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1.
Bioinformatics ; 2024 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-39153205

RESUMEN

SUMMARY: Recent methodology advances in computational signal deconvolution have enabled bulk transcriptome data analysis at a finer cell-type level. Through deconvolution, identifying cell-type-specific differentially expressed (csDE) genes is drawing increasing attention in clinical applications. However, researchers still face a number of difficulties in adopting csDE detection methods in practice, especially in their experimental design. Here we present cypress, the first experimental design and statistical power analysis tool in csDE identification. This tool can reliably model purified cell-type-specific (CTS) profiles, cell-type compositions, biological and technical variations, offering a high-fidelity simulator for bulk RNA-seq convolution and deconvolution. cypress conducts simulation and evaluates the impact of multiple influencing factors, by various biostatistical metrics, to help researchers optimize experimental design and conduct power analysis. AVAILABILITY AND IMPLEMENTATION: cypress is an open-source R/Bioconductor package at https://bioconductor.org/packages/cypress/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

2.
Med Res Rev ; 44(1): 169-234, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-37337403

RESUMEN

Mammalian cytochrome P450 1A (CYP1A) are key phase I xenobiotic-metabolizing enzymes that play a distinctive role in metabolic activation or metabolic clearance of a variety of procarcinogens, drugs, and endogenous substances. Human CYP1A subfamily contains two members (hCYP1A1 and hCYP1A2), which are known to catalyze the oxidative activation of some environmental procarcinogens into carcinogenic species. Increasing evidence has demonstrated that CYP1A inhibitor therapies are promising strategies for cancer chemoprevention or overcoming CYP1A-associated drug toxicity and resistance. Herein, we reviewed recent advances in the discovery and characterization of hCYP1A inhibitors, from the discovery approaches to structural features and biomedical applications of hCYP1A inhibitors. The inhibition potentials, inhibition modes, and inhibition constants of all reported hCYP1A inhibitors are comprehensively summarized. Meanwhile, the structural features and structure-activity relationships of different classes of hCYP1A1 and hCYP1A2 inhibitors are analyzed and discussed in depth. Furthermore, the major challenges and future directions for this field are presented and highlighted. Collectively, the information and knowledge presented here will strongly facilitate the researchers to discover and develop more efficacious CYP1A inhibitors for specific purposes, such as chemo-preventive agents or as tool molecules in hCYP1A-related fundamental studies.


Asunto(s)
Citocromo P-450 CYP1A1 , Citocromo P-450 CYP1A2 , Animales , Humanos , Citocromo P-450 CYP1A1/metabolismo , Citocromo P-450 CYP1A2/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , Mamíferos/metabolismo
3.
Phys Chem Chem Phys ; 26(8): 6590-6599, 2024 Feb 22.
Artículo en Inglés | MEDLINE | ID: mdl-38332732

RESUMEN

Tungsten coatings have unique properties such as high melting points and hardness and are widely used in the nuclear fusion and aviation fields. In experiments, compared to pure Na2WO4 molten salt, electrolysis with Na2WO4-WO3 molten salt results in a lower deposition voltage. Herein, an investigation combining experimental and computational approaches was conducted, involving molecular dynamics simulations with deep learning, high-temperature in situ Raman spectroscopy and activation strain model analysis. The results indicated that the molten salt system's behaviour, influenced by migration and polarization effects, led to increased formation of Na2W2O7 in the Na2WO4-WO3 molten salt, which has a lower decomposition voltage and subsequently accelerated the cathodic deposition of tungsten. We analyzed the mechanism of the effect of the electric field on the Na2W2O7 structure based on the bond strength and electron density. This research provides crucial theoretical support for the effect of electric field on tungsten in molten salt and demonstrates the feasibility of using machine learning-based DPMD methods in simulating tungsten-containing molten salt systems.

