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701
Original Article Open Access
Timothy A. Skyring, Judy R. Mullan, Wade Wallace, Sosan Nasir, Kylie J. Mansfield
Published online March 25, 2024
Cancer Screening and Prevention. doi:10.14218/CSP.2023.00029
Abstract
Patients with newly diagnosed prostate cancer (PCA) face the critical decision of whether to undergo treatment with curative intent (TCI, surgery or radiation) or conservative treatment [...] Read more.

Patients with newly diagnosed prostate cancer (PCA) face the critical decision of whether to undergo treatment with curative intent (TCI, surgery or radiation) or conservative treatment on the background of a cancer where the potential for over-treatment and under-treatment is real. This study aimed to investigate the influence of cancer- and patient-related factors on the initial treatment decision for men with a new diagnosis of PCA and to evaluate treatment decisions against relevant guidelines.

This study undertook a retrospective audit of the clinical records of 545 men who were diagnosed with PCA at four Australian urology services. Age, comorbidities, and cancer-related factors were recorded, with patients divided into risk groups based on cancer factors.

Cancer risk stratification emerged as a primary determinant influencing individual treatment choices, with low-risk patients being more likely to have active surveillance and those classified as intermediate or high-risk being more likely to have TCI. Surgery was more commonly offered to younger patients and those with fewer comorbidities. While 80% of patients received guideline-concordant treatment, 20% were identified as being over-treated, receiving TCI despite limited life expectancy and/or high comorbidities.

Managing men diagnosed with PCA should avoid under-treatment in young, otherwise healthy individuals with aggressive cancer by offering TCI. Conversely, over-treatment (unnecessary treatment), especially in men with low-grade cancer or individuals with limited life expectancy due to significant comorbidities, should be avoided to prevent unnecessary treatment when competing causes are more likely to be fatal than prostate cancer.

Full article
702
Review Article Open Access
Xi-Nuo Zhang, Sheng-Qiang Tong, Jiang-Jiang Qin, Xiao-Qing Guan
Published online March 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00007
Abstract
Huaier (Trametes robiniophila Murr) is a traditional Chinese medicine with a clinical application history of over 1,000 years. Its chemical components mainly include polysaccharides, [...] Read more.

Huaier (Trametes robiniophila Murr) is a traditional Chinese medicine with a clinical application history of over 1,000 years. Its chemical components mainly include polysaccharides, sterols, and alkaloids. Huaier has been shown to demonstrate potent antitumor effects in a variety of cancer types, including breast cancer, colorectal cancer, gastric cancer, liver cancer, lung cancer, and others. In recent years, multiple in-vitro experiments have confirmed the good antitumor effect of Huaier and its mechanism of action, such as inhibiting proliferation, inducing apoptosis and oxidative stress, interfering with cell cycle arrest, inhibiting tumor metastasis and angiogenesis, inducing autophagy, and regulating immune function. In addition, multiple in-vivo studies and clinical trials have demonstrated the multidimensional antitumor potential of Huaier, such as slowing tumor progression, reversing drug resistance, improving chemotherapy drug sensitivity, and extending the survival time of cancer patients. In this article, the extraction methods of Huaier and its properties for the treatment of many cancers are reviewed. Moreover, the current molecular mechanisms of Huaier are summarized, revealing that it has great potential as an anticancer drug and providing strong theoretical support for related research. Furthermore, this review also provides suggestions for further research on the anticancer effects of Huaier, hoping to offer fresh perspectives for researchers in the realm of anticancer medicine.

Full article
703
Review Article Open Access
Zahra Shafieizadeh, Zohreh Shafieizadeh, Maryam Davoudi, Reza Afrisham, Xiaolei Miao
Published online March 25, 2024
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2023.00397
Abstract
Partial hepatectomy is a first-line treatment for hepatocellular carcinoma. Within 2 weeks following partial hepatectomy, specific molecular pathways are activated to promote liver [...] Read more.

