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1.
STAR Protoc ; 5(3): 103269, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-39240711

RESUMO

Here, we present a protocol for conducting bibliometric analysis in biomedicine using CiteSpace and VOSviewer. We describe the steps for extracting data from Web of Science, data cleaning, and preprocessing. We then detail procedures for identifying research trends and collaboration networks by visualizing data with CiteSpace; mapping co-authorship, co-citation, and keyword co-occurrence using VOSviewer; and analyzing highly cited literature to identify key publications and trends. Finally, we outline techniques for interpreting the visualizations to draw meaningful conclusions about the research landscape. For complete details on the use and execution of this protocol, please refer to Li et al.1.

2.
Transl Oncol ; 50: 102130, 2024 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-39303357

RESUMO

Ovarian cancer is a highly heterogeneous tumor with a poor prognosis. The lack of reliable and efficient research models that can accurately mimic heterogeneity has impeded in-depth investigations and hindered the clinical translation of research findings in ovarian cancer. Organoid models have emerged as a promising in vitro approach, demonstrating remarkable fidelity to the histological, molecular, genomic, and transcriptomic features of their tissues of origin. In recent years, organoids have contributed to advancing our understanding of ovarian cancer initiation, metastasis, and drug resistance mechanisms, as well as facilitating clinical screening of effective therapeutic agents. The establishment of high-throughput organoid culture systems, coupled with cutting-edge technologies such as organ-on-a-chip, genetic engineering, and 3D printing, has tremendous potential for accelerating ovarian cancer research translation. In this review, we present a comprehensive overview of the latest exploration of organoids in basic ovarian cancer research and clinical translation. Furthermore, we discuss the prospects and challenges associated with the use of organoids and related novel technologies in the context of ovarian cancer. This review provides insights into the application of organoids in ovarian cancer.

3.
Microbiol Res ; 289: 127881, 2024 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-39241502

RESUMO

Mannitol, one of the most widespread sugar alcohols, has been integral to daily human life for two centuries. Global population growth and competition for freshwater, food, and land have prompted a shift in the fermentation industry from terrestrial to marine raw materials. Mannitol is a readily available carbohydrate in brown seaweed from the ocean and possess a higher reducing power than glucose, making it a promising substrate for biological manufacturing. This has spurred numerous explorations into converting mannitol into high-value chemicals. Researchers have engineered microorganisms to utilize mannitol in various synthetic biological applications, including: (1) employing mannitol as an inducer to control the activation and deactivation of genetic circuits; (2) using mannitol as a carbon source for synthesizing high-value chemicals through biomanufacturing. This review summarizes the latest advances in the application of mannitol in synthetic biology. AIM OF REVIEW: The aim is to present a thorough and in-depth knowledge of mannitol, a marine carbon source, and then use this carbon source in synthetic biology to improve the competitiveness of biosynthetic processes. We outlined the methods and difficulties of utilizing mannitol in synthetic biology with a variety of microbes serving as hosts. Furthermore, future research directions that could alleviate the carbon catabolite repression (CCR) relationship between glucose and mannitol are also covered. EXPECTED CONTRIBUTIONS OF REVIEW: Provide an overview of the current state, drawbacks, and directions for future study on mannitol as a carbon source or genetic circuit inducer in synthetic biology.

