RÉSUMÉ
This study investigates the effects of Physcion on esophageal cancer and its possible mechanisms of action. Potential Physcion targets were identified using databases. Transcriptomic data from 17 esophageal cancer and adjacent tissues were analyzed to find differentially expressed genes, intersecting with potential targets to select 16 key genes. Their expression and distribution were evaluated in patient sequencing data. Diagnostic potential was assessed through differential gene expression and ROC curves. Pathway enrichment analysis was performed using KEGG, and molecular docking simulations were conducted to assess Physcion's binding affinity to key genes. In vitro assays complemented these findings. A total of 161 drug targets were identified, narrowing down to 16 pivotal genes. Expression patterns were examined across cell populations, and enrichment analysis showed significant PI3K/AKT pathway involvement. Molecular docking indicated strong binding of Physcion to HSP90AA1 and MMP2. In vitro assays confirmed Physcion's dose- and time-dependent impact on esophageal cancer cells, with significant DAPI staining effects. Physcion shows promise as a therapeutic agent for esophageal cancer. The study supports its potential for clinical development and future research in esophageal cancer treatment.
RÉSUMÉ
The Hippo pathway is generally understood to inhibit tumor growth by phosphorylating the transcriptional cofactor YAP to sequester it to the cytoplasm and reduce the formation of YAP-TEAD transcriptional complexes. Aberrant activation of YAP occurs in various cancers. However, we found a tumor-suppressive function of YAP in clear cell renal cell carcinoma (ccRCC). Using cell cultures, xenografts, and patient-derived explant models, we found that the inhibition of upstream Hippo-pathway kinases MST1 and MST2 or expression of a constitutively active YAP mutant impeded ccRCC proliferation and decreased gene expression mediated by the transcription factor NF-κB. Mechanistically, the NF-κB subunit p65 bound to the transcriptional cofactor TEAD to facilitate NF-κB-target gene expression that promoted cell proliferation. However, by competing for TEAD, YAP disrupted its interaction with NF-κB and prompted the dissociation of p65 from target gene promoters, thereby inhibiting NF-κB transcriptional programs. This cross-talk between the Hippo and NF-κB pathways in ccRCC suggests that targeting the Hippo-YAP axis in an atypical manner-that is, by activating YAP-may be a strategy for slowing tumor growth in patients.
Sujet(s)
Protéines adaptatrices de la transduction du signal , Néphrocarcinome , Prolifération cellulaire , Tumeurs du rein , Protein-Serine-Threonine Kinases , Facteurs de transcription , Protéines de signalisation YAP , Humains , Néphrocarcinome/métabolisme , Néphrocarcinome/génétique , Néphrocarcinome/anatomopathologie , Tumeurs du rein/métabolisme , Tumeurs du rein/génétique , Tumeurs du rein/anatomopathologie , Facteurs de transcription/métabolisme , Facteurs de transcription/génétique , Protéines de signalisation YAP/métabolisme , Protéines de signalisation YAP/génétique , Animaux , Protéines adaptatrices de la transduction du signal/métabolisme , Protéines adaptatrices de la transduction du signal/génétique , Protein-Serine-Threonine Kinases/métabolisme , Protein-Serine-Threonine Kinases/génétique , Facteur de transcription RelA/métabolisme , Facteur de transcription RelA/génétique , Souris , Protéines de liaison à l'ADN/métabolisme , Protéines de liaison à l'ADN/génétique , Lignée cellulaire tumorale , Régulation de l'expression des gènes tumoraux , Voie de signalisation Hippo , Transduction du signal , Facteurs de transcription à domaine TEA/métabolisme , Facteur de transcription NF-kappa B/métabolisme , Facteur de transcription NF-kappa B/génétique , Souris nude , Protéines du cycle cellulaire/métabolisme , Protéines du cycle cellulaire/génétique , Serine-threonine kinase-3RÉSUMÉ
Polylactide/ethylene vinyl alcohol copolymer (PLA/EVOH) blends and fibers with different weight ratios were prepared by melt blending, and two-step melt spinning, respectively. PLA and EVOH in PLA/EVOH blends were immiscible. When EVOH content was ≤60 %, EVOH with the average diameter of about 3 µm was dispersed in PLA matrix uniformly. The dual continuous phases could be observed in PLA/EVOH blend with 70 wt% EVOH. When the EVOH content was ≥80 %, the spherical PLA phase with the diameter of 0.25 to 1 µm was dispersed in EVOH matrix. The introduction of EVOH as nucleating agent could promote the crystallization of PLA. Both PLA and EVOH components in PLA/EVOH blends formed individual crystal phases. The viscosity of PLA/EVOH blend with 5 % EVOH was lower than that of neat PLA. The viscosity of PLA/EVOH blends with the EVOH content of ≥10 % was much higher than that of neat PLA, which showed obvious shear thinning behavior. With the increase of EVOH content, the shear thinning behavior became obvious and the critical shear rate decreased gradually. The drawn PLA/EVOH fibers with the tensile strength of ≥16 cN/tex exhibited good mechanical properties. In addition, the introduction of EVOH could improve the hydrophilicity of PLA fibers.
