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1.
J Alzheimers Dis ; 101(3): 937-950, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39302372

RESUMEN

Background: Alzheimer's disease and related dementias (ADRD) are progressive conditions. Family caregivers of patients, especially those caring for patients with ADRD exhibiting behavioral and psychological symptoms of dementia (BPSD), undergo significant physical and mental changes during long-term care. While most researchers have focused on the specific needs of family caregivers, the comprehensive understanding of these needs is limited. In this study, Alderfer's existence, relatedness, and growth theory was used to develop an interview framework to systematically and comprehensively understand the needs of family caregivers of individuals with ADRD. Objective: The objective of this study was to understand family caregivers' needs in coping with BPSD in individuals with ADRD, aiming to alleviate caregivers' stress and promote their overall well-being. Methods: This study used a hermeneutic-phenomenological interview research design. Data were collected via remote conferences involving interviews with 17 participants selected via maximum variation sampling. The Colaizzi seven-step method was utilized, and the interview contents were analyzed using NVivo 12.0 software. Results: The needs of family caregivers in coping with the BPSD of individuals with ADRD could be summarized into three themes, namely existence needs, relatedness needs, and growth needs, and 10 sub-themes. Conclusions: The study findings provide new insights into the needs of family caregivers in coping with patients exhibiting BPSD. Family caregivers experience significant negative emotions, poor caregiving experiences, heavy caregiving burdens, and a desire for professional assistance and policy support.


Asunto(s)
Adaptación Psicológica , Cuidadores , Demencia , Humanos , Cuidadores/psicología , Adaptación Psicológica/fisiología , Femenino , Masculino , Demencia/psicología , Demencia/enfermería , Anciano , Persona de Mediana Edad , Hermenéutica , Estrés Psicológico/psicología , Anciano de 80 o más Años , Adulto , Familia/psicología
3.
Pain Ther ; 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39276309

RESUMEN

INTRODUCTION: In percutaneous endoscopic lumbar discectomy (PELD), pain occurs when the posterior longitudinal ligament (PLL) is exposed, removed, and decompressed. However, pain characteristics of the PLL stimulated in PELD have not been reported. METHODS: A total of 932 patients underwent PELD under local anesthesia. Pain distribution and intensity were recorded on a posterior body diagram during the operation. Pain intensity was assessed by the visual analog scale scores for the back (VAS-B). The PLL specimens were collected and observed using hematoxylin-eosin (HE) staining and immunohistochemistry. RESULTS: Patients with lumbar disc herniation (LDH) at L4/5 and L5/S1 had pain foci in different regions. The mean VAS-B scores between the ventral and dorsal sides of the PLL were 6.14 ± 0.97 and 4.80 ± 1.15, respectively (P < 0.05). The distribution of nociceptive nerve fibers in the dorsal side was uniform and scattered, while those in the ventral side were mainly distributed near the outer surface of the annulus fibrosus. The positive expression of substance P (SP) and calcitonin gene-related peptide (CGRP) was higher in the ventral side of the PLL than in the dorsal side (P < 0.0001). CONCLUSIONS: Differences in pain distribution and intensity were observed when the PLL was incited at different spinal levels during PELD surgery.

4.
J Atheroscler Thromb ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39231649

RESUMEN

AIM: We aimed to assess the association between non-high-density lipoprotein cholesterol (non-HDL-C) and symptomatic intracranial artery stenosis (sICAS), as well as the impact of non-HDL-C on recurrent vascular events in patients with mild ischemic stroke ( NIHSS score ≤ 5). METHODS: This prospective study was based on data from patients presenting within 72 hours of stroke occurrence. We included patients admitted to 8 Chinese hospitals between September 2019 and November 2021. The associations of non-HDL-C with sICAS and recurrent vascular risk were assessed using multivariate regression models and a restricted cubic spline analysis. RESULTS: Among the 2,544 patients analyzed at 12 months, 652 (25.6%) were diagnosed with sICAS. Elevated non-HDL-C was linked to a higher incidence of sICAS, and the adjusted odd ratios for quintile variables and continuous variables were 1.36 ([95% CI, 1.01-1.81]) and 1.14 ([95% CI, 1.04-1.24). In comparison to those in the first quintile, the adjusted hazard ratio of the fifth quintile of non-HDL-C was 1.19 ([95% CI 0.78-1.80]) for recurrent ischemic stroke and was 0.39 ([95% CI, 0.17-0.91]) for intracranialhemorrhage. CONCLUSIONS: The non-HDL-C level may be a useful predictor of sICAS. Higher non-HDL-C levels may be associated with a lower risk of intracranial hemorrhage in mild, noncardiogenic stroke, but not a higher risk of recurrent ischemic stroke.

