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501
Original Article Open Access
Yu Yang, Yingli Wu, Xujin Gong, Xiaolin Lv, Tingting Zhao, Lei Liu, Yanling Mu, Yanna Liu, Qingqiang Yao
Published online March 20, 2024
Oncology Advances. doi:10.14218/OnA.2023.00009
Abstract
Olaparib is a selective poly (ADP-ribose) polymerase inhibitor. However, its clinical application is hindered by low solubility and undesired pharmacokinetic profiles (e.g., relatively [...] Read more.

Olaparib is a selective poly (ADP-ribose) polymerase inhibitor. However, its clinical application is hindered by low solubility and undesired pharmacokinetic profiles (e.g., relatively short circulation). Therefore, the present study aims to exploit polymeric micelles as a safe solubilizer and nanocarrier of olaparib, in order to improve its solubility and pharmacokinetics.

Poly (ε-caprolactone)-co-poly (benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate), i.e., benzyl-functionalized trimethylene carbonate)-b-poly (ethylene glycol) (P(CL-co-TMC-Bz)-PEG), was synthesized by ring-opening polymerization, and used to prepare the π-π-stacked polymeric micelles for olaparib encapsulation. A series of olaparib-loaded micelles with different polymer concentrations and wt% loadings were prepared using different methods to investigate the effect of formulation variables on the size of polymeric micelles and drug loadings. In addition, the in vitro release of olaparib from the micelles, and the cytotoxicity of micellar olaparib formulations on the SKOV3 tumor cell line were evaluated by UV spectrophotometry and CCK-8 assay, respectively. Finally, the blood circulation kinetics and side effects of the incorporated olaparib in the micelles and free olaparib were investigated in SD rats using ultra-high performance liquid chromatography analysis and H&E staining, respectively.

It was found that P(CL11-co-TMC-Bz5)-PEG micelles served as a safe and excellent solubilizer for olaparib, and that the solubilization capacity was easily tailored by adjusting the polymer concentration. In addition, when loaded in micelles, olaparib exhibited a sustained release behavior in vitro, and obvious cytotoxicity on SKOV3 cells. The in vivo studies revealed that olaparib incorporated in P(CL11-co-TMC-Bz5)-PEG polymeric micelles exhibited prolonged circulation (t1/2 = 2.00 hours), when compared to free olaparib (t1/2 ≤ 0.25 hours), and excellent safety. However, in terms of taking advantage of the EPR effect of the micelle delivery system to achieve the targeted olaparib delivery, the circulation time of olaparib in the micelles remained rather short.

Improvements, such as chemical crosslinking and drug conjugation, are required to improve the retention of olaparib-loaded polymeric micelles in blood circulation, and benefit from the use of micelles as a targeted delivery system.

Full article
502
Review Article Open Access
Qian Zhang, Ju Zhang
Published online March 19, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00077
Abstract
Eurotium cristatum (E. cristatum), commonly known as “golden flower”, is the dominant strain in the microbial fermentation process of Fu brick tea. E. cristatum has favorable biological [...] Read more.

Eurotium cristatum (E. cristatum), commonly known as “golden flower”, is the dominant strain in the microbial fermentation process of Fu brick tea. E. cristatum has favorable biological characteristics, including enzyme production, antimicrobial properties, immune regulation, antitumor properties, fat reduction capabilities, and weight loss benefits. With its probiotic characteristics, E. cristatum can be combined with different varieties of tea substrates to make a variety of fermented teas. More importantly, in the process of tea fermentation, E. cristatum can secrete a variety of extracellular enzymes, including some hydrolytic enzymes and oxidoreductases. They metabolize and transform various chemical components in tea through a series of reactions such as oxidation, degradation, and condensation, which significantly affect the quality of tea. In this review, by summarizing its basic functional characteristics as well as its application in fermented tea, an in-depth analysis of the key problems existing in the fermentation application of E. cristatum is described and some beneficial suggestions are presented in order to provide a rich theoretical basis for the development and utilization of E. cristatum to a greater extent.

Full article
503
Original Article Open Access
Huixin Liu, Xiaoxiao Wang, Lijun Wang, Peng Yin, Feng Liu, Lai Wei, Yu Wang, Maigeng Zhou, Jinlei Qi, Huiying Rao
Published online March 19, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00455
Abstract
China accounts for nearly half of liver cancer deaths globally. A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention [...] Read more.