4.
Angew Chem Int Ed Engl ; : e202410356, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39107253

RESUMEN

Electrocatalytic nitrate (NO3-) reduction to ammonia (NRA) offers a promising pathway for ammonia synthesis. The interfacial electronic interactions (IEIs) can regulate the physicochemical capabilities of catalysts in electrochemical applications, while the impact of IEIs on electrocatalytic NRA remains largely unexplored in current literature. In this study, the high-efficiency electrode Ag-modified Co3O4 (Ag1.5Co/CC) is prepared for NRA in neutral media, exhibiting an impressive nitrate conversion rate of 96.86%, ammonia Faradaic efficiency of 96.11%, and ammonia selectivity of ~100%. Notably, the intrinsic activity of Ag1.5Co/CC is ~81 times that of Ag nanoparticles (Ag/CC). Multiple characterizations and theoretical computations confirm the presence of IEIs between Ag and Co3O4, which stabilize the CoO6 octahedrons within Co3O4 and significantly promote the adsorption of reactants (NO3-) as well as intermediates (NO2- and NO), while suppressing the Heyrovsky step, thereby improving nitrate electroreduction efficiency. Furthermore, our findings reveal a synergistic effect between different active sites that enables tandem catalysis for NRA: NO3- reduction to NO2- predominantly occurs at Ag sites while NO2- tends to hydrogenate to ammonia at Co sites. This study offers valuable insights for the development of high-performance NRA electrocatalysts.

5.
Front Immunol ; 15: 1378202, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38650945

RESUMEN

Interactions between macrophages and adipocytes in adipose tissue are critical for the regulation of energy metabolism and obesity. Macrophage polarization induced by cold or other stimulations can drive metabolic reprogramming of adipocytes, browning, and thermogenesis. Accordingly, investigating the roles of macrophages and adipocytes in the maintenance of energy homeostasis is critical for the development of novel therapeutic approaches specifically targeting macrophages in metabolic disorders such as obesity. Current review outlines macrophage polarization not only regulates the release of central nervous system and inflammatory factors, but controls mitochondrial function, and other factor that induce metabolic reprogramming of adipocytes and maintain energy homeostasis. We also emphasized on how the adipocytes conversely motivate the polarization of macrophage. Exploring the interactions between adipocytes and macrophages may provide new therapeutic strategies for the management of obesity-related metabolic diseases.


Asunto(s)
Adipocitos , Metabolismo Energético , Homeostasis , Macrófagos , Obesidad , Humanos , Macrófagos/metabolismo , Macrófagos/inmunología , Animales , Adipocitos/metabolismo , Obesidad/metabolismo , Obesidad/inmunología , Comunicación Celular , Termogénesis
6.
Nutrients ; 16(14)2024 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-39064789

RESUMEN

Diabetic nephropathy (DN), one of the leading causes of end-stage kidney failure worldwide, is closely associated with high mortality in diabetic patients. However, therapeutic drugs for DN are still lacking. Ramulus Mori alkaloids (SZ-A), an effective component of alkaloids extracted from Ramulus Mori, have been found to improve glucose and lipid metabolism to mitigate diabetes and obesity; however, few studies have focused on their effects on DN progression. Thus, we investigated the protective role of SZ-A on DN through 16S rRNA sequencing, non-targeted metabolomics, and fecal microbiota transplantation (FMT) experiments. To address our hypothesis, we established the DN mouse model by combining a high-fat diet (HFD) with streptozotocin (STZ) injection. Herein, we demonstrated that SZ-A supplementation was recalcitrant to renal injury in DN mice, improving glomerular morphology, reversing the blood biochemistry parameters, and ameliorating podocyte injury. Importantly, the composition of the gut microbiota altered after SZ-A treatment, especially with the elevated abundance of Dubosiella and the increased level of serum pentadecanoic acid. FMT experiments further revealed that the gut microbiota exerted critical effects in mediating the beneficial roles of SZ-A. In vitro experiments proved that pentadecanoic acid administration improved podocyte apoptosis induced by AGEs. Taken together, SZ-A play a renoprotective role, possibly through regulating the gut microbiota and promoting pentadecanoic acid production. Our current study lends support to more extensive clinical applications of SZ-A.


Asunto(s)
Alcaloides , Nefropatías Diabéticas , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Nefropatías Diabéticas/tratamiento farmacológico , Alcaloides/farmacología , Ratones , Masculino , Dieta Alta en Grasa/efectos adversos , Podocitos/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Modelos Animales de Enfermedad , Trasplante de Microbiota Fecal
8.
Front Neurol ; 15: 1400469, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38915803

RESUMEN

Stroke is a primary cause of noncommunicable disease-related death and disability worldwide. The most common form, ischemic stroke, is increasing in incidence resulting in a significant burden on patients and society. Urgent action is thus needed to address preventable risk factors and improve treatment methods. This review examines emerging technologies used in the management of ischemic stroke, including neuroimaging, regenerative medicine, biology, and nanomedicine, highlighting their benefits, clinical applications, and limitations. Additionally, we suggest strategies for technological development for the prevention, diagnosis, and treatment of ischemic stroke.