Partial hepatectomy is a first-line treatment for hepatocellular carcinoma. Within 2 weeks following partial hepatectomy, specific molecular pathways are activated to promote liver regeneration. Nevertheless, residual microtumors may also exploit these pathways to reappear and metastasize. Therapeutically targeting molecules that are differentially regulated between normal cells and malignancies, such as fibrinogen-like protein 1 (FGL1), appears to be an effective approach. The potential functions of FGL1 in both regenerative and malignant cells are discussed within the ambit of this review. While FGL1 is normally elevated in regenerative hepatocytes, it is normally downregulated in malignant cells. Hepatectomy does indeed upregulate FGL1 by increasing the release of transcription factors that promote FGL1, including HNF-1α and STAT3, and inflammatory effectors, such as TGF-β and IL6. This, in turn, stimulates certain proliferative pathways, including EGFR/Src/ERK. Hepatectomy alters the phase transition of highly differentiated hepatocytes from G0 to G1, thereby transforming susceptible cells into cancerous ones. Activation of the PI3K/Akt/mTOR pathway by FGL1 allele loss on chromosome 8, a tumor suppressor area, may also cause hepatocellular carcinoma. Interestingly, FGL1 is specifically expressed in the liver via HNF-1α histone acetylase activity, which triggers lipid metabolic reprogramming in malignancies. FGL1 might also be involved in other carcinogenesis processes such as hypoxia, epithelial-mesenchymal transition, immunosuppression, and sorafenib-mediated drug resistance. This study highlights a research gap in these disciplines and the necessity for additional research on FGL1 function in the described processes.

Full article
704
Case Report Open Access
Taha Khalid, Gavin Calpin, Alina Ahmed, Ala Yousif
Published online March 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00002
Abstract
Cancer treatment has been revolutionized in the last 10 years. Previously, highly toxic chemotherapy regimens that attack both healthy cells and cancer cells as well as induce significant [...] Read more.

Cancer treatment has been revolutionized in the last 10 years. Previously, highly toxic chemotherapy regimens that attack both healthy cells and cancer cells as well as induce significant side effects were used. Nowadays, a more targeted approach is employed. Cancer cells are being treated at the molecular level. Patients with carcinoma of unknown primary who previously only had “broad spectrum” combination therapy as a treatment option can now have their cancer’s genome sequenced with next-generation sequencing in a matter of hours and be offered a more targeted approach. Here, we report a case of a patient with metastatic cancer of an unknown primary origin who was progressing on multiple lines of treatment. Next-generation sequencing showed that the patient had a high tumor mutational burden; therefore, he was able to access immunotherapy through a compassionate access scheme, which resulted in a near complete and sustained clinical and radiological response.

Full article
705
Original Article Open Access
Emmanuel Sánchez, Alba Verdú, Arancha Carbonell, Juan Luis Alcazar
Published online March 25, 2024
Oncology Advances. doi:10.14218/OnA.2023.00034
Abstract
Three-dimensional power Doppler (3DPD) ultrasound has been used for assessing adnexal masses, and in this study, we aimed to perform a meta-analysis to evaluate its role in the [...] Read more.

Three-dimensional power Doppler (3DPD) ultrasound has been used for assessing adnexal masses, and in this study, we aimed to perform a meta-analysis to evaluate its role in the differential diagnosis of adnexal masses.

A search for primary studies assessing the diagnostic performance of 3DPD in discriminating benign from malignant masses carried out between January 1990 and May 2023 was performed in Medline (PubMed), Scopus, and Web of Science databases with study quality evaluated using QUADAS-2.

We identified 404 citations. Ultimately, 18 studies comprising 2,975 women were included, and the mean prevalence of malignant lesions was 37%. In most cases, the quality of studies was moderate. Overall, pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 3DPD vascular tree assessment for studies including any type of mass were 77% (95% confidence interval [CI] = 52%–91%), 80% (95% CI = 37%–97%), 3.9 (95% CI = 0.7–20.9), and 0.29 (95% CI = 0.10–0.81), respectively. Heterogeneity was high for both sensitivity and specificity. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio of 3DPD vascular tree assessment for studies including only “complex” or “suspicious” adnexal masses were 90% (95% CI = 82%–94%), 88% (95% CI = 74%–95%), 7.3 (95% CI = 3.2–16.4), and 0.12 (95% CI = 0.06–0.22), respectively. Heterogeneity was moderate for both sensitivity and specificity. We could not perform quantitative synthesis for studies estimating 3D vascular indexes.

