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2.
Int J Biol Macromol ; 267(Pt 2): 131518, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615865

RESUMO

D-Galactose derivatives, including galactosyl-conjugates and galactose-upgrading compounds, provide various physiological benefits and find applications in industries such as food, cosmetics, feed, pharmaceuticals. Many research on galactose derivatives focuses on identification, characterization, development, and mechanistic aspects of their physiological function, providing opportunities and challenges for the development of practical approaches for synthesizing galactose derivatives. This study focuses on recent advancements in enzymatic biosynthesis of galactose derivatives. Various strategies including isomerization, epimerization, transgalactosylation, and phosphorylation-dephosphorylation were extensively discussed under the perspectives of thermodynamic feasibility, theoretical yield, cost-effectiveness, and by-product elimination. Specifically, the enzymatic phosphorylation-dephosphorylation cascade is a promising enzymatic synthesis route for galactose derivatives because it can overcome the thermodynamic equilibrium of isomerization and utilize cost-effective raw materials. The study also elucidates the existing challenges and future trends in enzymatic biosynthesis of galactose derivatives. Collectively, this review provides a real-time summary aimed at promoting the practical biosynthesis of galactose derivatives through enzymatic catalysis.

3.
BMC Cancer ; 24(1): 330, 2024 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-38468232

RESUMO

TMEFF1 is a new protein involved in the physiological functions of the central nervous system, and we previously reported TMEFF1 can promote ovarian cancer. ST14 was determined to be involved in the processes of epidermal differentiation, epithelial cell integrity, and vascular endothelial cell migration, etc. The relationship between ST14 and TMEFF1 in the ovary remains unknown. In this study, we detected the expression of ST14 and TMEFF1 in 130 different ovarian cancer tissues through immunohistochemistry. We determined ST14 and TMEFF1 were highly expressed in ovarian cancer, indicating a higher degree of tumor malignancy and a worse prognosis. Tissues significantly expressing ST14 also highly expressed TMEFF1, and the expression of the two proteins was positively correlated. Consistently, immunofluorescence double staining demonstrated the co-localization of ST14 and TMEFF1 in the same region, and immunoprecipitation confirmed the interaction between ST14 and TMEFF1. TMEFF1 expression was also reduced after knocking down ST14 through Western blot. MTT, wound healing and Transwell assays results determined that knockdown of ST14 inhibited proliferation, migration and invasion of ovarian cancer cells in vitro, but the inhibitory effect was restored after adding TMEFF1 exogenous protein. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways analysis showed that ST14 and its related genes were enriched in the processes of epithelial formation, intercellular adhesion, protein localization, and mitosis regulation. We also clarified the kinase, microRNA, and transcription factor target networks and the impact of genetic mutations on prognosis. Overall, high expression of ST14 and TMEFF1 in ovarian cancer predicts higher tumor malignancy and a worse prognosis. ST14 and TMEFF1 co-localize and interact with each other in ovarian cancer. ST14 can regulate TMEFF1 expression to promote proliferation, migration and invasion of ovarian cancer cells. We speculate that the relationship between ST14 and TMEFF1 in ovarian cancer could become a potential target for anti-cancer therapy.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , MicroRNAs/genética , Fatores de Transcrição/genética , Mutação , Prognóstico , Proliferação de Células/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica
4.
Anticancer Drugs ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38527281

