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1.
Cureus ; 16(8): e68296, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39350874

RESUMO

While osteoporosis is the primary cause of vertebral compression fractures (VCFs), it's crucial to promptly recognize pathological fractures through comprehensive diagnostic tests, including vertebral biopsies, to determine the exact etiology. For instance, a 66-year-old male with osteoporosis experienced worsening lower limb weakness and back pain after an initial vertebroplasty for a T12 compression fracture. Subsequent MRI revealed severe circumferential extradural compression at T12, leading to further surgeries that eventually uncovered metastatic adenocarcinoma from a pancreatic tumor. This case highlights the importance of precise diagnosis through vertebral biopsy and the necessity of sufficient ventral decompression or corpectomy, coupled with extensive laminectomy, to address severe neurological impairments like paraplegia. Prompt and accurate interventions can significantly improve patient outcomes and quality of life.

2.
Int J Biochem Cell Biol ; 176: 106662, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39293559

RESUMO

Dysregulated protein homeostasis, characterized by abnormal protein accumulation and aggregation, is a key contributor to the progression of neurodegenerative disorders such as Huntington's disease and spinocerebellar ataxia type 3 (SCA3). Previous studies have identified PIAS1 gene variants in patients with late-onset SCA3 and Huntington's disease. This study aims to elucidate the role of PIAS1 and its S510G variant in modulating the pathogenic mechanisms of SCA3. Through in vitro biochemical analyses and in vivo assays, we demonstrate that PIAS1 stabilizes both wild-type and mutant ataxin-3 (ATXN3). The PIAS1 S510G variant, however, selectively reduces the stability and SUMOylation of mutant ATXN3, thereby decreasing its aggregation and toxicity while maintaining the stability of wild-type ATXN3. This effect is mediated by a weakened interaction with the SUMO-conjugating enzyme UBC9 in the presence of mutant ATXN3. In Drosophila models, downregulation of dPIAS1 resulted in reduced levels of mutant ATXN3 and alleviated associated phenotypes, including retinal degeneration and motor dysfunction. Our findings suggest that the PIAS1 S510G variant acts as a genetic modifier of SCA3, highlighting the potential of targeting SUMOylation as a therapeutic strategy for this disease.

3.
Public Health ; 236: 328-337, 2024 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-39299087

RESUMO

OBJECTIVES: This study aimed to assess the impact of pay-for-performance (P4P) programmes on healthcare in Taiwan. STUDY DESIGN: This was a systematic review and meta-analysis. METHODS: A systematic literature search was performed using the PubMed, Medline, Embase, Cochrane review, Scopus, Web of Science and PsycINFO databases up to July 2023. Meta-analysis of the available outcomes was conducted using a random-effects model. RESULTS: The search yielded 85 studies, of which 58 investigated the programme for diabetes mellitus (DM), eight looked at the programme for chronic kidney disease (CKD), and the remaining studies examined programmes for breast cancer, tuberculosis, schizophrenia and chronic obstructive pulmonary disease. The DM P4P programme was a cost-effective strategy associated with reduced hospitalisation and subsequent complications. The CKD P4P was associated with a lower risk of dialysis initiation. The P4P programme also improved outcomes in breast cancer, cure rates in tuberculosis, reduced admissions for schizophrenia and reduced acute exacerbation in chronic obstructive pulmonary disease. The meta-analysis revealed that the P4P programme for DM (odds ratio [OR] = 0.59; 95% confidence interval [CI] = 0.48-0.73) and CKD (OR = 0.73; 95% CI = 0.67-0.81) significantly reduced mortality risk. However, participation rate in the DM P4P programme was only 19% in 2014. CONCLUSIONS: P4P programmes in Taiwan improve quality of care. However, participation was voluntary and the participation rate was very low, raising the concern of selective enrolment of participants (i.e. 'cherry-picking' behaviour) by physicians. Future programme reforms should focus on well-designed features with the aim of reducing healthcare disparities.

