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1.
Nature ; 627(8005): 821-829, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38448584

RESUMO

Animals in the natural world constantly encounter geometrically complex landscapes. Successful navigation requires that they understand geometric features of these landscapes, including boundaries, landmarks, corners and curved areas, all of which collectively define the geometry of the environment1-12. Crucial to the reconstruction of the geometric layout of natural environments are concave and convex features, such as corners and protrusions. However, the neural substrates that could underlie the perception of concavity and convexity in the environment remain elusive. Here we show that the dorsal subiculum contains neurons that encode corners across environmental geometries in an allocentric reference frame. Using longitudinal calcium imaging in freely behaving mice, we find that corner cells tune their activity to reflect the geometric properties of corners, including corner angles, wall height and the degree of wall intersection. A separate population of subicular neurons encode convex corners of both larger environments and discrete objects. Both corner cells are non-overlapping with the population of subicular neurons that encode environmental boundaries. Furthermore, corner cells that encode concave or convex corners generalize their activity such that they respond, respectively, to concave or convex curvatures within an environment. Together, our findings suggest that the subiculum contains the geometric information needed to reconstruct the shape and layout of naturalistic spatial environments.


Assuntos
Meio Ambiente , Percepção de Forma , Hipocampo , Neurônios , Animais , Feminino , Masculino , Camundongos , Cálcio/análise , Cálcio/metabolismo , Percepção de Forma/fisiologia , Hipocampo/citologia , Hipocampo/fisiologia , Neurônios/metabolismo , Neurônios/fisiologia , Propriedades de Superfície
2.
Mamm Genome ; 35(2): 296-307, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38600211

RESUMO

Varicella-zoster virus (VZV), a common pathogen with humans as the sole host, causes primary infection and undergoes a latent period in sensory ganglia. The recurrence of VZV is often accompanied by severe neuralgia in skin tissue, which has a serious impact on the life of patients. During the acute infection of VZV, there are few related studies on the pathophysiological mechanism of skin tissue. In this study, transcriptome sequencing data from the acute response period within 2 days of VZV antigen stimulation of the skin were used to explore a model of the trajectory of skin tissue changes during VZV infection. It was found that early VZV antigen stimulation caused activation of mainly natural immune-related signaling pathways, while in the late phase activation of mainly active immune-related signaling pathways. JAK-STAT, NFκB, and TNFα signaling pathways are gradually activated with the progression of infection, while Hypoxia is progressively inhibited. In addition, we found that dendritic cell-mediated immune responses play a dominant role in the lesion damage caused by VZV antigen stimulation of the skin. This study provides a theoretical basis for the study of the molecular mechanisms of skin lesions during acute VZV infection.


Assuntos
Herpesvirus Humano 3 , Transdução de Sinais , Pele , Infecção pelo Vírus da Varicela-Zoster , Herpesvirus Humano 3/genética , Pele/patologia , Pele/virologia , Pele/imunologia , Animais , Infecção pelo Vírus da Varicela-Zoster/virologia , Infecção pelo Vírus da Varicela-Zoster/imunologia , Infecção pelo Vírus da Varicela-Zoster/genética , Infecção pelo Vírus da Varicela-Zoster/patologia , Humanos , Camundongos , Células Dendríticas/imunologia , Herpes Zoster/virologia , Herpes Zoster/patologia , Herpes Zoster/genética , Herpes Zoster/imunologia , Transcriptoma , Modelos Animais de Doenças , Antígenos Virais/imunologia , Antígenos Virais/genética , NF-kappa B/metabolismo , NF-kappa B/genética
3.
BMC Surg ; 24(1): 117, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38643065

RESUMO

BACKGROUND: This study investigated the clinical application of the indocyanine green (ICG) fluorescence navigation technique in bile duct identification during laparoscopic common bile duct exploration (LCBDE) for complex hepatolithiasis. METHODS: Eighty patients with complex hepatolithiasis were admitted to our department between January 2022 and June 2023 and randomly divided into control and observation groups. The control group underwent conventional LCBDE, while the observation group underwent LCBDE guided by ICG fluorescence. RESULTS: Intraoperatively, the observation group had shorter operation and search times for the common bile duct (CBD), as well as reduced intraoperative blood loss and fewer complications, such as conversion to laparotomy and various injuries (gastroduodenal, colon, pancreatic, and vascular) than the control group, with statistical significance (P < 0.05). Postoperatively, the observation group had lower rates of postoperative bile leakage, abdominal infection, postoperative hemorrhage, and residual stone than the control group. Additionally, the observation group demonstrated significantly shorter times for resuming flatus, removal of the abdominal drainage tube, and hospitalization than the control group, with statistical significance (P < 0.05). CONCLUSION: ICG fluorescence navigation technology effectively visualizes the bile duct, improves its identification rate, shortens the operation time, prevents biliary tract injury, and reduces the occurrence of complications.


