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Androgen receptor (AR) is one of the key targets for the treatment of castration-resistant prostate cancer (CRPC). Current endocrine therapy can greatly improve patients with CRPC. However, with the change of pathogenic mechanism, acquired resistance often leads to the failure of treatment. Studies have shown that tanshinone IIA (TS-IIA) and its derivatives have significant antitumor activity, and have certain AR-targeting effects, but the mechanism is unknown. In this study, the TS-IIA analog TB3 was found to significantly inhibit the growth of CRPC in vitro and in vivo. Molecular docking, cellular thermal shift assay, and cycloheximide experiments confirmed that AR was the target of TB3 and promoted the degradation of AR. Furthermore, TB3 can significantly inhibit glycolysis metabolism by targeting the AR/PKM2 axis. The addition of pyruvic acid could significantly alleviate the inhibitory effect of TB3 on CRPC cells. Besides, the knockdown of AR or PKM2 also could reverse the effect of TB3 on CRPC cells. Taken together, our study suggests that TS-IIA derivative TB3 inhibits glycolysis to prevent the CRPC process by targeting the AR/PKM2 axis.
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Abietanos , Glicólise , Neoplasias de Próstata Resistentes à Castração , Receptores Androgênicos , Proteínas de Ligação a Hormônio da Tireoide , Animais , Humanos , Masculino , Camundongos , Abietanos/farmacologia , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Glicólise/efeitos dos fármacos , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Nus , Neoplasias de Próstata Resistentes à Castração/metabolismo , Neoplasias de Próstata Resistentes à Castração/patologia , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Receptores Androgênicos/metabolismo , Receptores Androgênicos/genética , Hormônios Tireóideos/metabolismoRESUMO
Cervical cancer is the leading cause of death among gynecological malignant tumors, especially due to the poor prognosis of patients with advanced tumors due to recurrence, metastasis, and chemotherapy resistance. Therefore, exploring new antineoplastic drugs with high efficacy and low toxicity may bring new expectations in patients with cervical cancer. Natural products and their derivatives exert an antitumor activity. Therefore, in this work, combined with network pharmacology analysis and experimental validation, we investigated the anti-cervical cancer activity and molecular mechanism of a new trifluoromethyl quinoline (FKL) derivative in vivo and in vitro. FKL117 inhibited the proliferation of cervical cancer cells in a dose and time-dependent manner, induced apoptosis in HeLa cells, arrested the cell cycle in the G2/M phase, and regulated the expression of the apoptotic and cell cycle-related proteins Bcl-2, Bax, cyclin B1, and CDC2. We used online databases to obtain HDAC1 as one of the possible targets of FKL117 and the target binding and binding affinity were modeled by molecular docking. The results showed that FKL117 formed a hydrogen bond with HDAC1 and had good binding ability. We found that FKL117 targeted to inhibit the expression and function of HDAC1 and increased the acetylation of histone H3 and H4, which was also confirmed in vivo. The migration of HMGB1 from the nucleus to the cytoplasm further verified the above results. In conclusion, our study suggested that FKL117 might be used as a novel candidate for targeting the inhibition of HDAC1 against cervical cancer.
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Quinolinas , Neoplasias do Colo do Útero , Feminino , Humanos , Histonas/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Células HeLa , Acetilação , Simulação de Acoplamento Molecular , Linhagem Celular Tumoral , Apoptose , Quinolinas/farmacologia , Quinolinas/uso terapêutico , Proliferação de Células , Histona Desacetilase 1/metabolismoRESUMO
Paxlovid is a recent FDA approved specific drug for COVID-19. Extensive prescription of Paxlovid could induce potential synthetic cytotoxicity with drugs. Herein, we aimed to examine pairwise synthetic cytotoxicity between Paxlovid and 100 frequently FDA approved small molecule drugs. Liver cell line HL-7702 or L02 was adopted to evaluate synthetic cytotoxicity between Paxlovid and the 100 small molecule drugs. Inhibitory concentration IC-10 and IC-50 doses for all the 100 small molecule drugs and Paxlovid were experimentally acquired. Then, pairwise synthetic cytotoxicity was examined with the fixed dose IC-10 for each drug. The most 4 significant interactive pairs (2 positively interactive and 2 negatively interactive) were further subjected to molecular docking simulation to reveal the structural modulation with Caspase-8, a key mediator for cell apoptosis.
