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1.
Rev Esp Enferm Dig ; 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39421915

RESUMEN

A 54-year-old woman was admitted to the hospital due to unexplained weight loss Physical examination revealed a significant abdominal mass. CT scanning revealed a large mixed-density mass in the abdomen closely associated with the liver.

2.
Eco Environ Health ; 3(3): 369-380, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39281069

RESUMEN

Terrestrial invertebrates in urban ecosystems are extremely species-rich, have many important roles in material flow and energy circulation, and are host to many human pathogens that pose threats to human health. These invertebrates are widely distributed in urban areas, including both out- and in-door environments. Consequently, humans are frequently in contact with them, which provides many opportunities for them to pose human health risks. However, comprehensive knowledge on human pathogen transfer via invertebrates is lacking, with research to date primarily focused on dipterans (e.g., mosquitoes, flies). Here, we take a broad taxonomic approach and review terrestrial invertebrate hosts (incl. mosquitoes, flies, termites, cockroaches, mites, ticks, earthworms, collembola, fleas, snails, and beetles) of human pathogens, with a focus on transmission pathways. We also discuss how urbanization and global warming are likely to influence the communities of invertebrate hosts and have flow-on risks to human health. Finally, we identify current research gaps and provide perspectives on future directions.

3.
Med Phys ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225550

RESUMEN

BACKGROUND: Deep learning is the primary method for conducting automated analysis of SPECT bone scintigrams. The lack of available large-scale data significantly hinders the development of well-performing deep learning models, as the performance of a deep learning model is positively correlated with the size of the dataset used. Therefore, there is an urgent demand for an automated data generation method to enlarge the dataset of SPECT bone scintigrams. PURPOSE: We introduce a deep learning-based generation model that can generate realistic but not identical samples from the original SPECT bone scintigrams. METHODS: Following the generative adversarial learning architecture, a bone metastasis scintigram generation model christened BMS-Gen is proposed. First, BMS-Gen takes multiple input conditions and employs multi-receptive field learning to ensure that the generated samples are as realistic as possible. Second, BMS-Gen adopts generative adversarial learning to retain the diversity of the generated samples. Last, BMS-Gen uses a two-stage training strategy to improve the quality of the generated samples. RESULTS: Experimental evaluation conducted on a set of clinical data of SPECT BM scintigrams has shown the performance of the proposed BMS-Gen, achieving the best overall scores of 1678.0, 69.33, and 19.51 for FID (Fréchet Inception Distance), MSE (Mean Square Error), and PSNR (Peak Signal-to-Noise Ratio) metrics. The introduction of samples generated by BMS-Gen contributes a maximum (minimum) increase of 3.01% (0.15%) on the F-1 score and a maximum (minimum) increase of 6.83% (2.21%) on the DSC score for the image classification and segmentation tasks, respectively. CONCLUSIONS: The proposed BMS-Gen model can be used as a promising tool for augmenting the data of bone scintigrams, greatly facilitating the development of deep learning-based automated analysis of SPECT bone scintigrams.

4.
ACS Appl Mater Interfaces ; 16(36): 48094-48102, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39189509

RESUMEN

Lead halide perovskite anion exchange reactions tend to be spontaneous and rapid. To achieve precise control of anion exchange and modulate the bandgaps of perovskites to meet the demands in full-color displays, a laser-induced liquid-phase anion exchange method is developed in this paper. CsPbBr3 perovskites embedded in a polymer matrix are converted to CsPb(BrxCl1-x)3 and CsPb(BrxI1-x)3 perovskites, realizing the shift from green fluorescence to blue and red fluorescence. By changing the laser parameters, the anion exchange extent and luminescence wavelength are precisely tuned, with the maximum tuning wavelength range of 431-696 nm. Due to the focusing properties of the laser, the spatial position of anion exchange can be precisely controlled, which is significant for realizing fast and accurate patterning without masks. Based on this method, blue patterns with different light-emitting wavelengths are fabricated. RGB three-color patterns on a single perovskite composite film are successfully prepared by further replacement of halogen ions. More importantly, the polymer matrix provides ultraflexibility and good stability for the films; even if the composite films are arbitrarily folded or repeatedly bent, they can still maintain good luminous intensity. This method will show great potential in the field of flexible, full-color displays.