Assuntos
Coledocolitíase , Laparoscopia , Litíase , Hepatopatias , Humanos , Coledocolitíase/cirurgia , Ducto Colédoco/cirurgia , Verde de Indocianina , Laparoscopia/métodos , Tempo de Internação , Litíase/cirurgia , Hepatopatias/cirurgia , Estudos Retrospectivos
4.
Int J Clin Exp Pathol ; 17(1): 1-12, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322176

RESUMO

BACKGROUND: Echinoderm microtubule-associated protein-like 2 (EML2), a gene located on 19q13.32, is overexpressed in various cancers and has been identified as a prognostic factor. However, the function and carcinogenic mechanism of EML2 in colon cancer is yet to be explored. METHODS: This study aimed to demonstrate the relationship between EML2 expression and colon cancer using The Cancer Genome Atlas (TCGA) database. The EML2 expression, including GSE33113 and GSE39923, was validated in colon cancer in the Gene Expression Omnibus (GEO) database. The Receiver Operating Characteristic (ROC) curves were used to assess the feasibility of EML2 as a distinguishing factor from the area under the curve (AUC) scores. In addition, Cox regression and logistic regression analyses were conducted to evaluate the factors linked to the prognosis of colon cancer. Moreover, the STRING tool was used to establish the EML2 binding protein network. The enrichment analysis cluster Profiler of the R package was utilized to investigate the function of EML2. The relationship between the immune infiltration and EML2 expression level in colon cancer was investigated by the R package Gene Set Variation Analysis (GSVA) and the single sample Gene Set Enrichment Analysis (ssGSEA) method in the Tumor Immune Estimation Resource (TIMER) database. RESULTS: Pan-cancer data analysis revealed that EML2 expression was higher in most cancers, including colon cancer. This outcome was in line with the findings of the GEO database. The ROC curve demonstrated that EML2 can serve as a diagnostic biomarker for colon cancer (AUC = 0.738). High EML2 expression was associated with poorer overall survival (OS; P = 0.004). Moreover, the results of the enrichment and immune infiltration analysis revealed that high EML2 expression correlated with regulation of the infiltration level of GTPase binding and some immune cell types like NK cells and NK CD56 bright cells. CONCLUSION: The findings revealed that colon cancer tissues had a higher EML2 expression than normal colon epithelial tissues. This phenomenon was significantly associated with poor prognosis and altered immune cell infiltration. Consequently, EML2 has shown the capacity to serve as a prognostic biomarker for patients diagnosed with colon cancer.

