Pathophysiological Roles of Ion Channels in Epidermal Cells, Immune Cells, and Sensory Neurons in Psoriasis.

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, Ca2+ 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.

ANO1/TMEM16A regulates process maturation in radial glial cells in the developing brain.

Neural stem cells (NSCs) are primary progenitor cells in the early developmental stage in the brain that initiate a diverse lineage of differentiated neurons and glia. Radial glial cells (RGCs), a type of neural stem cell in the ventricular zone, are essential for nurturing and delivering new immature neurons to the appropriate cortical target layers. Here we report that Anoctamin 1 (ANO1)/TMEM16A, a Ca2+-activated chloride channel, mediates the Ca2+-dependent process extension of RGCs. ANO1 is highly expressed and functionally active in RGCs of the mouse embryonic ventricular zone. Knockdown of ANO1 suppresses RGC process extension and protrusions, whereas ANO1 overexpression stimulates process extension. Among various trophic factors, brain-derived neurotrophic factor (BDNF) activates ANO1, which is required for BDNF-induced process extension in RGCs. More importantly, Ano1-deficient mice exhibited disrupted cortical layers and reduced cortical thickness. We thus conclude that the regulation of RGC process extension by ANO1 contributes to the normal formation of mouse embryonic brain.

Physical state of cellulose in BmimCl: dependence of molar mass on viscoelasticity and sol-gel transition.

In this work, we investigated the correlation between the molar mass and the rheological properties of cellulose/1-butyl-3-methylimidazolium chloride (BmimCl) solutions, and provided the depolymerization kinetics of cellulose in BmimCl. Gel permeation chromatography was used to track the change in molar mass and kinetics as a function of the dissolution time. The molar mass of cellulose in BmimCl decreased significantly as the dissolution time increased, following a zeroth order rate law. The decrease of inter-chain friction induced by depolymerization resulted in a lower viscosity, shorter relaxation time, and lower activation energy. The activation energies for flow were distinctly different above and below the critical molar mass, which indicates that the relaxation mechanisms were not identical above and below the critical molar mass. The transition behavior of liquid crystalline phase also changed at the critical molar mass, which strongly demonstrated the effect of chain length on the formation of cholesteric phase. The exponents of Mark-Houwink-Sakurada and the radius of gyration showed that cellulose in BmimCl existed as a Gaussian chain in a theta solvent.

Biosynthesis of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(HB-co-HHx)) from butyrate using engineered Ralstonia eutropha.

Polyhydroxyalkanoates (PHAs), a promising family of bio-based polymers, are considered to be alternatives to traditional petroleum-based plastics. Copolymers like poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (P(HB-co-HHx)) have been shown to exhibit favorable physical and mechanical properties, due to decreased crystallinity resulting from the presence of medium-chain-length 3-hydroxyhexanoate (3HHx) monomers. In this study, we produced P(HB-co-HHx) using engineered Ralstonia eutropha strains containing deletions of the acetoacetyl-CoA reductase (phaB) genes and replacing the native PHA synthase with phaC2 from Rhodococcus aetherivorans I24 and by using butyrate, a short-chain organic acid, as the carbon source. Although the wild-type R. eutropha did not produce P(HB-co-HHx) when grown on mixed acids or on butyrate as the sole carbon source, we are able to produce polymer containing up to 40 wt% 3HHx monomer with the aforementioned engineered R. eutropha strains using various concentrations of just butyrate as the sole carbon source. This is the first report for the production of P(HB-co-HHx) copolymer in R. eutropha using butyrate.

Inhaled Volatile Molecules-Responsive TRP Channels as Non-Olfactory Receptors.