China accounts for nearly half of liver cancer deaths globally. A better understanding of the current liver cancer mortality will be helpful to establishing priorities for intervention and to decreasing the disease burden of liver cancer. The study aimed to explore and predict the mortality burden of liver cancer in China.

Data were extracted from the Disease Surveillance Point system of the Chinese Center for Disease Control and Prevention from 2008 to 2020. Crude and age-standardized liver cancer mortality rates were reported by sex, urban or rural residence, and region. Trends in liver cancer mortality rates from 2008 to 2020 were estimated as average annual percentage change (AAPC). The changing trend of live cancer mortality in the future is also predicted.

In 2020, the crude mortality of liver cancer was 25.57/100,000, and males and people lived in rural areas had higher age-standardized liver cancer mortality rates than females and people lived in people in urban areas. Crude mortality and age-standardized mortality rates in southwest provinces (Guangxi, Sichuan, Tibet) and in a northeast province (Heilongjiang) were higher than that in other provinces, and age-specific mortality rates increased with age. From 2008 to 2020, liver cancer mortality rates decreased, but people under 50 years of age had a higher AAPC than those over 50 years of age, possibly because of the adoption of hepatitis B virus vaccination in newborns and children. Furthermore, the mortality of liver cancer in 2021–2030 is predicted to have a downward trend.

Liver cancer mortality rates declined in China from 2008 to 2020. Future interventions to control liver cancer mortality need to focus on people of male sex, older age, and living in rural areas or less developed provinces.

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504
Review Article Open Access
Karthik Mathialagan, Madhumitha Rondla, Karthik Muralidharan, Sun-Joo Jang
Published online March 19, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00040
Abstract
Obesity is a global health burden and is closely associated with severe chronic co-morbidities, which remain the leading causes of death. Significant progress has been made in the [...] Read more.

Obesity is a global health burden and is closely associated with severe chronic co-morbidities, which remain the leading causes of death. Significant progress has been made in the treatment of hypertension, diabetes, and hyperlipidemia over the last half-century. However, advancements in the management of obesity have been slow, with some medications exhibiting inadequate efficacy and dangerous side effects. Improved understanding of the gut-brain axis has inspired the pursuit of novel medications aiming to provide sustainable and safe weight loss. Current evidence-based practices for obesity management involve multi-modal approaches, including lifestyle modification, mechanical gastric restriction, modulation in the secretion of multiple gut hormones, alteration in the composition and secretion of bile acids, and alterations of the gut microbiome. Each physician is responsible for recognizing obesity as a disease and assisting patients in appropriate management based on strong evidence and a good safety profile, aligned with the patient’s goals. Through this review, we aim to inform the readers of recent approaches for managing obesity and comparing their beneficial effects and efficacy on obesity and its long-term co-morbidities.

Full article
505
Original Article Open Access
Yasuaki Tatsumi, Motoyoshi Yano, Shinya Wakusawa, Hiroaki Miyajima, Tetsuya Ishikawa, Shinsaku Imashuku, Atsuko Takano, Wataru Nihei, Ayako Kato, Koichi Kato, Hisao Hayashi, Kentaro Yoshioka, Kazuhiko Hayashi
Published online March 19, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00290
Abstract
The clinical introduction of hepcidin25 (Hep25) has led to a more detailed understanding of its relationship with ferroportin (FP) and divalent metal transporter1 in primary iron [...] Read more.

The clinical introduction of hepcidin25 (Hep25) has led to a more detailed understanding of its relationship with ferroportin (FP) and divalent metal transporter1 in primary iron overload syndromes (PIOSs). In 2012, we proposed a classification of PIOSs based on the Hep25/FP system, which consists of prehepatic aceruloplasminemia, hepatic hemochromatosis (HC), and posthepatic FP disease (FP-D). However, in consideration of accumulated evidence on PIOSs, we aimed to renew the classification.

We reviewed the 2012 classification and retrospectively renewed it according to new information on PIOSs.

