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1.
Phys Rev E ; 109(6-1): 064208, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-39020871

RESUMO

The spectral form factor (SFF) plays a crucial role in revealing the statistical properties of energy-level distributions in complex systems. It is one of the tools to diagnose quantum chaos and unravel the universal dynamics therein. The definition of SFF in most literature only encapsulates the two-level correlation. In this manuscript, we extend the definition of SSF to include the high-order correlation. Specifically, we introduce the standard deviation of energy levels to define correlation functions, from which the generalized spectral form factor (GSFF) can be obtained by Fourier transforms. GSFF provides a more comprehensive knowledge of the dynamics of chaotic systems. Using random matrices as examples, we demonstrate dynamics features that are encoded in GSFF. Remarkably, the GSFF is complex, and the real and imaginary parts exhibit universal dynamics. For instance, in the two-level correlated case, the real part of GSFF shows a dip-ramp-plateau structure akin to the conventional counterpart, and the imaginary part for different system sizes converges in the long-time limit. For the two-level GSFF, the analytical forms of the real part are obtained and consistent with numerical results. The results of the imaginary part are obtained by numerical calculation. Similar analyses are extended to three-level GSFF.

2.
Spectrochim Acta A Mol Biomol Spectrosc ; 321: 124745, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38955071

RESUMO

H2S plays a crucial role in numerous physiological and pathological processes. In this project, a new fluorescent probe, SG-H2S, for the detection of H2S, was developed by introducing the recognition group 2,4-dinitrophenyl ether. The combination of rhodamine derivatives can produce both colorimetric reactions and fluorescence reactions. Compared with the current H2S probes, the main advantages of SG-H2S are its wide pH range (5-9), fast response (30 min), and high selectivity in competitive species (including biological mercaptan). The probe SG-H2S has low cytotoxicity and has been successfully applied to imaging in MCF-7 cells, HeLa cells, and BALB/c nude mice. We hope that SG-H2S will provide a vital method for the field of biology.

3.
Int Endod J ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38958220

RESUMO

AIM: In this study, we investigated the systemic implications of chronic apical periodontitis (CAP). CAP may contribute to the nonalcoholic fatty liver disease (NAFLD) progression through the gut microbiota and its metabolites, which are related to the degree of fibrosis. METHODOLOGY: Sixteen 7-week-old male apolipoprotein E knockout (apoE-/-) mice were randomly divided into two groups: the CAP and Con groups. A CAP model was established by sealing the first- and second-maxillary molars with bacterium-containing cotton balls. Apical lesions were evaluated by micro-CT. Histological evaluations of NAFLD were performed using second harmonic generation/two-photon excitation fluorescence (SHG/TPEF) assays. Additionally, we comprehensively analyzed the gut microbiota using 16S rRNA gene sequencing and explored metabolic profiles by liquid chromatography-mass spectrometry (LC-MS). Immunofluorescence analysis was used to examine the impact of CAP on tight junction proteins and mucin expression. Transcriptome assays have elucidated gene expression alterations in liver tissues. RESULTS: Micro-CT scans revealed an evident periapical bone loss in the CAP group, and the total collagen percentage was increased (Con, 0.0361 ± 0.00510%, CAP, 0.0589 ± 0.00731%, p < .05). 16S rRNA sequencing revealed reduced diversity and distinct taxonomic enrichment in the CAP group. Metabolomic assessments revealed that differentially enriched metabolites, including D-galactosamine, were enriched and that 16-hydroxyhexadecanoic acid and 3-methylindole were depleted in the CAP group. Immunofluorescence analyses revealed disruptions in tight junction proteins and mucin production, indicating intestinal barrier integrity disruption. Liver transcriptome analysis revealed upregulation of Lpin-1 expression in the CAP group. CONCLUSION: This study provides comprehensive evidence of the systemic effects of CAP on liver fibrosis in NAFLD patients by elucidating alterations in the gut microbiota composition and metabolism.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39031269

