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Over the past decade, the attrition rate of Chinese medical graduates has remained high, and the COVID-19 pandemic has exacerbated this situation. Medicine specialty students are the main force of the future healthcare industry. The career choices and career confidence of those entering the healthcare industry will have a huge influence on the quality of future healthcare provision. Considering the possible emergence of public health emergencies such as COVID-19 in the future, helping students develop good career adaptability will contribute to their future career development. However, the relationship between career adaptability, career coping styles and career decision-making self-efficacy remains unclear during the COVID-19. This study aims to examine the interconnections amongst career coping styles, career adaptability and career decision-making self-efficacy among Chinese medicine specialty students and the mediating role of career decision-making self-efficacy. Questionnaire survey was conducted on 747 medicine specialty students from China. The results showed that positive coping style has a significant positive correlation with career decision-making self-efficacy, career adaptability, and their sub-dimensions. There was a partial mediating effect of career decision self-efficacy between the predictor variable positive coping style and the outcome variable career adaptability. By promoting the level of positive coping style or career decision-making self-efficacy among medicine specialty students, the career adaptability can be directly or indirectly enhanced. This survey will help to guide future medical education decisions during a similar pandemic to prevent further loss of healthcare professionals in the medical service.
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Redox imbalance is reported to play a pivotal role in tumorigenesis, cancer development, and drug resistance. Severe oxidative damage is a general consequence of cancer cell responses to treatment and may cause cancer cell death or severe adverse effects. To maintain their longevity, cancer cells can rescue redox balance and enter a state of resistance to anticancer drugs. Therefore, targeting redox signalling pathways has emerged as an attractive and prospective strategy for enhancing the efficacy of anticancer drugs and decreasing their adverse effects. Over the past few decades, natural products (NPs) have become an invaluable source for developing new anticancer drugs due to their high efficacy and low toxicity. Increasing evidence has demonstrated that many NPs exhibit remarkable antitumour effects, whether used alone or as adjuvants, and are emerging as effective approaches to enhance sensitivity and decrease the adverse effects of conventional cancer therapies by regulating redox balance. Among them are several novel anticancer drugs based on NPs that have entered clinical trials. In this review, we summarize the synergistic anticancer effects and related redox mechanisms of the combination of NPs with conventional anticancer drugs. We believe that NPs targeting redox regulation will represent promising novel candidates and provide prospects for cancer treatment in the future.
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BACKGROUND: Non-Alcoholic Fatty Liver Disease (NAFLD) has become a significant health and economic burden globally. Yinchenhao decoction (YCHD) is a traditional Chinese medicine formula that has been validated to exert therapeutic effects on NAFLD. OBJECT: The current study aimed to explore the pharmacological mechanisms of YCHD on NAFLD and further identify the potential active compounds acting on the main targets. METHODS: Compounds in YCHD were screened and collected from TCMSP and published studies, and their corresponding targets were obtained from the SWISS and SEA databases. NAFLD-related targets were searched in the GeneCards and DisGeNet databases. The "compound- intersection target" network was constructed to recognize the key compounds. Moreover, a PPI network was constructed to identify potential targets. GO and KEGG analyses were performed to enrich the functional information of the intersection targets. Then, molecular docking was used to identify the most promising compounds and targets. Finally, molecular dynamics (MD) simulations were performed to verify the binding affinity of the most potential compounds with the key targets. RESULTS: A total of 53 compounds and 556 corresponding drug targets were collected. Moreover, 2684 NAFLD-related targets were obtained, and 201 intersection targets were identified. Biological processes, including the apoptotic process, inflammatory response, xenobiotic metabolic process, and regulation of MAP kinase activity, were closely related to the treatment of NAFLD. Metabolic pathways, non-alcoholic fatty liver disease, the MAPK signaling pathway, and the PI3K-Akt signaling pathway were found to be the key pathways. Molecular docking showed that quercetin and isorhamnetin were the potential active compounds, while AKT1, IL1B, and PPARG were the most promising targets. MD simulations further verified that the binding of PPARG-isorhamnetin (-35.96 ± 1.64 kcal/mol) and AKT1-quercetin (-31.47 ± 1.49 kcal/mol) was due to their lowest binding free energy. CONCLUSION: This study demonstrated that YCHD exerts therapeutic effects for the treatment of NAFLD through multiple targets and pathways, providing a theoretical basis for further pharmacological research on the potential mechanisms of YCHD in NAFLD.