9.
Front Surg ; 11: 1211325, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38660585

RESUMEN

Background: The success rate of periprosthetic joint infection (PJI) treatment is still low. Early diagnosis is the key to successful treatment. Therefore, it is necessary to find a biomarker with high sensitivity and specificity. The diagnostic value of serum procalcitonin (PCT) for PJI was systematically evaluated to provide the theoretical basis for clinical diagnosis and treatment in this study. Methods: We searched the Web of Science, Embase, Cochrane Library, and PubMed for studies that evaluated the diagnostic value of serum PCT for PJI (from the inception of each database until September 2020). Two authors independently screened the literature according to the inclusion and exclusion criteria. The quality of each selected literature was evaluated by using the Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2) tool. RevMan 5.3 software was used for the quality evaluation. The sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and diagnostic odds ratio (DOR) were merged by using Meta-DiSc 1.4 software. The area under the curve (AUC) and Q index were calculated after the summary receiver operating characteristic (SROC) was generated. We also performed subgroup analysis. Results: A total of 621 patients were enrolled in the nine studies. The pooled sensitivity of serum PCT for PJI diagnosis was 0.441 [95% confidence interval (CI), 0.384-0.500], the pooled specificity was 0.852 (95% CI, 0.811-0.888), the pooled PLR was 2.271 (95% CI, 1.808-2.853), the pooled NLR was 0.713 (95% CI, 0.646-0.786), and the pooled DOR was 5.756 (95% CI, 3.673-9.026). The area under SROC (the pooled AUC) was 0.76 (0.72-0.79). Q index was 0.6948. Conclusion: This study showed that PCT detection of PJI had poor diagnostic accuracy. Hence, the serum PCT is not suitable as a serum marker for PJI diagnosis.

10.
Phytomedicine ; 128: 155530, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38493723

RESUMEN

BACKGROUND: Ischemic stroke (IS) ranks as the second common cause of death worldwide. However, a narrow thrombolysis timeframe and ischemia-reperfusion (I/R) injury limits patient recovery. Moreover, anticoagulation and antithrombotic drugs do not meet the clinical requirements. Studies have demonstrated close communication between the brain and gut microbiota in IS. Notoginsenoside R1 (NG-R1), a significant component of the total saponins from Panax notoginseng, has been demonstrated to be effective against cerebral I/R injury. Total saponins have been used to treat IS in Chinese pharmacopoeia. Furthermore, previous research has indicated that the absorption of NG-R1 was controlled by gut microbiota. STUDY DESIGN: This study aimed to access the impact of NG-R1 treatment on neuroinflammation and investigate the microbiota-related mechanisms. RESULTS: NG-R1 significantly reduced neuronal death and neuroinflammation in middle cerebral artery occlusion/reperfusion (MCAO/R) models. 16S rRNA sequencing revealed that NG-R1 treatment displayed the reversal of microbiota related with MCAO/R models. Additionally, NG-R1 administration attenuated intestinal inflammation, gut barrier destruction, and systemic inflammation. Furthermore, microbiota transplantation from NG-R1 exhibited a similar effect in the MCAO/R models. CONCLUSION: In summary, NG-R1 treatment resulted in the restoration of the structure of the blood-brain barrier (BBB) and reduction in neuroinflammation via suppressing the stimulation of astrocytes and microglia in the cerebral ischemic area. Mechanistic research demonstrated that NG-R1 treatment suppressed the toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor kappa B (TLR4/MyD88/NF-κB) signaling pathway in both the ischemic brain and colon. NG-R1 treatment enhanced microbiota dysbiosis by inhibiting the TLR4 signaling pathway to protect MCAO/R models. These findings elucidate the mechanisms by which NG-R1 improve stroke outcomes and provide some basis for Panax notoginseng saponins in clinical treatment.