Sujet(s)
Polyesters , Polyvinyles , Polyesters/composition chimique , Polyvinyles/composition chimique , Viscosité , Résistance à la traction , CristallisationRÉSUMÉ
The emergence of drug-resistant bacteria poses a significant threat to people's lives and health as bacterial infections continue to persist. Currently, antibiotic therapy remains the primary approach for tackling bacterial infections. However, the escalating rates of drug resistance coupled with the lag in the development of novel drugs have led to diminishing effectiveness of conventional treatments. Therefore, the development of nonantibiotic-dependent therapeutic strategies has become imperative to impede the rise of bacterial resistance. The emergence of chemodynamic therapy (CDT) has opened up a new possibility due to the CDT can convert H2O2 into â¢OH via Fenton/Fenton-like reaction for drug-resistant bacterial treatment. However, the efficacy of CDT is limited by a variety of practical factors. To overcome this limitation, the sterilization efficiency of CDT can be enhanced by introducing the therapeutics with inherent antimicrobial capability. In addition, researchers have explored CDT-based combined therapies to augment its antimicrobial effects and mitigate its potential toxic side effects toward normal tissues. This review examines the research progress of CDT in the antimicrobial field, explores various strategies to enhance CDT efficacy and presents the synergistic effects of CDT in combination with other modalities. And last, the current challenges faced by CDT and the future research directions are discussed.
RÉSUMÉ
DNA methylation is an important mechanism for epigenetic modifications that have been shown to be associated with responses to plant development. Previous studies found that inverted Populus yunnanensis cuttings were still viable and could develop into complete plants. However, the growth status of inverted cuttings was weaker than that of upright cuttings, and the sprouting time of inverted cuttings was later than that of upright cuttings. There is currently no research on DNA methylation patterns in inverted cuttings of Populus yunnanensis. In this study, we detected genome-wide methylation patterns of stem tips of Populus yunnanensis at the early growth stage and the rapid growth stage by Oxford Nanopore Technologies (ONT) methylation sequencing. We found that the methylation levels of CpG, CHG, CHH, and 6mA were 41.34%, 33.79%, 17.27%, and 12.90%, respectively, in the genome of inverted poplar cuttings, while the methylation levels of the four methylation types were higher in the genome of upright poplar cuttings than in inverted cuttings, 41.90%, 34.57%, 18.09%, and 14.11%, suggesting important roles for DNA methylation in poplar cells. In all comparison groups, CpG-type methylation genes in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were annotated to pathways associated with carbon metabolism, ribosome biogenesis in eukaryotes, glycolysis/gluconeogenesis, pyruvate metabolism, and mRNA detection pathways, suggesting that different biological processes are activated in upright and inverted cuttings. The results show that methylation genes are commonly present in the poplar genome, but only a few of them are involved in the regulation of expression in the growth and development of inverted cuttings. From this, we screened the DET2 gene for significant differences in methylation levels in upright or inverted cuttings. The DET2 gene is a key gene in the Brassinolide (BRs) synthesis pathway, and BRs have an important influence on the growth and development process of plants. These results provide important clues for studying DNA methylation patterns in P. yunnanensis.
Sujet(s)
Méthylation de l'ADN , Régulation de l'expression des gènes végétaux , Populus , Populus/génétique , Populus/croissance et développement , Populus/métabolisme , Épigenèse génétique , Génome végétal , Protéines végétales/génétique , Protéines végétales/métabolismeRÉSUMÉ
The misuse of antibiotics has led to increased bacterial resistance, posing a global public health crisis and seriously endangering lives. Currently, antibiotic therapy remains the most common approach for treating bacterial infections, but its effectiveness against multidrug-resistant bacteria is diminishing due to the slow development of new antibiotics and the increase of bacterial drug resistance. Consequently, developing new a\ntimicrobial strategies and improving antibiotic efficacy to combat bacterial infection has become an urgent priority. The emergence of nanotechnology has revolutionized the traditional antibiotic treatment, presenting new opportunities for refractory bacterial infection. Here we comprehensively review the research progress in nanotechnology-based antimicrobial drug delivery and highlight diverse platforms designed to target different bacterial resistance mechanisms. We also outline the use of nanotechnology in combining antibiotic therapy with other therapeutic modalities to enhance the therapeutic effectiveness of drug-resistant bacterial infections. These innovative therapeutic strategies have the potential to enhance bacterial susceptibility and overcome bacterial resistance. Finally, the challenges and prospects for the application of nanomaterial-based antimicrobial strategies in combating bacterial resistance are discussed. This article is categorized under: Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.
