Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.897
Filtrar
1.
J Environ Sci (China) ; 150: 571-581, 2025 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-39306430

RESUMEN

Fifty agricultural soil samples collected from Fuzhou, southeast China, were first investigated for the occurrence, distribution, and potential risks of twelve organophosphate esters (OPEs). The total concentration of OPEs (ΣOPEs) in soil ranged from 1.33 to 96.5 ng/g dry weight (dw), with an average value of 17.1 ng/g dw. Especially, halogenated-OPEs were the predominant group with a mean level of 9.75 ng/g dw, and tris(1-chloro-2-propyl) phosphate (TCIPP) was the most abundant OPEs, accounting for 51.1% of ΣOPEs. The concentrations of TCIPP and ∑OPEs were found to be significantly higher (P < 0.05) in soils of urban areas than those in suburban areas. In addition, the use of agricultural plastic films and total organic carbon had a positive effect on the occurrence of OPE in this study. The positive matrix factorization model suggested complex sources of OPEs in agricultural soils from Fuzhou. The ecological risk assessment demonstrated that tricresyl phosphate presented a medium risk to land-based organisms (0.1 ≤ risk quotient < 1.0). Nevertheless, the carcinogenic and non-carcinogenic risks for human exposure to OPEs through soil ingestion and dermal absorption were negligible. These findings would facilitate further investigations into the pollution management and risk control of OPEs.


Asunto(s)
Agricultura , Monitoreo del Ambiente , Ésteres , Organofosfatos , Contaminantes del Suelo , Suelo , China , Contaminantes del Suelo/análisis , Suelo/química , Organofosfatos/análisis , Ésteres/análisis , Medición de Riesgo
2.
World J Clin Oncol ; 15(9): 1168-1176, 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39351453

RESUMEN

Homeobox (HOX) C9, a member of the HOX family, is an important transcription factor, and it plays a significant role in various biological processes. This family of genes is highly valued for their essential roles in establishing and maintaining the body axis during embryonic development and adult tissues. Further, HOXC9 plays a central role in neuronal differentiation, angiogenesis, and adipose distribution, which are essential for the development of the nervous system, maturation of tissues and organs, and maintenance of energy balance and metabolic health. Recent research has found that abnormal HOXC9 expression is closely associated with the development and progression of various tumor types. The HOXC9 expression level can be an indicator of tumor prognosis. Therefore, elucidating the association between HOXC9 expression and its regulatory mechanisms and tumorigenesis can provide novel insights on the diagnosis and treatment of patients with cancer.

3.
Pain Physician ; 27(7): E775-E784, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39353125

RESUMEN

BACKGROUND: Trigeminal herpetic neuralgia (THN) presents with severe pain hyperalgesia and is a high-risk factor for postherpetic neuralgia (PHN). The current clinical treatments for THN are unsatisfactory, and new treatments are desperately required. OBJECTIVES: This pilot study aimed to evaluate the efficacy of short-term trigeminal ganglion stimulation in treating patients with multi-branch THN. STUDY DESIGN: A prospective pilot study. SETTING: Multi-center study in 3 academic hospitals. METHODS: From July 2021 to October 2022, we enrolled 20 patients with multi-branch THN who received short-term trigeminal ganglion stimulation under general anesthesia from 3 hospitals. All patients completed a 12-month follow-up. The visual analog scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) were used to assess patients' pain and quality of sleep. The Barrow Neurological Institute (BNI) score was used to determine the global outcome of pain relief, and complications were recorded. RESULTS: Significant and sustained pain relief and sleep improvement were achieved by all the patients who underwent trigeminal ganglion electrode stimulation in the present study. Respective BNI scores of 80% and 85% at 3 and 12 months after surgery were considered good. There were no other serious complications except for 2 patients' experiences of transient trigeminal cardiac reflex during the surgery and transient numbness deterioration in one patient's V3 sensory area. LIMITATIONS: The present study is a pilot study. We expect prospective multi-center, large-sample studies in the future. CONCLUSION: Short-term trigeminal ganglion stimulation can be used safely and effectively to treat patients with multi-branch THN and significantly reduce the occurrence of PHN.


