Inhibitory effects of Acanthopanax sessiliflorus Harms extract on the etiology of rheumatoid arthritis in a collagen-induced arthritis mouse model.

BACKGROUND: The biological function of Acanthopanax sessiliflorus Harm (ASH) has been investigated on various diseases; however, the effects of ASH on arthritis have not been investigated so far. This study investigates the effects of ASH on rheumatoid arthritis (RA). METHODS: Supercritical carbon dioxide (CO2) was used for ASH extract preparation, and its primary components, pimaric and kaurenoic acids, were identified using gas chromatography-mass spectrometer (GC-MS). Collagenase-induced arthritis (CIA) was used as the RA model, and primary cultures of articular chondrocytes were used to examine the inhibitory effects of ASH extract on arthritis in three synovial joints: ankle, sole, and knee. RESULTS: Pimaric and kaurenoic acids attenuated pro-inflammatory cytokine-mediated increase in the catabolic factors and retrieved pro-inflammatory cytokine-mediated decrease in related anabolic factors in vitro; however, they did not affect pro-inflammatory cytokine (IL-1ß, TNF-α, and IL-6)-mediated cytotoxicity. ASH effectively inhibited cartilage degradation in the knee, ankle, and toe in the CIA model and decreased pannus development in the knee. Immunohistochemistry demonstrated that ASH mostly inhibited the IL-6-mediated matrix metalloproteinase. Gene Ontology and pathway studies bridge major gaps in the literature and provide insights into the pathophysiology and in-depth mechanisms of RA-like joint degeneration. CONCLUSIONS: To the best of our knowledge, this is the first study to conduct extensive research on the efficacy of ASH extract in inhibiting the pathogenesis of RA. However, additional animal models and clinical studies are required to validate this hypothesis.

Evaluation of dietary curcumin nanospheres as phytobiotics on growth performance, serum biochemistry, nutritional composition, meat quality, gastrointestinal health, and fecal condition of finishing pigs.

Curcumin is a bioactive functional feeding stimulant that is widely used as an additive in cuisine and animal feeds. Owing to its hydrophobic nature and low bioavailability, the nanoformulation of curcumin has recently received special attention from researchers. In this study, we investigated the effects of curcumin nanospheres (CN) on the growth performance, serum biochemistry, meat quality, intestinal immunohistochemistry, fecal malodors and microbes in finishing pigs. A total of 90 crossbred pigs (Duroc × [Yorkshire × Landrace]) with an average initial body weight of 73.77 ± 0.08 kg were randomized into 3 dietary groups in triplicate pens (10 pigs in each pen): control (CON) without supplementation of CN and the pigs in the remaining two groups were supplemented with CN at 1.0 (CN1) and 2.0 (CN2) mL/kg diet for a 40-day long experiment. The results showed that pigs fed the higher CN supplemented diet (CN2) had significantly higher final weight (FW) and weight gain (WG) than those fed the CON diet, and no significant differences were observed in the feed conversion ratio (FCR) and average daily feed intake (ADFI) after 28 days. At the end of the experiment, pigs fed the CN supplemented diet showed no significant difference in WG, ADFI or FCR compared to those on the CON diet. Overall, at the termination of the 40-day feeding trial, dietary CN had a significant effect on FW and WG, except for ADFI and FCR, in finishing pigs. After 40 days of the feeding trial, serum biochemical parameters such as glutamic-pyruvic transaminase, glutamic-oxaloacetic transaminase, triglycerides, and total cholesterol levels were significantly decreased in pigs fed the CN supplemented diet. However, high density lipoprotein levels were significantly increased in pigs fed the CN diets. Protein and lipid contents, as well as yellowness and lightness of the neck and longissimus dorsi muscles were not significantly affected by CN supplementation; however, there was a tendency to increase the redness of the longissimus dorsi muscle in pigs fed the CN2 supplemented diet compared to the CON diet. Meat grading and carcass weight significantly increased in pigs fed a higher CN supplemented diet. Fecal Escherichia coli and ammonia gas were significantly depleted in pigs fed CN diets. Histomorphological parameters, such as villus height, crypt depth and goblet cells in the jejunum of the intestine were significantly increased in pigs fed CN diet. Immunohistochemical staining showed that pro-inflammatory cytokine like tumor necrosis factor-α expression was reduced in pigs fed CN supplemented diets compared to the CON diet; however, antibodies such as immunoglobulin A and tight junction proteins such as claudin 3 were highly expressed in the intestine of pigs fed the CN diets. Overall, the results demonstrate the potential of dietary curcumin nanospheres as a nanobiotechnology tool as well as an effective feed additive for improving the performance and health status of finishing pigs.

