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20(S)-ginsenoside Rg3 exerts anti-fibrotic effect after myocardial infarction by alleviation of fibroblasts proliferation and collagen deposition through TGFBR1 signaling pathways

  • Honglin Xu;Haifeng Miao;Guanghong Chen;Guoyong Zhang;Yue Hua;Yuting Wu;Tong Xu;Xin Han;Changlei Hu;Mingjie Pang;Leyi Tan;Bin Liu;Yingchun Zhou
    • Journal of Ginseng Research
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    • v.47 no.6
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    • pp.743-754
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    • 2023
  • Background: Myocardial fibrosis post-myocardial infarction (MI) can induce maladaptive cardiac remodeling as well as heart failure. Although 20(S)-ginsenoside Rg3 (Rg3) has been applied to cardiovascular diseases, its efficacy and specific molecular mechanism in myocardial fibrosis are largely unknown. Herein, we aimed to explore whether TGFBR1 signaling was involved in Rg3's anti-fibrotic effect post-MI. Methods: Left anterior descending (LAD) coronary artery ligation-induced MI mice and TGF-β1-stimulated primary cardiac fibroblasts (CFs) were adopted. Echocardiography, hematoxlin-eosin and Masson staining, Western-blot and immunohistochemistry, CCK8 and Edu were used to study the effects of Rg3 on myocardial fibrosis and TGFBR1 signaling. The combination mechanism of Rg3 and TGFBR1 was explored by surface plasmon resonance imaging (SPRi). Moreover, myocardial Tgfbr1-deficient mice and TGFBR1 adenovirus were adopted to confirm the pharmacological mechanism of Rg3. Results: In vivo experiments, Rg3 ameliorated myocardial fibrosis and hypertrophy and enhanced cardiac function. Rg3-TGFBR1 had the 1.78×10-7 M equilibrium dissociation constant based on SPRi analysis, and Rg3 inhibited the activation of TGFBR1/Smads signaling dose-dependently. Cardiac-specific Tgfbr1 knockdown abolished Rg3's protection against myocardial fibrosis post-MI. In addition, Rg3 downregulated the TGF-β1-mediated CFs growth together with collagen production in vitro through TGFBR1 signaling. Moreover, TGFBR1 adenovirus partially blocked the inhibitory effect of Rg3. Conclusion: Rg3 improves myocardial fibrosis and cardiac function through suppressing CFs proliferation along with collagen deposition by inactivation of TGFBR1 pathway.

Effects of enzymolysis and fermentation of Chinese herbal medicines on serum component, egg production, and hormone receptor expression in laying hens

  • Mei Hong Jiang;Tao Zhang;Qing Ming Wang;Jin Shan Ge;Lu Lu Sun;Meng Qi Li;Qi Yuan Miao;Yuan Zhao Zhu
    • Animal Bioscience
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    • v.37 no.1
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    • pp.95-104
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    • 2024
  • Objective: In the present study, we aimed to investigate the effects of enzymolysis fermentation of Chinese herbal medicines (CHMs) on egg production performance, egg quality, lipid metabolism, serum reproductive hormone levels, and the mRNA expression of the ovarian hormone receptor of laying hens in the late-laying stage. Methods: A total of 360 Hy-Line Brown laying hens (age, 390 days) were randomly categorized into four groups. Hens in the control (C) group were fed a basic diet devoid of CHMs, the crushed CHM (CT), fermented CHM (FC), and enzymatically fermented CHM (EFT) groups received diets containing 2% crushed CHM, 2% fermented CHM, and 2% enzymatically fermented CHM, respectively. Results: Compared with crushed CHM, the acid detergent fiber, total flavonoids, and total saponins contents of fermented CHM showed improvement (p<0.05); furthermore, the neutral and acid detergent fiber, total flavonoids, and total saponins contents of enzymatically fermented CHM improved (p<0.05). At 5 to 8 weeks, hens in the FC and EFT groups showed increased laying rates, haugh unit, albumin height, yolk color, shell thickness, and shell strength compared with those in the C group (p<0.05). Compared with the FC group, the laying rate, albumin height, and Shell thickness in the EFT group was increased (p<0.05). Compared with the C, CT, and FC groups, the EFT group showed reduced serum total cholesterol and increased serum luteinizing hormone levels and mRNA expressions of follicle stimulating hormone receptor and luteinizing hormone receptor (p<0.05). Conclusion: These results indicated that the ETF group improved the laying rate and egg quality and regulated the lipid metabolism in aged hens. The mechanism underlying this effect was likely related to cell wall degradation of CHM and increased serum levels of luteinizing hormone and mRNA expression of the ovarian hormone receptor.