Asunto(s)
Terapia por Estimulación Eléctrica , Ganglio del Trigémino , Neuralgia del Trigémino , Humanos , Proyectos Piloto , Estudios Prospectivos , Neuralgia del Trigémino/terapia , Terapia por Estimulación Eléctrica/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neuralgia Posherpética/terapia , Dimensión del Dolor , Resultado del Tratamiento
4.
Biochem Biophys Res Commun ; 734: 150752, 2024 Sep 26.
Artículo en Inglés | MEDLINE | ID: mdl-39353358

RESUMEN

Neuropeptides play crucial roles in regulating various physiological processes in vertebrates. In this study, we identified a novel neuropeptide-encoding gene, nwk, in the genomes of some vertebrate species. The nwk cDNA was subsequently cloned from the brain of zebrafish. The Nwk precursor comprises 88 amino acids, with a putative mature peptide (Nwk-22) of 22 amino acids. Sequence analysis revealed that Nwk-22 is relatively conserved across vertebrate species. Nwk is predominantly expressed in the brain, with positive mRNA cells identified in the TPp and preoptic area. Intraperitoneal injection of Nwk-22 suppressed food intake and downregulated the mRNA expression of the orexigenic factor agouti-related peptide (agrp) in zebrafish. Additionally, a CRISPR/Cas9 approach was used to generate nwk mutant zebrafish. The nwk-/- zebrafish exhibited increased food consumption compared to wild-type controls. Furthermore, Nwk-22a injection in nwk-/- fish also suppressed agrp expression while stimulating the expression of the anorexigenic gene pomca, further supporting the anorexigenic role of Nwk. Taken together, these findings suggest that Nwk functions as an anorexigenic factor, reducing food intake by downregulating orexigenic genes like agrp and upregulating anorexigenic genes like pomc in zebrafish.

5.
Front Plant Sci ; 15: 1454046, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39354949

RESUMEN

Pectin is a vital component of plant cell walls and its methylation process is regulated by pectin methylesterase inhibitors (PMEIs). PMEIs regulate the structural and functional modifications of cell walls in plants and play an important role in plant processes such as seed germination, fruit ripening, and stress response. Although the PMEI gene family has been well characterized in model plants, the understanding of its molecular evolution and biological functions in watermelon remains limited. In this study, 60 ClPMEI genes were identified and characterized, revealing their dispersion on multiple chromosomes. Based on a systematic developmental analysis, these genes were classified into three subfamilies, which was further supported by the exon, intron, and conserved motif distribution. Analysis of cis-elements and expression patterns indicated that ClPMEIs might be involved in regulating the tolerance of watermelon to various abiotic stresses. Moreover, distinct ClPMEI genes exhibit specific functions under different abiotic stresses. For example, ClPMEI51 and ClPMEI54 showed a significant upregulation in expression levels during the late stage of drought treatments, whereas ClPMEI3 and ClPMEI12 displayed a significant downregulation under low-temperature induction. Subcellular localization prediction and analysis revealed that the ClPMEI family member proteins were localized to the cell membrane. This study provided an important foundation for the further exploration of the functions of ClPMEI genes in watermelon.

6.
Transl Oncol ; 50: 102138, 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39357466

RESUMEN

Adoptive cell therapy (ACT) has revolutionized the treatment of patients with cancer. The success of ACT depends largely on transferred T cell status, particularly their less-differentiated state with stem cell-like properties, which enhances ACT effectiveness. Stem cell-like memory T (TSCM) cells exhibit continuous self-renewal and multilineage differentiation similar to pluripotent stem cells. TSCM cells are promising candidates for cancer immunotherapies, whereas maintenance of a more stem-cell-like state before transfer is challenging. Here, we established a highly efficient protocol for generating CD8+ TSCM cells from peripheral blood mononuclear cells (PBMCs). The process involved activating PBMCs using anti-CD3 monoclonal antibody and RetroNectin, followed by a transient-resting culture period (24 h) and subsequent long-term expansion in vitro with interlukien-2. We report that this transient-resting culture after activation preserves CD8+ T cells in a stem memory phenotype (CD95+ CD45RA+ CCR7+) compared to the conventional culture method. Further, this approach reduces the expression of T cell immunoglobulin mucin-3, an exhaustion marker, and increases the expression of T cell factor-1, a master regulator of stemness even after long-term culture compared to the conventional culture method. In conclusion, our study presents a simplified and cost-effective method for generating and expanding CD8+ TSCM cells ex vivo. This approach streamlines the optimization of cancer immunotherapy using ACT.

