JAK-STAT pathway: Testicular development, spermatogenesis and fertility
Rajender Singh in Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Ligand molecules are the extracellular molecules that cannot cross the membrane but through ligand-receptor interaction have the potential to activate an intracellular cell signaling cascade. Initially, the JAK-STAT pathway was discovered by interferon (IFN)-induced intracellular signaling. But later, a large number of cytokines, interferons and growth hormones were known to induce JAK-STAT signaling. In mammals, these ligand molecules are classified into various families depending on their structural and functional characteristics (10) (Table 15.3). In Drosophila, Upd is the only known ligand molecule for inducing JAK-STAT signaling. The unpaired gene encodes a 47 kDa secretory glycoprotein, localized to an extracellular matrix (ECM) (16). While curating a Drosophila database, other Upd-like genes have also been identified, such as Upd2 (19) and Upd3 (17).
Magnesium
Linda M. Castell, Samantha J. Stear (Nottingham), Louise M. Burke in Nutritional Supplements in Sport, Exercise and Health, 2015
Magnesium (Mg) is an essential biological element which is predominantly located in bones (approx. 52%), in muscle cells (28%), soft tissue (19%), serum (0.3%; concentration range 0.75–1.1 mmol/l) and red blood cells (0.5%). Serum acts as a transit pathway between bone stores and actively metabolising tissues and is not representative of the body’s Mg status. Intracellular Mg is under hormonal control in some cell types and regulated by a secondary active transport system, the Na+-Mg2+-exchanger. In both extra- and intra-cellular compartments, an equilibrium between ionized Mg2+ and bound Mg is established. Only Mg2+ is available to react in physiological and biochemical processes during cellular homeostasis by binding to organic substances, such as proteins, nucleic acids and nucleotides. In general, Mg2+ is an important regulator of three main complexes: 1) enzyme activation, e.g. during energy metabolism, 2) stabilizing membrane function and integrity, and 3) cell signalling, e.g. as a natural antagonist of intracellular calcium signals (Mooren et al., 2011). Regarding energy metabolism, Mg has been shown to be involved at several steps. At the insulin receptor level Mg enhances the cell’s sensitivity towards an insulin stimulus thereby facilitating cellular glucose entry. Furthermore, Mg is an important cofactor of ATP generation at the inner mitochondrial membrane while Mg depletion seems to induce mitochondrial dysfunction.
Phytochemicals: Some Basics
Scott Mendelson in Herbal Treatment of Major Depression, 2019
Flavonoids are major contributors to the medicinal effects of herbs. These molecules tend to exhibit strong antioxidant effects. A number of them have been shown to have anti-inflammatory and antidiabetic effects, as well as affecting important cell signaling pathways in neurons that can be important in the treatment of mood disorders.15 A variety of flavonoids, such as the common quercetin, activate the PI3K and MAPK pathways that in turn result in inactivation of GSK-3β and activations of mTOR and BDNF.16 Some, such as quercetin and apigenin, have potent nanomolar and low micromolar abilities to inhibit monoamine oxidase.17 In preclinical studies, many isolated and purified flavonoids have been found to exhibit antidepressant effects.
Emerging molecular target antagonists for the treatment of biliary tract cancer
Published in Expert Opinion on Emerging Drugs, 2018
Pasquale Lombardi, Donatella Marino, Elisabetta Fenocchio, Giovanna Chilà, Massimo Aglietta, Francesco Leone
α-SMA positive CAFs are involved in cancer progression through production of matricellular proteins, growth factors, chemokines, and matrix metalloproteinases. Patients expressing high levels of α-SMA have poorer survival [93]. The desmoplastic matrix also allows the development of a niche fostering tumor spread rather than as a response to the anticancer treatments [94]. Transforming growth factor β (TGF- β) seems to be implicated in the generation of the niche. Indeed, preclinical models have demonstrated a reduction in fibrosis and tumor spread with TGF-β antagonist [95].CAFs produce numerous factors involved in autocrine and paracrine signaling that promote oncogenic processes like periostin, tenascin-c, thrombospandin 1, stromal cell-derived factor 1 (SDF-1), HGF and Wnt inducible signaling protein-1v (WISP1) [93]. These interact with cell signaling pathways. For example, periostin interacts with tenascin-C, HGF and SDF-1, which bind to their respective receptors, integrin, MET, and CXCR4 on CCA cells, leading to activation of the PIK3CA/AKT signaling pathway.
Improving cellular uptake of therapeutic entities through interaction with components of cell membrane
Published in Drug Delivery, 2019
Renshuai Zhang, Xiaofei Qin, Fandong Kong, Pengwei Chen, Guojun Pan
Proteins are the second major components of cell membranes and some of them can mediate cellular uptake termed also receptor-mediated uptake in general describing. In order to profound the understanding of key role of trans-membrane proteins in mediated drug delivery, they were divided into two categories, transporters and receptors in this review. For instance, some trans-membrane proteins are transporters that carry small molecules (e.g. glucose) into the cell. Some other proteins are known as receptors to mediate the cell signaling pathway for growth and proliferation. For transporters, they maintained the normal metabolism of cells via transferring necessary nutrients from the outside to the inside. Meanwhile, some transporters showed high affinity to ligand-drug conjugates and even ligand-drug carrier complexes. Thus, it provided an ideal opportunity for enhancing drug delivery and improving drug targeting. For receptors, they can be especially bound by natural ligands or monoclonal antibodies (mAbs), and thus mediated cellular signal or used in the treatment of disease. To date, lots of mAbs have been conjugated to small molecule drugs or drug carriers for drug delivery. Additionally, some transporters can also be targeted by mAbs, such as folate receptors (FR) which transport folate into cells, and meanwhile as antigens can specially bind anti-FR antibody. Importantly, covalent attachment of small molecule drugs or drug carriers to antibodies did not significantly influence their cell internalization, thus providing another delivery strategy utilizing interaction between antibody and membrane proteins.
Topical negative-pressure wound therapy: emerging devices and techniques
Published in Expert Review of Medical Devices, 2020
Raymund E. Horch, Ingo Ludolph, Wibke Müller-Seubert, Katharina Zetzmann, Theresa Hauck, Andreas Arkudas, Alexander Geierlehner
Cold plasma, one of the four fundamental states of matter, was recently introduced as a promising application to enhance wound healing. Especially in chronic and heavily contaminated wounds, the combination of cold plasma with sub-atmospheric pressure could be beneficial to the wound healing process. An increasing number of drug-resistant bacteria and the lack of new antibiotics make further optimization of NPWT as a delivery vehicle worthy. The delivery of adjunct therapies such as saline irrigation or instillation with antimicrobial solutions is increasingly used in the clinical wound management [116,122]. Wound instillation possesses the ability to deliver wound dependent and wound-specific substances. Cell suspensions containing prefabricated stem cells derived from the affected patient might also be able to promote wound healing. However, this is highly dependent on the type of tissue involved. Furthermore, substances known to have an impact on the physiological wound healing process could be applied in combination with NPWT in future studies. The combination with later techniques of tissue regeneration, such as tissue engineering and bioprinting in conjunction with biomolecular insights seems desirable, yet is not in the stage of clinical application [1]. Different vascular and collagen related growth factors might be of high interest [123]. Also applying perioperative analgesia or antibiotics using substances that interact directly at the foam–wound interface is a possible modification in the overall treatment concept of NPTW. Basic research for the detailed understanding of cell signaling mechanism is essential in this context.
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