Planar catechin increases bone mass by regulating differentiation of osteoclasts in mice.

OBJECTIVES: While catechins have been reported to exhibit potential to benefit osteoporosis patients, the effects of planar catechin (PCat), synthesized during the development of drugs for Alzheimer's disease, have not been clearly elucidated. Here, we examined the effects of PCat on mouse bone metabolism both in vivo and in vitro. METHODS: Six week old female mice were orally administered PCat (30 mg/kg) every other day for four weeks, and their femurs were analyzed using micro-computed tomography imaging. Osteoclasts and osteoblasts were collected from mice and cultured with PCat. Subsequently, osteoclast formation and differentiation and osteoblast differentiation were observed. RESULTS: Mice orally administered PCat displayed significantly increased femur bone mass compared to the control group. Quantitative polymerase chain reaction findings indicated that PCat addition to osteoclast progenitor cultures suppressed osteoclast formation and decreased osteoclast marker expression without affecting the proliferative potential of the osteoclast progenitor cells. Addition of PCat to osteoblast cultures increased osteoblast marker expression. CONCLUSIONS: PCat inhibits osteoclast differentiation and promotes osteoblast differentiation, resulting in increased bone mass in mice. These results suggest that PCat administration is a promising treatment option for conditions associated with bone loss, including osteoporosis.

[A Case of Laparoscopic Resection Following Preoperative Chemoradiotherapy of a Locally Recurrent Rectal Cancer after a Prior Endoscopic Curative Resection].

A man in his seventies underwent endoscopic mucosal resection(EMR)of a rectal cancer 3 years ago. Histopathological examination showed that the specimen had been resected curatively. However, a routine follow-up colonoscopy revealed a submucosal mass on the EMR scar. Computed tomography imaging revealed a mass in the posterior wall of the rectum, with suspected invasion of the sacrum. We performed a biopsy during endoscopic ultrasonography and diagnosed a local recurrence of the rectal cancer. After preoperative chemoradiotherapy(CRT), laparoscopic low anterior resection with ileostomy was performed. Histopathological examination revealed invasion of the rectal wall from the muscularis propria to the adventitia and tissue fibrosis at the radial margin, which was devoid of cancerous cells. Subsequently, the patient received adjuvant chemotherapy with uracil/tegafur and leucovorin for 6 months. No recurrence has been reported over a postoperative follow- up period of 4 years. Preoperative CRT may be an effective treatment for locally recurrent rectal cancer after endoscopic resection.

[A Case Report of Rectal MiNEN Laparoscopic Resection].

A 74-year-old woman underwent colonoscopy for positive fecal occult blood test. A colonoscopy revealed a Type 1 tumor in the rectosigmoid region. The tumor was diagnosed as well-differentiated adenocarcinoma(tub1)by biopsy. Laparoscopic high anterior resection was performed. The final diagnosis was MiNEN(adenocarcinoma:NEC=6:4), RS, pT4a(SE), INF c, Ly1c, V1b, Pn1b, BD2, pN2a(5/28), cM0, pStage Ⅲc. All lymph node metastases were of NEC origin. This case was considered to be at high risk of recurrence and require adjuvant chemotherapy focused on NEC. She was referred to an advanced medical institution for carboplatin and etoposide therapy. MiNEN is a rare disease, and has a poor prognosis. In order to establish a therapeutic strategy of MiNEN, it is important to accumulate further cases and evidence.

Cholesterol and fat in diet disrupt bone and tooth homeostasis in mice.

