Anti-obesity effects of a standardized ethanol extract of Eisenia bicyclis by regulating the AMPK signaling pathway in 3T3-L1 cells and HFD-induced mice.

Obesity requires treatment to mitigate the potential development of further metabolic disorders, including diabetes, hyperlipidemia, tumor growth, and non-alcoholic fatty liver disease. We investigated the anti-obesity effect of a 30% ethanol extract of Eisenia bicyclis (Kjellman) Setchell (EEB) on 3T3-L1 preadipocytes and high-fat diet (HFD)-induced obese C57BL/6 mice. Adipogenesis transcription factors including peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein-alpha (C/EBPα), and sterol regulatory element-binding protein-1 (SREBP-1) were ameliorated through the AMP-activated protein kinase (AMPK) pathway by EEB treatment in differentiated 3T3-L1 cells. EEB attenuated mitotic clonal expansion by upregulating cyclin-dependent kinase inhibitors (CDKIs) while downregulating cyclins and CDKs. In HFD-fed mice, EEB significantly decreased the total body weight, fat tissue weight, and fat in the tissue. The protein expression of PPARγ, C/EBPα, and SREBP-1 was increased in the subcutaneous fat and liver tissues, while EEB decreased the expression levels of these transcription factors. EEB also inhibited lipogenesis by downregulating acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS) expression in the subcutaneous fat and liver tissues. Moreover, the phosphorylation of AMPK and ACC was downregulated in the HFD-induced mouse group, whereas the administration of EEB improved AMPK and ACC phosphorylation; thus, EEB treatment may be related to the AMPK pathway. Histological analysis showed that EEB reduced the adipocyte size and fat accumulation in subcutaneous fat and liver tissues, respectively. EEB promotes thermogenesis in brown adipose tissue and improves insulin and leptin levels and blood lipid profiles. Our results suggest that EEB could be used as a potential agent to prevent obesity.

Vertical Ridge Augmentation with Customized Titanium Mesh Using a 3D-Printing Model: A Prospective Study in Humans.

PURPOSE: To evaluate the usefulness of ridge augmentation using a customized titanium mesh (CTM) that was preformed by trimming and bending the commercial titanium mesh on a virtually reconstructed 3D acrylic resin model using clinical, radiologic, histologic, and histomorphometric analyses. MATERIALS AND METHODS: This study was designed prospectively for patients who required vertical ridge augmentation using a staged approach before implant surgery. After installation of the CTM, grafting was performed using deproteinized porcine bone mineral covered with an absorbable membrane. Computed tomography was performed preoperatively and 6 months after simultaneous/staged guided bone regeneration to measure planned, reconstructed, and lacking bone volume, and the reconstruction rate was calculated based on these values. Clinical complications were also recorded, particularly the mesh exposure rate. At re-entry, the bone core was obtained using a trephine bur, and histologic and histomorphometric analyses were performed. RESULTS: A total of 10 sites in eight patients were used for the study analysis. The mean planned bone volume was 1.15 cm3 (range: 0.78 to 1.56 cm3), mean lacking bone volume was 0.13 cm3 (range: 0 to 0.59 cm3), and mean reconstructed bone volume was 1.02 cm3 (range: 0.56 to 1.43 cm3). The exposure rate was 30% (3 out of 10 sites). The reconstruction rate was over 80%, except for one case that showed suppuration. From histomorphometric analysis, 27.52% ± 16.87% of new bone, 7.62% ± 5.19% of residual graft, and 64.86% ± 23.76% of connective tissue were observed. The core biopsy samples demonstrated different pseudoperiosteum layer appearances based on the healing stage of the augmented sites. In the premature bone, the inner osteogenic layer consisted of multiple layers of osteoblast cells with adjacent large blood vessels. However, in the mature augmented site, there was no specific inner osteogenic layer, and the outer fibrous layer was dominant. CONCLUSIONS: The fabrication of CTM based on the application of the 3D-printing technique makes vertical ridge augmentation easier and can reduce complications and achieve target bone acquisition. In addition, it is expected that quantitative analysis of the pseudoperiosteum layer will be facilitated using the CTM.