5.
Int Immunopharmacol ; 140: 112801, 2024 Oct 25.
Artículo en Inglés | MEDLINE | ID: mdl-39121608

RESUMEN

AIM: The degradation of the cartilage endplate (CEP) plays a critical role in the initiation and progression of intervertebral disc degeneration (IVDD), a disease closely associated with inflammation and oxidative stress. Naringin (NGN), a flavonoid compound derived from citrus fruits, has been shown to exhibit significant anti-inflammatory and antioxidant properties. This suggests a promising avenue for NGN's application in IVDD therapy. This study aims to elucidate the therapeutic effects and underlying mechanisms of NGN on CEP degeneration, contributing to the formulation of evidence-based treatment strategies for IVDD. METHODS: In vivo, we developed an intervertebral disc degeneration (IVDD) model in mice by excising the bilateral facet joints and surrounding ligaments, and evaluated the effects of naringin using HE staining and Micro-CT analysis. In vitro, endplate chondrocytes were isolated and subjected to TBHP to replicate the IVDD pathological condition. The protective effects of NGN on these cells were confirmed through immunofluorescence, Western Blot, and flow cytometry. RESULTS: In vivo, NGN effectively mitigated IVDD progression and CEP calcification in mice. In vitro, NGN enhanced mitophagy and suppressed NLRP3 inflammasome activation through the SIRT3/FOXO3a/Parkin pathway. Furthermore, NGN safeguarded chondrocytes against apoptosis and calcification triggered by oxidative stress, in addition to mitigating the degradation of the extracellular matrix. However, silencing SIRT3 negated NGN's protective influence on chondrocytes. CONCLUSION: Our study demonstrated that NGN effectively shields chondrocytes from apoptosis and NLRP3 inflammasome activation by facilitating SIRT3-mediated mitophagy. These insights could pave the way for innovative approaches in the prevention and management of IVDD.


Asunto(s)
Apoptosis , Condrocitos , Flavanonas , Proteína Forkhead Box O3 , Inflamasomas , Degeneración del Disco Intervertebral , Ratones Endogámicos C57BL , Mitofagia , Proteína con Dominio Pirina 3 de la Familia NLR , Sirtuina 3 , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Condrocitos/patología , Mitofagia/efectos de los fármacos , Apoptosis/efectos de los fármacos , Inflamasomas/metabolismo , Flavanonas/farmacología , Flavanonas/uso terapéutico , Degeneración del Disco Intervertebral/tratamiento farmacológico , Degeneración del Disco Intervertebral/patología , Sirtuina 3/metabolismo , Ratones , Proteína Forkhead Box O3/metabolismo , Masculino , Modelos Animales de Enfermedad , Ubiquitina-Proteína Ligasas/metabolismo , Células Cultivadas , Transducción de Señal/efectos de los fármacos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico
7.
Sheng Wu Gong Cheng Xue Bao ; 40(8): 2418-2431, 2024 Aug 25.
Artículo en Chino | MEDLINE | ID: mdl-39174462

RESUMEN

Glycolic acid is an important chemical product widely used in various fields, including cosmetics, detergents, textiles, and more. Currently, microbial production of glycolic acid has disadvantages such as poor genetic stability, low yield, and high cost. Additionally, whole-cell catalytic production of glycolic acid typically requires the addition of relatively expensive sorbitol as a carbon source, which limits its industrial production. To develop an industrially applicable method for glycolic acid production, this study used ethylene glycol as a substrate to screen the glycolic acid-producing strains through whole-cell catalysis, obtaining a Rhodotorula sp. capable of producing glycolic acid. The strain was then subjected to UV mutagenesis and high throughput screening, and the positive mutant strain RMGly-20 was obtained. After optimization in shake flasks, the glycolic acid titer of RMGly-20 reached 17.8 g/L, a 10.1-fold increase compared to the original strain. Using glucose as the carbon source and employing a fed-batch culture in a 5 L fermenter, strain RMGly-20 produced 61.1 g/L of the glycolic acid. This achievement marks the preliminary breeding of a genetically stable glycolic acid-producing strain using a cheap carbon source, providing a new host for the biosynthesis of glycolic acid and promoting further progress toward industrial production.


