Advancements in the field of tissue engineering have led to the elucidation of physical and chemical characteristics of physiological basement membranes (BM) as specialized forms of the extracellular ...matrix. Efforts to recapitulate the intricate structure and biological composition of the BM have encountered various advancements due to its impact on cell fate, function, and regulation. More attention has been paid to synthesizing biocompatible and biofunctional fibrillar scaffolds that closely mimic the natural BM. Specific modifications in biomimetic BM have paved the way for the development of in vitro models like alveolar-capillary barrier, airway models, skin, blood-brain barrier, kidney barrier, and metastatic models, which can be used for personalized drug screening, understanding physiological and pathological pathways, and tissue implants. In this Review, we focus on the structure, composition, and functions of in vivo BM and the ongoing efforts to mimic it synthetically. Light has been shed on the advantages and limitations of various forms of biomimetic BM scaffolds including porous polymeric membranes, hydrogels, and electrospun membranes This Review further elaborates and justifies the significance of BM mimics in tissue engineering, in particular in the development of in vitro organ model systems.
The histone modifiers (HMs) are crucial for chromatin dynamics and gene expression; however, their dysregulated expression has been observed in various abnormalities including cancer. In this study, ...we have analyzed the expression of HMs in microarray profiles of head and neck cancer (HNC), wherein a highly significant overexpression of p21-activated kinase 2 (PAK2) was identified which was further validated in HNC patients. The elevated expression of PAK2 positively correlated with enhanced cell proliferation, aerobic glycolysis and chemoresistance and was associated with the poor clinical outcome of HNC patients. Further, dissection of molecular mechanism revealed an association of PAK2 with c-Myc and c-Myc-dependent PKM2 overexpression, wherein we showed that PAK2 upregulates c-Myc expression and c-Myc thereby binds to PKM promoter and induces PKM2 expression. We observed that PAK2-c-Myc-PKM2 axis is critical for oncogenic cellular proliferation. Depletion of PAK2 disturbs the axis and leads to downregulation of c-Myc and thereby PKM2 expression, which resulted in reduced aerobic glycolysis, proliferation and chemotherapeutic resistance of HNC cells. Moreover, the c-Myc complementation rescued PAK2 depletion effects and restored aerobic glycolysis, proliferation, migration and invasion in PAK2-depleted cells. The global transcriptome analysis of PAK2-depleted HNC cells revealed the downregulation of various genes involved in active cell proliferation, which indicates that PAK2 overexpression is critical for HNC progression. Together, these results suggest that the axis of PAK2-c-Myc-PKM2 is critical for HNC progression and could be a therapeutic target to reduce the cell proliferation and acquired chemoresistance and might enhance the efficacy of standard chemotherapy which will help in better management of HNC patients.
Functional unit of many organs like lung, kidney, intestine, and eye have their endothelial and epithelial monolayers physically separated by a specialized extracellular matrix called the basement ...membrane. The intricate and complex topography of this matrix influences cell function, behavior and overall homeostasis. In vitro barrier function replication of such organs requires mimicking of these native features on an artificial scaffold system. Apart from chemical and mechanical features, the choice of nano-scale topography of the artificial scaffold is integral, however its influence on monolayer barrier formation is unclear. Though studies have reported improved single cell adhesion and proliferation in presence of pores or pitted topology, corresponding influence on confluent monolayer formation is not well reported. In this work, basement membrane mimic with secondary topographical cues is developed and its influence on single cells and their monolayers is investigated. We show that single cells cultured on fibers with secondary cues form stronger focal adhesions and undergo increased proliferation. Counterintuitively, absence of secondary cues promoted stronger cell-cell interaction in endothelial monolayers and promoted formation of integral tight barriers in alveolar epithelial monolayers. Overall, this work highlights the importance of choice of scaffold topology to develop basement barrier function in in vitro models.
Horseradish peroxidase (HRP) can be used for the enzymatic cross‐linking of thiol‐functionalized polymers under mild conditions to form hydrogels and nanogels without the need for added H2O2. Cells ...can be embedded in the hydrogels and proteins can be entrapped and released from the nanogels. These gels are fully degradable under mild and cytocompatible reductive conditions.
Zinc oxide nanoparticles (ZnO NPs) are one of the most broadly used engineered nanomaterials. The toxicity potential of ZnO NPs has been explored in several studies; however, its neurotoxicity, ...especially its molecular mechanism, has not been studied in depth. In this study, we have used a cellular model of neuronal differentiation (nerve growth factor differentiated PC12 cells) to compare the effect of ZnO NPs exposure on neuronal (differentiated or mature neurons) and non-neuronal (undifferentiated) cells. Our studies have shown that the noncytotoxic concentration of ZnO NPs causes neurite shortening and degeneration in differentiated PC12 cells. Brain-specific microRNA (miRNA) array and liquid chromatography with tandem mass spectrometry (LC-MS/MS) are used to carry out profiling of miRNAs and proteins in PC12 cells exposed with ZnO NPs. Exposure of ZnO NPs produced significant deregulation of a higher number of miRNAs (15) and proteins (267) in neuronal cells in comparison to miRNAs (8) and proteins (207) of non-neuronal cells (8). In silico pathway analysis of miRNAs and proteins deregulated in ZnO NPs exposed differentiated PC12 cells have shown pathways leading to neurodegenerative diseases and mitochondrial dysfunctions are primarily targeted pathways. Further, a bioenergetics study carried out using Seahorse XFp metabolic flux analyzer has confirmed the involvement of mitochondrial dysfunctions in ZnO NPs exposed differentiated PC12 cells. In conclusion, differentiated PC12 cells (neuronal) were found more vulnerable than undifferentiated (non-neuronal PC12 cells) toward the exposure of ZnO NPs and deregulation of miRNAs and mitochondrial dysfunctions play a significant role in its toxicity.
