Korean red ginseng alleviates benign prostatic hyperplasia by dysregulating androgen receptor signaling and inhibiting DRP1-mediated mitochondrial fission.

Panax ginseng (C.A. Mey.) has been traditionally employed in Korea and China to alleviate fatigue and digestive disorders. In particular, Korean red ginseng (KRG), derived from streamed and dried P. ginseng, is known for its anti-aging and anti-inflammatory properties. However, its effects on benign prostatic hyperplasia (BPH), a representative aging-related disease, and the underlying mechanisms remain unclear. This study aims to elucidate the therapeutic effects of KRG on BPH, with a particular focus on mitochondrial dynamics, including fission and fusion processes. The effects of KRG on cell proliferation, apoptosis, and mitochondrial dynamics and morphology were evaluated in a rat model of testosterone propionate (TP)-induced BPH and TP-treated LNCaP cells, with mdivi-1 as a control. The results revealed that KRG treatment reduced the levels of androgen receptors (AR) and prostate-specific antigens in the BPH group. KRG inhibited cell proliferation by downregulating cyclin D and proliferating cell nuclear antigen (PCNA) levels, and it promoted apoptosis by increasing the ratio of B-cell lymphoma protein 2 (Bcl-2)-associated X protein (Bax) to Bcl-2 expression. Notably, KRG treatment enhanced the phosphorylation of dynamin-related protein 1 (DRP-1, serine 637) compared with that in the BPH group, which inhibited mitochondrial fission and led to mitochondrial elongation. This modulation of mitochondrial dynamics was associated with decreased cell proliferation and increased apoptosis. By dysregulating AR signaling and inhibiting mitochondrial fission through enhanced DRP-1 (ser637) phosphorylation, KRG effectively reduced cell proliferation and induced apoptosis. These findings suggest that KRG's regulation of mitochondrial dynamics offers a promising clinical approach for the treatment of BPH.

OTUD7B knockdown inhibits proliferation and autophagy through AKT/mTOR signaling pathway in human prostate cancer cell.

Prostate cancer (PCa) is the second leading disease of cancer-related death in men around the world, and it is almost impossible to treat advanced PCa. OTUD7B is a member of the deubiquitinase family that undergoes a post-translational transformation process, which is essential for cell stability and signaling and is known to play a critical role in cancer. However, its role in PCa has not been discovered. The aim of the study was to investigate the expression and mechanism of OTUD7B in PCa cells. According to the database, high OTUD7B expression showed a poor prognosis. Therefore, we downregulated OTUD7B using siRNA and confirmed the role of OTUD7B in PC3 prostate cancer cells. OTUD7B knockdown effectively induced apoptosis and inhibited the proliferation in PC3 cells. OTUD7B knockdown inhibited autophagy through AKT/mTOR signaling. We also confirmed the relationship between AKT/mTOR signaling and autophagy through rapamycin, an mTOR inhibitor. Taken together, OTUD7B promotes the proliferation, and autophagy, and inhibits apoptosis of prostate cancer cells via the AKT/mTOR signaling pathway.

Novel role of LLGL2 silencing in autophagy: reversing epithelial-mesenchymal transition in prostate cancer.

PURPOSE: Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo. METHODS: PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model. RESULTS: In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and α-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition. CONCLUSION: Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.

The longitudinal analysis for the association between smoking and the risk of depressive symptoms.

BACKGROUND: Despite high smoking rate in people with depressive symptoms, there is ongoing debate about relationship between smoking and depressive symptoms. METHODS: Study participants were 57,441 Korean men. We collected their baseline data between 2011 and 2012, and conducted follow-up from 2013 to 2019. They were categorized by smoking status (never: < 100 cigarettes smoking in life time, former: currently quitting smoking, and current smoker: currently smoking), smoking amount (pack/day and pack-year) and urine cotinine excretion. The development of depressive symptoms was determined in CES-D score ≥ 16. Cox proportional hazards model was used to analyze the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CI) for depressive symptoms in relation to smoking status, smoking amount, and urine cotinine excretion. RESULTS: During 6.7 years of median follow-up, the risk of depressive symptoms increased in order of never (reference), former (HR = 1.08, 95% CI: 1.01-1.15) and current smoker (HR = 1.24, 95% CI: 1.16-1.32). Among current smoker, the risk of depressive symptoms increased proportionally to daily smoking amount (< 1 pack; HR = 1.21, 95% CI: 1.13-1.29, and ≥ 1 pack; HR = 1.34, 95% CI: 1.23 - 1.45). This pattern of relationship was consistently observed for pack-year in former smoker and current smoker. Additionally, urine cotinine excretion was proportionally associated with the risk of depressive symptoms. CONCLUSION: Exposure to smoking was associated with the increased risk of depressive symptoms. Dose dependent relationship was observed between smoking amount and the risk of depressive symptoms.

