Drug review process advancement and required manufacturer and contract research oraganization responses.

The United States Senate passed the "FDA Modernization Act 2.0." on September 29, 2022.

Urinary liver-type fatty acid binding protein is a biomarker reflecting renal damage and the ameliorative effect of drugs at an early stage of histone-induced acute kidney injury.

Aim: Circulated histones play a crucial role in the pathogenesis of infectious diseases and severe trauma, and it is one of the potential molecular targets for therapeutics. Recently, we reported that histone is one of the causative agents for urinary L-FABP increase. However, the mechanism is still unclear, especially in severe cases.

Nonalcoholic steatohepatitis-associated hepatocarcinogenesis in mice fed a modified choline-deficient, methionine-lowered, L-amino acid-defined diet and the role of signal changes.

Nonalcoholic steatohepatitis (NASH) can progress to cirrhosis and even hepatocellular carcinoma (HCC). The incidence of NASH-associated HCC is increasing, posing a serious public health threat. Unfortunately, the underlying pathological mechanisms, including the possible differences between neoplastic and non-neoplastic lesions, remain largely unknown.

Time-Course of Transcriptomic Change in the Lungs of F344 Rats Repeatedly Exposed to a Multiwalled Carbon Nanotube in a 2-Year Test.

Despite intensive toxicological studies of carbon nanotubes (CNTs) over the last two decades, only a few studies have demonstrated their pulmonary carcinogenicities in chronic animal experiments, and the underlying molecular mechanisms are still unclear. To obtain molecular insights into CNT-induced lung carcinogenicity, we performed a transcriptomic analysis using a set of lung tissues collected from rats in a 2-year study, in which lung tumors were induced by repeated intratracheal instillations of a multiwalled carbon nanotube, MWNT-7. The RNA-seq-based transcriptome identified a large number of significantly differentially expressed genes at Year 0.

Urinary liver-type fatty acid binding protein is increased in the early stages of the disease with a risk of acute kidney injury induced by histone.

Aim: Urinary liver-type fatty acid binding protein (L-FABP) has potential utility as an early prognostic biomarker ahead of traditional severity scores in coronavirus disease 2019 and sepsis, however, the mechanism of elevated urinary L-FABP in the disease has not been clearly elucidated. We investigated the background mechanisms of urinary L-FABP excretion through non-clinical animal model focusing on histone, which is one of the aggravating factors in these infectious diseases.

Methods: Male Sprague-Dawley rats were placed in central intravenous catheters, and these rats were given a continuous intravenous infusion of 0.

Effects of extract on nonalcoholic steatohepatitis-like lesions in Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet.

is the fruit of a cucurbitaceous vine endemic to China. Its extract has been used as a sweetener and exhibits various anti-inflammatory and anticarcinogenic effects mediated via its antioxidant properties. In the present study, we aimed to clarify the preventive or ameliorative effects of extract (SGE) on nonalcoholic steatohepatitis-like lesions induced in male Hsd: Sprague Dawley rats fed a choline-deficient, methionine-lowered, l-amino acid-defined diet for 13 weeks.

CD44 expression in the bile duct epithelium is related to hepatic fibrosis in nonalcoholic steatohepatitis rats induced by a choline-deficient, methionine-lowered, L-amino acid diet.

Nonalcoholic steatohepatitis is a lifestyle-related disease and an increasing threat worldwide. Hepatic fibrosis, which results from chronic hepatic diseases including nonalcoholic steatohepatitis, is closely correlated with mortality among hepatic lesions, such as steatosis and inflammation. Thus, it is important to identify factors that can serve as diagnostic and therapeutic targets for hepatic fibrosis.

Effects of excessive sodium chloride loading in the spontaneously diabetic torii (SDT) fatty rats, a preclinical model of type 2 diabetes mellitus.

Type 2 diabetes mellitus represents an international health concern with its growing number of patients worldwide. At the same time, excessive salt consumption is also seen as a major cause of diseases such as hypertension and may expedite renal complications in diabetic patients. In this study, we investigated the effects of excessive sodium chloride supplementation on the kidney of the Spontaneously Diabetic Torii-Lepr (SDT fatty) rat, an obese type 2 diabetes model.

Iron oxide nanoparticles exert inhibitory effects on N-Bis(2-hydroxypropyl)nitrosamine (DHPN)-induced lung tumorigenesis in rats.

Iron oxide nanoparticles (magnetite) have been widely used in industry and medicine. However, the safety assessment of magnetite has not been fully completed. The present study was conducted to assess effects of magnetite on carcinogenic activity, using a medium-term bioassay protocol.

A case of spontaneous Zymbal's gland carcinoma with lung metastasis in an aged Fischer 344 rat.

Zymbal's gland neoplasms are induced in rats through the administration of various carcinogens, but spontaneous neoplasia is rare. This report describes a spontaneous Zymbal's gland carcinoma with lung metastasis found in an aged male Fischer 344 rat. Macroscopically, the dome-like tumor nodule, approximately 30 mm in diameter with ulceration, was located near the ear canal of the rat.

Nonobese mice with nonalcoholic steatohepatitis fed on a choline-deficient, l-amino acid-defined, high-fat diet exhibit alterations in signaling pathways.

Nonalcoholic steatohepatitis (NASH) is often associated with obesity, but some patients develop NASH without obesity. The physiological processes by which nonobese patients develop NASH and cirrhosis have not yet been determined. Here, we analyzed the effects of dietary methionine content on NASH induced in mice fed on a choline-deficient, methionine-lowered, l-amino acid-defined high-fat diet (CDAHFD).

Histological sequence of the development of rat mesothelioma by MWCNT, with the involvement of apolipoproteins.

