Safety, tolerability and pharmacokinetics and pharmacodynamics of HL2351, a novel hybrid fc-fused interleukin-1 receptor antagonist, in healthy subjects: A first-in-human study.

AIMS: We performed a first-in-human study with HL2351, a novel hybrid Fc-fused interleukin (IL)-1 receptor antagonist, to evaluate its tolerability, pharmacokinetics and pharmacodynamics (PD) after a single subcutaneous (SC) administration in healthy subjects. METHODS: A randomized, double-blind, placebo- and active-controlled, dose-escalation study was conducted. Eligible subjects randomly received a single SC administration of HL2351 (1, 2, 4, 8 and 12 mg/kg) or placebo in a ratio of 8:2. Subjects in the active-controlled group received a single SC administration of anakinra at 100 mg. Serial blood samples were collected for pharmacokinetics and PD analyses. An ex-vivo activation test was performed to evaluate the PD using peripheral blood mononuclear cells treated with IL-1ß. Anti-HL2351 antibodies were determined at baseline and 29 days postdose. Tolerability was assessed throughout the study. RESULTS: HL2351 was eliminated more slowly than anakinra (terminal half-life: 27.21-45.28 vs 3.97 h). Serum concentrations of HL2351 were increased dose-proportionally. The mean apparent clearance of HL2351 were 0.6, 0.66, 0.75, 0.51, 0.65 L/h at 1, 2, 4, 8 and 12 mg/kg, respectively. The percent inhibition of IL-6 expression varied widely (range: 0-92.1%), showing no clear trend or discernible difference between HL2351, anakinra and placebo. HL2351 was well tolerated after a single SC administration. CONCLUSION: HL2351 was well tolerated and showed linear pharmacokinetic characteristics after a single SC administration at doses up to 12 mg/kg in healthy subjects. HL2351 remained in the body 7-11 times longer than anakinra. HL2351 can be developed as a potential therapeutic alternative to anakinra.

Effect of a herbal extract powder (YY-312) from Imperata cylindrica Beauvois, Citrus unshiu Markovich, and Evodia officinalis Dode on body fat mass in overweight adults: a 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trial.

BACKGROUND: YY-312 is a herbal extract powder from Imperata cylindrica Beauvois, Citrus unshiu Markovich, and Evodia officinalis Dode, which have health promoting effects, including body fat reduction. We aimed to evaluate the efficacy and safety of YY-312 for body fat reduction in overweight adults. METHODS: This was a 12-week, randomized, double-blind, placebo-controlled, parallel-group clinical trial performed in overweight Korean adults aged 19-60 years with a body mass index of 25.0-29.9 kg/m2. The daily dose of YY-312 was 2400 mg (containing 1800 mg of active herbal extract and 600 mg of cyclodextrin). Primary outcomes were reductions in body fat mass (BFM) and body fat percentage (BF%) after 12 weeks. Secondary outcomes included reductions in body weight and waist circumference (WC) after 12 weeks. RESULTS: After 12 weeks, BFM (1.6 kg vs. 0.1 kg; P = 0.023) and BF% (1.5% vs. -0.2%; P = 0.018) decreased significantly more in the YY-312 group than in the placebo group, as did body weight (2.7 kg vs. 1.0 kg; P = 0.014) and WC (2.2 cm vs. 0.8 cm; P = 0.049). All safety parameters were within normal limits; no serious adverse events occurred in either group. CONCLUSIONS: In a 12-week clinical trial in overweight adults, YY-312 resulted in significantly greater reduction in body fat vs. placebo, while being safe and well tolerated. TRIAL REGISTRATION: cris.nih.go.kr: ( KCT0001225 ).

TWEAK promotes osteoclastogenesis in rheumatoid arthritis.

