• Korean Journal of Acupuncture
• /
• 제25권3호
• /
• pp.147-166
• /
• 2008

Objectives : Crohn's disease (CD) is characterized by a chronic relapsing inflammation of the bowel in which proinflammatory cytokines play an important perpetuating role. Methods : Mice (preventive animal model of gliotoxin) were treated with 5 % 2,4,6-trinitrobenzenesulfonic acid (TNBS) at day 1 and day 7. To investigate preventive effects of acupuncture with Gujin at $LI_{11}$, acupuncture was carried out at day -1, day 1, day 3. And, to investigate therapeutic effects, acupuncture with Gujin was carried out at day 3, day 5, day 7. For the data analysis, we checked weight and width of colon, diarrhea, edema, survival rate, changes of body weight, and myeloperoxygenase (MPO) activity. For analysing protein expression, we carried out immunohistochemical staining and Western blot and we analyzed mRNA expression by RT-PCR. Results : Colon of TNBS treated mice was erosive and shortening compared with the colon of control mice and induced damages of colon epithelial cell layer and induced infiltration of immune cells in all layer of colon. Acupuncture of gujin at $LI_{11}$ in preventive mode suppressed macorscopic damages such as erosive and shortening of colon by TNBS and damages of intestinal epithelial cells and infiltration of immune cells in the colon. The average weight of 5 cm distal colon was increased in TNBS treated mice (758${\mu}g$) compared with in control mice (112${\mu}g$) and width of distal colon was also increased in TNBS treated mice (4.9mm) compared with in control mice (1.3mm). Acupuncture with Gujin at $LI_{11}$ in preventive and therapeutic mode suppressed increase of colon weight and width by TNBS. TNBS induced edema of colon and diarrhea and Acupunctured with Gujin at $LI_{11}$ in preventive and therapeutic mode ameliorated these symptom by TNBS. In preventive and therapeutic mode, the effects of acupuncture with Gujin at $LI_{11}$ were increasing the motility, suppressing body weight decreasing, suppressing MPO activity, reducing expressing of TNF-${\alpha}$, IL-1b, and ICAM-1 in colon compared with that by TNBS Conclusions : This study demonstrates that acupuncture with Gujin at $LI_{11}$ represents a potential therapeutic method of Crohn's disease.

• 한국약용작물학회지
• /
• 제28권4호
• /
• pp.276-286
• /
• 2020

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease associated with multiple metabolic disorders. The medicinal plant Curcuma longa L. is widely distributed in Asia and has been used to treat a spectrum diseases in clinical practice. To date, there are inadequate reports of the effects of C. longa 50% EtOH extract (CE) on NAFLD. Therefore, in this study, we evaluate the CE on an NAFLD animal and elucidate the mechanism of action. Methods and Results: C57BL/6J mice fed a methionine-choline deficient diet (MCD) were treated with CE or milk thistle, and changes in inflammation and stetosis were assessed. Experimental animals were divided into six group (n = 10); Normal, MCD, MCD + CE 50 mg/kg/day (CE 50), MCD + CE 100 mg/kg/day (CE 100), MCD + CE 150 mg/kg/day (CE 150), and the Control, MCD + Milk thistle 150 mg/kg/day (MT 150). Body weight, liver weight, liver function, and histological changes were assessed in experimental animals. Quantitative real-time polymerase chain reaction and western blot analyses were performed on samples collected after 4 weeks of treatment. We observed that CE administration improved MCD-diet-induced lipid accumulation, and triglyceride (TG) and total cholesterol (TC) levels in serum. Treatment with CE also decreased hepatic lipogenesis through modulation of the sterol regulatory element binding protein-1 (SREBP-1), CCAAT-enhancer binding protein α (C/EBPα), fatty acid synthase (FAS), and peroxisome proliferator-activated receptor γ (PPARγ) expresion. In addition, the use of CE increased adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and inhibited the up-regulation of toll-like receptor (TLR)-2 and TLR-4 signaling and the production of inflammatory mediators. Conclusions: In this report, we observed that CE regulated lipid accumulation in an MCD dietinduced NAFLD model by decreasing lipogenesis. These data suggeste that CE could effectively protect mice against MCD-induced NAFLD, by inhibiting the TLR-2 and TLR-4 signaling cascades.

