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OBJECTIVE: Patients with late life depression sometimes refuse to receive electroconvulsive therapy (ECT) owing to its adverse reactions. To alleviate patient's resistance, a novel ECT stimulation strategy named mixed-strategy ECT (msECT) was designed in which patients are administered conventional ECT during the first three sessions, followed by low energy stimulation during the subsequent sessions. However, whether low energy electrical stimulation in the subsequent stage of therapy affect its efficacy and reduce adverse reactions in patients with late life depression remains unknown. To explore differences between msECT and regular ECT(RECT) with respect to clinical efficacy and side effects. METHODS: This randomized, controlled trial was conducted from 2019 to 2021 on 60 patients with late life depression who were randomly assigned to two groups: RECT or msECT. A generalized estimating equation (GEE) was used to compare the two stimulation strategies regarding their efficacy and side effects on cognition. Chi-squared test was used to compare side effects in the two strategies. RESULTS: In the intent-to-treat group, the GEE model suggested no differences between-group difference in Hamilton Depression Rating Scale-17 score over time (Wald χ2=7.275, p=0.064), whereas the comparison of side effects in the two strategies favored msECT (Wald χ2=8.463, p=0.015) as fewer patients had adverse events during the second phase of treatment with msECT (χ2 =13.467, p=0.004). CONCLUSION: msECT presents its similar efficacy to RECT. msECT may have milder side effects on cognition.
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Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.
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Trouble dépressif majeur , Transcriptome , Humains , Trouble dépressif majeur/génétique , Trouble dépressif majeur/physiopathologie , Femelle , Mâle , Adulte , Cortex cérébral/physiopathologie , Cortex cérébral/imagerie diagnostique , Cortex cérébral/métabolisme , Adulte d'âge moyen , Imagerie par résonance magnétique , Analyse de profil d'expression de gènesRÉSUMÉ
OBJECTIVE: Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are widely expressed in the brain and are associated with the development of neurological and neurodegenerative diseases. However, their roles and molecular mechanisms in major depressive disorder (MDD) remain largely unknown. This study aimed to identify lncRNAs and miRNAs involved in the development of MDD and elucidate their molecular mechanisms. METHODS: Transcriptome and bioinformatic analyses were performed to identify miRNAs and lncRNAs related to MDD. C57 mice were subjected to chronic unpredictable mild stress (CUMS) to establish a depression model. Lentiviruses containing either lncRNA NPTN-IT1-201 or miR-142-5p were microinjected into the hippocampal region of these mice. Behavioral tests including the sucrose preference test (SPT), tail suspension test (TST), and forced swim test (FST) were conducted to evaluate depressive-like behaviors. RESULTS: The results revealed that overexpression of lncRNA NPTN-IT1-201 or inhibition of miR-142-5p significantly ameliorated depressive-like behaviors in CUMS-treated mice. Dual-luciferase reporter assays confirmed interactions between miR-142-5p with both brain-derived neurotrophic factor (BDNF) and NPTN-IT1-201. ELISA analysis revealed significant alterations in relevant biomarkers in the blood samples of MDD patients compared to healthy controls. Histological analyses, including HE and Nissl staining, showed marked structural changes in brain tissues following CUMS treatment, which were partially reversed by lncRNA NPTN-IT1-201 overexpression or miR-142-5p inhibition. Immunofluorescence imaging demonstrated significant differences in the levels of BAX, Bcl2, p65, Iba1 among different treatment groups. TUNEL assays confirmed reduced apoptosis in brain tissues following these interventions. Western blotting showed the significant differences in BDNF, BAX, and Bcl2 protein levels among different treatment groups. CONCLUSION: NPTN-IT1-201 regulates inflammation and apoptosis in MDD by targeting BDNF via miR-142-5p, making it a potential therapeutic target for MDD.
