Oral biosciences: The annual review 2021

BackgroundThe Journal of Oral Biosciences is devoted to advancing and disseminating fundamental knowledge concerning every aspect of oral biosciences.HighlightThis review features review articles in the fields of “Extracellular Vesicles,” “Propolis,” “Odontogenic Tumors,” “Periodontitis,” “Periodontium,” “Flavonoids,” “Lactoferrin,” “Dental Plaque,” “Anatomy,” “Induced Pluripotent Stem Cells,” “Bone Cell Biology,” “Dysgeusia,” “Dental Caries,” and “Dental Pulp Cavity,” in addition to the review article by the winners of the “Lion Award” (“Sox9 function in salivary gland development”) presented by the Japanese Association for Oral Biology.ConclusionThese reviews in the Journal of Oral Biosciences have inspired its readers to broaden their knowledge regarding various aspects of oral biosciences. The current editorial review introduces these exciting review articles.     

Fluoxetine-induced hepatic lipid accumulation is mediated by prostaglandin endoperoxide synthase 1 and is linked to elevated 15-deoxy-Δ12,14PGJ2

Major depressive disorder and other neuropsychiatric disorders are often managed with long-term use of antidepressant medication. Fluoxetine, an SSRI antidepressant, is widely used as a first-line treatment for neuropsychiatric disorders. However, fluoxetine has also been shown to increase the risk of metabolic diseases such as non-alcoholic fatty liver disease. Fluoxetine has been shown to increase hepatic lipid accumulation in vivo and in vitro. In addition, fluoxetine has been shown to alter the production of prostaglandins which have also been implicated in the development of non-alcoholic fatty liver disease. The goal of this study was to assess the effect of fluoxetine exposure on the prostaglandin biosynthetic pathway and lipid accumulation in a hepatic cell line (H4-II-E-C3 cells). Fluoxetine treatment increased mRNA expression of prostaglandin biosynthetic enzymes (Ptgs1, Ptgs2, and Ptgds), PPAR gamma (Pparg), and PPAR gamma downstream targets involved in fatty acid uptake (Cd36, Fatp2, and Fatp5) as well as production of 15-deoxy-Δ^12,14PGJ₂ a PPAR gamma ligand. The effects of fluoxetine to induce lipid accumulation were attenuated with a PTGS1 specific inhibitor (SC-560), whereas inhibition of PTGS2 had no effect. Moreover, SC-560 attenuated 15-deoxy-Δ^12,14PGJ₂ production and expression of PPAR gamma downstream target genes. Taken together these results suggest that fluoxetine-induced lipid abnormalities appear to be mediated via PTGS1 and its downstream product 15d-PGJ₂ and suggest a novel therapeutic target to prevent some of the adverse effects of fluoxetine treatment.     

Gestational alloimmune liver disease treated with exchange transfusion and intravenous immunoglobulin: A case study

Gestational alloimmune liver disease (GALD) is a materno-fetal alloimmune disorder that targets the fetal liver and often causes neonatal liver failure. GALD most commonly presents as neonatal hemochromatosis (NH), which is a severe neonatal liver injury confirmed by extra-hepatic iron accumulation at various sites. With the discovery of the alloimmune mechanism of GALD, exchange transfusion and intravenous immunoglobulin (IVIG) administration are being used as novel treatments. Here, we present a rare case of an 11-day-old female infant who presented with marked hyperbilirubinemia. Laboratory findings showed significantly elevated direct and indirect bilirubin, high ferritin and alpha fetoprotein levels, high transferrin saturation, and severe coagulopathy. Abdominal magnetic resonance imaging revealed markedly reduced T2 signal intensity in the liver and pancreas compared to the spleen, suggesting iron deposition. The infant was diagnosed with NH and successfully treated with exchange transfusion and four doses of IVIG.     

