The advancement of polysaccharides in disease modulation: Multifaceted regulation of programmed cell death.

Programmed cell death (PCD), also known as regulatory cell death (RCD), is a process that occurs in all organisms and is closely linked to both normal physiological processes and disease states. Various signaling pathways, such as TP53, KRAS, NOTCH, hypoxia, and metabolic reprogramming, have been found to regulate RCD. Polysaccharides, which are essential natural products, have been the subject of extensive research in the fields of food, nutrition, and medicine due to their wide range of pharmacological effects.

Mitochondria-mediated Ferroptosis in Diseases Therapy: From Molecular Mechanisms to Implications.

Ferroptosis, a type of cell death involving iron and lipid peroxidation, has been found to be closely associated with the development of many diseases. Mitochondria are vital components of eukaryotic cells, serving important functions in energy production, cellular metabolism, and apoptosis regulation. Presently, the precise relationship between mitochondria and ferroptosis remains unclear.

Schisandrin A ameliorates airway inflammation in model of asthma by attenuating Th2 response.

Asthma is a persistent respiratory ailment that displays periodicity and is linked to the equilibrium of T cells. Several compounds obtained from Chinese herbal medicines display beneficial impacts on T cell regulation and the attenuation of inflammatory mediator synthesis. Schisandrin A, an active lignan derived from the Schisandra fruit, exhibits anti-inflammatory characteristics.

Structural characterization of a sulfated polysaccharide from and its potentiation of cisplatin antitumor activity in Colon-26 carcinoma tumor-bearing mice by inducing ferroptosis.

Ferroptosis, a form of regulated cell death caused by iron-mediated lipid peroxidation, has become a potential strategy to overcome drug resistance and improve the efficacy of traditional cancer treatments. In this study, we investigated whether treatment with the combination of polysaccharides and cisplatin (CP) potentiated the antitumor activity in a Colon-26 carcinoma tumor-bearing mouse model by ferroptosis activation. The polysaccharide GP90 was mainly composed of (1→3) linked 4--sulfate-β-D-galactose and (1→4) linked 3,6-anhydro-α-L-galactose with a molecular weight of 12.

MiR-449a downregulation alleviates the progression of renal interstitial fibrosis by mediating the KLF4/MFN2 axis.

Background: Renal interstitial fibrosis (RIF) seriously threatens the health of individuals. MiRNAs regulate the progression of fibrosis. Nevertheless, the detailed function of miR-449a in RIF is largely unknown.

circPlekha7 suppresses renal fibrosis via targeting miR-493-3p/KLF4.

The authors aim to investigate the function of circPlekha7 in renal fibrosis. Human renal tissues from chronic kidney disease patients, kidney cell line and primary cultured renal tubular epithelial cells were used. TGF-β1-treated human kidney 2 cells/tubular epithelial cells and a unilateral ureteral obstruction mouse model were employed to study renal fibrosis.

Evaluation of a Clinically Relevant Drug-Drug Interaction Between Rosuvastatin and Clopidogrel and the Risk of Hepatotoxicity.

The combination therapy of rosuvastatin (RSV) and the platelet inhibitor clopidogrel (CP) is widely accepted in the management of cardiovascular diseases. The objective of the present study was to identify the mechanism of RSV-CP DDI and evaluate the risk of hepatotoxicity associated with the concomitant use of CP. We first studied the effect of CP and its major circulating metabolite, carboxylic acid metabolite (CPC), on RSV transport by overexpressing cells and membrane vesicles.

TGF-β1-activated cancer-associated fibroblasts promote breast cancer invasion, metastasis and epithelial-mesenchymal transition by autophagy or overexpression of FAP-α.

Cancer-associated fibroblasts (CAFs) play an important role in the initiation, metastasis, and invasion of breast cancer. However, whether autophagy acts as a tumor promotion mechanism by inducing epithelial-mesenchymal transition (EMT) is still controversial and remains undefined at the mechanistic levels. In this study, we investigated whether autophagy or FAP-α is required for the invasion, pulmonary metastasis and EMT of breast cancer cells and underlying mechanism.

Clinically significant drug-drug interaction between tacrolimus and fluconazole in stable renal transplant recipient and literature review.

What Is Known And Objective: Clinical use of fluconazole against fungal infections in renal transplant patients is complicated by the potentially marked and unpredictable drug-drug interactions (DDIs). We report a case of tacrolimus-fluconazole DDI in a stable renal transplant recipient and describe the mechanism, magnitude and duration of this DDI through a literature review.

