Clinical And Experimental Medicine[JOURNAL]
Sun
200 papers
Novel therapeutic targets at the crossroad between epigenetics and signal transduction pathways in B-cell lymphomas.
Uddin Dekha J, Yami A, Quotti Tubi L … +5 more , Haxhiu I, Carrer A, Trentin L, Piazza F, Manni S
Clin Exp Med · 2026 Jun · PMID 42257744 · Publisher ↗
Lymphomas (Hodgkin lymphoma and non-Hodgkin lymphoma) constitute a heterogenous group of malignancies derived from immature and mature lymphoid cells. Despite improvements in therapeutic options in recent years, high rat...
Lymphomas (Hodgkin lymphoma and non-Hodgkin lymphoma) constitute a heterogenous group of malignancies derived from immature and mature lymphoid cells. Despite improvements in therapeutic options in recent years, high rates of recurrence and resistance to current treatments remain a significant and unmet clinical eliminate s from needs. Past and recent studies have identified important molecular signatures playing a role in the pathophysiology of lymphomas, including the B-cell receptor, NF-κB, PI3K/AKT, Wnt/β-catenin cascades, and have pointed to protein kinases, such as BTK, PI3K, CK1α and CK2, as drivers and therefore potential therapeutic targets. It has also been extensively demonstrated that various epigenetic changes, including DNA methylation and histone modifications, play critical roles in sustaining cell survival, proliferation and perturbed differentiation of lymphoma cells. Moreover, the interplay between signal transduction and epigenetic modifications in lymphoma cells may influence the lymphoma-associated tumor microenvironment and immune cell function, shaping the anti-lymphoma immune response. Therefore, the identification of new targets for the therapy of lymphomas requires a comprehensive understanding of how cell signaling and epigenetic modifications interact. This review explores the function of newly recognized kinases in lymphoma pathogenesis, such as CK1, CK2 and others, highlighting their interaction with epigenetic regulation. The therapeutic potential of targeting simultaneously signaling and epigenetic pathways is proposed as a potential innovative strategy in the treatment of lymphomas.
Venetoclax, azacitidine, and chidamide in combination with cytarabine, aclarubicin, and G-CSF as induction chemotherapy for myelodysplasia-related acute myeloid leukemia.
Lv L, Yang J, Liu Q … +7 more , Li Y, Xu L, Li M, Zhang R, Huang S, Jing Y, Dou L
Clin Exp Med · 2026 Jun · PMID 42236629 · Publisher ↗
Myelodysplasia-related acute myeloid leukemia (AML-MR) exhibits poor outcomes with intensive chemotherapy. This retrospective study was conducted to evaluate the clinical efficacy and safety of the Venetoclax, Azacitidin...
Myelodysplasia-related acute myeloid leukemia (AML-MR) exhibits poor outcomes with intensive chemotherapy. This retrospective study was conducted to evaluate the clinical efficacy and safety of the Venetoclax, Azacitidine, and Chidamide in combination with Cytarabine, Aclarubicin, and G-CSF (CACAG-VEN) regimen in AML-MR patients. We included 14-75-year-old AML-MR patients (n = 30) treated with CACAG-VEN between January 1, 2023 and December 31, 2024. And compared this cohort with patients (n = 30) who received the standard "3 + 7" regimen (daunorubicin plus cytarabine) from January 1, 2018 to December 31, 2022. The primary endpoint was the complete remission rate(CR) after one cycle of induction. In this retrospective analysis of 30 patients treated with CACAG-VEN, the median age was 50.5 (range, 23-62) years. The CACAG-VEN achieved a high CR (83.3%, 95% CI, 66.4-92.7) and composite complete response (CRc, 93.1% [95% CI, 78.7-98.8]). The 1-year overall survival (OS) and relapse incidences (CIR) were 90.0% (95% CI: 72.1-96.7) and 18.0% (95% CI: 6.4-34.4), respectively. No significant differences in OS (1-year: 85.7% [non-HSCT] vs. 93.8% [HSCT]) or CIR (1-year: 29.3% [non-HSCT] vs. 7.1% [HSCT]) were observed, regardless of whether patients underwent HSCT. The most frequent grade 1-4 adverse events were febrile neutropenia (73.3%), sepsis (16.7%), and pneumonia (50.0%). The median time to recovery was 16.5 days for platelet counts ≥ 20,000/µL and 20.0 days for absolute neutrophil counts ≥ 1,000 cells/µL after induction therapy. The outcomes in the "3 + 7" group were inferior to those of patients who received the CACAG-VEN regimen (CR: 55.7%, p = 0.003; CRc: 56.4%, p = 0.005; 1-year OS: 73.3%, p = 0.039). The CACAG-VEN regimen is a potential frontline therapy for AML-MR, yielding superior response rates and longer survival durations than the standard "3 + 7" chemotherapy.
Analysis of clinical features of lupus mesenteric vasculitis.
Han J, Li S, Xie P … +2 more , He Y, Li T
Clin Exp Med · 2026 Jun · PMID 42234033 · Publisher ↗
This study aimed to identify the clinical characteristics of systemic lupus erythematosus (SLE) patients with complicated with lupus mesenteric vasculitis (LMV), and to determine the impacts of the first-visit department...