5.
Ultrason Sonochem ; 102: 106755, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38219547

RESUMO

Milk fat globules or milk fat globule membranes (MFGs/MFGM) have been added to the infant formula to fortify the phospholipids and narrow the nutritional gap from breast milk. The main aim of this study was to profile the interfacial and thermal properties of MFGs/MFGM prepared from ultrasonicated bovine milk. Bovine milk was sonicated at ultrasonic intensities of 20 kHz and 40 kHz independently or synchronously with the duration time of 0 min (control), 5 min, 10 min, and 15 min (work/rest cycles = 5 s: 3 s). Ultrasonic treatments at 20 kHz/ 5 min and 20 + 40 kHz/ 5 min improved the volume density (%) of smaller particles (1-10 µm) while significantly decreasing the surface hydrophobicity (H0) (p < 0.05). 40 kHz/5 min samples showed significantly higher ζ- potential than the other samples (p < 0.05), which might be because more negative charges were detected. In comparison with control samples, ultrasonic treatments decreased the interfacial tension (π) between the air and MFGs/MFGM liquid phase. 20 kHz ultra-sonicated treatments decreased the diffusion rate (k diff) of MFGs/MFGM interfacial compositions significantly as the duration prolonged from 5 min to 15 min (p < 0.05) but did not affect the adsorption or penetration rate (k a) (p > 0.05). X-ray diffraction (XRD) results showed that α-crystal peaks only existed in control and ultrasonicated 5 min samples but disappeared in all 15 min samples. According to the different scanning calorimetry (DSC), one or two new exothermic events (in the range of 17.29 - 18.81 â„ƒ and 22.14 - 25.21 â„ƒ) appeared after ultrasonic treatments, which, however, were not found in control samples. Ultrasonic treatments resulted in the low-melting fractions (LMF) (TM1) peaks undetectable in MFGs/MFGM samples in which only peaks of medium-melting fractions (MMF) (TM2) and high-melting fractions (HMF) (TM3) were detected. Compared with the control, both enthalpies of crystallisation (ΔHC) and melting (ΔHM) decreased in ultrasonicated samples. In conclusion, ultrasonic treatment affects the interfacial and thermal properties of MFGs/MFGM.


Assuntos
Glicoproteínas , Leite , Humanos , Lactente , Feminino , Animais , Leite/química , Glicolipídeos , Gotículas Lipídicas
6.
Postgrad Med ; 136(3): 278-291, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38635593

RESUMO

Gallbladder cancer is a common type of biliary tract tumor. Optimal management for early stage cases typically involves radical excision as the primary treatment modality. Various surgical techniques, including laparoscopic, robotic, and navigational surgery, have demonstrated favorable clinical outcomes in radical gallbladder excision. Unfortunately, most patients are ineligible for surgical intervention because of the advanced stage of the disease upon diagnosis. Consequently, non-surgical interventions, such as chemotherapy, radiotherapy, immunotherapy, and targeted therapy, have become the mainstay of treatment for patients in advanced stages. This review focuses on elucidating various surgical techniques as well as advancements in immunotherapy and targeted therapy in the context of recent advancements in gallbladder cancer research.


Assuntos
Neoplasias da Vesícula Biliar , Imunoterapia , Humanos , Neoplasias da Vesícula Biliar/terapia , Neoplasias da Vesícula Biliar/cirurgia , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Colecistectomia/métodos
7.
Patient ; 17(4): 363-378, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38483691

RESUMO

BACKGROUND: Chinese rural women aged 35-64 years are encouraged to complete breast cancer screening (BCS) free of charge. However, it is challenging to reach a satisfying BCS uptake rate. In this study, rural women's preferences and preferences heterogeneity were measured for the development of strategies to enhance participation in BCS. METHODS: A cross-sectional survey with a discrete choice experiment (DCE) was conducted via convenience sampling via face-to-face interviews in Jiangsu, China. Six DCE attributes were identified through a systematic literature review; our previous study of Chinese rural women's BCS intentions; a qualitative work involving in-depth interviews with rural women (n = 13), medical staff (n = 4), and health care managers (n = 2); and knowledge of realistic and actionable policy. The D-efficient design was generated using Ngene 1.3.0. A mixed logit model (MXL) in Stata 18.0 was used to estimate the main effect of attribute levels on rural women's preferences. The relative importance and willingness to utilize BCS services (WTU) were also estimated. The heterogeneous preferences were analyzed by a latent class model (LCM). Sociodemographic status was used to predict the characteristics of class membership. The WTU for different classes was also calculated. RESULTS: A total of 451 rural women, aged 35-64 years, were recruited. The MXL results revealed that the screening interval (SI) was the most important attribute for rural women with regard to utilizing BCS services, followed by the level of screening, the attitude of medical staff, ways to get knowledge and information, people who recommend screening, and time spent on screening (TSS). Rural women preferred a BCS service with a shorter TSS; access to knowledge and information through multiple approaches; a shorter SI; a recommendation from medical staff or workers from the village or community, and others; the enthusiasm of medical staff; and medical staff with longer tenures in the field. Two classes named "process driven" and "efficiency driven" were identified by the preference heterogeneity analysis of the LCM. CONCLUSION: There is a higher uptake of breast cancer screening when services are tailored to women's preferences. The screening interval was the most important attribute for rural women in China with a preference for a yearly screening interval versus longer intervals.


