A Prediction Model for Osteoporosis Risk Using a Machine-Learning Approach and Its Validation in a Large Cohort

Wu Xuangao,Park Sunmin 대한의학회 2023 Journal of Korean medical science Vol.38 No.21

Background: Osteoporosis develops in the elderly due to decreased bone mineral density (BMD), potentially increasing bone fracture risk. However, the BMD is not regularly measured in a clinical setting. This study aimed to develop a good prediction model for the osteoporosis risk using a machine learning (ML) approach in adults over 40 years in the Ansan/Anseong cohort and the association of predicted osteoporosis risk with a fracture in the Health Examinees (HEXA) cohort. Methods: The 109 demographic, anthropometric, biochemical, genetic, nutrient, and lifestyle variables of 8,842 participants were manually selected in an Ansan/Anseong cohort and included in the ML algorithm. The polygenic risk score (PRS) of osteoporosis was generated with a genome-wide association study and added for the genetic impact of osteoporosis. Osteoporosis was defined with < −2.5 T scores of the tibia or radius compared to people in their 20s–30s. They were divided randomly into the training (n = 7,074) and test (n = 1,768) sets—Pearson’s correlation between the predicted osteoporosis risk and fracture in the HEXA cohort. Results: XGBoost, deep neural network, and random forest generated the prediction model with a high area under the curve (AUC, 0.86) of the receiver operating characteristic (ROC) with 10, 15, and 20 features; the prediction model by XGBoost had the highest AUC of ROC, high accuracy and k-fold values (> 0.85) in 15 features among seven ML approaches. The model included the genetic factor, genders, number of children and breastfed children, age, residence area, education, seasons to measure, height, smoking status, hormone replacement therapy, serum albumin, hip circumferences, vitamin B6 intake, and body weight. The prediction models for women alone were similar to those for both genders, with lower accuracy. When the prediction model was applied to the HEXA study, the correlation between the fracture incidence and predicted osteoporosis risk was significant but weak (r = 0.173, P < 0.001). Conclusion: The prediction model for osteoporosis risk generated by XGBoost can be applied to estimate osteoporosis risk. The biomarkers can be considered for enhancing the prevention, detection, and early therapy of osteoporosis risk in Asians.

A mixture of blackberry leaf and fruit extracts decreases fat deposition in HepG2 cells, modifying the gut microbiome

Xuangao Wu,진보람,양혜정,김민정,박선민 한국응용생명화학회 2019 Journal of Applied Biological Chemistry (J. Appl. Vol.62 No.3

More effective treatments are needed for non-alcoholic fatty liver disease (NAFLD). We hypothesized that water extracts of blackberry fruits (BF) and leaves (BL) and their combinations (BFL) reduce fat deposition in HepG2 cells and modulate shortchain fatty acids (SCFA) and fecal bacteria in vitro. HepG2 cells were treated with BF, BL, BFL1:2, and BFL1:3 for 1 h, and 0.5 mM palmitate was added to the cells. Moreover, low (30 μg/mL) and high doses (90 μg/mL) of BL and BF were applied to fecal bacteria in vitro, and SCFA was measured by GC. BL, BF, BFL1:2, and BFL1:3 reduced triglyceride deposition in the cells in a dose-dependent manner, and BFL1:2 and BFL1:3 had a stronger effect than BF. The content of malondialdehyde, an index of oxidative stress, was also reduced in BL, BF, and BFL1:2 with increasing superoxide dismutase and glutathione peroxidase activities. The mRNA expression of acetyl CoA carboxylase, fatty acid synthase, and sterol regulatory element-binding protein-1c was reduced in BL, BF, BFL1:2, and BFL1:3 compared to the control, and BFL1:2 had the strongest effect. By contrast, the carnitine palmitolytransferase-1expression, a regulator of fatty acid oxidation, increased mostly in BFL1:2 and BFL1:3. Tumor necrosis factor-α and interleukin-1β expression was reduced in BL compared to that in BF and BFL1:2 in HepG2 cells. Interestingly, BL increased propionate production, and BF increased butyrate and propionate production and increased total SCFA content in fecal incubation. BF increased the contents of Bifidobacteriales and Lactobacillales and decreased those of Clostridiales, whereas BL elevated the contents of Bacteroidales and decreased those of Enterobacteriales. In conclusion, BFL1:2 and BFL1:3 may be potential therapeutic candidates for NAFLD.

