Fermented milk with Lactobacillus curvatus SMFM2016-NK alleviates periodontal and gut inflammation, and alters oral and gut microbiota.

This study aimed to analyze the effect of milk fermented with Lactobacillus curvatus SMFM2016-NK on periodontal diseases and gut health in a rat model. To improve the effect of Lb. curvatus SMFM2016-NK-fermented milk administration for relieving periodontitis, the periodontitis rat models were treated with the following for 4 wk: 10% skim milk (normal), periodontitis + 10% skim milk (negative control), periodontitis + Lactobacillus rhamnosus GG-fermented milk (positive control), and periodontitis + Lb. curvatus SMFM2016-NK-fermented milk (PD+LCFM). Transcriptional analysis of inflammatory cytokines [tumor necrosis factor α (TNF-α), IL-1ß, IL-6, and IL-10] was performed via quantitative reverse-transcription PCR. The changes in the oral and gut microbiomes after administering Lb. curvatus SMFM2016-NK-fermented milk were analyzed with metagenomics sequencing using DNA extracted from the oral gingival tissues and feces from the cecum of the rat models. After treatment with Lb. curvatus SMFM2016-NK-fermented milk, the relative gene expression levels of TNFA and IL1B in the gingiva decreased in the PD+LCFM group compared with those in the negative control group. In the oral microbiome, the proportion of the phylum Proteobacteria in the PD+LCFM group was lower than that in the negative control after treatment with Lb. curvatus SMFM2016-NK-fermented milk. For the effect in the gut, the relative gene expression levels of inflammatory cytokines in the colon between the normal and negative control groups were not different; however, the expression levels of TNFA and IL1B in the PD+LCFM and positive control groups, respectively, were lower than those in the negative control group. The composition and diversity of the gut microbiome differed among normal, periodontitis, and Lb. curvatus SMFM2016-NK-fermented milk treatment groups. These results indicate that Lb. curvatus SMFM2016-NK-fermented milk could alleviate periodontal and gut inflammation and change oral and gut microbiota.

Late-onset bulky naevocytoma of the perineum masquerading as a malignant melanoma.

Bulky naevocytoma of the perineum is a very rare variant of giant congenital melanocytic naevus (GCMN). It presents as a bulky naevocytic tumour in the perineal region with characteristic histological findings, such as extensive areas with a neural appearance called 'lames foliacees', formation of a pseudofollicular structure and extension of naevus cells between collagen bundles in a row called 'Indian-file' pattern. We report a case of late-onset bulky naevocytoma of the perineum in a 13-year-old girl. The patient presented with two bulky, pedunculated, heavily pigmented masses in the vulvar area that developed in a pre-existing GCMN lesion, which began around puberty and caused severe gait disturbance. Given the possibility of malignant transformation, we conducted staged reduction surgery of the tumour masses, which were found to be intradermal naevi without evidence of malignancy. The patient's gait disturbance improved markedly after surgery.

Clinical assessment of lipid profiles in live kidney donors.

BACKGROUND: Abnormal serum lipid profiles are an issue in chronic kidney disease (CKD), but the clinical ramifications of dyslipidemia in live kidney donors are unclear. Thus, we explored the relationship between serum lipids and residual renal function in living donors post-nephrectomy. METHODS: Charts of living donors who underwent nephrectomy between January 2010 and March 2013 were reviewed, targeting those with 6-month follow-up examinations at minimum. Altogether, 282 donors were studied, examining total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels assayed before donation by standard techniques. Median follow-up time was 14 months. The relationship between postoperative renal function and allograft biopsy results was assessed. Recursive partitioning was applied to identify optimal cut-off points for each parameter. RESULTS: Median (interquartile range) serum TC, TG, LDL, and HDL levels were 183 (161-205) mg/dL, 86 (63-131) mg/dL, 108 (92-128) mg/dL, and 53 (44-62) mg/dL, respectively. The glomerular filtration rate at last follow-up was associated with TC (r = -0.187; P = .002) and LDL (r = -0.172; P = .005) levels, but showed no correlation with TG and HDL. Root nodes of TC and LDL determinations in recursive partitioning were 170.5 mg/dL and 80.5 mg/dL, respectively, serving as thresholds for further evaluation. On logistic regression analysis, the likelihood of CKD (glomerular filtration rate < 60 mL/min/1.73 m(2)) at last follow-up was greater in donors with elevated TC and LDL levels (odds ratio = 1.96 and 3.33; P = .021 and .029, respectively). CONCLUSION: Kidney donors with serum TC and LDL elevations require close observation, given their demonstrable predisposition to CKD after donation.

