Arachidonic acid-derived prostaglandins not only contribute to the development of inflammation as intercellular pro-inflammatory mediators, but also promote the excitability of the peripheral ...somatosensory system, contributing to pain exacerbation. Peripheral tissues undergo many forms of diseases that are frequently accompanied by inflammation. The somatosensory nerves innervating the inflamed areas experience heightened excitability and generate and transmit pain signals. Extensive studies have been carried out to elucidate how prostaglandins play their roles for such signaling at the cellular and molecular levels. Here, we briefly summarize the roles of arachidonic acid-derived prostaglandins, focusing on four prostaglandins and one thromboxane, particularly in terms of their actions on afferent nociceptors. We discuss the biosynthesis of the prostaglandins, their specific action sites, the pathological alteration of the expression levels of related proteins, the neuronal outcomes of receptor stimulation, their correlation with behavioral nociception, and the pharmacological efficacy of their regulators. This overview will help to a better understanding of the pathological roles that prostaglandins play in the somatosensory system and to a finding of critical molecular contributors to normalizing pain.
Sheath-run artificial muscles Mu, Jiuke; Jung de Andrade, Mônica; Fang, Shaoli ...
Science (American Association for the Advancement of Science),
07/2019, Letnik:
365, Številka:
6449
Journal Article
Recenzirano
Odprti dostop
Although guest-filled carbon nanotube yarns provide record performance as torsional and tensile artificial muscles, they are expensive, and only part of the muscle effectively contributes to ...actuation. We describe a muscle type that provides higher performance, in which the guest that drives actuation is a sheath on a twisted or coiled core that can be an inexpensive yarn. This change from guest-filled to sheath-run artificial muscles increases the maximum work capacity by factors of 1.70 to 2.15 for tensile muscles driven electrothermally or by vapor absorption. A sheath-run electrochemical muscle generates 1.98 watts per gram of average contractile power-40 times that for human muscle and 9.0 times that of the highest power alternative electrochemical muscle. Theory predicts the observed performance advantages of sheath-run muscles.
The orphan nuclear receptor Nurr1 is critical for the development, maintenance and protection of midbrain dopaminergic (mDA) neurons. Here we show that prostaglandin E1 (PGE1) and its dehydrated ...metabolite, PGA1, directly interact with the ligand-binding domain (LBD) of Nurr1 and stimulate its transcriptional function. We also report the crystallographic structure of Nurr1-LBD bound to PGA1 at 2.05 Å resolution. PGA1 couples covalently to Nurr1-LBD by forming a Michael adduct with Cys566, and induces notable conformational changes, including a 21° shift of the activation function-2 helix (H12) away from the protein core. Furthermore, PGE1/PGA1 exhibit neuroprotective effects in a Nurr1-dependent manner, prominently enhance expression of Nurr1 target genes in mDA neurons and improve motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse models of Parkinson's disease. Based on these results, we propose that PGE1/PGA1 represent native ligands of Nurr1 and can exert neuroprotective effects on mDA neurons, via activation of Nurr1's transcriptional function.
Electroceuticals refer to various forms of electronic neurostimulators used for therapy. Interdisciplinary advances in medical engineering and science have led to the development of the ...electroceutical approach, which involves therapeutic agents that specifically target neural circuits, to realize precision therapy for Alzheimer's disease (AD). To date, extensive studies have attempted to elucidate the disease-modifying effects of electroceuticals on areas in the brain of a patient with AD by the use of various physical stimuli, including electric, magnetic, and electromagnetic waves as well as ultrasound. Herein, we review non-invasive stimulatory systems and their effects on β-amyloid plaques and tau tangles, which are pathological molecular markers of AD. Therefore, this review will aid in better understanding the recent technological developments, applicable methods, and therapeutic effects of electronic stimulatory systems, including transcranial direct current stimulation, 40-Hz gamma oscillations, transcranial magnetic stimulation, electromagnetic field stimulation, infrared light stimulation and ionizing radiation therapy, and focused ultrasound for AD.
A helical configuration confers a great advantage in artificial muscle due to great movement potential. However, most helical fibers are exposed to a high temperature to produce the coiled helical ...structure. Hence, thermoset polymer-composed hydrogels are difficult to fabricate as helical fibers due to their thermal degeneration. Here, we describe a self-helical hydrogel fiber that is produced without thermal exposure as a glucose-responsive artificial muscle. The sheath–core fiber was spontaneously transformed into the helical structure during the swelling state by balancing the forces between the untwisting force of the twisted nylon fiber core and the recovery force of the hydrogel sheath. To induce controllable actuation, we also applied a reversible interaction between phenylboronic acid and glucose to the self-helical hydrogel. Consequently, the maximum tensile stroke was 2.3%, and the performance was six times greater than that of the nonhelical fiber. The fiber also exhibited tensile stroke with load and a maximum work density of 130 kJ/m3. Furthermore, we showed a reversible tensile stroke in response to the change in glucose level. Therefore, these results indicate that the self-helical hydrogel fiber has a high potential for use in artificial muscles, glucose sensors, and drug delivery systems.