RESUMO

Coronavirus disease 2019 (COVID-19), a kind of respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily spreads through the respiratory tract from human to human. Its extensive and rapid spread has led to a global pandemic, causing great harm to human health and economic development all over the world. Current known evidence indicates that SARS-CoV-2 has evolved accumulating multiple mutations, with altered infectivity and viral replication capacity. A better understanding of the complications of COVID-19 and its relationship with underlying diseases is crucial for the prevention and treatment of SARS-CoV-2. This case series reviewed case data of our 4 recent patients with severe or critical COVID-19, including treatment plan, status of pulmonary infection and their microbiology workup with metagenomic next-generation sequencing with bronchoalveolar lavage fluid. This report shed light on the significance of rapid and accurate clinical diagnosis and treatment on COVID-19.

5.
Life Sci ; 352: 122873, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38950643

RESUMO

Sepsis-induced acute kidney injury (S-AKI) is one of the most serious life-threatening complications of sepsis. The pathogenesis of S-AKI is complex and there is no effective specific treatment. Therefore, it is crucial to choose suitable preclinical models that are highly similar to human S-AKI to study the pathogenesis and drug treatment. In this review, we summarized recent advances in the development models of S-AKI, providing reference for the reasonable selection of experimental models as basic research and drug development of S-AKI.

6.
Eur J Pharm Sci ; : 106851, 2024 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-39009286

RESUMO

Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir(TFV), is an effective drug in treating patients infected with human immunodeficiency virus(HIV). Previous population pharmacokinetics(PPK) studies have showed the large variabilities in PK of TFV. Furthermore, limited information was known in Chinese populations. Therefore, the aim of this study was to characterize PPK of TDF in Chinese and identify factors that may affect its PK. TFV concentrations (n = 552) from 30 healthy subjects and 162 HIV-infected Chinese adult patients were pooled for PPK analysis by a nonlinear mixed-effects method. The PK of TFV was adequately described as a two-compartment model with first order absorption and elimination. The typical apparent clearance(CL/F) of TFV in 70-kg adults was 137 L/h, higher than that reported in Caucasians and Blacks(45.8-93L/h). Estimated glomerular filtration rate was identified to be a significant factor influencing CL/F. Monte Carlo simulation showed that the exposure of standard dosing regimen of TDF 300mg every 24 hours in Chinese people with mild renal impairment(60 to 90 ml/min/1.73m2) was close to that in individuals with normal renal function(90 mL/min). Dose adjustment is not required for patients with mild renal impairment. Our study might offer new clues for optimal dosing strategies in Chinese patients with HIV-infected.

7.
Plants (Basel) ; 13(11)2024 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-38891336

RESUMO

Natural plants contain numerous chemical compounds that are beneficial to human health. The berries from the Lycium genus are widely consumed and are highly nutritious. Moreover, their chemical constituents have attracted attention for their health-promoting properties. In East Asia, there are three varieties of the Lycium genus (Lycium barbarum L., Lycium chinense Miller, and L. ruthenicum Murray) that possess medicinal value and are commonly used for treating chronic diseases and improving metabolic disorders. These varieties are locally referred to as "red Goji berries" or "black Goji berries" due to their distinct colors, and they differ in their chemical compositions, primarily in terms of carotenoid and anthocyanin content. The pharmacological functions of these berries include anti-aging, antioxidant, anti-inflammatory, and anti-exercise fatigue effects. This review aims to analyze previous and recent studies on the active ingredients and pharmacological activities of these Lycium varieties, elucidating their signaling pathways and assessing their impact on the gut microbiota. Furthermore, the potential prospects for using these active ingredients in the treatment of COVID-19 are evaluated. This review explores the potential targets of these Lycium varieties in the treatment of relevant diseases, highlighting their potential value in drug development.

