STAT3 Signaling in Breast Cancer: Multicellular Actions and Therapeutic Potential

Interleukin (IL)-6 family cytokines, such as IL-6 and IL-11, are defined by the shared use of the gp130 receptor for the downstream activation of STAT3 signaling and the activation of genes which contribute to the “hallmarks of cancer”, including proliferation, survival, invasion and metastasis. Increased expression of these cytokines, or the ligand-specific receptors IL-6R and IL-11RA, in breast tumors positively correlate to disease progression and poorer patient outcome. In this review, we examine evidence from pre-clinical studies that correlate enhanced IL-6 and IL-11 mediated gp130/STAT3 signaling to the progression of breast cancer. Key processes by which the IL-6 family cytokines contribute to the heterogeneous nature of breast cancer, immune evasion and metastatic potential, are discussed. We examine the latest research into the therapeutic targeting of IL-6 family cytokines that inhibit STAT3 transcriptional activity as a potential breast cancer treatment, including current clinical trials. The importance of the IL-6 family of cytokines in cellular processes that promote the development and progression of breast cancer warrants further understanding of the molecular basis for its actions to help guide the development of future therapeutic targets.

The Future Potential of Biosensors to Investigate the Gut-Brain Axis

The multifaceted and heterogeneous nature of depression presents challenges in pinpointing treatments. Among these contributions are the interconnections between the gut microbiome and neurological function termed the gut-brain axis. A diverse range of microbiome-produced metabolites interact with host signaling and metabolic pathways through this gut-brain axis relationship. Therefore, biosensor detection of gut metabolites offers the potential to quantify the microbiome’s contributions to depression. Herein we review synthetic biology strategies to detect signals that indicate gut-brain axis dysregulation that may contribute to depression. We also highlight future challenges in developing living diagnostics of microbiome conditions influencing depression.

Obtaining of Copper- and Nickel-Based Polymetallic Gradient Products by Wire-Feed Electron Beam Additive Manufacturing

The structure and mechanical properties of gradient transition zones of the copper-nickel system formed by additive electron beam technology have been investigated. Pure copper and nickel alloy Ni80Cr20 were used for printing. The data obtained testify to the complex and heterogeneous nature of structure formation when printing both by single-wire method and using double-wire controlled feeding of material into the melt bath. In the samples, the formation of defects of different scale from local inhomogeneities of the structure to pores and cracks is possible. The mechanical properties of the structural gradient zone are at a sufficiently high level and depend on the ratio of the system components.

Outside Training of Spanish University Students of Education for the Didactic Application of Cinema: Formal, Non-Formal, and Informal Perspectives

Nowadays, audiovisual media play a central role in access to information and in personal relationships. Among the audiovisual media is cinema, which due to its heterogeneous nature, can fulfill diverse educational functions. The objective of this study was to learn about the training that future teachers in Spain receive outside of their teaching degree for the didactic use of cinema. In addition, we sought to understand the influence of training on perceptions regarding the educational potential of cinema and the predisposition to its use. Using a quantitative approach, information was collected from 4659 students from 58 Spanish universities. The questionnaire used covered perceptions about the potencialities of cinema as a didactic resource in pre-school and primary classrooms (PECID). The results showed that 95.1% of the students had not received training. In addition, we found a significant influence of training on their perceptions of the educational possibilities of cinema. Furthermore, we found an influence on their predisposition to use training in their future teaching practice. Overall, it is necessary to implement training actions to fill the gaps detected in favor of a quality education with active learning and linked to society.

Review: Serum Biomarkers of Lung Fibrosis in Interstitial Pneumonia with Autoimmune Features—What Do We Already Know?