Asunto(s)
Fermentación , Glicolatos , Rhodotorula , Glicolatos/metabolismo , Rhodotorula/metabolismo , Rhodotorula/genética , Microbiología Industrial/métodos , Glicol de Etileno/metabolismo , Mutagénesis
8.
Angew Chem Int Ed Engl ; : e202408686, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39118193

RESUMEN

ß-Branched chiral amines with contiguous stereocenters are valuable building blocks for preparing various biologically active molecules. However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo- and enantioselective biocatalytic approach for preparing a broad range of ß-branched chiral amines starting from their corresponding racemic ketones. This involves a dynamic kinetic resolution-asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds of protein engineering endowed wild-type PocIRED with higher reactivity, better stereoselectivity, and a broader substrate scope. Using the engineered enzyme, various chiral amine products were synthesized with up to >99.9% ee, >99:1 dr, and >99% conversion. The practicability of the developed biocatalytic method was confirmed by producing a key intermediate of tofacitinib in 74% yield, >99.9% ee, and 98:2 dr at a challenging substrate loading of 110 g L-1. Our study provides a highly capable imine reductase and a protocol for developing an efficient biocatalytic dynamic kinetic resolution-asymmetric reductive amination reaction system.

9.
J Proteome Res ; 23(9): 4005-4013, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39171377

RESUMEN

Ribosome profiling and mass spectrometry have revealed thousands of previously unannotated small and alternative open reading frames (sm/alt-ORFs) that are translated into micro/alt-proteins in mammalian cells. However, their prevalence across human tissues and biological roles remains largely undefined. The placenta is an ideal model for identifying unannotated microproteins and alt-proteins due to its considerable protein diversity that is required to sustain fetal development during pregnancy. Here, we profiled unannotated microproteins and alt-proteins in human placental tissues from preeclampsia patients or healthy individuals by proteomics, identified 52 unannotated microproteins or alt-proteins, and demonstrated that five microproteins can be translated from overexpression constructs in a heterologous cell line, although several are unstable. We further demonstrated that one microprotein, XRCC6P1, associates with translation initiation factor eIF3 and negatively regulates translation when exogenously overexpressed. Thus, we revealed a hidden sm/alt-ORF-encoded proteome in the human placenta, which may advance the mechanism studies for placenta development as well as placental disorders such as preeclampsia.


Asunto(s)
Placenta , Preeclampsia , Biosíntesis de Proteínas , Proteómica , Humanos , Embarazo , Femenino , Placenta/metabolismo , Proteómica/métodos , Preeclampsia/metabolismo , Preeclampsia/genética , Sistemas de Lectura Abierta , Factor 3 de Iniciación Eucariótica/metabolismo , Factor 3 de Iniciación Eucariótica/genética , Proteoma/análisis , Proteoma/metabolismo , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/genética , Micropéptidos
10.
Plant Methods ; 20(1): 131, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39169365

RESUMEN

Fungal diseases are the main factors affecting the quality and production of vegetables. Rapid and accurate detection of pathogenic spores is of great practical significance for early prediction and prevention of diseases. However, there are some problems with microscopic images collected in the natural environment, such as complex backgrounds, more disturbing materials, small size of spores, and various forms. Therefore, this study proposed an improved detection method of GCS-YOLOv8 (Global context and CARFAE and Small detector-optimized YOLOv8), effectively improving the detection accuracy of small-target pathogen spores in natural scenes. Firstly, by adding a small target detection layer in the network, the network's sensitivity to small targets is enhanced, and the problem of low detection accuracy of the small target is effectively improved. Secondly, Global Context attention is introduced in Backbone to optimize the CSPDarknet53 to 2-Stage FPN (C2F) module and model global context information. At the same time, the feature up-sampling module Content-Aware Reassembly of Features (CARAFE) was introduced into Neck to enhance the ability of the network to extract spore features in natural scenes further. Finally, we used an Explainable Artificial Intelligence (XAI) approach to interpret the model's predictions. The experimental results showed that the improved GCS-YOLOv8 model could detect the spores of the three fungi with an accuracy of 0.926 and a model size of 22.8 MB, which was significantly superior to the existing model and showed good robustness under different brightness conditions. The test on the microscopic images of the infection structure of cucumber down mildew also proved that the model had good generalization. Therefore, this study realized the accurate detection of pathogen spores in natural scenes and provided feasible technical support for early predicting and preventing fungal diseases.