Assuntos
Neoplasias da Mama , Comportamento de Escolha , Detecção Precoce de Câncer , Preferência do Paciente , População Rural , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/diagnóstico , China , Adulto , Detecção Precoce de Câncer/psicologia , População Rural/estatística & dados numéricos , Estudos Transversais , Fatores Socioeconômicos
8.
Front Cell Infect Microbiol ; 14: 1362933, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38558851

RESUMO

Introduction: The incidence of biliary system diseases has been continuously increasing in the past decade. Biliary system diseases bring a heavy burden to humanity and society. However, the specific etiology and pathogenesis are still unknown. The biliary system, as a bridge between the liver and intestine, plays an indispensable role in maintaining the physiological metabolism of the body. Therefore, prevention and treatment of biliary diseases are crucial. It is worth noting that the microorganisms participate in the lipid metabolism of the bile duct, especially the largest proportion of intestinal bacteria. Methods: We systematically reviewed the intestinal microbiota in patients with gallstones (GS), non-calculous biliary inflammatory, and biliary tract cancer (BTC). And searched Pubmed, Embase and Web of science for research studies published up to November 2023. Results: We found that the abundance of Faecalibacterium genus is decreased in GS, primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC) and BTC. Veillonella, Lactobacillus, Streptococcus and Enterococcus genus were significantly increased in PSC, PBC and BTC. Interestingly, we found that the relative abundance of Clostridium was generally reduced in GS, PBC and BTC. However, Clostridium was generally increased in PSC. Discussion: The existing research mostly focuses on exploring the mechanisms of bacteria targeting a single disease. Lacking comparison of multiple diseases and changes in bacteria during the disease process. We hope to provide biomarkers forearly diagnosis of biliary system diseases and provide new directions for the mechanism of intestinal microbiota in biliary diseases.


Assuntos
Doenças Biliares , Microbioma Gastrointestinal , Humanos , Doenças Biliares/microbiologia , Bactérias/classificação , Bactérias/isolamento & purificação , Bactérias/metabolismo , Cálculos Biliares/microbiologia , Faecalibacterium , Lactobacillus , Sistema Biliar/microbiologia , Neoplasias do Sistema Biliar/microbiologia , Clostridium/isolamento & purificação , Colangite Esclerosante/microbiologia , Enterococcus , Streptococcus/isolamento & purificação
9.
J Gastrointest Oncol ; 15(1): 190-202, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38482211

RESUMO

Background: The long non-coding RNA (lncRNA) prostate cancer-associated transcript 6 (PCAT6) has been studied in many cancers, yet its relationship with colorectal cancer (CRC) remains poorly defined. Here, we conducted an analysis of The Cancer Genome Atlas (TCGA) database to better clarify the role of PCAT6 in this cancer type. Methods: Wilcoxon rank-sum tests were utilized to assess relative levels of PCAT6 in CRC tumors and normal tissues, while logistic regression analyses were utilized to compare the relationships between PCAT6 levels and clinicopathological findings. Kaplan-Meier curves and Cox regression analyses were used to gauge correlations between PCAT6 and patient survival outcomes, while the biological roles of this lncRNA were investigated via a gene set enrichment analysis (GSEA) approach. The expression level of PCAT6 in CRC cell lines was detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results: PCAT6 levels were significantly correlated with CRC patient lymph node metastasis (N) stage [odds ratio (OR) =1.8 for N1 & N2 vs. N0], lymphatic invasion [OR =1.9 for yes vs. no), distant metastasis (M stage) (OR =2.1 for M1 vs. M0), carcinoembryonic antigen (CEA) level (OR =1.9 for >5 vs. ≤5), perineural invasion (OR =1.9 for yes vs. no), pathologic stage (OR =1.9 for stage III/IV vs. stage I/II), and neoplasm type (OR =2.1 for rectal adenocarcinoma vs. colon adenocarcinoma) (all P<0.05). CRC patients expressing higher PCAT6 levels exhibited poorer survival outcomes than those expressing low levels of this lncRNA (P=0.017), and in univariate analyses, higher PCAT6 levels were linked to worse overall survival [hazard ratio (HR) =1.540; 95% confidence interval (CI): 1.079-2.199; P=0.017], with this relationship also being preserved in a multivariate analysis (HR =6.892; 95% CI: 1.713-27.727, P=0.007). GSEA revealed high PCAT6 expression to be linked to differential DNA methylation enrichment, with high PCAT6 levels being associated with changes in base excision repair, cellular senescence, G2/M DNA damage checkpoint, chromatin-modifying enzyme, and gene silencing by RNA activity. The high expression of lncRNA PCAT6 in CRC cell lines was demonstrated by PCR experiments. Conclusions: PCAT6 represents a promising prognostic biomarker of poor CRC patient survival outcomes, with DNA methylation and RNA-mediated gene silencing being potentially promising mechanistic pathways whereby this lncRNA may shape patient outcomes.

