Tree shrew as a new animal model for musculoskeletal disorders and aging.

Intervertebral disc degeneration (IDD), osteoarthritis (OA), and osteoporosis (OP) are common musculoskeletal disorders (MSDs) with similar age-related risk factors, representing the leading causes of disability. However, successful therapeutic development and translation have been hampered by the lack of clinically-relevant animal models. In this study, we investigated the potential suitability of the tree shrew, a small mammal with a close genetic relationship to primates, as a new animal model for MSDs.

Mecp2 fine-tunes quiescence exit by targeting nuclear receptors.

Quiescence (G0) maintenance and exit are crucial for tissue homeostasis and regeneration in mammals. Here, we show that methyl-CpG binding protein 2 (Mecp2) expression is cell cycle-dependent and negatively regulates quiescence exit in cultured cells and in an injury-induced liver regeneration mouse model. Specifically, acute reduction of Mecp2 is required for efficient quiescence exit as deletion of Mecp2 accelerates, while overexpression of Mecp2 delays quiescence exit, and forced expression of Mecp2 after Mecp2 conditional knockout rescues cell cycle reentry.

Study on the Thermal Stabilizing Process of Layered Double Hydroxides in PVC Resin.

Poly(vinyl chloride) (PVC) is widely used in various fields and requires the use of thermal stabilizers to enhance its thermal stability during processing because of its poor thermal stability. Layered double hydroxides (LDHs) are widely considered to be one kind of highly efficient and environmentally friendly PVC thermal stabilizer. To investigate the thermal stabilizing process of layered double hydroxides (LDHs) in PVC resin, PVC and MgAl-LDHs powders with different interlayer anions (CO, Cl, and NO) were physically mixed and aged at 180 °C.

Individualized Delivery of Vancomycin by Model-Informed Bayesian Dosing Approach to Maintain an AUC24 Target in Critically Ill Patients.

Introduction: Monitoring of AUC24 was updated recommendation in the guideline for the therapeutic drug monitoring (TDM) of vancomycin in Chinese pharmacological society published in 2020. Vancomycin pharmacokinetic profiles are diverse and unique in critically ill patients because of the drastic variability of the patients' physiological parameters, while the study for population pharmacokinetic (PPK) models in Chinese critically ill patients has been rarely reported. The objectives of this study were to construct a PPK model to describe the pharmacokinetic characteristics of vancomycin in critically ill patients and to individualize vancomycin dosing by model-informed Bayesian estimation for maintenance of AUC24 target at 400-650 mg h/L recommended by the 2020 guideline.

A discussion on the relationship of Capila omeia (Leech, 1894) and C. pseudomeia Fan & Wang, 2004 syn. n. (Hesperiidae, Pyrginae).

Intraspecific variability of Capila omeia (Leech, 1894) from Chongqing is investigated based upon the comparison of the 658 bp COI gene sequences and adult morphology. The morphological characters used for distinguishing C. pseudomeia Fan & Wang, 2004 from C.

Learning Hand Kinematics for Parkinson's Disease Assessment Using a Multimodal Sensor Glove.

Hand dysfunctions in Parkinson's disease include rigidity, muscle weakness, and tremor, which can severely affect the patient's daily life. Herein, a multimodal sensor glove is developed for quantifying the severity of Parkinson's disease symptoms in patients' hands while assessing the hands' multifunctionality. Toward signal processing, various algorithms are used to quantify and analyze each signal: Exponentially Weighted Average algorithm and Kalman filter are used to filter out noise, normalization to process bending signals, K-Means Cluster Analysis to classify muscle strength grades, and Back Propagation Neural Network to identify and classify tremor signals with an accuracy of 95.

Airline Point-of-Care System on Seat Belt for Hybrid Physiological Signal Monitoring.

With a focus on disease prevention and health promotion, a reactive and disease-centric healthcare system is revolutionized to a point-of-care model by the application of wearable devices. The convenience and low cost made it possible for long-term monitoring of health problems in long-distance traveling such as flights. While most of the existing health monitoring systems on aircrafts are limited for pilots, point-of-care systems provide choices for passengers to enjoy healthcare at the same level.

Fusidic Acid and Its Major Active Metabolite Penetration into Cerebrospinal Fluid for Assessing Treatment of Intracranial Infections.