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Wound healing is a complex, dynamic process supported by a myriad of cellular events that must be tightly coordinated to efficiently repair damaged tissue. These wounds are a significant socioeconomic burden due to their high prevalence and recurrence, which is why the phenomenon of wounds has also been labeled as a "Silent Epidemic". Most of these wounds become "chronic", with around 15% of them remaining unresolved 1-year post incidence, which results in a prolonged yet avoidable burden to patients, families, and the health system. In this experimental study, we tried to purify the potent components in chick early amniotic fluid (ceAF) and applied these components to the wound healing mechanism. We first subjected ceAF to a series of purifications, including an HPLC purification system along with ion-exchange chromatography technology to purify other potential components. Upon narrowing down, we found two structural analogs: guanosine and deoxyinosine. We performed these components' cell scratch and trans-well migration assays to validate the accurate dosage. We also assessed these components via topical administration on the skin of murine model wounds. For this, we randomly divided C57BL/6 (all black, male, 5 weeks old) mice into groups. The wound model was established through excising the skin of mice and treated the wounds with different fractions of guanosine and deoxyinosine continuously for 8-10 day intervals. Once the healing was complete, the skin was excised to determine the inflammatory response and other biochemical parameters of the healed skin, including epidermal thickness, collagen density, macrophages, and neutrophil infiltration at the wounded site. Quantitative real-time PCR and immunoblot assays were performed to determine active gene expression and protein expression of proinflammatory molecules, growth factors, and cytokines. All these findings support our data indicating the promising healing properties of guanosine and deoxyinosine isolated from ceAF.
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Líquido Amniótico , Guanosina , Animais , Masculino , Camundongos , Galinhas , Camundongos Endogâmicos C57BL , CicatrizaçãoRESUMO
Lactic acidosis is a feature of solid tumors and plays fundamental role(s) rendering cancer cells to adapt to diverse metabolic stresses, but the mechanism underlying its roles in redox homeostasis remains elusive. Here we show that G6PD is phosphorylated at tyrosine 249/322 by the SRC through the formation of a GSTP1-G6PD-SRC complex. Lactic acid attenuates this formation and the phosphorylation of G6PD by non-covalently binding with GSTP1. Furthermore, lactic acid increases the activity of G6PD and facilitates the PPP (NADPH production) through its sensor GSTP1, thereby exhibiting resistance to reactive oxygen species when glucose is scarce. Abrogating a GSTP1-mediated lactic acid signaling showed attenuated tumor growth and reduced resistance to ROS in breast cancer cells. Importantly, positive correlations between immuno-enriched SRC protein and G6PD Y249/322 phosphorylation specifically manifest in ER/PR positive or HER negative types of breast cancer. Taken together, these results suggest that GSTP1 plays a key role in tumor development by functioning as a novel lactate sensor.
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Ácido Láctico , Neoplasias , Humanos , Carcinogênese , Transformação Celular Neoplásica , Espécies Reativas de Oxigênio/metabolismo , Estresse Oxidativo , Oxirredução , Glucosefosfato Desidrogenase/metabolismo , Glutationa S-Transferase pi/genética , Glutationa S-Transferase pi/metabolismoRESUMO
A series of new N-aryl-2-trifluoromethylquinazoline-4-amine analogs were designed and synthesized based on structure optimization of quinazoline by introducing a trifluoromethyl group into 2-position. The structures of the twenty-four newly synthesized compounds were confirmed by 1H NMR, 13C NMR and ESI-MS. The in vitro anti-cancer activity against chronic myeloid leukemia cells (K562), erythroleukemia cells (HEL), human prostate cancer cells (LNCaP), and cervical cancer cells (HeLa) of the target compounds was evaluated. Among them, compounds 15d, 15f, 15h, and 15i showed the significantly (P < 0.01) stronger growth inhibitory activity on K562 than those of the positive controls of paclitaxel and colchicine, while compounds 15a, 15d, 15e, and 15h displayed significantly stronger growth inhibitory activity on HEL than those of the positive controls. However, all the target compounds exhibited weaker growth inhibition activity against K562 and HeLa than those of the positive controls. The selectivity ratio of compounds 15h, 15d, and 15i were significantly higher than those of other active compounds, indicating that these three compounds had the lower hepatotoxicity. Several compounds displayed strong inhibition against leukemia cells. They inhibited tubulin polymerization, disrupted cellular microtubule networks by targeting the colchicine site, and promoted cell cycle arrest of leukemia cells at G2/M phase and cell apoptosis, as well as inhibiting angiogenesis. In summary, our research provided that novel synthesized N-aryl-2-trifluoromethyl-quinazoline-4-amine active derivatives as the inhibitors of tubulin polymerization in leukemia cells, which might be a valuable lead compounds for anti-leukemia agents.
