Bone formation by Irisin-Poly vinyl alchol modified bioglass ceramic beads in the rabbit model.

In the aging society, slow bone regeneration poses a serious hindrance to the quality of life. To deal with this problem, in this study, we have combined irisin with the bioglass regular beads to enhance the bone regeneration process. For this purpose, highly porous bioglass was obtained as spherical beads by using sodium alginate. The bioglass was evaluated by various analytical techniques such as SEM, EDS, XRD, and pore size distribution. The results depicted that porous bioglass was prepared correctly and SEM analysis showed a highly porous bioglass was formulated. On this bioglass, irisin was loaded with the assistance of polyvinyl alcohol (PVA) in three concentrations (50 ng/ml, 100 ng/ml, and 150 ng/ml per 1 g of bioglass). SEM analysis showed that pores are covered with PVA. The irisin release profile showed a sustained release over the time period of 7 days. In vitro, biocompatibility evaluation by the MC3T3E1 cells showed that prepared bioglass and irisin loaded bioglass (BGI50, BGI100, and BG150) are highly biocompatible. Alizarin Red staining analysis showed that after 2 weeks BGI50 samples showed highest calcium nodule formation. In vivo in the rabbit femur model was conducted for 1 and 2 months. BGI150 samples showed highest BV/TV ratio of 37.1 after 2 months. The histological data showed new bone formation surrounding the beads and with beads loaded with irisin. Immunohistochemistry using markers OPN, RUNX, COL, and ALP supported the osteogenic properties of the irisin-loaded bioglass beads. The results indicated that irisin-loaded bioglass displayed remarkable bone regeneration.

Incidence and outcomes of intraoperative periprosthetic acetabular fractures during cementless total hip arthroplasty: a prospective three-dimensional computer tomography-based study.

PURPOSE: Unlike periprosthetic femoral fractures, periprosthetic acetabular fractures during total hip arthroplasty (THA) have not been evaluated in detail. We prospectively evaluated the incidence, patterns, risk factors, and clinical outcomes of intraoperative periprosthetic acetabular fractures using pre- and postoperative computer tomography (CT). METHODS: In this prospective single-centre study, we evaluated 234 consecutive patients (250 hips) who underwent THA and three-dimensional CT before and after the surgery. We assessed the incidence, pattern of fractures, outcomes for each fracture pattern, reoperation and revision rates, Harris hip score, and visual analog scale (VAS) for pain. Multivariate regression models were used to identify risk factors for periprosthetic acetabular fractures. RESULTS: In total, 43 periprosthetic acetabular fractures (17.2%) were identified via CT. Fractures occurred most frequently at the superolateral wall. Early cup migration occurred in three hips. None of the patients underwent revision surgery for acetabular loosening. Regression modeling showed that rheumatoid arthritis was a significant predictor of periprosthetic acetabular fractures. CONCLUSIONS: Periprosthetic acetabular fractures are not infrequent during cementless THA and are more common in patients with rheumatoid arthritis.

Exosomes in ascites from patients with human pancreatic cancer enhance remote metastasis partially through endothelial-mesenchymal transition.

BACKGROUND: Despite advances in multidisciplinary treatment, the prognosis of pancreatic cancer remains poor. Since distant metastasis defines prognosis, elucidation of the mechanism of metastasis is important for improving survival. Exosomes are extracellular secretory vesicles and are responsible for intercellular communication. In this study, we investigated whether exosomes secreted by human pancreatic cancer cells are involved in promoting distant metastasis of cancer and the mechanism that underlies the promotion of metastasis. METHODS: Exosomes were isolated from ascites of a patient with pancreatic cancer and a patient with liver cirrhosis as a control. Three days after the administration of exosomes to nude mice, GFP-labeled human pancreatic cancer cells were injected via the spleen or tail vein, and then the liver and lungs were histologically analyzed. To elucidate the mechanism, vascular permeability was estimated using FITC-dextran in place of pancreatic cancer cells in vivo and human umbilical vascular endothelial cells (HUVECs) were used to analyze vascular permeability and the induction of endothelial-mesenchymal transition (EndMT) in vitro. RESULTS: Distant metastasis and vascular permeability were significantly enhanced in mice treated with exosomes from pancreatic cancer patients in comparison to exosomes from a control patient in vivo. In addition, exosomes from pancreatic cancer patients significantly enhanced vascular permeability and the induction of EndMT in HUVECs in vitro. CONCLUSION: Exosomes derived from pancreatic cancer cells form a pre-metastatic niche and promote the extravasation and colonization of pancreatic cancer cells to remote organs, partially through endothelial-mesenchymal transition.