Characteristics of operative pediatric trauma transfer patients.

BACKGROUND: Pediatric patients treated at trauma centers demonstrate improved outcomes, but investigation of optimal resource utilization surrounding the transfer is ongoing. We evaluated characteristics of operative pediatric trauma transfer patients for resource optimization. METHODS: A retrospective review of pediatric trauma patients transferred to a level 1 pediatric trauma center from 2009 to 2019 was performed. Patients were categorized by initial operative subspecialty. RESULTS: Of 4164 transferred patients, 33.9 â€‹% required operative intervention. 65 â€‹% of operations were performed on orthopedic patients, who were significantly less injured compared to other patients. General surgery patients were more likely to undergo surgery on day of transfer compared to orthopedic patients (39.4%vs 56.3 â€‹%, OR 2.0, CI 1.4-2.8). CONCLUSIONS: One-third of pediatric trauma transfer patients required operative intervention. The majority of surgeries were on orthopedic patients, who were less likely to undergo surgery on day of transfer. Critical evaluation of this patient population is required to safely utilize a less resource-intensive transfer process.

Methyl lucidone inhibits airway inflammatory response by reducing TAK1 activity in human bronchial epithelial NCI-H292 cells.

Background: Methyl lucidone (ML), a methyl derivative of lucidone, has anti-inflammatory properties. However, the molecular mechanisms that reduce the inflammatory effect of ML in human lung epithelial cells remain unkown. This study aimed to elucidate the molecular mechanisms underlying the anti-inflammatory effect of ML. Methods: Four compounds (ML, methyl linderone, kanakugiol, and linderone) from Lindera erythrocarpa Makino were evaluated for their ability to reduce MUC5AC secretion levels in phorbol-12-myristate-13-acetate (PMA)-stimulated NCI-H292 cells using ELISA. The expression and secretion levels of inflammatory response-related proteins were analyzed using quantitative reverse transcription-PCR, ELISA, and western blotting. To determine whether ML directly regulates TGF-ß-activated kinase 1 (TAK1), we performed an in vitro kinase assay. Results: ML treatment effectively reduced the levels of inflammatory cytokines, including interleukin-1ß and TNF-α, increased by stimulation. Furthermore, ML downregulated the pathway cascade of both IκB kinase (IKK)/NF-κB and p38 mitogen-activated protein (MAP) kinase/CREB by inhibiting the upstream kinase TAK1. An in vitro kinase analysis confirmed that ML treatment significantly reduced the kinase activity of TAK1. Conclusion: ML pretreatment repressed the PMA-stimulated inflammation reaction by reducing the TAK1-mediated IKK/NF-κB and p38 MAP kinase/CREB signaling. These findings suggest that ML may improve respiratory health and can be used as a dietary supplement or functional food to prevent inflammatory lung diseases.

Diplacone Isolated from Paulownia tomentosa Mature Fruit Induces Ferroptosis-Mediated Cell Death through Mitochondrial Ca2+ Influx and Mitochondrial Permeability Transition.

The recently defined type of cell death ferroptosis has garnered significant attention as a potential new approach to cancer treatment owing to its more immunogenic nature when compared with apoptosis. Ferroptosis is characterized by the depletion of glutathione (GSH)/glutathione peroxidase-4 (GPx4) and iron-dependent lipid peroxidation. Diplacone (DP), a geranylated flavonoid compound found in Paulownia tomentosa fruit, has been identified to have anti-inflammatory and anti-radical activity. In this study, the potential anticancer activity of DP was explored against A549 human lung cancer cells. It was found that DP induced a form of cytotoxicity distinct from apoptosis, which was accompanied by extensive mitochondrial-derived cytoplasmic vacuoles. DP was also shown to increase mitochondrial Ca2+ influx, reactive oxygen species (ROS) production, and mitochondrial permeability transition (MPT) pore-opening. These changes led to decreases in mitochondrial membrane potential and DP-induced cell death. DP also induced lipid peroxidation and ATF3 expression, which are hallmarks of ferroptosis. The ferroptosis inhibitors ferrostatin-1 and liproxstatin-1 were effective in counteracting the DP-mediated ferroptosis-related features. Our results could contribute to the use of DP as a ferroptosis-inducing agent, enabling studies focusing on the relationship between ferroptosis and the immunogenic cell death of cancer cells.

