Peptide-based vaccine targeting IL17A attenuates experimental spondyloarthritis in HLA-B27 transgenic rats.

Objectives: Spondyloarthritis (SpA) is known as series of immune-mediated inflammatory disease of the axial and peripheral joints. Human leucocyte antigen (HLA)-B27 is a genetic risk factor for SpA. Recent evidence suggests that the interleukin -17 (IL17) axis strongly contributes to SpA.

Preclinical study of a DNA vaccine targeting SARS-CoV-2.

To fight against the worldwide COVID-19 pandemic, the development of an effective and safe vaccine against SARS-CoV-2 is required. As potential pandemic vaccines, DNA/RNA vaccines, viral vector vaccines and protein-based vaccines have been rapidly developed to prevent pandemic spread worldwide. In this study, we designed plasmid DNA vaccine targeting the SARS-CoV-2 Spike glycoprotein (S protein) as pandemic vaccine, and the humoral, cellular, and functional immune responses were characterized to support proceeding to initial human clinical trials.

The CD153 vaccine is a senotherapeutic option for preventing the accumulation of senescent T cells in mice.

Senotherapy targeting for senescent cells is designed to attenuate age-related dysfunction. Senescent T cells, defined as CD4 CD44 CD62L PD-1 CD153 cells, accumulate in visceral adipose tissues (VAT) in obese individuals. Here, we show the long-lasting effect of using CD153 vaccination to remove senescent T cells from high-fat diet (HFD)-induced obese C57BL/6J mice.

AJP001, a novel helper T-cell epitope, induces a humoral immune response with activation of innate immunity when included in a peptide vaccine.

Vaccine design requires well-tailored formulations including a T-cell epitope and adjuvants. We identified a novel cationic peptide, AJP001, which possesses a strong affinity for murine MHC class II alleles (H2-IE and H2-IA) and low affinity for H2-IA. We designed an AJP001 and epitope peptide-conjugated vaccine, AJP001-angiotensin (Ang) II, which was intracutaneously administered to mice three times at 2-week intervals.

Beperminogene perplasmid for the treatment of critical limb ischemia.

Therapeutic angiogenesis for the treatment of ischemic disease can be attained through the delivery of recombinant growth factor proteins, through gene transfer or cell transplantation. Gene transfer associated with adenovirus or naked plasmid DNAs has been extensively studied in clinical trials. An investigational product, beperminogene perplasmid, is the naked plasmid DNA encoding the cDNA of human HGF, which has potent angiogenic activity.

OPG/RANKL/RANK axis is a critical inflammatory signaling system in ischemic brain in mice.

Osteoprotegerin (OPG) is a soluble secreted protein and a decoy receptor, which inhibits a receptor activator of nuclear factor κB (NF-κB) ligand (RANKL)/the receptor activator of NF-κB (RANK) signaling. Recent clinical studies have shown that a high-serum-OPG level is associated with unfavorable outcome in ischemic stroke, but it is unclear whether OPG is a culprit or an innocent bystander. Here we demonstrate that enhanced RANKL/RANK signaling in OPG(-/-) mice or recombinant RANKL-treated mice contributed to the reduction of infarct volume and brain edema via reduced postischemic inflammation.

Novel anti-microbial peptide SR-0379 accelerates wound healing via the PI3 kinase/Akt/mTOR pathway.

We developed a novel cationic antimicrobial peptide, AG30/5C, which demonstrates angiogenic properties similar to those of LL-37 or PR39. However, improvement of its stability and cost efficacy are required for clinical application. Therefore, we examined the metabolites of AG30/5C, which provided the further optimized compound, SR-0379.

Long-term expression of periostin during the chronic stage of ischemic stroke in mice.

Periostin is an extracellular matrix glycoprotein and has various cellular effects. Previously, we demonstrated the neuroprotective effects of periostin during the acute stage of cerebral ischemia. However, its expression during the chronic stage remains unknown.

Therapeutic vaccine against DPP4 improves glucose metabolism in mice.

The increasing prevalence of type 2 diabetes mellitus is associated with a significant economic burden. We developed a dipeptidyl peptidase 4 (DPP4)-targeted immune therapy to increase glucagon-like peptide 1 hormone levels and improve insulin sensitivity for the prevention and treatment of type 2 diabetes mellitus. Immunization with the DPP4 vaccine in C57BL/6J mice successfully increased DPP4 titer, inhibited plasma DPP4 activity, and induced an increase in the plasma glucagon-like peptide 1 level.

Development of novel DNA vaccine for VEGF in murine cancer model.

We developed DNA vaccine for vascular endothelial growth factor (VEGF), which may provide the therapeutic option instead of anti-VEGF antibody, bevacizumab. Plasmid containing VEGF mini-gene was constructed in the insertion of B-cell epitope of Hepatitis B core protein [HBc-VEGF], which was an epitope carrier. High titer of anti-VEGF antibody was observed in BALB/c mice which were intramuscularly immunized with HBc-VEGF by electropolator.

Inhibition of neointima formation through DNA vaccination for apolipoprotein(a): a new therapeutic strategy for lipoprotein(a).

Lipoprotein(a) [Lp(a)] is an unique lipoprotein consisting of the glycoprotein apolipoprotein(a) [apo(a)] in low-density lipoprotein. Although Lp(a) is a well-known independent risk factor for cardiovascular disease; however, there is no drugs to decrease plasma Lp(a) level. Thus, to inhibit the biological activity of Lp(a), we developed DNA vaccine for apo(a) by the targeting to the selected 12 hydrophilic amino acids in the kringle-4 type 2 domain of apo(a).

Relationship between bone mineral density of the distal radius and ulna and fracture characteristics.

Purpose: This study was designed to elucidate the different decrease patterns of bone mineral density (BMD) in the distal tenth and third of the radius and ulna that influence the incidence of fractures, the fracture type, and redisplacement after closed reduction and casting.

Methods: The BMD of 1024 healthy women and 86 women treated for distal radius and ulna fracture was measured in the distal tenth and distal third zones of the radius and ulna (termed R10, R3, U10, and U3, respectively) using dual-energy x-ray absorptiometry. The BMD in the fracture group was compared with age-matched BMD in the nonfracture group.