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2.
Front Public Health ; 12: 1371675, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694993

RESUMEN

Background: In China, little is known about the hope level of older people living with HIV/AIDS (PLWHA). This study was to examine the hope level of older PLWHA in China and identify related factors. Methods: This cross-sectional study was conducted in Sichuan province in China among older PLWHA. A standardized self-report questionnaire, the Herth Hope Index, was adopted. Multiple linear regression was used to identify factors influencing hope level. p-values <0.05 were considered statistically significant. Results: There were 314 participants with an average age of 64.5 (SD ± 8.7). Most of the participants were males (72.6%), primary school and below (65.9%), rural household registration (58.6%) and married (64.3%). More than half of the older adults had pension insurance, had a monthly income of more than RMB 1,000 and considered themselves to be in good health. About 80% confirmed being diagnosed for more than a year and disclosed their HIV status to family and friends. The majority of the population had low medium social support (79%). More than 80% had moderate and severe HIV stigma. Many older PLWHA had medium and high levels of hope, with an average score of 34.31 (SD ± 4.85). Multiple linear regression showed that having pension insurance (ß = 1.337, p = 0.015), longer diagnosis (ß = 0.497, p = 0.031), better self-reported health (ß = 1.416, p<0.001) and higher levels of social support (ß = 2.222, p < 0.001) were positively associated with higher levels of hope. HIV stigma (ß = -1.265, p < 0.001) was negatively correlated with hope level. Conclusion: The hope level of older PLWHA is good, but there is still room for improvement, and its hope is related to multiple factors. Therefore, the AIDS-related healthcare sector should pay special attention to the hope of older PLWHA, help them to improve their health, provide financial assistance and social aid to those with financial difficulties, and take measures to reduce HIV stigma, improve family support for the older adults, and guide the older adults to adopt a positive approach to life.


Asunto(s)
Infecciones por VIH , Esperanza , Apoyo Social , Humanos , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Infecciones por VIH/psicología , China , Anciano , Encuestas y Cuestionarios , Estigma Social , Autoinforme
3.
Heliyon ; 10(10): e31036, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38774323

RESUMEN

Objectives: This study aims to investigate the use of sodium iodide (NaI), dimethyl sulfoxide (DMSO), ethyl alcohol, and ethyl acetate as cone-beam CT (CBCT) contrast agents for diagnosing cracked teeth. The optimal delay time for detecting the number of crack lines beyond the dentino-enamel junction (Nd), the number of cracks extending from the occlusal surface to the pulp cavity (Np), and the depth of the crack lines was explored. Methods: 14 human extracted cracked teeth were collected, 12 were used for enhanced scanning, and 2 were used for exploring the characteristic of crack lines. The teeth were scanned in 3 CBCT enhanced scanning (ES) modes: ES1 using meglumine diatrizoate (MD); ES2 using NaI and DMSO, ES3 using NaI, DMSO, ethyl alcohol and ethyl acetate. Three delay times (15mins, 30mins, and 60mins) were set for scanning. Nd, Np, and depth of crack lines were evaluated. Results: There were totally 24 crack lines on 12 cracked teeth. Nd was 10 in ES1 at 60mins, 24 in ES2 at 60mins and 24 in ES3 at 15mins. Np was 1 in ES1 at 60mins, 10 in ES2 at 60mins and 21 in ES3 at 60mins, and there were significantly different among them (p < 0.01). The average depth presented on ES3 was significantly deeper than ES1 and ES2 (p < 0.01). Conclusion: NaI, DMSO, ethyl alcohol and ethyl acetate show potential as contrast agents for enhanced CBCT scanning in diagnosis of cracked teeth and their depth in vivo. A delay time of 15 min is necessary to confirm the existence of crack lines, while a longer delay time is required to ascertain if these crack lines extend to the pulp cavity.