Histological Validation of Cardiovascular Magnetic Resonance T1 Mapping for Assessing the Evolution of Myocardial Injury in Myocardial Infarction: An Experimental Study

  • Lu Zhang;Zhi-gang Yang;Huayan Xu;Meng-xi Yang;Rong Xu;Lin Chen;Ran Sun;Tianyu Miao;Jichun Zhao;Xiaoyue Zhou;Chuan Fu;Yingkun Guo
    • Korean Journal of Radiology
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    • v.21 no.12
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    • pp.1294-1304
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    • 2020
  • Objective: To determine whether T1 mapping could monitor the dynamic changes of injury in myocardial infarction (MI) and be histologically validated. Materials and Methods: In 22 pigs, MI was induced by ligating the left anterior descending artery and they underwent serial cardiovascular magnetic resonance examinations with modified Look-Locker inversion T1 mapping and extracellular volume (ECV) computation in acute (within 24 hours, n = 22), subacute (7 days, n = 13), and chronic (3 months, n = 7) phases of MI. Masson's trichrome staining was performed for histological ECV calculation. Myocardial native T1 and ECV were obtained by region of interest measurement in infarcted, peri-infarct, and remote myocardium. Results: Native T1 and ECV in peri-infarct myocardium differed from remote myocardium in acute (1181 ± 62 ms vs. 1113 ± 64 ms, p = 0.002; 24 ± 4% vs. 19 ± 4%, p = 0.031) and subacute phases (1264 ± 41 ms vs. 1171 ± 56 ms, p < 0.001; 27 ± 4% vs. 22 ± 2%, p = 0.009) but not in chronic phase (1157 ± 57 ms vs. 1120 ± 54 ms, p = 0.934; 23 ± 2% vs. 20 ± 1%, p = 0.109). From acute to chronic MI, infarcted native T1 peaked in subacute phase (1275 ± 63 ms vs. 1637 ± 123 ms vs. 1471 ± 98 ms, p < 0.001), while ECV progressively increased with time (35 ± 7% vs. 46 ± 6% vs. 52 ± 4%, p < 0.001). Native T1 correlated well with histological findings (R2 = 0.65 to 0.89, all p < 0.001) so did ECV (R2 = 0.73 to 0.94, all p < 0.001). Conclusion: T1 mapping allows the quantitative assessment of injury in MI and the noninvasive monitoring of tissue injury evolution, which correlates well with histological findings.

Serum Tumor Marker Levels might have Little Significance in Evaluating Neoadjuvant Treatment Response in Locally Advanced Breast Cancer

  • Wang, Yu-Jie;Huang, Xiao-Yan;Mo, Miao;Li, Jian-Wei;Jia, Xiao-Qing;Shao, Zhi-Min;Shen, Zhen-Zhou;Wu, Jiong;Liu, Guang-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.11
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    • pp.4603-4608
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    • 2015
  • Background: To determine the potential value of serum tumor markers in predicting pCR (pathological complete response) during neoadjuvant chemotherapy. Materials and Methods: We retrospectively monitored the pro-, mid-, and post-neoadjuvant treatment serum tumor marker concentrations in patients with locally advanced breast cancer (stage II-III) who accepted pre-surgical chemotherapy or chemotherapy in combination with targeted therapy at Fudan University Shanghai Cancer Center between September 2011 and January 2014 and investigated the association of serum tumor marker levels with therapeutic effect. Core needle biopsy samples were assessed using immunohistochemistry (IHC) prior to neoadjuvant treatment to determine hormone receptor, human epidermal growth factor receptor 2(HER2), and proliferation index Ki67 values. In our study, therapeutic response was evaluated by pCR, defined as the disappearance of all invasive cancer cells from excised tissue (including primary lesion and axillary lymph nodes) after completion of chemotherapy. Analysis of variance of repeated measures and receiver operating characteristic (ROC) curves were employed for statistical analysis of the data. Results: A total of 348 patients were recruited in our study after excluding patients with incomplete clinical information. Of these, 106 patients were observed to have acquired pCR status after treatment completion, accounting for approximately 30.5% of study individuals. In addition, 147patients were determined to be Her-2 positive, among whom the pCR rate was 45.6% (69 patients). General linear model analysis (repeated measures analysis of variance) showed that the concentration of cancer antigen (CA) 15-3 increased after neoadjuvant chemotherapy in both pCR and non-pCR groups, and that there were significant differences between the two groups (P=0.008). The areas under the ROC curves (AUCs) of pre-, mid-, and post-treatment CA15-3 concentrations demonstrated low-level predictive value (AUC=0.594, 0.644, 0.621, respectively). No significant differences in carcinoembryonic antigen (CEA) or CA12-5 serum levels were observed between the pCR and non-pCR groups (P=0.196 and 0.693, respectively). No efficient AUC of CEA or CA12-5 concentrations were observed to predict patient response toward neoadjuvant treatment (both less than 0.7), nor were differences between the two groups observed at different time points. We then analyzed the Her-2 positive subset of our cohort. Significant differences in CEA concentrations were identified between the pCR and non-pCR groups (P=0.039), but not in CA15-3 or CA12-5 levels (p=0.092 and 0.89, respectively). None of the ROC curves showed underlying prognostic value, as the AUCs of these three markers were less than 0.7. The ROC-AUCs for the CA12-5 concentrations of inter-and post-neoadjuvant chemotherapy in the estrogen receptor negative HER2 positive subgroup were 0.735 and 0.767, respectively. However, the specificity and sensitivity values were at odds with each other which meant that improving either the sensitivity or specificity would impair the efficiency of the other. Conclusions: Serum tumor markers CA15-3, CA12-5, and CEA might have little clinical significance in predicting neoadjuvant treatment response in locally advanced breast cancer.