11.
Curr Med Chem ; 31(28): 4549-4561, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38994652

RESUMEN

AIM: To explore an exosome-relevant molecular classification in lung adenocarcinoma (LUAD). BACKGROUND: Exosome genes or relevant non-coding RNAs are regulators of cancer treatment and prognosis, but their function in LUAD has not yet been determined. OBJECTIVE: Unraveling a molecular classification applying exosome-related RNA networks for LUAD prognosis evaluation. METHODS: MicroRNA sequencing data (miRNAs-seq) and RNA sequencing data (RNA- seq) were derived from The Cancer Genome Atlas (TCGA). The ConsensusCluster- Plus package was used for molecular typing in LUAD based on 121 Exosome-related genes. Then, a limma package was conducted to explore differentially expressed mRNAs (DEmRNAs), differentially expressed miRNAs (DEmiRNAs) and differentially expressed lncRNAs (DElncRNAs) in molecular typing for constructing an Exosome-driven competing endogenous RNA network (ceRNA). Dominant miRNAs, as well as target mRNAs, were identified by COX modeling and Kaplan-Meier survival analysis. RESULTS: Two Exosome-associated molecular clusters classified in LUAD. The C2 cluster favored high clinicopathology and showed a trend toward poor prognosis. 29 lncRNA- miRNA and 12 miRNA-mRNA interaction pairs were identified. The hsa-miR-429 was the pivotal miRNA in the network that affected the prognosis of LUAD. According to the interaction relationship and LUAD prognostic role, SNHG6-hsa- miR-429-CHRDL1/CCNA2 was identified. SNHG6-hsa-miR-429-CHRDL1 exerts oncogenic effects, and SNHG6-hsa-miR-429- CCNA2 exerts pro-oncogenic effects. CONCLUSION: Overall, our study identified an Exosome-driven ceRNA network in LUAD, and the SNHG6-hsa-miR-429-CHRDL1/CCNA2 axis could be a new therapeutic target for LUAD and our study provides new insights into the molecular mechanisms of LUAD.


Asunto(s)
Adenocarcinoma del Pulmón , Exosomas , Neoplasias Pulmonares , MicroARNs , ARN Largo no Codificante , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Exosomas/metabolismo , Exosomas/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Adenocarcinoma del Pulmón/diagnóstico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/diagnóstico , Pronóstico , Regulación Neoplásica de la Expresión Génica , Ciclina A2
12.
PLoS Pathog ; 20(7): e1012425, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39078849

RESUMEN

Pathogenic bacteria's metabolic adaptation for survival and proliferation within hosts is a crucial aspect of bacterial pathogenesis. Here, we demonstrate that citrate, the first intermediate of the tricarboxylic acid (TCA) cycle, plays a key role as a regulator of gene expression in Staphylococcus aureus. We show that citrate activates the transcriptional regulator CcpE and thus modulates the expression of numerous genes involved in key cellular pathways such as central carbon metabolism, iron uptake and the synthesis and export of virulence factors. Citrate can also suppress the transcriptional regulatory activity of ferric uptake regulator. Moreover, we determined that accumulated intracellular citrate, partly through the activation of CcpE, decreases the pathogenic potential of S. aureus in animal infection models. Therefore, citrate plays a pivotal role in coordinating carbon metabolism, iron homeostasis, and bacterial pathogenicity at the transcriptional level in S. aureus, going beyond its established role as a TCA cycle intermediate.


Asunto(s)
Carbono , Ácido Cítrico , Regulación Bacteriana de la Expresión Génica , Homeostasis , Hierro , Infecciones Estafilocócicas , Staphylococcus aureus , Staphylococcus aureus/metabolismo , Staphylococcus aureus/genética , Staphylococcus aureus/patogenicidad , Hierro/metabolismo , Carbono/metabolismo , Ácido Cítrico/metabolismo , Infecciones Estafilocócicas/metabolismo , Infecciones Estafilocócicas/microbiología , Animales , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Ciclo del Ácido Cítrico , Ratones , Transducción de Señal
13.
Front Microbiol ; 15: 1394775, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38946905

