• Journal of Ginseng Research
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• 제46권6호
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• pp.771-779
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• 2022

Background: As a kind of common complication of the surgery of perianal diseases, perianal ulcer is known as a nuisance. This study aims to develop a kind of 20(S)-ginsenoside Rg3 (Rg3)-loaded hydrogel to treat perianal ulcers in a rat model. Methods: The copolymers PLGA₁₆₀₀-PEG₁₀₀₀-PLGA₁₆₀₀ were synthesized by ring-opening polymerization process and Rg3-loaded hydrogel was then developed. The perianal ulcer rat model was established to analyze the treatment efficacy of Rg3-loaded hydrogel for ulceration healing for 15 days. The animals were divided into control group, hydrogel group, free Rg3 group, Rg3-loaded hydrogel group, and Lidocaine Gel® group. The residual wound area rate was calculated and the blood concentrations of interleukin-1 (IL-1), interleukin-6 (IL-6), and vascular endothelial growth factor (VEGF) were recorded. Hematoxylin and eosin (H&E) staining, Masson's Trichrome (MT) staining, and tumor necrosis factor α (TNF-α), Ki-67, CD31, ERK1/2, and NF-κB immunohistochemical staining were performed. Results: The biodegradable and biocompatible hydrogel carries a homogenous interactive porous structure with 10 ㎛ pore size and five weeks in vivo degradation time. The loaded Rg3 can be released sustainably. The in vitro cytotoxicity study showed that the hydrogel had no effect on survival rate of murine skin fibroblasts L929. The Rg3-loaded hydrogel can facilitate perianal ulcer healing by inhibiting local and systematic inflammatory responses, swelling the proliferation of nuclear cells, collagen deposition, and vascularization, and activating ERK signal pathway. Conclusion: The Rg3-loaded hydrogel shows the best treatment efficacy of perianal ulcer and may be a candidate for perianal ulcer treatment.

• The Korean Journal of Physiology and Pharmacology
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• 제27권1호
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• pp.1-8
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• 2023

Hypothyroidism alone can lead to myocardial fibrosis and result in heart failure, but traditional hormone replacement therapy does not improve the fibrotic situation. Hydrogen sulfide (H₂S), a new gas signaling molecule, possesses anti-inflammatory, antioxidant, and anti-fibrotic capabilities. Whether H₂S could improve hypothyroidism-induced myocardial fibrosis are not yet studied. In our study, H₂S could decrease collagen deposition in the myocardial tissue of rats caused by hypothyroidism. Furthermore, in hypothyroidism-induced rats, we found that H₂S could enhance cystathionine-gamma-lyase (CSE), not cystathionine β-synthase (CBS), protein expressions. Finally, we noticed that H₂S could elevate autophagy levels and inhibit the transforming growth factor-β1 (TGF-β1) signal transduction pathway. In conclusion, our experiments not only suggest that H₂S could alleviate hypothyroidism-induced myocardial fibrosis by activating autophagy and suppressing TGF-β1/SMAD family member 2 (Smad 2) signal transduction pathway, but also show that it can be used as a complementary treatment to conventional hormone therapy.

• Biomolecules & Therapeutics
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• 제31권4호
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• pp.434-445
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• 2023

We investigated whether FTY-720 might have an effect on bleomycin-induced pulmonary fibrosis through inhibiting TGF-β1 pathway, and up-regulating autophagy. The pulmonary fibrosis was induced by bleomycin. FTY-720 (1 mg/kg) drug was intraperitoneally injected into mice. Histological changes and inflammatory factors were observed, and EMT and autophagy protein markers were studied by immunohistochemistry and immunofluorescence. The effects of bleomycin on MLE-12 cells were detected by MTT assay and flow cytometry, and the related molecular mechanisms were studied by Western Blot. FTY-720 considerably attenuated bleomycin-induced disorganization of alveolar tissue, extracellular collagen deposition, and α-SMA and E-cadherin levels in mice. The levels of IL-1β, TNF-α, and IL-6 cytokines were attenuated in bronchoalveolar lavage fluid, as well as protein content and leukocyte count. COL1A1 and MMP9 protein expressions in lung tissue were significantly reduced. Additionally, FTY-720 treatment effectively inhibited the expressions of key proteins in TGF-β1/TAK1/P38MAPK pathway and regulated autophagy proteins. Similar results were additionally found in cellular assays with mouse alveolar epithelial cells. Our study provides proof for a new mechanism for FTY-720 to suppress pulmonary fibrosis. FTY-720 is also a target for treating pulmonary fibrosis.

