• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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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.

• Clinical and Experimental Reproductive Medicine
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• v.50 no.4
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• pp.292-298
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• 2023

Objective: Ovarian torsion is a gynecological disorder that causes ischemia-reperfusion injuries in the ovary. Our study investigated berberine's short- and long-term effects on ovarian ischemia-reperfusion injuries. Methods: This study included 28 Wistar albino female rats weighing 180 to 220 g, which were divided into four groups: sham (S), torsion/detorsion (T/D), torsion/ detorsion+single dose berberine (T/D+Bb), and torsion/detorsion+15 days berberine (T/D+15Bb). The torsion and detorsion model was applied in all non-sham groups. In the T/D+Bb group, a single dose of berberine was administered, while in the T/D+15Bb group, berberine was administered over a period of 15 days. After the rats were euthanized, their ovaries were excised. The left ovaries were used for histopathologic evaluation, which included ovarian injury scoring and follicle count, while the right ovaries were used for biochemical analyses (tissue transforming growth factor-β [TGF-β] and alpha-smooth muscle actin [α-SMA] levels). Results: The histopathologic evaluation scores for the ovaries were significantly lower in the T/D+B group (p<0.05) and the T/D+15B group (p<0.005) than in the T/D group. The follicle counts in the T/D group were lower than those in both the sham and treated groups (p<0.005). The TGF-β levels were significantly lower in the T/D+15B group (p<0.005), whereas the α-SMA levels did not show a significant difference. Conclusion: Both short- and long-term berberine use could potentially have therapeutic effects on ovarian torsion. Long-term berberine use exhibited anti-inflammatory effects by reducing TGF-β levels, thereby preventing ischemia-reperfusion injuries. Therefore, we suggest that long-term berberine use could be beneficial for ovarian torsion.

• Restorative Dentistry and Endodontics
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• v.30 no.1
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• pp.1-6
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• 2005

In order to examine the immunoresponse of host cells to Enterococcus faecalis, this in vitro study monitored the production of Interleukin-2 (IL-2), Interleukin-4 (IL-4) and Transforming growth factor-$\beta1\;(TGF-\beta1)$ in human lymphocytes. Lymphocytes were activated with PHA in the presence or abscence of sonicated extracts of E. Faecalis (SEF) and further incubated for 72 hours. The level of each cytokine was measured by ELISA. Data were analyzed with Kruskal-Wallis test and Mann-Whitney U test (P < 0.05). PHA-activated group did exhibit higher level of IL-2 and IL-4 than untreated control group. The levels of expression of both cytokines were significantly decreased following the treatment of high (25 ${\mu}g/ml$) and medium concentration (12.5 ${\mu}g/ml$)) of SEF (P > 0.05) than those of PHA activated group. But low concentration (5 ${\mu}g/ml$)) of SEF showed th similar level of IL-2 and IL-4 production as those of PHA activated group. $TGF-\beta1$ was unaffected by SEF treatment. These results suggested that E. faecalis may suppress IL-2 and IL-4 production by lymphocytes and this could be one of possible factors why E. faecalis are found frequently in the teeth with failed endodontic treatment.

• Journal of Korean Ophthalmic Optics Society
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• v.13 no.4
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• pp.161-169
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• 2008

Purpose: To better understand the corneal regeneration after alkali burn regarding the initial clinical progression and the therapy, we investigated the changes of the multi factors following chemical injury in cornea. Methods: This study was performed to observation on the healing process of alkali burned cornea in aspect of immunohistochemistry by immunofluorescence or H-E staining and TUNEL assay. Results: The results showed that although a healing process occurred after alkali burn, apoptosis of epithelial, stromal and endothelial cells in the cornea was continuously observed. Neovascularization and expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) from limbus and from injured cornea, respectively, were observed after 3 days of alkali burn. Formation of collagen III in corneal stroma and increased expression of chondroitin sulfate are coincident with expression of ${\alpha}$-SMA and transforming growth factor-${\beta}$ (TGF-${\beta}$). Conclusions: These data suggest that medical treatment within 3 days of alkali burn will be effective to inhibit neovascularization and formation of collagen III and chondroitin sulfate. This study extends our immumohistochemical understanding of healing process in alkali burned cornea, and the results get in this study will be cornerstones in the development of therapeutic agent for accelerating renewal of chemical damaged cornea.