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Livestock effluents are challenging to be treated owing that antibiotics and microplastics are untargeted for most biological technologies. As far, microalgal wastewater treatment is recognized as an effective technique for dealing with. In this study, a continuous-flow system was conducted over 45 days to evaluate the effectiveness of Chlamydomonas sp. JSC4 in removing tetracycline (TCH) under the influence of polystyrene (PS). It shows that PS significantly enhanced the dissipation efficiency of TCH from livestock effluents, and 9.83 % TCH removal was increased under 5 mg/L of both TCH and PS exposure. Meanwhile, higher microalgal bioactivity was a significant factor in achieving desirable pollutants removal efficiency, as 87.14 % microalgal biomass was improved owing to reduction of oxidative stress and augmentation of photosynthesis. Importantly, the pivotal active sites, NH2 and CO, were rapidly covered via π-π interactions and hydrogen bonds during adsorption process between TCH and PS, accounting for mitigation of TCH-PS complexes toxicity and improvement of microalgal ribosome metabolism. Additionally, co-exposure to TCH and PS resulted in maximum lipids (0.57 g/L) and energy (20.79 kJ/L) production, further encouraging a fantastic vision for the tertiary process of livestock effluents via advanced microalgal treatment.
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Antibactériens , Microalgues , Polystyrènes , Tétracycline , Polluants chimiques de l'eau , Tétracycline/composition chimique , Microalgues/métabolisme , Microalgues/effets des médicaments et des substances chimiques , Polluants chimiques de l'eau/composition chimique , Polluants chimiques de l'eau/toxicité , Polystyrènes/composition chimique , Antibactériens/composition chimique , Chlamydomonas/métabolisme , Chlamydomonas/effets des médicaments et des substances chimiques , Eaux usées/composition chimique , Photosynthèse/effets des médicaments et des substances chimiques , Élimination des déchets liquides/méthodes , Biomasse , Purification de l'eau/méthodes , AdsorptionRÉSUMÉ
The role of micropeptide in cardiomyocyte proliferation remains unknown. We found that MPM (micropeptide in mitochondria) was highly expressed in cardiomyocytes. Compared to MPM+/+ mice, MPM knockout (MPM-/-) mice exhibited reduction in left ventricular (LV) mass, myocardial thickness and LV fractional shortening. RNA-sequencing analysis in H9c2, a rat cardiomyocyte cell line, identified downregulation of cell cycle-promoting genes as the most significant alteration in MPM-silencing cells. Consistently, gain- and loss-of-function analyses in H9c2 cells revealed that cardiomyocyte proliferation was repressed by silencing MPM but was promoted by overexpressing MPM. Moreover, the cardiomyocytes in the hearts of MPM-/- mice displayed reduced proliferation rates. Mechanism investigations disclosed that MPM is crucial for AKT activation in cardiomyocytes. We also identified an interaction between MPM and PTPMT1, and found that silencing PTPMT1 attenuated the effect of MPM in activating the AKT pathway, whereas inhibition of the AKT pathway abrogated the role of MPM in promoting cardiomyocyte proliferation. Collectively, these results indicate that MPM may promote cardiomyocyte proliferation and thus heart growth by interacting with PTPMT1 to activate the AKT pathway. Our findings identify the novel function and regulatory network of MPM and highlight the importance of micropeptides in cardiomyocyte proliferation and heart growth.
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Antidepressants remain the first-line treatment for depression. However, the factors influencing medication response are still unclear. Accumulating evidence implicates an association between alterations in gut microbiota and antidepressant response. Therefore, the aim of this study is to investigate the role of the gut microbiota-brain axis in the treatment response of venlafaxine. After chronic social defeat stress and venlafaxine treatment, mice were divided into responders and non-responders groups. We compared the composition of gut microbiota using 16 S ribosomal RNA sequencing. Meanwhile, we quantified metabolomic alterations in serum and hippocampus, as well as hippocampal neurotransmitter levels using liquid chromatography-mass spectrometry. We found that the abundances of 29 amplicon sequence variants (ASVs) were significantly altered between the responders and non-responders groups. These ASVs belonged to 8 different families, particularly Muribaculaceae. Additionally, we identified 38 and 39 differential metabolites in serum and hippocampus between the responders and non-responders groups, respectively. Lipid, amino acid, and purine metabolisms were enriched in both serum and hippocampus. In hippocampus, the concentrations of tryptophan, phenylalanine, gamma-aminobutyric acid, glutamic acid, and glutamine were increased, while the level of succinic acid was decreased in the responders group, compared with the non-responders group. Our findings suggest that the gut microbiota may play a role in the antidepressant effect of venlafaxine by modulating metabolic processes in the central and peripheral tissues. This provides a novel microbial and metabolic framework for understanding the impact of the gut microbiota-brain axis on antidepressant response.