Bone destruction is critical in the functional disability of patients with rheumatoid arthritis (RA). Osteoclasts, specialized bone-resorbing cells regulated by cytokines, such as receptor activator of NF-κB ligand (RANKL), are primarily implicated in bone destruction in RA. The aim of the study was to examine whether tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, has osteoclastogenic activity in patients with RA and in animal models, including mice with collagen-induced arthritis (CIA) and IL-1 receptor antagonist knockout (IL-1RaKO) mice. TWEAK was increased in the synovium, synovial fluid, and serum of patients with RA and in the synovium of CIA mice and IL-1RaKO mice. TWEAK induced RANKL expression in mixed joint cells and splenocytes from CIA mice, IL-1RaKO mice, and fibroblast-like synoviocytes from patients with RA. Both osteoclast precursor cells and osteoclasts express TWEAK receptor fibroblast growth factor-inducible 14. In addition, TWEAK enhanced in vitro osteoclastogenesis without the presence of RANKL-providing cells and by inducing RANKL expression in fibroblast-like synoviocytes. Moreover, treatment with fibroblast growth factor-inducible 14-Fc inhibited RANKL-induced osteoclastogenesis, indicating that endogenous TWEAK also has osteoclastogenic activity. Our data demonstrated that TWEAK promotes osteoclastogenesis in RA, suggesting that therapeutic strategies targeting TWEAK could be effective for treatment of patients with RA, especially in preventing bone destruction.

Unhealthy Weight Control Behaviors according to the Status of Combustible Cigarette and Noncombustible Nicotine or Tobacco Product Use among Korean Adolescents with Experience Attempting to Reduce or Maintain Their Body Weight: The 15th Korea Youth Risk Behavior Survey, 2019.

Background: Noncombustible nicotine or tobacco product (NNTP) use, and cigarette smoking are associated with a high likelihood of unhealthy weight control behaviors (UWCBs) among adolescents. However, no study has addressed the differences in UWCBs among non-users, single users of combustible cigarettes (CCs) or NNTPs and dual users. This study compared the frequencies of weight control behaviors according to the status of CC and NNTP use among Korean adolescents. Methods: This was a cross-sectional study of 25,094 adolescents who had attempted to reduce or maintain their body weight during the past 30 days, using data from the 15th Korea Youth Risk Behavior Survey, 2019. Data on the status of CC and NNTP use, weight status, and weight control behaviors were obtained using self-report questionnaires. Subjects were categorized into four groups: non-users, cigarette-only users, NNTP-only users, and dual users. Results: Among boys and girls, current smokers and NNTP users were 8.9%±0.3% and 5.5%±0.3%, and 4.2%±0.2% and 1.7%±0.1%, respectively. Among boys, NNTP-only users were more likely to engage in extreme weight control behaviors than non-users. Among girls, users of either CCs or NNTPs were more likely to engage in extreme weight control behaviors and less extreme weight control behaviors than non-users. Conclusion: This study shows that users of either CCs or NNTPs are more likely to engage in UWCBs, and NNTP-only users are the most likely to do so.

Effect of Lactobacillus sakei OK67 in Reducing Body and Visceral Fat in Lifestyle-Modified Overweight Individuals: A 12-Week, Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Obesity is a global health problem that affects the quality of life. It is a multidimensional chronic risk factor for major medical conditions, such as cardiovascular diseases, diabetes, and cancer. This clinical trial evaluated the efficacy of Lactobacillus sakei OK67 (DW2010), a lactic acid bacterium, in reducing body and visceral fat in overweight individuals (body mass index ≥25 kg/m2 and <30 kg/m2), aged 20-60 years. A total of 100 subjects placed in a lifestyle modification program were randomly assigned to receive either DW2010 (2.0 g/day, 1.0 × 1010 CFU) or a placebo for 12 weeks. The efficacy of DW2010 was evaluated by measuring body fat mass using dual-energy X-ray absorptiometry and visceral fat area using computed tomography. After 12 weeks, the change in body fat in the DW2010 group was not markedly different from that in the placebo group. However, visceral fat area decreased more in the DW2010 group than in the placebo group (p = 0.035). During the clinical trial, no major adverse events were reported. Moreover, no statistical differences were observed in the biochemical parameters of the DW2010 and placebo groups. Overall, we concluded that the intake of DW2010 for 12 weeks is safe and potentially reduces visceral fat in lifestyle-modified overweight subjects.