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Biliary tract cancers (BTCs) are a group of deadly malignancies encompassing intrahepatic and extrahepatic cholangiocarcinoma, gallbladder carcinoma, and ampullary carcinoma. Here, we present the integrative analysis of 63 BTC cell lines via multi-omics clustering and genome- scale CRISPR screens, providing a platform to illuminate BTC biology and inform therapeutic development. We identify dependencies broadly enriched in BTC compared to other cancers as well as dependencies selective to the anatomic subtypes. Notably, cholangiocarcinoma cell lines are stratified into distinct lineage subtypes based on biliary or dual biliary/hepatocyte marker signatures, associated with dependency on specific lineage survival factors. Transcriptional analysis of patient specimens demonstrates the prognostic significance of these lineage subtypes. Additionally, we delineate strategies to enhance targeted therapies or to overcome resistance in cell lines with key driver gene mutations. Furthermore, clustering based on dependencies and proteomics data elucidates unexpected functional relationships, including a BTC subgroup with partial squamous differentiation. Thus, this cell line atlas reveals potential therapeutic targets in molecularly defined BTCs, unveils biologically distinct disease subtypes, and offers a vital resource for BTC research.
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Traditional Chinese medicine (TCM) formulae have been studied extensively in various human diseases and have proven to be effective due to their multi-component, multi-target advantage. However, its active metabolites are not clear and the specific mechanisms are not well established, which limits its scientific application. Recently, combination therapies are attracting increasing attention from the scientific community in the past few years and are considered as the next paradigm in drug discovery. Here, we tried to define a new concept of "active metabolites combination therapies (AMCT)" rules to elucidate how the bioactive metabolites from TCMs to produce their synergistic effects in this review. The AMCT rules integrate multidisciplinary technologies like molecular biology, biochemistry, pharmacology, analytical chemistry and pharmacodynamics, etc. Meanwhile, emerging technologies such as multi-omics combined analysis, network analysis, artificial intelligence conduce to better elucidate the mechanisms of these combination therapies in disease treatment, which provides new insights for the development of novel active metabolites combination drugs. AMCT rules will hopefully further guide the development of novel combination drugs that will promote the modernization and international needs of TCM.
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An increasing amount of research has shown that glycosylation plays a crucial role in autoimmune diseases (ADs), prompting our interest in conducting research on the knowledge framework and hot topics in this field based on bibliometric analysis. Studies on glycosylation in the field of ADs from 2003 to 2023 were collected by searching the Web of Science Core Collection database. Bibliometric analysis was conducted using VOSviewer, CiteSpace, and Bibliometrix software. This study included a total of 530 studies. According to the H, G, and M indices, the United States has made the most contributions worldwide, with China making significant contributions in recent years. Leiden University from the Netherlands ranks among the top institutions in terms of publication and citation rankings, with the institution's author Manfred Wuhrer contributing the most to this field. Frontiers in Immunology is the journal with the highest H-index. Research in this field has focused on antibody glycosylation, particularly the specific glycosylation of IgG and IgA, and its role in various ADs. The application of glycoengineering glycosylated proteins in the synthesis of targeted monoclonal antibodies, drug delivery, and regenerative medical materials may be a new trend in the treatment of ADs. Artificial intelligence is an emerging tool in glycobiology. This study summarizes the objective data on glycosylation in the field of AD publications in recent years, providing a reference for researchers in this field.