10.
Heliyon ; 10(7): e28442, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38560253

RESUMO

Background: According to statistics, ovarian cancer (OV) is the most prevalent type of gynecologic malignancy and has the highest mortality rate of all gynecologic tumors. Although several studies have shown that oxidative stress (OS) contributes significantly to the onset and progression of cancer, the role of OS in OV needs to be investigated further. Thus, it is critical to comprehend the function of OS-related genes in OV. Methods: In this study, all data related to the transcriptome and clinical status of the patients were retrieved from "The Cancer Genome Atlas" (TCGA) and "Gene Expression Omnibus" (GEO) databases. Using the unsupervised cluster analysis technique, all patients with OV were classified into two different subtypes (categories) based on the OS gene. All hub genes were screened using the weighted gene co-expression network analysis (WGCNA). Since the hub genes and the differentially expressed genes (DEGs) in both categories were found to intersect, the univariate Cox regression analysis was implemented. A multivariate Cox analysis was also performed to construct a novel clinical prognosis model, which was validated using data from the GEO cohort. In addition, the relationship between risk score and immune cell infiltration level was evaluated using CIBERSORT. Finally, qRT-PCR was used to confirm the expression of the genes used to construct the model. Results: Two subtypes of OS were obtained. The findings indicated that OS-C1 had a better survival outcome than OS-C2. The results of WGCNA yielded 112 hub genes. For univariate COX regression analyses, 49 OS-related trait genes were obtained. Finally, a clinical prognostic model containing two genes was constructed. This model could differentiate between patients with OV having varying years of survival in the TCGA and GEO cohorts. The model risk score was verified as an independent prognostic indicator. According to the results of CIBERSORT, many tumor-infiltrating immune cells were found to be significantly related to the risk score. Furthermore, the results revealed that patients with low-risk OV in the CTLA4 treatment group had a high likelihood of benefiting from immunotherapy. qRT-PCR results also showed that the expression of MARVELD1 and VSIG4 was high in the OV samples. Conclusions: Analysis of the results suggested that the newly developed model, which contained two characteristic OS-related genes, could successfully predict the survival outcomes of all patients with OV. The findings of this study could offer valuable information and insights into the refinement of personalized therapy and immunotherapy for OV in the future.

11.
J Agric Food Chem ; 72(2): 1082-1095, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38169320

RESUMO

Oligomycins are potent antifungal and antitumor agents. Mass spectrometry (MS)- and nuclear magnetic resonance (NMR)-based metabolomic fingerprinting analysis of marine-derived actinomycetes in our in-house library provided an oligomycin-producing strain, Streptomyces sp. FXY-T5. Chemical investigation led to the discovery of five new oligomycins, 24-lumooligomycin B (1), 4-lumooligomycin B (2), 6-lumooligomycin B (3), 40-homooligomycin B (4), and 15-hydroxy-oligomycin B (5), together with seven biosynthetically related known derivatives. Their structures were assigned by MS, NMR, electronic circular dichroism (ECD), and single-crystal X-ray diffraction analyses. The biosynthesis pathway of oligomycins was first proposed based on the analysis of a type I modular polyketide synthase (PKS) system and targeted gene disruption. As expected, the isolated oligomycins showed significant antiagricultural fungal pathogen activity and antiproliferative properties from which the possible structure-activity relationships were first suggested. More importantly, oligomycins induced significant G1-phase cell cycle arrest on cancer cells and significantly attenuated their Cyclin D1 and PCNA expression through a ß-catenin signaling pathway.