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BACKGROUND: Metabolic disorders exhibit strong inflammatory underpinnings and vice versa. This study aimed to investigate the association between metabolic health status, genetic predisposition, and the risk of inflammatory bowel disease (IBD), and to explore the potential benefits of maintaining ideal metabolic status for individuals with a predetermined genetic risk of IBD. METHOD: This population-based prospective study included 385,820 unrelated European descent participants from the UK Biobank. Using multivariable Cox regression, we assessed the relationship of metabolic phenotypes with risk of IBD and its subtypes. We also developed a polygenic risk score to examine how metabolic health status interacted with genetic risk in relation to IBD risk. RESULTS: During the follow-up period of 4,328,895 person-years, 2,044 newly-diagnosed IBD cases were identified. Higher genetic risk and an increasing number of abnormal metabolic phenotypes were associated with elevated IBD risk (p-trend <0.001). Individuals with high genetic risk and poor metabolic health had a significantly higher risk of IBD (HR=4.56, 95 % CI=3.27-6.36) compared to those with low genetic risk and ideal metabolic health. These results remained consistent for IBD subtypes. Maintaining ideal metabolic status reduced IBD risk within each genetic risk category and jointly decreased subsequent risk by 40 % in high genetic risk individuals. CONCLUSION: Our study reveals a combined impact of poor metabolic health and genetic risk on IBD incidence. Those with low genetic risk and optimal metabolic health exhibit the lowest IBD risk, offering insights into potential management strategies for individuals at predefined genetic risk.
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This study focuses on the design and synthesis of two novel coordination polymers (CPs), named 1 and 2, with excellent fluorescent properties. Their structures were characterized by X-ray single-crystal diffraction, revealing that both materials exhibit promising fluorescence performance, indicating their potential as fluorescent detection tools. Additionally, 1 was chosen to be combined with chitosan (CS), resulting in the successful fabrication of a biodegradable and non-toxic efficient drug carrier, termed CS-1@Cisplatin. This carrier possesses a large surface area and good solubility, enabling sustained drug release to target cells. Given that CXC motif chemokine receptor type 4 (CXCR4) is a key marker gene highly expressed in Rhabdomyosarcoma (RMS) cells and tissues, RMS was chosen as the biological model for testing. The results demonstrated that CS-1@Cisplatin effectively inhibited the invasiveness of RMS cells by significantly suppressing CXCR4 expression. Therefore, the system shows great potential for applications in RMS treatment, biometrics, and drug delivery, particularly in its unique advantage of targeting RMS by inhibiting the key marker gene CXCR4.
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We study, both theoretically and experimentally, strong interaction between a quasi-bound state in the continuum (QBIC) supported by a resonant metasurface with an epsilon-near-zero (ENZ) guided mode excited in an ultrathin ITO layer. We observe and quantify the strong coupling regime of the QBIC-ENZ interaction in the hybrid metasurface manifested through the mode splitting over 200 meV. We also measure experimentally the resonant nonlinear response enhanced near the ENZ frequency and observe the effective nonlinear refractive index up to â¼4 × 10-13 m2/W in the ITO-integrated dielectric nanoresonators, which provides a promising platform for low-power nonlinear photonic devices.