Review of Production, Husbandry and Sustainability of Free-range Pig Production Systems

  • Miao, Z.H.;Glatz, P.C.;Ru, Y.J.
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.11
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    • pp.1615-1634
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    • 2004
  • A review was undertaken to obtain information on the sustainability of pig free-range production systems including the management, performance and health of pigs in the system. Modern outdoor rearing systems requires simple portable and flexible housing with low cost fencing. Local pig breeds and outdoor-adapted breeds for certain environment are generally more suitable for free-range systems. Free-range farms should be located in a low rainfall area and paddocks should be relatively flat, with light topsoil overlying free-draining subsoil with the absence of sharp stones that can cause foot damage. Huts or shelters are crucial for protecting pigs from direct sun burn and heat stress, especially when shade from trees and other facilities is not available. Pigs commonly graze on strip pastures and are rotated between paddocks. The zones of thermal comfort for the sow and piglet differ markedly; between 12-22$^{\circ}C$ for the sow and 30-37$^{\circ}C$ for piglets. Offering wallows for free-range pigs meets their behavioural requirements, and also overcomes the effects of high ambient temperatures on feed intake. Pigs can increase their evaporative heat loss via an increase in the proportion of wet skin by using a wallow, or through water drips and spray. Mud from wallows can also coat the skin of pigs, preventing sunburn. Under grazing conditions, it is difficult to control the fibre intake of pigs although a high energy, low fibre diet can be used. In some countries outdoor sows are fitted with nose rings to prevent them from uprooting the grass. This reduces nutrient leaching of the land due to less rooting. In general, free-range pigs have a higher mortality compared to intensively housed pigs. Many factors can contribute to the death of the piglet including crushing, disease, heat stress and poor nutrition. With successful management, free-range pigs can have similar production to door pigs, although the growth rate of the litters is affected by season. Piglets grow quicker indoors during the cold season compared to outdoor systems. Pigs reared outdoors show calmer behaviour. Aggressive interactions during feeding are lower compared to indoor pigs while outdoor sows are more active than indoor sows. Outdoor pigs have a higher parasite burden, which increases the nutrient requirement for maintenance and reduces their feed utilization efficiency. Parasite infections in free-range pigs also risks the image of free-range pork as a clean and safe product. Diseases can be controlled to a certain degree by grazing management. Frequent rotation is required although most farmers are keeping their pigs for a longer period before rotating. The concept of using pasture species to minimise nematode infections in grazing pigs looks promising. Plants that can be grown locally and used as part of the normal feeding regime are most likely to be acceptable to farmers, particularly organic farmers. However, one of the key concerns from the public for free-range pig production system is the impact on the environment. In the past, the pigs were held in the same paddock at a high stocking rate, which resulted in damage to the vegetation, nutrient loading in the soil, nitrate leaching and gas emission. To avoid this, outdoor pigs should be integrated in the cropping pasture system, the stock should be mobile and stocking rate related to the amount of feed given to the animals.