Sujet(s)
Antibactériens , Infections bactériennes , Nanotechnologie , Humains , Infections bactériennes/traitement médicamenteux , Animaux , Résistance bactérienne aux médicaments/effets des médicaments et des substances chimiques , Systèmes de délivrance de médicaments , NanomédecineRÉSUMÉ
An electrochemical microsensor for mesothelin (MSLN) based on an acupuncture needle (AN) was constructed in this work. To prepare the microsensor, MSLN was self-assembled on 4-mercaptophenylboronic acid (4-MPBA) by an interaction force between the external cis-diol and phenylboronic acid. This was followed by the gradual electropolymerization of thionine (TH) and eriochrome black T (EBT) around the anchored protein. The thickness of the surface imprinted layers influenced the sensing performance and needed to be smaller than the height of the anchored protein. The polymerized EBT was not electrically active, but the polymerized TH provided a significant electrochemical signal. Therefore, electron transfer smoothly proceeded through the eluted nanocavities. The imprinted nanocavities were highly selective toward MSLN, and the rebinding of insulating proteins reduced the electrochemical signal of the embedded pTH. The functionalized interface was characterized by SEM and electrochemical methods, and the preparation conditions were studied. After optimization, the sensor showed a linear response in the range of 0.1 to 1000 ng mL-1 with a detection limit of 10 pg mL-1, indicating good performance compared with other reported methods. This microsensor also showed high sensitivity and stability, which can be attributed to the fine complementation of the imprinted organic nanocavities. The sensitivity of this sensor was related to the nanocavities used for electron transport around the AuNPs. In the future, microsensors that can directly provide electrochemical signals are expected to play important roles especially on AN matrices.
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Techniques de biocapteur , Techniques électrochimiques , Électrodes , Limite de détection , Mésothéline , Phénothiazines , Phénothiazines/composition chimique , Humains , Techniques de biocapteur/méthodes , Techniques de biocapteur/instrumentation , Techniques électrochimiques/méthodes , Techniques électrochimiques/instrumentation , Polymères à empreintes moléculaires/composition chimique , Aiguilles , Or/composition chimique , Protéines liées au GPI/analyseRÉSUMÉ
BACKGROUND: Colon cancer is a prevalent invasive neoplasm in the gastrointestinal system with a high degree of malignancy. Despite extensive research, the underlying mechanisms of its recurrence and metastasis remain elusive.Rho GTPase activating protein 4 (ARHGAP4), a member of the small GTPases protein family, may be closely related to tumor metastasis, and its expression is increased in colon cancer. However, the role of ARHGAP4 in colon cancer metastasis is uncertain. This study investigates the impact of ARHGAP4 on the metastasis of colon cancer cells. Our objective is to determine the role of ARHGAP4 in regulating the invasive behavior of colon cancer cells. METHODS: We downloaded colon adenocarcinoma (COAD) data from the Cancer Genome Atlas (TCGA), and performed differential analysis and survival analysis. By using the CIBERSORT algorithm, we evaluated the proportion of infiltrating immune cells in colon cancer. We further analyzed whether ARHGAP4 is associated with T cell exhaustion. Finally, we investigated the impact of ARHGAP4 knockdown on the migration and invasion of colon cancer cells through in vitro cell experiments. Additionally, we utilized western blotting to assess the expression of protein related to the TGF-ß signaling pathway and epithelial-mesenchymal transition (EMT). RESULTS: We found that ARHGAP4 is upregulated in colon cancer. Subsequent survival analysis revealed that the high-expression group had significantly lower survival rates compared to the low-expression group. Immune infiltration analysis showed that ARHGAP4 was not only positively correlated with CD8+ T cells, but also positively correlated with T cell exhaustion markers programmed cell death 1 (PDCD-1), cytotoxic T-lymphocyte associated protein 4 (CTLA-4), and lymphocyte activating 3 (LAG-3). In vitro cell experiments, the knockdown of ARHGAP4 inhibited the migration and invasion of colon cancer cells. Among EMT-related proteins, when ARHGAP4 was knocked down, the expression of E-cadherin was increased, while the expression of N-cadherin and Vimentin was decreased. Meanwhile, the expression of TGF-ß1, p-Smad2, and p-Smad3, which are associated with the TGF-ß/Smad pathway, all decreased. CONCLUSION: ARHGAP4 promotes colon cancer metastasis through the TGF-ß/Smad signaling pathway and may be associated with T cell exhaustion. It plays an important role in the progression of colon cancer and may serve as a potential target for diagnosis and treatment of colon cancer.
