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1.
Oncol Lett ; 28(2): 401, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38979553

RESUMO

Transcatheter arterial chemoembolization (TACE) combined with tyrosine kinase inhibitors (TKIs) and camrelizumab (collectively: T-T-C) is a novel treatment strategy for unresectable hepatocellular carcinoma (HCC). The present systematic review and meta-analysis aimed to evaluate the efficacy and safety of T-T-C compared with TACE combined with TKIs only (T-T) in the treatment of patients with unresectable HCC. A systematic literature search was conducted on T-T and T-T-C using PubMed, Embase and the Cochrane Library. Data regarding the clinical outcome, including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs), were independently extracted and analyzed by two researchers using standardized protocols. In total, 7 cohort studies, including 1,798 patients (T-T-C, 838; T-T, 960), were included in the meta-analysis. The results of the present study demonstrated that the T-T-C group had significantly prolonged OS [hazard ratio (HR), 0.38; 95% confidence interval (CI), 0.29-0.50; I2=61.5%; P=0.016)] and PFS (HR, 0.37; 95% CI, 0.30-0.46; I2=44.5%; P=0.109), and showed significantly higher objective response rates [risk ratio (RR), 0.82; 95% CI, 0.69-0.96; I2=25.1%; P=0.237)] and slightly higher disease control rates without a significant difference (RR, 0.96; 95% CI, 0.89-1.03; I2=0.0%; P=0.969). In addition, grade 3/4 AEs were more common in the T-T group, including hypertension (RR, 1.15; 95% CI, 0.85-1.56), vomiting or nausea (RR, 0.88; 95% CI, 0.44-1.76) and pain (RR, 0.74; 95% CI, 0.45-1.21); however, these results were not statistically significant. In conclusion, compared with T-T combination therapy, T-T-C demonstrated a notable advantage in terms of OS, PFS, ORR and DCR in patients with unresectable HCC. For manageable AEs, although the results were not statistically significant, the incidence of AEs in the T-T group was higher than that in the T-T-C group in terms of event probability.

2.
J Colloid Interface Sci ; 675: 471-480, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38986320

RESUMO

In addition to the intrinsic driving force of photocatalysis, the external thermal field from the photothermal effect can provide additional energy to the photo-catalytic system to improve the photo-catalytic hydrogen-evolution (PHE) efficiency. Herein, based on the results of density functional theory, we designed and constructed a hollow core-shell FeNi2S4@Mn0.3Cd0.7S (NFS@MCS) S-scheme heterojunction with a photothermal effect, thereby realising a significant enhancement of the PHE performance due to the thermal effect, S-scheme heterojunction and hollow core-shell morphology. As a light collector and heat source, the hollow NFS could absorb and convert photons into heat, resulting in the increased local temperature of photocatalyst particles. Moreover, the S-scheme charge path at the interface not only improved the carrier separation efficiency but also retained a higher redox potential. All these are favourable to increase the PHE activity. The PHE tests show that 0.5 %-NFS@MCS exhibits the highest PHE rate of 17.11 mmol·g-1·h-1, 7.7 times that of MCS. Moreover, through a combination of theoretical calculation and experimental evidence, the PHE mechanism of the NFS@MCS system is discussed and clarified in-depth.

3.
J Gastric Cancer ; 24(3): 300-315, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38960889

RESUMO

PURPOSE: Gastric cancer (GC) is among the deadliest malignancies and the third leading cause of cancer-related deaths worldwide. Galectin-1 (Gal-1) is a primary protein secreted by cancer-associated fibroblasts (CAFs); however, its role and mechanisms of action of Gal-1 in GC remain unclear. In this study, we stimulated GC cells with exogenous human recombinant galectin-1 protein (rhGal-1) to investigate its effects on the proliferation, migration, and resistance to cisplatin. MATERIALS AND METHODS: We used simulated rhGal-1 protein as a paracrine factor produced by CAFs to induce GC cells and investigated its promotional effects and mechanisms in GC progression and cisplatin resistance. Immunohistochemical (IHC) assay confirmed that Gal-1 expression was associated with clinicopathological parameters and correlated with the expression of neuropilin-1 (NRP-1), c-JUN, and Wee1. RESULTS: Our study reveals Gal-1 expression was significantly associated with poor outcomes. Gal-1 boosts the proliferation and metastasis of GC cells by activating the NRP-1/C-JUN/Wee1 pathway. Gal-1 notably increases GC cell resistance to cisplatin The NRP-1 inhibitor, EG00229, effectively counteracts these effects. CONCLUSIONS: These findings revealed a potential mechanism by which Gal-1 promotes GC growth and contributes to chemoresistance, offering new therapeutic targets for the treatment of GC.