Asunto(s)
Microbioma Gastrointestinal , Ginsenósidos , Factor 88 de Diferenciación Mieloide , FN-kappa B , Daño por Reperfusión , Transducción de Señal , Receptor Toll-Like 4 , Receptor Toll-Like 4/metabolismo , Animales , Factor 88 de Diferenciación Mieloide/metabolismo , Daño por Reperfusión/tratamiento farmacológico , FN-kappa B/metabolismo , Ginsenósidos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Masculino , Ratas Sprague-Dawley , Eje Cerebro-Intestino/efectos de los fármacos , Panax notoginseng/química , Ratas , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Modelos Animales de Enfermedad , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Isquemia Encefálica/tratamiento farmacológico
11.
Front Pharmacol ; 15: 1294620, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38318138

RESUMEN

Introduction: Diabetic retinopathy (DR) represents a major cause of adult blindness, and early discovery has led to significant increase in the number of patients with DR. The drugs currently used for treatment, such as ranibizumab, mainly focus on the middle and late periods of DR, and thus do not meet the clinical need. Here, the potential mechanisms by which compound Danshen Dripping Pills (CDDP) might protect against early DR were investigated. Methods: Db/db mice were used to establish a DR model. The initial weights and HbA1c levels of the mice were monitored, and retinal pathology was assessed by hematoxylin-eosin (HE) staining. The vascular permeability of the retina and thickness of each retinal layer were measured, and electroretinogram were performed together with fundus fluorescein angiography and optical coherence tomography. The levels of inflammatory factors were examined in retinal tissue, as well as those of intercellular adhesion molecule 1 (ICAM-1), IL-6, and monocyte chemoattractant protein 1 (MCP-1) in the serum using ELISA. Immunohistochemistry was used to evaluate levels of vascular endothelial growth factor (VEGF), B-cell lymphoma 2 (Bcl-2), and Bclassociated X protein (Bax). Retinal cell injury and apoptosis were examined by TdT-mediated dUTP Nick End Labeling (TUNEL) assays. Results: The data showed that CDDP significantly improved cellular disarrangement. Imaging data indicated that CDDP could reduce vascular permeability and the amplitude of oscillatory potentials (OPs), and restore the thickness of the ganglion cell layer. Moreover, CDDP reduced the expression levels of inflammatory factors in both the retina and serum. Conclusion: These findings strongly suggest that CDDP prevents early DR through vascular and neuroprotection.

12.
PLoS One ; 19(6): e0305541, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38885233

RESUMEN

BACKGROUND: The inflammatory response is a key factor in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI), and anti-inflammatory interventions may offer a promising therapeutic strategy. Forsythoside B (FB) is a phenylethanoid glycoside isolated from Forsythiae fructus, which has been reported to have anti-inflammatory effects. However, the mechanism of the neuroprotective effect of FB on CIRI remains unclear. METHODS: Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R). FB was administered intraperitoneally for 3 days prior to MCAO/R. Cerebral infarct volume and neurological deficit score were used as indices to evaluate MCAO/R injury. The serum levels of inflammatory factors and antioxidant enzymes were measured. The activation of silent information regulator 2 homolog 1 (Sirt1) and the inhibition of the nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 (NLRP3) pathway were assessed through western blot and immunohistochemistry analysis. Furthermore, the rats were treated with Sirt1 shRNA 3 days before MCAO/R by stereotactical injection into the ipsilateral hemispheric region to assess the impact of Sirt1 knockdown on the protection of FB during MCAO/R. RESULTS: FB reduced cerebral infarct volume and neurological deficit score in MCAO/R rats. FB reduced pathological changes and cell apoptosis in the hippocampal CA1 region and cortex on the ischemic side of rats. FB inhibited the serum levels of inflammatory factors and increased the activities of antioxidant enzymes. Further study showed that FB inhibited the activation of the NLRP3 pathway and induced Sirt1 activation. CONCLUSION: FB demonstrated neuroprotective and anti-inflammatory effects by inhibiting the NLRP3 pathway through Sirt1 activation in CIRI.


Asunto(s)
Infarto de la Arteria Cerebral Media , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLR , Ratas Sprague-Dawley , Daño por Reperfusión , Sirtuina 1 , Animales , Sirtuina 1/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismo , Masculino , Inflamasomas/metabolismo , Ratas , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/complicaciones , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Ácidos Cafeicos , Glucósidos
13.
J Ethnopharmacol ; 322: 117672, 2024 Mar 25.
Artículo en Inglés | MEDLINE | ID: mdl-38159826