• Biomedical Science Letters
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• v.19 no.3
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• pp.195-205
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• 2013

Obesity may cause metabolic syndrome and adult diseases. This study was undertaken to investigate the ameliorative or useful effects of beanleaves on inflammation and liver damage in obese rat models. Rats were divided into three groups: a control group (normal diet, n=6), a fat diet group (45%-fat diet, n=7), and a bean leaf group (45%-fat+Korean bean leaves diet, n=7). Body weights in the bean leaf group were lower than those of the fat group (P<0.05). Serum tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and prostaglandin $E_2$ ($PGE_2$) concentrations were lower in both the control and bean leaf groups than in the fat group (P<0.001). TNF-${\alpha}$ concentrations in the bean leaf group were slightly higher than in the control group but statistically significant (P<0.05). The bean leaf group histologically exhibited lower fatty degeneration, spotty necrosis, and leukocyte infiltrations in hepatic tissues than those of the fat group. In the homogenized liver tissues, the cyclooxygenase-2 (COX-2) gene was only expressed in the fat group. The gene expression levels of hepatic TNF-${\alpha}$, inducible nitric-oxide synthase, peroxiome proliferator-activated receptor-${\alpha}$ (PPAR-${\alpha}$), poly (ADP-ribose) polymerase (PARP), and transforming growth factor-${\beta}1$ (TGF-${\beta}1$) were weaker in the bean leaf group than in the fat group. These results suggest that adding bean-leaves to the diet may ameliorate obesity-induced systemic inflammation and liver damage and that bean leaves may be a useful food for preventing obesity and thereby metabolic syndrome and adult diseases.

• Food Science of Animal Resources
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• v.32 no.3
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• pp.339-345
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• 2012

This experiment was carried out in order to separate bovine colostral whey protein from Imsil province and to test the effect of immunological activity on RAW 264.7 cells. The colostral whey protein contained TGF-${\beta}$ 7, 475 pg/g in total. We first tested the effect of the colostral whey protein on the proliferation of RAW 264.7 cells and it demonstrated cytotoxicity at concentrations greater than 20 mg/mL. Therefore, the immunological activities of colostral whey protein were investigated in maximum concentration of 10 mg/mL on LPS-induced RAW 264.7 cells. Results indicated that colostral whey protein inhibited the LPS-induced nitric oxide (NO) production in a dose-dependent manner. The colostral whey protein also suppressed the productions of proinflammatory cytokines (TNF-${\alpha}$, IL-$1{\beta}$, IL-6) in a dose-dependent manner. In addition to the immunological activity, colostral whey protein led to the expression of heme oxygenase-1 (HO-1) in RAW 264.7 cells. In conclusion, colostral whey protein containing TGF-${\beta}$ inhibited the production of NO, TNF-${\alpha}$, IL-$1{\beta}$, and IL-6 via expression of HO-1.

• Radiation Oncology Journal
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• v.18 no.4
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• pp.314-320
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• 2000

Purpose :To investigate whether changes in plasma concentrations of transforming growth factor-$\beta$1(TGF-$\beta$1), tumor necrosis factor-alpha (TNF-$\alpha$) and interleukin-6 (IL-6) could be used to identify the development of radiation-induced pneumonitis in the lung cancer patients. Methods and Materials :Seventeen patients with lung cancer (11 NSCLC, 6 SCLC) were enrolled in a prospective study designed to evaluate clinical and molecular biologic correlation of radiation-induced pneumonitis. The study began in May 1998 and completed in July 1999. All patients were treated with radiotherapy with curative intent : 1.8 Gy per day, 5 fractions per week. Serial measurements of plasma TGF-$\beta$1, TNF-$\alpha$ and IL-6 were obtained in all patients before, weekly during radiotherapy and at each follow-up visits after completion of treatment. These measurements were quantified using enzyme linked immunosorbent assay (ELISA). All patients were evaluated for signs and symptoms of pneumonitis at each follow-up visit after completion of radiotherapy. High resolution CT (HRCT) scans were obtained when signs and symptoms of pneumonitis were developed after completion of radiotherapy. Results : Thirteen patients eventually developed signs and symptoms of clinical pneumonitis 씬file four patients did not. TGF-$\beta$ 1 levels were elevated in all 13 patients with pneumonitis, which showed characteristic pattern of elevation (38.45 ng/ml at pretreatment, 13.66 ng/ml during radiotherapy, then 60.63 ng/ml at 2-4 weeks after completion of radiotherapy). The levels of TNF- $\alpha$ and IL-6 were also elevated In the group of patients who developed pneumonitis but the pattern was not characteristic. Conclusions : Changes in plasma TGF$\beta$-1 levels before, during and after radiotherapy appears to be a useful means by which to identify patients at risk for the development of symptomatic pneumonitis. Other cytokines like TNF- $\alpha$ and IL-6 shows no meaningful changes in association with radiation pneumonitis.