Assuntos
Proliferação de Células , Cisplatino , Resistencia a Medicamentos Antineoplásicos , Galectina 1 , Neuropilina-1 , Neoplasias Gástricas , Neoplasias Gástricas/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/genética , Humanos , Galectina 1/genética , Galectina 1/metabolismo , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Neuropilina-1/metabolismo , Neuropilina-1/genética , Proliferação de Células/efeitos dos fármacos , Masculino , Feminino , Progressão da Doença , Linhagem Celular Tumoral , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Pessoa de Meia-Idade , Camundongos , Animais , Movimento Celular/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/efeitos dos fármacos , Fibroblastos Associados a Câncer/patologia
4.
Front Immunol ; 15: 1381802, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966637

RESUMO

Background: Yishen-Tongbi Decoction (YSTB), a traditional Chinese prescription, has been used to improve syndromes of rheumatoid arthritis (RA) for many years. Previous research has shown that YSTB has anti-inflammatory and analgesic properties. However, the underlying molecular mechanism of the anti-RA effects of YSTB remains unclear. Purpose and study design: The purpose of this research was to investigate how YSTB affected mice with collagen-induced arthritis (CIA) and RAW264.7 cells induced with lipopolysaccharide (LPS). Results: The findings show that YSTB could significantly improve the clinical arthritic symptoms of CIA mice (mitigate paw swelling, arthritis score, thymus and spleen indices, augment body weight), downregulated expression of pro-inflammatory cytokines like tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), IL-6 and IL-17, while upregulated the level of anti-inflammatory like IL-10 and transforming growth factor-ß (TGF-ß). Meanwhile, YSTB inhibits bone erosion and reduces inflammatory cell infiltration, synovial proliferation, and joint destruction in CIA mice. In addition, we found that YSTB was able to suppress the LPS-induced inflammation of RAW264.7 cells, which was ascribed to the suppression of nitric oxide (NO) production and reactive oxygen species formation (ROS). YSTB also inhibited the production of inducible nitric oxide synthase and reduced the releases of pro-inflammatory cytokines TNF-α, IL-1ß, and IL-6 in LPS-induced RAW264.7 cells. Furthermore, the phosphorylation expression of JAK2, JAK3, STAT3, p38, ERK and p65 protein could be suppressed by YSTB, while the expression of SOCS3 could be activated. Conclusion: Taken together, YSTB possesses anti-inflammatory and prevention bone destruction effects in RA disease by regulating the JAK/STAT3/SOCS3 signaling pathway.


Assuntos
Artrite Experimental , Artrite Reumatoide , Medicamentos de Ervas Chinesas , Janus Quinases , Fator de Transcrição STAT3 , Transdução de Sinais , Proteína 3 Supressora da Sinalização de Citocinas , Animais , Camundongos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/metabolismo , Células RAW 264.7 , Fator de Transcrição STAT3/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/metabolismo , Proteína 3 Supressora da Sinalização de Citocinas/genética , Artrite Experimental/tratamento farmacológico , Artrite Experimental/patologia , Artrite Experimental/metabolismo , Transdução de Sinais/efeitos dos fármacos , Janus Quinases/metabolismo , Masculino , Citocinas/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Inflamação/tratamento farmacológico , Camundongos Endogâmicos DBA , Modelos Animais de Doenças
5.
J Colloid Interface Sci ; 673: 463-474, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38878380

RESUMO

Rational design of the morphology and heterojunction to accelerate the separation of electron-hole pairs has played an indispensable role in improving the photocatalytic hydrogen evolution. ZnIn2S4 (ZIS) has aroused considerable attention in solar-to-chemical energy conversion due to its remarkable photoelectrical properties and relatively negative energy band, whereas it still suffers from the severe photogenerated carrier recombination and catalyst aggregation. Herein, guided by density functional theory calculations, the constructed FeSe2@ZnIn2S4 (FS@ZIS) heterojunction model has a hydrogen Gibbs free energy closer to zero compared with pure ZIS and FS, which is beneficial for hydrogen adsorption and desorption on the photocatalyst surface. Therefore, a novel cross-like core-shell FS@ZIS Step-scheme (S-scheme) heterojunction was synthesized successfully by in-situ growing ZIS nanosheets on the surface of cross-like FS. The structure with cross-like core-shell morphology not only inhibits the agglomeration of ZIS to increase specific surface area, but also provides a tight interface with S-scheme heterojunction. Moreover, the S-scheme heterojunction with a tight interface can effectively separate electron-hole pairs, leaving photoinduced charges with higher potentials. Furthermore, FS@ZIS-20 possesses exceptional photothermal capabilities, enabling the conversion of optical energy from visible and near infrared light to heat, thereby further enhancing the photocatalysis reaction. As a result, the cross-like core-shell FS@ZIS S-scheme heterojunction exhibits an excellent photocatalytic hydrogen evolution rate (7.640 mmol g-1 h-1), which is 24 times higher than that of pure ZIS (0.319 mmol g-1 h-1) under visible and near infrared light. Furthermore, employing more in-depth density functional theory calculations further investigates the charge transfer pathway of the FS@ZIS S-scheme heterojunction. This work provides insights into the construction of S-scheme heterojunctions with core-shell structure and photothermal effect for photocatalytic evolution hydrogen.