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Conventional macrolide-lincosamide-streptogramin B-ketolide (MLSBK) antibiotics are unable to counter the growing challenge of antibiotic resistance that is conferred by the constitutive methylation of rRNA base A2058 or its G2058 mutation, while the presence of unmodified A2058 is crucial for high selectivity of traditional MLSBK in targeting pathogens over human cells. The absence of effective modes of action reinforces the prevailing belief that constitutively antibiotic-resistant Staphylococcus aureus remains impervious to existing macrolides including telithromycin. Here, we report the design and synthesis of a novel series of macrolides, featuring the strategic fusion of ketolide and quinolone moieties. Our effort led to the discovery of two potent compounds, MCX-219 and MCX-190, demonstrating enhanced antibacterial efficacy against a broad spectrum of formidable pathogens, including A2058-methylated Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and notably, the clinical Mycoplasma pneumoniae isolates harboring A2058G mutations which are implicated in the recent pneumonia outbreak in China. Mechanistic studies reveal that the modified quinolone moiety of MCX-190 establishes a distinctive secondary binding site within the nascent peptide exit tunnel. Structure-activity relationship analysis underscores the importance of this secondary binding, maintained by a sandwich-like π-π stacking interaction and a water-magnesium bridge, for effective engagement with A2058-methylated ribosomes rather than topoisomerases targeted by quinolone antibiotics. Our findings not only highlight MCX-219 and MCX-190 as promising candidates for next-generation MLSBK antibiotics to combat antibiotic resistance, but also pave the way for the future rational design of the class of MLSBK antibiotics, offering a strategic framework to overcome the challenges posed by escalating antibiotic resistance.
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Introduction: Workplace violence against healthcare workers has become a serious global public health problem. The incidence of workplace violence towards Psychiatric nurses is higher than in all other medical institutions, up to 84.2% per year. It not only negatively affects many aspects of healthcare workers' lives, but also destroys the harmony of the nurse-patient relationship and reduces the quality of nursing care. The number of psychiatric nurses in China was approximately 96,000, far lower than most other countries and unable to meet the growing demand for mental health. However, the increase in workplace violence has future exacerbates the current shortage of nurses. Therefore, it is necessary to develop effective strategies to prevent psychiatric nurses from suffering from workplace violence, thereby to reduce nurse turnover and improve the quality of nursing care. A comprehensive understanding of psychiatric nurses' preferences and priorities for preventing workplace violence is an important prerequisite before formulating strategies and taking measures. Unfortunately, to date, no research has investigated the psychiatric nurses' preferences. Therefore, a discrete choice experiment (DCE) is conducting to explore the psychiatric nurses' preferences for workplace violence prevention. This article reports on methodological details of the DCE. Methods and analysis: Six attributes were developed through a literature review, one-on-one interviews and focus group discussions. D-efficient design in NGENE was used to generate choice sets. SPSS 24.0 will be used for descriptive analysis of social Demography, and Stata 16.0 will be used for analysis of DCE data. A multinomial logit model will be used to preliminarily explore trade-offs between workplace violence prevention characteristics included in the choice tasks. Then, in a mixed logit model, we plan to choose some arbitrarily defined base violence prevention program and will use the nlcom command to evaluate the probability of an alternative violence prevention program. Ethics and dissemination: The study was approved by the relevant ethics committees. Our findings will emphasize priority intervention areas based on the preferences of psychiatric nurses and provide references for hospitals to develop and improve workplace violence prevention strategies. The results will be shared through seminars, policy briefs, peer-reviewed journal articles and online blogs.
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Soins infirmiers en psychiatrie , Violence au travail , Humains , Violence au travail/prévention et contrôle , Violence au travail/psychologie , Violence au travail/statistiques et données numériques , Chine , Groupes de discussion , Comportement de choix , Attitude du personnel soignant , Mâle , Femelle , Adulte , Plan de rechercheRÉSUMÉ
BACKGROUND: Weight gain and metabolic disorders are commonly induced by antipsychotics. Orlistat is a lipase inhibitor used for weight control. The effect of orlistat on weight gain and metabolic disturbances in people (especially women) treated with antipsychotics has not been sufficiently studied. This study aimed to investigate the efficacy of orlistat in mitigating antipsychotic-induced weight gain and abnormal glycolipid metabolism. METHODS: Patients with schizophrenia or bipolar disorder with a weight gain ≥ 7% after taking antipsychotics were recruited. Participants were randomly allocated to two groups: one received eight weeks of orlistat (360 mg/day) and the other received a placebo. Anthropometric and fasting serum biochemical parameters were measured at baseline, week 4 and week 8. RESULTS: Sixty individuals (orlistat:placebo = 32:28) participated in the study. After controlling for the study center, the eight-week changes in body mass index (BMI), cholesterol (CHOL), high-density lipoprotein cholesterol (HDL-CH) and low-density lipoprotein cholesterol (LDL-CH) were significantly different between the groups. According to the mixed linear models, CHOL and LDL-CH were significantly lower in the orlistat group than in the control group at week 8. The week 0-to-8 slopes of BMI, CHOL and LDL-CH were also significantly lower in the orlistat group. CONCLUSIONS: These findings suggested that orlistat is an effective intervention for attenuating weight gain and serum lipid disturbances in antipsychotic-treated patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03451734.