4.
Oncol Lett ; 28(5): 509, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39268162

RESUMO

The current evidence for the use of nanoparticle albumin-bound paclitaxel (nab-PTX) for adjuvant breast cancer chemotherapy is insufficient. The present study aimed to assess the efficacy and toxicity of nab-PTX in comparison with solvent-based paclitaxel (sb-PTX) in postoperative adjuvant breast cancer treatment. A total of 345 patients were included in the study and separated into nab-PTX (n=289) and sb-PTX (n=56) groups based on the type of taxane used in the adjuvant chemotherapy regimen. The study evaluated the baseline characteristics in both groups and the risk factors for postoperative recurrence of mammary cancer. Furthermore, data concerning disease-free survival (DFS) and adverse effects were obtained and analyzed, and group confounding variables were addressed using 1:2 propensity score matching (PSM). Comparisons before PSM revealed significant differences in baseline characteristics including age, underlying disease, lymph node involvement, vascular invasion, human epidermal growth factor receptor 2 and axillary surgery (P<0.05). Following PSM, there were 90 patients in the nab-PTX group and 56 in the sb-PTX group, with no significant differences in the baseline differences (P>0.05). Before PSM, the 73-month DFS rate was 97.9% in the nab-PTX group compared with 91.1% in the sb-PTX group. However, there were no significant differences between the groups before or after PSM (P=0.15 and P=0.49, respectively). Additionally, Cox regression analysis demonstrated a significantly lower chance of recurrence in patients aged >45 years [hazard ratio (HR), 0.197; 95% confidence interval (CI), 0.052-0.753; P=0.018], whereas underlying disease (HR, 5.352; 95% CI, 1.310-21.854; P=0.019) and lymph node infiltration (HR, 8.930; 95% CI, 1.121-71.161; P=0.039) significantly increased the risk of recurrence. Regarding safety, the sb-PTX group had a significantly greater incidence of anaphylaxis, whereas the nab-PTX group had significantly increased rates of anemia and peripheral neuropathy (P<0.05). In summary, the 73-month DFS rate of the nab-PTX cohort exceeded that of the sb-PTX cohort, but no significant difference was detected between them. Underlying disease, lymph node metastasis and an age of ≤45 years are significant predictors of postoperative recurrence of breast cancer.

5.
Int J Mol Sci ; 25(17)2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-39273235

RESUMO

Ionizing radiation exposure can cause damage to diverse tissues and organs, with the hematopoietic system being the most sensitive. However, limited information is available regarding the radiosensitivity of various hematopoietic cell populations in the bone marrow due to the high heterogeneity of the hematopoietic system. In this study, we observed that granulocyte-macrophage progenitors, hematopoietic stem/progenitor cells, and B cells within the bone marrow showed the highest sensitivity, exhibiting a rapid decrease in cell numbers following irradiation. Nonetheless, neutrophils, natural killer (NK) cells, T cells, and dendritic cells demonstrated a certain degree of radioresistance, with neutrophils exhibiting the most pronounced resistance. By employing single-cell transcriptome sequencing, we investigated the early responsive genes in various cell types following irradiation, revealing that distinct gene expression profiles emerged between radiosensitive and radioresistant cells. In B cells, radiation exposure led to a specific upregulation of genes associated with mitochondrial respiratory chain complexes, suggesting a connection between these complexes and cell radiosensitivity. In neutrophils, radiation exposure resulted in fewer gene alterations, indicating their potential for distinct mechanisms in radiation resistance. Collectively, this study provides insights into the molecular mechanism for the heterogeneity of radiosensitivity among the various bone marrow hematopoietic cell populations.


Assuntos
Radiação Ionizante , Análise de Célula Única , Transcriptoma , Animais , Camundongos , Análise de Célula Única/métodos , Transcriptoma/efeitos da radiação , Células da Medula Óssea/efeitos da radiação , Células da Medula Óssea/metabolismo , Camundongos Endogâmicos C57BL , Tolerância a Radiação/genética , Perfilação da Expressão Gênica , Células-Tronco Hematopoéticas/efeitos da radiação , Células-Tronco Hematopoéticas/metabolismo , Neutrófilos/efeitos da radiação , Neutrófilos/metabolismo
6.
Surv Ophthalmol ; 2024 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-39270826

RESUMO

Retinal degeneration (RD) is a group of ocular diseases characterized by progressive photoreceptor apoptosis and visual impairment. Mitochondrial malfunction, excessive oxidative stress, and chronic activation of neuroglia collectively contribute to the development of RD. Currently, there is a lack of efficacious therapeutic interventions for RD. Stanniocalcin-1 (STC-1) is a promising candidate molecule to decelerate photoreceptor cell death. STC-1 is a secreted calcium/phosphorus regulatory protein that exerts diverse protective effects. Accumulating evidence suggests that STC-1 protects retinal cells from ischemic injury, oxidative stress, and excessive apoptosis through enhancing the expression of uncoupling protein-2 (UCP-2). Furthermore, STC-1 exerts its antiinflammatory effects by inhibiting the activation of microglia and macrophages, as well as the synthesis and secretion of proinflammatory cytokines, such as TNF-α, IL-1, and IL-6. By employing these mechanisms, STC-1 effectively shields the retinal photoreceptors and optic nerve, thereby slowing down the progression of RD. We summarize the STC-1-mediated therapeutic effects on the degenerating retina, with a particular focus on its underlying mechanisms. These findings highlight that STC-1 may act as a versatile molecule to treat degenerative retinopathy. Further research on STC-1 is imperative to establish optimal protocols for its clinical use.