6.
Ultrason Sonochem ; 107: 106932, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38824698

RESUMO

Artemisia argyi leaf polysaccharide (AALPs) were prepared through ultrasound-assisted extraction (UAE), and their antifatigue activities were evaluated. Extraction was optimized using response surface methodology (RSM), which yielded the following optimal UAE conditions: ultrasonication power of 300 W, extraction temperature of 51 °C, liquid:solid ratio of 20 mL/g, and ultrasonication time of 47 mins. The above optimal conditions resulted in the maximum extraction rate of 10.49 %. Compared with hot water extraction (HWE), UAE supported higher yields and total sugar, uronic acid, and sulfate contents of AALPs. Meanwhile, AALP prepared through UAE (AALP-U) exhibited higher stability due to its smaller particle size and higher absolute value of zeta potential than AALP prepared through HWE (AALP-H). In addition, AALP-U demonstrated stronger antioxidant activity than AALP-H. In forced swimming tests on mice, AALP-U could significantly prolong swimming time with a dose-dependent effect, increase liver and muscle glycogen levels, and improve other biochemical indices, thus showing great potential for application in functional food.


Assuntos
Artemisia , Folhas de Planta , Polissacarídeos , Polissacarídeos/farmacologia , Polissacarídeos/isolamento & purificação , Polissacarídeos/química , Artemisia/química , Folhas de Planta/química , Animais , Camundongos , Ondas Ultrassônicas , Fracionamento Químico/métodos , Antioxidantes/farmacologia , Antioxidantes/isolamento & purificação , Antioxidantes/química , Química Verde/métodos , Masculino , Glicogênio/metabolismo , Natação , Fígado/efeitos dos fármacos
7.
J Neuroimmune Pharmacol ; 19(1): 31, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38886223

RESUMO

Neuroinflammation is a key factor in cognitive dysfunction and neurodegenerative diseases such as Alzheimer's disease (AD), so inhibiting neuroinflammation is considered as a potential treatment for AD. Epigallocatechin-3-gallate (EGCG), a polyhydroxyphenol of green tea, has been found to exhibit anti-oxidative, anti-inflammatory and neuroprotective effects. The aim of this study was to investigate the inhibitory effect of EGCG on inflammation and its mechanism. In this study, BV2 cells were simultaneously exposed to lipopolysaccharides (LPS) and the amyloid-ß oligomer (AßO) to induce inflammatory microenvironments. Inflammatory cytokines and NLRP3 inflammasome-related molecules were detected by RT-PCR and Western Blot. The results show that EGCG inhibits LPS/AßO-induced inflammation in BV2 cells through regulating IL-1ß, IL-6, and TNF-α. Meanwhile, EGCG reduces the activation of the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome and levels of intracellular ROS in BV2 cells treated with LPS/AßO by affecting the mitochondrial membrane potential (MMP). Further research found that EGCG inhibited MMP through regulating thioredoxin-interacting protein (TXNIP) in LPS/AßO-induced neuroinflammation. In conclusion, EGCG may alleviate LPS/AßO-induced microglial neuroinflammation by suppressing the ROS/ TXNIP/ NLRP3 pathway. It may provide a potential mechanism underlying the anti-inflammatory properties of EGCG for alleviating AD.


Assuntos
Peptídeos beta-Amiloides , Proteínas de Transporte , Catequina , Lipopolissacarídeos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Doenças Neuroinflamatórias , Espécies Reativas de Oxigênio , Transdução de Sinais , Catequina/análogos & derivados , Catequina/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Lipopolissacarídeos/toxicidade , Animais , Peptídeos beta-Amiloides/toxicidade , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Transporte/metabolismo , Transdução de Sinais/efeitos dos fármacos , Doenças Neuroinflamatórias/tratamento farmacológico , Doenças Neuroinflamatórias/metabolismo , Linhagem Celular , Tiorredoxinas/metabolismo , Microglia/efeitos dos fármacos , Microglia/metabolismo
8.
Eur J Pharm Biopharm ; 200: 114327, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38759900

