Lagerstroemia macrocarpa extract inhibits Th2-mediated STAT6 signaling pathway in human keratinocytes.

In this study, we examined physiological functions as a key material to develop cosmeceuticals using extracts of Lagerstroemia macrocarpa Wall. Ex Kurz (L. macrocarpa). Initially, the L. macrocarpa extract was treated by different concentration and antioxidant assay (DPPH and ABTS) were performed to measure free radical scavenging ability. In the cytotoxicity experiment, the extract was treated into human epidermal keratinocytes with different concentrations to measure cytotoxicity. We found that the extract induces differentiation markers such as keratin (KRT)1, KRT2, KRT9, KRT10 in keratinocytes. Furthermore, the extract significantly induces involucrin (IVL), loricrin (LOR), claudin1 (CLDN1), and filaggrin (FLG) expression, suggesting that it may enhance skin barrier functions. Especially, the extract restored FLG expression inhibited by interleukin (IL)-4/IL-13 in in vitro atopic dermatitis-like model. Therefore, we expect L. macrocarpa extract will be an effective material to develop the therapeutic and cosmeceutical of atopic dermatitis.

Impact of albuminuria on early-onset type 2 diabetes mellitus: a nationwide population-based study.

Background: Early-onset diabetes mellitus has a significant lifetime burden and is associated with higher morbidity and mortality. Since insulin resistance is one of the mechanisms of podocyte injury, we aimed to evaluate the effect of albuminuria on newly developed early-onset type 2 diabetes mellitus (T2DM). Methods: We screened 6,891,399 subjects aged ≥20 and <40 years without a history of prediabetes or diabetes from the Korean National Health Insurance Service database between 2009 and 2012. A multivariate Cox proportional hazard model was used to identify the impact of albuminuria on early-onset T2DM. Results: Among a total of 5,383,779 subjects, 62,148 subjects (1.2%) developed early-onset diabetes over 7.3 ± 1.2 years. Albuminuria was significantly associated with early-onset T2DM (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.55-1.70) after adjustment for age, sex, anthropometric data, physical exercise status, serum glucose, and total cholesterol. The risk of early-onset T2DM increased more in subjects with more components of metabolic syndrome (MetS). Among each component of MetS, hypertriglyceridemia was prominently associated with early-onset T2DM (aHR, 2.02; 95% CI, 1.81-2.25) in subjects with albuminuria. Conclusion: Dipstick albuminuria was significantly associated with early-onset T2DM in young adult populations. Close monitoring of albuminuria is warranted for disease risk modification, especially in subjects with MetS.

Causal Effect of Chondroitin, Glucosamine, Vitamin, and Mineral Intake on Kidney Function: A Mendelian Randomization Study.

The causal effects of chondroitin, glucosamine, and vitamin/mineral supplement intake on kidney function remain unknown, despite being commonly used. We conducted a two-sample summary-level Mendelian randomization (MR) analysis to test for causal associations between regular dietary supplement intake and kidney function. Genetic instruments for chondroitin, glucosamine, and vitamin/mineral supplement intake were obtained from a genome-wide association study of European ancestry. Summary statistics for the log-transformed estimated glomerular filtration rate (log-eGFR) were provided by the CKDGen consortium. The multiplicative random-effects inverse-variance weighted method showed that genetically predicted chondroitin and glucosamine intake was causally associated with a lower eGFR (chondroitin, eGFR change beta = -0.113%, standard error (SE) = 0.03%, p-value = 2 × 10-4; glucosamine, eGFR change beta = -0.240%, SE = 0.035%, p-value = 6 × 10-12). However, a genetically predicted vitamin/mineral supplement intake was associated with a higher eGFR (eGFR change beta = 1.426%, SE = 0.136%, p-value = 1 × 10-25). Validation analyses and pleiotropy-robust MR results for chondroitin and vitamin/mineral supplement intake supported the main results. Our MR study suggests a potential causal effect of chondroitin and glucosamine intake on kidney function. Therefore, clinicians should carefully monitor their long-term effects.

