GLP-1 RA는 당뇨병 및 비만 치료 영역에서 뛰어난 효과를 보이고 있으나, 사용 초기부터 급성췌장염과의 연관성이 꾸준히 논란이 되어 왔다. GLP-1 RA 사용과 연관성이 의심되는 췌장염 증례가 다수 보고되었고 약물감시 데이터베이스 들에서도 췌장염 사례들이 보고되어 약제의 안전성에 대한 경각심을 높이기도 했다. 이에 따라 본 종설에서는 GLP-1 RA의 사용과 급성췌장염 발생 간의 상관관계에 대한 임상 연구 결과 및 메타분석, 병태생리학적 연구 결과를 살펴보고 최신 임상 근거 및 가이드라인 검토를 통해 적절한 GLP-1 RA 사용을 위한 임상 전략을 제시하고자 한다.

It is challenging to treat canine brucellosis due to the immune evading and stealthy characteristic of the causative bacteria, Brucella (B.) canis. Gold nanoparticle aptamer (AuNP-Apt) conjugated antimicrobial peptide (AMP) is a promising alternative to antibiotics for various bacterial infections. However, the toxicity of AuNP-Apt has been variable throughout research, and the in vivo toxic mechanism has not been fully elucidated. This study evaluated the therapeutic potential against B. canis, and the toxicity of AuNP-Apt conjugated antimicrobial peptide, RW-BP100 (AuNP-AptHis-RW-BP100His), in a mouse model. Intravenous (IV) treatment with AuNP-AptHis-RW-BP100His reduced the bacteria burden and histopathologic lesions. The IV treatment also induced CD4+ T cell differentiation and modulated serum cytokine levels. However, high-dose AuNP-Apt was lethal, resulting in tissue accumulation and vessel embolism. Therefore, AuNP-AptHis-RW-BP100His is a promising therapeutic agent for B. canis treatment, but due to its toxicity, further studies are needed for its utilization in clinical practice.

The vitrification of embryos is essential for animal reproduction and significantly contributes to assisted reproductive technologies, enabling fast cryopreservation without ice crystal formation. Mitochondria, vital organelles in cellular metabolism, are responsible for critical functions like ATP synthesis, calcium regulation, and apoptotic signaling. Preserving mitochondrial integrity is essential for ensuring embryonic strength. Studies demonstrate that vitrification, a widely used cryopreservation method, can markedly impair mitochondrial function in mammalian embryos. This study examines the efficacy of novel/modified antifreeze peptide as a biocompatible agent when used in an appropriate concentration with base vitrification media. Blastocysts vitrified in base media as well as supplemented with the peptide exhibited significantly enhanced post-thaw survival rates, attaining re-expansion and hatching rates of 96.89 ± 4.2% and 88.31 ± 1.3%, respectively, in contrast to 79.38 ± 3.7% and 52.57.9 ± 0.8% observed in the control group. Furthermore, peptide-treated BLs demonstrated elevated expression of PGC1α, BCL2, and Sirt-1, which are the key genes related to mitochondrial membrane potential and anti-apoptotic factors. The mitochondrial function was maintained, and the levels of reactive oxygen species (ROS) and the expression of genes such as Cyto-c, caspases 3, and caspase 9 were markedly diminished in the embryos vitrified with peptide. These findings highlight the ability of this modified peptide to preserve mitochondrial integrity and reduce oxidative stress, hence enhancing the survival of blastocysts post-vitrification.