Dietary Intake of Antioxidant Vitamins and Its Relation to the Progression of Chronic Kidney Disease in Adults With Preserved Renal Function.

OBJECTIVE: It is expected that antioxidants contribute to slow the progression of chronic kidney disease (CKD). However, there are no data on the protective effect of dietary antioxidant vitamins on CKD. The purpose of study was to evaluate the renoprotective effect of dietary antioxidant vitamins in the general population. DESIGN AND METHODS: The study participants were 127,081 Korean adults with preserved renal function with estimated glomerular filtration rate ≥60 mL/min/1.73 m2. They were categorized into 3 groups by tertile levels of dietary antioxidant vitamins intake including vitamins C, E, and A. Cox proportional hazard assumption was used to calculate multivariable hazard ratios and 95% confidence interval for the incident moderate to severe CKD (adjusted hazard ratio [95% confidence interval]) according to tertile levels of dietary intake of antioxidant vitamins. Subgroup analysis was conducted to evaluate the risk of progression from normal to mildly decreased renal function, and from mildly decreased renal function to moderate to severe CKD. RESULTS: The risk of moderate to severe CKD was not significantly associated with the third tertile of dietary antioxidant vitamin intake including vitamin C (1.02 [0.78-1.34]), E (0.96 [0.73-1.27]), and A (0.98 [0.74-1.29]). Additionally, any tertile groups didn't show the significant association with the risk of moderate to severe CKD. Subgroup analysis also didn't show the decreased risk of progression from normal to mildly decreased renal function, and from mildly decreased renal function to moderate to severe CKD in any tertile groups. CONCLUSION: Dietary intake of vitamins C, E, and A was not significantly associated with the risk of CKD progression.

Association Between Eight Autoimmune Diseases and Thyroid Cancer: A Nationwide Cohort Study.

Background: It has often been reported that thyroid-specific autoimmune diseases (ADs), such as Hashimoto's thyroiditis and Graves' disease, could increase the risk of thyroid cancer, but the association between other ADs beyond thyroid and thyroid cancer has not been well investigated. This study aimed to examine the risk of thyroid cancer in patients with eight ADs compared with those without ADs. Methods: This nationwide retrospective matched cohort study was conducted to investigate the relationship of eight ADs (Hashimoto's thyroiditis, Graves' disease, type 1 diabetes mellitus, Sjogren's disease, inflammatory bowel disease [IBD], vitiligo, systemic lupus erythematosus, and rheumatoid arthritis [RA]) with the risk of incident thyroid cancer using the National Health Insurance Service-National Sample Cohort. The Cox-proportional hazard model was used to estimate the adjusted hazard ratio (HR) and confidence intervals (CI) for thyroid cancer in relation to each of AD compared with control group without AD. Results: During the average follow-up of 9.49 years, 138 thyroid cancer cases were newly developed in control group and 268 cases were occurred in group with 8 ADs. For all of study participants, the risk of thyroid cancer was significantly increased in patients with Hashimoto's thyroiditis (HR = 2.10 [1.57-2.81]), Graves' disease (HR = 2.67 [1.99-3.62]), IBD (HR = 2.06 [1.50-2.83]), vitiligo (HR = 1.71 [1.13-2.59]), RA (HR = 1.76 [1.07-2.90]), and total of 8 ADs (HR = 1.97 [1.60-2.42]) compared with control group without ADs. When ADs were divided into three types, thyroid-specific ADs (HR = 2.37 [1.85-3.03]) showed the strongest and significant association with thyroid cancer, followed by local ADs (HR = 1.83 [1.41-2.38]), and systemic ADs (HR = 1.77 [1.14-2.74]). Conclusions: Specific ADs-especially for thyroid-specific AD, vitiligo, IBD, and RA-were associated with increased risk for thyroid cancer.