A rat model of mesothelioma development by peritoneal injection of multiwalled carbon nanotube (MWCNT) has been established and found to be useful to understand the mechanisms underlying fibrous particles-associated carcinogenesis. Its detailed histological sequence, however, remains largely obscure. We therefore aimed to assess the time-course of mesothelioma development by MWCNT and evaluate a set of lipoprotein-related molecules as potential mechanism-based biomarkers for the phenomenon.

A trans fatty acid substitute enhanced development of liver proliferative lesions induced in mice by feeding a choline-deficient, methionine-lowered, L-amino acid-defined, high-fat diet.

Background: Nonalcoholic steatohepatitis (NASH) is a form of liver disease characterized by steatosis, necroinflammation, and fibrosis, resulting in cirrhosis and cancer. Efforts have focused on reducing the intake of trans fatty acids (TFAs) because of potential hazards to human health and the increased risk for NASH. However, the health benefits of reducing dietary TFAs have not been fully elucidated.

Impact of altered dietary calcium-phosphorus ratio caused by high-phosphorus diets in a rat chronic kidney disease (CKD) model created by partial ligation of the renal arteries.

This study aimed to establish a rat chronic kidney disease (CKD) model by studying the effects of a high-phosphorus diet in rats that had undergone partial ligation of the renal arteries (RL). Separate groups of 10-week-old male Slc:Sprague-Dawley rats underwent RL and were fed diets with varying phosphorous levels for a period of 48 days. A marked suppression of body weight gain necessitating humane euthanization occurred on day 28 in rats that had undergone RL and were given high-phosphorus feed.

Identification of Descarbonsildenafil in an Adulterated Dietary Supplement and Evaluation of Its Inhibitory Activity for Phosphodiesterase Type 5 (PDE5).

Some illegal dietary supplements contain phosphodiesterase type 5 (PDE5) inhibitors, such as sildenafil, for exerting "therapeutic" effects in erectile dysfunction. This is apparently dangerous, and thus, should be appropriately regulated. Identification of descarbonsildenafil was first reported in Singapore in a coffee sample labeled to exert male sexual performance enhancement effects.

Establishment of the Global SEND Alliance (G-SEND) in Japan and efficient creation of electronic SEND datasets between CROs.

The Standard for Exchange of Nonclinical Data (SEND), adopted by the US Food and Drug Administration (FDA), is a set of regulations for digitalization and standardization of nonclinical study data; thus, related organizations have begun implementing processes in support of SEND. The Global Editorial and Steering Committee (GESC), which provides oversight of the International Harmonization of Nomenclature and Diagnostic Criteria (INHAND), has prepared the SEND Controlled Terminology (CT) for toxicologic pathology. SEND provides electronic data standards created by the Clinical Data Interchange Standards Consortium (CDISC), and CDISC also collaborates in the implementation of SEND.

Hepatic lesions induced by feeding Western diets to Zucker fatty rats, an insulin-resistant model.

Metabolic diseases including nonalcoholic steatohepatitis develop due to various environmental factors. In particular, the westernization of food is closely related to the development of these diseases. In this study, we investigated pathophysiological changes in the livers of Zucker fatty (ZF) rats induced by feeding Western diets.

Comparative study for carcinogenicity of 7 different multi-wall carbon nanotubes with different physicochemical characteristics by a single intraperitoneal injection in male Fischer 344 rats.

The present study comparatively examined carcinogenicity of 7 different multi-wall carbon nanotubes (MWCNTs) with different physicochemical characteristics. Physicochemical characteristics of MWCNTs (referred to as M-, N-, WL-, SD1-, WS-, SD2- and T-CNTs in the present study) were determined using scanning electron and light microscopes and a collision type inductively coupled plasma mass spectrometer. Male Fischer 344 rats (10 weeks old, 15 animals per group) were administered MWCNTs at a single intraperitoneal dose of 1 mg/kg body weight, and sacrificed up to 52 weeks after the commencement.

Effect of dosing frequency of teriparatide (PTH 1-34) on bone formation in rats: comparison of bone metabolism marker levels.

Teriparatide, a drug used in the treatment of osteoporosis, was administered to rats subcutaneously for the duration of 3 months, at a frequency of either once weekly or once daily to demonstrate the varying levels of anabolic action the drug can have on bone depending on the dosing frequency. The levels of biomarkers in the blood were compared and found to vary in osteocalcin (OC), a biomarker of bone formation, and cross-linked N-telopeptide of type 1 collagen (NTx), a biomarker of bone resorption, according to the dosing frequency. In the once-weekly regimen, teriparatide did not affect NTx levels at any of the doses studied, while OC levels increased with dose, peaking at 72 hr, then returning to normal before the next injection (after 1 week).

Establishment of an in vivo simulating co-culture assay platform for genotoxicity of multi-walled carbon nanotubes.

Engineered nanomaterials (ENM) are now used in a wide variety of fields, and, thus, their safety should urgently be assessed and secured. It has been suggested that inflammatory responses via the phagocytosis of ENM by macrophages is a key mechanism for their genotoxicity. The present study was conducted to establish a mechanism-based assay to evaluate the genotoxicity of ENM under conditions simulating an in vivo situation, featuring a co-culture system of murine lung resident cells (GDL1) and immune cells (RAW264.

Extracts of black and brown rice powders improve hepatic lipid accumulation via the activation of PPARα in obese and diabetic model mice.

Rice powder extract (RPE) from black and brown rice (Oryza sativa L. indica) improves hepatic lipid accumulation in obese and diabetic model mice via peroxisomal fatty acid oxidation. RPE showed PPARα agonistic activity which did not differ between black and brown RPE despite a higher anthocyanin content in black RPE.