5.
Cell Mol Biol Lett ; 29(1): 109, 2024 Aug 14.
Artículo en Inglés | MEDLINE | ID: mdl-39143552

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) have been shown to be involved in tumorigenesis and progression. However, the role of circGLIS3 (hsa_circ_0002874) in prostate cancer (PCa) has yet not been reported. METHODS: Candidate circRNA were determined through comprehensive analysis of public datasets, PCa cell lines, and tissues data. A series of cellular functional assays, including CCK-8, colony formation, wound healing, and transwell assays were performed. Subsequently, RNA sequencing, RNA immunoprecipitation, methylated RNA immunoprecipitation, microRNA pulldown, luciferase reporter assay, and western blot were used to explore the underlying molecular mechanisms. Moreover, the xenograft tumor mouse model was established to elucidate the function of circGLIS3. RESULTS: CircGLIS3, derived from exon 2 of the parental GLIS3 gene, was identified as a novel oncogenic circRNA in PCa that was closely associated with the biochemical recurrence. Its expression levels were upregulated in PCa tissues and cell lines as well as enzalutamide high-resistant cells. The cellular functional assays revealed that circGLIS3 promoted PCa cell proliferation, migration, and invasion. METTL3-mediated N6-methyladenosine (m6A) modification maintained its upregulation by enhancing its stability. Mechanically, CircGLIS3 sponged miR-661 to upregulate MDM2, thus regulating the p53 signaling pathway to promote cell proliferation, migration, and invasion. Furthermore, in vitro and in vivo experiments, the knockdown of circGLIS3 improved the response of PCa cells to ARSI therapies such as enzalutamide. CONCLUSIONS: METTL3-mediated m6A modification of circGLIS3 regulates the p53 signaling pathway via the miR-661/MDM2 axis, thereby facilitating PCa progression. Meanwhile, this study unveils a promising potential target for ARSI therapy for PCa.


Asunto(s)
Proliferación Celular , Progresión de la Enfermedad , Regulación Neoplásica de la Expresión Génica , Metiltransferasas , Neoplasias de la Próstata , ARN Circular , Masculino , Humanos , ARN Circular/genética , ARN Circular/metabolismo , Neoplasias de la Próstata/genética , Neoplasias de la Próstata/patología , Neoplasias de la Próstata/metabolismo , Animales , Metiltransferasas/metabolismo , Metiltransferasas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Ratones , Adenosina/análogos & derivados , Adenosina/metabolismo , Movimiento Celular/genética , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Feniltiohidantoína/farmacología , Feniltiohidantoína/análogos & derivados , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/genética , Resistencia a Antineoplásicos/genética , Ratones Endogámicos BALB C , Benzamidas , Nitrilos
6.
J Neurochem ; 168(9): 2379-2390, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39092633

RESUMEN

Orexin is exclusively produced in neurons localized within the lateral hypothalamic area (LHA) and perifornical area (PFA). Orexin has been identified as a key promotor of arousal. The selective loss of orexinergic neurons results in narcolepsy. It is known that the intrinsic electrophysiological properties are critical for neurons to perform their functions in corresponding brain regions. In addition to hypothalamic orexin, other brain nuclei are involved in the regulation of sleep and wakefulness. Quite a lot of studies focus on elucidating orexin-induced regulation of sleep-wake states and modulation of neuronal electrophysiological properties in several brain regions. Here, we summarize that the orexinergic neurons exhibit spontaneous firing activity which is associated with the states of sleep-wake cycle. Orexin mainly exerts postsynaptic excitatory effects on multiple brain nuclei associated with the process of sleep and wakefulness. This review may provide a background to guide future research about the cellular mechanisms of orexin-induced maintaining of arousal.


Asunto(s)
Nivel de Alerta , Encéfalo , Neuronas , Orexinas , Orexinas/metabolismo , Orexinas/fisiología , Nivel de Alerta/fisiología , Humanos , Animales , Neuronas/fisiología , Neuronas/efectos de los fármacos , Encéfalo/fisiología , Encéfalo/metabolismo , Vigilia/fisiología , Sueño/fisiología , Sueño/efectos de los fármacos
7.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3749-3757, 2024 Jul.
Artículo en Chino | MEDLINE | ID: mdl-39099349

RESUMEN

Lectin receptor-like kinase(LecRLK) is a class of phytokinase with lectin conserved domain, which plays an important role in plant resistance to biological and abiotic stresses, as well as plant growth and development. Cannabis sativa is an important multi-purpose plant, widely used in food, textile, medicine, and other fields. Genome-wide screening and expression analysis of the LecRLK family of C. sativa were performed in this paper, so as to provide scientific reference for functional analysis of the LecRLK family of C. sativa. Based on BLAST and HMM methods, 93 LecRLKs were identified in the whole genome of C. sativa, including 69 G types, 23 L types, and one C types. Subsequently, a series of bioinformatics analyses were performed on the LecRLK family members, and the physicochemical properties of the protein of the LecRLK family members were initially revealed. The prediction of cis-acting elements of promoters in family members showed that family members were regulated by hormones and stress response. The expression analysis showed that some family members were highly expressed in the roots, which may participate in the process of stress resistance. Several members were highly expressed in female flowers and may be involved in female flower development. This study provides a theoretical basis for further study of LecRLK gene function. Meanwhile, the expression analysis screens candidate LecRLK members who may participate in the resistance of C. sativa, which provides a theoretical basis for the subsequent selection of C. sativa varieties against resistance.