Novel role of LLGL2 silencing in autophagy: reversing epithelial-mesenchymal transition in prostate cancer

Purpose Prostate cancer (PCa) is a major urological disease that is associated with significant morbidity and mortality in men. LLGL2 is the mammalian homolog of Lgl. It acts as a tumor suppressor in breast and hepatic cancer. However, the role of LLGL2 and the underlying mechanisms in PCa have not yet been elucidated. Here, we investigate the role of LLGL2 in the regulation of epithelial-mesenchymal transition (EMT) in PCa through autophagy in vitro and in vivo. Methods PC3 cells were transfected with siLLGL2 or plasmid LLGL2 and autophagy was examined. Invasion, migration, and wound healing were assessed in PC3 cells under autophagy regulation. Tumor growth was evaluated using a shLLGL2 xenograft mouse model. Results In patients with PCa, LLGL2 levels were higher with defective autophagy and increased EMT. Our results showed that the knockdown of LLGL2 induced autophagy flux by upregulating Vps34 and ATG14L. LLGL2 knockdown inhibits EMT by upregulating E-cadherin and downregulating fibronectin and α-SMA. The pharmacological activation of autophagy by rapamycin suppressed EMT, and these effects were reversed by 3-methyladenine treatment. Interestingly, in a shLLGL2 xenograft mouse model, tumor size and EMT were decreased, which were improved by autophagy induction and worsened by autophagy inhibition. Conclusion Defective expression of LLGL2 leads to attenuation of EMT due to the upregulation of autophagy flux in PCa. Our results suggest that LLGL2 is a novel target for alleviating PCa via the regulation of autophagy.

Changes in smoking status, amount of smoking and their relation to the risk of microvascular complications in men with diabetes mellitus.

BACKGROUND: Smoking is a definite risk factor for macrovascular complications in diabetes mellitus (DM). However, the effect of smoking on microvascular complications is inconclusive. METHOD: Study participants were 26,673 diabetic men who received health check-up both in 2003-2004 and 2009, excluding women. Assessing smoking status (never, quitting and current) at 2003-2004 and 2009, changes in smoking status were categorised into 7 groups (never - never, never - quitting, never - current, quitting-quitting, quitting-current, current-quitting and current-current). Smoking amount was categorised into never, light (0-10 pack years), moderate (10-20 pack years), and heavy smoking (>20 pack years) based on 2009 data. They were followed-up until 2013 to identify incident microvascular complications. We calculated the adjusted hazard ratios (HR) and 95% confidence interval (CI) (adjusted HR [95% CI]) for incident microvascular complications according to changes in smoking status and smoking amount. RESULTS: Current-quitting (1.271 [1.050-1.538]), current-current (1.243 [1.070-1.444]) and heavy smoking (1.238 [1.078-1.422]) were associated with an increased risk of overall microvascular complications. The risk of nephropathy increased in current-current smoking (1.429 [1.098-1.860]) and heavy smoking (1.357 [1.061-1.734]). An increased risk of neuropathy was observed in current-quitting smoking (1.360 [1.076-1.719]), current-current smoking (1.237 [1.025-1.492]) and heavy smoking (1.246 [1.048-1.481]). However, we couldn't see the interpretable findings for the association between smoking and retinopathy. CONCLUSIONS: Lasting and heavy smoking increases the risk of microvascular complications, including nephropathy and neuropathy. Quitting smoking and reducing smoking amount are imperative in preventing microvascular complications in DM patients.

Longitudinal analysis for the risk of depression according to the consumption of sugar-sweetened carbonated beverage in non-diabetic and diabetic population.