Impact of metabolic syndrome on postdonation renal function in living kidney donors.

INTRODUCTION: Optimization of kidney donor selection is critical to ensure recovery of the donor. The goal of this study was to determine the influence of metabolic syndrome on renal histology and perioperative renal function in living kidney donors. PATIENTS AND METHODS: Between January 2010 and March 2013, a total of 363 living kidney donors who underwent donor nephrectomy at our institution were enrolled. Metabolic syndrome was diagnosed in patients according to the National Cholesterol Education Program's Adult Treatment Panel III, and renal histology of implantation biopsy specimens and perioperative renal function were compared in participants with or without metabolic syndrome. Using multivariate regression analysis, the goal was to identify which component of metabolic syndrome induces chronic histologic changes and delayed renal function recovery. RESULTS: We identified 30 donors (8.45%) with metabolic syndrome. Donors with metabolic syndrome were older (48.4 ± 9.2 years vs 39.7 ± 11.4 years; P < .001) and more likely to have chronic histologic changes (36.8% vs 9.7%; P = .001) than subjects without metabolic syndrome. Results of the multivariate regression analysis indicated that obesity, hyperglycemia, and hypertriglyceridemia were independently associated with chronic histologic changes. Perioperative renal function was correlated with the presence of metabolic syndrome rather than with chronic histologic changes, and patients with metabolic syndrome were more likely to experience delayed renal function recovery. Linear regression models found that the sum of the metabolic components correlated with renal function 6 months postoperatively, but among all risk factors, only obesity was significantly associated with the occurrence of delayed renal function recovery (odds ratio, 2.67; P = .001). CONCLUSIONS: Although metabolic syndrome in living kidney donors is characterized by chronic histologic changes, perioperative renal function is affected by the syndrome itself rather than by the histologic changes. Obesity is the most important metabolic factor for predicting delayed renal function recovery in living kidney donors, providing an important clinical indicator of postoperative renal function in these patients.

Do the abnormal results of an implantation renal biopsy affect the donor renal function?

BACKGROUND: Living kidney donation has become an important source for renal transplantation. Thus, renal function after donation is an important issue. In this study, we examined histological abnormalities in implantation biopsy specimens from living kidney donors and analyzed the renal function of the remaining kidney. METHODS: Using the 2007 Banff classification system, we analyzed 121 kidneys from living donors who underwent implantation biopsies (IBs) between 2010 and 2011. Donor characteristics, intraoperative factors, and perioperative renal functions, such as serum creatinine and glomerular filtration rate (GFR), were evaluated. Univariate and multivariate regression analyses were performed to identify the factors related to each histological abnormality and postoperative 1-year donor renal function. RESULTS: Most histological abnormalities in healthy living donors were scored as 1 on the Banff scale. Univariate and multivariate analyses revealed that donor age was the only preoperative factor related to tubular atrophy (odds ratio [OR] = 1.104; P = .012) and glomerular sclerosis (OR = 1.050; P = .019). Intraoperative factors were not related to histological parameters. And histological abnormalities did not affect postoperative 1-year renal function. In contrast, donor age, preoperative GFR, and estimated blood loss were significantly related to 1-year postoperative GFR. CONCLUSION: Most histological abnormalities in healthy living donors were minor. The incidence of abnormalities correlated with donor age. However, postoperative renal functions in living donors were not affected by histological abnormalities. Larger-scale investigations with long-term follow-up analysis will be needed.

Reduced pre-pregnancy proteinuria is associated with improving postnatal maternal renal outcomes in IgA nephropathy women.

AIMS: In patients with immunoglobulin A (IgA) nephropathy, postnatal renal outcomes vary depending on kidney function and proteinuria. However, whether a decrease in proteinuria prior to conception improves postnatal maternal renal outcomes is unknown. METHODS: This was a single-center retrospective study. A total of 52 pregnant women with biopsy-proven IgA nephropathy were enrolled in the study between January 2004 and December 2009. We collected data on proteinuria, which had been measured 1 year prior to conception, at conception, during pregnancy, and postnatally. The study outcomes included changes in estimated glomerular filtration rate (eGFR) and proteinuria. RESULTS: The median serum creatinine, eGFR, and proteinuria levels at conception were 0.8 (0.5 - 2.6) mg/dl, 91.2 (24.1 - 157.0) ml/min, 0.7 (0.0 - 3.5) g/g, respectively. Compared with values measured at conception, serum creatinine (0.8 - 1.0 mg/dl, p < 0.01) and proteinuria (0.7 - 1.5 g/g, p < 0.01) increased significantly postnatally, while eGFR decreased (91.2 - 77.8 ml/min, p < 0.01). In a multiple linear regression analysis, proteinuria at conception were independently associated with a faster decline in postnatal maternal eGFR (ß = 4.50, p < 0.05). In addition, a less decline in maternal eGFR was observed in patients with a reduction in proteinuria (> 30%) prior to pregnancy, compared with those with a less reduction (≤ 30%). As for newborn outcomes, preterm delivery, caesarean section, low birth weight < 2,500 g, and need for neonatal intensive care were 15.4%, 46.2%, 25.0% and 7.7%, respectively. CONCLUSIONS: This study showed that in women with IgA nephropathy, proteinuria was significantly associated with the deterioration of postnatal maternal renal outcomes. Our study also suggests that a strategy for reducing proteinuria prior to pregnancy is required to preserve kidney function after delivery.