Asunto(s)
Cannabis , Biología Computacional , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas , Cannabis/genética , Cannabis/crecimiento & desarrollo , Cannabis/química , Cannabis/enzimología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Filogenia , Familia de Multigenes , Genoma de Planta/genética
8.
Front Pharmacol ; 15: 1443667, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39185304

RESUMEN

Due to the pathological production of liver disease in utility particularly complexity, the morbidity and mortality of liver disease including viral hepatitis, liver fibrosis/cirrhosis and hepatocellular carcinoma (HCC) are rapidly increasing worldwide. Considering its insidious onset, rapid progression and drug resistance, finding an effective therapy is particularly worthwhile. Phyllanthus urinaria L. (P. urinaria), an ethnic medicine, can be applied at the stages of viral hepatitis, liver fibrosis/cirrhosis and HCC, which demonstrates great potential in the treatment of liver disease. Currently, there are numerous reports on the application of P. urinaria in treating liver diseases, but a detailed analysis of its metabolites and a complete summary of its pharmacological mechanism are still scarce. In this review, the phytochemical metabolites and ethnopharmacological applications of P. urinaria are summarized. Briefly, P. urinaria mainly contains flavonoids, lignans, tannins, phenolic acids, terpenoids and other metabolites. The mechanisms of P. urinaria are mainly reflected in reducing surface antigen secretion and interfering with DNA polymerase synthesis for anti-viral hepatitis activity, reducing hepatic stellate cells activity, inflammation and oxidative stress for anti-liver fibrosis/cirrhosis activity, as well as preventing tumor proliferation, invasion and angiogenesis for anti-HCC activity via relevant signaling pathways. Accordingly, this review provides insights into the future application of natural products in the trilogy of liver diseases and will provide a scientific basis for further research and rational utilization of P. urinaria.

9.
Circ Arrhythm Electrophysiol ; 17(10): e013054, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39212055

RESUMEN

BACKGROUND: Increased mitochondrial Ca2+ uptake has been implicated in the QT prolongation and lethal arrhythmias associated with nonischemic cardiomyopathy. We attempted to define the role of mitochondria in ischemic arrhythmic risk and to identify upstream regulators. METHODS: Myocardial infarction (MI) was induced in wild-type FVB/NJ mice by ligation of the left anterior descending coronary artery. Western blot, immunoprecipitation, ECG telemetry, and patch-clamp techniques were used. RESULTS: After MI, c-Src (proto-oncogene tyrosine-protein kinase Src) and its active form (phosphorylated Src, p-Src) were increased. The activation of c-Src was associated with increased diastolic Ca2+ sparks, action potential duration prolongation, and arrhythmia in MI mice. c-Src upregulation and arrhythmia could be reversed by treatment of mice with the Src inhibitor PP1 but not with the inactive analogue PP3. Tyrosine phosphorylated mitochondrial Ca2+ uniporter (MCU) was upregulated in the heart tissues of MI mice and patients with ischemic cardiomyopathy. In a heterologous expression system, c-Src could bind MCU and phosphorylate MCU tyrosines. Overexpression of wild-type c-Src significantly increased the mitochondrial Ca2+ transient while overexpression of dominant-negative c-Src significantly decreased the mitochondrial Ca2+ transient. c-Src inhibition by PP1, MCU inhibition by Ru360, or MCU knockdown could reduce the action potential duration, Ca2+ sparks, and arrhythmia after MI. The human heart tissue showed that patients with ischemic cardiomyopathy had significantly increased c-Src active form associated with increased MCU tyrosine phosphorylation and ventricular arrhythmia. CONCLUSIONS: MI leads to increased c-Src active form that results in MCU tyrosine phosphorylation, increased mitochondrial Ca2+ uptake, QT prolongation, and arrhythmia, suggesting c-Src or MCU may represent novel antiarrhythmic targets.