7.
Asian J Surg ; 2024 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-39358149
8.
Sci Adv ; 10(40): eadp8045, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39356757

RESUMEN

The construction of miniaturized light-emitting diodes (LEDs) with high external quantum efficiency (EQE) at room temperature remains a challenge for on-chip optoelectronics. Here, we demonstrate microsized LEDs fabricated by a dry-transfer van der Waals (vdW) integration method using typical layered Ruddlesden-Popper perovskites (RPPs). A single-crystalline layered RPP nanoflake is used as the active layer and sandwiched between two few-layer graphene contacts, forming van der Waals LEDs (vdWLEDs). Strong electroluminescence (EL) emission with a low turn-on current density of ~20 pA µm-2 and high EQE exceeding 10% is observed at room temperature, which sets the benchmark for the EQE of vdWLEDs ever recorded. Such efficient EL emission is attributed to the inherent multiple quantum well structure and high photoluminescence quantum yield (~35%) of RPPs and a low charge injection barrier of ~0.10 eV facilitated by the Fowler-Nordheim tunneling mechanism. These findings promise a scalable pathway for accessing high-performance miniaturized light sources for on-chip optical optoelectronics.

9.
Microbiol Spectr ; : e0071924, 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39365050

RESUMEN

Lung cancer accounts for the large majority of cancer incidence and mortality worldwide for decades. The dysbiotic microbiome and its metabolite secretions in the gut have been regarded as the dominant biological factors in oncogenesis, development, and progression, adding probiotic components of which have come to be potential therapeutic regimes. However, there still exists little knowledge about whether probiotic microorganisms in lower airways inhibit lung cancer by lung microenvironment remodulation. In this study, we performed bioinformatics analysis from previous sequencing data and specific microbiome databases to identify the potent protective microbes in lower airways, followed by bacterial cultivation and morphological verifications in vitro. We found that Paenibacillus odorifer was correlated closely with the anti-tumorous by-product acetic acid in lower respiratory tract. Additionally, the enrichment of this microorganism in the health, rather than in lung neoplasms from public data sets, further confirmed its protective activity in preserving pulmonary homeostasis. Colony cultivation of this strain and targeted metabolite analysis indicated that Paenibacillus odorifer proliferation was weakened at 37°C but lasted longer than it did at the optimal temperature. And performing as a candidate origin of acetic acid, this strain was liable to inhibit the growth of lung cancer cells in time- and dose-dependent approaches which was validated by colony formation assays. These results suggested that Paenibacillus odorifer functions as a candidate probiotic in lower airways to restrict lung cancer cell growth by releasing protective molecules, indicating a potential preventive microbial strategy.IMPORTANCEVarious types of microorganisms in lower respiratory tracts protect local homeostasis against oncogenesis. Although extensive efforts engaged in gut microbiome-mediated pulmonary carcinogenesis, emerging evidence suggested the crucial role of microbial metabolites from respiratory tracts in modulating carcinogenesis-related host inflammation and DNA damage in lung cancer, which was still not fully understood in lower respiratory tract microbes and its metabolite-mediated microecological environment homeostasis in preventing or alleviating lung cancer. In this study, we analyzed the lower respiratory tract microbiome and SCFAs expression among different lung segments from the same participants, further identifying that Paenibacillus odorifer was correlated closely with anti-tumorous by-product, acetate acid in lower respiratory tract by multi-omics analysis. And previous experiments showed this strain could inhibit the growth of lung cancer cells in vitro. These findings indicated that Paenibacillus odorifer in lower respiratory tracts might perform as a candidate probiotic against lung carcinogenesis by releasing protective factor acetate, which further presented a promising diagnostic and interventional approach in clinical settings of lung cancer.

