COVID-19 and Virtual Nutrition: A Pilot Study of Integrating Digital Food Models for Interactive Portion Size Education.

Background and aims: Digital food viewing is a vital skill for connecting dieticians to e-health. The aim of this study was to integrate a novel pedagogical framework that combines interactive three- (3-D) and two-dimensional (2-D) food models into a formal dietetic training course. The level of agreement between the digital food models (first semester) and the effectiveness of educational integration of digital food models during the school closure due to coronavirus disease 2019 (COVID-19) (second semester) were evaluated. Method: In total, 65 second-year undergraduate dietetic students were enrolled in a nutritional practicum course at the School of Nutrition and Health Sciences, Taipei Medical University (Taipei, Taiwan). A 3-D food model was created using Agisoft Metashape. Students' digital food viewing skills and receptiveness towards integrating digital food models were evaluated. Results: In the first semester, no statistical differences were observed between 2-D and 3-D food viewing skills in food identification (2-D: 89% vs. 3-D: 85%) and quantification (within ±10% difference in total calories) (2-D: 19.4% vs. 3-D: 19.3%). A Spearman correlation analysis showed moderate to strong correlations of estimated total calories (0.69~0.93; all p values < 0.05) between the 3-D and 2-D models. Further analysis showed that students who struggled to master both 2-D and 3-D food viewing skills had lower estimation accuracies than those who did not (equal performers: 28% vs. unequal performers:16%, p = 0.041), and interactive 3-D models may help them perform better than 2-D models. In the second semester, the digital food viewing skills significantly improved (food identification: 91.5% and quantification: 42.9%) even for those students who struggled to perform digital food viewing skills equally in the first semester (equal performers: 44% vs. unequal performers: 40%). Conclusion: Although repeated training greatly enhanced students' digital food viewing skills, a tailored training program may be needed to master 2-D and 3-D digital food viewing skills. Future study is needed to evaluate the effectiveness of digital food models for future "eHealth" care.

Ginsenoside compound K reduces the progression of Huntington's disease via the inhibition of oxidative stress and overactivation of the ATM/AMPK pathway.

Background: Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of trinucleotide CAG repeat in the Huntingtin (Htt) gene. The major pathogenic pathways underlying HD involve the impairment of cellular energy homeostasis and DNA damage in the brain. The protein kinase ataxia-telangiectasia mutated (ATM) is an important regulator of the DNA damage response. ATM is involved in the phosphorylation of AMP-activated protein kinase (AMPK), suggesting that AMPK plays a critical role in response to DNA damage. Herein, we demonstrated that expression of polyQ-expanded mutant Htt (mHtt) enhanced the phosphorylation of ATM. Ginsenoside is the main and most effective component of Panax ginseng. However, the protective effect of a ginsenoside (compound K, CK) in HD remains unclear and warrants further investigation. Methods: This study used the R6/2 transgenic mouse model of HD and performed behavioral tests, survival rate, histological analyses, and immunoblot assays. Results: The systematic administration of CK into R6/2 mice suppressed the activation of ATM/AMPK and reduced neuronal toxicity and mHTT aggregation. Most importantly, CK increased neuronal density and lifespan and improved motor dysfunction in R6/2 mice. Conversely, CK enhanced the expression of Bcl2 protected striatal cells from the toxicity induced by the overactivation of mHtt and AMPK. Conclusions: Thus, the oral administration of CK reduced the disease progression and markedly enhanced lifespan in the transgenic mouse model (R6/2) of HD.

Surgical outcome of benign cases with pelvic adhesions undergoing robotic total hysterectomy.