Studies have presented that high intake of sugar-sweetened carbonated beverage (SSCB) was more associated with the prevalence of depression. However, longitudinal evidence is still insufficient to identify whether the effect of SSCB on incident depression is independent of metabolic factors. Therefore, to evaluate the effect of SSCB consumption on the risk of depression, we analyzed the risk of depression according to the consumption of SSCB in 87,115 working aged Koreans who responded to Center for Epidemiologic Studies Depression (CES-D) scale. They were categorized into 5 groups by SSCB consumption based on one serving dose (200 ml) with never/almost never, < 1 serving/week, 1 ≤ serving/week < 3, 3 ≤ serving/week < 5, and 5 ≤ serving/week. During follow-up, CES-D ≥ 16 was determined as incident depressive symptom. Cox proportional hazards model was used to calculate the multivariable-adjusted hazard ratio (HR) and 95% confidence intervals (CI) for depressive symptom. In analysis for all study participants, the risk of depressive symptom significantly increased proportionally to SSCB consumption (never/almost never: reference, < 1 serving/week: 1.12 [1.07-1.17], 1 ≤ ~ < 3 serving/week: 1.26 [1.19-1.33], 3 ≤ ~ < 5 serving/week: 1.32 [1.23-1.42], and ≥ 5 serving/week: 1.45 [1.33-1.59]). This association was identically observed in men, women, normal glycemic subgroup and prediabetes subgroup.

Fasting blood glucose and risk of incident pancreatic cancer.

BACKGROUND: The number of patients with diabetes and impaired fasting blood glucose in Korea is rapidly increasing compared to the past, and other metabolic indicators of population are also changed in recent years. To clarify the mechanism more clearly, we investigated the association between fasting blood glucose and incidence of pancreatic cancer in this retrospective cohort study. METHODS: In Korea National Health Information Database, 19,050 participants without pancreatic cancer in 2009 were enrolled, and followed up until 2013. We assessed the risk of incident pancreatic cancer according to the quartile groups of fasting blood glucose level (quartile 1: <88 mg/dL, quartile 2: 88-97 mg/dL, quartile 3: 97-109 mg/dL and quartile 4: ≥109 mg/dL). Multivariate Cox-proportional hazard model was used in calculating hazard ratios (HRs) and 95% confidence interval (CI) for incident pancreatic cancer. RESULTS: Compared with quartile1 (reference), unadjusted HRs and 95% CI for incident pancreatic cancer significantly increased in order of quartile2 (1.39 [1.01-1.92]), quartile3 (1.50 [1.09-2.07]) and quartile4 (2.18 [1.62-2.95]), and fully adjusted HRs and 95% CI significantly increased from quartile2 (1.47 [1.05-2.04]), quartile3 (1.61 [1.05-2.04]) to quartile4 (2.31 [1.68-3.17]). CONCLUSION: Fasting blood glucose even with pre-diabetic range was significantly associated with the incident pancreatic cancer in Korean.

Decreased mitophagy aggravates benign prostatic hyperplasia in aged mice through DRP1 and estrogen receptor α.

Benign prostatic hyperplasia (BPH) is an age-related disease, whose etiology largely remains unclear. The regulation of mitophagy plays a key role in aging and associated diseases, however, its function in BPH has not been studied. Although the expression of the androgen receptor is primarily implicated in BPH, the estrogen receptor (ER) has been reported to be involved in the development of BPH by mediating the proliferation of prostate cells. Here, we studied the involvement of mitophagy and ERs in spontaneous BPH in aging mice and investigated their functions. To identify the activation of mitophagy and expression of ERs, 8-week, 12-month, and 24-month-old mice were used. Mice were treated with mitochondrial division inhibitor mdivi-1, a dynamin-related protein 1 (Drp1) inhibitor, to examine the expression of mitophagy-related proteins and the development of BPH. In addition, prostate stromal cells were treated with an ER antagonist to investigate the regulation of mitophagy following the expression of ERs. With aging, the Drp1 and phosphorylation of parkin reduce. Electron microscopy revealed reduced mitochondrial fission and mitophagy. In addition, the expression of androgen receptor was decreased and that of ERα was increased in aged mice with BPH. Treatment with mdivi-1 exacerbated BPH and increased cell proliferation. In addition, blockade of ERα increased mitophagy and decreased cell proliferation. In conclusion, mitophagy is reduced with aging during the development of BPH. We speculate that spontaneous BPH progresses through the reduction in the expression of ERα in aged mice by downregulating mitophagy.

