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1.
Proc Natl Acad Sci U S A ; 121(24): e2321758121, 2024 Jun 11.
Article En | MEDLINE | ID: mdl-38830093

Impulsivity is a personality construct frequently employed to explain and predict important human behaviors. Major inconsistencies in its definition and measurement, however, have led some researchers to call for an outright rejection of impulsivity as a psychological construct. We address this highly unsatisfactory state with a large-scale, preregistered study (N = 1,676) in which each participant completed 48 measures of impulsivity derived from 10 self-report scales and 10 behavioral tasks and reported frequencies of seven impulsivity-related behaviors (e.g., impulsive buying and social media usage); a subsample (N = 196) then completed a retest session 3 mo later. We found that correlations between self-report measures were substantially higher than those between behavioral tasks and between self-report measures and behavioral tasks. Bifactor analysis of these measures exacted one general factor of impulsivity I, akin to the general intelligence factor g, and six specific factors. Factor I was related mainly to self-report measures, had high test-retest reliability, and could predict impulsivity-related behaviors better than existing measures. We further developed a scale named the adjustable impulsivity scale (AIMS) to measure I. AIMS possesses excellent psychometric properties that are largely retained in shorter versions and could predict impulsivity-related behaviors equally well as I. These findings collectively support impulsivity as a stable, measurable, and predictive trait, indicating that it may be too early to reject it as a valid and useful psychological construct. The bifactorial structure of impulsivity and AIMS, meanwhile, significantly advance the conceptualization and measurement of construct impulsivity.


Impulsive Behavior , Humans , Male , Female , Adult , Self Report , Personality , Young Adult , Adolescent , Reproducibility of Results , Middle Aged
2.
iScience ; 27(6): 109979, 2024 Jun 21.
Article En | MEDLINE | ID: mdl-38832007

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

3.
Front Psychol ; 15: 1382693, 2024.
Article En | MEDLINE | ID: mdl-38694439

The rapid advancement of artificial intelligence (AI) has impacted society in many aspects. Alongside this progress, concerns such as privacy violation, discriminatory bias, and safety risks have also surfaced, highlighting the need for the development of ethical, responsible, and socially beneficial AI. In response, the concept of trustworthy AI has gained prominence, and several guidelines for developing trustworthy AI have been proposed. Against this background, we demonstrate the significance of psychological research in identifying factors that contribute to the formation of trust in AI. Specifically, we review research findings on interpersonal, human-automation, and human-AI trust from the perspective of a three-dimension framework (i.e., the trustor, the trustee, and their interactive context). The framework synthesizes common factors related to trust formation and maintenance across different trust types. These factors point out the foundational requirements for building trustworthy AI and provide pivotal guidance for its development that also involves communication, education, and training for users. We conclude by discussing how the insights in trust research can help enhance AI's trustworthiness and foster its adoption and application.

4.
Insect Mol Biol ; 2024 May 31.
Article En | MEDLINE | ID: mdl-38818901

Arylalkylamine N-acetyltransferase (aaNAT) is a crucial enzyme that catalyses the transfer of acetyl groups from acetyl coenzyme A to arylalkylamines and arylamines. Evolutionary studies have identified a distinct class of aaNATs specific to mosquitoes, yet their functions remain elusive. This study focuses on Ae-aaNAT7, a mosquito-unique gene in Aedes aegypti (Diptera:Culicidae), to explore its functionality. Temporal and spatial expression analysis of Ae-aaNAT7 mRNA revealed high expression during embryonic development and in first-instar larvae, with notable expression in the limbs of adult mosquitoes based on tissue expression profiling. By further employing CRISPR/Cas9 technology for loss-of-function studies, our investigation revealed a reduction in the area of white spotting in the limbs of Ae-aaNAT7 mutant adult mosquitoes. Further investigation revealed a significant decrease in the fecundity and hatchability of the mutants. Dissection of the ovaries from Ae-aaNAT7 heterozygous mutants showed a noticeable reduction in the oocyte area compared with wild type. Dissection of the exochorion of the eggs from Ae-aaNAT7 homozygous mutants consistently revealed a striking absence of mature embryos. In addition, RNA interference experiments targeting Ae-aaNAT7 in males resulted in a reduction in fecundity, but no effect on hatchability was observed. These collective insights underscore the substantial impact of Ae-aaNAT7 on reproduction and its pivotal contribution to adult limb pigmentation in Ae. aegypti. These revelations offer insights pivotal for the strategic design of future insecticide targets.

