RESUMO
Surgical site infections (SSIs) related to implants have always been a major challenge for clinical doctors and patients. Clinically, doctors may directly apply antibiotics into the wound to prevent SSIs. However, this strategy is strongly associated with experience of doctors on the amount and the location of antibiotics. Herein, an in situ constructable sol-gel system is developed containing antibiotics during surgical process and validated the efficacy against SSIs in beagles. The system involves chitosan (CS), ß-glycerophosphate (ß-GP) and vancomycin (VAN), which can be adsorbed onto porous hydroxyapatite (HA) and form VAN-CS/ß-GP@HA hydrogel in a short time. The VAN concentration from VAN-CS/ß-GP@HA hydrogel is higher than minimum inhibitory concentration (MIC) against Staphylococcus aureus (S. aureus) at the 21st day in vitro. In an in vivo canine model for the prevention of SSIs in the femoral condyle, VAN-CS/ß-GP@HA exhibits excellent biocompatibility, antimicrobial properties, and promotion of bone healing. In all, the CS/ß-GP instant sol-gel system is able to in situ encapsulate antibiotics and adhere on artificial bone implants during the surgery, effectively preventing SSIs related to implants.
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/metabolismoRESUMO
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/metabolismoRESUMO
Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, but seriously threatens to patients' body and mind. Constitutions of Chinese medicine (CM) are closely relat- ed to diseases. Individuals with different constitutions of CM have different responses to the same envi- ronment and the same pathogenic factor. Therefore, studying the application of constitution theory of CM in stable phase COPD is of great significance. In this paper clinical applications of constitution theory of CM in COPD were explored from etiology and mechanism, syndrome typing based treatment, prevention and care, aiming to prevent, diagnose, and treat COPD effectively.
Assuntos
Medicina Tradicional Chinesa , Doença Pulmonar Obstrutiva Crônica , Constituição Corporal , Humanos , SíndromeRESUMO
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 OvarianasRESUMO
The concentration of glucose, fructose, sucrose and total sugar were determined after exogenous ABA and GA3 treatment during young period of fruit and before fruit coloring in flesh of Cara Cara Navel Orange. The results showed that 10 mg x L(-1) ABA treatment improved glucose, fructose and total sugar concentration significantly or very significantly, 50 mg x L(-1) ABA treatment improved sucrose concentration very significantly, but 100 mg x L(-1) ABA treatment reduced glucose concentration very significantly. GA3 treatment of lower and middle concentrations (10, 50 and 250 mg x L(-1)) improved sucrose concentration very significantly, 10 mg x L(-1) GA3 treatment had no remarkable effect on glucose and fructose concentration but improved total sugar concentration very significantly, GA3 treatment of 50, 250 and 500 mg x L(-1) decreased glucose, fructose and total sugar concentration very significantly. Therefore, ABA treatment of lower concentration could improve one or several kinds of sugar concentration, but GA3 treatment of higher concentration (250 and 500 mg x L(-1)) prohibited sugar accumulation in flesh of Cara Cara Navel Orange seriously.