RESUMO

For critically ill patients with non-small cell lung cancer (NSCLC) in need of life-saving treatment, there is currently no reported evidence regarding the use of medication specifically targeting epidermal growth factor receptor (EGFR) p.C797S mutation, which is known to cause resistance to third-generation tyrosine kinase inhibitors (TKIs). Our report aims to investigate and explore treatment strategies to overcome resistance associated with EGFR p.C797S mutation in order to provide potential therapeutic options for these patients. Here, we reported two cases with NSCLC who initially harbored an EGFR-sensitive mutation and were both treated with osimertinib, a third-generation TKI. Next-generation sequencing tests conducted prior to the initiation of fifth-line therapy in critically ill patients revealed the presence of EGFR p.C797S mutations in both patients, suggesting acquired resistance. In the course of fifth-line therapy, the administration of a combination of brigatinib and cetuximab proved vital in saving critically ill patients, moderately extending their overall survival period. Our findings suggested that a combined regimen of brigatinib and cetuximab could serve as a potentially life-saving therapeutic strategy for critically ill patients with NSCLC, particularly those demonstrating EGFR p.C797S-mediated resistance. Further studies, however, are required to validate and expand upon these promising findings.

5.
J Sci Food Agric ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38436580

RESUMO

BACKGROUND: Isomaltulose is a 'generally recognized as safe' ingredient and is widely used in the food, pharmaceutical and chemical industries. The exploration and development of efficient technologies is essential for enhancing isomaltulose yield. RESULTS: In the present study, a simple and efficient surface display platform mediated by a non-yeast signal peptide was developed in Yarrowia lipolytica and utilized to efficiently produce isomaltulose from sucrose. We discovered that the signal peptide SP1 of sucrose isomerase from Pantoea dispersa UQ68J (PdSI) could guide SIs anchoring to the cell surface of Y. lipolytica, demonstrating a novel and simple cell surface display strategy. Furthermore, the PdSI expression level was significantly increased through optimizing the promoters and multi-site integrating genes into chromosome. The final strain gained 451.7 g L-1 isomaltulose with a conversion rate of 90.3% and a space-time yield of 50.2 g L-1 h-1 . CONCLUSION: The present study provides an efficient way for manufacturing isomaltulose with a high space-time yield. This heterogenous signal peptide-mediated cell surface display strategy featured with small fusion tag (approximately 2.2 kDa of SP1), absence of enzyme leakage in fermentation broth and ample room for optimization, providing a convenient way to construct whole-cell biocatalysts to synthesize other products and broadening the array of molecular toolboxes accessible for engineering Y. lipolytica. © 2024 Society of Chemical Industry.

6.
Bioresour Technol ; 399: 130611, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38508282

RESUMO

Glucosylglycerate (R-2-O-α-D-glucopyranosyl-glycerate, GG) is a negatively charged compatible solution with versatile functions. Here, an artificial in vitro enzymatic cascade was designed to feasibly and sustainably produce GG from affordable starch and glycerol. First, Spirochaeta thermophila glucosylglycerate phosphorylase (GGP) was carefully selected because of its excellent heterologous expression, specific activity, and thermostability. The optimized two-enzyme cascade, consisting of alpha-glucan phosphorylase (αGP) and GGP, achieved a remarkable 81 % conversion rate from maltodextrin and D-glycerate. Scaling up this cascade resulted in a practical concentration of 58 g/L GG with a 62 % conversion rate based on the added D-glycerate. Additionally, the production of GG from inexpensive starch and glycerol in one-pot using artificial four-enzyme cascade was successfully implemented, which integrates alditol oxidase and catalase with αGP and GGP. Collectively, this sustainable enzymatic cascade demonstrates the feasibility of the practical synthesis of GG and has the potential to produce other glycosides using the phosphorylase-and-phosphorylase paradigm.


Assuntos
Glicerol , Amido , Glucosídeos/metabolismo , Fosforilases/metabolismo
7.
J Cutan Med Surg ; : 12034754241229645, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38357853
8.
BMC Pediatr ; 24(1): 11, 2024 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-38178076

