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Glioblastoma multiforme (GBM) is one of the most common brain tumors with a poor prognosis. Previously, we reported that trifluoperazine (TFP), a well-known antipsychotic, has anti-glioma activity through the modulation of intracellular calcium levels. The present study aimed to investigate the anti-cancer mechanism of action of TFP on glioma cells.The effect of TFP on U87MG cells was examined using a viability assay, flow cytometry, enzyme-linked immunosorbent assay, quantitative real-time PCR, western blot analysis, colony formation, and immunocytochemistry.TFP treatment decreased cell viability. To test the possible involvement of COX-2 in the anticancer activity of TFP on U87MG cells, a COX-2 inhibitor was applied. COX-2 inhibitor pretreatment restored TFP-induced reduction in viability to the control level. Additionally, TFP-induced changes in the apoptotic cell population, production of prostaglandins (PGETFP suppressed the proliferation of U87MG glioma cell in a COX-2/PPARγ-dependent manner.

20 μM TFP-treated group. The cell were recorded in 2 h after seeding on 6-well plate equipped with x10 objective lens. The video were recorded by Cell Observer (Carl Zeiss, Germany).

Supplementary Figure S1. TFP induces morphological change of U87MG cells, and cell death; Supplementary Figure S2. Body weight is not changed during TFP injection in in vivo glioblastoma skin xenograft model; Supplementary Figure S3. IP3R1, 2 and 3 shRNA knockdown test by western blot and functional knockdown test using GBL 28 primary glioblastoma cells; Supplementary Figure S4. TFP reduces cell viability of several GBL cells;Supplementary Table S1. IP3R 1, 2, 3 and CaM shRNA sequences

0.9% saline-treated control group. The cell were recorded in 2 h after seeding on 6-well plate equipped with x10 objective lens.

Interest in foods that promote inner beauty increases with increases in exposure to ultraviolet (UV) rays and with improvements in quality of life. This study was performed to evaluate the efficacy of fermented and aged mountain-cultivated ginseng sprouts (FAMCGSs), which have higher anti-inflammatory and antioxidant effects compared to mountain-cultivated ginseng sprouts (MCGSs), as an inner beauty enhancing food. The effect of orally administered FAMCGSs on UV type B (UVB) radiation-induced skin aging was investigated in a hairless mouse model through analyzing skin parameters including epidermal thickness, transepidermal water loss (TEWL), roughness, moisture, elasticity, and collagen contents. The mice exposed to UVB had markedly greater epidermal thickness, TEWL, and skin roughness than those of the normal control (NC) group. In addition, the levels of collagen, skin moisture, and dermal elasticity were lower in the UVB radiation group than the NC group. These UVB-induced skin aging parameters were significantly lower in the groups administered FAMCGSs than in the groups not administered FAMCGSs (p < 0.05). These results show that FAMCGSs exhibit a photoprotective effect in mice exposed to UVB and suggest that FAMCGSs can be used as a food that promotes inner beauty and protects skin from UVB-induced photoaging.

Supplementary Figure 1 from Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

Supplementary Figure 4 from Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

Supplementary Figure 2 from Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

Supplementary Methods from Caffeine-Mediated Inhibition of Calcium Release Channel Inositol 1,4,5-Trisphosphate Receptor Subtype 3 Blocks Glioblastoma Invasion and Extends Survival

Perineural (Tarlov) cysts are a common benign pathology in the lumbosacral area but are rarely symptomatic, even when compressing the spinal root. Despite the rarity of Tarlov cyst formation in the foramen of the spine, this type is more symptomatic than those in other sites due to the narrow space. We introduce a biportal endoscopic fenestration for symptomatic foraminal Tarlov cysts. We present the case of a 40-year-old woman experiencing radiating pain in her right lower leg for 4 years. On seeking treatment, her great toe and ankle plantar flexion power had decreased. Magnetic resonance imaging revealed a cystic mass located in the L5-S1 intervertebral foramen that compressed the lumbar nerve root. Partial laminotomy was performed using a percutaneous biportal endoscopic system with a far lateral approach. An oval cystic mass of 2.6×1.1 cm was identified on high-definition images. Partial bone and foraminal ligament removal and cystic membrane fenestration were performed for nerve decompression. After decompression, the patient's motor weakness and radiating pain improved. Due to high-definition images and the minimally invasive laminotomy procedures associated with percutaneous biportal endoscopic fenestration, a foraminal Tarlov cyst was fenestrated safely, and weakness arising from radiculopathy was resolved in the current case. [ Orthopedics . 2023;46(2):e125–e128.]

