High fat diet deviates PtC-specific B1 B cell phagocytosis in obese mice

Phagocytosis had been attributed predominantly to "professional" phagocytes such as macrophages, which play critical roles in adipose tissue inflammation. However, recently, macrophage-like phagocytic activity has been reported in B1 B lymphocytes. Intrigued by the long-established correlation between high fat diet (HFD)-induced obesity and immune dysfunction, we investigated how HFD affects B1 B cell phagocytosis. A significant number of B1 B cells recognize phosphatidylcholine (PtC), a common phospholipid component of cell membrane. We report here that unlike macrophages, B1 B cells have a unique PtC-specific phagocytic function. In the presence of both PtC-coated and non-PtC control fluorescent nano-particles, B1 B cells from healthy lean mice selectively engulfed PtC-coated beads, whereas B1 B cells from HFD-fed obese mice non-discriminately phagocytosed both PtC-coated and control beads. Morphologically, B1 B cells from obese mice resembled macrophages, displaying enlarged cytosol and engulfed more beads. Our study suggests for the first time that HFD can affect B1 B cell phagocytosis, substantiating the link of HFD-induced obesity and immune deviation.R21 AR063387 - NIAMS NIH HHS; R25 CA153955 - NCI NIH HHS; UL1 TR000157 - NCATS NIH HH

Iron induces two distinct Ca²⁺ signalling cascades in astrocytes.

From Europe PMC via Jisc Publications RouterHistory: ppub 2021-05-01, epub 2021-05-05Publication status: PublishedFunder: National Natural Science Foundation of China (National Science Foundation of China); Grant(s): 81871852Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe2+), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe3+). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca2+]i) in astrocytes. Administration of Fe2+ or Fe3+ in μM concentrations evoked [Ca2+]i in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca2+]i through two distinct molecular cascades. Uptake of Fe2+ by DMT1 inhibits astroglial Na+-K+-ATPase, which leads to elevation in cytoplasmic Na+ concentration, thus reversing Na+/Ca2+ exchanger and thereby generating Ca2+ influx. Uptake of Fe3+ by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP3), thus triggering InsP3 receptor-mediated Ca2+ release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload

Accelerating the Phosphatase-like Activity of Uio-66-NH₂ by Catalytically Inactive Metal Ions and Its Application for Improved Fluorescence Detection of Cardiac Troponin I

Compared with natural enzymes, nanozymes usually exhibit much lower catalytic activities, which limit the sensitivities of nanozyme-based immunoassays. Herein, several metal ions without enzyme-like activities were engineered onto Uio-66-NH2 nanozyme through postsynthetic modification. The obtained Mn+@Uio-66-NH2 (Mn+ = Zn2+, Cd2+, Co2+, Ca2+and Ni2+) exhibited improved phosphatase-like catalytic activities. In particular, a 12-fold increase in the catalytic efficiency (kcat/Km) of Uio-66-NH2 was observed after the modification with Zn2+. Mechanism investigations indicate that both the amino groups and oxygen-containing functional groups in Uio-66-NH2 are the binding sites of Zn2+, and the modified Zn2+ ions on Uio-66-NH2 serve as the additional catalytic sites for improving the catalytic performance. Furthermore, the highly active Zn2+@Uio-66-NH2 was used as a nanozyme label to develop a fluorescence immunoassay method for the detection of cardiac troponin I (cTnI). Compared with pristine Uio-66-NH2, Zn2+@Uio-66-NH2 can widen the linear range by 1 order of magnitude (from 10 pg/mL–1 μg/mL to 1 pg/mL–1 μg/mL) and also lower the detection limit by 5 times (from 4.7 pg/mL to 0.9 pg/mL)

