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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease-2019 (COVID-19), is a pandemic disease that has been declared as modern history’s gravest health emergency worldwide. Until now, no precise treatment modality has been developed. The angiotensin-converting enzyme 2 (ACE2) receptor, a host cell receptor, has been found to play a crucial role in virus cell entry; therefore, ACE2 blockers can be a potential target for anti-viral intervention. In this study, we evaluated the ACE2 inhibitory effects of 10 essential oils. Among them, geranium and lemon oils displayed significant ACE2 inhibitory effects in epithelial cells. In addition, immunoblotting and qPCR analysis also confirmed that geranium and lemon oils possess potent ACE2 inhibitory effects. Furthermore, the gas chromatography-mass spectrometry (GC–MS) analysis displayed 22 compounds in geranium oil and 9 compounds in lemon oil. Citronellol, geraniol, and neryl acetate were the major compounds of geranium oil and limonene that represented major compound of lemon oil. Next, we found that treatment with citronellol and limonene significantly downregulated ACE2 expression in epithelial cells. The results suggest that geranium and lemon essential oils and their derivative compounds are valuable natural anti-viral agents that may contribute to the prevention of the invasion of SARS-CoV-2/COVID-19 into the human body.

Background Endothelial-to-mesenchymal transition (EndoMT) can provide a source of cancer-associated fibroblasts which contribute to desmoplasia of many malignancies including pancreatic ductal adenocarcinoma (PDAC). We investigated the clinical relevance of EndoMT in PDAC, and explored its underlying mechanism and therapeutic implication. Methods Expression levels of 29 long non-coding RNAs were analyzed from the cells undergoing EndoMT, and an EndoMT index was proposed to survey its clinical associations in the PDAC patients of The Cancer Genome Atlas database. The observed clinical correlation was further confirmed by a mouse model inoculated with EndoMT cells-involved PDAC cell grafts. In vitro co-culture with EndoMT cells or treatment with the conditioned medium were performed to explore the underlying mechanism. Because secreted HSP90α was involved, anti-HSP90α antibody was evaluated for its inhibitory efficacy against the EndoMT-involved PDAC tumor. Results A combination of low expressions of LOC340340, LOC101927256, and MNX1-AS1 was used as an EndoMT index. The clinical PDAC tissues with positive EndoMT index were significantly correlated with T4-staging and showed positive for M2-macrophage index. Our mouse model and in vitro cell-culture experiments revealed that HSP90α secreted by EndoMT cells could induce macrophage M2-polarization and more HSP90α secretion to promote PDAC tumor growth. Furthermore, anti-HSP90α antibody showed a potent therapeutic efficacy against the EndoMT and M2-macrophages-involved PDAC tumor growth. Conclusions EndoMT cells can secrete HSP90α to harness HSP90α-overproducing M2-type macrophages to promote PDAC tumor growth, and such effect can be targeted and abolished by anti-HSP90α antibody.

M2-polarization and the tumoricidal to tumor-promoting transition are commonly observed with tumor-infiltrating macrophages after interplay with cancer cells or/and other stroma cells. Our previous study indicated that macrophage M2-polarization can be induced by extracellular HSP90α (eHSP90α) secreted from endothelial-to-mesenchymal transition-derived cancer-associated fibroblasts. To extend the finding, we herein validated that eHSP90α-induced M2-polarized macrophages exhibited a tumor-promoting activity and the promoted tumor tissues had significant increases in microvascular density but decreases in CD4+ T-cell level. We further investigated the signaling pathways occurring in eHSP90α-stimulated macrophages. When macrophages were exposed to eHSP90α, CD91 and toll-like receptor 4 (TLR4) functioned as the receptor/co-receptor for eHSP90α binding to recruit interleukin (IL)-1 receptor-associated kinases (IRAKs) and myeloid differentiation factor 88 (MyD88), and next elicited a canonical CD91/MyD88–IRAK1/4–IκB kinase α/β (IKKα/β)–nuclear factor-κB (NF-κB)/interferon regulatory factor 3 (IRF3) signaling pathway. Despite TLR4-MyD88 complex-associated activations of IKKα/β, NF-κB and IRF3 being well-known as involved in macrophage M1-activation, our results demonstrated that the CD91-TLR4-MyD88 complex-associated IRAK1/4−IKKα/β−NF-κB/IRF3 pathway was not only directly involved in M2-associated CD163, CD204, and IL-10 gene expressions but also required for downregulation of M1 inflammatory cytokines. Additionally, Janus kinase 2 (JAK2) and tyrosine kinase 2 (TYK2) were recruited onto MyD88 to induce the phosphorylation and activation of the transcription factor signal transducer and activator of transcription-3 (STAT-3). The JAK2/TYK2−STAT-3 signaling is known to associate with tumor promotion. In this study, the MyD88−JAK2/TYK2−STAT-3 pathway was demonstrated to contribute to eHSP90α-induced macrophage M2-polarization by regulating the expressions of M1- and M2-related genes, proangiogenic protein vascular endothelial growth factor, and phagocytosis-interfering factor Sec22b.

