Anti-Obesity and Anti-Diabetic Effects of Ostericum koreanum (Ganghwal) Extract.

"Ganghwal" is a widely used herbal medicine in Republic of Korea, but it has not been reported as a treatment strategy for obesity and diabetes within adipocytes. In this study, we determined that Ostericum koreanum extract (OKE) exerts an anti-obesity effect by inhibiting adipogenesis and an anti-diabetic effect by increasing the expression of genes related to glucose uptake in adipocytes and inhibiting α-glucosidase activity. 3T3-L1 preadipocytes were differentiated for 8 days in methylisobutylxanthine, dexamethasone, and insulin medium, and the effect of OKE was confirmed by the addition of 50 and 100 µg/mL of OKE during the differentiation process. This resulted in a reduction in lipid accumulation and the expression of PPARγ (Peroxisome proliferator-activated receptor γ) and C/EBPα (CCAAT enhancer binding protein α). Significant activation of AMPK (AMP-activated protein kinase), increased expression of GLUT4 (Glucose Transporter Type 4), and inhibition of α-glucosidase activity were also observed. These findings provide the basis for the anti-obesity and anti-diabetic effects of OKE. In addition, OKE has a significant antioxidant effect. This study presents OKE as a potential natural product-derived material for the treatment of patients with metabolic diseases such as obesity- and obesity-induced diabetes.

Interleukin-2 is required for NKp30-dependent NK cell cytotoxicity by preferentially regulating NKp30 expression.

Natural killer (NK) cells are key effectors in cancer immunosurveillance, eliminating a broad spectrum of cancer cells without major histocompatibility complex (MHC) specificity and graft-versus-host diseases (GvHD) risk. The use of allogeneic NK cell therapies from healthy donors has demonstrated favorable clinical efficacies in treating diverse cancers, particularly hematologic malignancies, but it requires cytokines such as IL-2 to primarily support NK cell persistence and expansion. However, the role of IL-2 in the regulation of activating receptors and the function of NK cells expanded for clinical trials is poorly understood and needs clarification for the full engagement of NK cells in cancer immunotherapy. Here, we demonstrated that IL-2 deprivation significantly impaired the cytotoxicity of primary expanded NK cells by preferentially downregulating NKp30 but not NKp46 despite their common adaptor requirement for expression and function. Using NK92 and IL-2-producing NK92MI cells, we observed that NKp30-mediated cytotoxicity against myeloid leukemia cells such as K562 and THP-1 cells expressing B7-H6, a ligand for NKp30, was severely impaired by IL-2 deprivation. Furthermore, IL-2 deficiency-mediated NK cell dysfunction was overcome by the ectopic overexpression of an immunostimulatory NKp30 isoform such as NKp30a or NKp30b. In particular, NKp30a overexpression in NK92 cells improved the clearance of THP-1 cells in vivo without IL-2 supplementation. Collectively, our results highlight the distinct role of IL-2 in the regulation of NKp30 compared to that of NKp46 and suggest NKp30 upregulation, as shown here by ectopic overexpression, as a viable modality to harness NK cells in cancer immunotherapy, possibly in combination with IL-2 immunocytokines.

Evaluating the Nutritional Composition of Unripe Citrus and Its Effect on Inhibiting Adipogenesis and Adipocyte Differentiation.

Citrus fruits offer a range of health benefits due to their rich nutritional profile, including vitamin C, flavonoids, carotenoids, and fiber. It is known that unripe citrus has higher levels of vitamin C, dietary fiber, polyphenols, and flavonoids compared to mature fruits. In this study, we assessed the nutritional components of unripe citrus peel and pressed juices, as well as their anti-obesity potential through the modulation of adipocyte differentiation and the expression of adipogenesisrelated genes, specifically PPARγ and C/EBPα, in 3T3-L1 preadipocytes. Our analysis revealed that unripe citrus peel exhibited elevated levels of fiber and protein compared to pressed juice, with markedly low levels of free sugar, particularly sucrose. The content of hesperidin, a representative flavonoid in citrus fruits, was 3,157.6 mg/kg in unripe citrus peel and 455.5 mg/kg in pressed juice, indicating that it was approximately seven times higher in unripe citrus peel compared to pressed juice. Moreover, we observed that the peel had a dose-dependently inhibitory effect on adipocyte differentiation, which was linked to a significant downregulation of adipogenesis-related gene expression. Thus, our findings suggest that unripe citrus possesses anti-obesity effects by impeding adipogenesis and adipocyte differentiation, with the peel demonstrating a more pronounced effect compared to pressed juice.