5.
J Nanobiotechnology ; 22(1): 240, 2024 May 12.
Article En | MEDLINE | ID: mdl-38735931

Zinc oxide nanoparticles (ZnO NPs) stand as among the most significant metal oxide nanoparticles in trigger the formation of reactive oxygen species (ROS) and induce apoptosis. Nevertheless, the utilization of ZnO NPs has been limited by the shallowness of short-wavelength light and the constrained production of ROS. To overcome these limitations, a strategy involves achieving a red shift towards the near-infrared (NIR) light spectrum, promoting the separation and restraining the recombination of electron-hole (e--h+) pairs. Herein, the hybrid plasmonic system Au@ZnO (AZ) with graphene quantum dots (GQDs) doping (AZG) nano heterostructures is rationally designed for optimal NIR-driven cancer treatment. Significantly, a multifold increase in ROS generation can be achieved through the following creative initiatives: (i) plasmonic Au nanorods expands the photocatalytic capabilities of AZG into the NIR domain, offering a foundation for NIR-induced ROS generation for clinical utilization; (ii) elaborate design of mesoporous core-shell AZ structures facilitates the redistribution of electron-hole pairs; (iii) the incorporation GQDs in mesoporous structure could efficiently restrain the recombination of the e--h+ pairs; (iv) Modification of hyaluronic acid (HA) can enhance CD44 receptor mediated targeted triple-negative breast cancer (TNBC). In addition, the introduced Au NRs present as catalysts for enhancing photothermal therapy (PTT), effectively inducing apoptosis in tumor cells. The resulting HA-modified AZG (AZGH) exhibits efficient hot electron injection and e--h+ separation, affording unparalleled convenience for ROS production and enabling NIR-induced PDT for the cancer treanment. As a result, our well-designed mesoporous core-shell AZGH hybrid as photosensitizers can exhibit excellent PDT efficacy.


Gold , Graphite , Oxidative Stress , Quantum Dots , Reactive Oxygen Species , Triple Negative Breast Neoplasms , Zinc Oxide , Triple Negative Breast Neoplasms/drug therapy , Reactive Oxygen Species/metabolism , Humans , Oxidative Stress/drug effects , Female , Cell Line, Tumor , Gold/chemistry , Graphite/chemistry , Zinc Oxide/chemistry , Animals , Quantum Dots/chemistry , Mice , Metal Nanoparticles/chemistry , Apoptosis/drug effects , Hyaluronic Acid/chemistry , Electrons
6.
World J Gastroenterol ; 30(19): 2612-2614, 2024 May 21.
Article En | MEDLINE | ID: mdl-38817654

Heartburn is a common symptom shared by both gastroesophageal reflux disease (GERD) and functional heartburn (FHB), which can make it challenging to differentiate between the two conditions. However, examining oral manifestations of GERD can be a cost-effective and readily available method to aid in this differentiation process. It may serve as a valuable tool in distinguishing GERD from FHB.


Gastroesophageal Reflux , Heartburn , Pepsin A , Saliva , Humans , Gastroesophageal Reflux/diagnosis , Gastroesophageal Reflux/microbiology , Saliva/microbiology , Heartburn/diagnosis , Heartburn/etiology , Pepsin A/analysis , Pepsin A/metabolism , Diagnosis, Differential , Biomarkers/analysis , Biomarkers/metabolism
7.
Small ; : e2401147, 2024 May 21.
Article En | MEDLINE | ID: mdl-38770990

Cuproptosis, a recently discovered copper-dependent cell death, presents significant potential for the development of copper-based nanoparticles to induce cuproptosis in cancer therapy. Herein, a unique ternary heterojunction, denoted as HACT, composed of core-shell Au@Cu2O nanocubes with surface-deposited Titanium Dioxide quantum dots and modified with hyaluronic acid is introduced. Compared to core-shell AC NCs, the TiO2/Au@Cu2O exhibits improved energy structure optimization, successfully separating electron-hole pairs for redox use. This optimization results in a more rapid generation of singlet oxygen and hydroxyl radicals triggering oxidative stress under ultrasound radiation. Furthermore, the HACT NCs initiate cuproptosis by Fenton-like reaction and acidic environment, leading to the sequential release of cupric and cuprous ions. This accumulation of copper induces the aggregation of lipoylated proteins and reduces iron-sulfur proteins, ultimately initiating cuproptosis. More importantly, HACT NCs show a tendency to selectively target cancer cells, thereby granting them a degree of biosecurity. This report introduces a ternary heterojunction capable of triggering both cuproptosis and oxidative stress-related combination therapy in a stimulus-responsive manner. It can energize efforts to develop effective melanoma treatment strategies using Cu-based nanoparticles through rational design.