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Anestesia Raquidea , Cesárea , Hipotensión , Norepinefrina , Ondansetrón , Humanos , Anestesia Raquidea/efectos adversos , Cesárea/efectos adversos , Ondansetrón/administración & dosificación , Hipotensión/prevención & control , Hipotensión/etiología , Femenino , Norepinefrina/administración & dosificación , Embarazo , Relación Dosis-Respuesta a Droga , Ensayos Clínicos Controlados Aleatorios como Asunto , Infusiones IntravenosasRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Shugan Xiaozhi (SGXZ) decoction is a traditional Chinese medicine used for treating nonalcoholic steatohepatitis (NASH). It has been used clinically for over 20 years and proved to be effective; however, the molecular mechanism underlying the effects of SGXZ decoction remains unclear. AIM OF THE STUDY: We analyzed the chemical components, core targets, and molecular mechanisms of SGXZ decoction to improve NASH through network pharmacology and in vivo experiments. MATERIALS AND METHODS: The chemical components, core targets, and related signaling pathways of SGXZ decoction intervention in NASH were predicted using network pharmacology. Molecular docking was performed to verify chemical components and their core targets. The results were validated in the NASH model treated with SGXZ decoction. Mouse liver function was assessed by measuring ALT and AST levels. TC and TG levels were determined to evaluate lipid metabolism, and lipid deposition was assessed via oil red O staining. Mouse liver damage was determined via microscopy following hematoxylin and eosin staining. Liver fibrosis was assessed via Masson staining. Western blot (WB) and immunohistochemical (IHC) analyses were performed to detect inflammation and the expression of apoptosis-related proteins, including IL-1ß, IL-6, IL-18, TNF-α, MCP1, p53, FAS, Caspase-8, Caspase-3, Caspase-9, Bax, Bid, Cytochrome c, Bcl-2, and Bcl-XL. In addition, WB and IHC were used to assess protein expression associated with the TLR4/MyD88/NF-κB pathway. RESULTS: Quercetin, luteolin, kaempferol, naringenin, and nobiletin in SGXZ decoction were effective chemical components in improving NASH, and TNF-α, IL-6, and IL-1ß were the major core targets. Molecular docking indicated that these chemical components and major core targets might interact. KEGG pathway analysis showed that the pathways affected by SGXZ decoction, primarily including apoptosis and TLR4/NF-κB signaling pathways, interfere with NASH. In vivo experiments indicated that SGXZ decoction considerably ameliorated liver damage, fibrosis, and lipid metabolism disorder in MCD-induced NASH mouse models. In addition, WB and IHC verified the underlying molecular mechanisms of SGXZ decoction as predicted via network pharmacology. SGXZ decoction inhibited the activation of apoptosis-related pathways in MCD-induced NASH mice. Moreover, SGXZ decoction suppressed the activation of TLR4/MyD88/NF-κB pathway in MCD-induced NASH mice. CONCLUSION: SGXZ decoction can treat NASH through multiple targets and pathways. These findings provide new insights into the effective treatment of NASH using SGXZ decoction.
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Apoptosis , Medicamentos Herbarios Chinos , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Enfermedad del Hígado Graso no Alcohólico , Transducción de Señal , Animales , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Masculino , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/química , Ratones , Transducción de Señal/efectos de los fármacos , Deficiencia de Colina/complicaciones , Inflamación/tratamiento farmacológico , Hígado/efectos de los fármacos , Hígado/patología , Hígado/metabolismo , Modelos Animales de Enfermedad , Farmacología en Red , Antiinflamatorios/farmacología , Metabolismo de los Lípidos/efectos de los fármacosRESUMEN
Background: Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) account for a significant proportion of gynecological malignancies and represent a major global health concern. Globally, CESC is ranked as the fourth most common cancer among women. Conventional treatment of this disease has a less favorable prognosis for most patients. However, the discovery of early molecular biomarkers is therefore important for the diagnosis of CESC, as well as for slowing down their progression process. Methods: To identify differentially expressed genes strongly associated with prognosis, univariate Cox proportional hazard analysis and least absolute shrinkage and selection operator (LASSO) regression analysis were used. Using multiple Cox proportional hazard regression, a multifactorial model for prognostic risk assessment was then created. Results: The expression of biological clock-related genes, which varied considerably among distinct subtypes and were associated with significantly diverse prognoses, was used to categorize CESC patients. These findings demonstrate how the nomogram developed based on the 7-CRGs signature may assist physicians in creating more precise, accurate, and successful treatment plans that can aid CESC patients at 1, 3, and 5 years. Conclusions: By using machine learning techniques, we thoroughly investigated the impact of CRGs on the prognosis of CESC patients in this study. By creating a unique nomogram, we were able to accurately predict patient prognosis. At the same time, we showed new perspectives on the development of CESC and its treatment by analyzing the associations of the prognostic model with immunity, enrichment pathways, chemotherapy sensitivity, and so on. This research provides a new direction for clinical treatment.