BACKGROUND: Robotic total hysterectomies have been considered contraindicated for patients with intra-abdominal adherences, but the evidence for this is not strong, and we hypothesized that the procedure can be of benefit even in these cases. In our research, we analyzed how the severity of pelvic adhesions affects robotic total hysterectomy, and by comparing different types of adhesions, we can further identify the outcomes differences in between, which may aid in future surgical decision making. METHODS: Prospective cohort study (Canadian Task Force classification II-2). All 410 patients with uterine myoma or adenomyosis undergoing robotic total hysterectomies between 2011 and 2016 using the da Vinci Si system by the same surgeon in Taipei Medical University Hospital were included in the study. RESULTS: Baseline characteristics, blood loss, docking time, operation time, time to perform uterine artery ligation (UAL), pain score, hospital stay, complication rate, and laparotomy conversion rate were analyzed between benign cases with or without pelvic adhesions undergoing robotic total hysterectomy. Furthermore, in our subgroups analysis, we have divided the patients with adhesion into different groups according to the severity of adhesion. The abdomen and pelvic cavity was divided into nine sections, and the outcomes of different adhesion condition were compared. We found that patients with adhesions had increased docking time and operation time, but other differences between groups were not statistically significant. The results of the adhesion group showed no significant increases in blood loss, intra- and postoperative complications, and length of hospital stay. Only significantly longer surgical time compared with the normal group was noted. CONCLUSION: Our results suggest that robotic total hysterectomies with UAL are effective and safe for patients with benign gynecologic conditions, and the surgical method should be considered even for patients with adhesion risks.

Melatonin enhances osteogenic differentiation of dental pulp mesenchymal stem cells by regulating MAPK pathways and promotes the efficiency of bone regeneration in calvarial bone defects.

BACKGROUND: Mesenchymal stem cell (MSC)-based tissue engineering plays a major role in regenerative medicine. However, the efficiency of MSC transplantation and survival of engrafted stem cells remain challenging. Melatonin can regulate MSC biology. However, its function in the osteogenic differentiation of dental pulp-derived MSCs (DPSCs) remains unclear. We investigated the effects and mechanisms of melatonin on the osteogenic differentiation and bone regeneration capacities of DPSCs. METHODS: The biological effects and signaling mechanisms of melatonin with different concentrations on DPSCs were evaluated using a proliferation assay, the quantitative alkaline phosphatase (ALP) activity, Alizarin red staining, a real-time polymerase chain reaction, and a western blot in vitro cell culture model. The in vivo bone regeneration capacities were assessed among empty control, MBCP, MBCP + DPSCs, and MBCP + DPSCs + melatonin preconditioning in four-created calvarial bone defects by using micro-computed tomographic, histological, histomorphometric, and immunohistochemical analyses after 4 and 8 weeks of healing. RESULTS: In vitro experiments revealed that melatonin (1, 10, and 100 µM) significantly and concentration-dependently promoted proliferation, surface marker expression (CD 146), ALP activity and extracellular calcium deposition, and osteogenic gene expression of DPSCs (p < 0.05). Melatonin activated the protein expression of ALP, OCN, and RUNX-2 and inhibited COX-2/NF-κB expression. Furthermore, the phosphorylation of mitogen-activated protein kinase (MAPK) p38/ERK signaling was significantly increased in DPSCs treated with 100 µM melatonin, and their inhibitors significantly decreased osteogenic differentiation. In vivo experiments demonstrated that bone defects implanted with MBCP bone-grafting materials and melatonin-preconditioned DPSCs exhibited significantly greater bone volume fraction, trabecular bone structural modeling, new bone formation, and osteogenesis-related protein expression than the other three groups at 4 and 8 weeks postoperatively (p < 0.05). CONCLUSIONS: These results suggest that melatonin promotes the proliferation and osteogenic differentiation of DPSCs by regulating COX-2/NF-κB and p38/ERK MAPK signaling pathways. Preconditioning DPSCs with melatonin before transplantation can efficiently enhance MSCs function and regenerative capacities.

Development of a novel latent electrochemical molecular substrate for the real-time monitoring of the tumor marker aminopeptidase N in live cells, whole blood and urine.