This study aimed to identify the clinical characteristics of systemic lupus erythematosus (SLE) patients with complicated with lupus mesenteric vasculitis (LMV), and to determine the impacts of the first-visit department, the number and duration of digestive system symptoms on disease activity, and imaging features of LMV patients. We expected that our study would keep clinicians across specialties vigilant for SLE-LMV, enabling early diagnosis and prompt treatment, thereby improving prognosis and reducing mortality from this potentially fatal condition. Clinical data of 174 patients with LMV admitted to the First Affiliated Hospital of Zhengzhou University from January 2015 to December 2023 were collected and analyzed. The baseline clinical characteristics and laboratory data were analyzed and compared by the first-admission department: either the Rheumatology Department or other departments. In addition, the impact of the numbers and durations of various digestive system symptoms in these patients, as well as laboratory results, disease activity, and imaging findings, was analyzed. The independent-samples t-test and Mann-Whitney U-test were used to compare differences in continuous variables. In contrast, the Kruskal-Wallis test, chi-square test, or Fisher's exact test was used to compare differences in disease activity-related indicators, imaging features, and treatment regimens. A total of 174 patients with an initial diagnosis of LMV were included in this study. Among these patients, 87 (50.0%) had a prior SLE diagnosis, 76 (43.7%) were first diagnosed in the Rheumatology Department, and 36 (20.7%) and 31 (17.8%) were first diagnosed in the Departments of Gastroenterology and Emergency Medicine, respectively. All patients had mild to severe digestive symptoms, including abdominal pain, diarrhea, nausea, vomiting, and abdominal distension. Multiple digestive symptoms occurred in 151 (86.8%) patients. The patients were divided into two groups based on whether they were first diagnosed in the rheumatology department or other departments. The results showed that patients who were not initially diagnosed in the rheumatology department had longer hospital stays and lower disease activity. The patients were further categorized into groups based on the number and time of various digestive symptoms. Compared with those with fewer flares, the proportions of leukopenia, hypocomplementemia, and abdominal effusion were higher in those with frequent LMV recurrences. The white blood cell (WBC) and neutrophil counts in patients with abdominal pain of less than 7 days were higher than those with abdominal pain of more than 7 days. However, statistical analysis did not reveal significant differences among other inflammatory markers and the indices of disease activity. In terms of imaging features obtained by contrast-enhanced CT, a statistical difference was detected in patients with abdominal pain over 7 days compared to those with less than 7 days with respect to thickening of both small and large bowel walls. Due to atypical clinical manifestations of SLE patients with concomitant LMV, only approximately 50% patients were first diagnosed at the Rheumatology Department, with the rest being first diagnosed in other departments, which resulted in delayed diagnosis and treatments, prolonged hospital stay, and potentially, poor prognosis. Evaluation of the impacts of the number and duration of digestive symptom flares on disease activity and imaging features demonstrated that patients with multiple symptoms had more severe radiological findings. Therefore, clinicians, particularly rheumatologists, should keep vigilant when patients have multiple digestive system symptoms and frequent recurrence, as early diagnosis of LMV with prompt and aggressive treatments may improve the prognosis of these patients.
Analysis of the clinical characteristics of warfarin-associated purple toe syndrome.
Shi C, Zhang S, Chen S … +2 more , Guo R, Wu T
Clin Exp Med · 2026 Jun · PMID 42231033 · Publisher ↗
Purple toe syndrome (PTS) represents a critical yet underrecognized complication of warfarin therapy. To characterize this condition, we conducted a retrospective analysis of all reported warfarin-associated PTS cases th...
Purple toe syndrome (PTS) represents a critical yet underrecognized complication of warfarin therapy. To characterize this condition, we conducted a retrospective analysis of all reported warfarin-associated PTS cases through April 30, 2025, without language restrictions. A total of 26 patients (17 male, 9 female) with a median age of 68 years were identified. Of these, 76.9% had pre-existing atherosclerotic disease and 66.7% showed elevated serum creatinine. Symptom onset occurred within three months of warfarin initiation in 53.9% of cases, with 84.0% exhibiting classic bilateral lower extremity involvement characterized by painful violaceous discoloration. Management strategies included warfarin discontinuation (88.5%), dose reduction (7.7%), renal replacement therapy (15.4%), LDL apheresis (11.5%), surgical or endovascular interventions (7.7%), and transition to alternative anticoagulant therapy. Notably, no cross-reactivity between anticoagulant classes was observed, and warfarin rechallenge was not categorically contraindicated in all cases. Outcomes were favorable in 69.2% of patients (symptom resolution), though 3.8% required amputation and 19.2% died within one year, suggesting this complication carries substantial morbidity despite therapeutic intervention. These finding suggest that warfarin-associated PTS warrants clinical awareness, particularly in elderly patients with pre-existing atherosclerotic disease and renal impairment. Early detection, warfarin cessation, and initiation of alternative anticoagulation appear important to help prevent irreversible outcomes.
Circ-MAP4K3 promotes papillary thyroid cancer progression by sponging miR-758-3p to enhance RRM2 expression.
Dong Y, Dong J, Li J … +4 more , Qi Q, Wei L, Chen Y, Cai X
Clin Exp Med · 2026 Jun · PMID 42231000 · Publisher ↗
Papillary thyroid cancer (PTC) is an endocrine malignancy with a high incidence. PTC metastasizes more frequently in children and teenagers, although survival of these patients is usually considered excellent. Still, res...