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Antineoplásicos , Tubulina (Proteína) , Humanos , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/química , Relação Estrutura-Atividade , Polimerização , Antineoplásicos/farmacologia , Antineoplásicos/química , Proliferação de Células , Ensaios de Seleção de Medicamentos Antitumorais , Colchicina/farmacologia , Linhagem Celular TumoralRESUMO
Arsenic is a prevalent environmental pollutant that targets the nervous system of living beings. Recent studies indicated that microglial injury could contribute to neuroinflammation and is associated with neuronal damage. Nevertheless, the neurotoxic mechanism underlying the arsenic-induced microglial injury requires additional research. This study explores whether cathepsin B promotes microglia cell damage caused by NaAsO2. Through CCK-8 assay and Annexin V-FITC and PI staining, we discovered that NaAsO2 induced apoptosis in BV2 cells (a microglia cell line). NaAsO2 was verified to increase mitochondrial membrane permeabilization (MMP) and promote the generation of reactive oxygen species (ROS) through JC-1 staining and DCFDA assay, respectively. Mechanically, NaAsO2 was indicated to increase the expression of cathepsin B, which could stimulate pro-apoptotic molecule Bid into the activated form, tBid, and increase lysosomal membrane permeabilization by Immunofluorescence and Western blot assessment. Subsequently, apoptotic signaling downstream of increased mitochondrial membrane permeabilization was activated, promoting caspase activation and microglial apoptosis. Cathepsin B inhibitor CA074-Me could mitigate the damage of microglial. In general, we found that NaAsO2 induced microglia apoptosis and depended on the role of the cathepsin B-mediated lysosomal-mitochondrial apoptosis pathway. Our findings provided new insight into NaAsO2-induced neurological damage.
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Arsênio , Catepsina B , Catepsina B/metabolismo , Microglia/metabolismo , Apoptose/fisiologia , Lisossomos/metabolismoRESUMO
Sustained drug release has attracted increasing interest in targeted drug therapy. However, existing methods of drug therapy suffer drug action time, large fluctuations in the effective concentration of the drug, and the risk of side effects. Here, a biodegradable composite of polybutylene adipate co-terephthalate/polyvinylpyrrolidone (PBAT/PVP) consisting of electrospun hollow microspheres as sustained-released drug carriers is presented. The as-prepared PBAT/PVP composites show faster degradation rate and drug (Erlotinib) release than that of PBAT. Furthermore, PBAT/PVP composites loaded with Erlotinib provide sustained release effect, thus achieving a better efficacy than that after the direct injection of erlotinib due to the fact that the composites allow a high drug concentration in the tumor for a longer period. Hence, this work provides a potential effective solution for clinical drug therapy and tissue engineering using drug microspheres with a sustained release.
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Antibiotic resistance is a significant threat to the human race, as regular consumption of antibiotics may lead to antibiotic-resistant bacterial strains. Non-antibiotic drugs also have an extensive impact on bacterial strains, where persistent uptake alters the survival mechanisms of bacteria that could lead to cross-resistance towards other antibiotics. Here, we use time-lapse proteomics shift assays to examine Gram-negative (E. coli. O157:H7 and P. aeruginosa) and Gram-positive (E. faecalis and S. aureus) strains of bacteria for short and continuous exposure to the non-antibiotic drug Hydroxychloroquine (HCQ). Proteomic transitions from wild type to HCQ-exposed strains revealed bacterial transitions and their survival adaptabilities, which were different across all strains. In addition to their structural differences, some shared pathways were enriched among Gram-negative and positive strains. We also validated the cross-resistance and sensitivity towards 24 regularly prescribed antibiotics, indicating that long-term exposure to non-antibiotic drugs may induce general proteomics alterations in the bacterial strains, promoting antibiotic resistance. We validated that HCQ exposure renders Gram-negative strains resistant to Β-lactam and susceptible to macrolides and folic acid. In contrast, Gram-positive strains become susceptible to Β-lactam and resistant to aminoglycosides. Exposure to non-antibiotic drugs causes resistance or susceptibility toward other antibiotics, providing clinicians a reason to overcome antibiotic resistance.