Iron-loading anemia was included in PIOSs as a prehepatic form because of the newly discovered erythroferrone-induced suppression of Hep25, and the state of traditional FP-D was remodeled as the BIOIRON proposal. The key molecules responsible for prehepatic PIOSs are low transferrin saturation in aceruloplasminemia and increased erythroferrone production by erythroblasts in iron-loading anemia. Hepatic PIOSs comprise four genotypes of HC, in each of which the synthesis of Hep25 is inappropriately reduced in the liver. Hepatic Hep25 synthesis is adequate in posthepatic PIOSs; however, two mutant FP molecules may resist Hep25 differently, resulting in SLC40A1-HC and FP-D, respectively. PIOS phenotypes are diagnosed using laboratory tests, including circulating Hep25, followed by suitable treatments. Direct sequencing of the candidate genes may be outsourced to gene centers when needed. Laboratory kits for the prevalent mutations, such as C282Y, may be the first choice for a genetic analysis of HC in Caucasians.

The revised classification may be useful worldwide.

Full article
506
Review Article Open Access
Smita Nayak, Arya Sondkar, Gayatri Vinchurkar, Shreya Shirsath, Shruti Shintre, Bhaskar Vaidhun
Published online March 18, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00006S
Abstract
Although multiple intricate and drawn-out in vivo investigations and complex in vitro assays are carried out as a part of the routine safety screening of drugs, medication failures [...] Read more.

Although multiple intricate and drawn-out in vivo investigations and complex in vitro assays are carried out as a part of the routine safety screening of drugs, medication failures arising out of safety-related issues continue to be an area of concern for pharmaceutical operations. Some of these failures may be explained by a lack of mathematical models to translate animal data into human data. Moreover, there may be differences in the sensitivity and drug disposition between humans and animals. Microphysiological systems may offer a way to more accurately represent these target tissues and a chance to better evaluate certain facets of human safety. As such, the ability of organs-on-chips to provide information at various development phases in drug discovery has sparked interest in recent years. This cutting-edge technology may aid in shedding light on the functioning of human organs and the pathophysiology of diseases. Also, they can be used to accurately predict the efficacy and safety of experimental medications in humans. Organs-on-chips know-how has been employed to successfully imitate specific nephron components including but not limited to the glomeruli, proximal as well as distal tubules, and collecting duct, all of which can be used in the testing of drugs for genetic kidney disorders. This review includes an overview of this technology along with some of its applications, challenges, and recommendations for the future.

Full article
507
Original Article Open Access
Yamin Ma, Madhurima Kaushal, Louis P. Dehner, John Pfeifer, Mai He
Published online March 18, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00028
Abstract
Malignant rhabdoid tumor (MRT) is an aggressive malignancy driven by pathogenic variants of SMARCB1/INI1 or, rarely, SMARCA4/BRG1. The heterogeneity of MRT suggests that other genomic [...] Read more.

Malignant rhabdoid tumor (MRT) is an aggressive malignancy driven by pathogenic variants of SMARCB1/INI1 or, rarely, SMARCA4/BRG1. The heterogeneity of MRT suggests that other genomic alterations might contribute to tumor behavior. This study aimed to evaluate somatic copy number alterations (SCNAs) and mutation landscapes in MRT before and after treatment.

With IRB approval, five patients underwent normal-tumor paired whole exome sequencing. Subsequently, the results were further analyzed using MuTect v1.1 for variant DNA and cn.mops for SCNA.

Our study revealed recurrent SCNAs harboring genes known to be involved in tumorigenesis. These include 2q37.3 gain (4/5, 80%, programmed death 1, TWIST2), 7q32.1 gain (3/5, 60%), 11q12.2 gain (3/5, 60%), 14q32.3 gain (4/5, 80%), 19p13.2 loss (SMARCA4, 4/5, 80%), 21q22.3 gain (3/5, 60%), and 22q11.1 loss (2/5, 40%, involving SMARCB1). Alterations more common in posttreatment MRTs included 11p15.4 gain (3/3, 100%) and 11q12.2 gain (2/3, 67%). No actionable pathogenic variants were observed. PD-1 immunohistochemistry correlated with 2q37.3 gain.

Our study revealed recurrent SCNAs in MRT. Genes within these regions are known to be associated with the tumor immune response and metastasis. This preliminary study demonstrated the potential value of SCNAs in furthering the understanding of this highly malignant tumor.