Fusidic acid (FA) had excellent antimicrobial effects due to its unique mechanism of action. Since 1962, FA has been widely used in the systemic and topical treatment of staphylococcal infections and exhibits a well-characterized potency against methicillin-susceptible Staphylococcus aureus, methicillin-resistant Staphylococcus aureus, and methicillin-resistant coagulase-negative Staphylococci. In view of the spectrum of activity, no cross-resistance with other clinically used antibiotics, and potential penetration into brain tissue, FA was used to treat possible gra-positive bacteria in 3 patients with intracranial infections in the present report.

Screening and validation of biomarkers for cadmium-induced liver injury based on targeted bile acid metabolomics.

Although cadmium (Cd) is a toxic heavy metal that reportedly causes liver injury, few studies have investigated biomarkers of Cd-induced liver injury. The purpose of this study is to investigate the role of bile acid (BA) in Cd-induced liver injury and determine reliable and sensitive biochemical parameters for the diagnosis of Cd-induced liver injury. In this study, 48 Sprague-Dawley rats were randomly divided into six groups and administered either normal saline or 2.

Selective removal of common cyanotoxins: a review.

The development of cyanobacterial blooms can have adverse effects on water bodies and may produce cyanotoxins. Several physical and chemical methods have been applied to remove cyanotoxins, but they have been significantly challenged due to extensive energy footprint and over-used chemicals, which limits practical application on a large scale. Selective removal has been regarded as the most promising approach recently for the elimination of prevalent and major bloom-forming cyanotoxins (e.

An LC-MS/MS analytical method for the determination of uremic toxins in patients with end-stage renal disease.

End-stage renal disease (ESRD) is the last stage of chronic kidney disease, characterized by the progressive accumulation of uremic toxins (UTs). Hemodialysis is the standard approach to remove UTs from the body. Creatinine and urea levels are important indices of hemodialysis effectiveness, but the utility of those markers to estimate the removal of UTs, especially protein-binding UTs is limited.

Pyridoxal isonicotinoyl hydrazone inhibition of FXR is involved in the pathogenesis of isoniazid-induced liver injury.

Isoniazid (INH)-induced liver injury may be associated with inhibition of the liver farnesoid X receptor (FXR). However, the relationship between FXR and INH-induced liver injury remained unclear. The present study was performed to clarify the role of inhibition of FXR in the pathogenesis of INH-induced liver injury and to further identify potential inhibitors of FXR from INH and its metabolites.

Determination of Total and Unbound Meropenem, Imipenem/Cilastatin, and Cefoperazone/Sulbactam in Human Plasma: Application for Therapeutic Drug Monitoring in Critically Ill Patients.

Background: Critically ill patients show several pathophysiological alterations that can complicate antibiotic dosing. Hence, there is a strong rationale to individualize anti-infective dosing in these patients by using therapeutic drug monitoring (TDM). The current study aimed to develop and validate a liquid chromatography-tandem mass spectrometry method for the simultaneous determination of total and unbound plasma concentrations of 3 commonly used antibiotics (meropenem, imipenem/cilastatin, and cefoperazone/sulbactam) in the treatment of infections in critically ill patients in China, which could be suitable for routine TDM in hospital laboratories.

Effect of high uric acid on the disposition of metformin: in vivo and in vitro studies.

Metformin is always used as the baseline antidiabetic therapy for patients with type 2 diabetes mellitus (T2DM) and hyperuricemia. Metformin is excreted into urine through active secretion mediated by rOCTs and rMATE1.The aim of this study was to identify the effects of high uric acid on the disposition and its mechanism.

Synthesis of orange-red emissive carbon dots for fluorometric enzymatic determination of glucose.

The authors describe a method for the preparation of orange-red emissive carbon dots (CDs) with excitation/emission peaks at 520/582 nm. The CDs were hydrothermally prepared by a one-pot strategy from trimesic acid and 4-aminoacetanilide. The fluorescence of the CDs is strongly quenched by hydrogen peroxide.

Disabling tremor induced by long-term use of sodium valproate and lamotrigine: Case report.

Rationale: Sodium valproate (VPA) and lamotrigine (LTG) are widely used antiepileptic drugs, disabling postural, and action tremors after using LTG with VPA were reported in 1993. However, in this study, we describe a patient in whom disabling resting-type tremor induced by 2-year use of VPA and LTG.

Patient Concerns: A 50-year old man was referred to department of neurology because of involuntary upper limbs resting-type tremor with high amplitude that had begun 6 months previously and progressively worsened, and he could not work on the day of visit.

Multicomponent determination of traditional Chinese medicine preparation yin-zhi-huang injection by LC-MS/MS for screening of its potential bioactive candidates using HepaRG cells.