8.
Front Public Health ; 12: 1349514, 2024.
Article En | MEDLINE | ID: mdl-38601500

Objective: To test the validity and reliability of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) in oncology nurses, the Chinese version was developed. Methods: The Brislin double translation-back translation approach was employed to forward translation, back translation, synthesis, cross-cultural adaptation, and pre-survey, resulting in the first Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON). A convenience sample technique was used to select 350 study participants in Liaoning, Shandong, and Jiangsu, China, who satisfied the inclusion and exclusion criteria, to assess the validity and reliability of the scale. Results: The Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) had six subscales (perceived threat, perceived benefits, perceived barriers, self-efficacy, cues to action, and personal protective equipment availability and accessibility), including 29 items. The average scale level was 0.931, and the content validity level of the items varied from 0.857 to 1.000. Each Cronbach's α coefficient had an acceptable internal consistency reliability range of 0.806 to 0.902. X2/df = 1.667, RMSEA = 0.044, RMR = 0.018, CFI = 0.959, NFI = 0.905, TLI = 0.954, and IFI = 0.960 were the model fit outcomes in the validation factor analysis. All of the model fit markers fell within reasonable bounds. Conclusion: The Chinese version of the Oncology Nurses Health Behaviors Determinants Scale (HBDS-ON) has good reliability and validity and can be used as a tool to assess the influencing factors of chemotherapy exposure for oncology nurses in China.


Asian People , Humans , Cross-Sectional Studies , Psychometrics , Reproducibility of Results , Surveys and Questionnaires
9.
J Mater Chem B ; 12(17): 4063-4079, 2024 May 01.
Article En | MEDLINE | ID: mdl-38572575

DNA methylation is the process by which specific bases on a DNA sequence acquire methyl groups under the catalytic action of DNA methyltransferases (DNMT). Abnormal changes in the function of DNMT are important markers for cancers and other diseases; therefore, the detection of DNMT and the selection of its inhibitors are critical to biomedical research and clinical practice. DNA molecules can undergo intermolecular assembly to produce functional aggregates because of their inherently stable physical and chemical properties and unique structures. Conventional DNMT detection methods are cumbersome and complicated processes; therefore, it is necessary to develop biosensing technology based on the assembly of DNA nanostructures to achieve rapid analysis, simple operation, and high sensitivity. The design of the relevant program has been employed in life science, anticancer drug screening, and clinical diagnostics. In this review, we explore how DNA assembly, including 2D techniques like hybridization chain reaction (HCR), rolling circle amplification (RCA), catalytic hairpin assembly (CHA), and exponential isothermal amplified strand displacement reaction (EXPAR), as well as 3D structures such as DNA tetrahedra, G-quadruplexes, DNA hydrogels, and DNA origami, enhances DNMT detection. We highlight the benefits of these DNA nanostructure-based biosensing technologies for clinical use and critically examine the challenges of standardizing these methods. We aim to provide reference values for the application of these techniques in DNMT analysis and early cancer diagnosis and treatment, and to alert researchers to challenges in clinical application.


Biosensing Techniques , DNA , Nanostructures , Nanotechnology , Biosensing Techniques/methods , Humans , DNA/chemistry , DNA/metabolism , Nanostructures/chemistry , DNA Methylation , DNA Modification Methylases/metabolism , DNA Modification Methylases/analysis
10.
Sci Total Environ ; 930: 172341, 2024 Jun 20.
Article En | MEDLINE | ID: mdl-38642758

Lake ecological processes and nutrient patterns are increasingly affected by water level variation around the world. Still, the long-term effects of water level change on lake ecosystems and their implications for suitable lake level management have rarely been studied. Here, we studied the ecosystem dynamics of a mesotrophic lake located in the cold and arid region of northern China based on long-term paleo-diatom and fishery records. Utilizing a novel Copula-Bayesian Network model, possible hydrological-driven ecosystem evolution was discussed. Results show that increased nutrient concentration caused by the first water level drop in the early 1980s incurred a transition of sedimental diatoms towards pollution-resistant species, and the following water level rise in the mid-1980s brought about considerable external loading, which attributed to eutrophication and caused the miniaturization of fishery structure. In the 21st century, a continuous water level plummet further reduced the sediment diatom biomass and the fish biomass by altering nutrient concentration. However, with the implementation of the water diversion project in 2011, oligotrophic species increased, and the ecosystem developed for the better. From the perspective of water quality protection requirements and the ecological well-being of Lake Hulun, the appropriate water level should be around 542.42-544.15 m. In summary, our study highlights the coupling effect of water level and water quality on Lake Hulun ecosystem and gives shed to lake water level operation and management under future climate change and human activities.


