatosas/métodos
6.
Molecules ; 29(11)2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38893285

RESUMEN

In the study, natural deep eutectic solvents (NADESs) were used as alternatives to traditional chemical solvents for the extraction of polyphenols from Elaeagnus angustifolia L. Nine NADESs were tested for the first time and compared with ethanol and water (traditional solvents) regarding the extraction of phenolic compounds from E. angustifolia L. These solvents were particularly effective at extracting polyphenols, whose low water solubility usually requires high amounts of organic solvents. The solvent based on choline chloride and malonic acid provided optimal results and was selected for further optimization. The effects of material-to-liquid ratio, ultrasound time, and ultrasound temperature on the extraction efficiency were studied through single-factor experiments. These parameters were optimized by Box-Behnken design using response surface methodology. The optimal conditions identified were 49.86 g/mL of material-to-liquid ratio, 31.10 min of ultrasound time, and 62.35 °C of ultrasound temperature, resulting in a high yield of 140.30 ± 0.19 mg/g. The results indicated that the NADES extraction technique provided a higher yield than the conventional extraction process. The antioxidant activity of the extract of polyphenols from E. angustifolia L. was determined, and UPLC-IMS-QTOF-MS was used to analyze the phenolic compounds in it. The results revealed that the scavenging ability of 1,1-diphenyl-2-picryl-hydrazil and 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) extracted by NADES was higher than that of polyphenols extracted by water and ethanol. Furthermore, a total of 24 phenolic compounds were identified in the extract. To the best of our knowledge, this is the first study in which a green and efficient NADES extraction method has been used to extract bioactive polyphenols from E. angustifolia L., which could provide potential value in pharmaceuticals, cosmetics, and food additives.


Asunto(s)
Antioxidantes , Elaeagnaceae , Extractos Vegetales , Polifenoles , Polifenoles/química , Polifenoles/aislamiento & purificación , Extractos Vegetales/química , Antioxidantes/química , Antioxidantes/farmacología , Antioxidantes/aislamiento & purificación , Elaeagnaceae/química , Disolventes Eutécticos Profundos/química , Tecnología Química Verde , Solventes/química
7.
Bioact Mater ; 39: 206-223, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38827172

RESUMEN

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

8.
Sci Rep ; 14(1): 13101, 2024 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-38849465

RESUMEN

Currently, a comprehensive assessment of the relationship between ideal cardiovascular health (CVH) indicators and cataract risk is lacking. Life's Essential 8 (LE8) is the latest concept proposed by the American Heart Association to comprehensively reflect CVH status. LE8 includes four health behaviors (diet, physical activity, smoking, and sleep) and four health factors (blood lipid, blood sugar, blood pressure, and body mass index). This study tried to evaluate the association between LE8 and cataract using data from National Health and Nutrition Examination Survey (NHANES) 2005-2008, a continuous research program which aims to monitor and evaluate the health and nutrition status of the US population. A cross-sectional study of 2720 non-cataract participants and 602 cataract participants. All participants were assigned to the poor, intermediate, and ideal CVH status groups based on LE8 score. Weighted multiple logistic regression was used to investigate the correlation between the LE8 score and cataract, as well as the correlation between each of the eight subitems and cataract, with potential confounding variables being adjusted. Then, restricted cubic spline analysis was used to further explore whether there was a nonlinear relationship between LE8 score and cataract. The proportion of cataract participants was 14.1%, 18.2%, and 20.6% in the ideal, intermediate, and poor CVH groups, respectively (P < 0.05). LE8 score was inversely associated with cataract risk, with each 10-point increase in LE8 score associated with a 14% reduction in cataract risk [odds ratio (OR) = 0.86, 95% confidence interval (CI): 0.79-0.93, P < 0.01]. Among all the LE8 subitems, physical activity, sleep, and blood glucose were significantly associated with cataract risk (all P < 0.05). Better CVH, defined by a higher LE8 score, is associated with a lower cataract risk. Efforts to improve LE8 score (especially when it comes to physical activity, sleep, and blood glucose) may serve as a novel strategy to help reduce the risk of cataract.