7.
Front Pharmacol ; 15: 1324509, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246661

RESUMO

Background: Chinese patent medicines are specialty preparations in China that are produced using traditional prescriptions processed by modern pharmaceutical technology. They contain complex ingredients and much attention is paid to their clinical safety. Demonstrating the clinical safety of Chinese patent medicines containing toxic ingredients in modern pharmacological studies has become one of the urgent issues to be solved for the safe use of clinical medicines. Objectives: The aim of this research is to evaluate the safety of Chinese patent medicines containing toxic ingredients by applying the risk-benefit assessment method. Additionally, a database of 'toxic ingredients-toxic Chinese herbal medicines-adverse reactions' will be established to explore the relationship between toxic ingredients and adverse reactions. This will lay the foundation for the rational clinical use of Chinese patent medicines containing toxic ingredients. Methods: 1) Establish a database of 'toxic Chinese herbal medicines-toxic ingredients-toxic Chinese patent medicines' to count the Chinese patent medicines containing toxic ingredients in the 2020 edition of Chinese Pharmacopoeia. 2) Filtered the clinical studies, extracted the drug-related ADEs, and analyzed the characteristics and correlations of these ADEs. 3) Finally, this section summarizes the causes of ADEs related to Chinese patent medicines containing toxic ingredients and extracts the main risk factors to provide a reference for further study. Outcomes: 1) There are four main types of Chinese patent medicines containing toxic ingredients. These include medicines with diester aconitine metabolites, mineral composition, Araceae metabolites, and hydrogen cyanide. 2) Digestive system, skin and its appendages, and allergic reactions were the main types of ADEs related to four types of Chinese patent medicines containing toxic ingredients. 3) There are four primary risk factors associated with the clinical use of Chinese patent medicines containing toxic ingredients: medicine, medication, individual and regulatory factors.

8.
Ther Adv Med Oncol ; 16: 17588359241271845, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39246808

RESUMO

Background: Genetic studies of ovarian cancer (OC) have historically focused on BRCA1/2 mutations, lacking other studies of homologous recombination repair (HRR). Poly (ADP-ribose) polymerase inhibitors (PARPi) exploit synthetic lethality to significantly improve OC treatment outcomes, especially in BRCA1/2 deficiency patients. Objectives: Our study aims to construct a mutation map of HRR genes in OC and identify factors influencing the efficacy of PARPi. Design: A retrospective observational analysis of HRR gene variation data from 695 OC patients from March 2019 to February 2022 was performed. Methods: The HRR gene variation data of 695 OC patients who underwent next-generation sequencing (NGS) in the First Affiliated Hospital of Zhengzhou University were retrospectively collected. Clinical data on the use of PARPi in these patients were also gathered to identify factors that may interfere with the efficacy of PARPi. Results: Out of 127 pathogenic variants in the BRCA1/2 genes, 104 (81.9%) were BRCA1 mutations, and 23 (18.1%) were BRCA2 mutations. Among the 59 variants of uncertain significance (VUS), 20 (33.9%) were BRCA1, while 39 (66.1%) were BRCA2 mutations. In addition to BRCA1/2, HRR gene results showed that 9 (69%) of 13 were HRR pathway pathogenic variants; and 16 (1.7%) of 116 VUS were Food and Drug Administration (FDA)-approved mutated HRR genes. Notably, the treatment regimen significantly influenced the effectiveness of PARPi, especially when using first-line maintenance therapy, leading to enhanced progression-free survival (PFS) compared to alternative protocols. Conclusion: Focusing on HRR gene mutations and supporting clinical research about PARPi in OC patients is crucial for developing precision treatment strategies and enhancing prognosis.

