Microsatellite-stable colorectal cancer, which accounts for roughly 80–85% of cases, remains largely refractory to immune checkpoint inhibitors compared with microsatellite instability-high tumors. This review synthesizes current evidence on tumor-intrinsic and microenvironmental mechanisms underlying immune checkpoint inhibitor resistance in microsatellite-stable colorectal cancer—including low neoantigen burden and impaired antigen presentation, activation of Wnt/β-catenin and MAPK signaling that exclude T cells, an immunosuppressive cellular milieu (regulatory T cells, myeloid-derived suppressor cells, M2-like tumor-associated macrophages, cancer-associated fibroblasts), metabolic reprogramming, and gut microbiome dysbiosis—and evaluates translational strategies aimed at overcoming these barriers. Preclinical and early-phase clinical data indicate that rational, mechanism-guided combinations (vascular normalization, myeloid reprogramming, metabolic inhibitors, antigen-priming approaches, and microbiome modulation) can enhance immune infiltration and produce benefits in biomarker-defined subgroups. Moving the field forward will require biomarker-driven, adaptive clinical trials with embedded translational endpoints to optimize patient selection and manage toxicity.

Artemisia argyi H. Lév. & Vaniot essential oil (AAEO) holds significant pharmacological potential, but its application is constrained by hepatotoxicity. This study aimed to investigate the feasibility of reducing AAEO’s toxicity through storage and to evaluate changes in chemical composition, toxicity, and bioactivity.

Gas chromatography-mass spectrometry was used to analyze compositional changes during storage. Zebrafish acute toxicity tests and the liver-specific transgenic zebrafish model Tg(fabp10:EGFP) were used to assess toxicity. Antimicrobial, analgesic, and antioxidant assays evaluated variations in bioactivity.

Over the 150-day storage period, gas chromatography-mass spectrometry analysis identified 39 components. Zebrafish acute toxicity tests showed that the LD50 of AAEO stored for 0, 30, 60, 90, 120, and 150 days were 0.10 µL·mL−1, 0.10 µL·mL−1, 0.10 µL·mL−1, 0.11 µL·mL−1, 0.13 µL·mL−1, and 0.14 µL·mL−1, respectively, demonstrating a 40% reduction in acute toxicity after 150 days of storage. Using the liver-specific green fluorescent transgenic Tg(fabp10:EGFP) zebrafish model, the inhibition rates of AAEO on hepatic fluorescence intensity were measured at 68.5%, 43.5%, 42.6%, 37.8%, 34.6%, and 31.9% at different time points, confirming reduced hepatotoxicity after storage. Additionally, the antioxidant and analgesic activities of AAEO were significantly enhanced (p < 0.05) after storage, while the antibacterial activity decreased (p < 0.05).

After storage, AAEO significantly reduces hepatotoxicity, with a 40% decrease in acute toxicity after 150 days. Meanwhile, the antioxidant and analgesic activities of AAEO increase, while its antibacterial activity decreases after storage.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is now considered to be among the most prevalent chronic liver diseases worldwide. Its comprehensive management encompasses multiple stages, including risk assessment, early detection, stratified intervention, and long-term follow-up. Among these, improving diagnostic accuracy and optimizing individualized therapeutic strategies remain key challenges in both research and clinical practice. In recent years, artificial intelligence and smart devices have developed rapidly and have gradually been applied in the medical field, offering novel tools and pathways for MASLD risk stratification, non-invasive diagnosis, therapeutic evaluation, and patient self-management. This review summarizes the current applications of artificial intelligence and smart devices in MASLD care, highlights their benefits and limitations, and discusses future directions to support precision diagnosis and treatment strategies.

Regular exercise is fundamental for people with metabolic dysfunction-associated steatotic liver disease (MASLD), yet exercise maintenance is generally poor. This generative co-design process aimed to embed the voices and opinions of people with lived experience of MASLD and their care stakeholders to (i) frame barriers and enablers to exercise maintenance and (ii) highlight priorities for exercise-focused research agendas in MASLD.

A generative co-design framework was applied. Two virtual co-design sessions were undertaken: Session 1 – Framing the issue, where initial discovery was conducted with people with lived experience of MASLD; and Session 2 – Generative design and sharing ideas with lived experience partners and healthcare stakeholders. Sessions were audio-recorded and transcribed, and key determinants and considerations were discerned by two independent researchers.

Lived experience partners (n = 5, 53 ± 16 years, 40% male) ranked five equally important barriers to exercise maintenance: musculoskeletal and pain issues, lack of access to exercise equipment/facilities, cost, competing priorities, and low energy levels, which influenced core positive and negative determinants. Alongside lived experience partners, healthcare stakeholders (hepatologists [n = 3], exercise professionals [n = 3], 67% male) identified three core needs with eight considerations. Some disconnects in priorities were observed. Lived experience partners emphasized affordability, accessibility, and considerations for comorbidities, while healthcare partners advocated for research on natural history, prevention, behavior change, cost-effectiveness, and health system change.

