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1.
Sci Total Environ ; : 173511, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38825210

ABSTRACT

4-Hydroxychlorothalonil (4-OH CHT), the main metabolite of chlorothalonil and the most widely used fungicide, has been frequently detected in human samples during monitoring. 4-OH CHT may exhibit higher toxicity and persistence in the environment compared to its prototype. In this study, a total of 540 paired serum and breast milk samples from pregnant women in three provinces in China were monitored for contaminant residues. 4-OH CHT was analyzed in the samples using ultra high-performance liquid chromatography - high-resolution mass spectrometry with a detection limit of 20 ng/L. The study investigated the effects of demographic factors, such as BMI, region of residence, and education level, on the levels of 4-OH CHT residues in serum and breast milk. Among the three provinces, the highest median concentration of 4-OH CHT in serum samples was observed in Hebei (1.04 × 103 ng/L), while the highest median concentration of 4-OH CHT in breast milk samples was observed in Hubei and Guangdong (491 ng/L). Multiple linear regression was used to investigate the significant positive correlation between 4-OH CHT in serum and breast milk (p = 0.000) after adjusting for personal characteristics. Based on this, the study further explored the influencing factors of transfer efficiencies (TEs) in conjunction with the individual TEs and the personal characteristics of the participants. Our results demonstrated that the age of the volunteers and their exercise habits had an effect on TEs, but further studies are needed to determine whether exercise leads to an increase in TEs.

2.
bioRxiv ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38826432

ABSTRACT

Pain after surgery causes significant suffering. Opioid analgesics cause severe side effects and accidental death. Therefore, there is an urgent need to develop non-opioid therapies for managing post-surgical pain and, more importantly, preventing its transition to a chronic state. In a mouse model of post-surgical pain, local application of Clarix Flo (FLO), a human amniotic membrane (AM) product, attenuated established post-surgical pain hypersensitivity without exhibiting known side effects of opioid use in mice. Importantly, preemptive drug treatment also inhibited the transition of post-surgical pain to a prolonged state. This effect was achieved through direct inhibition of nociceptive dorsal root ganglion (DRG) neurons via CD44-dependent pathways, and indirect pain relief by attenuating immune cell recruitment. We further purified the major matrix component, the heavy chain-hyaluronic acid/pentraxin 3 (HC-HA/PTX3) from human AM that has greater purity and water solubility than FLO. HC-HA/PTX3 replicated FLO- induced neuronal and pain inhibition. Mechanistically, HC-HA/PTX3 induced cytoskeleton rearrangements to inhibit sodium current and high-voltage activated calcium current on nociceptive neurons, suggesting it is a key bioactive component mediating pain relief. Collectively, our findings highlight the potential of naturally derived biologics from human birth tissues as an effective non-opioid treatment for post-surgical pain and unravel the underlying mechanisms.

4.
Elife ; 122024 Jun 04.
Article in English | MEDLINE | ID: mdl-38832501

ABSTRACT

Bacteria in biofilms secrete potassium ions to attract free swimming cells. However, the basis of chemotaxis to potassium remains poorly understood. Here, using a microfluidic device, we found that Escherichia coli can rapidly accumulate in regions of high potassium concentration on the order of millimoles. Using a bead assay, we measured the dynamic response of individual flagellar motors to stepwise changes in potassium concentration, finding that the response resulted from the chemotaxis signaling pathway. To characterize the chemotactic response to potassium, we measured the dose-response curve and adaptation kinetics via an Förster resonance energy transfer (FRET) assay, finding that the chemotaxis pathway exhibited a sensitive response and fast adaptation to potassium. We further found that the two major chemoreceptors Tar and Tsr respond differently to potassium. Tar receptors exhibit a biphasic response, whereas Tsr receptors respond to potassium as an attractant. These different responses were consistent with the responses of the two receptors to intracellular pH changes. The sensitive response and fast adaptation allow bacteria to sense and localize small changes in potassium concentration. The differential responses of Tar and Tsr receptors to potassium suggest that cells at different growth stages respond differently to potassium and may have different requirements for potassium.


