Leukapheresis and Tisagenlecleucel Manufacturing Outcomes in Patients Age <3 Years with Relapsed/Refractory Acute Lymphoblastic Leukemia.

Tisagenlecleucel is approved for the treatment of relapsed/refractory (r/r) B cell acute lymphoblastic leukemia (B-ALL) in patients up to age 25 years based on the results of a pivotal trial (ELIANA) in pediatric and young adult patients. However, that trial did not include patients age <3 years because of the challenges posed by leukapheresis of very young and low-weight patients. Data on leukapheresis material and manufacturing outcomes among patients age <3 years have been collected since the time of global regulatory approval.

UDP-glucose dehydrogenase (UGDH) activity is suppressed by peroxide and promoted by PDGF in fibroblast-like synoviocytes: Evidence of a redox control mechanism.

UDP-glucose dehydrogenase (UGDH) generates essential precursors of hyaluronic acid (HA) synthesis, however mechanisms regulating its activity are unclear. We used enzyme histostaining and quantitative image analysis to test whether cytokines that stimulate HA synthesis upregulate UGDH activity. Fibroblast-like synoviocytes (FLS, from N = 6 human donors with knee pain) were cultured, freeze-thawed, and incubated for 1 hour with UDP-glucose, NAD+ and nitroblue tetrazolium (NBT) which allows UGDH to generate NADH, and NADH to reduce NBT to a blue stain.

Development of a QPatch-Automated Electrophysiology Assay for Identifying TMEM16A Small-Molecule Inhibitors.

The calcium-activated chloride channel, TMEM16A, is involved in airway hydration and bronchoconstriction and is a promising target for respiratory disease. Drug development efforts around channels require an electrophysiology-based assay for identifying inhibitors or activators. TMEM16A has proven to be a difficult channel to record on automated electrophysiology platforms due to its propensity for rundown.

Lysosomal rupture induced by structurally distinct chitosans either promotes a type 1 IFN response or activates the inflammasome in macrophages.

Chitosan is a family of glucosamine and N-acetyl glucosamine polysaccharides with poorly understood immune modulating properties. Here, functional U937 macrophage responses were analyzed in response to a novel library of twenty chitosans with controlled degree of deacetylation (DDA, 60-98%), molecular weight (1 to >100 kDa), and acetylation pattern (block vs. random).

Mesenchymal stem cell detachment with trace trypsin is superior to EDTA for in vitro chemotaxis and adhesion assays.

Trypsin is frequently used to dissociate mesenchymal stem cells (MSCs) for in vitro adhesion and chemotaxis assays. However, its potential impact on surface receptor degradation is poorly understood. The purpose of this study was to evaluate the effect of trypsin-EDTA exposure versus PBS-EDTA on MSC surface receptor integrity and function.

Efficacy of high dose Vitamin D supplementation in improving serum 25(OH)D among migrant and non migrant population: a retrospective study.

Background: Higher dose of vitamin D supplementation 50000 IU is required for those whose serum 25(OH)D levels are 50 nmol/L and below. The increment in serum 25(OH)D though not significantly affected by race, sex or age it is negatively correlated to the baseline 25(OH)D concentration. This study investigated whether the mean increase in serum 25(OH)D will be higher among participants with lower baseline 25(OH)D levels and whether the duration of supplementation has an influence on the serum 25(OH)D achieved.

Vitamin D testing patterns among general practitioners in a major Victorian primary health care service.

Objective: To examine 25(OH)D testing patterns and frequency among general practitioners in a major community health service.

Method: A clinical audit of patient records at a community health centre in Melbourne was undertaken. Patients aged 18 years and above were included.

Biodegradable chitosan microparticles induce delayed STAT-1 activation and lead to distinct cytokine responses in differentially polarized human macrophages in vitro.

Current data suggest that chitosan activates wound macrophages to release endogenous factors that guide mesenchymal stem cell (MSC) to bone fractures. We tested the hypothesis that chitosan, a polymer containing glucosamine and N-acetyl glucosamine, stimulates macrophages in different polarization states to release functional MSC chemokines and mainly anabolic factors. Low-serum conditioned medium was collected from M0, M1 and M2a U937 macrophages previously differentiated with phorbol myristate acetate (PMA) and exposed or not for 24h to chitosan microparticles (80% degree of deacetylation, DDA, 130kDa).