Aminopeptidase N (APN/CD13) plays an important role in the growth and metastasis, of tumor, and is a potential biomarker for the post-treatment surveillance of cancer reoccurrence and progression of various malignancies. Thus, we have designed and prepared a convenient and ultrasensitive APN-targeting activity-based ratiometric electrochemical molecular substrate (Ala-AFC) for direct real-time monitoring of APN activity in biosamples. The APN in our experiment was used to hydrolyze the alanine moiety of the Ala-AFC probe and, as a result of this hydrolysis, realize concomitantly a cascade reaction to unmask the electrochemical reporter N-alkylated amino ferrocene (AAF). The Ala-AFC probe exhibited high sensitivity with a wide detection range of 0.05-110 ng mL-1 and a low limit of detection of 23.18 pg mL-1. The electrochemical signals were found to be distinctly specific for APN and free of interference from other electroactive biological species. Furthermore, the Ala-AFC probe was employed to monitor and quantify, in real-time, the activity of APN in tumor cells, whole blood, and urine. In addition, the results of our direct electrochemical quantifications of the amount of APN in whole blood and urine were found to be consistent with the results of the use of commercially available fluorometric assay kits to sense APN in serum and urine. Thus our approach shows promise as a point-of-care tool for cancer diagnostics and post-treatment surveillance of cancer reoccurrence.

High-dose ferric citrate supplementation attenuates omega-3 polyunsaturated fatty acid biosynthesis via downregulating delta 5 and 6 desaturases in rats with high-fat diet-induced obesity.

Obesity is associated with an increased risk of an iron deficiency; however, a synergistic relationship between iron and lipid homeostasis was also observed. The aim of this study was to investigate the effects of pharmacological doses of iron supplementation on omega 3 (n-3) and omega 6 (n-6) polyunsaturated fatty acids (PUFAs). Sprague-Dawley (SD) rats were fed a normal diet or a 50% high-fat diet (HFD) without or with pharmacological doses of ferric citrate (0.25, 1, or 2 g ferric iron per kg diet) for 12 weeks, and erythrocyte profiles of n-3 and n-6 PUFAs were quantitated. Ferric citrate supplementation showed dose-related effects on liver inflammation, liver iron accumulation, and increasing circulating levels of iron, erythrocyte degradation biomarkers LVV-hemorphin-7, malondialdehyde (MDA), and insulin. Obese rats supplemented with 2 g ferric iron per kg diet also had decreased levels of eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and total n-3 PUFAs compared to rats fed a normal diet or HFD alone. A western blotting analysis revealed that iron-mediated downregulation of n-3 PUFA-converting enzymes (Δ5 and Δ6 desaturases) only occurred at high dosages (≥1 g ferric iron per kg diet). A Spearman correlation analysis showed that total liver iron and serum LVV-hemorphin-7 and MDA were negatively correlated with n-3 PUFAs and their converting enzymes (Δ5 and Δ6 desaturases) (all p < 0.05). In conclusion, obese rats that received high-dose ferric citrate supplementation (>1 g of ferric iron per kg diet) exhibited decreased n-3 PUFA levels via downregulation of expressions of Δ5 and Δ6 desaturase enzymes.

Three-dimensional Spheroid Culture Enhances Multipotent Differentiation and Stemness Capacities of Human Dental Pulp-derived Mesenchymal Stem Cells by Modulating MAPK and NF-kB Signaling Pathways.

BACKGROUND: Three-dimensional (3D) culture of mesenchymal stem cells has become an important research and development topic. However, comprehensive analysis of human dental pulp-derived mesenchymal stem cells (DPSCs) in 3D-spheroid culture remains unexplored. Thus, we evaluated the cellular characteristics, multipotent differentiation, gene expression, and related-signal transduction pathways of DPSCs in 3D-spheroid culture via magnetic levitation (3DM), compared with 2D-monolayer (2D) and 3D-aggregate (3D) cultures. METHODS: The gross morphology and cellular ultrastructure were observed in the 2D, 3D, and 3DM experimental groups using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Surface markers and trilineage differentiation were evaluated using flow cytometry and staining analysis. Quantitative reverse transcription-polymerase chain reaction and immunofluorescence staining (IF) were performed to investigate the expression of differentiation and stemness markers. Signaling transduction pathways were evaluated using western blot analysis. RESULTS: The morphology of cell aggregates and spheroids was largely influenced by the types of cell culture plates and initial cell seeding density. SEM and TEM experiments confirmed that the solid and firm structure of spheroids was quickly formed in the 3DM-medium without damaging cells. In addition, these three groups all expressed multilineage differentiation capabilities and surface marker expression. The trilineage differentiation capacities of the 3DM-group were significantly superior to the 2D and 3D-groups. The osteogenesis, angiogenesis, adipogenesis, and stemness-related genes were significantly enhanced in the 3D and 3DM-groups. The IF analysis showed that the extracellular matrix expression, osteogenesis, and angiogenesis proteins of the 3DM-group were significantly higher than those in the 2D and 3D-groups. Finally, 3DM-culture significantly activated the MAPK and NF-kB signaling transduction pathways and ameliorated the apoptosis effects of 3D-culture. CONCLUSIONS: This study confirmed that 3DM-spheroids efficiently enhanced the therapeutic efficiency of DPSCs.