RESUMEN

Introduction: Acinetobacter baumannii (A. baumannii) is an important opportunistic pathogen causing nosocomial infection in the clinic. The occurrence rate of antibiotic resistance is increasing year by year, resulting in a highly serious situation of bacterial resistance. Methods: To better understand the local epidemiology of multidrug-resistant A. baumannii, an investigation was conducted on the antibiotic resistance of different types of A. baumannii and its relationship with the genes of A. baumannii. Furthermore, the molecular mechanism underlying antibiotic resistance in A. baumannii was investigated through transcriptome analysis. Results: These results showed that a total of 9 STs were detected. It was found that 99% of the strains isolated in the hospital belonged to the same STs, and the clone complex CC208 was widely distributed in various departments and all kinds of samples. Furthermore, these A. baumannii strains showed high resistance to ertapenem, biapenem, meropenem, and imipenem, among which the resistance to ertapenem was the strongest. The detection rate of bla OXA-51 gene in these carbapenem resistance A. baumannii (CRAB) reached 100%; Additionally, the transcriptome results showed that the resistance genes were up-regulated in resistance strains, and these genes involved in biofilm formation, efflux pumps, peptidoglycan biosynthesis, and chaperonin synthesis. Discussion: These results suggest that the CC208 STs were the main clonal complex, and showed high carbapenem antibiotic resistance. All these resistant strains were distributed in various departments, but most of them were distributed in intensive care units (ICU). The bla OXA-23 was the main antibiotic resistance genotype; In summary, the epidemic trend of clinical A. baumannii in Guiyang, China was analyzed from the molecular level, and the resistance mechanism of A. baumannii to carbapenem antibiotics was analyzed with transcriptome, which provided a theoretical basis for better control of A. baumannii.

14.
Opt Express ; 32(11): 19567-19577, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38859089

RESUMEN

Chalcogenide glass has achieved great success in manufacturing axial-type infrared gradient refractive index (IR-GRIN) lenses. However, studies on radial-type IR-GRIN lenses, which are more ideal for optical design, remain rare. The present study introduces what we believe to be a new method for preparing radial IR-GRIN lens by creating high refractive index (n) In2S3 nanocrystals within a 65GeS2-25In2S3-10CsCl (GIC, in molar percentage) glass matrix. Upon introduction of multi-temperature field manipulation, we have successfully achieved central crystallization and simultaneous gradient attenuation spreading toward the edge within GIC glass, providing a radial GRIN profile with Δn over 0.1 while maintaining excellent IR transparency. In addition, the optical and structural properties of the GIC GRIN samples were characterized. The relationship between Raman intensity and the n of glass ceramics at different heat treatment temperatures was investigated, thereby enabling the indirect confirmation of the presence of radial gradient crystallization within the prepared GIC GRIN samples through Raman intensity. Multiple experimental results have shown that this approach has excellent reproducibility and potential for large-scale productions.

15.
Ir J Med Sci ; 2024 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-38878140

RESUMEN

OBJECTIVE: A few clinical studies have been conducted on the prognostic value of the Essen score in acute cerebral infarction (ACI), and this study explores whether the Essen score can assess the prognosis of ACI. METHODS: Data were collected from 1176 patients with ACI. The patients were divided into three groups on the basis of the Essen score, with groups 1, 2 and 3 having scores of 0-2, 3-6 and 7-9, respectively. Logistic multivariate analysis was performed to analyse the predictors of poor prognosis in patients with ACI. The X2 trend test was used to compare the poor-prognosis groups on the basis of the Essen score. The receiver operating characteristic (ROC) curve of patient prognosis was plotted using MedCalc software, and the area under the ROC curve (AUC) was calculated. P < 0.05 was considered statistically significant. RESULTS: Multivariate analysis of the good- and poor-prognosis groups of ACI showed that the Essen score and the male gender were predictors of poor prognosis. The X2 trend test was used to compare the poor-prognosis groups on the basis of the Essen score, and results suggested that the higher the Essen score was, the worse the prognosis was. The Essen score assessed the prognosis of ACI with an AUC of 0.787 and P < 0.001. CONCLUSION: The Essen score is a valuable scoring system for predicting the prognosis of patients with ACI.