Case Summary: A 38-year-old woman experienced a 9.

An LC-MS/MS Validated Method for Quantification of Chlorzoxazone in Human Plasma and Its Application to a Bioequivalence Study.

A simple, sensitive, specific, accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay for determination of chlorzoxazone in human plasma was developed and validated to evaluate the pharmacokinetic characteristics of chlorzoxazone test or reference formulation. Sample preparation was achieved by one step protein precipitation and dilution with acetontrile. The chromatographic separation was performed at 40°C with a gradient mobile phase (0.

Progression of systemic lupus erythematosus associated with propofol administration: a case report.

Propofol is a sedative-hypnotic agent used as a general anaesthetic with a good safety profile. However, the potential risk for patients with systemic lupuserythematosus (SLE) receiving propofol remains unclear. We report the case of a patient who received an intravenous infusion of propofol for painless gastroscopy which exacerbated acute SLE despite no history of allergies.

Evaluation of a Potential Clinical Significant Drug-Drug Interaction between Digoxin and Bupropion in Cynomolgus Monkeys.

Purpose: A three-period digoxin-bupropion drug-drug interaction study was performed in cynomolgus monkeys to assess the effect of bupropion and its metabolites on digoxin disposition.

Methods: Monkeys were administered either an i.v.

Evaluation of inhaled recombinant human insulin dry powders: pharmacokinetics, pharmacodynamics and 14-day inhalation.

Objectives: The present study was designed to assess the pharmacokinetic and pharmacodynamic performance of inhaled recombinant human insulin (rh-insulin) dry powders together with their safety profiles after 14-day inhalation.

Methods: In the pharmacokinetic and pharmacodynamic study, pulmonary surfactant (PS)-loaded and phospholipid hexadecanol tyloxapol (PHT)-loaded rh-insulin dry powders were intratracheally administered to male rats at the dose of 20 U/kg. Novolin R was used as control.

Variant rs2200733 and rs10033464 on chromosome 4q25 are associated with increased risk of atrial fibrillation after catheter ablation: Evidence from a meta-analysis.

Background: Common genetic polymorphisms at chromosome 4q25 were associated with increased susceptibility to atrial fibrillation (AF). However, it remained controversial whether these variants could be used as risk predictors for AF recurrence after catheter ablation. We therefore performed a metaanalysis to quantify the association between rs2200733 C>T/rs10033464 G>T and AF recurrence.

Pharmacokinetic evaluation of β-caryophyllene alcohol in rats and beagle dogs.

1. β-caryophyllene alcohol (BCPA) has shown therapeutic promise in the treatment of asthma and inflammation with low toxicity. The aim of the current study was to report the pharmacokinetic profiles of BCPA in rats and dogs.

Enantioselective HPLC determination of oxiracetam enantiomers and application to a pharmacokinetic study in beagle dogs.

An enantioselective high-performance liquid chromatography method was developed and validated for the determination of oxiracetam enantiomers, a cognition and memory enhancer, in beagle dog plasma. The plasma samples were prepared by methanol extraction from 200μL plasma, and then the baseline resolution was achieved on a Chiralpak ID column (250mm×4.6mm, 5μm) with mobile phase of hexane-ethanol-trifluoroacetic acid (78:22:0.

Comparative pharmacokinetic studies of racemic oxiracetam and its pure enantiomers after oral administration in rats by a stereoselective HPLC method.

Oxiracetam (ORC), a nootropic drug used for improving the cognition and memory, has an asymmetric carbon in its structure and exists as (S)- and (R)-ORC. The pharmacokinetic profiles of racemic oxiracetam and its pure enantiomers in rats were evaluated and compared by enantioselective high-performance liquid chromatography, which was performed on a Chiralpak ID column with a mobile phase of hexane-ethanol-trifluoroacetic acid (78:22:0.1, v/v/v).

Tissue distribution and ontogeny of multidrug resistance protein 2, a phosphatidylcholine translocator, in rats.

Multidrug resistance protein 2 (Mdr2), encoded by ATP-binding cassette b4 (Abcb4), serves as a phospholipid flippase that is indispensable for phosphatidylcholine translocation. However, little was known about the regulation of Mdr2 in Sprague-Dawley rats, although they are commonly used for pre-clinical investigation as well as mechanistic study. Present study aims at determining the tissue distribution, gender difference and ontogeny of Mdr2 in rats on both gene and protein levels.