• The Korean Journal of Physiology and Pharmacology
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• 제27권4호
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• pp.345-356
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• 2023

This study aimed to assess the effects of exogenous hydrogen sulfide (H₂S) on abdominal aorta coarctation (AAC) induced myocardial fibrosis (MF) and autophagy in rats. Forty-four Sprague-Dawley rats were randomly divided into control group, AAC group, AAC + H₂S group, and H₂S control group. After a model of rats with AAC was built surgically, AAC + H₂S group and H₂S group were injected intraperitoneally with H₂S (100 µmol/kg) daily. The rats in the control group and the AAC group were injected with the same amount of PBS. We observed that H₂S can improve left ventricular function and the deposition of myocardial collagen fibers, inhibit pyroptosis, down-regulate the expression of P-eif2α in myocardial tissue, and inhibit cell autophagy by activating the phosphatidylinositol 3-kinase (PI3K)/AKT1 signaling pathway (p < 0.05). In addition, angiotensin II (1 µM) H9c2 cardiomyocytes were injured in vitro experiments, and it was also observed that pyroptosis was inhibited after H₂S (400 µmol/kg) intervention, the expression of P-eif2α in cardiomyocytes was significantly down-regulated, and the PI3K/AKT1 signaling pathway was activated at the same time. Therefore, increasing the expression of P-eif2α reverses the activation of the PI3K/AKT1 signaling pathway by H₂S. In conclusion, these findings suggest that exogenous H₂S can ameliorate MF in rats with AAC by inhibiting pyroptosis, and the mechanism may be associated with inhibiting the phosphorylation of eif2α and activating the PI3K/AKT1 signaling pathway to inhibit excessive cell autophagy.

• The Korean Journal of Physiology and Pharmacology
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• 제28권3호
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• pp.229-237
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• 2024

Cough is a common symptom of several respiratory diseases. However, frequent coughing from acute to chronic often causes great pain to patients. It may turn into cough variant asthma, which seriously affects people's quality of life. For cough treatment, it is dominated by over-the-counter antitussive drugs, such as asmeton, but most currently available antitussive drugs have serious side effects. Thus, there is a great need for the development of new drugs with potent cough suppressant. BALB/c mice were used to construct mice model with cough to investigate the pharmacological effects of pectolinarigenin (PEC). Hematoxylin-eosin and Masson staining were used to assess lung injury and airway remodeling, and ELISA was used to assess the level of inflammatory factor release. In addition, inflammatory cell counts were measured to assess airway inflammation. Airway hyperresponsiveness assay was used to assess respiratory resistance in mice. Finally, we used Western blotting to explore the potential mechanisms of PEC. We found that PEC could alleviate lung tissue injury and reduce the release of inflammatory factors, inhibit of cough frequency and airway wall collagen deposition in mice model with cough. Meanwhile, PEC inhibited the Ras/ERK/c-Fos pathway to exhibit antitussive effect. Therefore, PEC may be a potential drug for cough suppression.

• Anatomy and Cell Biology
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• 제56권1호
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• pp.109-121
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• 2023

Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.

