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1.
Anal Methods ; 2024 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-38738644

RESUMEN

Extracellular vesicles (EVs) are nanoparticles secreted by cells with a closed phospholipid bilayer structure, which can participate in various physiological and pathological processes and have significant clinical value in disease diagnosis, targeted therapy and prognosis assessment. EV isolation methods currently include differential ultracentrifugation, ultrafiltration, size exclusion chromatography, immunoaffinity, polymer co-precipitation and microfluidics. In addition, material-based biochemical or biophysical approaches relying on intrinsic properties of the material or its surface-modified functionalized monomers, demonstrated unique advantages in the efficient isolation of EVs. In order to provide new ideas for the subsequent development of material-based EV isolation methods, this review will focus on the principle, research status and application prospects of material-based EV isolation methods based on different material carriers and functional monomers.

2.
Environ Sci Technol ; 58(20): 8955-8965, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38718175

RESUMEN

The development of Fe-based catalysts for the selective catalytic reduction of NOx by NH3 (NH3-SCR of NOx) has garnered significant attention due to their exceptional SO2 resistance. However, the influence of different sulfur-containing species (e.g., ferric sulfates and ammonium sulfates) on the NH3-SCR activity of Fe-based catalysts as well as its dependence on exposed crystal facets of Fe2O3 has not been revealed. This work disclosed that nanorod-like α-Fe2O3 (Fe2O3-NR) predominantly exposing (110) facet performed better than nanosheet-like α-Fe2O3 (Fe2O3-NS) predominantly exposing (001) facet in NH3-SCR reaction, due to the advantages of Fe2O3-NR in redox properties and surface acidity. Furthermore, the results of the SO2/H2O resistance test at a critical temperature of 250 °C, catalytic performance evaluations on Fe2O3-NR and Fe2O3-NS sulfated by SO2 + O2 or deposited with NH4HSO4 (ABS), and systematic characterization revealed that the reactivity of ammonium sulfates on Fe2O3 catalysts to NO(+O2) contributed to their improved catalytic performance, while ferric sulfates showed enhancing and inhibiting effects on NH3-SCR activity on Fe2O3-NR and Fe2O3-NS, respectively; despite this, Fe2O3-NR showed higher affinity for SO2 + O2. This work set a milestone in understanding the NH3-SCR reaction on Fe2O3 catalysts in the presence of SO2 from the aspect of crystal facet engineering.


Asunto(s)
Amoníaco , Catálisis , Amoníaco/química , Dióxido de Azufre/química , Compuestos Férricos/química , Oxidación-Reducción
3.
Technol Cancer Res Treat ; 23: 15330338241252605, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38759699

RESUMEN

OBJECTIVE: 1q21 gain/Amp is one of the most common cytogenetic abnormalities. There are controversies about its effects on prognosis and may be associated with inferior outcomes in patients with newly diagnosed multiple myeloma (NDMM). To explore the optimal induction treatment, we analyzed and compared the efficacy of combinations of bortezomib-lenalidomide-dexamethasone (VRD) and only bortezomib-based triplet regimens without lenalidomide (only bortezomib-based) as induction therapy in patients with NDMM with 1q21 gain/Amp. METHODS: Seventy-six NDMM patients with 1q21 gain/Amp who were admitted to our center from 2016 to 2022 were retrospectively analyzed in this study. The progression and efficacy of the patients were observed. RESULTS: Within our study group, the overall survival rate stood at 75.0%, and the progression-free survival (PFS) rate reached 40.8% in NDMM patients with 1q21 gain/Amp. The best outcome assessment was that 17.1% achieved complete response (CR) and 44.7% achieved very good partial response (VGPR). Patients in the VRD group had a deeper response (VGPR: 63.6% vs 37.0%, P = 0.034), lower disease progression rate (31.8% vs 70.3%, P = 0.002), longer sustained remission (median 49.7 months vs 18.3 months, P = 0.030), and longer PFS (median 61.9 months vs 22.9 months, P = 0.032) than those treated with only bortezomib-based induction therapy. No significant differences were found among patients with partial response or better (86.4% vs 77.8%, P = 0.532) or CR (27.3% vs 13.0%, P = 0.180). Multivariate analysis showed that only bortezomib-based induction therapy (P = 0.003, HR 0.246, 95% CI 0.097-0.620), International Staging System stage III (P = 0.003, HR 3.844, 95% CI 1.588-9.308) and LMR <3.6 (P = 0.032, HR 0.491, 95% CI 0.257-0.940) were significantly associated with adverse PFS. CONCLUSIONS: When compared with the sequential administration of bortezomib and lenalidomide or only bortezomib-based protocols, NDMM patients with 1q21 gain/Amp may benefit more from VRD as initial treatments.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib , Cromosomas Humanos Par 1 , Lenalidomida , Mieloma Múltiple , Humanos , Bortezomib/administración & dosificación , Lenalidomida/administración & dosificación , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/mortalidad , Mieloma Múltiple/genética , Femenino , Masculino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Anciano , Cromosomas Humanos Par 1/genética , Adulto , Estudios Retrospectivos , Pronóstico , Resultado del Tratamiento , Aberraciones Cromosómicas , Anciano de 80 o más Años , Dexametasona/administración & dosificación
4.
Glob Health Med ; 6(2): 160-163, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38690133