4.
Int J Biol Macromol ; 268(Pt 2): 132013, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38697412

RESUMEN

Osteoporosis is a prevalent condition characterized by bone loss and decreased skeletal strength, resulting in an elevated risk of fractures. Calcium plays a crucial role in preventing and managing osteoporosis. However, traditional calcium supplements have limited bioavailability, poor solubility, and adverse effects. In this study, we isolated a natural soluble biopolymer, calcium polymalate (PMACa), from the fermentation broth of the fungus Aureobasidium pullulans, to investigate its potential as an anti-osteoporosis therapeutic agent. Characterization revealed that linear PMA-Ca chains juxtaposed to form a porous, rod-like state, in the presence of Ca2+. In vivo mouse models demonstrated that PMA-Ca significantly promoted the conversion of serum calcium into bone calcium, and stimulated bone growth and osteogenesis. Additionally, PMA-Ca alleviated exercise fatigue in mice by facilitating the removal of essential metabolites, such as serum lactate (BLA) and blood urea nitrogen (BUN), from their bloodstream. In vitro studies further showed that PMA-Ca strengthened osteoblast cell activity, proliferation, and mineralization. And PMA-Ca upregulated the expression of some genes involved in osteoblast differentiation, indicating a potential correlation between bone formation and PMACa. These findings indicate that soluble PMA-Ca has the potential to be a novel biopolymer-based calcium supplement with sustainable production sourced from the fermentation industry.

5.
Mol Divers ; 2024 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-38709458

RESUMEN

Nitric oxide (NO), the smallest signaling molecule known, can be excessively produced by overexpressed inducible nitric oxide synthase (iNOS), and eventually leads to multiple inflammatory related diseases. Thus, reducing the overexpression of NO represents as very potential anti-inflammatory strategy. In current study, a series of compounds were designed and synthesized based on the hybridization of 7H-pyrrolo[2,3-d]pyrimidine and cinnamamide fragments in order to develop novel NO production inhibitors. Among them, compound S2h displayed a vigorous inhibitory activity on NO production with an IC50 value of 3.21 ± 0.67 µM, which was much lower than that of the positive control Nω-nitro-L-arginine (L-NNA, IC50 = 28.36 ± 3.13 µM). Due to its obeying Lipinski's and Veber's rules that guarantee compounds with good oral bioavailability, S2h effectively suppressed the paw swelling in carrageenan-induced mice. Additionally, compound S2h formed clear interactions with iNOS protein according to the docking analysis. Therefore, compounds S2h is a promising lead compound for further development of potent iNOS inhibitors or anti-inflammatory agents.

6.
Nat Commun ; 15(1): 3842, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38714674

RESUMEN

The development and utilization of bulk resources provide the basic material needs for industrial systems. However, most current resource utilization patterns are unsustainable, with low efficiencies and high carbon emissions. Here, we report a quantitative tool for resource-based industries to facilitate sustainable and low-carbon transitions within the regional economy. To evaluate the effectiveness of this tool, the saline Qinghai Lake region was chosen as a case study. After optimizing the industrial structure, the benefits of economic output, resource efficiency, energy consumption, solid waste reduction, and carbon emission reduction can be obtained. The scenario analyses exhibit disparities in different transition paths, where the carbon mitigation, economic output, and resource efficiency that benefit from optimal development paths are significantly better than those of the traditional path, indicating the urgency of adopting cleaner technology and industrial symbiosis for regional industries.

7.
Drug Des Devel Ther ; 18: 1385-1398, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38689609

RESUMEN

In the past few decades, chemotherapy has been one of the most effective cancer treatment options. Drug resistance is currently one of the greatest obstacles to effective cancer treatment. Even though drug resistance mechanisms have been extensively investigated, they have not been fully elucidated. Recent genome-wide investigations have revealed the existence of a substantial quantity of long non-coding RNAs (lncRNAs) transcribed from the human genome, which actively participate in numerous biological processes, such as transcription, splicing, epigenetics, the cell cycle, cell differentiation, development, pluripotency, immune microenvironment. The abnormal expression of lncRNA is considered a contributing factor to the drug resistance. Furthermore, drug resistance may be influenced by genetic and epigenetic variations, as well as individual differences in patient treatment response, attributable to polymorphisms in metabolic enzyme genes. This review focuses on the mechanism of lncRNAs resistance to target drugs in the study of tumors with high mortality, aiming to establish a theoretical foundation for targeted therapy.


Asunto(s)
Antineoplásicos , Resistencia a Antineoplásicos , Neoplasias , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Antineoplásicos/farmacología , Animales
8.
Plant Mol Biol ; 114(3): 37, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38602592

RESUMEN

Reactive oxygen species (ROS) is a chemically reactive chemical substance containing oxygen and a natural by-product of normal oxygen metabolism. Excessive ROS affect the growth process of crops, which will lead to the decrease of yield. Nitrogen, as a critical nutrient element in plants and plays a vital role in plant growth and crop production. Nitrate is the primary nitrogen source available to plants in agricultural soil and various natural environments. However, the molecular mechanism of ROS-nitrate crosstalk is still unclear. In this study, we used the foxtail millet (Setaria italica L.) as the material to figure it out. Here, we show that excessive NaCl inhibits nitrate-promoted plant growth and nitrogen use efficiency (NUE). NaCl induces ROS accumulation in roots, and ROS inhibits nitrate-induced gene expression in a short time. Surprisingly, low concentration ROS slight promotes and high concentration of ROS inhibits foxtail millet growth under long-term H2O2 treatment. These results may open a new perspective for further exploration of ROS-nitrate signaling pathway in plants.