Usefulness of intraoperative C-arm image intensifier in reducing errors of acetabular component during primary total hip arthroplasty: an application of Widmer's method.

BACKGROUND: Acetabular prosthesis positioning in total hip arthroplasty (THA) is crucial in reducing the risk of dislocation. There has been minimal research on the proper way to put the acetabular components into the safe zone intraoperatively. Assessment of version by intraoperative imaging intensifier is very valuable. The value of Widmer's method, using the intraoperative C-arm available to determine cup anteversion was assessed. METHODS: One hundred one hips in 91 patients who underwent primary THA were eligible for inclusion. Utilizing intraoperative C-arm images, measurement was performed using the technique described by Widmer. The values obtained using 3D computed tomography postoperatively, which determined the anteversion of the acetabular component, were regarded as the reference standard. RESULTS: The method of Widmer obtained values similar to those obtained using 3D computed tomography and was considered accurate (n.s.). All 101 hips were positioned in the set target zone. Among the 101 hips, the cup position in nine hips (8.9%) was changed. The dislocation rate in our study was 1.0% with all dislocations occurring in hips placed in the target zone. The mean Harris hip score after THA in 1 year was 94.2 (82-98). CONCLUSIONS: The method of Widmer was accurate using intraoperative imaging intensifier for the measurement of the anteversion of the acetabular component during THA, with reference to the anteversion obtained from the 3D computed tomography. Also, utilizing intraoperative C-arm imaging was very useful because it allowed for correction of the position of the acetabular cup.

Biochanin A induces a brown-fat phenotype via improvement of mitochondrial biogenesis and activation of AMPK signaling in murine C3H10T1/2 mesenchymal stem cells.

In this study, we investigated the effect of Biochanin A (BioA), an O-methylated isoflavone on the brown-fat phenotype formation and on the associated thermogenic program including mitochondrial biogenesis and lipolysis in C3H10T1/2 MSCs. Our data demonstrates that Treatment with BioA in an adipogenic differentiation cocktail induced formation of brown-fat-like adipocytes from C3H10T1/2 MSCs without treatment with a known browning inducer (rosiglitazone or T3) at an early stage of differentiation. The formation of brown-fat-like adipocytes by BioA treatment was evidenced by upregulation of key thermogenic markers: Ucp1, Pgc1α, Prdm16, and Pparγ. BioA also increased the expression of beige (Cd137 and Fgf21) and brown (Elovl3 and Zic1)-specific markers. Additionally, BioA treatment promoted mitochondrial biogenesis, judging by the upregulation of genes; Cox8b, Cidea, Dio2, Sirt1, Opa1, and Fis1. BioA treatment increased the amount of mitochondrial DNA and its encoded proteins: oxidative phosphorylation complexes (I-V); this change was associated with high oxygen consumption by C3H10T1/2 MSCs. A small-interfering-RNA-induced gene knockdown and experiments with dorsomorphin-driven competitive inhibition revealed that BioA exerts the thermogenic action via activation of AMPK signaling. Our study shows the mechanism of BioA-induced promotion of a brown-fat phenotype. Nonetheless, clinical research is necessary to validate BioA as a brown-fat-like signature inducer.

