EXCLI Journal最新文献

Anecdotal reports suggested an association between SARS-CoV-2 vaccination and some cancers, but no formal assessment has been published. This population-wide cohort analysis was aimed at evaluating the risk of all-cause death and cancer hospitalization by SARS-CoV-2 immunization status. Using National Health System official data, the entire population of the Pescara province, Italy was followed from June 2021 (six months after the first vaccination) to December 2023. Cox models were adjusted for age, gender, previous SARS-CoV-2 infection, and selected comorbidities. Of the 296,015 residents aged ≥11 years, 16.6% were unvaccinated, 83.3% received ≥1 dose, and 62.2% ≥3 doses. Compared with the unvaccinated, those receiving ≥1 dose showed a significantly lower likelihood of all-cause death, and a slightly higher likelihood of hospitalization for cancer (HR: 1.23; 95% CI: 1.11-1.37). The latter association was significant only among the subjects with no previous SARS-CoV-2 infection, and was reversed when the minimum time between vaccination and cancer hospitalization was set to 12 months. The subjects who received SARS-CoV-2 vaccination showed a substantial reduction in all-cause mortality, and a risk of cancer hospitalization that varied by infection status, cancer site, and the minimum lag-time after vaccination. Given that it was not possible to quantify the potential impact of the healthy vaccinee bias and unmeasured confounders, these findings are inevitably preliminary. See also the graphical abstract(Fig. 1).

A total of 147 patients, genotyped for glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) and for N-acetyltransferase 2 (NAT2), who had undergone total joint replacement of the knee or hip joint between August 2004 and June 2007, showed with 45% a remarkably lower portion of the GSTM1-negative genotype compared to both a local control (51%), an external control (52%) and the portion reported in the literature for the European population (50%). In contrast, the portions of GSTT1-positive (84%) and slow NAT2 (55.1%) patients of the initial collective were unremarkable, compared to both controls. To elucidate a possible impact of this interesting finding on the long-term outcome, the patients were contacted in December 2015. Afterwards, they were interviewed using a self-prepared questionnaire. The average follow-up time was 9 years. At the time of follow-up, 57 patients were deceased, 46 patients did not respond and 12 patients declined the interview. A total of 32 patients participated in the follow-up. The mean age of the followed-up patients was 75.9±8.3 years, whereas the mean age of all patients at the time of surgery was 70.9±9 years. The portions of the GSTM1-negative genotype (15 out of 32; 47%), the GSTT1-positive genotype (24 out of 32; 75%) and the slow NAT2 status (17 out of 32; 53%) in the followed-up patients were comparable to those of the initial collective. The follow-up results of the patients after 9 years were unable to clarify the significance of the observed lower portion of GSTM1-negative patients. In view of a recently published omics study reporting a reduced GSTM1 activity in tissue attached on hip implants explanted due to aseptic loosening, the striking portion of the GSTM1-negative genotype in this present study may encourage further investigation into the impact of this gene in patients with hip or knee replacement.

Ulcerative colitis (UC) is a chronic or recurrent inflammatory disease of the large intestine. Although the causes of UC are insufficiently understood, a complex interaction of several factors, including genetic factors, environmental factors, and gut microbiota, influences the onset of UC. The pathophysiology of UC involves intestinal barrier dysfunction, abnormal immune responses, and dysregulation of cytokines. Cytokine-targeted therapies have been approved for the treatment of UC, with several targeted therapies being currently available. The induction response rates range from 47.8 % to 73 %, and we often experience difficult-to-treat cases. In this review, we outlined the abnormal immune response and cytokine regulation underlying the complex pathology of UC. Moreover, we summarized the mode of action and the effects at the cellular and genetic levels of targeted therapies. A deeper understanding of the pathophysiology of UC and the effects of treatment is essential for advancing personalized medicine, which remains a key, challenging goal in the future management of UC.

In regulating cellular plasticity, epithelial to mesenchymal transition (EMT), and tumor progression across a broad range of cancer types, the Hippo signaling pathway depends on YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ binding motif) as core effectors. This pathway can become dysregulated, disrupting tissue homeostasis and promoting oncogenic processes such as metastasis, immune evasion, and therapy resistance. This review explores the multifaceted roles of YAP/TAZ in lung, breast, ovarian, liver, and renal cancers, detailing their interactions with key signaling pathways such as TGF-β, Wnt, and PI3K/AKT and their modulation by mechanical cues like extracellular matrix stiffness and fluid shear stress. Potential YAP/TAZ mediated therapy resistance in EGFR TKI-resistant lung cancer and platinum-resistant ovarian cancer and the impact this has on tumor metabolism as a result of YAP/TAZ controlling tumor mesenchymal stem cells in the hypoxic environment of hepatocellular carcinoma is highlighted. Additionally, we discuss their role in maintaining cancer stem cell traits, creating an immunosuppressive tumor microenvironment, and driving chemoresistance in breast and renal cancers. Small molecule inhibitors, natural compounds (luteolin, apigenin, honokiol), and novel agents (nanoparticles of zinc oxide) are discussed as promising routes for disrupting YAP/TAZ. The review underscores the complexity of YAP/TAZ signaling and the need for patient stratification based on their expression levels to optimize targeted therapies. See also the graphical abstract(Fig. 1).

Epilepsy is a highly complex and global neurological disorder, for which available treatments only inadequately control the disease in many patients. Recent advances in molecular research have identified N6-methyladenosine (m6A) RNA modifications as key regulators of neuronal processes that underpin the pathophysiology of epilepsy. This review critically discusses the emerging significance of m6A modifications in epilepsy, focusing on dynamic regulations of m6A "writers," "erasers," and "readers" for modulating gene expression, neuronal excitability, and synaptic plasticity in epilepsy. Dysregulation of m6A machinery promotes epilepsy by exacerbating oxidative stress, mitochondrial dysfunction, and neuronal damage. We also discuss the prognostic significance of m6A alterations as a potential biomarker in epilepsy diagnosis and disease progression, along with advanced therapeutic strategies against m6A, including small molecules, RNA editing technologies, and precision medicine. This review highlights the transformational significance of m6A modulation in epilepsy therapy and opens new avenues for personalized therapeutic strategies that may revolutionize the field of drug-resistant epilepsy and improve the prognosis for patients. See also the graphical abstract(Fig. 1).