• Anatomy and Cell Biology
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• 제56권1호
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• pp.122-136
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• 2023

Depression is a prevalent global problem since ages, predominately treated with SSRI. Cipralex, is an antidepressant of the SSRIs class used as a remedy for mood, depression and anxiety. Silymarin (SIL), a natural free radical scavenging, has an antioxidant and anti-inflammatory properties. This hypothesis evaluates, for the first time, the role of cipralex on the structure of the endocrine and exocrine components of the pancreas and assess the beneficial effects of SIL on these changes. Forty-five rats were divided into control, cipralex, and cipralex plus SIL groups. During sacrifice, all rats and pancreases were weighed and the ratio of pancreatic weight (PW) to rat weight (RW) was calculated, blood samples were collected to estimate fasting glucose, insulin and amylase levels, the specimens were prepared for histological, immunohistochemical (inducible nitric oxide synthase [iNOS], tumour necrosis factor-alpha [TNF-α], caspase 3, proliferating cell nuclear antigen [PCNA], and anti-insulin antibody), and morphometrical studies. Cipralex group exhibited marked destruction of the pancreatic architecture of the exocrine and endocrine parts, with a dense collagen fiber deposition. Also, there is highly significant decrease (P<0.001) of PW/RT ratio, insulin, and amylase levels, the number and diameter of islets of Langerhans, the number of PCNA positive immunoreactive cells, and the number of insulin positive β-cells. Furthermore, a highly significant increase of glucose level, iNOS, TNF-α, and caspase-3 positive immunoreactive cells in the islets of Langerhans and acinar cells were observed. SIL improves the pancreatic histological architecture, weight loss, biochemical, and immunohistochemical analyses. Administering SIL is advantageous in managing cipralex induced pancreatic injury via its anti-inflammatory, antioxidant, and anti-apoptotic qualities.

• The Korean Journal of Physiology and Pharmacology
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• 제28권1호
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• pp.39-48
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• 2024

Wogonin, extracted from the roots of Scutellaria baicalensis Georgi, has been shown to suppress collagen deposition in spontaneously hypertensive rats (SHRs). This study was performed to investigate the role and mechanism of wogonin underlying vascular remodeling in SHRs. After injection of SHRs with 40 mg/kg of wogonin, blood pressure in rats was measured once a week. Masson's trichrome staining was conducted to observe the changes in aortas and mesenteric arteries. Vascular smooth muscle cells (VSMCs) isolated from rat thoracic aortas were treated with Angiotensin II (Ang II; 100 nM) in the presence or absence of varying concentrations of wogonin. The viability and proliferation of VSMCs were examined using Cell Counting Kit-8 assay and 5-ethynyl-2'-deoxyuridine assay, respectively. The migration of VSMCs was examined using wound healing assay and transwell assay. We found that wogonin administration alleviated hypertension, increased lumen diameter, and reduced the thickness of the arterial media in SHRs. Ang II treatment enhanced the viability of VSMCs, which was inhibited by wogonin in a concentration-dependent manner. Wogonin reversed Ang II-induced increases in the viability, proliferation, and migration of VSMCs. Moreover, wogonin inhibited Ang II-induced activation of mitogen-activated protein kinase (MAPK) signaling in VSMCs. Overall, wogonin repressed the proliferative and migratory capacity of VSMCs by regulating the MAPK signaling pathway, thereby attenuating vascular remodeling in hypertensive rats, indicating that wogonin might be a therapeutic agent for the treatment of vascular diseases.

• Tuberculosis and Respiratory Diseases
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• 제50권2호
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• pp.182-195
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• 2001