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Neuroleptiques , Indice de masse corporelle , Lactones , Orlistat , Schizophrénie , Prise de poids , Humains , Orlistat/usage thérapeutique , Femelle , Neuroleptiques/effets indésirables , Neuroleptiques/usage thérapeutique , Mâle , Prise de poids/effets des médicaments et des substances chimiques , Adulte , Adulte d'âge moyen , Méthode en double aveugle , Schizophrénie/traitement médicamenteux , Schizophrénie/sang , Lactones/usage thérapeutique , Lactones/effets indésirables , Cholestérol LDL/sang , Cholestérol HDL/sang , Agents antiobésité/usage thérapeutique , Agents antiobésité/effets indésirables , Trouble bipolaire/traitement médicamenteuxRÉSUMÉ
SUMMARY: The advent of spatial transcriptomics has revolutionized our understanding of the spatial heterogeneity in tissues, providing unprecedented insights into the cellular and molecular mechanisms underlying biological processes. Although quality control (QC) critical for downstream data analyses, there is currently a lack of specialized tools for one-stop spatial transcriptome QC. Here, we introduce SpatialQC, a one-stop QC pipeline, which generates comprehensive QC reports and produces clean data in an interactive fashion. SpatialQC is widely applicable to spatial transcriptomic techniques. AVAILABILITY AND IMPLEMENTATION: source code and user manuals are available via https://github.com/mgy520/spatialQC, and deposited on Zenodo (https://doi.org/10.5281/zenodo.12634669).
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Contrôle de qualité , Logiciel , Transcriptome , Analyse de profil d'expression de gènes/méthodes , HumainsRÉSUMÉ
Sorghum, renowned for its substantial biomass production and remarkable tolerance to various stresses, possesses extensive gene resources and phenotypic variations. A comprehensive understanding of the genetic basis underlying complex agronomic traits is essential for unlocking the potential of sorghum in addressing food and feed security and utilizing marginal lands. In this context, we provide an overview of the major trends in genomic resource studies focusing on key agronomic traits over the past decade, accompanied by a summary of functional genomic platforms. We also delve into the molecular functions and regulatory networks of impactful genes for important agricultural traits. Lastly, we discuss and synthesize the current challenges and prospects for advancing molecular design breeding by gene-editing and polymerization of the excellent alleles, with the aim of accelerating the development of desired sorghum varieties.
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Self-hybridizing structures based on transition metal dichalcogenides (TMDCs) are becoming promising candidates for the study of an intrinsic strong light-matter coupling because of the efficient mode overlap with much simplified geometries. However, realizing flexible tuning of intrinsic strong coupling in such TMDC-based structures is still challenging. Here, we propose a strategy for flexible tuning of the intrinsic strong light-matter coupling based on a bulk TMDC material. We report the first demonstration of the strong coupling of intrinsic excitons to whispering gallery modes (WGMs) supported by an all-TMDC nanocavity. Importantly, by simply controlling angles of incidence, a selective excitation of WGMs and an anapole can be realized, which enables a direct modulation of self-hybridized interactions from a bright WGM-exciton coupling to a dark anapole-exciton coupling. Our work is expected to provide unique opportunities for engineering a strong light-matter coupling and to open exciting avenues for highly integrated novel nanophotonic devices.