• Biomolecules & Therapeutics
• /
• 제31권3호
• /
• pp.350-358
• /
• 2023

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

• 한국발생생물학회지:발생과생식
• /
• 제14권3호
• /
• pp.199-205
• /
• 2010

A neurotoxin, 6-hydroxydopamine (6-OHDA) has been widely used to create animal model for Parkinson's disease (PD). The present study was undertaken to examine whether depletion of brain dopamine (DA) stores with 6-OHDA can make alteration in the activities of the testicular steroidogenesis in adult rats. Young adult male rats (3 months old) were received a single dose of 6-OHDA (200 ${\mu}g$ in 10 ${\mu}{\ell}$/animal) by intracerebroventricular (icv) injection, and sacrificed after two weeks. The mRNA levels of steroidogenesis-related enzymes were measured by qRT-PCRs. Serum testosterone levels were measured by radioimmunoassay. Single icv infusion of 6-OHDA significantly decreased the mRNA levels of CYP11A1 (control:6-OHDA group=$1:0.68{\pm}0.14$ AU, p<0.05), CYP17 (control:6-OHDA group=$1:0.72{\pm}0.13$ AU, p<0.05). There were no changes in the mRNA levels of $3{\beta}$-HSD (control:6-OHDA group=$1:0.84{\pm}0.08$ AU) and $17{\beta}$-HSD (control: 6-OHDA group=$1:0.63{\pm}0.20$ AU), though the levels tended to be decreased in the 6-OHDA treated group. Administration of 6-OHDA decreased significantly the mRNA level of StAR when compared to the level of saline-injected control animals (control:6-OHDA group=$1:0.72{\pm}0.08$ AU, p<0.05). Treatment with single dose of 6-OHDA remarkably lowered serum testosterone levels compared to the levels of control group (control:6-OHDA group=$0.72{\pm}0.24:0.13{\pm}0.03ng/m{\ell}$, p<0.05). Taken together with our previous study, the present study demonstrated that the activities of hypothalamus-pituitary-testis hormonal axis could be negatively affected by blockade of brain DA biosynthesis, and suggested the reduced reproductive potential might be resulted in the animals. More precise information on the testicular steroidogenic activities in PD patients and PD-like animals should be required prior to the generalization of the sex steroid hormone therapy to meet the highest standards for safety and efficacy.

• BMB Reports
• /
• 제48권3호
• /
• pp.153-158
• /
• 2015

As FK506 binding proteins (FK506BPs) are known to play an important role in the regulation of a variety of biological processes related to cell survival, this study was designed to examined the protective effects of FK506 binding protein 12 (FK506BP) on low humidity air flow induced dry eye in a rat model using transduced PEP-1-FK506BP. After the topical application of PEP-1-FK506BP, tear volumes were markedly increased and significant prevention of cornea damage was observed compared with dry eye rats. Further, immunohistochemical analysis demonstrated that PEP-1-FK506BP markedly prevented damage to the cornea, the bulbar conjunctiva, and the palpebral conjunctiva epithelial lining compared with dry eye rats. In addition, caspase-3 and PARP expression levels were found to be decreased. These results demonstrated that topical application of PEP-1-FK506BP significantly ameliorates dry eye injury in an animal model. Thus, we suggest that PEP-1-FK506BP can be developed as a new ophthalmic drop to treat dry eye diseases.

• Toxicological Research
• /
• 제34권1호
• /
• pp.7-12
• /
• 2018

Laboratory animal models have been developed to investigate preventive or therapeutic effect of medicinal products, or occurrence or progression mechanism of atopic dermatitis (AD), a pruritic and persistent inflammatory skin disease. The murine model with immunologic phenomena resembling human AD was introduced, which demonstrated skewedness toward predominance of type-2 helper T cell reactivity and pathophysiological changes similar as human AD following 2,4-dinitrochlorobenzene (DNCB) sensitization and challenge. Molecular mechanism on the DNCB-mediated AD was further evaluated. Skin tissues were collected from mice treated with DNCB, and each tissue was equally divided into two sections; one for protein and the other for mRNA analysis. Expression of filaggrin, an important protein for keratinocyte integrity, was evaluated through SDS-PAGE. Level of mRNA expression for cytokines was determined through semi-quantitative reverse transcriptase polymerase chain reaction. Expression of filaggrin protein was significantly enhanced in the mice treated with DNCB compared with the vehicle (acetone : olive oil = 4 : 1 mixture) treatment group or the normal group without any treatment. Level of tumor necrosis factor-alpha and interleukin-18 mRNA expression, cytokines involved in activity of type-1 helper T ($T_H1$) cell, was significantly downregulated in the AD group compared with other control groups. These results suggest that suppression of $T_H1$ cell-mediated immune response could be reflected into the skin tissue of mice treated with DNCB for AD induction, and disturbance of keratinocyte integrity might evoke a compensatory mechanism.

• 대한수의학회지
• /
• 제50권4호
• /
• pp.311-317
• /
• 2010

Recently the micropig has been developed as human disease model. The dental and orofacial region of micropig is similar to that of humans, so it has been used for testing implant materials and techniques. The purpose of this study is on dental image at each age using radiography and computed tomography. Total twenty-two male micropigs, two or three animals of each 1, 3, 5, 7, 9, 12, 18 and 24 months old, were given radiographic examinations. After general anesthesia, extra- and intra-oral radiographic technique and computed tomographic scans were performed to assess the dental characterization of micropigs. The total deciduous dental formula comprised 28 teeth and was depicted as Di 3/3, Dc 1/1, Dp 3/3. The total permanent dental formula comprised 44 teeth and was depicted as I 3/3, C 1/1, P 4/4, M 3/3. Hypodontia of the first premolars was common in the micropig. The permanent teeth erupted from 3 to 24 month after birth. The sequence of eruption of the permanent teeth was M1, P1, I3, C, M2, I1 + P3 + P4, P2, I2, M3. Dental imaging enables visualization of the unerupted teeth and gives more information about the development of the teeth. The growth pattern of the teeth obtained through radiographic and computed tomographic examination provides basic data in the micropig as animal model for dental research.