Synovial chondromatosis in the temporomandibular joint: a case with typical imaging features and pathological findings.

Synovial chondromatosis of the temporomandibular joint is a rare benign joint disorder that has been reported in only a few studies. However, we recently encountered a pathologically proven case of this disorder. This case also showed the typical imaging findings on panoramic radiographs and on CT and MR images. Therefore, we report this case and the imaging and pathological findings.

Inhibition of myeloid cell leukemia-1 by tolfenamic acid induces apoptosis in mucoepidermoid carcinoma.

OBJECTIVES: The aim of this study was to evaluate the role of tolfenamic acid (Tol) and ampiroxicam (Amp) in the apoptotic regulation of YD-15 salivary mucoepidermoid carcinoma (MEC). MATERIALS AND METHODS: The effect of Tol on apoptosis and its mechanism were examined using a 3-(4,5-dimethylthiazol-2-yl)-5-(2,4-disulfophenyl)-2-(4-sulfophenyl)-2H-tetrazolium assay, Sub-G(1) population, Western blot analysis, 4'-6-Diamidino-2-phenylindole staining, reverse transcriptase polymerase chain reaction, immunostaining and small interfering RNA transfection. RESULTS: Tol inhibited cell growth of YD-15 cells but Amp did not. Tol induces apoptosis in YD-15 cells as evidenced by nuclear fragmentation, accumulation of the sub-G1 phase and the activation of caspase 3. Tol inhibited myeloid cell leukemia-1 (MCL-1) at the protein and mRNA levels. The treatment of MCL-1 siRNA to YD-15 cells resulted in the activation of caspase 3 and the inhibition of cell growth. Moreover, MCL-1 was regulated by specificity protein 1, but not by mitogen-activated protein kinases. CONCLUSION: These results suggest that Tol could be a potent anti-cancer drug for YD-15 MEC cells that acts by regulating the MCL-1 protein.

Downregulation of Spry2 by miR-21 triggers malignancy in human gliomas.

Gliomas are associated with high mortality because of their exceedingly invasive character. As these tumors acquire their invasiveness from low-grade tumors, it is very important to understand the detailed molecular mechanisms of invasion onset. Recent evidences suggest the significant role of microRNAs in tumor invasion. Thus, we hypothesized that deregulation of microRNAs may be important for the malignant progression of gliomas. We found that the aberrant expression of miR-21 is responsible for glioma invasion by disrupting the negative feedback circuit of Ras/MAPK signaling, which is mediated by Spry2. Upregulation of miR-21 was triggered by tumor microenvironmental factors such as hyaluronan and growth factors in glioma cells lacking functional phosphatase and tensin homolog (PTEN), but not harboring wild-type PTEN. Consistently with these in vitro results, Spry2 protein levels were significantly decreased in 79.7% of invasive WHO grade II-IV human glioma tissues, but not in non-invasive grade I and normal tissues. The Spry2 protein levels were not correlated with their mRNA levels, but inversely correlated with miR-21 levels. Taken together, these results suggest that the post-transcriptional regulation of Spry2 by miR-21 has an essential role on the malignant progression of human gliomas. Thus, Spry2 may be a novel therapeutic target for treating gliomas.

Apoptotic effect of Polygonum Cuspidatum in oral cancer cells through the regulation of specificity protein 1.

