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1.
Proc Natl Acad Sci U S A ; 121(28): e2321193121, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38954549

RESUMO

Iron antimonide (FeSb2) has been investigated for decades due to its puzzling electronic properties. It undergoes the temperature-controlled transition from an insulator to an ill-defined metal, with a cross-over from diamagnetism to paramagnetism. Extensive efforts have been made to uncover the underlying mechanism, but a consensus has yet to be reached. While macroscopic transport and magnetic measurements can be explained by different theoretical proposals, the essential spectroscopic evidence required to distinguish the physical origin is missing. In this paper, through the use of X-ray absorption spectroscopy and atomic multiplet simulations, we have observed the mixed spin states of 3d 6 configuration in FeSb2. Furthermore, we reveal that the enhancement of the conductivity, whether induced by temperature or doping, is characterized by populating the high-spin state from the low-spin state. Our work constitutes vital spectroscopic evidence that the electrical/magnetical transition in FeSb2 is directly associated with the spin-state excitation.

2.
Nanoscale ; 16(27): 12883-12908, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38919996

RESUMO

Gas sensors are essential for ensuring public safety and improving quality of life. Room-temperature gas sensors are notable for their potential economic benefits and low energy consumption, and their expected integration with wearable electronics, making them a focal point of contemporary research. Advances in nanomaterials and low-dimensional semiconductors have significantly contributed to the enhancement of room-temperature gas sensors. These advancements have focused on improving sensitivity, selectivity, and response/recovery times, with nanocomposites offering distinct advantages. The discussion here focuses on the use of semiconductor nanocomposites for gas sensing at room temperature, and provides a review of the latest synthesis techniques for these materials. This involves the precise adjustment of chemical compositions, microstructures, and morphologies. In addition, the design principles and potential functional mechanisms are examined. This is crucial for deepening the understanding and enhancing the operational capabilities of sensors. We also highlight the challenges faced in scaling up the production of nanocomposite materials. Looking ahead, semiconductor nanocomposites are expected to drive innovation in gas sensor technology due to their carefully crafted design and construction, paving the way for their extensive use in various sectors.

3.
Microsyst Nanoeng ; 10: 65, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38784375

RESUMO

The development of artificial intelligence-enabled medical health care has created both opportunities and challenges for next-generation biosensor technology. Proteins are extensively used as biological macromolecular markers in disease diagnosis and the analysis of therapeutic effects. Electrochemical protein biosensors have achieved desirable specificity by using the specific antibody-antigen binding principle in immunology. However, the active centers of protein biomarkers are surrounded by a peptide matrix, which hinders charge transfer and results in insufficient sensor sensitivity. Therefore, electrode-modified materials and transducer devices have been designed to increase the sensitivity and improve the practical application prospects of electrochemical protein sensors. In this review, we summarize recent reports of electrochemical biosensors for protein biomarker detection. We highlight the latest research on electrochemical protein biosensors for the detection of cancer, viral infectious diseases, inflammation, and other diseases. The corresponding sensitive materials, transducer structures, and detection principles associated with such biosensors are also addressed generally. Finally, we present an outlook on the use of electrochemical protein biosensors for disease marker detection for the next few years.

4.
Lab Chip ; 24(7): 1875-1886, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38372578

RESUMO

Recently protein binders have emerged as a promising substitute for antibodies due to their high specificity and low cost. Herein, we demonstrate an electrochemical biosensor chip through the electronic labelling strategy using lead sulfide (PbS) colloidal quantum dots (CQDs) and the unnatural SARS-CoV-2 spike miniprotein receptor LCB. The unnatural receptor can be utilized as a molecular probe for the construction of CQD-based electrochemical biosensor chips, through which the specific binding of LCB and the spike protein is transduced to sensor electrical signals. The biosensor exhibits a good linear response in the concentration range of 10 pg mL-1 to 1 µg mL-1 (13.94 fM to 1.394 nM) with the limit of detection (LOD) being 3.31 pg mL-1 (4.607 fM for the three-electrode system) and 9.58 fg mL-1 (0.013 fM for the HEMT device). Due to the high sensitivity of the electrochemical biosensor, it was also used to study the binding kinetics between the unnatural receptor LCB and spike protein, which has achieved comparable results as those obtained with commercial equipment. To the best of our knowledge, this is the first example of using a computationally designed miniprotein receptor based on electrochemical methods, and it is the first kinetic assay performed with an electrochemical assay alone. The miniprotein receptor electrochemical biosensor based on QDs is desirable for fabricating high-throughput, large-area, wafer-scale biochips.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Pontos Quânticos/química , Glicoproteína da Espícula de Coronavírus , Técnicas Eletroquímicas , Limite de Detecção
5.
Biomed Pharmacother ; 170: 115976, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38043444