• Toxicological Research
• /
• 제27권3호
• /
• pp.173-180
• /
• 2011

Atopic dermatitis (AD) is a chronic, recurrent inflammatory skin disease that is associated with Th2 cell-mediated allergy. The process that leads to infiltration of inflammatory cells into an AD lesion is remarkably dependent on various chemokines, especially TARC (thymus and activation-regulated chemokine/CCL17) and MDC (macrophage-derived chemokine/CCL22). Serum levels of these chemokines are over-expressed in AD patients. Citrus unshiu, which is known as Satsuma mandarin, has anti-oxidative, anti-inflammation, and anti-microviral activity. Therefore, we investigated the effect of EtOH extract of premature C. unshiu on AD. We did this using a DNCB-induced AD mouse model. We also tried to confirm an inhibitory effect for premature C. unshiu on the expression of inflammatory chemokines in IFN-${\gamma}$ and TNF-${\alpha}$ stimulated HaCaT human keratinocytes. We found that extract of premature C. unshiu reduced DNCB-induced symptoms such as hyperkeratosis, increased skin thickness, and infiltrated mast cells, in our AD-like animal model. The extract decreased levels of IFN-${\gamma}$ and IL-4 in ConA-stimulated splenocytes isolated from DNCB-treated mice. Also, extract of premature C. unshiu inhibited mRNA expression and protein production of TARC and MDC through the inhibition of STAT1 phosphorylation. These results suggest that C. unshiu has anti-atopic activity by regulating inflammatory chemokines such as TARC and MDC.

• 한국미생물·생명공학회지
• /
• 제45권2호
• /
• pp.93-100
• /
• 2017

인간노로바이러스는 바이러스성 식중독 원인의 대부분을 차지한다. 노로바이러스가 건강한 성인에 감염하면 설사 등의 병변을 몇 일간 일으키다 대부분 별다른 처치 없이도 치유되는 경우가 대부분이다. 그러나 면역기능이 약화된 환자에게 감염한 경우, 만성감염 내지 치명적 감염도 가능한 것으로 보고 되고 있다. 1968년에 처음 노로바이러스가 보고된 이후 세포 감염모델과 소동물감염 모델을 만들고자 하는 시도가 이어져 왔으나 대부분 실패하였다. 그러나 최근들어 세포감염 모델 개발에 있어 주목할 만한 기념비적인 연구들이 이루어졌다 것이 고무적이다 할 수 있다. 이번 총설에서는 새로 개발된 감염 모델들의 특징과 장단점을 살펴보고, 이를 더욱 개선할 수 있는 방향에 대하여 살펴보고자 한다.

• Journal of Korean Neurosurgical Society
• /
• 제49권2호
• /
• pp.83-91
• /
• 2011

Objective : Minocycline, a second-generation tetracycline-class antibiotic, has been well established to exert a neuroprotective effect in animal models and neurodegenerative disease through the inhibition of microglia. Here, we investigated the effects of minocycline on motor recovery and neuropathic pain in a rat model of spinal cord injury. Methods : To simulate spinal cord injury, the rats' spinal cords were hemisected at the 10th thoracic level (T10). Minocycline was injected intraperitoneally, and was administered 30 minutes prior surgery and every second postoperative day until sacrifice 28 days after surgery. Motor recovery was assessed via the Basso-Beattie-Bresnahan test Mechanical hyperalgesia was measured throughout the 28-day post -operative course via the von Frey test Microglial and astrocyte activation was assessed by immunohistochemical staining for ionized calcium binding adaptor molecule 1 (lba1) and glial fibrillary acidic protein (GFAP) at two sites: at the level of hemisection and at the 5th lumbar level (L5). Results : In rats, spinal cord hemisection reduced locomotor function and induced a mechanical hyperalgesia of the ipsilateral hind limb. The expression of lba1 and GFAP was also increased in the dorsal and ventral horns of the spinal cord at the site of hemisection and at the L5 level. Intraperitoneal injection of minocycline facilitated overall motor recovery and attenuated mechanical hyperalgesia. The expression of lba1 and GFAP in the spinal cord was also reduced in rats treated with minocycline. Conclusion : By inhibiting microglia and astrocyte activation, minocycline may facilitate motor recovery and attenuate mechanical hyperalgesia in individuals with spinal cord injuries.