Asunto(s)
Potenciales de Acción , Arritmias Cardíacas , Modelos Animales de Enfermedad , Mitocondrias Cardíacas , Familia-src Quinasas , Animales , Familia-src Quinasas/metabolismo , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatología , Arritmias Cardíacas/etiología , Arritmias Cardíacas/genética , Arritmias Cardíacas/enzimología , Mitocondrias Cardíacas/metabolismo , Mitocondrias Cardíacas/enzimología , Humanos , Ratones , Fosforilación , Masculino , Cardiomiopatías/metabolismo , Cardiomiopatías/genética , Cardiomiopatías/fisiopatología , Cardiomiopatías/etiología , Cardiomiopatías/enzimología , Proteína Tirosina Quinasa CSK/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/enzimología , Canales de Calcio/metabolismo , Canales de Calcio/genética , Señalización del Calcio , Infarto del Miocardio/metabolismo , Infarto del Miocardio/complicaciones , Infarto del Miocardio/fisiopatología , Infarto del Miocardio/genética , Factores de Riesgo
10.
Int J Nanomedicine ; 19: 6377-6397, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952677

RESUMEN

Background: How to ingeniously design multi-effect photosensitizers (PSs), including multimodal imaging and multi-channel therapy, is of great significance for highly spatiotemporal controllable precise phototherapy of malignant tumors. Methods: Herein, a novel multifunctional zinc(II) phthalocyanine-based planar micromolecule amphiphile (ZnPc 1) was successfully designed and synthesized, in which N atom with photoinduced electron transfer effect was introduced to enhance the near-infrared absorbance and nonradiative heat generation. After simple self-assembling into nanoparticles (NPs), ZnPc 1 NPs would exhibit enhanced multimodal imaging properties including fluorescence (FL) imaging (FLI) /photoacoustic (PA) imaging (PAI) /infrared (IR) thermal imaging, which was further used to guide the combined photodynamic therapy (PDT) and photothermal therapy (PTT). Results: It was that under the self-guidance of the multimodal imaging, ZnPc 1 NPs could precisely pinpoint the tumor from the vertical and horizontal boundaries achieving highly efficient and accurate treatment of cancer. Conclusion: Accordingly, the integration of FL/PA/IR multimodal imaging and PDT/PTT synergistic therapy pathway into one ZnPc 1 could provide a blueprint for the next generation of phototherapy, which offered a new paradigm for the integration of diagnosis and treatment in tumor and a promising prospect for precise cancer therapy.


Asunto(s)
Indoles , Isoindoles , Imagen Multimodal , Nanopartículas , Fotoquimioterapia , Fármacos Fotosensibilizantes , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Imagen Multimodal/métodos , Animales , Humanos , Indoles/química , Indoles/farmacología , Fotoquimioterapia/métodos , Nanopartículas/química , Ratones , Compuestos de Zinc/química , Compuestos Organometálicos/química , Compuestos Organometálicos/farmacología , Línea Celular Tumoral , Técnicas Fotoacústicas/métodos , Terapia Fototérmica/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Ratones Endogámicos BALB C , Fototerapia/métodos , Femenino
11.
J Orthop Surg Res ; 19(1): 414, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-39030606

RESUMEN

BACKGROUND: To explore and compare the values of 3.0T magnetic resonance imaging (MRI) T2 mapping in evaluating the degree of acetabular cartilage degeneration in hip replacement surgery. METHODS: A total of 26 elderly patients with femoral neck fractures who were scanned in 3.0T MRI T2 mapping quantification technique were included. Basing on MRI images, the degree of acetabular cartilage degeneration was classified into Grade 0, 1, 2, 3 and 4, according to the International Cartilage Repair Society (ICRS) scores. In addition, 8 healthy volunteers were included for control group. RESULTS: By comparison with health population, T2 relaxation values in the anterior, superior, and posterior regions of acetabular cartilage in patients with femoral neck fracture were obviously increased (P < 0.001). Among the patients with femoral neck fractures, there were 16 hip joint with Grade 1-2 (mild degeneration subgroup) and 10 hip joints with Grade 3-4 (severe degeneration subgroup), accounting for 61.54% and 38.46%, respectively. Additionally, T2 relaxation values in the anterior and superior bands of articular cartilage were positively related to the MRI-based grading (P < 0.05); while there was no significant difference of T2 relaxation values in the posterior areas of articular cartilage between severe degeneration subgroup and mild degeneration subgroup (P > 0.05). Importantly, acetabular cartilage degeneration can be detected through signal changes of T2 mapping pseudo-color images. CONCLUSION: 3.0T MRI T2 mapping technology can be used to determine the degree of acetabular cartilage degeneration, which can effectively monitor the disease course.