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Pseudolaric acid B (PAB), an acid isolated from the roots of Pseudolarix kaempferi gorden, has shown antitumour effects through multiple mechanisms of action. The objective of this study was to investigate the anticancer effect of PAB on non-small cell lung cancer (NSCLC) and its underlying mechanism. In our experiments, we observed that PAB decreased cell viability, inhibited colony formation, induced cell cycle arrest, impeded scratch healing, and increased apoptosis in H1975 and H1650 cells. Additionally, PAB treatment enhanced the fluorescence intensity of MDC staining in NSCLC cells, upregulated the protein expression of microtubule-associated protein light chain 3 II (LC3 II), and downregulated the expression of sequestosome 1 (SQSTM1/P62). Combined treatment with PAB and chloroquine (CQ) increased the protein expression levels of LC3 II and P62 while decreasing the apoptosis of H1975 and H1650 cells. Moreover, treatment with PAB led to significant mTOR inhibition and AMPK activation. PAB combined with compound C (CC) inhibited autophagy and apoptosis. Furthermore, PAB treatment increased intracellular reactive oxygen species (ROS) levels in NSCLC cells, which correlated with the modulation of the AMPK/mTOR signalling pathway and was associated with autophagy and apoptosis. Finally, we validated the antitumour growth activity and mechanism of PAB in vivo using athymic nude mice bearing H1975 tumour cells. In conclusion, our findings suggest that PAB can induce apoptosis and autophagic cell death in NSCLC through the ROS-triggered AMPK/mTOR signalling pathway, making it a promising candidate for future NSCLC treatment.
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Proteínas Quinasas Activadas por AMP , Apoptosis , Autofagia , Carcinoma de Pulmón de Células no Pequeñas , Diterpenos , Neoplasias Pulmonares , Ratones Desnudos , Especies Reactivas de Oxígeno , Transducción de Señal , Serina-Treonina Quinasas TOR , Serina-Treonina Quinasas TOR/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Humanos , Animales , Autofagia/efectos de los fármacos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Diterpenos/farmacología , Apoptosis/efectos de los fármacos , Ratones Endogámicos BALB C , Ratones , Progresión de la Enfermedad , Ensayos Antitumor por Modelo de Xenoinjerto , Supervivencia Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacosRESUMEN
This review explores the potential of integrating nano-delivery systems with traditional Chinese herbal medicine, acupuncture, and Chinese medical theory. It highlights the intersections and potential of nano-delivery systems in enhancing the effectiveness of traditional herbal medicine and acupuncture treatments. In addition, it discusses how the integration of nano-delivery systems with Chinese medical theory can modernize herbal medicine and make it more readily accessible on a global scale. Finally, it analyzes the challenges and future directions in this field.
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Sistemas de Liberación de Medicamentos , Medicina Tradicional China , Nanotecnología , Humanos , Terapia por Acupuntura , Medicamentos Herbarios Chinos/químicaRESUMEN
BACKGROUND: Non-small cell lung cancer (NSCLC) remains at the forefront of new cancer cases, and there is an urgent need to find new treatments or improve the efficacy of existing therapies. In addition to the application in the field of cerebrovascular diseases, recent studies have revealed that tanshinone IIA (Tan IIA) has anticancer activity in a variety of cancers. PURPOSE: To investigate the potential anticancer mechanism of Tan IIA and its impact on immunotherapy in NSCLC. METHODS: Cytotoxicity and colony formation assays were used to detect the Tan IIA inhibitory effect on NSCLC cells. This research clarified the mechanisms of Tan IIA in anti-tumor and programmed death-ligand 1 (PD-L1) regulation by using flow cytometry, transient transfection, western blotting and immunohistochemistry (IHC) methods. Besides, IHC was also used to analyze the nuclear factor of activated T cells 1 (NFAT2) expression in NSCLC clinical samples. Two animal models including xenograft mouse model and Lewis lung cancer model were used for evaluating tumor suppressive efficacy of Tan IIA. We also tested the efficacy of Tan IIA combined with programmed cell death protein 1 (PD-1) inhibitors in Lewis lung cancer model. RESULTS: Tan IIA exhibited good NSCLC inhibitory effect which was accompanied by endoplasmic reticulum (ER) stress response and increasing Ca2+ levels. Moreover, Tan IIA could suppress the NFAT2/ Myc proto oncogene protein (c-Myc) signaling, and it also was able to control the Jun Proto-Oncogene(c-Jun)/PD-L1 axis in NSCLC cells through the c-Jun N-terminal kinase (JNK) pathway. High NFAT2 levels were potential factors for poor prognosis in NSCLC patients. Finally, animal experiments data showed a stronger immune activation phenotype, when we performed treatment of Tan IIA combined with PD-1 monoclonal antibody. CONCLUSION: The findings of our research suggested a novel mechanism for Tan IIA to inhibit NSCLC, which could exert anti-cancer effects through the JNK/NFAT2/c-Myc pathway. Furthermore, Tan IIA could regulate tumor PD-L1 levels and has the potential to improve the efficacy of PD-1 inhibitors.