The Difference in the Prevalence of Metabolic Syndrome According to Meeting Guidelines for Aerobic Physical Activity and Muscle-Strengthening Exercise: A Cross-Sectional Study Performed Using the Korea National Health and Nutrition Examination Survey, 2014-2019.

Physical activity and muscle strengthening are essential for preventing and managing metabolic syndrome. This study was conducted to investigate the relationship between the prevalence of metabolic syndrome and meeting the guidelines for aerobic physical activity (APA), muscle strengthening exercise (MSE), and combined exercise. We used data from 22,467 Koreans aged 40 years or older, who participated in in the Korea National Health and Nutrition Examination Survey (KNHANES) 2014-2019. We used the Global Physical Activity Questionnaire (GPAQ) to measure physical activity and surveyed frequency of MSE through a questionnaire. Metabolic syndrome was defined according to the American heart association and the National Heart, Lung, and Blood Institute. Compared with none exercise group, odds ratios of APA, MSE, and combined exercise group (CEG) on metabolic syndrome prevalence were 0.85 (95% confidence interval (CI), 0.74-0.98), 0.81 (95% CI, 0.67-0.99), and 0.65 (95% CI, 0.54-0.78) among men, respectively. Among women, ORs of APA, MSE, and CEG were 0.83 (95% CI, 0.73-0.93), 0.73 (95% CI, 0.58-0.91), and 0.74 (95% CI, 0.58-0.93), respectively. This study showed that meeting guidelines for APA and MSE was associated with lower prevalence of metabolic syndrome. Furthermore, subjects who met both APA and MSE had the lowest metabolic syndrome prevalence.

Effect of MED-02 Containing Two Probiotic Strains, Limosilactobacillus fermentum MG4231 and MG4244, on Body Fat Reduction in Overweight or Obese Subjects: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Study.

MED-02 is a complex supplement containing two probiotic strains, Limosilactobacillus fermentum MG4231 and MG4244, isolated from humans. The anti-obesity effects and safety profile of MED-02 were assessed in overweight and obese subjects. In this randomized, double-blinded, placebo-controlled, multicenter study, 100 healthy obese and overweight subjects aged 19-65 years with a body mass index (BMI) between 25 and 31.9 kg/m2 were recruited and randomized to receive a placebo or MED-02 (5 × 109 CFU/day). After 12 weeks of consumption, body fat mass (-1166.82 g vs. -382.08 g; p = 0.024) and body fat percentage (-0.85% vs. -0.11%; p = 0.030), as evaluated by dual-energy X-ray absorptiometry (DEXA) and body weight (-2.06 kg vs. -1.22 kg; p = 0.041), were significantly reduced in the MED-02 group compared to the placebo group. The safety profile did not differ among the groups. No serious adverse effects were observed in either group. These results suggest that MED-02 is a safe and beneficial probiotics that reduces body fat and body weight in overweight or obese individuals.

Socioeconomic costs of overweight and obesity in Korean adults.

This study was conducted to estimate the socioeconomic costs of overweight and obesity in a sample of Korean adults aged 20 yr and older in 2005. The socioeconomic costs of overweight and obesity include direct costs (inpatient care, outpatient care and medication) and indirect costs (loss of productivity due to premature deaths and inpatient care, time costs, traffic costs and nursing fees). Hypertension, diabetes mellitus, dyslipidemia, ischemic heart disease, stroke, colon cancer and osteoarthritis were selected as obesity-related diseases. The population attributable fraction (PAF) of obesity was calculated from national representative data of Korea such as the National Health Insurance Corporation (NHIC) cohort data and the 2005 Korea National Health and Nutrition Examination Survey (KNHANES) data. Direct costs of overweight and obesity were estimated at approximately U$1,081 million equivalent (men: U$497 million, women: U$584 million) and indirect costs were estimated at approximately U$706 million (men: U$527 million, women: U$178 million). The estimated total socioeconomic costs of overweight and obesity were approximately U$1,787 million (men: U$1,081 million, women: U$706 million). These total costs represented about 0.22% of the gross domestic product (GDP) and 3.7% of the national health care expenditures in 2005. We found the socioeconomic costs of overweight and obesity in Korean adults aged 20 yr and older are substantial. In order to control the socioeconomic burden attributable to overweight and obesity, effective national strategies for prevention and management of obesity should be established and implemented.