Generally, odorant molecules are detected by olfactory receptors, which are specialized chemoreceptors expressed in olfactory neurons. Besides odorant molecules, certain volatile molecules can be inhaled through the respiratory tract, often leading to pathophysiological changes in the body. These inhaled molecules mediate cellular signaling through the activation of the Ca2+-permeable transient receptor potential (TRP) channels in peripheral tissues. This review provides a comprehensive overview of TRP channels that are involved in the detection and response to volatile molecules, including hazardous substances, anesthetics, plant-derived compounds, and pheromones. The review aims to shed light on the biological mechanisms underlying the sensing of inhaled volatile molecules. Therefore, this review will contribute to a better understanding of the roles of TRP channels in the response to inhaled molecules, providing insights into their implications for human health and disease.

Anoctamin 1, a multi-modal player in pain and itch.

Anoctamin 1 (ANO1/TMEM16A) encodes a Ca2+-activated Cl- channel. Among ANO1's many physiological functions, it plays a significant role in mediating nociception and itch. ANO1 is activated by intracellular Ca2+ and depolarization. Additionally, ANO1 is activated by heat above 44 °C, suggesting heat as another activation stimulus. ANO1 is highly expressed in nociceptors, indicating a role in nociception. Conditional Ano1 ablation in dorsal root ganglion (DRG) neurons results in a reduction in acute thermal pain, as well as thermal and mechanical allodynia or hyperalgesia evoked by inflammation or nerve injury. Pharmacological interventions also lead to a reduction in nocifensive behaviors. ANO1 is functionally linked to the bradykinin receptor and TRPV1. Bradykinin stimulates ANO1 via IP3-mediated Ca2+ release from intracellular stores, whereas TRPV1 stimulates ANO1 via a combination of Ca2+ influx and release. Nerve injury causes upregulation of ANO1 expression in DRG neurons, which is blocked by ANO1 antagonists. Due to its role in nociception, strong and specific ANO1 antagonists have been developed. ANO1 is also expressed in pruritoceptors, mediating Mas-related G protein-coupled receptors (Mrgprs)-dependent itch. The activation of ANO1 leads to chloride efflux and depolarization due to high intracellular chloride concentrations, causing pain and itch. Thus, ANO1 could be a potential target for the development of new drugs treating pain and itch.

Axonal neuropathy-associated TRPV4 regulates neurotrophic factor-derived axonal growth.

Spinal muscular atrophy and hereditary motor and sensory neuropathies are characterized by muscle weakness and atrophy caused by the degenerations of peripheral motor and sensory nerves. Recent advances in genetics have resulted in the identification of missense mutations in TRPV4 in patients with these hereditary neuropathies. Neurodegeneration caused by Ca(2+) overload due to the gain-of-function mutation of TRPV4 was suggested as the molecular mechanism for the neuropathies. Despite the importance of TRPV4 mutations in causing neuropathies, the precise role of TRPV4 in the sensory/motor neurons is unknown. Here, we report that TRPV4 mediates neurotrophic factor-derived neuritogenesis in developing peripheral neurons. TRPV4 was found to be highly expressed in sensory and spinal motor neurons in early development as well as in the adult, and the overexpression or chemical activation of TRPV4 was found to promote neuritogenesis in sensory neurons as well as PC12 cells, whereas its knockdown and pharmacologic inhibition had the opposite effect. More importantly, nerve growth factor or cAMP treatment up-regulated the expression of phospholipase A(2) and TRPV4. Neurotrophic factor-derived neuritogenesis appears to be regulated by the phospholipase A(2)-mediated TRPV4 pathway. These findings show that TRPV4 mediates neurotrophic factor-induced neuritogenesis in developing peripheral nerves. Because neurotrophic factors are essential for the maintenance of peripheral nerves, these findings suggest that aberrant TRPV4 activity may lead to some types of pathology of sensory and motor nerves.

Understanding viscoelastic behavior of hybrid nanocellulose film based on rheological and electrostatic observation in blended suspension.