Long-Term Results of Total Hip Arthroplasty in Young Patients With Osteonecrosis After Allogeneic Bone Marrow Transplantation for Hematological Disease: A Multicenter, Propensity-Matched Cohort Study With a Mean 11-Year Follow-Up.

BACKGROUND: The number of young patients with hematological disease requiring total hip arthroplasty (THA) is expected to increase. We aimed to investigate the long-term THA outcomes in patients with osteonecrosis of the femoral head (ONFH) following allogeneic bone marrow transplantation (BMT) for hematological disease. METHODS: All patients who underwent THA for osteonecrosis after BMT from 1997 to 2012 were identified at 2 institutions. Using propensity scores, 75 THAs in 45 patients were matched for age, gender, body mass index, American Society of Anesthesiologists score, and year of surgery with 75 THAs in 58 patients with idiopathic ONFH without a history of hematological disease (1:1 ratio). The mean age at surgery was 36.7 years and 52% were men. Clinical and radiographic evaluations were performed and clinical scores were obtained at last follow-up. Kaplan-Meier analyses were used to compare survivorship. RESULTS: At a mean follow-up of 10.6 ± 3.5 years, clinical, radiographic, and survivorship outcomes, and the Harris hip scores were similar between both groups. The 13-year survivorship for all-cause revision was 93.4% for the BMT group and 95% for the control group (P = .928). No significant differences were observed between groups in the rates of reoperation (4% vs 5.3%, P = 1.000), 90-day readmission (all 5.3%), or overall mortality (4.4% vs 1.7%, P = .681). No hips had periprosthetic joint infection or septic loosening in either group. Osteolysis occurred in none of the BMT patients and in 2 hips (2.7%) of the control patients (P = .497). CONCLUSION: This large cohort multicenter survey at 11-year follow-up shows that contemporary cementless THA in young hematological disease patients after allogeneic BMT is not associated with a higher risk for surgical complications, revision, reoperation, readmission, and mortality compared to a matched cohort of idiopathic ONFH.

Fourth-generation ceramic-on-ceramic THA results in improvements in midterm outcomes compared to third-generation THA but does not resolve noise problems: a cohort study of a single-hip system.

BACKGROUND: Using data from the Korean Hip Registry, we aimed to investigate mid-term clinical and radiographic outcomes, including the prevalence of periprosthetic joint infection (PJI), osteolysis, and component loosening or dislocation, and to analyze the incidence of bearing-related complications following modern ceramic-on-ceramic (COC) total hip arthroplasty (THA) using a single cementless hip system. METHODS: Four hundred eighty-two patients (602 hips) who underwent Forte or Delta COC THAs with a single hip system and had a minimum 5-year follow-up were identified. The sample included 243 (50.4%) women and 239 (49.6%) men with a mean age of 50.6 years (range: 18-83 years). The Forte group comprised 310 hips, and the Delta group comprised 292 hips. The mean follow-up was 6.1 years (range: 5-10.2 years). RESULTS: Cup orientation did not differ between groups. No hip had a PJI or osteolysis in either group. All acetabular components and all but two femoral components (in the Delta group) were well fixed. Dislocations occurred in six (1.9%) hips in the Forte group and one (0.3%) hip in the Delta group (p = 0.124). A total of nine (1.5%) revisions were performed. The 5-year survival rates for all-cause revisions were 98.4 and 98.6%, respectively. One (0.3%) ceramic head fracture occurred in the Forte group. Sixteen (5%) hips exhibited clicking and 6 (2%) hips had squeaking in the Forte group; 16 (6%) hips exhibited clicking and 5 (2%) hips had squeaking in the Delta group. Multiple regression analysis revealed that noise generation was unassociated with any factor. CONCLUSIONS: From the Korean Hip Registry data, THA with modern ceramic bearings showed encouraging results, with lower risks of PJI, osteolysis, and component loosening. In particular, Delta COC THA resulted in no PJI or ceramic fracture and had a reduced dislocation risk. However, associated noise remains a concern.