Targeting Oncogenic Rewiring of Lipid Metabolism for Glioblastoma Treatment.

Glioblastoma (GBM) is the most malignant primary brain tumor. Despite increasing research on GBM treatment, the overall survival rate has not significantly improved over the last two decades. Although recent studies have focused on aberrant metabolism in GBM, there have been few advances in clinical application. Thus, it is important to understand the systemic metabolism to eradicate GBM. Together with the Warburg effect, lipid metabolism has emerged as necessary for GBM progression. GBM cells utilize lipid metabolism to acquire energy, membrane components, and signaling molecules for proliferation, survival, and response to the tumor microenvironment. In this review, we discuss fundamental cholesterol, fatty acid, and sphingolipid metabolism in the brain and the distinct metabolic alterations in GBM. In addition, we summarize various studies on the regulation of factors involved in lipid metabolism in GBM therapy. Focusing on the rewiring of lipid metabolism will be an alternative and effective therapeutic strategy for GBM treatment.

RsTTG1, a WD40 Protein, Interacts with the bHLH Transcription Factor RsTT8 to Regulate Anthocyanin and Proanthocyanidin Biosynthesis in Raphanus sativus.

MBW complexes, consisting of MYB, basic helix-loop-helix (bHLH), and WD40 proteins, regulate multiple traits in plants, including anthocyanin and proanthocyanidin (PA) biosynthesis and the determination of epidermal cell fate. Here, a WD40 gene from Raphanus sativus, designated TRANSPARENT TESTA GLABRA 1 (RsTTG1), was cloned and functionally characterized. Heterologous expression of RsTTG1 in the Arabidopsis thaliana mutant ttg1-22 background restored accumulation of anthocyanin and PA in the mutant and rescued trichome development. In radish, RsTTG1 was abundantly expressed in all root and leaf tissues, independently of anthocyanin accumulation, while its MBW partners RsMYB1 and TRANSPARENT TESTA 8 (RsTT8) were expressed at higher levels in pigment-accumulating tissues. In yeast two-hybrid analysis, the full-length RsTTG1 protein interacted with RsTT8. Moreover, transient protoplast co-expression assays demonstrated that RsTTG1, which localized to both the cytoplasm and nucleus, moves from the cytoplasm to the nucleus in the presence of RsTT8. When co-expressed with RsMYB1 and RsTT8, RsTTG1 stably activated the promoters of the anthocyanin biosynthesis genes CHALCONE SYNTHASE (RsCHS) and DIHYDROFLAVONOL 4-REDUCTASE (RsDFR). Transient expression of RsTTG1 in tobacco leaves exhibited an increase in anthocyanin accumulation due to activation of the expression of anthocyanin biosynthesis genes when simultaneously expressed with RsMYB1 and RsTT8. These results indicate that RsTTG1 is a vital regulator of pigmentation and trichome development as a functional homolog of AtTTG1.

Association Between Changes in Alcohol Consumption and Cancer Risk.

Importance: Although numerous studies have shown an association between alcohol consumption and cancer, how changes in drinking behavior increase or decrease the incidence of cancer is not well understood. Objective: To investigate the association between the reduction, cessation, or increase of alcohol consumption and the development of alcohol-related cancers and all cancers. Design, Setting, and Participants: This population-based cohort study analyzed adult beneficiaries in the Korean National Health Insurance Service. Participants (aged ≥40 years) included those who underwent a national health screening in both 2009 and 2011 and had available data on their drinking status. Data were analyzed from April 16 to July 6, 2020. Exposures: Alcohol consumption level, which was self-reported by participants in health screening questionnaires, was categorized into none (0 g/d), mild (<15 g/d), moderate (15-29.9 g/d), and heavy (≥30 g/d) drinking. Based on changes in alcohol consumption level from 2009 to 2011, participants were categorized into the following groups: nondrinker, sustainer, increaser, quitter, and reducer. Main Outcomes and Measures: The primary outcome was newly diagnosed alcohol-related cancers (including cancers of the head and neck, esophagus, colorectum, liver, larynx, and female breast), and the secondary outcome was all newly diagnosed cancers (except for thyroid cancer). Results: Among the 4 513 746 participants (mean [SD] age, 53.6 [9.6] years; 2 324 172 [51.5%] men), the incidence rate of cancer was 7.7 per 1000 person-years during a median (IQR) follow-up of 6.4 (6.1-6.6) years. Compared with the sustainer groups at each drinking level, the increaser groups had a higher risk of alcohol-related cancers and all cancers. The increased alcohol-related cancer incidence was associated with dose; those who changed from nondrinking to mild (adjusted hazard ratio [aHR], 1.03; 95% CI, 1.00-1.06), moderate (aHR, 1.10; 95% CI, 1.02-1.18), or heavy (aHR, 1.34; 95% CI, 1.23-1.45) drinking levels had an associated higher risk than those who did not drink. Those with mild drinking levels who quit drinking had a lower risk of alcohol-related cancer (aHR, 0.96; 95% CI, 0.92-0.99) than those who sustained their drinking levels. Those with moderate (aHR, 1.07; 95% CI, 1.03-1.12) or heavy (aHR, 1.07; 95% CI, 1.02-1.12) drinking levels who quit drinking had a higher all cancer incidence than those who sustained their levels, but when quitting was sustained, this increase in risk disappeared. Compared with sustained heavy drinking, reduced heavy drinking levels to moderate levels (alcohol-related cancer: aHR, 0.91 [95% CI, 0.86-0.97]; all cancers: aHR, 0.96 [95% CI, 0.92-0.99]) or mild levels (alcohol-related cancer: aHR, 0.92 [95% CI, 0.86-0.98]; all cancers: aHR, 0.92 [95% CI, 0.89-0.96]) were associated with decreased cancer risk. Conclusions and Relevance: Results of this study showed that increased alcohol consumption was associated with higher risks for alcohol-related and all cancers, whereas sustained quitting and reduced drinking were associated with lower risks of alcohol-related and all cancers. Alcohol cessation and reduction should be reinforced for the prevention of cancer.