Yin-zhi-huang (YZH) injection is an injectable multiherbal prescription derived from the ancient Chinese medicine formula of Yin-chen-hao-tang, which is widely used in the clinic for the treatment of jaundice and chronic liver diseases. To date, the systematic study of the components in this multiherbal prescription still lacks suitable analytical methods that are able to simultaneously detect a broad array of components at low concentrations. In this study, a new liquid chromatography-tandem mass spectrometry method using dynamic multiple reaction monitoring mode was developed to determine multiple peaks in traditional Chinese medicine preparation YZH injection.

Effect of cholecystectomy on bile acids as well as relevant enzymes and transporters in mice: Implication for pharmacokinetic changes of rifampicin.

Background And Purpose: Long-term medical consequences of cholecystectomy are believed to be uncommon. It has been reported that bile acids (BAs) changed after cholecystectomy. As important signaling molecules, the alternations of BAs might favour the regulatory effect on enzymes and transporters involved in BAs physiological homeostasis at the transcriptional level, which could lead to pharmacokinetic changes of drugs.

Effect of hesperidin on the pharmacokinetics of CPT-11 and its active metabolite SN-38 by regulating hepatic Mrp2 in rats.

The usage of irinotecan hydrochloride (CPT-11) chemotherapy is hindered by its dose-limiting diarrhea which appears to be associated with the intestinal exposure to SN-38, the active metabolite of CPT-11. Hesperidin, a safe and natural food ingredient flavonoid, exhibits various biological properties. Accumulated evidence showed that the regulatory effect of hesperidin on the expression of Mrp2 in the liver may be one of the critical factors controlling the biliary excretion of SN-38.

Oridonin Alleviates Visceral Hyperalgesia in a Rat Model of Postinflammatory Irritable Bowel Syndrome: Role of Colonic Enterochromaffin Cell and Serotonin Availability.

The aim of this present study was to investigate the effect of oridonin on visceral hyperalgesia and colonic serotonin availability in a rat model of trinitrobenzenesulfonic acid-induced postinflammatory irritable bowel syndrome (PI-IBS). Rats were randomly divided into five groups: normal control, PI-IBS model, PI-IBS+low-dose oridonin (5 mg/kg), PI-IBS+median-dose oridonin (10 mg/kg), and PI-IBS+high-dose oridonin (20 mg/kg). Rats in control and model groups were orally administered with water by gavage, whereas rats in oridonin-treated groups were orally administered with different dosages of oridonin, and drugs were given for 14 consecutive days.

Anticolitis activity of Chinese herbal formula yupingfeng powder via regulating colonic enterochromaffin cells and serotonin.

Objective: To investigate whether traditional Chinese herbal formula Yupingfeng (YPF) powder has an anti-inflammatory effect on colonic inflammation, and to explore the mechanism involved.

Materials And Methods: YPF powder was orally administrated to trinitrobenzene sulfonic acid (TNBS)-induced colitis mice at the dose of 3, 6, and 12 g/kg/d for 7 consecutive days. Body weight, stool consistency, histopathological score, and myeloperoxidase (MPO) activity were tested to evaluate the effect of YPF powder on colonic inflammation while colonic enterochromaffin (EC) cell density and serotonin 5-hydroxytryptamine (5-HT) content were investigated to identify the effect of YPF powder on colonic 5-HT availability.

Simultaneous Determination of Metformin, Metoprolol and its Metabolites in Rat Plasma by LC-MS-MS: Application to Pharmacokinetic Interaction Study.

A simple, rapid and sensitive liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the simultaneous quantitation of metformin (MTF), metoprolol (MET), α-hydroxymetoprolol (HMT) and O-desmethylmetoprolol (DMT) in rat plasma using paracetamol as an internal standard (IS), respectively. The sample preparation involved a protein-precipitation method with methanol after the addition of IS. The separation was performed on an Agilent HC-C18 column (4.

Serum serotonin reduced the expression of hepatic transporter Mrp2 and P-gp via regulating nuclear receptor CAR in PI-IBS rats.

Hepatic transporters and drug metabolizing enzymes (DMEs) play important roles in the pharmacological effects and (or) side-effects of many drugs, and are regulated by several mediators, including neurotransmitters. This work aimed to investigate whether serum levels of 5-hydroxytryptamine (5-HT) affected the expression of hepatic transporters or DMEs. The expression of hepatic transporters was assessed using the Western-blot technique in a 2,4,6-trinitrobenzenesulfonic-acid-induced rat model of post-infectious irritable bowel syndrome (PI-IBS), in which serum levels of 5-HT were significantly elevated.