Nationwide changes in physical activity, nutrient intake, and obesity in South Korea during the COVID-19 pandemic era.

Background: This study aimed to examine changes in obesity rates and obesity-related factors during the COVID-19 pandemic compared to a previous period. Methods: An ecological time-series study was designed using the Korean National Health and Nutritional Examination Survey (KNHANES) database from 2014 to 2020. The expected values of obesity rate, physical activity rate, and nutrient intake for 2020 were estimated. The differences between the predicted and actual values for 2020 were also examined. In addition, a multiple logistic regression model was used to examine the changes in obesity and physical activity rates in 2020 compared to 2019. Results: The actual obesity rates in 2020 were higher, and the walking and aerobic physical activity rates were lower than the predicted values for the same year. However, the actual resistance training rates in 2020 were higher and the total energy intake was lower than the predicted values for 2020. In the multiple logistic regression model, the odds ratios for obesity, aerobic physical activity, and walking among men in 2020 were 1.29 (95% CI: 1.08 to 1.55), 0.86 (0.74 to 1.01), and 0.84 (0.73 to 0.97), respectively, compared to those in 2019. However, there were no significant differences between the values for women in 2020 and 2019. Conclusions: This study suggests that the male obesity rate in Korea has significantly increased during the COVID-19 epidemic, mainly due to a decrease in physical activity.

Change in smoking status and its relation to the risk of gastroduodenal ulcer in Korean men.

BACKGROUND AND AIM: Smoking is associated with the increased risk of gastroduodenal ulcer. However, although smoking status can vary over time, most of studies have analyzed this association with smoking status at a single point of time. We analyzed the risk of gastroduodenal ulcer according to change in smoking status for more than 5 years. METHODS: Study participants were 43 380 Korean adults free of gastroduodenal ulcer who received health check-up between 2002 and 2013. Through evaluating their smoking status (never, quitter, and current) at 2003-2004 and 2009, they were categorized them into seven groups (never-never, never-quitter, never-current, quitter-quitter, quitter-current, current-quitter, and current-current) and monitored until 2013 to identify incident gastroduodenal ulcer. Cox-proportional hazard model was used to calculate the adjusted hazard ratios (HRs) and 95% confidence interval (CI) for incident gastroduodenal ulcer according to changes in smoking status and smoking amount. RESULTS: Compared with never-never group (reference), other groups had the significantly increased adjusted HRs and 95% CI for gastroduodenal ulcer. In particular, participants with current smoking (never-current, quitter-current, and current-current) had the relatively higher HRs than other groups (never-quitter: 1.200 [1.070-1.346], never-current: 1.375 [1.156-1.636], quitter-quitter: 1.149 [1.010-1.306], quitter-current: 1.325 [1.058-1.660], current-quitter: 1.344 [1.188-1.519], and current-current: 1.379 [1.256-1.513]). Heavy smoker had the highest risk for gastroduodenal ulcer, followed by moderate and light smoker. CONCLUSION: People who ever experienced smoking had increased risk of gastroduodenal ulcer. Out of smoking status, current smoking is more associated with the increased risk of gastroduodenal ulcer than past smoking.

The protective effect of peanuts, pine nuts and almonds on gastric intestinal metaplasia in Korean men.