Inflammation is a fundamental host defense mechanism against external insults; however, excessive immune activation contributes to inflammatory diseases such as periodontitis, resulting in periodontal tissue destruction and tooth loss. Interleukin-1β (IL-1β), a key pro-inflammatory cytokine, stimulates oral epithelial cells to produce interleukin-8 (IL-8), which recruits neutrophils and amplifies local inflammation. Therefore, regulation of IL-1β– induced IL-8 secretion in oral epithelial cells is critical for controlling pathological inflammatory responses. Peptidebased therapeutics have attracted increasing interest due to their specificity and biocompatibility, highlighting their potential as anti-inflammatory agents. This study investigated the anti-inflammatory effects and mechanisms of a human stromal cell–derived factor-1 (SDF-1)–derived peptide in IL-1β–stimulated oral epithelial cells. Human oral epithelial KB cells and immortalized human oral keratinocytes were treated with IL-1β in the presence or absence of SDF-1–derived peptides. IL-8 secretion was measured by enzyme-linked immunosorbent assay, and activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and mitogen-activated protein kinase (MAPK) pathways was examined by western blotting. IL-1β significantly increased IL-8 secretion and induced phosphorylation of NF-κB p65 and MAPKs, including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase, and p38. Inhibition of ERK and p38 markedly reduced IL-8 expression, indicating their central roles in IL-1β signaling. Among 18 SDF-1δ–derived peptides, S12 exerted the strongest inhibitory effect, reducing IL-8 secretion and suppressing IL- 1β–induced NF-κB and MAPK phosphorylation. These results demonstrate that S12 attenuates IL-1β–driven IL-8 production by targeting key inflammatory signaling pathways, supporting its potential as a host-modulation therapeutic for periodontal disease.

Myxomatous mitral valve disease (MMVD) is the most prevalent cardiac disease in dogs worldwide. Left atrial enlargement is a prominent feature associated with an increased risk of congestive heart failure in dogs with MMVD. Left atrial anteroposterior diameter (LAD) has been suggested as a supplementary parameter for evaluating LA size in various species. The purpose of our study was to establish a correlation between the left atrial anteroposterior diameter normalized to body weight (LADn) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in dogs with MMVD and to assess the diagnostic potential of LADn for MMVD. We conducted this study on 35 dogs and categorized them into the control and MMVD groups. The control group consisted of 10 dogs, whereas the MMVD group included 25 dogs classified into stages B1, B2, and C according to the American College of Veterinary Internal Medicine (ACVIM) guidelines. LADn was measured using echocardiography, and NT-proBNP levels were assessed using a fluorescent immunoassay. In conclusion, LADn shows promise as a valuable diagnostic marker of MMVD in dogs. The strong positive correlation between LADn and NT-proBNP levels demonstrates the usefulness of LADn as a clinical index for evaluating cardiac function and disease progression in dogs with MMVD.

본 연구는 12주간의 맨손 근력운동 수행이 복부비만 여성노인의 혈청지질, 인슐린 및 C-peptide에 미치는 영향을 구명하기 위하여 운동군(EG, n=13), 대조군(CG, n=13)으로 구분하여 실시하 였다. 맨손근력운동 강도는 주관적 운동 자각도(rating of perceived exertion; RPE)를 사용하였으며, 1-4 주, RPE 12-13, 5-8주, RPE 13-14, 9-12주, RPE 14-15로 설정하여 주 3회, 1회 운동시간 60분 실시하 였다. 자료처리는 측정항목에 대한 평균값(M)과 표준편차(SD)를 산출하였고, 그룹 및 시기 간 상호작용 효 과검증은 two-way repeated measures ANOVA를 실시하였다. 상호작용 효과를 포함하여 필요에 따라 그 룹 내 시기 간 차이 검증은 paired t-test를 실시하였고, 그룹 간 차이 검증은 independent t-test, 각 항목 별 통계적 유의수준은 통계 방식에 따라 .05와 .025로 각각 달리 설정하였다. 그 결과, TG(p<.01) 및 HDL-C(p<.05)에서 상호작용 효과, 인슐린(p<.05) 및 C-peptide(p<.01)는 시기 간 주효과가 나타났다. 이 상의 결과, 12주간의 운동이 혈청지질 중 TG, HDL-C를 개선이 나타났고, 이는 혈관 및 대사 기능의 측 면에서 매우 중요한 결과라 생각된다. 하지만, 인슐린과 C-peptide에서는 운동군보다 대조군이 더 많이 증 가하여, 맨손근력운동에 대한 긍정적인 개선은 기대하기 힘들었다. 이는 복부비만 여성노인의 나이가 고령 임을 감안하였을 때, 비교적 짧은 저항운동 기간으로는 인슐린과 C-peptide의 변화를 기대하기 힘들다는 점을 시사한다. 하지만, 맨손근력운동은 노인이 부상의 위험없이 실시할 수 있으므로 후속 연구를 통해 다 양한 결과를 확인할 필요가 있다.