Asunto(s)
Acetábulo , Artroplastia de Reemplazo de Cadera , Cartílago Articular , Imagen por Resonancia Magnética , Humanos , Imagen por Resonancia Magnética/métodos , Masculino , Femenino , Acetábulo/diagnóstico por imagen , Acetábulo/patología , Anciano , Cartílago Articular/diagnóstico por imagen , Cartílago Articular/patología , Artroplastia de Reemplazo de Cadera/métodos , Persona de Mediana Edad , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Anciano de 80 o más Años , Enfermedades de los Cartílagos/diagnóstico por imagen , Enfermedades de los Cartílagos/patología , Índice de Severidad de la Enfermedad
12.
Aging (Albany NY) ; 16(13): 11062-11071, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38975935

RESUMEN

OBJECTIVE: To investigate the effect of sevoflurane on neuropathic pain induced by chronic constriction injury (CCI) of sciatic nerve in mice, and to elucidate its mechanism by animal experiments. METHODS AND RESULTS: Thirty-two C57BL/6 mice were randomly divided into four groups: Sham group, Model group, Control group and Sevoflurane group. First, a mouse model of neuropathic pain was established. Then, the mice in each group were killed on Day 14 after operation to harvest the enlarged lumbosacral spinal cord. In contrast with the Model group, the Sevoflurane group displayed a significantly increased paw withdrawal mechanical threshold (PWMT) and significantly prolonged paw withdrawal thermal latency (PWTL) from Day 5 after operation. The morphological changes of lumbosacral spinal cord were observed by hematoxylin-eosin (HE) staining and transmission electron microscopy. Pathological results showed that sevoflurane reduced nuclear pyknosis in lumbosacral spinal cord tissue, with a large number of mitochondrial crista disappearance and mitochondrial swelling. The results of Western blotting showed that sevoflurane significantly decreased the protein expressions of phosphorylated phospholipase Cγ (p-PLCγ), phosphorylated calcium/calmodulin-dependent protein kinase II (p-CaMKII) and phosphorylated inositol 1,4,5-triphosphate receptor (p-IP3R), and reduced the protein expressions of endoplasmic reticulum (ER) stress proteins glucose-regulated protein 78 (GRP78) and GRP94, oxidative stress-related proteins P22 and P47 and inflammatory factors nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), interleukin-1 ß (IL-1ß), and tumor necrosis factor-α (TNF-α). CONCLUSIONS: Sevoflurane inhibits neuropathic pain by maintaining ER stress and oxidative stress homeostasis through inhibiting the activation of the PLCγ/CaMKII/IP3R signaling pathway.


Asunto(s)
Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Chaperón BiP del Retículo Endoplásmico , Estrés del Retículo Endoplásmico , Receptores de Inositol 1,4,5-Trifosfato , Ratones Endogámicos C57BL , Neuralgia , Estrés Oxidativo , Fosfolipasa C gamma , Sevoflurano , Transducción de Señal , Animales , Sevoflurano/farmacología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Neuralgia/metabolismo , Neuralgia/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Ratones , Fosfolipasa C gamma/metabolismo , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Masculino , Médula Espinal/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/patología , Homeostasis/efectos de los fármacos , Modelos Animales de Enfermedad , Nervio Ciático/efectos de los fármacos , Nervio Ciático/metabolismo , Nervio Ciático/lesiones
13.
Transl Psychiatry ; 14(1): 293, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39019862

RESUMEN

Electronic cigarettes (e-cigs) use, especially among youngsters, has been on the rise in recent years. However, little is known about the long-term effects of the use of e-cigs on brain functional activity. We acquired the resting-state functional magnetic resonance imaging (rs-fMRI) data from 93 e-cigs users with nicotine dependence and 103 health controls (HC). The local synchronization was analyzed via the regional homogeneity (ReHo) method at voxel-wise level. The functional connectivity (FC) between the nucleus accumbens (NAcc), the ventral tegmental area (VTA), and the insula was calculated at ROI-wise level. The support vector machining classification model based on rs-fMRI measures was used to identify e-cigs users from HC. Compared with HC, nicotine-dependent e-cigs users showed increased ReHo in the right rolandic operculum and the right insula (p < 0.05, FDR corrected). At the ROI-wise level, abnormal FCs between the NAcc, the VTA, and the insula were found in e-cigs users compared to HC (p < 0.05, FDR corrected). Correlation analysis found a significant negative correlation between ReHo in the left NAcc and duration of e-cigs use (r = -0.273, p = 0.008, FDR corrected). The following support vector machine model based on significant results of rs-fMRI successfully differentiates chronic e-cigs users from HC with an accuracy of 73.47%, an AUC of 0.781, a sensitivity of 67.74%, and a specificity of 78.64%. Dysregulated spontaneous activity and FC of addiction-related regions were found in e-cigs users with nicotine dependence, which provides crucial insights into the prevention of its initial use and intervention for quitting e-cigs.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Imagen por Resonancia Magnética , Núcleo Accumbens , Tabaquismo , Humanos , Tabaquismo/fisiopatología , Tabaquismo/diagnóstico por imagen , Masculino , Femenino , Adulto , Núcleo Accumbens/diagnóstico por imagen , Núcleo Accumbens/fisiopatología , Adulto Joven , Corteza Insular/diagnóstico por imagen , Corteza Insular/fisiopatología , Área Tegmental Ventral/diagnóstico por imagen , Área Tegmental Ventral/fisiopatología , Máquina de Vectores de Soporte , Estudios de Casos y Controles , Vapeo/fisiopatología
14.
Br J Cancer ; 131(3): 430-443, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38877108