Dyslipidemia is a condition of high levels of triglycerides and cholesterol in the blood, and high levels of cholesterol is associated with a variety of systemic diseases. The effects of a high-fat diet on bone have been reported, however, it is not clear which components of a high-fat diet affect bone. This study was conducted to examine the effects of dietary lipids and cholesterol on bone homeostasis maintenance. Eight-week-old male mice (C57BL/6 J) were fed five types of feed with different amounts of fat (14 %, 36 %) and cholesterol (0.01 %, 1.25 %, 5 %) for 12 weeks. Blood, femur, tibia, and tooth samples were examined, and serum lipid markers and bone morphology were determined using µCT and histological analysis. Additionally, bone marrow cells were obtained and cultured, and osteoclast differentiation markers analyzed using qPCR. Mice fed a diet high in both fat (36 %) and cholesterol (1.25 %) showed increased total cholesterol and low-density lipoprotein levels in blood, and decreased bone volume fraction as compared to the standard diet group. However, bone mass was unaffected in the high fat only (36 %) and high cholesterol only (1.25 %, 5 %) groups. Mice given a high fat (36%) diet also demonstrated significantly narrowed incisor pulp. In contrast, osteoclast formation was not significantly different among the groups. These results suggest that a diet with high amounts of both fat and cholesterol induces bone loss.

Licochalcones extracted from Glycyrrhiza inflata inhibit platelet aggregation accompanied by inhibition of COX-1 activity.

Licochalcones extracted from Glycyrrhiza inflata are known to have a variety of biological properties such as anti-inflammatory, anti-bacterial, and anti-tumor activities, but their action on platelet aggregation has not yet been reported. Therefore, in this study we investigated the effects of licochalcones on platelet aggregation. Collagen and U46619, a thromboxane A2 receptor agonist, caused rabbit platelet aggregation, which was reversed by pretreatment with licochalcones A, C and D in concentration-dependent manners. Among these compounds, licochalcone A caused the most potent inhibitory effect on collagen-induced platelet aggregation. However, the licochalcones showed marginal inhibitory effects on thrombin or ADP-induced platelet aggregation. In addition to rabbit platelets, licochalcone A attenuated collagen-induced aggregation in human platelets. Because licochalcone A also inhibited arachidonic acid-induced platelet aggregation and production of thromboxane A2 induced by collagen in intact platelets, we further examined the direct interaction of licochalcone A with cyclooxygenase (COX)-1. As expected, licochalcone A caused an inhibitory effect on both COX-1 and COX-2 in vitro. Regarding the effect of licochalcone A on COX-1 enzyme reaction kinetics, although licochalcone A showed a stronger inhibition of prostaglandin E2 synthesis induced by lower concentrations of arachidonic acid, Vmax values in the presence or absence of licochalcone A were comparable, suggesting that it competes with arachidonic acid at the same binding site on COX-1. These results suggest that licochalcones inhibit collagen-induced platelet aggregation accompanied by inhibition of COX-1 activity.

Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA3.

The accumulated uremic toxins inhibit the expression of various renal transporters and this inhibition may further reduce renal function and subsequently cause the accumulation of uremic toxins. However, the precise mechanism of the nephrotoxicity of uremic toxins on renal transport has been poorly understood. Here we report that indoxyl sulfate, one of the potent uremic toxins, directly suppresses the renal-specific organic anion transporter SLCO4C1 expression through a transcription factor GATA3. The promoter region of SLCO4C1 gene has several GATA motifs, and indoxyl sulfate up-regulated GATA3 mRNA and subsequently down-regulated SLCO4C1 mRNA. Overexpression of GATA3 significantly reduced SLCO4C1 expression, and silencing of GATA3 increased SLCO4C1 expression vice versa. Administration of indoxyl sulfate in rats reduced renal expression of slco4c1 and under this condition, plasma level of guanidinosuccinate, one of the preferable substrates of slco4c1, was significantly increased without changing plasma creatinine. Furthermore, in 5/6 nephrectomized rats, treatment with oral adsorbent AST-120 significantly decreased plasma indoxyl sulfate level and conversely increased the expression of slco4c1, following the reduction of plasma level of guanidinosuccinate. These data suggest that the removal of indoxyl sulfate and blocking its signal pathway may help to restore the SLCO4C1-mediated renal excretion of uremic toxins in CKD.