Reliability and Validity of an Ultrasonic Device for Measuring Height in Adults.

BACKGROUND: The ultrasonic stadiometer was originally developed as a device to measure and monitor children's height. However, an ultrasonic stadiometer (InLab S50; InBody Co., Seoul, Korea) was used to measure adults' height in the 2018 Korea Community Health Survey (KCHS). This study was conducted to assess the reliability and validity of the InLab S50 in adults. METHODS: The study subjects were 120 adults (reliability test, n=20; validity test, n=100) who had visited a health screening center. The intra- and inter-rater reliabilities of InLab S50 were assessed using the intraclass correlation coefficient (ICC). The agreement between InLab S50 and an automatic stadiometer (HM-201; Fanics, Busan, Korea) was assessed using Pearson's correlation coefficient and Bland-Altman analysis. RESULTS: The intra- and inter-rater reliabilities of the InLab S50 were excellent (ICC=0.9999 and 0.9998, respectively). The correlation coefficient of the height measured by the two measurement devices was very high (r=0.996). The difference (Δheight [HM-201-InLab S50]) was -0.15±0.78 cm (95% limit of agreement [LOA], -1.69 to 1.38). After excluding the values outside 95% LOA, the difference was further reduced to -0.05±0.59 cm (95% LOA, -1.20 to 1.10). CONCLUSION: This study showed that the InLab S50 is a reliable and valid device for the measurement of adults' height. Therefore, we think that InLab S50 could be used to measure adults' height in household health surveys such as the KCHS.

Risk Factors of Unfavorable Outcomes, Major Bleeding, and All-Cause Mortality in Patients with Venous Thromboembolism.

PURPOSE: This study aimed to analyze the clinical outcomes of venous thromboembolism (VTE) patients and identify the risk factors for VTE-related unfavorable outcomes, major bleeding, and 30-day all-cause mortality. MATERIALS AND METHODS: From January 2016 to December 2020, 198 patients with confirmed VTE were enrolled. Potential risk factors for unfavorable outcomes, major bleeding, and all-cause mortality were analyzed. RESULTS: VTE-related unfavorable outcomes developed in 13.1%, while 30-day all-cause mortality was 8.6%. In the multivariate analysis, a pulse ≥110/min and respiratory rate ≥30/min were statistically significant predictors for VTE-related unfavorable outcomes. Diabetes was a significant risk factor for major bleeding. In addition, a history of malignancy, no anticoagulation treatment, and need for mechanical ventilation were significant predictors of all-cause mortality. CONCLUSION: VTE-related mortality and morbidity rates remained high. In cases of tachycardia and tachypnea, early aggressive treatment is needed to prevent unfavorable outcomes. Patients with risk factors should be closely monitored.

Genetic Parameters for Different Measures of Feed Efficiency and Their Relationship to Production Traits in Three Purebred Pigs.