10.
Mol Divers ; 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39377892

RESUMEN

Developing new fungicides to compensate for the deficiencies of existing fungicides resistance in phytopathogenic fungi is a research hotspot in the field of pesticides. Aiming to discover novel template small molecules with excellent antifungal activity, thirty-eight arylthiazolamine derivatives were synthesized through bromination, cyclization, halogenation, and acylation reactions. The synthesized compounds were screened for antifungal activity against ten typical fungal pathogens, and some halogenated arylthiazolamines and amides exhibited excellent broad-spectrum antifungal activity, especially compounds 4m (3.96-47.76 µg/mL), 5k (0.10-7.70 µg/mL) and 5n (2.08-11.21 µg/mL). Among them, compound 5k provided comparable protection and curative effects to chloroticonil and boscalid against B. dothidea and V. mali infection in apple and apple tree branches, respectively, and it could exert antifungal effects by inhibiting the differentiation of mycelium spores, spore germination, and bud tube growth. This study provides high-efficiency and inexpensive candidate compounds for managing of diseases caused by plant pathogenic fungi.

11.
Asian J Surg ; 2024 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-39368951

RESUMEN

OBJECTIVE: To delve deeper into the study of degenerative diseases, it becomes imperative to investigate whether deep-learning reconstruction (DLR) can improve the evaluation of white matter hyperintensity (WMH) on 3.0T scanners, and compare its lesion detection capabilities with conventional reconstruction (CR). METHODS: A total of 131 participants (mean age, 46 years ±17; 46 men) were included in the study. The images of these participants were evaluated by readers blinded to clinical data. Two readers independently assessed subjective image indicators on a 4-point scale. The severity of WMH was assessed by four raters using the Fazekas scale. To evaluate the relative detection capabilities of each method, we employed the Wilcoxon signed rank test to compare scores between the DLR and the CR group. Additionally, we assessed interrater reliability using weighted k statistics and intraclass correlation coefficient to test consistency among the raters. RESULTS: In terms of subjective image scoring, the DLR group exhibited significantly better scores compared to the CR group (P < 0.001). Regarding the severity of WMH, the DL group demonstrated superior performance in detecting lesions. Majority readers agreed that the DL group provided clearer visualization of the lesions compared to the conventional group. CONCLUSION: DLR exhibits notable advantages over CR, including subjective image quality, lesion detection sensitivity, and inter reader reliability.

12.
ACS Infect Dis ; 10(10): 3650-3663, 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39360613

RESUMEN

Cholesterol is a key carbon source for Mycobacterium tuberculosis (Mtb) survival and persistence within macrophages. However, little is known about the role of cholesterol metabolism by Mtb in host-Mtb interplay. Here, we report the immune suppression mediated by Mtb's cholesterol metabolites. Conducting the cholesterol metabolic profiling and loss-of-function experiments, we show that the cholesterol oxidation products catalyzed by a thiolase FadA5 from Mtb H37Ra, 4-androstenedione (AD), and its derivant 1,4-androstenedione (ADD) inhibit the expression of pro-inflammatory cytokines and thus promote bacterial survival in bone marrow-derived macrophages (BMDMs). Our time-resolved fluorescence resonance energy transfer (TR-FRET)-based screening further identifies the nuclear receptor LXRα as the target of ADD. Activation of LXRα via ADD impedes the nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPK) signaling and reduces cholesterol accumulation in lipid rafts upon TLR4 simulation, thereby compromising the inflammatory responses. Our findings provide the evidence that Mtb could suppress the host immunity through its cholesterol metabolic enzyme and products, which are potential targets for screening novel anti-tuberculosis (TB) agents.


Asunto(s)
Colesterol , Receptores X del Hígado , Macrófagos , Mycobacterium tuberculosis , Tuberculosis , Colesterol/metabolismo , Animales , Receptores X del Hígado/metabolismo , Ratones , Macrófagos/efectos de los fármacos , Macrófagos/microbiología , Macrófagos/metabolismo , Tuberculosis/microbiología , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Citocinas/metabolismo , Inflamación/metabolismo , Humanos , Interacciones Huésped-Patógeno
13.
Int J Biol Macromol ; 281(Pt 2): 136199, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39366613