Subject(s)
Chemotaxis , Escherichia coli , Potassium , Potassium/metabolism , Escherichia coli/physiology , Escherichia coli Proteins/metabolism , Fluorescence Resonance Energy Transfer , Signal Transduction , Receptors, Cell Surface
5.
Angew Chem Int Ed Engl ; : e202405358, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700137

ABSTRACT

Eosinophils are important immune effector cells that affect T cell-mediated antitumor immunity. However, the low frequency and restrained activity of eosinophils restricted the development of cancer immunotherapies. We herein report an eosinophil-activating semiconducting polymer nanoparticle (SPNe) to improve photodynamic tumor immunogenicity, modulate eosinophil chemotaxis, and reinvigorate T-cell immunity for activated cancer photo-immunotherapy. SPNe is composed of an amphiphilic semiconducting polymer and a dipeptidyl peptidase 4 (DPP4) inhibitor sitagliptin via a 1O2-cleavable thioketal linker. Upon localized NIR photoirradiation, SPNe can generate 1O2 to elicit immunogenic cell death of tumors and induce specific activation of sitagliptin. The subsequent inhibition of DPP4 increases intratumoral CCL11 levels to promote eosinophil chemotaxis and activation. SPNe-mediated photo-immunotherapy synergized with immune checkpoint blockade greatly promotes tumor infiltration and activation of both eosinophils and T cells, effectively inhibiting tumor growth and metastasis. Thus, this study presents a generic polymeric nanoplatform to modulate specific immune cells for precision cancer immunotherapy.

6.
J Mater Chem B ; 2024 May 03.
Article in English | MEDLINE | ID: mdl-38700242

ABSTRACT

Articular cartilage tissue has limited self-repair capabilities, with damage frequently progressing to irreversible degeneration. Engineered tissues constructed through bioprinting and embedded with stem cell aggregates offer promising therapeutic alternatives. Aggregates of bone marrow mesenchymal stromal cells (BMSCs) demonstrate enhanced and more rapid chondrogenic differentiation than isolated cells, thus facilitating cartilage repair. However, it remains a key challenge to precisely control biochemical microenvironments to regulate cellular adhesion and cohesion within bioprinted matrices simultaneously. Herein, this work reports a bioprintable hydrogel matrix with high cellular adhesion and aggregation properties for cartilage repair. The hydrogel comprises an enhanced cell-adhesive gelatin methacrylate and a cell-cohesive chitosan methacrylate (CHMA), both of which are subjected to photo-initiated crosslinking. By precisely adjusting the CHMA content, the mechanical stability and biochemical cues of the hydrogels are finely tuned to promote cellular aggregation, chondrogenic differentiation and cartilage repair implantation. Multi-layer constructs encapsulated with BMSCs, with high cell viability reaching 91.1%, are bioprinted and photo-crosslinked to support chondrogenic differentiation for 21 days. BMSCs rapidly form aggregates and display efficient chondrogenic differentiation both on the hydrogels and within bioprinted constructs, as evidenced by the upregulated expression of Sox9, Aggrecan and Collagen 2a1 genes, along with high protein levels. Transplantation of these BMSC-laden bioprinted hydrogels into cartilaginous defects demonstrates effective hyaline cartilage repair. Overall, this cell-responsive hydrogel scaffold holds immense promise for applications in cartilage tissue engineering.

