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1.
Biomater Sci ; 12(4): 990-1003, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38193333

RESUMO

Fungal infections contribute substantially to human morbidity and mortality. A particular concern is the high rate of mortality associated with invasive fungal infections, which often exceeds 50.0% despite the availability of several antifungal drugs. Herein, we show a self-assembling antifungal peptide (AFP), which is able to bind to chitin on the fungal cell wall and in situ form AFP nanofibers, wrapping fungi. As a result, AFP limits the proliferation of fungi, slows down the morphological transformation of biphasic fungi, and inhibits the adhesion of fungi to host cells and the formation of biofilms. Compared to the broad-spectrum antifungal fluconazole, AFP achieved a comparable inhibitory effect (MIC50 = 3.5 µM) on fungal proliferation. In addition, AFP significantly inhibited the formation of fungal biofilms with the inhibition rate of 69.6% at 1 µM, better than fluconazole (17.2% at 1 µM). In a skin infection model of mice, it was demonstrated that AFP showed significantly superior efficacy to fluconazole. In the systemic candidiasis mouse model, AFP showed similar efficacy to first-line antifungal amphotericin B (AmpB) and anidulafungin (AFG). This study provides a promising wrapping strategy for anti-fungal infection.


Assuntos
Antifúngicos , Fluconazol , Humanos , Animais , Camundongos , Antifúngicos/farmacologia , Fluconazol/farmacologia , Fluconazol/metabolismo , alfa-Fetoproteínas/metabolismo , alfa-Fetoproteínas/farmacologia , Peptídeos/farmacologia , Peptídeos/metabolismo , Fungos/metabolismo
2.
J Mater Chem B ; 11(1): 180-187, 2022 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-36484315

RESUMO

Tuberculosis is a major public health concern worldwide, and it is a serious threat to human health for a long period. Macrophage phagocytosis of Mycobacterium tuberculosis (M. tuberculosis) is a crucial process for granuloma formation, which shelters the bacteria and gives them an opportunity for re-activation and spread. Herein, we report an intelligent anti-microbial peptide that can recognize and trap the M. tuberculosis, inhibiting the macrophage phagocytosis process. The peptide (Bis-Pyrene-KLVFF-WHSGTPH, in abbreviation as BFH) first self-assembles into nanoparticles, and then forms nanofibers upon recognizing and binding M. tuberculosis. Subsequently, BFH traps M. tuberculosis by the in situ formed nanofibrous networks and the trapped M. tuberculosis are unable to invade host cells (macrophages). The intelligent anti-microbial peptide can significantly inhibit the phagocytosis of M. tuberculosis by macrophages, thereby providing a favorable theoretical basis for inhibiting the formation of tuberculosis granulomas.


Assuntos
Mycobacterium tuberculosis , Tuberculose , Humanos , Mycobacterium tuberculosis/fisiologia , Macrófagos/metabolismo , Fagocitose , Tuberculose/tratamento farmacológico , Tuberculose/metabolismo , Tuberculose/microbiologia , Peptídeos/farmacologia , Peptídeos/metabolismo
3.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 35(1): 57-62, 2015 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-25790676

RESUMO

OBJECTIVE: To study the growth inhibition effect of Brucea javanica Fruit Oil Emulsion (BJFOE) on human ovarian caner SKOV3 cells and the transplanted tumor of SKOV3 nude mice. METHODS: Growth inhibition effects of different concentrations BJFOE alone or its combination with cisplatin on human ovarian cancer cell SKOV3 were measured using MTT method. The orthotopic transplantation tumor model of human ovarian cancer SKOV3 cell lines was established in nude mice. Totally 32 ovarian cancer nude mice were randomly divided into 4 groups, i.e., the blank control group (Group A), the BJFOE group (Group B), the BJFOE combined Cisplatin group (Group C), and the Cisplatin control group (Group D), 8 in each group. Mice in Group A were intraperitoneally injected with normal saline (0.2 mL/ 20 g), once per two days. Mice in Group B were intraperitoneally injected with BJFOE (0.2 mL/20 g), once per two days. Mice in Group C were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL on the first day, and intraperitoneally injected with BJFOE on the second day. Mice in Group D were intraperitoneally injected with cisplatin (3 mg/kg) 0.2 mL, once per two days. All mice were injected for six times, and sacrificed 48 h after the last injection. The lesion formation of the abdominal tumor tissue was observed. Tumor specimens were obtained to perform HE staining. Expression levels of MRP-1/CD9 and integrinα-5 were detected using Western blot. RESULTS: The inhibition of BJFOE was time-dose depend- ently correlated with its inhibition effect of SKOV3 cells. The inhibition effect of BJFOE in combination of cisplatin was significantly superior to that of using any of the two drugs alone. Western blot results showed expression levels of MRP-1/CD9 and integrinα-5 were up-regulated in Group B and Group D with statistical difference (P < 0.05). But they were down-regulated in Group C with statistical difference (P < 0.05). CONCLUSIONS: Intraperitoneal injecting BJFOE was feasible and effective for treating ovarian cancer. BJFOE also could inhibit the invasion and migration of tumor cells targeting at MRP-1/CD9 and integrinα-5. But its specific anti-tumor mechanism was not clearly probed.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Óleos de Plantas/farmacologia , Animais , Brucea , Linhagem Celular Tumoral , Cisplatino , Feminino , Frutas , Humanos , Camundongos , Camundongos Nus , Transplante de Neoplasias , Neoplasias Ovarianas
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