RESUMO

P-glycoprotein (P-gp) overexpressed mutidrug resistance (MDR) is currently a key factor limiting the effectiveness of breast cancer chemotherapy. Systemic administration based on P-gp-associated mechanism leads to severe toxic side effects. Here, we designed a T7 peptide-modified mixed liposome (T7-MLP@DTX/SchB) that, by active targeting co-delivering chemotherapeutic agents and P-gp inhibitors, harnessed synergistic effects to improve the treatment of MDR breast cancer. This study established drug-resistant cell models and animal models. Subsequently, comprehensive evaluations involving cell uptake, cell apoptosis, cellular toxicity assays, in vivo tumor-targeting capability, and anti-tumor activity assays were conducted to assess the drug resistance reversal effects of T7-MLP@DTX/SchB. Additionally, a systematic assessment of the biosafety profile of T7-MLP@DTX/SchB was executed, including blood profiles, biochemical markers, and histopathological examination. It was found that this co-delivery strategy successfully exerted the synergistic effects, since there was a significant tumor growth inhibitory effect on multidrug-resistant breast cancer. Targeted modification with T7 peptide enhanced the therapeutic efficacy remarkably, while vastly ameliorating the biocompatibility compared to free drugs. The intriguing results supported the promising potential use of T7-MLP@DTX/SchB in overcoming MDR breast cancer treatment.


Assuntos
Neoplasias da Mama , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Lipossomos , Camundongos Endogâmicos BALB C , Feminino , Animais , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Humanos , Camundongos , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Linhagem Celular Tumoral , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Nus , Células MCF-7 , Fragmentos de Peptídeos/administração & dosagem , Doxorrubicina/administração & dosagem , Doxorrubicina/farmacologia , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Colágeno Tipo IV
9.
Eur J Surg Oncol ; 50(7): 108427, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38796968

RESUMO

BACKGROUND: Salvage liver transplantation (SLT) is an effective treatment option for recurrent hepatocellular carcinoma (rHCC) following primary curative treatment (CUR). However, its efficacy remains controversial compared to that of CURs, including repeat liver resection (RLR) and local ablation. This meta-analysis compared the efficacy and safety of these procedures. METHODS: A systematic literature search of the PubMed, Embase, Web of Science, and Cochrane Library databases for studies investigating SLT and CUR was performed. Outcome data, including overall and disease-free survival, tumor response, and operative and postoperative outcomes, were independently extracted and analyzed by two authors using a standardized protocol. RESULTS: Fifteen cohort studies comprising 508 and 2050 patients with rHCC, who underwent SLT or CUR, respectively, were included. SLT achieved significantly longer overall survival than both CUR (hazard ratio [HR]: 0.56, 95 % confidence interval [CI]: 0.45-0.68; I2 = 34.6 %, p = 0.105) and RLR (HR: 0.64, 95 % CI: 0.49-0.84; I2 = 0.0 %, p = 0.639). Similar significantly better survival benefits were observed compared with CUR (HR: 0.30, 95 % CI: 0.20-0.45; I2 = 51.1 %, p = 0.038) or RLR (HR: 0.31, 95 % CI: 0.18-0.56; I2 = 65.7 %, p = 0.005) regarding disease-free survival. However, SLT resulted in a longer operative duration and hospital stay, larger amount of blood loss, higher rate of transfusion and postoperative morbidity, and slightly higher postoperative mortality than CUR. CONCLUSION: SLT was associated with better long-term survival than CUR or RLR in patients with rHCC after primary curative treatment.


Assuntos
Carcinoma Hepatocelular , Hepatectomia , Neoplasias Hepáticas , Transplante de Fígado , Recidiva Local de Neoplasia , Terapia de Salvação , Humanos , Carcinoma Hepatocelular/cirurgia , Hepatectomia/métodos , Neoplasias Hepáticas/cirurgia , Terapia de Salvação/métodos , Taxa de Sobrevida
10.
Bioorg Med Chem ; 106: 117754, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38728869