Distinctive effects of licarin A on lipolysis mediated by PKA and on formation of brown adipocytes from C3H10T1/2 mesenchymal stem cells.

Obesity increases with the positive energy imbalance and correlates with increased risks for metabolic diseases. Promotion of white adipose tissue beiging has received considerable attention due to possible usefulness for preventing obesity and the comorbidities. Licarin A (LA) is a compound derived from Mexican medicinal plant Aristolochia taliscana. Here, we report that LA stimulates the development of brown-like and beige-like adipocytes from C3H10T1/2 mesenchymal stem cells with phenotypic shifts to formation of smaller lipid droplets. LA also markedly induced the expression of proteins characteristic of brown-like adipocytes in C3H10T1/2 mesenchymal stem cells. LA induced uncoupling protein 1 (Ucp1) and expression of other thermogenic genes in C3H10T1/2 mesenchymal stem cells via a mechanism involving protein kinase A (PKA). LA treatment also inhibited expression of white-adipocyte-specific genes. Moreover, LA treatment promoted lipolysis via PKA mediated pathway. Our findings inaugurate a new role of LA as an inducer of brown-like adipocytes formation with lipolytic properties, which in future might be studied in vivo as a potential anti-obesity agent.

Optical fiber Fabry-Pérot micro-displacement sensor for MEMS in-plane motion stage.

Fabry-Pérot interferometer sensors have been widely used in Micro-Electro-Mechanical-Systems (MEMS) due to high displacement accuracy and immunity to electromagnetic noises, but they are still limited by micro scale measurement range. In this paper, a Fabry-Pérot interferometer in-plane displacement sensor is proposed for measuring the displacement of MEMS devices utilizing a polished optical fiber and a modulated laser source. The polished optical fiber and a sidewall of a MEMS device form an optical cavity for the proposed sensor. The sinusoidal phase modulation with extreme point search algorithm enables the proposed sensor to measure displacements larger than the wavelengths of the laser light in real time. The experimental results show that the proposed displacement sensor has a capability to measure displacements larger than 3 µm and it shows the measurement accuracy less than 35 nm. The proposed displacement sensor is then embedded on a single degree-of-freedom MEMS motion stage and tested to monitor its displacement in real time.

Cryptotanshinone promotes commitment to the brown adipocyte lineage and mitochondrial biogenesis in C3H10T1/2 mesenchymal stem cells via AMPK and p38-MAPK signaling.

Although white adipose tissue (WAT) stores triglycerides and contributes to obesity, brown adipose tissue (BAT) dissipates energy as heat. Therefore, browning of WAT is regarded as an attractive way to counteract obesity. Our previous studies have revealed that treatment with cryptotanshinone (CT) during adipogenesis of 3T3-L1 cells inhibits their differentiation. Here, we found that pretreatment of C3H10T1/2 mesenchymal stem cells with CT before exposure to adipogenic hormonal stimuli promotes the commitment of these mesenchymal stem cells to the adipocyte lineage as confirmed by increased triglyceride accumulation. Furthermore, CT treatment induced the expression of early B-cell factor 2 (Ebf2) and bone morphogenetic protein 7 (Bmp7), which are known to drive differentiation of C3H10T1/2 mesenchymal stem cells toward preadipocytes and to the commitment to brown adipocytes. Consequently, CT treatment yielded brown-adipocyte-like features as evidenced by elevated expression of brown-fat signature genes including Ucp1, Prdm16, Pgc-1α, Cidea, Zic1, and beige-cell-specific genes such as CD137, Hspb7, Cox2, and Tmem26. Additionally, CT treatment induced mitochondrial biogenesis through upregulation of Sirt1, Tfam, Nrf1, and Cox7a and increased mitochondrial mass and DNA content. Our data also showed that cotreatment with CT and BMP4 was more effective at activating brown-adipocyte-specific genes. Mechanistic experiments revealed that treatment with CT activated AMPKα and p38-MAPK via their phosphorylation: the two major signaling pathways regulating energy metabolism. Thus, these findings suggest that CT is a candidate therapeutic agent against obesity working via activation of browning and mitochondrial biogenesis in C3H10T1/2 mesenchymal stem cells.

