Electrostatic

Poetry by MD MUJIB ULLA

World Literature, Neoliberalism, and the Culture of Discontent eds. Sharae Deckard and Stephen Shapiro: Cham, Switzerland: Palgrave Macmillan, 2019, Hardback, £ 79.99.

With the rise of far-right nationalism and at the edge of centre-left reformism, neoliberalism has been under severe scrutiny in regards not only to the world-system but also in the cultural atmosphere in recent times

Clinical Applications of RNA Editing Technology for the Early Detection of Cancer and Future Directions

Early detection of cancer has great clinical importance and potentially improves cure, survival rate and treatment outcome. RNA editing technology can be used as targeted and precise molecular scissors to cut and replace disease-causing genes with healthy ones. This is a post transcriptional modification that can lead to the recoding of proteins. RNA editing technology is in its infancy, but it can be used for early diagnoses and effective treatment of cancer. The full potential of precision medicine will be achieved by using the knowledge of RNA reversible-recoding to edit the protein. RNA editing technology could be used to expose chemo resistant cancer cells, dormant cancer stem cells and other malignant tumors. RNA editing generates RNA and protein diversity to accelerate and enhance the screening window for early detection of cancer. We propose that the RNA editing sites could be used as a novel tool for early detection of cancer.Fil: Mujib, Ullah. University of Stanford; Estados UnidosFil: Asma, Akbar. University of Stanford; Estados UnidosFil: Yannarelli, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Heat shock protein 20 promotes sirtuin 1-dependent cell proliferation in induced pluripotent stem cells

Background: Heat shock proteins (HSPs) are molecular chaperones that protect cells against cellular stresses or injury. However, it has been increasingly recognized that they also play crucial roles in regulating fundamental cellular processes. HSP20 has been implicated in cell proliferation, but conflicting studies have shown that it can either promote or suppress proliferation. The underlying mechanisms by which HSP20 regulates cell proliferation and pluripotency remain unexplored. While the effect of HSP20 on cell proliferation has been recognized, its role in inducing pluripotency in human-induced pluripotent stem cells (iPSCs) has not been addressed. AIM To evaluate the efficacy of HSP20 overexpression in human iPSCs and evaluate the ability to promote cell proliferation. The purpose of this study was to investigate whether overexpression of HSP20 in iPSCs can increase pluripotency and regeneration. Methods: We used iPSCs, which retain their potential for cell proliferation. HSP20 overexpression effectively enhanced cell proliferation and pluripotency. Overexpression of HSP20 in iPSCs was characterized by immunocytochemistry staining and realtime polymerase chain reaction. We also used cell culture, cell counting, western blotting, and flow cytometry analyses to validate HSP20 overexpression and its mechanism. Results: This study demonstrated that overexpression of HSP20 can increase the pluripotency in iPSCs. Furthermore, by overexpressing HSP20 in iPSCs, we showed that HSP20 upregulated proliferation markers, induced pluripotent genes, and drove cell proliferation in a sirtuin 1 (SIRT1)-dependent manner. These data have practical applications in the field of stem cell-based therapies where the mass expansion of cells is needed to generate large quantities of stem cell-derived cells for transplantation purposes. Conclusion: We found that the overexpression of HSP20 enhanced the proliferation of iPSCs in a SIRT1-dependent manner. Herein, we established the distinct crosstalk between HSP20 and SIRT1 in regulating cell proliferation and pluripotency. Our study provides novel insights into the mechanisms controlling cell proliferation that can potentially be exploited to improve the expansion and pluripotency of human iPSCs for cell transplantation therapies. These results suggest that iPSCs overexpressing HSP20 exert regenerative and proliferative effects and may have the potential to improve clinical outcomes.Fil: Ullah, Mujib. University of Stanford; Estados UnidosFil: Qian, Nicole Pek Min. University of Stanford; Estados UnidosFil: Yannarelli, Gustavo Gabriel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Akbar, Asma. University of Stanford; Estados Unido