Targeting cell surface glucose-regulated protein 94 in gastric cancer with an anti-GRP94 human monoclonal antibody.

Gastric cancer (GC), a leading cause of cancer-related mortality, remains a significant challenge despite recent therapeutic advancements. In this study, we explore the potential of targeting cell surface glucose-regulated protein 94 (GRP94) with antibodies as a novel therapeutic approach for GC. Our comprehensive analysis of GRP94 expression across various cancer types, with a specific focus on GC, revealed a substantial overexpression of GRP94, highlighting its potential as a promising target. Through in vitro and in vivo efficacy assessments, as well as toxicological analyses, we found that K101.1, a fully human monoclonal antibody designed to specifically target cell surface GRP94, effectively inhibits GC growth and angiogenesis without causing in vivo toxicity. Furthermore, our findings indicate that K101.1 promotes the internalization and concurrent downregulation of cell surface GRP94 on GC cells. In conclusion, our study suggests that cell surface GRP94 may be a potential therapeutic target in GC, and that antibody-based targeting of cell surface GRP94 may be an effective strategy for inhibiting GRP94-mediated GC growth and angiogenesis. [BMB Reports 2024; 57(4): 188-193].

Over-Expression of p190RhoGEF Regulates the Formation of Atherosclerotic Plaques in the Aorta of ApoE-/- Mice via Macrophage Polarization.

The RhoA-specific guanine nucleotide exchange factor p190RhoGEF has been implicated in the control of cell morphology, focal adhesion formation, and cell motility. Previously, we reported that p190RhoGEF is also active in various immune cells. In this study, we examined whether over-expression of p190RhoGEF could affect atherosclerotic plaque formation in mouse aortae. For that purpose, transgenic (TG) mice over-expressing p190RhoGEF were cross-bred with atherosclerosis-prone apolipoprotein E (ApoE)-/- mice to obtain p190RhoGEF-TG mice with ApoE-/- backgrounds (TG/ApoE-/-). Aortic plaque formation was significantly increased in TG/ApoE mice-/- at 30 to 40 weeks of age compared to that in ApoE-/- mice. Serum concentrations of inflammatory cytokines (IL-6 and TNF-α) were greater in TG/ApoE-/- mice than in ApoE-/- mice at ~40 weeks of age. Furthermore, TG/ApoE-/- mice had a greater proportion of peritoneal macrophages within the M1 subset at 30 to 40 weeks of age, together with higher production of inflammatory cytokines and stronger responses to bacterial lipopolysaccharide than ApoE-/- mice. Collectively, these results highlight a crucial role of enhanced p190RhoGEF expression in atherosclerosis progression, including the activation of pro-inflammatory M1 macrophages.

Euscaphis japonica Kanitz Fruit Exerts Antiobesity Effects by Inhibiting the Early Stage of Adipogenic Differentiation.

During the worldwide COVID-19 outbreak, there was an increase in the prevalence of obesity, including childhood obesity, due to which the awareness of obesity and interest in treatment increased. Accordingly, we describe EJF (Euscaphis japonica Kanitz fruit) extract as a candidate for naturally derived antiobesity agents. In this study, we found that EJF is involved in the early stage of adipogenic differentiation in vitro and finally inhibits adipogenesis. We propose two mechanisms for the antiobesity effect of EJF. First, EJF inhibits MDI-induced mitotic clonal expansion (MCE) by inducing cell cycle arrest at the initiation of adipogenic differentiation. The second aims to regulate stability and activation at the protein level of IRS1, which initiates differentiation in the early stage of differentiation. As a result, it was found that the activation of Akt decreased, leading to the inhibition of the expression of adipogenesis-related transcription factors (PPARγ, C/EBPα) and the subsequent suppression of adipogenic differentiation. In summary, we suggest that EJF can inhibit adipogenesis and lipid accumulation by suppressing the early stage of adipogenic differentiation in 3T3-L1 adipocytes. These findings indicate that EJF's functionality could be beneficial in the treatment of obesity, particularly childhood obesity associated with adipocyte hyperplasia.