The association between asthma and oxidative stress remains controversial. Oxidative stress-induced ferroptosis has not been extensively studied in asthma models. This study was performed to investigate the anti-asthmatic and anti-ferroptotic effects of fermented and aged ginseng sprouts (FAGS) with enhanced antioxidant activity and its main component, compound K (CK), in a mouse model of ovalbumin (OVA)-induced allergic asthma. The experimental asthma model was sensitized and challenged with OVA. During the challenge period, two different concentrations of FAGS and CK were administered via oral gavage. Asthmatic parameters were analyzed in bronchoalveolar lavage fluid (BALF), blood, and lung tissue. CK, among the ginsenosides analyzed, was highly increased in FAGS compared with GS. Asthma parameters, such as Th2 cytokine and IgE production, mast cell activation, goblet cell hyperplasia, hyperresponsiveness, and inflammation, were dramatically increased in the OVA group. Oxidation and ferroptosis markers were increased in the OVA group. The asthma parameters and ferroptosis markers were markedly decreased in the OVA + FAGS and OVA + CK groups. These results showed that FAGS and CK alleviated asthma parameters in an allergic asthma mouse model by inhibiting inflammation and ferroptosis. Our findings suggest that FAGS and CK could be used as potential treatments for allergic asthma.

We aimed to identify and compare microRNAs (miRNAs) from individual aqueous humor samples between normal-tension glaucoma (NTG) patients and normal controls. Aqueous humor (80 to 120 µl) was collected before cataract surgery. Six stable NTG patients and seven age-matched controls were included in the final analysis. RNA sequencing was conducted for RNA samples extracted from the 13 aqueous humor samples, and bioinformatics analysis was employed for the miRNA targets and related pathways. Two hundred and twenty-eight discrete miRNAs were detected in the aqueous humor and consistently expressed in all samples. Eight significantly upregulated miRNAs were found in the NTG patients compared to the controls (fold-change > 2, p

This study investigated changes in nutrients (fatty acids, amino acids, and minerals), ginsenosides, and volatile flavors, and antioxidant activities during food processing of mountain-cultivated ginseng (MCG) with the cocktail lactic acid bacteria. Fatty acid content increased, but the free amino acid content decreased, and minerals were practically unaffected during processing. Total phenolic and flavonoid contents and maillard reaction products increased markedly according to processing stage. The total ginsenosides levels increased from 31.25 mg/g (DMCG) to 32.36 mg/g (red MCG, RMCG) and then decreased (27.27 mg/g, at fermented RMCG) during processing. Particularly, the contents of F2 (0.31 → 1.02 → 2.27 mg/g), Rg3 (0.36 → 0.77 → 1.93 mg/g), and compound K (0.5 → 1.68 → 4.13 mg/g) of ginsenosides and β-panasinsene (17.28 → 22.69 → 31.61%), biocycloelemene (0.11 → 0.84 → 0.92%), δ-cadinene (0.39 → 0.5 → 0.94%), and alloaromadendrene (1.64 → 1.39 → 2.6%) of volatile flavor compounds increased during processing, along with to the antioxidant effects (such as DPPH, ABTS, and hydroxyl radical scavenging activities, and FRAP). This study may provide several choices for the use of ginseng in functional foods and functional cosmetics.

We analyzed the effectiveness of insulin for treating hyperkalemia (≥ 5 mEq/L) during anesthesia and the effects of the estimated glomerular filtration rate (eGFR) and diabetes mellitus (DM) on the insulin treatment. Patients 18 years of age and older who received intravenous insulin lispro for hyperkalemia under general anesthesia between January 2010 and March 2020 were enrolled. We performed three propensity score matching analyses according to eGFR stages (eGFR ≥ 60 vs. 30 ≤ eGFR

Background: Spinal epidural hematoma is rare condition that can rapidly develop into severe neurologic deficits. The pathophysiology of this development remains unclear. There are several case reports of emergency hematoma evacuations after epidural steroid injection. Case: We report on two patients who developed acute, large amounts of epidural hematoma without neurological deficits after transforaminal epidural steroid injection. After fluoroscopy guided aspiration for epidural hematoma was performed, neurological defects did not progress and the hematoma was shown to be absorbed on magnetic resonance imaging. Conclusions: These reports are believed to be the first of treating epidural hematoma occurring after transforaminal epidural steroid injection through non-surgical hematoma aspiration. If large amounts of epidural hematoma are not causing neurological issues, it can be aspirated until it is absorbed.