Papillary thyroid cancer (PTC) is an endocrine malignancy with a high incidence. PTC metastasizes more frequently in children and teenagers, although survival of these patients is usually considered excellent. Still, research on regulatory mechanisms has significant clinical implications. Circular RNAs (circRNAs) participate in PTC regulation. The present study analyzed the role of circ-MAP4K3 in PTC. High-throughput sequencing was used to determine circRNA expression differences between PTC and paracarcinoma tissues. The expression of circ-MAP4K3 was evaluated using RT-qPCR and FISH. TPC-1 and B-CPAP cell proliferation was analyzed utilizing CCK-8 and EdU, while cell migration was assessed based on Transwell and wound healing assays. The targeting relationship among circ-MAP4K3, miR-758-3p, and RRM2 was elucidated via dual-luciferase reporter assay. A xenograft mouse model was employed to determine the effect of circ-MAP4K3 on tumor formation in vivo. The expression of circ-MAP4K3 was increased in PTC tissues and cell lines compared to the levels in the control groups. Circ-MAP4K3 silencing inhibited PTC cell proliferation and migration and tumor growth both in vivo and in vitro. Bioinformatics analysis confirmed that both miR-758-3p and RRM2 were downstream targets of circ-MAP4K3. Inhibition of miR-758-3p or overexpression of RRM2 rescued the proliferation and migration abilities after circ-MAP4K3 downregulation. RRM2 overexpression also rescued the proliferation and migration abilities after miR-758-3p overexpression. Circ-MAP4K3 promotes PTC progression via the miR-758-3p/RRM2 signaling pathway.
Adipose-derived mesenchymal stem cell-derived extracellular vesicles reduce glycolysis and polarize macrophages toward M2 phenotype in sepsis-associated acute kidney injury via the miR-574-5p/GLUT1 axis.
Zhang J, Li J, Jin X … +1 more , Zhu J
Clin Exp Med · 2026 Jun · PMID 42230784 · Publisher ↗
Extracellular vesicles (EVs) from adipose-derived mesenchymal stem cells (ADSCs) may exert a therapeutic benefit in sepsis-associated organ dysfunction by delivering cargos to target cells. The aims of this study were to...
Extracellular vesicles (EVs) from adipose-derived mesenchymal stem cells (ADSCs) may exert a therapeutic benefit in sepsis-associated organ dysfunction by delivering cargos to target cells. The aims of this study were to explore the therapeutic efficacy and potential mechanism of microRNA (miR)-574-5p delivered by ADSC-EVs in sepsis-associated acute kidney injury (SA-AKI). EVs were isolated from mouse ADSCs and characterized by multilineage differentiation potency, morphology, and surface markers. miR-574-5p expression in ADSC-EVs was analyzed by biochemical testing. Luciferase reporter and RNA pull-down assays were employed to identify the binding relation between miR-574-5p and glucose transporter 1 (GLUT1). Cecal ligation and puncture (CLP)-induced mouse SA-AKI model administered with ADSC-EVs was used to evaluate therapeutic effects on kidney injury. ADSC-EVs were co-cultured with RAW264.7 macrophages to assess effects on inflammation, glycolysis (lactate levels, extracellular acidification rate), and macrophage polarization. ADSC-EVs elevated miR-574-5p expression and polarized macrophages toward M2 phenotype, reducing kidney dysfunction and inflammatory response in CLP mice. In vitro, ADSC-EVs arrested lipopolysaccharide-induced M1 macrophage polarization and induced M2 macrophage polarization by upregulating miR-574-5p expression. Mechanistically, ADSC-EVs transferred miR-574-5p into macrophages, where miR-574-5p targeted GLUT1 and limited its expression. This effect contributed to the inhibition of glycolysis and promotion of M2 macrophage polarization. In vivo studies confirmed these positive effects of ADSC-EVs in SA-AKI via the miR-574-5p/GLUT1 pathway. Altogether, our findings suggest that ADSC-EVs carrying miR-574-5p target GLUT1 to restrain glycolysis and prime M2 macrophage polarization in a SA-AKI model, paving the way for establishing a therapeutic approach for SA-AKI.
Morpho-functional plasticity of tumour-associated macrophages: linking cell shape, ultrastructure, and immune regulation in cancer.
Kizhakkanoodan KS, Inigo VJ, Koulmane Laxminarayana SL … +3 more , Seetharam RN, Guruprasad KP, Guru BR
Clin Exp Med · 2026 May · PMID 42223750 · Publisher ↗
Macrophages are highly adaptable immune cells that play dual roles in the tumor microenvironment (TME), either promoting or restraining tumor progression. Their polarization into M1 and M2 tumor-associated macrophage (TA...
Macrophages are highly adaptable immune cells that play dual roles in the tumor microenvironment (TME), either promoting or restraining tumor progression. Their polarization into M1 and M2 tumor-associated macrophage (TAM) phenotypes is classically defined by molecular and biochemical cues. Recent evidence shows that morphology also significantly influences the macrophage function and behavior. This review highlights the correlation between macrophage shape and function, and how cytoskeletal remodeling, extracellular matrix (ECM) stiffness, and topographical patterning regulate macrophage polarization under in vitro and in vivo conditions. We further discuss the ultrastructural features of distinct phenotypes and their mechanistic links to tumor growth and metastasis. Therapeutic strategies that target morphology through ECM modulation, engineered biomaterials, and nanoparticle platforms are examined alongside modern imaging and machine learning tools that enable precise morphometric analysis. Finally, we address the translational progress and limitations of current 2D versus 3D model systems. Overall, this review emphasizes macrophage morphology as a critical yet underexplored determinant of immune function and tumor dynamics.
Integrated multi-omics analysis: exploring the molecular regulatory mechanisms of HIV infection and identifying the key gene WFDC2.
Yan B, Jiang T, Wu Y … +3 more , Zhu R, Wang S, Sun Y
Clin Exp Med · 2026 Jun · PMID 42223712 · Publisher ↗
Although substantial progress has been made in the treatment of HIV infection, the regulatory mechanisms linking genetic variation, transcriptomic alterations, immune-cell changes, and post-transcriptional control remain...