Bayes Theorem , Diatoms , Ecosystem , Environmental Monitoring , Fishes , Lakes , Lakes/chemistry , Animals , China , Eutrophication
11.
Biosens Bioelectron ; 256: 116278, 2024 Jul 15.
Article En | MEDLINE | ID: mdl-38608497

The DNA-based logic circuit, constructed to mimic biochemical reaction networks, is highly significant in detecting biomarkers at the molecular level. The differences in the expression levels of microRNAs (miRNAs) within different types of cells provide hope for distinguishing cell subtypes. However, reliance on a single miRNA often leads to unreliable results. Herein, we constructed an enzyme-triggered cascade logic circuit based on the AND gate, which is capable of generating corresponding fluorescence signals in the presence of target miRNAs. The introduction of apurinic/apyrimidinic (AP) sites effectively reduces the likelihood of false signal generation. Amplification of the fluorescence signal relies on the catalytic hairpin assembly and the repetitive reuse of the multicomponent nucleic acid enzyme (MNAzyme). We demonstrated that the logic circuit can not only distinguish cancer cells from normal cells but also identify different types of cancer cells. The programmability of the logic circuits and the simplicity of the assay system allow us to modify the functional sequences to recognize different types of biomarkers, thus providing a reference for the identification of various cell subtypes.


Biosensing Techniques , DNA , MicroRNAs , Humans , Biosensing Techniques/methods , MicroRNAs/genetics , DNA/genetics , DNA/chemistry , Neoplasms/genetics , Computers, Molecular , Cell Line, Tumor , Biomarkers, Tumor/genetics , DNA-(Apurinic or Apyrimidinic Site) Lyase/metabolism , DNA-(Apurinic or Apyrimidinic Site) Lyase/genetics
12.
Pestic Biochem Physiol ; 201: 105899, 2024 May.
Article En | MEDLINE | ID: mdl-38685208

This study investigated the function of the MDR49 gene in Aedes aegypti. MDR49 mutants were constructed using CRISPR/Cas9 technology; the mutation led to increased sensitivity to ivermectin (LC50: from 1.3090 mg L-1 to 0.5904 mg L-1), and a reduction in midgut trypsin activity. These findings suggest that the P-gp encoded by MDR49 confers resistance to ivermectin and impacts the reproductive function in Ae. aegypti. RNA interference technology showed that knockdown of MDR49 gene resulted in a significant decrease in the expression of VGA1 after a blood meal, as well as a decrease in the number of eggs laid and their hatching rate. LC-MS revealed that following ivermectin treatment, the MDR493d+2s/3d+2s strain larvae exhibited significantly higher drug concentrations in the head and fat body compared to the wild type. Modeling of inward-facing P-gp and molecular docking found almost no difference in the affinity of P-gp for ivermectin before and after the mutation. However, modeling of the outward-facing conformation demonstrated that the flexible linker loop between TM5 and TM6 of P-gp undergoes changes after the mutation, resulting in a decrease in trypsin activity and an increase in sensitivity to ivermectin. These results provide useful insights into ivermectin resistance and the other roles played by the MDR49 gene.


Aedes , Insect Proteins , Ivermectin , Animals , Aedes/drug effects , Aedes/genetics , Aedes/metabolism , Ivermectin/pharmacology , Insect Proteins/metabolism , Insect Proteins/genetics , Trypsin/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , ATP Binding Cassette Transporter, Subfamily B, Member 1/genetics , Fertility/drug effects , Insecticide Resistance/genetics , Trypsin Inhibitors/metabolism , Trypsin Inhibitors/pharmacology , Molecular Docking Simulation , Insecticides/pharmacology
13.
Medicine (Baltimore) ; 103(12): e37520, 2024 Mar 22.
Article En | MEDLINE | ID: mdl-38518036

Oral behavior management methods include basic behavior management methods and drug behavior management methods. In many cases, dental treatment that cannot be done simply through basic behavior management is not possible. The uncooperative behavior of children with dental fear in oral treatment has increased the demand for medication based behavior management methods. Drug sedation can provide more effective analgesic and anti-anxiety effects, thereby helping to provide comfortable, efficient, and high-quality dental services. This article will review the drug sedation methods selected in clinical treatment of pediatric dental fear in recent years, as well as the safety and effectiveness of commonly used drugs, in order to provide guidance for dental professionals in clinical practice.


