Novel lipopeptides of ESAT-6 induce strong protective immunity against Mycobacterium tuberculosis: Routes of immunization and TLR agonists critically impact vaccine’s efficacy

Mycobacterium tuberculosis (Mtb), the bacterial cause of tuberculosis, is a leading infectious agent worldwide. The development of a new vaccine against Mtb is essential to control global spread of tuberculosis, since the current vaccine BCG is not very effective and antibiotic resistance is a serious, burgeoning problem. ESAT-6 is a secreted protein of Mtb, which is absent in BCG but has been implicated in inducing protective immunity against Mtb. Peptide based subunit vaccines are attractive due to their safety and high specificity in eliciting immune responses, but small synthetic peptides are usually not very immunogenic. We have designed a novel subunit vaccine for Mtb by using simple lipid (palmitic acid) modified derivatives of peptides from ESAT-6 protein corresponding to dominant human T cell epitopes and examined their ability to stimulate protective immunity against Mtb by intranasal and subcutaneous immunization in mice. We also investigated how individual TLR agonists as adjuvants (PolyI:C, MPL and GDQ) contribute to enhancing the induced immune responses and resulting protective efficacy of our vaccine. We observed that single C-terminal palmitoyl-lysine modified lipopeptides derived from ESAT-6 induce significant cellular immune responses on their own upon mucosal and subcutaneous immunizations. Intriguingly, a combination of immunogenic lipopeptides of ESAT-6 antigen exhibited local (pulmonary) and systemic immune responses along with efficient protective efficacy when administered intranasally or subcutaneously. Surprisingly, combination of ESAT-6 derived lipopeptides with a TLR-4 agonist (MPL) enhanced protection, whereas TLR-3 (Poly I:C) and TLR-7/8 agonists (gardiquimod, GDQ) led to reduced protection associated with specific local and systemic immune modulation. Our studies demonstrate the potential of ESAT-6 derived lipopeptides as a promising vaccine candidate against Mtb, and emphasize that selection of adjuvant is critical for the success of vaccines. These findings demonstrate the promise of synthetic lipopeptides as the basis of a subunit vaccine for TB.     

Polymorphism of the ABO blood group genes in Han, Kazak and Uygur populations in the Silk Route of northwestern China

Genetic polymorphism in the ABO blood group gene of Han, Kazak and Uygur populations inhabiting the most northwestern part of China was investigated using polymerase chain reaction-based techniques. The present study enrolled 43 healthy unrelated Han, 37 Kazak and 59 Uygur volunteers. The allele in A1 blood group is distinguished A0101 and A0102 in difference of nucleotide position 467. The A0101 allele is more frequent in Caucasian and the A0102 allele is characteristic in Mongoloid. It must be notable that A0201 in the A2 group (with a single base deletion at nucleotides 1059 to 1061) which was characteristic of Caucasian was observed in Kazak and Uygur populations but not in Han. Further, 00201 (with no nucleotide deletion at 261 and three nucleotide differences), which is frequent in different races including Caucasian except for Mongoloid, was detected also in Kazak and Uygur populations. The frequencies of B0101 in Kazak, Uygur and Han were comparable to those of other Asian populations but higher than those of Caucasian populations. Collectively, these results reveal that the allele frequencies of Kazak and Uygur at the ABO blood group locus are an intermediate between those of Mongoloid and Caucasian, suggesting the admixed feature of Kazak and Uygur with Mongoloid and Caucasian.     

HLA antigens in affective disorders and schizophrenia

The distribution of HLA antigen frequencies has been studied in patients with affective disorders. There were no significant differences between bipolar patients, unipolar patients, or controls. Preliminary data on HLA antigen distribution in schizophrenic patients are reported. Our negative results in affective disorders are discussed in relation to HLA studies reported from other laboratories, with special reference to some potential methodological problems.     

湖北钉螺在非适宜地东平湖生存繁殖的纵向观察

目的在南水北调条件下,观察人工北移至非适宜地区山东省东平湖区湖北钉螺生存繁殖的能力。方法近年,在东平湖区的湖心岛以螺笼放养钉螺,定量观察其生存繁殖情况。结果亲代钉螺可以在东平湖越冬生存,存活率为60.51%(118/195);经过2个冬季24个月放养,繁殖产生了子2代钉螺228只,其螺口数量较亲代钉螺数量增长了14.00%;经过3个冬季36个月放养,钉螺繁殖产生了子3代钉螺86只,其数量较亲代钉螺减少了57.00%,与子2代钉螺数量比较减少了62.28%;经过4个冬季48个月放养,钉螺存活率为0。结论南水北调东线南端长江取水口地区的湖北钉螺在血吸虫病非流行区山东省东平湖区可以繁殖到子3代,生存繁殖的时间不超过4个冬季、48个月,呈现逐年消亡趋势。报道了在中国大陆北纬35 055/地区,人工北移到此地的钉螺在湖滩铁丝笼内放养状态下生存繁殖的纵向观察结果。     

