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Original Article Open Access
Floating Nanoballoons for Improved Bioavailability and Sustained Release Anti-inflammatory Effect of Ibuprofen
Anil K. Philip, Betty Annie Samuel, Bassim A Mohammed, Hayder A Al-Aubaidy
Published online December 25, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00027
Abstract
Poor bioavailability and a short half-life limit the therapeutic efficacy of ibuprofen. This study developed floating nanoballoons to enhance ibuprofen’s bioavailability and sustain [...] Read more.

Poor bioavailability and a short half-life limit the therapeutic efficacy of ibuprofen. This study developed floating nanoballoons to enhance ibuprofen’s bioavailability and sustain its anti-inflammatory effects through improved gastric retention.

Ibuprofen-loaded nanoballoons were synthesized using solvent evaporation with ethyl cellulose as the polymer matrix. The formulation was characterized for morphology, buoyancy, drug loading, and release kinetics. In vivo studies assessed the anti-inflammatory efficacy in acute and chronic inflammation models using male Sprague-Dawley rats.

The nanoballoons exhibited optimal characteristics, including 96% buoyancy and a drug loading efficiency of 96.54 ± 1.32%. Scanning Electron Microscopy revealed a spherical morphology with a porous structure. Drug release followed a biphasic pattern: an initial release of 35.23 ± 2.13% over 2 h, followed by sustained release reaching 97.54 ± 1.30% at 12 h. In acute inflammation studies, the nanoballoon formulation showed superior edema inhibition (68.12%) compared to pure ibuprofen (51.67%). Chronic inflammation studies demonstrated significant improvements in inflammatory markers: reduced TNF-α (19.12 ± 0.48 vs. 31.11 ± 1.23 pg/mL), hs-CRP (201.7 ± 11.02 vs. 232.12 ± 11.33 ng/mL), and IL-6 (100.01 ± 18.40 vs. 135 ± 11.22 pg/mL), with increased anti-inflammatory IL-10 (507.18 ± 10.11 vs. 276.11 ± 19.16 pg/mL).

The developed floating nanoballoon system significantly enhanced ibuprofen’s bioavailability and anti-inflammatory efficacy, presenting a promising gastro-retentive delivery platform for poorly water-soluble drugs.

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Original Article Open Access
Oleanolic Acid Restores Drug Sensitivity in Sorafenib-resistant Hepatocellular Carcinoma: Evidence from In Vitro and In Vivo Studies
Tongtong Li, Xuan Shen, Tao Zhang, Jiaheng Ren, Wang Wang, Didi Wang, Pengxia Zhang
Published online April 18, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00369
Abstract
Hepatocellular carcinoma (HCC) remains challenging to treat in advanced stages, primarily due to the development of resistance to sorafenib. There is an urgent need for novel therapeutic [...] Read more.

Hepatocellular carcinoma (HCC) remains challenging to treat in advanced stages, primarily due to the development of resistance to sorafenib. There is an urgent need for novel therapeutic strategies to overcome this resistance. This study aimed to investigate the potential of oleanolic acid (OA), a natural hepatoprotective compound, in mitigating sorafenib resistance and elucidate its underlying molecular mechanisms.

Sorafenib-resistant Huh7 and HepG2 cell lines were established to mimic the resistant phenotype. The effects of OA on these cells were evaluated by assessing cell invasion, migration, and sensitivity to sorafenib. Gene expression analysis was conducted to identify molecular changes induced by OA treatment, with a focus on fabp3 expression.

Oleanolic acid significantly inhibited the invasive and migratory capabilities of sorafenib-resistant Huh7 and HepG2 cells (p < 0.01). Furthermore, OA treatment downregulated fabp3 expression and restored the cells’ sensitivity to sorafenib.

Oleanolic acid shows promise as an adjunct therapy for overcoming sorafenib resistance in HCC. By reducing cell aggressiveness and restoring drug sensitivity, OA may enhance the therapeutic efficacy of current treatments for advanced HCC.

Full article
Mini Review Open Access
Role of Exosomes in the Progression, Diagnosis, and Therapy Targeting of Malignant Brain Gliomas
Przemysław Panek
Published online December 25, 2024
Oncology Advances. doi:10.14218/OnA.2024.00023
Abstract
Glioblastoma is the most common primary tumor of the central nervous system, characterized by an infiltrative growth pattern, which results in the most unfavorable prognosis. The [...] Read more.