8.
Biomed Pharmacother ; 176: 116832, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38850659

RESUMO

Berberine (BBR) is a compound derived from Chinese herbal medicine, known for its anticancer properties through multiple signaling pathways. However, whether BBR can inhibit tumor growth by participating in ferroptosis remains unconfirmed. In this study, we demonstrated that berberine synergistically inhibited NSCLC in combination with multiple ferroptosis inducers, and this combination synergistically down-regulated the mRNA and protein expression of SLC7A11, GPX4, and NRF2, resulting in ferroptosis accompanied by significant depletion of GSH, and aberrant accumulation of reactive oxygen species and malondialdehyde. In a lung cancer allograft model, the combination treatment exhibited enhanced anticancer effects compared to using either drug alone. Notably, p53 is critical in determining the ferroptosis sensitivity. We found that the combination treatment did not elicit a synergistic anticancer effect in cells with a p53 mutation or with exogenous expression of mutant p53. These findings provide insight into the mechanism by which combination induces ferroptosis and the regulatory role of p53 in this process. It may guide the development of new strategies for treating NSCLC, offering great medical potential for personal diagnosis and treatment.


Assuntos
Sistema y+ de Transporte de Aminoácidos , Berberina , Carcinoma Pulmonar de Células não Pequenas , Sinergismo Farmacológico , Ferroptose , Neoplasias Pulmonares , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Transdução de Sinais , Proteína Supressora de Tumor p53 , Ferroptose/efeitos dos fármacos , Berberina/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Humanos , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/genética , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Animais , Transdução de Sinais/efeitos dos fármacos , Linhagem Celular Tumoral , Espécies Reativas de Oxigênio/metabolismo , Camundongos , Camundongos Nus , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Células A549
9.
Int J Oral Sci ; 16(1): 39, 2024 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-38740741

RESUMO

The aim of this study was to explore the impact of chronic apical periodontitis (CAP) on atherosclerosis in apoE-/- mice fed high-fat diet (HFD). This investigation focused on the gut microbiota, metabolites, and intestinal barrier function to uncover potential links between oral health and cardiovascular disease (CVD). In this study, CAP was shown to exacerbate atherosclerosis in HFD-fed apoE-/- mice, as evidenced by the increase in plaque size and volume in the aortic walls observed via Oil Red O staining. 16S rRNA sequencing revealed significant alterations in the gut microbiota, with harmful bacterial species thriving while beneficial species declining. Metabolomic profiling indicated disruptions in lipid metabolism and primary bile acid synthesis, leading to elevated levels of taurochenodeoxycholic acid (TCDCA), taurocholic acid (TCA), and tauroursodeoxycholic acid (TDCA). These metabolic shifts may contribute to atherosclerosis development. Furthermore, impaired intestinal barrier function, characterized by reduced mucin expression and disrupted tight junction proteins, was observed. The increased intestinal permeability observed was positively correlated with the severity of atherosclerotic lesions, highlighting the importance of the intestinal barrier in cardiovascular health. In conclusion, this research underscores the intricate interplay among oral health, gut microbiota composition, metabolite profiles, and CVD incidence. These findings emphasize the importance of maintaining good oral hygiene as a potential preventive measure against cardiovascular issues, as well as the need for further investigations into the intricate mechanisms linking oral health, gut microbiota, and metabolic pathways in CVD development.


Assuntos
Aterosclerose , Dieta Hiperlipídica , Disbiose , Microbioma Gastrointestinal , Animais , Dieta Hiperlipídica/efeitos adversos , Aterosclerose/metabolismo , Camundongos , Masculino , Periodontite Periapical/metabolismo , Periodontite Periapical/microbiologia , Apolipoproteínas E/metabolismo , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S
10.
J Neurosurg Spine ; : 1-10, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38788239