4.
Clocks Sleep ; 6(3): 499-516, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39311228

RESUMO

The application of far-infrared blankets has shown certain benefits in health promotion and therapy, such as improving blood circulation and alleviating muscle pain. However, the effects of such blankets on increasing deep sleep, reducing blood pressure, enhancing memory, dilating microvessels for blood flow, reducing chronic inflammation, and decreasing fatigue remain to be studied. We aim to investigate the effects of the DAZZEON αSleep® far-infrared blanket on these indicators. This study adopted a double-blind design, recruiting 24 male participants aged over 45 years, divided into two groups of 12 each: (A) a placebo group and (B) a DAZZEON αSleep® group. The participants used the blanket every night for two weeks, with sleep records taken using a wearable device and blood pressure, blood oxygen levels, arterial stiffness, and surface temperature measured before and after the intervention. Blood samples were collected for an analysis of inflammation and sleep-related blood indicators (serotonin and melatonin), and exercise tests were conducted to assess fatigue improvement. Compared with before the intervention, the blanket significantly increased changes in grip strength and reaction time. Additionally, it significantly increased blood serotonin, melatonin, and nitric oxide concentrations (p < 0.05), thus significantly increasing deep sleep and REM sleep durations (p < 0.05) and improving subjective sleep quality (p < 0.05). This study confirmed that using the DAZZEON αSleep® far-infrared blanket for 14 consecutive days helps to improve blood circulation, reduce vascular age and arterial stiffness, increase serotonin and melatonin levels, and improve sleep quality, as well as enhances muscle strength and reaction time.

5.
Mol Cancer ; 23(1): 215, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39350121

RESUMO

The Nab-paclitaxel combined with gemcitabine (AG) regimen is the main chemotherapy regimen for pancreatic cancer, but drug resistance often occurs. Currently, the ability to promote sensitization in drug-resistant cases is an important clinical issue, and the strategy of repurposing conventional drugs is a promising strategy. This study aimed to identify a classic drug that targets chemotherapy resistance's core signaling pathways and combine it with the AG regimen to enhance chemosensitivity. We also aimed to find reliable predictive biomarkers of drug combination sensitivity. Using RNA sequencing, we found that abnormal PI3K/Akt pathway activation plays a central role in mediating resistance to the AG regimen. Subsequently, through internal and external verification of randomly selected AG-resistant patient-derived organoid (PDO) and PDO xenograft models, we discovered for the first time that the classic anti-inflammatory drug sulindac K-80003, an inhibitor of the PI3K/Akt pathway that we focused on, promoted sensitization in half (14/28) of AG-resistant pancreatic ductal adenocarcinoma cases. Through RNA-sequencing, multiplex immunofluorescent staining, and immunohistochemistry experiments, we identified cFAM124A as a novel biomarker through which sulindac K-80003 promotes AG sensitization. Its role as a sensitization marker is explained via the following mechanism: cFAM124A enhances both the mRNA expression of cathepsin L and the activity of the cathepsin L enzyme. This dual effect stimulates the cleavage of RXRα, leading to large amounts of truncated RXRα, which serves as a direct target of K-80003. Consequently, this process results in the pathological activation of the PI3K/Akt pathway. In summary, our study provides a new treatment strategy and novel biological target for patients with drug-resistant pancreatic cancer.


Assuntos
Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Resistencia a Medicamentos Antineoplásicos , Gencitabina , Paclitaxel , Neoplasias Pancreáticas , Sulindaco , Ensaios Antitumorais Modelo de Xenoenxerto , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacologia , Humanos , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Animais , Camundongos , Albuminas/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Sulindaco/farmacologia , Sulindaco/análogos & derivados , Linhagem Celular Tumoral , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Feminino , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/metabolismo , Masculino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
6.
Phys Rev Lett ; 133(11): 116303, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39331964

RESUMO

In isolated nonlinear optical waveguide arrays, simultaneous conservation of longitudinal momentum flow ("internal energy") and optical power ("particle number") of the optical modes enables study of coupled thermal and particle transport in the negative temperature regime. Based on exact numerical simulation and rationale from Landauer formalism, we predict generic photonic version of the Wiedemann-Franz law in such systems, with the Lorenz number L∝|T|^{-2}. This is rooted in the spectral decoupling of thermal and particle current, and their different temperature dependence. In addition, in asymmetric junctions, relaxation of the system toward equilibrium shows apparent asymmetry for positive and negative biases, indicating rectification behavior. This Letter illustrates the possibility of simulate nonequilibrium transport processes using optical networks, in parameter regimes difficult to reach in natural condensed matter or atomic gas systems. It also provides new insights in manipulating power and momentum flow of optical waves in artificial waveguide arrays.