Residual feed intake (RFI) gained attention as a potential alternative to the feed conversion ratio (FCR). Thus, this study aimed to estimate genetic parameters for different feed efficiency (FE) traits (FCR, RFI1 to RFI5) and their genetic correlation to on-test daily weight gain (ADG), backfat (BFT), loin muscle area (LMA), lean percentage (LP), and total feed intake (FI) for 603 Male Duroc (DD), 295 Landrace (LL), and 341 Yorkshire (YY). The common spatial pen effect was also estimated in these traits. Five RFI measures were estimated by regressing daily feed intake on initial testing age (ITA), initial testing weight (IBW), and ADG for RFI1; other models were the same as RFI1 except for additional BFT for RFI2; LMA for RFI3; BFT and LMA for RFI4; BFT, LMA, and average metabolic body weight (AMBW) instead of IBW for RFI5. Genetic parameters estimated using two animal models and the REML method showed moderate heritability for FCR in all breeds (0.22 and 0.28 for DD, 0.31 and 0.39 for LL, 0.17 and 0.22 for YY), low heritability for the majority of RFI measures in DD (0.15 to 0.23) and YY (0.14 to 0.20) and moderate heritability for all RFI measures in LL (0.31 to 0.34). Pen variance explained 7% to 22% for FE and 0% to 9% for production traits' phenotypic variance. The genetic correlation revealed that selection against less complex RFI1 in DD and LL and RFI2 in YY would bring the most advantageous reduction to FI (0.71 for DD, 0.49 for LL, 0.43 YY) without affecting ADG in all breeds (0.06 for DD, -0.11 for LL, 0.05 for YY), decrease in BFT, and increase in LP in DD (0.51 in BFT, -0.77 in LP) and LL (0.45 in BFT, -0.83 in LP). Therefore, inclusion of these breed-specific RFI measures in the future selection criteria would help improve feed efficiency in the swine industry.

Efficacy and Tolerability of Cyproheptadine in Poor Appetite: A Multicenter, Randomized, Double-blind, Placebo-controlled Study.

PURPOSE: Cyproheptadine, an antihistamine and antiserotonergic agent, is an appetite stimulant that is efficacious in promoting weight gain in children and adults with poor appetite. Despite numerous studies showing that cyproheptadine achieved positive outcomes, studies documenting its effectiveness on appetite are limited. This study evaluated the efficacy and tolerability of cyproheptadine in adults with poor appetite in South Korea. METHODS: Patients aged 19 to 64 years with poor appetite were randomly assigned to receive either cyproheptadine or placebo for 8 weeks. The primary end point was the difference between the groups in change in appetite, as measured by the Korean version of the Edmonton Symptom Assessment System from the beginning to the end of the study period. The secondary end points included effects on weight, anthropometrics, body composition, Simplified Nutritional Appetite Questionnaire-measured appetite, and toxicities. A total of 375 patients were randomly assigned to the two groups (189 cyproheptadine, 186 placebo). FINDINGS: The cyproheptadine group experienced a mean (SD) change in appetite score of -2.42 (0.12) compared with -2.03 (0.13) in the placebo arm, representing a statistically significant appetite gain in the cyproheptadine group (difference, +0.38 [0.18]; 95% CI, -0.73 to -0.04; P = 0.0307). Patients in the cyproheptadine group experienced significant increases in weight and body mass index. The most common adverse event was somnolence, as predicted. Cyproheptadine was well tolerated, with one serious adverse event (colitis) which was classified as a moderate adverse effect unlikely to be related to the study drug. IMPLICATIONS: We present the largest randomized, double-blind, placebo-controlled clinical trial of cyproheptadine versus placebo in healthy adults with poor appetite using the lowest effective dosage of cyproheptadine. Cyproheptadine is a safe treatment option in patients with poor appetite. Our findings provide important information for the use of cyproheptadine to ameliorate poor appetite in adults. Further randomized studies focused on the effect of cyproheptadine in older populations are needed.

IL-23 induces receptor activator of NF-kappaB ligand expression on CD4+ T cells and promotes osteoclastogenesis in an autoimmune arthritis model.

IL-23, a clinically novel cytokine, targets CD4(+) T cells. Recent IL-1Ra(-/-) mouse studies have demonstrated that IL-23 indirectly stimulates the differentiation of osteoclast precursors by enhancing IL-17 release from CD4(+) T cells. IL-17, in turn, stimulates osteoclastogenesis in osteoclast precursor cells. In this study, we found that IL-23 up-regulates receptor activator of NF-kappaB ligand expression by CD4(+) T cells, and thus contributes to osteoclastogenesis. This indirect pathway is mediated by NF-kappaB and STAT3. We have also demonstrated that IL-23 can influence osteoclastogenesis positively under the special conditions in the IL-1-dominant milieu of IL-1Ra(-/-) mice. We propose that IL-23-enhanced osteoclastogenesis is mediated mainly by CD4(+) T cells. The results of this study show that IL-23 is a promising therapeutic target for the treatment of arthritis-associated bone destruction.