본 연구는 기능성 화장품 소재 개발을 목표로 효모 유래 MPC의 세포 생리활성을 조사하였 다. 피부 세포주에 처리된 Cu와 Zn 이온 모두 세포 독성이 확인되었지만, 정제된 MPC는 결합된 금속 이온의 세포 독성을 획기적으로 제거하였다. 게다가 특정 농도의 MPC는 대조군과 비교하여 세포 생존 율을 오히려 약 20% 증가시켰다. MPC 중 효모 펩타이드-Cu(YP-Cu)는 UVB 자극으로 유도되는 세포 내 활성산소의 양을 약 30% 정도 유의하게 감소시켰지만, YP-Zn은 영향을 미치지 못했다. 또한, YP-Cu 처리는 피부 세포에서 콜라겐 유전자의 발현량을 2배 증가시켰고, 프로콜라겐 분비량은 1.7배 증 가시켰으며, UVB 자극에 의한 콜라겐 유전자의 발현 저해에도 효과적으로 대응했다. 결론적으로, 유리 금속 이온 자체는 세포독성 효과로 인해 화장품 소재에 적합하지 않지만, 정제된 MPC, 특히 YP-Cu는 이러한 금속 이온의 독성을 효과적으로 상쇄하고 세포 생존율을 향상시킬 뿐만 아니라, UVB 자극에 따 른 유해 효과를 완화하기 때문에 잠재적 기능성 화장품 소재로 사용될 수 있다.

Xenorhabdus와 Photorhabdus 속은 각각 곤충병원성 선충인 Steinernema와 Heterorhabditis에 공생하는 공생세 균이다. 감염성 선충의 유충은 공생세균을 표적 곤충의 혈강에 전달하고, 여기서 세균이 증식하여 숙주 선충의 발달을 돕는다. 이러한 선충과 세균 복합체의 성공적 공생관계는 세균의 이차대사산물을 통한 숙주의 면역억제 에 달려져 있다고 알려져 있다. 본 연구에서는 서로 다른 살충력을 보이는 6종의 Xenorhabdus를 확보하고 이러한 차이가 세균의 성장속도와 NRPS (Non ribosomal peptide synthease)에 의해 생성되는 세균의 이차대사산물 발현에 서 기원한다는 것을 확인하였다. 서로 다른 균주들은 콩명나방 (Tenebrio molitor)에 대한 살충력에 차이를 가지고 있었다. 이러한 세균들은 TSB 배지에서는 세균 성장 속도에 차이가 존재하지 않았지만 콩명나방 혈강 내에서는 세균의 성장 속도에 차이가 존재하는 것으로 나타났다. 또한 각 세균의 이차대사산물 추출물을 통한 곤충의 면역 억제 실험 결과 PLA2 활성 억제, 세포독성 능력들이 살충력과 상관관계가 있는 것으로 나타났다. 이러한 이차대 사산물의 경우 많은 물질이NRPS (Non ribosomal peptide synthease)에 의해 생성되므로 각 세균 별 NRPS의 유전자 발현을 보았을 때 흥미롭게도 살충력이 더 높은 스트레인의 세균이 일부 NRPS 유전자의 발현이 더 높은 것으로 나타났다. NRPS에 의해 합성되는 물질을 포함한 세균의 이차대사산물의 차이를 서로 비교하기 위하여 이차대사 산물 추출액을 GC-MS/MS를 이용하여 분석하였다. 본 연구를 통해 곤충병원세균에 살충력의 기원이 NRPS를 통해 합성되는 이차대사산물에 있다는 것을 확인하였으며 이를 이용한 다양한 NRPS 유래 물질 연구는 신규 살충 물질 개발에 들어가는 비용과 시간을 획기적으로 줄일 수 있을 것으로 기대된다.