Asunto(s)
Catarata , Encuestas Nutricionales , Humanos , Catarata/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Estudios Transversales , Estados Unidos/epidemiología , Adulto , Anciano , Factores de Riesgo , Ejercicio Físico , Índice de Masa Corporal , Conductas Relacionadas con la Salud , Dieta , Presión Sanguínea , Enfermedades Cardiovasculares/epidemiología , Glucemia/análisis , Glucemia/metabolismo
9.
Chem Sci ; 15(24): 9345-9352, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38903234

RESUMEN

Methylation of microRNAs (miRNAs) is a post-transcriptional modification that affects miRNA activity by altering the specificity of miRNAs to target mRNAs. Abnormal methylation of miRNAs in cancer suggests their potential as a tumor marker. However, the traditional methylated miRNA detection mainly includes mass spectrometry, sequencing and others; complex procedures and reliance on large instruments greatly limit their application in point-of-care testing (POCT). Based on this, we developed DNAzyme-RCA-based gold nanoparticle (AuNP) colorimetric and lateral flow dipstick (LFD) assays to achieve convenient detection of exosomal 5-methylcytosine miRNA-21 (m5C-miRNA-21) for the first time. The two assays achieved specific recognition and linear amplification of m5C-miRNA-21 through the DNAzyme triggered RCA reaction and color output with low background interference through AuNP aggregation induced by base complementary pairing. The lowest concentration of m5C-miRNA-21 visible to the naked eye of the two assays can reach 1 pM and 0.1 pM, respectively. Detection of exosomal m5C-miRNA-21 in clinical blood samples showed that the expression level of m5C-miRNA-21 in colorectal cancer patients was significantly higher than that in healthy individuals. This approach not only demonstrates a new strategy for the detection of colorectal cancer but also provides a reference for the development of novel diagnostic tools for other miRNA methylation-related diseases.

10.
Nat Commun ; 15(1): 5312, 2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38906856

RESUMEN

Drug exposure during pregnancy lacks global fetal safety data. The maternal drug exposure birth cohort (DEBC) study, a prospective longitudinal investigation, aims to explore the correlation of maternal drug exposure during pregnancy with pregnancy outcomes, and establish a human biospecimen biobank. Here we describe the process of establishing DEBC and show that the drug exposure rate in the first trimester of pregnant women in DEBC (n = 112,986) is 30.70%. Among the drugs used, dydrogesterone and progesterone have the highest exposure rates, which are 11.97% and 10.82%, respectively. The overall incidence of adverse pregnancy outcomes is 13.49%. Dydrogesterone exposure during the first trimester is correlated with higher incidences of stillbirth, preterm birth, low birth weight, and birth defects, along with a lower incidence of miscarriage/abortion. Due to the limitations of this cohort study, causative conclusions cannot be drawn. Further follow-up and in-depth data analysis are planned for future studies.


Asunto(s)
Exposición Materna , Resultado del Embarazo , Primer Trimestre del Embarazo , Nacimiento Prematuro , Humanos , Femenino , Embarazo , China/epidemiología , Exposición Materna/efectos adversos , Adulto , Nacimiento Prematuro/epidemiología , Estudios Prospectivos , Resultado del Embarazo/epidemiología , Didrogesterona/efectos adversos , Progesterona , Cohorte de Nacimiento , Recién Nacido , Aborto Espontáneo/epidemiología , Aborto Espontáneo/inducido químicamente , Mortinato/epidemiología , Recién Nacido de Bajo Peso , Estudios Longitudinales , Incidencia , Adulto Joven
11.
Surg Endosc ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38874610

