Search Results (147)

The urokinase-receptor (uPAR) exerts multiple functions supporting most cancer hallmarks. Increased uPAR expression is associated with an unfavorable prognosis in several cancer types, including hematologic malignancies. We previously reported that three oncosuppressor microRNAs (miRNAs) can target the 3′untranslated region (3′UTR) of the uPAR mRNA and that uPAR mRNA is a competitive endogenous RNA (ceRNA) able to recruit oncosuppressor miRs, thus impairing their activity. We now show that uPAR mRNA can also be targeted by oncosuppressor members of the let-7 miRNA family in acute myeloid leukemia (AML) cell lines. Indeed, let-7a, let7d and let-7g directly target the 3′UTR of uPAR mRNA, thus down-regulating uPAR expression. These let-7 miRNAs are expressed in KG1 and U937 AML cells; their levels are high in KG1 cells, which express low uPAR levels, and low in the U937 cell line, expressing high levels of uPAR. Overexpression of these miRNAs down-regulates uPAR expression and impairs the adhesion to fibronectin and migration of U937 cells, without affecting their proliferation. Accordingly, the overexpression of specific inhibitors targeting these let-7 miRNAs efficiently increases uPAR expression in KG1 cells. These results indicate that selected let-7 miRNAs regulate uPAR expression and impair the adhesion and migration of AML cells. Full article

Background and Objective. The significance of microRNAs (miRNAs) in relation to neoplastic diseases; such as renal carcinoma carcinoma (RCC); has been brought to light by recent studies. Analyzing the main urinary miRNAs implicated in RCC and their potential diagnostic use was the goal of this systematic review of the literature. Methods. This systematic review was performed following the PROSPERO protocol CRD42024550716. Our literature search strategies were deciding which database to include (Pubmed; EMBASE and Clinicaltrial.gov) and composing strings with words related to urinary miRNA in patients with RCC. Key findings and limitations. After screening; 10 papers were included from the 593 records that the systematic review found. No miRNA was investigated in more than one paper by different authors. The miR-210 and let-7 family were the most investigated and resulted upregulated in RCC cases compared to controls. Five papers reported different expression of miRNAs in urine samples before and after surgery: miR-15a; miR-34a-5p; miR-200a-3p; miR-205-5p; miR-210; miR-210-3p; miR-365a-3p and let-7d-5p levels decreased after nephrectomy. Meta-analysis was not performed since the included studies were heterogeneous; in terms of studied miRNA; of the normalizer used during stabilization phase; and histologic type of RCC (clear cell RCC; papillary RCC; unspecified RCC). Conclusions. Considering the variability and heterogeneity of the obtained results; as well as the vastness of the topic; expanding research in this field appears highly promising. To support further advancements; it would be useful to establish a database that consolidates international findings. Full article

MicroRNAs (miRNAs) are small RNA molecules that do not have coding functions but play essential roles in various biological processes. In lung cancer, miRNAs affect the processes of tumor initiation, progression, metastasis, and resistance to treatment by regulating gene expression. Tumor-suppressive miRNAs inhibit oncogenic pathways, while oncogenic miRNAs, known as oncomiRs, promote malignant transformation and tumor growth. These dual roles position miRNAs as critical players in lung cancer biology. Studies in recent years have shown the significant potential of miRNAs as both prognostic and diagnostic biomarkers. Circulating miRNAs in plasma or sputum demonstrate specificity and sensitivity in detecting early-stage lung cancer. Liquid biopsy-based miRNA panels distinguish malignant from benign lesions, and specific miRNA expression patterns correlate with disease progression, response to treatment, and overall survival. Therapeutically, miRNAs hold promise for targeted interventions. Strategies such as miRNA replacement therapy using mimics for tumor-suppressive miRNAs and inhibition of oncomiRs with antagomiRs or miRNA sponges have shown preclinical success. Key miRNAs, including the let-7 family, miR-34a, and miR-21, are under investigation for their therapeutic potential. It should be emphasized that delivery difficulties, side effects, and limited stability of therapeutic miRNA molecules remain obstacles to their clinical use. This article examines the roles of miRNAs in lung cancer by indicating their mechanisms of action, diagnostic significance, and therapeutic potential. By addressing current limitations, miRNA-based approaches could revolutionize lung cancer management, offering precise, personalized, and minimally invasive solutions for diagnosis and treatment. Full article