Previous studies have shown that proline mutations in the heptad repeat region stabilize the coronavirus spike (S) protein in a pre-fusion state. To understand the impact of proline substitutions on the fusogenicity of the S protein, we engineered the swine acute diarrhea syndrome coronavirus (SADS-CoV) S protein with two proline substitutions (S-PP) and examined its fusogenicity using dual-split-protein based cell-cell fusion assay. Unlike the wild-type S (S-WT), S-PP rarely formed syncytia. Additionally, protein expression of S-PP was impaired compared to S-WT, as previously reported. Our results indicate that pre-fusion stabilized S protein is unable to induce membrane fusion and provide a better understanding of SADS-CoV S and vaccine antigen design.

Salivary gland dysfunction is a common complication of diabetes. Decreased saliva production and changes in saliva composition may cause oral diseases. Reactive oxygen species (ROS) generation in the salivary glands results in the loss of acinar cells and decreased saliva secretion. Glucagon-like peptide 1 (GLP-1) is the incretin hormone that regulates blood glucose level and can suppress ROS production and inflammation through its antioxidant effects. Dipeptidyl peptidase-4 (DPP-4) is an enzyme that breaks down GLP-1. In this study, we evaluated the pathological role of DPP-4 and GLP-1 on salivary gland dysfunction in type 2 diabetic db/db mice. We observed reduced salivary secretion and histopathological alteration of salivary glands in the db/db mice. The increased DPP-4 and decreased GLP-1 levels in the salivary glands were also detected in the db/db mice. Furthermore, the db/db mice had increased apoptosis and oxidative injury in salivary glands. There was an accumulation of advanced glycation end products and mucus in the salivary glands of the db/db mice. In conclusion, these results showed the possible involvement of DPP-4 and GLP-1, leading to increased ROS-induced apoptosis in diabetes-related salivary gland dysfunction. DPP-4 and GLP-1 may be a pharmacological target for patients with diabetes-related salivary gland dysfunction.

This study investigates the influence of the type of lipid phase (corn oil [CO], palm oil [PO], MCT oil [MO], lemon oil [LO]) on the physical characteristics and bioactive peptide (BP) encapsulation in food-grade water-in-oil-in-water (W/O/W) double emulsions. The stabilities of the double emulsions were analyzed for droplet size characteristics, viscosity, dynamic rheological properties, encapsulation efficiency (EE), and release rate of BP (at different temperatures: 4, 25, 37, and 60oC) for 28 days. The encapsulated BP acts as an active substance in the osmotic balance and destabilization of the double emulsion system. For the effect of the oil phase, double emulsions prepared with PO showed the best droplet stability without phase separation (D50 < 1 m) and high BP retention (EE > 60%). In the release rate at high temperatures (60oC), the BP released from double emulsions was in the order of MO > CO > LO > PO over time. In contrast, the BP release from double emulsions at low temperatures (< 37oC) had no difference depending on the oil type. Therefore, the information obtained from this work is useful for preparing stable, functional food or cosmetic products from double emulsions using a BP.