The electromagnetic pollution issues have been arising from the fast-growing development for electronic devices. Hence, the demand for materials with high electromagnetic interference (EMI) shielding ...performance has increased. Here, we developed self-healable, flexible and printable graphene oxide/silver nanowire films and textiles with excellent EMI shielding performance. The maximum electromagnetic interference shielding effectiveness (EMI SE) of 92 dB was recorded for an 18 μm-thickness film. In addition, the specific EMI shielding effectiveness was 31 dB cm3/g or 48,275 dB cm2/g when normalized to film thickness. Both values are higher than reported EMI shielding products. The composite film and coated textile were tolerant of damage induced by cracking or scratching. Damaging the films by cracking reduced the electrical conductivity, mechanical properties, and the EMI SE was decreased from 72 dB to 56 dB at 8.2 GHz. After the healing process, the EMI SE was recovered to 71 dB and mechanical properties restored. The EMI SE of textile reached a maximum of 30 dB which is suitable to use as a commercial EMI shielding product. In addition, the textile exhibited high flexibility, and showed excellent mechanical stability with no change in performance after 1000 bending cycles.
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A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the 'Warburg effect', which is also observed in primed human ...pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase. Remarkably, knockdown of SIRT2 in human fibroblasts resulted in significantly decreased OXPHOS and increased glycolysis. In addition, we found that miR-200c-5p specifically targets SIRT2, downregulating its expression. Furthermore, SIRT2 overexpression in hPSCs significantly affected energy metabolism, altering stem cell functions such as pluripotent differentiation properties. Taken together, our results identify the miR-200c-SIRT2 axis as a key regulator of metabolic reprogramming (Warburg-like effect), via regulation of glycolytic enzymes, during human induced pluripotency and pluripotent stem cell function.
Axillary odor is a malodor produced by bacterial metabolism near the apocrine glands, which often causes discomfort in an individual's daily life and social interactions. A deodorant is a personal ...care product designed to alleviate or mask body odor. Currently, most deodorants contain antimicrobial chemicals and fragrances for odor management; however, direct application to the underarm skin can result in irritation or sensitivity. Therefore, there is a growing interest in technologies that enable disinfection and odor control without the antiperspirants or perfumes. The cold atmospheric plasma temporally generates reactive radicals that can eliminate bacteria and surrounding odors. In this study, cultured Staphylococcus hominis and Corynebacterium xerosis, the causative bacteria of axillary bromhidrosis, were killed after 90% plasma exposure for 3 min. Moreover, the electronic nose system indicated a significant reduction of approximately 51% in 3-hydroxy-3-methylhexanoic acid and approximately 34% in 3-methyl-3-sulfanylhexan-1-ol, the primary components of axillary odor, following a 5-min plasma exposure. These results support the dual function of our deodorant in eliminating bacteria and axillary odors without the chemical agents. Therefore, cold atmospheric plasma-applied deodorant devices have great potential for the treatment and management of axillary odors as a non-contact approach without chemical use in daily life.
Nociceptors are a subset of small primary afferent neurons that respond to noxious chemical, thermal and mechanical stimuli. Ion channels in nociceptors respond differently to noxious stimuli and ...generate electrical signals in different ways. Anoctamin 1 (ANO1 also known as TMEM16A) is a Ca(2+)-activated chloride channel that is essential for numerous physiological functions. We found that ANO1 was activated by temperatures over 44 °C with steep heat sensitivity. ANO1 was expressed in small sensory neurons and was highly colocalized with nociceptor markers, which suggests that it may be involved in nociception. Application of heat ramps to dorsal root ganglion (DRG) neurons elicited robust ANO1-dependent depolarization. Furthermore, knockdown or deletion of ANO1 in DRG neurons substantially reduced nociceptive behavior in thermal pain models. These results indicate that ANO1 is a heat sensor that detects nociceptive thermal stimuli in sensory neurons and possibly mediates nociception.
Psoriasis is a chronic inflammatory skin disease characterized by the rapid abnormal growth of skin cells in the epidermis, driven by an overactive immune system. Consequently, a complex interplay ...among epidermal cells, immune cells, and sensory neurons contributes to the development and progression of psoriasis. In these cellular contexts, various ion channels, such as acetylcholine receptors, TRP channels, Ca
release-activated channels, chloride channels, and potassium channels, each serve specific functions to maintain the homeostasis of the skin. The dysregulation of ion channels plays a major role in the pathophysiology of psoriasis, affecting various aspects of epidermal cells, immune responses, and sensory neuron signaling. Impaired function of ion channels can lead to altered calcium signaling, inflammation, proliferation, and sensory signaling, all of which are central features of psoriasis. This overview summarizes the pathophysiological roles of ion channels in epidermal cells, immune cells, and sensory neurons during early and late psoriatic processes, thereby contributing to a deeper understanding of ion channel involvement in the interplay of psoriasis and making a crucial advance toward more precise and personalized approaches for psoriasis treatment.
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