RESUMEN

BACKGROUND: Targeting DNA damage repair factors, such as DNA-dependent protein kinase catalytic subunit (DNA-PKcs), may offer an opportunity for effective treatment of multiple myeloma (MM). In combination with DNA damage-inducing agents, this strategy has been shown to improve chemotherapies partially via activation of cGAS-STING pathway by an elevated level of cytosolic DNA. However, as cGAS is primarily sequestered by chromatin in the nucleus, it remains unclear how cGAS is released from chromatin and translocated into the cytoplasm upon DNA damage, leading to cGAS-STING activation. METHODS: We examined the role of DNA-PKcs inhibition on cGAS-STING-mediated MM chemosensitivity by performing mass spectrometry and mechanism study. RESULTS: Here, we found DNA-PKcs inhibition potentiated DNA damage-inducing agent doxorubicin-induced anti-MM effect by activating cGAS-STING signaling. The cGAS-STING activation in MM cells caused cell death partly via IRF3-NOXA-BAK axis and induced M1 polarization of macrophages. Moreover, this activation was not caused by defective classical non-homologous end joining (c-NHEJ). Instead, upon DNA damage induced by doxorubicin, inhibition of DNA-PKcs promoted cGAS release from cytoplasmic chromatin fragments and increased the amount of cytosolic cGAS and DNA, activating cGAS-STING. CONCLUSIONS: Inhibition of DNA-PKcs could improve the efficacy of doxorubicin in treatment of MM by de-sequestrating cGAS in damaged chromatin.


Asunto(s)
Cromatina , Daño del ADN , Proteína Quinasa Activada por ADN , Doxorrubicina , Proteínas de la Membrana , Mieloma Múltiple , Nucleotidiltransferasas , Humanos , Mieloma Múltiple/tratamiento farmacológico , Mieloma Múltiple/patología , Mieloma Múltiple/metabolismo , Mieloma Múltiple/genética , Nucleotidiltransferasas/metabolismo , Nucleotidiltransferasas/genética , Proteína Quinasa Activada por ADN/metabolismo , Proteína Quinasa Activada por ADN/antagonistas & inhibidores , Cromatina/metabolismo , Cromatina/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Doxorrubicina/farmacología , Proteínas de la Membrana/metabolismo , Proteínas de la Membrana/genética , Línea Celular Tumoral , Ratones , Animales , Transducción de Señal/efectos de los fármacos
15.
Front Psychiatry ; 15: 1353103, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827448

RESUMEN

Background: Insular subdivisions show distinct patterns of resting state functional connectivity with specific brain regions, each with different functional significance in chronic cigarette smokers. This study aimed to explore the altered dynamic functional connectivity (dFC) of distinct insular subdivisions in smokers. Methods: Resting-state BOLD data of 31 smokers with nicotine dependence and 27 age-matched non-smokers were collected. Three bilateral insular regions of interest (dorsal, ventral, and posterior) were set as seeds for analyses. Sliding windows method was used to acquire the dFC metrics of different insular seeds. Support vector machine based on abnormal insular dFC was applied to classify smokers from non-smokers. Results: We found that smokers showed lower dFC variance between the left ventral anterior insula and both the right superior parietal cortex and the left inferior parietal cortex, as well as greater dFC variance the right ventral anterior insula with the right middle cingulum cortex relative to non-smokers. Moreover, compared to non-smokers, it is found that smokers demonstrated altered dFC variance of the right dorsal insula and the right middle temporal gyrus. Correlation analysis showed the higher dFC between the right dorsal insula and the right middle temporal gyrus was associated with longer years of smoking. The altered insular subdivision dFC can classify smokers from non-smokers with an accuracy of 89.66%, a sensitivity of 96.30% and a specify of 83.87%. Conclusions: Our findings highlighted the abnormal patterns of fluctuating connectivity of insular subdivision circuits in smokers and suggested that these abnormalities may play a significant role in the mechanisms underlying nicotine addiction and could potentially serve as a neural biomarker for addiction treatment.