Correlation between the time elapsed after liposuction and the risk of fat embolism: An animal model.

BACKGROUND: Liposuction has become one of the most frequently performed procedures in the field of aesthetic surgery. Fat embolism syndrome after liposuction can easily be overlooked or underestimated; however, occasionally, fulminating fat embolism syndrome can develop and lead to a critical situation within 2-3 days after lipoplasty. Changes over time in the amount of circulating fat particles and the histology of major organs have not yet been studied. METHODS: This study was conducted using 18 male Sprague-Dawley rats aged 12 weeks and weighing 500-628 g (average, 562 g). Fifteen rats were used as the experimental group and 3 as the control group. Under general anesthesia, tumescent-technique liposuction was performed at the lateral flank areas and abdomen for 1 hour. Blood, lung, and brain tissue specimens were obtained at 1 hour, 1 day, and 2 days after the liposuction procedure. RESULTS: The average number of fat particles in the blood samples was 25,960/dL at 1 hour, 111,100/dL at 24 hours, and 21,780/dL at 48 hours. The differences between study groups were statistically significant. Both intravascular and extravascular fat particles with inflammation were seen in all 15 rats, as were inflammatory cell infiltration, hemorrhage, and consolidation with shrinkage of the lung alveoli. CONCLUSIONS: These results imply that there is a strong possibility of fat embolism syndrome after liposuction in real clinical practice, and the first 24-48 hours after the operation were found to be the most important period for preventing pulmonary embolism and progression to fulminating fat embolism syndrome.

Solitary Fibrous Tumor in Buccal Cheek Mucosa.

A solitary fibrous tumor is a relatively uncommon neoplasm that usually occurs in the pleura but occurs extremely rarely in the oral cavity. Reported herein is a rare case of a solitary fibrous tumor in the buccal cheek mucosa. A 50-year-old man visited the authors' hospital due to a buccal cheek mass whose size had increased. Excisional biopsy was done under local anesthesia. After the excisional biopsy, the patient was diagnosed to have a solitary fibrous tumor. In immunohistochemistry, the patient's solitary fibrous tumor was characterized by the expression of CD34 and CD99 on the neoplastic cells, and negativity for Bcl-2 and S-100. No recurrence or complication occurred for a period of 5 years. The growth of a primary solitary fibrous tumor in the buccal cheek mucosa is extremely rare and has been rarely reported in the South Korean medical literature. A solitary fibrous tumor must be distinguished from other spindle cell tumors. Presented herein is a case of primary solitary fibrous tumor in the buccal cheek mucosa. The relevant literature is briefly reviewed.

The Efficacy of Coblator in Turbinoplasty.

BACKGROUND: Turbinate hypertrophy is one of the common causes of chronic nasal obstruction. In principle, therapeutic guidelines recommend medical treatment. Failure to treat turbinate thickening despite drug therapy may indicate the need for surgery. The main aim of this study was to determine the effect of radiofrequency surgery, among various other surgical procedures, on people with both nasal septal deviation and turbinate hypertrophy. METHODS: Among people with nasal deviation who visited the subject hospital between July 2008 to July 2014, 21 people with nasal septal deviation and severe turbinate hypertrophy before their surgery had undergone septoplasty with turbinoplasty using radiofrequency combined with septoplasty. The degree of the turbinate's hypertrophy was appraised in all the patients before and after the surgery using the rhinoscopy, and acoustic rhinometry was objectively carried out. The subjective effect of the turbinoplasty using radiofrequency was explored through the visual analog scale (VAS) score. RESULTS: The degree of contraction of the nasal mucosa after the rhinoscopy changed from Grades 3 and 4 (100%) to Grades 1 and 2 (95.2%) and Grades 3 (4.8%). The minimal cross-sectional area significantly increased from 0.44±0.07 to 0.70±0.07 cm2 (p<0.05). The nasal cavity volume increased from 4.79±0.49 to 6.76±0.55 cm2 (p<0.05). The subjective symptoms evaluated with VAS score a year after the surgery significantly improved (p<0.05). CONCLUSION: Turbinoplasty using Coblator with septoplasty is an effective treatment method because it expands nasal cavity, has a low incidence of complications, subjectively improves symptoms, and has short treatment duration.