The diagnostic performance of 3DPD for discriminating benign from malignant adnexal masses is good, and there is great heterogeneity in diagnostic criteria when using this technique.

Full article
706
Original Article Open Access
Patrick L. Carolan, Shea M. Lammers, Cynthia M. Anderson, Yoav H. Messinger
Published online March 25, 2024
Oncology Advances. doi:10.14218/OnA.2023.00047
Abstract
Oncology patients undergoing cancer treatment and experiencing episodes of fever are known to be at increased risk for invasive bacterial infection, including bloodstream infection. [...] Read more.

Oncology patients undergoing cancer treatment and experiencing episodes of fever are known to be at increased risk for invasive bacterial infection, including bloodstream infection. This study aimed to identify the incidence of bacteremia along with the bloodstream isolates for immunocompromised oncology patients referred to the emergency department (ED) due to fever.

Oncology patients with fever were referred to the ED according to a protocol previously reported. Virtually all children had central venous access devices (CVAD) that underwent sterile access according to Hematology-Oncology (Hem-Onc) and ED protocol. Antibiotics were administered to all patients once CVAD were accessed and laboratory studies, including blood culture, were obtained. Data collected included patient demographic features, complete blood count profiles, proportions receiving antibiotics within 60 minutes of ED arrival and subsequent blood culture results.

Of 1,088 consecutively referred Hem-Onc patients, 439 were eligible for inclusion. The overall blood culture positive rate was 5.7%. Fifty-six percent of patients with positive blood cultures had an absolute neutrophil count greater than 500 µL at the time of ED presentation. Gram-positive organisms comprised 64% of isolates while gram-negative organisms accounted for 36% of the total isolates.

Immunocompromised oncology patients presenting to the ED with fever are susceptible to bloodstream infection caused by an array of gram-positive and gram-negative organisms. Bloodstream infection during episodes of fever includes many patients without severe neutropenia at presentation and with bloodstream isolates not typically associated with catheter-related bloodstream infection alone, highlighting the diversity and variability within this patient population.

Full article
707
Research Letter Open Access
Yuki Takahashi, Yutaka Shimazu, Keisuke Shindo, Mototaka Fukui, Yusuke Chihara, Takashi Miyoshi, Shinsaku Imashuku
Published online March 25, 2024
Oncology Advances. doi:10.14218/OnA.2023.00046
708
Review Article Open Access
Nilamoni Chelleng, Hage Sonia, Chandan Tamuly
Published online March 25, 2024
Future Integrative Medicine. doi:10.14218/FIM.2023.00082
Abstract
Coptis teeta Wall. (C. teeta) is a herb that goes by the name “Mishmi Tita”, and holds significant value as a medicinal plant for treating various health conditions. This endangered [...] Read more.

