Perspectives on 3D printed personalized medicines for pediatrics.

In recent years, the rapid advancement of three-dimensional (3D) printing technology has yielded distinct benefits across various sectors, including pharmaceuticals. The pharmaceutical industry has particularly experienced advantages from the utilization of 3D-printed medications, which have invigorated the development of tailored drug formulations. The approval of 3D-printed drugs by the U.

Berberine prevents NAFLD and HCC by modulating metabolic disorders.

Non-alcoholic fatty liver disease (NAFLD) is a global metabolic disease with high prevalence in both adults and children. Importantly, NAFLD is becoming the main cause of hepatocellular carcinoma (HCC). Berberine (BBR), a naturally occurring plant component, has been demonstrated to have advantageous effects on a number of metabolic pathways as well as the ability to kill liver tumor cells by causing cell death and other routes.

High altitude hypoxia and oxidative stress: The new hope brought by free radical scavengers.

Various strategies can be employed to prevent and manage altitude illnesses, including habituation, oxygenation, nutritional support, and medication. Nevertheless, the utilization of drugs for the prevention and treatment of hypoxia is accompanied by certain adverse effects. Consequently, the quest for medications that exhibit minimal side effects while demonstrating high efficacy remains a prominent area of research.

Comprehensive Investigation of the Influence of High-Altitude Hypoxia on Clopidogrel Metabolism and Gut Microbiota.

Background: The amount of metabolites converted into active metabolites is correspondingly reduced since only more than 50% of clopidogrel is absorbed.

Objective: Exploring the effect of gut microbiota altered by altitude hypoxia on the pre-absorption metabolism of clopidogrel.

Methods: In vitro and in vivo experiments were conducted to analyze the metabolism of clopidogrel through LCMS/ MS, while 16S rRNA analysis was used to investigate the changes in the gut microbiota of high-altitude animals.

Pharmacokinetics, absorption and transport mechanism for ginseng polysaccharides.

Background: Ginseng polysaccharide (GP) is one of the most abundant components in Panax ginseng. However, the absorption pathways and mechanisms of GPs have not been investigated systematically due to the challenges of their detection.

Methods: The fluorescein isothiocyanate derivative (FITC) was employed to label GP and ginseng acidic polysaccharide (GAP) to obtain target samples.

Multiple initiatives to conquer KRAS G12C inhibitor resistance from the perspective of clinical therapy.

Introduction: KRAS G12C targeted covalent inhibitors for cancer therapy are revolutionary. However, resistance to KRAS G12C inhibitors in clinical trials is a proven fact.

Areas Covered: The authors focus on providing coverage and emphasizing the strategy of conquering KRAS G12C inhibitor resistance from the perspective of clinical therapy.

Upgrade of chrysomycin A as a novel topoisomerase II inhibitor to curb KRAS-mutant lung adenocarcinoma progression.

A primary strategy employed in cancer therapy is the inhibition of topoisomerase II (Topo II), implicated in cell survival. However, side effects and adverse reactions restrict the utilization of Topo II inhibitors. Thus, investigations focus on the discovery of novel compounds that are capable of inhibiting the Topo II enzyme and feature safer toxicological profiles.

Novel Anticancer Strategy by Targeting the Gut Microbial Neurotransmitter Signaling to Overcome Immunotherapy Resistance.

Microbial neurotransmitters, as potential targets for cancer therapy, are expected to provide a new perspective on the interaction between the gut microbiome and cancer immunotherapy. Mounting data reveal that most neurotransmitters can be derived from gut microbiota. Furthermore, modulation of neurotransmitter signaling can limit tumor growth and enhance antitumor immunity.

Changes in CYP3A4 Enzyme Expression and Biochemical Markers Under Acute Hypoxia Affect the Pharmacokinetics of Sildenafil.

To investigate the effects of pathological, physiological, biochemical and metabolic enzymes CYP3A4 on the pharmacokinetics of sildenafil under acute hypoxia, rats were randomly divided into the plain group (50 m above sea level), acute plateau group 1 (2300 m above sea level), and acute plateau group 2 (4300 m above sea level), and blood samples and liver tissues were collected. Our results showed that the blood gas, physiological and biochemical indexes of rats changed under acute hypoxia, and the protein expression of CYP3A4 enzyme decreased. The process of absorption, distribution, metabolism and excretion of sildenafil in rats has changed.

