Clinical outcome and safety of holmium laser prostate enucleation after transrectal prostate biopsies for benign prostatic hyperplasia.

PURPOSE: This study aimed to assess the clinical outcome and safety of holmium laser enucleation of the prostate (HoLEP) following transrectal ultrasound-guided prostate biopsy (TR biopsy) in the treatment of benign prostate hyperplasia. MATERIALS AND METHODS: We retrospectively analyzed data from 556 patients who underwent HoLEP between 2014 and 2021. The patients were categorized into six groups: Group 1-A (n=45) underwent HoLEP within four months post TR biopsy. Group 1-B (n=94) underwent HoLEP more than four months post TR biopsy. Group 1-C (n=120) underwent HoLEP after a single TR biopsy. Group 1-D (n=19) underwent HoLEP after two or more TR biopsies. Group 1-total (n=139, group 1-A+group 1-B or group 1-C+group 1-D) underwent HoLEP post TR biopsy. Group 2 (control group, n=417) underwent HoLEP without prior TR biopsy. We examined perioperative parameters, safety, and functional outcomes. RESULTS: The age, body mass index, International Prostate Symptom Score (IPSS), uroflowmetry, and comorbid diseases between group 1-total and group 2 were comparable. However, group 1-total exhibited significantly elevated prostate-specific antigen levels and larger prostate volumes (p<0.01). Perioperative factors like enucleation time, enucleation weight, and catheterization duration were notably higher in group 1-total (p<0.01). All groups showed significant improvements in IPSS, postvoid residual urine, and maximum flow rate during the 1-year postoperative period (p<0.05). The rates of postoperative complications were similar between group 1-total and group 2. CONCLUSIONS: Enucleation time and catheterization duration were significantly longer in the TR biopsy group. However, postoperative complications were not significantly different between TR biopsy and non-TR biopsy groups.

Mass spectrometry-based ginsenoside profiling: Recent applications, limitations, and perspectives.

Ginseng, the roots of Panax species, is an important medicinal herb used as a tonic. As ginsenosides are key bioactive components of ginseng, holistic chemical profiling of them has provided many insights into understanding ginseng. Mass spectrometry has been a major methodology for profiling, which has been applied to realize numerous goals in ginseng research, such as the discrimination of different species, geographical origins, and ages, and the monitoring of processing and biotransformation. This review summarizes the various applications of ginsenoside profiling in ginseng research over the last three decades that have contributed to expanding our understanding of ginseng. However, we also note that most of the studies overlooked a crucial factor that influences the levels of ginsenosides: genetic variation. To highlight the effects of genetic variation on the chemical contents, we present our results of untargeted and targeted ginsenoside profiling of different genotypes cultivated under identical conditions, in addition to data regarding genome-level genetic diversity. Additionally, we analyze the other limitations of previous studies, such as imperfect variable control, deficient metadata, and lack of additional effort to validate causation. We conclude that the values of ginsenoside profiling studies can be enhanced by overcoming such limitations, as well as by integrating with other -omics techniques.

Combination Therapy of Choline Alfoscerate With Ginkgo biloba Monotherapy in Age-Related Hearing Loss: Effects and Outcomes.

BACKGROUND AND OBJECTIVES: Ginkgo biloba and choline alfoscerate are used as adjuvant treatment for presbycusis, but studies on how the monotherapy differs from the combination therapy are lacking. Therefore, this study aimed to compare the audiologic outcomes between Ginkgo biloba monotherapy and Ginkgo biloba and choline alfoscerate combination therapy. Subjects and. METHODS: The study groups are divided into three: negative control, monotherapy, and combination therapy groups. All groups' pure tone audiometry was measured by dividing the study period into Initial, 3-6, 6-9, 9-12, 12-15 months, and checked whether differences between groups were present. RESULTS: The combination therapy showed less gradient gap than the monotherapy, indicating less hearing loss rate than the monotherapy. Based on the Kaplan-Meier curve, the combination therapy showed better results in terms of survival time of hearing. CONCLUSIONS: As a pharmacological treatment for presbycusis, combination therapy shows better results than monotherapy.