RESUMO

To improve the biodistribution of the drug in the tumor, a supramolecular prodrug of SN38 was fabricated in situ between endogenous albumin and SN38 prodrug modified with semaglutide side chain. Firstly, SN38 was conjugated with semaglutide side chain and octadecanedioic acid via glycine linkers to obtain SI-Gly-SN38 and OA-Gly-SN38 prodrugs, respectively. Both SI-Gly-SN38 and OA-Gly-SN38 exhibited excellent stability in PBS for over 24 h. Due to the strong binding affinity of the semaglutide side chain with albumin, the plasma half-life of SI-Gly-SN38 was 2.7 times higher than that of OA-Gly-SN38. Furthermore, with addition of HSA, the fluorescence intensity of SI-Gly-SN38 was 4 times higher than that of OA-Gly-SN38, confirming its strong binding capability with HSA. MTT assay showed that the cytotoxicity of SI-Gly-SN38 and OA-Gly-SN38 was higher than that of Irinotecan. Even incubated with HSA, the SI-Gly-SN38 and OA-Gly-SN38 still maintained high cytotoxicity, indicating minimal influence of HSA on their cytotoxicity. In vivo pharmacokinetic studies demonstrated that the circulation half-life of SI-Gly-SN38 was twice that of OA-Gly-SN38. SI-Gly-SN38 exhibited significantly reduced accumulation in the lungs, being only 0.23 times that of OA-Gly-SN38. The release of free SN38 in the lungs from SI-Gly-SN38 was only 0.4 times that from OA-Gly-SN38 and Irinotecan. The SI-Gly-SN38 showed the highest accumulation in tumors. The tumor inhibition rate of SI-Gly-SN38 was 6.42% higher than that of OA-Gly-SN38, and 8.67% higher than that of Irinotecan, respectively. These results indicate that the supramolecular prodrug delivery system can be constructed between SI-Gly-SN38 and endogenous albumin, which improves drug biodistribution in vivo, enhances tumor accumulation, and plays a crucial role in tumor growth inhibition.


Assuntos
Irinotecano , Pró-Fármacos , Irinotecano/química , Irinotecano/farmacologia , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Pró-Fármacos/síntese química , Animais , Humanos , Camundongos , Distribuição Tecidual , Antineoplásicos/química , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacocinética , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Linhagem Celular Tumoral , Camundongos Endogâmicos BALB C , Camundongos Nus , Albuminas/química , Masculino , Relação Estrutura-Atividade , Albumina Sérica Humana/química , Peptídeos Semelhantes ao Glucagon
11.
J Control Release ; 369: 622-629, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38604383

RESUMO

Enhancing the delivery and release efficiency of hydroxyl agents, constrained by high pKa values and issues of release rate or unstable linkage, is a critical challenge. To address this, a self-immolative linker, composed of a modifiable p-hydroxybenzyl ether and a fast cyclization adapter (N-(ortho-hydroxyphenyl)-N-methylcarbamate) was strategically designed, for the synthesis of prodrugs. The innovative linker not only provides a side chain modification but also facilitates the rapid release of the active payloads, thereby enabling precise drug delivery. Particularly, five prodrug model compounds (J1, J2, J3, J5 and J6) were synthesized to evaluate the release rates by using ß-glucuronic acid as trigger and five hydroxyl compounds as model payloads. Significantly, all prodrug model compounds could efficiently release the hydroxyl payloads under the action of ß-glucuronidase, validating the robustness of the linker. And then, to assess the drug delivery and release efficiency using endogenous albumin as a transport vehicle, J1148, a SN38 prodrug modified with maleimide side chain was synthesized. Results demonstrated that J1148 covalently bound to plasma albumin through in situ Michael addition, effectively targeting the tumor microenvironment. Activated by ß-glucuronidase, J1148 underwent a classical 1, 6-elimination, followed by rapid cyclization of the adapter, thereby releasing SN38. Impressively, J1148 showed excellent therapeutic efficacy against human colonic cancer xenograft model, leading to a significant reduction or even disappearance of tumors (3/6 of mice cured). These findings underscore the potential of the designed linker in the delivery system of hydroxyl agents, positioning it at the forefront of advancements in drug delivery technology.


Assuntos
Sistemas de Liberação de Medicamentos , Irinotecano , Pró-Fármacos , Pró-Fármacos/administração & dosagem , Pró-Fármacos/química , Pró-Fármacos/farmacocinética , Animais , Humanos , Irinotecano/administração & dosagem , Irinotecano/farmacocinética , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/farmacocinética , Camptotecina/química , Liberação Controlada de Fármacos , Camundongos Nus , Linhagem Celular Tumoral , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/farmacocinética , Feminino , Camundongos , Albuminas/administração & dosagem , Albuminas/química , Glucuronidase/metabolismo , Camundongos Endogâmicos BALB C
12.
Molecules ; 29(7)2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38611904