연구배경 : IPF에 의한 유병률과 사망률은 점차 증가하는 추세이나 좋은 치료는 없는 상태이다. 폐 섬유화 과정에서 TGF-${\beta}_1$, TNF-$\alpha$, ET-1, IFN-$\gamma$등의 사이토카인이 중요한 역할을 함이 알려져 있다. 본 실험은 파라콰트를 기관지 내로 주입하여 섬유화가 유발되는 과정의 백서의 폐 조직 내에서 ET-1과 TGF-${\beta}_1$의 발현을 살펴보고, 또한 비선택적 ET-1 receptor blocker인 Bosentan이 폐 섬유화의 치료에 효과가 있는지를 보고자 하였다. 방 법 : 웅성 7-8 주령의 백서 120 마리를 세 그룹으로 나누고 제 1그룹은 대조군으로 하여 기관지 내로 생리 식염수를 투여하였고, 제2그룹은 파라콰트를 투여하였으며, 제3그룹은 첫날 파라콰트를 투여한 후 매일 gastric gavage 방법으로 보센탄을 투여하였다. 파라콰트 혹은 생리식염수를 투여한 지 1, 3, 5, 7, 10, 14일째 각각 세 그룹의 일정 수를 희생하여 폐의 병리조직을 보고 면역세포화학염색으로 ET-1과 TGF-${\beta}_1$의 발현 율을 조사하여 분석하였다. 폐 섬유화의 정도는 H&E 염색과 Masson trichrome 염색을 하여 컴퓨터 영상분석을 시행하였고, 면역세포화학염색은 염색정도에 따라 반정량화하여 분석하였다. 결 과 : 파라콰트를 투여한 군이 대조군에 비해 콜라겐의 침착이 실험 3일째부터 현저히 증가하였고, ET-1과 TGF-${\beta}_1$의 발현이 주로 실험 초기에 증가하였다. 그러나 보센탄을 투여한 경우 콜라겐이 침착된 양에는 유의한 변화가 없었고 파라콰트군과 비교해서 ET-1과 TGF-${\beta}_1$의 발현에 뚜렷한 변화는 없었다. 결 론: 파라콰트를 투여한 경우 폐 섬유화가 증가하였다. 그리고 ET-1과 TGF-${\beta}_1$의 발현이 증가하였다. 그러나 ET-1 에 대한 receptor blocker인 보센탄이 폐 섬유화를 막지는 못하였다. 파라콰트에 의한 폐 섬유화에 ET-1이 연관성이 있으나 그 역할에 대해서는 추후 더 연구가 필요할 것으로 사료된다.

• 대한치과교정학회지
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• 제32권6호
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• pp.455-466
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• 2002

본 연구의 목적은 periodontal distraction을 통해 급속 견인된 치아의 치조골과 치주인대에서 일어나는 변화를 조직학적으로 관찰하고, 치주조직이 정상적으로 재생될 수 있는지를 규명하는 것이다. 4 마리의 성견을 대상으로 하여, 좌우 상악 제2소구치를 발치 후에 상악 제1소구치 원심측 치간골에 홈을 주는 치조골 수술을 통해 골 저항을 약화시키고 제1소구치와 제3소구치에 periodontal distraction 장치를 장착하였다. 장치는 0.225mm씩, 하루에 2회 활성화시키며 상악 제1소구치를 발치와 공간으로 급속 견인하였다. 치아의 급속 견인은 5 일, 10 일, 20 일간 시행하였으며, 20 일간 견인한 대상에서는 2 주, 4 주, 8 주 후까지 유지기간을 두었다. 20 일간의 periodontal distraction을 통해 상악 제1소구치는 평균 5.02mm 원심 이동하였고, 고정원인 제3소구치는 0.58mm 근심 이동하였다. 조직학적 검사에서 distraction된 치주인대 공간에서는 골 재생과 개조가 빠르게 일어나, 견인 10일에 유골조직이 치아의 견인방향에 평행하게 생성되었고, 새로운 골 조직의 형성과 골 개조를 통한 골 성숙은 periodontal distraction 방향을 따라 활발히 진행되었으며, 이는 다른 골의 distraction osteogenesis에서 나타나는 결과와 비슷하였다. 급속 견인된 치아의 치주인대는 상당히 넓게 나타났고, 교원섬유와 치아간의 정상 관계는 급속 견인이 끝난 후 2주에 나타나기 시작하여 8주에 거의 회복되었다. 그러나, 치주인대의 골 쪽에서는 치아 급속 견인 후 8주까지도 새로운 골이 계속 형성되고 있었고, 교원섬유속이나 Sharpey 섬유는 보이지 않았다. 고정원으로 이용된 치아 주위의 조직반응은 통상적인 교정치료에서와 같이 압박 측에서의 골 흡수와 신장 측에서의 골 형성 소견을 나타냈다. 이상의 결과로 볼 때, periodontal distraction을 통한 치아의 급속 견인 시, 치주인대 조직은 잘 반응하여 치주조직의 재생이 활발히 일어남을 알 수 있었다.