Browsing by Author "Weiskirchen, Ralf"

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Apoptosis and Pharmacological Therapies for Targeting Thereof for Cancer Therapeutics
(MDPI, 2022-04-08T00:00:00) Singh, Vishakha; Khurana, Amit; Navik, Umashanker; Allawadhi, Prince; Bharani, Kala Kumar; Weiskirchen, Ralf
Apoptosis is an evolutionarily conserved sequential process of cell death to maintain a homeostatic balance between cell formation and cell death. It is a vital process for normal eukaryotic development as it contributes to the renewal of cells and tissues. Further, it plays a crucial role in the elimination of unnecessary cells through phagocytosis and prevents undesirable immune responses. Apoptosis is regulated by a complex signaling mechanism, which is driven by interactions among several protein families such as caspases, inhibitors of apoptosis proteins, B-cell lymphoma 2 (BCL-2) family proteins, and several other proteases such as perforins and granzyme. The signaling pathway consists of both pro-apoptotic and pro-survival members, which stabilize the selection of cellular survival or death. However, any aberration in this pathway can lead to abnormal cell proliferation, ultimately leading to the development of cancer, autoimmune disorders, etc. This review aims to elaborate on apoptotic signaling pathways and mechanisms, interacting members involved in signaling, and how apoptosis is associated with carcinogenesis, along with insights into targeting apoptosis for disease resolution. � 2022 by the authors.
Biomedical applications of polysaccharide nanoparticles for chronic inflammatory disorders: Focus on rheumatoid arthritis, diabetes and organ fibrosis
(Elsevier Ltd, 2021-11-22T00:00:00) Allawadhi, Prince; Singh, Vishakha; Govindaraj, Kannan; Khurana, Isha; Sarode, Lopmudra P.; Navik, Umashanker; Banothu, Anil Kumar; Weiskirchen, Ralf; Bharani, Kala Kumar; Khurana, Amit
Polysaccharides are biopolymers distinguished by their complex secondary structures executing various roles in microorganisms, plants, and animals. They are made up of long monomers of similar type or as a combination of other monomeric chains. Polysaccharides are considered superior as compared to other polymers due to their diversity in charge and size, biodegradability, abundance, bio-compatibility, and less toxicity. These natural polymers are widely used in designing of nanoparticles (NPs) which possess wide applications in therapeutics, diagnostics, delivery and protection of bioactive compounds or drugs. The side chain reactive groups of polysaccharides are advantageous for functionalization with nanoparticle-based conjugates or therapeutic agents such as small molecules, proteins, peptides and nucleic acids. Polysaccharide NPs show excellent pharmacokinetic and drug delivery properties, facilitate improved oral absorption, control the release of drugs, increases in vivo retention capability, targeted delivery, and exert synergistic effects. This review updates the usage of polysaccharides based NPs particularly cellulose, chitosan, hyaluronic acid, alginate, dextran, starch, cyclodextrins, pullulan, and their combinations with promising applications in diabetes, organ fibrosis and arthritis. � 2021 Elsevier Ltd
A comprehensive overview of CRISPR/Cas 9 technology and application thereof in drug discovery
(John Wiley and Sons Inc, 2022-09-21T00:00:00) Khurana, Amit; Sayed, Nilofer; Singh, Vishakha; Khurana, Isha; Allawadhi, Prince; Rawat, Pushkar Singh; Navik, Umashanker; Pasumarthi, Sravan Kumar; Bharani, Kala Kumar; Weiskirchen, Ralf
Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR)-Cas technology possesses revolutionary potential to positively affect various domains of drug discovery. It has initiated a rise in the area of genetic engineering and its advantages range from classical science to translational medicine. These genome editing systems have given a new dimension to our capabilities to alter, detect�and annotate specified gene sequences. Moreover, the ease, robustness�and adaptability of the CRISPR/Cas9 technology have led to its extensive utilization in research areas in such a short period of time. The applications include the development of model cell lines, understanding disease mechanisms, discovering disease targets, developing transgenic animals and plants, and transcriptional modulation. Further, the technology is rapidly growing; hence, an overlook of progressive success is crucial. This review presents the current status of the CRISPR�Cas technology in a tailor-made format from its discovery to several advancements for drug discovery alongwith future trends associated with possibilities and hurdles including ethical concerns. � 2022 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC.