Science fiction writer William Gibson is widely recognised for revolutionising the field as he is often considered to be the father of the sub-genre called cyberpunk. He had a significant cultural ...impact and his seminal novel
has been lauded for the use of ‘cyberspace.’ The concept of ‘cyberspace’ posits the notion of disembodiment, which postulates the probable dissolution of the duality between the mind and the body and the subsequent transgression of this binary. It promises a space beyond the mortal flesh, but it also reinstates the power relations that we get to experience in the real world. The novel offers an insight into transgressions of the limitations of the flesh; however, in Gibson’s narrative there seems to be no overcoming the relentless assault of capitalism onto the bodies. In other words, the power relations of the real world are also implicated in the virtual space of
’s characters. This article will look into disembodied labour and how the body of the worker becomes the site that the capitalists manipulate and control for their own profit, and almost always at the expense of the well-being of the worker.
Lung cancer (LC) has high morbidity and fatality rate that can be attributed to its poor diagnostic and monitoring facilities. Hence, there is a need to design advanced detection and monitoring ...systems to facilitate fast, efficient, and early diagnosis. The emerging research on novel nanotechnology-based strategies and conceptual models has made early-stage detection of LC possible by employing magnetic nanoparticles (MNPs) to surmount the barriers of slow diagnostic efficiency. Herein, the emphasis is on the recent advancement of MNP-based detection and monitoring systems for LC diagnosis, and future perspectives in the current scenario are discussed. The integration of MNP-based advanced diagnostic tools (microfluidic chips, artificial intelligence, biosensors, biomarkers detection, machine learning, nanotheranostics, deep learning, and internet of things platform) with conventional ones bronchoscopy, computed tomography scan, positron emission tomography, distant metastases, transthoracic biopsy, and magnetic resonance imaging might help to resolve current challenges related to early diagnosis of LC.
With the world transitioning to an online reality and a surge in social media users, detecting online harassment and threats has become more pressing than ever. Gendered cyber-hate causes women ...significant social, psychological, reputational, economic, and political harm. To tackle this problem, we develop a dataset and propose a transformer-based model to classify tweets into threats or non-threats that are either sexist or non-sexist. We have developed a model to identify sexist and non-sexist threats from a collection of sexist, non-sexist tweets. BREE-HD performs extraordinarily well with an accuracy of 97% when trained on the dataset we developed to detect threats from a collection of derogatory tweets. To provide insight into how BREE-HD makes classifications, we apply explainable A.I. (XAI) concepts to provide a detailed qualitative analysis of our proposed methodology. As an extension of our work, BREE-HD could be used as a part of a system that could detect threats targeting people specifically tailored to classify them in real-time adequately.
In an era of Anthropocene, habitat loss and species extinction due to anthropogenic factors, and the upsurge in animal exploitation force us to reconsider the “animal question” and relationships ...between humans and animals. All forms of animal abuse violate the subjectivity of the animals by othering them as objects who are mercilessly exploited. Purportedly influenced by the social consciousness of the moral rights of animals and the animal advocacy movement, Sara Gruen’s novel “Water for Elephants” (2006), exposes the horrible reality of animals being mistreated for entertainment in the circus industry through a fictitious description of the events in the Benzini Brothers’ Shows. The framework of this research is based on two arguments: the crucial link between human insensitivity or empathy erosion and animal abuse; and the significance of empathy, in particular, “entangled empathy”, in acknowledging animals as moral subjects, taking care of them, and creating the harmonious human-animal relationship in the novel.
Occupation was assessed as possible risk factors for prostate (PCa) and pancreatic cancer in a large Canadian worker cohort.
The Canadian Census Health and Environment Cohort (CanCHEC) was derived ...from linking the 1991 Canadian Census Cohort to the Canadian Cancer Database (1969-2010), Canadian Mortality Database (1991-2011), and Tax Summary Files (1981-2011). From the total sample of 1,931,110 persons, we identified and derived two samples of 28,610 men and 3,220 men and women with a past history of PCa and pancreatic cancer diagnoses, respectively. Cox proportional hazards models were used to estimate hazards ratios and 95% confidence intervals for occupation.
In Canadian men aged 24-64 years, the highest elevated risks of PCa were observed for library clerks (HR = 2.36, 95% CI:1.12-4.97), medical radiation technologists (HR = 1.66, 95% CI:1.04-2.65), telecommunications and line cable workers (HR = 1.62, 95% CI: 1.22-3.16) and commissioned police officers (HR = 1.54, 95% CI: 1.10-2.16. The highest elevated risk for pancreatic cancer were observed for commissioned police officers (HR = 4.34, 95% CI: 1.85-10.21), photographic and film processors (HR = 3.97, 95% CI:1.69-9.34), railway and motor transport labourers (HR = 3.94, 95% CI: 1.67-9.29), and computer engineers (HR = 3.82, 95%CI: 1.52-9.61).
These findings emphasize the need for further study of job-related exposures and the potential influence of non-occupational factors such as screening practices.
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