Acute myeloid leukemia (AML) is a type of cancer that affects the blood and bone marrow. This review conducts a thorough analysis of AML, addressing its genetic modification. The examination extends to the current therapeutic approaches employed for AML, shedding light on their efficacy and the notable side effects experienced by patients undergoing these treatments, leading to a low overall survival rate. Therefore, exploring alternative treatments, such as phytochemicals, is necessary. Furthermore, the review explores the complex landscape of phytochemicals, categorizing them based on their diverse properties, which include alkaloids, phenols, terpenoids, organo-sulfur compounds, and other compounds, including quinones, and elucidating their mechanisms of action. Special emphasis is placed on their involvement in critical signaling pathways, with a particular focus on how these phytochemicals impact AML when evaluated across a spectrum of cell lines. This in-depth exploration aims to uncover potential targets within the molecular landscape of AML where phytochemicals can exert their therapeutic effects. The review investigates the potential role of plant-derived phytochemicals as adjunctive therapies for AML. This exploration encompasses the identification of specific phytochemicals that exhibit promising anti-leukemic properties and evaluates their potential in clinical settings. Beyond conventional treatments, the review explores the integration of complementary and alternative medicine as a holistic approach to managing AML. The examination encompasses the synergy between conventional therapies and alternative interventions, exploring how these combined strategies may enhance overall therapeutic outcomes and mitigate side effects. From a forward-looking perspective, the overarching goal is to contribute to the evolving landscape of AML treatment by considering innovative approaches that harness the therapeutic potential of phytochemicals, both independently and in conjunction with established medical interventions.
Proteins possessing double active sites have the potential to revolutionise enzyme design strategies. This study extensively explored an enzyme that contains both a natural active site (NAS) and an engineered active site (EAS), focusing on understanding its structural and functional properties. Metadynamics simulations were employed to investigate how substrates interacted with their respective active sites. The results revealed that both the NAS and EAS exhibited similar minimum energy states, indicating comparable binding affinities. However, it became apparent that the EAS had a weaker binding site for the substrate due to its smaller pocket and constrained conformation. Interestingly, the EAS also displayed dynamic behaviour, with the substrate observed to move outside the pocket, suggesting the possibility of substrate translocation. To gain further insights, steered molecular dynamics (SMD) simulations were conducted to study the conformational changes of the substrate and its interactions with catalytic residues. Notably, the substrate adopted distinct conformations, including near-attack conformations, in both the EAS and NAS. Nevertheless, the NAS demonstrated superior binding minima for the substrate compared to the EAS, reinforcing the observation that the engineered active site was less favourable for substrate binding due to its limitations. The QM/MM (Quantum mechanics and molecular mechanics) analyses highlight the energy disparity between NAS and EAS. Specifically, EAS exhibited elevated energy levels due to its engineered active site being located on the surface. This positioning exposes the substrate to solvents and water molecules, adding to the energy challenge. Consequently, the engineered enzyme did not provide a significant advantage in substrate binding over the single active site protein. Further, the investigation of internal channels and tunnels within the protein shed light on the pathways facilitating transport between the two active sites. By unravelling the complex dynamics and functional characteristics of this double-active site protein, this study offers valuable insights into novel strategies of enzyme engineering. These findings establish a solid foundation for future research endeavours aimed at harnessing the potential of double-active site proteins in diverse biotechnological applications.
A chronic condition of glucose metabolism known as diabetes mellitus (DM) is defined by uncontrolled hyperglycemia brought on by the body's decreased capacity to either create or react to insulin. Due to its yearly role in 11.2% of global fatalities, DM is sometimes referred to as a silent killer. DM is one of the most common diseases of metabolism. The prevalence of both type 1 and type 2 DM is rising, making it a worldwide epidemic. Diabetes that is not well controlled can have serious life-threatening effects. The most widely used method of treating diabetes to restore the destroyed pancreatic beta-cells is islet transplantation, along with insulin and oral antidiabetic drugs. Doctors are using cell treatments that combine adult mesenchymal stem cells (MSCs), human pluripotent stem cells (hPSCs), and embryonic stem cells (ESCs) to benefit patients. One example of ESCs' practically limitless plasticity is their development into beta-cells, which make insulin. It is difficult to apply this treatment broadly because to a lack of donors. An alternate source of beta-cells for transplantation is hPSCs, which include ESCs, pancreatic stem cells, and MSCs. Despite significant progress over the past 20 years that resulted in the development of pancreatic beta-like stem cells that have much more characteristics with real pancreatic beta-cells, it is still difficult to produce completely mature pancreatic beta-cells. In this chapter, we go through the most recent techniques for differentiating beta-cells and emphasize difficulties with beta cell maturation. The difficulties and possibilities presented by monogenic types of diabetes are discussed. We conclude by talking about the challenges that still exist in using beta-cells created from stem cells for therapeutic purposes as well as the current state of ongoing clinical studies.
