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Background Body weight gain is a social issue all over the world. When body weight increased, hepatic fat accumulation also increased and it causes fatty liver disease. Therefore, developing a new treatment method and elucidating its mechanism is necessary. L‐citrulline (L‐Cit) is a free amino acid found mainly in watermelon. No reports regarding its effects on the improvement of hepatic steatosis and fibrogenesis are currently available. The aim of this study was to clarify the effect and the mechanism of L‐Cit on inhibition of body weight gain and hepatic fat accumulation in high‐fat and high‐cholesterol fed SHRSP5/Dmcr rats. Methods L‐Cit or water (controls) was administered to six‐week‐old male SHRSP5/Dmcr rats by gavage for nine weeks. We recorded the level of body weight and food intake while performing the administration and sacrificed rats. After that, the blood and lipid metabolism‐related organs and tissues were collected and analyzed. Results L‐Cit treatment reduced body weight gain and hepatic TC and TG levels, and serum levels of AST and ALT. L‐Cit enhanced AMPK, LKB1, PKA, and hormone‐sensitive lipase (HSL) protein phosphorylation levels in the epididymal fat. L‐Cit treatment improved steatosis as revealed by HE staining of liver tissues and enhanced AMPK and LKB1 phosphorylation levels. Moreover, activation of Sirt1 was higher, while the liver fatty acid synthase (FAS) level was lower. Azan staining of liver sections revealed a reduction in fibrogenesis following L‐Cit treatment. Further, the liver levels of TGF‐β, Smad2/3, and α‐SMA, fibrogenesis‐related proteins and genes, were lower in the L‐Cit‐treated group. Conclusions From the results of analysis of the epididymal fat and the liver, L‐Cit inhibits body weight gain and hepatic fat accumulation by activating lipid metabolism and promoting fatty acid β‐oxidation in SHRSP5/Dmcr rats., L‐citrulline is a free amino acid found mainly in watermelon. Our study suggested that L‐citrulline inhibited body weight gain and improved hepatic steatosis via lipid metabolism pathway in high‐fat and high‐cholesterol fed SHRSP5/Dmcr rats. L‐citrulline may be used as a functional food of improving of body weight gain and fatty liver disease in the future.

Increased body fat mass can lead to lifestyle diseases such as hypertension, diabetes, and hyperlipidemia. Metabolic syndrome is a cluster of conditions that increases the onset of multiple diseases, such as cardiovascular diseases, stroke, and type 2 diabetes, which are closely related to lipid metabolism; therefore, new prevention approaches and treatments are needed. Our study investigated the effects and mechanism of YNCRG on anti-obesity in metabolic syndrome model SHR.Cg-Leprcp/NDmcr (SHRCP) rats. Eight-week-old male SHRCP rats were administered YNCRG or water by gavage for eight weeks and sacrificed. The tissues were immediately dissected for future experiments. We also used WKY rats as a rodent model. YNCRG induced reductions in food intake, body weight, and body fat mass in SHRCP rats. We also analyzed the mechanism of food intake regulation in the hypothalamus. Expression of POMC was significantly increased in the YNCRG group. However, JAK2 showed no change between the two groups. Phosphorylation levels of Akt (Ser473) and FoxO1 were significantly increased in the YNCRG group. Moreover, mTOR was significantly phosphorylated by YNCRG treatment. These results suggest that YNCRG can induce appetite suppression through the mTOR-Akt-FoxO1-POMC signaling pathway. YNCRG also induced a reduction in body fat mass. In adipose tissue, phosphorylation of AMPK was significantly increased in the YNCRG group. Also, LKB1 and PKA (upstream factors of AMPK), and ACC and HSL (downstream factors of AMPK) were significantly phosphorylated with the YNCRG treatment. Our results indicate that YNCRG can treat MetS by decreasing body fat mass of SHRCP rats through appetite suppression and improvement of lipid metabolism.

AIM An investigator-initiated clinical study was carried out to evaluate the therapeutic potency of SR-0379 for the treatment of leg ulcers in patients with Werner syndrome. METHODS A multicenter, open-label study was carried out from September 2017 to February 2018. The inclusion criteria for leg ulcers were: (i) leg ulcers in patients with Werner syndrome, diabetes or critical limb ischemia/venous stasis; and (ii) a wound size of >1 cm and

Background: Madecassoside (MA) is a pentacyclic triterpene saponin that is obtained from Centella asiatica and possesses a wide variety of pharmacological activities. Pre-clinical research studies have shown that MA has favorable therapeutic effects on arthritis, acne, vitiligo and other diseases. However, the effects of MA on obesity have not yet been studied. This study mainly aimed to investigate the effects of MA in protecting against obesity and its underlying mechanism in reducing obesity. Methods: Obese diabetic KKay/TaJcl mice model were randomly divided into two groups: control group (n=8), wherein the mice were given water, and MA group (n=8), wherein the mice were given MA (40mg/kg/day). The body weight of all animals was recorded daily during the initiation of the experiment and they were given single doses of MA through oral gavage daily for 8 weeks. The blood glucose, blood lipid, and serum aminotransferase levels were examined at weeks 4 and 8, respectively. The expression of P-AMPK, SIRT1, P-LKB1, P-ACC, and P-HSL in abdominal fat, mesenteric fat and epididymal fat was measured by western blotting, and the levels of PPARα, CPT1, PGC-1α, UCP-1, Cidea, Cox7a1, and Cox8b were examined by real-time quantitative PCR (RT-qPCR). Results: The results revealed that the body weight of the mice in MA group was significantly reduced, and the body mass index (BMI) showed significant difference between the two groups after 8 weeks of MA treatment. Further research revealed that it affected the mesenteric fat and epididymis fat by activating SIRT1/AMPK signaling pathway, and then promoted fatty acid oxidation of epididymal fat (PPARα , CPT1, and PGC-1α). Last but not the least, it also promoted the expression of UCP-1 and stimulated thermoregulatory genes (Cidea, Cox7a1, and Cox8b) in brown fat and mesenteric fat. Conclusions: Taken together, these findings suggest that MA can inhibit the weight gain in obese diabetic mice, and reduce triglyceride levels, inhibit lipogenesis of mesenteric fat, promote epididymal fat lipolysis and fatty acid oxidation. Furthermore, MA treatment might promote mesenteric fat browning and activate mitochondrial function in brown fat as well as mesenteric fat.