Sujet(s)
Tumeurs du côlon , Transition épithélio-mésenchymateuse , Protéines d'activation de la GTPase , Transduction du signal , Facteur de croissance transformant bêta , Humains , Tumeurs du côlon/anatomopathologie , Tumeurs du côlon/génétique , Tumeurs du côlon/métabolisme , Protéines d'activation de la GTPase/métabolisme , Protéines d'activation de la GTPase/génétique , Facteur de croissance transformant bêta/métabolisme , Transition épithélio-mésenchymateuse/génétique , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Métastase tumorale , Lymphocytes T/métabolisme , Lymphocytes T/immunologie , Lymphocytes T/anatomopathologie , Invasion tumorale , Régulation de l'expression des gènes tumoraux , Épuisement des cellules TRÉSUMÉ
Reticulocalbin 1 (RCN1) is a calcium-binding protein involved in the regulation of calcium homeostasis in the endoplasmic reticulum. The aim of this study was to explore the clinical value and biological role of RCN1 in esophageal squamous cell carcinoma (ESCC). In addition, we investigated the effect of RCN1 on the polarization of tumor-associated macrophages (TAMs). The GSE53625 dataset from the Gene Expression Omnibus database was used to analyze the expression of RCN1 mRNA and its relationship with clinical value and immune cell infiltration. Immunohistochemistry was used to validate the expression of RCN1 and its correlation with clinicopathological characteristics. Subsequently, transwell and cell scratch assays were conducted to evaluate the migration and invasion abilities of ESCC cells. The expression levels of epithelial-mesenchymal transition (EMT)-related proteins were evaluated by western blot, while apoptosis was detected by flow cytometry and western blot. Additionally, qRTâPCR was utilized to evaluate the role of RCN1 in macrophage polarization. RCN1 was significantly upregulated in ESCC tissues and was closely associated with lymphatic metastasis and a poor prognosis, and was an independent prognostic factor for ESCC in patients. Knockdown of RCN1 significantly inhibited the migration, invasion, and EMT of ESCC cells, and promoted cell apoptosis. In addition, RCN1 downregulation inhibited M2 polarization. RCN1 is upregulated in ESCC patients and is negatively correlated with patient prognosis. Knocking down RCN1 inhibits ESCC progression and M2 polarization. RCN1 can serve as a potential diagnostic and prognostic indicator for ESCC, and targeting RCN1 is a very promising therapeutic strategy.
Sujet(s)
Protéines de liaison au calcium , Transition épithélio-mésenchymateuse , Tumeurs de l'oesophage , Carcinome épidermoïde de l'oesophage , Régulation de l'expression des gènes tumoraux , Macrophages , Femelle , Humains , Mâle , Apoptose , Protéines de liaison au calcium/métabolisme , Protéines de liaison au calcium/génétique , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Évolution de la maladie , Régulation négative , Transition épithélio-mésenchymateuse/génétique , Tumeurs de l'oesophage/anatomopathologie , Tumeurs de l'oesophage/génétique , Tumeurs de l'oesophage/métabolisme , Carcinome épidermoïde de l'oesophage/génétique , Carcinome épidermoïde de l'oesophage/anatomopathologie , Carcinome épidermoïde de l'oesophage/métabolisme , Macrophages/métabolisme , Pronostic , Macrophages associés aux tumeurs/métabolisme , Macrophages associés aux tumeurs/anatomopathologieRÉSUMÉ
BACKGROUND: Ribosome biogenesis is excessively activated in tumor cells, yet it is little known whether oncogenic transcription factors (TFs) are involved in the ribosomal RNA (rRNA) transactivation. METHODS: Nucleolar proteomics data and large-scale immunofluorescence were re-analyzed to jointly identify the proteins localized at nucleolus. RNA-Seq data of five prostate cancer (PCa) cohorts were combined and integrated with multi-dimensional data to define the upregulated nucleolar TFs in PCa tissues. Then, ChIP-Seq data of PCa cell lines and two PCa clinical cohorts were re-analyzed to reveal the TF binding patterns at ribosomal DNA (rDNA) repeats. The TF binding at rDNA was validated by ChIP-qPCR. The effect of the TF on rRNA transcription was determined by rDNA luciferase reporter, nascent RNA synthesis, and global protein translation assays. RESULTS: In this study, we reveal the role of oncogenic TF FOXA1 in regulating rRNA transcription within nucleolar organization regions. By analyzing human TFs in prostate cancer clinical datasets and nucleolar proteomics data, we identified that FOXA1 is partially localized in the nucleolus and correlated with global protein translation. Our extensive FOXA1 ChIP-Seq analysis provides robust evidence of FOXA1 binding across rDNA repeats in prostate cancer cell lines, primary tumors, and castration-resistant variants. Notably, FOXA1 occupancy at rDNA repeats correlates with histone modifications associated with active transcription, namely H3K27ac and H3K4me3. Reducing FOXA1 expression results in decreased transactivation at rDNA, subsequently diminishing global protein synthesis. CONCLUSIONS: Our results suggest FOXA1 regulates aberrant ribosome biogenesis downstream of oncogenic signaling in prostate cancer.