Renal protection by 3H-1,2-dithiole-3-thione against cisplatin through the Nrf2-antioxidant pathway.

Cisplatin is commonly used for the treatment of several solid tumors. However, its clinical use is often limited by renal toxicity. The indirect antioxidant 3H-1,2-dithiole-3-thione (D3T) has been known to protect cells from oxidative damage by up-regulating the expression of antioxidative genes through the transcription factor NF-E2-related factor 2 (Nrf2) pathway. We hypothesized that D3T treatment may be protective against cisplatin-induced nephrotoxicity by enhancing the antioxidative capacity of renal cells. In cultured murine tubular epithelial cells, D3T facilitates the nuclear accumulation of Nrf2 and the subsequent expression of its target genes such as glutamate cysteine ligase (GCL). Increased GSH pool in D3T-treated renal cells appears to be associated with amelioration of cisplatin-mediated cell death. Protective effects of D3T were also observed in mice. Oral administration of D3T (0.25mmol/kg) increased the expression of GCL in mouse kidney, which resulted in suppression of cisplatin-mediated increases in blood urea nitrogen and serum creatinine. Histopathological changes representing cisplatin-induced acute renal failure were also effectively ameliorated by D3T treatment. Collectively, these results indicate that pharmacological activation of the Nrf2 pathway might have a beneficial effect on reducing chemotherapy-associated cytotoxic adverse effects.

Adaptive response to GSH depletion and resistance to L-buthionine-(S,R)-sulfoximine: involvement of Nrf2 activation.

Pharmacological depletion of L-gamma-glutamyl-L-cysteinyl-glycine (GSH) has been implicated in the sensitization of cancer cells to alkylating agents and apoptosis. However, some types of cells do not induce apoptotic response following chemical depletion of GSH. In the present study, we report that murine embryonic fibroblasts (MEFs) can survive in the presence of GSH inhibitor L-buthionine-(S,R)-sulfoximine (BSO), even though most intracellular GSH was depleted. As a cellular adaptive mechanism, BSO treatment effectively activated the NF-E2-related factor 2 (Nrf2) pathway, which led to up-regulation of antioxidant enzymes in these cells through the extracellular signal-regulated kinase cascade. While nrf2-deficient MEFs lost the inducibility of antioxidant genes, which resulted in higher levels of reactive oxygen species accumulation, caspase-3 activation, and cell death than wild-type cells. Finally, nrf2-deficient cells can be more sensitized to doxorubicin-induced cell death by BSO pre-incubation, while wild-type cells were not. In addition, BSO-mediated cell death was facilitated by administering Nrf2 siRNA to chemoresistant human ovarian cancer cells. These results indicate that Nrf2 is the primary factor inducing the cell survival system under GSH depletion and that the effect of BSO as a chemosensitizer might be enhanced by inhibition of Nrf2.

Role of the Nrf2-antioxidant system in cytotoxicity mediated by anticancer cisplatin: implication to cancer cell resistance.

The treatment of alkylating cytotoxic drug cisplatin is often limited by high incidence rate of resistance. In the present study, the potential involvement of the transcription factor Nrf2 in determination of cisplatin cytotoxicity has been investigated. Nrf2-deficient murine embryonic fibroblasts showed increased cell death, cytotoxicity, and apoptosis in response to cisplatin treatment compared to wild-type cells. Cisplatin-resistant human ovarian cancer SK-OV cells, which are retaining 25-fold higher levels of GSH than murine fibroblasts, could be sensitized by inhibition of Nrf2. Transfection with Nrf2 siRNA into SK-OV cells resulted in severe degree of GSH depletion and exacerbated cytotoxicity following cisplatin treatment compared to scrambled RNA control. In conclusion, we propose that the Nrf2 pathway, which plays a protective role in normal cells, can be a potential target to control cancer cell resistance to oxidants, cytotoxic chemicals, and radiation.