Benefits and Harms of Standard Versus Reduced-Dose Direct Oral Anticoagulant Therapy for Older Adults With Multiple Morbidities and Atrial Fibrillation.

Background Dose reduction of direct oral anticoagulant (DOAC) medications is inconsistently applied to older adults with multiple morbidities, potentially due to perceived harms and unknown benefits of standard dosing. Methods and Results Using 2013 to 2017 US Medicare claims linked to Minimum Data Set records, we conducted a retrospective cohort study. We identified DOAC initiators (apixaban, dabigatran, rivaroxaban) aged ≥65 years with nonvalvular atrial fibrillation residing in a nursing home. We estimated inverse-probability of treatment weights for DOAC dose using propensity scores. We examined safety (hospitalization for major bleeding) and effectiveness outcomes (all-cause mortality, thrombosis [myocardial infarction, stroke, systemic embolism, venous thromboembolism]). We estimated hazard ratios (HRs) and 95% CIs using cause-specific hazard-regression models. Of 21 878 DOAC initiators, 48% received reduced dosing. The mean age of residents was 82.0 years, 66% were female, and 31% had moderate/severe cognitive impairment. After estimating inverse-probability of treatment weights, standard dosing was associated with a higher rate of bleeding (HR, 1.18 [95% CI, 1.03-1.37]; 9.4 versus 8.0 events per 100 person-years). Standard-dose therapy was associated with the highest rates of bleeding among those aged >80 years (9.1 versus 6.7 events per 100 person-years) and with a body mass index <30 kg/m2 (9.4 versus 7.4 events per 100 person-years). There was no association of dosing with mortality (HR, 0.99 [95% CI, 0.96-1.06]) or thrombotic events (HR, 1.16 [95% CI, 0.96-1.41]). Conclusions In this nationwide study of nursing home residents with nonvalvular atrial fibrillation, we found a higher rate of bleeding and little difference in effectiveness of standard versus reduced-dose DOAC treatment. Our results support the use of reduced-dose DOACs for many older adults with multiple morbidities.

Efficacy and Safety of Low Fluence Nd:YAG Laser Treatment in Melasma: A Meta-Analysis and Systematic Review.

BACKGROUND: Low-fluence, multisession therapy of Nd:YAG laser has been widely used for treating melasma. OBJECTIVE: To evaluate the efficacy and safety of low-fluence Nd:YAG laser toning for melasma using a systematic review and meta-analysis. METHODS: The PubMed, Web of Science, Embase, and Cochrane Library databases were searched till December 2020. A total of 50 studies (1,772 patients) and 66 studies were selected for the evaluation of the efficacy and complications, retrospectively. RESULTS: The mean Melasma Area and Severity Index/modified Melasma Area and Severity Index scores for laser toning as monotherapy at <4, 4 to <8, 8 to <12, 12 to <24, and ≥24 weeks after treatment compared with that at pretreatment were -0.51, -0.91, -0.97, -0.92, 0.01 SD, whereas those as combination therapy were -1.64, -1.26, -0.94, not available, -1.45 SD, respectively. An increase in light value and a decrease in relative lightness index have remained up to 8 weeks after laser toning. Complications including hypopigmentation/leukoderma, postinflammatory hyperpigmentation, and recurrence were noted. The incidence of hypopigmentation/leukoderma correlated with the number of laser sessions (p = .036). CONCLUSION: Low-fluence Nd:YAG laser toning as combination therapy has shown better efficacy than monotherapy and the efficacy seems to diminish with time. This study suggests the positive correlation of hypopigmentation/leukoderma with the number of laser sessions.

SMP30-mediated synthesis of vitamin C activates the liver PPARα/FGF21 axis to regulate thermogenesis in mice.