Sujet(s)
Facteur nucléaire hépatocytaire HNF-3 alpha , Tumeurs de la prostate , ARN ribosomique , Humains , Mâle , Tumeurs de la prostate/métabolisme , Tumeurs de la prostate/génétique , Tumeurs de la prostate/anatomopathologie , ARN ribosomique/génétique , ARN ribosomique/métabolisme , ARN ribosomique/biosynthèse , Facteur nucléaire hépatocytaire HNF-3 alpha/métabolisme , Facteur nucléaire hépatocytaire HNF-3 alpha/génétique , Lignée cellulaire tumorale , Transcription génétique , Régulation de l'expression des gènes tumoraux , Nucléole/métabolismeRÉSUMÉ
Polylactide/chlorogenic acid (PLA/CGA) blends with different weight ratios were prepared by melt mixing, and corresponding PLA/CGA fibers were produced via a two-step melt spinning process. For PLA/CGA blends, CGA was distributed uniformly in the PLA matrix. The intermolecular interactions between CGA and PLA existed. The viscosity of PLA/CGA blends was much lower than that of neat PLA. With the increase of CGA content, the viscosity of PLA/CGA blends decreased. As the CGA content increased, the crystallinity of both PLA/CGA blends and fibers decreased. In addition, the tensile strength of PLA/CGA fibers was slightly lower than that of neat PLA fiber. For PLA/CGA fibers, the 6-fold drawn PLA/CGA fiber with 3 % CGA owned the highest tensile strength of 420 MPa. The ultraviolet (UV) resistance of PLA/CGA fibers were enhanced significantly by the introduction of CGA. When the CGA content was not <3 %, the UV transmittance of PLA/CGA fibers was <8 %. Moreover, PLA/CGA fibers exhibited good antioxidant properties. PLA/CGA fibers with 10 % CGA owned the highest antioxidant rate of >90 %. In addition, the 6-fold drawn PLA/CGA fiber with 10 % CGA presented excellent release performance with a 7-day cumulative CGA release rate of 19 %.
Sujet(s)
Antioxydants , Acide chlorogénique , Polyesters/composition chimique , CongélationRÉSUMÉ
BACKGROUND: Colorectal cancer (CRC) is an aggressive tumor of the gastrointestinal tract, which is a major public health concern worldwide. Despite numerous studies, the precise mechanism of metastasis behind its progression remains elusive. As a member of the containing olfactomedin domains protein family, olfactomedin 2 (OLFM2) may play a role in tumor metastasis. It is highly expressed in colorectal cancer, and its role in the metastasis of CRC is still unclear. As such, this study seeks to explore the function of OLFM2 on CRC metastasis and its potential mechanisms. METHODS: Real-time fluorescence quantitative PCR and western blotting were used to study the expression of OLFM2 in human CRC and adjacent normal tissues. Knockdown and overexpression OLFM2 cell lines were constructed using siRNA and overexpression plasmids to explore the role of OLFM2 in the migration and invasion of CRC through transwell, and wound healing experiments. Finally, the expression of epithelial-mesenchymal transition (EMT) -related proteins and TGF-ß/Smad signaling pathway-related proteins was investigated using western blotting. RESULTS: In this study, we observed an elevation of OLFM2 expression levels in CRC tissues. To investigate the function of OLFM2, we overexpressed and knocked down OLFM2. We discovered that OLFM2 knockdown inhibited migration and invasion of colon cancer cells. Furthermore, E-cadherin expression increased while N-cadherin and Vimentin expression were opposite. It is no surprise that overexpressing OLFM2 had the opposite effects. We also identified that OLFM2 knockdown resulted in reduced TGF-ßR1 and downstream molecules p-Smad2 and p-Smad3, which are related to the TGF-ß / Smad pathway. In contrast, overexpressing OLFM2 significantly boosted their expression levels. CONCLUSION: The protein OLFM2 has been identified as a crucial determinant in the progression of CRC. Its mechanism of action involves the facilitation of EMT through the TGF-ß/Smad signaling pathway. Given its pivotal role in CRC, OLFM2 has emerged as a promising diagnostic and therapeutic target for the disease. These results indicate the potential of OLFM2 as a valuable biomarker for CRC diagnosis and treatment and highlight the need for further research exploring its clinical significance.
