Explore the vast range of titles available.

Tumor-associated macrophages (TAMs) are an important part of tumor microenvironment (TME) and play a key role in TME, participating in the process of tumor occurrence, growth, invasion, and metastasis. Among them, metastasis to tumor tissue is the key step of malignant development of tumor. In this paper, the latest progress in the role of TAMs in the formation of tumor microenvironment is summarized. It is particularly noteworthy that cell and animal experiments show that TAMs can provide a favorable microenvironment for the occurrence and development of tumors. At the same time, clinical pathological experiments show that the accumulation of TAMs in tumor is related to poor clinical efficacy. Finally, this paper discusses the feasibility of TAMs-targeted therapy as a new indirect cancer therapy. This paper provides a theoretical basis for finding a potentially effective macrophage-targeted tumor therapy.

Propofol is a commonly used drug for the induction and maintenance of anesthesia. Previous studies have reported that propofol is involved in the progression of numerous human cancer types, including hepatocellular carcinoma (HCC). However, the underlying molecular mechanisms in HCC are yet to be elucidated. The present study aimed to investigate the potential mechanism of propofol in HCC development. MTT assay, flow cytometry analysis and Transwell assays were conducted to examine cell proliferation, apoptosis, migration and invasion, respectively. Western blotting was also performed to determine the protein expression levels of Bcl-2 and cleaved-caspase 3. An in vivo experiment was performed to assess the effect of propofol on tumor growth. Moreover, reverse transcription-quantitative PCR was conducted to measure the mRNA expression levels of HOMEOBOX A11 (HOXA11) antisense RNA (HOXA11-AS) and microRNA (miR)-4458. Dual-luciferase reporter and RNA pull-down assays were performed to evaluate the target relationship between HOXA11-AS and miR-4458. It was demonstrated that propofol inhibited HCC cell proliferation, migration and invasion, and promoted cell apoptosis in vitro. Furthermore, propofol could suppress tumor growth in vivo. Propofol suppressed the expression of HOXA11-AS in HCC cells, while HOXA11-AS overexpression reversed the inhibitory effect of propofol treatment on cell progression in HCC. In addition, miR-4458 was identified as a target of HOXA11-AS, and miR-4458 inhibition reversed the effect of HOXA11-AS knockdown on HCC cell progression. The results also indicated that propofol promoted the expression of miR-4458, while HOXA11-AS restored this effect in HCC. Thus, it was suggested that propofol suppressed cell progression by modulating the HOXA11-AS/miR-4458 axis in HCC.

Acute kidney injury (AKI) is a common complication of sepsis. Long noncoding RNA nuclear-enriched abundant transcript 1 (NEAT1) plays a vital role in various diseases, including AKI. This study aimed to investigate the function and mechanism of NEAT1 in sepsis-induced AKI. A septic AKI model was established by treating HK-2 cells with lipopolysaccharide (LPS). The levels of NEAT1 and miR-22-3p were measured by quantitative real-time PCR. Cell apoptosis was assessed by flow cytometry. The levels of apoptosis-related protein and autophagy-related factors were examined by the western blot assay. An enzyme-linked immunosorbent assay was used to calculate the contents of inflammatory factors. The interaction between NEAT1 and miR-22-3p was validated by dual-luciferase reporter assay, RNA immunoprecipitation assay, and RNA pull-down assay. The levels of nuclear factor (NF)-κB pathway-related proteins were evaluated by the western blot assay. NEAT1 was upregulated, while miR-22-3p was downregulated in patients with sepsis and in LPS-stimulated HK-2 cells. LPS treatment triggered cell apoptosis, autophagy, and inflammatory response in HK-2 cells. NEAT1 knockdown attenuated LPS-induced cell injury. NEAT1 modulated LPS-triggered cell injury by targeting miR-22-3p. Furthermore, NEAT1 regulated the NF-κB pathway by modulating miR-22-3p. Depletion of NEAT1 alleviated sepsis-induced AKI via regulating the miR-22-3p/NF-κB pathway.