RESUMO

In recent years, caffeic acid and its derivatives have received increasing attention due to their obvious physiological activities and wide distribution in nature. In this paper, to clarify the status of research on plant-derived caffeic acid and its derivatives, nuclear magnetic resonance spectroscopy data and possible biosynthetic pathways of these compounds were collected from scientific databases (SciFinder, PubMed and China Knowledge). According to different types of substituents, 17 caffeic acid and its derivatives can be divided into the following classes: caffeoyl ester derivatives, caffeyltartaric acid, caffeic acid amide derivatives, caffeoyl shikimic acid, caffeoyl quinic acid, caffeoyl danshens and caffeoyl glycoside. Generalization of their 13C-NMR and 1H-NMR data revealed that acylation with caffeic acid to form esters involves acylation shifts, which increase the chemical shift values of the corresponding carbons and decrease the chemical shift values of the corresponding carbons of caffeoyl. Once the hydroxyl group is ester, the hydrogen signal connected to the same carbon shifts to the low field (1.1~1.6). The biosynthetic pathways were summarized, and it was found that caffeic acid and its derivatives are first synthesized in plants through the shikimic acid pathway, in which phenylalanine is deaminated to cinnamic acid and then transformed into caffeic acid and its derivatives. The purpose of this review is to provide a reference for further research on the rapid structural identification and biofabrication of caffeic acid and its derivatives.


Assuntos
Vias Biossintéticas , Ácidos Cafeicos , Ácido Chiquímico , Carbono , Ésteres , Espectroscopia de Ressonância Magnética
13.
Bioorg Chem ; 147: 107370, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38621338

RESUMO

Here, we introduce a novel and effective approach utilizing a cathepsin B cleavage albumin-binding SN38 prodrug specifically designed for the treatment of metastatic breast cancer. Termed Mal-va-mac-SN38, our prodrug exhibits a unique ability to rapidly and covalently bind with endogenous albumin, resulting in the formation of HSA-va-mac-SN38. This prodrug demonstrates exceptional stability in human plasma. Importantly, HSA-va-mac-SN38 showcases an impressive enhancement in cellular uptake by 4T1 breast cancer cells, primarily facilitated through caveolin-mediated endocytosis. Intriguingly, the release of the active SN38, is triggered by the enzymatic activity of cathepsin B within the lysosomal environment. In vivo studies employing a lung metastasis 4T1 breast cancer model underscore the potency of HSA-va-mac-SN38. Histological immunohistochemical analyses further illuminate the multifaceted impact of our prodrug, showcasing elevated levels of apoptosis, downregulated expression of matrix metalloproteinases, and inhibition of angiogenesis, all critical factors contributing to the anti-metastatic effect observed. Biodistribution studies elucidate the capacity of Mal-va-mac-SN38 to augment tumor accumulation through covalent binding to serum albumin, presenting a potential avenue for targeted therapeutic interventions. Collectively, our findings propose a promising therapeutic avenue for metastatic breast cancer, through the utilization of a cathepsin B-cleavable albumin-binding prodrug.


Assuntos
Antineoplásicos , Neoplasias da Mama , Catepsina B , Desenho de Fármacos , Pró-Fármacos , Pró-Fármacos/síntese química , Pró-Fármacos/química , Pró-Fármacos/farmacologia , Catepsina B/metabolismo , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Animais , Camundongos , Estrutura Molecular , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Relação Dose-Resposta a Droga , Apoptose/efeitos dos fármacos
14.
Front Nutr ; 11: 1335831, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38562487

RESUMO

Background: Despite the rapid increase in the global prevalence of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), there are no approved therapeutic drugs for MAFLD yet. Nutrient supplementation might mitigate the risk of MAFLD. It is more typical for individuals to consume multiple nutrients simultaneously. However, the studies exploring the combined effects of multiple nutrients on MAFLD are limited. This study aimed to investigate the relationship between both individual nutrients and their combined influence on the risk of MAFLD. Methods: Data were obtained from National Health and Nutrition Examination Survey (NHANES), and 18 types of nutrients were considered in this study. Logistic regression analysis was performed to evaluate the correlation between single nutrients and the risk of MAFLD. The Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis was performed to pinpoint the most relevant nutrient associated with the risk of MAFLD. Subsequently, both Weighted Quantile Sum (WQS) regression and Quantile g-computation (Qgcomp) were used to assess the combined effects of multiple nutrients on the risk of MAFLD. Results: A total of 3,069 participants were included in this study. LASSO regression analysis showed that Se, α-tocopherol, and γ-tocopherol exhibited a positive association with the risk of MAFLD. In contrast, the serum levels of Co, P, α-cryptoxanthin, LZ, and trans-ß-carotene were inversely associated with the prevalence of MAFLD. When Se and two types of vitamin E were excluded, the WQS index showed a significant inverse relationship between the remaining 15 nutrients and the risk of MAFLD; α-cryptoxanthin showed the most substantial contribution. Similarly, Qgcomp suggested that the combined effects of these 15 nutrients were associated with a lower risk of MAFLD, with α-cryptoxanthin possessing the most significant negative weights. Conclusion: This study suggested that the complex nutrients with either a low proportion of Se, α-tocopherol, and γ-tocopherol or without them should be recommended for patients with MAFLD to reduce its risk.

