Journal of Translational Internal Medicine

Open Access Published by De Gruyter Open Access

Volume 10 Issue 2

June 2022

Issue of Journal of Translational Internal Medicine

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Contents
Journal Overview

Editorial

Open Access March 10, 2022

Research progress on the role of probiotics in acute liver failure

Chen Xue, Qingfei Chu, Lanjuan Li

Page range: 83-85

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Commentary

Open Access June 10, 2022

A bifunctional enzyme of Legionella that distinctly regulates phosphoribosyl ubiquitination of the SidE family effectors

Jun Jiao, Xuan Ouyang, You Xu, Xiaolu Xiong

Page range: 86-88

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Open Access July 2, 2022

The potential role of the brain–gut axis in the development and progression of Alzheimer's disease

Guisheng Zhou, You Yin, Xiaoyu Huan, Yu Zhuang, Shiyu Xu, Jiashuai Liu, Shijia Liu, Jin'ao Duan

Page range: 89-91

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Review Article

Open Access July 10, 2022

Novel insights into alcoholic liver disease: Iron overload, iron sensing and hemolysis

Sebastian Mueller, Cheng Chen, Johannes Mueller, Shijin Wang

Page range: 92-124

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Abstract

The liver is the major target organ of continued alcohol consumption at risk and resulting alcoholic liver disease (ALD) is the most common liver disease worldwide. The underlying molecular mechanisms are still poorly understood despite decades of scientific effort limiting our abilities to identify those individuals who are at risk to develop the disease, to develop appropriate screening strategies and, in addition, to develop targeted therapeutic approaches. ALD is predestined for the newly evolving translational medicine, as conventional clinical and health care structures seem to be constrained to fully appreciate this disease. This concept paper aims at summarizing the 15 years translational experience at the Center of Alcohol Research in Heidelberg, namely based on the long-term prospective and detailed characterization of heavy drinkers with mortality data. In addition, novel experimental findings will be presented. A special focus will be the long-known hepatic iron accumulation, the somewhat overlooked role of the hematopoietic system and novel insights into iron sensing and the role of hepcidin. Our preliminary work indicates that enhanced red blood cell (RBC) turnover is critical for survival in ALD patients. RBC turnover is not primarily due to vitamin deficiency but rather to ethanol toxicity directly targeted to erythrocytes but also to the bone marrow stem cell compartment. These novel insights also help to explain long-known aspects of ALD such as mean corpuscular volume of erythrocytes (MCV) and elevated aspartate transaminase (GOT/AST) levels. This work also aims at identifying future projects, naming unresolved observations, and presenting novel hypothetical concepts still requiring future validation.

Open Access July 2, 2022

Right ventricle remodeling in chronic thromboembolic pulmonary hypertension

Jixiang Liu, Peiran Yang, Han Tian, Kaiyuan Zhen, Colm McCabe, Lan Zhao, Zhenguo Zhai

Page range: 125-133

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Abstract

Chronic thromboembolic pulmonary hypertension (CTEPH) is an underdiagnosed, but potentially curable pulmonary vascular disease. The increased pulmonary vascular resistance in CTEPH is caused by unresolved proximal thrombus and secondary microvasculopathy in the pulmonary vasculature, leading to adaptive and maladaptive remodeling of the right ventricle (RV), eventual right heart failure, and death. Knowledge on the RV remodeling process in CTEPH is limited. The progression to RV failure in CTEPH is a markedly slower process. A detailed understanding of the pathophysiology and underlying mechanisms of RV remodeling may facilitate early diagnosis and the development of targeted therapy. While ultrasound, magnetic resonance imaging, right heart catheterization, and serum biomarkers have been used to assess cardiac function, the current treatment strategies reduce the afterload of the right heart, but are less effective in improving the maladaptive remodeling of the right heart. This review systematically summarizes the current knowledge on adaptive and maladaptive remodeling of the right heart in CTEPH from molecular mechanisms to clinical practice.

