RESUMO
Globally, breast cancer (BC) has the highest prevalence among malignant diseases. BC is also the primary cause of death among women. Notably, BC morbidity has been increasing continuously at an approximate growth rate of 2.2% per year. Persistent BC is a major public health issue worldwide. Consequently, novel chemotherapeutic agents to combat this lethal disease should be developed urgently. Coumarins with interesting structural and mechanistic variations exhibit promising activity in several forms of BC, including BCs with multidrug resistance. In particular, coumarin hybrids composed of coumarin and one or more anti-BC pharmacophores can target different biological components in BC cells simultaneously. Thus, coumarin hybrids are useful scaffolds that can help improve the anti-BC efficacy of coumarins, reduce side effects, improve pharmacokinetics, minimize drug-drug interactions, and circumvent drug resistance. This review, in which articles published from 2020 to the present day have been evaluated, highlights the landscape of coumarin hybrids that exhibit therapeutic effects against breast cancer. These findings can aid further investigations on novel antibreast-cancer therapeutics.
RESUMO
This study extracted and purified a polysaccharide from Rehmanniae radix praeparata (RGP) with an average molecular weight. The structural characteristics of RGP and its ironâ (III) complex, RGP-Fe(III), were examined for their antioxidant properties and potential in treating iron deficiency anemia (IDA). Analysis revealed that RGP comprised Man, Rha, Gal, and Xyl, with a sugar residue skeleton featuring 1â3; 1â2, 3; and 1â2, 3, 4 linkages, among others. RGP-Fe(III) had a molecular weight of 4.39×104â Da. Notably, RGP-Fe(III) exhibited superior antioxidant activity compared to RGP alone. In IDA rat models, treatment with RGP-Fe(III) led to increased weight gain, restoration of key blood parameters including hemoglobin, red blood cells, and mean hemoglobin content, elevated serum iron levels, and decreased total iron-binding capacity. Histological examination revealed no observable toxic effects of RGP-Fe(III) on the liver and spleen. These findings suggest the potential of RGP-Fe(III) as a therapeutic agent for managing IDA and highlight its promising antioxidant properties.
Assuntos
Anemia Ferropriva , Antioxidantes , Polissacarídeos , Rehmannia , Animais , Polissacarídeos/farmacologia , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Rehmannia/química , Ratos , Antioxidantes/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Anemia Ferropriva/tratamento farmacológico , Compostos Férricos/química , Masculino , Ferro/química , Baço/efeitos dos fármacos , Ratos Sprague-Dawley , Fígado/efeitos dos fármacos , Fígado/metabolismo , Modelos Animais de DoençasRESUMO
Naturally occurring protein nanocages like ferritin are self-assembled from multiple subunits. Because of their unique cage-like structure and biocompatibility, there is a growing interest in their biomedical use. A multipurpose and straightforward engineering approach does not exist for using nanocages to make drug-delivery systems by encapsulating hydrophilic or hydrophobic drugs and developing vaccines by surface functionalization with a protein like an antigen. Here, a versatile engineering approach is described by mimicking the HIV-1 Gap polyprotein precursor. Various PREcursors of nanoCages (PREC) are designed and created by linking two ferritin subunits via a flexible linker peptide containing a protease cleavage site. These precursors can have additional proteins at their N-terminus, and their protease cleavage generates ferritin-like nanocages named protease-induced nanocages (PINCs). It is demonstrated that PINC formation allows concurrent surface decoration with a protein and hydrophilic or hydrophobic drug encapsulation up to fourfold more than the amount achieved using other methods. The PINCs/Drug complex is stable and efficiently kills cancer cells. This work provides insight into the precursors' design rules and the mechanism of PINCs formation. The engineering approach and mechanistic insight described here will facilitate nanocages' applications in drug delivery or as a platform for making multifunctional therapeutics like mosaic vaccines.
Assuntos
Ferritinas , Humanos , Ferritinas/química , Propriedades de Superfície , HIV-1 , Interações Hidrofóbicas e Hidrofílicas , Sistemas de Liberação de Medicamentos/métodos , Nanoestruturas/química , Materiais Biomiméticos/química , Biomimética/métodosRESUMO
OBJECTIVE: To observe the residual of lumbago and leg pain with contained type ï¼CTï¼ and non-contained type ï¼NCTï¼ lumbar disc herniation ï¼LDHï¼ after transforaminal endoscopic treatment, and to explore the role of hypoxia-inducible factor-1αï¼HIF-1αï¼ and transient receptor potential vanillate 1ï¼TRPV1ï¼ pathway. METHODS: A total of 68 single-segment LDH patients were selected from July 2021 to October 2022, including 44 males and 24 femalesï¼aged 26 to 67 years old with an average ofï¼43.63±11.94ï¼ years oldï¼course of disease was 4 to 36 ï¼18.91±10.34ï¼ monthsï¼body mass index was ï¼24.45±4.00ï¼ kg·m-2ï¼there were 7 cases of L3,4 segments, 32 cases of L4,5 segments, and 29 cases of L5S1 segments. All of them were performed with percutaneous intervertebral endoscopic extraction of nucleus pulposus and were divided into contained groupï¼CT groupï¼ and non-contained group ï¼NCT groupï¼ with 34 cases respectively according to the integrity of outer layer of fibrous annulus observed during operation. A total of 17 patients who underwent open surgery for scoliosis or vertebral fracture were selected as control group, including 12 males and 5 femalesï¼aged 21 to 65 years old with an average of ï¼39.41±12.80ï¼ years oldï¼body mass index was ï¼24.86±4.11ï¼ kg·m-2. The relative mRNA expression quantity of HIF-1α, TRPV1 in nucleus pulposus were measured by quantitative real-time PCR. The contents of neurokinin 1 receptor ï¼NK1Rï¼, nerve growth factor ï¼NGFï¼, vascular endothelial growth factor ï¼VEGFï¼ in nucleus pulposus and the serum substance P ï¼SPï¼ and calcitonin gene-related peptide ï¼CGRPï¼ were detected by enzyme linked immunosorbent assay ï¼ELISAï¼. The threshold of lumbar tenderness was detected by a pressure pain meter. The degree of lumbago and lumbar function were evaluated by visual analog scale ï¼VASï¼ and Oswestry disability index ï¼ODIï¼ separately. The residual rate of postoperative lumbago and leg pain was assessed. RESULTS: The mRNA relative expression quantity of HIF-1α and TRPV1, and the contents of NK1R, NGF and VEGF in nucleus pulposus, and the levels of serum SP and CGRP before surgery in the NCT group were higher than those in the CT groupï¼P<0.05ï¼, and those in the CT group were higher than the control groupï¼P<0.05ï¼. At day 7 after surgery, the serum SP and CGRP levels, lumbago and leg pain VAS scores and lumbar ODI index in two LDH groups were lower than before surgery ï¼P<0.05ï¼, and those in the NCT group were higher than the CT groupï¼P<0.05ï¼, and the threshold of lumbar tenderness in the NCT group was lower than the CT groupï¼P<0.05ï¼. The differences of lumbago and leg pain VAS scores, lumbar ODI index and lumbar tenderness threshold between preoperative and postoperative 7 days in the NCT group were lower than those in the CT groupï¼P<0.05ï¼. The residual rate of lumbago and leg pain at 7 days after surgery in the NCT group was higher than that in the CT groupï¼P<0.05ï¼. CONCLUSION: HIF-1α and TRPV1 pathway promoted the excessive production of NGF, VEGF, NK1R in nucleus pulposus and serum neuropeptides SP and CGRP, which may lead to the higher residual rate of lumbago and leg pain with non-contained lumbar disc herniation postoperative.