RESUMO

Community-acquired bacterial meningitis (CABM) is the main cause of morbidity and mortality in children. The epidemiology of CABM is regional and highly dynamic. To clarify the diagnostic status and epidemiological characteristics of children with CABM in this region, and pay attention to the disease burden, so as to provide evidence for the prevention and treatment of CABM. By retrospective case analysis, the clinical data of 918 CABM cases in children aged 0-14 years in Zhejiang Province from January, 2019 to December, 2020 were collected. The etiological diagnosis rate of CABM in children was 23.1%, the annual incidence rate 4.42-6.15/100,000, the annual mortality rate 0.06-0.09/100,000,the cure and improvement rate 94.4%, and the case fatality rate 1.4%. The total incidence of neuroimaging abnormalities was 20.6%. The median length of stay for CABM children was 20(16) days, with an average cost of 21,531(24,835) yuan. In addition, the incidence rate was decreased with age. Escherichia coli(E.coli) and group B Streptococcus agalactiae(GBS) were the principal pathogens in CABM infant<3 months(43.3%, 34.1%), and Streptococcus pneumoniae(S. pneumoniae) was the most common pathogen in children ≥ 3 months(33.9%). In conclusion, the annual incidence and mortality of CABM in children aged 0-14 years in Zhejiang Province are at intermediate and low level. The distribution of CABM incidence and pathogen spectrum are different in age; the incidence of abnormal neuroimaging is high; and the economic burden is heavy.


Assuntos
Meningites Bacterianas , Criança , Lactente , Humanos , Estudos Retrospectivos , Meningites Bacterianas/diagnóstico , Meningites Bacterianas/epidemiologia , Meningites Bacterianas/tratamento farmacológico , Streptococcus pneumoniae , Streptococcus agalactiae , Escherichia coli , Incidência
9.
Appl Microbiol Biotechnol ; 108(1): 135, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38229306

RESUMO

Apoptotic-like programmed cell death (PCD) is one of the main strategies for fungi to resist environmental stresses and maintain homeostasis. The apoptosis-inducing factor (AIF) has been shown in different fungi to trigger PCD through upregulating reactive oxygen species (ROS). This study identified a mitochondrial localized AIF homolog, CcAIF1, from Coprinopsis cinerea monokaryon Okayama 7. Heterologous overexpression of CcAIF1 in Saccharomyces cerevisiae caused apoptotic-like PCD of the yeast cells. Ccaif1 was increased in transcription when C. cinerea interacted with Gongronella sp. w5, accompanied by typical apoptotic-like PCD in C. cinerea, including phosphatidylserine externalization and DNA fragmentation. Decreased mycelial ROS levels were observed in Ccaif1 silenced C. cinerea transformants during cocultivation, as well as reduction of the apoptotic levels, mycelial growth, and asexual sporulation. By comparison, Ccaif1 overexpression led to the opposite phenotypes. Moreover, the transcription and expression levels of laccase Lcc9 decreased by Ccaif1 silencing but increased firmly in Ccaif1 overexpression C. cinerea transformants in coculture. Thus, in conjunction with our previous report that intracellular ROS act as signal molecules to stimulate defense responses, we conclude that CcAIF1 is a regulator of ROS to promote apoptotic-like PCD and laccase expression in fungal-fungal interactions. In an axenic culture of C. cinerea, CcAIF1 overexpression and H2O2 stimulation together increased laccase secretion with multiplied production yield. The expression of two other normally silent isozymes, Lcc8 and Lcc13, was unexpectedly triggered along with Lcc9. KEY POINTS: • Mitochondrial CcAIF1 induces PCD during fungal-fungal interactions • CcAIF1 is a regulator of ROS to trigger the expression of Lcc9 for defense • CcAIF1 overexpression and H2O2 stimulation dramatically increase laccase production.


