RESUMEN
In situ self-assembly in vivo can be used in the enhanced diagnosis and therapy of major diseases such as cancer and bacterial infections on the basis of an assembly/aggregation-induced-retention (AIR) effect. However, the aggregation degree (αagg) is a significant parameter for determining the delivery efficiency to lesions in a complex physiological environment and a real-time quantitative calculation of the aggregation degree in vivo is still a great challenge. Here, we developed a magnetic resonance imaging (MRI) method for sensitive and quantitative calculation of αagg with a detection limit of 10-4 M and a bioactivated in vivo assembly (BIVA) magnetic resonance (MR) probe was optimized for enhanced T1-weighted MR imaging of M2 macrophages in tumors. Our MRI quantitative calculation method had a high fitting degree (R2 = 0.987) with the gold standard fluorescence (FL) method. On the basis of the BIVA mechanism of CD206 active targeting and cathepsin B specific tailoring to induce an in situ nanofiber assembly, our optimized BIVA probe exhibited a high intracellular aggregation degree of over 70% and a high in vivo αagg value of over 55%. Finally, the aggregation-enhanced T1 MR signal and the AIR effect both contributed to enhanced T1-weighted MR imaging of M2 macrophages in triple-negative breast cancer. We believe that our αagg real-time quantitative calculation method of MRI will help to further screen and optimize the in vivo enhanced imaging and treatment of the BIVA drug.
Asunto(s)
Nanofibras , Neoplasias de la Mama Triple Negativas , Medios de Contraste , Humanos , Macrófagos , Imagen por Resonancia Magnética/métodos , Neoplasias de la Mama Triple Negativas/diagnóstico por imagenRESUMEN
The tumor targetability and stimulus responsivity of drug delivery systems are crucial in cancer diagnosis and treatment. In this study, hepatoma-targeting mixed micelles composed of a hyaluronic acid-glycyrrhetinic acid conjugate and a hyaluronic acid-l-histidine conjugate (HA-GA/HA-His) were prepared through ultrasonic dispersion. The formation and characterization of the mixed micelles were confirmed via ¹H-NMR, particle size, and ζ potential measurements. The in vitro cellular uptake of the micelles was evaluated using human liver carcinoma (HepG2) cells. The antitumor effect of doxorubicin (DOX)-loaded micelles was investigated in vitro and in vivo. Results indicated that the DOX-loaded HA-GA/HA-His micelles showed a pH-dependent controlled release and were remarkably absorbed by HepG2 cells. Compared with free DOX, the DOX-loaded HA-GA/HA-His micelles showed a higher cytotoxicity to HepG2 cells. Moreover, the micelles effectively inhibited tumor growth in H22 cell-bearing mice. These results suggest that the HA-GA/HA-His mixed micelles are a good candidate for drug delivery in the prevention and treatment of hepatocarcinoma.
Asunto(s)
Antibióticos Antineoplásicos/química , Doxorrubicina/química , Portadores de Fármacos/química , Ácido Hialurónico/química , Micelas , Animales , Antibióticos Antineoplásicos/administración & dosificación , Antibióticos Antineoplásicos/farmacología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/administración & dosificación , Doxorrubicina/farmacología , Femenino , Células Hep G2 , Histidina/química , Humanos , Concentración de Iones de Hidrógeno , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Espectroscopía de Resonancia Magnética , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Microscopía Electrónica de Transmisión , Tamaño de la Partícula , Trasplante HeterólogoRESUMEN
The skin transcriptome of Bufu bufo gargarizans was determined by conventional methods. A novel full length cDNA coding for a Cathelicidin precursor was identified by transcriptomic data assembling, annotation and blast search of corresponding data banks. According to the known processing methods of Cathelicidin family members, present reported novel Cathelicidin precursor of B. bufo gargarizans might be cleaved at 2 possible sites of the same precursor and generate both BG-CATH25 and BG-CATH29 as mature molecules. The deduced BG-CATH25 and BG-CATH29 were synthesized with purity>95% to evaluate the properties and bactericidal activities. The secondary structural characteristics of both BG-CATH25 and BG-CATH29 in different solutions were determined by Circular Dichroism (CD) Analysis. CD results indicated that random coil conformation were the main structural elements for both BG-CATH25 and BG-CATH29 in different buffer systems. Antimicrobial activities against tested bacterial strains were carried out by plating method. Both BG-CATH25 and BG-CATH29 showed strong antibacterial activities against Aeromonas hydrophila, with MIC values of 1.25, 10 mgâ¢L⻹, respectively. However, both of them showed weak bactericidal activities against human pathogenic bacteria, like Escherichia coli (ATCC25922ï¼,Staphylococcus aureus (ATCC25923ï¼and Pseudomonas aeruginosa (ATCC 27853).