Integration of an Image-Based Dietary Assessment Paradigm into Dietetic Training Improves Food Portion Estimates by Future Dietitians.

The use of image-based dietary assessments (IBDAs) has rapidly increased; however, there is no formalized training program to enhance the digital viewing skills of dieticians. An IBDA was integrated into a nutritional practicum course in the School of Nutrition and Health Sciences, Taipei Medical University Taiwan. An online IBDA platform was created as an off-campus remedial teaching tool to reinforce the conceptualization of food portion sizes. Dietetic students' receptiveness and response to the IBDA, and their performance in food identification and quantification, were compared between the IBDA and real food visual estimations (RFVEs). No differences were found between the IBDA and RFVE in terms of food identification (67% vs. 71%) or quantification (±10% of estimated calories: 23% vs. 24%). A Spearman correlation analysis showed a moderate to high correlation for calorie estimates between the IBDA and RFVE (r ≥ 0.33~0.75, all p < 0.0001). Repeated IBDA training significantly improved students' image-viewing skills [food identification: first semester: 67%; pretest: 77%; second semester: 84%) and quantification [±10%: first semester: 23%; pretest: 28%; second semester: 32%; and ±20%: first semester: 38%; pretest: 48%; second semester: 59%] and reduced absolute estimated errors from 27% (first semester) to 16% (second semester). Training also greatly improved the identification of omitted foods (e.g., condiments, sugar, cooking oil, and batter coatings) and the accuracy of food portion size estimates. The integration of an IBDA into dietetic courses has the potential to help students develop knowledge and skills related to "e-dietetics".

Development of ratiometric electrochemical molecular switches to assay endogenous formaldehyde in live cells, whole blood and creatinine in saliva.

Formaldehyde is a reactive carbonyl species (RCS) that is produced naturally in the human body via metabolic and epigenetic biochemical processes, yet in high concentrations is highly toxic to the environment as well as to living organisms. Therefore, we designed two ratiometric electrochemical molecular redox probes, Formaldehyde oxidative latent probe (FOLP) and dihydroxy-formaldehyde oxidative latent probe (HFOLP), for the selective profiling of endogenous formaldehyde. FOLP and HFOLP each underwent the aza-Cope reaction with formaldehyde followed by hydrolysis to eliminate unmask redox reporter N-alkylated aminoferrocene (AAF) to monitor their response current. The FOLP and HFOLP sensors showed broad dynamic ranges of 0.12-1000 µM and 0.09-3 mM for formaldehyde with detection limits of 48.2 nM and 31.6 µM, respectively. Also, since formaldehyde is the byproduct of biochemical reactions for detecting creatinine and creatinine is an important biomarker for chronic kidney disease (CKD), we tested the FOLP probe for its ability to monitor creatinine. It successfully did so, and this ability was used to develop an electrochemical platform for the quantification of creatinine; it showed a dynamic range of 3.25-200 µM and a limit of detection (1.3 µM). In addition, the FOLP-based assay platform delivered a reliable analytical performance for the quantification of formaldehyde in human whole blood and of creatinine in saliva, and also for the real-time monitoring of endogenous formaldehyde secretion in HeLa cells. Moreover, the concentrations determined using our method were found to be consistent with those determined using formaldehyde and creatinine fluorometric assay kits.