RESUMEN

Long COVID (LC)-related health problems are highly concerned. Many patients seem to have "recovered" from an acute SARS-CoV-2 infection, however, they might experience various symptoms, almost involving all organs and systems. Of those, neuropsychiatric symptoms like depression, anxiety, and post-traumatic stress disorder (PTSD) are not rare. These problems significantly impact the quality of life (QOL) of patients, family, and caregivers, even lead a tragic suicide outcome. Other than the conventional psychological and medical approaches, here, we proposal a positive emotion, engagement, relationships, meaning, and accomplishment (PERMA)-based approach to fight against these COVID-19-related mental health problems (CRMHPs). This approach is characterized by positive psychological interventions and self-achievements, which has been proved to be a powerful tool against mood disorders in common people. Nowadays, abolishment of certain prophylactic measures (such as isolation, lockdown, compulsorily wearing a mask and maintaining social distance, measures to avoid crowding) enables us to have more opportunities to contact patients and implement the PERMA-based approach to the patients with CRMHPs. We believe that application of PERMA-based approach is conducive to alleviate the influence of the CRMHPs and improve their QOL.

5.
ACS Med Chem Lett ; 15(5): 659-666, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38746900

RESUMEN

Dual-specificity tyrosine phosphorylation-regulated kinase 2 (DYRK2) has been identified as a promising oncogenic driver of several types of cancer and is considered to be a critical cancer therapeutic target. Several inhibitors of DYRK2 have been reported, but no degraders have been found yet. In this work, we designed and synthesized the first series of proteolysis-targeting chimeras (PROTACs) using curcumin and its analogs as warheads to target and degrade DYRK2. The results of degradation assays showed that the compound CP134 could effectively downregulate the intracellular DYRK2 level (DC50 = 1.607 µM). Further mechanism of action experiments revealed that CP134 induced DYRK2 degradation through the ubiquitin-proteasome system. Altogether, CP134 disclosed in this study is the first potent DYRK2 degrader, which could serve as a valuable chemical tool for further evaluation of its therapeutic potential, and our results broaden the substrate spectrum of PROTAC-based degraders for further therapeutic applications.

6.
Heliyon ; 10(5): e26965, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38562495

RESUMEN

This paper introduces a novel, Simple-based Dynamic Decentralized Community Detection Algorithm (S-DCDA) for Socially Aware Networks. This algorithm aims to address the resource-intensive nature, instabilities and inaccuracies of traditional distributed community detection algorithms. The dynamics of decentralization is evident in the threefold nature of the algorithm: (i) each node of the community is the core of the entire network or community for a certain period of time dependent on their need, (ii) nodes are not centralized around themselves, requiring the consent of the other node to join a community, and (iii) Communities start from a single node to form an initial scale community, the number of nodes and the relationship among them are constantly changing. The algorithm requires low processor performance and memory capacity size of each node, to a certain extent, effectively improve the accuracy and stability of community detection and maintenance. Experimental results demonstrate that in comparison to classical and classical-based improved community detection algorithms, S-DCDA yields superior detection results.