Background Little evidence exists regarding the prevalence of pathogens in bloodstream infections (BSIs), the mortality risk, and the benefit of combination therapy over monotherapy. This study aims to describe patterns of empiric antimicrobial therapy, and the epidemiology of Gram-negative pathogens, and to investigate the effect of appropriate therapy and appropriate combination therapy on the mortality of patients with BSIs. Methods This was a retrospective cohort study including all patients with BSIs of Gram-negative pathogens from January 2017 to December 2022 in a Chinese general hospital. The in-hospital mortality was compared between appropriate and inappropriate therapy, and between monotherapy and combination therapy for patients receiving appropriate therapy. We used Cox regression analysis to identify factors independently associated with in-hospital mortality. Results We included 205 patients in the study, of whom 147 (71.71%) patients received appropriate therapy compared with 58 (28.29%) who received inappropriate therapy. The most common Gram-negative pathogen was Escherichia coli (37.56%). 131 (63.90%) patients received monotherapy and 74 (36.10%) patients received combination therapy. The in-hospital mortality was significantly lower in patients administered appropriate therapy than inappropriate therapy (16.33% vs. 48.28%, p = 0.004); adjusted hazard ratio [HR] 0.55 [95% CI 0.35–0.84], p = 0.006). In-hospital mortality was also not different in combination therapy and monotherapy in the multivariate Cox regression analyses (adjusted HR 0.42 [95% CI 0.15–1.17], p = 0.096). However, combination therapy was associated with lower mortality than monotherapy in patients with sepsis or septic shock (adjusted HR 0.94 [95% CI 0.86–1.02], p = 0.047). Conclusions Appropriate therapy was associated with a protective effect on mortality among patients with BSIs due to Gram-negative pathogens. Combination therapy was associated with improved survival in patients with sepsis or septic shock. Clinicians need to choose optical empirical antimicrobials to improve survival outcomes in patients with BSIs.

Curcumin is known to exhibit anticancer effects on various cancers with selective cytotoxicity in tumor cells. In the present study, the effects of curcumin-induced multiple PCDs on human non-small cell lung cancer (NSCLC) cells and the potential molecular mechanisms of apoptosis and autophagy triggered by curcumin via the PI3K/Akt/mTOR signaling pathway were explored, further confirmed by co-culture of curcumin with mTOR blocker rapamycin and PI3K/Akt inhibitor LY294002. The anti-proliferation effect of different stimulus was measured by MTT assay. Apoptosis was detected by flow cytometry. Autophagy induction was detected by MDC labeling and western blotting of Beclin1, LC3, and p62 expression. The mRNA and protein expression levels of Akt and mTOR were assayed by real-time fluorescence quantitative (qRT-PCR) technique and western blotting. Our results showed that curcumin inhibited the viability of A549 cells time- and dose-dependently. In addition, a dosage-dependent A549 cell apoptosis-induction phenomena was observed by the curcumin intervention. Moreover, obvious autophagy was induced after curcumin-treatment, characterized by the formation of fluorescent particles [autophagic vesicles (AVs)] and significant increase in ratio of LC3-II/LC3-I and Beclin1 as well as decreased p62 expression. Furthermore, the effect of curcumin on a substantial downregulation of phosphatidylinositol 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway was observed. It is worth noting that the inhibition of mTOR by rapamycin or of PI3K/Akt by LY294002 augmented curcumin-induced apoptosis and autophagy, leading to significant inhibition of cell proliferation. From these findings, it can be speculated that curcumin potently inhibit the cell growth of NSCLC A549 cells through inducing both apoptosis and autophagy by inhibition of the PI3K/Akt/mTOR pathway. These results support the potential use of curcumin as a novel candidate in treatment of human lung cancer.

Regulatory T cells (Tregs) are critically involved in neovascularization, an important compensatory mechanism in peripheral artery disease. The contribution of G protein coupled receptor 174 (GPR174), which is a regulator of Treg function and development, in neovascularization remains elusive. Here, we show that genetic deletion of GPR174 in Tregs potentiated blood flow recovery in mice after hindlimb ischemia. GPR174 deficiency upregulates amphiregulin (AREG) expression in Tregs, thereby enhancing endothelial cell functions and reducing pro-inflammatory macrophage polarization and endothelial cell apoptosis. Mechanically, GPR174 regulates AREG expression by inhibiting the nuclear accumulation of early growth response protein 1 (EGR1) via Gαs/cAMP/PKA signal pathway activation. Collectively, these findings demonstrate that GPR174 negatively regulates angiogenesis and vascular remodeling in response to ischemic injury and that GPR174 may be a potential molecular target for therapeutic interventions of ischemic vascular diseases. Gpr174 is a regulator of regulatory T cells, which play an important role in angiogenesis after hindlimb ischemia. Here, the authors show GPR174-deficient Tregs promote AREG expression by inhibiting Gαs/cAMP/PKA signal pathway and increasing EGR1 nuclear accumulation to improve angiogenesis and vascular remodeling in response to ischemic injury.