The vitamin-C-synthesizing enzyme senescent marker protein 30 (SMP30) is a cold resistance gene in Drosophila, and vitamin C concentration increases in brown adipose tissue post-cold exposure. However, the roles of SMP30 in thermogenesis are unknown. Here, we tested the molecular mechanism of thermogenesis using wild-type (WT) and vitamin C-deficient SMP30-knockout (KO) mice. SMP30-KO mice gained more weight than WT mice without a change in food intake in response to short-term high-fat diet feeding. Indirect calorimetry and cold-challenge experiments indicated that energy expenditure is lower in SMP30-KO mice, which is associated with decreased thermogenesis in adipose tissues. Therefore, SMP30-KO mice do not lose weight during cold exposure, whereas WT mice lose weight markedly. Mechanistically, the levels of serum FGF21 were notably lower in SMP30-KO mice, and vitamin C supplementation in SMP30-KO mice recovered FGF21 expression and thermogenesis, with a marked reduction in body weight during cold exposure. Further experiments revealed that vitamin C activates PPARα to upregulate FGF21. Our findings demonstrate that SMP30-mediated synthesis of vitamin C activates the PPARα/FGF21 axis, contributing to the maintenance of thermogenesis in mice.

Epigallocatechin-3-gallate suppresses hemin-aggravated colon carcinogenesis through Nrf2-inhibited mitochondrial reactive oxygen species accumulation.

BACKGROUND: Previous studies have presented evidence to support the significant association between red meat intake and colon cancer, suggesting that heme iron plays a key role in colon carcinogenesis. Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, exhibits anti-oxidative and anti-cancer effects. However, the effect of EGCG on red meat-associated colon carcinogenesis is not well understood. OBJECTIVES: We aimed to investigate the regulatory effects of hemin and EGCG on colon carcinogenesis and the underlying mechanism of action. METHODS: Hemin and EGCG were treated in Caco2 cells to perform the water-soluble tetrazolium salt-1 assay, lactate dehydrogenase release assay, reactive oxygen species (ROS) detection assay, real-time quantitative polymerase chain reaction and western blot. We investigated the regulatory effects of hemin and EGCG on an azoxymethane (AOM) and dextran sodium sulfate (DSS)-induced colon carcinogenesis mouse model. RESULTS: In Caco2 cells, hemin increased cell proliferation and the expression of cell cycle regulatory proteins, and ROS levels. EGCG suppressed hemin-induced cell proliferation and cell cycle regulatory protein expression as well as mitochondrial ROS accumulation. Hemin increased nuclear factor erythroid-2-related factor 2 (Nrf2) expression, but decreased Keap1 expression. EGCG enhanced hemin-induced Nrf2 and antioxidant gene expression. Nrf2 inhibitor reversed EGCG reduced cell proliferation and cell cycle regulatory protein expression. In AOM/DSS mice, hemin treatment induced hyperplastic changes in colon tissues, inhibited by EGCG supplementation. EGCG reduced the hemin-induced numbers of total aberrant crypts and malondialdehyde concentration in the AOM/DSS model. CONCLUSIONS: We demonstrated that EGCG reduced hemin-induced proliferation and colon carcinogenesis through Nrf2-inhibited mitochondrial ROS accumulation.

Protective mechanisms of loquat leaf extract and ursolic acid against diabetic pro-inflammation.