Sujet(s)
Tumeurs colorectales , Humains , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Tumeurs colorectales/anatomopathologie , Transition épithélio-mésenchymateuse/génétique , Régulation de l'expression des gènes tumoraux , Transduction du signal , Protéines Smad/métabolisme , Facteur de croissance transformant bêta/métabolismeRÉSUMÉ
(1) Background: Brassinosteroids (BRs) are important hormones involved in almost all stages of plant growth and development, and sterol dehydrogenase is a key enzyme involved in BRs biosynthesis. However, the sterol dehydrogenase gene family of Populus yunnanensis Dode (P. yunnanensis) has not been studied. (2) Methods: The PyDET2 (DEETIOLATED2) gene family was identified and analyzed. Three genes were screened based on RNA-seq of the stem tips, and the PyDET2e was further investigated via qRT-PCR (quantitative real-time polymerase chain reaction) and subcellular localization. (3) Results: The 14 DET2 family genes in P. yunnanensis were categorized into four groups, and 10 conserved protein motifs were identified. The gene structure, chromosome distribution, collinearity, and codon preference of all PyDET2 genes in the P. yunnanensis genome were analyzed. The codon preference of this family is towards the A/U ending, which is strongly influenced by natural selection. The PyDET2e gene was expressed at a higher level in September than in July, and it was significantly expressed in stems, stem tips, and leaves. The PyDET2e protein was localized in chloroplasts. (4) Conclusions: The PyDET2e plays an important role in the rapid growth period of P. yunnanensis. This systematic analysis provides a basis for the genome-wide identification of genes related to the brassinolide biosynthesis process in P. yunnanensis, and lays a foundation for the study of the rapid growth mechanism of P. yunnanensis.
Sujet(s)
Populus , Populus/génétique , Analyse de profil d'expression de gènes , Gènes de plante , Famille multigénique , Oxidoreductases/génétiqueRÉSUMÉ
The current use of immune checkpoint inhibitors (ICIs) for the treatment of lung cancer has dramatically changed the clinical strategy for metastatic non-small cell lung cancer (mNSCLC). As a result of great achievements in clinical trials, 6 programmed death-1 inhibitors (sintilimab, camrelizumab, tislelizumab, pembrolizumab, cemiplimab, and nivolumab), 2 programmed death-ligand 1 inhibitors (sugemalimab and atezolizumab), and 1 cytotoxic T lymphocyte-associated antigen-4 inhibitor (ipilimumab) have been approved as first-line treatment for mNSCLC by the US Food and Drug Administration. Recently, research on ICIs has shifted from a large number of second-line to first-line settings in clinical trials. Results from first-line trials have shown that almost all driver-negative mNSCLC are treated with ICIs and significantly prolong patient survival; however, the low response rate and adverse reactions to immunotherapy remain to be addressed. Here, we summarize the use of ICIs, including monotherapy and combination therapy, in the first-line treatment of mNSCLC in recent years and discuss the low response rate and adverse reactions of ICIs as well as the challenges and expectations for the first-line treatment of mNSCLC in the future.