The effects of TEMPO-mediated oxidized cellulose nanofibril (TOCN) on the viscoelastic behavior and phase of cellulose nanocrystal (CNC) in suspension and film were investigated using polarized optical microscopy, rotational rheometry, and dynamic mechanical analysis. The sodium cation from TOCN changed the electrostatic state of CNC by screening the CNC surface charge. The volume inflation of TOCN locally increased the CNC concentration in the suspension. In turn, the CNC-CNC interactions increased the viscosity and the yield stress. Based on the experimental observation, the changing mechanisms of electrostatic state and particular interaction in the TOCN/CNC suspensions were suggested. In the hybrid film, the time dependency of complex moduli was changed owing to the different networking between CNCs and TOCNs. The CNC-CNC contacts easily collapsed by strain, while the TOCN-TOCN entanglements were slowly altered. This study provides a fundamental understanding of CNC behavior for optimizing processes and composite properties.

Comparison of the pretreatment methods for enhancing hydration of water-soaked adzuki beans (Vigna angularis).

Five pretreatments methods, cold plasma, pressure drop, heating, and bath-type and probe-type sonications were compared to shorten the rehydration process of adzuki bean (Vigna angularis) soaked before the cooking in terms of the hydration and softening efficacies. Moisture content and water activity of the probe-type sonicated beans were most dramatically increased as 11-45% and 0.59-0.97 after soaking for only 2 h, respectively (non-treated: 11-12% and 0.59-0.66). Accordingly, the probe-type sonicated beans were most rapidly softened as 27-5 N in the 2 h-soaking and exhibited the lowest hardness after soaking/cooking as ~ 0.97 N (non-treated: 27-21 N and ~ 5.5 N, respectively). According to scanning electron micrographs, these results can be attributed to formation of prominent fissures or scars in the hilum of the probe-type sonicated beans. Consequently, this study will be provide valuable information for developing a rational process in food industry to shorten the rehydration of the adzuki beans.

Rheological analysis of physical states of cellulose nanocrystal suspension and synergetic effect of aligned gel state.

The viscoelastic behavior of cellulose nanocrystals (CNCs) in highly concentrated suspension was studied using various rheological tools. As the concentration increased, the physical state of CNC suspension changed from an isotropic phase to an aligned gel state via a cholesteric phase. The physical network originating from hydrogen bond and van der Waals forces gave the suspension elastic and solid-like features. With large shear deformation, the CNC became aligned after network destruction. The aligned gel was not easily relaxed or destroyed by shear deformation or time. The aligned gel state of CNCs provides a better chance for a robust structure of films or composites.

High performance and sustainable CNF membrane via facile in-situ envelopment of hydrochar for water treatment.

In this study, cellulose nanofiber (CNF) membranes for water treatment are prepared via in-situ hydrothermal carbonization of glucose in a CNF suspension. The in-situ carbonized CNFs were fabricated into the membranes via dead-end filtration under hydraulic pressure (1 bar). The in-situ carbonized CNF membranes showed high pure water flux (56.25 L·h-1·m-2) without critical flux drop for 12 h of membrane fabrication. The hydrochar chemically bonded with CNF enhanced the durability of CNF during membrane fabrication. Owing to the strong and stable electrostatic interaction between the target dye and hydrochar, the in-situ carbonized membrane also displayed excellent dye rejection for dilute and concentrated solutions, with high selectivity and good reusability. This study provides a successful strategy for fabricating an all-carbohydrate-based high-performance water treatment membrane.

Pore-size control of chitin nanofibrous composite membrane using metal-organic frameworks.

Herein, environmentally benign chitin nanofiber (ChNF) membranes were fabricated by regulating suspension behavior. The introduction of zeolitic imidazole frameworks (ZIF-8) into the composite membranes led to the domain formation of ChNF derived by coordinative interaction, resulting in pore size-tunable membranes. Based on the rheological, morphological, and structural characterizations, the driving force of pore-size control was studied in the aqueous suspension of ChNF and ZIF-8 according to the relative concentration. At critical concentration, the 30-ChNF membrane presents superior water permeance (40 LMH h-1) while maintaining a high rejection rate (>80% for all organic dyes). Moreover, the molecular size cut-off of the composite membranes for dyes can be controlled in the range of less than 1 nm to 2 nm. The experimental results provide a simple strategy for the preparation of pore tunable ChNF membranes using MOF with high mechanical strength, good durability, high flux, dye rejection, and antifouling ability.