DNA methylation, and consequent down-regulation, of tumour suppressor genes occurs in response to epigenetic stimuli during cancer development. Similarly, human oncoviruses, including human papillomavirus (HPV), up-regulate and augment DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities, thereby decreasing tumour suppressor genes (TSGs) expression. Ubiquitin-like containing PHD and RING finger domain 1 (UHRF1), an epigenetic regulator of DNA methylation, is overexpressed in HPV-induced cervical cancers. Here, we investigated the role of UHRF1 in cervical cancer by knocking down its expression in HeLa cells using lentiviral-encoded short hairpin (sh)RNA and performing cDNA microarrays. We detected significantly elevated expression of thioredoxin-interacting protein (TXNIP), a known TSG, in UHRF1-knockdown cells, and this gene is hypermethylated in cervical cancer tissue and cell lines, as indicated by whole-genome methylation analysis. Up-regulation of UHRF1 and decreased TXNIP were further detected in cervical cancer by western blot and immunohistochemistry and confirmed by Oncomine database analysis. Using chromatin immunoprecipitation, we identified the inverted CCAAT domain-containing UHRF1-binding site in the TXNIP promoter and demonstrated UHRF1 knockdown decreases UHRF1 promoter binding and enhances TXNIP expression through demethylation of this region. TXNIP promoter CpG methylation was further confirmed in cervical cancer tissue by pyrosequencing and methylation-specific polymerase chain reaction. Critically, down-regulation of UHRF1 by siRNA or UHRF1 antagonist (thymoquinone) induces cell cycle arrest and apoptosis, and ubiquitin-specific protease 7 (USP7), which stabilises and promotes UHRF1 function, is increased by HPV viral protein E6/E7 overexpression. These results indicate HPV might induce carcinogenesis through UHRF1-mediated TXNIP promoter methylation, thus suggesting a possible link between CpG methylation and cervical cancer.

Spinal percutaneous biportal endoscopic surgery (PBES) is a minimally invasive surgery; however, it is associated with several poor outcomes. This study aimed to analyze unsuccessful PBES outcomes and verify their relationships with patient satisfaction. From May 2015 to June 2018, PBES was performed at several institutions. Unsuccessful outcomes (reoperation and prolonged hospital stay) due to various reasons (hematoma, lesion recurrence, incomplete decompression, dural tear, instability, ascites, and infection) were analyzed. To verify the relationships between surgical experience and unsuccessful outcomes, the first 50 cases and the later cases were compared. Logistic regression was used to assess the relationships between unsuccessful outcomes and patient dissatisfaction. Among 866 patients, 797 cases with 1-year follow-up and complete data were analyzed. In total, 82 patients with unsuccessful outcomes were identified (10.29%). The incidences of hematoma (p

The biochemical modification using microorganisms had an excellent functional values. This research was the first to investigate changes in nutritional components (ginsenosides, flavonols, and phenolic acids) and biological properties (antioxidant and anti-inflammatory) of mountain-cultivated ginseng sprouts (MCGS) during the aging (AMCGS) and fermentation (FAMCGS) processes. Total ginsenosides were considerably reduced (45.1 → 4.9 → 31.7 mg/g) in the 50% ethanol extracts of processed ginseng sources, while flavonol and phenolic acid contents increased with 586.0 → 746.2 → 898.7 and 192.5 → 312.0 → 367.4 μg/g, respectively. Especially, ginsenoside Rg2 (3.4 → 4.6 mg/g, 1.5-fold), Rg3 (1.0 → 2.9 mg/g, 2.9-fold), compound K (0.6 → 6.3 mg/g, 10.5-fold), epigallocatechin (53.9 → 146.1 µg/g), and ferulic acid (nd → 62.4 µg/g) exhibited remarkable increase rates. The antioxidant abilities significantly increased with approximately 20% for MCGS → AMCGS → FAMCGS processes, followed by ABTS > DPPH > hydroxyl > FRAP. The inhibitions on inflammatory mediators were also observed about 2-fold higher activities with increasing order as NO > MCP-1 > IL-6 > TNF-α in AMCGS and FAMCGS than MCGS.

The aim of this study is to explore anti-inflammatory phytochemicals from B. chinensis based on the inhibition of pro-inflammatory enzyme, human neutrophil elastase (HNE) and anti-inflammatory activities in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophage. Three stereoisomers of iridal-type triterpenoids (1–3) were isolated from the roots of B. chinensis and their stereochemistries were completely identified by NOESY spectra. These compounds were confirmed as reversible noncompetitive inhibitors against HNE with IC50 values of 6.8–27.0 µM. The binding affinity experiment proved that iridal-type triterpenoids had only a single binding site to the HNE enzyme. Among them, isoiridogermanal (1) and iridobelamal A (2) displayed significant anti-inflammatory effects by suppressing the expressions of pro-inflammatory cytokines, such as iNOS, IL-1β, and TNF-α through the NF-κB pathway in LPS-stimulated RAW264.7 cells. This is the first report that iridal-type triterpenoids are considered responsible phytochemicals for anti-inflammatory effects of B. chinensis.