Targeting Glioblastoma Stem Cells to Overcome Chemoresistance: An Overview of Current Therapeutic Strategies.

Glioblastoma (GBM) is the most malignant primary brain tumor. The current standard approach in GBM is surgery, followed by treatment with radiation and temozolomide (TMZ); however, GBM is highly resistant to current therapies, and the standard of care has not been revised over the last two decades, indicating an unmet need for new therapies. GBM stem cells (GSCs) are a major cause of chemoresistance due to their ability to confer heterogeneity and tumorigenic capacity. To improve patient outcomes and survival, it is necessary to understand the properties and mechanisms underlying GSC chemoresistance. In this review, we describe the current knowledge on various resistance mechanisms of GBM to therapeutic agents, with a special focus on TMZ, and summarize the recent findings on the intrinsic and extrinsic mechanisms of chemoresistance in GSCs. We also discuss novel therapeutic strategies, including molecular targeting, autophagy inhibition, oncolytic viral therapy, drug repositioning, and targeting of GSC niches, to eliminate GSCs, from basic research findings to ongoing clinical trials. Although the development of effective therapies for GBM is still challenging, this review provides a better understanding of GSCs and offers future directions for successful GBM therapy.

Novel Bacillus ginsengihumi CMRO6 Inhibits Adipogenesis via p38MAPK/Erk44/42 and Stimulates Glucose Uptake in 3T3-L1 Pre-Adipocytes through Akt/AS160 Signaling.

The health benefits of probiotics have been known for decades, but there has only been limited use of probiotics in the treatment of obesity. In this study, we describe, for the first time, the role of cell-free metabolites (CM) from Bacillus ginsengihumi-RO6 (CMRO6) in adipogenesis and lipogenesis in 3T3-L1 pre-adipocytes. The experimental results show that CMRO6 treatment effectively reduced lipid droplet accumulation and the expression of CCAAT/enhancer-binding protein α and ß (C/EBPα and C/EBPß), peroxisome proliferator-activated receptor γ (PPAR-γ), serum regulatory binding protein 1c (SREBP-1c), fatty acid-binding protein 4 (FABP4), fatty acid synthase (FAS), acetyl CoA carboxylase (ACC), phosphorylated p38MAPK, and Erk44/42. Additionally, CMRO6 treatment significantly increased glucose uptake and phosphorylated Akt (S473), AS160, and TBC1D1 protein expressions. Considering the results of this study, B. ginsengihumi may be a novel probiotic used for the treatment of obesity and its associated metabolic disorders.

Association of Change in Alcohol Consumption With Risk of Ischemic Stroke.