RESUMO

T helper (Th) cells have received extensive attention owing to their indispensable roles in anti-tumor immune responses. Th1 and Th2 cells are two key subsets of Th cells that exist in relative equilibrium through the secretion of cytokines that suppress their respective immune response. When the type of cytokine in the tumor microenvironment is altered, this equilibrium may be disrupted, leading to a shift from Th1 to Th2 immune response. Th1/Th2 imbalance is one of the decisive factors in the development of malignant tumors. Therefore, focusing on the balance of Th1/Th2 anti-tumor immune responses may enable future breakthroughs in cancer immunotherapy. Polysaccharides can regulate the imbalance between Th1 and Th2 cells and their characteristic cytokine profiles, thereby improving the tumor immune microenvironment. To our knowledge, this study is the most comprehensive assessment of the regulation of the tumor Th1/Th2 balance by polysaccharides. Herein, we systematically summarized the intrinsic molecular mechanisms of polysaccharides in the regulation of Th1 and Th2 cells to provide a new perspective and potential target drugs for improved anti-tumor immunity and delayed tumor progression.


Assuntos
Neoplasias , Células Th1 , Humanos , Células Th2 , Citocinas , Imunoterapia , Neoplasias/tratamento farmacológico , Polissacarídeos/uso terapêutico , Microambiente Tumoral
6.
Br J Pharmacol ; 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37940117

RESUMO

Angiogenesis is the process by which new blood vessels form and is required for tumour growth and metastasis. It helps in supplying oxygen and nutrients to tumour cells and plays a crucial role in the local progression and distant metastasis of, and development of treatment resistance in, breast cancer. Tumour angiogenesis is currently regarded as a critical therapeutic target; however, anti-angiogenic therapy for breast cancer fails to produce satisfactory results, owing to issues such as inconsistent efficacy and significant adverse reactions. As a result, new anti-angiogenic drugs are urgently needed. Flavonoids, a class of natural compounds found in many foods, are inexpensive, widely available, and exhibit a broad range of biological activities, low toxicity, and favourable safety profiles. Several studies find that various flavonoids inhibit angiogenesis in breast cancer, indicating great therapeutic potential. In this review, we summarize the role of angiogenesis in breast cancer and the potential of natural flavonoids as anti-angiogenic agents for breast cancer treatment. We discuss the value and significance of nanotechnology for improving flavonoid absorption and utilization and anti-angiogenic effects, as well as the challenges of using natural flavonoids as drugs.

7.
Lipids Health Dis ; 22(1): 186, 2023 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-37924128

RESUMO

BACKGROUND: The elevation of TyG is considered an important factor in promoting the progression of non-alcoholic fatty liver disease (NAFLD), but its impact on the degree of liver steatosis remains unclear. This study aims to explore the relationship between TyG and TyG-related indices, such as triglyceride glucose-body mass index (TyG-BMI), with the degree of liver fat accumulation. METHODS: From January 2021 to March 2022, 1171 participants underwent health check-ups, and all underwent FibroScan transient elastography. The analysis focused on identifying the factors that contribute to the onset of NAFLD and the degree of hepatic steatosis. RESULTS: The predictive value of TyG-BMI (OR = 1.039, 95% CI 1.031-1.046) in triggering NAFLD development was greater than that of TyG alone. The areas under the curve for TyG-BMI and TyG were calculated at 0.808 and 0.720, respectively. TyG-BMI (OR = 1.034, P < 0.001) was identified as a main independent factor affecting hepatic steatosis severity. With each incremental increase in TyG-BMI, the likelihood of experiencing an increase in the extent of hepatic steatosis was 1.034 times higher than that of the preceding unit. CONCLUSIONS: The TyG-BMI showed higher accuracy in predicting NAFLD than did the TyG, and was more closely linked to the severity of hepatic steatosis. Therefore, it can be included as a parameter in health management centers and should be widely used to screen and evaluate patients with NAFLD.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Glucose , Índice de Massa Corporal , Triglicerídeos
8.
Biomed Pharmacother ; 168: 115707, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37862969