Aged black garlic (Allium sativum L.) and aged black elephant garlic (Allium ampeloprasum L.) alleviate obesity and attenuate obesity-induced muscle atrophy in diet-induced obese C57BL/6 mice.

Garlic (Allium sativum L.) is a primary dietary component worldwide because of its health benefits and use as a traditional medicine. Elephant garlic (Allium ampeloprasum L.), a related species in the same genus, is less intense and sweeter than A. sativum. The object of this study was to investigate the alleviative effects of aged black garlic (ABG) and aged black elephant garlic (ABEG) on obesity and muscle atrophy induced by obesity in high fat diet-induced obese mice. We demonstrated that ABG and ABEG alleviated obesity and muscle atrophy and enhanced myogenic differentiation and myotube hypertrophy, and this effect was mediated by the upregulation of Akt/mTOR/p70S6K signaling. Furthermore, a candidate bioactive compound of ABG and ABEG was suggested in this study through analysis using gas chromatography-mass spectroscopy and ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectroscopy. In conclusion, ABG and ABEG may alleviate obesity and treat obesity-induced muscle atrophy.

Bioconverted Fruit Extract of Akebia Quinata Exhibits Anti-Obesity Effects in High-Fat Diet-Induced Obese Rats.

Akebia quinata, commonly called chocolate vine, has various bioactivities, including antioxidant and anti-obesity properties. However, the anti-obesity effects of bioconverted extracts of A. quinate have not been examined. In this study, A. quinata fruit extracts was bioconverted using the enzyme isolated from the soybean paste fungi Aspergillus kawachii. To determine whether the bioconversion process could influence the anti-obesity effects of A. quinata fruit extracts, we employed 3T3-L1 adipocytes and HFD-induced obese rats. We observed that the bioconverted fruit extract of A. quinata (BFE) afforded anti-obesity effects, which were stronger than that for the non-bioconverted fruit extract (FE) of A. quinata. In 3T3-L1 adipocytes, treatment with BFE at concentrations of 20 and 40 µg reduced intracellular lipids by 74.8 (p < 0.05) and 54.9% (p < 0.01), respectively, without inducing cytotoxicity in preadipocytes. Moreover, the oral administration of BFE at the concentration of 300 mg/kg/day significantly reduced body and adipose tissue weights (p < 0.01) in HFD-induced obese rats. Plasma cholesterol values were reduced, whereas HDL was increased in BFE receiving rats. Although FE could exert anti-obesity effects, BFE supplementation induced more robust effects than FE. These results could be attributed to the bioconversion-induced alteration of bioactive compound content within the extract.

Nidus vespae Built by an Invasive Alien Hornet, Vespa velutina nigrithorax, Inhibits Adipose Tissue Expansion in High-Fat Diet-Induced Obese Mice

Nidus vespae, commonly known as the wasp nest, has antioxidative, anti-inflammatory, antimicrobial, and antitumor properties. However, the anti-obesity effects of Nidus vespae extract (NV) have not yet been reported. This study aimed to elucidate the potential anti-obesity effects of NV in vivo and in vitro, using a high-fat diet (HFD)-induced obese mouse model and 3T3-L1 adipocytes, respectively. NV administration to HFD-induced obese mice significantly decreased the mass and plasma lipid content of adipose tissues. Uncoupling protein-1 expression was significantly higher in the inguinal white adipose tissues of NV-treated mice than in those of HFD-fed mice. Furthermore, we found that NV inhibited the differentiation and intracellular lipid accumulation of 3T3-L1 adipocytes by regulating the insulin signaling cascade, including protein kinase B, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer binding protein alpha, and adiponectin. These findings suggest that NV may exhibit therapeutic effects against obesity by suppressing adipose tissue expansion and preadipocyte differentiation, thereby providing critical information for the development of new drugs for disease prevention and treatment. To our knowledge, this study provides the first evidence of the anti-obesity effects of NV.