RESUMO

OBJECTIVE: The aim of this study was to design a novel lumbar cortical bone trajectory (CBT) penetrating the anterior, middle, and posterior vertebral area using imaging; measure the relevant parameters to find theoretical parameters and screw placement possibilities; and investigate the optimal implantation trajectory of the CBT in patients with osteoporosis. METHODS: Three types of CBTs with appropriate lengths were selected to simulate screw placement using Mimics software. These CBTs were classified as the leading tip of the trajectory pointing to the posterior quarter area (original CBT [CBT-O]) and middle (novel CBT A [CBT-A]) and anterior quarter (novel CBT B [CBT-B]) of the superior endplate. The authors then measured the maximum screw diameter (MSD) and length (MSL), cephalad (CA) and lateral (LA) angles, and bone mineral density (Hounsfield unit [HU] values) of the planned novel 3-column CBT screw placements. The differences in the parameters of the novel CBTs, the percentages of successfully planned CBT screws, and the factors that influenced the successful planning of 3-column CBT screws were analyzed. RESULTS: Three-column CBT screws were successfully designed in all segments of the lumbar spine. The success rate of the 3-column CBT planned screws was 72.25% (83.25% for CBT-A and 61.25% for CBT-B). From the CBT-O type, to the CBT-A type, to the CBT-B type, the LA, CA, and MSD of the novel CBT screws decreased with increasing trajectory length. The HU values of the three types of trajectories were all significantly higher than that of the traditional pedicle screw trajectory (p < 0.001). The main factor affecting successful planning of the 3-column CBT screw was pedicle width. CONCLUSIONS: Moderating adjustment of the original screw parameters by reducing LAs and CAs to penetrate the anterior, middle, and posterior columns of the vertebral body using the 3-column CBT screw is feasible, especially in the lower lumbar spine.

11.
World J Clin Oncol ; 15(4): 554-565, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38689624

RESUMO

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy with a high morbidity and mortality rate. TMEM100 has been shown to be suppressor gene in a variety of tumors, but there are no reports on the role of TMEM100 in esophageal cancer (EC). AIM: To investigate epigenetic regulation of TMEM100 expression in ESCC and the effect of TMEM100 on ESCC proliferation and invasion. METHODS: Firstly, we found the expression of TMEM100 in EC through The Cancer Genome Atlas database. The correlation between TMEM100 gene expression and the survival of patients with EC was further confirmed through Kaplan-Meier analysis. We then added the demethylating agent 5-AZA to ESCC cell lines to explore the regulation of TMEM100 expression by epigenetic modification. To observe the effect of TMEM100 expression on tumor proliferation and invasion by overexpressing TMEM100. Finally, we performed gene set enrichment analysis using the Kyoto Encyclopaedia of Genes and Genomes Orthology-Based Annotation System database to look for pathways that might be affected by TMEM100 and verified the effect of TMEM100 expression on the mitogen-activated protein kinases (MAPK) pathway. RESULTS: In the present study, by bioinformatic analysis we found that TMEM100 was lowly expressed in EC patients compared to normal subjects. Kaplan-meier survival analysis showed that low expression of TMEM100 was associated with poor prognosis in patients with EC. Then, we found that the demethylating agent 5-AZA resulted in increased expression of TMEM100 in ESCC cells [quantitative real-time PCR (qRT-PCR) and western blotting]. Subsequently, we confirmed that overexpression of TMEM100 leads to its increased expression in ESCC cells (qRT-PCR and western blotting). Overexpression of TMEM100 also inhibited proliferation, invasion and migration of ESCC cells (cell counting kit-8 and clone formation assays). Next, by enrichment analysis, we found that the gene set was significantly enriched in the MAPK signaling pathway. The involvement of TMEM100 in the regulation of MAPK signaling pathway in ESCC cell was subsequently verified by western blotting. CONCLUSION: TMEM100 is a suppressor gene in ESCC, and its low expression may lead to aberrant activation of the MAPK pathway. Promoter methylation may play a key role in regulating TMEM100 expression.

12.
Biomaterials ; 310: 122635, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38810386

RESUMO

Hepatocellular carcinoma (HCC) seriously threatens the human health. Previous investigations revealed that γ-glutamyltranspeptidase (GGT) was tightly associated with the chronic injury, hepatic fibrosis, and the development of HCC, therefore might act as a potential indicator for monitoring the HCC-related processes. Herein, with the contribution of a structurally optimized probe ETYZE-GGT, the bimodal imaging in both far red fluorescence (FL) and photoacoustic (PA) modes has been achieved in multiple HCC-related models. To our knowledge, this work covered the most comprehensive models including the fibrosis and developed HCC processes as well as the premonitory induction stages (autoimmune hepatitis, drug-induced liver injury, non-alcoholic fatty liver disease). ETYZE-GGT exhibited steady and practical monitoring performances on reporting the HCC stages via visualizing the GGT dynamics. The two modes exhibited working consistency and complementarity with high spatial resolution, precise apparatus and desirable biocompatibility. In cooperation with the existing techniques including testing serum indexes and conducting pathological staining, ETYZE-GGT basically realized the universal application for the accurate pre-clinical diagnosis of as many HCC stages as possible. By deeply exploring the mechanically correlation between GGT and the HCC process, especially during the premonitory induction stages, we may further raise the efficacy for the early diagnosis and treatment of HCC.