Assuntos
Antineoplásicos , Streptomyces , Streptomyces/química , Oligomicinas/farmacologia , Oligomicinas/química , Antineoplásicos/farmacologia , Antineoplásicos/metabolismo , Relação Estrutura-Atividade , Antifúngicos/farmacologia
12.
Sci Rep ; 14(1): 12163, 2024 05 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806553

RESUMO

Hepatocellular carcinoma (HCC) is a significant contributor to morbidity and mortality worldwide. The interaction between receptors and ligands is the primary mode of intercellular signaling and plays a vital role in the progression of HCC. This study aimed to identify the macrophage-related receptor ligand marker genes associated with HCC and further explored the molecular immune mechanisms attributed to altered biomarkers. Single-cell RNA sequencing data containing primary and recurrent samples were downloaded from the China National GeneBank. Cell types were first identified to explore differences between immune cells from different sample sources. CellChat analysis was used to infer and analyze intercellular communication networks quantitatively. Three molecular subtypes were constructed based on the screened twenty macrophage-associated receptor ligand genes. Bulk RNA-Seq data were downloaded from The Cancer Genome Atlas and Gene Expression Omnibus databases. After the screening, the minor absolute shrinkage and selection operator (LASSO) regression model was employed to identify key markers. After collecting peripheral blood and clinical information from patients, an enzyme-linked immunosorbent assay (ELISA) was used to detect the correlation between key markers and IL-10, one of the macrophage markers. After developing a new HCC risk adjustment model and conducting analysis, it was found that there were significant differences in immune status and gene mutations between the high-risk and low-risk groups of patients based on macrophage-associated receptor and ligand genes. This study identified SPP1, ANGPT2, and NCL as key biological targets for HCC. The drug-gene interaction network analysis identified wortmannin, ribavirin, and tarnafloxin as potential therapeutic drugs for the three key markers. In a clinical cohort study, patients with immune checkpoint inhibitor (ICI) resistance had significantly higher expression levels of OPN, ANGPT2, NCL, and IL-10 than patients with ICI-responsiveness. These three key markers were positively correlated with the expression level of IL-10. The signature based on macrophage-associated receptor and ligand genes can accurately predict the prognosis of patients with HCC and the sensitivity to immunotherapy. These results may help guide the development of targeted prevention and personalized treatment of HCC.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/metabolismo , Prognóstico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Ligantes , Masculino , Feminino , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Receptores Imunológicos/genética , Receptores Imunológicos/metabolismo , Interleucina-10/genética , Interleucina-10/metabolismo , Macrófagos/metabolismo , Macrófagos/imunologia , Multiômica
13.
Phytomedicine ; 129: 155661, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38677269

RESUMO

BACKGROUND: Gallbladder cancer (GBC) poses a significant risk to human health. Its development is influenced by numerous factors, particularly the homeostasis of reactive oxygen species (ROS) within cells. This homeostasis is crucial for tumor cell survival, and abnormal regulation of ROS is associated with the occurrence and progression of many cancers. Dihydrotanshinone I (DHT I), a biologically effective ingredient isolated from Salvia miltiorrhiza, has exhibited cytotoxic properties against various tumor cells by inducing apoptosis. However, the precise molecular mechanisms by which dht I exerts its cytotoxic effects remain unclear. PURPOSE: To explore the anti-tumor impact of dht I on GBC and elucidate the potential molecular mechanisms. METHODS: The proliferation of GBC cells, NOZ and SGC-996, was assessed using various assays, including CCK-8 assay, colony formation assay and EdU staining. We also examined cell apoptosis, cell cycle progression, ROS levels, and alterations in mitochondrial membrane potential to delve into the intricate molecular mechanism. Quantitative PCR (qPCR), immunofluorescence staining, and Western blotting were performed to evaluate target gene expression at both the mRNA and protein levels. The correlation between nuclear factor erythroid 2-related factor 2 (Nrf2) and kelch-like ECH-associated protein 1 (Keap1) were examined using co-immunoprecipitation. Finally, the in vivo effect of dht I was investigated using a xenograft model of gallbladder cancer in mice. RESULTS: Our research findings indicated that dht I exerted cytotoxic effects on GBC cells, including inhibiting proliferation, disrupting mitochondrial membrane potential, inducing oxidative stress and apoptosis. Our in vivo studies substantiated the inhibition of dht I on tumor growth in xenograft nude mice. Mechanistically, dht I primarily targeted Nrf2 by promoting Keap1 mediated Nrf2 degradation and inhibiting protein kinase C (PKC) induced Nrf2 phosphorylation. This leads to the suppression of Nrf2 nuclear translocation and reduction of its target gene expression. Moreover, Nrf2 overexpression effectively counteracted the anti-tumor effects of dht I, while Nrf2 knockdown significantly enhanced the inhibitory effect of dht I on GBC. Meanwhile, PKC inhibitors and nuclear import inhibitors increased the sensitivity of GBC cells to dht I treatment. Conversely, Nrf2 activators, proteasome inhibitors, antioxidants and PKC activators all antagonized dht I induced apoptosis and ROS generation in NOZ and SGC-996 cells. CONCLUSION: Our findings indicated that dht I inhibited the growth of GBC cells by regulating the Keap1-Nrf2 signaling pathway and Nrf2 phosphorylation. These insights provide a strong rationale for further investigation of dht I as a potential therapeutic agent for GBC treatment.