7.
Chin J Cancer Res ; 36(4): 351-367, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39246704

RESUMO

Objective: CD8+ T cells are the key effector cells in the anti-tumor immune response. The mechanism underlying the infiltration of CD8+ T cells in esophageal squamous cell carcinoma (ESCC) has not been clearly elucidated. Methods: Fresh ESCC tissues were collected and grouped according to the infiltration density of CD8+ T cells. After the transcriptome sequencing on these samples and the combined analyses with The Cancer Genome Atlas (TCGA) ESCC data, a secreted protein DEFB1 was selected to explore its potential role in the infiltration of CD8+ T cells. Bioinformatics analyses, histological verification and in vitro experiments were then performed. Results: DEFB1 was highly expressed in ESCC, and the high expression of DEFB1 was an independent risk factor for overall survival. Since the up-regulation or down-regulation of DEFB1 did not affect the proliferation, migration and apoptosis of ESCC cells, we speculated that the oncogenic effect of DEFB1 was achieved by regulating microenvironmental characteristics. Bioinformatics analyses suggested that DEFB1 might play a major role in the inflammatory response and anti-tumor immune response, and correlate to the infiltration of immature dendritic cell (imDC) in ESCC. Histological analyses further confirmed that there were less CD8+ T cells infiltrated, less CD83+ mature DC (mDC) infiltrated and more CD1a+ imDC infiltrated in those ESCC samples with high expression of DEFB1. After the treatment with recombinant DEFB1 protein, the maturation of DC was hindered significantly, followed by the impairment of the killing effects of T cells in both 2D and 3D culture in vitro. Conclusions: Tumor-derived DEFB1 can inhibit the maturation of DC and weaken the function of CD8+ T cells, accounting for the immune tolerance in ESCC. The role of DEFB1 in ESCC deserves further exploration.

8.
Heliyon ; 10(16): e36307, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39247310

RESUMO

Objective: Carbon nanoparticle (CNP)-guided sentinel lymph node biopsy (SLNB) has been extensively adopted as a cost-effective and highly efficient method for tracing malignant tumors except for those associated with vulvar cancer. The current study aimed to validate the feasibility and efficacy of CNPs in tracking sentinel lymph nodes (SLNs) in patients with early vulvar cancer. Methods: We retrospectively reviewed patients with vulvar cancer at our institution from January 2016 to April 2022 who were pathologically diagnosed and underwent SLNB or inguinofemoral lymphadenectomy (IFLND). CNPs were the only lymphatic tracer used in SLNB. Patient demographics, perioperative outcomes and follow-up results, including overall survival (OS) and progression-free survival (PFS), were compared between the SLNB and IFLND groups. Results: Data from 52 patients were collected and investigated. Forty groins of 22 patients who underwent SLNB with CNP tracing were included. Black-stained SLNs were detected in 32 groins of 19 patients, and the rates of CNP detection by patient and by groin were 86.4 % and 80 %, respectively. Patients who underwent SLNB had better perioperative outcomes than those who underwent IFLND in certain aspects (groin drainage rate: 41.2 % and 80 %, respectively, p < 0.05; daily drainage volume (ml): 12.49 and 36.4, respectively, p < 0.05; and inguinal wound healing rate: 100 % and 80 %, respectively, p < 0.05). The results of survival analysis indicated similar prognoses for node-negative patients who underwent CNP-guided SLNB or IFLND. Conclusions: Sentinel lymph node mapping with CNPs in vulvar cancer is feasible and demonstrates considerable biosecurity. With a satisfactory SLN detection rate achieved expediently, CNPs are a promising lymphatic tracer worthy of further utilization in vulvar cancer and could be an alternative option to canonical tracers.

9.
Future Microbiol ; : 1-7, 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39258425

RESUMO

Aim: Mycoplasma pneumoniae (MP) is a common cause of respiratory infections, and its incidence has increased post-COVID-19 due to "immune debt." Real-time quantitative polymerase chain reaction (qPCR) is the standard for detecting MP, but it has a lengthy detection time. This study aimed to establish a highly sensitive rapid detection method for MP.Materials & methods: We developed an integrated assay combining multienzyme isothermal rapid amplification (MIRA) with qPCR, referred to as MIRA-qPCR, for the rapid detection of MP, delivering results within approximately 40 min.Results: The analytic sensitivity of the MIRA-qPCR assay was 10 copies per reaction, and it exhibited no cross-reactivity with other respiratory pathogens, ensuring high specificity. Clinical sample analysis demonstrated higher sensitivity for MIRA-qPCR compared to qPCR reported in the literature, and 100% concordance with commercial qPCR kit.Conclusion: The MIRA-qPCR method established in this study is a promising tool for the clinical detection of MP, offering significant advantages for the rapid diagnosis of MP infections.