9.
Adv Mater ; : e2412379, 2024 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-39252633

RESUMO

Organic thin film transistors (OTFTs) enable rapid and label-free high-sensitivity detection of target analytes due to their low cost, large-area processing, biocompatibility, and inherent signal amplification. At the same time, the freedom of synthesis, tailorability, and functionalization of organic semiconductor materials and their ability to be combined with flexible substrates make them one of the ideal platforms for biosensing. However, OTFTs-based biosensors still face significant challenges, such as unexpected surface adsorption, disordered conformation, inhomogeneous graft density, and flexibility of probe molecules that biological sensing probes would face during immobilization. In this review, efficient immobilization strategies based on OTFTs biological sensing probes developed in the last 5 years are highlighted. First, the biosensors are classified according to their sensing interface. Second, a comprehensive discussion of the types of biological sensing probes is presented. Third, three commonly used methods for immobilizing biological sensing probes and their challenges are briefly described. Finally, the applications of OTFTs-based biosensors for liquid phase detection are summarized. This review provides a comprehensive and timely review of optimization in sensing interface engineering so that efficient immobilization of biological sensing probes with sensing interfaces will contribute to the development of high-performance OTFTs-based biosensors.

10.
Adv Sci (Weinh) ; : e2306018, 2024 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-39283032

RESUMO

Stress concentration surrounding wounds drives fibroblasts into a state of high mechanical tension, leading to the delay of wound healing, exacerbating pathological fibrosis, and even causing tissue dysfunction. Here, an innovative skin stress-shielding hydrogel wound dressing is reported that makes the wound sites shrink as a response to body temperature and then remolds the stress micro-environment of wound sites to reduce the formation of skin scars. Composed of a modified natural temperature-sensitive polymer cross-linked with polyacrylic acid networks, this hydrogel wound dressing has demonstrated a substantial decrease in scar area for full-thickness wounds in rat models. The physical forces exerted by the wound dressing are instrumental in attenuating the activation and transduction of fibroblasts within the wound sites, thereby mitigating the excessive deposition of the extracellular matrix (ECM). Notably, the wound dressing significantly down-regulates the expression of transforming growth factor-ß1(TGF-ß1) and collagen I, while concurrently exerting a dramatic inhibitory effect on the integrin-focal adhesion kinase (FAK)/phosphorylated-FAK (p-FAK) signaling pathway. Collectively, the fabrication of functional hydrogels with a stress-shielding profile is a new route for achieving scar-less wound healing, thus offering immense potential for improving clinical outcomes and restoring tissue integrity.

11.
Food Res Int ; 194: 114883, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39232555

RESUMO

In this research, accelerated aroma release experiments and malvidin-3-O-glucoside copigmentation experiments in model red wine solutions were designed to investigate the abilities and molecular mechanisms of mannoproteins in modulating olfactory/chromatic properties of red wines. Results indicate that under orthonasal condition, mannoprotein MP2 was promising aroma modulator due to its predictable behaviors in expelling and retaining the aroma compounds during different periods. Low field nuclear magnetic resonance and molecular dynamic simulation proved that the modulation ability of MP2 should be explained by its transitionary interacting preferences with water/aroma compound molecules. Retronasal results show that the release of aroma compounds and olfactory perceptions were irregular and difficult to predict, probably due to the complexity of the retronasal condition. All mannoproteins protected malvidin-3-O-glucoside and quercetin via the formation of binary/ternary complexes, and quercetin was found prior to be protected than malvidin-3-O-glucoside. Principal mannoprotein A0A6C1DV26 might be the critical malvidin-3-O-glucoside protector. With the presence of quercetin, principal mannoproteins B3LQU1/B5VL26 in mannoprotein MP1 might exhibit intramolecular and/or intermolecular mechanisms that strengthened the hyperchromic effect, thus enhanced the copigmentation.


Assuntos
Antocianinas , Glucosídeos , Glicoproteínas de Membrana , Vinho , Vinho/análise , Glucosídeos/química , Glicoproteínas de Membrana/metabolismo , Antocianinas/química , Odorantes/análise , Quercetina/química , Percepção Olfatória , Simulação de Dinâmica Molecular , Humanos
12.
J Adv Res ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39181200