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/química , Bufonidae/metabolismo , Piel/metabolismo , Animales , Antibacterianos/metabolismo , Péptidos Catiónicos Antimicrobianos/genética , Péptidos Catiónicos Antimicrobianos/metabolismo , Péptidos Catiónicos Antimicrobianos/farmacología , Bufonidae/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/crecimiento & desarrollo , Pruebas de Sensibilidad Microbiana , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Piel/química , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , CatelicidinasRESUMEN
The incorporation of well-designed antibiotic nanocarriers, along with an antibiotic adjuvant effect, in combination with various antibiotics, offers an opportunity to combat drug-resistant strains. However, precise control over morphology and encapsulated payload release can significantly impact their antibacterial efficacy and synergistic effects when used alongside antibiotics. Here, this study focuses on developing lipopeptide-based nanoantibiotics, which demonstrate an antibiotic adjuvant effect by inducing pH-induced collapse and negative-charged-surface-induced deformation. This enhances the disruption of the bacterial outer membrane and facilitates drug penetration, effectively boosting the antimicrobial activity against drug-resistant strains. The modulation regulations of the lipopeptide nanocarriers with modular design are governed by the authors. The nanoantibiotics, made from lipopeptide and ciprofloxacin (Cip), have a drug loading efficiency of over 80%. The combination with Cip results in a significantly low fractional inhibitory concentration index of 0.375 and a remarkable reduction in the minimum inhibitory concentration of Cip against multidrug-resistant (MDR) Escherichia coli (clinical isolated strains) by up to 32-fold. The survival rate of MDR E. coli peritonitis treated with nanoantibiotics is significantly higher, reaching over 87%, compared to only 25% for Cip and no survival for the control group. Meanwhile, the nanoantibiotic shows no obvious toxicity to major organs.
RESUMEN
Inflammatory pain is a chronic pain caused by peripheral tissue inflammation, seriously impacting the patient's life quality. Cinobufacini injection, as a traditional Chinese medicine injection preparation, shows excellent efficacy in anti-inflammatory and analgesic treatment in patients with advanced tumors. In this study, a novel analgesic peptide CI5 with anti-inflammatory and analgesic bio-functions that naturally presents in Cinobufacini injection and its regulatory mechanism are reported. Our results showed that the administration of CI5 significantly relieved the pain of mice in the acetic acid twisting analgesic model and formalin inflammatory pain model. Furthermore, CI5 effectively reduced the inflammatory cytokines (IL-6, TNF-α and IL-1ß) and inflammatory mediator (PGE2) expressions, and prevented the carrageenan-induced paw edema in mice. Further LC-MS/MS results showed the anti-inflammatory and analgesic bio-functions of CI5 depended on its interaction with the Rac-2 protein upstream of ERK1/2 and the inflammatory signaling pathway (ERK1/2/COX-2 axis). In summary, CI5, as a novel natural candidate identified from Cinobufacini injection, showed substantial clinical promise for inflammatory pain treatments.