In many cases, obesity is associated with metabolic disorders. Recently, natural compounds that may be beneficial for improving obesity have received increasing attention. Bitter melon has received attention as a diabetes treatment. NAD+-dependent deacetylase (Sirtuin 1, SIRT1) has emerged as a novel therapeutic target for metabolic diseases. In this study, ethanol extract of bitter melon (BME) suppressed adipocyte differentiation and significantly increased the expression of SIRT1 in fully differentiated 3T3-L1 cells. Moreover, it enhanced the activation of AMP-activated protein kinase (AMPK). In high-fat diet (HFD)-fed induced-obesity mice, BME suppressed HFD-induced increases in body weight and white adipose tissue (WAT) weight. BME also increased the expression of SIRT1 and suppressed peroxisome proliferator-activated receptor and sterol regulatory element binding protein 1 expressions of WAT from HFD-fed mice. These findings suggest that BME prevents obesity by activating the SIRT1 and AMPK pathway and that it may be a useful dietary supplement for preventing obesity.

Chronic immobilization stress (CIS) induces low levels of glutamate (Glu) and glutamine (Gln) and hypoactive glutamatergic signaling in the mouse prefrontal cortex (PFC), which is closely related to the Glu-Gln cycle. A Gln-supplemented diet ameliorates CIS-induced deleterious changes. Here, we investigated the effects of CIS and Gln supplementation on Glu-Gln cycle-related proteins to characterize the underlying mechanisms. Using the CIS-induced depression mouse model, we examined the expression of 11 proteins involved in the Glu-Gln cycle in the PFC. CIS decreased levels of glutamate transporter 1 (GLT1) and sodium-coupled neutral amino acid transporter (SNAT) 1, SANT2, SNAT3, and SNAT5. Gln supplementation did not affect the non-stressed group but significantly increased GLT1 and SNATs of the stressed group. By immunohistochemical analysis, we confirmed that SNAT1 and SNAT2 were decreased in neurons and GLT1, SNAT3, and SNAT5 were decreased in astrocytes in the medial PFC of the stressed group, but Gln-supplemented diet ameliorated these decrements. Collectively, these results suggest that CIS may cause depressive-like behaviors by decreasing Glu and Gln transportation in the PFC and that a Gln-supplemented diet could prevent the deleterious effects of CIS., Graphical Abstract

Objective: The main objectives of this article were to assess the effect of preoperative transdermal fentanyl patch (TFP) on interleukin (IL)-6 and IL-8 levels and pain after laparoscopic cholecystectomy. Materials and Methods: Patients received a TFP (25 μg/h) (patch group, n=30) or a placebo patch (control group, n=30) applied 14 hours before operation. After surgery, control group received intravenous continuous fentanyl (25 μg/h) with loading dose (25 μg). IL-6 and IL-8 levels were measured at admission and 1, 6, 12, 24, and 48 hours postoperatively. Pain score and consumption of rescue analgesic were evaluated too. Results: At 24 hours postoperatively, IL-6 and IL-8 reached a peak and then decreased. The peak IL-6 levels were 21.92(±6.22) and 24.91(±6.81) pg/mL in the patch and control group. The significant differences of IL-6 between groups were shown at 6 and 12 hours postoperatively (P=0.032, 0.0001). There were no significant differences in IL-8 levels and pain score. Conclusions: Preoperative TFP attenuated the increase in IL-6 levels after surgery and provided similar analgesia to continuous fentanyl infusion. Preemptive TFP may have influence on proinflammatory reactions and pain control after surgery.

Despite significant advances in diagnostic and therapeutic technologies, lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Recently, some antipsychotics have been shown to possess anticancer activity. However, the effects of antipsychotics on NSCLC need to be further explored. We examined the effects of trifluoperazine (TFP), a commonly used antipsychotic drug, and its synthetic analogs on A549 human lung cancer cells. In addition, cell proliferation analysis, colony formation assay, flow cytometry, western blot analysis, and in vivo xenograft experiments were performed. Key genes and mechanisms possibly affected by TFP are significantly related to better survival outcomes in lung cancer patients. Treatment with TFP and a selected TFP analog 3dc significantly inhibited the proliferation, anchorage-dependent/independent colony formation, and migration of A549 cells. Treatment with 3dc affected the expression of genes related to the apoptosis and survival of A549 cells. Treatment with 3dc promoted apoptosis and DNA fragmentation. In all experiments, including in vivo studies of metastatic lung cancer development, 3dc had more substantial anticancer effects than TFP. According to our analysis of publicly available clinical data and in vitro and in vivo experiments, we suggest that some kinds of antipsychotics prevent the progression of NSCLC. Furthermore, this study indicates a synthetic TFP analog that could be a potential therapeutic for lung cancer.