Asunto(s)
Nitratos , Setaria (Planta) , Especies Reactivas de Oxígeno , Nitratos/farmacología , Setaria (Planta)/genética , Peróxido de Hidrógeno , Cloruro de Sodio , Oxígeno , Transducción de Señal , Perfilación de la Expresión Génica , Nitrógeno
9.
Nat Commun ; 15(1): 3252, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627384

RESUMEN

The adenosine A3 receptor (A3AR), a key member of the G protein-coupled receptor family, is a promising therapeutic target for inflammatory and cancerous conditions. The selective A3AR agonists, CF101 and CF102, are clinically significant, yet their recognition mechanisms remained elusive. Here we report the cryogenic electron microscopy structures of the full-length human A3AR bound to CF101 and CF102 with heterotrimeric Gi protein in complex at 3.3-3.2 Å resolution. These agonists reside in the orthosteric pocket, forming conserved interactions via their adenine moieties, while their 3-iodobenzyl groups exhibit distinct orientations. Functional assays reveal the critical role of extracellular loop 3 in A3AR's ligand selectivity and receptor activation. Key mutations, including His3.37, Ser5.42, and Ser6.52, in a unique sub-pocket of A3AR, significantly impact receptor activation. Comparative analysis with the inactive A2AAR structure highlights a conserved receptor activation mechanism. Our findings provide comprehensive insights into the molecular recognition and signaling of A3AR, paving the way for designing subtype-selective adenosine receptor ligands.


Asunto(s)
Receptor de Adenosina A3 , Transducción de Señal , Humanos , Receptor de Adenosina A3/metabolismo , Microscopía por Crioelectrón
10.
Cancer Lett ; 589: 216831, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38574882

RESUMEN

How tumors arise or the cause of precancerous lesions is a fundamental question in cancer biology. It is generally accepted that tumors originate from normal cells that undergo uncontrolled proliferation owing to genetic alterations. At the onset of adenoma formation, cancer driver mutations confer clonal growth advantage, enabling mutant cells to outcompete and eliminate the surrounding healthy cells. Hence, the development of precancerous lesions is not only attributed to the expansion of pre-malignant clones, but also relies on the relative fitness of mutated cells compared to the neighboring cells. Colorectal cancer (CRC) is an excellent model to investigate cancer origin as it follows a stereotypical process from mutant cell hyperplasia to adenoma formation and progression. Here, we review the evolving understanding of colonic tumor development, focusing on how cell intrinsic and extrinsic factors impact cell competition and the "clone war" between cancer-initiating cells and normal stem cells. We also discuss the promises and limitations of targeting cell competitiveness in cancer prevention and early intervention. The field of tumor initiation is currently in its infancy, elucidating the adenoma origin is crucial for designing effective prevention strategies and early treatments before cancer becomes incurable.


Asunto(s)
Adenoma , Neoplasias del Colon , Neoplasias Colorrectales , Lesiones Precancerosas , Humanos , Lesiones Precancerosas/genética , Mutación , Adenoma/genética , Adenoma/prevención & control , Adenoma/patología , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/prevención & control , Neoplasias Colorrectales/patología
11.
Ophthalmol Ther ; 13(6): 1589-1599, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38587772