RESUMEN
Purpose: Diabetic foot ulcers (DFU) are severe complications of diabetes, posing significant health and societal challenges. Elevated levels of reactive oxygen species (ROS) at the ulcer site hinder wound healing in most patients, while individuals with diabetes are also more susceptible to bacterial infections. This study aims to synthesize a comprehensive therapeutic material using polysaccharides from Pycnoporus sanguineus to promote DFU wound healing, reduce ROS levels, and minimize bacterial infections. Methods: Polysaccharides from P.sanguineus were employed as reducing and stabilizing agents to fabricate polysaccharide-based composite particles (PCPs) utilizing silver ions as templates. PCPs were characterized via UV-Vis, TEM, FTIR, XRD, and DLS. The antioxidant, antimicrobial, and cytotoxic properties of PCPs were assessed through in vitro and cellular experiments. The effects and mechanisms of PCPs on wound healing were evaluated using a diabetic ulcer mouse model. Results: PCPs exhibited spherical particles with an average size of 57.29±22.41 nm and effectively combined polysaccharides' antioxidant capacity with silver nanoparticles' antimicrobial function, showcasing synergistic therapeutic effects. In vitro and cellular experiments demonstrated that PCPs reduced cellular ROS levels by 54% at a concentration of 31.25 µg/mL and displayed potent antibacterial activity at 8 µg/mL. In vivo experiments revealed that PCPs enhanced the activities of superoxide dismutase (SOD) and catalase (CAT), promoting wound healing in DFUs and lowering the risk of bacterial infections. Conclusion: The synthesized PCPs offer a novel strategy for the comprehensive treatment of DFU. By integrating antioxidant and antimicrobial functions, PCPs effectively promote wound healing and alleviate patient suffering. The present study demonstrates a new strategy for the integrated treatment of diabetic wounds and expands the way for developing and applying the polysaccharide properties of P. sanguineus.
Asunto(s)
Antiinfecciosos , Infecciones Bacterianas , Diabetes Mellitus , Pie Diabético , Nanopartículas del Metal , Animales , Ratones , Humanos , Sustancias Reductoras/uso terapéutico , Antioxidantes/farmacología , Antioxidantes/uso terapéutico , Plata/farmacología , Plata/uso terapéutico , Especies Reactivas de Oxígeno , Pie Diabético/tratamiento farmacológico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Polisacáridos/farmacologíaRESUMEN
Distal metastasis of breast cancer is a primary cause of death, and the lung is a common metastatic target of breast cancer. However, the role of the lung niche in promoting breast cancer progression is not well understood. Engineered three-dimensional (3D) in vitro models capable of bridging this knowledge gap can be specifically designed to mimic crucial characteristics of the lung niche in a more physiologically relevant context than conventional two-dimensional systems. In this study, two 3D culture systems were developed to mimic the late stage of breast cancer progression at a lung metastatic site. These 3D models were created based on a novel decellularized lung extracellular matrix/chondroitin sulfate/gelatin/chitosan composite material and on a porcine decellularized lung matrix (PDLM), with the former tailored with comparable properties (stiffness, pore size, biochemical composition, and microstructure) to that of the in vivo lung matrix. The different microstructure and stiffness of the two types of scaffolds yielded diverse presentations of MCF-7 cells in terms of cell distribution, cell morphology, and migration. Cells showed better extensions with apparent pseudopods and more homogeneous and reduced migration activity on the composite scaffold compared to those on the PDLM scaffold. Furthermore, alveolar-like structures with superior porous connectivity in the composite scaffold remarkably promoted aggressive cell proliferation and viability. In conclusion, a novel lung matrix-mimetic 3D in vitro breast cancer lung metastasis model was developed to clarify the underlying correlativity between lung ECM and breast cancer cells after lung colonization. A better understanding of the effects of biochemical and biophysical environments of the lung matrix on cell behaviors can help elucidate the potential mechanisms of breast cancer progression and further improve target discovery of therapeutic strategies.