Prenatal Rupture of Hydrocolpos in a Cloacal Malformation.

INTRODUCTION: Cloacal dysgenesis occurs from failure of embryological division of urogenital sinus and hindgut, leading to a single common perineal opening for genitourinary and gastrointestinal tracts. The prenatal diagnosis of cloacal malformation is imprecise, but the clinical correlation of postnatal findings to prenatal history can help reveal explanations for unusual pathological findings in patients with urogenital abnormalities. CASE PRESENTATION: A 21-year-old woman was referred after her 20-week ultrasound demonstrated anhydramnios and concern for dilated fetal bowel. Fetal MRI confirmed anhydramnios and a dilated fetal colon, in addition to hydronephrosis and a pelvic cyst. Repeat ultrasound at 27 weeks showed unexpected complete resolution of her anhydramnios but new fetal ascites. The newborn girl was postnatally diagnosed with a cloacal malformation and an unusual near-complete fusion of her labia. She underwent proximal sigmoid colostomy and a tube vaginostomy at birth followed by cloacal reconstruction at 1.5 years old. CONCLUSION: In female fetus with a pelvic cyst, one should have a high index of suspicion for cloacal anomaly and consider the possibility of urinary obstruction leading to alteration in amniotic fluid.

Tannic-Acid-Enriched Poly(vinyl alcohol) Nanofibrous Membrane as a UV-Shie lding and Antibacterial Face Mask Filter Material.

Face masks are increasingly important in the battle against infectious diseases and air pollution. Nanofibrous membranes (NFMs) are promising filter layers for removing particulate matter (PM) without restricting air permeability. In this study, tannic-acid-enriched poly(vinyl alcohol) (PVA-TA) NFMs were fabricated by electrospinning PVA solutions containing large amounts of tannic acid (TA), a multifunctional polyphenol compound. We were able to prepare uniform electrospinning solution without coacervate formation by inhibiting the robust hydrogen bonding between PVA and TA. Notably, the NFM maintained its fibrous structure even under moist conditions after heat treatment without the use of a cross-linking agent. Further, the mechanical strength and thermal stability of the PVA NFM were improved by the introduction of TA. The functional PVA NFM with a high TA content showed excellent UV-shielding (UV-A: 95.7%, UV-B: 100%) and antibacterial activity against Escherichia coli (inhibition zone: 8.7 ± 1.2 mm) and Staphylococcus aureus (inhibition zone: 13.7 ± 0.6 mm). Moreover, the particle filtration efficiency of the PVA-TA NFM for PM0.6 particles was 97.7% at 32 L min-1 and 99.5% at 85 L min-1, indicating excellent filtration performance and a low pressure drop. Therefore, the TA-enriched PVA NFM is a promising mask filter layer material with excellent UV-blocking and antibacterial properties and has the potential for various practical applications.

SIC50: Determining drug inhibitory concentrations using a vision transformer and an optimized Sobel operator.

As a measure of cytotoxic potency, half-maximal inhibitory concentration (IC50) is the concentration at which a drug exerts half of its maximal inhibitory effect against target cells. It can be determined by various methods that require applying additional reagents or lysing the cells. Here, we describe a label-free Sobel-edge-based method, which we name SIC50, for the evaluation of IC50. SIC50 classifies preprocessed phase-contrast images with a state-of-the-art vision transformer and allows for the continuous assessment of IC50 in a faster and more cost-efficient manner. We have validated this method using four drugs and 1,536-well plates and also built a web application. We anticipate that this method will assist in the high-throughput screening of chemical libraries (e.g., small-molecule drugs, small interfering RNA [siRNA], and microRNA and drug discovery).

Gender Disparity in Pediatric Surgery: An Evaluation of Pediatric Surgery Conference Participation.