Assuntos
Carcinoma Hepatocelular , Técnicas Fotoacústicas , gama-Glutamiltransferase , gama-Glutamiltransferase/metabolismo , Animais , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Técnicas Fotoacústicas/métodos , Neoplasias Hepáticas/diagnóstico por imagem , Hepatopatias/diagnóstico por imagem , Imagem Óptica/métodos , Camundongos , Masculino , Camundongos Endogâmicos BALB C , Fígado/patologia , Fígado/diagnóstico por imagem , Fígado/enzimologia , Corantes Fluorescentes/química
14.
World J Gastrointest Oncol ; 16(3): 1059-1075, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38577469

RESUMO

BACKGROUND: Glycosylation, a commonly occurring post-translational modification, is highly expressed in several tumors, specifically in those of the digestive system, and plays a role in various cellular pathophysiological mechanisms. Although the importance and detection methods of glycosylation in digestive system tumors have garnered increasing attention in recent years, bibliometric analysis of this field remains scarce. The present study aims to identify the developmental trends and research hotspots of glycosylation in digestive system tumors. AIM: To find and identify the developmental trends and research hotspots of glycosylation in digestive system tumors. METHODS: We obtained relevant literature from the Web of Science Core Collection and employed VOSviewer 1.6.19 and CiteSpace (version 6.1.R6) to perform bibliometric analysis. RESULTS: A total of 2042 documents spanning from 1978 to the present were analyzed, with the research process divided into three phases: the period of obscurity (1978-1990), continuous development period (1991-2006), and the rapid outbreak period (2007-2023). These documents were authored by researchers from 66 countries or regions, with the United States and China leading in terms of publication output. Reis Celso A had the highest number of publications, while Pinho SS was the most cited author. Co-occurrence analysis revealed the most popular keywords in this field are glycosylation, expression, cancer, colorectal cancer, and pancreatic cancer. Furthermore, the Journal of Proteome Research was the most prolific journal in terms of publications, while the Journal of Biological Chemistry had the most citations. CONCLUSION: The bibliometric analysis shows current research focus is primarily on basic research in this field. However, future research should aim to utilize glycosylation as a target for treating tumor patients.

15.
Commun Biol ; 7(1): 394, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38561421

RESUMO

Brainbow is a genetic cell-labeling technique that allows random colorization of multiple cells and real-time visualization of cell fate within a tissue, providing valuable insights into understanding complex biological processes. However, fluorescent proteins (FPs) in Brainbow have distinct excitation spectra with peak difference greater than 35 nm, which requires sequential imaging under multiple excitations and thus leads to long acquisition times. In addition, they are not easily used together with other fluorophores due to severe spectral bleed-through. Here, we report the development of a single-wavelength excitable Brainbow, UFObow, incorporating three newly developed blue-excitable FPs. We have demonstrated that UFObow enables not only tracking the growth dynamics of tumor cells in vivo but also mapping spatial distribution of immune cells within a sub-cubic centimeter tissue, revealing cell heterogeneity. This provides a powerful means to explore complex biology in a simultaneous imaging manner at a single-cell resolution in organs or in vivo.