7.
Int J Cancer ; 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38577882

RESUMEN

Patient-derived organoids (PDOs) may facilitate treatment selection. This retrospective cohort study evaluated the feasibility and clinical benefit of using PDOs to guide personalized treatment in metastatic breast cancer (MBC). Patients diagnosed with MBC were recruited between January 2019 and August 2022. PDOs were established and the efficacy of customized drug panels was determined by measuring cell mortality after drug exposure. Patients receiving organoid-guided treatment (OGT) were matched 1:2 by nearest neighbor propensity scores with patients receiving treatment of physician's choice (TPC). The primary outcome was progression-free survival. Secondary outcomes included objective response rate and disease control rate. Targeted gene sequencing and pathway enrichment analysis were performed. Forty-six PDOs (46 of 51, 90.2%) were generated from 45 MBC patients. PDO drug screening showed an accuracy of 78.4% (95% CI 64.9%-91.9%) in predicting clinical responses. Thirty-six OGT patients were matched to 69 TPC patients. OGT was associated with prolonged median progression-free survival (11.0 months vs. 5.0 months; hazard ratio 0.53 [95% CI 0.33-0.85]; p = .01) and improved disease control (88.9% vs. 63.8%; odd ratio 4.26 [1.44-18.62]) compared with TPC. The objective response rate of both groups was similar. Pathway enrichment analysis in hormone receptor-positive, human epidermal growth factor receptor 2-negative patients demonstrated differentially modulated pathways implicated in DNA repair and transcriptional regulation in those with reduced response to capecitabine/gemcitabine, and pathways associated with cell cycle regulation in those with reduced response to palbociclib. Our study shows that PDO-based functional precision medicine is a feasible and effective strategy for MBC treatment optimization and customization.

8.
J Mol Neurosci ; 74(2): 42, 2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38613644

RESUMEN

Alzheimer's disease (AD) is a severe neurological illness that causes memory loss and is a global problem. The calcium hypothesis recently steadily evolved in AD. The prospective targets for calcium homeostasis therapy, however, are limited, and gene expression-level research connected to calcium homeostasis in AD remains hazy. In this study, we analyzed the microarray dataset (GSE132903) taken from the Gene Expression Omnibus (GEO) database to investigate calcium homeostasis-related genes for AD. Using immunoblot analysis, we examined the association of ITPKB with inflammation in AD. Additionally, the immunofluorescence technique was employed to assess the impact of pharmacological inhibition of ITPKB on the amyloid-ß (Aß) plaque deposition in APP/PS1 mice. This article's further exploration of calcium homeostasis-related genes has propelled the validation of the calcium homeostasis theory in AD.


Asunto(s)
Enfermedad de Alzheimer , Placa Amiloide , Animales , Ratones , Placa Amiloide/genética , Transcriptoma , Calcio , Enfermedad de Alzheimer/genética , Modelos Animales , Homeostasis
9.
Discov Oncol ; 15(1): 120, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38619648

RESUMEN

OBJECTIVE: Circular RNAs (circRNAs), pivotal in the pathogenesis and progression of nasopharyngeal carcinoma (NPC), remain a significant point of investigation for potential therapeutic interventions. Our research was driven by the objective to decipher the roles and underlying mechanisms of hsa_circ_0044569 (circCOL1A1) in governing the malignant phenotypes and the Warburg effect in NPC. METHODS: We systematically collected samples from NPC tissues and normal nasopharyngeal epithelial counterparts. The expression levels of circCOL1A1, microRNA-370-5p (miR-370-5p), and prothymosin alpha (PTMA) were quantitatively determined using quantitative polymerase chain reaction (qPCR) and Western blotting. Transfections in NPC cell lines were conducted using small interfering RNAs (siRNAs) or vectors carrying the pcDNA 3.1 construct for overexpression studies. We interrogated the circCOL1A1/miR-370-5p/PTMA axis's role in cellular functions through a series of assays: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide for cell viability, colony formation for growth, Transwell assays for migration and invasion, and Western blotting for protein expression profiling. To elucidate the molecular interactions, we employed luciferase reporter assays and RNA immunoprecipitation techniques. RESULTS: Our investigations revealed that circCOL1A1 was a stable circRNA, highly expressed in both NPC tissues and derived cell lines. A correlation analysis with clinical pathological features demonstrated a significant association between circCOL1A1 expression, lymph node metastasis, and the tumor node metastasis staging system of NPC. Functionally, silencing circCOL1A1 led to substantial suppression of cell proliferation, migration, invasion, and metabolic alterations characteristic of the Warburg effect in NPC cells. At the molecular level, circCOL1A1 appeared to modulate PTMA expression by acting as a competitive endogenous RNA or 'sponge' for miR-370-5p, which in turn promoted the malignant characteristics of NPC cells. CONCLUSION: To conclude, our findings delineate that circCOL1A1 exerts its oncogenic influence in NPC through the modulation of the miR-370-5p/PTMA signaling axis.