This paper describes the co-design of a participatory group intervention developed to promote and enhance parental involvement in supporting the education of children with disabilities in Malawi. The intervention was developed through participatory co-design workshops and consensus meetings involving 23 stakeholders, including parents, teachers, and community leaders. The Behaviour Change Wheel framework and the Delphi technique guided the intervention development process, ensuring theoretical robustness and contextual relevance. The proposed intervention, Tiyanjane (‘Let Us Unite’), includes facilitator and participant training and practical face-to-face sessions over 12 weeks. The intervention targets four key areas: developing family action plans, holding regular meetings, providing ongoing support at home and school, and facilitating training and information exchange. This participatory approach, involving a wide range of local stakeholders, offers valuable insights into the process and outcomes of co-developing culturally relevant and theoretically grounded interventions to address the needs of families with children with disabilities in low-resource settings. Future research should include an evaluation of the feasibility and acceptability of the intervention and examine its applicability in diverse sociocultural settings within LMICs (low- and middle-income countries). Full article

Background: The work main purposes were to identify the sources of problems and demands causing parental burnout and to specify the resources/support factors during the COVID-19 pandemic. The study was based on the Balance Theory of Risk and Support/Resource Factors (BR² Model) by Mikolajczak and Roskam. Methods: The study explored the predictive value of socio-economic variables, religiosity, the meaning of life, positivity, perceived social support, family functionality, and balance between risks and resources in parental burnout using the structural equation modelling method on a sample of 337 parents. Results: The presence of children’s learning difficulties and behavioural problems are the most important risk factors and aggravate parental burnout, and the presence of a meaning of life, support coming from the family, family affection, and relationship lengths are the main protective resources, allowing parental burnout to decrease during the pandemic crisis. Conclusions: The findings are instructive for both theory and practice. The study successfully operationalised the BR² model—the model obtained from the path analysis fits well, confirms the structure of parental burnout theory, and demonstrates the appropriateness of the application of BR² theory in crisis conditions. The most effective way to help parents in a crisis situation is (in addition to psychological support) the effective provision of specialist help for children, resulting in a reduced risk of an unfavourable balance between demands and family resources. The family- or parent-oriented interventions that address professional help in problems with children can be the most effective at reducing the negative consequences of a pandemic on children and their parents. The COVID-19 pandemic has shown the importance of investing in healthcare infrastructures. Full article

Family factors significantly influence rural-to-urban migrant children’s educational opportunities within the framework of education policies. In this research, we examined rural-to-urban migrant families’ strategies for the urban education of their children in the context of China’s points-based admission policy. We investigated how family capital and willingness to participate impact their children’s access to educational opportunities. The results reveal that the points-based admission policy prioritizes “ability first” while allowing for diverse indicators that accommodate various types of rural-to-urban migrant families. In the points-based admission process, different family types adopt distinct strategies, including the “capital transformation” strategy of high-capital–high-willingness families; the “quit voluntarily” strategy of high-capital–low-willingness families; the “try one’s best” strategy of low-capital–high-willingness families; and the “let nature take its course” strategy of low-capital–low-willingness families. The admission policy based on allocating points favors rural-to-urban migrant children from families with high capital. Nevertheless, those from families with low capital are not entirely excluded from educational opportunities in other locations. These families possess a strong capacity for action, propelled by their eagerness to engage. Within the framework of educational policies, the amalgamation of family capital and willingness to participate serves as the driving force behind rural-to-urban migrant children’s access to educational prospects, with educational expectations serving a regulatory function. Exploring the family strategies for rural-to-urban migrant children’s urban education can enhance educational policies for this demographic and offer valuable recommendations for their sustainable development. Full article