Emerging evidence has shown the low levels of glutamate (Glu) and glutamine (Gln) and the hypoactivity in the cortex of patients with depression. The hypoactivity is closely related with low frequency of glutamatergic signaling that is affected by the levels of Glu and Gln. Thus, we hypothesized that there might be a causality among low levels of Glu and Gln, hypoactive glutamatergic neurotransmissions, and depressive behaviors. Here, we found low Glu and Gln levels and low frequency of spontaneous excitatory postsynaptic current (sEPSC) of glutamatergic neurons in the medial prefrontal cortex (mPFC) of chronic immobilization stress (CIS)-induced depressed mice. The depressed mice also showed hypoactive Gln synthetase (GS). Inhibition of GS by methionine sulfoximine (MSO) decreased Glu and Gln levels and increased depressive behaviors with low frequency of sEPSC in the mPFC, indicating that Glu and Gln decrements cause hypoactive glutamatergic neurotransmissions and depressive behaviors. Both Glu and Gln could increase sEPSC of glutamatergic neurons in the mPFC on slice patch, but only Gln overcame MSO to increase sEPSC, suggesting that exogenous Gln would recover CIS-induced low frequency of sEPSC caused by hypoactive GS and act as an antidepressant. Expectedly, Gln supplementation showed antidepressant effects against CIS; it increased glutamatergic neurotransmissions with Glu and Gln increment in the mPFC and attenuated depressive behaviors. Moreover, selective glutamatergic activation in the mPFC by optogenetics decreased depressive behavior. In conclusion, depressive behaviors evoked by chronic stress were due to hypoactive glutamatergic neurons in the mPFC caused by low levels of Glu and Gln, and exogenous Gln can be used as an alternative antidepressant to increase glutamatergic neurotransmission.

AIM: To confirm the changes in proteins related with hypoxia-induced retinal cell death and to assess the effects of resveratrol (Res). METHODS: The therapeutic effect of Res was verified using an ischemic/reperfusion (I/R) model in vivo and a hypoxia modelin retinal ganglion cells (RGCs) in vitro. Death of RGCs were confirmed by TUNEL assay. Protein expression was confirmed by Western blotting and immunohistochemistry. In addition, flow cytometric analysis was used to confirm the response in the cell unit to obtain more accurate data. RESULTS: ErbB2 expression and apoptosis in the ganglion cell layer (GCL) increased after I/R injury. Treatment of Res rescued I/R-induced ganglion cell death, downregulated apoptosis and ErbB2 protein expression in the retina. In subsequent in vitro models, Res affects apoptosis by regulating the phosphorylation and expression of mouse double minute 2 homolog (MDM2), along with those of ErbB2. These results suggest that Res reverses GCL-specific apoptosis via downregulation of ErbB2 in ischemic injury. CONCLUSION: In light of Res favorable properties, it should be evaluated in the treatment of RGC death and related retinal disease characterized by ErbB2 and MDM2 expression. Therefore, Res is appropriate therapeutic agent for treating ischemic injury-related eye diseases by targeting the expression of ErbB2 and MDM2.

Accumulative alcohol hangovers cause liver damage through oxidative and inflammatory stress. Numerous antioxidant and anti-inflammatory reagents have been developed to reduce alcohol hangovers, but these reagents are still insignificant and have limitations in that they can cause liver toxicity. Oyster hydrolysate (OH), another reagent that has antioxidant and anti-inflammatory activity, is a product extracted through an enzymatic hydrolysis process from oysters (Crassostrea gigas), which can be easily eaten in meals. This study was aimed at determining the effects of OH on alcohol metabolism, using a single high dose of ethanol (EtOH) administered to rodents, by monitoring alcohol metabolic enzymes, oxidative stress signals, and inflammatory mediators. The effect of tyrosine-alanine (YA) peptide, a main component of OH, on EtOH metabolism was also identified. In vitro experiments showed that OH pretreatment inhibited EtOH-induced cell death, oxidative stress, and inflammation in liver cells and macrophages. In vivo experiments showed that OH and YA pre-administration increased alcohol dehydrogenase, aldehyde dehydrogenase, and catalase activity in EtOH binge treatment. In addition, OH pre-administration alleviated CYP2E1 activity, ROS production, apoptotic signals, and inflammatory mediators in liver tissues. These results showed that OH and YA enhanced EtOH metabolism and had a protective effect against acute alcohol liver damage. Our findings offer new insights into a single high dose of EtOH drinking and suggest that OH and YA could be used as potential marine functional foods to prevent acute alcohol-induced liver damage.