15.
Appl Radiat Isot ; 209: 111330, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38657372

RESUMO

Boron neutron capture therapy (BNCT) has received extensive attention as an advanced binary radiotherapy method. However, BNCT still faces poor selectivity of boron agent and is insufficient boron content in tumor tissues. To improve the tumor-targeted ability and boron content, this research aims to design, synthesize and preliminary evaluate a new borane agent Carborane-FAPI, which coupling the o-carborane to the compound skeleton of a mature fibroblast activating protein (FAP) inhibitor (FAPI). FAP is a tumor-associated antigen. FAP expressed lowly in normal organs and highly expressed in tumors, so it is a potential target for diagnosis and treatment. Boronophenylalanine (BPA) is the most widely investigated BNCT drug in present. Compared with BPA, the boron content of a single molecule is increased and drug targeting is enhanced. The results show that Carboaren-FAPI has low toxicity to normal cells, and selective enrichment in tumor tissues. It is a promising boron drug that has the potential to be used in BNCT.


Assuntos
Boranos , Terapia por Captura de Nêutron de Boro , Boro , Terapia por Captura de Nêutron de Boro/métodos , Humanos , Animais , Camundongos , Proteínas de Membrana/metabolismo , Endopeptidases , Serina Endopeptidases/metabolismo , Gelatinases/metabolismo , Compostos de Boro/uso terapêutico , Compostos de Boro/farmacocinética , Linhagem Celular Tumoral
16.
Adv Sci (Weinh) ; 11(22): e2400310, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38489751

RESUMO

Solar desalination is a promising strategy to utilize solar energy to purify saline water. However, the accumulation of salt on the solar evaporator surface severely reduces light absorption and evaporation performance. Herein, a simple and eco-friendly method to fabricate a 3D gradient graphene spiral sponge (GGS sponge) is presented that enables high-rate solar evaporation and zero liquid discharge (ZLD) desalination of high-salinity brine. The spiral structure of the GGS sponge enhances energy recovery, while the gradient network structures facilitate radial brine transport and directional salt crystallization, which cooperate to endow the sponge with superior solar evaporation (6.5 kg m-2 h-1 for 20 wt.% brine), efficient salt collection (1.5 kg m-2 h-1 for 20 wt.% brine), ZLD desalination, and long-term durability (continuous 144 h in 20 wt.% brine). Moreover, the GGS sponge shows an ultrahigh freshwater production rate of 3.1 kg m-2 h-1 during the outdoor desalination tests. A continuous desalination-irrigation system based on the GGS sponge for crop growth, which has the potential for self-sustainable agriculture in remote areas is demonstrated. This work introduces a novel evaporator design and also provides insight into the structural principles for designing next-generation solar desalination devices that are salt-tolerant and highly efficient.

17.
Food Chem ; 448: 139026, 2024 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-38531298

RESUMO

Linusorbs (LOs), significantly influence oil quality and sensory properties of flaxseed oil. Trp-containing LOs exhibit distinct oxidative behavior when γ-tocopherol (γ-T) is present. Polar fractions of crude flaxseed oil were stripped via silica absorption, and reintroduced (LO and γ-T) separately into the oil matrix to investigate their interaction during storage. Compared with crude oil, LOs account for 18.49% reduction of p-anisidine value, while LOs with γ-T contributed to most of the endogenous antioxidant effect in crude oil. γ-T was found to suppress oxidation of Trp-containing LO at early stage (Met form), while facilitate oxidation while at their mid-stage (MetO form, Methionine sulfoxide). In vitro oxidation shows that CLD more likely cleaved into peptide fragments, while few products retain intact ring structures. LC-MS/MS analysis and silicon simulation revealed proximity between MetO and Trp residues, facilitating inter- or intra-molecular reactions and ring structure rupture. Remarkably, the presence of γ-T facilitate these phenomena.


Assuntos
Óleo de Semente do Linho , Triptofano , gama-Tocoferol , Triptofano/química , Óleo de Semente do Linho/química , gama-Tocoferol/química , Oxirredução , Antioxidantes/química , Espectrometria de Massas em Tandem , Linho/química
18.
Obes Surg ; 34(5): 1608-1617, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38530552