Surgical accuracy, function, and quality of life of simultaneous versus staged bilateral Total hip Arthroplasty in patients with Osteonecrosis of the femoral head.

BACKGROUND: The optimal surgical option for patients requiring bilateral hip replacement remains controversial. The purpose of this study was to compare surgical accuracy; functional outcome and health-related quality of life; and prosthetic-related complications and revision surgery of a simultaneous bilateral total hip arthroplasty (THA) with those of a staged bilateral THA with an interval between procedures <12 months. METHODS: A total of 123 unselected consecutive patients (mean age, 43.3 years) who underwent bilateral THAs for osteonecrosis of the femoral head (ONFH) with a minimum follow-up of two years (mean, 60.2 months) were studied retrospectively; 63 simultaneous procedures served as a test group and 60 staged procedures served as a control group. RESULTS: The mean postoperative leg-length discrepancy (LLD) and the percentage of patients who had an LLD >3 mm were significantly lower in the simultaneous group (P < 0.001 and P = 0.001, respectively). A higher number of cups within the safe zones, a higher correction rate, and a lower failure rate for the cup placement in the second-operated hip were also identified in the simultaneous group. The mean Harris hip score, EuroQol-5D index, and EuroQol-visual analogue scale score were all better in the simultaneous group at the latest follow-up (P < 0.001, in all comparisons). We found that the simultaneous procedure was associated with a lower incidence of postoperative prosthetic-related complications and revision surgery. CONCLUSIONS: We suggest that bilateral ONFH could be treated with a simultaneous THA rather than a staged THA to achieve a better surgical outcome.

Wnt/ß-catenin signaling plays a distinct role in methyl gallate-mediated inhibition of adipogenesis.

The canonical Wnt/ß-catenin signaling not only features in many developmental processes but also recently emerged as an attractive negative regulator of differentiation of preadipocytes into adipocytes. Here, we show that ß-catenin signaling plays a distinct role in methyl gallate (MG)-mediated inhibition of 3T3-L1 adipocytes differentiation. We found that the expression of ß-catenin decreased after adipogenic hormonal induction, whereas incubation of the differentiating cells with a physiological concentration of MG during adipogenic hormonal induction significantly prevented ß-catenin degradation by activating Wnt signaling components such as Wnt1, Wnt10b, Fzd1, Fzd2, Lrp5, Lrp6, Dvl1, and Dvl2. Mechanistic experiments revealed that MG treatment during early adipocytic differentiation specifically inhibited degradation of ß-catenin caused by phosphorylation at serine-33. In addition, MG treatment led to phosphorylation of GSK3ß, which is one of ß-catenin-degrading enzymes. Consequently, MG treatment facilitated translocation of the stabilized ß-catenin from the cytoplasm to nucleus, and activates its target genes cyclin D1 and c-Myc. Furthermore, MG-induced stabilization of ß-catenin suppresses PPARγ expression. Moreover, pharmacological activation or inhibition of ß-catenin signaling during adipocytes differentiation decreased and increased, respectively, the level of the key adipogenic marker, PPARγ, and of its downstream targets, aP2 and adiponectin while MG treatment effectively reversed their expression level. Collectively, our data suggest that MG is a novel pharmacological stimulator of canonical Wnt/ß-catenin signaling, and therefore represents a promising therapeutic agent in obesity.

Comparative Analysis of Radiographic Hip Joint Geometry Using Measurement Tools on Picture Archiving and Communication System: A Prospective Study of 100 Pelvic Radiographs of Koreans.