Full article
508
Case Report Open Access
Ruddy Dalfeor, Danilo de Oliveira Tavares, Israel Bendit, Luciana Nardinelli, Daniel Goldberg Tabak, Robert Peter Gale
Published online March 18, 2024
Oncology Advances. doi:10.14218/OnA.2023.00040
Abstract
Chronic myeloid leukemia with a BCR::ABL1 b2a3 transcript is difficult to detect by conventional polymerase chain reaction (PCR). This can result in an incorrect diagnosis. We report [...] Read more.

Chronic myeloid leukemia with a BCR::ABL1 b2a3 transcript is difficult to detect by conventional polymerase chain reaction (PCR). This can result in an incorrect diagnosis. We report a man with typical features of chronic myeloid leukemia but with a negative conventional PCR test for BCR::ABL1 in whom we identified a BCR::ABL1 fusion gene by fluorescence in situ hybridization and PCR with custom BCR and ABL1 primers.

Full article
509
Original Article Open Access
Ziyang Zeng, Yuhao Lei, Chunyong Yang, Xianfeng Wu, Liang Zhang, Zhiyong Yang, Lin Chen, Xiaobo Wang, Karine Belguise, Yujie Li, Bin Yi
Published online March 18, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00513
Abstract
Hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease. To date, liver transplantation remains the only [...] Read more.

Hepatopulmonary syndrome (HPS) is characterized by arterial oxygenation defects due to pulmonary vascular dilation in liver disease. To date, liver transplantation remains the only effective treatment for HPS. This study aimed to explore the preventative role of baicalein in HPS development.

Sixty male rats were randomly assigned to three groups: sham, common bile duct ligation (CBDL), and baicalein, receiving intraperitoneal injections of baicalein (40 mg·kg−1·d−1, diluted in saline) for 21 days. Survival rate, liver and kidney function, and bile acid metabolism levels were evaluated. Liver and lung angiogenesis and hepatic glycogen staining were assessed, and the expression of relevant proteins was evaluated by immunohistochemistry.

Baicalein improved survival rates and hypoxemia in rats post-CBDL, reducing angiogenic protein levels and enhancing glucose homeostasis. Compared to the untreated group, baicalein suppressed the expression of vascular endothelial growth factor, placental growth factors, matrix metalloprotease 9 and C-X-C motif chemokine 2, and it increased the expression of glycemic regulatory proteins, including dipeptidyl peptidase-4, sirtuin 1, peroxisome proliferator-activated receptor gamma co-activator 1α, and 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3.

Baicalein significantly improves hepatic function and hypoxia in HPS rats by attenuating pathological angiogenesis in the liver and lungs, showing promise as a treatment for HPS.

Full article
510
Original Article Open Access
Muneer Ahmad, Atif Ali, Hira Khan
Published online March 18, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2023.00012
Abstract
Honey is a viscous, hygroscopic liquid in nature. It has the ability to treat wounds, wrinkles, aging, and inflammation. This study’s objective was to create and characterize a [...] Read more.

Honey is a viscous, hygroscopic liquid in nature. It has the ability to treat wounds, wrinkles, aging, and inflammation. This study’s objective was to create and characterize a nanoemulsion containing honey and evaluate its stability.

A pseudo-ternary phase diagram was retraced with several concentrations of the Smix, water, and liquid paraffin oil to formulate nanoemulsions containing honey. From the results of pre-formulation stability studies, formulation HNE-19, with a hydrophilic lipophilic balance value of 10, and a surfactant and oil ratio of 1:1, was selected as the most stable formulation. HNE-19 and base (B-19) were further subjected to thermodynamic studies of heating and cooling cycles and centrifugation. HNE-19 and its respective base B-19 were characterized for physical changes, droplet size analysis, pH measurements, turbidity, viscosity, and rheological parameters for a period of 90 days.

Results showed that the nanoemulsion containing honey was clear and milky white. There was no evidence of phase separation in HNE-19 and B-19 after the thermodynamic study. The droplet size of fresh HNE-19 was 91.07 nm with a zeta potential of −38.5 mV. After three months, the droplet size and zeta potential were 197.06 nm and −32.5 mV respectively. The observed pH was between 5.8 and 6.7, which corresponds with the pH of the skin. HNE-19 showed non-Newtonian flow and pseudo-plastic behaviour.