Assuntos
Fator de Indução de Apoptose , Lacase , Lacase/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Peróxido de Hidrogênio/metabolismo , Apoptose , Saccharomyces cerevisiae/metabolismo
10.
Plant J ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38271098

RESUMO

Rhus chinensis Mill., an economically valuable Anacardiaceae species, is parasitized by the galling aphid Schlechtendalia chinensis, resulting in the formation of the Chinese gallnut (CG). Here, we report a chromosomal-level genome assembly of R. chinensis, with a total size of 389.40 Mb and scaffold N50 of 23.02 Mb. Comparative genomic and transcriptome analysis revealed that the enhanced structure of CG and nutritional metabolism contribute to improving the adaptability of R. chinensis to S. chinensis by supporting CG and galling aphid growth. CG was observed to be abundant in hydrolysable tannins (HT), particularly gallotannin and its isomers. Tandem repeat clusters of dehydroquinate dehydratase/shikimate dehydrogenase (DQD/SDH) and serine carboxypeptidase-like (SCPL) and their homologs involved in HT production were determined as specific to HT-rich species. The functional differentiation of DQD/SDH tandem duplicate genes and the significant contraction in the phenylalanine ammonia-lyase (PAL) gene family contributed to the accumulation of gallic acid and HT while minimizing the production of shikimic acid, flavonoids, and condensed tannins in CG. Furthermore, we identified one UDP glucosyltransferase (UGT84A), three carboxylesterase (CXE), and six SCPL genes from conserved tandem repeat clusters that are involved in gallotannin biosynthesis and hydrolysis in CG. We then constructed a regulatory network of these genes based on co-expression and transcription factor motif analysis. Our findings provide a genomic resource for the exploration of the underlying mechanisms of plant-galling insect interaction and highlight the importance of the functional divergence of tandem duplicate genes in the accumulation of secondary metabolites.

11.
Int J Biol Macromol ; 260(Pt 2): 129641, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262552

RESUMO

Cellobionic acid (CBA), a kind of aldobionic acid, offers potential applications in the fields of pharmaceutical, cosmetic, food, and chemical industry. To tackle the high cost of the substrate cellobiose in CBA production using quinoprotein glucose dehydrogenase, this study developed a coenzyme-free and phosphate-balanced in vitro synthetic enzymatic biosystem (ivSEBS) to enable the sustainable CBA synthesis from cost-effective starch in one-pot via the CBA-synthesis module and gluconic acid-supply module. The metabolic fluxes of this artificial biosystem were strengthened using design-build-test-analysis strategy, which involved exquisite pathway design, meticulous enzyme selection, module validation and integration, and optimization of the key enzyme dosage. Under the optimized conditions, a remarkable concentration of 6.2 g/L CBA was achieved from initial 10 g/L maltodextrin with a starch-to-CBA molar conversion rate of 60 %. Taking into account that the biosystem simultaneously accumulated 3.6 g/L of gluconic acid, the maltodextrin utilization rate was calculated to be 93.3 %. Furthermore, a straightforward scaling-up process was performed to evaluate the industrial potential of this enzymatic biosystem, resulting in a yield of 21.2 g/L CBA from 50 g/L maltodextrin. This study presents an artificial ivSEBS for sustainable production of CBA from inexpensive starch, demonstrating an alternative paradigm for biomanufacturing of other aldobionic acids.


Assuntos
Gluconatos , Amido , Dissacarídeos/metabolismo
12.
Endocrine ; 2024 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-38195969

RESUMO

BACKGROUND: Inhibitor of DNA Binding 2 (ID2) plays a crucial role in tumor cell proliferation, invasion, metastasis, and stemness. Aberrant ID2 expression is associated with poor prognosis in various cancers. However, the specific function of ID2 in thyroid cancer remain unclear. METHOD: The TCGA database were utilized to explore the clinical relevance of ID2 in cancer. GO, KEGG, and TIMER were employed to predict the potential roles of ID2 in cancer. Functional analysis, including CCK-8, colony formation, transwell, wound healing, and sphere formation experiments, were conducted to determine the biological functions of ID2 in human cancers. Western blot (WB), RT-qPCR, and immunohistochemical (IHC) analyses were used to investigate the relationship between ID2 and downstream targets. RESULTS: Our study revealed significant overexpression of ID2 in various malignant tumor cells. Knocking ID2 significantly inhibited cancer cell proliferation and invasion, while overexpressing ID2 enhanced these capabilities. Additionally, ID2 mediates resistance of cancer cells to protein kinase B (or Akt) inhibitions. Further WB and IHC experiments indicated that ID2 promotes the phosphorylation activation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway, thereby upregulating the expression of downstream proliferation, epithelial-mesenchymal transition (EMT), and stemness-related markers. CONCLUSION: We found that ID2 significantly promotes thyroid cancer cell proliferation, migration, EMT, and stemness through the PI3K/Akt pathway. Moreover, ID2 plays a crucial role in regulating cancer immune responses. It may serve as a potential biomarker for enhancing the efficacy of chemotherapy, targeted therapy, and immunotherapy against cancer.