RESUMO

INTRODUCTION: Metabolic syndrome is a serious public health concern across the globe. However, the typical metabolites and mechanisms underlying the decreased fertility related to metabolic syndrome is still elusive. OBJECTIVES: The aim of the present study was to explore the typical metabolites and mechanisms underlying the decreased fertility related with metabolic syndrome. METHODS: Utilizing metabolomics, a comparative analysis was conducted on fatty acid compositions in various tissues of sows with high and low reproductive performance. Additionally, serum fatty acid compositions in a metabolic syndrome model (obese mice) induced by a high-fat diet (HFD) were investigated to elucidate the lipid metabolites associated with metabolic syndrome. Furthermore, the impact of nervonic acid (NA) on ovarian function was examined using rodent animal models (rats and mice). Through biological techniques such as transcriptomics, CUT&Tag, and analysis of post-translational protein modifications, the molecular mechanisms underlying NA mediated ovarian inflammation were further elucidated based on models utilizing ovarian granulosa cells from pigs, humans, and mice. Finally, validation was performed on ovaries from patients diagnosed with polycystic ovary syndrome. RESULTS: In vitro, targeted serum lipidomic analysis revealed that sows with low embryo survival rates exhibited abnormal lipid metabolism characterized by abnormal accumulation of NA in the liver, ovary, and adipose tissue. Additionally, elevated NA levels trigger ovarian inflammation to cause ovarian dysfunction in both sows and rats. Mechanistically, NA induce mitochondrial oxidative stress through inhibiting respiratory chain proteins CYTB and NDFUB8 to activate NLRP3 inflammasome, which triggers procaspase-1 into active caspase-1, and convert the cytokine precursors pro-IL-1ß into biologically active IL-1ß in ovarian granulosa cells. Notably, we evidenced that NA promotes IL-1ß activities by increasing H3K9ac modification level of IL-1ß promoter regions and regulating the expression of the transcription factor AP-1. Finally, we found that the decreased expression of CerS2 in ovaries and the increased level of chemokine CXCL14 may be the cause of abnormal NA accumulation. Surprisingly, individuals with polycystic ovary syndrome, obesity, non-alcoholic fatty liver or gestational diabetes mellitus exhibit a high level of serum NA. CONCLUSION: Collectively, our current study suggests that NA is a typical metabolite of metabolic syndrome, which strongly influences the ovarian function and embryo survival and also provides that interfering with mitochondrial ROS production is a potential strong strategy for target solving abnormal NA accumulation.

13.
Brain Behav ; 14(8): e3636, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39169445

RESUMO

BACKGROUND: Depression is known as the "mental cold" and is also considered a major cause of disability worldwide. It is estimated that over 300 million people worldwide suffer from severe depression, equivalent to 4.4% of the world's population. The monoamine hypothesis of depression predicts the underlying pathophysiological mechanisms of depression, but in-depth research has failed to find convincing evidence. METHOD: In this study, we will dynamically and strictly quantitatively monitor the concentration changes of monoamine transmitters in the cerebrospinal fluid (CSF) of macaques, based on our previous work. In the experiment, timed and quantitative collection of CSF samples from macaques was performed and the concentration of monoamine transmitters was determined. RESULT: The results showed that after 2 months of chronic stress, the concentrations of high vanillin acid (HVA) and 3,4-dihydroxy-phenylacetic acid were significantly higher in the maternal separation (MS) group, whereas there was no significant difference in dopamine and 5-hydroxyindoleacetic acid. CONCLUSION: This study is the first to observe the long-term dynamic relationship between early adversity, chronic stress, adolescent depression, and CSF monoamine concentrations. The research suggests that MS and chronic stress play an undeniable role in the pathogenesis of depression and that concentrations of HVA and dihydroxyphenylacetic acid are likely to serve as early markers of depressive-like symptoms in macaques.


Assuntos
Depressão , Modelos Animais de Doenças , Macaca mulatta , Estresse Psicológico , Animais , Estresse Psicológico/líquido cefalorraquidiano , Estresse Psicológico/metabolismo , Masculino , Depressão/líquido cefalorraquidiano , Ácido 3,4-Di-Hidroxifenilacético/líquido cefalorraquidiano , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Biomarcadores/líquido cefalorraquidiano , Benzaldeídos/farmacologia , Privação Materna , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Dopamina/líquido cefalorraquidiano , Dopamina/metabolismo , Feminino , Monoaminas Biogênicas/líquido cefalorraquidiano , Monoaminas Biogênicas/metabolismo , Ácido Homovanílico/líquido cefalorraquidiano
14.
Microorganisms ; 12(8)2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39203534