A 57-year-old man had a 2-year history of a painful nodule on the right sole. Physical examination revealed an 8 × 8 mm hyperkeratotic plaque with a central fissure. Excisional biopsy disclosed epithelial invagination surrounded by the acanthotic epidermis with parakeratotic hyperkeratosis and focal hypergranulosis. The invaginated epithelium lacked a cornified layer and was composed of a mixture of small basaloid squamous cells and goblet cells showing tubular structures. The patient was diagnosed with mucinous syringometaplasia. Our literature review established that surrounding acanthosis with hyperkeratosis typically tends to conceal mucinous syringometaplastic changes. Because mucinous syringometaplasia often presents as an asymptomatic papule/nodule with no distinct ulcer, fissure, or depressed area, cases may be overlooked.

Aim In patients with diabetes or ischemia, angiogenesis and infection control are required for chronic leg ulcers, which substantially impair patients’ quality of life. We developed a novel functional peptide, named AG30/5C, with angiogenic and anti-microbial properties. Treatment with AG30/5C significantly accelerated the wound healing of full-thickness defects in mice. To evaluate the safety of AG30/5C in the treatment of leg ulcers, a physician-initiated clinical study was carried out. Methods The first-in-human trial was designed as an open-label treatment with AG30/5C (0.1 mg/mL) given twice per day for 11 days, and with a follow-up period of 17 days. The inclusion criteria for severe skin ulcers were: (i) diabetes or critical limb ischemia; (ii) resistance to standard therapy for 1 month; and (iii) detection of methicillin-resistant Staphylococcus aureus in the skin ulcer. Results Four patients were enrolled in this study, and two patients met these criteria. For the evaluation of safety, three adverse effects were reported as possibly related to AG30/5C treatment; however, these adverse effects were not severe and resolved during or after treatment. Thus, there were no safety concerns. In both patients, the size of the ulcer decreased after treatment (44.62% and 10.23% decrease), and further decreased after the follow-up period (73.85% and 10.23% decrease). The former patient was diagnosed as Werner syndrome and the skin ulcer was resistant to standard therapy; however, it was sensitive to AG30/5C treatment. Conclusions Topical treatment with AG30/5C for severe leg ulcers was safe, well tolerated and effective. Geriatr Gerontol Int 2017; ••: ••–••.

SR-0379 is a functional peptide that has wound healing effect with anti-microbial action, making it an ideal drug to prevent infection. To evaluate the safety, efficacy, and pharmacokinetics of SR-0379 for the treatment of leg ulcers, a physician-initiated, phase I/IIa, first-in-patient clinical study was designed. A multi-center, double-blind, randomized clinical study was conducted from October 2015 to September 2016. The inclusion criteria for leg ulcers were (1) diabetes or critical limb ischemia and (2) wound size, Dermatology: peptide drug development for skin ulcers Chronic leg ulcers result in substantial impairment of patient quality of life with a socioeconomic impact both in terms of medical care and missed work days. A teams led by Hironori Nakagami at Osaka University originally identified a functional peptide, SR-0379, and evaluated the safety and efficacy of SR-0379 for the treatment of leg ulcers in a physician-initiated, first-in-patient, a multi-center, double-blind, randomized clinical study. In the evaluation of efficiency, the skin ulcer reduction rates were improved for the SR-0379 treated groups in a dose-dependent manner, compared for the placebo group with no causal adverse events. Since treatment with SR-0379 for chronic leg ulcers was safe, well tolerated, and effective in this initial clinical trial, the clinical trial on next stage will be designed toward peptide drug development.

An elderly male noticed urticarial patches corresponding to cutaneous B cell lymphoma lesions after rituximab treatment. Along with the resolution of urticaria, the lymphoma lesions completely remitted without recurrence. In this communication, we present an interesting case and the pathophysiological findings of a wheal attack in a case with tumor remission following systemic treatment with rituximab, a monoclonal anti-CD20 antibody.

Adalimumab, a fully human anti-tumor necrosis factor monoclonal antibody, was retrospectively evaluated for its effect on musculoskeletal manifestations and health-related quality of life in patients with psoriatic arthritis (PsA) during daily clinical practice.Patients who initiated adalimumab therapy after March 2010 were followed for at least 24 weeks with the clinical outcome measures. Eleven patients, all men with a mean age of 45.4 years, had mean psoriasis durations of 16.2 and 8.4 years at baseline.After 24 weeks, 72.7, 63.6, and 45.5 % of the patients met the ACR 20, 50, and 70 response criteria, respectively, while 81.8 % achieved the PsA response criteria. Disease Activity Score using the 28-joint count and CRP declined from 3.2 ± 1.2 at baseline to 1.3 ± 0.4 at week 24 (P0.01). The Bath Ankylosing Spondylitis Disease Activity Index and Bath Ankylosing Spondylitis Functional Index scores also decreased significantly (both P values were0.01). After 24 weeks, three out of eight dimensions of the Medical Outcomes Study 36-Item Short Form Health Survey and Physical Component Summary were significantly improved (all P values were0.05).Adalimumab exerted its effect as early as week 4, and it was sustained until the end of the 24-week observation period in the PsA patients.