Biosynthesis and Modulation of Terpenoid Indole Alkaloids in Catharanthus roseus: A Review of Targeting Genes and Secondary Metabolites

The medicinal plant C. roseus synthesizes biologically active alkaloids via the terpenoid indole alkaloid (TIAs) biosynthetic pathway. Most of these alkaloids have high therapeutic value, such as vinblastine and vincristine. Plant signaling components, plant hormones, precursors, growth hormones, prenylated proteins, and transcriptomic factors regulate the complex networks of TIA biosynthesis. For many years, researchers have been evaluating the scientific value of the TIA biosynthetic pathway and its potential in commercial applications for market opportunities. Metabolic engineering has revealed the major blocks in metabolic pathways regulated at the molecular level, unknown structures, metabolites, genes, enzyme expression, and regulatory genes. Conceptually, this information is necessary to create transgenic plants and microorganisms for the commercial production of high-value dimer alkaloids, such as vinca alkaloids, vinblastine, and vincristine In this review, we present current knowledge of the regulatory mechanisms of these components in the C. roseus TIA pathway, from genes to metabolites.

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The critical roles of histone deacetylase 3 in the pathogenesis of solid organ injury

Cell Death and Disease ◽

10.1038/s41419-021-04019-6 ◽

2021 ◽

Vol 12 (8) ◽

Author(s):

Li Ning ◽

Xiong Rui ◽

Wang Bo ◽

Geng Qing

Keyword(s):

Histone Deacetylase ◽

Chromatin Remodeling ◽

Current Knowledge ◽

Organ Injury ◽

Solid Organ ◽

Solid Organ Injury ◽

Histone Deacetylase 3 ◽

Physiological Conditions ◽

Inflammatory Conditions ◽

Therapeutic Value

AbstractHistone deacetylase 3 (HDAC3) plays a crucial role in chromatin remodeling, which, in turn, regulates gene transcription. Hence, HDAC3 has been implicated in various diseases, including ischemic injury, fibrosis, neurodegeneration, infections, and inflammatory conditions. In addition, HDAC3 plays vital roles under physiological conditions by regulating circadian rhythms, metabolism, and development. In this review, we summarize the current knowledge of the physiological functions of HDAC3 and its role in organ injury. We also discuss the therapeutic value of HDAC3 in various diseases.

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Electrospun fibers enhanced the paracrine signaling of mesenchymal stem cells for cartilage regeneration

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02137-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Nurul Dinah Kadir ◽

Zheng Yang ◽

Afizah Hassan ◽

Vinitha Denslin ◽

Eng Hin Lee

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Electrospun Fiber ◽

Cartilage Regeneration ◽

Conditioned Media ◽

Biologically Active ◽

Paracrine Signaling ◽

Therapeutic Value ◽

A Cell ◽

Fiber Sheet

Abstract Background Secretome profiles of mesenchymal stem cells (MSCs) are reflective of their local microenvironments. These biologically active factors exert an impact on the surrounding cells, eliciting regenerative responses that create an opportunity for exploiting MSCs towards a cell-free therapy for cartilage regeneration. The conventional method of culturing MSCs on a tissue culture plate (TCP) does not provide the physiological microenvironment for optimum secretome production. In this study, we explored the potential of electrospun fiber sheets with specific orientation in influencing the MSC secretome production and its therapeutic value in repairing cartilage. Methods Conditioned media (CM) were generated from MSCs cultured either on TCP or electrospun fiber sheets of distinct aligned or random fiber orientation. The paracrine potential of CM in affecting chondrogenic differentiation, migration, proliferation, inflammatory modulation, and survival of MSCs and chondrocytes was assessed. The involvement of FAK and ERK mechanotransduction pathways in modulating MSC secretome were also investigated. Results We showed that conditioned media of MSCs cultured on electrospun fiber sheets compared to that generated from TCP have improved secretome yield and profile, which enhanced the migration and proliferation of MSCs and chondrocytes, promoted MSC chondrogenesis, mitigated inflammation in both MSCs and chondrocytes, as well as protected chondrocytes from apoptosis. Amongst the fiber sheet-generated CM, aligned fiber-generated CM (ACM) was better at promoting cell proliferation and augmenting MSC chondrogenesis, while randomly oriented fiber-generated CM (RCM) was more efficient in mitigating the inflammation assault. FAK and ERK signalings were shown to participate in the modulation of MSC morphology and its secretome production. Conclusions This study demonstrates topographical-dependent MSC paracrine activities and the potential of employing electrospun fiber sheets to improve the MSC secretome for cartilage regeneration.