RESUMEN

INTRODUCTION: Herpes zoster ophthalmicus (HZO) results from the reactivation of varicella zoster virus (VZV) in the ophthalmic branch of the trigeminal nerve. The inflammation caused by VZV involves multiple tissues in the eyes. Our goal is to evaluate pattern electroretinogram (PERG) changes and their relationship with corneal sub-basal nerve changes in patients with HZO. METHODS: Twenty-two patients with herpes zoster keratitis or conjunctivitis and 20 healthy volunteers were recruited for this cross-sectional study. A PERG test was performed on both eyes of HZO patients and one eye of the healthy controls. In vivo confocal microscopy (IVCM) was also performed on both eyes of the HZO patients to detect corneal nerve damage. RESULTS: Our results showed changes in the PERG parameters in both eyes of HZO patients compared to the healthy controls. Affected eyes showed delayed N95 peak time and decreased P50 and N95 amplitude compared to the unaffected eyes (p < 0.05, respectively). Both affected and unaffected eyes in HZO patients showed delayed P50 peak time and decreased N95 amplitude (p < 0.05, respectively) compared to controls. In HZO patients, no significant differences in each PERG parameter were found between eyes with and without corneal lesions or between eyes with and without increased Langham's cells in the corneal epithelial sub-basal layer. The IVCM images showed decreased total nerve length and number at the sub-basal layer of the epithelial cornea in affected eyes compared to unaffected eyes (p < 0.05). No significant correlation was found between total nerve length and PERG changes. CONCLUSIONS: Our results showed that VZV-affected eyes without central cornea involvement displayed reduced N95 amplitude and prolonged P50 peak time in bilateral eyes compared to the healthy controls. Larger studies are needed to further explore the effect of HZO on the electrophysiological response of the eye and the posterior segment.

12.
Ann Anat ; 254: 152267, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38649115

RESUMEN

BACKGROUND: Reasonable postoperative humeroradial and humeroulnar joint spaces maybe an important indicator in biomechanical stability of smart internal fixation surgery for coronoid process basal fractures (CPBF). The aim of this study is to compare elbow articular stresses and elbow-forearm stability under smart internal fixations for the CPBF between normal elbow joint spaces and radius-shortening, and to determine the occult factor of radius-ulna load sharing. METHODS: CT images of 70 volunteers with intact elbow joints were retrospectively collected for accurate three-dimensional reconstruction to measure the longitudinal and transverse joint spaces. Two groups of ten finite element (FE) models were established prospectively between normal joint space and radius-shortening with 2.0 mm, including intact elbow joint and forearm, elbow-forearm with CPBF trauma, anterior or posterior double screws-cancellous bone fixation, mini-plate-cancellous bone fixation. Three sets of physiological loads (compression, valgus, varus) were used for FE intelligent calculation, FE model verification, and biomechanical and motion analysis. RESULTS: The stress distribution between coronoid process and radial head, compression displacements and valgus angles of elbow-forearm in the three smart fixation models of the normal joint spaces were close to those of corresponding intact elbow model, but were significantly different from those of preoperative CPBF models and fixed radius-shortening models. The maximum stresses of three smart fixation instrument models of normal joint spaces were significantly smaller than those of the corresponding fixed radius-shortening models. CONCLUSIONS: On the basis of the existing trauma of the elbow-forearm system in clinical practice, which is a dominant factor affecting radius-ulna load sharing, the elbow joint longitudinal space has been found to be the occult factor affecting radius-ulna load sharing. The stability and load sharing of radius and ulna after three kinds of smart fixations of the CPBF is not only related to the anatomical and biomechanical stability principles of smart internal fixations, but also closely related to postoperative elbow joint longitudinal space.


Asunto(s)
Articulación del Codo , Fijación Interna de Fracturas , Radio (Anatomía) , Humanos , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Masculino , Femenino , Articulación del Codo/cirugía , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/anatomía & histología , Radio (Anatomía)/cirugía , Radio (Anatomía)/diagnóstico por imagen , Radio (Anatomía)/anatomía & histología , Adulto , Persona de Mediana Edad , Análisis de Elementos Finitos , Fenómenos Biomecánicos , Cúbito/cirugía , Soporte de Peso , Estudios Retrospectivos , Adulto Joven , Fracturas del Radio/cirugía , Fracturas del Radio/diagnóstico por imagen , Tomografía Computarizada por Rayos X , Anciano
13.
Orphanet J Rare Dis ; 19(1): 171, 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38641832