Ginsenoside M1 Induces Apoptosis and Inhibits the Migration of Human Oral Cancer Cells.

Oral squamous cell carcinoma (OSCC) accounts for 5.8% of all malignancies in Taiwan, and the incidence of OSCC is on the rise. OSCC is also a common malignancy worldwide, and the five-year survival rate remains poor. Therefore, new and effective treatments are needed to control OSCC. In the present study, we prepared ginsenoside M1 (20-O-beta-d-glucopyranosyl-20(S)-protopanaxadiol), a major deglycosylated metabolite of ginsenoside, through the biotransformation of Panax notoginseng leaves by the fungus SP-LSL-002. We investigated the anti-OSCC activity and associated mechanisms of ginsenoside M1 in vitro and in vivo. We demonstrated that ginsenoside M1 dose-dependently inhibited the viability of human OSCC SAS and OEC-M1 cells. To gain further insight into the mode of action of ginsenoside M1, we demonstrated that ginsenoside M1 increased the expression levels of Bak, Bad, and p53 and induced apoptotic DNA breaks, G1 phase arrest, PI/Annexin V double-positive staining, and caspase-3/9 activation. In addition, we demonstrated that ginsenoside M1 dose-dependently inhibited the colony formation and migration ability of SAS and OEC-M1 cells and reduced the expression of metastasis-related protein vimentin. Furthermore, oral administration or subcutaneous injection of ginsenoside M1 significantly reduced tumor growth in SAS xenograft mice. These results indicate that ginsenoside M1 can be translated into a potential therapeutic against OSCC.

Evaluation of adenomyosis after gonadotrophin-releasing hormone agonist therapy using ultrasound post-processing imaging: a pilot study.

OBJECTIVE: We explored a method for the quantitative sonographic analysis of myometrial texture using computer-aided image analysis software to assess outcomes following treatment with gonadotrophin-releasing hormone (GnRH) agonist for adenomyosis in women with infertility. METHOD: Data for patients with ultrasound images of the myometrium obtained at Taipei Medical University Hospital from 1 September 2018 to 5 April 5 2019 were analyzed. Only 10 patients with 20 ultrasound images matched the eligibility criteria. The images were divided into pre-treatment (n = 10) and post-treatment images (n = 10) and quantitative grayscale histograms were obtained from the ultrasound images using publicly available ImageJ computer-aided image analysis software. We analyzed the differences between the pre- and post-treatment images using the Mann-Whitney test and compared the results with outcomes assessed by serum CA-125 levels. RESULTS: Image analysis of the grayscale histograms revealed significant differences between before and after treatment. The classification of the myometrium pre-treatment and post-treatment was similar using CA-125 and histogram grayscale analysis. CONCLUSION: Computer-aided image analysis of grayscale histograms of the myometrium obtained from ultrasound images is an alternative method for assessing myometrial conditions after GnRH agonist treatment in patients with adenomyosis.

IgA Nephropathy Benefits from Compound K Treatment by Inhibiting NF-κB/NLRP3 Inflammasome and Enhancing Autophagy and SIRT1.

IgA nephropathy (IgAN), the most common primary glomerular disorder, has a relatively poor prognosis yet lacks a pathogenesis-based treatment. Compound K (CK) is a major absorbable intestinal bacterial metabolite of ginsenosides, which are bioactive components of ginseng. The present study revealed promising therapeutic effects of CK in two complementary IgAN models: a passively induced one developed by repeated injections of IgA immune complexes and a spontaneously occurring model of spontaneous grouped ddY mice. The potential mechanism for CK includes 1) inhibiting the activation of NLRP3 inflammasome in renal tissues, macrophages and bone marrow-derived dendritic cells, 2) enhancing the induction of autophagy through increased SIRT1 expression, and 3) eliciting autophagy-mediated NLRP3 inflammasome inhibition. The results support CK as a drug candidate for IgAN.

Iron and Advanced Glycation End Products: Emerging Role of Iron in Androgen Deficiency in Obesity.