RESUMO

Bacillus licheniformis is recognised as an exceptional expression platform in biomanufacturing due to its ability to produce high-value products. Consequently, metabolic engineering of B. licheniformis is increasingly pursued to enhance its utility as a biomanufacturing vehicle. Effective B. licheniformis cell factories require promoters that enable regulated expression of target genes. This review discusses recent advancements in the characterisation, synthesis, and engineering of B. licheniformis promoters. We highlight the application of constitutive promoters, quorum sensing promoters, and inducible promoters in protein and chemical synthesis. Additionally, we summarise efforts to expand the promoter toolbox through hybrid promoter engineering, transcription factor-based inducible promoter engineering, and ribosome binding site (RBS) engineering.

15.
Ecotoxicol Environ Saf ; 284: 116906, 2024 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-39182283

RESUMO

BACKGROUND: Calcitriol (Cal) is the most active metabolite of vitamin D and has antioxidant and anti-inflammatory properties. The aim of this study was to investigate the role of Cal in noise-induced hearing loss (NIHL) to further elucidate the mechanism of noise-induced oxidative stress in the mouse cochlea. METHODS: C57BL/6 J mice were given six intraperitoneal injections of Cal (500 ng/kg/d). After 14 days of noise exposure, auditory brainstem response (ABR) thresholds, and the cochlear outer hair cell loss rate were analysed to evaluate auditory function. Real-time fluorescence quantitative PCR, immunofluorescence and western blotting were performed in vitro after the treatment of cochlear explants with 100 µM tert-butyl hydroperoxide (TBHP) for 2.5 h and HEI-OC1 cells with 250 µM TBHP for 1.5 h. RESULTS: In vivo experiments confirmed that Cal pretreatment mitigated NIHL and outer hair cell death. The in vitro results demonstrated that Cal significantly reduced TBHP-induced cochlear auditory nerve fibre degradation and spiral ganglion neuron damage. Moreover, treatment with Cal inhibited the expression of oxidative stress-related factors (3-NT and 4-HNE) and DNA damage-related factors (γ-H2A.X) and attenuated TBHP-induced apoptosis in cochlear explants and HEI-OC1 cells. A total of 1479 upregulated genes and 1443 downregulated genes were screened in cochlear tissue 1 h after noise exposure. The level of transcription factor 3 (ATF3) was significantly elevated in HEI-OC1 cells after TBHP stimulation. Gene Transcription Regulation Database (GTRD)and Cistrome database analyses revealed that the downstream target gene of ATF3 is dual specificity phosphatase 1 (DUSP1). Cistrome DB Toolkit database results showed that the transcription factor of DUSP1 was ATF3. In addition, the ChIP-PCR results indicated that ATF3 might be a direct transcription factor of DUSP1. CONCLUSION: The results of our study suggest that Cal attenuates NIHL and inhibits noise-induced apoptosis by regulating the ATF3/DUSP1 signalling pathway.

16.
Zhongguo Zhong Yao Za Zhi ; 49(14): 3804-3817, 2024 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-39099354

RESUMO

The chemical composition of Ganoderma lucidum ethanol extracts was systematically analyzed and identified by ultra-high performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry(UPLC-Orbitrap-HRMS). The fragmentation pattern of the representative chemical compounds was summarized, and the potential anti-liver fibrosis active compounds of G. lucidum acting on the farnesoid X receptor(FXR) target were studied to elucidate its pharmacodynamic substance basis. Preliminarily, 95 chemical constituents of G. lucidum ethanol extracts were identified, including 24 ganoderic acids, 9 ganoderenic acids, 13 lucidenic acids, 3 ganolucidic acids, 1 ganoderma lactone, 40 other triterpenoids, 4 fatty acids, and 1 other constituent. In addition, the fragmentation patterns of the representative compounds were also analyzed. The structural characteristics of ganoderic acids and ganoderenic acids were the C30 skeleton, containing free-COOH and-OH groups, which could easily lose H_2O and CO_2 to form fragment ions. The D-ring was mostly a five-membered ring, which was prone to breakage. Lucidenic acids were the lanosterolane-type of the C27 skeleton, and the side-chain structure became shorter and contained the same free-COOH and-OH compared with ganoderic acids, which had been reduced from 8 to 5 cartons and prone to lose H_2O and CO_2. Then, six reported FXR receptor agonists were selected to form a training set for establishing a pharmacophore model based on FXR ligands. The 95 identified chemical constituents of G. lucidum were matched with the pharmacophore, and the optimal pharmacophore model 02(sensitivity=0.750 00, specificity=0.555 56, ROC=0.750) was selected for the virtual screening of the G. lucidum compound library through the validation of the test set. Finally, 31 potential G. lucidum active constituents were screened and chosen to activate the FXRs. The ADMET results showed that ganoderic acid H and lucidenic acid J had less than 90% plasma protein binding rate and no hepatotoxicity, which could be used as FXR activators for developing clinical drugs for the treatment of liver fibrosis, either alone or in combination.


