Trideoxycytidine Diphosphate Promotes Neural Stem Cell Proliferation and Neurogenesis in Mice.

Background: Food-derived nucleic acids exhibit various biological activities and may act as nutrients. Oral ingestion of the nucleic acid fraction (NAF) of salmon milt extract hydrolysates enhances cognitive function in mice, although their active ingredients have not yet been identified, and detailed mechanisms of action are unknown.

Objectives: To identify active ingredients enhancing cognitive function contained in the NAF and its possible underlying mechanism.

Examination of common culture medium for human hepatocytes and engineered heart tissue: Towards an evaluation of cardiotoxicity associated with hepatic drug metabolism in vitro.

Cardiotoxicity associated with hepatic metabolism and drug-drug interactions is a serious concern. Predicting drug toxicity using animals remains challenging due to species and ethical concerns, necessitating the need to develop alternative approaches. Drug cardiotoxicity associated with hepatic metabolism cannot be detected using a cardiomyocyte-only evaluation system.

Effect of changes in skin properties due to diabetes mellitus on the titration period of transdermal fentanyl: single-center retrospective study and diabetic animal model study.

Background: In the dose titration of transdermal fentanyl to prevent unrelieved pain, it is important to consider not only dose adjustment, but also the titration period, which is influenced by the time required to reach the steady state. Many patients with cancer pain experience comorbidities that might affect the skin properties and influence transdermal absorption. We hypothesized that skin changes due to diabetes mellitus (DM) would affect the titration period of transdermal fentanyl.

Effect of obesity on pharmacokinetics of transdermal fentanyl: Single-center retrospective study and animal study.

A retrospective study and an animal study were conducted to investigate factors affecting the transdermal fentanyl dose to achieve adequate pain relief in patients switched from other opioids. In the retrospective study, patient factors were included as gender, age, body mass index (BMI), and serum albumin concentration. In obese (BMI ≥25) patients, the post-titration dose of transdermal fentanyl was significantly lower than in normal (BMI 18.

A Supramolecular Biosensor for Rapid and High-Throughput Quantification of a Disease-Associated Niacin Metabolite.

Metabolic abnormalities play a pivotal role in various pathological conditions, necessitating the quantification of specific metabolites for diagnosis. While mass spectrometry remains the primary method for metabolite measurement, its limited throughput underscores the need for biosensors capable of rapid detection. Previously, we reported that pillar[6]arene with 12 carboxylate groups (P6AC) forms host-guest complexes with 1-methylnicotinamide (1-MNA), which is produced in vivo by nicotinamide -methyltransferase (NNMT).

Transdermal pilocarpine on the skin over salivary glands to increase salivation: an in vivo study.

Background: Hyposalivation is treated using oral cholinergic drugs; however, systemic side effects occasionally lead to discontinuation of treatment. We aimed to investigate the effects of transdermal pilocarpine on the salivary gland skin on saliva secretion and safety in rats.

Methods: Pilocarpine was administered to rats orally (0.

Solute Transporter OCTN1/Slc22a4 Affects Disease Severity and Response to Infliximab in Experimental Colitis: Role of Gut Microbiota and Immune Modulation.

Background: Inflammatory bowel diseases are chronic disabling conditions with a complex and multifactorial etiology, still incompletely understood. OCTN1, an organic cation transporter, could have a role in modulating the inflammatory response, and some genetic polymorphisms of this molecule have been associated with increased risk of inflammatory bowel diseases. Until now, limited information exists on its potential in predicting/modulating patient's response to therapies.

Effects of an ergothioneine-rich sp. on skin moisturizing functions and facial conditions: a randomized, double-blind, placebo-controlled trial.

Background: L-ergothioneine (EGT), an antioxidative and anti-inflammatory amino acid, is abundant in various mushroom fruiting bodies. Meanwhile, the effects of EGT-containing mushrooms on human skin are unknown. This study investigated the effects of oral ingestion of a novel EGT-rich strain of species (hiratake) on skin conditions in humans.

Endoplasmic reticulum transporter OAT2 regulates drug metabolism and interaction.

Xenobiotic metabolic reactions in the hepatocyte endoplasmic reticulum (ER) including UDP-glucuronosyltransferase and carboxylesterase play central roles in the detoxification of medical agents with small- and medium-sized molecules. Although the catalytic sites of these enzymes exist inside of ER, the molecular mechanism for membrane permeation in the ER remains enigmatic. Here, we investigated that organic anion transporter 2 (OAT2) regulates the detoxification reactions of xenobiotic agents including anti-cancer capecitabine and antiviral zidovudine, via the permeation process across the ER membrane in the liver.

Quantification of Unencapsulated Drug in Target Tissues Demonstrates Pharmacological Properties and Therapeutic Effects of Liposomal Topotecan (FF-10850).

Purpose: Quantifying unencapsulated drug concentrations in tissues is crucial for understanding the mechanisms underlying the efficacy and safety of liposomal drugs; however, the methodology for this has not been fully established. Herein, we aimed to investigate the enhanced therapeutic potential of a pegylated liposomal formulation of topotecan (FF-10850) by analyzing the concentrations of the unencapsulated drug in target tissues, to guide the improvement of its dosing regimen.

Methods: We developed a method for measuring unencapsulated topotecan concentrations in tumor and bone marrow interstitial fluid (BM-ISF) and applied this method to pharmacokinetic assessments.

Dynamic, IPSC-derived hepatic tissue tri-culture system for the evaluation of liver physiology.