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NANOTECHNOLOGY PATENT LANDSCAPE 2006

NANO ◽

10.1142/s1793292006000148 ◽

2006 ◽

Vol 01 (02) ◽

pp. 101-113 ◽

Cited By ~ 8

Author(s):

LINDA L. LEE ◽

CASEY K. CHAN ◽

MICHELLE NGIAM ◽

SEERAM RAMAKRISHNA

Keyword(s):

Patent Protection ◽

Current Knowledge ◽

Emerging Technology ◽

Commercial Sector ◽

Systematic Method ◽

Technological Revolution ◽

News Stories ◽

Patent Landscape ◽

Nanotechnology Patent ◽

Commercial Applications

Touted as the technological revolution of the 21st century, nanotechnology has already been the topic of numerous publications, patents and news stories. While the commercial applications of nanotechnology are still relatively few, they are beginning to attract the attention of the commercial sector. For successful commercialization of this emerging technology, patent protection is imperative. Patents are publicly available documents forming a rich repository of current knowledge. By a systematic method of collecting, organizing and analyzing these publicly available documents, valuable information can be distilled about the activities and opportunities within this emerging field. As this field is rapidly progressing, this paper provides a summary of current patent issues in nanotechnology, an overview of nanotechnology patent analyses and the latest update of the current landscape of nanotechnology patents.

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PHARMACEUTICAL POTENTIAL OF LABORATORY GROWN CULTURES OF BLUE-GREEN ALGAE: A COMPREHENSIVE REVIEW AND FUTURE POSSIBILITIES

Journal of Experimental Biology and Agricultural Sciences ◽

10.18006/2021.9(5).543.571 ◽

2021 ◽

Vol 9 (5) ◽

pp. 543-571

Author(s):

Ritu Chauhan ◽

◽

Abhishek Chauhan ◽

Ashutosh Tripathi ◽

Anuj Ranjan ◽

...

Keyword(s):

Green Algae ◽

Bioactive Compounds ◽

Current Knowledge ◽

Biological Activities ◽

Biologically Active ◽

Primary And Secondary Metabolites ◽

Blue Green Algae ◽

Green Algal ◽

Algal Group ◽

Diverse Application

COVID-19 pandemic has taught the world researchers the urgent need for new sources and novel pharmaceuticals not only for existing diseases but also for both seasonal epidemics and future pandemics. Pharmaceutical drug discoveries for the past fifty years depended deeply on the procedure of empirical transmission of a huge number of pure bioactive compounds to provide new leads. The screening of extracts or isolating compounds is a common way to discover novel biologically active molecules. Most of the valuable Blue-Green algal metabolites are concentrated in their biomass. For existence in nature, Blue-Green algae (BGA) secrete and contain various organic substances like proteins, fatty acids, vitamins, pigments, primary and secondary metabolites, and these compounds are explored for potential biological activities such as antibacterial, antifungal, antiviral (including the anti-SARS-CoV-2 virus that causes COVID-19), anticancer, antioxidant, antidiabetic, protease inhibitory activity, anti-inflammatory activity, etc. Due to their diverse application, pharmaceutical companies have shown commercial interest in the Blue-green algal group for the discovery and development of novel molecules to combat deadly diseases for the benefit of society and mankind. The current review paper highlights and discusses the diverse pharmaceutical potential of laboratory-grown cultures of BGA along with comprehensive and current knowledge on bioactive compounds discovered by researchers globally.

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The Flavonoid Biosynthesis Network in Plants

International Journal of Molecular Sciences ◽

10.3390/ijms222312824 ◽

2021 ◽

Vol 22 (23) ◽

pp. 12824

Author(s):

Weixin Liu ◽

Yi Feng ◽

Suhang Yu ◽

Zhengqi Fan ◽

Xinlei Li ◽

...