Original Article

Open Access July 7, 2022

Prevalence and risk factors of hyperuricemia and gout: a cross-sectional survey from 31 provinces in mainland China

Jing Song, Chenye Jin, Zhongyan Shan, Weiping Teng, Jing Li

Page range: 134-145

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Abstract

Background and Objetives Hyperuricemia (HUA) and gout seriously influence patients’ quality of life. The current study was performed to investigate the prevalence of HUA and gout and the related risk factors in Chinese adults. Methods Data were collected from the National Survey of Thyroid Disorders and Diabetes (the Thyroid Disease, Iodine Status, and Diabetes National Epidemiological survey [TIDE]), a cross-sectional investigation conducted during 2015–2017. Using a random, multistage, and stratified sampling strategy, a representative sample (78,130 participants aged 18 years and above) was selected from the general population in 31 provinces of mainland China. The weighted prevalence rates of HUA and gout were calculated, and the related risk factors were analyzed. Results The weighted prevalence rates of HUA and gout in Chinese adults were 17.7% and 3.2%, respectively. The prevalence of HUA in males linearly decreased with age, while the prevalence in females showed the opposite trend (both P for trend < 0.01). The prevalence rate of gout exhibited a rising tendency with age in both genders (both P for trend < 0.05). The HUA and gout prevalence rates in males were the highest in Han and Tibetan nationalities, respectively. Logistic regression analysis showed that the morbidities of HUA and gout were differentially associated with age, residence location, nationality, smoking, and other complicating metabolic diseases in the two genders. Conclusions There are relatively high prevalence rates of gout and HUA in China, which is currently a developing country. Reducing their burden has become an urgent issue for Chinese people.

Open Access July 2, 2022

Binding domain characterization of growth hormone secretagogue receptor

Yuxiang Sun, Xiangcang Ye, Hilda Kennedy, Alexander G. A. Smith, Roy G. Smith

Page range: 146-155

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Abstract

Background and Objectives Activation of ghrelin receptor growth hormone secretagogue receptor (GHS-R) by endogenous or synthetic ligands amplifies pulsatile release of growth hormone (GH) and enhances food intake, very relevant to development and growth. GHS-R is a G-protein coupled receptor that has great druggable potential. Understanding the precise ligand and receptor interactions is crucial to advance the application of GHS-R. Materials and Methods We used radiolabeled ligand-binding assay and growth hormone release assay to assess the binding and functional characteristics of GHS-R to synthetic agonists MK-0677 and GHS-25, as well as to endogenous peptide ligand ghrelin. We analyzed the ligand-dependent activity of GHS-R by measuring aequorin-based [Ca ++ ] i responses. To define a ligand-binding pocket of GHS-R, we generated a series of human/puffer fish GHS-R chimeras by domain swapping, as well as a series of mutants by site-directed mutagenesis. Results We found that the synthetic ligands have high binding affinity to GHS-R in the in vitro competitive binding assay. Remarkably, the in vivo GH secretagogue activity is higher with the synthetic agonists MK-0677 and GHS-25 than that of ghrelin. Importantly, the activity was completely abolished in GHS-R knockout mice. In GHS-R chimera analysis, we identified the C-terminal region, particularly the transmembrane domain 6 (TM6), to be critical for the ligand-dependent activity. Our site-directed mutagenesis study further revealed that amino acid residues D99 and W276 in GHS-R are essential for ligand binding. Interestingly, critical residues distinctively interact with different ligands, MK-0677 activation depends on E124, while ghrelin and GHS-25 preferentially interact with F279. Conclusion The ligand-binding pocket of human GHS-R is mainly defined by interactive residues in TM6 and the adjacent region of the receptor. This novel finding in GHS-R binding domains advances the structural/ functional understanding of GHS-R, which will help to select/design better GHS-R agonists/ antagonists for future therapeutic applications.

