Lrig1-expression confers suppressive function to CD4+ cells and is essential for averting autoimmunity via the Smad2/3/Foxp3 axis

AbstractRegulatory T cells (Treg) are CD4+ T cells with immune-suppressive function, which is defined by Foxp3 expression. However, the molecular determinants defining the suppressive population of T cells have yet to be discovered. Here we report that the cell surface protein Lrig1 is enriched in suppressive T cells and controls their suppressive behaviors. Within CD4+ T cells, Treg cells express the highest levels of Lrig1, and the expression level is further increasing with activation. The Lrig1+ subpopulation from T helper (Th) 17 cells showed higher suppressive activity than the Lrig1- subpopulation. Lrig1-deficiency impairs the suppressive function of Treg cells, while Lrig1-deficient naïve T cells normally differentiate into other T cell subsets. Adoptive transfer of CD4+Lrig1+ T cells alleviates autoimmune symptoms in colitis and lupus nephritis mouse models. A monoclonal anti-Lrig1 antibody significantly improves the symptoms of experimental autoimmune encephalomyelitis. In conclusion, Lrig1 is an important regulator of suppressive T cell function and an exploitable target for treating autoimmune conditions.</jats:p

Suppression Effect of Astaxanthin on Osteoclast Formation In Vitro and Bone Loss In Vivo

Osteoporosis is characterized by a reduction of the bone mineral density (BMD) and microarchitectural deterioration of the bone, which lead to bone fragility and susceptibility to fracture. Astaxanthin (AST) has a variety of biological activities, such as a protective effect against asthma or neuroinflammation, antioxidant effect, and decrease of the osteoclast number in the right mandibles in the periodontitis model. Although treatment with AST is known to have an effect on inflammation, no studies on the effect of AST exposure on bone loss have been performed. Thus, in the present study, we examined the antiosteoporotic effect of AST on bone mass in ovariectomized (OVX) mice and its possible mechanism of action. The administration of AST (5, 10 mg/kg) for 6 weeks suppressed the enhancement of serum calcium, inorganic phosphorus, alkaline phosphatase, total cholesterol, and tartrate-resistant acid phosphatase (TRAP) activity. The bone mineral density (BMD) and bone microarchitecture of the trabecular bone in the tibia and femur were recovered by AST exposure. Moreover, in the in vitro experiment, we demonstrated that AST inhibits osteoclast formation through the expression of the nuclear factor of activated T cells (NFAT) c1, dendritic cell-specific transmembrane protein (DC-STAMP), TRAP, and cathepsin K without any cytotoxic effects on bone marrow-derived macrophages (BMMs). Therefore, we suggest that AST may have therapeutic potential for the treatment of postmenopausal osteoporosis

Impact of Red Sea Bream Iridovirus Infection on Rock Bream (<i>Oplegnathus fasciatus</i>) and Other Fish Species: A Study of Horizontal Transmission

Red sea bream iridovirus (RSIV) causes significant economic losses in aquaculture. Here, we analyzed the pathogenicity, viral shedding, and transmission dynamics of RSIV in rock bream (Oplegnathus fasciatus) by employing immersion infection and cohabitation challenge models. Rock bream challenged by immersion exposure exhibited 100% mortality within 35 days post RSIV exposure, indicating that the viral shedding in seawater peaked after mortality. At 25 °C, a positive correlation between the viral loads within infected rock bream and virus shedding into the seawater was observed. Specific RSIV lesions were observed in the spleen and kidney of the infected rock bream, and the viral load in the spleen had the highest correlation with the histopathological grade. A cohabitation challenge mimicking the natural transmission conditions was performed to assess the virus transmission and determine the pathogenicity and viral load. The RSIV-infected rock breams (donors) were cohabited with uninfected rock bream, red sea bream (Pagrus major), and flathead grey mullet (Mugil cephalus) (recipients) at both 25 °C and 15 °C. In the cohabitation challenge group maintained at 15 °C, no mortality was observed across all experimental groups. However, RSIV was detected in both seawater and the recipient fish. Our results provide preliminary data for further epidemiological analyses and aid in the development of preventive measures and management of RSIVD in aquaculture

Red Sea Bream Iridovirus Kinetics, Tissue Tropism, and Interspecies Horizontal Transmission in Flathead Grey Mullets (<i>Mugil cephalus</i>)