The pigeon circovirus (PiCV), first described in the literature in the early 1990s, is considered one of the most important infectious agents affecting pigeon health. Thirty years after its discovery, the current review has employed bibliometric strategies to map the entire accessible PiCV-related research corpus with the aim of understanding its present research landscape, particularly in consideration of its historical context. Subsequently, developments, current knowledge, and important updates were provided. Additionally, this review also provides a textual analysis examining the relationship between PiCV and the young pigeon disease syndrome (YPDS), as described and propagated in the literature. Our examination revealed that usages of the term ‘YPDS’ in the literature are characterizations that are diverse in range, and neither standard nor equivalent. Guided by our understanding of the PiCV research corpus, a conceptualization of PiCV diseases was also presented in this review. Proposed definitions and diagnostic criteria for PiCV subclinical infection (PiCV-SI) and PiCV systemic disease (PiCV-SD) were also provided. Lastly, knowledge gaps and open research questions relevant to future PiCV-related studies were identified and discussed.

Airborne fine particulate matter (PM2.5) is a severe problem and is associated with health issues including liver diseases. Workers performing manual labor tend to be alcohol consumers during work, where they are also exposed to PM2.5. Long-term PM2.5 exposure can increase oxidative stress, leading to inflammation. Whether long-term exposure to air pollution and alcohol synergistically increases liver fibrosis risk warrants investigation. Oleanolic acid (OA)—a triterpenoid—has antioxidant and anti-inflammatory activities, but its low water solubility and cytotoxicity impair its potential applications. In this study, we fabricated liposomal OA nanoparticles (Lipo-OAs); then, we evaluated the anti-inflammatory effect on exposed cells and the ameliorative effect of Lipo-OAs on PM2.5 and alcohol-induced liver fibrosis in mice. The half maximal inhibitory concentration of PM2.5 for hepatic stellate cells was 900 μg/mL; at a concentration of ≥600 μg/mL, PM2.5 significantly increased interleukin-6 and tumor necrosis factor-α production. OA encapsulation in Lipo-OAs, 353 ± 140 nm in diameter with 79% encapsulation efficiency, significantly reduced OA cytotoxicity. Lipo-OAs treatment significantly reduced alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase levels; histologically, it alleviated steatosis and improved Ishak’s modified HAI score. In conclusion, Lipo-OAs have potential anti-inflammatory and reparative effects for PM2.5 and alcohol-induced liver injury treatment.

is an important causative pathogen of nosocomial infections, resulting in poor prognosis owing to its hypervirulence and antibiotic resistance. A simplified quicker version of the Pitt bacteremia score (PBS) (qPitt) for acute illness severity measurement was developed recently. The goal of this study was to explore the prognostic value of qPitt in patients with infection. Demographic information and management strategies were retrospectively collected from the records of all adult patients who visited the emergency department between January 1, 2021, and December 31, 2021, with culture-positive . The qPitt score was calculated based on: temperature <36°C, systolic blood pressure ≤90 mmHg or vasopressor administration, respiratory rate ≥25 times/min or need of mechanical ventilation, altered mental status, and cardiac arrest event. The 30-day mortality prediction abilities of the qPitt were compared with the PBS, the sequential organ failure assessment (SOFA), and the quick sequential organ failure assessment (qSOFA) using receiver operating characteristic curves. Data from 867 patients (57.8% men) with a mean age of 66.9 were compiled. The 30-day mortality rate of the enrolled patients was 13.4%, and the area under the curve (AUC) of the scoring systems were as follows: SOFA, 0.91 (95% confidence interval [CI]=0.89-0.93), qPitt, 0.87 (95% CI=0.84-0.89), PBS, 0.87 (95% CI=0.85-0.89), and qSOFA, 0.73 (95% CI=0.70-0.76). The AUC of qPitt was significantly higher than that of qSOFA ( <0.01) and similar to that of PBS ( =0.65).The qPitt also demonstrated excellent mortality discrimination ability in non-bacteremic patients, AUC= 0.85 (95% CI=0.82-0.88). The qPitt revealed excellent 30-day mortality prediction ability and also predicted mortality in non-bacteremic patients with infection. Clinicians can use this simplified scoring system to stratify patients earlier and initiate prompt treatment in high-risk patients.

This Opinion summarizes the strategies for anticancer treatment in p53-mutated head and neck squamous cell carcinoma (HNSCC). It examines six strategies for anticancer treatment in p53-mutated HNSCC: 1. direct reactivation of mutated p53; 2. activation of p63; 3. activation of p73; 4. degradation of mutated p53; 5. blocking the p53-regulated oncogenic microRNA; and 6. blocking the p53-regulated oncogenic long non-coding RNA. Since HNSCC has a high p53 mutation rate compared to other types of cancers, these strategies for combating p53-mutated HNSCC may prove useful for generating new ideas or methods for developing treatments for other cancers with p53 mutations. This article also explores other factors that may impact the effectiveness of anticancer therapies in p53-mutated HNSCC.