RESUMEN

Sirtuins (SRTs) are nicotinamide adenine dinucleotide (NAD+) dependent II histone deacetylases (HDACs) that have been understudied in horticultural crops. However, their functions in regulating mitochondrial energy metabolism and influencing fruit development and quality formation remain unclear. In this study, we found that FaSRT2-1 exhibits diverse subcellular localizations. Overexpression of FaSRT2-1 promoted strawberry fruit quality formation (soluble sugars, organic acids, anthocyanins) and accelerated ripening. Conversely, knockout of FaSRT2-1 yielded opposite results. During fruit ripening, ATP content and ATP/ADP ratio gradually increased, and FaSRT2-1 promoted ATP accumulation and decreased before and after the deep red stage, respectively, indicating its role in fruit ripening and senescence. FaSRT2-1 interacted with energy-related proteins (FaRPT4a, FaATPß and FaATPγ) to increase ATP content and the ATP/ADP ratio. Additionally, FaSRT2-1 collaborated with FaGDH2 and FaWDR5B to increase the accumulation of soluble sugars, organic acids and anthocyanins. Meanwhile, FaRPT4a, FaATPγ, FaGDH2 and FaWDR5B were co-localized with FaSRT2-1, while FaATPß was localized in both the cytoplasm and mitochondria. Transient overexpression experiments further highlight the roles of FaRPT4a and FaGDH2/FaWDR5B in modulating ATP accumulation and fruit ripening, respectively. In summary, FaSRT2-1 plays important roles in promoting strawberry fruit ripening, senescence and quality formation by regulating energy metabolism.

14.
Heliyon ; 10(18): e38203, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39381249

RESUMEN

Background: Hemorrhagic events cause numerous deaths annually worldwide, highlighting the urgent need for effective hemostatic drugs. The glucosyloxybenzyl 2-isobutylmalates Control Extract (BSCE) from the orchid plant Bletilla striata (Thunb.) Rchb.f. has demonstrated significant hemostatic activity in both in vitro and in vivo studies. However, the effect and mechanism of BSCE on non-traumatic bleeding remain unclear. Methods: Pulmonary hemorrhage was induced in 40 Sprague-Dawley rats by administering Zingiber officinale Roscoe. for 14 days. These rats were then randomly divided into five groups: model (Mod), positive control (YNBY), and BSCE low, medium, and high-dose groups. An additional 8 rats served as the control group (Con). The BSCE groups received different doses of BSCE for 10 days, while the YNBY group received Yunnan Baiyao suspension. The effects on body weight, food and water intake, red blood cell count (RBC), hemoglobin concentration (HGB), lung tissue pathology, platelet count, coagulation parameters, and fibrinolytic system markers were evaluated. Network pharmacology and molecular docking analyses were also conducted to identify potential targets and pathways involved in BSCE's effects. Results: BSCE treatment significantly improved body weight, food intake, and water consumption in rats with pulmonary hemorrhage. RBC and HGB levels increased significantly in the BSCE medium and high-dose groups compared to the Mod group (P < 0.05). Pathological examination revealed that BSCE reduced lung tissue hemorrhage and inflammation, with improvements in alveolar structure. BSCE also positively affected platelet count, thrombin time (TT), activated partial thromboplastin time (APTT), fibrinogen (FIB) levels, and fibrinolytic markers (D-dimer, PAI-1, and t-PA). Network pharmacology and molecular docking identified key targets such as MMPs, CASPs, and pathways including IL-17 and TNF signaling, suggesting BSCE's involvement in hemostasis and anti-inflammatory processes. Conclusions: BSCE exhibits significant hemostatic and protective effects on Z.officinale-induced pulmonary hemorrhage in rats by improving hematological parameters, reducing lung tissue damage, and modulating the coagulation and fibrinolytic systems. The study provides evidence supporting the potential of BSCE as a therapeutic agent for hemorrhagic diseases, with its efficacy linked to multi-target and multi-pathway interactions.