Explainable Malware Detection System Using Transformers-Based Transfer Learning and Multi-Model Visual Representation

Android has become the leading mobile ecosystem because of its accessibility and adaptability. It has also become the primary target of widespread malicious apps. This situation needs the immediate implementation of an effective malware detection system. In this study, an explainable malware detection system was proposed using transfer learning and malware visual features. For effective malware detection, our technique leverages both textual and visual features. First, a pre-trained model called the Bidirectional Encoder Representations from Transformers (BERT) model was designed to extract the trained textual features. Second, the malware-to-image conversion algorithm was proposed to transform the network byte streams into a visual representation. In addition, the FAST (Features from Accelerated Segment Test) extractor and BRIEF (Binary Robust Independent Elementary Features) descriptor were used to efficiently extract and mark important features. Third, the trained and texture features were combined and balanced using the Synthetic Minority Over-Sampling (SMOTE) method; then, the CNN network was used to mine the deep features. The balanced features were then input into the ensemble model for efficient malware classification and detection. The proposed method was analyzed extensively using two public datasets, CICMalDroid 2020 and CIC-InvesAndMal2019. To explain and validate the proposed methodology, an interpretable artificial intelligence (AI) experiment was conducted

Stem cell-derived extracellular vesicles: role in oncogenic processes, bioengineering potential, and technical challenges

Extracellular vesicles (EVs) are cellular-derived versatile transporters with a specialized property for trafficking a variety of cargo, including metabolites, growth factors, cytokines, proteins, lipids, and nucleic acids, throughout the microenvironment. EVs can act in a paracrine manner to facilitate communication between cells as well as modulate immune, inflammatory, regenerative, and remodeling processes. Of particular interest is the emerging association between EVs and stem cells, given their ability to integrate complex inputs for facilitating cellular migration to the sites of tissue injury. Additionally, stem cell-derived EVs can also act in an autocrine manner to influence stem cell proliferation, mobilization, differentiation, and self-renewal. Hence, it has been postulated that stem cells and EVs may work synergistically in the process of tissue repair and that dysregulation of EVs may cause a loss of homeostasis in the microenvironment leading to disease. By harnessing the property of EVs for delivery of small molecules, stem cell-derived EVs possess significant potential as a platform for developing bioengineering approaches for next-generation cancer therapies and targeted drug delivery methods. Although one of the main challenges of clinical cancer treatment remains a lack of specificity for the delivery of effective treatment options, EVs can be modified via genetic, biochemical, or synthetic methods for enhanced targeting ability of chemotherapeutic agents in promoting tumor regression. Here, we summarize recent research on the bioengineering potential of EV-based cancer therapies. A comprehensive understanding of EV modification may provide a novel strategy for cancer therapy and for the utilization of EVs in the targeting of oncogenic processes. Furthermore, innovative and emerging new technologies are shifting the paradigm and playing pivotal roles by continually expanding novel methods and materials for synthetic processes involved in the bioengineering of EVs for enhanced precision therapeutics

Cancer cells enter dormancy after cannibalizing mesenchymal stem/stromal cells (MSCs)

Patients with breast cancer often develop malignant regrowth of residual drug-resistant dormant tumor cells years after primary treatment, a process defined as cancer relapse. Deciphering the causal basis of tumor dormancy therefore has obvious therapeutic significance. Because cancer cell behavior is strongly influenced by stromal cells, particularly the mesenchymal stem/stromal cells (MSCs) that are actively recruited into tumor-associated stroma, we assessed the impact of MSCs on breast cancer cell (BCC) dormancy. Using 3D cocultures to mimic the cellular interactions of an emerging tumor niche, we observed that MSCs sequentially surrounded the BCCs, promoted formation of cancer spheroids, and then were internalized/degraded through a process resembling the well-documented yet ill-defined clinical phenomenon of cancer cell cannibalism. This suspected feeding behavior was less appreciable in the presence of a rho kinase inhibitor and in 2D monolayer cocultures. Notably, cannibalism of MSCs enhanced survival of BCCs deprived of nutrients but suppressed their tumorigenicity, together suggesting the cancer cells entered dormancy. Transcriptome profiles revealed that the resulting BCCs acquired a unique molecular signature enriched in prosurvival factors and tumor suppressors, as well as inflammatory mediators that demarcate the secretome of senescent cells, also referred to as the senescence-associated secretory phenotype. Overall, our results provide intriguing evidence that cancer cells under duress enter dormancy after cannibalizing MSCs. Importantly, our practical 3D coculture model could provide a valuable tool to understand the antitumor activity of MSCs and cell cannibalism further, and therefore open new therapeutic avenues for the prevention of cancer recurrence