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Abietanos , Carcinoma de Pulmón de Células no Pequeñas , Estrés del Retículo Endoplásmico , Neoplasias Pulmonares , Factores de Transcripción NFATC , Abietanos/farmacología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Animales , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones , Factores de Transcripción NFATC/metabolismo , Línea Celular Tumoral , Antineoplásicos Fitogénicos/farmacología , Proto-Oncogenes Mas , Antígeno B7-H1/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto , Receptor de Muerte Celular Programada 1 , Inmunoterapia/métodos , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Células A549 , Ratones Desnudos , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-myc/metabolismo , Masculino , FemeninoRESUMEN
PURPOSE: FGFR2 and FGFR3 show oncogenic activation in many cancer types, often through chromosomal fusion or extracellular domain mutation. FGFR2 and FGFR3 alterations are most prevalent in intrahepatic cholangiocarcinoma (ICC) and bladder cancers, respectively, and multiple selective reversible and covalent pan-FGFR tyrosine kinase inhibitors (TKI) have been approved in these contexts. However, resistance, often due to acquired secondary mutations in the FGFR2/3 kinase domain, limits efficacy. Resistance is typically polyclonal, involving a spectrum of different mutations that most frequently affect the molecular brake and gatekeeper residues (N550 and V565 in FGFR2). EXPERIMENTAL DESIGN: Here, we characterize the activity of the next-generation covalent FGFR inhibitor, KIN-3248, in preclinical models of FGFR2 fusion+ ICC harboring a series of secondary kinase domain mutations, in vitro and in vivo. We also test select FGFR3 alleles in bladder cancer models. RESULTS: KIN-3248 exhibits potent selectivity for FGFR1-3 and retains activity against various FGFR2 kinase domain mutations, in addition to being effective against FGFR3 V555M and N540K mutations. Notably, KIN-3248 activity extends to the FGFR2 V565F gatekeeper mutation, which causes profound resistance to currently approved FGFR inhibitors. Combination treatment with EGFR or MEK inhibitors potentiates KIN-3248 efficacy in vivo, including in models harboring FGFR2 kinase domain mutations. CONCLUSIONS: Thus, KIN-3248 is a novel FGFR1-4 inhibitor whose distinct activity profile against FGFR kinase domain mutations highlights its potential for the treatment of ICC and other FGFR-driven cancers.
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Mutación , Inhibidores de Proteínas Quinasas , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos , Neoplasias de la Vejiga Urinaria , Animales , Humanos , Ratones , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Colangiocarcinoma/tratamiento farmacológico , Colangiocarcinoma/genética , Colangiocarcinoma/patología , Resistencia a Antineoplásicos/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 3 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patología , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
BACKGROUND: The study on Head and Neck Squamous Cell Carcinoma (HNSCC), a prevalent and aggressive form of head and neck cancer, focuses on the often-overlooked role of soluble mediators. The objective is to leverage a transcriptome-based risk analysis utilizing soluble mediator-related genes (SMRGs) to provide novel insights into prognosis and immunotherapy efficacy in HNSCC patients. METHODS: We analyzed the expression and prognostic significance of 10,859 SMRGs using 502 HNSCC and 44 normal samples from the TCGA-HNSC cohort in The Cancer Genome Atlas (TCGA). The samples were divided into training and test sets in a 7:3 ratio, with an additional external validation using 40 tumor samples from the International Cancer Genome Consortium (ICGC). Key differentially expressed genes (DEGs) with prognostic significance were identified through univariate and Lasso-Cox regression analyses. A prognostic model based on 20 SMRGs was developed using Lasso and multivariate Cox regression. We assessed the clinical outcomes and immune status in high-risk (HR) and low-risk (LR) HNSCC patients utilizing the BEST databases and single-sample Gene Set Enrichment Analysis (ssGSEA). RESULTS: The 20 SMRGs were crucial in predicting the prognosis of HNSCC, with the SMRG signature emerging as an independent prognostic indicator. Patients classified in the HR group exhibited poorer outcomes compared to those in the LR group. A nomogram, integrating clinical characteristics and risk scores, demonstrated substantial prognostic value. Immunotherapy appeared to be more effective in the LR group, possibly attributed to enhanced immune infiltration and expression of immune checkpoints. CONCLUSIONS: The model based on soluble mediator-associated genes offers a fresh perspective for assessing the pre-immune efficacy and showcases robust predictive capabilities. This innovative approach holds significant promise in advancing the field of precision immuno-oncology research, providing valuable insights for personalized treatment strategies in HNSCC.