7.
ACS Omega ; 9(17): 19669-19678, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38708271

ABSTRACT

The temperature factor is an important factor affecting the intercomponent forces while maintaining the physical stability of solid-liquid mixed fuels. Through self-designed experimental equipment, feedback was provided on the fuel stratification and density distribution uniformity with solid-liquid volume ratios of 1.25:1 and 1:1 under different temperature conditions. As the viscosity of the liquid increased with decreasing temperature, the ability of the fuel to overcome particle deposition was enhanced. Although none of the three fuel ratios with a solid-liquid volume ratio of 1.25:1 showed stratification, the differences in the liquid bridging forces of the components resulted in an increasingly uneven distribution of density with increasing surface tension of the liquid components. By analyzing the imaging results and measuring the liquid bridge force, it was found that the fuel with a nitromethane mass ratio of 40% had the lowest temperature effect on the solid-liquid contact area and the most uniform density distribution. Properly reducing the surface tension of liquid components could effectively resist the influence of the temperature on the liquid bridge force while maintaining the physical stability of the fuel.

8.
BMC Public Health ; 24(1): 1206, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38693495

ABSTRACT

BACKGROUND: Dementia is a leading cause of disability in people older than 65 years worldwide. However, diagnosing dementia in its earliest symptomatic stages remains challenging. This study combined specific questions from the AD8 scale with comprehensive health-related characteristics, and used machine learning (ML) to construct diagnostic models of cognitive impairment (CI). METHODS: The study was based on the Shenzhen Healthy Ageing Research (SHARE) project, and we recruited 823 participants aged 65 years and older, who completed a comprehensive health assessment and cognitive function assessments. Permutation importance was used to select features. Five ML models using BalanceCascade were applied to predict CI: a support vector machine (SVM), multilayer perceptron (MLP), AdaBoost, gradient boosting decision tree (GBDT), and logistic regression (LR). An AD8 score ≥ 2 was used to define CI as a baseline. SHapley Additive exPlanations (SHAP) values were used to interpret the results of ML models. RESULTS: The first and sixth items of AD8, platelets, waist circumference, body mass index, carcinoembryonic antigens, age, serum uric acid, white blood cells, abnormal electrocardiogram, heart rate, and sex were selected as predictive features. Compared to the baseline (AUC = 0.65), the MLP showed the highest performance (AUC: 0.83 ± 0.04), followed by AdaBoost (AUC: 0.80 ± 0.04), SVM (AUC: 0.78 ± 0.04), GBDT (0.76 ± 0.04). Furthermore, the accuracy, sensitivity and specificity of four ML models were higher than the baseline. SHAP summary plots based on MLP showed the most influential feature on model decision for positive CI prediction was female sex, followed by older age and lower waist circumference. CONCLUSIONS: The diagnostic models of CI applying ML, especially the MLP, were substantially more effective than the traditional AD8 scale with a score of ≥ 2 points. Our findings may provide new ideas for community dementia screening and to promote such screening while minimizing medical and health resources.


Subject(s)
Dementia , Machine Learning , Mass Screening , Humans , Aged , Male , Female , China , Dementia/diagnosis , Mass Screening/methods , Aged, 80 and over , Cognitive Dysfunction/diagnosis
10.
Appl Environ Microbiol ; : e0050824, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38717126

ABSTRACT

Solid surfaces submerged in liquid in natural environments alter bacterial swimming behavior and serve as platforms for bacteria to form biofilms. In the initial stage of biofilm formation, bacteria detect surfaces and increase the intracellular level of the second messenger c-di-GMP, leading to a reduction in swimming speed. The impact of this speed reduction on bacterial surface swimming remains unclear. In this study, we utilized advanced microscopy techniques to examine the effect of swimming speed on bacterial surface swimming behavior. We found that a decrease in swimming speed reduces the cell-surface distance and prolongs the surface trapping time. Both these effects would enhance bacterial surface sensing and increase the likelihood of cells adhering to the surface, thereby promoting biofilm formation. We also examined the surface-escaping behavior of wild-type Escherichia coli and Pseudomonas aeruginosa, noting distinct surface-escaping mechanisms between the two bacterial species. IMPORTANCE: In the early phase of biofilm formation, bacteria identify surfaces and increase the intracellular level of the second messenger c-di-GMP, resulting in a decrease in swimming speed. Here, we utilized advanced microscopy techniques to investigate the impact of swimming speed on bacterial surface swimming, focusing on Escherichia coli and Pseudomonas aeruginosa. We found that an increase in swimming speed led to an increase in the radius of curvature and a decrease in surface detention time. These effects were explained through hydrodynamic modeling as a result of an increase in the cell-surface distance with increasing swimming speed. We also observed distinct surface-escaping mechanisms between the two bacterial species. Our study suggests that a decrease in swimming speed could enhance the likelihood of cells adhering to the surface, promoting biofilm formation. This sheds light on the role of reduced swimming speed in the transition from motile to sedentary bacterial lifestyles.