Stability and characterization showed that the nanoemulsion containing honey is a remarkable topical delivery formulation and could be evaluated comparatively with conventional topical applications against skin-related diseases like wounds, wrinkles, aging, and inflammations.

Full article
511
Original Article Open Access
Keen Yang, Jieying Zeng, Huaiyu Wu, Huiyu Liu, Zhimin Ding, Weiyu Liang, Linghu Wu, Ziwei Lin, Wenhui Huang, Jinfeng Xu, Fajin Dong
Published online March 18, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00199
Abstract
The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal [...] Read more.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) is 25%. This study aimed to explore differences in the gut microbial community and blood lipids between normal livers and those affected by NAFLD using 16S ribosomal deoxyribonucleic acid sequencing.

Gut microbiome profiles of 40 NAFLD and 20 non-NAFLD controls were analyzed. Information about four blood lipids and 13 other clinical features was collected. Patients were divided into three groups by ultrasound and FibroScan, those with a normal liver, mild FL (FL1), and moderate-to-severe FL (FL2). FL1 and FL2 patients were divided into two groups, those with either hyperlipidemia or non-hyperlipidemia based on their blood lipids. Potential keystone species within the groups were identified using univariate analysis and a specificity–occupancy plot. Significant difference in biochemical parameters ion NAFLD patients and healthy individuals were identified by detrended correspondence analysis and canonical correspondence analysis.

Decreased gut bacterial diversity was found in patients with NAFLD. Firmicutes/Bacteroidetes decreased as NAFLD progressed. Faecalibacterium and Ruminococcus 2 were the most representative fatty-related bacteria. Glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count were selected as the most significant biochemical indexes. Calculation of areas under the curve identified two microbiomes combined with the three biochemical indexes that identified normal liver and FL2 very well but performed poorly in diagnosing FL1.

Faecalibacterium and Ruminococcus 2, combined with glutamate pyruvic transaminase, aspartate aminotransferase, and white blood cell count distinguished NAFLD. We speculate that regulating the health of gut microbiota may release NAFLD, in addition to providing new targets for clinicians to treat NAFLD.

Full article
512
Review Article Open Access
Elham M. Youssef, George Y. Wu
Published online March 18, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00446
Abstract
Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases [...] Read more.

Subnormal levels of liver enzymes, below the lower limit of normal on local laboratory reports, can be useful diagnostically. For instance, subnormal levels of aminotransferases can be observed in vitamin B6 deficiency and chronic kidney disease. Subnormal alkaline phosphatase levels may indicate the presence of hypophosphatasia, Wilson’s disease, deficiencies of divalent ions, or malnutrition. Subnormal levels of gamma glutamyl transferase may be seen in cases of acute intrahepatic cholestasis, the use of certain medications, and in bone disease. Finally, subnormal levels of 5′-nucleotidase have been reported in lead poisoning and nonspherocytic hemolytic anemia. The aim of this review is to bring attention to the fact that subnormal levels of these enzymes should not be ignored as they may indicate pathological conditions and provide a means of early diagnosis.

Full article
513
Illuminating and Instructive Clinical Case Open Access
Jiajun Li, Sile Wan, Fukai Wen, Qingyu Li, Yifeng Cui, Zhaoyang Lu, Han Lin
Published online March 13, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00487
Abstract
Hepatic myelopathy (HM) is a rare neurological complication in the end stage of many liver diseases and is characterized by bilateral spastic paraparesis without sensory and sphincter [...] Read more.

Hepatic myelopathy (HM) is a rare neurological complication in the end stage of many liver diseases and is characterized by bilateral spastic paraparesis without sensory and sphincter dysfunction. It occurs owing to metabolic disorders and central nervous system dysfunction associated with cirrhosis. Without timely and effective clinical intervention, the prognosis of these patients is devastating. Although liver transplantation (LT) is an effective treatment for HM, the prognosis of these patients remains unsatisfactory. Early recognition and diagnosis of this disease are essential for improving patient prognosis. Here, we report a case of hepatitis B virus-associated decompensated cirrhosis with HM. The patient recovered well after LT. We also summarize the clinical characteristics and post-transplant outcomes of 25 patients with HM treated by LT through 2023, including this case.