15.
Plant Cell ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39383255

RESUMEN

Plant height is an important agronomic characteristic of rice (Oryza sativa L.). Map-based cloning analyses of a natural semi-dwarf rice mutant with inwardly curled leaves found in the field revealed that the defects were due to a mutation of a SHAQKYF-class MYB family transcription factor, OsKANADI1 (OsKAN1). OsKAN1 directly bound to the OsYABBY5 (OsYAB5) promoter to repress its expression and interacted with OsYAB5 to form a functional OsKAN1-OsYAB5 complex. GIBERELLIN 2-OXIDASE6 (OsGA2ox6), encoding an enzyme in the gibberellin (GA) catabolic pathway, was activated by OsYAB5. Furthermore, the OsKAN1-OsYAB5 complex suppressed the inhibitory effect of OsKAN1 toward OsYAB5 and inhibited OsYAB5-induced OsGA2ox6 expression. The proOsKAN1:OsYAB5 transgenic plants were taller than wild-type plants, whereas oskan1 proOsKAN1:OsYAB5 plants exhibited a severe dwarf phenotype due to the absence of the OsKAN1-OsYAB5 complex. The OsKAN1-OsYAB5 complex modulated OsGA2ox6 expression, thereby regulating the levels of bioactive gibberellins and, consequently, plant height. This study elucidated the mechanism underlying the effect of the OsKAN1-OsYAB5-OsGA2ox6 regulatory pathway on plant height at different positions in rice stems and provided insights on stem development and candidate genes for the aerial architecture improvement of crop plants.

16.
Brain Cogn ; 181: 106223, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39383675

RESUMEN

INTRODUCTION: This study aims to explore the impact of smoking on intrinsic brain activity among high-altitude (HA) populations. Smoking is associated with various neural alterations, but it remains unclear whether smokers in HA environments exhibit specific neural characteristics. METHODS: We employed ALFF and fALFF methods across different frequency bands to investigate differences in brain functional activity between high-altitude smokers and non-smokers. 31 smokers and 31 non-smokers from HA regions participated, undergoing resting-state functional magnetic resonance imaging (rs-fMRI) scans. ALFF/fALFF values were compared between the two groups. Correlation analyses explored relationships between brain activity and clinical data. RESULTS: Smokers showed increased ALFF values in the right superior frontal gyrus (R-SFG), right middle frontal gyrus (R-MFG), right anterior cingulate cortex (R-ACC), right inferior frontal gyrus (R-IFG), right superior/medial frontal gyrus (R-MSFG), and left SFG compared to non-smokers in HA. In sub-frequency bands (0.01-0.027 Hz and 0.027-0.073 Hz), smokers showed increased ALFF values in R-SFG, R-MFG, right middle cingulate cortex (R-MCC), R-MSFG, Right precentral gyrus and L-SFG while decreased fALFF values were noted in the right postcentral and precentral gyrus in the 0.01-0.027 Hz band. Negative correlations were found between ALFF values in the R-SFG and smoking years. CONCLUSION: Our study reveals the neural characteristics of smokers in high-altitude environments, highlighting the potential impact of smoking on brain function. These results provide new insights into the neural mechanisms of high-altitude smoking addiction and may inform the development of relevant intervention measures.

17.
ACS Appl Bio Mater ; 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39392531

RESUMEN

Atherosclerosis, characterized by chronic inflammation within the arterial wall, remains a pivotal concern in cardiovascular health. We developed a dual-targeted liposomal system encapsulating Dll4-targeting siRNA, designed to selectively bind to pro-inflammatory M1 macrophages through surface conjugation with anti-F4/80 and anti-CD68 antibodies. The Dll4-targeting siRNA is then delivered to the macrophages, where it silences Dll4 expression, inhibiting Notch signaling and reducing plaque vulnerability. Emphasizing accuracy in targeting, the system demonstrates effective suppression of Dll4, a key modulator of atherosclerotic progression, and vulnerability via VSMCs phenotypic conversion and senescence. By employing liposomes for siRNA delivery, we observed enhanced stability and specificity of the siRNA. Alongside the therapeutic efficacy, our study also evaluated the safety profile and pharmacokinetics of the dual-targeted liposomal system, revealing favorable outcomes with minimal off-target effects and optimal biodistribution. The integration of RNA interference techniques with advanced nanotechnological methodologies signifies the importance of targeted delivery in this therapeutic approach. Preliminary findings suggest a potential attenuation in plaque development and vulnerability, indicating the therapeutic promise of this approach. This research emphasizes the potential of nanocarrier-mediated precision targeting combined with a reassuring safety and pharmacokinetic profile for advancing atherosclerosis therapeutic strategies.