Glioblastoma is the most common primary tumor of the central nervous system, characterized by an infiltrative growth pattern, which results in the most unfavorable prognosis. The average survival time of patients after diagnosis of this tumor is typically several months, with complete recovery from glioma being very rare. In recent years, significant involvement of exosomes in the development of cancer, including malignant brain tumors, has been discovered. Exosomes are extracellular vesicles that carry signaling molecules and participate in communication between cells. They influence cell survival, proliferation, migration, and increased neoangiogenesis, all of which significantly contribute to tumor recurrence. Molecules carried by exosomes are considered potential diagnostic markers, enabling early diagnosis of cancer and prompt implementation of appropriate treatment. Of particular diagnostic importance are microRNA molecules, which promote increased cell proliferation and inhibition of apoptosis. Equally important exosomal transmitters include proteins such as PSMD2 and EGFR, which enhance tumor invasiveness and resistance to chemotherapeutic agents. Recent studies suggest the possibility of using exosomes as carriers for new anticancer drugs, potentially improving the therapeutic treatment of cancers resistant to standard treatment methods. This review aimed to provide a comprehensive analysis of recent research on glioblastoma, the role of exosomes in its progression, the potential of exosomes as diagnostic biomarkers, and their use as therapeutic targets for patients who have not responded to conventional treatments.

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Original Article Open Access
Improved Discrimination and Predictive Ability of Novel Prognostic Scores for Long-term Mortality in Hospitalized Patients with Cirrhosis
Sipu Wang, Gaoyue Guo, Han Wang, Xuqian Zhang, Wanting Yang, Jie Yang, Liping Wu, Chao Sun
Published online March 11, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2025.00004
Abstract
Since the adoption of novel prognostic scores, such as the iterative model for end-stage liver disease (MELD 3.0) and the gender-equity model for liver allocation (GEMA), their [...] Read more.

Since the adoption of novel prognostic scores, such as the iterative model for end-stage liver disease (MELD 3.0) and the gender-equity model for liver allocation (GEMA), their utility has markedly expanded to diverse clinical scenarios. However, data concerning their prognostic value in more generalized cirrhotic populations are scarce. In this study, we aimed to elucidate the MELD 3.0/GEMA-Na for long-term mortality risk stratification and refine their usage scope.

This study retrospectively reviewed 310 hospitalized patients with decompensated cirrhosis. Discrimination and stratification were compared between MELD 3.0/GEMA-Na and other scores. Validation was performed in another 120 subjects.

In the investigated cohort, the median MELD-Na, MELD 3.0, and GEMA-Na were 9 (7, 12), 12 (10, 17), and 12 (9, 17), respectively. Compared to their predecessors, both MELD 3.0 and GEMA-Na models exhibited consistently better discriminative ability, especially in relation to long-term mortality. This effect was more pronounced for GEMA-Na, which was the only score to present an area under the receiver operating characteristic curve greater than 0.8 up to two years (0.807). Statistical analysis indicated that a MELD 3.0 score of 18 and a GEMA-Na score of 20 were the most optimal cutoffs to rank the risk of death, both of which were independently associated with two-year all-cause transplant-free mortality (MELD 3.0: hazard ratio: 1.13, 95% confidence interval: 1.10, 1.17; GEMA-Na: hazard ratio: 1.12, 95% confidence interval: 1.10, 1.17, both P < 0.001). Similar findings were affirmed in the validation cohort.

MELD 3.0 is superior to other MELD-based scores for long-term prognostication in hospitalized patients with cirrhosis, while GEMA-Na demonstrated even better accuracy and performance.

Full article
Original Article Open Access
Use of Traditional Chinese Medicine in Chinese Patients with Cancer Receiving Outpatient Care: Primary Reasons and Communication with Oncologists
Shan Liu, Yiyuan Sun, Jia Liu, Jun He
Published online March 30, 2025
Future Integrative Medicine. doi:10.14218/FIM.2025.00006
Abstract
Traditional Chinese medicine (TCM) is widely used in cancer care in China as an integral part of treatment. This study aimed to understand the motivations of cancer patients in [...] Read more.

Traditional Chinese medicine (TCM) is widely used in cancer care in China as an integral part of treatment. This study aimed to understand the motivations of cancer patients in China for adopting TCM in their treatment and to examine their communication with oncologists. Gaining insights into these factors can enhance culturally sensitive, patient-centered oncology care.