RESUMO

In Chinese medicine, the Cucurbitaceae family contains many compounds known as cucurbitacins, which have been categorized into 12 classes ranging from A to T and more than 200 derivatives. Cucurbitacins are a class of highly oxidized tetracyclic triterpenoids with potent anticancer properties. The eight components of cucurbitacins with the strongest anticancer activity are cucurbitacins B, D, E, I, IIa, L-glucoside, Q, and R. Cucurbitacins have also been reported to suppress JAK-STAT 3, mTOR, VEGFR, Wnt/ß-catenin, and MAPK signaling pathways, all of which are crucial for the survival and demise of cancer cells. In this paper, we review the progress in research on cucurbitacin-induced apoptosis, autophagy, cytoskeleton disruption, cell cycle arrest, inhibition of cell proliferation, inhibition of invasion and migration, inhibition of angiogenesis, epigenetic alterations, and synergistic anticancer effects in tumor cells. Recent studies have identified cucurbitacins as promising molecules for therapeutic innovation with broad versatility in immune response. Thus, cucurbitacin is a promising class of anticancer agents that can be used alone or in combination with chemotherapy and radiotherapy for the treatment of many types of cancer.Therefore, based on the research reports in the past five years at home and abroad, we further summarize and review the structural characteristics, chemical and biological activities, and studies of cucurbitacins based on the previous studies to provide a reference for further development and utilization of cucurbitacins.


Assuntos
Antineoplásicos , Neoplasias , Triterpenos , Humanos , Cucurbitacinas/farmacologia , Cucurbitacinas/uso terapêutico , Cucurbitacinas/química , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pontos de Checagem do Ciclo Celular , Proliferação de Células
9.
Front Pharmacol ; 14: 1250893, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37841927

RESUMO

The Wnt/ß-catenin pathway is abnormally activated in most lung cancer tissues and considered to be an accelerator of carcinogenesis and lung cancer progression, which is closely related to increased morbidity rates, malignant progression, and treatment resistance. Although targeting the canonical Wnt/ß-catenin pathway shows significant potential for lung cancer therapy, it still faces challenges owing to its complexity, tumor heterogeneity and wide physiological activity. Therefore, it is necessary to elucidate the role of the abnormal activation of the Wnt/ß-catenin pathway in lung cancer progression. Moreover, Wnt inhibitors used in lung cancer clinical trials are expected to break existing therapeutic patterns, although their adverse effects limit the treatment window. This is the first study to summarize the research progress on various compounds, including natural products and derivatives, that target the canonical Wnt pathway in lung cancer to develop safer and more targeted drugs or alternatives. Various natural products have been found to inhibit Wnt/ß-catenin in various ways, such as through upstream and downstream intervention pathways, and have shown encouraging preclinical anti-tumor efficacy. Their diversity and low toxicity make them a popular research topic, laying the foundation for further combination therapies and drug development.

10.
Adv Sci (Weinh) ; 10(26): e2302778, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37442769

RESUMO

Various catalysts are developed to improve the performance of metal oxide semiconductor gas sensors, but achieving high selectivity and response intensity in chemiresistive gas sensors (CGSs) remains a significant challenge. In this study, an in situ-annealing approach to synthesize Cu catalytic sites on ultrathin WO2.72 nanowires for detecting toluene at ultralow concentrations (Ra /Rg = 1.9 at 10 ppb) with high selectivity is developed. Experimental and molecular dynamic studies reveal that the Cu single atoms (SAs) act as active sites, promoting the oxidation of toluene and increasing the affinity of Cu single-atom catalysts (SACs)-containing sensing materials for toluene while weakening the association with carbon dioxide or water vapor. Density functional theory studies show that the selective binding of toluene to Cu SAs is due to the favorable binding sites provided by Cu SAs for toluene molecules over other gaseous species, which aids the adsorption of toluene on WO2.72 nanowires. This study demonstrates the successful atomic-level interface regulation engineering of WO2.72 nanowire-supported Cu SAs, providing a potential strategy for the development of highly active and durable CGSs.