11.
Ther Adv Psychopharmacol ; 14: 20451253241243290, 2024.
Article in English | MEDLINE | ID: mdl-38708374

ABSTRACT

Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis.

12.
Nucleic Acids Res ; 2024 May 06.
Article in English | MEDLINE | ID: mdl-38709873

ABSTRACT

Small ubiquitin-like modifiers (SUMOs) are tiny but important protein regulators involved in orchestrating a broad spectrum of biological processes, either by covalently modifying protein substrates or by noncovalently interacting with other proteins. Here, we report an updated server, GPS-SUMO 2.0, for the prediction of SUMOylation sites and SUMO-interacting motifs (SIMs). For predictor training, we adopted three machine learning algorithms, penalized logistic regression (PLR), a deep neural network (DNN), and a transformer, and used 52 404 nonredundant SUMOylation sites in 8262 proteins and 163 SIMs in 102 proteins. To further increase the accuracy of predicting SUMOylation sites, a pretraining model was first constructed using 145 545 protein lysine modification sites, followed by transfer learning to fine-tune the model. GPS-SUMO 2.0 exhibited greater accuracy in predicting SUMOylation sites than did other existing tools. For users, one or multiple protein sequences or identifiers can be input, and the prediction results are shown in a tabular list. In addition to the basic statistics, we integrated knowledge from 35 public resources to annotate SUMOylation sites or SIMs. The GPS-SUMO 2.0 server is freely available at https://sumo.biocuckoo.cn/. We believe that GPS-SUMO 2.0 can serve as a useful tool for further analysis of SUMOylation and SUMO interactions.

13.
Heart Rhythm ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38750908

ABSTRACT

BACKGROUND: Cardiac sodium channel NaV1.5 encoded by SCN5A is associated with arrhythmia disorders. However, the molecular mechanism underlying NaV1.5 expression remains to be fully elucidated. Previous studies have reported that 14-3-3 family acts as an adaptor involved in regulating kinetic characteristics of cardiac ion channels. OBJECTIVE: The purpose of this study was to establish 14-3-3ε/YWHAE, a member of 14-3-3 family, as a crucial regulator of NaV1.5 and explore the potential role of 14-3-3ε in the heart. METHODS: Western blotting, patch-clamping, real-time RT-PCR, RNA immunoprecipitation, electrocardiogram recording, echocardiography and histological analysis were performed. RESULTS: YWHAE overexpression significantly reduced the expression level of SCN5A mRNA and sodium current density, whereas YWHAE knockdown significantly increased SCN5A mRNA expression and sodium current density in HEK293/NaV1.5 and H9c2 cells. Similar results were observed in mice injected with adeno-associated virus serotype 9 (AAV9)-mediated YWHAE knockdown. The effect of 14-3-3ε on NaV1.5 expression was abrogated by knockdown of TBX5, a transcription factor of NaV1.5. An interaction between 14-3-3ε protein and TBX5 mRNA was identified, and YWHAE overexpression significantly decreased TBX5 mRNA stability without affecting SCN5A mRNA stability. Additionally, mice subjected to AAV9-mediated YWHAE knockdown exhibited shorter R-R intervals and higher prevalence of premature ventricular contractions. CONCLUSION: Our data unveil a novel regulatory mechanism of NaV1.5 by 14-3-3ε, and highlight the significance of 14-3-3ε in transcriptional regulation of NaV1.5 expression and cardiac arrhythmias.