Expression of a RhoA-Specific Guanine Nucleotide Exchange Factor, p190RhoGEF, in Mouse Macrophages Negatively Affects M1 Polarization and Inflammatory Responses.

A RhoA-specific guanine nucleotide exchange factor, p190RhoGEF, was first cloned and identified in neuronal cells. In immune cells, we first reported the role of p190RhoGEF in B cells: expression of p190RhoGEF increased after CD40 stimulation and was required for CD40-mediated B cell activation and differentiation. We also showed that over-expression of p190RhoGEF negatively affected dendritic cell function in response to bacterial lipopolysaccharide (LPS). In this study, we examined the role of p190RhoGEF in macrophages using p190RhoGEF over-expressing transgenic (TG) mice. We found macrophages from TG mice to be more round than those from control mice, with enriched polymerized actin at the edge attached to the glass. TG macrophages also responded less to LPS: production of reactive oxygen species, phagocytosis, chemokine-dependent migration, and pro-inflammatory cytokine secretion were all reduced compared with the responses of macrophages from littermate (LTM) control mice. Furthermore, the classical M1 subset population was observed less in the peritoneal macrophages of TG mice than the LTM control mice during LPS-elicited peritoneal inflammation. When the activity of RhoA was inhibited in TG macrophages, their morphology and LPS responses became similar to those of the LTM macrophages. These results suggest that over-expression of p190RhoGEF in macrophages could reduce M1 polarization and inflammatory responses by regulating the actin cytoskeleton.

Discovery of Mycobacterium tuberculosis Rv3364c-Derived Small Molecules as Potential Therapeutic Agents to Target SNX9 for Sepsis.

The serine protease inhibitor Rv3364c of Mycobacterium tuberculosis (MTB) is highly expressed in cells during MTB exposure. In this study, we showed that the 12WLVSKF17 motif of Rv3364c interacts with the BAR domain of SNX9 and inhibits endosome trafficking to interact with p47phox, thereby suppressing TLR4 inflammatory signaling in macrophages. Derived from the structure of this Rv3364c peptide motif, 2,4-diamino-6-(4-tert-butylphenyl)-1,3,5-trazine, DATPT as a 12WLVSKF17 peptide-mimetic small molecule has been identified. DATPT can block the SNX9-p47phox interaction in the endosome and suppress reactive oxygen species and inflammatory cytokine production; it demonstrated significant therapeutic effects in a mouse model of cecal ligation and puncture-induced sepsis. DATPT has considerably improved potency, with an IC50 500-fold (in vitro) or 2000-fold (in vivo) lower than that of the 12WLVSKF17 peptide. Furthermore, DATPT shows potent antibacterial activities by reduction in ATP production and leakage of intracellular ATP out of bacteria. These results provide evidence for peptide-derived small molecule DATPT with anti-inflammatory and antibacterial functions for the treatment of sepsis.

Leisure-time physical activity interventions for children and adults with cerebral palsy: a scoping review.