RESUMEN

AIM OF THE STUDY: Naoxinqing (NXQ) tablets are derived from persimmon leaves and are widely used in China for promoting blood circulation and removing blood stasis in China. We aimed to explore whether NXQ has the therapeutic effect on ischemic stroke and explored its possible mechanism. MATERIALS AND METHODS: The cerebral artery occlusion/reperfusion (MCAO/R) surgery was used to establish the cerebral ischemic/reperfusion rat model. NXQ (60 mg/kg and 120 mg/kg) were administered orally. The TTC staining, whole brain water content, histopathology staining, immunofluorescent staining, enzyme-linked immunosorbent assay (ELISA) and Western blot analyses were performed to determine the therapeutical effect of NXQ on MCAO/R rats. RESULTS: The study demonstrated that NXQ reduced the cerebral infarction volumes and neurologic deficits in MCAO/R rats. The neuroprotective effects of NXQ were accompanied by inhibited oxidative stress and inflammation. The nerve regeneration effects of NXQ were related to regulating the AMPKα/NAMPT/SIRT1/PGC-1α pathway. CONCLUSION: In summary, our results revealed that NXQ had a significant protective effect on cerebral ischemia-reperfusion injury in rats. This study broadens the therapeutic scope of NXQ tablets and provides new neuroprotective mechanisms of NXQ as an anti-stroke therapeutic agent.


Asunto(s)
Isquemia Encefálica , Enfermedades Metabólicas , Fármacos Neuroprotectores , Daño por Reperfusión , Accidente Cerebrovascular , Ratas , Animales , Sirtuina 1/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Encéfalo , Isquemia Encefálica/metabolismo , Enfermedades Metabólicas/tratamiento farmacológico , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Infarto de la Arteria Cerebral Media/patología , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/metabolismo
14.
Sci Rep ; 14(1): 7679, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561368

RESUMEN

Allelopathy is a process whereby a plant directly or indirectly promotes or inhibits growth of surrounding plants. Perennial sugarcane root extracts from various years significantly inhibited Bidens pilosa, Digitaria sanguinalis, sugarcane stem seedlings, and sugarcane tissue-cultured seedlings (P < 0.05), with maximum respective allelopathies of - 0.60, - 0.62, - 0.20, and - 0.29. Allelopathy increased with increasing concentrations for the same-year root extract, and inhibitory effects of the neutral, acidic, and alkaline components of perennial sugarcane root extract from different years were significantly stronger than those of the control for sugarcane stem seedlings (P < 0.05). The results suggest that allelopathic effects of perennial sugarcane root extract vary yearly, acids, esters and phenols could be a main reason for the allelopathic autotoxicity of sugarcane ratoons and depend on the type and content of allelochemicals present, and that allelopathy is influenced by other environmental factors within the rhizosphere such as the presence of old perennial sugarcane roots. This may be a crucial factor contributing to the decline of perennial sugarcane root health.


Asunto(s)
Saccharum , Plantones , Raíces de Plantas/química , Malezas/fisiología , Alelopatía , Extractos Vegetales/química
15.
Expert Opin Drug Saf ; 23(4): 487-495, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38497691

RESUMEN

BACKGROUND: Hemorrhage represents the most common and serious side effect of antithrombotic agents. Many studies have compared the risk of bleeding between different antithrombotic agents, but analysis of time-to-onset for hemorrhage induced by these drugs is yet sparse. METHODS: We conducted a retrospective study based on the adverse drug reaction reports on antithrombotic agents collected by the Henan Adverse Drug Reaction Monitoring Center. We assessed the reporting odds ratio to determine the disproportionate reporting signals for bleeding and the Weibull shape parameter was used to evaluate the time-to-onset data. RESULTS: In the signal detection, crude low molecular weight heparin-hemorrhage was found as a positive signal. The hemorrhage for most antithrombotic agents was random failure profiles. In particular, the hazard of hemorrhage decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole. CONCLUSION: We found that the risk of bleeding in patients taking Crude low molecular weight heparins was significantly higher compared to other antithrombotic agents, but with a small magnificence, which may be attributed to the severely irrational use of this medication under improper management. Statistics in days, results showed that the risk of bleeding decreased over time for warfarin and clopidogrel and increased for alteplase, nadroparin, and dipyridamole.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Fibrinolíticos , Humanos , Fibrinolíticos/efectos adversos , Warfarina/efectos adversos , Nadroparina/efectos adversos , Clopidogrel/efectos adversos , Activador de Tejido Plasminógeno/efectos adversos , Estudios Retrospectivos , Farmacovigilancia , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Anticoagulantes/efectos adversos , Dipiridamol/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos
16.
Mult Scler Relat Disord ; 82: 105405, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38194895