There are reports that nut consumption provides potential benefit for gastric pathologies including stomach cancer and Helicobacter pylori infection. However, there are no studies investigating the effect of nut consumption on gastric intestinal metaplasia (GIM). In a Korean cohort of 53 424 men (average age 38.7 ± 7.0 years) and 33 024 women (average age 38.0 ± 7.0 years), we analysed the risk of GIM according to the frequency of nut consumption (peanuts, pine nuts and almonds only) as the following: rare (<1 serving/month), ≤1 serving/month and <1 serving/week, ≤1 serving/week and <3 serving/week, ≤3 serving/week and <5 serving/week and ≥5 serving/week where one serving is 15 g. Cox proportional hazards model was used to calculate the multivariable-adjusted hazard ratio (HR) for GIM and their 95% confidence intervals (CI) in each group (adjusted HR [95% CI]). Subgroup analysis was conducted by body mass index (BMI, non-obesity <25 and obesity ≥25). The models were adjusted for age, regular exercise, BMI, smoking, alcohol intake (g/day), diabetes mellitus, hypertension, dietary fibre intake, sodium intake and total calorie intake. After 5.3 years (median 5.9 years) of follow-up, GIM was observed in 5073 subjects. In men, compared with rare nuts consumption, greater nuts consumption was associated with a lower risk of GIM (rare consumption: reference, 1/month-1/week: 0.85 [0.79-0.91], 1-3/week: 0.81 [0.72-0.91], 3-5/week: 0.70 [0.57-0.86] and ≥5/week: 0.59 [0.48-0.73]). Subgroup analysis indicated that the inverse relationship between nuts consumption and the risk of GIM is more distinct in men without obesity (rare consumption: reference, 1/month-1/week: 0.83 [0.76-0.91], 1-3/week: 0.78 [0.67-0.91], 3-5/week: 0.68 [0.51-0.89] and ≥5/week: 0.51 [0.37-0.69]). However, this association was not observed in women. In conclusion, increased nuts consumption was associated with a decreased risk of GIM in working aged Korean men.

The influence of the dietary intake of vitamin C and vitamin E on the risk of gastric intestinal metaplasia in a cohort of Koreans.

OBJECTIVES: Studies have suggested that the dietary intake of antioxidant vitamins, such as vitamin C and vitamin E, has a potential role in inhibiting gastric carcinogenesis. The present study investigated the effect of antioxidant vitamins on the incidence of gastric intestinal metaplasia (GIM). METHODS: This study included 67,657 Koreans free of GIM who periodically underwent health check-ups. Dietary intake was assessed by a semiquantitative food frequency questionnaire based on the Korean National Health and Nutrition Examination Survey. Participants were categorized into 4 groups by quartiles of dietary vitamin C and vitamin E intake. The Cox proportional hazard assumption was used to determine the multivariable hazard ratio (HR) and 95% confidence interval (95% CI) for GIM. RESULTS: The third and fourth quartiles of vitamin C intake had a lower risk of GIM than the first quartile (multivariable-adjusted HR, 0.95; 95% CI, 0.88 to 1.03 in the second quartile, HR, 0.88; 95% CI, 0.81 to 0.97 in the third quartile, and HR, 0.85; 95% CI, 0.76 to 0.95 in the fourth quartile). Vitamin E intake greater than the second quartile level was significantly associated with a lower risk of GIM than the first quartile (multivariable-adjusted HR, 0.90; 95% CI, 0.82 to 0.97 in the second quartile, HR, 0.90; 95% CI, 0.82 to 0.99 in the third quartile, and HR, 0.83; 95% CI, 0.74 to 0.94 in the fourth quartile). This association was observed only in the subgroup analysis for men. CONCLUSIONS: Higher dietary intake of vitamin C and vitamin E was associated with a lower risk of GIM.

The extract of Celtis choseniana Nakai alleviates testosterone-induced benign prostatic hyperplasia through inhibiting 5α reductase type 2 and the Akt/NF-κB/AR pathway.