BACKGROUND: A contralateral normal hip joint has been often used as a reference standard in preoperative planning and intraoperative assessment of hip arthroplasty, with the assumption that bilateral hip joint geometries have no significant differences. However, one previous study using analog measurements on hardcopy films reported significant bilateral variation in hip joint geometry. We therefore investigated the level of agreement between the right and left hips for each measurement and determined index values and the range of normal bilateral variations. METHODS: We assessed 100 standard anteroposterior radiographs of the pelvis in this study. Two independent observers measured the actual value of femoral head diameter, location of the femoral head center, acetabular offset, femoral offset, hip offset, greater trochanteric height, neck-shaft angle, medullary canal diameter, and proximal femoral diameter. Intraclass correlation coefficients (ICCs) and values of mean difference were calculated for each measurement. RESULTS: The results demonstrated perfect agreement (ICC >0.8) between the right and left hips for most parameters and substantial agreement for greater trochanteric height (ICC = 0.735) and femoral offset (ICC = 0.773). The mean difference and standard deviation in the measurement between the right and left hips for the location of the femoral head center and the acetabular offset were 0.60 ± 0.48 mm and 0.42 ± 0.30 mm, respectively. CONCLUSION: Hip joint geometry is not influenced by side. In hip arthroplasty, a contralateral normal hip can be reliably used as a guide for preoperative planning using measurement tools on a picture archiving and communication system.

Dioscorea batatas extract attenuates high-fat diet-induced obesity in mice by decreasing expression of inflammatory cytokines.

BACKGROUND: The objective of the present study was to determine whether Dioscorea batatas (DB) extract reduces visceral fat accumulation and obesity-related biomarkers in mice fed a high-fat diet (HFD) and whether genes associated with adipogenesis and inflammation could be modulated by a diet containing DB extract. MATERIAL AND METHODS: Male C57BL/6J mice were divided into 4 groups (n=10 per group): normal diet (ND), HFD, 100 mg/kg DB extract-gavage with HFD, and 200 mg/kg DB extract-gavage with HFD. The mice were fed the experimental diets for 14 weeks. At 12 weeks, micro-computed X-ray tomography (micro-CT) was performed. RESULTS: Supplementation of the diet with DB extract for 14 weeks significantly prevented HFD-induced increases in body weight, visceral adipose tissue, plasma lipid levels, and leptins. The area of visceral fat was reduced by DB extract supplementation when examined by micro-CT. Supplementation with DB extract resulted in the downregulation of the adipogenic transcription factor (C/ERBa) and its target gene (CD36) in epididymal adipose tissue, compared to HFD alone. DB extract decreased the expression of proinflammatory cytokines (TNF-α, MCP-1, and IL-6) in epididymal adipose tissue. CONCLUSIONS: Our results suggest that DB extract may prevent HFD-induced obesity by downregulating the expression of genes related to adipogenesis and inflammation in visceral adipose tissue.

Does size difference in allogeneic cancellous bone granules loaded with differentiated autologous cultured osteoblasts affect osteogenic potential?

We study the efficacy of bone regeneration by using two differently sized allogeneic cancellous bone granules loaded with autologous cultured osteoblasts in a rabbit model. Critical-sized bone defects of the radial shaft were made in 40 New Zealand White rabbits. Small allogeneic bone granules (150-300 µm in diameter) loaded with cultured differentiated autologous osteoblasts were implanted into one forearm (SBG group) and large bone granules (500-710 µm) loaded with osteoblasts were implanted into the forearm of the other side (LBG group). Radiographic evaluations were performed at 3, 6, 9 and 12 weeks and histology and micro-CT image analysis were carried out at 6 and 12 weeks post-implantation. On radiographic evaluation, the LBG group showed a higher bone quantity index at 3 and 6 weeks post-implantation (P < 0.05) but statistical significance was lost at 9 and 12 weeks. The progression of biological processes of the SBG group was faster than that of the LBG group. On micro-CT image analysis, the LBG group revealed a higher total bone volume and surface area than the SBG group at 6 weeks (P < 0.05) but the difference decreased at 12 weeks and was without statistical significance. Histological evaluation also revealed faster progression of new bone formation and maturation in the SBG group. Thus, the two differently sized allogeneic bone granules loaded with co-cultured autologous osteoblasts show no differences in the amount of bone regeneration, although the SBG group exhibits faster progression of bone regeneration and remodeling. This method might therefore provide benefits, such as a short healing time and easy application in an injectable form, in a clinical setting.