BACKGROUND: Leadership in academic conferences is an important factor for academic advancement. Underrepresentation of women in academic surgical conferences has been demonstrated in other subspecialties, but it has not been well-studied in pediatric surgery. METHODS: This retrospective descriptive study analyzes conference participation at 2 national pediatric surgery annual conference programs from 2003 to 2022. Moderator, speakers, and research presenter sex was collected. The primary outcome was the proportion of female participants in each of these roles. Mann-Kendall trend test was conducted to assess for significance. RESULTS: Across 29 meetings, a total of 523 sessions were examined. Overall, female participation in all roles increased from 2003 to 2022. There were statistically positive trends of female participation in leadership roles as moderator (p = 0.003) and speaker (p = 0.01), with moderator role demonstrating the largest proportional female increase over time - with a 7-fold increase from 7.1% in 2003 to 50.0% in 2022. There was also a significant increasing trend in female participation as research presenters (p < 0.01) from 25.4% to 46.4%. CONCLUSION: Gender representation in pediatric surgery conferences has improved over the last two decades. Women now represent approximately half of all participatory roles, and efforts to continue providing equal opportunities for women at pediatric surgery academic conferences should continue. LEVEL OF EVIDENCE: N/A. TYPE OF STUDY: Retrospective Descriptive.

Evaluation of a biodegradable polyurethane patch for repair of diaphragmatic hernia in a rat model: A pilot study.

INTRODUCTION: Congenital diaphragmatic hernia (CDH) repair is an area of active research. Large defects requiring patches have a hernia recurrence rate of up to 50%. We designed a biodegradable polyurethane (PU)-based elastic patch that matches the mechanical properties of native diaphragm muscle. We compared the PU patch to a non-biodegradable Gore-Tex™ (polytetrafluoroethylene) patch. METHODS: The biodegradable polyurethane was synthesized from polycaprolactone, hexadiisocyanate and putrescine, and then processed into fibrous PU patches by electrospinning. Rats underwent 4 mm diaphragmatic hernia (DH) creation via laparotomy followed by immediate repair with Gore-Tex™ (n = 6) or PU (n = 6) patches. Six rats underwent sham laparotomy without DH creation/repair. Diaphragm function was evaluated by fluoroscopy at 1 and 4 weeks. At 4 weeks, animals underwent gross inspection for recurrence and histologic evaluation for inflammatory reaction to the patch materials. RESULTS: There were no hernia recurrences in either cohort. Gore-Tex™ had limited diaphragm rise compared to sham at 4 weeks (1.3 mm vs 2.9 mm, p = 0.003), but no difference was found between PU and sham (1.7 mm vs 2.9 mm, p = 0.09). There were no differences between PU and Gore-Tex™ at any time point. Both patches formed an inflammatory capsule, with similar thicknesses between cohorts on the abdominal (Gore-Tex™ 0.07 mm vs. PU 0.13 mm, p = 0.39) and thoracic (Gore-Tex™ 0.3 mm vs. PU 0.6 mm, p = 0.09) sides. CONCLUSION: The biodegradable PU patch allowed for similar diaphragmatic excursion compared to control animals. There were similar inflammatory responses to both patches. Further work is needed to evaluate long-term functional outcomes and further optimize the properties of the novel PU patch in vitro and in vivo. LEVEL OF EVIDENCE: Level II, Prospective Comparative Study.

HO-1089 and HO-1197, Novel Herbal Formulas, Have Antitumor Effects via Suppression of PLK1 (Polo-like Kinase 1) Expression in Hepatocellular Carcinoma.

The treatment for hepatocellular carcinoma (HCC), a severe cancer with a very high mortality rate, begins with the surgical resection of the primary tumor. For metastasis or for tumors that cannot be resected, sorafenib, a multi-tyrosine protein kinase inhibitor, is usually the drug of choice. However, typically, neither resection nor sorafenib provides a cure. The drug discovery strategy for HCC therapy is shifting from monotherapies to combination regimens that combine an immuno-oncology agent with an angiogenesis inhibitor. Herbal formulas can be included in the combinations used for this personalized medicine approach. In this study, we evaluated the HCC anticancer efficacy of the new herbal formula, HO-1089. Treatment with HO-1089 inhibited HCC tumor growth by inducing DNA damage-mediated apoptosis and by arresting HCC cell replication during the G2/M phase. HO-1089 also attenuated the migratory capacity of HCC cells via the inhibition of the expression of EMT-related proteins. Biological pathways involved in metabolism and the mitotic cell cycle were suppressed in HO-1089-treated HCC cells. HO-1089 attenuated expression of the G2/M phase regulatory protein, PLK1 (polo-like kinase 1), in HCC cells. HCC xenograft mouse models revealed that the daily oral administration of HO-1089 retarded tumor growth without systemic toxicity in vivo. The use of HO-1197, a novel herbal formula derived from HO-1089, resulted in statistically significant improved anticancer efficacy relative to HO-1089 in HCC. These results suggest that HO-1089 is a safe and potent integrated natural medicine for HCC therapy.