Keyword(s):

Biosynthetic Pathway ◽

Current Knowledge ◽

Anthocyanin Biosynthesis ◽

Basic Structure ◽

Ring Structure ◽

Flavonoid Biosynthesis ◽

Comprehensive Overview ◽

Flavonoid Biosynthetic Pathway ◽

Intermediate Metabolites ◽

Important Intermediate

Flavonoids are an important class of secondary metabolites widely found in plants, contributing to plant growth and development and having prominent applications in food and medicine. The biosynthesis of flavonoids has long been the focus of intense research in plant biology. Flavonoids are derived from the phenylpropanoid metabolic pathway, and have a basic structure that comprises a C15 benzene ring structure of C6-C3-C6. Over recent decades, a considerable number of studies have been directed at elucidating the mechanisms involved in flavonoid biosynthesis in plants. In this review, we systematically summarize the flavonoid biosynthetic pathway. We further assemble an exhaustive map of flavonoid biosynthesis in plants comprising eight branches (stilbene, aurone, flavone, isoflavone, flavonol, phlobaphene, proanthocyanidin, and anthocyanin biosynthesis) and four important intermediate metabolites (chalcone, flavanone, dihydroflavonol, and leucoanthocyanidin). This review affords a comprehensive overview of the current knowledge regarding flavonoid biosynthesis, and provides the theoretical basis for further elucidating the pathways involved in the biosynthesis of flavonoids, which will aid in better understanding their functions and potential uses.

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Biologically Active and Antimicrobial Peptides from Plants

BioMed Research International ◽

10.1155/2015/102129 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 58

Author(s):

Carlos E. Salas ◽

Jesus A. Badillo-Corona ◽

Guadalupe Ramírez-Sotelo ◽

Carmen Oliver-Salvador

Keyword(s):

Antimicrobial Activity ◽

Potential Application ◽

Bioactive Peptides ◽

Biological Action ◽

Biologically Active ◽

Plant Signaling ◽

Innate Response ◽

Physiological Importance ◽

Target Membrane ◽

Stems And Leaves

Bioactive peptides are part of an innate response elicited by most living forms. In plants, they are produced ubiquitously in roots, seeds, flowers, stems, and leaves, highlighting their physiological importance. While most of the bioactive peptides produced in plants possess microbicide properties, there is evidence that they are also involved in cellular signaling. Structurally, there is an overall similarity when comparing them with those derived from animal or insect sources. The biological action of bioactive peptides initiates with the binding to the target membrane followed in most cases by membrane permeabilization and rupture. Here we present an overview of what is currently known about bioactive peptides from plants, focusing on their antimicrobial activity and their role in the plant signaling network and offering perspectives on their potential application.

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Angiogenesis-Related Functions of Wnt Signaling in Colorectal Carcinogenesis

Cancers ◽

10.3390/cancers12123601 ◽

2020 ◽

Vol 12 (12) ◽

pp. 3601

Author(s):

Aldona Kasprzak

Keyword(s):

Signaling Pathway ◽

Wnt Pathway ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Biologically Active ◽

Colorectal Carcinogenesis ◽

Downstream Signaling ◽

Vegf Family Members ◽

Canonical Wnt ◽

Cell Dissemination

Aberrant activation of the Wnt/Fzd/β-catenin signaling pathway is one of the major molecular mechanisms of colorectal cancer (CRC) development and progression. On the other hand, one of the most common clinical CRC characteristics include high levels of angiogenesis, which is a key event in cancer cell dissemination and distant metastasis. The canonical Wnt/β-catenin downstream signaling regulates the most important pro-angiogenic molecules including vascular endothelial growth factor (VEGF) family members, matrix metalloproteinases (MMPs), and chemokines. Furthermore, mutations of the β-catenin gene associated with nuclear localization of the protein have been mainly detected in microsatellite unstable CRC. Elevated nuclear β-catenin increases the expression of many genes involved in tumor angiogenesis. Factors regulating angiogenesis with the participation of Wnt/β-catenin signaling include different groups of biologically active molecules including Wnt pathway components (e.g., Wnt2, DKK, BCL9 proteins), and non-Wnt pathway factors (e.g., chemoattractant cytokines, enzymatic proteins, and bioactive compounds of plants). Several lines of evidence argue for the use of angiogenesis inhibition in the treatment of CRC. In the context of this paper, components of the Wnt pathway are among the most promising targets for CRC therapy. This review summarizes the current knowledge about the role of the Wnt/Fzd/β-catenin signaling pathway in the process of CRC angiogenesis, aiming to improve the understanding of the mechanisms of metastasis as well as improvements in the management of this cancer.

