Effect of an Enteral Formula Enriched With ω-3 Fatty Acids, Carnitine, and Vitamin D on Body Weight, Heart Weight, and Blood Biochemical Parameters in a Dahl Rat Heart Failure Model.

Malnutrition is known to worsen the prognosis of chronic heart failure (HF). To gain information that may be helpful in establishing appropriate nutritional interventions for chronic HF, this study was performed to investigate the efficacy of nutritional management with 2 enteral formulas, EH, with a standard nutritional composition, and ER, fortified with omega-3 fatty acids, vitamin D, and carnitine. Experiments were performed in a Dahl rat HF model.

Efficacy of KPR-5714, a selective transient receptor potential melastatin 8 antagonist, on chronic psychological stress-induced bladder overactivity in male rats.

Aims: Chronic psychological stress aggravates lower urinary tract symptoms. Among others, water avoidance stress is a chronic psychological stressor that plays a causal role in the exacerbation and development of bladder dysfunction in rats. In this report, the effects of KPR-5714, which is a selective transient receptor potential melastatin 8 (TRPM8) antagonist, on bladder overactivity induced by water avoidance stress were examined.

Zamamiphidins B and C, Manzamine-Related Alkaloids from an sp. Marine Sponge Collected in Okinawa.

Zamamiphidins B () and C (), two new manzamine-related alkaloids with an unprecedented fused diazahexacyclic ring system, were isolated from an sp. marine sponge collected in Okinawa. The structures of zamamiphidins B () and C () including the relative configurations were elucidated on the basis of spectroscopic data.

KPR-5714, a selective transient receptor potential melastatin 8 antagonist, improves voiding dysfunction in rats with bladder overactivity but does not affect voiding behavior in normal rats.

Aims: Transient receptor potential melastatin 8 (TRPM8) has a role in the abnormal sensory transduction of the bladder and is involved in the pathophysiology of hyperactivity bladder disorders. The aim of this study is to examine the effects of KPR-5714, a novel and selective TRPM8 antagonist, on voiding dysfunction induced by bladder afferent hyperactivity via mechanosensitive C-fibers in rats.

Methods: The effects of intragastric administration of KPR-5714 on bladder overactivity induced by intravesical instillation of 10 mM ATP were investigated using cystometry in conscious female rats.

Efficacy of the combination of KPR-5714, a novel transient receptor potential melastatin 8 (TRPM8) antagonist, and β-adrenoceptor agonist or anticholinergic agent on bladder dysfunction in rats with bladder overactivity.

Transient receptor potential melastatin 8 (TRPM8) channels may contribute to the pathophysiological bladder afferent hyperactivity, thus a TRPM8 antagonist would be a promising therapeutic target for the bladder hypersensitive disorders including urinary urgency in overactive bladder (OAB). We aimed to investigate a pharmacological effect of KPR-5714, a novel selective TRPM8 antagonist, on TRPM8 channels, M receptors and β-adrenoceptors using the transfected cells of each gene at first. Then, combination effects of KPR-5714 and mirabegron, a β-adrenoceptor agonist, or tolterodine tartrate, an anticholinergic agent, were studied on rhythmic bladder contractions (RBCs) in normal rats and bladder function in frequent-voiding rats.

Identification of N-acyl-N-indanyl-α-phenylglycinamides as selective TRPM8 antagonists designed to mitigate the risk of adverse effects.

Transient receptor potential melastatin 8 (TRPM8), a temperature-sensitive ion channel responsible for detecting cold, is an attractive molecular target for the treatment of pain and other disorders. We have previously discovered a selective TRPM8 antagonist, KPR-2579, which inhibited bladder afferent hyperactivity induced by acetic acid instillation into the bladder. However, additional studies have revealed potential adverse effects with KPR-2579, such as the formation of a reactive metabolite, CYP3A4 induction, and convulsions.

Agesasines A and B, Bromopyrrole Alkaloids from Marine Sponges spp.

Exploration for specialized metabolites of Okinawan marine sponges spp. resulted in the isolation of five new bromopyrrole alkaloids, agesasines A () and B (), 9-hydroxydihydrodispacamide (), 9-hydroxydihydrooroidin (), and 9-keramadine (). Their structures were elucidated on the basis of spectroscopic analyses.