Benign prostatic hyperplasia (BPH) is a chronic male disease characterized by the enlarged prostate. Celtis chosenianaNakai (C. choseniana) is medicinally used to alleviate pain, gastric disease, and lung abscess. In this study, the effect of C. choseniana extract on BPH was investigated using testosterone-induced rats. Sprague Dawley rats were divided into five groups: control, BPH (testosterone 5 mg·kg-1), Fina (finasteride 2 mg·kg-1), and C. choseniana (50 and 100 mg·kg-1). After four weeks of TP treatment with finasteride or C. choseniana, prostate weights and DHT levels were measured. In addition, the prostates were histopathologically examined and measured for protein kinase B (Akt)/nuclear factor-κB (NF-κB)/AR signaling, proliferation, apoptosis, and autophagy. Prostate weight and epithelial thickness were reduced in the C. choseniana groups compared with that in the BPH group. The extract of C. choseniana acted as a 5α reductase inhibitor, reducing DHT levels in the prostate. Furthermore, the extract of C. choseniana blocked the activation of p-Akt, nuclear NF-κB activation and reduced the expression of AR and PSA compared with BPH. Moreover, the expression of Bax, PARP-1, and p53 increased, while the expression of bcl-2 decreased. The present study demonstrated that C. choseniana extract alleviated testosterone-induced BPH by suppressing 5α reductase and Akt/NF-κB activation, reducing AR signaling and inducing apoptosis and autophagy in the prostate. These results suggested that C. choseniana probably contain potential herbal agents to alleviate BPH.

Effects and Mechanism of Particulate Matter on Tendon Healing Based on Integrated Analysis of DNA Methylation and RNA Sequencing Data in a Rat Model.

Exposure to particulate matter (PM) has been linked with the severity of various diseases. To date, there is no study on the relationship between PM exposure and tendon healing. Open Achilles tenotomy of 20 rats was performed. The animals were divided into two groups according to exposure to PM: a PM group and a non-PM group. After 6 weeks of PM exposure, the harvest and investigations of lungs, blood samples, and Achilles tendons were performed. Compared to the non-PM group, the white blood cell count and tumor necrosis factor-alpha expression in the PM group were significantly higher. The Achilles tendons in PM group showed significantly increased inflammatory outcomes. A TEM analysis showed reduced collagen fibrils in the PM group. A biomechanical analysis demonstrated that the load to failure value was lower in the PM group. An upregulation of the gene encoding cyclic AMP response element-binding protein (CREB) was detected in the PM group by an integrated analysis of DNA methylation and RNA sequencing data, as confirmed via a Western blot analysis showing significantly elevated levels of phosphorylated CREB. In summary, PM exposure caused a deleterious effect on tendon healing. The molecular data indicate that the action mechanism of PM may be associated with upregulated CREB signaling.

Daily Vigorous Intensity Physical Activity and Its Preventive Effect on Pancreatic Cancer.

PURPOSE: There has been accumulating evidence for the preventive effect of high physical activity on cancer. However, it is still unclear which level of physical activity is associated with the decreased risk of pancreatic cancer. The purpose of current study is to assess the association between the frequency of vigorous intensity physical activity and the risk of pancreatic cancer. MATERIALS AND METHODS: The nationwide retrospective cohort study was conducted using the National Health Information Database. Study participants were 220,357 Koreans who received health check-up in 2009. They were divided into four groups by the weekly frequency of vigorous intensity physical activity longer than 20 minutes (group 1, no vigorous intensity physical activity (reference); group 2, 1-3 days; group 3, 4-5 days and group 4, 6-7 days). Cox proportional hazard model was used to calculate the adjusted hazard ratios (HRs) and 95% confidence interval (CI) for incident pancreatic cancer (adjusted HRs [95% CI]) according to the weekly frequency of vigorous intensity physical activity. RESULTS: For 4.38 years' follow-up on average, 377 cases of pancreatic cancer developed. Subjects without incident pancreatic cancer had more favorable metabolic condition and higher physical activity than subjects with incident pancreatic cancer. Adjusted HRs and 95% CI indicated that only group 4 was significantly associated with the decreased risk of pancreatic cancer (group 1, reference; group 2, 1.10 [0.86-1.40]; group 3, 0.75 [0.45-1.25] and group 4, 0.47 [0.25-0.89]). CONCLUSION: In this nationwide representative cohort study, near daily vigorous intensity physical activity showed the preventive effect on pancreatic cancer.

Smoking Status, Intensity of Smoking, and Their Relation to Left Ventricular Hypertrophy in Working Aged Korean Men.