13.
Anal Bioanal Chem ; 416(1): 203-214, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37914955

RESUMO

In this study, an integrated QuEChERS method was developed for the rapid determination of 22 per- and polyfluoroalkyl substances (PFASs) in milk by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The extraction and purification processes were combined into one step with this method. Meanwhile, the solid-liquid separation was carried out by magnetic suction (Fe3O4-SiO2) instead of the centrifugal process. The primary experimental parameters were optimized, including the type of extraction solvent, the amounts of magnetic nanomaterials (Fe3O4-SiO2), and the purification materials (ZrO2 and C18). The developed method exhibits high precision (RSDs < 9.9%), low limits of detection (0.004-0.079 µg/kg) and limits of quantitation (0.01-0.26 µg/kg), and acceptable recovery (71.7-116%) under optimized conditions. The developed integrated QuEChERS method had clear superiority in terms of sample pretreatment time, operating procedures, reagent amount, and recovery. This makes it an excellent alternative analytical technique for PFAS residue measurement at low micrograms-per-kilogram ranges with desirable sensitivity.


Assuntos
Fluorocarbonos , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Extração em Fase Sólida/métodos , Leite/química , Dióxido de Silício , Fluorocarbonos/análise
14.
Thorac Cancer ; 15(1): 3-14, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38093497

RESUMO

Small cell lung cancer (SCLC) is one of the highly aggressive malignancies characterized by rapid growth and early metastasis, but treatment options are limited. For SCLC, carboplatin or cisplatin in combination with etoposide chemotherapy has been considered the only standard of care, but the standard first-line treatment only results in 10-month survival. The majority of patients relapse within a few weeks to months after treatment, despite the relatively sensitive response to chemotherapy. Over the past decade, immunotherapy has made significant progress in the treatment of SCLC patients. However, there have been limited improvements in survival rates for SCLC patients with the current immune checkpoint inhibitors PD-1/PD-L1 and CTLA-4. In the face of high recurrence rates, small beneficiary populations, and low survival benefits, the exploration of new targets for key molecules and signals in SCLC and the development of drugs with novel mechanisms may provide fresh hope for immunotherapy in SCLC. Therefore, the aim of this review was to explore four new targets, DLL3, TIGIT, LAG-3, and GD2, which may play a role in the immunotherapy of SCLC to find useful clues and strategies to improve the outcome for SCLC patients.


Assuntos
Neoplasias Pulmonares , Carcinoma de Pequenas Células do Pulmão , Humanos , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia , Cisplatino/uso terapêutico , Imunoterapia/métodos , Proteínas de Membrana , Peptídeos e Proteínas de Sinalização Intracelular
15.
Hum Immunol ; 85(1): 110745, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38142184