Assuntos
Apoptose , Proliferação de Células , Neoplasias da Vesícula Biliar , Proteína 1 Associada a ECH Semelhante a Kelch , Camundongos Nus , Fator 2 Relacionado a NF-E2 , Fenantrenos , Espécies Reativas de Oxigênio , Transdução de Sinais , Animais , Humanos , Camundongos , Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Furanos/farmacologia , Neoplasias da Vesícula Biliar/tratamento farmacológico , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , Fenantrenos/farmacologia , Fosforilação/efeitos dos fármacos , Quinonas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Salvia miltiorrhiza/química , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Micromachines (Basel) ; 15(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38276832

RESUMO

The EOF of a viscoelastic Maxwell fluid driven by an alternating pressure gradient and electric field in a parallel plate microchannel with sinusoidal roughness has been investigated within the Debye-Hückel approximation based on boundary perturbation expansion and separation of variables. Perturbation solutions were obtained for the potential distribution, the velocity and the mean velocity, and the relation between the mean velocity and the roughness. There are significant differences in the velocity amplitudes of the Newtonian and Maxwell fluids. It is shown here that the velocity distribution of the viscoelastic fluid is significantly affected by the roughness of the walls, which leads to the appearance of fluctuations in the fluid. Also, the velocity is strongly dependent on the phase difference θ of the roughness of the upper and lower plates. As the oscillation Reynolds number ReΩ increases, the velocity profile and the average velocity um(t) of AC EOF oscillate rapidly but the velocity amplitude decreases. The Deborah number De plays a similar role to ReΩ, which makes the AC EOF velocity profile more likely to oscillate. Meanwhile, phase lag χ (representing the phase difference between the electric field and the mean velocity) decreases when G and θ are increased. However, for larger λ (e.g., λ > 3), it almost has no phase lag χ.

15.
Front Psychiatry ; 14: 1281847, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38260802

RESUMO

Background: Psychological problems often occur in college students, with the most common ones being depression and anxiety symptoms. Exploring the risk factors that influence depression and anxiety symptoms in college students is essential to promote their physical and mental health. Objective: This study aimed to investigate the independent and interaction effects of problematic mobile phone use (PMPU) and the number of close friends (NCFs) on depression and anxiety symptoms and the comorbidity of these symptoms among college students. Methods: A cross-sectional survey was conducted in Huainan, Anhui Province, and Suzhou, Jiangsu Province in China from October to December 2022. Data from 7,617 college students were collected. The Patient Health Questionnaire and Generalized Anxiety Disorder-7 were used to evaluate depression and anxiety symptoms. The PMPU data were collected by the Mobile Phone Addiction Type Scale. Multinomial logistic regression models were performed to examine the associations of PMPU and NCFs with depression and anxiety symptoms and their interaction effects. Results: PMPU and lack of close friends significantly increased the risk of depression and anxiety symptoms and the comorbidity of these symptoms in college students (p < 0.001). In addition, the effects of PMPU and lack of close friends on depression and anxiety symptoms in college students were interactive (p < 0.001). No significant sex differences were found. Conclusion: PMPU and lack of close friends are important risk factors for depression, anxiety, and the comorbidity of these symptoms in college students in China.

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