Mycoplasma pneumoniae is a bacteria that can make us sick. It mainly affects the lungs and can cause a sickness called "walking pneumonia". This is because it can make you poorly, but not so badly that you are unable to walk around. This bacteria spreads when someone that is infected sneezes or coughs. It is important that M. pneumoniae can be diagnosed quickly. This article looks at a new, fast way to identify infection called MIRA-quantitative PCR.

10.
Artigo em Inglês | MEDLINE | ID: mdl-39271437

RESUMO

BACKGROUND: A predominate azole-resistant Candida tropicalis clade 4 genotype causing candidemia has been detected in not only Taiwan but also China, Singapore, and Australia. It can also be detected on fruit surfaces. In addition to determining distribution and drug susceptibilities of pathogenic yeasts in environments of intensive care units of 25 hospitals in Taiwan, we would also like to investigate whether the azole-resistant C. tropicalis exists in Taiwan's hospital environment. METHODS: The swabs of hospital environments were collected from August to November in 2020 and were cultured for yeasts. The yeasts were identified by rDNA sequence and the antifungal susceptibilities of those isolates were determined by the broth microdilution method. RESULTS: The average yeast-culture rate of hospitals was 9.4% (217/2299). Sinks had the highest yeast-positive culture rate (32.7%), followed by bedside tables (28.9%), floors (26.0%), water-dispenser buttons (23.8%), and TV controller/touch panels (19.0%). Of 262 identified isolates, Candida parapsilosis was the most common species, accounting for 22.1%, followed by Filobasidium uniguttulatum (18.3%), Candida albicans (9.5%), C. tropicalis (8.0%), Candida glabrata (Nakaseomyces glabratus) (6.9%), and 30 other species (35.1%). Of the 21 C. tropicalis isolates from 11 units in 9 hospitals, 15 diploid sequence types (DSTs) were identified. The two DST506 fluconazole-resistant ones belonged to clade 4. CONCLUSION: We detected not only various pathogenic yeast species but also the predominant clade 4 genotype of azole-resistant C. tropicalis. Our findings highlight and re-emphasize the importance of regular cleaning and disinfection practices.

11.
J Mot Behav ; : 1-10, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39266044

RESUMO

The present study aims to develop and present a proof-of-concept for a stop signal task with effector-specificity and higher complexity. Sixteen participants performed a stop signal task developed for lower extremities using Fitlight System™. The effect of four different delays and two sessions on response time, stop signal reaction time and accuracy was assessed using two-way repeated-measures ANOVA. The reliability of outcomes was assessed using intraclass correlation coefficients. There was a significant main effect of delay on all outcomes and an interaction of delay and session on accuracy. The reliability of outcomes was substantial with dependency on delays. Our preliminary findings suggest the feasibility of stop signal principles within more complex movements and provide an example for the development of further tests in sports context.

12.
Artigo em Inglês | MEDLINE | ID: mdl-39220635

RESUMO

It is well established that Nrf2 plays a crucial role in anti-oxidant and anti-inflammatory functions. However, its antiviral capabilities remain less explored. Despite this, several Nrf2 activators have demonstrated anti-SARS-CoV-2 properties, though the mechanisms behind these effects are not fully understood. In this study, using two mouse models of SARS-CoV-2 infection, we observed that the absence of Nrf2 significantly increased viral load and altered inflammatory responses. Additionally, we evaluated five Nrf2 modulators. Notably, epigallocatechin gallate (EGCG), sulforaphane (SFN), and dimethyl fumarate (DMF) exhibited significant antiviral effects, with SFN being the most effective. SFN did not impact viral entry but appeared to inhibit the main protease (MPro) of SARS-CoV-2, encoded by the Nsp5 gene, as indicated by two protease inhibition assays. Moreover, using two Nrf2 knockout cell lines, we confirmed that SFN's antiviral activity occurs independently of Nrf2 activation in vitro. Paradoxically, in vivo tests using the MA30 model showed that SFN's antiviral function was completely lost in Nrf2 knockout mice. Thus, although SFN and potentially other Nrf2 modulators can inhibit SARS-CoV-2 independently of Nrf2 activation in cell models, their Nrf2-dependent activities might be crucial for antiviral defense under physiological conditions.