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Carcinome pulmonaire non à petites cellules , Tumeurs du poumon , Humains , Carcinome pulmonaire non à petites cellules/traitement médicamenteux , Carcinome pulmonaire non à petites cellules/anatomopathologie , Tumeurs du poumon/traitement médicamenteux , Nivolumab/usage thérapeutique , Ipilimumab/usage thérapeutique , Immunothérapie/méthodesRÉSUMÉ
Peptic ulcer disease caused by environmental factors increases the risk of developing gastric cancer (GC), one of the most common and deadly cancers in the world. However, the mechanisms underlying this association remain unclear. A major type of GC uniquely undergoes spasmolytic polypeptide-expressing metaplasia (SPEM) followed by intestinal metaplasia. Notably, intestinal-type GC patients with high levels of YAP signaling exhibit a lower survival rate and poor prognosis. YAP overexpression in gastric cells induces atrophy, metaplasia, and hyperproliferation, while its deletion in a Notch-activated gastric adenoma model suppresses them. By defining the YAP targetome genome-wide, we demonstrate that YAP binds to active chromatin elements of SPEM-related genes, which correlates with the activation of their expression in both metaplasia and ulcers. Single-cell analysis combined with our YAP signature reveals that YAP signaling is activated during SPEM, demonstrating YAP as a central regulator of SPEM in gastric neoplasia and regeneration.
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Peptides , Tumeurs de l'estomac , Humains , Peptides/métabolisme , Estomac , Protéines et peptides de signalisation intercellulaire/métabolisme , Tumeurs de l'estomac/génétique , Métaplasie/métabolisme , Muqueuse gastrique/métabolismeRÉSUMÉ
The dysregulation of some solute carrier (SLC) proteins has been linked to a variety of diseases, including diabetes and chronic kidney disease. However, SLC-related genes (SLCs) has not been extensively studied in acute myocardial infarction (AMI). The GSE66360 and GSE60993 datasets, and SLCs geneset were enrolled in this study. Differentially expressed SLCs (DE-SLCs) were screened by overlapping DEGs between the AMI and control groups and SLCs. Next, functional enrichment analysis was carried out to research the function of DE-SLCs. Consistent clustering of samples from the GSE66360 dataset was accomplished based on DE-SLCs selected. Next, the gene set enrichment analysis (GSEA) was performed on the DEGs-cluster (cluster 1 vs cluster 2). Three machine learning models were performed to obtain key genes. Subsequently, biomarkers were obtained through receiver operating characteristic (ROC) curves and expression analysis. Then, the immune infiltration analysis was performed. Afterwards, single-gene GSEA was carried out, and the biomarker-drug network was established. Finally, quantitative real-time fluorescence PCR (qRT-PCR) was performed to verify the expression levels of biomarkers. In this study, 13 DE-SLCs were filtered by overlapping 366 SLCs and 448 DEGs. The functional enrichment results indicated that the genes were implicated with amino acid transport and TNF signaling pathway. After the consistency clustering analysis, the samples were classified into cluster 1 and cluster 2 subtypes. The functional enrichment results showed that DEGs-cluster were implicated with chemokine signaling pathway and so on. Further, SLC11A1 and SLC2A3 were identified as SLC-related biomarkers, which had the strongest negative relationship with resting memory CD4 T cells and the strongest positive association with activated mast cells. In addition, the single-gene GSEA results showed that cytosolic ribosome was enriched by the biomarkers. Five drugs targeting SLC2A3 were predicted as well. Lastly, the experimental results showed that the biomarkers expression trends were consistent with public database. In this study, 2 SLC-related biomarkers (SLC11A1 and SLC2A3) were screened and drug predictions were carried out to explore the prediction and treatment of AMI.
Sujet(s)
Infarctus du myocarde , Humains , Marqueurs biologiques , Infarctus du myocarde/génétique , Infarctus du myocarde/métabolismeRÉSUMÉ
BACKGROUND: Expression quantitative trait locus (eQTL) analysis has emerged as an important tool in elucidating the link between genetic variants and gene expression, thereby bridging the gap between risk SNPs and associated diseases. We recently identified and validated a specific case where the methylation of a CpG site influences the relationship between the genetic variant and gene expression. RESULTS: Here, to systematically evaluate this regulatory mechanism, we develop an extended eQTL mapping method, termed DNA methylation modulated eQTL (memo-eQTL). Applying this memo-eQTL mapping method to 128 normal prostate samples enables identification of 1063 memo-eQTLs, the majority of which are not recognized as conventional eQTLs in the same cohort. We observe that the methylation of the memo-eQTL CpG sites can either enhance or insulate the interaction between SNP and gene expression by altering CTCF-based chromatin 3D structure. CONCLUSIONS: This study demonstrates the prevalence of memo-eQTLs paving the way to identify novel causal genes for traits or diseases associated with genetic variations.