Let $G=(V,E)$ be a graph and $\mathcal{F}$ be a family of graphs; a subset ($S\subseteq V\left(G\right)$) is said to be an $\mathcal{F}$-isolating set if $G[V\left(G\right)\setminus N_G\left[S\right]]$ does not contain F as a subgraph for all $F\in \mathcal{F}$. The $\mathcal{F}$-isolation number of G is the minimum cardinality of an $\mathcal{F}$-isolating set (S) of G, denoted by $\iota (G,\mathcal{F})$. When $\mathcal{F}=\left\{K_{1,k+1}\right\}$, we use ${\iota }_k\left(G\right)$ to define the $\mathcal{F}$-isolation number ($\iota (G,\mathcal{F})$). In particular, when $k=0$, we use the short form of $\iota \left(G\right)$ instead of ${\iota }_0\left(G\right)$. A subset ($S\subseteq V\left(G\right)$) is called an isolating set if $V\left(G\right)\setminus N_G\left[S\right]$ is an independent set of G. The isolation number of G is the minimum cardinality of an isolating set, denoted by $\iota \left(G\right)$. In this paper, we mainly focus on research on the isolation number and $\mathcal{F}$-isolation number of a $B\left(G\right)$ graph, total graph and central graph of graph G. Full article

Let $G=(V,E)$ be a connected graph. A bijection $f:E\to \{1,\dots ,|E\left|\right\}$ is called a local antimagic labeling if, for any two adjacent vertices x and y, $f^{+}\left(x\right)\ne f^{+}\left(y\right)$, where $f^{+}\left(x\right)={\sum }_{e\in E\left(x\right)}f\left(e\right)$, and $E\left(x\right)$ is the set of edges incident to x. Thus, a local antimagic labeling induces a proper vertex coloring of G, where the vertex x is assigned the color $f^{+}\left(x\right)$. The local antimagic chromatic number ${\chi }_{la}\left(G\right)$ is the minimum number of colors taken over all colorings induced by local antimagic labelings of G. In this paper, we present some families of bridge graphs with ${\chi }_{la}\left(G\right)=3$ and give several ways to construct bridge graphs with ${\chi }_{la}\left(G\right)=3$. Full article

The efficacy of statins as anti-cancer drugs has been demonstrated in several malignancies but has been poorly investigated in hematological malignancies (HM). By studying its effect on oncogenic miRNAs, we investigated the effect of statin therapy on HM patients. The data were used to identify enriched pathways that were altered due to statin treatment. The main aim of this study was to identify significantly differentially expressed miRNAs and involved regulatory pathways post-atorvastatin treatment in HM patients. A panel of 95 plasma circulating miRNAs involved in tumorigenesis, apoptosis, and differentiation were relatively quantified using qPCR for blood samples obtained from 12 HM patients, 4 with Chronic Myeloid Leukemia (CML), 4 with Non-Hodgkin Lymphoma (NHL), and 4 with Essential Thrombocythemia. Pre- and post-administration of a 6-week atorvastatin course miRNA expression levels were measured. Significantly differentially expressed miRNAs were those with a fold change >2 or <0.5 using the Livak method with a two-sided p-value < 0.05. To further understand the underlying mechanism of statin regulated miRNA, GO and KEGG pathway enrichment analyses were conducted for identified target genes using the DAVID 6.8 bioinformatics tool. Out of 95 miRNAs, 14 exhibited significant fold changes post-treatment with statins including miR-198, miR-29a+b+c, miR-204, miR-222, miR-224, miR-155, miR-128b, miR-296, miR-199a+b, miR-194, miR-125a, miR-200a, and the let-7-family that were upregulated and miR-150 that was downregulated post-statin treatment. Higher mir-222, mir-194, mir-128b, and mir-199b expressions were significantly associated with better overall survival using the Cancer Genomic Atlas leukemia and lymphoma patient cohorts. Enrichment analysis identified the PI3k-Akt pathway as well as other pathways involved in the epithelial–mesenchymal transition. Atorvastatin upregulated several tumor suppressor genes involved in mediating better prognosis. The data can be used to enhance personalized treatments for patients with hematological malignancies by helping to predict the different pathways that may be targeted and, therefore, result in better survival outcomes in these patients. Full article