BACKGROUND: The effect of serial change in alcohol consumption on stroke risk has been limitedly evaluated. We investigated the association of change in alcohol consumption with risk of stroke. METHODS: This study is a population-based retrospective cohort study from National Health Insurance Service database of all Koreans. Four lakh five hundred thirteen thousand seven hundred forty-six participants aged ≥40 years who underwent 2 subsequent national health examinations in both 2009 and 2011. Alcohol consumption was assessed by average alcohol intake (g/day) based on self-questionnaires and categorized into non-, mild, moderate, and heavy drinking. Change in alcohol consumption was defined by shift of category from baseline. Cox proportional hazards model was used with adjustment for age, sex, smoking status, regular exercise, socioeconomic information, and comorbidities, Charlson Comorbidity Index, systolic blood pressure, and laboratory results. Subgroup analysis among those with the third examination was conducted to reflect further change in alcohol consumption. RESULTS: During 28 424 497 person-years of follow-up, 74 923 ischemic stroke events were identified. Sustained mild drinking was associated with a decreased risk of ischemic stroke (adjusted hazard ratio, 0.88 [95% CI, 0.86-0.90]) compared with sustained nondrinking, whereas sustained heavy drinking was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.06 [95% CI, 1.02-1.10]). Increasing alcohol consumption was associated with an increased risk of ischemic stroke (adjusted hazard ratio, 1.11 [95% CI, 1.06-1.17] from mild to moderate; adjusted hazard ratio, 1.28 [95% CI, 1.19-1.38] from mild to heavy) compared with sustained mild drinkers. Reduction of alcohol consumption from heavy to mild level was associated with 17% decreased risk of ischemic stroke through 3× of examinations. CONCLUSIONS: Light-to-moderate alcohol consumption is associated with a decreased risk of ischemic stroke, although it might be not causal and could be impacted by sick people abstaining from drinking. Reduction of alcohol consumption from heavy drinking is associated with a decreased risk of ischemic stroke.

Smoking, Alcohol Consumption, and the Risk of Thyroid Cancer: A Population-Based Korean Cohort Study of 10 Million People.

Background: It is unclear if cigarette smoking and alcohol consumption are associated with thyroid cancer risk. Our aim was to explore for any associations between cigarette smoking and alcohol consumption with thyroid cancer, after adjusting for potential confounders. Methods: Using data from the Korean National Health Insurance database, we retrospectively identified individuals aged ≥20 years who participated in the 2009 health screening program and were followed until 2017. We estimated the adjusted hazard ratio (aHR) for the risk of thyroid cancer using a Cox proportional hazard model, adjusted for age, sex, regular exercise, monthly income, body mass index, diabetes mellitus, and dyslipidemia. Results: During a mean follow-up period of 8.33 ± 0.57 years, of 9,699,104 participants, 89,527 (0.9%) were diagnosed with thyroid cancer. Compared with those who never smoked, current smokers had a lower risk of thyroid cancer (aHR: 0.74, 95% confidence interval [CI]: 0.72-0.76), while ex-smokers did not (aHR: 0.98, 95% CI: 0.96-1.01). There was no significant dose-response relationship with regard to daily amount smoked, duration of smoking, or pack-years. A reduced risk of thyroid cancer was observed in subjects who reported the following categories of alcohol intake (compared with none): mild (aHR: 0.92, 95% CI: 0.90-0.93), moderate (aHR: 0.86, 95% CI: 0.84-0.89), and heavy (aHR: 0.86, 95% CI: 0.82-0.89). Inverse associations with thyroid cancer risk were observed regarding the number of drinking episodes per week and the number of drinks per occasion. A submultiplicative effect of smoking and alcohol consumption was observed (p-interaction <0.001). Conclusions: We observed that thyroid cancer risk was inversely associated with smoking and alcohol consumption, with a significant interaction between these variables.

Chili Pepper AN2 (CaAN2): A Visible Selection Marker for Nondestructive Monitoring of Transgenic Plants.

Selecting transformed plants is generally time consuming and laborious. To develop a method for transgenic plant selection without the need for antibiotics or herbicides, we evaluated the suitability of the R2R3 MYB transcription factor gene CaAN2 from purple chili pepper (Capsicum annuum) for use as a visible selection marker. CaAN2 positively regulates anthocyanin biosynthesis. Transient expression assays in tobacco (Nicotiana tabacum) leaves revealed that CaAN2 actively induced sufficient pigment accumulation for easy detection without the need for a basic helix-loop-helix (bHLH) protein as a cofactor; similar results were obtained for tobacco leaves transiently co-expressing the anthocyanin biosynthesis regulators bHLH B-Peru from maize and R2R3 MYB mPAP1D from Arabidopsis. Tobacco plants harboring CaAN2 were readily selected based on their red color at the shoot regeneration stage due to anthocyanin accumulation without the need to impose selective pressure from herbicides. Transgenic tobacco plants harboring CaAN2 showed strong pigment accumulation throughout the plant body. The ectopic expression of CaAN2 dramatically promoted the transcription of anthocyanin biosynthetic genes as well as regulators of this process. The red coloration of tobacco plants harboring CaAN2 was stably transferred to the next generation. Therefore, anthocyanin accumulation due to CaAN2 expression is a useful visible trait for stable transformation, representing an excellent alternative selection system for transgenic plants.