Resistance looms for KRAS G12C inhibitors and rational tackling strategies.

KRAS mutations are one of the most frequent activating alterations in carcinoma. Recent efforts have witnessed a revolutionary strategy for KRAS G12C inhibitors with exhibiting conspicuous clinical responses across multiple tumor types, providing new impetus for renewed drug development and culminating in sotorasib with approximately 6-month median progression-free survival in KRAS G12C-driven lung cancer. However, diverse genomic and histological mechanisms conferring resistance to KRAS G12C inhibitors may limit their clinical efficacy.

Composition Changes in Fruit Dried by Different Methods.

The fruit of (LRF), known as black wolfberry, is a medicinal and edible fruit. The fresh LRF is perishable and has only about 3 days of shelf life. Drying could prolong the shelf life of LRF.

Identification wild and cultivated licorice by multidimensional analysis.

Licorice is known as a botanical source in medicine and a sweetening agent in food products. Commercial licorice is from the source of wild and cultivated G. uralensis.

Enhanced P-glycoprotein expression under high-altitude hypoxia contributes to increased phenytoin levels and reduced clearance in rats.

To study the effect of plateau hypoxia on the concentration of P-glycoprotein (P-gp) substrate phenytoin, Wistar rats are randomly divided into the control group and the hypoxic group, including P-gp inhibited groups respectively. Blood, cerebrospinal fluid, brain tissue, and blood-brain barrier were collected in plain areas at an altitude of 1500 m and plateau areas at an altitude of 4010 m. Evans Blue exclusion was used to assess the integrity of the blood-brain barrier.

Effects of intestinal flora on the pharmacokinetics and pharmacodynamics of aspirin in high-altitude hypoxia.

Since hypobaric hypoxia significantly affects metabolic characteristics of intestinal flora, which plays an important role in the biotransformation of aspirin, high altitudes may influence the pharmacokinetics and therapeutic effects of aspirin in the intestines. In the present study, to test alterations of intestinal microbiota at high altitude comparing to that at low altitude, we analyzed rat feces from plain group and high-altitude group by 16S rRNA analysis. To detect concentrations of aspirin and salicylic acid, we established a reliable liquid chromatography tandem mass spectrometry method to measure aspirin and salicylic acid concentrations in fecal suspensions and plasma.

Gut Microbiota-Mediated Drug-Drug Interaction between Amoxicillin and Aspirin.

The effects of antibiotics on the intestinal flora can create potential drug-drug interactions. The combination of amoxicillin and aspirin is high and there is a high probability of interaction. We used 16S rRNA, incubation experiments and liquid chromatography-tandem mass spectrometry to analyze rat biological samples to characterize the effect of amoxicillin on the pharmacokinetics of aspirin metabolites.

[Modulation of drug-metabolizing enzymes and transporters under hypoxia environment].

Drug metabolism is significantly affected under hypoxia environment with changes of pharmacokinetics, expression and function of drug-metabolizing enzymes and transporters. Studies have shown that hypoxia increases the release of a series of inflammatory cytokines which can modulate drug metabolism. Besides, both hypoxia inducible factor 1α (HIF-1α) and microRNA-mediated pathways play a role in regulating drug metabolism.

Disordered Metabolic Profiling in Plasma and Tissues of Mice Infected with Artemisinin-Sensitive and -Resistant Plasmodium berghei K173 Determined by H NMR Spectroscopy.

Artemisinin resistance has inevitably emerged in several malaria-endemic areas and led to an incremental clinical failure rate for artemisinin-based combination therapy (ACT), which is strongly recommended by the World Health Organization (WHO). Genetically resilient malaria parasites have evolved antimalarial drug-evasion mechanisms; meanwhile, the metabolic cross-talk between the malaria parasites and the host is of significance during the invasion. The intention of this work, therefore, is to propose a feasible method to discover the systematic metabolic phenotypes of mice invaded with artemisinin-sensitive or -resistant Plasmodium berghei K173 when compared with healthy mice.