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Advances in Mast Cell Activation by IL-1 and IL-33 in Sjögren’s Syndrome: Promising Inhibitory Effect of IL-37

International Journal of Molecular Sciences ◽

10.3390/ijms21124297 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4297 ◽

Cited By ~ 1

Author(s):

Pio Conti ◽

Luisa Stellin ◽

Alesssandro Caraffa ◽

Carla E. Gallenga ◽

Rhiannon Ross ◽

...

Keyword(s):

Autoimmune Diseases ◽

Sjögren’S Syndrome ◽

Sjögren's Syndrome ◽

Current Knowledge ◽

Sjogren’S Syndrome ◽

Sjogren's Syndrome ◽

Biologically Active ◽

Mast Cell Activation ◽

Mediators Of Inflammation ◽

Sjögren‘S Syndrome

Sjögren’s syndrome (SS) is a chronic autoimmune inflammatory disease that affects primarily older women and is characterized by irreversible damage of the exocrine glands, including tear (xerophthalmia) and salivary glands (xerostomia). Secretory glands lose their functionality due to the infiltration of immune cells, which produce cytokines and cause inflammation. Primary SS is characterized by dry syndrome with or without systemic commitment in the absence of other pathologies. Secondary SS is accompanied by other autoimmune diseases with high activation of B lymphocytes and the production of autoantibodies, including the rheumatoid factor. Other cells, such as CD4+ T cells and mast cells (MCs), participate in SS inflammation. MCs are ubiquitous, but are primarily located close to blood vessels and nerves and can be activated early in autoimmune diseases to express a wide variety of cytokines and chemokines. In the SS acute phase, MCs react by generating chemical mediators of inflammation, tumor necrosis factor (TNF), and other pro-inflammatory cytokines such as interleukin (IL)-1 and IL-33. IL-33 is the specific ligand for ST2 capable of inducing some adaptive immunity TH2 cytokines but also has pro-inflammatory properties. IL-33 causes impressive pathological changes and inflammatory cell infiltration. IL-1 family members can have paracrine and autocrine effects by exacerbating autoimmune inflammation. IL-37 is an IL-1 family cytokine that binds IL-18Rα receptor and/or Toll-like Receptor (TLR)4, exerting an anti-inflammatory action. IL-37 is a natural inhibitor of innate and acquired immunity, and the level is abnormal in patients with autoimmune disorders. After TLR ligand activation, IL-37 mRNA is generated in the cytoplasm, with the production of pro-IL-37 and later mature IL-37 caspase-1 mediated; both precursor and mature IL-37 are biologically active. Here, we discuss, for the first time, the current knowledge of IL-37 in autoimmune disease SS and propose a new therapeutic role.

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Size Matters: Molecular Weight Specificity of Hyaluronan Effects in Cell Biology

International Journal of Cell Biology ◽

10.1155/2015/563818 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 128

Author(s):

Jaime M. Cyphert ◽

Carol S. Trempus ◽

Stavros Garantziotis

Keyword(s):

Molecular Weight ◽

Cell Biology ◽

Current Knowledge ◽

Fragment Size ◽

Biological Effects ◽

Biologically Active ◽

Molecular Modification ◽

Size Dependent

Hyaluronan signaling properties are unique among other biologically active molecules, that they are apparently not influenced by postsynthetic molecular modification, but by hyaluronan fragment size. This review summarizes the current knowledge about the generation of hyaluronan fragments of different size and size-dependent differences in hyaluronan signaling as well as their downstream biological effects.

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