Dual-Mechanism Glycolipidpeptide with High Antimicrobial Activity, Immunomodulatory Activity, and Potential Application for Combined Antibacterial Therapy.

Bacterial drug resistance is becoming increasingly serious, and it is urgent to develop effective antibacterial drugs. Antimicrobial peptides (AMPs), as potential candidates against bacteria, have a broad prospect for development. Herein, a series of AMPs with biological characteristics (net positive charge, amphiphilicity, and α-helix), an AXA motif recognized by membrane bound serine protease type I signal peptidases (SPase I), an FLPII motif to reduce hemolysis, and a monosaccharide motif to improve the stability and activity were designed and synthesized, and among which, the glycolipidpeptide GLP6 (glycosylated LP6 lipopeptide) had excellent antibacterial and immunomodulatory activity, good stability and biocompatibility, and excellent biofilm eradication and membrane penetrating activity. The positively charged spherical aggregates formed by self-assembly of GLP6 could encapsulate tetracycline (TC) to form GLP6@TC with a sustained-release effect, which could enhance the sensitivity of bacteria to the antibiotic and realize combined sterilization. The results of acute peritonitis and bacterial keratitis showed that GLP6@TC had a good combined antibacterial effect and the ability to inhibit interleukin-2 (IL-2), which could significantly reduce the inflammatory response while treating bacterial infection, and it had great potential for application. The results of computer molecular docking showed the AXA motif could effectively bind to SPase I, which was consistent with the results of biological experiments. In general, the study could provide a perspective for the design of AMPs and combined antibacterial therapy.

Development of KLA-RGD integrated lipopeptide with the effect of penetrating membrane which target the αvß3 receptor and the application of combined antitumor.

Herein, an amphiphilic cationic anticancer lipopeptide P17 with α-helical structure was synthesized based on the integration of KLA and RGD peptide which could bind with the receptor of integrin αvß3. P17 could self assemble into stable spherical aggregates in aqueous solution, and which could encapsulate the anticancer drugs (Such as Dox) to form P17 @ Anticancer drug nanomedicine (P17 @ Dox nanomedicine) which could play the combined therapy of P17 and anticancer drugs (Dox). The encapsulation efficiency of P17 aggregates to Dox was 80.4 ± 3.2 %, and the release behavior of P17 @ Dox nanomedicine in vitro had the characteristics of slow-release and pH responsiveness. The experiments in vitro showed that P17 lipopeptide had low cytotoxicity, high serum stability, low hemolysis and strong penetrating membrane ability. The release of Dox from P17 @ Dox in cells was time-dependment, and the P17 @ Dox nanomedicine had a good anticancer effect. The experiments in vivo showed that P17 and P17 @ Dox nanomedicine both had low hemolysis, and P17 @ Dox nanomedicine could effectively inhibit tumor growth and significantly reduce the toxic and side effects of Dox. Molecular docking experiments showed that P17 could effectively interact with the receptor of integrin αvß3. In conclusion, P17 lipopeptide could be used as an excellent drug carrier and play the combined anticancer effect of P17 and anticancer drugs.

Development of Drug Carriers with Biocompatibility Based On Human Serum Albumin and ß-Cyclodextrin Molecules and Study of Anticancer Activity.

Herein, a novel molecule S4, which could form a uniform S4 spherical aggregate in water, was synthesized, and the S4 aggregate was used to load Dox to prepare the S4@Dox nanomedicine. The loading efficiency was 80.0 ± 4.5%. The pH response and slow release of Dox were the typical characteristics of the S4@Dox nanomedicine. In vitro experiments showed that cancer cells could successfully phagocytose S4 aggregates and the S4@Dox nanomedicine. The toxicity of S4 aggregates to MCF-7, HepG2, and H22 cells was low, and the S4@Dox nanomedicine had better antitumor activity and specific targeting, especially to the MCF-7 cells. The antitumor activity in vivo and in the tissue section showed that the S4@Dox nanomedicine could significantly reduce Dox toxicity, effectively induce the apoptosis of cancer cells, and effectively inhibit tumor growth, which showed that the nanomedicine had better antitumor activity.

Development of anticancer peptides with low hemolysis, high penetrating membrane activity, certain analgesic activity and the synergistic anticancer effect.

Herein, an amphiphilic cationic α-helical anticancer lipopeptide, P10 with low toxicity and high penetrating membrane activity was developed. This lipopeptide could self-assemble into stable spherical aggregates in aqueous solution and encapsulate Dox with a hydrophobic structure to form the P10@Dox nanomedicine. The Dox encapsulation efficiency was 81.3% ± 3.48% and its release from the P10@Dox nanomedicine had the characteristics of slow release and pH response. The in vitro experiments showed that the P10 lipopeptide had low toxicity, excellent membrane penetrating activity and high serum stability, the release of Dox from P10@Dox in cells was time and concentration dependent, and the P10@Dox nanomedicine played a good anti-cancer role. The animal experiments and tissue sections showed that the P10 lipopeptide and P10@Dox nanomedicine both had low hemolysis, and P10@Dox nanomedicine not only greatly reduced the toxicity and side effects of Dox, but also effectively inhibited the tumor growth. Additionally, it was surprising that P10 exhibited certain analgesic activity, which could reduce the accompanying cancer pain, while playing an effective role in cancer therapy. Thus, the results showed that the P10 lipopeptide can be used as an ideal drug carrier and it has great application potential in the field of clinical cancer therapy.