18.
Clin Ophthalmol ; 18: 2721-2730, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39372223

RESUMEN

Purpose: The objective of this research was to assess the effectiveness and safety of using Conbercept injection and dexamethasone implant (DEX I) in sequence for treating refractory macular edema (ME) caused by central retinal vein occlusion (CRVO) in patients. Methods: A study was conducted on 34 patients with persistent macular edema caused by central retinal vein occlusion, reviewing their medical history and interventions performed. Sequential implantation of DEX I was performed 1 week after the Conbercept injection. OCTA images were used to measure central retinal thickness (CRT), best-corrected visual acuity (BCVA), intraocular pressure (IOP), and pre- and post-treatment vessel density of the superficial capillary plexus (SCP) and deep capillary plexus (DCP), with a 1-year follow-up period. Results: At the 12-month follow-up, participants demonstrated notable improvements in central retinal thickness and intraocular pressure (p < 0.05). Throughout the monitoring period, no significant differences were found in BCVA improvement or vessel density reduction (p > 0.05). Two patients required topical treatment to lower their intraocular pressure during the study period. Conclusion: In conclusion, patients experiencing persistent ME due to secondary CRVO may benefit from transitioning to a treatment regimen involving Conbercept and DEX I, potentially resulting in a reduction in CRT. However, no significant improvement was observed in BCVA or deep and superficial capillary plexus vessel density.

19.
MedComm (2020) ; 5(10): e760, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39372389

RESUMEN

Glycoproteins, representing a significant proportion of posttranslational products, play pivotal roles in various biological processes, such as signal transduction and immune response. Abnormal glycosylation may lead to structural and functional changes of glycoprotein, which is closely related to the occurrence and development of various diseases. Consequently, exploring protein glycosylation can shed light on the mechanisms behind disease manifestation and pave the way for innovative diagnostic and therapeutic strategies. Nonetheless, the study of clinical glycoproteomics is fraught with challenges due to the low abundance and intricate structures of glycosylation. Recent advancements in mass spectrometry-based clinical glycoproteomics have improved our ability to identify abnormal glycoproteins in clinical samples. In this review, we aim to provide a comprehensive overview of the foundational principles and recent advancements in clinical glycoproteomic methodologies and applications. Furthermore, we discussed the typical characteristics, underlying functions, and mechanisms of glycoproteins in various diseases, such as brain diseases, cardiovascular diseases, cancers, kidney diseases, and metabolic diseases. Additionally, we highlighted potential avenues for future development in clinical glycoproteomics. These insights provided in this review will enhance the comprehension of clinical glycoproteomic methods and diseases and promote the elucidation of pathogenesis and the discovery of novel diagnostic biomarkers and therapeutic targets.

20.
J Hepatocell Carcinoma ; 11: 1861-1874, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39372710

RESUMEN

Background: To develop and validate an innovative predictive model that integrates multisequence magnetic resonance (MR) radiomics, deep learning features, and clinical indicators to accurately predict the recurrence of hepatocellular carcinoma (HCC) after thermal ablation. Methods: This retrospective multicenter cohort study enrolled patients who were diagnosed with HCC and treated via thermal ablation. We extracted radiomic features from multisequence 3T MR images, analyzed these images using a 3D convolutional neural network (3D CNN), and incorporated clinical data into the model. Model performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. Results: The study included 535 patients from three hospitals, comprising 462 males and 43 females. The RDC model, which stands for the Radiomics-Deep Learning-Clinical data model, demonstrated high predictive accuracy, achieving AUCs of 0.794 in the training set, 0.777 in the validation set, and 0.787 in the test set. Statistical analysis confirmed the model's robustness and the significant contribution of the integrated features to its predictive capabilities. Conclusion: The RDC model effectively predicts HCC recurrence after thermal ablation by synergistically combining advanced imaging analysis and clinical parameters. This study highlights the potential of such integrative approaches to enhance prognostic assessments in HCC patients and offers a promising tool for clinical decision-making.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA