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1.
J Youth Adolesc ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38877364

RESUMO

Depressive symptoms and aggression frequently occur together, and this co-occurrence may result in more severe developmental problems. However, it is unclear if there are distinct patterns of co-occurrence. This study investigated the co-occurrence patterns of depressive symptoms and aggression, and examined their stability and demographic characteristics. A total of 1010 Chinese adolescents (50.6% girls; mean age at T1 = 12.54 years, SD = 0.42) participated in annual surveys over three years (2019-2021). Three different patterns of co-occurrence were found except for the normal group: depression-dominant co-occurrence (13.6%), aggression-dominant co-occurrence (3.2%), and moderate co-occurrence (6.0%) (T1). In these co-occurrence patterns, adolescents classified as aggression-dominant co-occurrence exhibited the most instability and frequent changes, while adolescents classified as depression-dominant co-occurrence exhibited the most stability. Boys or younger adolescents were more likely to exhibit the aggression-dominant co-occurrence, while girls or older adolescents were more likely to exhibit the depression-dominant co-occurrence. The findings indicate that the co-occurrence patterns observed are distinct and are dominated by aggression or depression, which implies the need for targeted intervention practices.

2.
Front Psychol ; 15: 1384053, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38863669

RESUMO

Background: Depression is one of the primary global public health issues, and there has been a dramatic increase in depression levels among young people over the past decade. The neuroplasticity theory of depression postulates that a malfunction in neural plasticity, which is responsible for learning, memory, and adaptive behavior, is the primary source of the disorder's clinical manifestations. Nevertheless, the impact of depression symptoms on associative learning remains underexplored. Methods: We used the differential fear conditioning paradigm to investigate the effects of depressive symptoms on fear acquisition and extinction learning. Skin conductance response (SCR) is an objective evaluation indicator, and ratings of nervousness, likeability, and unconditioned stimuli (US) expectancy are subjective evaluation indicators. In addition, we used associability generated by a computational reinforcement learning model to characterize the skin conductance response. Results: The findings indicate that individuals with depressive symptoms exhibited significant impairment in fear acquisition learning compared to those without depressive symptoms based on the results of the skin conductance response. Moreover, in the discrimination fear learning task, the skin conductance response was positively correlated with associability, as estimated by the hybrid model in the group without depressive symptoms. Additionally, the likeability rating scores improved post-extinction learning in the group without depressive symptoms, and no such increase was observed in the group with depressive symptoms. Conclusion: The study highlights that individuals with pronounced depressive symptoms exhibit impaired fear acquisition and extinction learning, suggesting a possible deficit in associative learning. Employing the hybrid model to analyze the learning process offers a deeper insight into the associative learning processes of humans, thus allowing for improved comprehension and treatment of these mental health problems.

3.
BMC Med ; 22(1): 253, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902735

RESUMO

BACKGROUND: Cognitive dysfunction is one of the common symptoms in patients with major depressive disorder (MDD). Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) have been studied separately in the treatment of cognitive dysfunction in MDD patients. We aimed to investigate the effectiveness and safety of rTMS combined with tDCS as a new therapy to improve neurocognitive impairment in MDD patients. METHODS: In this brief 2-week, double-blind, randomized, and sham-controlled trial, a total of 550 patients were screened, and 240 MDD inpatients were randomized into four groups (active rTMS + active tDCS, active rTMS + sham tDCS, sham rTMS + active tDCS, sham rTMS + sham tDCS). Finally, 203 patients completed the study and received 10 treatment sessions over a 2-week period. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) was performed to assess patients' cognitive function at baseline and week 2. Also, we applied the 24-item Hamilton Depression Rating Scale (HDRS-24) to assess patients' depressive symptoms at baseline and week 2. RESULTS: After 10 sessions of treatment, the rTMS combined with the tDCS group showed more significant improvements in the RBANS total score, immediate memory, and visuospatial/constructional index score (all p < 0.05). Moreover, post hoc tests revealed a significant increase in the RBANS total score and Visuospatial/Constructional in the combined treatment group compared to the other three groups but in the immediate memory, the combined treatment group only showed a better improvement than the sham group. The results also showed the RBANS total score increased significantly higher in the active rTMS group compared with the sham group. However, rTMS or tDCS alone was not superior to the sham group in terms of other cognitive performance. In addition, the rTMS combined with the tDCS group showed a greater reduction in HDRS-24 total score and a better depression response rate than the other three groups. CONCLUSIONS: rTMS combined with tDCS treatment is more effective than any single intervention in treating cognitive dysfunction and depressive symptoms in MDD patients. TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR2100052122).


Assuntos
Cognição , Transtorno Depressivo Maior , Estimulação Transcraniana por Corrente Contínua , Estimulação Magnética Transcraniana , Humanos , Transtorno Depressivo Maior/terapia , Masculino , Feminino , Estimulação Transcraniana por Corrente Contínua/métodos , Método Duplo-Cego , Adulto , Estimulação Magnética Transcraniana/métodos , Pessoa de Meia-Idade , Cognição/fisiologia , Resultado do Tratamento , Terapia Combinada , Adulto Jovem
4.
BMC Plant Biol ; 24(1): 493, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38831288

RESUMO

Drought is one of the natural stresses that greatly impact plants. Castor bean (Ricinus communis L.) is an oil crop with high economic value. Drought is one of the factors limiting castor bean growth. The drought resistance mechanisms of castor bean have become a research focus. In this study, we used castor germinating embryos as experimental materials, and screened genes related to drought resistance through physiological measurements, proteomics and metabolomics joint analysis; castor drought-related genes were subjected to transient silencing expression analysis in castor leaves to validate their drought-resistant functions, and heterologous overexpression and backward complementary expression in Arabidopsis thaliana, and analysed the mechanism of the genes' response to the participation of Arabidopsis thaliana in drought-resistance.Three drought tolerance-related genes, RcECP 63, RcDDX 31 and RcA/HD1, were obtained by screening and analysis, and transient silencing of expression in castor leaves further verified that these three genes corresponded to drought stress, and heterologous overexpression and back-complementary expression of the three genes in Arabidopsis thaliana revealed that the function of these three genes in drought stress response.In this study, three drought tolerance related genes, RcECP 63, RcDDX 31 and RcA/HD1, were screened and analysed for gene function, which were found to be responsive to drought stress and to function in drought stress, laying the foundation for the study of drought tolerance mechanism in castor bean.


Assuntos
Arabidopsis , Secas , Ricinus communis , Sementes , Ricinus communis/genética , Ricinus communis/fisiologia , Sementes/genética , Sementes/fisiologia , Sementes/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/fisiologia , Genes de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , Resistência à Seca
5.
Viruses ; 16(6)2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38932205

RESUMO

African swine fever (ASF) is a contagious viral disease affecting pigs and wild boars. It typically presents as a hemorrhagic fever but can also manifest in various forms, ranging from acute to asymptomatic. ASF has spread extensively globally, significantly impacting the swine industry. The complex and highly variable character of the ASFV genome makes vaccine development and disease surveillance extremely difficult. The overall trend in ASFV evolution is towards decreased virulence and increased transmissibility. Factors such as gene mutation, viral recombination, and the strain-specificity of virulence-associated genes facilitate viral variations. This review deeply discusses the influence of these factors on viral immune evasion, pathogenicity, and the ensuing complexities encountered in vaccine development, disease detection, and surveillance. The ultimate goal of this review is to thoroughly explore the genetic evolution patterns and variation mechanisms of ASFV, providing a theoretical foundation for advancement in vaccine and diagnostic technologies.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Variação Genética , Genoma Viral , Vírus da Febre Suína Africana/genética , Animais , Suínos , Febre Suína Africana/virologia , Virulência , Vacinas Virais/imunologia , Vacinas Virais/genética , Evolução Molecular , Evasão da Resposta Imune/genética , Mutação , Desenvolvimento de Vacinas
6.
Viruses ; 16(6)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38932241

RESUMO

African swine fever (ASF) is an acute, hemorrhagic, highly contagious disease in pigs caused by African swine fever virus (ASFV). Our previous study identified that the ASFV MGF300-2R protein functions as a virulence factor and found that MGF300-2R degrades IKKß via selective autophagy. However, the E3 ubiquitin ligase responsible for IKKß ubiquitination during autophagic degradation still remains unknown. In order to solve this problem, we first pulled down 328 proteins interacting with MGF300-2R through immunoprecipitation-mass spectrometry. Next, we analyzed and confirmed the interaction between the E3 ubiquitin ligase TRIM21 and MGF300-2R and demonstrated the catalytic role of TRIM21 in IKKß ubiquitination. Finally, we indicated that the degradation of IKKß by MGF300-2R was dependent on TRIM21. In summary, our results indicate TRIM21 is the E3 ubiquitin ligase involved in the degradation of IKKß by MGF300-2R, thereby augmenting our understanding of the functions of MGF300-2R and offering insights into the rational design of live attenuated vaccines and antiviral strategies against ASF.


Assuntos
Vírus da Febre Suína Africana , Quinase I-kappa B , Ribonucleoproteínas , Ubiquitina-Proteína Ligases , Ubiquitinação , Proteínas Virais , Animais , Vírus da Febre Suína Africana/metabolismo , Vírus da Febre Suína Africana/genética , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Suínos , Quinase I-kappa B/metabolismo , Ribonucleoproteínas/metabolismo , Ribonucleoproteínas/genética , Proteínas Virais/metabolismo , Proteínas Virais/genética , Febre Suína Africana/virologia , Febre Suína Africana/metabolismo , Humanos , Células HEK293 , Interações Hospedeiro-Patógeno , Fatores de Virulência/metabolismo , Autofagia , Ligação Proteica
7.
BMC Genomics ; 25(1): 524, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802777

RESUMO

BACKGROUND: The filamentous temperature-sensitive H protease (ftsH) gene family belongs to the ATP-dependent zinc metalloproteins, and ftsH genes play critical roles in plant chloroplast development and photosynthesis. RESULTS: In this study, we performed genome-wide identification and a systematic analysis of soybean ftsH genes. A total of 18 GmftsH genes were identified. The subcellular localization was predicted to be mainly in cell membranes and chloroplasts, and the gene structures, conserved motifs, evolutionary relationships, and expression patterns were comprehensively analyzed. Phylogenetic analysis of the ftsH gene family from soybean and various other species revealed six distinct clades, all of which showed a close relationship to Arabidopsis thaliana. The members of the GmftsH gene family were distributed on 13 soybean chromosomes, with intron numbers ranging from 3 to 15, 13 pairs of repetitive segment. The covariance between these genes and related genes in different species of Oryza sativa, Zea mays, and Arabidopsis thaliana was further investigated. The transcript expression data revealed that the genes of this family showed different expression patterns in three parts, the root, stem, and leaf, and most of the genes were highly expressed in the leaves of the soybean plants. Fluorescence-based real-time quantitative PCR (qRT-PCR) showed that the expression level of GmftsH genes varied under different stress treatments. Specifically, the genes within this family exhibited various induction levels in response to stress conditions of 4℃, 20% PEG-6000, and 100 mmol/L NaCl. These findings suggest that the GmftsH gene family may play a crucial role in the abiotic stress response in soybeans. It was also found that the GmftsH7 gene was localized on the cell membrane, and its expression was significantly upregulated under 4 ℃ treatment. In summary, by conducting a genome-wide analysis of the GmftsH gene family, a strong theoretical basis is established for future studies on the functionality of GmftsH genes. CONCLUSIONS: This research can potentially serve as a guide for enhancing the stress tolerance characteristics of soybean.


Assuntos
Regulação da Expressão Gênica de Plantas , Glycine max , Família Multigênica , Filogenia , Glycine max/genética , Glycine max/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Perfilação da Expressão Gênica , Arabidopsis/genética , Estresse Fisiológico/genética , Estudo de Associação Genômica Ampla , Cromossomos de Plantas/genética
8.
Int J Cancer ; 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38738976

RESUMO

The primary objective of this study is to develop a prediction model for peritoneal metastasis (PM) in colorectal cancer by integrating the genomic features of primary colorectal cancer, along with clinicopathological features. Concurrently, we aim to identify potential target implicated in the peritoneal dissemination of colorectal cancer through bioinformatics exploration and experimental validation. By analyzing the genomic landscape of primary colorectal cancer and clinicopathological features from 363 metastatic colorectal cancer patients, we identified 22 differently distributed variables, which were used for subsequent LASSO regression to construct a PM prediction model. The integrated model established by LASSO regression, which incorporated two clinicopathological variables and seven genomic variables, precisely discriminated PM cases (AUC 0.899; 95% CI 0.860-0.937) with good calibration (Hosmer-Lemeshow test p = .147). Model validation yielded AUCs of 0.898 (95% CI 0.896-0.899) and 0.704 (95% CI 0.622-0.787) internally and externally, respectively. Additionally, the peritoneal metastasis-related genomic signature (PGS), which was composed of the seven genes in the integrated model, has prognostic stratification capability for colorectal cancer. The divergent genomic landscape drives the driver genes of PM. Bioinformatic analysis concerning these driver genes indicated SERINC1 may be associated with PM. Subsequent experiments indicate that knocking down of SERINC1 functionally suppresses peritoneal dissemination, emphasizing its importance in CRCPM. In summary, the genomic landscape of primary cancer in colorectal cancer defines peritoneal metastatic pattern and reveals the potential target of SERINC1 for PM in colorectal cancer.

9.
Front Oncol ; 14: 1393650, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38737904

RESUMO

Objectives: To investigate the role of MRI measurements of peri-prostatic adipose tissue (PPAT) in predicting bone metastasis (BM) in patients with newly diagnosed prostate cancer (PCa). Methods: We performed a retrospective study on 156 patients newly diagnosed with PCa by prostate biopsy between October 2010 and November 2022. Clinicopathologic characteristics were collected. Measurements including PPAT volume and prostate volume were calculated by MRI, and the normalized PPAT (PPAT volume/prostate volume) was computed. Independent predictors of BM were determined by univariate and multivariate logistic regression analysis, and a new nomogram was developed based on the predictors. Receiver operating characteristic (ROC) curves were used to estimate predictive performance. Results: PPAT and normalized PPAT were associated with BM (P<0.001). Normalized PPAT positively correlated with clinical T stage(cT), clinical N stage(cN), and Grading Groups(P<0.05). The results of ROC curves indicated that PPAT and normalized PPAT had promising predictive value for BM with the AUC of 0.684 and 0.775 respectively. Univariate and multivariate analysis revealed that high normalized PPAT, cN, and alkaline phosphatase(ALP) were independently predictors of BM. The nomogram was developed and the concordance index(C-index) was 0.856. Conclusions: Normalized PPAT is an independent predictor for BM among with cN, and ALP. Normalized PPAT may help predict BM in patients with newly diagnosed prostate cancer, thus providing adjunctive information for BM risk stratification and bone scan selection.

10.
Domest Anim Endocrinol ; 88: 106851, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38733944

RESUMO

Colostrum and milk offer a complete diet and vital immune protection for newborn mammals with developing immune systems. High immunoglobulin levels in colostrum serve as the primary antibody source for newborn piglets and calves. Subsequent milk feeding support continued local antibody protection against enteric pathogens, as well as maturation of the developing immune system and provide nutrients for newborn growth. Mammals have evolved hormonal strategies that modulate the levels of immunoglobulins in colostrum and milk to facilitate effective lactational immunity. In addition, hormones regulate the gut-mammary gland-secretory immunoglobulin A (sIgA) axis in pregnant mammals, controlling the levels of sIgA in milk, which serves as the primary source of IgA for piglets and helps them resist pathogens such as PEDV and TGEV. In the present study, we review the existing studies on the interactions between hormones and the gut-mammary-sIgA axis/lactogenic immunity in mammals and explore the potential mechanisms of hormonal regulation that have not been studied in detail, to draw attention to the role of hormones in influencing the immune response of pregnant and lactating mammals and their offspring, and highlight the effect of hormones in regulating sIgA-mediated anti-infection processes in colostrum and milk. Discussion of the relationship between hormones and lactogenic immunity may lead to a better way of improving lactogenic immunity by determining a better injection time and developing new vaccines.