14.
Phytomedicine ; 130: 155710, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38759311

ABSTRACT

BACKGROUND: Sepsis, a life-threatening condition resulting from uncontrolled host responses to infection, poses a global health challenge with limited therapeutic options. Due to high heterogeneity, sepsis lacks specific therapeutic drugs. Additionally, there remains a significant gap in the clinical management of sepsis regarding personalized and precise medicine. PURPOSE: This review critically examines the scientific landscape surrounding natural products in sepsis and sepsis-mediated inflammation, highlighting their clinical potential. METHODS: Following the PRISMA guidelines, we retrieved articles from PubMed to explore potential natural products with therapeutic effects in sepsis-mediated inflammation. RESULTS: 434 relevant in vitro and in vivo studies were identified and screened. Ultimately, 55 studies were obtained as the supporting resources for the present review. We divided the 55 natural products into three categories: those influencing the synthesis of inflammatory factors, those affecting surface receptors and modulatory factors, and those influencing signaling pathways and the inflammatory cascade. CONCLUSION: Natural products' potential as game-changers in sepsis-mediated inflammation management lies in their ability to modulate hallmarks in sepsis, including inflammation, immunity, and coagulopathy, which provides new therapeutic avenues that are readily accessible and capable of undergoing rapid clinical validation and deployment, offering a gift from nature to humanity. Innovative techniques like bioinformatics, metabolomics, and systems biology offer promising solutions to overcome these obstacles and facilitate the development of natural product-based therapeutics, holding promise for personalized and precise sepsis management and improving patient outcomes. However, standardization, bioavailability, and safety challenges arise during experimental validation and clinical trials of natural products.

15.
Angew Chem Int Ed Engl ; : e202407102, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38744673

ABSTRACT

Lead halide molecular ferroelectrics represent an important class of luminescent ferroelectrics, distinguished by their high chemical and structural tunability, excellent processability and distinctive luminescent characteristics. However, their inherent instability, prone to decomposition upon exposure to moisture and light, hinders their broader ferroelectric applications. Herein, for the first time, we present a series of isoreticular metal-organic framework (MOF)-type lead halide luminescent ferroelectrics, demonstrating exceptional robustness under ambient conditions for at least 15 months and even when subjected to aqueous boiling conditions. Unlike conventional metal-oxo secondary building units (SBUs) in MOFs adopting highly centrosymmetric structure with limited structural distortion, our lead halide-based MOFs occupy structurally deformable [Pb2X]+ (X=Cl-/Br-/I-) SBUs that facilitate a c-axis-biased displacement of Pb2+ centers and substantially contribute to thermoinducible structural transformation. Importantly, this class of MOF-type lead halide ferroelectrics undergo ferroelectric-to-paraelectric phase transitions with remarkably high Curie temperature of up to 505 K, superior to most of molecular ferroelectrics. Moreover, the covalent bonding between phosphorescent organic component and the light-harvesting inorganic component achieves efficient spin-orbit coupling and intersystem crossing, resulting in long-lived afterglow emission. The compelling combination of high stability, ferroelectricity and afterglow emission exhibited by lead halide MOFs opens up many potential opportunities in energy-conversion applications.

16.
Bioconjug Chem ; 35(5): 674-681, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38695582

ABSTRACT

Aptamers are widely used molecular recognition tools in targeted therapy, but their ability to effectively penetrate deep into solid tumors remains a significant challenge, leading to suboptimal treatment efficacy. Here, we developed a polyfluoroalkyl (PFA) decoration strategy to enhance aptamer recognition, cell internalization, and solid tumor penetration. Our results indicate that PFA with around 11 fluorine atoms significantly improves aptamer internalization both in vitro and in vivo settings. However, we also observed that the use of PFA tags containing 19 and 23 fluorine atoms on aptamers resulted in nonspecific cell anchoring in control cell lines, affecting the specificity of aptamers. Overall, we found that using a chemical modification strategy could enhance the deep tumor penetration ability of aptamers and validate their effectiveness in vivo. This approach has significant practical applications in targeted drug delivery for cancer treatment.