The pharmacological effectiveness of loquat leaf extract (LE) and its important component, ursolic acid (UA), in the treatment of diabetes mellitus, has been well established in traditional medicine; however, the mechanism underlying their action is still unclear. We evaluated the protective effects of LE and UA against hyperglycemia-induced advanced glycation end product (AGE) formations and hepatic pro-inflammation. Oral administration of UA and LE at a dose of 50 mg/kg/day for 15 days yielded no significant hypoglycemic effect in diabetic db/db mice. UA and LE suppressed hepatic oxidative stress and AGE formation in diabetic mice, and this was followed by the downregulated mitogen-activated protein kinase signaling and nuclear factor κ B (NF-κB) activity. To identify the molecular target of LE and UA, a docking simulation was performed, and this predicted UA to bind to liver kinase B1 (LKB1), an upstream of AMP-activated protein kinase (AMPK)/transcription factor forkhead box O3 (FOXO3) axis. UA reversed the high-glucose-induced downregulation of LKB1-AMPK1-FOXO3 activation and antioxidant gene transcription. These findings demonstrated the antioxidant and anti-inflammatory effects of UA and LE against hyperglycemia-induced hepatic inflammation. Furthermore, we speculate that the LKB1/AMPK/FOXO3 pathway is a potential target responsible for these beneficial effects of LE and UA.

Management and leadership competencies among spiritual care managers.

Both the healthcare and religious landscapes in the United States are rapidly changing. Despite the dynamic environment that spiritual care managers face, many do not receive management training prior to assuming their roles and many receive little or no training once they are in their roles. This study used mixed methods to examine the applicability of the National Center for Healthcare Leadership (NCHL) competency model to spiritual care manager roles. Interviews were conducted with 10 spiritual care managers across the country, using a Behavioral Event Interviewing (BEI) methodology. Interviews were quantitatively analyzed by using Natural Language Processing and qualitatively analyzed by thematic approach using NVIVO. The results found the EXECUTION domain to be the most discussed theme, followed by RELATIONS, TRANSFORMATION, and BOUNDARY SPANNING. Collectively these analyses suggest the NCHL Leadership Competency Model can provide a useful framework for understanding the roles and development needs of spiritual care managers.

Effects of sling-based manual therapy on cervicothoracic junction in patients with neck pain and forward head posture: A randomized clinical trial.

OBJECTIVE: The purpose of this study was to investigate the effect of 4 weeks of sling-based manual therapy on the cervicothoracic junction (CTJ) area in patients with neck pain and forward head posture. DESIGN: Single-blind randomized controlled trial. SETTING: Outpatient, Chonbuk National University hospital, Republic of Korea. SUBJECTS: A total of 22 participants with neck pain (Numeric Pain Rating Scale >3) and forward head posture (craniovertebral angle <51) were randomly assigned to a CTJ group or a control group (n = 11 each). INTERVENTION: In the control group, joint mobilization and motor control training was applied for the upper cervical spine (C0-C1). The CTJ group applied the same intervention to the upper cervical spine and cervicothoracic junction (C7-T3). MAIN MEASURES: Numeric pain rating scale and neck disability index, craniovertebral angle, active range of motion, and muscle activity were evaluated before and after 4 weeks of intervention. RESULT: The CTJ group participants showed significant improvement in the craniovertebral angle and cervical extension range after the intervention than the control group (P = 0.025, P = 0.001). While both groups presented significant differences after the intervention regarding Numeric pain rating scale, neck disability index, and muscle activity (sternocleidomastoid and anterior scalene muscle), there were no statistically significant differences between the groups (P > 0.05). CONCLUSION: Our results suggest that the CTJ and the upper cervical region in patients with neck pain and forward head posture represent an area which if approached by manual therapy, improves cervical mobility and posture.

Comparison of immediate effects of sling-based manual therapy on specific spine levels in subjects with neck pain and forward head posture: a randomized clinical trial.