RESUMEN

BACKGROUND: There is an age-dependent change in the clinical phenotype of Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, the clinical features of late-onset MOGAD have not been well described. METHODS: Clinical data of 110 MOGAD patients, including 21 late-onset patients with onset age greater than or equal to 50 years old were retrospectively analyzed. RESULTS: Compared to pediatric- and younger adult-onset ones, late-onset MOGAD patients experienced milder disease onset (p < 0.001), more monophasic course (p < 0.001), fewer relapses (p = 0.007), less cerebrospinal fluid leukocytosis (p = 0.021), less longitudinally extensive transverse myelitis (onset p = 0.026, whole course p = 0.028), fewer lesions in basal ganglia (whole course p = 0.012), thalamus (whole course p = 0.040) and cerebellum (whole course p = 0.028). However, they had more cerebral symptoms (p = 0.021 onset and whole course), more lesions in white matter (onset p = 0.005, whole course p < 0.001) and periventricular area (onset p = 0.026), along with longer and delayed therapeutic intervention (p < 0.001). The main differences in clinical characteristics between late-onset patients with and without these brain involvements might be comorbidities. CONCLUSIONS: Late-onset MOGAD are more likely to experience delayed diagnosis. Brain involvement may be modulated by comorbidities of the elderly, which alter the clinical manifestations of late-onset MOGAD.


Asunto(s)
Ganglios Basales , Neuromielitis Óptica , Adulto , Anciano , Humanos , Niño , Glicoproteína Mielina-Oligodendrócito , Estudios Retrospectivos , Encéfalo/diagnóstico por imagen , Cerebelo , Autoanticuerpos , Acuaporina 4
18.
Sci China Life Sci ; 67(4): 680-697, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38206438

RESUMEN

The study of tumor nanovaccines (NVs) has gained interest because they specifically recognize and eliminate tumor cells. However, the poor recognition and internalization by dendritic cells (DCs) and insufficient immunogenicity restricted the vaccine efficacy. Herein, we extracted two molecular-weight Astragalus polysaccharides (APS, 12.19 kD; APSHMw, 135.67 kD) from Radix Astragali and made them self-assemble with OVA257-264 directly forming OVA/APS integrated nanocomplexes through the microfluidic method. The nanocomplexes were wrapped with a sheddable calcium phosphate layer to improve stability. APS in the formed nanocomplexes served as drug carriers and immune adjuvants for potent tumor immunotherapy. The optimal APS-NVs were approximately 160 nm with uniform size distribution and could remain stable in physiological saline solution. The FITC-OVA in APS-NVs could be effectively taken up by DCs, and APS-NVs could stimulate the maturation of DCs, improving the antigen cross-presentation efficiency in vitro. The possible mechanism was that APS can induce DC activation via multiple receptors such as dectin-1 and Toll-like receptors 2 and 4. Enhanced accumulation of APS-NVs both in draining and distal lymph nodes were observed following s.c. injection. Smaller APS-NVs could easily access the lymph nodes. Furthermore, APS-NVs could markedly promote antigen delivery efficiency to DCs and activate cytotoxic T cells. In addition, APS-NVs achieve a better antitumor effect in established B16-OVA melanoma tumors compared with the OVA+Alum treatment group. The antitumor mechanism correlated with the increase in cytotoxic T cells in the tumor region. Subsequently, the poor tumor inhibitory effect of APS-NVs on the nude mouse model of melanoma also confirmed the participation of antitumor adaptive immune response induced by NVs. Therefore, this study developed a promising APS-based tumor NV that is an efficient tumor immunotherapy without systemic side effects.