Although substantial progress has been made in the treatment of HIV infection, the regulatory mechanisms linking genetic variation, transcriptomic alterations, immune-cell changes, and post-transcriptional control remain poorly defined. A systematic multi-omics framework is needed to identify key molecular drivers and candidate biomarkers associated with HIV infection. We performed an integrated multi-omics analysis combining protein quantitative trait locus (cis-pQTL)-based summary-data Mendelian randomization (SMR) for 555 plasma proteins with multiple HIV-related genome-wide association study (GWAS) outcomes, followed by HEIDI testing to exclude linkage. In parallel, we conducted differential expression analyses of mRNA and miRNA from blood of healthy controls (n = 7), individuals with low viral load (n = 14), and individuals with high viral load (n = 16). Weighted gene co-expression network analysis (WGCNA) was used to define co-expression modules, which were overlaid with SMR hits and differentially expressed genes (DEGs) and further embedded into transcription-factor (TF) regulon networks. Plasma WFDC2 levels were quantified by ELISA in untreated HIV-infected, ART-treated, and control cohorts. Immune-cell deconvolution, gene set enrichment, and miRNA-mRNA network modeling were used to characterize the functional context of candidate genes.Lastly, HIV-associated cellular models were constructed, followed by functional validation experiments based on WFDC2 overexpression. Transcriptomic profiling revealed strong concordance between the HVL-CON and LVL-CON contrasts, identifying 803 commonly up-regulated and 1,108 commonly down-regulated genes. Integration of SMR results with DEGs highlighted eight overlapping candidate genes-including WFDC2-whose encoded proteins were supported by both genetic instruments and transcriptional deregulation. These genes were embedded in immune-related co-expression modules and TF regulons. Among them, WFDC2 emerged as a key candidate, showing consistent down-regulation at the mRNA and protein levels, extensive correlations with inferred immune-cell subsets, and co-expressed genes enriched for chromatin remodeling, antiviral defense, RNA processing, and translation. Plasma WFDC2 concentrations were reduced in untreated HIV-infected individuals and partially restored under ART compared with healthy controls. Differentially expressed miRNAs potentially targeting WFDC2 and its co-expressed partners suggested additional post-transcriptional regulation. This multi-omics framework delineates a layered network connecting genetic regulation, transcriptional changes, immune-cell shifts, and miRNA-mediated control in HIV infection. Within this network, WFDC2 stands out as a putative hub integrating immune modulation and RNA metabolic pathways, and may represent a promising biomarker and potential therapeutic targets in HIV.
Exosomal integrin αvβ3 derived from colorectal cancer promotes the liver pre-metastatic niche formation by inducing cancer-associated fibroblasts activation.
Yu J, Xiang J, Yao L … +7 more , Wang S, Liu Y, Chen E, Liu X, Wu J, Wang Y, Zhao L
Clin Exp Med · 2026 May · PMID 42223705 · Publisher ↗
The formation of the liver pre-metastatic niche (PMN) is a critical factor in the development of colorectal cancer liver metastasis (CRLM), so understanding the mechanism of the liver PMN is crucial for the prevention an...
The formation of the liver pre-metastatic niche (PMN) is a critical factor in the development of colorectal cancer liver metastasis (CRLM), so understanding the mechanism of the liver PMN is crucial for the prevention and treatment of CRLM. Hepatic stellate cells (HSCs) can promote CRLM by forming cancer-associated fibroblasts (CAFs), but the mechanism remains unclear. In this study, we found that integrin αvβ3 is associated with CRLM and the poor clinical prognosis. Exosomal integrin αvβ3 derived from CRC can target HSCs via fibronectin to mediate their activation. We further explored the mechanism and found that exosomal integrin αvβ3 activates the MEK-ERK signaling pathway through the vitronectin-Integrin αvβ3-FAK axis, thereby promoting HSCs activation. After HSCs become CAFs, they promote the formation of the PMN through EMT, angiogenesis, and inflammatory factors, thereby promoting CRLM. In summary, this study clarifies that exosomal integrin αvβ3 derived from CRC can promote the formation of liver PMN by mediating HSC activation into CAFs, providing a novel therapeutic strategy for the prevention and treatment of CRLM.
Current advances in immunotherapy for KRAS-Mutant pancreatic cancer.
Li M, Wang X, Li P … +3 more , Gong H, Wu J, Mao Y
Clin Exp Med · 2026 May · PMID 42218726 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive gastrointestinal cancers, with over 90% of cases harboring KRAS gene mutations. These mutations not only serve as key drivers of tumorigenesis but als...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive gastrointestinal cancers, with over 90% of cases harboring KRAS gene mutations. These mutations not only serve as key drivers of tumorigenesis but also reshape the tumor microenvironment (TME), creating a highly immunosuppressive "cold tumor" characterized by immune cell dysfunction, a dense fibrotic stroma, and a unique metabolic state. This immunosuppressive TME contributes to the widespread resistance of PDAC to immune therapies, such as immune checkpoint inhibitors (ICIs). This review systematically elucidates the mechanisms by which KRAS mutations shape the immune-suppressive TME, with a focus on the multimodal combination strategies developed to overcome this resistance. These strategies include combinations of ICIs with chemotherapy, radiotherapy, and targeted therapies (e.g., KRAS G12C/D inhibitors, PARP inhibitors, FAK inhibitors, MEK inhibitors), as well as explorations of novel immunotherapies like CAR-T cell therapy, oncolytic viruses, and T-cell agonists. Additionally, we discuss the potential of innovative localized drug delivery technologies, such as hydrogels, intelligent nanoparticle carriers, and oral spore systems, in enhancing intratumoral drug concentrations while reducing systemic toxicity. Despite the limited efficacy of monotherapy in immune treatment, increasing preclinical and clinical evidence suggests that well-designed combination strategies, by remodeling the TME through multiple targets, hold the promise of converting "cold tumors" into "hot tumors," thereby restoring anti-tumor immune responses. Future breakthroughs in therapy will depend on the use of multi-omic biomarkers, including ctDNA, exosomes, and microbiomes, for precise patient stratification, guiding tailored immune combination therapies, and ultimately improving the survival outcomes of PDAC patients.