Aim of the study is to report the clinical characteristics and prognostic factors in hypertensive anterior uveitis (AU) diagnosed with multiplex polymerase chain reaction (PCR). Eighty-eight eyes of 88 patients with hypertensive AU were enrolled from 2015 to 2019 in a tertiary center in South Korea. All patients underwent multiplex PCR that was performed using aqueous humor samples collected at first visit to detect the DNA of six herpesviruses. Twenty-eight (31.8%) eyes were PCR positive. Herpes simplex virus was found in 6 (6.8%) eyes, varicella-zoster virus in 7 (8.0%) eyes, cytomegalovirus in 14 (15.9%) eyes, and Epstein–Barr virus in 1 (1.1%) eye. On multivariate regression analysis, PCR positivity was significantly associated with coin-shaped keratic precipitates (odds ratio (OR) = 6.01, P = 0.044). Recurrence and final visual acuity were significantly associated with a presumed diagnosis of viral endotheliitis (OR = 21.69, P = 0.04 and OR = 6.3, P = 0.004, respectively). This study showed the importance of PCR positivity, suggesting that identification of the virus through active PCR testing could affect the course, treatment, and prognosis of hypertensive AU.

Neovascularization in the retina can cause loss of vision. Vascular endothelial growth factor (VEGF) serves an important role in the pathogenesis of retinal vascular diseases. Hypoxia is a notable cause of VEGF release and both STAT3 and ERBB2 are known to be associated with VEGF. In addition, STAT3 and ERBB2 interact with each other. In the present study, it was hypothesized that signal transducer and activator of transcription 3 (STAT3) and erbB-2 receptor tyrosine kinase 2 (ERBB2) may be involved in the regulation of hypoxia-induced VEGF in the retina. Cells of the retinal pigment epithelium (RPE) are an important source of VEGF. Therefore, the RPE-derived human cell line ARPE-19 was exposed to hypoxia. Hypoxia-induced phosphorylation of STAT3 and ERBB2 in ARPE-19 cells was decreased by AG490, an inhibitor of Janus kinase 2, as were hypoxia-induced VEGF release and tube formation in human umbilical vein endothelial cells. Thus, phosphorylation of ERBB2 and STAT3 regulates hypoxia-induced VEGF release in ARPE-19 cells. The results of the present study suggested that inhibition of ERBB2 and STAT3-mediated pathways under hypoxia may represent a new strategy for treating retinal vascular disease.

Background With an increasing aging population, postmenopausal osteoporosis has become a global public health problem. Previous evidence has shown that postmenopausal osteoporosis is a skeletal disease mainly caused by estrogen deficiency, generally accompanied by inflammation, and dietary isoflavones may ameliorate postmenopausal osteoporosis by anti-inflammatory activity. We have generated isoflavone-enriched soybean leaves (IESLs), but their anti-inflammatory activity and effect on attenuating osteoporosis are still obscure. Here, we determined the isoflavone profiles of IESLs and evaluated their anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells and anti-osteoporotic effects on ovariectomy-induced osteoporosis in rats. Results IESLs had a high content of total isoflavone. Hydrolysate of IESLs (HIESLs) was rich with the aglycones daidzein and genistein, and HIESLs can significantly inhibit lipopolysaccharide-induced inflammation by reducing messenger RNA expression of iNOS, COX-2, IL6, and IL1β. Moreover, ovariectomized rats receiving aqueous extracts of IESLs (HIESLs) orally maintained more bone mass than control rats did, which was attributed to inhibition of osteoclastogenesis by downregulating the messenger RNA expression of the bone-specific genes RANKL/OPG, OC, and cathepsin K, and the inflammation-related genes IL6, NFκB, and COX-2. Conclusion IESLs may attenuate postmenopausal osteoporosis by suppressing osteoclastogenesis with anti-inflammatory activity and be a potential source of functional food ingredients for the prevention of osteoporosis. © 2020 Society of Chemical Industry.