RESUMO

In this study, we aimed to investigate the expression of OX40, OX40L, PD-1 and PD-L1 in patients with unexplained recurrent spontaneous abortion (URSA) compared to normal pregnancies (NP). A total of 50 patients who were diagnosed with URSA and 41 NP were recruited to this study. Real-time polymerase chain reaction (RT-PCR) was used to determine the expression of OX40, OX40L, PD-1 and PD-L1 in decidual tissues; Immunohistochemistry (IHC) was conducted to characterize the distribution of the involved genes in decidual tissues; Double immunofluorescence staining was used to prove the localization of the involved genes in decidual tissues. The concentrations of OX40L and PD-L1 in plasma were measured with enzyme-linked immunosorbent assay (ELISA). The expression of OX40L in the decidua of URSA patients was significantly increased compared to that in the NP group, while the expression of PD-L1 in the URSA group was decreased compared to that in the NP group. Both proteins are localized in the decidual stroma as analyzed by double immunofluorescence staining. The staining results were confirmed at the mRNA level of decidual tissues, while the mRNA level of peripheral blood showed no significant difference. In conclusion, the results suggest that decidual stromal cells may promote the interaction with OX40 on T cells by upregulating the expression of OX40L and reduce the interaction with PD-1 on T cells by downregulating the expression of PD-L1 in URSA patients, which may interfere with the immune tolerance of the maternal-fetal interface, leading to poor pregnancy outcomes.


Assuntos
Aborto Habitual , Receptor de Morte Celular Programada 1 , Gravidez , Humanos , Feminino , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Aborto Habitual/genética , Decídua , RNA Mensageiro
16.
ACS Appl Mater Interfaces ; 15(50): 58888-58896, 2023 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-38083815

RESUMO

Developing a free radical emission system in different states, especially in water, is highly challenging and desired. Herein, a host-guest coassembly strategy was used to protect the in situ photoactivated radical emission of carbonyl compounds in solid and aqueous solutions by doping them into a series of small molecules with hydroxyl groups. The intermolecular interactions between host and guest and the electron-donating ability of the hydroxyl group can significantly promote the formation and stabilization of luminescence by carbonyl radicals. Accordingly, the stimuli-responsive property of the free radical system was investigated in detail, and the self-assembled aggregates showed photoactive and thermoresponsive behaviors. In addition, an advanced ammonia compound identification system can be built based on a radical emission system. Our design strategy sheds light on developing free radical systems that can emit in various states, which will greatly broaden the application range of free radicals.

17.
Int J Biochem Cell Biol ; 165: 106491, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38149579

RESUMO

Cancer cells prefer to utilizing aerobic glycolysis to generate energy and anabolic metabolic intermediates for cell growth. However, whether the activities of glycolytic enzymes can be regulated by specific posttranslational modifications, such as SUMOylation, in response to oncogenic signallings, thereby promoting the Warburg effect, remain largely unclear. Here, we demonstrate that phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key glycolytic enzyme, interacts with SUMO-conjugating enzyme UBC9 and is SUMOylated at K302 in glioblastoma cells. Expression of UBC9, which competitively prevents the binding of ubiquitin E3 ligase APC/C to PFKFB3 and subsequent PFKFB3 polyubiquitination, increases PFKFB3 stability and expression. Importantly, EGFR activation increases the interaction between UBC9 and PFKFB3, leading to increased SUMOylation and expression of PFKFB3. This increase is blocked by inhibition of EGFR-induced AKT activation whereas expression of activate AKT by itself was sufficient to recapitulate EGF-induced effect. Knockout of PFKFB3 expression decreases EGF-enhanced lactate production and GBM cell proliferation and this decrease was fully rescued by reconstituted expression of WT PFKFB3 whereas PFKFB3 K302R mutant expression abrogates EGF- and UBC9-regulated lactate production and GBM cell proliferation. These findings reveal a previously unknown mechanism underlying the regulation of the Warburg effect through the EGFR activation-induced and UBC9-mediated SUMOylation and stabilization of PFKFB3.