Exosomal lncRNAs as molecular switches driving macrophage-tumor co-evolution in breast cancer.
Javadian M, Zeinali T, Rajabi M … +12 more , Mehrasa Z, Boogari M, Ramezani F, Samaeinasab S, Mahmoudi Z, Hakimi H, Sabzehban R, Najafi K, Esmaeili K, Khaksarhaghani Z, Tahmasebi S, Rezaei R
Clin Exp Med · 2026 May · PMID 42218707 · Publisher ↗
Breast cancer progression is increasingly recognized as a dynamic process shaped by reciprocal communication between malignant cells and the tumor microenvironment (TME). Among immune-cell populations, tumor-associated m...
Breast cancer progression is increasingly recognized as a dynamic process shaped by reciprocal communication between malignant cells and the tumor microenvironment (TME). Among immune-cell populations, tumor-associated macrophages (TAMs) are major regulators of immune suppression, metabolic adaptation, angiogenesis, and therapeutic resistance. Emerging evidence indicates that extracellular vesicle (EV)-mediated transfer of long non-coding RNAs (lncRNAs) constitutes an important mechanism underlying tumor-immune communication in breast cancer. In this review, we summarize mechanistically characterized studies examining how exosomal lncRNAs regulate bidirectional signaling between breast cancer cells and macrophages and contribute to tumor progression, immune remodeling, and resistance-associated phenotypes. Tumor-derived exosomal lncRNAs modulate macrophage signaling through pathways associated with signal transducer and activator of transcription 3 (STAT3), transforming growth factor beta (TGF-β), Hippo/Yes-associated protein (YAP), hypoxia-responsive signaling, and autophagy-related remodeling, thereby promoting immunoregulatory and tumor-supportive macrophage phenotypes. Conversely, macrophage-derived exosomal lncRNAs, including hypoxia-inducible factor-1 alpha (HIF-1α)-stabilizing long non-coding RNA (HISLA), reinforce glycolytic adaptation, epithelial-mesenchymal transition, epigenetic remodeling, metastatic plasticity, and resistance to therapy in recipient tumor cells. Exosomal lncRNA signaling additionally influences γδ T cells, endothelial cells, and stromal compartments, supporting broader multicellular regulation within the TME. Collectively, current evidence supports exosomal lncRNAs as biologically important mediators of tumor-immune adaptation in breast cancer. We further discuss the translational potential of circulating exosomal lncRNAs as minimally invasive biomarkers and evaluate therapeutic strategies targeting EV biogenesis, vesicle trafficking, and oncogenic lncRNA cargo molecules. Finally, we highlight current limitations involving EV heterogeneity, lncRNA stoichiometry, and incomplete in vivo validation that remain critical barriers to clinical translation.
B3GNT7 preserves intestinal barrier integrity: a key defense mechanism against acute pancreatitis progression.
Hu J, Fu Y, Huang Z … +8 more , Yin N, Xu B, Huang H, Cui M, Mei Q, Huang C, Zeng Y, Fan J
Clin Exp Med · 2026 May · PMID 42218343 · Publisher ↗
Mucin-2 (MUC2) plays a crucial role in maintaining intestinal homeostasis during acute pancreatitis (AP). We aimed to investigate the role of B3GNT7 (β-1,3-N-acetylglucosamine transferase) in the O-glycosylation of MUC2...
Mucin-2 (MUC2) plays a crucial role in maintaining intestinal homeostasis during acute pancreatitis (AP). We aimed to investigate the role of B3GNT7 (β-1,3-N-acetylglucosamine transferase) in the O-glycosylation of MUC2 in AP. We used two mouse models of AP induced by caerulein/lipopolysaccharide or L-arginine, and observed colonic goblet cells using electron microscopy, noting that Golgi damage was linked to decreased levels of mature MUC2. Golgi stress-associated proteins (reduced GM130 and elevated GOLPH3) were identified using immunofluorescence. Transcriptome analysis revealed the downregulation of B3gnt7, a glycosyltransferase that is highly enriched in the Golgi apparatus of goblet cells in AP mice. B3GNT7 expression was negatively correlated with pancreatic and colonic pathological scores. In patients with AP, intestinal B3GNT7 levels are markedly reduced and correlated with Ranson scores, C-reactive protein levels, and intestinal permeability markers (serum diamine oxidase and D-lactate). Adeno-associated virus (AAV)-mediated knockdown of B3GNT7 reduced O-glycosylated MUC2 levels, exacerbated pancreatic and systemic inflammation, and worsened intestinal permeability and dysbiosis. In vitro, LPS-treated HT-29 cells exhibited Golgi stress (decreased levels of B3GNT7 and O-glycosylated MUC2) that was reversed by L-glutathione (GSH). These findings demonstrate that B3GNT7 downregulation, mediated by Golgi stress, disrupts MUC2 O-glycosylation, exacerbating AP by impairing intestinal homeostasis.