Asunto(s)
Quitosano , Neoplasias Pulmonares , Porcinos , Animales , Andamios del Tejido/química , Gelatina/química , Sulfatos de Condroitina , Pulmón , Matriz ExtracelularRESUMEN
Aerobic vaginitis (AV) is a gynecological disease associated with vaginal flora imbalance. The nonselective bactericidal nature of antibiotics and low customization rate of probiotic supplementation in existing treatments lead to AV recurrence. Here, a drug delivery strategy is proposed that works with the changing dynamics of the bacterial flora. In particular, a core-shell nanogel (CSNG) is designed to encapsulate prebiotic inulin and antimicrobial peptide Cath 30. The proposed strategy allows for the sequential release of both drugs using gelatinase produced by AV pathogenic bacteria, initially selectively killing pathogenic bacteria and subsequently promoting the proliferation of beneficial bacteria in the vagina. In a simulated infection environment in vitro, the outer layer of CSNGs, Cath 30 is rapidly degraded and potently killed the pathogenic bacterium Staphylococcus aureus at 2-6 h. CSNGs enhances proliferation of the beneficial bacterium Lactobacillus crispatus by more than 50% at 24 h. In a rat AV model, the drug delivery strategy precisely regulated the bacterial microenvironment while controlling the inflammatory response of the vaginal microenvironment. This new treatment approach, configured on demand and precisely controlled, offers a new strategy for the treatment of vaginal diseases.
Asunto(s)
Vaginitis , Vaginosis Bacteriana , Femenino , Humanos , Animales , Ratas , Vaginosis Bacteriana/tratamiento farmacológico , Vaginosis Bacteriana/microbiología , Nanogeles , Vaginitis/tratamiento farmacológico , Vaginitis/microbiología , Vagina , Bacterias , Bacterias Aerobias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , EsterilizaciónRESUMEN
Wound treatment remains one of the most prevalent healthcare issues. Tylotoin is a skin repair peptide identified from salamander (Tylototriton verrucosus) and exhibits skin wound healing properties. Noticeably, the easy degradation and frequent administration limit its application in wound healing. Chitosan (CS) -PLGA-Tylotoin nanoparticles (CPT NPs) were prepared to circumvent this limitation and deliver Tylotoin for the promotion of the healing of skin wounds. Results showed that optimized CPT NPs particle size, zeta potential, encapsulation efficiency and drug loading were 297.80 ± 5.37 nm, 20.37 ± 0.83 mV, 81.00 % and 1.74 %, respectively. In vitro, CPT NPs exhibited good antibacterial properties and biocompatibility and persistently promoted the cell migration of HaCaT cells and HUVECs due to the long-term sustained release of Tylotoin within 14 days (64.81 %). In vivo, the scarless healing of skin wound promotion was evaluated in mouse back full-thickness wound models. We demonstrated that mouse back full-thickness wounds topically treated with CPT NPs once every two weeks exhibited better scarless healing than those treated with Tylotoin once daily. We envision that CPT NPs, as a Tylotoin delivery platform might, may be potentially utilized to in skin wounds healing in clinics in the future.
Asunto(s)
Quitosano , Nanopartículas , Animales , Antibacterianos , Quitosano/química , Preparaciones de Acción Retardada , Ratones , Nanopartículas/química , Péptidos , Cicatrización de HeridasRESUMEN
The extensive spread of multidrug resistance to Gram-negative bacteria has become a huge threat to human health, where peptide-based antibacterial agents have emerged as a powerful star weapon. Here we report a lipopeptide (LP-20) constructed nanomicelle with a different antibacterial mechanism of membrane curvature modulation, which induced dynamic membrane fission resulting in acceleration and enhancement of antibacterial activity to clinically isolated ESKAPE strains, including multidrug-resistant (MDR) pathogens. The minimum inhibitory concentration was reduced to 2-10 µM, and the minimum duration for killing was shortened to less than an hour by LP-20. This is an improvement over antimicrobial peptides and traditional antibiotics, such as ciprofloxacin and tetracycline, significantly enhancing antibacterial activity for MDR, and we observed no acquisition of resistance for one month. This accelerated germicidal mechanism was attributed to multitargeting with lipopolysaccharides, phosphoethanolamine, phosphatidylglycerol, and cardiolipin, and the synergetic interactions induced a high curvature of the bacterial membrane, which facilitated simultaneously efficient damage to both inner and outer membrane. The LP-20 effectively prolonged the lifetime of myositis mice with Escherichia coli MDR and pneumonia mice with Klebsiella pneumoniae through a hepatic metabolism with ignorable toxicity. This study provides critical information for the fabrication of lipopeptide-based nano-antibiotics for the efficient control of intractable MDR caused by Gram-negative pathogens.