A consecutive sample of 287 outpatients with cancer was recruited. Sociodemographic and clinical data, TCM usage, primary reasons for adopting TCM, and communication about TCM with oncologists were collected. Descriptive statistics, binary logistic regression, and thematic analysis were used to analyze the data.

Patients’ primary reasons for choosing TCM fell into five main categories: (1) belief in the benefits of TCM itself, (2) recommendations from others (family, friends, or oncologists), (3) belief in the benefits of combining TCM with Western medicine (WM), (4) previous positive experiences with TCM, and (5) dissatisfaction with or intolerance to WM. Among the 103 patients who consulted external TCM providers, 65% disclosed this to their oncologists. A longer time since diagnosis was associated with a higher likelihood of disclosure, while employed patients were less likely to inform their oncologists. Oncologists’ responses varied, with 55% neither approving nor disapproving of external TCM prescriptions.

The primary reasons for TCM use were perceived benefits and recommendations from oncologists and family members. However, communication about TCM with oncologists remains inconsistent. Enhancing patient-provider communication through education and fostering the integration of TCM and WM can improve holistic cancer care.

Full article
Case Report Open Access
Therapy-related B-lymphoblastic Leukemia Following Treatment for Multiple Myeloma with Unusual Surface Light Chain Expression: A Case Report
Andrew J. Conoley, Tina E. Ishii, Jiehao Zhou
Published online March 11, 2025
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00046
Abstract
Therapy-related B-lymphoblastic leukemia (B-ALL) following treatment for multiple myeloma is a rare occurrence. Despite its rarity and the lack of recognition by the World Health [...] Read more.

Therapy-related B-lymphoblastic leukemia (B-ALL) following treatment for multiple myeloma is a rare occurrence. Despite its rarity and the lack of recognition by the World Health Organization as a distinct disease entity, previous publications indicate its possible emergence following myeloma treatment.

The patient is a 65-year-old gentleman with a history of IgG kappa multiple myeloma, status post multiple lines of therapy. The patient presented with a fever, and a complete blood count showed cytopenia. Bone marrow morphologic evaluation revealed numerous blasts. Immunophenotypic analysis demonstrated that these blasts were B lymphoblasts, despite MYC and unusual surface kappa light chain expression. A diagnosis of B-ALL with surface kappa light chain expression post-myeloma treatment was made. Ancillary studies indicated that the B-ALL and the previous myeloma were clonally unrelated. Next-generation gene sequencing revealed pathogenic mutations in KDM6A and KRAS.

This case highlights the potential for therapy-related B-ALL following myeloma treatment, a phenomenon deserving further investigation. The expression of surface light chain in blasts can present a diagnostic pitfall.

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Research Letter Open Access
Prevalence of Hepatitis B Core Antibody in Intravenous Immunoglobulin Products by Chemiluminescent Microparticle Immunoassay
Laura Victoria, Anu S. Maharjan, Julia Kostka, Raphael Assenso-Bediako, Wesley Merkert, Lisa Chirch, Kevin Dieckhaus
Published online February 26, 2025
Journal of Clinical and Translational Hepatology. doi:10.14218/JCTH.2024.00464
Original Article Open Access
Dihydroartemisinin Inhibits T Cell Activation in People Living with HIV with Incomplete Immune Reconstitution In Vitro
Yang Zhang, Jiahao Ji, Xiaodong Dou, Rui Wang, Hao Wu, Zhen Li, Tong Zhang
Published online December 25, 2024
Journal of Exploratory Research in Pharmacology. doi:10.14218/JERP.2024.00014
Abstract
Incomplete immune reconstitution is characterized by chronic immune activation and systemic inflammation, which are not fully reversed by antiretroviral therapy. Dihydroartemisinin [...] Read more.

Incomplete immune reconstitution is characterized by chronic immune activation and systemic inflammation, which are not fully reversed by antiretroviral therapy. Dihydroartemisinin (DHA) has demonstrated anti-inflammatory and immunosuppressive properties, which may benefit individuals with incomplete immune reconstitution. This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs). This study aimed to investigate the biological mechanisms underlying incomplete immune reconstitution and evaluate the therapeutic potential of DHA in modulating immune activation in immunological non-responders (INRs).

