Relevance of CYP3A5 Expression on the Clinical Outcome of Patients With Renal Cell Carcinoma

Background/Aim: This study aimed to elucidate the detailed characteristics of CYP3A5 expression and the association between CYP3A5 expression and clinical outcomes in patients with renal cell carcinoma (RCC). Patients and Methods: This study retrospectively enrolled 124 Japanese patients with RCC treated at the Okayama University Hospital. The commonest CYP3A5 gene polymorphism, CYP3A5*3, and expression levels of CYP3A5 mRNA and protein in each tissue were examined. Results: Expression of CYP3A5 mRNA and protein in RCC tissues was significantly down-regulated compared to that in adjacent normal tissues. High level of CYP3A5 mRNA expression significantly extended cancer-specific survival (p=0.004) and overall survival (p=0.002). The CYP3A5 mRNA expression level was identified as a significant independent prognostic factor for both cancer-specific survival and overall survival. Conclusion: CYP3A5 could serve as a potential marker for prognostication and treatment planning for patients with RCC

The Downregulation of the Expression of CD147 by Tumor Suppressor REIC/Dkk-3, and Its Implication in Human Prostate Cancer Cell Growth Inhibition

The cluster of differentiation 147 (CD147), also known as EMMPRIN, is a key molecule that promotes cancer progression. We previously developed an adenoviral vector encoding a tumor suppressor REIC/Dkk-3 gene (Ad-REIC) for cancer gene therapy. The therapeutic effects are based on suppressing the growth of cancer cells, but, the underlying molecular mechanism has not been fully clarified. To elucidate this mechanism, we investigated the effects of Ad-REIC on the expression of CD147 in LNCaP prostate cancer cells. Western blotting revealed that the expression of CD147 was significantly suppressed by Ad-REIC. Ad-REIC also suppressed the cell growth of LNCaP cells. Since other researchers have demonstrated that phosphorylated mitogen-activated protein kinases (MAPKs) and c-Myc protein positively regulate the expression of CD147, we investigated the correlation between the CD147 level and the activation of MAPK and c-Myc expression. Unexpectedly, no positive correlation was observed between CD147 and its possible regulators, suggesting that another signaling pathway was involved in the downregulation of CD147. This is the first study to show the downregulation of CD147 by Ad-REIC in prostate cancer cells. At least some of the therapeutic effects of Ad-REIC may be due to the downregulation of the cancer-progression factor, CD147

Oral Clostridium butyricum on mice endometritis through uterine microbiome and metabolic alternations

Endometritis occurs frequently in humans and animals, which can negatively affect fertility and cause preterm parturition syndrome. Orally administered Clostridium butyricum, a butyrate-producing gram-positive anaerobe, exhibits anti-inflammatory effects. However, the precise mechanism by which Clostridium butyricum attenuates endometritis remains unclear. This in vivo study evaluated the anti-inflammatory effects of orally administered Clostridium butyricum on uterine tissues. In addition, we conducted uterine microbiome and lipid metabolome analyses to determine the underlying mechanisms. Female Balb/c mice were divided into the following four groups (n = 5–20): (1) mock group, (2) only operation group (mice only underwent operation to exposed uterine horns from the side), (3) control group (mice underwent the same operation with the operation group + perfusion of lipopolysaccharide solution from uterine horns), and (4) Clostridium butyricum administration group (mice underwent the same operation with the control group + oral Clostridium butyricum administration from days 0 to 9). Clostridium butyricum was administered via oral gavage. On day 10, we investigated protein expression, uterine microbiome, and lipid metabolism in uterine tissues. Consequently, orally administered Clostridium butyricum altered the uterine microbiome and induced proliferation of Lactobacillus and Limosilactobacillus species. The effects can contribute to show the anti-inflammatory effect through the interferon-β upregulation in uterine tissues. Additionally, oral Clostridium butyricum administration resulted in the upregulations of some lipid metabolites, such as ω-3 polyunsaturated fatty acid resolvin D5, in uterine tissues, and resolvin D5 showed anti-inflammatory effects. However, the orally administered Clostridium butyricum induced anti-inflammatory effect was attenuated with the deletion of G protein-coupled receptor 120 and 15-lipooxgenase inhibition. In conclusion, Clostridium butyricum in the gut has anti-inflammatory effects on uterine tissues through alterations in the uterine microbiome and lipid metabolism. This study revealed a gut-uterus axis mechanism and provided insights into the treatment and prophylaxis of endometritis

Assessment of Feeding and Swallowing by Cone Beam Computed Tomography: Changes in Oropharyngeal Airway Shape with Aging

With super aged society in Japan, the death rate from choking due to blockage of the oropharynx has increased; it is now greater than that from traffic accidents and it is believed that this rate will continue to increase. The shape and function of the oropharyngeal crossing with the respiratory tract are most influential in ensuring that food is carried from the oral cavity to the pharynx and the esophagus. We sought to clarify the changes in the shape and features of the oropharyngeal airway from teenagers to those in their 70 s. A total of 57 patients were grouped by age (teenagers, 20s, 30s, 40s, 50s, 60s and 70s), and all underwent cone beam computed tomography (CBCT) to measure the oropharynx volume, height, cross-sectional area, and length of the superior and inferior extremities. Kruskal-Wallis analysis indicated that the volume and height of the oropharynx did no significant difference among age groups, but there was a different tendency when cross-sectional areas of the superior and inferior extremities were compared between younger and older patients. Further, the shape of the inferior extremity was also different features between younger and older patients. In humans, the oropharyngeal airway plays an important role in carrying food through the esophagus and facilitating phonation. Ideally, it is important for this airway to maintain a constant volume and height. Recently, there has been an increase in the incidence of oropharyngeal airway blockage accidents among the elderly. Declines in feeding and swallowing functions and changes in the form of the oropharynx are major factors in these accidents

Novel Benzothiazole Derivatives as Fluorescent Probes for Detection of β‑Amyloid and α‑Synuclein Aggregates

Deposits of β-amyloid (Aβ) and α-synuclein (α-syn) are the hallmark of Alzheimer’s disease (AD) and Parkinson’s disease (PD), respectively. The detection of these protein aggregates with fluorescent probes is particularly of interest for preclinical studies using fluorescence microscopy on human brain tissue. In this study, we newly designed and synthesized three push–pull benzothiazole (PP-BTA) derivatives as fluorescent probes for detection of Aβ and α-syn aggregates. Fluorescence intensity of all PP-BTA derivatives significantly increased upon binding to Aβ(1–42) and α-syn aggregates in solution. In in vitro saturation binding assays, PP-BTA derivatives demonstrated affinity for both Aβ(1–42) (<i>K</i>_d = 40–148 nM) and α-syn (<i>K</i>_d = 48–353 nM) aggregates. In particular, PP-BTA-4 clearly stained senile plaques composed of Aβ aggregates in the AD brain section. Moreover, it also labeled Lewy bodies composed of α-syn aggregates in the PD brain section. These results suggest that PP-BTA-4 may serve as a promising fluorescent probe for the detection of Aβ and α-syn aggregates