Assuntos
Colostro , Hormônios , Lactação , Animais , Suínos/imunologia , Bovinos/imunologia , Bovinos/fisiologia , Feminino , Lactação/fisiologia , Colostro/imunologia , Colostro/química , Hormônios/fisiologia , Gravidez , Leite/química , Imunoglobulina A Secretora
11.
ACS Biomater Sci Eng ; 10(6): 3612-3630, 2024 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-38816677

RESUMO

Hydrophilic and biocompatible hydrogels are widely applied as ideal scaffolds in tissue engineering. The "smart" gelation material can alter its structural, physiochemical, and functional features in answer to various endo/exogenous stimuli to better biomimic the endogenous extracellular matrix for the engineering of cells and tissues. Light irradiation owns a high spatial-temporal resolution, complete biorthogonal reactivity, and fine-tunability and can thus induce physiochemical reactions within the matrix of photoresponsive hydrogels with good precision, efficiency, and safety. Both gel structure (e.g., geometry, porosity, and dimension) and performance (like conductivity and thermogenic or mechanical properties) can hence be programmed on-demand to yield the biochemical and biophysical signals regulating the morphology, growth, motility, and phenotype of engineered cells and tissues. Here we summarize the strategies and mechanisms for encoding light-reactivity into a hydrogel and demonstrate how fantastically such responsive gels change their structure and properties with light irradiation as desired and thus improve their applications in tissue engineering including cargo delivery, dynamic three-dimensional cell culture, and tissue repair and regeneration, aiming to provide a basis for more and better translation of photoresponsive hydrogels in the clinic.


Assuntos
Hidrogéis , Engenharia Tecidual , Hidrogéis/química , Engenharia Tecidual/métodos , Humanos , Luz , Alicerces Teciduais/química , Materiais Biocompatíveis/química , Animais , Matriz Extracelular/química
12.
Artigo em Inglês | MEDLINE | ID: mdl-38722344

RESUMO

Previous research has demonstrated that Dexmedetomidine (DEX), an α2 adrenergic agonist commonly used for its sedative and analgesic properties, can attenuate lipopolysaccharide (LPS)-induced acute kidney injury (AKI). This study explores the possibility that DEX's protective effects in LPS-induced AKI are mediated through the inhibition of ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, and the activation of the antioxidant response through the Keap1/Nrf2/HO-1 signaling pathway. We induced AKI in 42 mice using LPS and divided them into six groups: saline control, LPS, LPS + DEX, LPS + Ferrostatin-1 (LPS + Fer-1; a ferroptosis inhibitor), LPS + DEX with α2-receptor antagonist Altipamizole (LPS + DEX + ATI), and LPS + DEX with Nrf2 inhibitor ML385 (LPS + DEX + ML385). After 24 h, we analyzed blood and kidney tissues. LPS exposure resulted in AKI, with increased serum creatinine, BUN, and cystatin C, and tubular damage, which DEX and Fer-1 ameliorated. However, Altipamizole and ML385 negated these improvements. The LPS group exhibited elevated oxidative stress markers and mitochondrial damage, reduced by DEX and Fer-1, but not when α2-adrenergic or Nrf2 pathways were blocked. Nrf2 and HO-1 expression declined in the LPS group, rebounded with LPS + DEX and LPS + Fer-1, and fell again with inhibitors; inversely, Keap1 expression varied. Our results demonstrate that DEX may protect against LPS-induced AKI, at least partially by regulating ferroptosis and the α2-adrenergic receptor/Keap1/Nrf2/HO-1 pathway, suggesting a potential therapeutic role for DEX in AKI management by modulating cell death and antioxidant defenses.