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Antibacterianos , Escherichia coli , Humanos , Antibacterianos/farmacologia , Staphylococcus aureus , Proteômica , Imagem com Lapso de Tempo , Bactérias , beta-Lactamas , Testes de Sensibilidade Microbiana , Farmacorresistência BacterianaRESUMO
In the present study, a series of novel L-phenylalanine dipeptides were designed and synthesized by a multi-step sequence of reactions, including carbodiimide-mediated condensation, hydrolysis, mixed anhydride condensation, and nucleophilic substitution. Among them, compound 7c exhibited potent antitumor activity against prostate cancer cell PC3 in vitro and in vivo via inducing apoptosis. We investigated the significantly differentially expressed proteins in the cells caused by the compound 7c to unravel the molecular mechanisms underlying the regulation of PCa cell growth, which indicated that 7c mainly regulated the protein expression of apoptosis-related transcription factors, including c-Jun, IL6, LAMB3, OSMR, STC1, OLR1, SDC4 and PLAU; and 7c also regulated the protein expression of inflammatory cytokines including IL6, CXCL8, TNFSF9, TNFRSF12A and OSMR, and the phosphorylation levels of RelA. The action target confirmed that TNFSF9 protein is the critical binding target of 7c. These findings suggested that 7c could regulate the apoptosis and inflammatory response related signaling pathways for the inhibition of the proliferation of PC3 cells, implying that 7c could be considered a promising therapeutic candidate for PCa therapy.
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Hiperplasia Prostática , Neoplasias da Próstata , Masculino , Humanos , Fenilalanina/farmacologia , Fenilalanina/uso terapêutico , Interleucina-6 , Neoplasias da Próstata/patologia , Proliferação de Células , Apoptose , Linhagem Celular Tumoral , Ligante 4-1BBRESUMO
In recent years, the prevalence of hyperglycemia has been increasing, and patients’ bodies have been seriously damaged. Compared with conventional Western drugs, natural products have fewer adverse reactions and delay the complications of hyperglycemia. As a valuable natural product resource, Small-leaf Kuding (SLK) contains various beneficial components for the human body. The aim of this study was to study the regulation effect of SLK extract at different doses on blood glucose metabolism in hyperglycemic mice. Lipopolysaccharide and streptozotocin were used to induce hyperglycemia in mice. Extract of SLK were administered intragastrically at low, medium, and high doses (5 g·kg
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In recent years, amniotic fluids have gained attention in cancer research. They have an influential role in protecting embryos against several anomalies. Chick early amniotic fluid (ceAF)-amniotic fluid isolated from growing chicken-has been used in many other studies, including myocardial infarctions and skin regeneration. In this study, we employed ceAF's promising therapeutic applications against tumorigenesis in both in vitro and in vivo studies. We selected three robust proliferating tumor cell lines: BCaP37, MCF7, and RKO. We found that selective dosage is required to obtain maximum impact to deter tumorigenesis. ceAF not only disrupted the uniform colonies of tumor cell lines via disturbing mitochondrial transmembrane potential, but also arrested many cells at growing G1 state via working agonistically with aphidicolin. The significant inhibition of tumor metastasis by ceAF was indicated by in vivo models. This leads to apoptosis analysis as verified by annexin-V staining stays and immunoblotting of critical proteins as cell cycle meditators and apoptosis regulators. Not only on the protein level, but we also tested ceAF's therapeutic potentials on mRNA levels as indicated by quantitative real-time PCR summarizing the promising role of ceAF in deterring tumor progression. In conclusion, our study reveals the potent role of ceAF against tumorigenesis in breast cancer and colon carcinoma. Further studies will be required to determine the critical components present in ceAF and its purification to narrow down this study.