Assuntos
Medicamentos de Ervas Chinesas , Cirrose Hepática , Receptores Citoplasmáticos e Nucleares , Reishi , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/química , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Reishi/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Espectrometria de Massas/métodos , Estrutura Molecular , Simulação de Acoplamento Molecular
17.
Cardiovasc Diabetol ; 23(1): 304, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39152445

RESUMO

BACKGROUND: Insulin resistance is linked to an increased risk of frailty, yet the comprehensive relationship between the triglyceride glucose-body mass index (TyG-BMI), which reflects weight, and frailty, remains unclear. This relationship is investigated in this study. METHODS: Data from 9135 participants in the China Health and Retirement Longitudinal Study (2011-2020) were analysed. Baseline TyG-BMI, changes in the TyG-BMI and cumulative TyG-BMI between baseline and 2015, along with the frailty index (FI) over nine years, were calculated. Participants were grouped into different categories based on TyG-BMI changes using K-means clustering. FI trajectories were assessed using a group-based trajectory model. Logistic and Cox regression models were used to analyse the associations between the TyG-BMI and FI trajectory and frail incidence. Nonlinear relationships were explored using restricted cubic splines, and a linear mixed-effects model was used to evaluate FI development speed. Weighted quantile regression was used to identify the primary contributing factors. RESULTS: Four classes of changes in the TyG-BMI and two FI trajectories were identified. Individuals in the third (OR = 1.25, 95% CI: 1.10-1.42) and fourth (OR = 1.83, 95% CI: 1.61-2.09) quartiles of baseline TyG-BMI, those with consistently second to highest (OR = 1.49, 95% CI: 1.32-1.70) and the highest (OR = 2.17, 95% CI: 1.84-2.56) TyG-BMI changes, and those in the third (OR = 1.20, 95% CI: 1.05-1.36) and fourth (OR = 1.94, 95% CI: 1.70-2.22) quartiles of the cumulative TyG-BMI had greater odds of experiencing a rapid FI trajectory. Higher frail risk was noted in those in the fourth quartile of baseline TyG-BMI (HR = 1.42, 95% CI: 1.28-1.58), with consistently second to highest (HR = 1.23, 95% CI: 1.12-1.34) and the highest TyG-BMI changes (HR = 1.58, 95% CI: 1.42-1.77), and those in the third (HR = 1.10, 95% CI: 1.00-1.21) and fourth quartile of cumulative TyG-BMI (HR = 1.46, 95% CI: 1.33-1.60). Participants with persistently second-lowest to the highest TyG-BMI changes (ß = 0.15, 0.38 and 0.76 respectively) and those experiencing the third to fourth cumulative TyG-BMI (ß = 0.25 and 0.56, respectively) demonstrated accelerated FI progression. A U-shaped association was observed between TyG-BMI levels and both rapid FI trajectory and higher frail risk, with BMI being the primary factor. CONCLUSION: A higher TyG-BMI is associated with the rapid development of FI trajectory and a greater frail risk. However, excessively low TyG-BMI levels also appear to contribute to frail development. Maintaining a healthy TyG-BMI, especially a healthy BMI, may help prevent or delay the frail onset.