Anoctamin 1/TMEM16A in pruritoceptors is essential for Mas-related G protein receptor-dependent itch.

ABSTRACT: Itch is an unpleasant sensation that evokes a desire to scratch. Pathologic conditions such as allergy or atopic dermatitis produce severe itching sensation. Mas-related G protein receptors (Mrgprs) are receptors for many endogenous pruritogens. However, signaling pathways downstream to these receptors in dorsal root ganglion (DRG) neurons are not yet understood. We found that anoctamin 1 (ANO1), a Ca 2+ -activated chloride channel, is a transduction channel mediating Mrgpr-dependent itch signals. Genetic ablation of Ano1 in DRG neurons displayed a significant reduction in scratching behaviors in response to acute and chronic Mrgpr-dependent itch models and the epidermal hyperplasia induced by dry skin. In vivo Ca 2+ imaging and electrophysiological recording revealed that chloroquine and other agonists of Mrgprs excited DRG neurons via ANO1. More importantly, the overexpression of Ano1 in DRG neurons of Ano1 -deficient mice rescued the impaired itching observed in Ano1 -deficient mice. These results demonstrate that ANO1 mediates the Mrgpr-dependent itch signaling in pruriceptors and provides clues to treating pathologic itch syndromes.

Amplification of olfactory signals by Anoctamin 9 is important for mammalian olfaction.

Sensing smells of foods, prey, or predators determines animal survival. Olfactory sensory neurons in the olfactory epithelium (OE) detect odorants, where cAMP and Ca2+ play a significant role in transducing odorant inputs to electrical activity. Here we show Anoctamin 9, a cation channel activated by cAMP/PKA pathway, is expressed in the OE and amplifies olfactory signals. Ano9-deficient mice had reduced olfactory behavioral sensitivity, electro-olfactogram signals, and neural activity in the olfactory bulb. In line with the difference in olfaction between birds and other vertebrates, chick ANO9 failed to respond to odorants, whereas chick CNGA2, a major transduction channel, showed greater responses to cAMP. Thus, we concluded that the signal amplification by ANO9 is important for mammalian olfactory transduction.

In-situ synthesis of carbon dot at cellulose nanofiber for durable water treatment membrane with high selectivity.

In this work, carbon dot (CD) was in-situ synthesized and attached to cellulose nanofiber (CNF) via hydrothermal process. The in-situ synthesized CD uniformly enveloped the CNF surface by means of amide bonding, without significant changes of the chemical structure of CNF. The prepared CD@CNF composite showed rough and bumpy morphology. The attached CD increased the interaction between the fibers and enhanced the thermal stability and the dimensional stability in aqueous solution. CD@CNF showed excellent performance as a dye-rejection membrane with high-water flux (∼32 LMH bar-1) and high rejection rate (∼99.8 %), as well as the selective removal of cationic dye. This study suggests a novel synthesizing method of durable CNF membrane by envelopment of CD for effective water treatment.

Carbon dot/cellulose nanofiber composite: Dataset for its water treatment performance.

Carbon dot (CD) obtained via one-step hydrothermal carbonization was attached to cellulose nanofiber (CNF) via physical blending and in-situ synthesis. The data represent the morphological, chemical and optical differences of the samples, according to the amount and introducing method of CD. The morphological durability of the samples was also shown. The water treatment membrane performance was analysed using methylene blue as a representative pollutant. The related article was published in Carbohydr. Polym. 255 (2021) 117387.

Robust Nanocellulose/Metal-Organic Framework Aerogel Composites: Superior Performance for Static and Continuous Disposal of Chemical Warfare Agent Simulants.