High fat diet deviates PtC‐specific B1 B cell phagocytosis in obese mice

Phagocytosis had been attributed predominantly to "professional" phagocytes such as macrophages, which play critical roles in adipose tissue inflammation. However, recently, macrophage-like phagocytic activity has been reported in B1 B lymphocytes. Intrigued by the long-established correlation between high fat diet (HFD)-induced obesity and immune dysfunction, we investigated how HFD affects B1 B cell phagocytosis. A significant number of B1 B cells recognize phosphatidylcholine (PtC), a common phospholipid component of cell membrane. We report here that unlike macrophages, B1 B cells have a unique PtC-specific phagocytic function. In the presence of both PtC-coated and non-PtC control fluorescent nano-particles, B1 B cells from healthy lean mice selectively engulfed PtC-coated beads, whereas B1 B cells from HFD-fed obese mice non-discriminately phagocytosed both PtC-coated and control beads. Morphologically, B1 B cells from obese mice resembled macrophages, displaying enlarged cytosol and engulfed more beads. Our study suggests for the first time that HFD can affect B1 B cell phagocytosis, substantiating the link of HFD-induced obesity and immune deviation.R21 AR063387 - NIAMS NIH HHS; R25 CA153955 - NCI NIH HHS; UL1 TR000157 - NCATS NIH HH

Combined Cold and Drought Stress-Induced Response of Photosynthesis and Osmotic Adjustment in <i>Elymus nutans</i> Griseb.

Elymus nutans Griseb. is a dominant forage in the Qinghai–Tibetan Plateau. However, the combined cold and drought (CD) stress is a major problem inhibiting its growth, development, and yield. Here, the responses of morphological, photosynthetic, osmoregulation levels, and signal transduction under cold, drought, and CD stress were explored. Both cold- and drought-stressed plants showed varying degrees of damage. In addition, CD stress led to more severe damage than single stress, especially in total biomass, photosynthetic capacity, and electron transfer efficiency. The total biomass, net photosynthetic rate, and maximal quantum yield of photosystem II (PSII) photochemistry reduced by 61.47%, 95.80%, and 16.06% in comparison with the control, respectively. Meanwhile, CD stress was accompanied by lower chlorophyll contents, down-regulated expression level of key photosynthetic enzymes (EnRbcS, EnRbcL, and EnRCA), stomatal closure, disrupted chloroplast ultrastructure, and reduced starch content. Furthermore, CD stress induced some adaptability responses in cold- and drought-tolerant E. nutans seedlings. The combined stress provoked alterations in both cold- and drought-related transcription factors and responsive genes. EnCBF12, EnCBF9, EnCBF14, and EnCOR14α were significantly up-regulated under cold or drought stress, and the transcript level of EnCBF3 and EnCBF12 was even 2.94 and 12.59 times higher than control under CD treatment, which indicated the key role of transcription factors activation in coping with CD stress. In addition, the content of soluble sugar, reducing sugar, proline, glycine betaine, and other osmolytes was significantly improved under CD stress. Therefore, we demonstrated that exposure to CD stress led to severe morphological and photosynthetic damage and revealed the acclimation to the cold and drought stress combination via osmotic adjustment and transcription factors activation in the Tibetan wild E. nutans

Paclobutrazol Ameliorates Low-Light-Induced Damage by Improving Photosynthesis, Antioxidant Defense System, and Regulating Hormone Levels in Tall Fescue

Paclobutrazol (PBZ) is a plant-growth regulator (PGR) in the triazole family that enhances plant tolerance to environmental stresses. Low-light (LL) intensity is a critical factor adversely affecting the growth of tall fescue (Festuca arundinacea Schreb.). Therefore, in this study, tall fescue seedlings were treated with PBZ under control and LL conditions to investigate the effects of PBZ on enhancing LL stress resistance by regulating the growth, photosynthesis, oxidative defense, and hormone levels. Our results reveal that LL stress reduced the total biomass, chlorophyll (Chl) content, photosynthetic capacity, and photochemical efficiency of photosystem II (PSII) but increased the membrane lipid peroxidation level and reactive oxygen species (ROS) generation. However, the application of PBZ increased the photosynthetic pigment contents, net photosynthetic rate (Pn), maximum quantum yield of PSII photochemistry (Fv/Fm), ribulose-1,5-bisphosphate carboxylase (RuBisCO) activity, and starch content. In addition, PBZ treatment activated the antioxidant enzyme activities, antioxidants contents, ascorbate acid-glutathione (AsA-GSH) cycle, and related gene expression, lessening the ROS burst (H2O2 and O2&#8729;&minus;). However, the gibberellic acid (GA) anabolism was remarkably decreased by PBZ treatment under LL stress, downregulating the transcript levels of kaurene oxidase (KO), kaurenoic acid oxidase (KAO), and GA 20-oxidases (GA20ox). At the same time, PBZ treatment up-regulated 9-cis-epoxycarotenoid dioxygenase (NCED) gene expression, significantly increasing the endogenous abscisic acid (ABA) concentration under LL stress. Thus, our study revealed that PBZ improves the antioxidation and photosynthetic capacity, meanwhile increasing the ABA concentration and decreasing GA concentration, which ultimately enhances the LL stress tolerance in tall fescue