Efficacy of the Oriental herbal medicine, Jie Yu Dan, for alleviating post-stroke aphasia: A Systematic Review and meta-analysis of randomized clinical trials

Zhang, Ting,Wu, Xuangao,Cao, Shihua,Park, Sunmin Elsevier 2018 European journal of integrative medicine Vol.24 No.-

<P><B>Abstract</B></P> <P><B>Introduction</B></P> <P>Jie Yu Dan(JYD), a traditional Chinese medicine, is used to promote circulation and has been used for people experiencing speech and language difficulties with post-stroke aphasia. The objectives of this study were to systematically evaluate randomized clinical trials (RCTs) to assess the efficacy of JYD for improving post-stroke aphasia.</P> <P><B>Methods</B></P> <P>All RCTs that studied JYD treatment in post-stroke aphasia were selected from English, Korean and Chinese language databases until February 2018. Studies of participants with post-stroke aphasia were divided into 2 groups that had common treatments with JYD and placebo or Western medicine, respectively. Risk ratio and mean differences with 95% confidence intervals (CI) were calculated for the pooled RCTs with a fixed or random model in the meta-analysis. Since the RCTs had some heterogeneity in JYD prescriptions, duration of the therapy and the control group, some subgroup analysis was conducted. Risk of bias and publication bias was assessed for all included RCTs.</P> <P><B>Results</B></P> <P>The JYD with conventional therapy (n = 439) additionally improved the overall efficacy of post-stroke aphasia by 1.34 fold in comparison to the conventional therapy (n = 370) in the fixed effect model including 10 RCTs(P < 0.00001). JYD plus conventional therapy (n = 374) was more effective for improving aphasia by 4.88 fold (95% CI = 2.87–6.78) than the conventional therapy (n = 307) as a control group in pooling 8 RCTs(P < 0.00001). There were no differences in JYD efficacy according to treatment duration and original and modified JYD treatments in subgroup analysis. No adverse effects were observed in any of the studies. All 10 studies used an appropriate method for randomization of the subjects but about 25% did not include allocation concealment and blinding of patients and practitioners. The 10 studies included had low to moderate risk of bias. There was no significant publication bias in the meta-analysis.</P> <P><B>Conclusions</B></P> <P>JYD might improve the efficacy of conventional therapy and/or acupuncture for treating post-stroke aphasia considering the quality of RCTs included. However, larger and highly controlled RCTs are needed to confirm the results.</P>

Mulberry and dandelion water extracts prevent alcohol-induced steatosis with alleviating gut microbiome dysbiosis

Park, Sunmin,Kim, Da S,Wu, Xuangao,J Yi, Qiu SAGE Publications 2018 Experimental biology and medicine Vol.243 No.11

<P> Chronic alcohol intake causes hepatic steatosis and changes the body composition and glucose metabolism. We examined whether water extracts of mulberry (WMB) and white flower dandelion ( Taraxacum coreanum Nakai, WTC) can prevent and/or delay the symptoms of chronic ethanol-induced hepatic steatosis in male Sprague Dawley rats, and explored the mechanisms. Ethanol degradation was examined by orally administering 3 g ethanol/kg bw after giving them 0.3 g/kg bw WMB or WTC. All rats were continuously provided about 7 g ethanol/kg bw/day for four weeks and were given either of 0.1% dextrin (control), WMB, WTC, or water extracts of Hovenia dulcis Thunb fruit (positive-control) in high-fat diets. Area under the curve of serum ethanol levels was lowered in descending order of control, WTC and positive-control, and WMB in acute ethanol challenge. WMB and WTC prevented alcohol intake-related decrease in bone mineral density and lean body mass compared to the control. After glucose challenge, serum glucose levels increased more in the control group than other groups in the first part and the rate of decrease after 40 min was similar among all groups. These changes were associated with decreasing serum insulin levels. WMB had the greatest efficacy for decreasing triglyceride and increasing glycogen deposits. WMB and WTC prevented the disruption of the hepatic cells and nuclei while reducing malondialdehyde contents in rats fed alcohol, but the prevention was not as much as the normal-control. The ratio of Firmicutes to Bacteroidetes in the gut was much higher in the control than the normal-control, but WTC and WMB decreased the ratio compared to the control. WMB and WTC separated the gut microbiota community from the control. In conclusion, WMB and WTC protected against alcoholic liver steatosis by accelerating ethanol degradation and also improved body composition and glucose metabolism while alleviating the dysbiosis of gut microbiome by chronic alcohol intake. </P><B>Impact statement</B><P> Excessive alcohol consumption is associated with serious pathologies and is common in much of the world. Pathologies include liver damage, glucose intolerance, and loss of lean body mass and bone mass. These pathologies are mediated by changes in metabolism as well as toxic metabolic byproducts, and possibly by gut dysbiosis. In this study, we demonstrate that aqueous extracts of mulberry and dandelion protected rats against ethanol-induced losses in lean body and bone masses, improved glucose tolerance and partially normalized gut bacterial populations, with mulberry extract being generally more effective. This research suggests that mulberry and dandelion extracts may have the potential to improve some of the pathologies associated with excess alcohol consumption, and that further clinical research is warranted. </P>