OBJECTIVES: The aim of this study was to evaluate the growth inhibitory and apoptosis-inducing effects and mechanisms of Polygonum cuspidatum root in oral cancer cells. MATERIALS AND METHODS: The testing materials were separated by normal-phase silica gel liquid chromatography. The effect of P. cuspidatum root on apoptotsis and its mechanism were performed using 3-(4,5-dimethylthiazol-20yl)-(3-carboxymethoxyphenyl)-2-(4-sulphophenyl)-2H-tetrazolium) (MTS) assay, western blot analysis, RT-PCR, promoter assay, and (4'-6-Diamidino-2-phenylindole) (DAPI) staining. RESULTS: The methanol extract of P. cuspidatum (MEPC) inhibited the proliferation of oral cancer cells by inducing caspase-dependent apoptosis. Protein and mRNA expression levels and the transactivation of Specificity protein 1 (Sp1) were markedly decreased in KB cells treated with MEPC. Ethyl acetate fraction (EA) from MEPC was more potent than aqueous fraction (AQ) from MEPC to induce apoptosis. F2, F3, and F4 from EA differentially inhibited the growth of KB cells, and it depends on the amount of Emodin in F2, F3, and F4. Moreover, Emodin inhibited oral cancer cell growth and induced caspase-dependent apoptosis by decreasing Sp1. MEPC also decreased an apoptosis-related downstream target of Sp1 protein, survivin. CONCLUSION: The results from this study strongly suggest that MEPC, its fraction, and Emodin may be potential bioactive materials to cause apoptosis mechanism via the down-regulation of Sp1 in oral cancer cells.

Amphiphysin IIb-1, a novel splicing variant of amphiphysin II, regulates p73beta function through protein-protein interactions.

p73 is a nuclear protein that is similar in structure and function to p53. Notably, the C-terminal region of p73 has a regulatory function, through interactions with a positive or negative regulator. In this study, we use the yeast two-hybrid technique to identify a novel p73beta binding protein, designated amphiphysin IIb-1. Amphiphysin IIb-1 is one of the splicing variants of amphiphysin II, and has a shorter protein product than amphiphysin IIb, which has been previously reported. We confirmed that amphiphysin IIb-1 binds full-length p73beta, both in vitro and in vivo. This association is mediated via the SH3 domain of amphiphysin IIb-1 and C-terminal amino acids 321-376 of p73beta. Double immunofluorescence patterns revealed that p73beta is relocalized to the cytoplasm in the presence of amphiphysin IIb-1. Overexpression of amphiphysin IIb-1 was found to significantly inhibit the transcriptional activity of p73beta in a dose-dependent manner. In addition, the cell death function of p73beta was inhibited by amphiphysin IIb-1. These findings offer a new insight into the regulation mechanism of p73beta, and suggest that amphiphysin IIb-1 modulates p73beta function by direct binding.

Intraventricular hemorrhage caused by lateral ventricular meningioma: a case report.

Meningiomas causing intracranial hemorrhage are rare, and hemorrhage from a lateral ventricular meningioma seems to be even rarer. We report a case of trigonal meningioma in a 43-year-old woman who presented with intraventricular hemorrhage, and describe the CT, MRI and angiographic findings.

Deflazacort increases osteoclast formation in mouse bone marrow culture and the ratio of RANKL/OPG mRNA expression in marrow stromal cells.

Information on precise effects of deflazacort on bone cell function, especially osteoclasts, is quite limited. Therefore, the present study was undertaken to test effects of deflazacort on osteoclast-like cell formation in mouse bone marrow cultures and on the regulation of osteoprotegerin (OPG) and its ligand (RANKL) mRNA expressions by RT-PCR in the ST2 marrow stromal cells. TRAP-positive mononuclear cells increased after the treatment of deflazacort at 10(-9) to 10(-7) M alone for 6 days in a dose-dependent manner. Number of TRAP-positive multi-nucleated cells (MNCs) increased significantly with combined treatment of deflazacort at 10(-7) M and 1,25-(OH)2D3 at 10(-9) M compared to that of cultures treated with 1,25-(OH)2D3 alone (p<0.05). Exposure to deflazacort at 10(-7) M in the presence of 1,25-(OH)2D3 at 10(-9) M in the last 3-day culture had greater stimulatory effect on osteoclast-like cell formation than that of the first 3-day culture did. Deflazacort at 10(-10) -10(-6) M downregulated OPG and upregulated RANKL in mRNA levels in a dose-dependent manner. These observations suggest that deflazacort stimulate osteoclast precursor in the absence of 1,25-(OH)2D3 and enhance differentiation of osteoclasts in the presence of 1,25-(OH)2D3. These effects are, in part, thought to be mediated by the regulation of the expression of OPG and RANKL mRNA in marrow stromal cells.

Transfusion-induced malaria in a child after open heart surgery in Korea.

We had an opportunity to evaluate a child who developed fever approximately two to three weeks after the open heart surgery for tetralogy of Fallot. His peripheral blood smear showed rings and various stages of Plasmodium vivax. The patient had received packed red blood cells during the surgery and postoperative care, one unit of which was later proved sero-positive for malaria. The possibility of malaria should be included in the differential diagnosis of the patients with unexplained fever after multiple blood product transfusions for the open heart surgery.