Assuntos
Glioblastoma , Humanos , Glioblastoma/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Proliferação de Células , Receptores ErbB/genética , Receptores ErbB/metabolismo , Glicólise , Lactatos/farmacologia , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismo
18.
Hepatology ; 2023 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-38016019

RESUMO

BACKGROUND AND AIMS: Base editing has shown great potential for treating human diseases with mutated genes. However, its potential for treating hepatocarcinoma (HCC) has not yet explored. APPROACH AND RESULTS: We employed adenine base editors (ABEs) to correct a TERT promoter mutation, which frequently occurs in various human cancers, including HCC. The mutated TERT promoter -124 C>T is corrected to -124 C by a single guide (sg) RNA-guided and deactivated Campylobacter jejuni Cas9 (CjCas9)-fused adenine base editor (CjABE). This edit impairs the binding of the ETS (ETS/TCF) transcription factor family, including ETS1 and GABPA, to the TERT promoter, leading to suppressed TERT promoter and telomerase activity, decreased TERT expression and cell proliferation, and increased cell senescence. Importantly, injection of adeno-associated viruses expressing sgRNA-guided CjABE or employment of lipid nanoparticle-mediated delivery of CjABE mRNA and sgRNA inhibits the growth of liver tumors harboring TERT promoter mutations. CONCLUSIONS: These findings demonstrate that a sgRNA-guided CjABE efficiently converts the mutated TERT promoter -124 C>T to -124 C in HCC cells and underscore the potential to treat HCC by the base editing-mediated correction of TERT promoter mutations.

19.
Heliyon ; 9(10): e20325, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37780757

RESUMO

Background: Salvia miltiorrhiza (Salvia miltiorrhiza Radix et Rhizoma) is the dried root and rhizome of Salvia miltiorrhiza Bge., a plant of the labiate family. It is a type of traditional Chinese medicine that can promote blood circulation for removing blood stasis. It is often used to treat cardiovascular and cerebrovascular diseases in a clinic.Aim of the study: High-quality Chinese herbal medicines are the premise of the safe and effective use of Traditional Chinese Medicine (TCM) in clinics. We aim to prove the rationality of the traditional identification method, namely, 'the redder the root colour and the thicker the root, the better is the quality', to use the morphological features of Salvia miltiorrhiza as the main index to quickly and directly evaluate its quality. Materials and methods: By referring to relevant ancient books, domestic and foreign literature, and academic papers, we summarised the research progress regarding the morphological features, functional substances, pharmacological action, and clinical efficacy of Salvia miltiorrhiza. Results: The redder the colour, the thicker the root, and the denser the texture, the better is the quality of Salvia miltiorrhiza. In Salvia miltiorrhiza, tanshinone ⅡA and salvianolic acid B are the main functional substances that protect the cardiovascular and cerebrovascular functions. The higher the content of these two functional substances, the better is the clinical efficacy of Salvia miltiorrhiza. Conclusion: The research idea of the correlation between the 'morphological features, functional substances, pharmacological action, and clinical efficacy' can be applied to evaluate the quality of Salvia miltiorrhiza. This research idea and method can also be applied to more Chinese herbal medicines.

20.
Molecules ; 28(19)2023 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-37836792

RESUMO

Fabricating heterostructures with abundant interfaces and delicate nanoarchitectures is an attractive approach for optimizing photocatalysts. Herein, we report the facile synthesis of BiOCl nanoflake/FeOCl nanospindle heterostructures through a solution chemistry method at room temperature. Characterizations, including XRD, SEM, TEM, EDS, and XPS, were employed to investigate the synthesized materials. The results demonstrate that the in situ reaction between the Bi precursors and the surface Cl- of FeOCl enabled the bounded nucleation and growth of BiOCl on the surface of FeOCl nanospindles. Stable interfacial structures were established between BiOCl nanoflakes and FeOCl nanospindles using Cl- as the bridge. Regulating the Bi-to-Fe ratios allowed for the optimization of the BiOCl/FeOCl interface, thereby facilitating the separation of photogenerated carriers and accelerating the photocatalytic degradation of RhB. The BiOCl/FeOCl heterostructures with an optimal composition of 15% BiOCl exhibited ~90 times higher visible-light photocatalytic activity than FeOCl. Based on an analysis of the band structures and reactive oxygen species, we propose an S-scheme mechanism to elucidate the significantly enhanced photocatalytic performance observed in the BiOCl/FeOCl heterostructures.

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