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Pancreatic adenocarcinoma is the fourth leading cause of malignancy-related deaths, with rapid development of drug resistance driven by pancreatic cancer stem cells. However, the mechanisms sustaining stemness and chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Here, we demonstrate that Bicaudal C homolog 1 (BICC1), an RNA binding protein regulating numerous cytoplasmic mRNAs, facilitates chemoresistance and stemness in PDAC. Mechanistically, BICC1 activated tryptophan catabolism in PDAC by up-regulating indoleamine 2,3-dioxygenase-1 (IDO1) expression, a tryptophan-catabolizing enzyme. Increased levels of tryptophan metabolites contribute to NAD+ synthesis and oxidative phosphorylation, leading to a stem cell-like phenotype. Blocking BICC1/IDO1/tryptophan metabolism signaling greatly improves the gemcitabine (GEM) efficacy in several PDAC models with high BICC1 level. These findings indicate that BICC1 is a critical tryptophan metabolism regulator that drives the stemness and chemoresistance of PDAC and thus a potential target for combinatorial therapeutic strategy against chemoresistance.
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Résistance aux médicaments antinéoplasiques , Cellules souches tumorales , Tumeurs du pancréas , Tryptophane , Tryptophane/métabolisme , Humains , Résistance aux médicaments antinéoplasiques/génétique , Cellules souches tumorales/métabolisme , Cellules souches tumorales/anatomopathologie , Tumeurs du pancréas/métabolisme , Tumeurs du pancréas/anatomopathologie , Tumeurs du pancréas/génétique , Tumeurs du pancréas/traitement médicamenteux , Lignée cellulaire tumorale , Animaux , Souris , Régulation de l'expression des gènes tumoraux , Carcinome du canal pancréatique/métabolisme , Carcinome du canal pancréatique/anatomopathologie , Carcinome du canal pancréatique/traitement médicamenteux , Carcinome du canal pancréatique/génétique , , Désoxycytidine/analogues et dérivés , Désoxycytidine/pharmacologie , Protéines de liaison à l'ARN/métabolisme , Protéines de liaison à l'ARN/génétique , Indoleamine-pyrrole 2,3,-dioxygenase/métabolisme , Indoleamine-pyrrole 2,3,-dioxygenase/génétiqueRÉSUMÉ
Hepatocellular carcinoma (HCC) is a malignant tumor that occurs in the liver, with a high degree of malignancy and relatively poor prognosis. Gypenoside L has inhibitory effects on liver cancer cells. However, its mechanism of action is still unclear. This study aims to investigate the inhibitory effects of gypenoside L on HCC in vitro and in vivo, and explore its potential mechanisms. The results showed that gypenoside L reduced the cholesterol and triglyceride content in HepG2 and Huh-7 cells, inhibited cell proliferation, invasion and metastasis, arrested cell cycle at G0/G1 phase, promoted cell apoptosis. Mechanistically, it targeted the transcription factor SREPB2 to inhibit the expression of HMGCS1 protein and inhibited the downstream proteins HMGCR and MVK, thereby regulating the mevalonate (MVA) pathway. Overexpression HMGCS1 led to significant alterations in the cholesterol metabolism pathway of HCC, which mediated HCC cell proliferation and conferred resistance to the therapeutic effect of gypenoside L. In vivo, gypenoside L effectively suppressed HCC growth in tumor-bearing mice by reducing cholesterol production, exhibiting favorable safety profiles and minimal toxic side effects. Gypenoside L modulated cholesterol homeostasis, enhanced expression of inflammatory factors by regulating MHC I pathway-related proteins to augment anticancer immune responses. Clinical samples from HCC patients also exhibited high expression levels of MVA pathway-related genes in tumor tissues. These findings highlight gypenoside L as a promising agent for targeting cholesterol metabolism in HCC while emphasizing the effectiveness of regulating the SREBP2-HMGCS1 axis as a therapeutic strategy.