Purpose: Forward head posture is identified as the flexion of the lower cervical spine along with the extension of the upper cervical spine, with an overall increase in the cervical curve. This study aimed to compare the immediate effect of upper-cervical level and cervicothoracic junction level manual therapy on head posture, cervical range of motion and muscle activity of the subjects with forward head posture.Methods: A total 22 subjects with chronic neck pain (numeric pain rating scale >3, forward head posture: cranio-vertebral angle <51°) participated in the study and were randomly allocated into the upper-cervical (n = 11) and cervicothoracic junction (n = 11) groups. Cranio-vertebral angle, cervical range of motion, and electromyography amplitude during performance of the craniocervical flexion test were measured before and immediately after the intervention.Results/findings: There were no significant main effects for the group by time outcome score of craniovertebral angle and electromyography amplitude. However, in the range of motion of the cervical area, the cervicothoracic junction group showed a significant increase in extension and right rotation than the upper-cervical group (p < 0.05). Moreover, in both groups, the electromyography amplitude of the sternocleidomastoid muscle was significantly reduced after intervention. The electromyography amplitude of the anterior scalene muscle in only the cervicothoracic junction group was significantly reduced after intervention (p < 0.05).Conclusion: Cervicothoracic junction manual therapy improved cervical alignment, cervical mobility (extension, rotation), and muscle recruitment ability in subjects with forward head posture. These observations may partially explain the efficacy of this manual therapy in rehabilitation of individuals with mechanical neck disorder (with forward head posture).Implications for rehabilitationForward head posture is identified as the flexion of the lower cervical spine along with the extension of the upper cervical spine, with an overall increase in the cervical curve.Cervicothoracic area manual therapy in subjects with neck pain and forward head posture better improved the muscle recruitment ability than upper cervical area manual therapy during motor tasks.

Effects of a Newly Developed Therapeutic Deep Heating Device Using High Frequency in Patients with Shoulder Pain and Disability: A Pilot Study.

Objectives: The newly developed therapeutic deep heating device can generate deep heat in focal tissue using high-frequency wave stimulation. The objective of this study was to evaluate and compare the effectiveness of this deep heating device (HIPER-500®) with ultrasound in alleviating pain and improving function in patients with shoulder disability. Methods: This noninferiority trial was designed to compare the treatment effect of HIPER-500® to that of SonoStim® (ultrasound) on shoulder pain and disability. Thirty-eight patients with shoulder problems were assigned to either the HIPER-500® or SonoStim® group, and each participated in 10 min therapy sessions, five days a week for two weeks (for a total of ten sessions). Shoulder pain and disability were evaluated using the Visual Analogue Scale (VAS), the University of California at Los Angeles score (UCLA score), the Shoulder Pain and Disability Index (SPADI), and the Constant score in both groups before, immediately after, and four weeks after treatment. Statistical analysis was performed to compare the effects of treatment within and between the groups. Results: A total of 34 patients completed the study. The 18 patients in the HIPER-500® group and 16 patients in the SonoStim® group all showed significant improvements in shoulder pain and function when comparing pretreatment values with the results immediately after treatment and four weeks later. The results before and after treatment did not show a statistically significant difference between the two groups. Conclusions: The newly developed HIPER-500® for high-frequency deep heat therapy showed similar effects to those of SonoStim® for relieving pain and improving physical performance in the patients of this study. HIPER-500® may be a useful modality for treating shoulder pain and improving physical activity in patients with shoulder disease.

Cannabidiol Enhances the Therapeutic Effects of TRAIL by Upregulating DR5 in Colorectal Cancer.

Cannabidiol, a major non-psychotomimetic compound derived from Cannabis sativa, is a potential therapeutic agent for a variety of diseases such as inflammatory diseases, chronic neurodegenerative diseases, and cancers. Here, we found that the combination of cannabidiol and TNF-related apoptosis-inducing ligand (TRAIL) produces synergistic antitumor effects in vitro. However, this synergistic effect was not observed in normal colonic cells. The levels of ER stress-related proteins, including C/EBP homologous protein (CHOP) and phosphorylated protein kinase RNA-like ER kinase (PERK) were increased in treatment of cannabidiol. Cannabidiol enhanced significantly DR5 expression by ER stress. Knockdown of DR5 decreased the combined effect of cannabidiol and TRAIL. Additionally, the combination of TRAIL and cannabidiol decreased tumor growth in xenograft models. Our studies demonstrate that cannabidiol enhances TRAIL-induced apoptosis by upregulating DR5 and suggests that cannabidiol is a novel agent for increasing sensitivity to TRAIL.