Inhibition of Melanogenesis by Essential Oils from the Citrus Cultivars Peels.

Citrus is one of the most popular and widely grown fruit crops in the world. However, the bioactivity of only certain species of citrus cultivars is studied. In this study, the effects of essential oils from 21 citrus cultivars on melanogenesis were investigated in an effort to identify active anti-melanogenesis constituents. The essential oils from the peels of 21 citrus cultivars obtained by hydro-distillation were analyzed using gas chromatography-mass spectrometry. Mouse melanoma B16BL6 cells were used in all assays conducted in this study. The tyrosinase activity and melanin content were determined using the lysate of α-Melanocyte-stimulated B16BL6 cells. In addition, the melanogenic gene expression was determined by quantitative reverse transcription-polymerase chain reaction. Overall, the essential oils of (Citrus unshiu X Citrus sinensis) X Citrus reticulata, Citrus reticulata, and ((Citrus unshiu X Citrus sinensis) X Citrus reticulata) X Citrus reticulata provided the best bioactivity and comprised five distinct constituents compared to other essential oils such as limonene, farnesene, ß-elemene, terpinen-4-ol, and sabinene. The anti-melanogenesis activities of the five individual compounds were evaluated. Among the five essential oils, ß-elemene, farnesene, and limonene showed dominating properties. The experimental results indicated that (Citrus unshiu X Citrus sinensis) X Citrus reticulata, Citrus reticulata, and ((Citrus unshiu X Citrus sinensis) X Citrus reticulata) X Citrus reticulara are potential candidates with anti-melanogenesis activity for use as cosmetics and pharmaceutical agents against skin hyperpigmentation.

Deciphering the underlying mechanism of liver diseases through utilization of multicellular hepatic spheroid models.

Hepatocellular carcinoma (HCC) is a very common form of cancer worldwide and is often fatal. Although the histopathology of HCC is characterized by metabolic pathophysiology, fibrosis, and cirrhosis, the focus of treatment has been on eliminating HCC. Recently, three-dimensional (3D) multicellular hepatic spheroid (MCHS) models have provided a) new therapeutic strategies for progressive fibrotic liver diseases, such as antifibrotic and anti-inflammatory drugs, b) molecular targets, and c) treatments for metabolic dysregulation. MCHS models provide a potent anti-cancer tool because they can mimic a) tumor complexity and heterogeneity, b) the 3D context of tumor cells, and c) the gradients of physiological parameters that are characteristic of tumors in vivo. However, the information provided by an multicelluar tumor spheroid (MCTS) model must always be considered in the context of tumors in vivo. This mini-review summarizes what is known about tumor HCC heterogeneity and complexity and the advances provided by MCHS models for innovations in drug development to combat liver diseases. [BMB Reports 2023; 56(4): 225-233].

The health effects of low blood lead level in oxidative stress as a marker, serum gamma-glutamyl transpeptidase level, in male steelworkers.