Availability of hepatic tissue for the investigation of metabolic processes is severely limited. While primary hepatocytes or animal models are widely used in pharmacological applications, a change in methodology towards more sustainable and ethical assays is highly desirable. Stem cell derived hepatic cells are generally regarded as a viable alternative for the above model systems, if current limitations in functionality and maturation can be overcome.

Ergothioneine promotes longevity and healthy aging in male mice.

Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives.

Gut-liver microphysiological systems revealed potential crosstalk mechanism modulating drug metabolism.

The small intestine and liver play important role in determining oral drug's fate. Both organs are also interconnected through enterohepatic circulation, which imply there are crosstalk through circulating factors such as signaling molecules or metabolites that may affect drug metabolism. Coculture of hepatocytes and intestinal cells have shown to increase hepatic drug metabolism, yet its crosstalk mechanism is still unclear.

Development of the anterior pituitary: diverse lineages of the stem/progenitor cells.

The pituitary gland is endocrine tissue composed of two distinct parts with different origins: the adenohypophysis (adenohypophyseal placode origin) and the neurohypophysis (neuroectoderm origin). Differentiation of endocrine cells in the pituitary gland leads to hormone synthesis, secretion into the capillary network, and transportation to target organs. In 1988, the discovery of the pituitary transcription factor PIT1 sparked research on endocrine cell differentiation.

A highly efficient cell culture method using oxygen-permeable PDMS-based honeycomb microwells produces functional liver organoids from human induced pluripotent stem cell-derived carboxypeptidase M liver progenitor cells.

Recent advancements in bioengineering have introduced potential alternatives to liver transplantation via the development of self-assembled liver organoids, derived from human-induced pluripotent stem cells (hiPSCs). However, the limited maturity of the tissue makes it challenging to implement this technology on a large scale in clinical settings. In this study, we developed a highly efficient method for generating functional liver organoids from hiPSC-derived carboxypeptidase M liver progenitor cells (CPM+ LPCs), using a microwell structure, and enhanced maturation through direct oxygenation in oxygen-permeable culture plates.

Mechanobiological stimulation in organ-on-a-chip systems reduces hepatic drug metabolic capacity in favor of regenerative specialization.

Hepatic physiology depends on the liver's complex structural composition which among others, provides high oxygen supply rates, locally differential oxygen tension, endothelial paracrine signaling, as well as residual hemodynamic shear stress to resident hepatocytes. While functional improvements were shown by implementing these factors into hepatic culture systems, direct cause-effect relationships are often not well characterized-obfuscating their individual contribution in more complex microphysiological systems. By comparing increasingly complex hepatic in vitro culture systems that gradually implement these parameters, we investigate the influence of the cellular microenvironment to overall hepatic functionality in pharmacological applications.

The balance between fetal oxytocin and placental leucine aminopeptidase (P-LAP) controls human uterine contraction around labor onset.

A fetal pituitary hormone, oxytocin which causes uterine contractions, increases throughout gestation, and its increase reaches 10-fold from week 32 afterward. Oxytocin is, on the other hand, degraded by placental leucine aminopeptidase (P-LAP) which exists in both terminal villi and maternal blood. Maternal blood P-LAP increases with advancing gestation under the control of non-genomic effects of progesterone, which is also produced from the placenta.

Missing pieces of the pituitary puzzle: participation of extra-adenohypophyseal placode-lineage cells in the adult pituitary gland.

The pituitary gland is a major endocrine tissue composing of two distinct entities, the adenohypophysis (anterior pituitary, cranial placode origin) and the neurohypophysis (posterior pituitary, neural ectoderm origin), and plays important roles in maintaining vital homeostasis. This tissue is maintained by a slow, consistent cell-renewal system of adult stem/progenitor cells. Recent accumulating evidence shows that neural crest-, head mesenchyme-, and endoderm lineage cells invade during pituitary development and contribute to the maintenance of the adult pituitary gland.

Renal Pharmacokinetic Adaptation to Cholestasis Causes Increased Nephrotoxic Drug Accumulation by Mrp6 Downregulation in Mice.

In hepatic dysfunction, renal pharmacokinetic adaptation can be observed, although information on the changes in drug exposure and the interorgan regulation of membrane transporters in kidney in liver diseases is limited. This study aimed to clarify the effects of renal exposure to nephrotoxic drugs during cholestasis induced by bile duct ligation (BDL). Among the 11 nephrotoxic drugs examined, the tissue accumulation of imatinib and cisplatin in kidney slices obtained from mice 2 weeks after BDL operation was higher than that in sham-operated mice.

l-Type amino acid transporter 1 in hypothalamic neurons in mice maintains energy and bone homeostasis.

Hypothalamic neurons regulate body homeostasis by sensing and integrating changes in the levels of key hormones and primary nutrients (amino acids, glucose, and lipids). However, the molecular mechanisms that enable hypothalamic neurons to detect primary nutrients remain elusive. Here, we identified l-type amino acid transporter 1 (LAT1) in hypothalamic leptin receptor-expressing (LepR-expressing) neurons as being important for systemic energy and bone homeostasis.

Emerging Roles of Uremic Toxins and Inflammatory Cytokines in the Alteration of Hepatic Drug Disposition in Patients with Kidney Dysfunction.

Patients with kidney dysfunction exhibit distinct pharmacokinetic profiles compared to those with normal kidney function. Hence, it is desirable to monitor the drug efficacy and toxicity caused by fluctuations in plasma drug concentrations associated with kidney dysfunction. Recently, pharmacokinetic information of drugs excreted mainly through the urine of patients with kidney dysfunction has been reported via drug-labeling information.