Stem cells are the group of cells that has the potential of differentiating into any type of cells. Recent decades have witnessed the application of stem cells in medicine and therapies. The very discovery led to the need for detailed study and exploration of types of stem cells. Some organs are considered to not have stem cells post organogenesis and kidney is considered to be one among them. But recent studies have thrown light on renal stem cells and the ease of kidney regeneration. Wilms tumor, a nephroblastoma found in children have a lot of active pathways, which are also common in renal stem cells and renal organogenesis: the blastemal-cells, mesenchymal stem cells, Wilms tumor suppressor 1, catenin beta-1, sine oculis-related homeobox 2, wingless-related integration site signaling pathway, and microRNA processing pathway. The current chapter gives an idea about the common signaling pathways and genes involved in renal stem cells and nephroblastoma with Wilms tumor as the referral prototype, aspiring for the understanding of link between the genes, signaling pathways and molecules involved in renal development and nephroblastoma.
The physiological and clinical relevance of the phospholipases enzyme family has been extensively researched. Phospholipases catalyze the hydrolysis of phospholipids, which results in the generation of secondary messengers that play an important part in signal transmission. Phospholipases are divided into different groups, based on their expression and physiologic functions; these include cardiolipin biosynthesis regulation, cardioprotection during oxidative stress, and cognitive development. Phospholipase C (PLC) isoforms are involved in tissue-specific signaling and are triggered by a variety of signaling receptors, including G-protein coupled receptors and tyrosine kinase receptors. The PLC isoform plays a key role in the phosphatidylinositol pathway, in which G-protein activates PLC, which catalyzes the conversion of PIP2 to IP3 and 1, 2-DAG. IP3 and DAG are secondary messengers that are involved in the regulation of cytosolic Ca++ ions and activation of protein kinase (PKC), respectively, which regulate the glycogen metabolism. On the other hand, PLC activated via tyrosine kinase receptor modulates the signal transduction in immune cells by promoting the transcription of genes required for immune response. Furthermore, PLC-γ-1 is abundant in the brain, and plays a role in regulating neurite outgrowth, neuronal cell migration, and postsynaptic signal transduction via PI3/DAG signaling cascade. In vitro and in vivo studies conducted on transgenic mouse showed that PKC activation directs the production of neuroprotective substances and inhibits the production and accumulation of neurotoxic amyloid proteins in AD. Furthermore, PKC is categorized as one of the cognitive kinases controlling memory and learning. Nevertheless, the role of PLC isoform in cognitive development and mechanism is still unclear. In this chapter, we focus on the pathophysiology of neurodegenerative disorders, metabolic dysfunction, and inflammatory diseases by dissecting out the tissue-specific signal transduction by PLC isoform.
Cancer drugs fail in clinical trials at a rate of more than 90% due to infiltration of myofibroblast, fibroblast, and an increase in collagen, resulting in a poor prognosis. Cancer tissues have a tumor microenvironment (TME) that is made up of cancerous and noncancerous cells, growth factors, extracellular matrix (ECM), and other substances. Tumor cells' ECM is constantly remodeled to increase stiffness, survival, proliferation, and immunosuppression. Most of the studies involve cellular models in vitro, which many a times are grown as 2D cultures. Many features are lost in vitro because of continuous ECM remodeling. To overcome this, decellularized scaffolds known as decellularized tumor ECM (dt-ECM) are used, which retain composition as well as mechanical structure. They have the potential to be a very useful tool in understanding cancer progression and formation. One of the powerful approaches to understand diseases is tissue engineering, which is a culmination cell biology, developmental biology, nanobiotechnology, material science, and related fields. Tissue engineering assists researchers in producing engineered and functional cells that will give rise to tissues, which might then go on to become organs. Engineered tissues and organoids (miniature forms) are used in drug development, screening, and disease modeling. The 3D tissue model is useful in understanding various diseases. Organoids are miniature versions of organs that are used to reduce animal usage and to develop body-on-a-chip or organ-on-a-chip. They can help to support tumor heterogeneity, which will aid in personalized medicine and reduce the likelihood of drug failure. While growing cells to 3D tissues is quite interesting, finding the right type of scaffolds is equally important, which might play major role in cell adhesion, cell motility, cell differentiation, etc. Alginate with RGD and other biomaterials, for example, has been a major focus due to important properties demonstrated by alginate that aid in cancer research. Since 3D engineered organs and tissues require an environment similar to in vivo, advanced bioreactors are being developed. Tissue-engineered organs will aid in drug screening, development of more effective drugs, and, most importantly, understanding of cancer. Recently, the use of microfluidics system which is combination of microelectronics and TE looks very promising; it offers more advantages than 3D and 2D culture. It comes with various application like study of metastasis cancer which is main causative of cancer death across the world. Integration of nanotechnology in TE helps in building new biomaterials which have shown enhanced cell adhesion and various other properties. There are various 3D models which have been developed to study and understand different types of cancer.