13.
Work ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39240606

RESUMO

BACKGROUND: Emotional intelligence refers to an individual's awareness of their emotions and their ability to effectively regulate them. Emotional intelligence also encompasses the ability to empathize with and establish meaningful relationships with others. OBJECTIVE: In this study, a comprehensive meta-analysis approach was employed to investigate the relationships between emotional intelligence and various factors including social support, organizational aspects, satisfaction, and stressors. METHODS: Moreover, the extent to which emotional intelligence influenced these factors was investigated and analyzed through meta-analysis. RESULTS: A data analysis revealed that emotional intelligence correlated positively with social support, organizational aspects, and satisfaction and negatively with stressors. CONCLUSIONS: These results suggest that organizations should adopt management strategies for enhancing the emotional intelligence of their employees, thereby strengthening their social support systems and their organizational cohesion and efficiency. To achieve this, organizations are advised to implement reasonable management systems and emotional management education and training to enable employees to effectively manage their emotions and understand the emotions of others. Subsequently, the job and life satisfaction of the employees can be enhanced and the negative effects of stressors can be mitigated.

14.
J Hazard Mater ; 479: 135536, 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39191015

RESUMO

This study investigated the influence of photoaging on a nanoscale metal-organic framework (MOF), truncated rhombic dodecahedron nano-zeolitic imidazolate framework-8 (nZIF-8), focusing on its oxidative stress, inflammation, and implications for pulmonary diseases. We observed significant photodegradation-induced transformations in nZIF-8, characterized by a reduction in particle size from 200.5 to 101.4 nm and notable structural disintegration after prolonged exposure to simulated solar radiation. This alteration resulted in a marked decrease in oxidative cytotoxicity in BEAS-2B cells, which was attributed to changes in surface properties and reduced reactive oxygen species (ROS) production. Gene expression analysis further revealed a decrease in cytotoxic and inflammatory responses, which potentially lowers the risk of chronic obstructive pulmonary disease (COPD). Aged nZIF-8 also showed diminished capacity to induce pro-inflammatory cytokines and influence COPD-related gene expression, reducing its potential to exacerbate COPD pathogenesis. Our findings highlight the critical need for comprehensive safety evaluations of these materials, while considering their long-term environmental and biological impacts. The diminished cytotoxicity and inflammatory potential of aged nZIF-8 highlighted its enhanced suitability for broader applications, indicating that photoaging may lead to safer and more sustainable material utilization.


Assuntos
Estruturas Metalorgânicas , Estresse Oxidativo , Espécies Reativas de Oxigênio , Zeolitas , Humanos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/toxicidade , Estruturas Metalorgânicas/efeitos da radiação , Espécies Reativas de Oxigênio/metabolismo , Linhagem Celular , Estresse Oxidativo/efeitos dos fármacos , Zeolitas/química , Zeolitas/toxicidade , Imidazóis/toxicidade , Imidazóis/química , Sobrevivência Celular/efeitos dos fármacos , Fotólise , Citocinas/metabolismo , Tamanho da Partícula , Nanopartículas/toxicidade , Nanopartículas/química
15.
Food Chem ; 461: 140842, 2024 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-39173256

RESUMO

A GPE-PET (graphene-polyethylene terephthalate) bipolar electrode-electrochemiluminescence (BPE-ECL) platform was developed for ochratoxin A (OTA) detection. PET served as the electrode sheet substrate, and GPE was drop-coated onto the surface of PET to form a conductive line. On the functional sensing interface, the thiol (-SH) modified OTA aptamer (OTA-Aptamer) are fixed on the surface of the gold-plated cathode through AuS bonds. The efficient electron transfer ability of methylene blue (MB) made the anode ECL signal strong. Due to competition between OTA and MB with OTA-Aptamer, leading to a decrease in ECL intensity of the [Ru(bpy)3]2+/TPA system on the BPE anode. Under optimized conditions, the GPE-PET BPE-ECL biosensor displayed superior sensitivity for OTA with a detection limit of 2 ng mL-1 and a wide linear concentration range of 5-100 ng mL-1. This method could be further applied to detect various toxins and had broad application prospects.