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Neoplasias de Cabeza y Cuello , Humanos , Pronóstico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Factores de Riesgo , Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapiaRESUMEN
This comprehensive review delves into the complex interplay between mitochondrial gene defects and pancreatic cancer pathogenesis through a multiomics approach. By amalgamating data from genomic, transcriptomic, proteomic, and metabolomic studies, we dissected the mechanisms by which mitochondrial genetic variations dictate cancer progression. Emphasis has been placed on the roles of these genes in altering cellular metabolic processes, signal transduction pathways, and immune system interactions. We further explored how these findings could refine therapeutic interventions, with a particular focus on precision medicine applications. This analysis not only fills pivotal knowledge gaps about mitochondrial anomalies in pancreatic cancer but also paves the way for future investigations into personalized therapy options. This finding underscores the crucial nexus between mitochondrial genetics and oncological immunology, opening new avenues for targeted cancer treatment strategies.
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Neoplasias Pancreáticas , Proteómica , Humanos , Genes Mitocondriales , Multiómica , Neoplasias Pancreáticas/terapia , GenómicaRESUMEN
Due to the unique characteristics of breast cancer initiation sites and significant alterations in tumor metabolism, breast cancer cells rely on lipid metabolic reprogramming to effectively regulate metabolic programs during the disease progression cascade. This adaptation enables them to meet the energy demands required for proliferation, invasion, metastasis, and responses to signaling molecules in the breast cancer microenvironment. In this review, we comprehensively examined the distinctive features of lipid metabolic reprogramming in breast cancer and elucidated the underlying mechanisms driving aberrant behavior of tumor cells. Additionally, we emphasize the potential role and adaptive changes in lipid metabolism within the breast cancer microenvironment, while summarizing recent preclinical studies. Overall, precise control over lipid metabolism rewiring and understanding of plasticity within the breast cancer microenvironment hold promising implications for developing targeted treatment strategies against this disease. Therefore, interventions targeting the lipid metabolism in breast cancer may facilitate innovative advancements in clinical applications.
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Neoplasias de la Mama , Neoplasias , Humanos , Femenino , Neoplasias de la Mama/metabolismo , Metabolismo de los Lípidos/genética , Neoplasias/metabolismo , Reprogramación Metabólica , Microambiente Tumoral/fisiología , LípidosRESUMEN
The development of effective inhibitors targeting the Kirsten rat sarcoma viral proto-oncogene (KRASG12D) mutation, a prevalent oncogenic driver in cancer, represents a significant unmet need in precision medicine. In this study, an integrated computational approach combining structure-based virtual screening and molecular dynamics simulation was employed to identify novel noncovalent inhibitors targeting the KRASG12D variant. Through virtual screening of over 1.7 million diverse compounds, potential lead compounds with high binding affinity and specificity were identified using molecular docking and scoring techniques. Subsequently, 200 ns molecular dynamics simulations provided critical insights into the dynamic behavior, stability, and conformational changes of the inhibitor-KRASG12D complexes, facilitating the selection of lead compounds with robust binding profiles. Additionally, in silico absorption, distribution, metabolism, excretion (ADME) profiling, and toxicity predictions were applied to prioritize the lead compounds for further experimental validation. The discovered noncovalent KRASG12D inhibitors exhibit promises as potential candidates for targeted therapy against KRASG12D-driven cancers. This comprehensive computational framework not only expedites the discovery of novel KRASG12D inhibitors but also provides valuable insights for the development of precision treatments tailored to this oncogenic mutation.