Molekulare Charakterisierung der Differenzierung humaner mesenchymaler Stammzellen zur Identifizierung von Biomarkern für die Qualitätssicherung in der Stammzelltherapie

Human mesenchymal stem cells (MSC) are promising candidates for regenerative medicine. Obviously, for practical and regulatory issues, knowledge of transdifferentiation (conversion of one lineage cells into another), new biomarkers characterizing MSC and their differentiated progeny could be crucial. However, after differentiation, whether stem cells increase or decrease their potency and stemness abilities, and whether transdifferentiation proceeds via a direct cell-to-cell conversion or needs dedifferentiation, is not adequately answered. Moreover, little is known about MSC and their adipogenic progeny in terms of lineage specific gene filtration, biomarker selection and matrix analysis. To investigate such issues, MSC were differentiated into adipogenic, osteogenic and chondrogenic lineage cells, and then the vital cells were isolated from their differentiated matrix. Subsequently, in different approaches, the isolated cells were used for the experiments of transdifferentiation, identification of new gene and glycan based biomarkers, matrix analysis, and cellular migration. In this work, it is shown that transdifferentiation was successful via dedifferentiation as confirmed by single cell analysis. On molecular level, a fine tuned association of cell cycle arrest (DHCR24, G0S2, MAP2K6, SESN3, RB1) and progression (CCND1, CHEK, HGF, HMGA2, SMAD3, CCPG1, RGS2) genes with transdifferentiation was observed. However, the direct transdifferentiation (without dedifferentiation) of adipogenic lineage cells into osteogenic or chondrogenic resulted in mixed cultures of both lineage cells (adipogenic and new acquiring osteogenic/chondrogenic phenotypes), as confirmed by histology and significantly upregulated gene expression of PPARG, FABP4, SPP1, RUNX2, SOX9, and COL2A1. Beside transdifferentiation, the differentiated cells were screened for the identification of biomarkers. Not only a new method “reverse adipogenesis” for fat marker filtration was established, but also 4 new fat markers APCDD1, CHI3L1, RARRES1, and SEMA3G were identified. Apart from this, glycan based biomarkers were discovered (H6N5F1, H7N6F1, and S1H7N6F1 for MSC; highly expressed levels of biantennary fucosylated and sialylated structures for fat cells). Beside biomarker identification, differentiated cells were analyzed for their secreted matrix. Collagen type I, II and IV filaments were found in the adipogenic matrix. The genetic machinery behind the matrix was identified with a significantly regulated expression of COL4A1, GPC1, GPC4, ITGA7, ICAM3, SDC2, TIMP4, BGN, CLDN11, ITGA2, ITGB1, and LAMA3. Next, the directional cell migration was investigated, and similar migration rates for both, chondrogenically differentiated cells and MSC towards the stimulus of CCL25 chemokine were found. The presented data of transdifferentiation, gene and glycan based biomarkers for identification and tracking of cells, matrix analysis and directional cell migration could be vital for quality assurance in stem cell therapy.Humane mesenchymale Stammzellen sind vielversprechende Kandidaten für Anwendungen in der regenerativen Medizin. Für praktische und regulatorische Fragen ist dabei das Wissen über Transdifferenzierungsprozesse der Zellen (Umwandlung von einer