Assessment of vitamin D and its association with cardiovascular disease risk factors in an adult migrant population: an audit of patient records at a Community Health Centre in Kensington, Melbourne, Australia.

Background: Vitamin D deficiency is a global public health problem associated with increased risk of cardio-metabolic diseases and osteoarthritis. Migrants with dark skin settled in temperate climates are at greater risk of both vitamin D deficiency and cardiovascular diseases. This study aims to identify the risk of vitamin D deficiency and associations with cardiovascular disease in a migrant population in Australia.

Expression of ORAII, a plasma membrane resident subunit of the CRAC channel, in rodent and non-rodent species.

We determined the expression of ORAI1 protein in rodent and non-rodent tissues using a monoclonal antibody directed against an extracellular loop of the protein. Previous reports using antibodies directed at the C-terminus of ORAI1 have not detected central nervous system (CNS) expression. Our results demonstrate broad tissue expression that includes the CNS using a unique monoclonal antibody specific to an extracellular loop of ORAI1.

UHPLC UHD Q-TOF MS/MS analysis of the impact of sulfur fumigation on the chemical profile of Codonopsis Radix (Dangshen).

Over recent decades sulfur fumigation has been becoming abused in processing some freshly harvested Chinese medicinal herbs, although it is questioned whether sulfur fumigation can result in changes in efficacy and safety of the herbs. One of the herbs commonly processed by sulfur fumigation is Codonopsis Radix (Dangshen). A report showed that lobetyolin content in sulfur-fumigated Dangshen was lower than in air-dried Dangshen.

Bone morphogenetic protein-9 activates Smad and ERK pathways and supports human osteoclast function and survival in vitro.

BMP-9 is a potent osteogenic factor; however, its effects on osteoclasts, the bone-resorbing cells, remain unknown. To determine the effects of BMP-9 on osteoclast formation, activity and survival, we used human cord blood monocytes as osteoclast precursors that form multinucleated osteoclasts in the presence of RANKL and M-CSF in long-term cultures. BMP-9 did not affect osteoclast formation, but adding BMP-9 at the end of the culture period significantly increased bone resorption compared to untreated cultures, and reduced both the rate of apoptosis and caspase-9 activity.

Chemical differentiation of two taste variants of Gynostemma pentaphyllum by using UPLC-Q-TOF-MS and HPLC-ELSD.

To differentiate the sweet and bitter taste variants of a Chinese medicinal tea Gynostemma pentaphyllum (GP), a method for the quantitative analysis of ginsenosides Rb(1), Rb(3), Rd, and F(2) in GP by using UPLC-Q-TOF-MS was developed. According to the different contents of the four ginsenosides, chemical differentiation of the two taste variants of GP was achieved by principal component analysis (PCA). A supplementary quantitative analysis method of using HPLC-ELSD for determination of 20(S)-panaxadiol in the hydrolysates of GP was also developed.

Discovery and in vivo evaluation of dual PI3Kβ/δ inhibitors.

Structure-based rational design led to the synthesis of a novel series of potent PI3K inhibitors. The optimized pyrrolopyridine analogue 63 was a potent and selective PI3Kβ/δ dual inhibitor that displayed suitable physicochemical properties and pharmacokinetic profile for animal studies. Analogue 63 was found to be efficacious in animal models of inflammation including a keyhole limpet hemocyanin (KLH) study and a collagen-induced arthritis (CIA) disease model of rheumatoid arthritis.

Prevalence of vitamin D insufficiency and risk factors for type 2 diabetes and cardiovascular disease among African migrant and refugee adults in Melbourne: a pilot study.

Migration to industrialised countries poses a "double whammy" for type 2 diabetes among sub-Saharan African migrant and refugee adults. This population group has been found to be at an increased risk of obesity and type 2 diabetes, which may be further aggravated by inadequate vitamin D status. Thus, this study aimed to describe the demographics of vitamin D insufficiency, obesity, and risk factors for type 2 diabetes among sub-Saharan African migrants and refugees aged 20 years or older living in Melbourne, Australia (n=49).

In vivo anti-tumour activity of corilagin on Hep3B hepatocellular carcinoma.