Introduction Momordica charantia (bitter melon) is widely used for its glucose-lowering effects. This study was conducted to assess the efficacy and safety of M. charantia as an adjuvant treatment in patients with type 2 diabetes. Methods We performed a randomized, placebo-controlled study. Blood glucose levels, lipid profile, and adverse events were investigated after 12 weeks of treatment. Ninety subjects were included in the final analysis for glucose lowering efficacy of bitter melon. Results There were no differences in age, sex, or glycated hemoglobin (HbA1c) levels between the bitter melon extract and placebo groups. After treatment with bitter melon extract for 12 weeks, the HbA1c levels of the bitter melon and placebo groups remained unchanged; however, the average fasting glucose level of the bitter melon group decreased (p = 0.014). No serious adverse events were reported during the treatment period. Conclusions Our data showed that bitter melon has effects of glucose lowering in patients with type 2 diabetes.

Oxidative stress plays an important role in the development of diabetic retinopathy. Here, we examined whether α-lipoic acid (α-LA), a natural antioxidant, attenuated retinal injury in diabetic mice. The α-LA was orally administered to control mice or mice with streptozotocin-induced diabetes. We found that α-LA reduced oxidative stress, decreased and increased retinal 4-hydroxy-2-nonenal and glutathione peroxidase, respectively, and inhibited retinal cell death. Concomitantly, α-LA reversed the decreased activation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase, and increased the levels of peroxisome proliferator-activated receptor delta and sirtuin3 in diabetic mouse retinas, similar to results shown after metformin treatment of retinal pigment epithelial cells (RPE) exposed to high glucose. Moreover, α-LA lowered the levels of O-linked β-N-acetylglucosamine transferase (OGT) and thioredoxin-interacting protein (TXNIP) in diabetic retinas that were more pronounced after metformin treatment of RPE cells. Importantly, α-LA lowered interactions between AMPK and OGT as shown by co-immunoprecipitation analyses, and this was accompanied by less cell death as measured by double immunofluorescence staining by terminal deoxynucleotide transferase-mediated dUTP nick-end labelling and OGT or TXNIP in retinal ganglion cells. Consistently, α-LA lowered the levels of cleaved poly(ADP-ribose) polymerase and pro-apoptotic marker cleaved caspase-3 in diabetic retinas. Our results indicated that α-LA reduced retinal cell death partly through AMPK activation or OGT inhibition in diabetic mice.

Background The aim of this study was to develop a formula guiding the peripherally inserted central catheter (PICC) tip placement based on anatomical landmarks such as the upper arm, clavicle, and sternum as well as the patient's height, weight, and body mass index. Methods Fifty-five patients who were scheduled to have PICCs were included in the study. We measured four distances along the passage of the PICC, which were as follows; the tip of the third finger to the middle of the elbow crease (Distance A), the middle of the elbow crease to the acromion process (Distance B), the acromion process to the sternal head of the clavicle (Distance C), and the sternal head of the clavicle to the end of the xiphoid process (Distance D). The lengths from the elbow creases to their carina bifurcations as determined by fluoroscopy during PICC insertions were recorded and used as reference. Results The formula for determining PICC depth based on the four distances was determined by regression analysis. The optimal formula was determined to be 25.3 + 0.5 × (Distance C) + 0.6 × (Distance D) which yielded an R2 value of 0.3. Conclusions The formula proposed for proper depth of the adult, 25.0 + 0.5 × (clavicle length) + 0.6 × (sternum length) for PICC insertion can be used to place the tip at the carina bifurcation level. The distance from elbow crease to catheter insertion point should be added to the length generated by this formula.

Objective To determine the rate and anatomical location of dural tears associated with spinal surgery using a percutaneous biportal endoscopic surgery (PBES) technique. We investigated the relationship between dural tears and the type of procedure and type of instrument used. Methods We retrospectively analyzed 643 PBES cases by reviewing the medical records, operative records, and operative videos. Incidental durotomy was identified in 29 cases. We analyzed the size and anatomical location of the dural tears, the surgical instrument that caused the tear, and the technique used to seal the tear. Results The dural tear incidence was 4.5% (29 of 643 cases). Tears in the exiting nerve area (2 cases; 6.9%) had mainly been caused by curettage, tears in the thecal sac area (18 cases; 62.1%) were associated with electric drill and forceps use; and tears in the traversing nerve area were associated with the use of a Kerrison punch (9 cases; 31%). Of the 29 cases of dural tear, 12 were treated with in-hospital monitoring and bed rest, 14 were treated with a fibrin sealant, 2 were treated with a nonpenetrating titanium clip, and 1 was converted to microscopic surgery. One case of postoperative meningocele after conservative treatment required endoscopic revision surgery to close the dural tear. Conclusions Most cases of incidental dural tear during PBES were treated with an endoscopic procedure. The incidence of dural tear was no greater than that associated with microscopic surgery. Our management strategy for incidental dural tears during PBES has been shown to be safe and effective.