The R3-Type MYB Transcription Factor BrMYBL2.1 Negatively Regulates Anthocyanin Biosynthesis in Chinese Cabbage (Brassica rapa L.) by Repressing MYB-bHLH-WD40 Complex Activity.

Chinese cabbage (Brassica rapa L.) leaves are purple in color due to anthocyanin accumulation and have nutritional and aesthetic value, as well as antioxidant properties. Here, we identified the R3 MYB transcription factor BrMYBL2.1 as a key negative regulator of anthocyanin biosynthesis. A Chinese cabbage cultivar with green leaves harbored a functional BrMYBL2.1 protein, designated BrMYBL2.1-G, with transcriptional repressor activity of anthocyanin biosynthetic genes. By contrast, BrMYBL2.1 from a Chinese cabbage cultivar with purple leaves carried a poly(A) insertion in the third exon of the gene, resulting in the insertion of multiple lysine residues in the predicted protein, designated BrMYBL2.1-P. Although both BrMYBL2.1 variants localized to the nucleus, only BrMYBL2.1-G interacted with its cognate partner BrTT8. Transient infiltration assays in tobacco leaves revealed that BrMYBL2.1-G, but not BrMYBL2.1-P, actively represses pigment accumulation by inhibiting the transcription of anthocyanin biosynthetic genes. Transient promoter activation assay in Arabidopsis protoplasts verified that BrMYBL2.1-G, but not BrMYBL2.1-P, can repress transcriptional activation of BrCHS and BrDFR, which was activated by co-expression with BrPAP1 and BrTT8. We determined that BrMYBL2.1-P may be more prone to degradation than BrMYBL2.1-G via ubiquitination. Taken together, these results demonstrate that BrMYBL2.1-G blocks the activity of the MBW complex and thus represses anthocyanin biosynthesis, whereas the variant BrMYBL2.1-P from purple Chinese cabbage cannot, thus leading to higher anthocyanin accumulation.

Effect of smoking reduction, cessation, and resumption on cancer risk: A nationwide cohort study.

BACKGROUND: The objective of this study was to investigate the effects of reduction, cessation, and resumption of smoking on cancer development. METHODS: The authors identified 893,582 participants who currently smoked, had undergone a health screening in 2009, and had a follow-up screening in 2011. Among them, 682,996 participated in a third screening in 2013. Participants were categorized as quitters, reducers I (≥50% reduction), reducers II (<50% reduction), sustainers (referent), or increasers (≥20% increase). Outcome data were obtained through December 31, 2018. RESULTS: Reducers I exhibited a decreased risk of all cancers (adjusted hazard ratio [aHR], 0.96; 95% confidence interval [CI], 0.93-0.99), smoking-related cancers (aHR, 0.95; 95% CI, 0.92-0.99), and lung cancer (aHR, 0.83; 95% CI, 0.77-0.88). Quitters had the lowest risk of all cancers (aHR, 0.94; 95% CI, 0.92-0.96), smoking-related cancers (aHR, 0.91; 95% CI, 0.89-0.93), and lung cancer (aHR, 0.79; 95% CI, 0.76-0.83). In further analysis with 3 consecutive screenings, additional smoking reduction (from reducers II to reducers I) lowered the risk of lung cancer (aHR, 0.74; 95% CI, 0.58-0.94) in comparison with sustainers. Quitting among reducers I further decreased the risk of all cancers (aHR, 0.90; 95% CI, 0.80-1.00), smoking-related cancers (aHR, 0.81; 95% CI, 0.81-0.92), and lung cancer (aHR, 0.66; 95% CI, 0.52-0.84) in comparison with sustainers. Smoking resumption after quitting, even at a lower level, increased the risk of smoking-related cancers (aHR, 1.19; 95% CI, 1.06-1.33) and lung cancer (aHR, 1.48; 95% CI, 1.21-1.80) in comparison with sustained quitting. CONCLUSIONS: Smoking cessation and, to a lesser extent, smoking reduction decreased the risks of cancer. Smoking resumption increased cancer risks in comparison with sustained quitting. LAY SUMMARY: Worldwide, tobacco use is the single leading preventable risk factor for cancer and cancer death. This study examined the effects of reduction, cessation, and resumption of smoking on cancer development by measuring smoking behavior repetitively. Although smoking reduction has a substantial cancer prevention benefit for those who cannot quit, cessation should be encouraged whenever possible. Quitters should be monitored to ensure that they do not resume smoking.

Association between Kidney Function, Proteinuria and the Risk of Multiple Myeloma: A Population-Based Retrospective Cohort Study in South Korea.