Background:Infertility can have a significant impact on the identity of women. Individual women, who are infertile, experience tragic emotions, as well as those who are sad for great losses, like the death of a loved one. In this case, the woman is experiencing the loss of the ability to procreate. Aim:In the present study, our major concern was to implement the health-related quality of life (HRQOL) Questionnaire on South Indian polycystic ovarian syndrome (PCOS) women to assess the impact of various clinical features of polycystic ovary syndrome on the HRQOL of South Indian women diagnosed. Settings and Design:A total of 126 females in the first phase and 356 females in the second phase between the age group of 18-40 years characterised under the Rotterdam criteria were selected for the study. Materials and Methods:The study was carried out in three different phases which included a one-to-one interview, group discussion and questionnaire session. In our study, we found that all the females who attend the study showed positivity for all the domains developed in the previous study and suggested that further domain can be developed. Statistical Analysis Used:Suitable statistical methods were used with Graph pad PRISM (version 6). Results:Hence, in our study, we developed a further new sixth domain called as 'social impact domain'. Among South Indian PCOS women, we found that infertility and social issue have the most significant impact on HRQOL. Conclusion:The revised questionnaire by including the sixth domain called 'Social issue' is likely to be useful in measuring the quality of health of female having PCOS in regard to South Indian population.
Cancer has been a complex disease, and for many decades, research has been going on for designing a novel strategy for the cure and successful treatment; promising results and efforts are required. Although remarkable progress has been made in cancer medicine research concerning more efficient, specific, and less invasive modalities of cancer treatments recently, currently targeted therapy is one of the approaches aimed at targeting a particular location linked to cancer, such as tumor microenvironment or intracellular organelles, without affecting its normal surrounding and therefore benefits by increasing the specificity of the treatment. Targeted therapies are now one of the most promising therapies and have been embarking on their importance in oncological research and clinical oncology due to the revolution in the treatment of cancer in terms of diagnosis and the use of sophisticated diagnostic and molecular characterization technologies due to the advent of targeted therapy and immunotherapy. The advantage of targeted therapies is that it promotes effective dendritic cell (DC) maturation, T cell priming, activation, and differentiation into memory T cells that are long-lived, and thereby suggest combining cancer vaccinesCancer vaccines along with targeted therapies for boosted immune response and functioning of effector T cell. In this chapter, aspects of immunotherapy as a strategy for cancer therapy will be reviewed by analyzing the different approaches of immunotherapy and the upcoming promising therapies for cancer generally as well as for specific cancers while attempting to understand the latest developments in using immunotherapy as a novel strategy for cancer cure.
Cancer is the most deadly disease that causes death. Most likely, cancer is a problem in developed nations, with liver cancer coming in third in terms of mortality rates globally. Other than breast cancer, which is ranked fourth in the world, ovarian cancerOvarian Cancer is the most dangerous cancer in terms of maternal cancer. Ovarian cancerOvarian Cancer which is epithelial ovarian cancerEpithelial Ovarian cancer (EOC) accounts for 90% of cases. Hox genesHomeobox (Hox) genes are typically expressed during organogenesis, but HOXA9 and HOXA11 are responsible for and involved in the molecular pathway of ovarian cancerOvarian Cancer. Ovarian cancerOvarian Cancer has many genes involved in the molecular pathway, and it can validate ovarian cancerOvarian Cancer treatment and therapies. In this current study, we examined bioinformatics resources for ovarian cancerOvarian Cancer biomarker validation for ovarian cancerOvarian Cancer therapies. In ovarian cancerOvarian Cancer, the genes CREB1, CD38, SIRTs, TP53, WT1Wilms tumour gene (WT1), many miRNAs, etc., play novel biomarker roles and can be validated for ovarian cancerOvarian Cancer treatment. Many ovarian cancerOvarian Cancer biomarkers are reviewed and validated through bioinformatics tools. Different genes were discovered and validated using GEO and common DEGsDifferentially expressed genes (DEGs) through cBioPortalCBio Cancer Genomics Portal (cBioPortal), KEGGKEGG, functional enrichment analysis, PPI, and oncomineONCOMINE along with immunohistology. Many hub genes were found and reviewed using common DEGsDifferentially expressed genes (DEGs) and GEO.
Cardiovascular diseasesCardiovascular diseases are a worldwide issue, accounting for a significant number of deaths each year. Various types of prostheses made of synthetic textile fibers were initially used to treat cardiovascular diseases but were later abandoned. This is because it was found that the degradation of the implantation causes some of the polymers to lose mechanical strength. These polymers would also pollute the environment significantly. It became crucial to create a biomaterialBiomaterials that would be stable for a longer time while generating little to no pollution as a result. As collagenCollagen defines the majority of tissues, it is extensively used in cardiac tissue engineeringTissue engineering and regeneration. Collagen networks are typically highly organized three-dimensional structures that entrap other materials. This chapter will discuss various methods for using collagenCollagen-based biomaterials in treating cardiovascular diseasesCardiovascular diseases, both existing and in development.