Assuntos
Biomarcadores , Glicemia , Índice de Massa Corporal , Idoso Fragilizado , Fragilidade , Avaliação Geriátrica , Triglicerídeos , Humanos , Masculino , Fragilidade/epidemiologia , Fragilidade/diagnóstico , Fragilidade/sangue , Feminino , Pessoa de Meia-Idade , Idoso , China/epidemiologia , Incidência , Glicemia/metabolismo , Triglicerídeos/sangue , Fatores de Risco , Medição de Risco , Estudos Longitudinais , Fatores de Tempo , Fatores Etários , Biomarcadores/sangue , Resistência à Insulina , Prognóstico , Idoso de 80 Anos ou mais
19.
ACS Appl Polym Mater ; 6(15): 8830-8841, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39144275

RESUMO

Water-borne coatings often contain nanofillers to enhance their mechanical or optical properties. The aggregation of these fillers may, however, lead to undesired effects such as brittle and opaque coatings, reducing their performance and lifetime. By controlling the distribution and structural arrangement of the nanofillers in the coatings and inserting reversible chemical bonds, both the elasticity and strength of the coatings may be effectively improved, while healing properties, via the reversible chemistry, extend the coating's lifetime. Aqueous dispersions of polymer-core/silica-corona supracolloidal particles were used to prepare water-borne coatings. Polymer and silica nanoparticles were prefunctionalized with thiol/disulfide groups during the supracolloid assembly. Disulfide bridges were further established between a cross-linker and the supracolloids during drying and coating formation. The supracolloidal nanocomposite coatings were submitted to intentional (physical) damages, i.e., blunt and sharp surface scratches or cut through into two pieces, and subsequently UV irradiated to induce the recovery of the damage(s). The viscoelasticity and healing properties of the coatings were examined by dynamic, static, and surface mechanical analyses. The nanocomposite coatings showed a great extent of interfacial restoration of cut damage and surface scratches. The healing properties are strongly related to the coating's viscoelasticity and interfacial (re)activation of the disulfide bridges. Nanocomposite coatings with silica concentrations below their critical volume fraction show higher in situ healing efficiency, as compared to coatings with higher silica concentration. This work provides insights into the control of nanofillers distribution in water-borne coatings and strategies to increase the coating lifetime via mechanical damage recovery.

20.
Food Res Int ; 192: 114803, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39147502

RESUMO

Mannoproteins have traditionally been recognized as effective wine organoleptic modulators, however, ambiguous understanding of the relationship between their organoleptic functions and physiochemical characteristics often lead to inappropriate application in winemaking. To reveal the possible role the physiochemical characteristics of mannoproteins play in modulating wine color and aroma properties, three water-soluble mannoproteins (MP1, MP2, MP3) with different physiochemical characteristics have been prepared, and accelerated red wine aging, malvidin pigments formation experiments, accelerated aroma release experiments have been designed to observe their organoleptic modulating functions in this research. Results suggest that the phenolic/chromatic stability of red wines could be enhanced by MP3, probably due to its low steric hindrance potential, high reactivity, and good hydro-alcoholic stability conferred by its high Mannan/Glucan ratio (8.68), abundant hydrophobic/hydrophilic amino acids (65.29 % of total protein), and low/medium molecular weight level (30.71-57.77 kDa), respectively, which protected the phenolic compounds and promoted the formation of pyranoanthocyanins. Mannoproteins could modulate the volatility of aroma compounds by expelling or retention effects, which depended on the duration of mannoprotein application (the expelling effect was firstly observed possibly because of the significant adsorption of free H2O by MPs) and the types of mannoproteins. MP1 and MP2 were prone to retain and expel aroma compounds, respectively, probably due to their medium/high molecular weight levels (60.48-135.39 kDa) that conferred abundant interacting sites, and the high proportion of hydrophobic and hydrophilic components in MP1 (97.71 % polysaccharides of total mannoprotein, 34.58 % hydrophobic amino acids of total protein) and MP2 (97.96 % polysaccharides of total mannoprotein, 28.36 % hydrophobic amino acids of total protein) guaranteed a relatively higher interacting frequency with aroma compounds and free H2O molecules, respectively.


Assuntos
Glicoproteínas de Membrana , Odorantes , Vinho , Vinho/análise , Glicoproteínas de Membrana/metabolismo , Odorantes/análise , Cor , Mucoproteínas/química , Interações Hidrofóbicas e Hidrofílicas , Humanos , Compostos Orgânicos Voláteis/análise , Compostos Orgânicos Voláteis/química
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