急性胰腺炎早期肠内营养研究进展

急性胰腺炎是临床常见的急危重症,病死率高,恰当的营养支持在机体高代谢及负氮平衡状态下可降低感染率及病死率,是我们一直关注的热点。过去,我们主张通过禁食让胰腺获得休息,从而改善疾病预后。但是,目前越来越多的试验研究表明,相比禁食早期肠内营养让胰腺炎病人获益显著。接下来我将从肠道屏障功能障碍、肠内营养途径、启动时间、营养制剂及营养量的选择等方面就急性胰腺炎早期肠内营养的最新进展作一综述。     

Genipin-crosslinked polyvinyl alcohol/silk fibroin/nano-hydroxyapatite hydrogel for fabrication of artificial cornea scaffolds—a novel approach to corneal tissue engineering

Abstract

Design of artificial corneal scaffolds substitute is crucial for replacement of impaired cornea. In this paper, porous polyvinyl alcohol/silk fibroin/nano-hydroxyapatite (PVA/SF/n-HA) composite hydrogel was prepared via the genipin (GP) cross-linking, the pore diameter of the hydrogel ranged from 8.138?nm and 90.269?nm, and the physical and physiological function of hydrogel were investigated. The resulting hydrogel exhibited favourable physical properties. With the GP content increasing, the structural regularity of PVA/SF/n-HA composite hydrogel was enhanced and the thermal stability was improved. The moisture content was slightly decreased and generally maintained at approximately 70%. The tensile strength was heightened up to 0.64?MPa, while the breaking elongation was decreased slightly. Moreover, the biofunction was investigated. The in vitro degradation test demonstrated that with the addition of GP, the stability of the composite hydrogels in protease XIV solution was promoted and the three-dimensional porosity structure of composite hydrogels was maintained as ever. And the human corneal fibroblasts (HCFs) were employed to examine the cells cytotoxicity of the PVA/SF/n-HA composite hydrogels with different GP content by CCK-8 assay. Based on confocal laser scanning microscope (CLSM) and scanning electron microscope (SEM), HCFs had individually commendable adhesion and proliferation on PVA/n-HA/SF composite hydrogel. HCFs proliferated and grew into the pores of composite hydrogel. The results of biocompatibility experiments of composite hydrogel suggested that it was no acute toxicity, in vitro cytotoxicity was 0 or 1 grade. Overall, results from this paper, PVA/n-HA/SF composite hydrogel was a qualified medical material which conformed to the national standard, could be a promising alternative for artificial cornea scaffold material—a novel approach to corneal tissue engineering.     

Innovation According to C. Walton Lillehei

C. Walton Lillehei (1918–1999) represents the most distinguished American surgeon of his time and perhaps the greatest surgeon in history. As his mentor, Owen H. Wangenesteen (1898–1981), so accurately declared, Walt Lillehei was “one of the surgical immortals.” Indeed, similar words were echoed by the famous cardiac surgeon, Denton A. Cooley (b. 1920), who said, “Hardly any other cardiac surgeon has introduced a greater number of innovative techniques and concepts.”

Born in Minneapolis, Lillehei attended the University of Minnesota, where he completed his college, medical, physiology, and surgical studies. Because of his extraordinary contributions to make open heart surgery feasible and safe, he is considered the father of open heart surgery. Many other contributions followed the initial innovations, particularly the use of the bubble oxygenator, the total intracardiac repair of tetralogy malformation, the use of myocardial electrodes for treating complete heart block, and the development of three cardiac valve prostheses, among other discoveries.

The noted Minnesota surgeon was an innovator for his entire professional career. He believed in innovation and practiced innovation in any way possible. “Determination, persistence, and stubbornness” were, according to Lillehei, “the most important components of research and successful discovery.”     

Sodium oleate induced rapid gelation of silk fibroin

Silk fibroin has acquired increasing interest in the last years for application in medicine and namely in tissue engineering. Several methods have been developed to process fibroin and for the fabrication of nets, sponges, films and gels. This paper deals with the fabrication and characterization of fibroin hydrogels obtained by using sodium oleate as gelation agent. Gels have been prepared by mixing Silk fibroin (SF) and Sodium oleate (SO) water solutions in different concentrations, and a quite wide frame of compositions have been explored. Rheological tests have been performed to determine the gelation times, scanning electron microscopies have been made to evaluate morphologies, FTIR analysis has been done to determine the conformation of the starting materials and of the resulting gels, water content has been measured and cytotoxicity tests have been performed to validate the potential biomedical use of the hydrogels. Depending on the SF and SO different gelation times have been obtained thanks to the formation of intermolecular bonds between the fibroin chains. The obtained fastest gelation of about 80 s could make this specific formulation compatible with in situ gelation. By changing composition, gels with different morphologies, rheological properties and water contents have been prepared.     

CYTED Network to develop an immunogen compatible with integrated management strategies for tick control in cattle

INCOGARR is a thematic network recently approved to be financially supported by the Ibero-American Program of Science and Technology for Development (CYTED). The objectives of this Network are the design and evaluation of an efficient and feasible anti-tick vaccine candidate from the technical and economical points of view and also sharing experiences in the immunological control of ticks as part of an Integrated Control Program. The Network consists of seven laboratories and one company from six countries. The first meeting of the Network took place with the representation of each laboratory involved. In the meeting, general and specific objectives and activities of the Network were discussed and it was a very nice example of international collaboration to address an unsolved worldwide topic on tick control in which laboratories with different competencies and expertise join their efforts in a common goal.