Two bacterial genera, Xenorhabdus and Photorhabdus, are mutually symbiotic to the entomopathogenic nematodes, Steinernema and Heterorhabditis, respectively. Success parasitism of the nematode-bacterial complex depends on the host immunosuppression by the bacteria via their secondary metabolites. Lrp (Leucine-responsive regulatory protein) is a global transcriptional factor of the bacteria and play a crucial role in the parasitism. However, its regulatory targets to suppress the insect immunity were not clearly determined. This study investigated the regulatory target genes and subsequent secondary metabolites by Lrp in Xenorhabdus hominickii. Lrp expression occurred at the early infection stage in a target insect, Spodoptera exigua. Among eight non-ribosomal peptide synthetase (NRPS1-NRPS8) genes, six gene (NRPS3-NRPS8) expressions were positively correlated with Lrp expression in the infected larvae of S. exigua. Exchange of the Lrp promoter with an inducible promoter altered the production of the secondary metabolites along with alteration of the NRPS expression levels. The immunosuppressive activities of X. hominickii depended on the Lrp expression level. The metabolites produced by Lrp expression possessed the eicosanoid-biosynthesis inhibitors and hemolytic factors. A cyclic dipeptide (= cPF) was produced under Lrp control and identified to inhibit phospholipase A2 activity of S. exigua in a competitive inhibitory manner. These results suggest that Lrp is a global transcriptional factor of X. hominickii and plays crucial role in insect immunosuppression by modulating NRPS expressions.

Collagen peptides have garnered significant attention as functional foods across multiple fields due to their capacity to regulate physiological and hormonal processes, offering numerous advantages. However, despite their broad range of applications, comprehensive research on the potential toxicity of these substances remains lacking. Therefore, this study sought to assess the acute oral toxicity of a collagen peptide derived from skate (Raja kenojei) skin (CPSS) in both rats and dogs. In the rat model, CPSS was orally administered at doses of 300 and 2,000 mg/kg to Sprague-Dawley rats. An escalating single-dose oral toxicity assessment at doses of 500, 1,000, and 2,000 mg/kg was carried out in beagle dogs with 3-day intervals between doses. Throughout the 14-day post-administration assessment period, clinical signs, mortality rates, changes in body weight, and necropsy observations were closely monitored. After oral administration, no signs of toxicity associated with CPSS were observed in either rats or dogs. Therefore, the oral LD50 (approximate lethal dose for 50% mortality) for CPSS in rats was determined to exceed 5,000 mg/kg, and the maximum tolerated dose for dogs was estimated to be above 2,000 mg/kg. Consequently, this study offers safety data on the use of CPSS in functional foods and medicinal applications.

본 연구는 우리나라 해안에서 널리 서식 중인 해양 자원 중 하나인 전복(Haliotis discus hannai) 의 차세대염기서열분석 데이터 기반으로 선별한 신규 펩타이드의 항암 활성을 평가한 연구이 다. 펩타이드의 항암 활성은 교모세포종 세포주인 SNU-489에서 농도 의존적으로 처리 시간에 비례하여 증가하였으며, 200 μM로 48시간 처리하였을 때 암 세포 사멸율이 67%로 가장 높게 나타났다. 반면 정상 세포인 HaCaT에서 가장 높은 세포 사멸율은 18%로 농도 의존적이었으나 처리 시간과는 무관하였다. 또한 신규 펩타이드의 항암 메커니즘 과정을 밝히기 위해 세포자 멸괴사(Necroptosis) 관련 유전자의 발현 변화를 qRT-PCR 방법을 통해 검증하였다. RIPK3는 신 규 펩타이드 처리군에서 200 μM 처리 시 9배 이상 발현 증가, MLKL는 100 μM 처리군에서 대조군 대비 2배 이상 유의미하게 발현이 증가되었다. 이러한 결과로 미루어 볼 때, 전복 유래 신규 펩타이드는 암 세포 특이적으로 세포 독성을 가지며, 세포자멸괴사 메커니즘을 통해 암 세포 사멸을 일으키는 것으로 추측되므로 신규 펩타이드가 추후 교모세포종 치료제의 후보 물질로 활용될 수 있을 것으로 사료된다.