10.
J Investig Med ; : 10815589241249994, 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38632825

RESUMEN

Liver and lung tissue damage caused by sepsis is still one of the causes of death. B-lymphocyte-induced maturation protein-1 (Blimp-1) has a protective role in inflammation-related disease. However, whether Blimp-1 can regulate cell pyroptosis and affect disease progression in sepsis is still unclear. Animal and cell models were established by the cecal ligation and puncture method and lipopolysaccharides (LPS)-induced RAW 264.7 cells, respectively, and the role of Blimp-1 in regulation inflammatory response and pyroptosis was verified. The changes of inflammation and pyroptosis in liver and lung tissues of septic mice were determined by the addition of TAK-242 (TLR4 inhibitor). Cell pyroptosis and the level of inflammation was detected after Blimp-1 knockdown and TAK-242 treatment in the cell model. The expression of Blimp-1 was continuously increased in a septic mice model. After treatment with TAK-242, the expression of Blimp-1, pyroptosis and inflammatory levels were reduced in mice. In the LPS-induced cell model, cell injury by knockout Blimp-1 was increased, and cell activity was restored after TAK-242 intervention. Overexpression of Blimp-1 relieved LPS-induced cellular inflammatory damage and pyroptosis. Our study had shown that Blimp-1 could improve septic damage by regulating the level of cellular inflammation and pyroptosis in sepsis.

11.
PLoS One ; 19(4): e0299890, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38662717

RESUMEN

BACKGROUND: Preventive care is important for managing inflammatory bowel disease (IBD), yet primary care providers (PCPs) often face challenges in delivering such care due to discomfort and unfamiliarity with IBD-specific guidelines. This study aims to assess PCPs' attitudes towards, and practices in, providing preventive screenings for IBD patients, highlighting areas for improvement in guideline dissemination and education. METHODS: Using a web-based opt-in panel of PCPs (DocStyles survey, spring 2022), we assessed PCPs' comfort level with providing/recommending screenings and the reasons PCPs felt uncomfortable (n = 1,503). Being likely to provide/recommend screenings for depression/anxiety, skin cancer, osteoporosis, and cervical cancer were compared by PCPs' comfort level and frequency of seeing patients with IBD. We estimated adjusted odd ratios (AORs) of being likely to recommend screenings and selecting responses aligned with IBD-specific guidelines by use of clinical practice methods. RESULTS: About 72% of PCPs reported being comfortable recommending screenings to patients with IBD. The top reason identified for not feeling comfortable was unfamiliarity with IBD-specific screening guidelines (55%). Being comfortable was significantly associated with being likely to provide/recommend depression/anxiety (AOR = 3.99) and skin cancer screenings (AOR = 3.19) compared to being uncomfortable or unsure. Percentages of responses aligned with IBD-specific guidelines were lower than those aligned with general population guidelines for osteoporosis (21.7% vs. 27.8%) and cervical cancer screenings (34.9% vs. 43.9%), and responses aligned with IBD-specific guidelines did not differ by comfort level for both screenings. Timely review of guidelines specific to immunosuppressed patients was associated with being likely to provide/recommend screenings and selecting responses aligned with IBD-specific guidelines. CONCLUSIONS: Despite a general comfort among PCPs in recommending preventive screenings for IBD patients, gaps in knowledge regarding IBD-specific screening guidelines persist. Enhancing awareness and understanding of these guidelines through targeted education and resource provision may bridge this gap.