• Journal of Korean Neurosurgical Society
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• v.62 no.2
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• pp.153-165
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• 2019

Objective : Spinal cord injury (SCI) is a very serious health problem, usually caused by a trauma and accompanied by elevated levels of inflammation indicators. Stem cell-based therapy is promising some valuable strategies for its functional recovery. Nestin-positive progenitor and/or stem cells (SC) isolated from pancreatic islets (PI) show mesenchymal stem cell (MSC) characteristics. For this reason, we aimed to analyze the effects of rat pancreatic islet derived stem cell (rPI-SC) delivery on functional recovery, as well as the levels of inflammation factors following SCI. Methods : rPI-SCs were isolated, cultured and their MSC characteristics were determined through flow cytometry and immunofluorescence analysis. The experimental rat population was divided into three groups : 1) laminectomy & trauma, 2) laminectomy & trauma & phosphate-buffered saline (PBS), and 3) laminectomy+trauma+SCs. Green fluorescent protein (GFP) labelled rPI-SCs were transplanted into the injured rat spinal cord. Their motilities were evaluated with Basso, Beattie and Bresnahan (BBB) Score. After 4-weeks, spinal cord sections were analyzed for GFP labeled SCs and stained for vimentin, $S100{\beta}$, brain derived neurotrophic factor (BDNF), 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase), vascular endothelial growth factor (VEGF) and proinflammatory (interleukin [IL]-6, transforming growth factor $[TGF]-{\beta}$, macrophage inflammatory protein [MIP]-2, myeloperoxidase [MPO]) and anti-inflammatory (IL-1 receptor antagonis) factors. Results : rPI-SCs were revealed to display MSC characteristics and express neural and glial cell markers including BDNF, glial fibrillary acidic protein (GFAP), fibronectin, microtubule associated protein-2a,b (MAP2a,b), ${\beta}3$-tubulin and nestin as well as anti-inflammatory prostaglandin E2 receptor, EP3. The BBB scores showed significant motor recovery in group 3. GFP-labelled cells were localized on the injury site. In addition, decreased proinflammatory factor levels and increased intensity of anti-inflammatory factors were determined. Conclusion : Transplantation of PI-SCs might be an effective strategy to improve functional recovery following spinal cord trauma.

• International Journal of Industrial Entomology and Biomaterials
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• v.27 no.1
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• pp.159-165
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• 2013

Bone morphogenetic proteins (BMPs) belong to the transforming growth factor (TGF-${\beta}$) superfamily and are involved in osteoblastic differentiation. The largest TGF-${\beta}$ superfamily subgroup shares genetic homology with human BMPs (hBMPs) and silkworm decapentaplegic (dpp). In addition, hBMPs are functionally interchangeable with Drosophila dpp. Bombyx mori dpp may induce bone formation in mammalian cells. To test this hypothesis, we synthesized the 1,285-base pairs cDNA of full-length B. mori dpp using total RNAs obtained from the fat body of 3-day-old of the $5^{th}$ instar larvae and cloned the cDNA into the pCEP4 mammalian expression vector. Next, B. mori dpp was expressed in C3H10T1/2 cells. The target cells transfected with the pCEP4-Bm dpp plasmid showed biological functions similar to those of osteogenic differentiation induction growth factors such as hBMPs. We determined the relative mRNA expression rates of Runt-related transcription factor 2 (RUNX2), osterix, osteocalcin, and alkaline phosphatase (ALP) to validate the osteoblast-specific differentiation effects of B. mori dpp by performing quantitative real-time RT-PCR. Interestingly, mRNA expression levels of the 3 marker genes except RUNX2, in cells expressing B. mori dpp were much higher than those in control cells and C3H10T1/2 cells transfected with pCEP4. These results suggested that B. mori dpp signaling regulates osterix expression during osteogenic differentiation via RUNX2-independent mechanisms.

• Korean Journal of Clinical Laboratory Science
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• v.39 no.3
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• pp.210-216
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• 2007

There is increasing evidence that stromal reaction in cancer has an important diagnostic and prognostic significance. The aim of our study is to analyze the relation between the increase in mast cell number and the expression CD34 and alpha-smooth muscle actin (${\alpha}$-SMA) in the stroma of cervical intraepithelial neoplasia (CIN) and squamous cell carcinoma (SCC). We investigated a total of 29 CIN (1,2,3) and 21 SCC (microinvasive and invasive) specimens and compared the distribution of $CD34^+$ stromal cells, ${\alpha}-SMA^+$ cells, transforming growth factor-${\beta}1$ $(TGF-{\beta}1)^+$ cells, and the density of mast cells using immunohistochemistry with antibodies against CD34, ${\alpha}$-SMA, TGF-${\beta}1$, and c-Kit (CD117) respectively. Computerized image analysis was to evaluate the positive area (%) and density of the respective immunoreactive cells. In CIN $CD34^+$ cells were abundant in the stroma but no ${\alpha}-SMA^+$ cells were identified except the wall of blood vessels. $CD34^+$ cells were progressively decreased along the continuum from CIN 2 to microinvasive SCC and not observed in the stroma of invasive SCC. Whereas ${\alpha}-SMA^+$ cells were only observed in the stroma of microinvasive and invasive SCC. We found more intense TGF-${\beta}1$ expression in the increased mast cells in the stroma of invasive SCCs than that in the stroma of CIN. These results indicate that disappearance of $CD34^+$ stromal cells and appearance of ${\alpha}-SMA^+$ cells are associated with the stromal change of CIN to SCC and the transformation of $CD34^+$ stromal cells into ${\alpha}-SMA^+$ cells is mediated by TGF-${\beta}1$ secretions in the stromal mast cell of SCC.