Outcomes of allogeneic hematopoietic stem cell transplantation in patients with blast phase myelofibrosis: molecular signature and intensive chemotherapy matter.
Valsecchi F, Finazzi MC, Salmoiraghi S … +14 more , Pavoni C, Grassi A, Algarotti A, Bellini M, Frigeni M, Condorelli A, Rambaldi B, Rizzuto G, Cavallaro G, Belotti C, Milani M, Spinelli O, Lussana F, Rambaldi A
Clin Exp Med · 2026 May · PMID 42216977 · Publisher ↗
Patients with blast-phase (BP) myeloproliferative neoplasms have dismal outcomes, but allogeneic hematopoietic stem cell transplantation (alloHSCT) may offer a potential cure. However, the optimal pre-transplant blast-re...
Patients with blast-phase (BP) myeloproliferative neoplasms have dismal outcomes, but allogeneic hematopoietic stem cell transplantation (alloHSCT) may offer a potential cure. However, the optimal pre-transplant blast-reduction therapy remains to be determined. We retrospectively analyzed outcomes in a molecularly annotated cohort of 24 patients with BP myelofibrosis (MF) who underwent alloHSCT between 2008 and 2023. Before conditioning, 20 patients received intensive induction chemotherapy, 1 received decitabine plus venetoclax, and 3 proceeded directly to transplant. At transplantation, 13 patients (54%) were in complete remission (CR), defined as bone marrow blast < 5%, or CR with incomplete count recovery (CRi), while 11 (46%) had active disease. The median follow-up was 2.9 years (range 0.02-15.5). The 3-year overall survival (OS) was 62%, progression-free survival (PFS) was 49%, relapse incidence was 38%, and non-relapse mortality was 12%. There was a trend toward better OS and PFS in patients transplanted in CR/CRi compared with those with active disease (OS 68% vs. 55%, HR 0.42, p = 0.16; PFS 61% vs. 36%, HR 0.49, p = 0.21). Mutations in TP53 and EZH2 were associated with significantly inferior PFS (HR 6.28, p = 0.008 for TP53 and HR 3.8, p = 0.04 for EZH2).Compared with a historical cohort of 50 patients transplanted during the same period for chronic-phase MF, outcomes were similar (3-year OS: 62% vs. 58%; p = 0.6181). In conclusion, our results suggest that achieving remission before alloHSCT in BP-MF is associated with favorable outcomes. The adverse impact of TP53 or EZH2 mutations supports early post-transplant strategies to prevent relapse.
The diagnostic and short-term prognostic significance of miR-183-5p in pulmonary embolism and its regulation of disease progression through PDCD4.
Wang S, Wu Q, Xu W … +1 more , Wu Y
Clin Exp Med · 2026 May · PMID 42207293 · Publisher ↗
The incidence of pulmonary thromboembolism (PTE) has increased year on year, with high rates of misdiagnosis and recurrence, as well as significant heterogeneity in prognosis. This study investigated the clinical value o...
The incidence of pulmonary thromboembolism (PTE) has increased year on year, with high rates of misdiagnosis and recurrence, as well as significant heterogeneity in prognosis. This study investigated the clinical value of miR-183-5p in PTE, as well as its mechanism of regulating disease progression through PDCD4. This study enrolled 126 PTE patients and 103 non-PTE patients. Serum miR-183-5p was detected using qPCR, and its diagnostic and prognostic significance were analyzed using ROC and logistic analyses. A PTE cell model was established using 150 µg/mL ox-LDL. The effects of inhibiting only miR-183-5p, and co-inhibiting with PDCD4, on the HPMECs functions, inflammation/oxidative stress, and adhesion molecules were analyzed. Serum miR-183-5p in PTE patients increased gradually with risk stratification. The diagnostic efficacy of miR-183-5p for PTE was superior to that of D-dimer, and combining the two provides even better diagnostic results. miR-183-5p was an independent risk factor for prognosis in PTE patients. In a PTE cell model, inhibiting miR-183-5p restored HPMECs proliferation and suppressed apoptosis and autophagy. It also reduced the inflammatory factors release, alleviated oxidative stress damage and down-regulated the adhesion molecules expression. There was a direct target relationship between miR-183-5p and PDCD4. Co-suppression both miR-183-5p and PDCD4 reversed the hindering effect of inhibiting only miR-183-5p on PTE progression. miR-183-5p is a novel biomarker for the supplementary diagnosis and 30-day short-term prognosis assessment of PTE, and it participates in PTE progression by targeting PDCD4 to regulate vascular endothelial cell function.
Acute myeloid leukemia in HIV-positive patients: biological crossroads and therapeutic Hurdles.
Saadh MJ, Muhammad FA, Albadr RJ … +9 more , Arora V, Ganesan S, Shankhyan A, Sharma A, Rizaev J, Taher WM, Alwan M, Jawad MJ, Al-Nuaimi AMA
Clin Exp Med · 2026 May · PMID 42201404 · Publisher ↗
Acute myeloid leukemia (AML), characterized by aberrant hematopoiesis and aggressive clinical behavior, remains a therapeutic challenge even with advances in targeted therapies and hematopoietic stem cell transplantation...