Asunto(s)
Antiinfecciosos , Neumonía Bacteriana , Ratones , Animales , Humanos , Lipopéptidos/farmacología , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple , Antiinfecciosos/farmacología , Neumonía Bacteriana/tratamiento farmacológico , Pruebas de Sensibilidad MicrobianaRESUMEN
Tumor-associated antigen mucin 1 (MUC1) is highly expressed in colorectal cancer and is positively correlated with advanced stage at diagnosis and poor patient outcomes. The combination of irinotecan and capecitabine is standard chemotherapy for metastatic colorectal cancer and is known as XELIRI or CAPIRI, which significantly prolongs the progression-free survival and overall survival of colorectal cancer patients compared to a single drug alone. We previously reported that peanut agglutinin (PNA)-conjugated liposomes showed enhanced drug delivery efficiency to MUC1-positive liver cancer cells. In this study, we prepared irinotecan hydrochloride (IRI) and capecitabine (CAP)-coloaded liposomes modified by peanut agglutinin (IRI/CAP-PNA-Lips) to target MUC1-positive colorectal cancer. The results showed that IRI/CAP-PNA-Lips showed an enhanced ability to target MUC1-positive colorectal cancer cells compared to unmodified liposomes. Treatment with IRI/CAP-PNA-Lips also increased the proportion of apoptotic cells and inhibited the proliferation of colorectal cancer cells. The targeting specificity for tumor cells and the antitumor effects of PNA-modified liposomes were significantly increased in tumor-bearing mice with no severe cytotoxicity to normal tissues. These results suggest that PNA-modified liposomes could provide a new delivery strategy for the synergistic treatment of colorectal cancer with clinical chemotherapeutic agents.
RESUMEN
Amauroderma rugosum is one of the traditional Chinese medicinal mushrooms and is used to reduce inflammation, treat diuretic and upset stomach, and prevent cancer. Here, we present a genomic resource of Amauroderma rugosum (ACCC 51706) for further understanding its biology and exploration of the synthesis pathway of bioactive compounds. Genomic DNA was extracted and then subjected to Illumina HiSeq X Ten and PacBio Sequel I sequencing. The final genome is 40.66 Mb in size, with an N50 scaffold size of 36.6 Mb, and encodes 10 181 putative predicted genes. Among them, 6931 genes were functionally annotated. Phylogenomic analysis suggested that A. rugosum and Ganoderma sinense were not clustered together into a group and the latter was grouped with the Polyporaceae. Further, we also identified 377 carbohydrate-active enzymes (CAZymes) and 15 secondary metabolite biosynthetic gene clusters. This is the first genome-scale assembly and annotation for an Amauroderma species. The identification of novel secondary metabolite biosynthetic gene clusters would promote pharmacological research and development of novel bioactive compounds in the future.
Asunto(s)
Familia de Multigenes , Filogenia , Polyporaceae/clasificación , Polyporaceae/genética , Secuencia de Bases , Vías Biosintéticas/genética , Genoma Fúngico , Medicina Tradicional China , Anotación de Secuencia Molecular , Polyporaceae/metabolismo , Metabolismo Secundario/genéticaRESUMEN
The modified of polysaccharides show various bio-activities. In our work, Phellinus igniarius Selenium-enriched mycelias polysaccharides (PSeP) were prepared from Phellinus igniarius, and its antioxidant and anti-inflammatory effects on injured mice were evaluated. The selenium content and physical properties of polysaccharides were characterized by GC, HPGPC, and FT-IR analysis. The results showed that PSeP could reduce reactive oxygen species (ROS) levels, myeloperoxidase (MPO) activity as well as malondialdehyde (MDA) content. Meanwhile, it increased the enzyme activities of glutathione peroxidase (GSH-Px) and catalase (CAT). Finally, it showed obvious wound healing effects in vivo. Moreover, PSeP could clear the ROS without obvious cytotoxicity. PSeP could further improve its ability to clear ROS level to promote skin wound healing in mice three days in advance.