16.
Adv Respir Med ; 92(3): 230-240, 2024 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-38921062

RESUMEN

BACKGROUND: Chronic obstructive pulmonary disease (COPD), characterized by high-energy metabolism, often leads to malnutrition and is linked to exacerbations. This study investigates the association of malnutrition-related body composition and handgrip strength changes with exacerbation frequencies in COPD patients. METHODS: We analyzed 77 acute exacerbation COPD (AECOPD) patients and 82 stable COPD patients, categorized as frequent and infrequent exacerbators. Assessments included body composition, handgrip strength, nutritional risk, dyspnea scale, and COPD assessment. RESULTS: Among AECOPD patients, there were 22 infrequent and 55 frequent exacerbators. Infrequent exacerbators showed better muscle parameters, extracellular water ratio, phase angle, and handgrip strength. Significant differences in intracellular water, total cellular water, protein, and body cell mass were observed between groups. Logistic regression indicated that extracellular water ratio (OR = 1.086) and phase angle (OR = 0.396) were independently associated with exacerbation risk. Thresholds for exacerbation risk were identified as 0.393 for extracellular water ratio and 4.85° for phase angle. In stable COPD, 13 frequent and 69 infrequent exacerbators were compared, showing no significant differences in weight, muscle, and adipose parameters, but significant differences in extracellular water ratio, phase angle, and handgrip strength. CONCLUSIONS: These findings suggest that increased exacerbations in COPD patients correlate with higher extracellular water ratios and lower phase angles.


Asunto(s)
Composición Corporal , Fuerza de la Mano , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Fuerza de la Mano/fisiología , Masculino , Femenino , Anciano , Persona de Mediana Edad , Progresión de la Enfermedad
17.
Sheng Li Xue Bao ; 76(3): 418-428, 2024 Jun 25.
Artículo en Chino | MEDLINE | ID: mdl-38939936

RESUMEN

Aging refers to a progressive decline in biological functions, leading to age-related diseases and mortality. The transition metals, including iron, copper, and manganese, play important roles in human physiological and pathological processes. Substantial research has demonstrated that senescent cells accumulate higher levels of transition metals, which in turn accelerates the process of cellular senescence and related diseases through mechanisms such as production of excessive reactive oxygen species (ROS), induction of oxidative stress, DNA damage, and mitochondrial dysfunction. This review article provides a comprehensive overview of the causes of transition metal accumulation in senescent cells, as well as the mechanisms by which it further promotes cellular senescence and related diseases. The aim is to provide insights into anti-aging and treatment of aging-related diseases caused by transition metal accumulation.


Asunto(s)
Envejecimiento , Senescencia Celular , Daño del ADN , Estrés Oxidativo , Especies Reactivas de Oxígeno , Senescencia Celular/fisiología , Humanos , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Envejecimiento/fisiología , Envejecimiento/metabolismo , Animales , Elementos de Transición/metabolismo , Hierro/metabolismo , Mitocondrias/metabolismo , Mitocondrias/fisiología , Cobre/metabolismo , Manganeso/metabolismo
18.
J Psychiatry Neurosci ; 49(3): E182-E191, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38816028

RESUMEN

BACKGROUND: Esketamine is a version of ketamine that has been approved for treatment-resistant depression, but our previous studies showed a link between non-medical use of ketamine and brain structural and functional alterations, including dorsal prefrontal grey matter reduction among chronic ketamine users. In this study, we sought to determine cortical thickness abnormalities following long-term, non-medical use of ketamine. METHODS: We acquired structural brain images for patients with ketamine use disorder and drug-free healthy controls. We used FreeSurfer software to measure cortical thickness for 68 brain regions. We compared cortical thickness between the 2 groups using analysis of covariance with covariates of age, gender, educational level, smoking, drinking, and whole-brain mean cortical thickness. RESULTS: We included images from 95 patients with ketamine use disorder and 169 controls. Compared with healthy controls, patients with ketamine use disorder had widespread decreased cortical thickness, with the most extensive reductions in the frontal (including the dorsolateral prefrontal cortex) and parietal (including the precuneus) lobes. Increased cortical thickness was not observed among ketamine users relative to comparison participants. Estimated total lifetime ketamine consumption was correlated with reductions in the right inferior parietal and the right rostral middle frontal cortical thickness. LIMITATIONS: We conducted a retrospective cross-sectional study, but longitudinal studies are needed to further validate decreased cortical thickness after nonmedical use of ketamine. CONCLUSION: This study provided evidence that, compared with healthy controls, chronic ketamine users have widespread reductions in cortical thickness. Our study underscores the importance of the long-term effects of ketamine on brain structure and serves as a reference for the antidepressant use of ketamine.