13.
J Adv Nurs ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38712981

RESUMO

AIMS: This study aimed to explore the mediating effect of self-management (SM) on the relationship between illness perception and quality of life (QOL) among Human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). DESIGN: A cross-sectional study. METHODS: We explored the effect of illness perception and self-management on QOL using the multiple regression model. Moreover, we conducted a simple mediation analysis to examine the role of SM in the relationship between illness perception and QOL. In addition, a parallel mediation analysis was performed to investigate the differences in domains of SM on the relationship between illness perception and QOL. RESULTS: Among 300 Chinese HIV-positive MSM, the mean score of SM was 39.9 ± 6.97, with a range of 14.0-54.0. The higher score in SM indicated a higher level of HIV SM. SM was negatively related to illness perception (r = -0.47) while positively related to QOL (r = 0.56). SM partially mediated the relationship between illness perception and QOL, accounting for 25.3% of the total effect. Specifically, both daily self-management health practices and the chronic nature of the self-management domain played a parallel role in mediating the relationship between illness perception and QOL. CONCLUSION: Our study demonstrated that SM was a significant factor influencing QOL among HIV-positive MSM. Focusing on daily self-management health practices and the chronic nature of self-management could be the potential key targets for enhancing HIV self-management strategies. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: This study emphasized the role of SM in the well-being of HIV-positive MSM and underscored the importance of developing interventions that integrate SM strategies to improve QOL in this population. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

14.
J Am Chem Soc ; 146(18): 12723-12733, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38654452

RESUMO

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis. Here, we show that a 4-gene (fsoA, fsoD, fsoE, fsoF) biosynthetic gene cluster is sufficient to yield fuscoatroside by heterologous expression in Aspergillus oryzae. Notably, FsoA is an unheard-of terpene cyclase-glycosyltransferase fusion enzyme, affording a triterpene glycoside product that relies on enzymatic fusion. FsoE is a P450 enzyme that catalyzes successive oxidation reactions at C19 to facilitate a C-C bond cleavage, producing an oxidized carboxyl group and a reduced methyl group that have never been observed in known P450 enzymes. Our study thus sets the important foundation for the manufacture of enfumafungin-type antibiotics using biosynthetic approaches.


Assuntos
Antifúngicos , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Aspergillus oryzae/enzimologia , Aspergillus oryzae/metabolismo , Família Multigênica , Triterpenos/química , Triterpenos/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo
15.
Xenobiotica ; 54(5): 233-247, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38638108

RESUMO

This study explored the distribution of esculin microspheres in rabbit brain tissue following intravitreal injection and investigated the possibility of direct entry of the drug into the brain through the eye, to develop a formulation with enhanced therapeutic efficacy against Parkinson's disease.Chitosan microspheres of esculin were prepared via an emulsification cross-linking method and their characteristics were evaluated, including angle of repose, bulk density, and swelling ratio. Furthermore, the pharmacokinetic parameters and brain tissue distribution in rabbits were compared among groups administered esculin eye drops, intravitreal esculin solution, and intravitreal esculin microspheres, to determine whether esculin could enter the brain through an ocular route.The results showed that the prepared esculin microspheres were spherical and had good fluidity. Notably, intravitreal administration enhanced the area under the curve (AUC) of esculin in the thalamus. Delivery through microspheres prolonged the drug retention time in both rabbit plasma and brain tissues, as well as the brain-targeting efficiency of esculin.The collective findings indicated that there may be a direct eye-brain pathway facilitating enter of esculin microspheres into brain tissue after intravitreal injection, supporting the utility of intravitreal esculin microspheres as an effective therapeutic formulation for Parkinson's disease, a long-term chronic condition.


Assuntos
Encéfalo , Esculina , Injeções Intravítreas , Microesferas , Animais , Coelhos , Encéfalo/metabolismo , Esculina/farmacocinética , Esculina/administração & dosagem , Distribuição Tecidual
16.
Viruses ; 16(4)2024 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-38675947

RESUMO

Tibetan pig is a geographically isolated pig breed that inhabits high-altitude areas of the Qinghai-Tibetan plateau. At present, there is limited research on viral diseases in Tibetan pigs. This study provides a novel metagenomic exploration of the gut virome in Tibetan pigs (altitude ≈ 3000 m) across three critical developmental stages, including lactation, nursery, and fattening. The composition of viral communities in the Tibetan pig intestine, with a dominant presence of Microviridae phages observed across all stages of development, in combination with the previous literature, suggest that it may be associated with geographical locations with high altitude. Functional annotation of viral operational taxonomic units (vOTUs) highlights that, among the constantly increasing vOTUs groups, the adaptability of viruses to environmental stressors such as salt and heat indicates an evolutionary response to high-altitude conditions. It shows that the lactation group has more abundant viral auxiliary metabolic genes (vAMGs) than the nursery and fattening groups. During the nursery and fattening stages, this leaves only DNMT1 at a high level. which may be a contributing factor in promoting gut health. The study found that viruses preferentially adopt lytic lifestyles at all three developmental stages. These findings not only elucidate the dynamic interplay between the gut virome and host development, offering novel insights into the virome ecology of Tibetan pigs and their adaptation to high-altitude environments, but also provide a theoretical basis for further studies on pig production and epidemic prevention under extreme environmental conditions.