Subject(s)
Aptamers, Nucleotide , Receptor Protein-Tyrosine Kinases , Aptamers, Nucleotide/chemistry , Humans , Animals , Receptor Protein-Tyrosine Kinases/antagonists & inhibitors , Receptor Protein-Tyrosine Kinases/metabolism , Cell Line, Tumor , Mice , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/antagonists & inhibitors , Neoplasms/drug therapy , Neoplasms/metabolism , Drug Delivery Systems/methods
17.
Microbiol Spectr ; : e0391423, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38742903

ABSTRACT

Porcine parvovirus (PPV) is one of the most important pathogens that cause reproductive failure in pigs. However, the pathogenesis of PPV infection remains unclear. Proteomics is a powerful tool to understand the interaction between virus and host cells. In the present study, we analyzed the proteomics of PPV-infected PK-15 cells. A total of 32 and 345 proteins were differentially expressed at the early and replication stages, respectively. Subsequent gene ontology annotation and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed these differentially expressed proteins were significantly enriched in pathways including toll-like receptor signaling pathway, tumor necrosis factor signaling pathway, and viral carcinogenesis. The expression of poly (rC) binding protein 1 (PCBP1) was observed to decrease after PPV infection. Overexpressed or silenced PCBP1 expression inhibited or promoted PPV infection. Our studies established a foundation for further exploration of the multiplication mechanism of PPV. IMPORTANCE: Porcine parvovirus (PPV) is a cause of reproductive failure in the swine industry. Our knowledge of PPV remains limited, and there is no effective treatment for PPV infection. Proteomics of PPV-infected PK-15 cells was conducted to identify differentially expressed proteins at 6 hours post-infection (hpi) and 36 hpi. Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that various pathways participate in PPV infection. Poly (rC) binding protein 1 was confirmed to inhibit PPV replication, which provided potential targets for anti-PPV infection. Our findings improve the understanding of PPV infection and pave the way for future research in this area.

18.
J Exp Clin Cancer Res ; 43(1): 142, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38745188

ABSTRACT

BACKGROUND: Mounting evidences shows that the ubiquitin‒proteasome pathway plays a pivotal role in tumor progression. The expression of 26S proteasome non-ATPase regulatory subunit 9 (PSMD9) is correlated with recurrence and radiotherapy resistance in several tumor types. However, the role and mechanism of PSMD9 in hepatocellular carcinoma (HCC) progression remain largely unclear. METHODS: PSMD9 was identified as a prognosis-related biomarker for HCC based on analysis of clinical characteristics and RNA-seq data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and the JP Project of the International Cancer Genome Consortium (ICGC-LIRI-JP). PSMD9 expression was analyzed in cancer tissues and adjacent noncancerous tissues via immunohistochemistry and Western blotting. Multiple in vivo and in vitro experimental techniques (such as CCK-8, colony formation, EdU, and Transwell assays; flow cytometry; Western blotting; quantitative RT-PCR; Coimmunoprecipitation assay and immunofluorescence confocal imaging) were used to assess the functions of PSMD9 in the pathogenesis of HCC. RESULTS: We found that the expression of PSMD9 was upregulated and associated with a poor prognosis in HCC patients. PSMD9 promoted HCC cell proliferation, migration, invasion and metastasis. Knockdown of PSMD9 significantly inhibited HCC cell proliferation by inducing G1/S cell cycle arrest and apoptosis. Mechanistically, we demonstrated that PSMD9 promoted HCC cell proliferation and metastasis via direct interaction with the E3 ubiquitin ligase c-Cbl, suppresses EGFR ubiquitination, influenced EGFR endosomal trafficking and degradation and subsequently activated ERK1/2 and Akt signaling. In addition, we showed that PSMD9 knockdown sensitized HCC cells to the tyrosine kinase inhibitor erlotinib in vitro and in vivo. CONCLUSIONS: Collectively, our results indicate that PSMD9 drives HCC progression and erlotinib resistance by suppressing c-Cbl mediated EGFR ubiquitination and therefore can be a potential therapeutic target for HCC.