Asunto(s)
Antioxidantes/farmacología , Polisacáridos Fúngicos/farmacología , Phellinus/química , Selenio/química , Cicatrización de Heridas/efectos de los fármacos , Heridas y Lesiones/tratamiento farmacológico , Animales , Antiinflamatorios/farmacología , Antioxidantes/química , Catalasa/metabolismo , Cromatografía de Gases/métodos , Polisacáridos Fúngicos/química , Glutatión Peroxidasa/metabolismo , Masculino , Malondialdehído/metabolismo , Ratones , Peroxidasa/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Piel/lesiones , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Heridas y Lesiones/metabolismoRESUMEN
BACKGROUND: The treatment of Staphylococcus aureus (S. aureus)-infected wounds is difficult. It causes extreme pain to tens of thousands of patients and increases the cost of medical care. The antimicrobial peptide OH-CATH30 (OH30) has a good killing activity against S. aureus and can play a role in accelerating wound healing and immune regulation. Therefore, it shows great potential for wound healing. PURPOSE: The aim of this study was to overcome the short half-life and easy enzymolysis of OH30 by using graphene oxide conjugated with polyethylene glycol to load OH30 (denoted as PGO-OH30), as well as to evaluate its effect on wounds infected by S. aureus. METHODS: PGO-OH30 nanoparticles were prepared by π-π conjugation and characterized. Their cell cytotoxicity, cell migration, infectious full-thickness dermotomy models, and histopathology were evaluated. RESULTS: Characterization and cytotoxicity experiments revealed that the PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability. Cell-migration experiments showed that PGO-OH30 could promote the migration of human immortalized keratinocytes (HaCaT) cells compared with the control group (P<0.05). In a mouse model of skin wound infection, PGO-OH30 accelerated skin-wound healing and reduced the amount of S. aureus in wounds compared with the control group (P<0.05). In particular, on day 7, the number of S. aureus was 100 times lower in the PGO-OH30 group than in the control group. CONCLUSION: The PGO-OH30 drug-delivery system had good biocompatibility and excellent drug-delivery ability, indicating its good therapeutic effect on a skin wound-infection model.
Asunto(s)
Staphylococcus aureus , Infección de Heridas , Animales , Grafito , Humanos , Ratones , Péptidos , Polietilenglicoles , Piel , Cicatrización de Heridas , Infección de Heridas/tratamiento farmacológicoRESUMEN
Liver cancer is one of the most common malignancies worldwide and poses a serious threat to human health. The most important treatment method, liver cancer chemotherapy, is limited due to its high toxicity and poor specificity. Targeted drug delivery systems have emerged as novel therapeutic strategies that deliver precise, substantial drug doses to target sites via targeting vectors and enhance the therapeutic efficacy. In the present study, glycyrrhetinic acid-modified hyaluronic acid (GA-HA) was used as a carrier for the model drug docetaxel (DTX) to prepare DTX-loaded GA-HA nanoparticles (DTX/GA-HA-NPs). The results indicated that the DTX/GA-HA-NPs exhibited high monodispersity (particle dispersity index, 0.209±0.116) and desirable particle size (208.73±5.0 nm) and zeta potential (-27.83±3.14 mV). The drug loading capacity and encapsulation efficiency of the NPs were 12.59±0.68 and 85.38±4.62%, respectively. Furthermore, it was determined that FITC-GA-HA was taken up by cells and distributed in the cytoplasm. DTX and DTX/GA-HA (just the DTX delivered by the nanoparticle) aggregated and altered the structure of cellular microtubules. Compared with DTX alone, DTX/GA-HA-NPs had a stronger inhibitory effect on HepG2 cell proliferation and promoted apoptosis of HepG2 cells. All experimental results indicated that DTX/GA-HA-NPs were successfully prepared and had liver-targeting and antitumor activities in vitro, which provided a foundation for future in vivo studies of the antitumor effects of DTX/GA-HA-NPs.