Dietary isoflavones have been gaining increased interest in the field of functional foods due to their ability to ameliorate several postmenopausal symptoms. Using ovariectomized (OVX) rats supplemented with isoflavone-enriched soybean leaves (IESLs), we investigated the effect of dietary isoflavones on menopausal-associated obesity. Oral administration of IESLs significantly reduced OVX-induced weight gain and visceral fat mass. Additionally, IESLs significantly ameliorated OVX-induced hepatic steatosis as reflected by decreased triacylglycerol accumulation in the liver and decreased serum alanine transaminase and aspartate aminotransferase levels. These anti-obesity effects of IESLs were confirmed to be due to enhanced fatty acid oxidation via up-regulation of peroxisome proliferator activated receptor alpha, peroxisomal acyl-coenzyme A oxidase 1, and carnitine palmitoyltransferase 1a mRNA expression. These results demonstrate that IESLs may be an effective functional food-based approach to protect against menopause-associated obesity.

This research was the first to investigate the variations of conjugated linoleic acid (CLA), isoflavone, digestive enzyme inhibition, and antioxidant properties in hydrolysate soybean milks under fermentation using Lactobacillus plantarum P1201. The average CLA contents increased significantly in the range of ND → 0.91–1.75 mg/g during fermentation, whereas the isoflavone glucosides were markedly reduced (1570.01 → 548.41 µg/g, 65%) with the increase of aglycone contents (58.75 → 453.45 µg/g, 7.7 times). In particular, daidzein and cis-9, trans-11 CLA exhibited the predominant compositions (>50% and >90%) with considerable increases in fermented soybean milks. Total phenolic and flavonoid contents also slightly increased. Interestingly, fermented soybean extracts possessed potent α-glucosidase and pancreatic lipase inhibitory effects with average 32.4 → 55.5% and ND → 43.4% at a concentration of 500 μg/ml. Moreover, the antioxidant properties against three radicals increased markedly as the following order: ABTS (46.1 → 87.6%) > DPPH (38.8 → 77.4%) > hydroxyl (15.6 → 47.0%). Therefore, fermented hydrolysate milks might have attributed to enhance the soybean value.

// Mahmoud Ahmed 1 , Huynh Quoc Nguyen 1 , Jin Seok Hwang 1 , Sahib Zada 1 , Trang Huyen Lai 1 , Sang Soo Kang 2 and Deok Ryong Kim 1 1 Department of Biochemistry and Convergence Medical Sciences and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, Republic of Korea 2 Department of Anatomy and Convergence Medical Sciences and Institute of Health Sciences, Gyeongsang National University School of Medicine, Jinju 527-27, Republic of Korea Correspondence to: Deok Ryong Kim, email: drkim@gnu.ac.kr Keywords: autophagy; adipocyte differentiation; 3T3-L1; RNA-seq; gene ontology Received: June 24, 2017 Accepted: February 10, 2018 Epub: February 15, 2018 Published: March 20, 2018 ABSTRACT Autophagy contributes to reorganizing intracellular components and forming fat droplets during the adipocyte differentiation. Here, we systematically describe the role of autophagy-related genes and gene sets during the differentiation of adipocytes. We used a public dataset from the European Nucleotide Archive from an RNA-seq experiment in which 3T3-L1 cells were induced by a differentiation induction medium, total RNA was extracted and sequenced at four different time points. Raw reads were aligned to the UCSC mouse reference genome (mm10) using HISAT2, and aligned reads were summarized at the gene or exon level using HTSeq. DESeq2 and DEXSeq were used to model the gene and exon counts and test for differential expression and relative exon usage, respectively. After applying the appropriate transformation, gene counts were used to perform the gene set and pathway enrichment analysis. Data were obtained, processed and annotated using R and Bioconductor. Several autophagy-related genes and autophagy gene sets, as defined in the Gene Ontology, were actively regulated during the course of the adipocyte differentiation. We further characterized these gene sets by clustering their members to a few distinct temporal profiles. Other potential functionally related genes were identified using a machine learning procedure. In summary, we characterized the autophagy gene sets and their members to biologically meaningful groups and elected a number of genes to be functionally related based on their expression patterns, suggesting that autophagy plays a critical role in removal of some intracellular components and supply of energy sources for lipid biogenesis during adipogenesis.