RESUMEN

BACKGROUND: Many studies have investigated the transfer of skills between laparoscopic and robot-assisted surgery (RAS). These studies have considered time, error, and clinical outcomes in the assessment of skill transfer. However, little is known about the specific operations of the surgeon. Clutch control use is an important skill in RAS. Therefore, the present study aimed to propose a novel objective algorithm based on computer vision that can automatically evaluate a surgeon's clutch use. Additionally, the study aimed to evaluate the correlation between clutch metrics and surgical skill on different surgical robot platforms. METHODS: The robotic surgery training center of Wuhan University trained 30 laparoscopic surgeons as the study group between 2023 and 2024. Laparoscopic surgeons were trained by combining robotic simulator exercises and RAS animal experiments. During the training, video and hand movement data were collected. Hand movements identified by a skin-color model were combined with labeling information to classify clutch use. The metrics were validated on different robotic platforms (dv-Trainer, EDGE MP1000, Toumai™ MT1000, and DaVinci Xi system) and among surgeons with different surgical skill levels. RESULTS: On the robotic simulator, clutch accuracy in the expert group was significantly higher than in the study group for all tasks. No significant differences were observed in the number of clutches between the expert and study groups. In the RAS experiment, the number of clutches decreased significantly for both study and expert groups. The accuracy was maintained at a high level in the expert group but decreased rapidly in the study group. CONCLUSIONS: We proposed a new objective assessment of surgical skills, clutch use metrics, in cross-platform RAS. Additionally, we verified that the metrics significantly correlated with the surgical skill levels of the surgeons.

12.
J Mol Cell Cardiol ; 192: 79-93, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38761990

RESUMEN

Ferroptosis is an iron-dependent programmed cell death form resulting from lipid peroxidation damage, it plays a key role in organ damage and tumor development from various causes. Sepsis leads to severe host response after infection with high mortality. The long non-coding RNAs (LncRNAs) are involved in different pathophysiological mechanisms of multiple diseases. Here, we used cecal ligation and puncture (CLP) operation to mimic sepsis induced myocardial injury (SIMI) in mouse model, and LncRNAs and mRNAs were profiled by Arraystar mouse LncRNA Array V3.0. Based on the microarray results, 552 LncRNAs and 520 mRNAs were differentially expressed in the sham and CLP groups, among them, LncRNA Lcn2-204 was the highest differentially expressed up-regulated LncRNA. Iron metabolism disorder was involved in SIMI by bioinformatics analysis, meanwhile, myocardial iron content and lipocalin-2 (Lcn2) protein expressions were increased. The CNC network comprised 137 positive interactions and 138 negative interactions. Bioinformatics analysis showed several iron-related terms were enriched and six genes (Scara5, Tfrc, Lcn2, Cp, Clic5, Ank1) were closely associated with iron metabolism. Then, we constructed knockdown LncRNA Lcn2-204 targeting myocardium and found that it ameliorated cardiac injury in mouse sepsis model through modulating iron overload and ferroptosis. In addition, we found that LncRNA Lcn2-204 was involved in the regulation of Lcn2 expression in septic myocardial injury. Based on these findings, we conclude that iron overload and ferroptosis are the key mechanisms leading to myocardial injury in sepsis, knockdown of LncRNA Lcn2-204 plays the cardioprotective effect through inhibition of iron overload, ferroptosis and Lcn2 expression. It may provide a novel therapeutic approach to ameliorate sepsis-induced myocardial injury.


Asunto(s)
Ferroptosis , Técnicas de Silenciamiento del Gen , Sobrecarga de Hierro , Lipocalina 2 , Miocardio , ARN Largo no Codificante , Sepsis , Animales , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Ferroptosis/genética , Sepsis/complicaciones , Sepsis/genética , Sepsis/metabolismo , Ratones , Lipocalina 2/metabolismo , Lipocalina 2/genética , Masculino , Sobrecarga de Hierro/genética , Sobrecarga de Hierro/metabolismo , Sobrecarga de Hierro/complicaciones , Miocardio/metabolismo , Miocardio/patología , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad , Regulación de la Expresión Génica , Hierro/metabolismo , Lesiones Cardíacas/etiología , Lesiones Cardíacas/metabolismo , Lesiones Cardíacas/genética , Perfilación de la Expresión Génica
13.
Adv Sci (Weinh) ; : e2401377, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760901