Effect of Early Management on Pain and Depression in Patients with Pancreatobiliary Cancer: A Randomized Clinical Trial.

Background: The present study assessed whether early palliative care (EPC) targeting pain and depression and automated symptom monitoring could improve symptoms in patients with advanced pancreatobiliary cancer. Methods: Patients diagnosed with pathologically confirmed locally advanced or metastatic pancreatic or biliary tract cancer who had cancer-related pain (brief pain inventory (BPI) worst pain score >3) and/or depression (Center for Epidemiological Studies-Depression Scale (CES-D) >16) were randomized within 8 weeks after diagnosis to receive EPC or on-demand palliative care (n = 144 each). EPC included (1) nursing assessment of pain and depression, (2) pain control based on National Comprehensive Cancer Network guidelines, (3) depression control by psychoeducation and/or consultation with a psychiatric specialist, and (4) patient education. The primary end points were ≥50% reductions from baseline to week 4 in pain and depression scores. Results: The proportion of patients in the EPC and usual care groups with ≥50% reductions in pain (29.5% vs. 25.2%; p = 0.4194) and depression (30.8% vs. 36.8%; p = 0.5732) scores from baseline to week 4 did not differ significantly. The proportion of patients with BPI worst pain score ≤3 was significantly higher (51.1% vs. 38.9%, p = 0.0404) and the reduction in pain intensity score significantly greater (1.5 vs. 1.0 points, p = 0.0318) in the EPC than in the usual care group. At 4 weeks, patients in the EPC group reported significant increases in global health status, role of functioning, nausea and vomiting, and pain scores on the European Organization for Research and Treatment of Cancer Core Quality of Life questionnaire (EORTC QLQ-C30) general questionnaire. Conclusions: Although the primary outcome was not met, this trial indicates that EPC may improve early pain relief in patients with advanced pancreatobiliary cancers.

A multicomponent frailty intervention for socioeconomically vulnerable older adults: a designed-delay study.

PURPOSE: The primary aim of this study was to evaluate the effectiveness of a 6-month multicomponent intervention on physical function in socioeconomically vulnerable older adults in rural communities. As secondary aims, we evaluated the effectiveness of the intervention on frailty and other geriatric syndromes, sustained benefit at 12 months, and baseline characteristics associated with poor response. PATIENTS AND METHODS: This designed-delay study was conducted in 187 adults (mean age: 77 years; 75% women) who were living alone or on a low income in three rural regions of Korea. A 24-week multicomponent program that consisted of group exercise, nutritional supplementation, depression management, deprescribing medications, and home hazard reduction was implemented with a planned 6-month interval from August 2015 through January 2017. The primary outcome was physical function, measured using the Short Physical Performance Battery (SPPB) score (range: 0-12; minimum clinically important difference ≥1) at 6 months. Secondary outcomes included frailty phenotype, sarcopenia, Mini Nutritional Assessment-Short Form score (range: 0-14), Center for Epidemiologic Studies-Depression Scale score (range: 0-60), and falls. RESULTS: At 6 months, the SPPB score increased by 3.18 points (95% CI: 2.89, 3.48) from baseline. The program improved frailty (odds ratio: 0.06; 95% CI: 0.02, 0.16), sarcopenia (odds ratio: 0.32; 95% CI: 0.15, 0.68), Mini Nutritional Assessment-Short Form score by 1.67 points (95% CI: 1.28, 2.06), and Center for Epidemiologic Studies-Depression Scale score by -3.83 points (95% CI: -5.26, -2.39), except for fall (rate ratio: 0.99; 95% CI: 0.69, 1.43). These beneficial effects were sustained at 12 months. Body mass index ≥27 kg/m2 and instrumental activities of daily living disability at baseline were associated with poor improvement in the SPPB score. CONCLUSION: This 24-week multicomponent program had sustained beneficial effects up to 1 year on physical function, frailty, sarcopenia, depressive symptoms, and nutritional status in socioeconomically vulnerable older adults in rural communities. (ClinicalTrials.gov, NCT 02554994).