Asunto(s)
Corteza Cerebral , Ketamina , Imagen por Resonancia Magnética , Trastornos Relacionados con Sustancias , Humanos , Ketamina/administración & dosificación , Masculino , Femenino , Adulto , Trastornos Relacionados con Sustancias/diagnóstico por imagen , Trastornos Relacionados con Sustancias/patología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/patología , Adulto Joven , Grosor de la Corteza Cerebral , Persona de Mediana Edad
19.
Analyst ; 149(13): 3585-3595, 2024 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-38767148

RESUMEN

The main protease of SARS-CoV-2 (SARS-CoV-2 Mpro) plays a critical role in the replication and life cycle of the virus. Currently, how to screen SARS-CoV-2 Mpro inhibitors from complex traditional Chinese medicine (TCM) is the bottleneck for exploring the pharmacodynamic substances of TCM against SARS-CoV-2. In this study, a simple, cost-effective, rapid, and selective fluorescent sensor (TPE-S-TLG sensor) was designed with an AIE (aggregation-induced emission) probe (TPE-Ph-In) and the SARS-CoV-2 Mpro substrate (S-TLG). The TPE-S-TLG sensor was characterized using UV-Vis absorption spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS), transmission electron microscopy (TEM), zeta potential, and Fourier transform infrared (FTIR) spectroscopy techniques. The limit of detection of this method to detect SARS-CoV-2 Mpro was measured to be 5 ng mL-1. Furthermore, the TPE-S-TLG sensor was also successfully applied to screen Mpro inhibitors from Xuebijing injection using the separation and collection of the HPLC-fully automatic partial fraction collector (HPLC-FC). Six active compounds, including protocatechualdehyde, chlorogenic acid, hydroxysafflower yellow A, caffeic acid, isoquercetin, and pentagalloylglucose, were identified using UHPLC-Q-TOF/MS that could achieve 90% of the Mpro inhibition rate for the Xuebijing injection. Accordingly, the strategy can be broadly applied in the detection of disease-related proteases as well as screening active substances from TCM.


Asunto(s)
Proteasas 3C de Coronavirus , Colorantes Fluorescentes , Medicina Tradicional China , SARS-CoV-2 , Espectrometría de Fluorescencia , SARS-CoV-2/aislamiento & purificación , SARS-CoV-2/efectos de los fármacos , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Humanos , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Antivirales/farmacología , Antivirales/análisis , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/análisis , COVID-19/virología , COVID-19/diagnóstico , Límite de Detección , Tratamiento Farmacológico de COVID-19
20.
Adv Sci (Weinh) ; 11(28): e2403116, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38816935

RESUMEN

To overcome current limitations in photoimmunotherapy, such as insufficient tumor antigen generation and a subdued immune response, a novel photo-/metallo dual-mode immunotherapeutic agent (PMIA) is introduced for potent near-infrared (NIR) light-triggered cancer therapy. PMIA features a dumbbell-like AuPt heterostructure decorated with starry Pt nanoclusters, meticulously engineered for enhancing plasmonic catalysis through multi-dimensional regulation of Pt growth on Au nanorods. Under NIR laser exposure, end-tipped Pt nanoclusters induce efficient electron-hole spatial separation along the longitudinal axis, resulting in radial and axial electron distribution polarization, conferring unique anisotropic properties to PMIA. Additionally, starry Pt nanoclusters on the sides of Au nanorods augment the local electron enrichment field. Validated through finite-difference time-domain analysis and Raman scattering, this configuration fosters local electron enrichment, facilitating robust reactive oxygen species generation for potent photoimmunotherapy. Moreover, Pt nanoclusters facilitate Pt2+ ion release, instigating intranuclear DNA damage and inducing synergistic immunogenic cell death (ICD) for metalloimmunotherapy. Consequently, PMIA elicits abundant danger-associated molecular patterns, promotes T cell infiltration, and triggers systemic immune responses, effectively treating primary and distant tumors, inhibiting metastasis in vivo. This study unveils a pioneering dual-mode ICD amplification strategy driven by NIR light, synergistically integrating photoimmunotherapy and metalloimmunotherapy, culminating in potent cancer photometalloimmunotherapy.


Asunto(s)
Oro , Inmunoterapia , Nanopartículas del Metal , Platino (Metal) , Inmunoterapia/métodos , Ratones , Animales , Platino (Metal)/química , Platino (Metal)/uso terapéutico , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Oro/química , Fototerapia/métodos , Neoplasias/terapia , Neoplasias/inmunología , Modelos Animales de Enfermedad , Anisotropía , Catálisis , Humanos , Línea Celular Tumoral
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