The neuroprotective mechanism of lithium after ischaemic stroke

Stroke causes degeneration and death of neurones leading to the loss of motor function and frequent occurrence of cognitive impairment and depression. Lithium (Li+), the archetypal mood stabiliser, is neuroprotective in animal models of stroke, albeit underlying mechanisms remain unknown. We discover that Li+ inhibits activation of nucleotide-binding oligomerisation domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasomes in the middle cerebral artery occlusion (MCAO) stroke model in mice. This action of Li+ is mediated by two signalling pathways of AKT/GSK3β/β-catenin and AKT/FoxO3a/β-catenin which converge in suppressing the production of reactive oxygen species (ROS). Using immunocytochemstry, MRI imaging, and cell sorting with subsequent mRNA and protein quantification, we demonstrate that Li+ decreases the infarct volume, improves motor function, and alleviates associated cognitive and depressive impairments. In conclusion, this study reveals molecular mechanisms of Li+ neuroprotection during brain ischaemia, thus providing the theoretical background to extend clinical applications of Li+ for treatment of ischemic stroke.</p

Iatrogenic Iron Promotes Neurodegeneration and Activates Self-Protection of Neural Cells against Exogenous Iron Attacks

Metal implants are used worldwide, with millions of nails, plates, and fixtures grafted during orthopedic surgeries. Iron is the most common element of these metal implants. As time passes, implants can be corroded and iron can be released. Ionized iron permeates the surrounding tissues and enters circulation; importantly, iron ions pass through the blood-brain barrier. Can iron from implants represent a risk factor for neurological diseases? This remains an unanswered question. In this study, we discovered that patients with metal implants delivered through orthopedic surgeries have higher incidence of Parkinson's disease or ischemic stroke compared to patients who underwent similar surgeries but did not have implants. Concentration of serum iron and ferritin was increased in subjects with metal implants. In experiments in vivo, we found that injection of iron dextran selectively decreased the presence of divalent metal transporter 1 (DMT1) in neurons through increasing the expression of Ndfip1, which degrades DMT1 and does not exist in glial cells. At the same time, excess of iron increased expression of DMT1 in astrocytes and microglial cells and triggered reactive astrogliosis and microgliosis. Facing the attack of excess iron, glial cells act as neuroprotectors to accumulate more extracellular iron by upregulating DMT1, whereas neurons limit iron uptake through increasing DMT1 degradation. Cerebral accumulation of iron in animals is associated with impaired cognition, locomotion, and mood. Excess iron from surgical implants thus can affect neural cells and may be regarded as a risk factor for neurodegeneration.</p

Iron induces two distinct Ca

From PubMed via Jisc Publications RouterHistory: received 2020-09-18, accepted 2021-03-30Publication status: epublishFunder: National Natural Science Foundation of China (National Science Foundation of China); Grant(s): 81871852Iron is the fundamental element for numerous physiological functions. Plasmalemmal divalent metal ion transporter 1 (DMT1) is responsible for cellular uptake of ferrous (Fe ), whereas transferrin receptors (TFR) carry transferrin (TF)-bound ferric (Fe ). In this study we performed detailed analysis of the action of Fe ions on cytoplasmic free calcium ion concentration ([Ca ] ) in astrocytes. Administration of Fe or Fe in μM concentrations evoked [Ca ] in astrocytes in vitro and in vivo. Iron ions trigger increase in [Ca ] through two distinct molecular cascades. Uptake of Fe by DMT1 inhibits astroglial Na -K -ATPase, which leads to elevation in cytoplasmic Na concentration, thus reversing Na /Ca exchanger and thereby generating Ca influx. Uptake of Fe by TF-TFR stimulates phospholipase C to produce inositol 1,4,5-trisphosphate (InsP ), thus triggering InsP receptor-mediated Ca release from endoplasmic reticulum. In summary, these findings reveal the mechanisms of iron-induced astrocytic signalling operational in conditions of iron overload