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Prostate cancer (PCa) is a common malignant cancer of the urinary system. Drug therapy, chemotherapy, and radical prostatectomy are the primary treatment methods, but drug resistance and postoperative recurrence often occur. Therefore, seeking novel anti-tumor compounds with high efficiency and low toxicity from natural products can produce a new tumor treatment method. Matijin-Su [N-(N-benzoyl-L-phenylalanyl)-O-acetyl-L-phenylalanol, MTS] is a phenylalanine dipeptide monomer compound that is isolated from the Chinese ethnic medicine Matijin (Dichondra repens Forst.). Its derivatives exhibit various pharmacological activities, especially anti-tumor. Among them, the novel MTS derivative HXL131 has a significant inhibitory effect against prostate tumor growth and metastasis. This study is designed to investigate the effects of HXL131 on the growth and metastasis of human PCa cell lines PC3 and its molecular mechanism through in vitro experiments combined with proteomics, molecular docking, and gene silencing. The in vitro results showed that HXL131 concentration dependently inhibited PC3 cell proliferation, induced apoptosis, arrested cell cycle at the G2/M phase, and inhibited cell migration capacity. A proteomic analysis and a Western blot showed that HXL131 up-regulated the expression of proliferation, apoptosis, cell cycle, and migration-related proteins CYR61, TIMP1, SOD2, IL6, SERPINE2, DUSP1, TNFSF9, OSMR, TNFRSF10D, and TNFRSF12A. Molecular docking, a cellular thermal shift assay (CETSA), and gene silencing showed that HXL131 had a strong binding affinity with DUSP1 and TNFSF9, which are important target genes for inhibiting the growth and metastasis of PC3 cells. This study demonstrates that HXL131 exhibited excellent anti-prostate cancer activity and inhibited the growth and metastasis of prostate cancer cells by regulating the expression of DUSP1 and TNFSF9.
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Produtos Biológicos , Neoplasias da Próstata , Ligante 4-1BB , Apoptose , Produtos Biológicos/farmacologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Dipeptídeos/farmacologia , Dipeptídeos/uso terapêutico , Fosfatase 1 de Especificidade Dupla/genética , Humanos , Interleucina-6/farmacologia , Masculino , Simulação de Acoplamento Molecular , Fenilalanina/farmacologia , Neoplasias da Próstata/metabolismo , Proteômica , Serpina E2/farmacologiaRESUMO
Inflammatory, proliferative and remodeling phases constitute a cutaneous wound healing program. Therapeutic applications and medication are available; however, they commonly are comprised of fortified preservatives that might prolong the healing process. Chick early amniotic fluids (ceAF) contain native therapeutic factors with balanced chemokines, cytokines and growth-related factors; their origins in principle dictate no existence of harmful agents that would otherwise hamper embryo development. Instead, they possess a spectrum of molecules driving expeditious mitotic divisions and possibly exerting other functions. Employing both in vitro and in vivo models, we examined ceAF's therapeutic potentials in wound healing and found intriguing involvement of transient senescence, known to be intimately intermingled with Senescence Associated Secretory Phenotypes (SASP) that function in addition to or in conjunction with ceAF to facilitate wound healing. In our cutaneous wound healing models, a low dose of ceAF exhibited the best efficacies; however, higher doses attenuated the wound healing presumably by inducing p16 expression over a threshold. Our studies thus link an INK4/ARF locus-mediated signaling cascade to cutaneous wound healing, suggesting therapeutic potentials of ceAF exerting functions likely by driving transient senescence, expediting cellular proliferation, migration, and describing a homeostatic and balanced dosage strategy in medical intervention.