Bone regeneration potential of allogeneic or autogeneic mesenchymal stem cells loaded onto cancellous bone granules in a rabbit radial defect model.

For developing a clinically effective bone regeneration strategy, we compare the bone regeneration potential of cultured allogeneic bone marrow-derived mesenchymal stem cells (BM-MSCs) and of autologous BM-MSCs loaded onto allogeneic cancellous bone granule scaffolds. A critical-sized segmental bone defect was made at the mid-shaft of both radiuses in 19 New Zealand White rabbits (NWRs). In the experimental group, allogeneic BM-MSCs loaded onto small-sized allogeneic cancellous bone granules (300~700 um in diameter) were implanted in one side of a bone defect. In the control group, autologous BM-MSCs loaded onto allogeneic cancellous granules were grafted in the other side. Bone regeneration was assessed by radiographic evaluation at 4, 8, 12 and 16 weeks post-implantation and by micro-computed tomography (micro-CT) and histological evaluation at 8 and 16 weeks. The experimental groups showed lower bone quantity indices (BQIs) than the control groups at 12 and 16 weeks (p < 0.05), although no significant difference was observed at 4 and 8 weeks (p > 0.05). Micro-CT analysis revealed that both groups had similar mean total bone volume and other parameters including trabecular thickness, number and separation at either 8 or 16 weeks. Only bone surface area revealed less area in the experimental group at 16 weeks. Histological evaluation of 8-week and 16-week specimens showed similar biologic processes of new bone formation and maturation. There was no inflammatory reaction indicating an adverse immune response in both allogeneic and autologous MSC groups. In conclusion, allogeneic BM-MSCs loaded onto allogeneic cancellous bone granules had comparable bone regeneration potential to autologous BM-MSCs in a rabbit radial defect model.

Cytoprotective effect of kaempferol on paraquat-exposed BEAS-2B cells via modulating expression of MUC5AC.

Mucins are highly glycosylated secretary proteins produced by most epithelial cells. Hypersecretion of mucins is one of the prominent symptoms of several airway diseases, including asthma, cystic fibrosis, nasal allergy, rhinitis, and sinusitis. Paraquat (PQ), a common herbicide, has been associated with pulmonary damage and is a potent reactive oxygen species (ROS) producer. However, until now the role of PQ on mucin overproduction has not been studied. The aim of this study is to explore how kaempferol (KM), a widely used dietary flavonoid, affects the protection of human PQ-exposed bronchial epithelium BEAS-2B cells by suppressing Mucin gene expression via nuclear factor-kappa B (NF-κB). We observed that PQ generates intracellular ROS, and also induces lipid peroxidation in BEAS-2B cells. Additionally, we found that PQ effectively induces the expression of the MUC5AC gene; however, co-treatment of PQ with KM drastically reduces its expression. Furthermore, we observed that PQ activates NF-κB, while co-treatment with KM occludes its nuclear translocation, and additionally KM repressed the PQ phosphorylation of c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in BEAS-2B cells. Based on our data, we believe that KM can suppress the over-expression of the MUC5AC gene. This would contribute to the protection of PQ cytotoxicity to exposed BEAS-2B cells, and allow further study toward a better understanding of ROS-associated diseases.

A comprehensive review and advanced biomolecule-based therapies for osteoporosis.