Assuntos
Altitude , Microbioma Gastrointestinal , Metagenômica , Viroma , Animais , Suínos , Viroma/genética , Microbioma Gastrointestinal/genética , Tibet , Vírus/genética , Vírus/classificação , Metagenoma , Feminino , Genoma Viral
17.
Int J Biol Macromol ; 266(Pt 2): 131383, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38580030

RESUMO

The development of antibiotic-loaded microneedles has been hindered for years by limited excipient options, restricted drug-loading space, poor microneedle formability, and short-term drug retention. Therefore, this study proposes a dissolving microneedle fabricated from the host-defense peptide ε-poly-l-lysine (EPL) as an antibacterial adjuvant system for delivering antibiotics. EPL serves not only as a major matrix material for the microneedle tips, but also as a broad-spectrum antibacterial agent that facilitates the intracellular accumulation of the antibiotic doxycycline (DOX) by increasing bacterial cell membrane permeability. Furthermore, the formation of physically crosslinked networks of EPL affords microneedle tips with improved formability, good mechanical properties, and amorphous nanoparticles (approximately 7.2 nm) of encapsulated DOX. As a result, a high total loading content of both antimicrobials up to 2319.1 µg/patch is achieved for efficient transdermal drug delivery. In a Pseudomonas aeruginosa-induced deep cutaneous infection model, the EPL microneedles demonstrates potent and long-term effects by synergistically enhancing antibiotic activities and prolonging drug retention in infected lesions, resulting in remarkable therapeutic efficacy with 99.91 % (3.04 log) reduction in skin bacterial burden after a single administration. Overall, our study highlights the distinct advantages of EPL microneedles and their potential in clinical antibacterial practice when loaded with amorphous DOX nanoparticles.


Assuntos
Antibacterianos , Doxiciclina , Nanopartículas , Agulhas , Polilisina , Polilisina/química , Doxiciclina/administração & dosagem , Doxiciclina/farmacologia , Doxiciclina/química , Nanopartículas/química , Antibacterianos/farmacologia , Antibacterianos/administração & dosagem , Antibacterianos/química , Animais , Pseudomonas aeruginosa/efeitos dos fármacos , Camundongos , Sistemas de Liberação de Medicamentos , Administração Cutânea , Pele/efeitos dos fármacos , Pele/microbiologia , Infecções por Pseudomonas/tratamento farmacológico
18.
Front Psychol ; 15: 1327822, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38659667

RESUMO

Exercise can induce brain plasticity. Functional near-infrared spectroscopy (fNIRS) is a functional neuroimaging technique that exploits cerebral hemodynamics and has been widely used in the field of sports psychology to reveal the neural mechanisms underlying the effects of exercise. However, most existing fNIRS studies are cross-sectional and do not include exercise interventions. In addition, attributed to differences in experimental designs, the causal relationship between exercise and brain functions remains elusive. Hence, this systematic review aimed to determine the effects of exercise interventions on alterations in brain functional activity in healthy individuals using fNIRS and to determine the applicability of fNIRS in the research design of the effects of various exercise interventions on brain function. Scopus, Web of Science, PubMed, CNKI, Wanfang, and Weipu databases were searched for studies published up to June 15, 2021. This study was performed in accordance with the PRISMA guidelines. Two investigators independently selected articles and extracted relevant information. Disagreements were resolved by discussion with another author. Quality was assessed using the Cochrane risk-of-bias method. Data were pooled using random-effects models. A total of 29 studies were included in the analysis. Our results indicated that exercise interventions alter oxygenated hemoglobin levels in the prefrontal cortex and motor cortex, which are associated with improvements in higher cognitive functions (e.g., inhibitory control and working memory). The frontal cortex and motor cortex may be key regions for exercise-induced promotion of brain health. Future research is warranted on fluctuations in cerebral blood flow during exercise to elucidate the neural mechanism underlying the effects of exercise. Moreover, given that fNIRS is insensitive to motion, this technique is ideally suited for research during exercise interventions. Important factors include the study design, fNIRS device parameters, and exercise protocol. The examination of cerebral blood flow during exercise intervention is a future research direction that has the potential to identify cortical hemodynamic changes and elucidate the relationship between exercise and cognition. Future studies can combine multiple study designs to measure blood flow prior to and after exercise and during exercise in a more in-depth and comprehensive manner.