Full article
514
Systematic Review Open Access
Gabriela Silva Neubern de Oliveira, Cassia Senger, Rodrigo Cardoso de Oliveira
Published online March 11, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00042
Abstract
Medicinal plants have been recognized as a promising alternative treatment against some types of cancer, being rich sources of effective biochemical agents. The aim of this study, [...] Read more.

Medicinal plants have been recognized as a promising alternative treatment against some types of cancer, being rich sources of effective biochemical agents. The aim of this study, therefore, was to gather, through a systematic literature review, articles related to plants from the Brazilian Cerrado biome that have an action on different tumor cells.

Different keywords were used in the search mechanisms of Pubmed, Scielo, Science Direct, Scopus, and Lilacs databases. Of the studies found, titles that did not reflect the purpose of this review, those that did not provide access to the full text, and those that were published before 2005 were excluded. Articles referring to the activity of Cerrado plants in tumor cells published in the last sixteen years were selected, totaling thirty-nine articles. Registration number of this review: #CRD42020205579.

The extracts from the studied plants demonstrated significant antiproliferative effects against several tumor cell lines. 39 species of plants were identified belonging to the families: Combretaceae, Annonaceae, Celastraceae, Verbenaceae, Solanaceae, Myrtaceae, Rubiaceae, Bignoniaceae, Erythroxylaceae, Sapotaceae, Asteraceae, Elaeocarpaceae, Apocynaceae, Anacardiaceae, Calophyllaceae, Lythraceae, Mimosaceae, and Morseraceae. The extracts were obtained from different parts of the plants and different fractions were used.

It can be concluded that the Cerrado contains a wide variety of plants with antitumor actions, and further studies are needed to discover other species with anticancer potential, in addition to in vivo studies.

Full article
515
Review Article Open Access
Darin Dolezal, Ivana Kholová, Guoping Cai
Published online March 11, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00068
Abstract
The World Health Organization Reporting System for lung cytopathology is the first international system that was developed to standardize the reporting of lung cytopathology specimens [...] Read more.

The World Health Organization Reporting System for lung cytopathology is the first international system that was developed to standardize the reporting of lung cytopathology specimens across all settings of cytopathology practice. The system is composed of five diagnostic categories, which apply to all lung cytopathology specimen types. Each category contains cytomorphologic criteria, an estimated risk of malignancy, and clinical management recommendations. International uniformity in the reporting of lung cytopathology will refine the communication between cytopathologists and clinicians and ultimately improve patient care. Furthermore, standardizing the cytomorphologic criteria for each lesion will improve reproducibility among cytopathologists and highlight areas in lung cytopathology that require further research. The system also provides best practice recommendations for the selection of ancillary tests to aid in the diagnosis of each lesion, or group of lesions, keeping in mind that resources will vary across different practice settings. The goal of this review is to summarize the cytomorphologic criteria, potential diagnostic pitfalls, ancillary testing, estimated risk of malignancy, and clinical management recommendations for each diagnostic category.

Full article
516
Original Article Open Access
Colby Adamson, Jourdain Dong, Lauren D. Hagenstein, Joseph Jenkins, Mark Lee, Jing Gao
Published online March 7, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00047
Abstract
Clinical unmet need in managing nonalcoholic fatty liver disease (NAFLD), a common liver disorder affecting 25–30% of American adults is to develop noninvasive and robust biomarkers. We [...] Read more.

Clinical unmet need in managing nonalcoholic fatty liver disease (NAFLD), a common liver disorder affecting 25–30% of American adults is to develop noninvasive and robust biomarkers.

We re-measured liver AC by placing a region of interest (ROI, 3 cm tall and 3 cm wide) at 4.5 cm, 6 cm, and 7.5 cm from the skin and a large ROI (6.0 cm tall and 7.3 cm wide) on pre-recorded ATI images from 117 participants screened for NAFLD. The difference in AC value at variable ROI depths was tested using one-way ANOVA (analysis of variance). Diagnostic performances of AC at variable depths in determining hepatic steatosis were examined by area under receiver operating characteristic curve (AUC) using MRI-proton density fat fraction (MRI-PDFF) as reference and were compared using paired-sample Z-test.