Environment-friendly and robust nanocellulose/metal-organic framework aerogel composites were prepared for effective detoxification of chemical warfare agent simulants both in static and dynamic continuous flow systems. For this, we fabricated a durable porous composite of the UiO-66 catalyst and TEMPO-oxidized cellulose nanofibers (TOCN) to examine as a detoxification filter. Even with over 50 wt % UiO-66, the obtained cellulose aerogel composites exhibited high stability without leaking of UiO-66 for 4 weeks under an aqueous state. The cellulose aerogel composite with 54 wt % UiO-66 showed a quite high surface area (483 m2 g-1) despite the presence of TOCN, which caused fast degradation of methyl paraoxon (MPO), a nerve agent simulant, with a 0.7 min half-life in an aqueous solution with N-ethylmorpholine buffer. This aerogel composite was then examined as the detoxification filter in the continuous flow system under a 7.2 mL h-1 flow rate, which surprisingly decomposed 53.7 g of MPO within 1 h with 1 m2 of the effective area.

Tentonin 3/TMEM150C regulates glucose-stimulated insulin secretion in pancreatic ß-cells.

Glucose homeostasis is initially regulated by the pancreatic hormone insulin. Glucose-stimulated insulin secretion in ß-cells is composed of two cellular mechanisms: a high glucose concentration not only depolarizes the membrane potential of the ß-cells by ATP-sensitive K+ channels but also induces cell inflation, which is sufficient to release insulin granules. However, the molecular identity of the stretch-activated cation channel responsible for the latter pathway remains unknown. Here, we demonstrate that Tentonin 3/TMEM150C (TTN3), a mechanosensitive channel, contributes to glucose-stimulated insulin secretion by mediating cation influx. TTN3 is expressed specifically in ß-cells and mediates cation currents to glucose and hypotonic stimulations. The glucose-induced depolarization, firing activity, and Ca2+ influx of ß-cells were significantly lower in Ttn3-/- mice. More importantly, Ttn3-/- mice show impaired glucose tolerance with decreased insulin secretion in vivo. We propose that TTN3, as a stretch-activated cation channel, contributes to glucose-stimulated insulin secretion.

Preparation of chitosan aerogel crosslinked in chemical and ionical ways by non-acid condition for wound dressing.

Herein, the dual-crosslinked chitosan aerogel was prepared using 1-butyl-3-methylimidazolium chloride, an ionic liquid, as a solvent. The hydroxyl groups were covalently crosslinked by epichlorohydrin (ECH), while the amino groups were ionically crosslinked by itaconic acid (IA). The chemical and ionic crosslinkings of the aerogels were analyzed using FT-IR and NMR. Both the types and the degree of crosslinking gave significant influences on the structures of the aerogels. The dual crosslinked aerogel with proper chemical crosslinking dose had the excellent swelling behavior. The prepared aerogel shows potential as a wound healing matrix, with low toxicity and antibacterial function.

Tentonin 3/TMEM150C senses blood pressure changes in the aortic arch.

The baroreceptor reflex is a powerful neural feedback that regulates arterial pressure (AP). Mechanosensitive channels transduce pulsatile AP to electrical signals in baroreceptors. Here we show that tentonin 3 (TTN3/TMEM150C), a cation channel activated by mechanical strokes, is essential for detecting AP changes in the aortic arch. TTN3 was expressed in nerve terminals in the aortic arch and nodose ganglion (NG) neurons. Genetic ablation of Ttn3 induced ambient hypertension, tachycardia, AP fluctuations, and impaired baroreflex sensitivity. Chemogenetic silencing or activation of Ttn3+ neurons in the NG resulted in an increase in AP and heart rate, or vice versa. More important, overexpression of Ttn3 in the NG of Ttn3-/- mice reversed the cardiovascular changes observed in Ttn3-/- mice. We conclude that TTN3 is a molecular component contributing to the sensing of dynamic AP changes in baroreceptors.