Borderline Microenvironment Fibrosis Is a Novel Poor Prognostic Marker of Oral Squamous Cell Carcinoma.

Background/aim: The tumor microenvironment (TME) balances tumor growth and suppression through humoral factors and cell-cell interactions. In oral squamous cell carcinoma (OSCC), TMEs have been associated with prognosis of cancer patients and are evaluated by microscopy; however, these methods of evaluation vary among studies.

Materials And Methods: To evaluate the TME, borderline microenvironment fibrosis (bMF) was evaluated histologically in 236 OSCC cases and used to determine the clinicopathological status.

The manzamine alkaloids.

The manzamine alkaloids are absolutely one of the most fascinating marine natural products. The representative manzamine alkaloids, manzamines A-C, were isolated from a marine sponge Haliclona sp. collected off Cape Manzamo, Okinawa, Japan.

KPR-5714, a Novel Transient Receptor Potential Melastatin 8 Antagonist, Improves Overactive Bladder via Inhibition of Bladder Afferent Hyperactivity in Rats.

Transient receptor potential (TRP) melastatin 8 (TRPM8) is a temperature-sensing ion channel mainly expressed in primary sensory neurons (A-fibers and C-fibers in the dorsal root ganglion). In this report, we characterized KPR-5714 (-[()-3,3-difluoro-4-hydroxy-1-(2-1,2,3-triazol-2-yl)butan-2-yl]-3-fluoro-2-[5-(4-fluorophenyl)-1-pyrazol-3-yl]benzamide), a novel and selective TRPM8 antagonist, to assess its therapeutic potential against frequent urination in rat models with overactive bladder (OAB). In calcium influx assays with HEK293T cells transiently expressing various TRP channels, KPR-5714 showed a potent TRPM8 antagonistic effect and high selectivity against other TRP channels.

Ma'edamines C and D, New Bromotyrosine Alkaloids Possessing a Unique Tetrasubstituted Pyridinium Moiety from an Okinawan Marine Sponge sp.

Two new bromotyrosine alkaloids, ma'edamines C and D, were isolated from an Okinawan marine sponge sp. The structures of ma'edamines C and D were elucidated on the basis of spectroscopic data. Ma'edamines C and D were the first natural products possessing a unique tetrasubstituted pyridinium moiety such as -alkyl-3,5-diethyl-2-propylpyridinium and -alkyl-3,5-diethyl-4-propylpyridinium, respectively.

Quantitative Evaluation of Cephalometric Radiographs of Patients With Hemifacial Microsomia.

Objective: To clarify the morphological characteristics of hemifacial microsomia (HFM) by quantitative analysis of cephalometric radiographs.

Design: Retrospective study of imaging data.

Setting: Imaging data were obtained from the records of Sapporo Medical University Hospital.

Ceratinadins E and F, New Bromotyrosine Alkaloids from an Okinawan Marine Sponge sp.

Two new bromotyrosine alkaloids, ceratinadins E () and F (), were isolated from an Okinawan marine sponge sp. as well as a known bromotyrosine alkaloid, psammaplysin F (). The gross structures of and were elucidated on the basis of spectroscopic data.

Uncommon presentation of desmoplastic fibroblastoma on the tongue of a female patient.

Desmoplastic fibroblastoma (DF) is a rare benign soft tissue with spindle-to-stellate-shaped fibroblasts and myofibroblasts embedded in a prominent collagenous background. DF, mainly affecting subcutaneous and muscle tissue, very rarely occurs in the oral cavity. Hitherto, only one case of DF on the tongue has been reported.

Screening for long noncoding RNAs associated with oral squamous cell carcinoma reveals the potentially oncogenic actions of DLEU1.

Recent studies have shown that long noncoding RNAs (lncRNAs) have pivotal roles in human malignancies, although their significance in oral squamous cell carcinoma (OSCC) is not fully understood. In the present study, we identified lncRNAs functionally associated with OSCC. By analyzing RNA-seq datasets obtained from primary head and neck squamous cell carcinoma (HNSCC), we identified 15 lncRNAs aberrantly expressed in cancer tissues.

Diverticulum of the buccal mucosa: a rare case report and review of the literature.

Background: Cases of diverticula of the buccal mucosa are extremely rare. Literature searches of databases such as PubMed/MEDLINE for this condition have revealed only 10 case reports. In this case report, we describe our experience in the management of this rare condition and review the previous 10 previously reported cases.