16.
Langmuir ; 40(26): 13467-13475, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38889438

RESUMEN

Because of the deep and zigzag microporous structure, porous carbon materials exhibit inferior capacitive performance and sluggish electrochemical kinetics for supercapacitor electrode materials. Herein, a single-step carbonation and activation approach was utilized to synthesize coal-based porous carbon with an adjustable pore structure, using CaO as a hard template, KOH as an activator, and oxidized coal as precursors to carbon. The obtained sample possesses an interconnected and hierarchical porous structure, higher SSA (1060 m2 g-1), suitable mesopore volume (0.25 cm3 g-1), and abundant surface heteroatomic functional groups. Consequently, the synthesized carbon exhibits an exceptionally high specific capacitance of 323 F g-1 at 1 A g-1, along with 80.3% capacitance retention at 50 A g-1. The assembled two-electrode configuration demonstrates a remarkable capacitance retention of up to 95% and achieves Coulombic efficiency of nearly 100% with 10,000 cycles in a 6 M KOH electrolyte. Furthermore, the Zn-ion hybrid capacitor also exhibits a specific capacity of up to 139.1 mA h g-1 under conditions of 0.2 A g-1. This work offers a simple method in preparation of coal-based porous carbon with controllable pore structure.

17.
J Med Chem ; 67(11): 8791-8816, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38775356

RESUMEN

The spread of the influenza virus has caused devastating pandemics and huge economic losses worldwide. Antiviral drugs with diverse action modes are urgently required to overcome the challenges of viral mutation and drug resistance, and targeted protein degradation strategies constitute excellent candidates for this purpose. Herein, the first degradation of the influenza virus polymerase acidic (PA) protein using small-molecule degraders developed by hydrophobic tagging (HyT) technology to effectively combat the influenza virus was reported. The SAR results revealed that compound 19b with Boc2-(L)-Lys demonstrated excellent inhibitory activity against A/WSN/33/H1N1 (EC50 = 0.015 µM) and amantadine-resistant strain (A/PR/8/H1N1), low cytotoxicity, high selectivity, substantial degradation ability, and good drug-like properties. Mechanistic studies demonstrated that the proteasome system and autophagic lysosome pathway were the potential drivers of these HyT degraders. Thus, this study provides a powerful tool for investigating the targeted degradation of influenza virus proteins and for antiviral drug development.


Asunto(s)
Antivirales , Interacciones Hidrofóbicas e Hidrofílicas , Tiourea , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Humanos , Perros , Animales , Tiourea/farmacología , Tiourea/análogos & derivados , Tiourea/química , Relación Estructura-Actividad , Subtipo H1N1 del Virus de la Influenza A/efectos de los fármacos , Células de Riñón Canino Madin Darby , Proteolisis/efectos de los fármacos , Proteínas Virales/metabolismo , Proteínas Virales/química , Proteínas Virales/antagonistas & inhibidores , ARN Polimerasa Dependiente del ARN/antagonistas & inhibidores , ARN Polimerasa Dependiente del ARN/metabolismo , Farmacorresistencia Viral/efectos de los fármacos
18.
Syst Rev ; 13(1): 145, 2024 May 30.
Artículo en Inglés | MEDLINE | ID: mdl-38816878

RESUMEN

BACKGROUND: Functional endoscopic sinus surgery is a principal option for treating chronic rhinosinusitis with nasal polyps (CRSwNP) after medication failures. Unfortunately, some patients still have unsatisfactory postoperative recovery. The type of inflammatory cell infiltration in nasal polyp tissue has been reported available for recurrence prediction. As it is invasive and time-consuming, this technique is hard to promote clinically under the existing technical conditions. And during the course of clinical treatment, we have noted that differences in the postoperative recurrence rate of patients present among different traditional Chinese medicine syndrome types. METHODS AND ANALYSIS: This is a non-randomized, single-center, and prospective cohort study started in Chengdu Sichuan Province, People's Republic of China, in January 2021. A total of 200 participants will be recruited from patients who are diagnosed with CRSwNP and prepared for functional endoscopic sinus surgery. We collect preoperative data which includes general information, medical history, TCM syndromes, visual analogue scale (VAS) of subjective symptoms, Lund-Kennedy endoscopic score, and Lund-Mackay score of computed tomography (CT) scanning of sinuses. We acquire the VAS score and Lund-Kennedy score of subjective symptoms through multiple planned follow-up after surgery. After 1 year of follow-up, the recurrence rate will be calculated, and the curative effect will be assessed. Meanwhile, the patients' pathological sections will be sorted out, and inflammatory cell infiltration will be analyzed. Statistical analysis will be carried out to evaluate the correlation among CRSwNP recurrence and TCM syndrome types and tissue inflammatory cell infiltration types. Then we will establish a predictive model for CRSwNP recurrence. Analyses of survey data include descriptive and inferential statistical approaches. DISCUSSION: This is the first prospective cohort study on investigating the correlation of CRSwNP recurrence with TCM syndrome types and tissue inflammatory cell infiltration types. Through this study, we hope to discover a new and simple, effective, and noninvasive way to predict the recurrence rate rapidly after CRSwNP and provide reference for the intervention timing of traditional Chinese medicine application, thereby achieving customized diagnosis and treatment, minimizing risks of surgical events, and delaying postoperative recurrence of CRSwNP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO ChiCTR2100041646.