BACKGROUND: The prevalence of osteoporosis (OP) on a global scale is significantly elevated that causes life threatening issues. The potential of groundbreaking biomolecular therapeutics in the field of OP is highly encouraging. The administration of biomolecular agents has the potential to mitigate the process of bone demineralization while concurrently augmenting the regenerative capacity of bone tissue, thereby facilitating a personalized therapeutic approach. Biomolecules-based therapies showed promising results in term of bone mass protection and restoration in OP. AIM OF REVIEW: We summarized the recent biomolecular therapies with notable progress in clinical, demonstrating the potential to transform illness management. These treatments frequently utilize different biomolecule based strategies. Biomolecular therapeutics has a targeted character, which results in heightened specificity and less off-target effects, ultimately leading to increased patient outcomes. These aspects have the capacity to greatly enhance the management of OP, thus resulting in a major enhancement in the quality of life encountered by individuals affected by this condition.

Anti-Obesity Effect of Lactobacillus acidophilus DS0079 (YBS1) by Inhibition of Adipocyte Differentiation through Regulation of p38 MAPK/PPARγ Signaling.

Obesity is spawned by an inequality between the portion of energy consumed and the quantity of energy expended. Disease entities such as cardiovascular disease, arteriosclerosis, hypertension, and cancer, which are correlated with obesity, influence society and the economy. Suppression of adipogenesis, the process of white adipocyte generation, remains a promising approach for treating obesity. Oil Red O staining was used to differentiate 3T3-L1 cells for screening 20 distinct Lactobacillus species. Among these, Lactobacillus acidophilus DS0079, referred to as YBS1, was selected for further study. YBS1 therapy decreased 3T3-L1 cell development. Triglyceride accumulation and mRNA expression of the primary adipogenic marker, peroxisome proliferator-activated receptor gamma (PPARγ), including its downstream target genes, adipocyte fatty acid binding protein 4 and adiponectin, were almost eliminated. YBS1 inhibited adipocyte differentiation at the early stage (days 0-2), but no significant difference was noted between the mid-stage (days 2-4) and late-stage (days 4-6) development. YBS1 stimulated the activation of p38 mitogen-activated protein kinase (p38 MAPK) during the early stages of adipogenesis; however, this effect was eliminated by the SB203580 inhibitor. The data showed that YBS1 administration inhibited the initial development of adipocytes via stimulation of the p38 MAPK signaling pathway, which in turn controlled PPARγ expression. In summary, YBS1 has potential efficacy as an anti-obesity supplement and requires further exploration.

Reappraisal of a Renovated Cell-free and Concentrated Ascites Reinfusion Therapy for Malignant Ascites.

BACKGROUND/AIM: Cell-free and concentrated ascites reinfusion therapy (CART) was established for refractory ascites and renovated CART (Keisuke Matsusaki (KM) -CART) has been recently developed especially for malignant ascites; however, the actual clinical efficacy of KM-CART has been rarely reported. PATIENTS AND METHODS: We performed 226 KM-CART procedures in 104 patients with malignant ascites in three hospitals from August 2013 to September 2018. Medical records were retrospectively reviewed for ascites data, related complications, symptoms before and after each CART and prognosis after the first CART. The modified Glasgow Prognostic Score (mGPS) was reviewed before every procedure, as an indicator of nutritional status. RESULTS: Pancreatic cancer was the most common indication for the KM-CART procedure, followed by gastric cancer, hepatocellular carcinoma, ovarian cancer, and cholangiocarcinoma (five major diseases). The 50% survival times of these five major diseases after the first procedure were 25, 39, 31, 49, and 33 days, respectively. The mean survival time for all patients was 73.5 days, and 75.6 days for those with the five major diseases. All patients experienced symptomatic relief, and complications were rare. Repeated KM-CART was performed in 47.1% of the patients, most often in those with ovarian cancer (66.7%). Regarding the mGPS at the first CART procedure, 89% of patients were in the group with the poorest nutritional status. Patients who underwent KM-CART three or more times had longer survival than those who were treated once or twice. CONCLUSION: Repeated KM-CART provides a survival benefit for patients with malignant ascites, even in cases of poor nutritional status.