RESUMEN

BACKGROUND: Clinical studies on progressive familial intrahepatic cholestasis (PFIC) type 5 caused by mutations in NR1H4 are limited. METHODS: New patients with biallelic NR1H4 variants from our center and all patients from literature were retrospectively analyzed. RESULTS: Three new patients were identified to be carrying five new variants. Liver phenotypes of our patients manifests as low-γ-glutamyl transferase cholestasis, liver failure and related complications. One patient underwent liver transplantation (LT) and survived, and two other patients died without LT. Nine other patients were collected through literature review. Twelve out of 13 patients showed neonatal jaundice, with the median age of onset being 7 days after birth. Reported clinical manifestations included cholestasis (13/13, 100%), elevated AFP (11/11, 100%), coagulopathy (11/11, 100%), hypoglycemia (9/13, 69%), failure to thrive (8/13, 62%), splenomegaly (7/13, 54%), hyperammonemia (7/13, 54%), and hepatomegaly (6/13, 46%). Six of 13 patients received LT at a median age of 6.2 months, and only one patient died of acute infection at one year after LT. Other 7 patients had no LT and died with a median age of 5 months (range 1.2-8). There were 8 patients with homozygous genotype and 5 patients with compound heterozygous genotype. In total, 13 different variants were detected, and 5 out of 12 single or multiple nucleotides variants were located in exon 5. CONCLUSIONS: We identified three newly-diagnosed patients and five novel mutations. NR1H4-related PFIC typically cause progressive disease and early death. LT may be the only lifesaving therapy leading to cure.


Asunto(s)
Colestasis Intrahepática , Colestasis , Humanos , Recién Nacido , Lactante , Estudios Retrospectivos , Colestasis Intrahepática/genética , Colestasis Intrahepática/diagnóstico , Colestasis Intrahepática/terapia , Colestasis/genética
14.
Front Psychol ; 15: 1373454, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38680289

RESUMEN

This quantitative study aimed to explore the relationships among music performance anxiety (MPA), teacher anxiety (TA), and self-efficacy (SE) through a survey study of Chinese preservice music teachers (N = 237). We also examined gender, grade, primary instrument, secondary instrument, music learning time length, and time spent in four activities: peer teaching, practicum, internship, and private teaching as potential predictors of MPA, TA, and SE. Results indicated that the higher the self-efficacy, the lower music performance anxiety and teaching anxiety; Simultaneously, the increased music performance anxiety was associated with an increased teaching anxiety. Partial correlation results indicated a significant but negative correlation between TA and SE with MPA controlled. Teaching anxiety, followed by primary piano, was the strongest predictor of MPA. MPA, followed by SE and peer teaching, was the strongest predictor of TA. TA, followed by grade level, was the strongest predictor of SE. The results from the multivariate analysis of variance revealed that the SE of male preservice music teachers were significantly higher than their female counterparts. As a study implication, music teacher educators may consider interventions and support mechanisms that address both types of anxiety simultaneously to improve overall teacher preparedness.

15.
Neurobiol Stress ; 30: 100632, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38601361

RESUMEN

The involvement of lipids in the mechanism of depression has triggered extensive discussions. Earlier studies have identified diminished levels of lysophosphatidic acid (LPA) and autotaxin (ATX) in individuals experiencing depression. However, the exact significance of this phenomenon in relation to depression remains inconclusive. This study seeks to explore the deeper implications of these observations. We assessed alterations in ATX and LPA in both the control group and the chronic unpredictable mild stress (CUMS) model group. Additionally, the impact of ATX adeno-associated virus (AAV-ATX) injection into the hippocampus was validated through behavioral tests in CUMS-exposed mice. Furthermore, we probed the effects of LPA on synapse-associated proteins both in HT22 cells and within the mouse hippocampus. The mechanisms underpinning the LPA-triggered shifts in protein expression were further scrutinized. Hippocampal tissues were augmented with ATX to assess its potential to alleviate depression-like behavior by modulating synaptic-related proteins. Our findings suggest that the decrement in ATX and LPA levels alters the expression of proteins associated with synaptic plasticity in vitro and in vivo, such as synapsin-I (SYN), synaptophysin (SYP), and brain-derived neurotrophic factor (BDNF). Moreover, we discerned a role for the ERK/CREB signaling pathway in mediating the effects of ATX and LPA. Importantly, strategic supplementation of ATX effectively mitigated depression-like behaviors. This study indicates that the ATX-LPA pathway may influence depression-like behaviors by modulating synaptic plasticity in the brains of CUMS-exposed mice. These insights augment our understanding of depression's potential pathogenic mechanism in the context of lipid metabolism and propose promising therapeutic strategies for ameliorating the disease.