Acute myeloid leukemia (AML), characterized by aberrant hematopoiesis and aggressive clinical behavior, remains a therapeutic challenge even with advances in targeted therapies and hematopoietic stem cell transplantation. In human immunodeficiency virus (HIV)-infected individuals, leukemogenesis may be accelerated through mechanisms such as chronic inflammation, oxidative stress, and bone marrow microenvironment dysregulation. Conversely, AML-associated immunosuppression can exacerbate HIV pathogenesis, increasing the risk of opportunistic infections and complicating disease management. The overlapping clinical presentations of AML and HIV, including cytopenias and recurrent infections, often obscure diagnosis and complicate treatment decisions. While intensive chemotherapy remains the mainstay of AML treatment, HIV-positive patients face unique challenges, including potential drug-drug interactions and compounded toxicities from concurrent antiretroviral therapy (ART) and chemotherapeutic regimens. This review aims to elucidate the bidirectional relationship between HIV and AML, focusing on relevant epidemiological data, underlying molecular mechanisms, and distinct clinical features. More importantly, it identifies critical knowledge gaps that must be addressed to optimize diagnostic and therapeutic approaches for the high-risk population.
CDK9 and hematologic malignancies: pioneering novel therapeutic approaches.
Raufi H, Zahmatkesh P, Safaei S … +2 more , Bahadori A, Solali S
Clin Exp Med · 2026 May · PMID 42201387 · Publisher ↗
cyclin-dependent kinase 9 (CDK9) A key regulator of transcriptional elongation influences the transcription of oncogenes and anti-apoptotic proteins. Within the context of the positive transcription elongation factor b (...
cyclin-dependent kinase 9 (CDK9) A key regulator of transcriptional elongation influences the transcription of oncogenes and anti-apoptotic proteins. Within the context of the positive transcription elongation factor b (P-TEFb) complex, CDK9 facilitates the phosphorylation of the C-terminal domain of RNA polymerase II. It also contributes to epigenetic regulation by phosphorylating histones and altering chromatin accessibility, thereby sustaining the transcription of oncogenic programs. This mechanism initiates the transcription of genes that are crucial for the proliferation and survival of cancer cells. A variety of hematological malignancies, including acute myeloid leukemia (AML), multiple myeloma (MM), and diffuse large B-cell lymphoma (DLBCL), have been associated with dysregulated CDK9 activity, which sustains oncogene expression and contributes to resistance to treatment. A notable therapeutic approach focuses on the inhibition of CDK9. This method may function as a therapeutic strategy that exploits the transcriptional addiction of malignant cells to short-lived oncogenic transcripts. By targeting a central regulator of transcriptional elongation, this approach selectively disrupts the sustained expression of survival-critical proteins such as MCL-1 and MYC, thereby exposing a therapeutic vulnerability in hematologic malignancies. Promising outcomes in preclinical and early clinical studies have been achieved by developing selective and pharmacokinetically more effective CDK9 inhibitors. Candidates for the combination of conventional chemotherapeutic drugs with other targeted therapy modalities. Research findings indicate that innovative CDK9 inhibitors and the silencing of CDK9 through siRNA may drastically change the therapeutic approach to hematological malignancies, particularly for patients facing recurrence or resistance to prior treatments. This review focuses primarily on hematologic malignancies because they exhibit pronounced transcriptional addiction to short-lived super-enhancer-driven transcripts (MYC, MCL-1), making CDK9 inhibition particularly effective. In contrast, solid tumors often display greater microenvironmental heterogeneity and compensatory pathways that limit single-agent efficacy.
Integrative analysis and experimental validation of dioxin-interacting genes reveal diagnostic and prognostic biomarkers in lung adenocarcinoma.
Yin G, Li B, Fan S … +8 more , Wang Z, Jiang Q, He F, Cao H, Liang Y, Luo Y, Jiang F, Fan X
Clin Exp Med · 2026 May · PMID 42189270 · Publisher ↗
Dioxins are persistent environmental pollutants and key components of the human exposome with established carcinogenic potential. As airborne toxicants, they link environmental pollution to lung adenocarcinoma (LUAD), ye...
Dioxins are persistent environmental pollutants and key components of the human exposome with established carcinogenic potential. As airborne toxicants, they link environmental pollution to lung adenocarcinoma (LUAD), yet their molecular mechanisms remain unclear. Dioxin-interacting genes were curated from toxicogenomic databases and intersected with LUAD differentially expressed genes to identify dioxin-related molecular signatures. Consensus clustering was performed to define LUAD subtypes with distinct clinical and transcriptomic characteristics. Weighted gene co-expression network analysis (WGCNA) was applied to identify key gene modules associated with dioxin exposure and tumor progression. Hub genes were further integrated into diagnostic and prognostic models using multiple machine-learning algorithms based on both tumor tissue and peripheral blood transcriptomic datasets. Genome-exposome interactions were explored through pathway enrichment and chemical-gene interaction analyses. Single-cell RNA sequencing data were used to characterize cell-type-specific expression patterns. In vitro functional assays were conducted to validate the biological roles of candidate genes. Both models demonstrated robust predictive performance across cohorts. SLC15A2 was consistently identified as a hub gene and showed predominant expression in lung epithelial cells based on single-cell RNA sequencing. Pan-cancer analyses revealed significant dysregulation of SLC15A2, with lower expression in LUAD associated with poorer survival. Functional experiments confirmed that SLC15A2 overexpression suppressed LUAD cell proliferation and invasion, supporting a tumor-suppressive role. This integrative exposome-genome analysis highlights dioxin-related transcriptomic dysregulation in LUAD and identifies SLC15A2 as a potential tumor suppressor and biomarker for precision stratification.
A review of deep learning-based multimodal data integration of lung cancer.