PURPOSE: While renal impairment is one of the first clinical manifestations of multiple myeloma (MM), declined renal function may conversely be a risk factor for cancers including MM. In this study, we investigated the relationship between chronic kidney disease and MM at a population level. MATERIALS AND METHODS: A total of 9,809,376 adults who participated in a nationwide health screening program and had no MM, cancer or end-stage renal disease at baseline were investigated for incidence of MM. The impact of estimated glomerular filtration rate (eGFR) and random urine dipstick proteinuria, and interactive associations of the two factors on the MM incidence were evaluated. RESULTS: The general incidence of MM was 4.8 per 100,000 person-years (mean follow-up of 8.3 years). Participants with eGFR < 60 mL/min/1.73 m2 (5.8% of participants) had higher MM incidence than those with eGFR ≥ 60 mL/min/1.73 m2 (adjusted hazard ratio, 1.29; 95% confidence interval, 1.17 to 1.43). When eGFR was graded into five levels, there was a significant inverse dose-response relationship between eGFR level and MM incidence at the lower eGFR levels (reference: eGFR 60-89 mL/min/1.73 m2). A dose-response relationship was also found with degree of dipstick proteinuria and incidence of MM. CONCLUSION: Adults with decreased renal function indicated either by decreased eGFR or presence of proteinuria are at a higher risk of developing MM compared to those without, and there is a dose-response relationship between the severity of renal impairment and MM incidence.

Curriculum of gross anatomy education in Korean dental hygiene programs: Perceptions of clinical dental hygienists.

It is essential for dental hygienists to have basic knowledge of gross anatomy to provide efficient treatment. However, gross anatomy course is relatively neglected due to their disparity from actual clinical dental practice. This study aimed to propose an effective dental hygiene gross anatomy curriculum that reflects the opinions of professional clinical dental hygienists. The study had an online-based cross-sectional design and the survey was distributed to clinical dental hygienists via social networks (n = 200). The questionnaire consisted of questions on the utilization of anatomical knowledge in clinical practice, opinions on the contents and methods of gross anatomy education, and general characteristics. The present study found that 186 (93%) used anatomical knowledge at an above-average level. Qualitative analysis indicated that dental implant surgery, radiography, and extraction were the clinical procedures that required the most anatomical knowledge. The clinical dental hygienists answered that the most-necessary knowledge is that of the mandibular nerve, followed by that on the temporomandibular joint, mandible, maxilla, maxillary nerve, and masticatory muscle. The methods proposed to improve gross anatomy education were (in decreasing order of importance) using videos or photographs (X-rays, CT, MRI, etc.), integrating education with clinical subjects, and using a three-dimensional visualization program. Higher education levels of respondents have increased their tendency to believe that the contents and methods of the presented education were necessary. Dental hygienists who utilized anatomical knowledge more often tended to be had a greater appreciation of the necessity of all educational contents and methods.

Associations between Alcohol Consumption Patterns and Risk of Multiple Myeloma: A Nationwide Cohort Study in South Korea.

BACKGROUND: Among the potential modifiable risk factors, the association between alcohol consumption and the risk of multiple myeloma remains controversial. We investigated the effects of weekly average alcohol consumption and drinking pattern on the risk of multiple myeloma using a nationwide representative database. METHODS: We identified 11,737,467 subjects who participated in the Korean National Health Screening Program in 2009 and 2010. Cox regression analyses were performed to calculate the risk of multiple myeloma according to weekly alcohol consumption, drinking frequency, and amount per session. RESULTS: During a mean follow-up period of 6.8 years after a one-year time lag, 6,981 subjects (3,921 men and 3,060 women) were diagnosed with multiple myeloma. Compared with nondrinkers, all drinkers were at a significantly lower risk for multiple myeloma. The risk of multiple myeloma was reduced in a dose-dependent manner: mild drinkers [adjusted HR (aHR), 0.89; 95% confidence interval (CI), 0.84-0.95], moderate drinkers (aHR, 0.83; 95% CI, 0.76-0.91), and heavy drinkers (aHR, 0.76; 95% CI, 0.69-0.85). Furthermore, both drinking frequency and amount per drinking session showed inverse association with the risk of multiple myeloma. CONCLUSIONS: Our large population-based study suggested an inverse dose-dependent association between total average alcohol consumption and the risk of multiple myeloma, and drinking frequency and amount per drinking session seemed to not differ in their relative contribution to the risk of multiple myeloma. IMPACT: On the basis of the unprecedentedly large number of study population analyzed in this study, our study provides solid epidemiologic evidence of alcohol consumption on multiple myeloma risk.

Alcohol Drinking Pattern and Risk of Head and Neck Cancer: A Nationwide Cohort Study.