Coptis teeta Wall. (C. teeta) is a herb that goes by the name “Mishmi Tita”, and holds significant value as a medicinal plant for treating various health conditions. This endangered plant, listed in the Red Data Book, is commonly found in India, Nepal, Bhutan and China. The present review aims to comprehensively summarize the traditional, pharmaceutical, and phytochemical aspects of C. teeta, providing a foundation for researchers to explore this endangered plant, and take bold steps to conserve, cultivate, and promote awareness among local people. A thorough literature search was conducted on PubMed, Google Scholar, Research Gate, SciFinder, and the ISI Web of Knowledge, using the following terms: “Coptis teeta”, “Coptis teeta Wall.”, “Mishmi tita”, “Rhizoma coptidis”, “Chinese medicine from Coptis teeta”, and “Traditional uses of Coptis teeta”. A comprehensive examination of 69 articles published between 1982 and 2023 was conducted to explore the properties and traditional applications of C. teeta. It was found that this plant and its active compounds exhibit a range of effects, such as fighting against microbes, alleviating diarrhoea, lowering blood pressure, regulating heart rhythm, reducing inflammation, improving mood, treating trachoma, managing diabetes, providing pain relief, and countering reactions. A total of 27 compounds were identified in different parts of this plant, according to the surveyed literature. These have been traditionally utilized to address ailments, including conditions, eye disorders, skin issues, gastrointestinal troubles like constipation and jaundice, and urinary disorders. Furthermore, these have shown potential in cancer treatment and mitigating inflammation. C. teeta boasts diverse traditional uses and promising pharmacological activities due to its rich chemical composition. Berberine is the main constituent, and various communities utilize it for various ailments. While endangered, C. teeta offers exciting medicinal potential, warranting further research and sustainable conservation efforts. Cultivating the plant and raising public awareness are crucial steps towards its preservation.

Full article
709
Review Article Open Access
Joshua M. Germany, Julie Martin
Published online March 23, 2024
Exploratory Research and Hypothesis in Medicine. doi:10.14218/ERHM.2023.00087
Abstract
Prostate cancer (PC) is the second leading cause of death among American men, with most patients receiving androgen deprivation therapy and eventually developing resistance to treatment. [...] Read more.

Prostate cancer (PC) is the second leading cause of death among American men, with most patients receiving androgen deprivation therapy and eventually developing resistance to treatment. The 5-year survival rate from 2015–2020 for men with distant disease was 33%, demonstrating the need for more optimal treatment regimens for patients with distant or metastatic PC. Pharmacogenomic (PGx) testing, a component of precision medicine, focuses on the way a patient’s genome affects drug metabolism. Combining PGx testing with current genetic testing provides an innovative and personalized approach to treating PC while both reducing adverse events and optimizing treatment dosages to fit the patient’s genetic make-up. This review paper describes how clinicians can use PGx testing in combination with genetic testing for PC patients.

Full article
710
Case Report Open Access
Yaxi Wang, Pei Yuan, Weihua Li, Hua Zeng, Jianming Ying
Published online March 23, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2023.00066
Abstract
High-grade endometrial stromal sarcoma (HGESS) is a rare sarcoma with aggressive biological behavior. Here we reported a case of molecularly confirmed ZC3H7B-BCOR HGESS in an extrauterine [...] Read more.

High-grade endometrial stromal sarcoma (HGESS) is a rare sarcoma with aggressive biological behavior. Here we reported a case of molecularly confirmed ZC3H7B-BCOR HGESS in an extrauterine location, with morphologic and immunohistochemical findings resembling a gastrointestinal stromal tumor. The patient, a 51-year-old woman, presented with extensive pelvic and abdominal masses. Histologically, the tumor displayed fascicles of spindle cells with myxoid stroma and abundant mitosis. Immunohistochemical staining revealed that the tumor cells were diffusely positive for cluster of differentiation 117 (CD117) and discovered on gastrointestinal stromal tumor 1 (DOG1). Gastrointestinal stromal tumor was initially diagnosed, and DNA sequencing was performed for targeted therapy. Unexpectedly, no mutations in KIT proto-oncogene, receptor tyrosine kinase (CKIT) or platelet-derived growth factor receptor, alpha polypeptide (PDGFRA) were identified, but amplification of murine double minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) was found. Further, ZC3H7B-BCOR fusion was detected via RNA sequencing. Additional immunostaining showed that CD10 was diffusely positive, the estrogen receptor was negative, and the progesterone receptor was weakly positive. ZC3H7B-BCOR HGESS was definitively diagnosed. In conclusion, the coexpression of CD117 and DOG1 may present a potential diagnostic pitfall in the evaluation of pelvic/abdominal masses, which should be paid great attention to.

Full article
711
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
712
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.

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713
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.

Full article
714
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
715
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.

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716
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
717
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.

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718
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
719
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
720
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.

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