16.
Anal Chem ; 96(16): 6180-6185, 2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38593062

RESUMEN

Chemical recycling is a promising approach to reduce plastic pollution. Timely and accurate size analysis of produced nanoplastics is necessary to monitor the process and assess the quality of chemical recycling. In this work, a sandwich-type microelectrode sensor was developed for the size assessment of nanoplastics. ß-Mercaptoethylamine was modified on the microelectrode to enhance its surface positive charge density. Polystyrene (PS) nanoplastics were captured on the sensor through electrostatic interactions. Ferrocene was used as an electrochemical beacon and attached to PS via hydrophobic interactions. The results show a nonlinear dependence of the sensor's current response on the PS particle size. The size resolving ability of the microelectrode is mainly attributed to the small size of the electrode and the resulting attenuation of the electric field strength. For mixed samples with different particle sizes, this method can provide accurate average particle sizes. Through an effective pretreatment process, the method can be applied to PS nanoplastics with different surface properties, ensuring its application in evaluating different chemical recycling methods.

17.
ACS Appl Mater Interfaces ; 16(13): 15879-15892, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38529805

RESUMEN

Tendon regeneration is greatly influenced by the oxidant and the inflammatory microenvironment. Persistent inflammation during the tendon repair can cause matrix degradation, tendon adhesion, and excessive accumulation of reactive oxygen species (ROS), while excessive ROS affect extracellular matrix remodeling and tendon integration. Herein, we used tannic acid (TA) to modify a decellularized tendon slice (DTS) to fabricate a functional scaffold (DTS-TA) with antioxidant and anti-inflammatory properties for tendon repair. The characterizations and cytocompatibility of the scaffolds were examined in vitro. The antioxidant and anti-inflammatory activities of the scaffold were evaluated in vitro and further studied in vivo using a subcutaneous implantation model. It was found that the modified DTS combined with TA via hydrogen bonds and covalent bonds, and the hydrophilicity, thermal stability, biodegradability, and mechanical characteristics of the scaffold were significantly improved. Afterward, the results demonstrated that DTS-TA could effectively reduce inflammation by increasing the M2/M1 macrophage ratio and interleukin-4 (IL-4) expression, decreasing the secretion of interleukin-6 (IL-6) and interleukin-1ß (IL-1ß), as well as scavenging excessive ROS in vitro and in vivo. In summary, DTS modified with TA provides a potential versatile scaffold for tendon regeneration.


Asunto(s)
Antioxidantes , Polifenoles , Andamios del Tejido , Humanos , Andamios del Tejido/química , Antioxidantes/farmacología , Especies Reactivas de Oxígeno , Tendones , Antiinflamatorios/farmacología , Inflamación/tratamiento farmacológico , Regeneración
18.
Spectrochim Acta A Mol Biomol Spectrosc ; 314: 124181, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38527410

RESUMEN

Distinct diagnosis between Lung cancer (LC) and gastric cancer (GC) according to the same biomarkers (e.g. aldehydes) in exhaled breath based on surface-enhanced Raman spectroscopy (SERS) remains a challenge in current studies. Here, an accurate diagnosis of LC and GC is demonstrated, using artificial intelligence technologies (AI) based on SERS spectrum of exhaled breath in plasmonic metal organic frameworks nanoparticle (PMN) film. In the PMN film with optimal structure parameters, 1780 SERS spectra are collected, in which 940 spectra come from healthy people (n = 49), another 440 come from LC patients (n = 22) and the rest 400 come from GC patients (n = 8). The SERS spectra are trained through artificial neural network (ANN) model with the deep learning (DL) algorithm, and the result exhibits a good identification accuracy of LC and GC with an accuracy over 89 %. Furthermore, combined with information of SERS peaks, the data mining in ANN model is successfully employed to explore the subtle compositional difference in exhaled breath from healthy people (H) and L/GC patients. This work achieves excellent noninvasive diagnosis of multiple cancer diseases in breath analysis and provides a new avenue to explore the feature of disease based on SERS spectrum.


Asunto(s)
Neoplasias Pulmonares , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Inteligencia Artificial , Neoplasias Pulmonares/diagnóstico , Espectrometría Raman , Pruebas Respiratorias/métodos , Pulmón
19.
Hypertens Res ; 47(5): 1273-1287, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38438725

RESUMEN

m6A (N6­methyladenosine) is the most common and abundant apparent modification in mRNA of eukaryotes. The modification of m6A is regulated dynamically and reversibly by methyltransferase (writer), demethylase (eraser), and binding protein (reader). It plays a significant role in various processes of mRNA metabolism, including regulation of transcription, maturation, translation, degradation, and stability. Pulmonary arterial hypertension (PAH) is a malignant cardiopulmonary vascular disease characterized by abnormal proliferation of pulmonary artery smooth muscle cells. Despite the existence of several effective and targeted therapies, there is currently no cure for PAH and the prognosis remains poor. Recent studies have highlighted the crucial role of m6A modification in cardiovascular diseases. Investigating the role of RNA m6A methylation in PAH could provide valuable insights for drug development. This review aims to explore the mechanism and function of m6A in the pathogenesis of PAH and discuss the potential targeting of RNA m6A methylation modification as a treatment for PAH.