The widespread use of the term “foster fail” in animal rescue suggests that it happens often, but no research has explored the prevalence of volunteers adopting their foster animals or whether the phenomenon is really a “failure”. This survey-based study focused on the following questions: 1. How common are foster fails among volunteers on shelter and rescue lists and why do they occur? 2. What types of volunteers are most likely to adopt their foster animals? 3. Do different attachment styles to pets affect foster adoption? 4. Is the adoption of foster animals a way to deal with the potential grief of letting them go to adoption? 5. What are the impacts of foster fails on animal shelters in terms of longevity of volunteers and satisfaction with the volunteer experience? Data were collected through surveys of foster volunteers. Two nonprofit organizations, the Pedigree Foundation and Shelter Animals Count, distributed information about the survey and shelter directors distributed the survey link to their population of foster volunteers. Nine hundred and forty-seven individuals responded. To address the research questions, frequency, correlation, and regression analyses were employed. A total of 38% of volunteers had not adopted a foster in the past ten years, and another 38% had adopted one or two; 90 (11%) and 103 (13%) had adopted three to four or more than four, respectively. Volunteers that had significantly higher numbers of foster fails were those that were older (r = 0.22, p < 0.001), retired (chi-squared = 9.05, p = 0.029), lower on educational attainment (r = −0.13, p < 0.001), female with their own cats (r = 0.16, p < 0.001), and part of a fostering family (r = 0.08, p = 0.043). Volunteers that expressed higher levels of both people-substituting (r = 0.16, p = 0.003) and general (r = 0.13, p = 0.017) attachment to their fosters were more likely to adopt them, as were those that more frequently fostered animals with special medical or behavioral needs (r = 0.25, p < 0.001). Volunteers that had longer tenures (r = 0.43, p < 0.001), fostered more frequently (r = 0.24, p < 0.001), and reported greater resilience (r = 0.10, p = 0.009) had adopted significantly more animals. Finally, there was a significant and positive relationship between satisfaction with fostering and adopting more foster animals (r = 0.16, p < 0.001). The findings indicated that instead of being a “failure,” foster adoptions can be a positive force for the animal in question, their adopters, and shelters and rescues because they have more resilient, satisfied, and active volunteers. Full article

We open here many new tracks of research in anti-Ramsey Theory, considering edge-coloring problems inspired by rainbow coloring and further by odd colorings and conflict-free colorings. Let G be a graph and $\mathcal{F}$ any given family of graphs. For every integer $n\ge \left|G\right|$, let $f(n,G|\mathcal{F})$ denote the smallest integer k such that any edge coloring of $K_n$ with at least k colors forces a copy of G in which each color class induces a member of $\mathcal{F}$. Observe that in anti-Ramsey problems, each color class is a single edge, i.e., $\mathcal{F}=\left\{K_2\right\}$. Among the many results introduced in this paper, we mention the following. (1) For every graph G, there exists a constant $c=c\left(G\right)$ such that in any edge coloring of $K_n$ with at least $cn$ colors there is a copy of G in which every vertex v is incident with an edge whose color appears only once among all edges incident with v. (2) In sharp contrast to the above result we prove that if $\mathcal{F}$ is the class of all odd graphs (having vertices with odd degrees only) then $f(n,K_k|\mathcal{F})=(1+o\left(1\right))\mathrm{ex}(n,K_{\lceil k/2\rceil })$, which is quadratic for $k\ge 5$. (3) We exactly determine $f(n,G|\mathcal{F})$ for small graphs when $\mathcal{F}$ belongs to several families representing various odd/even coloring constraints. Full article

Let G be a compact connected Lie group, $(X,\omega ,\mu )$ a Hamiltonian G-manifold with moment map $\mu$, and Z a codimension-2 Hamiltonian G-submanifold of X. We study the boundedness of the differential of symplectic vortices $(A,u)$ near Z, where A is a connection 1-form of a principal G-bundle P over a punctured Riemann surface $\mathring{\Sigma }$, and u is a G-equivariant map from P to an open cylinder model near Z. We show that if the total energy of a family of symplectic vortices on $\mathring{\Sigma }\cong [0,+\infty )\times S^1$ is finite, then the A-twisted differential $d_{A}u(r,\theta )$ is uniformly bounded for all $(r,\theta )\in [0,+\infty )\times S^1$. Full article