Efficacy and Safety of Combined Extracts of Cornus officinalis and Ribes fasciculatum for Body Fat Reduction in Overweight Women.

Obesity is a medical condition that presents excessive fat accumulation with high risk of serious chronic diseases. The aim of this clinical trial is to investigate the anti-obesity effects of Cornus officinalis (CO) and Ribes fasciculatum (RF) on body fat reduction in Korean overweight women. A total of 147 overweight female participants enrolled in double-blinded clinical trial for 12 weeks and 76 participants completed the clinical study. Participants were treated with four CO and RF mixture (COEC; 400 mg per tablet) or four placebo tablets once a day. Obesity associated parameters (body weight, body mass index (BMI), waist circumference, waist-to-hip ratio, body fat percentage and body fat mass) and safety assessment were analyzed. After 12 weeks of COEC treatment, primary outcomes such as body fat percentage (0.76% vs. 0.01%; p = 0.022) and mass (1.1 kg vs. 0.5 kg; p = 0.049) were significantly decreased. In addition, the results were statistically significant between the COEC and placebo groups, strongly indicated that COEC had anti-obesity effects on overweight women. Secondary outcomes-including body weight, waist and hip circumference, waist-to-hip ratio, body mass index and computed tomography measurement of visceral fat area, subcutaneous fat area, total abdominal fat area and visceral-to-subcutaneous fat ratio-were reduced in COEC-treated group, but no statistical differences were found between the COEC and placebo groups. The safety assessment did not differ between the two groups. These results suggest that treatment of COEC extract reduces body fat percentage and mass in Korean overweight women, indicating it as a protective functional agent for obesity.

Different Associations of Socioeconomic Status on Protein Intake in the Korean Elderly Population: A Cross-Sectional Analysis of the Korea National Health and Nutrition Examination Survey.

Socioeconomic status affects food choices. This study examined the relationships between socioeconomic status (SES) and animal and plant protein intake in the Korean elderly population whose protein intake is insufficient. We used cross-sectional data from 3512 Koreans aged 60 years or older, who had participated in the Nutrition Survey of the 2013-14 Korea National Health and Nutrition Examination Survey (KNHANES). One day 24-h recall data was used to estimate the daily total, animal, and plant protein intake. Household income and educational attainment were assessed by trained interviewers. After making adjustment, household income was positively associated with animal protein intake with a statistical significance in females (p = 0.030) and with a marginal significance in males (p = 0.069). However, plant protein intake did not show any significant association. In both sexes, educational attainment was positively associated with animal protein intake (p = 0.007 for males, p = 0.001 for females). Association of educational attainment with plant protein intake was negative in males (p = 0.037) and non-significant in females. (p = 0.945). High SES was associated with higher total protein intake and animal protein intake in the Korean elderly. Health policies and nutrition education are needed to improve protein intake of the vulnerable Korean elderly with low SES.

Oral administration of type-II collagen suppresses IL-17-associated RANKL expression of CD4+ T cells in collagen-induced arthritis.

The receptor activator of nuclear factor kappaB ligand (RANKL) is an osteoclastogenic mediator, which is mainly expressed by stromal cells and osteoblast. However, T cells can also be an important provider for RANKL in special condition such as autoimmune arthritis. We examined the RANKL expression of hyporesponsive CD4+ T cells induced by oral feeding with type II collagen in collagen-induced arthritis (CIA) mice. The potential of RANKL expression in CD4+ T cells was downregulated in tolerance, as compared with CIA. One of possible explanations for this phenomenon is that CII-specific T cell activation was intrinsically impaired in oral tolerance, which caused suppression of RANKL expression of CD4+ T cells. We also investigated the extrinsic role of cytokine in this process. IL-17, well-known pro-inflammatory cytokine was upregulated in CIA and downregulated in tolerance. IL-17 had a potential to stimulate T cells to express RANKL in dose-dependent manner. IL-17-associated RANKL expression of CD4+ T cells was downregulated in oral tolerance, suggesting that the induction of tolerance ameliorates IL-17-induced RANKL expression of T cells in murine CIA. We also discovered that CIA - T cells could enhance osteoclastogenesis but not oral tolerance - T cells. Oral tolerance might be promising therapeutic option in viewpoints of modulating autoreactivity of CII which can induce not only IL-17 production but also RANKL expression in CD4+ T cells.