11.
Crit Rev Food Sci Nutr ; : 1-17, 2023 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-37128778

RESUMO

Natural plants have acquired an increasing attention in biomedical research. Recent studies have revealed that plant-derived nanoparticles (PDNPs), which are nano-sized membrane vesicles released by plants, are one of the important material bases for the health promotion of natural plants. A great deal of research in this field has focused on nanoparticles derived from fresh vegetables and fruits. Generally, PDNPs contain lipids, proteins, nucleic acids, and other active small molecules and exhibit unique biological regulatory activity and editability. Specifically, they have emerged as important mediators of intercellular communication, and thus, are potentially suitable for therapeutic purposes. In this review, PDNPs were extensively explored; by evaluating them systematically starting from the origin and isolation, toward their characteristics, including morphological compositions, biological functions, and delivery potentials, as well as distinguishing them from plant-derived exosomes and highlighting the limitations of the current research. Meanwhile, we elucidated the variations in PDNPs infected by pathogenic microorganisms and emphasized on the biological functions and characteristics of plant virus nanoparticles. After clarifying these problems, it is beneficial to further research on PDNPs in the future and develop their clinical application value.

12.
Biomed Pharmacother ; 162: 114698, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37060661

RESUMO

With the rapid development of next-generation sequencing technology, several studies have shown that ncRNAs can act as competitive endogenous RNAs (ceRNAs) and are involved in various biological processes, such as proliferation, differentiation, apoptosis, and migration of breast cancer (BC) cells, and plays an important role in BC progression as a molecular target for its diagnosis, treatment, prognosis, and differentiation of subtypes and age groups of BC patients. Based on the description of ceRNA-related biological functions, this study screened and sorted the sequencing analysis and experimental verification conclusions of BC-related ceRNAs and found that the ncRNAs mediated ceRNA networks can promote the development of BC by promoting the expression of genes related to BC proliferation, drug resistance, and apoptosis, inducing the production of epithelial-mesenchymal transition (EMT) to promote metastasis and activating cancer-related signaling pathways.


Assuntos
Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Humanos , Feminino , Neoplasias da Mama/genética , MicroRNAs/genética , Transcriptoma , RNA não Traduzido/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , RNA Longo não Codificante/genética , Regulação Neoplásica da Expressão Gênica
13.
ACS Appl Mater Interfaces ; 15(12): 15707-15720, 2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-36924356

RESUMO

The analysis of exhaled breath has opened up new exciting avenues in medical diagnostics, sleep monitoring, and drunk driving detection. Nevertheless, the detection accuracy is greatly affected due to high humidity in the exhaled breath. Here, we propose a regulation method to solve the problem of humidity adaptability in the ethanol-monitoring process by building a heterojunction and hollow-out nanostructure. Therefore, large specific surface area hollow-out Fe2O3-loaded NiO heterojunction nanorods assembled by porous ultrathin nanosheets were prepared by a well-tailored interface reaction. The excellent response (51.2 toward 10 ppm ethanol at 80% relative humidity) and selectivity to ethanol under high relative humidity with a lower operating temperature (150 °C) were obtained, and the detection limit was as low as 0.5 ppb with excellent long-term stability. The superior gas-sensing performance was attributed to the high surface activity of the heterojunction and hollow-out nanostructure. More importantly, GC-MS, diffuse reflectance Fourier transform infrared spectroscopy, and DFT were utilized to analyze the mechanisms of heterojunction sensitization, ethanol-sensing reaction, and high-humidity adaptability. Our integrated low-power MEMS Internet of Things (IoT) system based on Fe2O3@NiO successfully demonstrates the functional verification of ethanol detection in human exhalation, and the integrated voice alarm and IoT positioning functions are expected to solve the problem of real-time monitoring and rapid initial screening of drunk driving. Overall, this novel method plays a vital role in areas such as control of material morphology and composition, breath analysis, gas-sensing mechanism research, and artificial olfaction.


Assuntos
Nanoestruturas , Nanotubos , Humanos , Umidade , Expiração , Etanol/análise , Nanoestruturas/química
14.
Biosensors (Basel) ; 13(2)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36832021

RESUMO

Myeloperoxidase (MPO) has been demonstrated to be a biomarker of neutrophilic inflammation in various diseases. Rapid detection and quantitative analysis of MPO are of great significance for human health. Herein, an MPO protein flexible amperometric immunosensor based on a colloidal quantum dot (CQD)-modified electrode was demonstrated. The remarkable surface activity of CQDs allows them to bind directly and stably to the surface of proteins and to convert antigen-antibody specific binding reactions into significant currents. The flexible amperometric immunosensor provides quantitative analysis of MPO protein with an ultra-low limit of detection (LOD) (31.6 fg mL-1), as well as good reproducibility and stability. The detection method is expected to be applied in clinical examination, POCT (bedside test), community physical examination, home self-examination and other practical scenarios.