Ojayeonjonghwan, an oriental medicine composed of five seeds, protects against vasomotor and neurological disorders in estrogen-deficient rats

Ko, Byoung-Seob,Ryuk, Jin Ah,Hwang, Joo Tae,Zhang, Ting,Wu, Xuangao,Park, Sunmin SAGE Publications 2019 Experimental biology and medicine Vol.244 No.3

<P> The different ojayeonjonghwan remedies all contain five fruit and seed water extracts, and they have been used for reproductive health in men and women. We hypothesized that the two OJa remedies would differently improve the early menopause-related vasomotor and neurological symptoms in estrogen-deficient animals. Ovariectomized (OVX) rats had either 0.5% dextrin (OVX-control), conjugated equine estrogen (150 μg/kg body weight; positive-control), 0.5% ojayeonjonghwan remedy-1 (OJa1), or 0.5% ojayeonjonghwan remedy-2(OJa2) in high-fat diet for 12 weeks. Normal-control rats (sham operation) were fed the same high-fat diet as OVX-control rats. Tail skin temperature, depressiveness, memory function, and body composition were determined. The mRNA expressions of hippocampal serotonin receptor (5HT)1A and 5HT2A and brain-derived neurotrophic factor(BDNF) were measured. OJa1 and OJa2 groups had lower tail skin temperatures than OVX-control. Bone mineral density (BMD) and lean body mass (LBM) measured by DEXA increased only in OJa2, and were similar to the positive- and normal-controls ( P < 0.05). In the forced swim test immobile time, an index of depressiveness was much lower in OJa1 and OJa2 than the control group. Memory as measured by passive avoidance, water maze, and Y maze tests was impaired in the OVX-control group, compared to the normal-control ( P < 0.05), but normalized in OJa1 comparable to the positive- and normal-control groups. The neurological impairments were associated with serum serotonin levels and 5HT2A mRNA expression in the midbrain, and decreased hippocampal BDNF mRNA and protein expressions in the OVX-control group compared to normal-controls ( P < 0.05). OJa1 increased serum serotonin levels and 5HT2A expression in the midbrain, and hippocampal BDNF expression to similar levels as normal-controls ( P < 0.05). In conclusion, OJa1 and OJa2 improved hot flashes and depression and maintained BMD and LBM. OJa2 prevented the impairment of memory function in OVX rats. OJa1 and OJa2 have the potential to be effective therapies for postmenopausal vasomotor and neurological symptoms. </P><B>Impact statement</B><P> Menopausal symptoms impair the quality of life of many women, and although conventional treatments are often effective, their use is limited by adverse effects. Ojayeonjonghwan, OJa, is a traditional Oriental medicine that is used for both male and female reproductive health and has a long history of safe use. We evaluated the effectiveness of two variations of OJa (OJa1 and OJa2) for treating menopausal symptoms in ovariectomized (OVX) rats. Both OJa preparations were effective for relieving indicators of hot flashes and depression, and for preventing loss of bone mineral density and lean body mass. Only OJa 2 prevented memory dysfunction. These results show that the traditional Oriental medicine, Ojayeonjonghwan, has the potential to relieve menopausal symptoms in women and should be further evaluated in human clinical trials as an alternative to convention therapies in women for whom conventional therapies are not indicated or found to be ineffective. </P>