AIM: To summarize current evidence on the effects and reach of leisure-time physical activity (LTPA) interventions among children and adults with cerebral palsy (CP). METHOD: Systematic searches were conducted in PubMed, CINAHL, and Google Scholar to identify randomized controlled trials (RCTs) of LTPA interventions in CP. Data from eligible studies were extracted for qualitative synthesis. RESULTS: Forty-nine studies enrolled a total of 1513 participants (mean [SD] age 13y [7y], range 5-43y; 818 males, 655 females, 40 not reported) and primarily included ambulatory children. RCTs underrepresented adults and people in Gross Motor Function Classification System (GMFCS) levels IV and V. Forty-one studies reported at least one favorable benefit from LTPA. Benefits included improvements to musculoskeletal strength, cardiorespiratory fitness, quality of life, spasticity, participation, and core aspects of physical function. Regarding reach, only 34% of people that were contacted to participate enrolled within a study. A smaller percentage of participants dropped out from intervention (8%) and follow-up periods (3%). INTERPRETATION: Study findings highlight effective interventions to improve health, fitness, and function. To enhance the reach and generalizability of LTPA trials for CP, future studies should examine how to increase study sample sizes and aim to include a better representation of adults and people in GMFCS levels IV and V. WHAT THIS PAPER ADDS: People with cerebral palsy (CP) may experience improvements in health, fitness, and physical function from leisure-time physical activity (LTPA) interventions. Effective interventions include exercise training, active video games, recreation activities, behavioral coaching, and motor skills training. Interventions that incorporate telehealth technology, behavioral coaching, and community resources may enhance LTPA. Interventions primarily include children in Gross Motor Functional Classification System (GMFCS) levels I to III. Adults, wheelchair users, and those in GMFCS levels IV and V are underrepresented.

A Review of Recent Evidence from Meal-Based Diet Interventions and Clinical Biomarkers for Improvement of Glucose Regulation.

In recent decades, the prevalence of diabetes has rapidly increased worldwide. Medical nutrition therapy has been identified as a major therapeutic support for diabetic patients, while preventive strategies in prediabetic or high-risk individuals have mainly focused on supplementation with bioactive compounds. Recently, meal-based interventions have been investigated as novel and safe long-term strategies for improving glucose regulation. However, evaluation of meal-based interventions is difficult since it requires analysis of sensitive markers. Biomarkers can also be used to identify individuals at risk for diabetes, which is important for disease prevention. In this review, we summarize current evidence from meal-based intervention studies conducted with the aim of improving glucose homeostasis in individuals at risk of diabetes using clinical biomarkers currently used to assess diabetic risk. Very low-calorie diets have significantly improved glucose regulation in obese adults and in adults with type 2 diabetes mellitus. In particular, changing the ratios of macronutrients through calorie restriction reduces fasting glucose level and hemoglobin A1c levels in patients with diabetes mellitus. However, this effect is limited in both obese and healthy adults. To date, multiple glucose-related markers have been identified as clinical biomarkers of diabetes. Additional clinical biomarkers include cholesterol levels, hematological markers, and inflammatory markers. Taken together, the evidence presented in this review may help for selection of clinical biomarkers for meal-based preventive approaches for non- or pre-diabetic individuals to prevent onset of diabetes.

Induction of DEAD Box helicase 5 in early adipogenesis is regulated by Ten-eleven translocation 2.

Dead box helicase 5 (DDX5) is an RNA helicase that is has cellular function on RNA splicing and transcriptional regulation. It has been reported to be involved in cell differentiation including adipogenesis. However, it is not clear how DDX5 is regulated during adipogenesis. Our previous report demonstrated that the Ten-eleven translocation methyl-cytosine dioxygenase 2 (TET2) is required for adipogenesis. This study was aimed to investigate DDX5 as a direct target of TET2 upon adipogenic induction of 3T3-L1 preadipocyte. Microarray-based screening of differentially expressed genes upon TET2 knockdown identified genes involved in cell cycle, DNA replication, and ribosome biology as major targets of TET2 in the initial step of adipogenic induction. The Ddx5 gene was identified and validated as the target. TET2-mediated epigenetic regulation of the Ddx5 gene was measured by two independent methods including immunoprecipitation against 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) as well as EpiMark 5hmC and 5mC analysis. Ddx5 expression was downregulated upon TET2 knockdown, coincided with a significant decrease of 5hmC at the Ddx5 locus. DDX5 knockdown significantly suppressed adipogenesis, while DDX5 overexpression promoted it. Importantly, DDX5 overexpression, when co-transfected, rescued the process of adipogenesis, which was hindered by TET2 siRNA treatment. The findings suggest TET2-mediated regulation of the Ddx5 gene is required for an initial step of adipogenesis.