Anesthesia, Dental , Anesthesia , Anti-Anxiety Agents , Child , Humans , Dental Anxiety/drug therapy , Dental Anxiety/prevention & control , Behavior Therapy , Conscious Sedation
14.
Environ Sci Technol ; 2024 Feb 05.
Article En | MEDLINE | ID: mdl-38316131

China's online food delivery (OFD) services consume enormous amounts of disposable plastics. Here, we investigated and modeled the national mass inventories and environmental release of plastics and chemical additives in the plastic. The extra-tree regression identified six key descriptors in determining OFD sales in Chinese cities. Approximately 847 kt of OFD plastic waste was generated in 2021 (per capita 1.10 kg/yr in the megacities and 0.39 kg/yr in other cities). Various additives were extensively detected, with geomean concentrations of 140.96, 4.76, and 0.25 µg/g for ∑8antioxidants, ∑21phthalates, and bisphenol A (BPA), respectively. The estimated mass inventory of these additives in the OFD plastics was 164.7 t, of which 51.1 t was released into the atmosphere via incineration plants and 51.0 t was landfilled. The incineration also released 8.07 t of polycyclic aromatic hydrocarbons and 39.1 kt of particulate matter into the atmosphere. Takeout food may increase the dietary intake of phthalates and BPA by 30% to 50% and raise concerns about considerable exposure to antioxidant transformation products. This study provides profound environmental implications for plastic waste in the Chinese OFD industry. We call for a sustainable circular economy action plan for waste disposal, but mitigating the hazardous substance content and their emissions is urgent.

15.
Small ; : e2310604, 2024 Feb 08.
Article En | MEDLINE | ID: mdl-38329190

Nanoparticle-based drug delivery strategies have emerged as a crucial avenue for comprehensive sensorineural hearing loss treatment. Nevertheless, developing therapy vectors crossing both biological and cellular barriers has encountered significant challenges deriving from various external factors. Herein, the rational integration of gelatin nanoparticles (GNPs) with tetrahedral DNA nanostructures (TDNs) to engineer a distinct drug-delivery nanosystem (designed as TDN@GNP) efficiently enhances the biological permeability and cellular internalization, further resolving the dilemma of noise-induced hearing loss via loading epigallocatechin gallate (EGCG) with anti-lipid peroxidation property. Rationally engineering of TDN@GNP demonstrates dramatic alterations in the physicochemical key parameters of TDNs that are pivotal in cell-particle interactions and promote cellular uptake through multiple endocytic pathways. Furthermore, the EGCG-loaded nanosystem (TDN-EGCG@GNP) facilitates efficient inner ear drug delivery by superior permeability through the biological barrier (round window membrane), maintaining high drug concentration within the inner ear. The TDN-EGCG@GNP actively overcomes the cell membrane, exhibiting hearing protection from noise insults via reduced lipid peroxidation in outer hair cells and spiral ganglion neurons. This work exemplifies how integrating diverse vector functionalities can overcome biological and cellular barriers in the inner ear, offering promising applications for inner ear disorders.

16.
J Pharm Anal ; 14(1): 128-139, 2024 Jan.
Article En | MEDLINE | ID: mdl-38352953

Pharmacological perturbation studies based on protein-level signatures are fundamental for drug discovery. In the present study, we used a mass spectrometry (MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds. The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells. Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol, as well as the noncanonical targets of clinically approved tamoxifen, lovastatin, and their derivatives. Furthermore, the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints. This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

17.
Clin Proteomics ; 21(1): 2, 2024 Jan 05.
Article En | MEDLINE | ID: mdl-38182978

Despite recent innovations in imaging and genomic screening promotes advance in diagnosis and treatment of lung adenocarcinoma (LUAD), there remains high mortality of LUAD and insufficient understanding of LUAD biology. Our previous study performed an integrative multi-omic analysis of LUAD, filling the gap between genomic alterations and their biological proteome effects. However, more detailed molecular characterization and biomarker resources at proteome level still need to be uncovered. In this study, a quantitative proteomic experiment of patient-derived benign lung disease samples was carried out. After that, we integrated the proteomic data with previous dataset of 103 paired LUAD samples. We depicted the proteomic differences between non-cancerous and tumor samples and among diverse pathological subtypes. We also found that up-regulated mitophagy was a significant characteristic of early-stage LUAD. Additionally, our integrative analysis filtered out 75 potential prognostic biomarkers and validated two of them in an independent LUAD serum cohort. This study provided insights for improved understanding proteome abnormalities of LUAD and the novel prognostic biomarker discovery offered an opportunity for LUAD precise management.