19.
BMC Oral Health ; 24(1): 469, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632580

RESUMO

BACKGROUND: Oral leukoplakia (OLK) is a prevalent precancerous lesion with limited non-pharmacological treatment options. Surgery and various lasers are the mainstay of treatment; however, their relative efficacy and optimal choice remain unclear. This first network meta-analysis compared the effects of different lasers and surgical excision on post-treatment recurrence and comfort in OLK patients. METHODS: We searched four databases for relevant randomized controlled trials (RCTs) up to April 2023. The primary outcome was post-treatment recurrence, and secondary outcomes included intraoperative hemorrhage and postoperative pain scores. The Cochrane Risk of Bias tool was used to assess the study quality. Meta-analysis and network meta-analysis were employed to determine efficacy and identify the optimal intervention. RESULTS: A total of 11 RCTs including 917 patients and 1138 lesions were included. Er,Cr:YSGG laser treatment showed significantly lower recurrence rates compared to CO2 laser (OR: 0.04; 95% CI: 0.01-0.18), CO2 laser with margin extension (OR: 0.06; 95% CI: 0.01-0.60), Er:YAG laser (OR: 0.10; 95% CI: 0.03-0.37), electrocautery (OR: 0.03; 95% CI: 0.00-0.18), and standard care (OR: 0.08; 95% CI: 0.02-0.33). Er,Cr:YSGG laser also ranked the best for reducing recurrence, followed by standard care and CO2 laser combined with photodynamic therapy (PDT). Er:YAG and Er:Cr:YSGG lasers minimized bleeding and pain, respectively. None of the interventions caused severe adverse effects. CONCLUSION: For non-homogeneous OLK, Er:YAG, Er:Cr:YSGG, and CO2 laser combined with PDT offer promising alternatives to surgical excision, potentially reducing recurrence and improving patient comfort. Further high-quality RCTs are necessary to confirm these findings and determine the optimal laser-PDT combination for OLK treatment.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Humanos , Metanálise em Rede , Dióxido de Carbono/uso terapêutico , Conforto do Paciente , Leucoplasia Oral , Lasers de Estado Sólido/uso terapêutico
20.
IDCases ; 36: e01970, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38681082

RESUMO

A 30-year-old man presented to otolaryngology department complaining of nasal congestion and runny nose for six months, with repeated fever, and shortness of breath.The weight loss in the past 20 days was about 5 kg. At first, he was diagnosed with respiratory infection and was treated with antibiotics, but it didn't work. Nasopharynx CT scan showed soft tissue thickening without bone destruction, with obvious inhomogeneous enhancement. Chest CT scan revealed multiple patchy clouding nodules and ground-glass opacity with poorly-defined border. Urine test showed urine microalbumin ≥ 150 mg per liter (reference range, 0-20), white-cell count of 11.0 cells per microliter (reference range, 0-5). Histology of nasopharynx biopsy showed small-medium-vessel necrotizing vasulitis.Although nasopharyngeal histopathology didn't reveal peri- and extravascular granulomatosis and antineutrophilic cytoplasmic antibodies (ANCA) was negtive, he had ENT signs, lung nodules, and kidney involvement and condition developed fast and biopsy showed small- and- medium-vessel vasculitis. Therefore, the patient met the classification criteria for GPA and his symptoms were disappeared 1 week after starting GPA treatment, the chest CT showed ground-glass opacity decreased and CRP、ESR became normal. He was treated with rituximab combined with glucocorticoids for 4 weeks, after which he was discharged.

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