Assuntos
Técnicas Biossensoriais , Técnicas Eletroquímicas , Eletrodos , Medições Luminescentes , Ocratoxinas , Ocratoxinas/análise , Técnicas Biossensoriais/instrumentação , Medições Luminescentes/instrumentação , Medições Luminescentes/métodos , Técnicas Eletroquímicas/instrumentação , Grafite/química , Contaminação de Alimentos/análise , Polietilenotereftalatos/química , Limite de Detecção
16.
Water Res ; 265: 122259, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39154398

RESUMO

As a pervasive microbial aggregate found at the water-soil interface in paddy fields, periphyton plays crucial roles in modulating nutrient biogeochemical cycling. Consequently, it effectively mitigates non-point source pollution due to its diverse composition. Despite its significance, the mechanisms governing periphyton diversity across different rice planting regions remain poorly understood. To bridge this gap, we investigated periphyton grown in 200 paddy fields spanning 25° of latitude. Initially, we analyzed local diversity and latitudinal variations in prokaryotic communities within paddy field periphyton, identifying 7 abundant taxa, 42 moderate taxa, and 39 rare taxa as the fundamental prokaryotic framework. Subsequently, to elucidate the mechanisms governing periphyton diversity across large scales, we constructed interaction models illustrating triangular relationships among local richness, assembly, and regional variation of prokaryotic subcommunities. Our findings suggest that accumulated temperature-driven environmental filtering partially influences the assembly process of prokaryotes, thereby impacting local species richness and ultimately governing regional structural variations in periphyton. Furthermore, we determined that a latitude of 39° represents the critical threshold maximizing local species richness of periphyton in paddy fields. This study advances our understanding of the factors shaping periphyton geo-imprints and provides valuable insights into predicting their responses to environmental changes, potentially influencing rice production outcomes.


Assuntos
Oryza , Microbiologia do Solo , Solo , Temperatura , Solo/química , Perifíton , Água , Biodiversidade , Bactérias
18.
Eur J Pharmacol ; 980: 176867, 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39111683

RESUMO

BACKGROUND: MARCKS (myristoylated alanine-rich C kinase substrates) serves as a substrate for protein kinase C, residing in the plasma membrane while acts as an actin filament crosslinking protein. This investigation aims to elucidate phosphorylated MARCKS (p-MARCKS) levels and activity in allergic asthma patients and explore the therapeutic potential of peptide inhibitors targeting p-MARCKS in an acute mouse model of allergic asthma. METHODS: Immunohistochemistry and histology staining were employed on lung tissue slides to evaluate p-MARCKS expression and allergic asthma symptoms. Airway resistance was measured using invasive whole-body plethysmography. Flow cytometry detected lung dendritic cell migration, and migration/maturation assays were conducted on isolated murine bone marrow-derived dendritic cells (BM-DCs). RESULTS: Elevated p-MARCKS expression was observed in both human asthmatic tissues and animal models immunized with ovalbumin or Alternaria alternata. Remarkably, asthmatic individuals showed elevated high p-MARCKS expression in lung tissues. Intraperitoneal injection of the peptide MPS, targeting the MARCKS phosphorylation site domain, before allergen challenged, effectively suppressed MARCKS phosphorylation in murine lung tissues. MPS inhibited both in vivo and in vitro migration and maturation of dendritic cells (BM-DCs) and reduced Th2-related lymphocyte activation in bronchoalveolar lavage fluid (BALF). MPS pretreatment additionally suppressed all symptoms associated with allergic airway asthma, including a reduction in inflammatory cell influx, airway mucous cell metaplasia, and airway hyperreactivity. CONCLUSION: These findings suggest that phosphorylated MARCKS occurs in asthmatic lung tissue, and the inhibition of MARCKS phosphorylation by the MPS peptide reduces dendritic cell migration and Th2-related lymphocytes in the lungs in a murine model of acute asthma.