Based on MRI-PDFF, 117 livers were divided to 27 normal livers (MRI-PDFF < 5%) or 90 steatotic livers (MRI-PDFF ≥ 5%). Differences in AUC and AC value at variable depths and size were statistically significant (p < 0.01). The best performance for determining hepatic steatosis was the AC measured at 6 cm from the skin (AUC = 0.92). Sources of errors in performing ATI included reverberation, blank color region, and acoustic shadowing within the measurement ROI.

ROI depth significantly influences liver AC estimation. The best ROI depth to measure liver AC in patients with BMI ≥ 30 may be at a depth of 6 cm from the skin. Technical considerations should be taken in performing liver ATI.

Full article
517
Original Article Open Access
Shi Chen, Benhua Li, Wei Luo, Adeel ur Rehman, Miao He, Qian Yang, Shunyao Wang, Jinjun Guo, Ling Chen, Xiaosong Li
Published online March 6, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00537
Abstract
Hepatitis B virus (HBV) reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy. Paclitaxel (PTX) treatment has been identified [...] Read more.

Hepatitis B virus (HBV) reactivation is commonly observed in individuals with chronic HBV infection undergoing antineoplastic drug therapy. Paclitaxel (PTX) treatment has been identified as a potential trigger for HBV reactivation. This study aimed to uncover the mechanisms of PTX-induced HBV reactivation in vitro and in vivo, which may inform new strategies for HBV antiviral treatment.

The impact of PTX on HBV replication was assessed through various methods including enzyme-linked immunosorbent assay, dual-luciferase reporter assay, quantitative real-time PCR, chromatin immunoprecipitation, and immunohistochemical staining. Transcriptome sequencing and 16S rRNA sequencing were employed to assess alterations in the transcriptome and microbial diversity in PTX-treated HBV transgenic mice.

PTX enhanced the levels of HBV 3.5-kb mRNA, HBV DNA, HBeAg, and HBsAg both in vitro and in vivo. PTX also promoted the activity of the HBV core promoter and transcription factor AP-1. Inhibition of AP-1 gene expression markedly suppressed PTX-induced HBV reactivation. Transcriptome sequencing revealed that PTX activated the immune-related signaling networks such as IL-17, NF-κB, and MAPK signaling pathways, with the pivotal common key molecule being AP-1. The 16S rRNA sequencing revealed that PTX induced dysbiosis of gut microbiota.

PTX-induced HBV reactivation was likely a synergistic outcome of immune suppression and direct stimulation of HBV replication through the enhancement of HBV core promoter activity mediated by the transcription factor AP-1. These findings propose a novel molecular mechanism, underscoring the critical role of AP-1 in PTX-induced HBV reactivation.

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518
Review Article Open Access
Dmitry Victorovich Garbuzenko
Published online March 1, 2024
Journal of Translational Gastroenterology. doi:10.14218/JTG.2023.00071
Abstract
This review summarizes the current investigations that confirm the significance of liver fibrosis (LF) as an independent cardiovascular risk factor in non-alcoholic fatty liver [...] Read more.

This review summarizes the current investigations that confirm the significance of liver fibrosis (LF) as an independent cardiovascular risk factor in non-alcoholic fatty liver disease (NAFLD). PubMed, Google Scholar, Web of Science platform, Reference Citation Analysis, and Cochrane Systematic Reviews were searched for articles published between 2008 and 2023. Relevant articles were identified using the following keywords: “cardiovascular diseases”, “cardiovascular risk factors”, “non-alcoholic fatty liver disease”, “nonalcoholic steatohepatitis”, and “liver fibrosis”. The reference lists of the identified articles were also searched for other relevant publications. The investigations that described LF as a cardiovascular risk factor in NAFLD met the inclusion criteria. NAFLD occupies a leading position among liver diseases worldwide. Cardiovascular disorders are the most significant cause of unfavorable outcomes in NAFLD patients. Currently, the relationship between them is well established. The pathophysiological mechanisms predisposing to the development of cardiovascular disorders in NAFLD include atherogenic dyslipidemia, impaired glucose metabolism and liver insulin resistance, low-grade systemic inflammation, endothelial dysfunction, cardiovascular remodeling, as well as gut dysbiosis, which are influenced by numerous genetic and epigenetic factors. Identification of cardiovascular risk factors in NAFLD is an important public health issue. At present, there is evidence that the presence of advanced LF may be a strong independent predictor and risk factor for cardiovascular disorders in NAFLD. It is obvious that early diagnosis of LF will allow to stratify NAFLD patients by cardiovascular risk groups and thereby determine the most optimal therapeutic interventions.