Assuntos
Diagnóstico por Imagem , Técnicas Genéticas , Animais , Proteínas Luminescentes/genética , Proteínas Luminescentes/metabolismo , Corantes , Mamíferos/genética
16.
New Phytol ; 242(6): 2872-2887, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581199

RESUMO

In the Vetrix clade of Salix, a genus of woody flowering plants, sex determination involves chromosome 15, but an XY system has changed to a ZW system. We studied the detailed genetic changes involved. We used genome sequencing, with chromosome conformation capture (Hi-C) and PacBio HiFi reads to assemble chromosome level gap-free X and Y of Salix arbutifolia, and distinguished the haplotypes in the 15X- and 15Y-linked regions, to study the evolutionary history of the sex-linked regions (SLRs). Our sequencing revealed heteromorphism of the X and Y haplotypes of the SLR, with the X-linked region being considerably larger than the corresponding Y region, mainly due to accumulated repetitive sequences and gene duplications. The phylogenies of single-copy orthogroups within the SLRs indicate that S. arbutifolia and Salix purpurea share an ancestral SLR within a repeat-rich region near the chromosome 15 centromere. During the change in heterogamety, the X-linked region changed to a W-linked one, while the Z was derived from the Y.


Assuntos
Cromossomos de Plantas , Filogenia , Salix , Cromossomos de Plantas/genética , Salix/genética , Haplótipos/genética , Evolução Biológica , Evolução Molecular , Loci Gênicos , Processos de Determinação Sexual/genética
17.
Int Immunopharmacol ; 132: 111935, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38599096

RESUMO

Finding novel therapeutic modalities, improving drug delivery efficiency and targeting, and reducing the immune escape of tumor cells are currently hot topics in the field of tumor therapy. Bacterial therapeutics have proven highly effective in preventing tumor spread and recurrence, used alone or in combination with traditional therapies. In recent years, a growing number of researchers have significantly improved the targeting and penetration of bacteria by using genetic engineering technology, which has received widespread attention in the field of tumor therapy. In this paper, we provide an overview and assessment of the advancements made in the field of tumor therapy using genetically engineered bacteria. We cover three major aspects: the development of engineered bacteria, their integration with other therapeutic techniques, and the current state of clinical trials. Lastly, we discuss the limitations and challenges that are currently being faced in the utilization of engineered bacteria for tumor therapy.


Assuntos
Bactérias , Engenharia Genética , Neoplasias , Humanos , Neoplasias/terapia , Neoplasias/imunologia , Animais , Bactérias/genética , Imunoterapia/métodos , Sistemas de Liberação de Medicamentos
18.
J Ethnopharmacol ; 329: 118081, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38570148

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Liujunzi formula has been used to treat liver cancer in China for many years, but its underlying mechanism remains unclear. We previously found that decreased expression of miR-122-3p was associated with liver cancer. In this study, we aimed to explore the target of miR-122-3p and the effect of the Liujunzi formula on miR-122-3p and its downstream events in liver cancer. MATERIAL AND METHODS: Bioinformatics pinpointed potential targets of miR-122-3p. The actual target was confirmed by miRNA mimic/inhibitor transfections and a dual-luciferase reporter assay. RNA-seq looked at downstream genes impacted by this target. Flow cytometry checked for changes in T cell apoptosis levels after exposing them to liver cancer cells. Gene expression was measured by RT-qPCR, western blotting, and immunofluorescence staining. RESULTS: Cell experiments found the Liujunzi extract (LJZ) upregulated miR-122-3p and in a dose-dependent manner. Bioinformatics analysis found UBE2I was a potential target of miR-122-3p, which was validated through experiments using miRNA mimics/inhibitors and a dual-luciferase reporter assay. RNA-seq data implicated the NF-κB pathway as being downstream of the miR-122-3p/UBE2I axis, further confirmed by forcing overexpression of UBE2I. Bioinformatic evidence suggested a link between UBE2I and T cell infiltration in liver cancer. Given that the NF-κB pathway drives PD-L1 expression, which can inhibit T cell infiltration, we investigated whether PD-L1 is a downstream effector of miR-122-3p/UBE2I. This was corroborated through mining public databases, UBE2I overexpression studies, and tumor-T cell co-culture assays. In addition, we also confirmed that LJZ downregulates UBE2I and NF-κB/PD-L1 pathways through miR-122-3p. LJZ also suppressed SUMOylation in liver cancer cells and protected PD-1+ T cells from apoptosis induced by co-culture with tumor cells. Strikingly, a miR-122-3p inhibitor abrogated LJZ's effects on UBE2I and PD-L1, and UBE2I overexpression rescued the LJZ-mediated effects on NF-κB and PD-L1. CONCLUSIONS: miR-122-3p targets UBE2I, thereby suppressing the NF-κB signaling cascade and downregulating PD-L1 expression, which potentiates anti-tumor immune responses. LJZ bolsters anti-tumor immunity by modulating the miR-122-3p/UBE2I/NF-κB/PD-L1 axis in liver cancer cells.