Asunto(s)
Adenosina , Adenosina/análogos & derivados , Hipertensión Arterial Pulmonar , Humanos , Metilación , Adenosina/metabolismo , Hipertensión Arterial Pulmonar/genética , Hipertensión Arterial Pulmonar/metabolismo , Animales , ARN Mensajero/metabolismo , ARN Mensajero/genética , Metiltransferasas/metabolismo , Metiltransferasas/genética , Metilación de ARN
20.
Front Immunol ; 15: 1342810, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38464512

RESUMEN

Background: Clinicians and healthcare policymakers have been drenched with a deluge of overlapping meta-analyses (MAs), and the necessity for comprehensive and clearly defined evidence of Janus kinase inhibitors (JKIs) in atopic dermatitis (AD) is urgent. Methods: Six databases were searched for MAs published until October 2023. Qualitative description of MAs was mainly used, and Investigator's Global Assessment response (IGA response), the 75% improvement in Eczema Area and Severity Index (the EASI75), peak pruritus Numerical rating score (PP-NRS), and adverse effects were cited to describe the efficacy and safety of JKIs. The methodological quality of the included MAs was assessed by A Measurement Tool to Assess Systematic Reviews II (AMSTAR II), and the quality of evidence was evaluated by the grading of recommendations, assessment, development, and evaluation (GRADE). Results: Sixteen MAs were pooled in this review, of which five studies appraised JKIs, five appraised systemic JKIs, five papers assessed abrocitinib only, and one assessed baricitinib. Two studies were of "high" methodological quality and 14 MAs were of "moderate" quality. Eleven MAs integrated the results of JKIs and reported that JKIs provide faster onset of IGA response (RR=2.83, 95% CI [2.25, 3.56], high-quality evidence). Similarly, 10 MAs showed that JAK inhibitors were more effective in improving the EASI75 (RR=2.84, 95% CI [2.2, 3.67], high-quality evidence). Results from 12 MAs showed JKIs were active in reducing the PP-NRS (SMD=-0.49, 95% CI [-0.67, -0.32]). All MAs affirmed JKIs added no adverse effects leading to discontinuation and serious adverse events (P<0.05). However, 200mg of abrocitinib had a higher risk of acne (RR=4.34, 95% CI [1.61, 11.71), herpes zoster (RR=1.64, 95% CI [0.42, 6.39]), headache (RR=1.76, 95% CI [1.03, 3]), and nausea (RR=7.81, 95% CI [3.84, 15.87]). Upadacitinib was known to increase acne (RR=6.23, 95% CI [4.08, 9.49]), nasopharyngitis (RR=1.36, 95% CI [1.03, 1.8]) and blood creatine phosphokinase (blood CPK) (RR=2.41, 95% CI [1.47, 3.95]). Baricitinib at 2mg was associated with increased blood CPK (RR=2.25, 95% CI [1.1, 2.97]). Conclusion: Compared to placebo or dupilumab, the administration of JKIs can ameliorate IGA response more effectively, improve the EASI75, and relieve pruritus without severe adverse effect, while accompanied by more acne, nasopharyngitis, headache, and digestive disturbances. The curative effect of 200 mg of abrocitinib is significant and more caution should be given in patients with gastrointestinal dysfunction, herpes zoster, and those who are acne-prone. Baricitinib and upadacitinib should be avoided in populations at high risk for cardiovascular events. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=369369, PROSPERO (CRD42022369369).


Asunto(s)
Acné Vulgar , Azetidinas , Dermatitis Atópica , Herpes Zóster , Inhibidores de las Cinasas Janus , Nasofaringitis , Purinas , Pirazoles , Pirimidinas , Sulfonamidas , Humanos , Dermatitis Atópica/tratamiento farmacológico , Inhibidores de las Cinasas Janus/efectos adversos , Prurito/tratamiento farmacológico , Cefalea , Inmunoglobulina A/uso terapéutico
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