Development of antibacterial peptides with efficient antibacterial activity, low toxicity, high membrane disruptive activity and a synergistic antibacterial effect.

The development of new antimicrobial drugs is urgently required to overcome bacterial resistance which is a serious threat to human health. Antimicrobial peptides (AMPs) which are ideal substitutes for traditional antibiotics have a unique mechanism of action and do not easily cause bacterial resistance. Herein, a series of new AMPs were designed and synthesized based on the biological characteristics of natural AMPs (such as the positive charge, α-helical structure and amphiphilicity). Biological screening of the AMPs provided an antimicrobial lipopeptide LP21 with efficient antimicrobial activity, serum stability, low cytotoxicity and high membrane-disruptive activity. Besides, LP21 could self-assemble into spherical aggregates in aqueous solutions which encapsulated TC to form LP21@TC nanomedicine, and the encapsulation efficiency was about 50.03 ± 3.03%. More impressively, both LP21 and LP21@TC nanomedicine displayed significant therapeutic effects in vivo, and the LP21@TC nanomedicine could exert a synergistic antimicrobial effect. This work is expected to provide a new research vision for the design of AMPs and synergistic antibacterial sensitization treatment.

Novel Hierarchical Fe(III)-Doped Cu-MOFs With Enhanced Adsorption of Benzene Vapor.

New hierarchical Fe(III)-doped Cu-MOFs (Fe-HK) were developed via introduction of Fe3+ ions during HKUST-1 synthesis. The obtained products were characterized by N2 adsorption, X-ray diffraction, scanning electron microscopy, energy dispersive spectroscopy, FTIR spectroscopy, and thermal analysis. The adsorption isotherms and kinetics of benzene vapor were measured and consecutive adsorption-desorption cycles were performed. It was found that the hierarchical-pore Fe-HK-2 exhibited optimal textural properties with high BET surface area of 1,707 m2/g and total pore volume of 0.93 cm3/g, which were higher than those of the unmodified HKUST-1. Significantly, the hierarchical-pore Fe-HK-2 possessed outstanding benzene adsorption capacity, which was 1.5 times greater than the value on HKUST-1. Benzene diffusivity of Fe-HK-2 was 1.7 times faster than that of parent HKUST-1. Furthermore, the benzene adsorption on Fe-HK-2 was highly reversible. The hierarchical-pore Fe-HK-2 with high porosity, outstanding adsorption capacity, enhanced diffusion rate, and excellent reversibility might be an attractive candidate for VOCs adsorption. This may offer a simple and effective strategy to synthesize hierarchical-pore MOFs by doping with other metal ions.

Clinical Features of Pituitary Stalk Interruption Syndrome in 114 Cases.

Objective To analyze the clinical characteristics of pituitary stalk interruption syndrome(PSIS). Methods The clinical data including clinical manifestations,laboratory tests,and imaging findings of 114 PSIS patients in our hospital were retrospectively analyzed. Results Of these 114 PSIS patients,102 cases (89.4%) were male. The average age was 21.1?6.1 years. A history of breech delivery was documented in 91 cases (91.9%). Short stature was found in 89 cases (71.8%) and bone age delayed (6.1?5.1) years. Secondary sex characteristics were poor or undeveloped in most patients. The prevalence of deficiencies in growth hormone,gonadotropins,corticotropin,and thyrotropin were 100.0%,94.0%,84.2%,and 74.6%,respectively. Hyperprolactinemia was found in 28.1% of patients. Three or more pituitary hormone abnormalities were found in 105 cases(92.1%). Compared with the 5 cases with history of cephalic delivery,no difference were found in the aspects of height(t=0.297,P=0.634),penile length(t=1.205,P=0.882),testicular volume (U=99.000,P=0.348),growth hormone peak (U=89.000,P=0.186),adrenocorticotropic hormone peak(U=131.000,P=0.967),luteinizing hormone peak(U=98.500,P=0.582),thyroid-stimulating hormone (U=82.000,P=0.162),and the height of anterior pituitary (t=1.676,P=0.107) in the 53 cases with history of breech delivery. Conclusions The clinical manifestations,symptoms,hormone deficiencies were severe in our series. The condition severities were not remarkably different in patients with different delivery ways.

An in vitro study of pcDNA 3.0-hVEGF165 gene transfection in endothelial progenitor cells derived from peripheral blood of rabbits.

The present study investigated the effect of the VEGF165 gene on adhesion, migration, and proliferation of endothelial progenitor cells (EPCs) derived from peripheral blood of rabbits. Peripheral blood mononuclear cells were isolated from rabbits by density gradient centrifugation with Ficoll-Plaque Plus. EPCs were characterized by immunofluorescence and immunostaining. A pcDNA 3.0-hVEGF165 expression vector was constructed and EPCs were transfected with the pcDNA 3.0-hVEGF165 gene. The EPCs derived from peripheral blood of rabbits were successfully transfected with pcDNA 3.0-hVEGF165. ELISA showed that the expression of VEGF165 increased significantly in the EPCs transfected with the hVEGF165 gene compared to control cells. Compared to control EPCs, EPCs transfected with the hVEGF165 gene had significantly enhanced adhesion, migration, and proliferative ability in vitro.