Tumor budding is an independent prognostic marker in early stage oral squamous cell carcinoma: With special reference to the mode of invasion and worst pattern of invasion.

Pathologically proven regional lymph node metastasis affects the prognosis in early stage oral cancer. Therefore we investigated invasive tumor patterns predicting nodal involvement and survival in patients with clinically node-negative T1 and T2 oral squamous cell carcinoma (cT1,2N0M0 OSCC). Ninety-one cases of cT1,2N0M0 OSCC treated with transoral resection of the primary tumor were assessed based on 3 types of invasive tumor patterns on histopathologic and pancytokeratin-stained immunohistological sections: the mode of invasion, worst pattern of invasion (WPOI), and tumor budding.

KPR-2579, a novel TRPM8 antagonist, inhibits acetic acid-induced bladder afferent hyperactivity in rats.

Aims: Transient receptor potential melastatin 8 (TRPM8) is proposed to be a promising therapeutic target for hypersensitive bladder disorders. We examined the effects of KPR-2579, a novel selective TRPM8 antagonist, on body temperature and on mechanosensitive bladder single-unit afferent activities (SAAs) provoked by intravesical acetic acid (AA) instillation in rats.

Methods: Female Sprague-Dawley rats were used.

Agelamasines A and B, diterpene alkaloids from an Okinawan marine sponge Agelas sp.

Two new diterpene alkaloids having an N-methyladenine moiety, agelamasines A (1) and B (2), were isolated from an Okinawan marine sponge Agelas sp. The structures of 1 and 2 were elucidated on the basis of spectroscopic analyses. Agelamasine A (1) is the first diterpene alkaloid with a rearranged (4 → 2)-abeo-clerodane skeleton from a marine source, while agelamasine B (2) is a clerodane diterpene alkaloid.

Induction and Analysis of Cytotoxic T-Lymphocytes that Recognize Autologous Oral Squamous Cell Carcinoma.

Background: It is essential that cytotoxic T-lymphocytes (CTLs) recognize tumor-associated antigens (TAAs) and exhibit antitumor effects in immunological responses for tumor rejection. However, only a few cases with oral squamous cell carcinoma (OSCC) have been studied for these antitumor mechanisms. We established a cancer cell line and autologous CTL pair for identifying TAAs in OSCC, despite difficulties in establishing such a pair.

New merosesquiterpenes from a Vietnamese marine sponge of Spongia sp. and their biological activities.

The investigation of the Vietnamese marine sponge Spongia sp. led to the isolation of three new sesquiterpene phenols, langconols A-C (1-3), and one new sesquiterpene hydroxyquinone, langcoquinone C (4), together with two known meroterpenoids (5 and 6). Their structures were determined on the basis of spectroscopic analyses and comparisons with published data.

Zamamidine D, a Manzamine Alkaloid from an Okinawan Amphimedon sp. Marine Sponge.

A new manzamine alkaloid, zamamidine D (1), was isolated from an Okinawan Amphimedon sp. marine sponge. The structure of zamamidine D (1) including the relative configuration was elucidated on the basis of spectroscopic data.

Unfolding of the myosin head by purealin in glycerol.

Purealin is a small bioactive compound obtained from the marine sponge. The compound modulates various types of ATPase activity of myosin from skeletal muscle, cardiac muscle, and smooth muscle. To elucidate the structural basis of these effects of purealin on myosin ATPases, we examined the effect of purealin on the conformation of skeletal muscle myosin in aqueous solution and in glycerol.

Synthesis and optimization of novel α-phenylglycinamides as selective TRPM8 antagonists.

Transient receptor potential melastatin 8 (TRPM8) is activated by innocuous cold and chemical substances, and antagonists of this channel have been considered to be effective for pain and urinary diseases. N-(3-aminopropyl)-2-{[(3-methylphenyl)methyl]oxy}-N-(2-thienylmethyl)benzamide hydrochloride (AMTB), a TRPM8 antagonist, was proposed to be effective for overactive bladder and painful bladder syndrome; however, there is a potential risk of low blood pressure. We report herein the synthesis and structure-activity relationships of novel phenylglycine derivatives that led to the identification of KPR-2579 (20l), a TRPM8 selective antagonist.