18.
Org Lett ; 26(1): 338-343, 2024 01 12.
Article En | MEDLINE | ID: mdl-38174895

Sativene (1) and seco-sativene are an important family of fungal sesquiterpenoids that feature unique tricyclo[4.4.0.01,7]decane and bicyclo[3.2.1]octane skeletons, respectively. Herein, we identify a three-enzyme cassette: SatA cyclizes farnesyl diphosphate (FPP) to form compound 1; CYP450 SatB catalyzes C14-C15 dihydroxylations and subsequent bond cleavage; and reductase SatC regioselectively reduces C14 aldehyde and mediates hemiacetal ring closure to generate prehelminthosporol (2). Our findings clarify the synthetic step of sativene and its oxidative transformation processes into seco-sativene.


Sesquiterpenes , Sesquiterpenes/chemistry , Oxidative Stress
19.
J Transl Med ; 22(1): 15, 2024 Jan 03.
Article En | MEDLINE | ID: mdl-38172946

Breast cancer (BC) is a multifaceted disease characterized by distinct molecular subtypes and varying responses to treatment. In BC, the phosphatidylinositol 3-kinase (PI3K) pathway has emerged as a crucial contributor to the development, advancement, and resistance to treatment. This review article explores the implications of the PI3K pathway in predictive, preventive, and personalized medicine for BC. It emphasizes the identification of predictive biomarkers, such as PIK3CA mutations, and the utility of molecular profiling in guiding treatment decisions. The review also discusses the potential of targeting the PI3K pathway for preventive strategies and the customization of therapy based on tumor stage, molecular subtypes, and genetic alterations. Overcoming resistance to PI3K inhibitors and exploring combination therapies are addressed as important considerations. While this field holds promise in improving patient outcomes, further research and clinical trials are needed to validate these approaches and translate them into clinical practice.


Breast Neoplasms , Phosphatidylinositol 3-Kinase , Humans , Female , Phosphatidylinositol 3-Kinases/metabolism , Breast Neoplasms/pathology , Precision Medicine , Phosphoinositide-3 Kinase Inhibitors/therapeutic use , Mutation/genetics , Class I Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt/metabolism
20.
Biochem Genet ; 62(2): 1055-1069, 2024 Apr.
Article En | MEDLINE | ID: mdl-37526864

Oral submucous fibrosis (OSF) is a chronic disorder with a high malignant transformation rate. Epithelial-mesenchymal transition (EMT) and angiogenesis are key events in OSF. The Notch signaling plays an essential role in the pathogenesis of various fibrotic diseases, including OSF. Our study aimed to explore the effects of Notch on the EMT and angiogenesis processes during the development of OSF. The expression of Notch in OSF tissues versus normal buccal mucosa samples was compared. Arecoline was used to induce myofibroblast transdifferentiation of buccal mucosal fibroblasts (BMFs). Short hairpin RNA technique was used to knockdown Notch in BMFs. Pirfenidone and SRI-011381 were used to inhibit and activate the TGF-ß1 signaling pathway in BMFs, respectively. The expression of Notch was markedly upregulated in OSF tissues and fibrotic BMFs. Knockdown of Notch significantly decreased the viability and promoted apoptosis in BMFs subjected to arecoline stimulation. Downregulation of Notch also significantly suppressed the EMT process, as shown by the reduction of N-cadherin and vimentin with concomitant upregulation of E-cadherin. In addition, knockdown of Notch upregulated VEGF and enhanced the angiogenic activity of fBMFs. Moreover, inhibition of TGF-ß1 suppressed viability and EMT, promoted apoptosis, and induced angiogenesis of fBMFs, while activation of TGF-ß1 significantly diminished the effects of Notch knockdown on fBMFs. Knockdown of Notch suppressed EMT and induced angiogenesis in OSF by regulating TGF-ß1, suggesting that the Notch-TGF-ß1 pathway may serve as a therapeutic intervention target for OSF.

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