The literature suggests a bidirectional relationship between testosterone (T) and iron, but mechanisms underlying this relationship remain unclear. We investigated effects of iron on advanced glycation end products (AGEs) in obesity-related androgen deficiency. In total, 111 men were recruited, and iron biomarkers and N(ɛ)-(carboxymethyl)lysine (CML) were measured. In an animal study, rats were fed a 50% high-fat diet (HFD) with (0.25, 1, and 2 g ferric iron/kg diet) or without ferric citrate for 12 weeks. Obese rats supplemented with >1 g iron/kg diet had decreased testicular total T compared to HFD alone. Immunohistochemical staining showed that >1 g of ferric iron increased iron and AGE retention in testicular interstitial tissues, which is associated with increased expression of the receptor for AGEs (RAGE), tumor necrosis factor-α, and nitric oxide. Compared with normal weight, overweight/obese men had lower T levels and higher rates of hypogonadism (19% vs. 11.3%) and iron overload (29.8% vs.15.9%). A correlation analysis showed serum total T was positively correlated with transferrin saturation (r = 0.242, p = 0.007) and cathepsin D (r = 0.330, p = 0.001), but negatively correlated with red blood cell aggregation (r = -0.419, p<0.0001) and CML (r = -0.209, p < 0.05). In conclusion, AGEs may partially explain the underlying relationship between dysregulated iron and T deficiency.

Electrochemical substrate for active profiling of cellular surface leucine aminopeptidase activity and drug resistance in cancer cells.

Leucine aminopeptidase (LAP) is an essential proteolytic enzyme and potential biomarker for liver malignancy. Overexpression of LAP is directly linked with some fatal physiological and pathological disorders. In this regard, we have designed an activity based electrochemical substrate leucine-benzyl ferrocene carbamate (Leu-FC) for selective profiling of LAP activity in live cells. In practice, LAP instantaneously hydrolyze the Leu residue of the substrate Leu-FC to eliminate the unmasked electrochemical reporter amino ferrocene via predefined self-immolative cascade. The electrochemical signal is distinctly specific for LAP and free of other electroactive biological interference. The substrate Leu-FC empowered sensor displayed broad dynamic range with admirable detection limits. On top of this, the probe Leu-FC was employed in real-time active profiling of cellular LAP activity in HepG2 cells and effect of LAP inhibitor. In extent, the substrate Leu-FC can effectively monitor cisplatin induced overexpression of LAP activity in HepG2 cells in presence and absence of bestatin. The sensor showcased an excellent reliability towards monitoring cellular LAP activity in HepG2 cells. Unlike the traditional antibody-based immunoassays, our approach is capable of monitoring in-situ activity of LAP in live cells.

Compound K inhibits priming and mitochondria-associated activating signals of NLRP3 inflammasome in renal tubulointerstitial lesions.

BACKGROUND: Renal tubulointerstitial lesions (TILs), a key pathological hallmark for chronic kidney disease to progress to end-stage renal disease, feature renal tubular atrophy, interstitial mononuclear leukocyte infiltration and fibrosis in the kidney. Our study tested the renoprotective and therapeutic effects of compound K (CK), as described in our US patent (US7932057B2), on renal TILs using a mouse unilateral ureteral obstruction (UUO) model. METHODS: Renal pathology was performed and renal draining lymph nodes were subjected to flow cytometry analysis. Mechanism-based experiments included the analysis of mitochondrial dysfunction, a model of tubular epithelial cells (TECs) under mechanically induced constant pressure (MICP) and tandem mass tags (TMT)-based proteomics analysis. RESULTS: Administration of CK ameliorated renal TILs by reducing urine levels of proinflammatory cytokines, and preventing mononuclear leukocyte infiltration and fibrosis in the kidney. The beneficial effects clearly correlated with its inhibition of: (i) NF-κB-associated priming and the mitochondria-associated activating signals of the NLRP3 inflammasome; (ii) STAT3 signalling, which in part prevents NLRP3 inflammasome activation; and (iii) the TGF-ß-dependent Smad2/Smad3 fibrotic pathway, in renal tissues, renal TECs under MICP and/or activated macrophages, the latter as a major inflammatory player contributing to renal TILs. Meanwhile, TMT-based proteomics analysis revealed downregulated renal NLRP3 inflammasome activation-associated signalling pathways in CK-treated UUO mice. CONCLUSIONS: The present study, for the first time, presents the potent renoprotective and therapeutic effects of CK on renal TILs by targeting the NLRP3 inflammasome and STAT3 signalling.