Myocardial infarction, more often known as cardiac arrest, occurs when the supply of blood to the heart’s coronary artery decreases or ceases, causing damage to the heart muscle. Xyloglucan is a plant polysaccharide. Xyloglucan has been proven in several studies utilizing model organisms to reduce the risk of coronary heart disease by avoiding post-occlusion phases inhibiting apoptosis and enhancing energy metabolism. Many studies utilize Drosophila melanogaster because its SRY-related HMG-box 5 (SOX5) gene encodes a SOX family transcription factor; the human SOX5 ortholog, Sox102F, is well conserved in Drosophila melanogaster. Suppressing Sox102F in flies resulted in significant heart dysfunction, structural defects, and a disturbance in notch signal transduction. This demonstrates that SOX5 serves an important functional part in the heart and that variations in SOX5 concentrations may contribute to the possibility of myocardial infarction. Xyloglucan activity is significant in myocardial infarction and may be lowered in the myocardium after H/R damage by stimulating Notch signaling, which may benefit myocardial survival, angiogenesis, and cardiac function. This review discusses the roles of the human SOX5 and Drosophila SOX102F genes, the notch signaling system, and how xyloglucan in tamarind seeds may defend against heart damage by preventing apoptosis along with improving energy metabolism.
There is a shred of evidence to suggest that Emblica officinalis Gaertn, the botanical name for amla seeds, has greater medicinal potential than amla fruit. We conducted this work to assess the anti-inflammatory, antibacterial, and antioxidant capacities of E. officinalis seed extracts. The bioactive components from the seeds were fractionated using chloroform, hexane, methanol, and diethyl ether, according to the polarity of the solvents. The total amount of phenolic and flavonoid was estimated. Both the reducing power and antioxidant capacities of the extracts were evaluated using the DPPH (1,1-diphenyl-2-picryl-hydrazyl) technique. 15-lipoxygenase (LOX) was inhibited by seed extracts at doses ranging from 5 to 25 micrograms. In silico docking was employed to assess the results. Some human pathogenic microorganisms were tested for their antibacterial activity using the agar disc diffusion method. Escherichia coli, Proteus vulgaris, and Klebsiella pneumonia were inhibited by a methanolic extract with an IC50 value of 58g, making it the most common organic solvent extract. Methanolic extracts also showed good antioxidant and antibacterial activity. Our investigation led us to discover that amla seeds have anti-inflammatory, antioxidant, and antibacterial effects.
Allium sativum commonly known as Garlic is a familiar herb, highly studied for its valuable medicinal properties. The main objective involved in the current research is to analyze inhibitor and antibacterial action of bioactive compounds (ligands) present in the methanolic extract of Allium sativum bulbs against phytopathogen protein (receptor) through molecular docking. The effector protein AvrRps4 (4B6X) from phytopathogen Pseudomonas syringae pv. pisi, a protein responsible for Effector triggered immunity (ETI) activation and to subvert host responses in Pea plant was selected as protein target. The docking interactions between opted ligands and target protein, with ampicillin as control was done using PyRx software tool and analysed using Discovery studio 3.1 Visualiser. The outcomes obtained from in silico analysis suggested that the bioactive compound namely Diethyl 3-methyl-5-[(2,2,2-trifluoroacetyl)amino]thiophene-2,4-dicarboxylate bind effectively showing-5.7 binding energy value in comparison with antibiotic ampicillin which showed binding energy-5.8 value. This research study concluded that the bioactive compounds from methanolic extract of Allium sativum bulbs displayed a potential inhibitory activity against effector AvrRps4 protein exhibiting antibacterial properties and may be considered as possible substantial lead molecules in future prospects.
Taro (Colocasia esculenta) has been reported to have 70-80% of starch which could play a vital role as a disintegrating agent in pharmaceutical tablet formulation.The purpose of the study was to extract and evaluate the starch from Taro (Colocasia esculenta), as well as to use taro starch as a disintegrating agent in tablet formulation.In this study starch was extracted from Taro by simple, wet milling and centrifugation process and physiochemical tests of the extract revealed that the starch extracted from wet milling showed better properties, while rendering no harm to the chemical composition of the extract which was then was used to formulate twenty placebo tablets by using direct compression, wet granulation as well as dry granulation for comparison study.The formulated tablets were evaluated by its hardness, friability, weight variation, solubility and disintegration time.Results from disintegration efficiency study showed that the tablets formulated from Taro starch disintegrated in 3 minutes out of which tablets