RESUMEN
Pycnoporus sanguineus, an edible mushroom, produces antimicrobial and antitumor bioactive compounds and pH- and thermo- stable laccases that have multiple potential biotechnological applications. Here we reported the complete genome of the species Pycnoporus sanguineus ACCC 51,180 by using the combination of Illumina HiSeq X Ten and the PacBio sequencing technology. The represented genome is 36.6 Mb composed of 59 scaffolds with 12,086 functionally annotated protein-coding genes. The genome of Pycnoporus sanguineus encodes at least 19 biosynthetic gene clusters for secondary metabolites, including a terpene cluster for biosynthesis of the antitumor clavaric acid. Seven laccases were identified, while 22 genes were found to be involved in the kynurenine pathway in which the intermediate metabolite 3-hydroxyanthranilic acid were catalyzed by laccases into cinnabarinic acid. This study represented the third genome of the genus Pycnoporus, and wound facilitate the exploration of useful sources from Pycnoporus sanguineus for future industrial applications.
Asunto(s)
Proteínas Fúngicas/genética , Genoma Fúngico/genética , Microbiología Industrial/métodos , Lacasa/genética , Pycnoporus/genética , Proteínas Fúngicas/metabolismo , Concentración de Iones de Hidrógeno , Quinurenina/metabolismo , Lacasa/metabolismo , Ingeniería Metabólica , Oxazinas/metabolismo , Estabilidad Proteica , Pycnoporus/enzimología , Metabolismo Secundario/genéticaRESUMEN
Astragalus polysaccharide (APS) has attracted growing interests in the field of anti-cancer by direct killing effect and improving immune function. In this study, the structure and composition of APS was determined, following the evaluation of in vitro and in vivo anti-tumor activity of APS targeted macrophages and host immune system based on immunoregulated strategy. The results indicated that APS had no direct cytotoxicity against 4T1 cells, but APS mediated macrophages could significantly inhibit the growth of 4T1 cells by the induction of cell cycle arrest (G2 phase) and cell apoptosis. APS mediated macrophages promoted the apoptosis of 4T1 cells mainly through the mitochondrial apoptosis pathway. The in vivo findings demonstrated that APS could markedly improve the thymus index and spleen index, and restore the structure of the damaged thymus and spleen tissue. APS could significantly enhance the proliferation of spleen lymphocytes and increase phagocytosis of peritoneal macrophages in mice. Furthermore, APS was capable of up-regulating the expression of IL-2, TNF-α and IFN-γ in peripheral blood. APS combined with 5-FU could improve the anti-tumor effect accompanied by the immunosuppressive alleviation of 5-FU on immune system, which may be suitable as an immune adjuvant for chemotherapy.