Zelldifferenzierungslinie in ein andere), sowie über neue Biomarker zur Charakterisierung von MSC und deren differenzierten Nachkommen von entscheidender Bedeutung. Jedoch bleibt die Frage, ob Stammzellen ihre Potenz und ihre Stammzellfähigkeiten nach Differenzierungen verlieren oder ob sie diese Merkmale behalten oder sogar verbessern. Weiterhin ist es noch nicht ausreichend beantwortet, ob Transdifferenzierungen über eine direkte Zell-zu-Zell Umwandlung ablaufen oder eine Dedifferenzierung benötigen. Darüber hinaus ist nur wenig über MSC und deren adipogen differenzierte Nachkommen in Bezug auf Linien-spezifische Genfiltration, Biomarker Auswahl und Matrixanalyse bekannt. Um solche Probleme zu untersuchen, wurden MSC in die adipogene, osteogene und chondrogene Richtung differenziert, und anschließend vitale Zellen aus ihrer differenzierten Matrix isoliert. Anschließend wurden die isolierten Zellen in verschiedenen Ansätzen für die Experimente zur Transdifferenzierung, Identifizierung neuer Gen- und Glykan-basierter Biomarker, Matrixanalyse und Zellmigration verwendet. In dieser Arbeit konnte gezeigt werden, dass die Transdifferenzierung über einen Dedifferenzierungsschritt erfolgreich war. Dies konnte durch eine Einzelzellanalyse bestätigt werden. Auf molekularer Ebene konnte eine fein abgestimmte Assoziation der Zellzyklusarrest-spezifischen Gene (DHCR24, G0S2, MAP2K6, SESN3 und RB1) und der Gene der Progression (CCND1, CHEK, HGF, HMGA2, SMAD3, CCPG1 und RGS2) mit der Transdifferenzierung festgestellt werden. Allerdings führte die direkte Transdifferenzierung (ohne Dedifferenzierung) von adipogen differenzierten Zellen in die osteogene oder chondrogene Richtung zu Mischkulturen beider Zelltypen (adipogener und neu entwickelter osteogener/chondrogener Phänotyp), wie durch histologische Färbungen und die deutlich erhöhten Genexpressionen von PPARG, FABP4, SPP1, RUNX2 , SOX9 und COL2A1 bestätigt werden konnte. Neben der Transdifferenzierung wurden die differenzierten Zellen auch zur Identifizierung neuer Biomarker untersucht. Dabei konnte nicht nur eine neue Methode "reverse Adipogenese" für die Fettmarker Filtration etabliert werden, sondern es wurden auch 4 neue Fettmarker APCDD1, CHI3L1, RARRES1 und SEMA3G identifiziert. Abgesehen davon wurden Glykan-basierte Biomarker entdeckt (H6N5F1, H7N6F1 und S1H7N6F1 für MSC; stark exprimierte, biantennär fukosylierte und sialylierte Strukturen für Fettzellen). Neben der Identifizierung der Biomarker erfolgte die Untersuchung der sezernierten Matrix von differenzierten Zellen. In der adipogenen Matrix wurden Filamente von Kollagen Typ I, II und IV gefunden. Bei der Indentifizierung der genetischen Maschinerie hinter der Matrix zeigte die Expression von COL4A1, GPC1, GPC4, ITGA7, ICAM3, SDC2, TIMP4, BGN, CLDN11, ITGA2, ITGB1 und LAMA3 eine signifikante Regulierung. Als nächstes wurde die gerichtete Zellwanderung untersucht und eine ähnliche Migrationsrate für chondrogen differenzierte Zellen und MSC in Richtung des Chemokins CCL25 als Stimulus gefunden. Die gewonnenen Erkenntnisse über die Transdifferenzierung, die Gen- und Glykan-basierten Biomarker zur Identifizierung und Nachverfolgung von Zellen, der Matrix Analyse und der gerichteten Zellwanderung könnten entscheidend für die Qualitätssicherung in der Stammzelltherapie sein

Teaching Creative Writing in Asia

Review of Whetter, Darryl, ed. Teaching Creative Writing in Asia. Routledge, 2022. 228 pages