Asunto(s)
Medicina Tradicional China , Pólipos Nasales , Recurrencia , Rinitis , Sinusitis , Humanos , Medicina Tradicional China/métodos , Pólipos Nasales/cirugía , Pólipos Nasales/patología , Sinusitis/cirugía , Estudios Prospectivos , Enfermedad Crónica , Rinitis/cirugía , Rinitis/patología , Inflamación , Endoscopía/métodos , Síndrome
19.
Artículo en Inglés | MEDLINE | ID: mdl-38692348

RESUMEN

Heat stress seriously threatens fish survival and health, demanding immediate attention. Teprenone is a gastric mucosal protective agent that can induce heat shock protein expression. This research investigated the effects of teprenone on largemouth bass (Micropterus salmoides) subjected to heat stress. Juvenile fish were assigned to different groups: group C (control group, 0 mg teprenone/kg diet), T0, T200, T400, and T800 (0, 200, 400, and 800 mg teprenone/kg diet, respectively), which were fed for 3 days, followed by a day without the diet. All groups except group C were subjected to acute heat stress (from 24 °C to 35 °C at 1 °C per hour and then maintained at 35 °C for 3 h). The results were as follows: The critical thermal maxima were significantly higher in the T200, T400, and T800 groups compared with the T0 group (P < 0.05). Heat stress caused severe damage to the tissue morphology of the liver, while teprenone significantly reduced this injury (P < 0.05). Serum cortisol concentration decreased gradually as teprenone concentration increased, and the lowest concentration was observed in the T800 group (P < 0.05). Compared with the T0 group, the serum activities of aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyl transferase were significantly lower in the T200, T400, and T800 groups (P < 0.05). The liver activities of catalase, total superoxide dismutase, and peroxidase were significantly higher in the T200 group than in the T0 group (P < 0.05). Transcript levels of the heat shock proteins (hsp90, hsp70, hspa5, and hsf1) and caspase family (caspase3 and caspase9) in the liver of the T200 group were significantly higher than those of the T0 group (P < 0.05). Western blot results showed that HSP70 and HSPA5 in the liver were significantly upregulated in the T200 group compared with the T0 group (P < 0.05). In summary, dietary teprenone improved thermal tolerance, alleviated heat stress damage in the liver, enhanced antioxidant capacity, and upregulated heat shock proteins in juvenile largemouth bass. This study offers theoretical support for applying teprenone in aquaculture to reduce financial losses caused by abiotic factors.


Asunto(s)
Lubina , Diterpenos , Respuesta al Choque Térmico , Hígado , Animales , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Respuesta al Choque Térmico/efectos de los fármacos , Diterpenos/farmacología , Suplementos Dietéticos , Proteínas de Peces/metabolismo , Proteínas de Peces/genética , Alimentación Animal/análisis , Dieta , Termotolerancia/efectos de los fármacos
20.
Mitochondrial DNA B Resour ; 9(5): 683-686, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38800623

RESUMEN

Calystegia hederacea Wall. in Roxb. 1824 is a perennial herbaceous vine in the family Convolvulaceae and has several biological effects. Herein, we reported the first complete chloroplast genome of C. hederacea. The chloroplast genome sequence was 152,057 bp in length, comparing a large single-copy (LSC) region of 87,891 bp, a small single-copy (SSC) region of 19,866 bp, and a pair of inverted repeat (IR) regions of 22,150 bp. This sequenced chloroplast genome contained 126 predicted genes, including 81 protein-coding genes, 37 tRNA genes, and eight rRNA genes, and the total GC content of the chloroplast genome was 37.79%. Phylogenetic analysis revealed that C. hederacea was closely related to C. soldanella. The chloroplast genome presented in this study will enrich the genome information of the genus Calystegia and provide deeper insights into the evolution study of the family Convolvulaceae.

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