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Simulación de Dinámica Molecular , Neoplasias , Humanos , Proteínas Proto-Oncogénicas p21(ras)/genética , Simulación del Acoplamiento Molecular , MutaciónRESUMEN
Objective: The effectiveness of manual acupuncture for treating bronchial asthma is still debatable and broad, and the effects of different acupuncture points, treatment durations, or illness trajectories have never been rigorously assessed. The objective of this revised systematic review and subgroup meta-analysis of randomized controlled trials (RCTs) is to ascertain the clinical efficacy of manual acupuncture on bronchial asthma and whether these effects varied depending on the acupuncture points, length of treatment, or course of the disease. Materials and methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria were followed for creating a systematic review and meta-analysis. From the beginning through March 25, 2022, six electronic databases were checked. For the treatment of asthma, all RCTs contrasting acupuncture therapy along with conventional treatment against conventional treatment alone were chosen. The information was examined using Review Manager version 5.3 and Comprehensive Meta-Analysis version 3. Clinical efficacy (including the effective rate and the recurrence rate) was the primary outcome, and pulmonary function (including FEV1%, PEF) and The secondary results were T-lymphocyte immunity (containing CD3+, CD4+, and CD8+). Based on the acupuncture points, length of therapy, and nature of the condition, subgroup analyses were carried out. Results: There were a total of 21 RCTs that enrolled 2510 individuals. According to the meta-findings, analysis's manual acupuncture in addition to conventional treatment significantly increased the effective rate when compared to conventional treatment alone [OR = 5.14 95% CI 3.58-7.38, P < .00001], lung functions [FEV1% (MD = 6.18, 95% CI 2.40-9.96, P = .001) and PEF (MD = 0.45 95% CI 0.18-0.73, P = .001)], immune functions [CD3+ T lymphocytes (MD = 7.55 95% CI 6.55-8.56, P < .00001), CD4+ T-lymphocytes (MD = 5.11 95% CI 4.09-6.13, P < .00001), T-lymphocyte CD8+ (MD = -0.37.11 95% CI -3.62--2.51, P < .00001)] and noteworthy reduction in the recurrence rate (OR = 0.19 95% CI 0.10-0.38, P < .00001). Results from the subgroup analysis were consistent. Conclusion: Manual acupuncture combined with Western Medicine is more effective than conventional treatment alone for bronchial asthma. Combination therapy can significantly improve clinical efficacy, lung function, and immune function while reducing the relapse rate. But to further support the results of this investigation, high-quality RCTs with long-term outcomes are still required, taking into account the inherent limitations of the included studies. Registration number: PROSPERO (no. CRD42022357805) (https://www.crd.york.ac.uk/prospero/).
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BACKGROUND: Invasive mucinous adenocarcinoma of the lung (IMA) is a unique and rare subtype of lung adenocarcinoma with poorly defined prognostic factors and highly controversial studies. Hence, this study aimed to comprehensively identify and summarize the prognostic factors associated with IMA. METHODS: A comprehensive search of relevant literature was conducted in the PubMed, Embase, Cochrane, and Web of Science databases from their inception until June 2023. The pooled hazard ratio (HR) and corresponding 95% confidence intervals (CI) of overall survival (OS) and/or disease-free survival (DFS) were obtained to evaluate potential prognostic factors. RESULTS: A total of 1062 patients from 11 studies were included. In univariate analysis, we found that gender, age, TNM stage, smoking history, lymph node metastasis, pleural metastasis, spread through air spaces (STAS), tumor size, pathological grade, computed tomography (CT) findings of consolidative-type morphology, pneumonia type, and well-defined heterogeneous ground-glass opacity (GGO) were risk factors for IMA, and spiculated margin sign was a protective factor. In multivariate analysis, smoking history, lymph node metastasis, pathological grade, STAS, tumor size, and pneumonia type sign were found to be risk factors. There was not enough evidence that epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) mutations, CT signs of lobulated margin, and air bronchogram were related to the prognosis for IMA. CONCLUSION: In this study, we comprehensively analyzed prognostic factors for invasive mucinous adenocarcinoma of the lung in univariate and multivariate analyses of OS and/or DFS. Finally, 12 risk factors and 1 protective factor were identified. These findings may help guide the clinical management of patients with invasive mucinous adenocarcinoma of the lung.