Clinical Implications of p57KIP2 Expression in Breast Cancer

  • Xu, Xiao-Yin;Wang, Wen-Qian;Zhang, Lei;Li, Yi-Ming;Tang, Miao;Jiang, Nan;Cai, Shou-Liang;Wei, Liang;Jin, Feng;Chen, Bo
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5033-5036
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    • 2012
  • Objective: To study the relationship between expression of $p57^{KIP2}$ and prognosis and other clinicopathological parameters in invasive breast cancers. Methods: We assessed the expression of $p57^{KIP2}$ in 89 cases of invasive breast cancer and 20 cases of normal breast tissue by immunohistochemical methods and analyzed the results with SPSS software (ver. 16.0). Result: The positive expression rates of $p57^{KIP2}$ protein in the invasive breast cancers and surrounding normal tissue were 30.3% (27/89) and 65% (13/20), respectively. Cases with no $p57^{KIP2}$ expression exhibited a significantly higher post-operative distant metastasis rate than those with $p57^{KIP2}$ expression (37.9% vs. 14.8%; P = 0.01). DFS analysis showed that $p57^{KIP2}$-/C-erbB-2+ tumors also exhibited a significantly higher post-operative distant metastasis rate than the other groups (66.7% vs. 29.2%; P = 0.007), as did $p57^{KIP2}$-/p53+ tumors (64.3% vs. 22.7%; P = 0.001). Survival analysis revealed that $p57^{KIP2}$ was associated with breast cancer-specific survival overall (P = 0.045, log-rank test). Subgroup analysis demonstrated that individuals with $p57^{KIP2}$-/C-erbB-2+tumors experienced significantly worse post-operative survival than those with $p57^{KIP2}$-/C-erbB-2- or other tumors (P = 0.006, log-rank test). $p57^{KIP2}$-/p53+ tumors were associated with significantly worse post-operative survival than $p57^{KIP2}$-/p53- or other tumors (P = 0.001, log-rank test). Cox regression analysis showed that $p57^{KIP2}$ was a non-independent prognostic factor for breast cancer (P = 0.303). Conclusions: $p57^{KIP2}$ is expressed at low levels in invasive breast cancer and is associated with better overall survival rate and disease-free survival in breast cancer patients, but it was a non-independent prognostic factor for breast cancer. Thus, the connection between $p57^{KIP2}$/p53 and $p57^{KIP2}$/C-erbB-2 may provide biomarkers for breast cancer.

The Effect of Spiritual Well-being on the Mental Health of the Cho-Sun Tribal Women Residing in P.R. of China (중국거주 조선족 여성의 영적 안녕정도가 정신건강에 미치는 영향)

  • Cheung, Seung-Deuk;Lee, Jong-Bum;Kim, Jin-Sung;Seo, Wan-Seok;Bai, Dai-Seg;Park, Soon-Jae;Joo, Yeol;Youm, Hyoung-Uk;Jin, Cheung-Yuan;Jin, Jiu-Miao;Ahn, Yeung-Log;Huang, Da-Hong;Biao, Mei-Zi;Zheng, Tai-Ji;Zhao, Chang-Lie
    • Journal of Yeungnam Medical Science
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    • v.21 no.2
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    • pp.151-166
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    • 2004
  • Background: Spirituality has been an important part of Transpersonal Psychology and is believed to have a large effect on the mental health because it has been systematized. The aim of this study was to determine the level of spiritual disposition on human beings along with its effects on one's mental health. Materials and Methods: The study targeted 400 women residing in Youn-Gil city of JiLin Prov., which is a district of the Cho-Sun tribe in China. Their spiritual well-being was studied using the Spiritual Well-being Scale-Korean Version. The spiritual well-being scale consists of 2 sub-scales of religious well-being and existential well-being. The study was evaluated using a lie scale, psychotic trend, and a combined anxiety-depression scale. The results were considered to be factors of one's mental health. The correlation between the spiritual well-being and each tendency was analyzed by regression analysis. Results: The total score of the Cho-Sun tribal women according to the spiritual well-being scale was 68.29 which was much less than the 100.65 of Korean Christian women. There was no significant correlation between the spiritual well-being and the Lie trend. However, it was found that 86%(344) of Cho-Sun tribal women scored above 70 in the Lie trend with a mean score of 74.57 which is higher than normal populations. Regarding the correlation between the spiritual well-being and psychotic trend, the psychotic trend became significantly higher when the religious well-being was at a high level. On the other hand, the psychotic trend became significantly lower when the existential well-being was at a high level. Regarding the correlation between the spiritual well-being and anxiety, the anxiety was significantly higher when the religious well-being was at a high level. However, the anxiety level was significantly low when the existential well-being was at a high level. Regarding the correlation between the spiritual well-being and depression, the depression level was somewhat significantly high when the religious well-being was at a high level. However, the depression level was significantly low when the existential well-being was at a high level. Conclusion: This study evaluated the effects of spiritual well-being on a person's mental health among Cho-Sun tribal women in Youn-Gil city of JiLIn Prov., P.R. of China. The results found that the religious well-being, which is a sub-scale of spiritual well-being, had negative effects while the existential well-being had positive effects on the mental health. These results proved that a person's religious disposition had negative effects on their mental health in a communitarian society.

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