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519
Original Article Open Access
Yongsheng Tang, Zenan Yuan, Xu Lu, Yingqiu Song, Shuguang Zhu, Chunhui Qiu, Qi zhang, Binsheng Fu, Changchang Jia, Hua Li
Published online February 29, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00339
Abstract
Hepatic ischemia-reperfusion injury (HIRI) is a prevalent complication of liver transplantation, partial hepatectomy, and severe infection, necessitating the development of more [...] Read more.

Hepatic ischemia-reperfusion injury (HIRI) is a prevalent complication of liver transplantation, partial hepatectomy, and severe infection, necessitating the development of more effective clinical strategies. Receptor activity–modifying protein 1 (RAMP1), a member of the G protein–coupled receptor adapter family, has been implicated in numerous physiological and pathological processes. The study aimed to investigate the pathogenesis of RAMP1 in HIRI.

We established a 70% liver ischemia-reperfusion model in RAMP1 knockout (KO) and wild-type mice. Liver and blood samples were collected after 0, 6, and 24 h of hypoxia/reperfusion. Liver histological and serological analyses were performed to evaluate liver damage. We also conducted in-vitro and in-vivo experiments to explore the molecular mechanism underlying RAMP1 function.

Liver injury was exacerbated in RAMP1-KO mice compared with the sham group, as evidenced by increased cell death and elevated serum transaminase and inflammation levels. HIRI was promoted in RAMP1-KO mice via the induction of hepatocyte apoptosis and inhibition of proliferation. The absence of RAMP1 led to increased activation of the extracellular signal–regulated kinase (ERK)/mitogen-activated protein kinase (MAPK) pathway and yes-associated protein (YAP) phosphorylation, ultimately promoting apoptosis. SCH772984, an ERK/MAPK phosphorylation inhibitor, and PY-60, a YAP phosphorylation inhibitor, reduced apoptosis in in-vitro and in-vivo experiments.

Our findings suggest that RAMP1 protects against HIRI by inhibiting ERK and YAP phosphorylation signal transduction, highlighting its potential as a therapeutic target for HIRI and providing a new avenue for intervention.

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Review Article Open Access
Sruthi Suriyakumar, Shalini Sivadasan, Thiruvengadarajan Vasanthi Srinivass, Rajasekaran Aiyalu
Published online February 29, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00026
Abstract
Chronic Obstructive Pulmonary Disease (COPD) is a prevalent and progressive respiratory disorder characterized by persistent airflow limitation, often associated with chronic bronchitis [...] Read more.

Chronic Obstructive Pulmonary Disease (COPD) is a prevalent and progressive respiratory disorder characterized by persistent airflow limitation, often associated with chronic bronchitis and emphysema. This abstract provides a comprehensive overview of COPD, emphasizing its clinical significance and impact on global health. COPD represents a significant public health concern, with escalating prevalence and mortality rates worldwide. Understanding epidemiological trends and risk factors is crucial for effective disease management and prevention strategies. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines serve as a compass in COPD management. It provides a comprehensive overview of the GOLD guidelines, elucidating their role in risk stratification, treatment escalation, and personalized care for individuals across varying disease severities. The management of COPD involves a multidimensional approach targeting symptom relief, improving lung function, and enhancing overall quality of life. Pharmacological interventions, such as bronchodilators and anti-inflammatory agents, play a pivotal role. Beyond conventional pharmacological treatments, various traditional therapies have gained attention in COPD management. These may include complementary and alternative medicine practices, such as acupuncture, herbal supplements, and yoga. While evidence supporting the efficacy of these interventions is still evolving, exploring their potential benefits. A comprehensive and integrative approach is crucial for optimizing COPD care and improving the lives of individuals affected by this intricate respiratory condition. This abstract concludes by encouraging continued collaboration among clinicians and patients to shape the future of COPD care. Ultimately fostering hope for improved outcomes and an enhanced prospect for those living with severe respiratory ailments.

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