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Carcinome hépatocellulaire , Prolifération cellulaire , Gynostemma , Tumeurs du foie , Protéine-2 de liaison à l'élément de régulation des stérols , Humains , Carcinome hépatocellulaire/traitement médicamenteux , Carcinome hépatocellulaire/anatomopathologie , Carcinome hépatocellulaire/métabolisme , Gynostemma/composition chimique , Tumeurs du foie/traitement médicamenteux , Tumeurs du foie/anatomopathologie , Tumeurs du foie/métabolisme , Protéine-2 de liaison à l'élément de régulation des stérols/métabolisme , Protéine-2 de liaison à l'élément de régulation des stérols/antagonistes et inhibiteurs , Prolifération cellulaire/effets des médicaments et des substances chimiques , Animaux , Souris , Relation dose-effet des médicaments , Structure moléculaire , Tests de criblage d'agents antitumoraux , Apoptose/effets des médicaments et des substances chimiques , Relation structure-activité , Antinéoplasiques d'origine végétale/pharmacologie , Antinéoplasiques d'origine végétale/composition chimique , Souris de lignée BALB C , Souris nude , Tumeurs expérimentales du foie/traitement médicamenteux , Tumeurs expérimentales du foie/anatomopathologie , Tumeurs expérimentales du foie/métabolisme , Extraits de plantesRÉSUMÉ
AIM: Sepsis-induced myocardial injury (SIMI) may be associated with insufficient mitophagy in cardiomyocytes, but the exact mechanism involved remains unknown. Sirtuin 3 (Sirt3) is mainly found in the mitochondrial matrix and is involved in repairing mitochondrial function through means such as the activation of autophagy. Previously, we demonstrated that the annexin-A1 small peptide (ANXA1sp) can promote Sirt3 expression in mitochondria. In this study, we hypothesized that the activation of Sirt3 by ANXA1sp induces mitophagy, thereby providing a protective effect against SIMI in mice. METHODS: A mouse model of SIMI was established via cecal ligation and puncture. Intraperitoneal injections of ANXA1sp, 3TYP, and 3MA were administered prior to modeling. After successful modeling, IL-6, TNF-α, CK-MB, and CTn-I levels were measured; cardiac function was assessed using echocardiography; myocardial mitochondrial membrane potential, ROS, and ATP production were determined; myocardial mitochondrial ultrastructure was observed using transmission electron microscopy; and the expression levels of Sirt3 and autophagy-related proteins were detected using western blotting. RESULTS: ANXA1sp significantly reduced serum IL-6, TNF-α, CK-MB, and CTn-I levels; decreased myocardial ROS production; increased mitochondrial membrane potential and ATP synthesis; and improved myocardial mitochondrial ultrastructure in septic mice. Furthermore, ANXA1sp promoted Sirt3 expression and activated the AMPK-mTOR pathway to induce myocardial mitophagy. These protective effects of ANXA1sp were reversed upon treatment with the Sirt3 blocker, 3-TYP. CONCLUSION: ANXA1sp can reverse SIMI, and the underlying mechanism may be related to the activation of the AMPK-mTOR pathway following upregulation of Sirt3 by ANXA1sp, which, in turn, induces autophagy.
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Annexine A1 , Mitophagie , Sepsie , Sirtuine-3 , Animaux , Sepsie/complications , Sepsie/métabolisme , Mitophagie/effets des médicaments et des substances chimiques , Sirtuine-3/métabolisme , Sirtuine-3/génétique , Souris , Annexine A1/métabolisme , Mâle , Souris de lignée C57BL , Myocytes cardiaques/métabolisme , Myocytes cardiaques/anatomopathologie , Modèles animaux de maladie humaine , Autophagie , PeptidesRÉSUMÉ
ABSTRACT: A 72-year-old man with pancreatic tail cancer underwent distal pancreatectomy and splenectomy 1 year ago. Routine postoperative follow-up CT detected multiple pulmonary nodules. 18 F-FDG PET/CT showed multiple FDG-avid nodules in the bilateral lungs, which highly suggested the possibility of lung metastases of pancreatic cancer. Finally, the bronchoalveolar lavage fluid and pathology confirmed the diagnosis of simple pulmonary eosinophilia.