Here, we present the rational design of a pinwheel-shaped three-dimensional microfluidic paper-based analytical device (3D-μPAD) for specific, sensitive and multiplexed detection of heavy metals in coastal waters. A more homogeneous permeation of fluids along the chip than common design, even under unskilled performance, has been achieved by the elaborate chip design of the hydrostatic balancing inlet port and uniformly stressed reversible sealing. With the combination of ion imprinted polymer grafted CdTe quantum-dots and fluid accumulation pad, 4 metals (Cu2+, Cd2+, Pb2+, and Hg2+) in 1 analysis and 25-fold enrichment for each metal can be simultaneously performed within 20 min, with detection limits of 0.007–0.015 μg/L. It has the ability to selectively recognize these 4 metals in mixtures and immunizing to interferences from components found in coastal waters, which provided results that were in agreement with values gained from atomic absorption. The inexpensive and portable nature as well as the highly sensitive and flexible performance of the new developed 3D-μPAD could make it attractive as an on-site testing approach for marine environmental monitoring.

Chronic obstructive pulmonary disease (COPD), marked by dyspnea, cough, and sputum production, significantly impairs patients' quality of life and functionality. Effective management strategies, particularly those empowering patients to manage their condition, are essential to reduce this burden and health care use. Digital health interventions-such as mobile apps for symptom tracking, wearable sensors for vital sign monitoring, and web-based pulmonary rehabilitation programs-can enhance self-efficacy and promote greater patient engagement. By improving self-management skills, these interventions also help alleviate pressure on health care systems. This systematic review and meta-analysis assesses the clinical effectiveness of smartphone apps, wearable monitors, and web-delivered platforms in four COPD management areas: (1) quality of life (measured by the COPD Assessment Test [CAT] and St George's Respiratory Questionnaire), (2) self-efficacy (assessed by the General Self-Efficacy Scale), (3) functional capacity (evaluated via the 6-minute walk test and Modified Medical Research Council Dyspnea Scale), and (4) health care use (indicated by hospital and emergency department visits). A systematic review was conducted using predefined search terms in PubMed, Embase, Cochrane, and Web of Science up to January 26, 2025, to identify randomized trials on digital health interventions for COPD. Two reviewers independently screened studies and extracted data. Outcomes included quality of life, self-efficacy, functional status, and health care use. This review included 17 studies with 2027 participants from 11 countries. Eleven trials involved health care professionals in digital platform use, and 12 reported adherence strategies. Digital tools for COPD primarily focused on telerehabilitation (eg, video-guided exercises) and self-management systems (eg, artificial intelligence-driven exacerbation alerts). The study participants were predominantly older adults. Meta-analysis results indicated that digital health interventions significantly improved quality of life at 3 months on the CAT (mean difference [MD] -1.65, 95% CI -3.17 to -0.14; P=.03); at 6 months on the CAT (MD -2.43, 95% CI -3.93 to -0.94; P=.001) and St George's Respiratory Questionnaire (MD 3.25, 95% CI 0.69-5.81; P=.01); at 12 months on the CAT (MD -2.53, 95% CI -3.91 to -1.16; P<.001), EQ-5D (MD 0.04, 95% CI 0.01-0.07; P=.02), and EQ-5D visual analogue scale (MD 5.88, 95% CI 0.38-11.37; P=.04); the General Self-Efficacy Scale at 3 months (MD 1.65, 95% CI 0.62-2.69; P=.002) and 6 months (MD 1.94, 95% CI 0.83-3.05; P<.001); and the Modified Medical Research Council Dyspnea Scale at more than 3 months (MD -0.23, 95% CI -0.36 to -0.11; P=.003). However, no significant differences were observed in the 6-minute walk test, emergency department admissions, hospital admissions, emergency department admissions for COPD, or hospital admissions for COPD. Our findings suggest that digital health interventions may benefit COPD patients, but their clinical effectiveness remains uncertain. Further robust studies are needed, particularly those involving larger numbers of older adults with COPD. PROSPERO CRD420251032053; https://www.crd.york.ac.uk/PROSPERO/view/CRD420251032053.