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In Asia, prostate cancer is becoming a growing concern, impacting both socially and economically, compared with what is seen in western countries. Hence, it is essential to know the mechanisms associated with the development and tumorigenesis of PCa for primary diagnosis, risk management, and development of therapy strategies against PCa. Kinesin family member 15 (KIF15), a kinesin family member, is a plus-end-directed kinesin that functions to form bipolar spindles. There is emerging evidence indicating that KIF15 plays a significant role in several malignancies, such as pancreatic cancer, hepatocellular carcinoma, lung adenocarcinoma, and breast cancer. Still, the function of KIF15 remains unclear in prostate cancer. Here, we study the functional importance of KIF15 in the tumorigenesis of PCa. The bioinformatic analysis from PCa patients revealed high KIF15 expression compared to normal prostate tissues. High expression hinting at a possible functional role of KIF15 in regulating cell proliferation of PCa, which was demonstrated by both in vitro and in vivo assays. Downregulation of KIF15 silenced the expression of CDK2, p-RB, and Cyclin D1 and likewise blocked the cells at the G1 stage of the cell cycle. In addition, KIF15 downregulation inhibited MEK-ERK signaling by significantly silencing p-ERK and p-MEK levels. In conclusion, this study confirmed the functional significance of KIF15 in the growth and development of prostate cancer and could be a novel therapeutic target for the treatment of PCa.
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Cinesinas/genética , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Animais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Biologia Computacional/métodos , Bases de Dados Genéticas , Humanos , Cinesinas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias da Próstata/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND: Observational studies indicate that phospholipid fatty acids (FAs) have an impact on the etiology in cancers, but the results are conflicting. We aimed to investigate the causal association of phospholipid FAs with breast cancer and prostate cancer. METHODS: Fourteen single nucleotide polymorphisms (SNPs) were selected as instrumental variables to predict the level of 10 phospholipid FAs from Genome-wide association studies (GWAS). We obtained the summary statistics for the latest and largest GWAS datasets for breast cancer (113,789 controls and 133,384 cases) and prostate cancer (61,106 controls and 79,148 cases) from the Breast Cancer Association Consortium (BCAC) and Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome (PRACTICAL) consortium. Two-sample Mendelian randomization analysis was applied. RESULTS: The results demonstrate that the 10 individual plasma phospholipid FAs are not significantly associated with breast cancer risk and prostate cancer risk. CONCLUSION: The evidence is insufficient to support the causal association of the 10 individual plasma phospholipid FAs with breast cancer and prostate cancer.
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Despite 50 years of extensive research, no definite drug is currently available to treat acute respiratory distress syndrome (ARDS), and the supportive therapies remain the mainstay of treatment. To improve drug development for ARDS, researchers need to deeply analyze the "omics" approaches, reevaluate the suitable therapeutic targets, resolve the problems of inadequate animal modeling, develop the strategies to reduce the heterogeneity, and reconsider new therapeutic and analytical approaches for better designs of clinical trials.
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Desenvolvimento de Medicamentos/métodos , Descoberta de Drogas/métodos , Síndrome do Desconforto Respiratório/tratamento farmacológico , Medicamentos para o Sistema Respiratório/uso terapêutico , Pesquisa Translacional Biomédica/métodos , Animais , Qualidade de Produtos para o Consumidor , Desenvolvimento de Medicamentos/história , Descoberta de Drogas/história , Predisposição Genética para Doença , Genômica , História do Século XX , História do Século XXI , Humanos , Medicina de Precisão , Síndrome do Desconforto Respiratório/diagnóstico , Síndrome do Desconforto Respiratório/genética , Síndrome do Desconforto Respiratório/fisiopatologia , Medicamentos para o Sistema Respiratório/efeitos adversos , Medicamentos para o Sistema Respiratório/história , Medição de Risco , Pesquisa Translacional Biomédica/históriaRESUMO
Lung development is mediated by assorted signaling proteins and orchestrated by complex mesenchymal-epithelial interactions. Notch signaling is an evolutionarily conserved cell-cell communication mechanism that exhibits a pivotal role in lung development. Notably, both aberrant expression and loss of regulation of Notch signaling are critically linked to the pathogenesis of various lung diseases, in particular, pulmonary fibrosis, lung cancer, pulmonary arterial hypertension, and asthmatic airway remodeling; implying that precise regulation of intensity and duration of Notch signaling is imperative for appropriate lung development. Moreover, evidence suggests that Notch signaling links embryonic lung development and asthmatic airway remodeling. Herein, we summarized all-recent advances associated with the mechanistic role of Notch signaling in lung development, consequences of aberrant expression or deletion of Notch signaling in linking early-impaired lung development and asthmatic airway remodeling, and all recently investigated potential therapeutic strategies to treat asthmatic airway remodeling.