Qin Y, Wang S, Wu D … +5 more , Fei Y, Ding W, Wang Q, Guan R, Liang X
Clin Exp Med · 2026 May · PMID 42184020 · Publisher ↗
This is a narrative review that provides a perspective on the recent advances in deep learning (DL)-driven multimodal data integration for lung cancer. Lung cancer remains the most prevalent malignancy and the leading ca...
This is a narrative review that provides a perspective on the recent advances in deep learning (DL)-driven multimodal data integration for lung cancer. Lung cancer remains the most prevalent malignancy and the leading cause of cancer-related mortality worldwide. Despite growing awareness and therapeutic innovations, the majority of cases are diagnosed at advanced stages, resulting in persistently poor survival rates. In recent years, artificial intelligence (AI) has demonstrated transformative potential in oncology research, particularly through the integration of heterogeneous biomedical data modalities. The fusion of radiological imaging, histopathological slides, genomic and transcriptomic profiles, and electronic health records has consistently outperformed unimodal approaches by capturing complementary biological and clinical information. DL-based multimodal integration frameworks have shown promise in improving diagnostic accuracy, stratifying patients according to therapeutic response, and predicting long-term prognosis, thereby contributing to precision oncology. By leveraging the synergistic strengths of diverse data sources, multimodal AI models can enable more accurate and individualized strategies for diagnosis, treatment planning, and longitudinal disease monitoring, ultimately improving clinical outcomes for patients with lung cancer.
PSMC2 promotes hepatocellular carcinoma progression through interaction with EGFR.
Li Y, Su Q, Feng Z … +2 more , Xu H, He T
Clin Exp Med · 2026 May · PMID 42177695 · Publisher ↗
Growing evidence highlights the critical involvement of the ubiquitin-proteasome system in cancer development. As an essential component of the 26 S proteasome, Proteasome 26 S Subunit ATPase 2 (PSMC2) has been implicate...
Growing evidence highlights the critical involvement of the ubiquitin-proteasome system in cancer development. As an essential component of the 26 S proteasome, Proteasome 26 S Subunit ATPase 2 (PSMC2) has been implicated in various malignancies, but its role in hepatocellular carcinoma (HCC) progression remains poorly understood. We analyzed PSMC2 expression using The Cancer Genome Atlas database (TCGA) database, and validated findings in clinical HCC specimens and cell lines through immunohistochemistry (IHC) and Western blot. Functional assays (CCK-8, colony formation, Scratch test and transwell invasion assay) were performed to assess the oncogenic properties of PSMC2 in the progression of HCC. Mechanistic studies employed co-immunoprecipitation, Western blot, immunofluorescence and in vivo xenograft models to investigate PSMC2-EGFR interactions and downstream signaling. PSMC2 was significantly overexpressed in HCC tissues and correlated with poor patient prognosis. Genetic knockdown of PSMC2 inhibited HCC cell proliferation, migration, and invasion in vitro, while suppressing tumor growth in vivo. Conversely, PSMC2 overexpression enhanced malignant phenotypes. Mechanistically, PSMC2 physically interacted with EGFR, stabilizing EGFR protein levels and enhancing phosphorylation of downstream AKT and ERK1/2 pathways. Our study identifies PSMC2 as a novel regulator of HCC progression through EGFR-AKT/ERK1/2 signaling axis activation. These findings position PSMC2 as both a prognostic biomarker and a potential therapeutic target for HCC intervention.
Plasma exosome lncRNA panel as a non-invasive biomarker for molecular diagnosis of systemic lupus erythematosus.
Li Z, Wan S, Li X … +4 more , Yang H, Lv K, Zhu X, Zhang M
Clin Exp Med · 2026 May · PMID 42177684 · Publisher ↗
Exosome-derived long non-coding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers in various diseases. However, their diagnostic potential in systemic lupus erythematosus (SLE) remains largely unexplored. Th...
Exosome-derived long non-coding RNAs (lncRNAs) have emerged as promising diagnostic biomarkers in various diseases. However, their diagnostic potential in systemic lupus erythematosus (SLE) remains largely unexplored. This study aimed to characterize plasma exosomal lncRNA profiles and identify candidate lncRNAs with diagnostic and disease-monitoring potential in SLE. Plasma exosomes were isolated from SLE patients and healthy controls (HCs), followed by high-throughput sequencing to characterize exosomal lncRNA expression profiles. Differentially expressed lncRNAs were identified and subsequently validated using quantitative real-time PCR (qRT-PCR). Correlations between the validated exosomal lncRNAs and clinical indicators of SLE were assessed. Receiver operating characteristic (ROC) curve and multivariate logistic regression analyses were performed to evaluate the diagnostic performance of the identified lncRNAs. Three plasma-derived exosomal lncRNAs-ENSG00000229882, MIR4713HG, and LINC00620-were significantly upregulated in SLE patients compared with HCs. Logistic regression analysis identified MIR4713HG and LINC00620 as predictors of SLE. A combined diagnostic model incorporating these two lncRNAs demonstrated diagnostic capacity for distinguishing SLE patients from HCs, with an area under the curve (AUC) of 0.759. Notably, exosomal LINC00620 expression was significantly upregulated in patients with active SLE compared with those with inactive disease and showed a positive correlation with SLE Disease Activity Index 2000 (SLEDAI-2 K scores). Plasma exosomal ENSG00000229882, MIR4713HG, and LINC00620 were significantly upregulated in SLE, indicating their potential as non-invasive diagnostic biomarkers. Particularly, LINC00620 showed a positive correlation with disease activity, suggesting its clinical utility for both SLE diagnosis and disease monitoring.
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