[Research progress of long chain non-coding RNA H19 in anoxic environment mechanism].

LncRNA H19 encoded by the H19 imprinting gene plays an important regulatory role in the cell. Recently study has found that in hypoxic cells, the expression of H19 gene changes, and the transcription factors and protein involved in the expression change accordingly. Through the involvement of specific protein 1 (SP1), hypoxia-inducible factor-1α (HIF-1α) binds directly to the H19 promoter and induces the up-regulation of H19 expression under hypoxic conditions.

Effects of Gut Microbiota on Drug Metabolism and Guidance for Rational Drug Use Under Hypoxic Conditions at High Altitudes.

Background: Modern features of drug development such as low permeability, low solubility, and improved release affect the interplay of the gut microbiota and drug metabolism. In recent years, studies have established the impact of plateau hypoxia on gut microbiota, where drug use by plateau populations is affected by hypoxia- induced changes in intestinal microflora-mediated drug metabolism.

Methods: In this review, we summarized the effects of gut microbiota on drug metabolism, and of plateau hypoxia on the intestinal flora, with the aim of providing guidance for the rational use of drugs in high-altitude populations.

Gut microbiota modulates drug pharmacokinetics.

Gut microbiota, one of the determinants of pharmacokinetics, has long been underestimated. It is now generally accepted that the gut microbiota plays an important role in drug metabolism during enterohepatic circulation either before drug absorption or through various microbial enzymatic reactions in the gut. In addition, some drugs are metabolized by the intestinal microbiota to specific metabolites that cannot be formed in the liver.

Evaluation of renal excretion and pharmacokinetics of furosemide in rats after acute exposure to high altitude at 4300 m.

With studies indicative of altered renal excretion under high altitude-induced hypobaric hypoxia, the consideration of better therapeutic approaches has long been the aim of research on the management of high altitude related illness. The pharmacokinetics of drugs such as furosemide might be altered under hypoxic conditions, making it essential to establish different dose-regimens to maintain therapeutic efficacy or to avoid toxic side effects at high altitude. Simultaneously, drug-drug interactions (DDIs) mediated by OAT1 occur at high altitude, severely affecting furosemide pharmacokinetics.

Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine.

Nifedipine is completely absorbed by the gastrointestinal tract and its pharmacokinetics and metabolism may be influenced by microorganisms. If gut microbes are involved in the metabolism of nifedipine, plateau hypoxia may regulate the bioavailability and the therapeutic effect of nifedipine by altering the metabolic activity of the gut microbiota. We herein demonstrated for the first time that gut flora is involved in the metabolism of nifedipine by in vitro experiments.

Pharmacokinetic changes of norfloxacin based on expression of MRP2 after acute exposure to high altitude at 4300m.

Background: This study was to investigate the influence of physiological changes and the expression of MRP2 efflux transporter on the pharmacokinetics of norfloxacin after acute exposure to high altitude 4300m.

Methods And Results: The rats were randomly divided into high altitude group and plain group. Blood gas and biochemical analysis showed that the physiological parameters significantly changed at high altitude.

Changes of pathological and physiological indicators affecting drug metabolism in rats after acute exposure to high altitude.

High altitude environments cause the human body to undergo a series of pathological, physiological and biochemical changes, which have a certain effect on drug pharmacokinetics. The objective of the present study was to observe changes in factors affecting pharmacokinetics in rats following acute exposure to high altitude and return to low altitude. A total of 21 male Wistar rats were randomly assigned to three groups.

Effects on Pharmacokinetics of Propranolol and Other Factors in Rats After Acute Exposure to High Altitude at 4,010 m.

A series of pathological, physiological, and biochemical changes, even anatomical histological changes happen while humans arrive at the high plateau region from plain area. There is a certain relationship between the body's compensatory or decompensated adjustments to the environment and the changes of absorption, distribution, metabolism, and excretion of drugs. The objective of the study is to observe the effects of acute exposure to high altitude at 4,010 m on pharmacokinetics of propranolol in rats, and to provide basis and new ideas to adjust drug dosage and administration, so as to promote rational drug use in high altitude.