Alcohol consumption is a major risk factor for head and neck cancer (HNC), yet little data exist examining drinking patterns and HNC risk. In this population-based, retrospective cohort study, 11,737,467 subjects were recruited from the Korean National Health Insurance Service database. The risks of overall HNC and HNC subtypes according to average alcohol consumption, drinking frequency, and daily amount were examined using Cox proportional hazard models. Over the median follow-up of 6.4 years, 15,832 HNC cases were identified. HNC risk linearly increased with drinking frequency (p-trend < 0.01; adjusted hazard ratio [aHR] 1.55, 95% confidence interval [CI] 1.45-1.67 in subjects who drank 7 days/week). HNC risk also increased according to daily amount of alcohol consumption (p-trend < 0.01), but plateaued from 5-7 units/occasion (aHR 1.25, 95% CI 1.19-1.31) to >14 units/occasion (aHR 1.26, 95% CI 1.13-1.40). When stratified by average alcohol consumption, drinking frequency, but not daily amount, showed a linear relationship with HNC risk in moderate and heavy drinkers. When comparing the HNC subtypes, similar tendencies were observed in cancers of the oral cavity, pharynx, and larynx, but not in the salivary gland. In conclusion, drinking frequency is a stronger risk factor for HNC, especially for cancer of the oral cavity, pharynx, and larynx, than the daily amount of alcohol consumption.

Obesity-Independent Association between Glycemic Status and the Risk of Hematologic Malignancy: A Nationwide Population-Based Longitudinal Cohort Study.

There have been conflicting results regarding the association between diabetes and the risk of hematologic malignancies, and its interaction with obesity is unknown. This study determined the risk of hematologic malignancies according to the glycemic status in a population-based study involving health screening 9,774,625 participants. The baseline glycemic status of the participants was categorized into no diabetes, impaired fasting glucose (IFG), newly detected diabetes, diabetes duration <5 years, and diabetes duration ≥5 year groups. The risks of overall and specific hematologic malignancies were estimated using a Cox regression analysis. During a median follow up of 7.3 years, 14,733 hematologic malignancies developed. The adjusted hazard ratio (aHR) for the risk of all the hematologic malignancies was 0.99 (95% confidence interval (CI) 0.95-1.02) for IFG, 0.99 (95% CI 0.91-1.08) for newly detected diabetes, 1.03 (95% CI 0.96-1.11) for diabetes duration <5 years, and 1.11 (95% CI 1.03, 1.20) for diabetes duration ≥5 year groups. The association was independent from obesity. The risk of non-Hodgkin's lymphoma (NHL) increased according to the progression of dysglycemia towards a longer diabetes duration, while Hodgkin's lymphoma did not. This study in Korea demonstrated diabetes to be associated with an increased risk of hematologic malignancies independent of obesity. The NHL risk increased with the diabetes duration.

Loss of the R2R3 MYB Transcription Factor RsMYB1 Shapes Anthocyanin Biosynthesis and Accumulation in Raphanus sativus.

The red or purple color of radish (Raphanus sativus L.) taproots is due to anthocyanins, which have nutritional and aesthetic value, as well as antioxidant properties. Moreover, the varied patterns and levels of anthocyanin accumulation in radish roots make them an interesting system for studying the transcriptional regulation of anthocyanin biosynthesis. The R2R3 MYB transcription factor RsMYB1 is a key positive regulator of anthocyanin biosynthesis in radish. Here, we isolated an allele of RsMYB1, named RsMYB1Short, in radish cultivars with white taproots. The RsMYB1Short allele carried a 4 bp insertion in the first exon causing a frame-shift mutation of RsMYB1, generating a truncated protein with only a partial R2 domain at the N-terminus. Unlike RsMYB1Full, RsMYB1Short was localized to the nucleus and the cytoplasm and failed to interact with their cognate partner RsTT8. Transient expression of genomic or cDNA sequences for RsMYB1Short in radish cotyledons failed to induce anthocyanin accumulation, but that for RsMYB1Full activated it. Additionally, RsMYB1Short showed the lost ability to induce pigment accumulation and to enhance the transcript level of anthocyanin biosynthetic genes, while RsMYB1Full promoted both processes when co-expressed with RsTT8 in tobacco leaves. As the result of the transient assay, co-expressing RsTT8 and RsMYB1Full, but not RsMYB1Short, also enhanced the promoter activity of RsCHS and RsDFR. We designed a molecular marker for RsMYB1 genotyping, and revealed that the RsMYB1Short allele is common in white radish cultivars, underscoring the importance of variation at the RsMYB1 locus in anthocyanin biosynthesis in the radish taproot. Together, these results indicate that the nonsense mutation of RsMYB1 generated the truncated protein, RsMYB1Short, that had the loss of ability to regulate anthocyanin biosynthesis. Our findings highlight that the frame shift mutation of RsMYB1 plays a key role in anthocyanin biosynthesis in the radish taproot.

