Green tea polyphenol sensing

Green tea polyphenols have emerged over the past two decades as an important dietary factor for health promotion. There is considerable evidence that tea polyphenols, in particular (−)-epigallocatechin-3-gallate (EGCG) inhibit carcinogenesis. However, the mechanisms for the cancer-preventive activity of EGCG are not completely characterized and many features remain to be elucidated. Recently we have identified a cell-surface EGCG receptor and the relating molecules that confer EGCG responsiveness to many cancer cells at physiological concentrations. Here, we review some of the reported mechanisms for the cancer chemopreventive action of EGCG and provide an overview of several molecules that sense and manage the physiological functions of EGCG

Oxygen partial pressure modulates 67-kDa laminin receptor expression, leading to altered activity of the green tea polyphenol, EGCG

Abstract(−)-Epigallocatechin-3-O-gallate (EGCG) exhibits anti-tumor activity mediated via the 67-kDa laminin receptor (67LR). In this study, we found that 67LR protein levels are reduced by exposure to low O2 levels (5%), without affecting the expression of HIF-1α. We also found that EGCG-induced anti-cancer activity is abrogated under low O2 levels (5%) in various cancer cells. Notably, treatment with the proteasome inhibitor, prevented down-regulation of 67LR and restored sensitivity to EGCG under 5% O2. In summary, 67LR expression is highly sensitive to O2 partial pressure, and the activity of EGCG can be regulated in cancer cells by O2 partial pressure

Nuclear Hormone Receptor Expression in Mouse Kidney and Renal Cell Lines

Nuclear hormone receptors (NHRs) are transcription factors that regulate carbohydrate and lipid metabolism, immune responses, and inflammation. Although several NHRs, including peroxisome proliferator-activated receptor-γ (PPARγ) and PPARα, demonstrate a renoprotective effect in the context of diabetic nephropathy (DN), the expression and role of other NHRs in the kidney are still unrecognized. To investigate potential roles of NHRs in the biology of the kidney, we used quantitative real-time polymerase chain reaction to profile the expression of all 49 members of the mouse NHR superfamily in mouse kidney tissue (C57BL/6 and db/m), and cell lines of mesangial (MES13), podocyte (MPC), proximal tubular epithelial (mProx24) and collecting duct (mIMCD3) origins in both normal and high-glucose conditions. In C57BL/6 mouse kidney cells, hepatocyte nuclear factor 4α, chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) and COUP-TFIII were highly expressed. During hyperglycemia, the expression of the NHR 4A subgroup including neuron-derived clone 77 (Nur77), nuclear receptor-related factor 1, and neuron-derived orphan receptor 1 significantly increased in diabetic C57BL/6 and db/db mice. In renal cell lines, PPARδ was highly expressed in mesangial and proximal tubular epithelial cells, while COUP-TFs were highly expressed in podocytes, proximal tubular epithelial cells, and collecting duct cells. High-glucose conditions increased the expression of Nur77 in mesangial and collecting duct cells, and liver x receptor α in podocytes. These data demonstrate NHR expression in mouse kidney cells and cultured renal cell lines and suggest potential therapeutic targets in the kidney for the treatment of DN

Oxidative Deamination Activity of EGCG

(-)-Epigallocatechin-3-O-gallate (EGCG), the most abundant polyphenol in green tea, mediates the oxidative modification of proteins, generating protein carbonyls. However, the underlying molecular mechanism remains unclear. Here we analyzed the EGCG-derived intermediates generated upon incubation with the human serum albumin (HSA) and established that EGCG selectively oxidized the lysine residues via its oxidative deamination activity. In addition, we characterized the EGCG-oxidized proteins and discovered that the EGCG could be an endogenous source of the electrically-transformed proteins that could be recognized by the natural antibodies. When HSA was incubated with EGCG in the phosphate-buffered saline (pH 7.4) at 37°C, the protein carbonylation was associated with the formation of EGCG-derived products, such as the protein-bound EGCG, oxidized EGCG, and aminated EGCG. The aminated EGCG was also detected in the sera from the mice treated with EGCG in vivo. EGCG selectively oxidized lysine residues at the EGCG-binding domains in HSA to generate an oxidatively deaminated product, aminoadipic semialdehyde. In addition, EGCG treatment results in the increased negative charge of the protein due to the oxidative deamination of the lysine residues. More strikingly, the formation of protein carbonyls by EGCG markedly increased its cross-reactivity with the natural IgM antibodies. These findings suggest that many of the beneficial effects of EGCG may be partly attributed to its oxidative deamination activity, generating the oxidized proteins as a target of natural antibodies