Red sea bream iridovirus (RSIV) causes significant economic losses in the aquaculture industry. We analyzed the pathogenicity of RSIV in flathead grey mullets (Mugil cephalus), the correlation of histopathological lesions, and interspecies horizontal transmission, through immersion infection and cohabitation challenges. Flathead grey mullets, which were challenged by immersion infection, exhibited mortality at 14 and 24 days after RSIV exposure. Viral shedding in seawater peaked 2–3 days before or after the observed mortality. Specific lesions of RSIV were observed in the spleen and kidney, and the correlation between histopathological grade and viral load was the highest in the spleen. In a cohabitation challenge, flathead grey mullets were the donors, and healthy rock bream, red sea bream, and flathead grey mullets were the recipients. Viral shedding in seawater was the highest in flathead grey mullet and rock bream at 25 °C, with 106.0 RSIV copies L/g at 14 dpi. No mortality was observed in any group challenged at 15 °C, and no RSIV was detected in seawater after 30 dpi. The virus shed from RSIV-infected flathead grey mullets caused horizontal transmission through seawater. These findings suggest that rapid decision-making is warranted when managing disease in fish farms

Protective Effects of 2,3,5,4′-Tetrahydroxystilbene-2-O-β-d-glucoside on Ovariectomy Induced Osteoporosis Mouse Model

2,3,5,4&prime;-Tetrahydroxystilbene-2-O-&beta;-d-glucoside (TSG), an active polyphenolic component of Polygonum multiflorum, exhibits many pharmacological activities including antioxidant, anti-inflammation, and anti-aging effects. A previous study demonstrated that TSG protected MC3T3-E1 cells from hydrogen peroxide (H2O2) induced cell damage and the inhibition of osteoblastic differentiation. However, no studies have investigated the prevention of ovariectomy-induced bone loss in mice. Therefore, we investigated the effects of TSG on bone loss in ovariectomized mice (OVX). Treatment with TSG (1 and 3 &mu;g/g; i.p.) for six weeks positively affected body weight, uterine weight, organ weight, bone length, and weight change because of estrogen deficiency. The levels of the serum biochemical markers of calcium (Ca), inorganic phosphorus (IP), alkaline phosphatase (ALP), and total cholesterol (TCHO) decreased in the TSG-treated mice when compared with the OVX mice. Additionally, the serum bone alkaline phosphatase (BALP) levels in the TSG-treated OVX mice were significantly increased compared with the OVX mice, while the tartrate-resistant acid phosphatase (TRAP) activity was significantly reduced. Furthermore, the OVX mice treated with TSG showed a significantly reduced bone loss compared to the untreated OVX mice upon micro-computed tomography (CT) analysis. Consequently, bone destruction in osteoporotic mice as a result of ovariectomy was inhibited by the administration of TSG. These findings indicate that TSG effectively prevents bone loss in OVX mice; therefore, it can be considered as a potential therapeutic for the treatment of postmenopausal osteoporosis

Single-Step LRET Aptasensor for Rapid Mycotoxin Detection

Contamination of foods by mycotoxins is a common yet serious problem. Owing to the increase in consumption of fresh produce, consumers have become aware of food safety issues caused by mycotoxins. Therefore, rapid and sensitive mycotoxin detection is in great demand in fields such as food safety and public health. Here we report a single-step luminescence resonance energy transfer (LRET) aptasensor for mycotoxin detection. To accomplish the single-step sensor, our sensor was constructed by linking a quencher-labeled aptamer through a linker to the surface of upconversion nanoparticles (UCNPs). Our LRET aptasensor is composed of Mn²⁺-doped NaYF₄:Yb³⁺,Er³⁺ UCNPs as the LRET donor, and black hole quencher 3 (BHQ3) as the acceptor. The maximum quenching efficiency is obtained by modulating the linker length, which controls the distance between the quencher and the UCNPs. Our distinctive design of LRET aptasensor allows detection of mycotoxins selectively in colored food samples within 10 min without multiple bioassay steps. We believe our single-step aptasensor has a significant potential for on-site detection of food contaminants, environmental pollutants, and biological metabolites

Controlled Grafting of Colloidal Nanoparticles on Graphene through Tailored Electrostatic Interaction

Nanoparticle/graphene hybrid composites have been of great interest in various disciplines due to their unique synergistic physicochemical properties. In this study, we report a facile and generalized synthesis method for preparing nanoparticle/exfoliated graphene (EG) composites by tailored electrostatic interactions. EG was synthesized by an electrochemical method, which produced selectively oxidized graphene sheets at the edges and grain boundaries. These EG sheets were further conjugated with polyethyleneimine to provide positive charges at the edges. The primary organic ligands of the colloidal nanoparticles were exchanged with Cl- or MoS42- anions, generating negatively charged colloidal nanoparticles in polar solvents. By simple electrostatic interactions between the EG and nanoparticles in a solution, nanoparticles were controllably assembled at the edges of the EG. Furthermore, the generality of this process was verified for a wide range of nanoparticles, such as semiconductors, metals, and magnets, on the EG. As a model application, designed composites with size-controlled FeCo nanoparticle/EG were utilized as electromagnetic interference countermeasure materials that showed a size-dependent shift of the frequency ranges on the electromagnetic absorption properties. The current generalized process will offer great potential for the large-scale production of well-designed graphene nanocomposites for electronic and energy applications