Asunto(s)
Antineoplásicos/farmacología , Planta del Astrágalo/química , Inmunomodulación/efectos de los fármacos , Polisacáridos/química , Polisacáridos/farmacología , Adyuvantes Inmunológicos , Animales , Apoptosis/efectos de los fármacos , Neoplasias de la Mama , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citocinas/sangre , Modelos Animales de Enfermedad , Femenino , Macrófagos/efectos de los fármacos , Ratones , Ratones Endogámicos BALB C , Mitocondrias/metabolismo , Fagocitosis/efectos de los fármacos , Células RAW 264.7 , Bazo/inmunología , TimoRESUMEN
Bacterial infections, especially the refractory treatment of drug-resistant bacteria, are one of the greatest threats to human health. During the past decades, biomedical nanomaterials have been developed in an increasing number of fields, which significantly contribute to our public healthcare systems. Peptide-based drugs, such as antimicrobial peptides, cyclopeptides, and glycopeptides, play important roles in the treatment of drug-resistant bacterial infections, due to their unique lower resistance antibacterial mechanism. Among them, biomimetic nanostructures fabricated by self-assembled peptide nanomaterials have received considerable development in surface protection, tissue engineering, bactericides, etc. Besides, bacterial diagnostic reagents based on self-assembled peptide materials also provide strong support for early detection and infection imaging of bacterial infections. In this review, we have systematically discussed peptide-based self-assembled nanomaterials, including their sequences, subunits, secondary structures, assembled nanostructures, and biomedical applications for antibacterial therapy and diagnosis. We have reviewed and discussed the structure-function relationship, molecular design strategy, and structure effect of antimicrobial peptides. The sequence design of self-assembled peptides and the application of self-assembled peptide nanomaterials in the diagnosis and treatment of bacterial infections are emphasized. Also, we analyzed and summarized the design and development of smart materials, reviewed the innovative "in vivo self-assembly" nanotechnology, and proposed the future design and prospect of smart self-assembly nanomaterials based on peptides in the biological antibacterial field.
Asunto(s)
Antiinfecciosos , Nanoestructuras , Antibacterianos/uso terapéutico , Humanos , Péptidos , Ingeniería de TejidosRESUMEN
Novel nanomaterials have been developed for antimicrobial and wound healing applications. Here, we report the preparation of a polyvinyl alcohol/chitosan (PVA/CS) nanofiber with carboxymethyl chitosan nanoparticles (CMCS-OH30 NPs) encapsulating the antibacterial peptide OH-CATH30 (OH-30). The PVA/CS nanofibers containing OH-30 NPs (NP-30-NFs) obtained via electrospinning could achieve a secondary embedded OH-30. The effect of NP-30-NFs on the release of OH-30 was investigated through high-performance liquid chromatography. The antibacterial activities of NP-30-NFs against Escherichia coli and Staphylococcus aureus were studied by bacterial plate counting. NP-30-NFs containing different concentrations of NPs were applied to mouse skin wounds to determine their effectiveness in promoting wound healing. Results showed that NP-30-NFs exhibited antibacterial properties and promoted skin wound healing.
Asunto(s)
Antibacterianos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Quitosano/farmacología , Nanofibras/química , Alcohol Polivinílico/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antibacterianos/administración & dosificación , Antibacterianos/química , Péptidos Catiónicos Antimicrobianos/administración & dosificación , Péptidos Catiónicos Antimicrobianos/química , Quitosano/administración & dosificación , Quitosano/química , Relación Dosis-Respuesta a Droga , Escherichia coli/efectos de los fármacos , Femenino , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos , Pruebas de Sensibilidad Microbiana , Nanofibras/administración & dosificación , Nanopartículas/administración & dosificación , Nanopartículas/química , Tamaño de la Partícula , Alcohol Polivinílico/administración & dosificación , Alcohol Polivinílico/química , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-Actividad , Propiedades de SuperficieRESUMEN
Liposomes have been widely used as drug carriers in both biomedical research and for clinical applications, allowing the stabilisation of therapeutic compounds and overcoming obstacles to cellular and tissue uptake. However, liposomes still have low targeting efficiency, resulting in insufficient killing of tumour cells and unnecessary damage to normal cells. In this study, glycyrrhetinic acid (GA) and peanut agglutinin (PNA) were used as ligands to prepare dual-ligand-modified doxorubicin-loaded liposomes (DOX-GA/PNA-Lips) to enhance the targeting accuracy and efficacy of drug delivery against malignant liver cancer. PNA and GA modification enhanced the binding ability of liposomes to liver cancer cells, leading to excellent tissue and cell targeting of DOX-GA/PNA-Lips. DOX-GA/PNA-Lips showed an effective anti-tumour effect in vivo and in vitro, with its targeted delivery facilitating attenuation of the toxic side effects of DOX. These results demonstrated that dual-ligand-modified liposomes may provide an effective strategy for the treatment of hepatocellular carcinoma.