RESUMO

INTRODUCTION: Bariatric surgery (BS) patients are advised to consume protein supplements to prevent fat-free mass (FFM) loss. However, limited research has explored the efficacy of diverse protein presentations on FFM preservation. This study assesses if short peptide-based (SPB) supplements surpass complex protein-based (CPB) supplements in reducing early FFM loss post-surgery. METHODS: In this retrospective cohort study, 138 patients who underwent BS other than Roux-en-Y-gastric bypass (RYGB) between January 2021 and March 2021 at the Department of Bariatric Surgery of the Third People's Hospital of Chengdu were included for analysis. Patients were divided into two groups based on their consumption of protein supplements after surgery: SPB group and CPB group. Multiple linear regressions separated by sex were employed to examine the associations between SPB supplements and FFM loss and percentage of FFM (%FFM) loss, respectively. RESULTS: Among participants, 69.6% were female, with a mean age of 33.3 years. In multiple linear regression analyses, SPB supplements were significantly and positively associated with a lower FFM loss in both female (ꞵ = - 1.14, P = 0.047) and male (ꞵ = - 2.36, P = 0.024), and were positively associated with a lower %FFM loss in both female (ꞵ = - 1.83) and male (ꞵ = - 2.26) but only significant in male (P = 0.049). CONCLUSION: SPB supplements may be more effective in preventing early FFM loss after BS, compared to CPB supplements, particularly among male patients. Therefore, SPB supplements may be recommended to patients undergoing BS. Further research is needed to validate these findings.


Assuntos
Cirurgia Bariátrica , Derivação Gástrica , Obesidade Mórbida , Humanos , Masculino , Feminino , Adulto , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Composição Corporal , Derivação Gástrica/efeitos adversos , Peptídeos
19.
Front Pharmacol ; 15: 1378292, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523637

RESUMO

Aldo-Keto Reductase Family 1 Member C3 (AKR1C3), also known as type 5 17ß-hydroxysteroid dehydrogenase (17ß-HSD5) or prostaglandin F (PGF) synthase, functions as a pivotal enzyme in androgen biosynthesis. It catalyzes the conversion of weak androgens, estrone (a weak estrogen), and PGD2 into potent androgens (testosterone and 5α-dihydrotestosterone), 17ß-estradiol (a potent estrogen), and 11ß-PGF2α, respectively. Elevated levels of AKR1C3 activate androgen receptor (AR) signaling pathway, contributing to tumor recurrence and imparting resistance to cancer therapies. The overexpression of AKR1C3 serves as an oncogenic factor, promoting carcinoma cell proliferation, invasion, and metastasis, and is correlated with unfavorable prognosis and overall survival in carcinoma patients. Inhibiting AKR1C3 has demonstrated potent efficacy in suppressing tumor progression and overcoming treatment resistance. As a result, the development and design of AKR1C3 inhibitors have garnered increasing interest among researchers, with significant progress witnessed in recent years. Novel AKR1C3 inhibitors, including natural products and analogues of existing drugs designed based on their structures and frameworks, continue to be discovered and developed in laboratories worldwide. The AKR1C3 enzyme has emerged as a key player in carcinoma progression and therapeutic resistance, posing challenges in cancer treatment. This review aims to provide a comprehensive analysis of AKR1C3's role in carcinoma development, its implications in therapeutic resistance, and recent advancements in the development of AKR1C3 inhibitors for tumor therapies.

20.
World Neurosurg ; 184: e794-e802, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38364895

RESUMO

OBJECTIVE: This study aimed to investigate the mediating role of perceived social support and illness uncertainty in posttraumatic growth (PTG) and fear of progression (FoP) among young and middle-aged primary brain tumor (PBT) patients. METHODS: A total of 252 young and middle-aged benign PBT patients were investigated. Data were collected by using self-designed general and disease-related data questionnaires, PTG Inventory, FoP Questinaire-Short Form, Mischel Uncertainty in Illness Scale, and Perceived Social Support Scale. Parallel mediation effect models were used to explore the relationship between PTG and FoP mediation effects. Bootstrap analysis was conducted to examine the mediation effect of PTG on FoP. RESULTS: The total FoP and PTG scores were 35.15 ± 4.85 and 55.04 ± 7.86. Furthermore, mediation effect analyses revealed that perceived social support and illness uncertainty were partially associated with the mediated relationship between PTG and FoP. (std.ß = -0.026, P-value = 0.001, std. ß = -0.393, P value <0.001, respectively). CONCLUSIONS: Illness uncertainty and perceived social support were identified as partially parallel mediators between PTG and FoP. Thus, we should ensure adequate social support and improve the enthusiasm and input of family members for better patient recovery. Strengthening the nursing support, reducing the uncertainty of young and middle-aged PBT patients, and improving the patients' PTG can help reduce the fear of disease progression.


Assuntos
Neoplasias Encefálicas , Crescimento Psicológico Pós-Traumático , Pessoa de Meia-Idade , Humanos , Adaptação Psicológica , Incerteza , Medo , Apoio Social
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