Comparing the Osteogenic Potentials and Bone Regeneration Capacities of Bone Marrow and Dental Pulp Mesenchymal Stem Cells in a Rabbit Calvarial Bone Defect Model.

The bone regeneration efficiency of bone marrow mesenchymal stem cells (BMSCs) and dental pulp mesenchymal stem cells (DPSCs) combined with xenografts in the craniofacial region remains unclear. Accordingly, this study commenced by comparing the cell morphology, cell proliferation, trilineage differentiation, mineral synthesis, and osteogenic gene expression of BMSCs and DPSCs in vitro. Four experimental groups (empty control, Bio-Oss only, Bio-Oss+BMSCs, and Bio-Oss+DPSCs) were then designed and implanted in rabbit calvarial defects. The BMSCs and DPSCs showed a similar morphology, proliferative ability, surface marker profile, and trilineage-differentiation potential in vitro. However, the BMSCs exhibited a higher mineral deposition and expression levels of osteogenic marker genes, including alkaline phosphatase (ALP), runt related transcription factor 2 (RUNX2), and osteocalcin (OCN). In the in vivo studies, the bone volume density in both MSC groups was significantly greater than that in the empty control or Bio-Oss only group. Moreover, the new bone formation and Collagen I / osteoprotegerin protein expressions of the scaffold+MSC groups were higher than those of the Bio-Oss only group. Finally, the Bio-Oss+BMSC and Bio-Oss+DPSC groups had a similar bone mineral density, new bone formation, and osteogenesis-related protein expression. Overall, the DPSCs seeded on Bio-Oss matched the bone regeneration efficacy of BMSCs in vivo and hence appear to be a promising strategy for craniofacial defect repair in future clinical applications.

Radical Hysterectomy After Neoadjuvant Chemotherapy for Locally Bulky-Size Cervical Cancer: A Retrospective Comparative Analysis between the Robotic and Abdominal Approaches.

Radical hysterectomy (RH) is the standard treatment for early stage cervical cancer, but the surgical approach for locally bulky-size cervical cancer (LBS-CC) is still unclear. We retrospectively compared the outcomes of women with LBS-CC treated with neoadjuvant chemotherapy (NACT) and subsequent RH between the robotic (R-RH) and abdominal approaches (A-RH). Between 2012 and 2014, 39 women with LBS-CC FIGO (International Federation of Gynecology and Obstetrics) stage IB2-IIB were treated with NACT-R-RH (n = 18) or NACT-A-RH (n = 21). Surgical parameters and prognosis were compared. Patient characteristics were not significantly different between the groups, but the NACT-R-RH group had significantly more patients with FIGO stage IIB disease, received multi-agent-based NACT, and had a lower percentage of deep stromal invasion than the NACT-A-RH group. After NACT-R-RH, surgical parameters were better, but survival outcomes, such as disease-free survival (DFS) and overall survival (OS), were significantly worse. On multivariate analysis, FIGO stage IIB contributed to worse DFS (p = 0.003) and worse OS (p = 0.012) in the NACT-A-RH group. Women with LBS-CC treated with NACT-R-RH have better perioperative outcomes but poorer survival outcomes compared with those treated with NACT-A-RH. Thus, patients with FIGO stage IIB LBS-CC disease might not be suitable for surgery after multi-agent-based NACT.

Accelerated and Severe Lupus Nephritis Benefits From M1, an Active Metabolite of Ginsenoside, by Regulating NLRP3 Inflammasome and T Cell Functions in Mice.

