L-Asparaginase delivered by Salmonella typhimurium suppresses solid tumors

Bacteria can be engineered to deliver anticancer proteins to tumors via a controlled expression system that maximizes the concentration of the therapeutic agent in the tumor. L-asparaginase (L-ASNase), which primarily converts asparagine to aspartate, is an anticancer protein used to treat acute lymphoblastic leukemia. In this study, Salmonellae were engineered to express L-ASNase selectively within tumor tissues using the inducible araBAD promoter system of Escherichia coli. Antitumor efficacy of the engineered bacteria was demonstrated in vivo in solid malignancies. This result demonstrates the merit of bacteria as cancer drug delivery vehicles to administer cancer-starving proteins such as L-ASNase to be effective selectively within the microenvironment of cancer tissue

Breath analyzer for personalized monitoring of exercise-induced metabolic fat burning

Dionisio V. Del Orbe recibió su Licenciatura en Ingeniería Aeronáutica de la Universidad de Western Michigan (2012), EE. UU., y una Maestría en Ingeniería de Manufactura Microelectrónica del Instituto de Tecnología de Rochester (2015), EE. UU. Recibió su doctorado en Ingeniería Mecánica KAIST (2022), Corea del Sur, y trabajó como investigador de posgrado en el Departamento de Investigación de TIC Médicas y de Bienestar en ETRI, Corea del Sur. Su investigación se centra en sensores de gases químicos para diversas aplicaciones, especialmente, análisis de aliento y detección de gases tóxicos/inflamables; también tiene intereses en dispositivos portátiles y flexibles. Actualmente, es docente e investigador en UNAPEC, República Dominicana.Obesity increases the risk of chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and cardiovascular diseases. Simple anthropometric measurements have time limitations in reflecting short-term weight and body fat changes. Thus, for detecting, losing or maintaining weight in short term, it is desirable to develop portable/ compact devices to monitor exercise-induced fat burn in real time. Exhaled breath acetone and blood-borne β-hydroxybutyric acid (BOHB) are both correlated biomarkers of the metabolic fat burning process that takes place in the liver, predominantly post-exercise. Here, we have fabricated a compact breath analyzer for convenient, noninvasive and personalized estimation of fat burning in real time in a highly automated manner. The analyzer collects end-tidal breath in a standardized, user-friendly manner and it is equipped with an array of four low-power MEMS sensors for enhanced accuracy; this device presents a combination of required and desirable design features in modern portable/compact breath analyzers. We analyzed the exhaled breath (with our analyzer) and the blood samples (for BOHB) in 20 participants after exercise; we estimated the values of BOHB, as indication of the fat burn, resulting in Pearson coefficient r between the actual and predicted BOHB of 0.8. The estimation uses the responses from the sensor array in our analyzer and demographic and anthropo- metric information from the participants as inputs to a machine learning algorithm. The system and approach herein may help guide regular exercise for weight loss and its maintenance based on individuals’ own metabolic changes

Detection of an intermediate during the unfolding process of the dimeric ketosteroid isomerase

AbstractFailure to detect the intermediate in spite of its existence often leads to the conclusion that two-state transition in the unfolding process of the protein can be justified. In contrast to the previous equilibrium unfolding experiment fitted to a two-state model by circular dichroism and fluorescence spectroscopies, an equilibrium unfolding intermediate of a dimeric ketosteroid isomerase (KSI) could be detected by small angle X-ray scattering (SAXS) and analytical ultracentrifugation. The sizes of KSI were determined to be 18.7Å in 0M urea, 17.3Å in 5.2M urea, and 25.1Å in 7M urea by SAXS. The size of KSI in 5.2M urea was significantly decreased compared with those in 0M and 7M urea, suggesting the existence of a compact intermediate. Sedimentation velocity as obtained by ultracentrifugation confirmed that KSI in 5.2M urea is distinctly different from native and fully-unfolded forms. The sizes measured by pulse field gradient nuclear magnetic resonance (NMR) spectroscopy were consistent with those obtained by SAXS. Discrepancy of equilibrium unfolding studies between size measurement methods and optical spectroscopies might be due to the failure in detecting the intermediate by optical spectroscopic methods. Further characterization of the intermediate using 1H NMR spectroscopy and Kratky plot supported the existence of a partially-folded form of KSI which is distinct from those of native and fully-unfolded KSIs. Taken together, our results suggest that the formation of a compact intermediate should precede the association of monomers prior to the dimerization process during the folding of KSI

Determination of the Distal Fusion Level in the Management of Thoracolumbar and Lumbar Adolescent Idiopathic Scoliosis Using Pedicle Screw Instrumentation