High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

Metallothionein (MT) is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2) are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy

Development of stepping measurement device for evaluation of and training in walking

急性膵炎の回復後その発症原因の検索において発見された小膵癌の3例を報告し，膵炎の発症原因の一つとして膵癌を常に念頭におく必要があることを強調した。またスクリーニング検査および精査において小膵癌を診断する手順について考察を加えた。症例1は初回発作の回復後に，症例2および症例3は再発発作の回復後に急性膵炎の発症原因の検索を目的に紹介された。いずれの症例においても血清腫瘍マーカーは正常植を示し，腹部USおよびCTは腫瘍から尾側の膵管の拡張を示したが腫瘍そのものは描出はできなかった。症例1ではERCP像から膵体部癌を強く疑い，症例2と症例3ではERCP像と細胞診陽性所見から膵頭部癌と確診し，手術を行った。腫瘍の最大径は症例1では0.9cm，症例2では1.5cm，症例3では2.0cmであり，いずれも転移を認めず根治切除可能であった。Although gait training equipment such as the bicycle ergometer and treadmill exists for patients whose walking ability is high, there is no appropriate gait training mehtod or training instrument for patients whose walking ability has become impaired, who often use a cane or walker, etc. in the course of daily life. In the case of gait training for persons whose walking ability involves impaired locomotion, there is always the danger of a fall. Consequently, a caregiver is required, and the effect of the training is cut by half because the patient's anxiety about falling is exacerbated. Slow stepping affords strengthening and balance training of the leg muscles for patients whose walking ability has become low, and walking ability is improved. However,whether such training appropriately carries out stepping and the degree of the effect of such training has not been evaluated. Therefore, we have developed a stepping measturement device that monitors stepping for evaluation and training of walking ability. This system consists of two mat switches for stepping, a measuring circuit for stepping detection, and a book-sized personal computer with a PC card-type AD converter. This system can detect a left or right single stance phase and a double stance phase relative to the ON, OFF condition of the mat switch. After measurement, the following items are analyzed and displayed : ・number of steps, ・average time of double stance phase, ・the average time of single stance phase, and so on. Finally, we measured the stepping of subjects whose walking ability is low, and showed the relationship between daily walking conditions and stepping conditions. The effectiveness of this system was considered in light of the results

MEFV gene mutations in neuro-Behçet's disease and neuro-Sweet disease

ArticleAnnals of clinical and translational neurology. 6(12): 2595-2600 (2019)journal articl

Usefulness of Endoscopic Managements in Patients with Ceftriaxone-Induced Pseudolithiasis Causing Biliary Obstruction

Ceftriaxone (CTRX) is known to cause reversible biliary stones/sludge, which is called biliary pseudolithiasis. We report two rare cases of biliary obstruction by pseudolithiasis shortly after completing CTRX treatment. Stones and sludge, which had not been detected before CTRX administration, appeared in the gallbladder and common bile duct and led to biliary obstruction and acute cholangitis. The obstructions were successfully treated with endoscopic retrograde biliary drainage and endoscopic sphincterotomy. CTRX-induced biliary pseudolithiasis has been reported mainly in children and adolescents but is also seen in adults with similar incidence rate. Although CTRX-induced biliary pseudolithiasis is usually asymptomatic and disappears spontaneously after discontinuing the drug, some patients develop biliary obstruction. Endoscopic managements should be considered in such cases