RNA sequencing data (GSE106792) was retrieved from the Gene Expression Omnibus database. R software and Bioconductor packages were used to identify differentially expressed genes (DEGs) among INRs, immune responders (IRs), and healthy controls (HCs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, along with protein-protein interaction (PPI) network construction, were performed. Potential DHA-binding proteins were predicted using the STITCH server and molecular docking studies. Validation experiments were conducted on peripheral blood mononuclear cells from 18 INRs. Cells were treated with varying concentrations of DHA, and CD4+ and CD8+ T cell activation markers (CD38 and HLA-DR) were measured via flow cytometry.

Enrichment and PPI network analysis identified 119, 56, and 189 DEGs in the INR vs. HC, INR vs. IR, and IR vs. HC comparisons, respectively. Enrichment and PPI analyses showed that DEGs were mainly involved in immune response pathways. DHA was predicted to interact with multiple target proteins, indicating anti-inflammatory effects. In vitro, DHA significantly reduced the frequency of CD38− HLA-DR+ CD4+ T cells and CD38+ HLA-DR+ CD8+ T cells at 1,000 µM and 500 µM compared to the control.

This study provides insights into the biological mechanisms underlying incomplete immune reconstitution and supports DHA’s potential as a therapeutic agent. DHA effectively inhibits T cell activation in INRs, presenting a novel and promising treatment strategy.

Full article
Original Article Open Access
Prognostic Power of the Micropapillary Pattern in Pancreatic Ductal Adenocarcinoma: A Game Changer
Ceren Utku, Deniz Nart, Gurdeniz Serin, Duygu Doga Ekizalioglu, Tufan Gumus, Alper Uguz, Funda Yilmaz
Published online December 25, 2024
Journal of Clinical and Translational Pathology. doi:10.14218/JCTP.2024.00045
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by distinct histological subtypes and a poor prognosis. Among these, the micropapillary pattern, [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy characterized by distinct histological subtypes and a poor prognosis. Among these, the micropapillary pattern, typically observed focally, has been associated with worse outcomes in various cancers. This study aimed to evaluate the prognostic significance of the micropapillary pattern in PDAC, focusing on its percentage within the tumor and its impact on overall survival.

A retrospective analysis was conducted on 71 patients with surgically resected PDAC. Micropapillary patterns were categorized based on their percentage within the tumor (≥20%) and compared to non-micropapillary cases. Demographic, clinical, and histological data, including tumor nodule metastasis stage, tumor grade, peripancreatic fat tissue invasion, and resection margin status, were analyzed. Survival data were assessed using Kaplan-Meier and Cox proportional hazards models. A p-value < 0.05 was considered statistically significant.

The cohort included 28 female and 43 male patients, with a mean age of 63.25 years. Of the 71 cases, 23.9% (n = 17) exhibited a micropapillary pattern. The median overall survival for the micropapillary group was eight months, compared to 18 months for the non-micropapillary group (p = 0.017). Multivariate analysis revealed that the micropapillary group had an increased risk of mortality (hazard ratio = 1.892, p = 0.042), independent of tumor nodule metastasis stage.

Our findings indicate that the micropapillary pattern, even when present in as little as 20% of the tumor, serves as an independent prognostic factor for decreased survival in PDAC. Incorporating the percentage of the micropapillary pattern into pathology reports could provide valuable insights into the tumor’s biological behavior, potentially enhancing patient management strategies.

Full article
Mini Review Open Access
Microscopic Colitis: A Review of the Literature and Histopathologic Mimickers
Alden Miller, Charmi Patel, Jingjing Hu
Published online April 24, 2025
Journal of Translational Gastroenterology. doi:10.14218/JTG.2024.00025
Abstract
Microscopic colitis is a chronic inflammatory disease of the colon that describes patients who present with watery diarrhea, normal or minimal endoscopic findings, and chronic inflammation [...] Read more.

Microscopic colitis is a chronic inflammatory disease of the colon that describes patients who present with watery diarrhea, normal or minimal endoscopic findings, and chronic inflammation identified on colonic biopsy. As the name suggests, microscopic colitis requires histologic evaluation for diagnosis. The two most well-established histologic patterns are collagenous colitis and lymphocytic colitis. In this review, we highlighted the key histologic features of microscopic colitis on biopsy specimens, along with its endoscopic findings, pathogenesis, and underlying molecular mechanisms. We also discussed important mimickers—including amyloidosis, collagenous colitis, ischemic colitis, and radiation colitis—emphasizing their distinguishing histopathologic characteristics. Recognizing these mimickers is crucial, as their treatment strategies are significantly different.

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