Open Access July 10, 2022

Pan-cancer landscape of the RUNX protein family reveals their potential as carcinogenic biomarkers and the mechanisms underlying their action

Shen Pan, Siyu Sun, Bitian Liu, Yang Hou

Page range: 156-174

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Abstract

Background The RUNX family of transcription factors plays an important regulatory role in tumor development. Although the importance of RUNX in certain cancer types is well known, the pan-cancer landscape remains unclear. Materials and Methods Data from The Cancer Genome Atlas (TCGA) provides a pan-cancer overview of the RUNX genes. Hence, herein, we performed a pan-cancer analysis of abnormal RUNX expression and deciphered the potential regulatory mechanism. Specifically, we used TCGA multi-omics data combined with multiple online tools to analyze transcripts, genetic alterations, DNA methylation, clinical prognoses, miRNA networks, and potential target genes. Results RUNX genes are consistently overexpressed in esophageal, gastric, pancreatic, and pan-renal cancers. The total protein expression of RUNX1 in lung adenocarcinoma, kidney renal clear cell carcinoma (KIRC), and uterine corpus endometrial carcinoma (UCEC) is consistent with the mRNA expression results. Moreover, increased phosphorylation on the T14 and T18 residues of RUNX1 may represent potential pathogenic factors. The RUNX genes are significantly associated with survival in pan-renal cancer, brain lower-grade glioma, and uveal melanoma. Meanwhile, various mutations and posttranscriptional changes, including the RUNX1 D96 mutation in invasive breast carcinoma, the co-occurrence of RUNX gene mutations in UCEC, and methylation changes in the RUNX2 promoter in KIRC, may be associated with cancer development. Finally, analysis of epigenetic regulator co-expression, miRNA networks, and target genes revealed the carcinogenicity, abnormal expression, and direct regulation of RUNX genes. Conclusions We successfully analyzed the pan-cancer abnormal expression and prognostic value of RUNX genes, thereby providing potential biomarkers for various cancers. Further, mutations revealed via genetic alteration analysis may serve as a basis for personalized patient therapies.

Letter to Editor

Open Access June 16, 2022

Extracorporeal membrane oxygenation using a modified cardiopulmonary bypass system

Xuan Song, Hao Wang, Kianoush B. Kashani, Chunting Wang

Page range: 175-177

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Open Access June 28, 2022

A Case of abdominal pain and diarrhea post immunotherapy: Hypophysitis associated with immune checkpoint inhibitors

Akankcha Alok, Kieun Seok, Jacqueline Wesolow

Page range: 178-180

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About this journal

Print ISSN 2450-131X
Online ISSN 2224-4018

Journal of Translational Internal Medicine (JTIM), launched in Dec 2013, is an open access journal publishing articles in all areas of translational internal medicine. The journal focuses on information derived from human disease-related experimentations so as to optimize the communication between basic scientific research and clinical science. It has a cycling nature, namely from basic research to clinical practice and then from clinical practice back to basic research.

Aims and Scope

Journal of Translational Internal Medicine (JTIM) is devoted to promoting science and practice in translational medicine and internal medicine in the world. To this end, JTIM publishes articles from all areas of internal medicine. The journal publishes original articles, rapid communications, editorials, reviews, highlights, perspective and other information closed relevant to translational medicine, internal medicine and related fields. Other types of articles include advanced experience, ideological highlights, and Q&A from scholars and scientists in related fields. JTIM will also launch Special Issues in rapid response to the newest development directions of scientific research fields.

JTIM has the ambition to and will become the EXCELLENT international platform for the publication of outstanding studies from all over the world. JTIM is designed to report research progress and the most recent findings in Translational Internal Medicine field, accelerating successful transformation from basic research results to clinically practical theories，diagnosis and treatment techniques, methodologies and drug discovery. With the aims of health care delivery and policy making, JTIM will help to best balance benefits, qualities and costs of medications. At JTIM, we have a challenging mission: to improve the quality of human life and enable people live longer by facilitating disease prevention, treatment and eventually the CURE.

Journal of Translational Internal Medicine is academically supported by:

International Society of Translational Sciences,
Infectious Diseases Society of China,
Chinese Hypertension Committee of Chinese Medical Doctors Association,
China Alliance of COPD, China RTI Optimal Treatment Committee,
Drug Clinical Assessment Committee of Chinese Pharmaceutical Association.