Gene therapy: Comprehensive overview and therapeutic applications
(Elsevier Inc., 2022-02-03T00:00:00) Sayed, Nilofer; Allawadhi, Prince; Khurana, Amit; Singh, Vishakha; Navik, Umashanker; Pasumarthi, Sravan Kumar; Khurana, Isha; Banothu, Anil Kumar; Weiskirchen, Ralf; Bharani, Kala Kumar
Gene therapy is the product of man's quest to eliminate diseases. Gene therapy has three facets namely, gene silencing using siRNA, shRNA and miRNA, gene replacement where the desired gene in the form of plasmids and viral vectors, are directly administered and finally gene editing based therapy where mutations are modified using specific nucleases such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs) and clustered regulatory interspaced short tandem repeats (CRISPR)/CRISPR-associated protein (Cas)-associated nucleases. Transfer of gene is either through transformation where under specific conditions the gene is directly taken up by the bacterial cells, transduction where a bacteriophage is used to transfer the genetic material and lastly transfection that involves forceful delivery of gene using either viral or non-viral vectors. The non-viral transfection methods are subdivided into physical, chemical and biological. The physical methods include electroporation, biolistic, microinjection, laser, elevated temperature, ultrasound and hydrodynamic gene transfer. The chemical methods utilize calcium- phosphate, DAE-dextran, liposomes and nanoparticles for transfection. The biological methods are increasingly using viruses for gene transfer, these viruses could either integrate within the genome of the host cell conferring a stable gene expression, whereas few other non-integrating viruses are episomal and their expression is diluted proportional to the cell division. So far, gene therapy has been wielded in a plethora of diseases. However, coherent and innocuous delivery of genes is among the major hurdles in the use of this promising therapy. Hence this review aims to highlight the current options available for gene transfer along with the advantages and limitations of every method. � 2022
Glucagon-like peptide 1 and fibroblast growth factor-21 in non-alcoholic steatohepatitis: An experimental to clinical perspective
(Academic Press, 2022-09-06T00:00:00) Yadav, Poonam; Khurana, Amit; Bhatti, Jasvinder Singh; Weiskirchen, Ralf; Navik, Umashanker
Non-alcoholic steatohepatitis (NASH) is a progressive form of Non-alcoholic fatty liver disease (NAFLD), which slowly progresses toward cirrhosis and finally leads to the development of hepatocellular carcinoma. Obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome are major risk factors contributing to NAFLD. Targeting these risk factors is a rational option for inhibiting NASH progression. In addition, NASH could be treated with therapies that target the metabolic abnormalities causing disease pathogenesis (such as de novo lipogenesis and insulin resistance) as well with medications targeting downstream processes such as cellular damage, apoptosis, inflammation, and fibrosis. Glucagon-like peptide (GLP-1), is an incretin hormone dysregulated in both experimental and clinical NASH, which triggers many signaling pathways including fibroblast growth factor (FGF) that augments NASH pathogenesis. Growing evidence indicates that GLP-1 in concert with FGF-21 plays crucial roles in the conservation of glucose and lipid homeostasis in metabolic disorders. In line, GLP-1 stimulation improves hepatic ballooning, steatosis, and fibrosis in NASH. A recent clinical trial on NASH patients showed that the upregulation of FGF-21 decreases liver fibrosis and hepatic steatosis, thus improving the pathogenesis of NASH. Hence, therapeutic targeting of the GLP-1/FGF axis could be therapeutically beneficial for the remission of NASH. This review outlines the significance of the GLP-1/FGF-21 axis in experimental and clinical NASH and highlights the activity of modulators targeting this axis as potential salutary agents for the treatment of NASH. � 2022 Elsevier Ltd
Spotlight on liver macrophages for halting liver disease progression and injury
(Taylor and Francis Ltd., 2022-10-07T00:00:00) Khurana, Amit; Navik, Umashanker; Allawadhi, Prince; Yadav, Poonam; Weiskirchen, Ralf
Introduction: Over the past two decades, understanding of hepatic macrophage biology has provided astounding details of their role in the progression and regression of liver diseases. The hepatic macrophages constitute resident macrophages, Kupffer cells, and circulating bone marrow monocyte-derived macrophages, which play a diverse role in liver injury and repair. Imbalance in the macrophage population leads to pathological consequences and is responsible for the initiation and progression of acute and chronic liver injuries. Further, distinct populations of hepatic macrophages and their high heterogeneity make their complex role enigmatic. The unique features of distinct phenotypes of macrophages have provided novel biomarkers for defining the stages of liver diseases. The distinct mechanisms of hepatic macrophages polarization and recruitment have been at the fore front of research. In addition, the secretome of hepatic macrophages and their immune regulation has provided clinically relevant therapeutic targets. Areas covered: Herein, we have highlighted the current understanding in the area of hepatic macrophages, and their role in the progression of liver injury. Expert opinion: It is essential to ascertain the physiological and pathological role of evolutionarily conserved distinct macrophage phenotypes in different liver diseases before viable approaches may see a clinical translation. � 2022 Informa UK Limited, trading as Taylor & Francis Group.