This co-design methodology highlights unique consumer-informed research questions. Exercise interventions and their associated implementation trials will benefit from being co-designed with both people with MASLD and care stakeholders.

Bone marrow metastasis (BMM) from non-hematolymphoid malignancies with resultant cytopenia(s) can mimic primary hematolymphoid disorders. This study aimed to investigate the clinical and pathological characteristics of BMM from non-hematopoietic tumors.

We conducted a retrospective cohort study of patients diagnosed with BMM by non-hematolymphoid malignancies at our institution over the past 10 years. Demographic and clinical characteristics, histopathological findings of bone marrow, types of metastatic tumors, and prognosis were analyzed.

A total of 54 cases were included. The four most common malignancies with BMM, regardless of gender, were prostatic adenocarcinoma (29.6%), breast carcinoma (25.9%), colorectal adenocarcinoma (5.5%), and lung carcinoma (5.5%). The main clinical and laboratory manifestations were anemia (90.7%), reticulocytosis (80.5%), thrombocytopenia (73.9%), bone pain (55.5%), disseminated intravascular coagulation (39.6%), leukoerythroblastosis (35.3%), and leukopenia (24%). The vast majority (96.3%) of metastatic tumors were identified by morphology alone; however, in approximately 2.7% of cases, immunohistochemistry was required due to subtle morphologic features. In 29.6% (16/54) of patients, BMM was identified prior to or concurrently with other metastatic sites. The median time interval between the initial diagnosis of non-hematolymphoid malignancies and BMM was 29 months. Although patients who received anti-tumor treatment after BMM diagnosis showed significantly improved prognosis (P < 0.01), no significant differences were observed between those treated with immunotherapy versus chemotherapy and/or radiotherapy (P = 0.145).

Prostate and breast carcinomas are the most common malignancies associated with BMM, with anemia, reticulocytosis, and thrombocytopenia being the most frequent clinical manifestations. While our data demonstrate that anti-neoplastic treatments, regardless of regimen, significantly improve overall survival after BMM, no significant survival differences were observed when prostate and breast carcinomas were compared with other types of BMM.

In the post-genomic era, long non-coding RNAs (lncRNAs) have emerged as critical regulators in various cancers and hold potential as minimally invasive diagnostic biomarkers. This study aimed to perform microarray analysis of the peripheral blood mononuclear cell (PBMC) transcriptome to evaluate differential lncRNA expression in women with luminal A breast cancer.

A one-color microarray analysis was conducted using SurePrint G3 Human Unrestricted 8×60K arrays and a SureScan Microarray Scanner (Agilent Technologies, USA). The study cohort comprised 16 participants: eight patients diagnosed with luminal A breast cancer and eight healthy controls. Bioinformatic analysis was performed using the “limma” and “tidyverse” packages in the R statistical environment. Functional enrichment analysis was conducted to identify significantly differentially expressed gene clusters. The false discovery rate-adjusted p-value (padj) was applied to ensure methodological rigor. Associations between lncRNAs and disease progression were explored using the LncRNADisease 2.0 database.

Differential expression was observed for long intergenic non-coding (LINC), LOC, and antisense RNA genes. Notably, LINC RNA 974 (LINC00974) exhibited significant differential expression (log fold change > |1.5|, padj < 0.05) after multiple comparison correction. Analysis using the LncRNADisease 2.0 database revealed associations between LINC and antisense RNAs and other oncological disorders.

This study is the first to demonstrate differential lncRNA expression in PBMCs of patients with luminal A breast cancer. Despite the limited sample size, the study demonstrates statistically significant differences between groups, highlighting the potential of PBMC-derived lncRNAs as minimally invasive biomarkers. These findings enhance our understanding of the utility of PBMC-derived lncRNAs as biomarkers for breast cancer.

Terminal ileum intubation is considered the completion step of colonoscopy and is usually performed to assess the ileum. The histological examination of the ileal mucosa, which is acquired during terminal ileum intubation, may allow an accurate diagnosis. However, there is no absolute consensus on when ileoscopy and biopsy should be attempted. As a result, we aimed to evaluate whether terminal ileum intubation and biopsy should be performed routinely.

Systematic searches were performed in the PubMed, EMBASE, and Cochrane Library databases, as well as the Science Citation Index via the Web of Science platform. Reference lists from the identified papers were manually searched. Systematic searches were performed from January 1, 1971, to October 1, 2025. Studies reporting on terminal ileum intubation and biopsy during colonoscopy were included. Case reports, letters, reviews, and animal studies were excluded. The primary outcomes were the diagnostic yield of terminal ileum intubation and the rate of necessitating a change in management. Data were extracted independently by three reviewers.