Asunto(s)
Actitud del Personal de Salud , Enfermedades Inflamatorias del Intestino , Médicos de Atención Primaria , Humanos , Enfermedades Inflamatorias del Intestino/diagnóstico , Enfermedades Inflamatorias del Intestino/psicología , Femenino , Masculino , Persona de Mediana Edad , Adulto , Médicos de Atención Primaria/psicología , Tamizaje Masivo/métodos , Atención Primaria de Salud , Encuestas y Cuestionarios , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/prevención & control , Conocimientos, Actitudes y Práctica en Salud , Anciano , Pautas de la Práctica en Medicina , Osteoporosis/diagnóstico , Osteoporosis/prevención & control
13.
Nano Lett ; 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602471

RESUMEN

Mimicking the function of human skin is highly desired for electronic skins (e-skins) to perceive the tactile stimuli by both their intensity and spatial location. The common strategy using pixelated pressure sensor arrays and display panels greatly increases the device complexity and compromises the portability of e-skins. Herein, we tackled this challenge by developing a user-interactive iontronic skin that simultaneously achieves electrical pressure sensing and on-site, nonpixelated pressure mapping visualization. By merging the electrochromic and iontronic pressure sensing units into an integrated multilayer device, the interlayer charge transfer is regulated by applied pressure, which induces both color shifting and a capacitance change. The iontronic skin could visualize the trajectory of dynamic forces and reveal both the intensity and spatial information on various human activities. The integration of dual-mode pressure responsivity, together with the scalable fabrication and explicit signal output, makes the iontronic skin highly promising in biosignal monitoring and human-machine interaction.

14.
Eur J Med Chem ; 270: 116345, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38564826

RESUMEN

Several generations of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have been developed for the treatment of non-small cell lung cancer (NSCLC) in clinic. However, emerging drug resistance mediated by new EGFR mutations or activations by pass, leads to malignant progression of NSCLC. Proteolysis targeting chimeras (PROTACs) have been utilized to overcome the drug resistance acquired by mutant EGFR, newly potent and selective degraders are still need to be developed for clinical applications. Herein, we developed autophagosome-tethering compounds (ATTECs) in which EGFR can be anchored to microtubule-associated protein-1 light chain-3B (LC3B) on the autophagosome with the assistance of the LC3 ligand GW5074. A series of EGFR-ATTECs have been designed and synthesized. Biological evaluations showed that these compounds could degrade EGFR and exhibited moderate inhibitory effects on certain NSCLC cell lines. The ATTEC 12c potently induced the degradation of EGFR with a DC50 value of 0.98 µM and a Dmax value of 81% in HCC827 cells. Mechanistic exploration revealed that the lysosomal pathway was mainly involved in this degradation. Compound 12c also exhibited promising inhibitory activity, as well as degradation efficiency in vivo. Our study highlights that EGFR-ATTECs could be developed as a new expandable EGFR degradation tool and also reveals a novel potential therapeutic strategy to prevent drug resistance acquired EGFR mutations.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Proliferación Celular , Autofagosomas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Línea Celular Tumoral , Receptores ErbB , Mutación , Resistencia a Antineoplásicos
15.
JACC Case Rep ; 29(6): 102253, 2024 Mar 20.
Artículo en Inglés | MEDLINE | ID: mdl-38549853

RESUMEN

We present a unique case of left atrial (LA) dissection in a 46-year-old man following aortic dissection surgery. The LA dissection was attributed to coronary sinus catheter-related injury. This report highlights the importance of recognizing this rare complication and the crucial role of transesophageal echocardiography in its diagnosis. We discuss the pathogenesis, diagnostic criteria, and management strategies for LA dissection.