Patients with chronic kidney disease (CKD) are particularly vulnerable to the risks of polypharmacy, largely owing to various comorbid conditions. This vulnerability is further compounded by an escalated risk of renal function deterioration when exposed to nephrotoxic medications. As part of the national health insurance program in Taiwan, the pre-end-stage kidney disease patient care and education plan has included pharmaceutical care since October 2021. This study aims to explore the effect of pharmacist involvement in a multidisciplinary care team for patients with kidney disease in outpatient settings. This retrospective observational study was conducted at a single center. It analyzed data from May 2022 to May 2023, focusing on patients who received medication therapy management in the kidney disease pharmacist-managed clinic. The study assessed changes in patient medication adherence, non-steroidal anti-inflammatory drugs (NSAIDs) usage, CKD stage, and urine protein-to-creatinine ratio (UPCR) after pharmacist intervention. It also documented pharmacists' medication recommendations and the rate of acceptance by physicians. A total of 202 patients who had at least two clinic visits were included in the study. After pharmacist intervention, the proportion of poor medication adherence reduced significantly from 67.8% to 43.1% (p<0.001). The proportion of NSAID users also decreased significantly from 19.8% to 8.4% (p=0.001). CKD stage showed a significant reduction (p=0.007), and the average UPCR improved from 2828.4 to 2111.0 mg/g (p<0.001). The pharmacists provided a total of 56 medication recommendations, with an acceptance rate of 86%. The involvement of pharmacists in the multidisciplinary care team can effectively provide medication-related recommendations, ensuring the effectiveness and safety of patients' medication use, and lead to better kidney function and lower proteinuria.

Transcription factor MYB proto-oncogene like 2 (MYBL2) is involved in cell cycle regulation and proliferation, and it has been implicated in various cancers. However, its expression pattern and clinical significance in hepatocellular carcinoma (HCC) are unclear. Therefore, the aim of this study was to evaluate the tissue expression of MYBL2 in patients with HCC and evaluate associations with clinicopathological factors and prognosis. We enrolled 88 patients with HCC who underwent hepatectomy from October 2023 to January 2025 and analyzed MYBL2 expressions in non-tumorous and tumorous tissue samples using immunohistochemistry. The patients were then categorized into high and low expression groups, and clinicopathological factors were compared. Cox proportional hazard regression and Kaplan-Meier survival analyses were used to explore the prognostic significance of MYBL2 expression. MYBL2 immunohistochemistry score was significantly associated with survival (p for trend = 0.038). Kaplan-Meier analysis demonstrated that those with a high MYBL2 expression were associated with lower overall survival compared to those with a low MYBL2 expression (p = 0.029). An independent association was found between high MYBL2 expression in tumorous tissues and poor overall survival (p = 0.047). However, multivariate analysis indicated that MYBL2 expression was not an independent risk factor for overall survival. The results indicated an association between MYBL2 and HCC prognosis, suggesting that it could be used as a prognostic biomarker and potentially be a therapeutic target. Further research is required to clarify the molecular mechanisms by which MYBL2 drives tumor progression and to explore its potential in targeted therapy for HCC.

Breast cancer is the second most common malignancy globally and a leading cause of cancer death in women. Analysis of factors related to disease-free survival (DFS) has improved understanding of the disease and characteristics related to recurrence. The aim of this study was to investigate the predictors of DFS in patients with breast cancer to enable the identification of patients at high risk who may benefit from prevention interventions. We retrospectively analyzed 559 women with breast cancer who underwent treatment between 2004 and 2022. The study endpoint was DFS. Recurrence was defined as local recurrence, regional recurrence, distant metastases, contralateral breast cancer, other second primary cancer, and death. Baseline tumor-related characteristics, treatment-related characteristics, sociodemographic and biochemical data were analyzed using Cox proportional hazards analysis. The median DFS was 45 months (range, 2 to 225 months). Breast cancer recurred in 86 patients (15.4%), of whom 10 had local recurrence, 10 had regional recurrence, 17 had contralateral breast cancer, 29 had distant metastases, 10 had second primary cancer, and 10 patients died. Multivariate forward stepwise Cox regression analysis showed that AJCC stage III, Ki67 ≥14%, albumin, platelet, and red cell distribution width-standard deviation (RDW-SD) were predictors of worse DFS. In addition, the effects of albumin, platelet, and RDW-SD on disease recurrence were confirmed by structural equation model (SEM) analysis. In addition to the traditional predictors of worse DFS such as AJCC stage III and Ki67 ≥14%, lower pretreatment circulating albumin, higher pretreatment circulating platelet count and RDW-SD could significantly predict worse DFS in this study, and SEM delineated possible causal pathways and inter-relationships of albumin, platelet, and RDW-SD contributing to the disease recurrence among Chinese women with breast cancer.