Background: This study aimed to investigate the association between lead exposure and serum gamma-glutamyl transpeptidase (γGT) levels as an oxidative stress marker in male steelworkers. Methods: Data were collected during the annual health examination of workers in 2020. A total of 1,654 steelworkers were selected, and the variables for adjustment included the workers' general characteristics, lifestyle, and occupational characteristics. The association between the blood lead level (BLL) and serum γGT level was investigated by multiple linear and logistic regression analyses. The BLL and serum γGT values that were transformed into natural logarithms were used in multiple linear regression analysis, and the tertile of BLL was used in logistic regression analysis. Results: The geometric mean of the participants' BLLs and serum γGT level was 1.36 µg/dL and 27.72 IU/L, respectively. Their BLLs differed depending on age, body mass index (BMI), smoking status, drinking status, shift work, and working period, while their serum γGT levels differed depending on age, BMI, smoking status, drinking status, physical activity, and working period. In multiple linear regression analysis, the difference in models 1, 2, and 3 was significant, obtaining 0.326, 0.176, and 0.172 (all: p < 0.001), respectively. In the multiple linear regression analysis stratified according to drinking status, BMI, and age, BLLs were positively associated with serum γGT levels. Regarding the logistic regression analysis, the odds ratio of the third BLL tertile in models 1, 2, and 3 (for having an elevated serum γGT level within the first tertile reference) was 2.74, 1.83, and 1.81, respectively. Conclusions: BLL was positively associated with serum γGT levels in male steelworkers even at low lead concentrations (< 5 µg/dL).

Fetal Repair of Neural Tube Defects.

Myelomeningocele is the most common congenital neurologic defect, and the only nonlethal disease addressed by fetal surgery. A randomized control trial has established amelioration of the Arnold-Chiari II malformation, reduced ventriculoperitoneal shunt rate, and improvement in distal neurologic function in patients that receive in utero repair. Long-term follow-up of these school-age children demonstrates the persistence of these effects. The use of stem cells in fetal repair is being investigated to further improve distal motor function.

Sorbitol dehydrogenase induction of cancer cell necroptosis and macrophage polarization in the HCC microenvironment suppresses tumor progression.

Hepatocellular carcinoma (HCC) is among the most common malignant cancers worldwide, with an increasing incidence associated with an increase in deaths due to liver cancer. HCC is typically detected at an advanced stage in patients with underlying liver dysfunction, resulting in high mortality. The identification of HCC-specific targets represents a desired but unmet need for liver cancer treatment. To identify potentially novel HCC therapeutic targets, we performed a secretome analysis using HCC spheroids. Sorbitol dehydrogenase (SORD) was identified as uniquely enriched in the secretomes and lysates derived from HCC spheroids, and high SORD expression in HCC tissues was associated with favorable effects on overall survival among patients with liver cancer. We found that the introduction of excess SORD in HCC cells inhibited tumor growth and stemness by enhancing necroptosis signal and bypassing energy-yielding pathways through regulation of lactate dehydrogenase A (LDHA) expression and mitochondrial dynamics. Treatment with human recombinant SORD (hrSORD) controlled HCC cell growth and regulated macrophage polarization in the tumor microenvironment. These results demonstrate that SORD plays critical functional roles in HCC suppression through polyol pathway-independent mechanisms, suggesting that targeting SORD expression might represent a promising therapeutic strategy for liver cancer therapy.

A Botanical Mixture Consisting of Inula japonica and Potentilla chinensis Relieves Obesity via the AMPK Signaling Pathway in 3T3-L1 Adipocytes and HFD-Fed Obese Mice.

Excessive lipid accumulation in white adipose tissue (WAT) is the major cause of obesity. Herein, we investigated the anti-obesity effect and molecular mechanism of a botanical mixture of 30% EtOH extract from the leaves of Inula japonica and Potentilla chinensis (EEIP) in 3T3-L1 preadipocytes and high-fat diet (HFD)-fed obese mice. In vitro, EEIP prevented lipid accumulation by downregulating the expression of lipogenesis-related transcription factors such as CCAAT/enhancer binding protein (C/EBP)α, peroxisome proliferator-activated receptor (PPAR)γ, and sterol regulatory element binding protein (SREBP)-1 via AMP-activated protein kinase (AMPK) activation and G0/G1 cell cycle arrest by regulating the Akt-mTOR pathways without inducing cytotoxicity. In vivo, EEIP significantly reduced body weight gain and body fat mass in the group administered concurrently with HFD (pre-) or administered during the maintenance of HFD (post-) including subcutaneous, gonadal, renal, and mesenteric fats, and improved blood lipid profiles and metabolic hormones. EEIP pre-administration also alleviated WAT hypertrophy and liver lipid accumulation by reducing C/EBPα, PPARγ, and SREBP-1 expression via AMPK activation. In the brown adipose tissue, EEIP pre-administration upregulated the expression of thermogenic factors. Furthermore, EEIP improved the HFD-induced altered gut microbiota in mice. Taken together, our data indicated that EEIP improves HFD-induced obesity through adipogenesis inhibition in the WAT and liver and is a promising dietary natural material for improving obesity.