Thirty-six studies were included. The subtotal diagnostic yield and the rate of necessary change among the selected patients were much greater than those among the unselected patients (5.1% versus 2.5% and 1.5% versus 0.4%, respectively). In addition, the diagnostic yield was found more frequently for inflammatory bowel disease, anemia, abdominal pain, and chronic diarrhea than for the other indications (26.7%, 16.1%, 14.9%, 12.4%, and 3.2%, respectively). The yield of ileal histopathology with a normal endoscopic appearance was low in both unselected and selected patients (3.5% and 2.4%, respectively).

Terminal ileum intubation is recommended as gold standard for completing colonoscopy. Biopsy should be considered in patients with abnormal endoscopic findings or specific high-risk symptoms.

Chimeric antigen receptor (CAR)-T cell therapy faces significant challenges in treating solid tumors, including immune evasion, suppressive tumor microenvironments, and on-target/off-tumor toxicity, which limit its clinical efficacy. Although it has revolutionized treatment for hematological malignancies, these obstacles hinder its broader application in solid tumors. Nanotechnology offers innovative strategies to address these limitations through enhanced delivery, localization, and control. This review summarizes recent advances in nanotechnology-assisted CAR-T cell therapies for gynecologic cancers, with a particular focus on messenger RNA (mRNA)-based delivery systems, lipid nanoparticles, hydrogels, and external activation techniques such as photothermal and acoustogenetic modulation. The integration of nanotechnology, especially mRNA-based delivery systems, holds transformative potential for overcoming these barriers. mRNA enables transient, non-integrating expression of CARs, meaning the genetic modifications are temporary. This improves safety and allows flexible control over treatment intensity, while rational sequence optimization (e.g., codon usage, guanine-cytosine content, secondary structure) enhances mRNA stability and protein translation efficiency. Lipid nanoparticles, the leading delivery platform, can be engineered for cell-type specificity and tissue targeting through modulation of their components and surface functionalization. Recent innovations, including siloxane-modified lipid nanoparticles, injectable hydrogels, and photothermal or acoustogenetic activation strategies, enable precise spatiotemporal control of CAR-T cell function in vivo. In ovarian cancer, preclinical studies targeting nfP2X7 and employing multifunctional nanoparticles have demonstrated synergistic efficacy and tumor-specific delivery. This review highlights how nanotechnology platforms can be integrated with CAR-T cell therapies to enhance safety, precision, and therapeutic outcomes in ovarian cancer.

Amoebiasis, or amoebic dysentery, is a gastrointestinal disorder caused by the parasite Entamoeba histolytica. The disease is endemic in parts of Africa, Asia, North and South America, leading to several deaths annually. Reported adverse effects associated with the current first-line treatment for amoebiasis, coupled with the evolution of resistance to it, call for the need to search for plant-based alternatives. This study systematically reviews medicinal plants with activity against Entamoeba histolytica.

The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to retrieve scholarly literature. The study reviewed 70 articles from 7 popular databases: Google Scholar, PubMed, ScienceDirect, Booksc.org, Emerald, Scopus, and MEDLINE, highlighting several plants with anti-amoebic properties.

The primary parts of the plant used in the treatment of Entamoeba histolytica were the leaves (61%), followed by rhizomes (13%), roots (8%), seeds (8%), stems (4%), and fruits (4%). The families Asteraceae (18%) and Zingiberaceae (18%) contain most plants that are effective against Entamoeba histolytica. These medicinal plants families are rich in phytochemicals such as terpenoids and flavonoids that have anti-entamoeba histolytica activity. Maceration is the most commonly used extraction method.

The results suggest that plants are a promising source of new agents to combat amoebiasis caused by Entamoeba histolytica. The most frequently used plant parts were leaves (61%), and the maceration method was the most common extraction technique due to its simplicity and cost-effectiveness. The majority of studies were limited to in vitro models, with only one plant (Adenophyllum aurantium) tested in vivo. Further research is needed to establish their mechanisms of action, toxicities, and clinical potential.

This review presents the Oncodarwinian Hypothesis, which proposes a new medical paradigm: that of cancer as a potential macro-immunoadaptive response (susceptible to fine-tuning or reprogramming/management via artificial intelligence-based 3D printed p53 superproteins). A traditional hypothesis-generation method was adopted; it entails observing a biophenomenon longitudinally (tumor-precursor out-of-control cell division), formulating and refining targeted research questions, and then, rooted in a prior interdisciplinary theoretical framework, outlining (per deductive reasoning) a testable answer or statement apt to predict outcomes. Two main theoretical findings emerge from this review: the plausibility of a wireless p53 superprotein molecular biochip (3D printed) and cancer cells’ dual-focus immunological nature. It will be necessary to approach the key issue and prognosis of (supposedly meaningless) uncontrolled cell division in a different light. Basically, the same diseasing cancer also constitutes a self-replicating immunoadaptive algorithm that needs to be deciphered. An interdisciplinary quest to unravel its “source code” involves genomic palaeontology and learning the natural selection programming language — for developing (personalized) artificial intelligence-assisted p53 superproteins.