Assuntos
Técnicas Biossensoriais , Pontos Quânticos , Humanos , Peroxidase , Técnicas Biossensoriais/métodos , Reprodutibilidade dos Testes , Imunoensaio/métodos , Proteínas , Limite de Detecção , Biomarcadores
15.
Ground Water ; 61(5): 692-705, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36524846

RESUMO

Although groundwater overexploitation is a global problem, there are no unified standards for its identification and determination. To date, groundwater overexploitation has mainly been evaluated using the groundwater quantity balance and effect of groundwater exploitation on the environment. However, it is difficult to determine groundwater exploitation for an agricultural irrigation area owing to the lack of detailed environmental monitoring data. We used the experience of previous studies to introduce a novel identification model for groundwater overexploitation by relying on groundwater regime information and multi-factor analysis. The model was applied to the Songhua River-Naoli River area, Sanjiang Plain (China). In the demonstrated model, the study area was divided in the context of the risk of overexploitation into natural and non-natural regime areas according to groundwater regime characteristics. The areas were identified by analyzing groundwater flow fields, cones of groundwater depression, and storage variation. The analysis demonstrated that the study area could be divided into high-risk, medium-risk, low-risk, and non-overexploitation areas with corresponding area ratios of 10.12%, 1.38%, 54.8%, and 33.7%. Moreover, the total amount of overexploited groundwater was estimated to be 30.41 × 108 m3 (average annual decrease = 1.69 × 108 m3 ). Overall, the proposed identification model was shown to be applicable to agricultural irrigation areas, thereby offering promising implications.

16.
Front Cell Dev Biol ; 11: 1332205, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38264357

RESUMO

Galectin-9 (Gal-9) is a vital member of the galectin family, functioning as a multi-subtype galactose lectin with diverse biological roles. Recent research has revealed that Gal-9's interaction with tumors is an independent factor that influences tumor progression. Furthermore, Gal-9 in the immune microenvironment cross-talks with tumor-associated immune cells, informing the clarification of Gal-9's identity as an immune checkpoint. A thorough investigation into Gal-9's role in various cancer types and its interaction with the immune microenvironment could yield novel strategies for subsequent targeted immunotherapy. This review focuses on the latest advances in understanding the direct and indirect cross-talk between Gal-9 and hematologic malignancies, in addition to solid tumors. In addition, we discuss the prospects of Gal-9 in tumor immunotherapy, including its cross-talk with the ligand TIM-3 and its potential in immune-combination therapy.

17.
Molecules ; 29(1)2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38202588

RESUMO

The demand for the ubiquitous detection of gases in complex environments is driving the design of highly specific gas sensors for the development of the Internet of Things, such as indoor air quality testing, human exhaled disease detection, monitoring gas emissions, etc. The interaction between analytes and bioreceptors can described as a "lock-and-key", in which the specific catalysis between enzymes and gas molecules provides a new paradigm for the construction of high-sensitivity and -specificity gas sensors. The electrochemical method has been widely used in gas detection and in the design and construction of enzyme-based electrochemical gas sensors, in which the specificity of an enzyme to a substrate is determined by a specific functional domain or recognition interface, which is the active site of the enzyme that can specifically catalyze the gas reaction, and the electrode-solution interface, where the chemical reaction occurs, respectively. As a result, the engineering design of the enzyme electrode interface is crucial in the process of designing and constructing enzyme-based electrochemical gas sensors. In this review, we summarize the design of enzyme-based electrochemical gas sensors. We particularly focus on the main concepts of enzyme electrodes and the selection and design of materials, as well as the immobilization of enzymes and construction methods. Furthermore, we discuss the fundamental factors that affect electron transfer at the enzyme electrode interface for electrochemical gas sensors and the challenges and opportunities related to the design and construction of these sensors.