IL-17 induces the production of IL-16 in rheumatoid arthritis.

The purpose of this study was to investigate the expression of IL-16 in the rheumatoid synovium and the role of inflammatory cytokines and Toll-like receptor (TLR) ligands in IL-16 production by fibroblast-like synoviocytes (FLS) of rheumatoid arthritis (RA) patients. Immunohistochemical staining was performed with a monoclonal antibody to IL-16 in synovial tissues from patients with RA and likewise in patients with osteoarthritis (OA). FLS were isolated from RA synovial tissues and stimulated with IL-15, IL-1beta, IFN-gamma, and IL-17. The IL-16 mRNA level was assessed by semiquantitative RT-PCR and real time (RT) PCR and a comparison was made between IL-16 mRNA levels produced by RA-FLS and OA-FLS. Production of IL-16 was identified by a western blot assay, and IL-16 production after stimulation by specific ligands of TLR2 and TLR4 was assessed by RT-PCR. While immunohistochemical staining demonstrated strong expression of IL-16 mRNA in synovial tissues from patients with RA, similar findings were not present in the OA group. Moreover, mRNA expression of IL-16 by RA-FLS increased after treatment with IL-17 but not with IL-15, IL-1beta, and IFN-gamma. Specifically, IL-17 increased IL-16 mRNA level by RA-FLS and peripheral blood mononuclear cells in a dose-dependent manner. However, IL-17 did not stimulate IL-16 production in OA-FLS. Peptidoglycan, a selective TLR2 ligand, also increased production of IL-16 by RA-FLS dose- dependently, whereas LPS, a selective TLR4 ligand, had no such stimulatory effect. The results from our data demonstrate that IL-17 and TLR2 ligands stimulate the production of IL-16 by RA-FLS.

Animal and Plant Protein Intake and Body Mass Index and Waist Circumference in a Korean Elderly Population.

Controversy exists on whether animal and plant proteins influence obesity differently. The purpose of this study was to evaluate the association between total, animal, and plant protein intake with the body mass index (BMI), waist circumference (WC), and renal function in the Korean elderly. Study participants included Korean adults aged 60 years or older from the Korean National Health and Nutrition Examination Survey in 2013⁻2014. Height, weight, and waist circumference were measured and the body mass index was calculated. One-day 24-hour recall data were used to estimate daily total, animal, and plant protein intake. Glomerular filtration rate (GFR) was calculated by using the Modification of Diet in Renal Disease (MDRD) equation. General linear modellings were used to assess the relationships between protein intake, BMI and WC. The mean age was 69.2 ± 0.2 years and 44.2% were male. The total daily protein intake was 1.1 ± 0.02 g/kg/day and 0.9 ± 0.02 g/kg/day for males and females, respectively. Only one third of protein intake was from animal sources. In males, BMI (regression coefficient (95% CI); −1.30 (−1.55, −1.06), p < 0.001; −0.29 (−0.52, −0.05), p = 0.016; −1.30 (−1.8, −1.02), p < 0.001, respectively) and WC (−3.87 (−4.58, −3.16), p < 0.001; −0.90 (−1.58, −0.22), p = 0.010; −3.88 (−4.68, −3.08), p < 0.001, respectively) decreased as daily intake of plant protein (g/kg/day), animal protein (g/kg/day) and total protein (g/kg/day) increased. Similar associations were shown in Korean females. GFR was not associated with protein intake regardless of protein source in both sexes. In Korean adults aged 60 years or older, the protein intake was associated with a favorable obesity index without decrease in renal function. The effect was similar in both males and females, with both animal and plant proteins.