Interstitial pneumonia with autoimmune features (IPAF) belongs to a group of diseases called interstitial lung diseases (ILDs), which are disorders of a varied prognosis and course. Finding sufficiently specific and sensitive biomarkers would enable the progression to be predicted, the natural history to be monitored and patients to be stratified according to their treatment. To assess the significance of pulmonary fibrosis biomarkers studied thus far, we searched the PubMed, Medline and Cochrane Library databases for papers published between January 2015 and June 2021. We focused on circulating biomarkers. A primary review of the databases identified 38 articles of potential interest. Overall, seven articles fulfilled the inclusion criteria. This review aims to assess the diagnostic and prognostic value of molecules such as KL-6, SP-A, SP-D, circulating fibrocytes, CCL2, CXCL13, CXCL9, CXCL10 and CXCL11. All of these biomarkers have previously been studied in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-associated interstitial lung disease (CTD-ILD). IPAF is a disorder of a heterogeneous nature. It explains the lack of coherent observations in terms of correlations with functional parameters. There is still no meta-analysis of pulmonary fibrosis biomarkers in IPAF. This is mainly due to the heterogeneity of the methodology and groups analysed in the research. More research in this area is needed.

Glycans for the greater good

Carbohydrates are ubiquitous in nature and present across all kingdoms of life – bacteria, fungi, viruses, yeast, plants, animals and humans. They are essential to many biological processes. However, due to their complexity and heterogeneous nature they are often neglected, sometimes referred to as the ‘dark matter’ of biology. Nevertheless, due to their extensive biological impact on health and disease, glycans and the field of glycobiology have become increasingly popular in recent years, giving rise to glycan-based drug development and therapeutics. Forecasting of communicable diseases predicts that we will see an increase in pandemics of humans and livestock due to global loss of biodiversity from changes to land use, intensification of agriculture, climate change and disruption of ecosystems. As such, the development of point-of-care devices to detect pathogens is vital to prevent the transmission of infectious disease, as we have seen with the COVID-19 pandemic. So, can glycans be exploited to detect COVID-19 and other infectious diseases? And is this technology sensitive and accurate? Here, I discuss the structure and function of glycans, the current glycan-based therapeutics and how glycan binding can be exploited for detection of infectious disease, like COVID-19.

The Bumpy Road towards mTOR Inhibition in Glioblastoma: Quo Vadis?

Glioblastoma multiforme (GBM), a grade IV astrocytoma, is a lethal brain tumor with a poor prognosis. Despite recent advances in the molecular biology of GBM, neuro-oncologists have very limited treatment options available to improve the survival of GBM patients. A prominent signaling pathway implicated in GBM pathogenesis is that of the mechanistic target of rapamycin (mTOR). Attempts to target the mTOR pathway with first-generation mTOR inhibitors appeared promising in the preclinical stage; however, results have been disappointing in clinical trials, owing to the heterogeneous nature of GBM, escape mechanisms against treatment, the blood–brain barrier, drug-related toxicities, and the imperfect design of clinical trials, among others. The development of next-generation mTOR inhibitors and their current evaluation in clinical trials have sparked new hope to realize the clinical potential of mTOR inhibitors in GBM. Meanwhile, studies are continuously furthering our understanding of mTOR signaling dysregulation, its downstream effects, and interplay with other signaling pathways in GBM tumors. Therefore, it remains to be seen whether targeting mTOR in GBM will eventually prove to be fruitful or futile.

Linguistic Movements and Political Heterogeneity: Rethinking Unification Movement across British and ‘Princely’ Karnataka

Subsequent to the Partition of Bengal in 1905, the consolidation of linguistic identities and movements emerged as an important assertion of core democratic values, positing that governance must be in a language intelligible to the majority. Like other linguistic movements in late-colonial India, the Karnataka Ekikarana (Karnataka unification) movement did not proceed with a spatially uniform logic nor followed a uniform temporality in realising its objectives of uniting Kannada speakers from disparate sub-regions. Attempting to reconcile elite literary ambitions, popular aspirations and political differences, the movement shifted gears through several phases as it worked across multiple territorial jurisdictions and political systems, including the demarcations of British India and princely India. Focussing on the period between 1860 and 1938, the present article examines the heterogeneous nature of the unification movement across British-Karnataka and two Kannada-speaking princely states, namely, Mysore in the south and Jamakhandi in the north. It explores the ways in which the ruling family of ‘model’ Mysore sought legitimacy in embracing their Kannada heritage; in contrast, the Jamakhandi rulers resisted any concession to Kannada linguistic sentiments. The article shows how, in arriving at monolingually indexed territorial entities, the bridging of ‘internal’ frontiers across these divergent political and linguistic contours proved just as crucial as the claiming of dominance over other language groups within an intensely polyglot world.