RESUMEN

Tumor-associated chronic inflammation severely restricts the efficacy of immunotherapy in cold tumors. Here, a programmable release hydrogel-based engineering scaffold with multi-stimulation and reactive oxygen species (ROS)-response (PHOENIX) is demonstrated to break the chronic inflammatory balance in cold tumors to induce potent immunity. PHOENIX can undergo programmable release of resiquimod and anti-OX40 under ROS. Resiquimod is first released, leading to antigen-presenting cell maturation and the transformation of myeloid-derived suppressor cells and M2 macrophages into an antitumor immune phenotype. Subsequently, anti-OX40 is transported into the tumor microenvironment, leading to effector T-cell activation and inhibition of Treg function. PHOENIX consequently breaks the chronic inflammation in the tumor microenvironment and leads to a potent immune response. In mice bearing subcutaneous triple-negative breast cancer and metastasis models, PHOENIX effectively inhibited 80% and 60% of tumor growth, respectively. Moreover, PHOENIX protected 100% of the mice against TNBC tumor rechallenge by electing a robust long-term antigen-specific immune response. An excellent inhibition and prolonged survival in PHOENIX-treated mice with colorectal cancer and melanoma is also observed. This work presents a potent therapeutic scaffold to improve immunotherapy efficiency, representing a generalizable and facile regimen for cold tumors.

14.
J Nanobiotechnology ; 22(1): 261, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760744

RESUMEN

Delayed repair of fractures seriously impacts patients' health and significantly increases financial burdens. Consequently, there is a growing clinical demand for effective fracture treatment. While current materials used for fracture repair have partially addressed bone integrity issues, they still possess limitations. These challenges include issues associated with autologous material donor sites, intricate preparation procedures for artificial biomaterials, suboptimal biocompatibility, and extended degradation cycles, all of which are detrimental to bone regeneration. Hence, there is an urgent need to design a novel material with a straightforward preparation method that can substantially enhance bone regeneration. In this context, we developed a novel nanoparticle, mPPTMP195, to enhance the bioavailability of TMP195 for fracture treatment. Our results demonstrate that mPPTMP195 effectively promotes the differentiation of bone marrow mesenchymal stem cells into osteoblasts while inhibiting the differentiation of bone marrow mononuclear macrophages into osteoclasts. Moreover, in a mouse femur fracture model, mPPTMP195 nanoparticles exhibited superior therapeutic effects compared to free TMP195. Ultimately, our study highlights that mPPTMP195 accelerates fracture repair by preventing HDAC4 translocation from the cytoplasm to the nucleus, thereby activating the NRF2/HO-1 signaling pathway. In conclusion, our study not only proposes a new strategy for fracture treatment but also provides an efficient nano-delivery system for the widespread application of TMP195 in various other diseases.


Asunto(s)
Diferenciación Celular , Histona Desacetilasas , Células Madre Mesenquimatosas , Nanopartículas , Animales , Ratones , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Nanopartículas/química , Diferenciación Celular/efectos de los fármacos , Histona Desacetilasas/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratones Endogámicos C57BL , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Osteoblastos/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Hemo-Oxigenasa 1/metabolismo , Masculino , Regeneración Ósea/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Núcleo Celular/metabolismo , Curación de Fractura/efectos de los fármacos , Humanos , Proteínas de la Membrana
15.
Front Psychiatry ; 15: 1248424, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38726382