Asunto(s)
Vacunas contra el Cáncer , Melanoma , Ratones , Animales , Nanovacunas , Melanoma/patología , Células Dendríticas , Adyuvantes Inmunológicos/farmacología , Inmunoterapia , Antígenos , Polisacáridos/química , Ratones Endogámicos C57BL
19.
Mult Scler Relat Disord ; 85: 105478, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38457885

RESUMEN

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) and multiple sclerosis (MS), autoimmune inflammatory diseases of the central nervous system, affect the optic nerve and brain. A lumbar puncture to obtain biomarkers is highly invasive. Serum biomarkers and optical coherence tomography angiography (OCTA) are more accessible and less expensive than magnetic resonance imaging and provide reliable, reproducible measures of neuroaxonal damage. This study investigated the association between serum neurofilament light chain (sNfL), serum glial fibrillary acidic protein (sGFAP), and OCTA metrics. Serum sNfL and sGFAP levels, OCTA values, and clinical characteristics were compared among 91 patients with NMOSD, 81 patients with MS, and 34 healthy controls (HCs) at baseline and 1-year follow-up. RESULTS: sNfL and sGFAP levels were higher while the sGFAP/sNfL quotients were significantly lower in NMOSD and MS patients than those in HCs. At baseline, the average thicknesses of the peripapillary retinal nerve fibre layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGC-IPL) were significantly smaller in NMOSD and MS patients than those in HCs (pRNFL: MS 92.0 [80.2; 101] µm, NMOSD 80.0 [59.0; 95.8] µm, vs HC 99.0 [92.0; 104] µm, p < 0.001; mGC-IPL: MS 74.5 [64.2; 81.0] µm, NMOSD 68.0 [56.0; 81.0] µm, vs HC 83.5 [78.0; 88.0] µm, p < 0.001). The vessel density (VD) and perfusion density (PD) were increased in MS patients without optic neuritis compared to HCs (VD: MS 16.7 [15.6; 17.9] HC 15.3 [13.4; 16.9], p = 0.008; PD: MS 0.41 [0.38; 0.43], HC 0.37 [0.32; 0.41], p = 0.017). In NMOSD patients without optic neuritis, sNfL was significantly associated with PD at baseline (r = 0.329, q = 0.041). The baseline and follow-up values of the sNfL level and average pRNFL and mGC-IPL thicknesses in MS patients showed significant differences. NMOSD patients showed significant differences between baseline and follow-up sNfL and sGFAP levels but not OCTA metrics. CONCLUSION: Changes in retinal microvasculature might occur earlier than those in retinal structure and may therefore serve as a promising diagnostic marker for early NMOSD. The combination of serum markers and OCTA metrics could be used to evaluate and differentiate between MS and NMOSD.


Asunto(s)
Biomarcadores , Proteína Ácida Fibrilar de la Glía , Esclerosis Múltiple , Proteínas de Neurofilamentos , Neuromielitis Óptica , Tomografía de Coherencia Óptica , Humanos , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/sangre , Femenino , Masculino , Adulto , Esclerosis Múltiple/sangre , Esclerosis Múltiple/diagnóstico por imagen , Biomarcadores/sangre , Persona de Mediana Edad , Proteínas de Neurofilamentos/sangre , Proteína Ácida Fibrilar de la Glía/sangre
20.
Eur J Med Res ; 29(1): 401, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39095855

RESUMEN

BACKGROUND: Small-cell lung cancer (SCLC) is a leading cause of cancer-related death. However, the prognostic value of the tumor shrinkage rate (TSR) after chemotherapy for SCLC is still unknown. METHODS: We performed a retrospective analysis of 235 patients with SCLC. The TSR cutoff was determined based on receiver-operating characteristic curve analysis. The associations of TSR with progression-free survival (PFS) and overall survival (OS) were assessed using univariate and multivariate Cox proportional hazards models. Survival curves were obtained by the Kaplan-Meier method and compared using the log-rank test. Recurrence patterns after first-line treatment were summarized in a pie chart. A nomogram was constructed to validate the predictive role of the TSR in SCLC. RESULTS: The TSR cutoff was identified to be - 6.6%. Median PFS and OS were longer in the group with a TSR < -6.6% than in the group with a TSR ≥ - 6.6%. PFS and OS were also longer in patients with extensive SCLC when the TSR was < - 6.6% than when it was > - 6.6%. Brain metastasis-free survival was better in the group with a TSR < - 6.6%. There was a significant positive correlation between TSR and PFS. Furthermore, univariate and multivariate regression analyses showed that the TSR, patient age, and previous radiotherapy were independent prognostic factors for OS while TSR and M stage were independent prognostic factors for PFS. CONCLUSIONS: The TSR may prove to be a good indicator of OS and PFS in patients receiving chemotherapy-based first-line treatment for SCLC.


Asunto(s)
Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Masculino , Femenino , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Persona de Mediana Edad , Anciano , Pronóstico , Estudios Retrospectivos , Adulto , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Radiómica
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