Study DesignA retrospective study.PurposeTo determine the exact distal fusion level in the management of thoracolumbar/lumbar adolescent idiopathic scoliosis (TL/L AIS) using pedicle screw instrumentation (PSI).Overview of LiteratureThe selection of distal fusion level remains controversial in TL/L AIS.MethodsRadiographic parameters of 66 TL/L AIS patients were analyzed. The patients were grouped according to the distal fusion level; L3 group (fusion to L3, n=58) and L4 group (fusion to L4, n=8). The L3 group was subdivided into L3A (L3 crosses the mid-sacral line with rotation of less than grade II, n=33) and L3B (L3 does not cross the mid-sacral line or rotation is grade II or more, n=25) based on both bending radiographs. All of the patients in the L4 group had the same location and rotation of L3 in bending films as that of patients in the L3B group. An unsatisfactory result was defined as a lowest instrumented vertebral tilt (LIVT) of more than 10° or coronal balance of more than 15 mm.ResultsAmong the 3 groups, there was a significantly lesser correction in the TL/L curve and LIVT in the L3B group. Unsatisfactory results were obtained in 3 patients (9.1%) of the L3A group, in 15 patients (68.2%) of the L3B group, and in 1 patient (12.5%) of the L4 group with a significant difference.ConclusionsIn TL/L AIS treatment with PSI, the curve can be fused to L3 with favorable radiographic outcomes when L3 crosses the mid-sacral line with rotation of less than grade II in bending films. Otherwise, fusion has to be extended to L4

Effect of chitinase- 3- like protein 1 on glucose metabolism: In vitro skeletal muscle and human genetic association study

We investigated the effect of chitinase- 3- like protein 1 (CHI3L1) on glucose metabolism and its underlying mechanisms in skeletal muscle cells, and evaluated whether the observed effects are relevant in humans. CHI3L1 was associated with increased glucose uptake in skeletal muscles in an AMP- activated protein kinase (AMPK)- dependent manner, and with increased intracellular calcium levels via PAR2. The improvement in glucose metabolism observed in an intraperitoneal glucose tolerance test on male C57BL/6J mice supported this association. Inhibition of the CaMKK was associated with suppression of CHI3L1- mediated glucose uptake. Additionally, CHI3L1 was found to influence glucose uptake through the PI3K/AKT pathway. Results suggested that CHI3L1 stimulated the phosphorylation of AS160 and p38 MAPK downstream of AMPK and AKT, and the resultant GLUT4 translocation. In primary myoblast cells, stimulation of AMPK and AKT was observed in response to CHI3L1, underscoring the biological relevance of CHI3L1. CHI3L1 levels were elevated in cells under conditions that mimic exercise in vitro and in exercised mice in vivo, indicating that CHI3L1 is secreted during muscle contraction. Finally, similar associations between CHI3L1 and metabolic parameters were observed in humans alongside genotype associations between CHI3L1 and diabetes at the population level. CHI3L1 may be a potential therapeutic target for the treatment of diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162777/2/fsb220907.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162777/1/fsb220907_am.pd

Aortic Stenosis: Evaluation with Multidetector CT Angiography and MR Imaging

Aortic valvular stenosis (AS) is the most common valve disease which results in the need for a valve replacement. Although a Doppler echocardiography is the current reference imaging method, the multidetector computerized tomograpghy (MDCT) and magnetic resonance imaging (MRI) have recently emerged as a promising method for noninvasive valve imaging. In this study, we briefly describe the usefulness and comparative merits of the MDCT and MRI for the evaluation of AS in terms of valvular morphology (as the causes of AS), quantification of aortic valve area, pressure gradient of flow (for assessment severity of AS), and the evaluation of the ascending aorta and cardiac function (as the secondary effects of AS). The familiarity with the MDCT and MRI features of AS is considered to be helpful for the accurate diagnosis and proper management of patients with a poor acoustic window

A New Steroidal Saponin from the Tubers of Ophiopogon japonicus and Its Protective Effect Against Cisplatin-Induced Renal Cell Toxicity

A new furostanol saponin, ophiopogonin T, was isolated from the tubers of Ophiopogon japonicus. Its structure was established by extensive spectroscopic techniques including 1D ( 1 H and 13 C) and 2D nuclear magnetic resonance (NMR) experiments (correlation spectroscopy (COSY), heteronuclear single quantum coherence (HSQC), heteronuclear multiple bond correlation (HMBC) and nuclear Overhauser effect spectroscopy (NOESY)), high-resolution electrospray ionization mass spectrometry (ESIMS), and chemical methods. Using cell-based assays, this compound was evaluated for its cytotoxic effect on cancer cell lines and its protective effect against anticancer drug-induced nephrotoxicity. Cisplatin-induced cytotoxicity in porcine kidney (LLC-PK1) cells was significantly reduced upon treatment with ophiopogonin T, without affecting human hepatoma (HepG2) cancer cell proliferation or tube formation in human umbilical vein endothelial cells (HUVECs). These results collectively reflect the beneficial effect of ophiopogonin T on the side effects of cisplatin