16.
Gen Hosp Psychiatry ; 88: 61-67, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38508077

RESUMEN

CONTEXT: Many patients recovering from surgery in wards are disturbed by environmental noise. However, the effects of environmental noise on postoperative pain are unclear. OBJECTIVES: This study aimed to assess the association between postoperative noise and pain. METHODS: This prospective study included 182 women who underwent cesarean sections. Postoperative noise was continuously recorded, and pain intensity at rest was assessed using a numerical rating scale (NRS) for 0-6, 6-12, 12-18, and 18-24 h after the patients were returned to the ward. Cumulative pain scores were calculated by summing the NRS scores at each time point and comprised the primary outcome. The maximum pain NRS score and analgesic consumption during the 24 h after surgery were also recorded. RESULTS: Mean environmental noise intensity during the daytime was an independent factor for cumulative pain scores, maximum pain scores, and analgesic use during the first postoperative 24 h (ß, 0.37; 95% CI, 0.21-0.53 and ß, 0.12; 95% CI, 0.07-0.17; P < 0.001 for both; ß, 0.86; 95% CI, 0.25-1.46; P = 0.006). Cumulative and maximum NRS pain scores as well as the incidence of NRS ≥ 4 were significantly higher in patients under mean daytime environmental noise of ≥58, than <58 decibels (dB) (8.0 [6.0-11.3] vs. 6.0 (5.0-7.0); 3.0 [2.0-4.0] vs. 2.0 [2.0-2.0, and 25.6% vs. 11.0%; RR, 2.32; 95% CI, 1.19-4.54, respectively; P < 0.001 for all). CONCLUSIONS: Higher-level postoperative noise exposure was associated with more severe postoperative pain and increased analgesic needs, as well as a higher incidence of moderate-to-severe pain in patients recovering from cesarean delivery. Our findings indicate that reducing environmental ward noise might benefit for postoperative pain management.


Asunto(s)
Analgésicos , Dolor Postoperatorio , Embarazo , Humanos , Femenino , Estudios Prospectivos , Analgésicos/uso terapéutico , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Dimensión del Dolor , Analgésicos Opioides
17.
Heart Rhythm ; 2024 Mar 13.
Artículo en Inglés | MEDLINE | ID: mdl-38490601

RESUMEN

BACKGROUND: Left bundle branch block (LBBB) represents a frequently encountered conduction system disorder. Despite its widespread occurrence, a continual dilemma persists regarding its intricate association with underlying cardiomyopathy and its pivotal role in the initiation of dilated cardiomyopathy. The pathologic alterations linked to LBBB-induced cardiomyopathy (LBBB-CM) have remained elusive. OBJECTIVE: This study sought to investigate the chronologic dynamics of LBBB to left ventricular dysfunction and the pathologic mechanism of LBBB-CM. METHODS: LBBB model was established through main left bundle branch trunk ablation in 14 canines. All LBBB dogs underwent transesophageal echocardiography and electrocardiography before ablation and at 1 month, 3 months, 6 months, and 12 months after LBBB induction. Single-photon emission computed tomography imaging was performed at 12 months. We then harvested the heart from all LBBB dogs and 14 healthy adult dogs as normal controls for anatomic observation, Purkinje fiber staining, histologic staining, and connexin43 protein expression quantitation. RESULTS: LBBB induction caused significant fibrotic changes in the endocardium and mid-myocardium. Purkinje fibers exhibited fatty degeneration, vacuolization, and fibrosis along with downregulated connexin43 protein expression. During a 12-month follow-up, left ventricular dysfunction progressively worsened, peaking at the end of the observation period. The association between myocardial dysfunction, hypoperfusion, and fibrosis was observed in the LBBB-afflicted canines. CONCLUSION: LBBB may lead to profound myocardial injury beyond its conduction impairment effects. The temporal progression of left ventricular dysfunction and the pathologic alterations observed shed light on the complex relationship between LBBB and cardiomyopathy. These findings offer insights into potential mechanisms and clinical implications of LBBB-CM.