PET imaging of Oatp-mediated hepatobiliary transport of [(11)C] rosuvastatin in the rat.

Unlabelled: A novel positron emission tomography (PET) tracer, [(11)C]-rosuvastatin (RSV), was developed to dynamically and noninvasively measure hepatobiliary transport and tissue distribution of [(11)C]-RSV in rats.

Methods: Male Sprague-Dawley rats were administered either an Oatp inhibitor, rifampin (RIF, 40 mg/kg iv bolus plus 1.85 mg/min/kg iv infusion, n = 3), or the corresponding vehicle (saline, n = 3) for at least 90 min.

Mechanism of an unusual, but clinically significant, digoxin-bupropion drug interaction.

An unusual, but clinically significant, digoxin (DIG)-bupropion (BUP) drug interaction (DDI), in which BUP increased DIG renal clearance by 80% is reported. To investigate the mechanism(s) of this unusual DDI, first the effect of BUP, its circulating metabolites or their combination on [(3) H]-DIG transport by cells expressing human P-gp or human OATP4C1 was determined. Second, the study asked whether this DDI could be replicated in the rat so that it could be used to conduct mechanistic studies.

Evaluation of insulin lispro and biosynthetic human insulin in pulmonary absorption: in vivo and in vitro studies.

Objective: To compare the pulmonary absorption characteristics of two insulin solutions-humalog (insulin lispro) and Novolin R (Biosynthetic Human insulin) with in vivo and in vitro methods.

Methods: Investigate the pharmacodynamics in Sprague Dawley (SD) rat model (in vivo studies) and permeability across Rana catesbeiana pulmonary membrane (in vitro studies) of Biosynthetic Human insulin (BHI) and insulin lispro (LI) at different doses.

Results: Both of the insulins could reduce blood glucose levels promptly after pulmonary administration.

Enhanced pulmonary absorption of recombinant human insulin by pulmonary surfactant and phospholipid hexadecanol tyloxapol through Calu-3 monolayers.

Natural pulmonary surfactant (PS) and its artificial substitute phospholipid hexadecanol tyloxapol (PHT) are effective absorption enhancers on promoting recombinant human insulin (Rh-ins) absorption in vivo, but the in vitro efficacy and underlying mechanism remains unclear. In the current study, the permeation promoting effects of PS and PHT of insulin through Calu-3 monolayers in Transwell were evaluated. The viability of Calu-3 cells on conducting the permeation study was confirmed by TER and Electron Microscopy.

Identification and characterization of human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of salvianolic acid A.

Glucuronidation is an important pathway in the elimination of salvianolic acid A (Sal A); however the mechanism of UDP-glucuronosyltransferases (UGTs) in this process remains to be investigated. In this study, the kinetics of Sal A glucuronidation by pooled human liver microsomes (HLMs), pooled human intestinal microsomes (HIMs) and 12 recombinant UGT isozymes were investigated. The glucuronidation of Sal A can be shown both in HLMs and HIMs with K(m) values of 39.

Simultaneous determination of six phenolic constituents of Danshen injection in rat plasma by LC-ESI-MS and its application to a pharmacokinetic study.

Salvianolic acid A, salvianolic acid B, danshensu, protocatechuic aldehyde, rosmarinic acid and lithospermic acid are the six major active constituents in Danshen injection. In this study, a rapid, sensitive and specific liquid chromatographic-electrospray ionization-mass spectrometry method for the simultaneous quantitative determination of these compounds in rat plasma was developed. After a single step of liquid-liquid extraction with ethyl acetate, they were eluted by a Hypersil C18 column (5 µm, i.

Effects of SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of repaglinide in healthy Chinese volunteers.

Purpose: Repaglinide is commonly used in the treatment of patients with type 2 diabetes mellitus to reduce postprandial hyperglycemia. The objective of this research was to study the effects of SLCO1B1 polymorphisms on the pharmacokinetics and pharmacodynamics of repaglinide in healthy Chinese volunteers.

Methods: A total of 22 healthy young male participants were recruited from a pool of pharmacogenetically characterized participants genotyped for SLCO1B1, CYP3A4, and CYP2C8 SNPs by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).