The findings of ruptured hepatocellular carcinoma on helical CT.

To evaluate the helical CT findings of ruptured hepatocellular carcinoma (HCC), 12 patients with ruptured HCC were reviewed with regard to the tumour's location, size and contour protrusion, the appearance of the mass, the enhancement pattern, multiplicity and secondary changes. All ruptured tumours were located at the periphery of the liver and had a protruding contour. The maximum diameter of tumours ranged from 2 cm to 16 cm. Discontinuity of the hepatic surface was seen in 11 cases. In eight cases, CT images during the arterial phase showed a non-enhancing low attenuating lesion with focal discontinuity and peripheral rim enhancement. Seven cases showed separation of tumour content from the peripheral enhancing rim and intraperitoneal rupture of tumour content into the perihepatic space. Because of the similar appearance to an enucleated orbital globe with remaining sclera, this was termed the "enucleation sign". As well as ruptured masses, 10 cases with non-ruptured masses also showed a non-enhancing low attenuating pattern. Seven cases showed a haematoma with high attenuation around the ruptured mass. The peripheral location, protruding contour, discontinuity of the hepatic surface and surrounding haematoma are helpful signs in the diagnosis of ruptured HCC. The "enucleation sign" may be a characteristic finding in ruptured HCC.

Fas-independent apoptosis induced by UVC in p53-mutated human epithelial tumor A431 cells through activation of caspase-8 and JNK/SAPK.

A431 cells/UVC-induced apoptosis/Caspase 8/Fas/JNK/PAPK. We previously observed that p53-mutated human epithelial tumor A431 cells underwent apoptosis after ultraviolet C (UVC) irradiation through the caspases-8 and -3 pathway. Fas/FasL is known to initiate apoptosis in several cell lines via caspase-8 activation. Then, to determine if Fas/FasL mediates apoptosis in A431. we investigated Fas expression and modulation in UVC-irradiated A431 cells. A431 constitutively expressed Fas, which gradually decreased after UVC-irradiation. Pretreatment with a neutralizing anti-Fas antibody, ZB4, did not abrogate the UVC-induced apoptosis. An agonistic anti-Fas antibody, CH11, very slowly induced apoptosis in A431. suggesting that the constitutively expressed Fas had a low functional potential. Hence, UVC-induced apoptosis in A431 seems to occur independent of the Fas signal. Interestingly, however, a pretreatment with CH11 remarkably potentiated UVC-induced apoptosis. An inhibitor of caspase-8, Ac-IETD-CHO, partially inhibited UVC-induced apoptosis. JNK was phosphorylated immediately after exposure to UVC. prior to apoptotic chromatin condensation. Our data suggest that the activation of caspase-8 occurs independent of Fas upregulation, and that JNK/ SAPK contributes to UVC-induced apoptosis in human epithelial A431 cells.

Inducible RGS2 is a cross-talk regulator for parathyroid hormone signaling in rat osteoblast-like UMR106 cells.

Parathyroid hormone (PTH) activates dual signal transduction systems via Galphas and Galphaq proteins. We now report a novel mechanism by which "cross-talk" may occur between the Galphas and Galphaq signaling pathways. RGS2 (Regulator of G protein Signaling 2) mRNA was rapidly and transiently increased only by PTH analogs (PTH1-84, 1-34, 1-31, and PTHrP) that activated the Galphas-mediated cAMP/PKA signaling pathway, whereas activation of the Galphaq-mediated Ca(2+)/PKC signaling pathway by PTH3-34 had no effect on RGS2 expression. Treatment of UMR106 cells with nonPTH activators of the cAMP/PKA signaling pathway such as cholera toxin, forskolin, 8-Br-cAMP, and dibutyryl-cAMP also significantly elevated RGS2 mRNA levels, while activator of the Galphaq pathway PMA did not. Pretreatment using the Galphas signaling pathway inhibitors SQ22536 and H89 significantly blocked PTH-induced RGS2 expression, but the Galphaq signaling pathway inhibitor bisindolylmaleimide I had no effect. Therefore, RGS2 expression is governed solely by the Galphas signaling pathway. Additionally, we demonstrate for the first time that RGS2 binds to both Galphas and Galphaq subunits in their transition state (GDP/AlF(-4)-bound) forms, suggesting that RGS2 has the potential to act as a bridge between the cAMP/PKA and Ca(2+)/PKC pathways, and that it may act as a cross-talk regulator for these two PTH signaling pathways.