Assuntos
Asma , Movimento Celular , Células Dendríticas , Substrato Quinase C Rico em Alanina Miristoilada , Animais , Feminino , Humanos , Masculino , Camundongos , Doença Aguda , Asma/imunologia , Asma/tratamento farmacológico , Asma/patologia , Asma/metabolismo , Movimento Celular/efeitos dos fármacos , Células Dendríticas/imunologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Modelos Animais de Doenças , Pulmão/patologia , Pulmão/imunologia , Pulmão/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Substrato Quinase C Rico em Alanina Miristoilada/metabolismo , Peptídeos/farmacologia , Fosforilação
19.
Viruses ; 16(8)2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-39205213

RESUMO

Emergence of newer variants of SARS-CoV-2 underscores the need for effective antivirals to complement the vaccination program in managing COVID-19. The multi-functional papain-like protease (PLpro) of SARS-CoV-2 is an essential viral protein that not only regulates the viral replication but also modulates the host immune system, making it a promising therapeutic target. To this end, we developed an in vitro interferon stimulating gene 15 (ISG15)-based Förster resonance energy transfer (FRET) assay and screened the National Cancer Institute (NCI) Diversity Set VI compound library, which comprises 1584 small molecules. Subsequently, we assessed the PLpro enzymatic activity in the presence of screened molecules. We identified three potential PLpro inhibitors, namely, NSC338106, 651084, and 679525, with IC50 values in the range from 3.3 to 6.0 µM. These molecules demonstrated in vitro inhibition of the enzyme activity and exhibited antiviral activity against SARS-CoV-2, with EC50 values ranging from 0.4 to 4.6 µM. The molecular docking of all three small molecules to PLpro suggested their specificity towards the enzyme's active site. Overall, our study contributes promising prospects for further developing potential antivirals to combat SARS-CoV-2 infection.


Assuntos
Antivirais , Proteases Semelhantes à Papaína de Coronavírus , Citocinas , Ensaios de Triagem em Larga Escala , SARS-CoV-2 , Ubiquitinas , SARS-CoV-2/efeitos dos fármacos , SARS-CoV-2/enzimologia , Antivirais/farmacologia , Antivirais/química , Humanos , Ensaios de Triagem em Larga Escala/métodos , Proteases Semelhantes à Papaína de Coronavírus/antagonistas & inibidores , Proteases Semelhantes à Papaína de Coronavírus/química , Proteases Semelhantes à Papaína de Coronavírus/metabolismo , Citocinas/metabolismo , Ubiquitinas/metabolismo , Ubiquitinas/química , Ubiquitinas/antagonistas & inibidores , Simulação de Acoplamento Molecular , Tratamento Farmacológico da COVID-19 , Inibidores de Proteases/farmacologia , Inibidores de Proteases/química , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , Proteases 3C de Coronavírus/química , Transferência Ressonante de Energia de Fluorescência , COVID-19/virologia
20.
Neurol Sci ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39196497

RESUMO

INTRODUCTION: Here, we describe the clinical characteristics and therapeutic effects of myasthenia gravis (MG) coexisting with thyroid eye disease (TED). METHODS: We collated clinical data from MG patients in our hospital between 2012 and 2022 and analyzed the clinical characteristics of MG patients with hyperthyroidism, MG patients with TED and ocular myasthenia gravis (OMG) patients with TED. RESULTS: We recruited 62 MG patients with hyperthyroidism, including 13 MG patients with TED and 10 OMG patients with TED. There were 70 MG patients without hyperthyroidism; 29 of these were OMG. Compared with patients without hyperthyroidism, patients with hyperthyroidism had an earlier age at onset and milder clinical symptoms (P < 0.05). The incidence of thymus hyperplasia in patients with hyperthyroidism and TED was significantly lower than that in patients without TED (38.5% vs. 69.4%, P < 0.05); these patients also had a significantly lower antibody titer for the acetylcholine receptor [0.72 (0.27, 14.93) nmol/L vs. 2.38 (0.28, 49.51) nmol/L, P < 0.05]. Diplopia was significantly more frequent in OMG patients with TED than in patients with OMG (84.6% vs. 44.8%, P < 0.05), and the rate of diplopia in OMG patients with TED was significantly higher after treatment with bromostigmine and glucocorticoid (69.2% vs. 3.4%, P < 0.05). CONCLUSIONS: MG patients with TED had a significantly lower incidence of thymus hyperplasia and a lower antibody titer for the acetylcholine receptor. Patients with OMG and TED are more likely to develop diplopia; it is very difficult to treat diplopia in these patients.

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