Mechanism of Action of Magnesium Lithospermate B against Aging and Obesity-Induced ER Stress, Insulin Resistance, and Inflammsome Formation in the Liver.

Magnesium lithospermate B (MLB) is the biologically active compound of the water-soluble fraction of Salvia miltiorrhiza. Magnesium lithospermate B exhibits various biological functions, including antidiabetic, neuroprotective, and antioxidant effects. However, its beneficial effects on insulin sensitivity and related signaling pathways in the liver need to be elucidated. Our previous study reported that MLB is a PPARß/δ agonist in fibroblasts. Because insulin-sensitizing and anti-inflammatory effects of PPARß/δ has been reported in the liver, we investigated whether MLB has a beneficial effect on insulin-, ER stress- and inflammasome-related signaling in the livers of aging and obese animal models. Western blotting and protein-ligand docking simulation showed that MLB activated PPARß/δ and improved glucose tolerance in the livers of aging and obese animal models. MLB supplementation ameliorated aging or obesity-induced disruption of insulin signaling in the liver. Consistently, aging and obesity-induced increase in the protein levels of a gluconeogenic phosphoenolpyruvate carboxykinase was decreased by MLB. When molecular signaling pathways related to insulin signaling were examined in the liver, MLB supplementation suppressed ER stress- and inflammasome-related signaling molecules induced by aging and obesity. These results suggest that MLB may improve insulin resistance in the liver at least partially by suppressing ER stress and inflammasome formation in aging and obese animal models.

Identification of candidate UDP-glycosyltransferases involved in protopanaxadiol-type ginsenoside biosynthesis in Panax ginseng.

Ginsenosides are dammarane-type or triterpenoidal saponins that contribute to the various pharmacological activities of the medicinal herb Panax ginseng. The putative biosynthetic pathway for ginsenoside biosynthesis is known in P. ginseng, as are some of the transcripts and enzyme-encoding genes. However, few genes related to the UDP-glycosyltransferases (UGTs), enzymes that mediate glycosylation processes in final saponin biosynthesis, have been identified. Here, we generated three replicated Illumina RNA-Seq datasets from the adventitious roots of P. ginseng cultivar Cheongsun (CS) after 0, 12, 24, and 48 h of treatment with methyl jasmonate (MeJA). Using the same CS cultivar, metabolomic data were also generated at 0 h and every 12-24 h thereafter until 120 h of MeJA treatment. Differential gene expression, phylogenetic analysis, and metabolic profiling were used to identify candidate UGTs. Eleven candidate UGTs likely to be involved in ginsenoside glycosylation were identified. Eight of these were considered novel UGTs, newly identified in this study, and three were matched to previously characterized UGTs in P. ginseng. Phylogenetic analysis further asserted their association with ginsenoside biosynthesis. Additionally, metabolomic analysis revealed that the newly identified UGTs might be involved in the elongation of glycosyl chains of ginsenosides, especially of protopanaxadiol (PPD)-type ginsenosides.

Antihypertensive Effect of Ethanolic Extract from Acanthopanax sessiliflorus Fruits and Quality Control of Active Compounds.