Sujet(s)
Méthylation de l'ADN , Régulation de l'expression des gènes , Mâle , Humains , Cartographie chromosomique , Locus de caractère quantitatif , Polymorphisme de nucléotide simple , Étude d'association pangénomique/méthodesRÉSUMÉ
Reticulocalbin 1 (RCN1), a calcium-binding protein located in the endoplasmic reticulum (ER) lumen, contains six conserved regions. Its main functions include maintaining intracellular homeostasis and regulating cell proliferation and apoptosis, and it plays an important role in the development of various tumours. However, the exact function of RCN1 in oral squamous cell carcinoma (OSCC) is not fully understood. Therefore, the aim of this study was to investigate the effects of RCN1 on the biological behaviour of OSCC and the regulation of tumour-associated macrophage (TAM) polarization. The expression of RCN1 in OSCC and normal oral mucosa was evaluated through bioinformatics analysis and immunohistochemical staining. The growth, migration, and invasion of OSCC cells were observed after knockdown of RCN1 using CCK-8 and Transwell assays. Apoptosis was detected by flow cytometry. The effect of tumour cell-derived RCN1 on the polarization of THP-1 macrophages was investigated by establishing a coculture model of THP-1 macrophages and OSCC cells. Additionally, changes in the expression levels of relevant proteins were detected using Western blotting. The upregulation of RCN1 in tumour tissues compared to normal oral mucosal tissues is associated with a poor prognosis and can be utilized as a prognostic indicator for OSCC. Knockdown of RCN1 inhibited the proliferation, migration, and invasion of OSCC cells. Additionally, knockdown of RCN1 in Cal-27 and SCC-25 cells resulted in inhibition of the M2 polarization of THP-1 macrophages. RCN1 knockdown inhibits OSCC progression and M2 macrophage polarization. Targeting RCN1 may be a promising approach for OSCC treatment.
Sujet(s)
Carcinome épidermoïde , Tumeurs de la tête et du cou , Tumeurs de la bouche , Humains , Carcinome épidermoïde/anatomopathologie , Lignée cellulaire tumorale , Mouvement cellulaire/génétique , Prolifération cellulaire/génétique , Régulation de l'expression des gènes tumoraux , Tumeurs de la tête et du cou/anatomopathologie , Macrophages/métabolisme , Tumeurs de la bouche/anatomopathologie , Carcinome épidermoïde de la tête et du cou/anatomopathologieRÉSUMÉ
Biomass resources are widely considered potential alternatives to formaldehyde-based wood adhesives because of their abundance. In this study, an environmentally friendly biomass adhesive, carboxylated chitosan-glucose (CSC-G), was prepared using chitosan, maleic anhydride, and glucose. The structure and water resistance of the adhesive were analyzed in detail. Maleic anhydride act as a bridge connecting chitosan and glucose, giving the adhesive good water solubility and resistance. The improved water resistance of the CSC-G adhesive was attributed to the formation of covalent cross-linked structures and an increased degree of system cross-linking. Additionally, the curing temperature of the CSC-G adhesive was superior to those of previously reported polyester adhesives. This study not only expands the application scope of fishery waste, but also demonstrates its great potential for the preparation of high-performance plywood.
Sujet(s)
Adhésifs , Chitosane , Adhésifs/composition chimique , Chitosane/composition chimique , Anhydrides maléiques , Solubilité , Eau/composition chimiqueRÉSUMÉ
Traditional wood adhesives have the problems of excessive dependence on fossil resources and environmental pollution. Cellulose, a renewable biomass resource with a low price and huge output, provides a basis for preparing biomass wood adhesives. In this study, a new type of polyamide resin was prepared by modifying microcrystalline cellulose and reacting with natural citric acid. Specifically, toluenesulfonyl cellulose (TS) was synthesized, and functional amino cellulose (AC) was prepared by a nucleophilic substitution reaction with hyperbranched polyamide (HP). Then cellulose-based hyperbranched polyamide resin (CHP) was prepared by polycondensation with citric acid. The structure of CHP resin was investigated by FTIR, XPS, 13C NMR and GPC, and plywood was prepared to study its mechanical properties. Due to the formation of hyperbranched cross-linked network structure inside the resin, the prepared plywood has excellent properties. The dry shear strength reaches 2.24 MPa, and the strength reaches 1.25 and 1.31 MPa after soaking in water at 63 °C and 93 °C for 3 h. The resin in this study has a simple preparation process and excellent performance, which provides a solid foundation for developing high-performance cellulose-based wood adhesives.