Induction of Nrf2-regulated genes by 3H-1, 2-dithiole-3-thione through the ERK signaling pathway in murine keratinocytes.

Electrophile and free radical detoxifying enzymes including NAD(P)H:quinine oxidoreductase 1 (Nqo1) play an important role in the defense system by enhancing cellular antioxidant capacity. Chemopreventive efficacy of 3H-1,2-dithiole-3-thione (D3T) is mediated through activation of the transcription factor Nrf2 and subsequent elevation of detoxifying enzymes. In the present study, we have investigated the potential role of extracellular signal-regulated kinase (ERK) in regulation of D3T-induced and Nrf2-dependent gene expression in murine keratinocytes. Expression levels of Nqo1 were highly inducible by D3T treatment and increased nuclear levels of Nrf2 were observed in these cells. Treatment with pharmacological inhibitor of ERK1/2 largely blocked nuclear accumulation of Nrf2, ARE-driven reporter gene expression, and induction of Nqo1, as well as other phase 2 genes. Activation of ERK1/2 has been demonstrated following treatment with D3T. While, inhibitors of p38, PKC and PI3K did not affect ARE-driven gene expression. Involvement of the ERK1/2 cascade in inducible ARE-transcription activities was also observed in cells treated with other types of inducers oltipraz, sulforaphane and hydrogen peroxide. Collectively, current study suggests that phosphorylation cascade via ERK1/2 is associated with the activation process of Nrf2 and subsequent transactivation of its target gene Nqo1 following treatment with dithiolethione in murine keratinocyte.

Role of increased expression of the proteasome in the protective effects of sulforaphane against hydrogen peroxide-mediated cytotoxicity in murine neuroblastoma cells.

The 26S proteasome is responsible for degradation of abnormal proteins and may play a role in cell survival upon oxidative stress. The indirect antioxidant sulforaphane (SFN) protects animal tissues from chemical toxicants by increasing the expression of several families of Nrf2-regulated genes. The role of induction of the 26S proteasome in cytoprotection by SFN was investigated in murine neuroblastoma Neuro2A cells. SFN enhanced the expression of the catalytic subunits of the proteasome, as well as proteasomal peptidase activities in these cells. Such treatment with SFN protected cells from hydrogen peroxide-mediated cytotoxicity in a manner dependent on proteasomal function. Inhibition of proteasome activities using pharmacological interventions significantly attenuated the protective effects of SFN against hydrogen peroxide cytotoxicity, as well as protein oxidation. Moreover, overexpression of the catalytic subunit PSMB5 enhanced proteasome function and led to elevated resistance against hydrogen peroxide toxicity and extent of protein oxidation compared to blank-plasmid-transfected cells. Pretreatment of PSMB5-overexpressing cells with SFN did not further enhance this resistance. Collectively, these results suggest that the cytoprotective effects of SFN against oxidative stress are in part due to up-regulation of the proteasome system. Therefore, inducers of proteasome expression may ameliorate the accumulation of damaged proteins associated with neurodegeneration and other diseases in whose etiologies protein oxidation plays a role.

Direct surface force measurement in water using a nanosize colloidal probe technique.

The direct force measurement between colloidal surfaces has been an essential topic in both theories and applications of surface chemistry. As particle size is decreased from micron size down to true nano size (<10 nm), surface forces are increasingly important. Nanoparticles at close proximity or high solids loading are expected to show a different behavior than what can be estimated from continuum and mean field theories. The current tools for directly measuring interaction forces such as a surface force apparatus or atomic force microscopy (AFM) are limited to particles much larger than nanosize. Here a modified colloidal probe technique is suggested using a multiwalled carbon nanotube (MWNT) to overcome this problem. Determination of zero separation in AFM is critical to extract a reliable force-separation curve when MWNT is used as a probe. Hence, a systematic approach to the data collection for a nanosize colloidal probe is proposed and a sample of a direct surface force measurement curve obtained with the MWNT probe is presented.