Acanthopanax sessiliflorus (Rupr. & Maxim.) Seem., which belongs to the Araliaceae family, mainly inhabits Korea, China, and Japan. Traditionally, Acanthopanax species have been used as treatment for several diseases such as diabetes, tumors, and rheumatoid arthritis. Especially, its fruits have many biological functions including antitumor, immunostimulating, antithrombosis, and antiplatelet activities. Recently, the extract of A. sessiliflorus fruit has been reported to have antithrombotic and antiplatelet activities related to the alleviation of hypertension. Therefore, we investigated the antihypertensive effect of ethanolic extract from A. sessiliflorus fruits (DHP1501) through in vivo, ex vivo, and in vitro studies. In this study, DHP1501 demonstrated free radical scavenging capacity, enhanced endothelial nitric oxide (NO) production, and inhibited angiotensin-converting enzyme (ACE) activity in spontaneously hypertensive rats (SHRs), resulting in the improvement of vascular relaxation and decrease in blood pressure in the hypertensive animal model. These results suggest that A. sessiliflorus fruit extract may be a promising functional material for the prevention and treatment of hypertension. Furthermore, this study demonstrated the utility of MS-based active compounds for the quality control of DHP1501.

Proton range verification in inhomogeneous tissue: Treatment planning system vs. measurement vs. Monte Carlo simulation.

In particle radiotherapy, range uncertainty is an important issue that needs to be overcome. Because high-dose conformality can be achieved using a particle beam, a small uncertainty can affect tumor control or cause normal-tissue complications. From this perspective, the treatment planning system (TPS) must be accurate. However, there is a well-known inaccuracy regarding dose computation in heterogeneous media. This means that verifying the uncertainty level is one of the prerequisites for TPS commissioning. We evaluated the range accuracy of the dose computation algorithm implemented in a commercial TPS, and Monte Carlo (MC) simulation against measurement using a CT calibration phantom. A treatment plan was produced for eight different materials plugged into a phantom, and two-dimensional doses were measured using a chamber array. The measurement setup and beam delivery were simulated by MC code. For an infinite solid water phantom, the gamma passing rate between the measurement and TPS was 97.7%, and that between the measurement and MC was 96.5%. However, gamma passing rates between the measurement and TPS were 49.4% for the lung and 67.8% for bone, and between the measurement and MC were 85.6% for the lung and 100.0% for bone tissue. For adipose, breast, brain, liver, and bone mineral, the gamma passing rates computed by TPS were 91.7%, 90.6%, 81.7%, 85.6%, and 85.6%, respectively. The gamma passing rates for MC for adipose, breast, brain, liver, and bone mineral were 100.0%, 97.2%, 95.0%, 98.9%, and 97.8%, respectively. In conclusion, the described procedure successfully evaluated the allowable range uncertainty for TPS commissioning. The TPS dose calculation is inefficient in heterogeneous media with large differences in density, such as lung or bone tissue. Therefore, the limitations of TPS in heterogeneous media should be understood and applied in clinical practice.

Magnesium Lithospermate B from Salvia miltiorrhiza Bunge Ameliorates Aging-Induced Renal Inflammation and Senescence via NADPH Oxidase-Mediated Reactive Oxygen Generation.

The present study was conducted to examine whether magnesium lithospermate B (MLB) extracted from Salviae miltiorrhizae radix was renoprotective in pathways related to age-related oxidative stress in aged rats. Magnesium lithospermate B was orally administered at a dose of 2- or 8-mg/kg body weight for 16 consecutive days, and the effects were compared with those of vehicle in old and young rats. Magnesium lithospermate B administration to old rats ameliorated renal oxidative stress through reduction of reactive oxygen species. The old rats exhibited a dysregulation of the expression of proteins related to oxidative stress and inflammation in the kidneys, and MLB administration significantly reduced the protein expression of major subunits of nicotinamide adenine dinucleotide phosphate oxidase (Nox4 and p22phox ), phospho-p38, nuclear factor-kappa B p65, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, MLB-treated old rats showed lower levels of senescence-related proteins such as p16, ADP-ribosylation factor 6, p53, and p21 through effects on the mitogen-activated protein kinase pathway. Magnesium lithospermate B administration also significantly attenuated the age-related increase in serum urea nitrogen, reflecting renal dysfunction, up-regulated podocyte structural proteins, and reduced renal structural injury. Our results provide important evidence that MLB reduces the renal damage of oxidative stress in old rats. Copyright © 2017 John Wiley & Sons, Ltd.