Chromenopyrimidinone exhibit antitumor effects through inhibition of CAP1 (Adenylyl cyclase-associated protein 1) expression in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most malignant human cancers, with a high mortality rate worldwide. Within an HCC tumor, cancer stem cells (CSCs) are responsible for tumor maintenance and progression and may contribute to resistance to standard HCC treatments. Previously, we characterized CD133+ cells as CSCs in primary HCC and identified chromenopyrimidinone (CPO) as a novel therapeutic for the effective treatment of CD133+ HCC. However, the biological function and molecular mechanism of CD133 remain unclear. Epigenetic alterations of CSCs have impacts on tumor initiation, progression, and therapeutic response. Here, we found that pharmacological and genetic depletion of CD133 in HCC attenuated the activity of DNA methyltransferases via control of DNMT3B stabilization. Genes were ranked by degree of promoter hypo/hyper methylation and significantly differential expression to create an "epigenetically activated by CPO" ranked genes list. Through this epigenetic analysis, we found that CPO treatment altered DNA methylation-mediated oncogenic signaling in HCCs. Specifically, CPO treatment inhibited Adenylyl cyclase-associated protein 1 (CAP1) expression, thereby reducing FAK/ERK activity and EMT-related proteins in HCC. Moreover, CPO improved the efficacy of sorafenib by inhibiting CAP1 expression and FAK/ERK activation in sorafenib-resistant HCC. These novel mechanistic insights may ultimately open up avenues for strategies targeting DNA methylation in liver cancer stem cells and provides novel therapeutic function of CPO for the effective treatment of sorafenib-resistant HCC.

Poly(vinyl alcohol) nanofibrous membranes via green electrospinning and tannin coating for selective removal of Pb(II) ion.

The conventional adsorbent fabrication methods involve complicated processes and may cause secondary contaminations. Therefore, an effective eco-friendly method is required for the fabrication of heavy metal adsorbents using inexpensive and eco-friendly materials without secondary pollution during their process. In this study, nanofibrous membranes (NFMs) were fabricated via green electrospinning of poly(vinyl alcohol) (PVA), a hydrophilic polymer, and their water resistance was improved through simple heat treatment without using additional additives. Then, nanofibrous heavy metal adsorbents were prepared by dip-coating the NFMs in an aqueous solution of tannic acid (TA), a natural polyphenol. First, the adsorption/desorption behavior of TA on PVA NFMs during the TA coating process was investigated. In addition, the effects of TA coating on the mechanical properties and heavy metal adsorption characteristics of the PVA NFMs were analyzed. The TA coating significantly increased the mechanical strength, heat resistance, and heavy metal (Pb(II)) adsorption capacity of the PVA NFM. The Pb2+ adsorption amount of TA-coated PVA NFMs exhibited about 5-7 times higher than those of other heavy metal ions, indicating excellent selectivity for Pb2+. In addition, the TA-coated PVA NFMs retained >70% of its initial adsorption capacity even after four cycles of adsorption/desorption, indicating its reusability.

Spina Bifida: A Review of the Genetics, Pathophysiology and Emerging Cellular Therapies.

Spina bifida is the most common congenital defect of the central nervous system which can portend lifelong disability to those afflicted. While the complete underpinnings of this disease are yet to be fully understood, there have been great advances in the genetic and molecular underpinnings of this disease. Moreover, the treatment for spina bifida has made great advancements, from surgical closure of the defect after birth to the now state-of-the-art intrauterine repair. This review will touch upon the genetics, embryology, and pathophysiology and conclude with a discussion on current therapy, as well as the first FDA-approved clinical trial utilizing stem cells as treatment for spina bifida.