Subject(s)
Carcinoma, Hepatocellular , Disease Progression , ErbB Receptors , Liver Neoplasms , Proto-Oncogene Proteins c-cbl , Signal Transduction , Humans , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/genetics , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/genetics , Proto-Oncogene Proteins c-cbl/metabolism , Proto-Oncogene Proteins c-cbl/genetics , ErbB Receptors/metabolism , ErbB Receptors/genetics , Mice , Animals , Male , Female , Cell Line, Tumor , Proteasome Endopeptidase Complex/metabolism , Cell Proliferation , Prognosis , Mice, Nude , Apoptosis , Middle Aged , Cell Movement
19.
Clin Nutr ESPEN ; 61: 203-211, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38777434

ABSTRACT

BACKGROUND: Taurine is considered an immunomodulatory agent. From current reports on clinical studies, we conducted a systematic review and meta-analysis to investigate the effects of taurine-enhanced enteral nutrition (EN) on the outcomes of critically ill patients to resolve conflicting evidence in literature. METHODS: Literature from PubMed, EMBASE, Web of Science, Cochrane Library, CNKI, SINOMED, and WanFang databases were retrieved, and randomized controlled trials (RCTs) were identified. The time range spanned from January 1, 2000, to January 31, 2024. The Cochrane Collaboration Tool was used to evaluate the risk of bias. We used the GRADE approach to rate the quality of evidence and the I2 test to assess the statistical heterogeneity of the results. Risk ratio (RR), mean difference (MD), and 95% confidence interval (95% CI) were used to analyze measurement data. RESULTS: Four trials involving 236 patients were finally included. The meta-analysis results indicated that taurine-enhanced EN did not reduce mortality (RR = 0.70, p = 0.45, 95% CI [0.28, 1.80], two trials, 176 participants, low quality). There was also no significant difference in length of stay in the intensive care unit (ICU) between the taurine-enhanced EN and control groups. Taurine-enhanced EN may reduce pro-inflammatory factor interleukin-6 (IL-6) levels in critically ill patients(the result about IL-6 cannot be pooled). However, taurine-enhanced EN had no significant impact on high-sensitivity-C-reactive protein levels (MD = -0.41, p = 0.40, 95% CI [-1.35, 0.54], two trials, 60 participants, low quality). DISCUSSION: Taurine-enhanced EN may reduce IL-6 levels and is not associated with improved clinical outcomes in critically ill patients, which may have potential immunoregulatory effects in critically ill patients. Given that published studies have small samples, the above conclusions need to be verified by more rigorously designed large-sample clinical trials.


Subject(s)
Critical Illness , Enteral Nutrition , Taurine , Taurine/therapeutic use , Humans , Critical Illness/therapy , Enteral Nutrition/methods , Treatment Outcome , Intensive Care Units , Length of Stay , Randomized Controlled Trials as Topic
20.
Chem Commun (Camb) ; 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780308

ABSTRACT

In this study, a benzoselenadiazole- and pyridine-bifunctionalized hydrogen-bonded arylamide foldamer was synthesized. A co-crystallization experiment with 1,4-diiodotetrafluorobenzene showed that a new type of supramolecular double helices, which were induced by three orthogonal interactions, namely, three-center hydrogen bonding (O⋯H⋯O), I⋯N halogen bonding and Se⋯N chalcogen bonding, have been constructed in the solid state. This work presents a novel instance of multiple non-covalent interactions that work together to construct supramolecular architectures.

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