INTRODUCTION: Smoking is an established risk factor for atherosclerotic cardiovascular disease. However, the effect of smoking on left ventricular (LV) structure has been less studied. This study was designed to assess the association of smoking status and smoking intensity with left ventricular hypertrophy (LVH). METHODS: Study subjects were 53,666 working aged Korean men who received echocardiography as an item of health check up. They were grouped by smoking status (never, former, and current smokers), pack-year of smoking (never, <10, 10-19.9, and ≥20 pack-year), and urine cotinine excretion (<100, 100-999, ≥1000 ng/mL). Multivariate logistic regression analysis was used in calculating adjusted odds ratios (ORs) and 95% confidence interval for LVH (adjusted odds ratios [95% confidence interval]). The proportions of abnormal LV geometry patterns were compared among groups. RESULTS: Former and current smokers had the higher levels in LV mass index, relative wall thickness, and the prevalence of LVH than never smoker. The association with LVH increased in order of never (reference), former (1.44 [1.01-2.04]), and current smokers (2.10 [1.44-3.05]). LVH showed the proportional relationship with pack-year of smoking (never smoker: reference, <10: 1.45 [1.01-2.08], 10-19.9: 1.73 [1.17-2.57], ≥20: 2.43 [1.58-3.74]) and urine cotinine excretion (never smoker: reference, 100-999: 1.70 [1.21-2.37], >1000: 1.97 [1.43-2.72]). The proportions of abnormal LV geometry patterns were higher in smoking groups than never smoking group. CONCLUSION: Exposure to tobacco use and intensity of smoking was associated with LVH in working aged population. IMPLICATIONS: In working aged Koreans with mean age of 39.9 ± 7.0 years, former and current smokers are more likely to have LVH than never smoker. Dose-dependent relationship was found between the smoking status (never, former, and current smokers), pack-year of smoking, urine cotinine excretion, and LVH. These findings indicate that smoking has an adverse influence on LV structure even in relatively young age group.

Protective effects of combination of Stauntonia hexaphylla and Cornus officinalis on testosterone-induced benign prostatic hyperplasia through inhibition of 5α- reductase type 2 and induced cell apoptosis.

Benign prostatic hyperplasia (BPH) is a progressive pathological condition associated with proliferation of prostatic tissues, prostate enlargement, and lower-urinary tract symptoms. However, the mechanism underlying the pathogenesis of BPH is unclear. The aim of this study was to investigate the protective effects of a combination of Stauntonia hexaphylla and Cornus officinalis (SC extract) on a testosterone propionate (TP)-induced BPH model. The effect of SC extract was examined in a TP-induced human prostate adenocarcinoma cell line. Male Sprague-Dawley rats were randomly divided into 5 groups (n = 6) for in vivo experiments. To induce BPH, all rats, except those in the control group, were administered daily with subcutaneous injections of TP (5 mg/kg) and orally treated with appropriate phosphate buffered saline/drugs (finasteride/saw palmetto/SC extract) for 4 consecutive weeks. SC extract significantly downregulated the androgen receptor (AR), prostate specific antigen (PSA), and 5α-reductase type 2 in TP-induced BPH in vitro. In in vivo experiments, SC extract significantly reduced prostate weight, size, serum testosterone, and dihydrotestosterone (DHT) levels. Histologically, SC extract markedly recovered TP-induced abnormalities and reduced prostatic hyperplasia, thereby improving the histo-architecture of TP-induced BPH rats. SC extract also significantly downregulated AR and PSA expression, as assayed using immunoblotting. Immunostaining revealed that SC extract markedly reduced the 5α-reductase type 2 and significantly downregulated the expression of proliferating cell nuclear antigen. In addition, immunoblotting of B-cell lymphoma 2 (Bcl-2) family proteins indicated that SC extract significantly downregulated anti-apoptotic Bcl-2 and markedly upregulated pro-apoptotic B cell lymphoma-associated X (Bax) expression. Furthermore, SC treatment significantly decreased the Bcl-2/Bax ratio, indicating induced prostate cell apoptosis in TP-induced BPH rats. Thus, our findings demonstrated that SC extract protects against BPH by inhibiting 5α-reductase type 2 and inducing prostate cell apoptosis. Therefore, SC extract might be useful in the clinical treatment of BPH.