Association of the Frequency and Quantity of Alcohol Consumption With Gastrointestinal Cancer.

Importance: Although total alcohol consumption is a known risk factor for gastrointestinal (GI) cancers, few studies have attempted to assess the pattern of alcohol drinking in association with GI cancers. Objective: To evaluate the relative association of the frequency of drinking vs the amount of alcohol consumed per occasion with the development of GI cancers. Design, Setting, and Participants: A population-based retrospective cohort study used data from the Korean National Health Insurance System database on 11 737 467 participants without cancer who underwent a national health screening program from January 1, 2009, to December 31, 2010. Participants were followed up from the year after their health screening date until they received a diagnosis of GI cancer, death, or December 31, 2017. The median follow-up duration was 6.4 years (interquartile range, 6.4-7.4 years). Statistical analysis was performed from January 1, 2019, to March 31, 2020. Exposures: Weekly alcohol consumption (nondrinker [0 g/week], mild drinker [0-104 g/week], moderate drinker [105-209 g/week], and heavy drinker [≥210 g/week]), drinking frequency, and amount per occasion. Main Outcomes and Measures: Incident GI cancers at 6 specific sites (esophagus, stomach, colorectal, liver, biliary, and pancreas). Results: Among 11 737 467 participants (6 124 776 women [52.2%]; mean [SD] age, 54.6 [10.4] years), 319 202 (2.7%) developed GI cancer. Compared with nondrinkers, the risk of GI cancer was higher for mild drinkers (adjusted hazard ratio [aHR], 1.04; 95% CI, 1.03-1.05), moderate drinkers (aHR, 1.14; 95% CI, 1.12-1.15), and heavy drinkers (aHR, 1.28; 95% CI, 1.26-1.29). The risk of GI cancer increased linearly with the frequency of drinking in a dose-dependent manner (aHR, 1.39; 95% CI, 1.36-1.41 for individuals who drink every day). In contrast, the risk of GI cancer appeared to increase with consumption up to 5 to 7 units per occasion (aHR, 1.15; 95% CI, 1.14-1.16), and then the HRs were no higher for those with a higher intake per session than 5 to 7 units (8-14 units per occasion: aHR, 1.11; 95% CI, 1.09-1.12; >14 units per occasion: aHR, 1.11; 95% CI, 1.08-1.14). Given similar weekly alcohol consumption levels, the risk of GI cancer increased with a higher frequency of drinking and decreased with a higher amount per occasion. Risk patterns for 6 specific cancers were generally similar to that of all GI cancers. Conclusions and Relevance: In this cohort study, frequent drinking was a more important risk factor for incident GI cancers than the amount of alcohol consumed per occasion. Individuals should be cautioned about regular consumption of small amounts of alcohol in addition to the total amount of alcohol consumption or amount per occasion.

Microbial Dynamics and In Vitro Degradation of Plant Secondary Metabolites in Hanwoo Steer Rumen Fluids.

Plant secondary metabolite (PSM) degradations and feed breakdown into small particles may occur primarily in the rumen. It is possible to predict the rate and extent of feed disappearance in the rumen during incubation by different in vitro techniques, which differ based on the PSM structures, including phenolics, and flavonoids. However, PSM degradation and conversion efficiency in the rumen remains unclear. This study's objective was to evaluate the in vitro degradation of a group of PSMs in the rumen fluid, collected from Hanwoo steer samples. PSMs including rutin, vitexin, myricetin, p-coumaric acid, ferulic acid, caffeic acid, quercetin, luteolin, propyl gallate, and kaempferol were used in their pure forms at 1mg/250 mL in a rumen fluid buffer system. The mixture of selected PSMs and buffer was incubated at 39 °C for 12-72 h, and samples were collected every 12 h and analyzed by a high-performance liquid chromatography-diode array detector (HPLC-DAD) to determine the biotransformation of the polyphenolics. The results revealed that the luteolin, ferulic acid, caffeic acid, coumaric acid, rutin, myricetin, vitexin, kaempferol, and quercetin were decreased after 12 h of incubation in the rumen fluid (p ≤ 0.05) and were more than 70% decreased at 72 h. In contrast, the propyl gallate concentrations were not significantly changed after 24 h of incubation in rumen fluid compared to other metabolites. Finally, microbial dynamics study showed that the Firmicutes, Bacterodetes, Actinobacteria, and Syngergistetes were the dominant phyla found in rumen fluids. The data suggest that most polyphenolic compounds may degrade or reform new complex structures in the rumen.