We have investigated the potential in vivo anti-tumour activity of corilagin using the Hep3B hepatocellular carcinoma cell line and an athymic nude mice xenograft model. The purity of corilagin was confirmed by high performance liquid chromatographic analysis. Corilagin was administrated intraperitoneally for a continuous period of 7 days at a concentration of 15 mg/kg of body weight per day.

Novel use of silymarin as delayed therapy for acetaminophen-induced acute hepatic injury.

Aim: Recently, we have demonstrated that silymarin has a comparable pharmaceutical activity as Phyllanthus urinaria extract when used to rescue mice from acetaminophen-induced acute liver injury. In the present study, we further compared the therapeutic action of silymarin with N-acetyl cysteine (commonly used in clinical practice for emergency treatments) as a rescuer in mice after administering a lethal dose of acetaminophen for 24 h.

Methods: Acute liver injury was induced in the treatment groups by intraperitoneally administered acetaminophen at a dose of 550 mg/kg body weight on day 1.

Proteomic identification of proteins involved in the anticancer activities of oridonin in HepG2 cells.

Oridonin is the main bioactive constituent of the Chinese medicinal herb Isodon rubescens and has been shown to have anti-neoplastic effects against a number of cancers in vitro and in vivo. Here we report the proteomic identification of proteins involved in the anticancer properties of oridonin in hepatocarcinoma HepG2 cells. Cell viability assay showed that oridonin dose-dependently inhibited cell growth with an IC(50) of 41.

Oridonin induces G2/M cell cycle arrest and apoptosis through MAPK and p53 signaling pathways in HepG2 cells.

Oridonin, the main active constituent of Isodon rubescen, has antihepatocarcinoma activity in experimental and clinical settings. The aims of the study were to explore the anticancer effect of oridonin in HepG2 cells and to investigate the underlying mechanisms. Results showed that oridonin treatment for 24 or 48 h resulted in a marked decrease in cell viability time- and dose-dependently.

Phyllanthus urinaria extract attenuates acetaminophen induced hepatotoxicity: involvement of cytochrome P450 CYP2E1.

Acetaminophen is a commonly used drug for the treatment of patients with common cold and influenza. However, an overdose of acetaminophen may be fatal. In this study we investigated whether mice, administered intraperitoneally with a lethal dose of acetaminophen, when followed by oral administration of Phyllanthus urinaria extract, may be prevented from death.

Liposomes modulate docetaxel-induced lipid oxidization and membrane damage in human hepatoma cells.

The aim of this study was to investigate the effect of liposomes on docetaxel-induced lipid oxidization and membrane damage in human hepatoma cells. Cytotoxicity of free docetaxel and docetaxel-containing liposomes was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay in human hepatoma cell lines HepG2 and SMMC-7721. To the cell lines, blank liposomes prepared with soybean phosphatidylcholine (SPC), dimyristoylphosphocholine (DMPC), and dioleoylphosphocholine (DOPC) did not show any significant toxicity below a 0.

Anti-inflammatory and analgesic effects of the ethanol extract of Rosa multiflora Thunb. hips.

This study aimed to assess the anti-inflammatory and analgesic effects of Fructus Rosae Multiflorae (FRM, hips of Rosa multiflora Thunb.). FRM was extracted with 75% ethanol and the dried extract (FRME) was administered intragastrically (i.

Antiangiogenic activity of a concentrated effective microorganism fermentation extract.

We have previously demonstrated the possible growth inhibitory activity of both first generation of the effective microorganism fermentation extract (EM-X) as well as the second generation (EM-X2) on cancer cell lines in vitro. The possible anti-angiogenic potential of EM-X has not been reported. Herein we show that using the concentrated EM-X, the growth of human umbilical cord endothelial cells (HUCE) was significantly inhibited in vitro.

Apoptotic potential of the concentrated effective microorganism fermentation extract on human cancer cells.

The effective microorganism fermentation extract (EM-X, the first generation) was claimed to possess strong anti-oxidation property. On the other hand, we have shown that the second generation of the effective microorganism fermentation extract (EM-X2) possessed growth inhibition on human cancer cells involving MDA-MB231 breast cancer and K-562 chronic myelogenous leukaemia cells. Elevation of super oxide dismutase activity from EM-X2 treated cancer cell extract was observed.