김치와 식초 유래 젖산균으로 발효시킨 오디와 실크 단백질을 첨가한 발효유의 물리 화학적 특성 연구

정성엽 ( Seong-yeop Jeong ),강선아 ( Suna Kang ),김민주 ( Min Joo Kim ),강은선 ( Eun Seon Kang ),오현호 ( Xuangao Wu ),이나라 ( Na Ra Lee ),박선민 ( Sunmin Park ) 한국응용생명화학회(구 한국농화학회) 2018 Journal of Applied Biological Chemistry (J. Appl. Vol.61 No.1

본 실험에서는 오디와 실크 단백질을 첨가하고 식물성 젖산균인 Lactobacillus plantarum와 Bacillus acidiproducens로 발효시킨 기능성 발효유를 제조하고 이들의 발효유의 물리화학적 품질을 조사하고자 한다. 제조한 발효유의 물리화학적 특성과 품질은 발효유의 총 페놀 함량 및 안토시아닌 함량, 점도, 색도값을 측정하고 기호도를 조사하여 결정하였다. LP와 BA로 제조한 발효유는 대조균주인 YF과 유사한 pH와 산도를 나타내었으나, 오디와 실크 단백질을 첨가한 발효유는 유의적으로 낮은 pH값와 높은 산도를 나타내었다. 발효유의 색도는 오디와 실크 단백질을 첨가한 발효유에서 높은 적색도와 낮은 명도, 황색도 값을 나타내었고, 생균수와 점도에서도 오디와 실크 단백질을 첨가한 발효유에서 높은 값을 나타내었다(p <0.05). 생균수의 경우 BA + MS, LP + MS, YF, BA, LP순으로 높은 값을 나타내었는데, YF를 기준으로 오디와 실크 단백질을 첨가한 발효유와 첨가하지 않은 발효유간의 유의적인 차이를 보였다. 관능평가에서도 오디와 실크 단백질을 첨가한 발효유에서 높은 선호도를 보였으며, 전체적인 기호도에서는 BA +MS, LP + MS, BA, YF, LP 순으로 높은 점수를 받았고 식초에서 얻은 균으로 제조한 발효유가 높은 선호도를 보였다. 결론적으로 김치 및 식초 유래 유산균으로 발효유는 기존에 상업적으로 사용하는 유산균으로 제조한 것과 물리화학적 특징에 차이가 없었다. 더 나아가 오디추출물과 실크 단백질을 첨가한 발효유는 오디추출물과 실크 단백질이 첨가되지 않은 발효유보다 물리화학적 품질도 향상되고, 기호도도 높여서 향후 제품화 가능성도 기대할 수 있겠다. The purpose of this study was to produce mulberry extract and silk protein (MS) added yogurt fermented with vegetable lactic acid bacteria (Lactobacillus plantarum and Bacillus acidiproducens) and to determine their physicochemical properties and preference. The physicochemical properties were examined total phenol and antocyanins contents, viscosity, visible cell counts, chromaticity and sensory evaluation. Yogurt made with LP (PL) and BA (BA) had similar pH and titrable acidity and mulberry and MS addition made lower pH and higher titrable acidity than the control (YF) (p <0.05). The MS added yogurt exhibited adaptable acidity in the market. As expected, MS added yogurt had higher redness, and lower lightness and yellowness than no added one regardless of bacteria kinds, in chromaticity (p <0.05). MS added yogurt showed higher value of total phenols and anthocyanins than no MS added one. MS added yogurt also increased the number of live bacteria in the ascending order of than LP, BA, YF, LP +MS, and BA + MS. In sensory evaluation, BA +MS had the higher overall acceptance than the others. In conclusion, yogurt fermented with Lactobacillus plantarum and Bacillus acidiproducens was acceptable as much as the commercial Lactobacillus. Moreover, MS added yogurt fermented with Bacillus acidiproducens was the most preferred, based on physicochemical properties and overall acceptability for sensory evaluation.

Alleviation of Metabolic Disturbance by Substituting Kanjang High in Bacillus for Salt through Modulation of Gut Microbiota in Estrogen-Deficient Rats

Ji-Won Seo,Sunmin Park,Ting Zhang,Yu Yue,Su-Ji Jeong,Myeong Seon Ryu,Xuangao Wu,Hee-Jong Yang,Do-Yeon Jeong 한국식품영양과학회 2022 한국식품영양과학회 학술대회발표집 Vol.2022 No.10