Mechanism of action of Orthosiphon stamineus against non-alcoholic fatty liver disease: Insights from systems pharmacology and molecular docking approaches

Non-alcoholic fatty liver disease (NAFLD) is one of the most common complications of a metabolic syndrome caused by excessive accumulation of fat in the liver. Orthosiphon stamineus also known as Orthosiphon aristatus is a medicinal plant with possible potential beneficial effects on various metabolic disorders. This study aims to investigate the in vitro inhibitory effects of O. stamineus on hepatic fat accumulation and to further use the computational systems pharmacology approach to identify the pharmacokinetic properties of the bioactive compounds of O. stamineus and to predict their molecular mechanisms against NAFLD. Methods: The effects of an ethanolic extract of O. stamineus leaves on cytotoxicity, fat accumulation and antioxidant activity were assessed using HepG2 cells. The bioactive compounds of O. stamineus were identified using LC/MS and two bioinformatics databases, namely the Traditional Chinese Medicine Integrated Database (TCMID) and the Bioinformatics Analysis Tool for the Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM). Pathway enrichment analysis was performed on the predicted targets of the bioactive compounds to provide a systematic overview of the molecular mechanism of action, while molecular docking was used to validate the predicted targets. Results: A total of 27 bioactive compounds corresponding to 50 potential NAFLD-related targets were identified. O. stamineus exerts its anti-NAFLD effects by modulating a variety of cellular processes, including oxidative stress, mitochondrial β-oxidation, inflammatory signalling pathways, insulin signalling, and fatty acid homeostasis pathways. O. stamineus is significantly targeting many oxidative stress regulators, including JNK, mammalian target of rapamycin (mTOR), NFKB1, PPAR, and AKT1. Molecular docking analysis confirmed the expected high affinity for the potential targets, while the in vitro assay indicates the ability of O. stamineus to inhibit hepatic fat accumulation. Conclusion: Using the computational systems pharmacology approach, the potentially beneficial effect of O. stamineus in NAFLD was indicated through the combination of multiple compounds, multiple targets, and multicellular components.     

Protective activities of ellagic acid and urolithins against kidney toxicity of environmental pollutants: A review

Oxidative stress and inflammation are two possible mechanisms related to nephrotoxicity caused by environmental pollutants. Ellagic acid, a powerful antioxidant phytochemical, may have great relevance in mitigating pollutant-induced nephrotoxicity and preventing the progression of kidney disease. This review discusses the latest findings on the protective effects of ellagic acid, its metabolic derivatives, the urolithins, against kidney toxicity caused by heavy metals, pesticides, mycotoxins, and organic air pollutants. We describe the chelating, antioxidant, anti-inflammatory, antifibrotic, antiautophagic, and antiapoptotic properties of ellagic acid to attenuate nephrotoxicity. Furthermore, we present the molecular targets and signaling pathways that are regulated by these antioxidants, and suggest some others that should be explored. Nevertheless, the number of reports is still limited to establish the efficacy of ellagic acid against kidney damage induced by environmental pollutants. Therefore, additional preclinical studies on this topic are required, as well as the development of well-designed clinical trials.     

肾周脂肪梅奥粘连概率评分系统在肾癌后腹腔镜肾部分切除术中的应用

目的探讨肾周脂肪梅奥粘连概率评分系统（MAP）在肾癌后腹腔镜肾部分切除术中的临床应用价值。 方法回顾性分析2015年1月至2020年6月徐州医科大学附属淮安医院泌尿外科收治的行后腹腔镜肾部分切除术的153例肾癌患者的临床病例资料。依据MAP评分系统将其分为低度复杂组、中度复杂组和高度复杂组三组。比较各组间的手术时间、术中出血量、术中及术后并发症、术中热缺血时间、术后住院时间及术后血肌酐变化情况。 结果在153例患者中，低度复杂组68例，中度复杂组58例和高度复杂组27例。三组患者在年龄、性别、术前血肌酐水平、肿瘤最大径、肿瘤位置、BMI、RENAL评分等方面差异无统计学意义（P>0.05）。随着复杂程度的提高，手术时间、术中出血量也在不断增加（P<0.05）；而术中热缺血时间、术后住院时间及术后血肌酐水平无明显变化（P>0.05）。在术中并发症方面，随着复杂程度的提高，术中并发症的发生率也在增加（P<0.05），且高度复杂组的术后并发症发生风险是低度复杂组的13.895倍（P=0.002)，MAP评分系统预测术中并发症发生的精度较高（AUC=0.757，P=0.002）。但是术后并发症各组比较差异无统计学意义（P>0.05）。 结论MAP评分系统在肾癌后腹腔镜肾部分切除术中，对预估手术难度及术中并发症发生风险有较好的临床应用价值。