Research Trends and Recommendations for Physical Activity Interventions Among Children and Youth With Disabilities: A Review of Reviews.

This scoping review synthesized reviews of physical activity (PA) interventions for children and youth with disabilities to highlight promising elements of effective interventions, research methodological limitations, and research priorities. Twenty studies were eligible and underwent three rounds of review by an expert panel. Rich and diverse PA programs derived potential short-term benefits toward health, function, and PA. Strategies to increase sample sizes included embedding programs in the community and using information communication technology to deliver exercise programs. Methodological limitations of interventions included a lack of generalizability, transferability, and scientific rigor. Three research priorities were identified: develop and report precision-based intervention strategies, identify strategies that promote both long-term and sustainable PA participation and outcomes, and develop scalable interventions and recruitment strategies. If addressed, these areas could enhance the impact of PA interventions for children and youth with disabilities.

Improving the Vertical Thermal Conductivity of Carbon Fiber-Reinforced Epoxy Composites by Forming Layer-by-Layer Contact of Inorganic Crystals.

A carbon fiber-reinforced polymer (CFRP) is a light and rigid composite applicable in various fields, such as in aviation and automobile industry. However, due to its low thermal conductivity, it does not dissipate heat sufficiently and thus accumulates heat stress. Here, we reported a facile and effective strategy to improve the through-thickness thermal conductivity of CFRP composites by using a layer-by-layer coating of inorganic crystals. They could provide efficient heat transfer pathways through layer-by-layer contact within the resulting composite material. The high thermally conductive CFRP composites were prepared by employing three types of inorganic crystal fillers composed of aluminum, magnesium, and copper on prepreg through the layer-by-layer coating process. The vertical thermal conductivity of pure CFRP was increased by up to 87% on using magnesium filler at a very low content of 0.01 wt %. It was also confirmed that the higher the thermal conductivity enhancement was, the better were the mechanical properties. Thus, we could demonstrate that the layer-by-layer inclusion of inorganic crystals can lead to improved through-thickness thermal conductivity and mechanical properties of composites, which might find applications in varied industrial fields.

A comparison of using the DSM-5 and MABC-2 for estimating the developmental coordination disorder prevalence in Korean children.

BACKGROUND: Previous literature has shown inconsistency in the prevalence of developmental coordination disorder (DCD). The Movement Assessment Battery for Children, Second Edition (MABC-2) is often used for DCD prevalence studies, although the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) recommends four criteria. AIMS: The purpose of this study was to compare the prevalence of DCD in Korean children using the DSM-5 and MABC-2. METHODS: A total of 548 Korean elementary school students (mean age: 8.5 years ± 4.5 months) completed this study procedure. All four criteria defined by the DSM-5 were used to classify children with DCD. MABC-2 test scores were used to classify students into four subgroups: high-risk DCD, mild-risk DCD, probable DCD and typical development. RESULTS: Cohen's kappa revealed that the estimates of DCD prevalence were not significantly different between MABC-2 and DSM-5. When DSM-5 criteria were applied, 60 children out of 548 were classified as probable DCD (10.94%) compared to 70 children with probable DCD (12.77%) when MABC-2 was used. CONCLUSIONS: DCD prevalence based on DSM-5 is not significantly different from MABC-2, though it tends to estimate less than MABC-2. Future studies should consider our findings when selecting an assessment tool.

The biomechanical investigation of the relationship between balance and muscular strength in people with chronic stroke: a pilot cross-sectional study.