Assuntos
Técnicas Eletroquímicas , Gases , Humanos , Catálise , Eletrodos , Transporte de Elétrons
18.
Biomed Pharmacother ; 156: 113951, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36411636

RESUMO

Polyphenol compounds are natural antioxidants, which are rich in anti-inflammatory and antioxidant components. They have a wide range of medicinal benefits that are believed to improve human health across various aspects; especially its anticancer effect has been gradually confirmed. The anticancer effect of polyphenols is mainly based on their strong antioxidant and immunomodulatory effects. The innate and adaptive immune responses as well as the development and maintenance of cells and tissues of the immune system are regulated by the NF-κB family of transcription factors. Dysregulation of NF-κB can lead to autoimmune diseases, chronic inflammation, and even cancer. Polyphenol compounds can exert antioxidant and immunomodulatory effects by targeting NF-κB, thus hindering the occurrence and development of tumors.Polyphenol compounds have unique advantages over conventional anticancer therapies such as chemotherapy because they have few side effects and do not cause toxicity to healthy cells. Additionally, they can attenuate the toxic effects of current anticancer therapies. Based on these characteristics, polyphenols have great potential in the prevention and treatment of cancer. This article systematically summarizes the mechanism of NF-κB in tumor genesis, progression, metastasis, angiogenesis, and drug resistance. In addition, we present the anticancer effect of polyphenol compounds by targeting NF-κB during the different stages of tumorigenesis.


Assuntos
NF-kappa B , Neoplasias , Humanos , NF-kappa B/fisiologia , Polifenóis/farmacologia , Polifenóis/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Proteínas I-kappa B , Neoplasias/tratamento farmacológico
19.
Front Nutr ; 9: 989989, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204371

RESUMO

High-throughput next-generation sequencing (NGS) provides insights into genome-wide mutations and can be used to identify biomarkers for the prediction of immune and targeted responses. A deeper understanding of the molecular biological significance of genetic variation and effective interventions is required and ultimately needs to be associated with clinical benefits. We conducted a retrospective observational study of patients in two cancer cohorts who underwent NGS in a "real-world" setting. The association between differences in tumor mutational burden (TMB) and clinical presentation was evaluated. We aimed to identify several key mutation targets and describe their biological characteristics and potential clinical value. A pan-cancer dataset was downloaded as a verification set for further analysis and summary. Natural product screening for the targeted intervention of key markers was also achieved. The majority of tumor patients were younger adult males with advanced cancer. The gene identified with the highest mutation rate was TP53, followed by PIK3CA, EGFR, and LRP1B. The association of TMB (0-103.7 muts/Mb) with various clinical subgroups was determined. More frequent mutations, such as in LRP1B, as well as higher levels of ferritin and neuron-specific enolase, led to higher TMB levels. Further analysis of the key targets, LRP1B and APC, was performed, and mutations in LRP1B led to better immune benefits compared to APC. APC, one of the most frequently mutated genes in gastrointestinal tumors, was further investigated, and the potential interventions by cochinchinone B and rottlerin were clarified. In summary, based on the analysis of the characteristics of gene mutations in the "real world," we obtained the potential association indicators of TMB, found the key signatures LRP1B and APC, and further described their biological significance and potential interventions.

20.
Biomed Pharmacother ; 156: 113861, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36228375

RESUMO

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that is highly aggressive and hypoxic compared with other subtypes. The role of hypoxia inducible factor 1α (HIF-1α) as a key hypoxic transcription factor in oncogenic processes has been extensively studied. Recently, it has been shown that HIF-1α regulates the complex biological processes of TNBC, such as glycolysis, angiogenesis, invasion and metastasis, breast cancer stem cells (BCSCs) enrichment, and immune escape, to promote TNBC survival and development through the activation of downstream target genes. In addition, inflammatory mediators, oxygen levels, noncoding RNAs, complex signaling regulatory networks, epigenetic regulators are involved in the upstream regulatory expression of HIF-1α. However, further studies are needed to determine the potential and future directions of targeting HIF-1α in TNBC. This article discusses the expression of the HIF-1α transcription factor in TNBC. We also explored the mechanism by which HIF-1α drives TNBC progression. The potential significance of targeting HIF-1α for immunotherapy, chemotherapy, anti-angiogenic therapy, and photodynamic therapy is discussed. The intrinsic mechanism, existing problems and future directions of targeting HIF-1α are also studied.


Assuntos
Neoplasias de Mama Triplo Negativas , Humanos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neovascularização Patológica/metabolismo , Transdução de Sinais , Linhagem Celular Tumoral
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