18.
Hepatol Commun ; 8(3)2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-38437062

RESUMEN

BACKGROUND: HCC is a leading cause of cancer-related death. The role of reactive oxygen species (ROS) in HCC remains elusive. Since a primary ROS source is the mitochondrial electron transport chain complex Ι and the NADH:ubiquinone Oxidoreductase Subunit B3 (NDUFB3), a complex I subunit, is critical for complex I assembly and regulates the associated ROS production, we hypothesize that some HCCs progress by hijacking NDUFB3 to maintain ROS homeostasis. METHODS: NDUFB3 in human HCC lines was either knocked down or overexpressed. The cells were then analyzed in vitro for proliferation, migration, invasiveness, colony formation, complex I activity, ROS production, oxygen consumption, apoptosis, and cell cycle. In addition, the in vivo growth of the cells was evaluated in nude mice. Moreover, the role of ROS in the NDUFB3-mediated changes in the HCC lines was determined using cellular and mitochondrion-targeted ROS scavengers. RESULTS: HCC tissues showed reduced NDUFB3 protein expression compared to adjacent healthy tissues. In addition, NDUFB3 knockdown promoted, while its overexpression suppressed, HCC cells' growth, migration, and invasiveness. Moreover, NDUFB3 knockdown significantly decreased, whereas its overexpression increased complex I activity. Further studies revealed that NDUFB3 overexpression elevated mitochondrial ROS production, causing cell apoptosis, as manifested by the enhanced expressions of proapoptotic molecules and the suppressed expression of the antiapoptotic molecule B cell lymphoma 2. Finally, our data demonstrated that the apoptosis was due to the activation of the c-Jun N-terminal kinase (JNK) signaling pathway and cell cycle arrest at G0/G1 phase. CONCLUSIONS: Because ROS plays essential roles in many biological processes, such as aging and cancers, our findings suggest that NDFUB3 can be targeted for treating HCC and other human diseases.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Animales , Ratones , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Ratones Desnudos , NAD , Especies Reactivas de Oxígeno , Ubiquinona , Homeostasis , Oxidorreductasas
19.
J Colloid Interface Sci ; 665: 152-162, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38520932

RESUMEN

H2 and formate are important energy carriers in fuel-cells and feedstocks in chemical industry. The hydrogen evolution reaction (HER) coupling with electro-oxidative cleavage of thermodynamically favorable polyols is a promising way to coproduce H2 and formate via electrochemical means, highly active catalysts for HER and electrooxidative cleavage of polycols are the key to achieve such a goal. Herein, molybdenum (Mo), tungsten (W) doped cobalt phosphides (Co2P) deposited onto nickel foam (NF) substrate, denoted as Mo-Co2P/NF and W-Co2P/NF, respectively, were investigated as catalytic electrodes for HER and electrochemical glycerol oxidation reaction (GOR) to yield H2 and formate. The W-Co2P/NF electrode exhibited low overpotential (η) of 113 mV to attain a current density (J) of -100 mA cm-2 for HER, while the Mo-Co2P/NF electrode demonstrated high GOR efficiency for selective production of formate. In situ Raman and infrared spectroscopic characterizations revealed that the evolved CoO2 from Co2P is the genuine catalytic sites for GOR. The asymmetric electrolyzer based on W-Co2P/NF cathode and Mo-Co2P/NF anode delivered a J = 100 mA cm-2 at 1.8 V voltage for glycerol electrolysis, which led to 18.2 % reduced electricity consumption relative to water electrolysis. This work highlights the potential of heteroelement doped phosphide in catalytic performances for HER and GOR, and opens up new avenue to coproduce more widespread commodity chemicals via gentle and sustainable electrocatalytic means.

20.
Psychophysiology ; : e14564, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38487932

RESUMEN

Anxiety is a common psychological disorder associated with other mental disorders, with depression being the most common comorbidity. Few studies have examined the neural mechanisms underlying anxiety after controlling for depression. This study aimed to explore whether there are differences in cortical activation in anxiety patients with different severities whose depression are normal. In the current study, depression levels were normal for 366 subjects-139 healthy subjects, 117 with mild anxiety, and 110 with major anxiety. Using the Hospital Anxiety and Depression Scale (HADS) and a verbal fluency task (VFT) to test subjects' anxiety and depression and cognitive function, respectively. A 53-channel guided near-infrared spectroscopic imaging technology (fNIRS) detected the concentration of oxyhemoglobin (oxy-Hb). Correlation analysis between anxiety severity and oxy-Hb concentration in the brain cortex was performed, as well as ANOVA analysis of oxy-Hb concentration among the three anxiety severity groups. The results showed that anxiety severity was significantly and negatively correlated with oxy-Hb concentrations in the left frontal eye field (lFEF) and in the right dorsolateral prefrontal area (rDLPFC). The oxy-Hb concentration in the lFEF and the rDLPFC were significantly lower in the major anxiety disorder group than that in the control group. This suggests that decreased cortical activity of the lFEF and rDLPFC may be neural markers of anxiety symptoms after controlling for depression. Anxiety symptoms without depression may be result from the dysfunction of the cognitive control network (CCN) which includes the lFEF and rDLPFC.

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