BACKGROUND: Impaired balance and weak muscle strength are common deficits associated with stroke. Limited research has examined the relationship between balance and strength in people post-stroke. OBJECTIVE: To investigate the association between balance and muscular strength in people post-stroke. METHODS: A total of 11 people with chronic stroke, who were community dwelling and ambulatory, completed balance and strength assessments. A computerized dynamic posturography system was used for Limits of Stability (LOS) test, Sit-to-Stand (STS) test, and the Modified Clinical Test of Sensory Interaction on Balance (mCTSIB). Additionally, a computerized dynamometer was used to assess the isometric muscle strength of flexion/extension in the core (the trunk) and the leg (the hip, knee, and ankle). Pearson correlation analysis was used to investigate the relationship between balance and muscle strength measurements. RESULTS: Endpoint excursion (EPE) (r = .646; p < 0.032) and maximum excursion (MXE) (r = .613; p < 0.045) of LOS test were positively correlated with core and leg strength (C&L). Specifically, both EPE (r = -.792; p < 0.004) and MXE (r = -.623; p < 0.041) in backward direction had strong correlations with C&L. Core strength also showed a positive correlation with EPE of LOS test (r = .636; p < 0.035) while the composite leg strength did not. Lastly, STS and mCTSIB tests did not demonstrate significant associations with muscle strength. CONCLUSIONS: The results indicate that the C&L have a strong relationship with the ability to shift body weight in multiple directions, particularly backward, among people post-stroke. However, static balance and STS performance do not appear to be related to muscle strength.

A retrospective comparison of outcome in IB2 and IIA cervical cancer patients treated with primary concurrent chemoradiation versus radical hysterectomy with or without tailored adjuvant therapy.

OBJECTIVE: The aim of our study is to compare the overall survival (OS), progression-free survival (PFS), and treatment-related morbidities between primary concurrent chemoradiation therapy (CCRT) vs. radical hysterectomy (RH) with or without tailored adjuvant therapy in patients with stages IB2 and IIA cervical cancer. METHODS: This was a retrospective study of 113 patients with IB2 or IIA cervical cancer treated with either primary CCRT (n=49) or RH (n=64) with or without tailored adjuvant therapy between 2002 and 2011 at Keimyung University Dongsan Medical Center. Patients in RH group was divided into those undergoing surgery alone (n=26) and those undergoing surgery with adjuvant therapy (n=38). RESULTS: The median follow up period was 66 months. The 5-year OS by treatment modality was 88.7% for the 64 patients in the RH group and 72.8% for 49 patients in the CCRT group (P=0.044). The 5-year PFS was 82.3% and 65.6% after RH group and CCRT group (P=0.048), respectively. Grade 3-4 complication was less frequent after RH alone (7.7%) than RH with adjuvant therapy (34.2%) or CCRT group (28.6%) (P=0.047). CONCLUSION: The RH group seems to be superior to the CCRT group in oncologic outcomes. However, considering the selection bias including tumor size, lymph node meta, and parametrial invasion in pretreatment magnetic resonance imaging, both treatment modalities are reasonable and feasible in cervical cancer IB2 and IIA. It is important to choose the appropriate treatment modality considering the age and general condition of the patient. Randomized controlled study is needed to confirm the result of our study and determine the optimal treatment.

Antioxidant effects of selenocysteine on replicative senescence in human adipose-derived mesenchymal stem cells.

In most clinical applications, human mesenchymal stem cells (hMSCs) are expanded in large scale before their administration. Prolonged culture in vitro results in cellular senescenceassociated phenotypes, including accumulation of reactive oxygen species (ROS) and decreased cell viabilities. Profiling of stem cell-related genes during in vitro expansion revealed that numerous canonical pathways were significantly changed. To determine the effect of selenocysteine (Sec), a rare amino acid found in several antioxidant enzymes, on the replicative senescence in hMSCs, we treated senescent hMSCs with Sec. Supplementation of Sec in the culture medium in late-passage hMSCs reduced ROS levels and improved the survival of hMSCs. In addition, a subset of key antioxidant genes and Sec-containing selenoproteins showed increased mRNA levels after Sec treatment. Furthermore, ROS metabolism and inflammation pathways were predicted to be downregulated. Taken together, our results suggest that Sec has antioxidant effects on the replicative senescence of hMSCs. [BMB Reports 2017; 50(11): 572-577].