Assuntos
Medicamentos de Ervas Chinesas , Neoplasias Hepáticas , MicroRNAs , Enzimas de Conjugação de Ubiquitina , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Humanos , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Apoptose/efeitos dos fármacos , NF-kappa B/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células Hep G2 , Tolerância Imunológica/efeitos dos fármacos
19.
Trends Endocrinol Metab ; 35(6): 490-504, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38521668

RESUMO

The regulation of triglyceride (TG) tissue distribution, storage, and utilization, a fundamental process of energy homeostasis, critically depends on lipoprotein lipase (LPL). We review the intricate mechanisms by which LPL activity is regulated by angiopoietin-like proteins (ANGPTL3, 4, 8), apolipoproteins (APOA5, APOC3, APOC2), and the cAMP-responsive element-binding protein H (CREBH). ANGPTL8 functions as a molecular switch, through complex formation, activating ANGPTL3 while deactivating ANGPTL4 in their LPL inhibition. The ANGPTL3-4-8 model integrates the roles of the aforementioned proteins in TG partitioning between white adipose tissue (WAT) and oxidative tissues (heart and skeletal muscles) during the feed/fast cycle. This model offers a unified perspective on LPL regulation, providing insights into TG metabolism, metabolic diseases, and therapeutics.


Assuntos
Lipase Lipoproteica , Humanos , Lipase Lipoproteica/metabolismo , Animais , Triglicerídeos/metabolismo , Proteínas Semelhantes a Angiopoietina/metabolismo , Proteínas Semelhantes a Angiopoietina/genética , Proteína 8 Semelhante a Angiopoietina , Proteína 4 Semelhante a Angiopoietina/metabolismo , Proteína 4 Semelhante a Angiopoietina/genética , Proteína 3 Semelhante a Angiopoietina/metabolismo
20.
J Affect Disord ; 354: 1-10, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38452936

RESUMO

BACKGROUND: Prenatal depression, associated with adverse effects on mothers and fetuses, has received little attention. We conducted a large-sample study to investigate the risk factors of, and develop a predictive model for, prenatal depression in the Chinese population. METHODS: This study enrolled 14,329 pregnant women who delivered at the West China Second University Hospital, Sichuan University from January 2017 to December 2020. Participants were divided into a training or validation cohort. Multiple variables were collected and selected using univariate logistic regression and least absolute shrinkage and selection operator penalty regression. After multivariate logistic analysis, a predictive model was developed and validated internally and externally. RESULTS: Nine variables (employment, planned pregnancy, pregnancy number, conception methods, gestational diabetes mellitus, twin pregnancy, placenta previa, umbilical cord encirclement, and educational attainment) were identified as independent risk factors for prenatal depression. Receiver operating characteristic curves in both the training and validation cohorts showed excellent discrimination of the predictive model (the area under the curve: 0.746 and 0.732, respectively). LIMITATIONS: The results of this retrospective study may be affected by confounding and information bias. Some important variables were excluded, such as family history of mental disorders. The study was conducted in China; its results may not be generalizable to other regions. CONCLUSION: Our study identified nine significant risk factors for prenatal depression and constructed an accurate predictive model. This model could be applied as a clinical decision aid for individualized risk estimates and prevention of prenatal depression.


Assuntos
Depressão , Diabetes Gestacional , Gravidez , Humanos , Feminino , Estudos Retrospectivos , Depressão/epidemiologia , Fatores de Risco , Modelos Logísticos , Vitaminas , China/epidemiologia
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