Chinese herbal medicines used in combination have long-term been shown to be mild remedies with "integrated effects." However, our study provides the first demonstration that M1, an active metabolite of ginsenoside, exerted its dramatic therapeutic effects on accelerated and severe lupus nephritis (ASLN) mice, featuring acute renal function impairment, heavy proteinuria, high serum levels of anti-dsDNA, and high-grade, diffuse proliferative renal lesions. In the present study, NZB/WF1 mice were given injections of lipopolysaccharide to induce the ASLN model. M1 (30 mg/kg) was then administered to the mice by gavage daily, and the mice were sacrificed on week 3 and week 5 after the induction of disease. To identify the potential mechanism of action for the pure compound, levels of NLRP3 inflammasome activation in bone marrow-derived dendritic cells (BMDCs), podocytes and macrophages, and antigen-specific T cell activation in BMDCs were determined in addition to mechanistic experiments in vivo. Treatment with M1 dramatically improved renal function, albuminuria and renal lesions and reduced serum levels of anti-dsDNA in the ASLN mice. These beneficial effects with M1 treatment involved the following cellular and molecular mechanistic events: [1] inhibition of NLRP3 inflammasome associated with autophagy induction, [2] modulation of T help cell activation, and [3] induction of regulatory T cell differentiation. M1 improved the ASLN mice by blunting NLRP3 inflammasome activation and differentially regulating T cell functions, and the results support M1 as a new therapeutic candidate for LN patients with a status of abrupt transformation of lower-grade (mesangial) to higher-grade (diffuse proliferative) nephritis.

Alteration in iron efflux affects male sex hormone testosterone biosynthesis in a diet-induced obese rat model.

This study was motivated by clinical observations that dysmetabolic iron overload syndrome (DIOS) and an androgen deficiency are common features observed in obese adult men; however, the molecular mechanism underlying the effects of DIOS on androgen deficiency remains to be elucidated. We established a DIOS animal model by feeding Sprague-Dawley rats an iron/fat-enriched diet (50% fat plus 0.25, 1, or 2 g ferric iron per kg diet) for 12 weeks to induce iron dysfunction (indicated by decreased tissue iron efflux) in obese rats. Obese rats fed an iron/fat-enriched diet showed decreased levels of testicular total Testosterone (T) and iron exporter ferroportin but increased levels of testicular iron and hepcidin, and these effects were more evident with a >1 g ferric iron per kg diet. A western blot analysis showed that an iron/fat-enriched diet triggered testicular endoplasmic reticular (ER) stress but decreased mitochondrion biogenesis proteins (PGC1α and TFAM) and T-converting proteins (StAR, CYP11A, and 17ß-HSD). TUNEL staining showed that >1 g ferric iron induced apoptosis mainly in germ cells and Leydig's cells. Uncontrolled testicular iron efflux may cause mitochondrial-ER dysfunction and affect T biosynthesis. Future study targeting the testicular hepcidin-ferroportin axis may offer a therapeutic tool to alleviate testicular iron retention and mitochondrial-ER stress in Leydig's cells.

Iatrogenic Teratoma Rupture during TVOR Complicated with Peritonitis, Pleuritis, and Septic Shock.

OBJECTIVE: To obtain a better understanding of the clinical course and the subsequent complications of teratoma rupture. CASE: We report a rare case of chemical peritonitis and pleuritis caused by teratoma rupture during ultrasonographically guided transvaginal oocyte retrieval (TVOR). The patient initially presented with nonspecific and digestive symptoms after TVOR, but the condition deteriorated rapidly after three weeks with peritonitis and septic shock. Thus, exploratory laparoscopy was performed with the findings of a ruptured teratoma at left adnexa, severe adhesions, and purulent fluid in her peritoneal cavity. Bilateral pleuritis was also noted after the operation, which was suspected to be caused by chemical irritation of the spilled contents of the teratoma. The patient's condition improved after surgical treatment and was discharged 28 days after admission. CONCLUSION: Our case showed that the timing of peritoneal irritation caused by teratoma rupture converting to severe chemical peritonitis was approximately 3 weeks. Physicians should avoid cyst puncture during TVOR and closely observe or even perform surgical treatment when iatrogenic teratoma ruptures are suspected.