RESUMEN

Background: Coronary heart disease has a high incidence rate, a high mortality rate, a high recurrence rate, and a high medical cost. In addition, some patients need to undergo percutaneous coronary artery stent implantation (CASI), which is a kind of traumatic treatment. Patients can easily experience negative emotions such as anxiety and depression after surgery, which seriously affects quality of life. Objectives: The aim of this study was to evaluate the effectiveness of an empowerment-based telephone follow-up intervention on resilience and quality of life in patients who underwent CASI. Design: The design of the study is a randomized controlled trial. Methods: A total of 92 patients were recruited after CASI from the Internal Medicine Cardiovascular Department of a Grade A tertiary hospital in Xi'an, China. The patients were randomly divided into a control group and an intervention group. The control group performed routine care, whereas the intervention group developed a telephone follow-up program based on empowerment theory while carrying out routine care. Patients were investigated using the coronary heart disease-related knowledge questionnaire, the Connor-Davidson Resilience Scale (CD-RISC), and the 36-Item Short-Form Health Survey (SF-36) to compare the effects of the intervention before and after 1 month of intervention. Results: After a 1-month telephone follow-up intervention based on the empowerment theory for patients after CASI, the variations in knowledge related to coronary heart disease and all of its subscale scores were greater in the intervention group than in the control group. Except for the three dimensions of risk factor, induction factor, and rehabilitation-related knowledge, the variations in knowledge related to coronary heart disease and the other subscale scores were significantly different between the two groups (p < 0.05). The variations in resilience and scores on the three subscales in the intervention group were greater than those in the control group, and the difference between the two groups was statistically significant (p < 0.05). The variations in the quality of life and overall health, emotional functions, and social functions were significantly greater in the intervention group than in the control group (p < 0.05). Conclusions: A telephone follow-up intervention based on the empowerment theory can effectively improve the resilience and quality of life of patients after CASI. This follow-up approach can provide a theoretical basis and practical reference for hospitals and communities to carry out targeted continuing nursing for patients after CASI. The long-term effects of the intervention and its underlying mechanisms require further study. Clinical trial registration: http://www.chictr.org.cn/showproj.aspx?proj=173682, identifier ChiCTR2200064950.

16.
Front Neurol ; 15: 1342844, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715690

RESUMEN

The brachial plexus injury (BPI) is one of the most severe types of peripheral nerve injuries, often caused by upper limb traction injury. In clinic, the surgery is widely used to treat the BPI. However, surgery may need to be performed multiple times at different stages, which carries risks and brings heavy economic burden. In non-surgical treatment, splinting, local injection of corticosteroids, and oral corticosteroids can achieve significant short-term benefits, but they are prone to recurrence and may cause complications of mechanical or chemical nerve damage. In this report, we present a case of a 46-year-old female patient with BPI. The patient had difficulty in raising, flexing and extending of the left upper limb, and accompanied with the soreness and pain of neck and shoulder. After 3 months of EA treatment, a significant reduction in the inner diameter of the left C5 to C7 root at the outlet of brachial plexus nerve was detected by musculoskeletal ultrasound, and the soreness and pain in the left neck and shoulder were significantly reduced. The soreness and pain in the left neck and shoulder did not recur for 2 years. Case summary: The patient is a 46-year-old female with BPI. She experienced difficult in lifting, flexing and extending of the left upper limb, which accompanied by soreness and pain in the left neck and shoulder. After 3 months of EA treatment, the patient's pain and limb's movement disorder was improved. After 2 years of follow-up, the patient's left neck and shoulder showed no further pain. Conclusion: EA has shown satisfied efficacy in BPI, improving limb restrictions and relieving pain in patients for at least 2 years.

18.
Abdom Radiol (NY) ; 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38744698

RESUMEN

OBJECTIVE: The objective of this study was to develop a combined model based on radiomics features of Sonazoid contrast-enhanced ultrasound (CEUS) during the Kupffer phase and to evaluate its value in differentiating well-differentiated hepatocellular carcinoma (w-HCC) from atypical benign focal liver lesions (FLLs). METHODS: A total of 116 patients with preoperatively Sonazoid-CEUS confirmed w-HCC or benign FLL were selected from a prospective multiple study on the clinical application of Sonazoid in FLLs conducted from August 2020 to March 2021. According to the randomization principle, the patients were divided into a training cohort and a test cohort in a 7:3 ratio. Seventy-nine patients were used for establishing and training the radiomics model and combined model. In comparison, 37 patients were used for validating and comparing the performance of the models. The diagnostic efficacy of the models for w-HCC and atypical benign FLLs was evaluated using ROCs curves and decision curves. A combined model nomogram was created to assess its value in reducing unnecessary biopsies. RESULTS: Among the patients, there were 55 cases of w-HCC and 61 cases of atypical benign FLLs, including 28 cases of early liver abscess, 16 cases of atypical hepatic hemangioma, 8 cases of hepatocellular dysplastic nodules (DN), and 9 cases of focal nodular hyperplasia (FNH). The radiomics model and combined model we established had AUCs of 0.905 and 0.951, respectively, in the training cohort, and the AUCs of the two models in the test cohort were 0.826 and 0.912, respectively. The combined model outperformed the radiomics feature model significantly. Decision curve analysis demonstrated that the combined model achieved a higher net benefit within a specific threshold probability range (0.25 to 1.00). A nomogram of the combined model was developed. CONCLUSION: The combined model based on the radiomics features of Sonazoid-CEUS in the Kupffer phase showed satisfactory performance in diagnosing w-HCC and atypical benign FLLs. It can assist clinicians in timely detecting malignant FLLs and reducing unnecessary biopsies for benign diseases.