Let $\mathfrak{F}\left({\nu }_j\right)=\{Q_{m_j}^{{\nu }_j},m_j\in (m_{-}^{{\nu }_j},m_{+}^{{\nu }_j})\}$, $j=1,2$, be two Cauchy–Stieltjes Kernel (CSK) families induced by non-degenerate compactly supported probability measures ${\nu }_1$ and ${\nu }_2$. Introduce the set of measures $\mathcal{F}=\mathfrak{F}\left({\nu }_1\right)⊞\mathfrak{F}\left({\nu }_2\right)=\{Q_{m_1}^{{\nu }_1}⊞Q_{m_2}^{{\nu }_2},m_1\in (m_{-}^{{\nu }_1},m_{+}^{{\nu }_1})and{m}_2\in (m_{-}^{{\nu }_2},m_{+}^{{\nu }_2})\}.$ We show that if $\mathcal{F}$ remains a CSK family, (i.e., $\mathcal{F}=\mathfrak{F}\left(\mu \right)$ where $\mu$ is a non-degenerate compactly supported measure), then the measures $\mu$, ${\nu }_1$ and ${\nu }_2$ are of the Marchenko–Pastur type measure up to affinity. A similar conclusion is obtained if we substitute (in the definition of $\mathcal{F}$) the additive free convolution ⊞ by the additive Boolean convolution ⊎. The cases where the additive free convolution ⊞ is replaced (in the definition of $\mathcal{F}$) by the multiplicative free convolution ⊠ or the multiplicative Boolean convolution ⨃ are also studied. Full article

Liver fibrosis, a critical precursor to hepatocellular carcinoma (HCC), results from chronic liver injury and significantly contributes to HCC progression. Schistosomiasis, a neglected tropical disease, is known to cause liver fibrosis; however, this process can be modulated by schistosome-derived miRNAs. Previous studies from our laboratory have demonstrated that Schistosoma japonicum extracellular vesicles (EVs) deliver sja-let-7 to hepatic stellate cells, leading to the inhibition of Col1α2 expression and alleviation of liver fibrosis. Given the well-documented antifibrotic and antiproliferative properties of the let-7 miRNA family, this study aims to preliminarily investigate the effects of the sja-let-7/Col1α2 axis on BALB/c mice and HCC cell line SNU387, providing a basis for the potential application of parasite-derived molecules in HCC therapy. In the present study, schistosome-induced fibrosis datasets were analyzed to identify the role of Col1α2 in extracellular matrix organization. Pan-cancer analysis revealed that Col1α2 is upregulated in various cancers, including HCC, with significant associations with immune cell infiltration and clinical parameters, highlighting its diagnostic importance. Functional assays demonstrated that transfection with sja-let-7 mimics significantly reduced Col1α2 expression, inhibited HCC cell proliferation, migration, and colony formation. These findings suggest that sja-let-7, by targeting Col1α2, has the potential to serve as a therapeutic agent in HCC treatment. This study indicates the pivotal role of Col1α2 in liver fibrosis and HCC, and the promising therapeutic application of helminth-derived miRNAs. Full article

Rhinovirus C (RV-C) infects airway epithelial cells and is an important cause of acute respiratory disease in humans. To interrogate the mechanisms of RV-C-mediated disease, animal models are essential. Towards this, RV-C infection was recently reported in wild-type (WT) mice, yet, titers were not sustained. Therefore, the requirements for RV-C infection in mice remain unclear. Notably, prior work has implicated human cadherin-related family member 3 (CDHR3) and stimulator of interferon genes (STING) as essential host factors for virus uptake and replication, respectively. Here, we report that even though human (h) and murine (m) CDHR3 orthologs have similar tissue distribution, amino acid sequence homology is limited. Further, while RV-C can replicate in mouse lung epithelial type 1 (LET1) cells and produce infectious virus, we observed a significant increase in the frequency and intensity of dsRNA-positive cells following hSTING expression. Based on these findings, we sought to assess the impact of hCDHR3 and hSTING on RV-C infection in mice in vivo. Thus, we developed hCDHR3 transgenic mice, and utilized adeno-associated virus (AAV) to deliver hSTING to the murine airways. Subsequent challenge of these mice with RV-C15 revealed significantly higher titers 24 h post-infection in mice expressing both hCDHR3 and hSTING—compared to either WT mice, or mice with hCDHR3 or hSTING alone, indicating more efficient infection. Ultimately, this mouse model can be further engineered to establish a robust in vivo model, recapitulating viral dynamics and disease. Full article