19.
J Clin Ultrasound ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38786768

RESUMEN

Liver involvement in lymphoma often manifests as nonoccupying diffuse infiltration, posing challenges in distinguishing it from primary liver disorder. Herein, we present the case of a 21-year-old female who underwent two separate diagnoses within a nine-month interval before being ultimately diagnosed with peripheral T-cell lymphoma, not otherwise specified. Our review of this case identified an ultrasound imaging feature, the hypoechoic periportal cuffing. When combined with associated increased lymphocyte count and liver enlargement, it can serve as a noninvasive suggestion for malignant disorders, in particular hemic and lymphatic diseases.

20.
J Ethnopharmacol ; 331: 118274, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38697410

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive dysfunction and metabolic abnormalities, particularly characterized by insulin resistance and chronic low-grade inflammation. Multiple clinical studies have clearly demonstrated the significant efficacy and safety of the combination of Bailing capsules (BL) in the treatment of PCOS, but its pharmacological effects and mechanisms still require further study. AIM OF THE STUDY: To evaluate the effect of BL on improving PCOS in mice and explore the mechanism. METHODS: In this study, Dehydroepiandrosterone (DHEA) injection was administered alone and in combination with a high-fat and high-sugar diet to induce PCOS-like mouse. They were randomly divided into five groups: normal group (N), PCOS group (P), Bailing capsule low-dose group (BL-L), Bailing capsule high-dose group (BL-H) and Metformin + Daine-35 group (M + D). Firstly, the effects of BL on ovarian lesions, serum hormone levels, HOMA-IR, intestinal barrier function, inflammation levels, along with the expression of IRS1, PI3K, AKT, TLR4, Myd88, NF-κB p65, TNF-α, IL-6, and Occludin of the ovary, liver and colon were investigated. Finally, the composition of the gut microbiome of fecal was tested. RESULTS: The administration of BL significantly reduced body weight, improved hormone levels, improved IR, and attenuated pathological damage to ovarian tissues, up-regulated the expression of IRS1, PI3K, and AKT in liver. It also decreased serum LPS, TNF-α, and IL-6 levels, while downregulating the expression of Myd88, TLR4, and NF-κB p65. Additionally, BL improved intestinal barrier damage and upregulated the expression of Occludin. Interestingly, the abundance of norank_f__Muribaculacea and Lactobacillus was down-regulated, while the abundance of Akkermansia was significantly up-regulated. CONCLUSION: The results of the study showed that BL exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota, the improvement of insulin resistance and the intestinal-derived LPS-TLR4 inflammatory pathway. Our research will provide a theoretical basis for the clinical treatment of PCOS.


Asunto(s)
Medicamentos Herbarios Chinos , Lipopolisacáridos , Síndrome del Ovario Poliquístico , Transducción de Señal , Receptor Toll-Like 4 , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/inducido químicamente , Animales , Femenino , Receptor Toll-Like 4/metabolismo , Ratones , Transducción de Señal/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Resistencia a la Insulina , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Deshidroepiandrosterona/farmacología , Cápsulas , Intestinos/efectos de los fármacos , Ratones Endogámicos C57BL , Ovario/efectos de los fármacos , Ovario/metabolismo , Ovario/patología
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