RESUMO
Further understanding the mechanism for microglia activation is necessary for developing novel anti-inflammatory strategies. Our previous study found that the activation of sigma-1 receptor can effectively inhibit the neuroinflammation, independent of the canonical mechanisms, such as NF-κB, JNK and ERK inflammatory pathways. Thus, it is reasonable that an un-identified, non-canonical pathway contributes to the activation of microglia. In the present study, we found that a sigma-1 receptor agonist of 2-morpholin-4-ylethyl 1-phenylcyclohexane-1-carboxylate (PRE-084) suppressed lipopolysaccharide (LPS) elevated nitric oxide (NO) content in BV-2 microglia culture supernatant and LPS-raised mRNA levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS) in BV-2 microglia. Moreover, PRE-084 alleviated LPS-increased Ser 9 de-phosphorylation of glycogen synthase kinase-3 beta (GSK-3ß), LPS-elevated catalytic activity of calcineurin, and LPS-raised percent and frequency of Ca2+ oscillatory BV-2 cells. We further found that the inhibitory effect of PRE-084 was reversed by a calcineurin activator of chlorogenic acid and a GSK-3ß activator of pyrvinium. Moreover, an IP3 receptor inhibitor of 2-aminoethoxydiphenyl borate mimicked the anti-inflammatory activity of PRE-084. Thus, we identified a noncanonical pro-neuroinflammary pathway of Ca2+ oscillation/Calcineurin/GSK-3ß and the inhibition of this pathway is necessary for the anti-inflammatory activity of sigma-1 receptor activation.
Assuntos
Calcineurina , Microglia , Anti-Inflamatórios/farmacologia , Calcineurina/metabolismo , Linhagem Celular , Glicogênio Sintase Quinase 3 beta/metabolismo , Lipopolissacarídeos/farmacologia , Microglia/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Receptores sigma , Fator de Necrose Tumoral alfa/metabolismo , Receptor Sigma-1RESUMO
It has been reported that drought stress adversely affects the growth and yield of Glycyrrhiza uralensis, Chinese liquorice, in agricultural production. Bacillus pumilus, an important plant growth-promoting bacterium, play a significant role in improving plant tolerance to abiotic stress. However, the role of Bacillus pumilus G5 in resisting drought stress is largely unknown. In the present study, we found that drought stress significantly inhibited the growth and reduced the biomass of G. uralensis seedlings by restraining C- and N-metabolism, while this could be effectively reversed by B. pumilus G5 inoculation. Specifically, B. pumilus G5 significantly increased the content of primary metabolites such as soluble sugar, soluble protein, and free amino acids by regulating the C and N metabolic processes in G. uralensis seedlings. Moreover, B. pumilus G5 increased the content of glycyrrhizic acid, one of the important secondary metabolites, likely mediated through the increased content of primary metabolites and by recovering the expression of three key enzymes, HMGR, SQS, and ß-AS, in the biosynthesis of glycyrrhizic acid. Interestingly, the regulating effect of B. pumilus G5 inoculation on promoting the accumulation of glycyrrhizic acid and increasing the expression of synthesis-related genes is spatially selective. In summary, our findings suggest that B. pumilus G5 could alleviate adverse effects induced by drought stress on the growth of G. uralensis seedlings by regulating C- and N-metabolisms that further triggered the accumulation of secondary metabolites, and this finally improved the drought tolerance of cultivated G. uralensis seedlings.
Assuntos
Bacillus pumilus , Glycyrrhiza uralensis , Secas , Metabolismo Secundário , PlântulaRESUMO
An ideal material for C2H6/C2H4 separation would simultaneously have the highest C2H6 uptake capacity and the highest C2H6/C2H4 selectivity. But such material is elusive. A benchmark material for ethane-selective C2H6/C2H4 separation is peroxo-functionalized MOF-74-Fe that exhibits the best known separation performance due to its high C2H6/C2H4 selectivity (4.4), although its C2H6 uptake capacity is moderate (74.3 cm3/g). Here, we report a family of pore-space-partitioned crystalline porous materials (CPMs) with exceptional C2H6 uptake capacity and C2H6/C2H4 separation potential (i.e., C2H4 recovered from the mixture) despite their moderate C2H6/C2H4 selectivity (up to 1.75). The ethane uptake capacity as high as 166.8 cm3/g at 1 atm and 298 K, more than twice that of peroxo-MOF-74-Fe, has been achieved even though the isosteric heat of adsorption (21.9-30.4 kJ/mol) for these CPMs is as low as about one-third of that for peroxo-MOF-74-Fe (66.8 kJ/mol). While the overall C2H6/C2H4 separation potentials have not yet surpassed peroxo-MOF-74-Fe, these robust CPMs exhibit outstanding properties including high thermal stability (up to 450 °C) and aqueous stability, low regeneration energy, and a high degree of chemical and geometrical tunability within the same isoreticular framework.
RESUMO
Introduction of pore partition agents into hexagonal channels of MIL-88 type (acs topology) endows materials with high tunability in gas sorption. Here, we report a strategy to partition acs framework into pacs (partitioned acs) crystalline porous materials (CPM). This strategy is based on insertion of inâ situ synthesized 4,4'-dipyridylsulfide (dps) ligands. One third of open metal sites in the acs net are retained in pacs MOFs; two thirds are used for pore-space partition. The Co2 V-pacs MOFs exhibit near or at record high uptake capacities for C2 H2 , C2 H4 , C2 H6 , and CO2 among MOFs. The storage capacity of C2 H2 is 234â cm3 g-1 (298â K) and 330â cm3 g-1 (273â K) at 1â atm for CPM-733-dps (the Co2 V-BDC form, BDC=1,4-benzenedicarboxylate). These high uptake capacities are accomplished with low heat of adsorption, a feature desirable for low-energy-cost adsorbent regeneration. CPM-733-dps is stable and shows no loss of C2 H2 adsorption capacity following multiple adsorption-desorption cycles.
RESUMO
The introduction of a symmetry- and size-matching pore-partitioning agent in the form of either a molecular ligand, such as 2,4,6-tri(4-pyridinyl)-1,3,5-triazine (tpt), or a metal-complex cluster, into the hexagonal channels of MIL-88/MOF-235-type (the acs net) to create pacs-type (partitioned acs) crystalline porous materials is an effective strategy to develop high-performance gas adsorbents. We have developed an integrated COF-MOF coassembly strategy as a new method for pore-space partitioning through the coassembly of [(M3 (OH)1-x (O)x (COO)6 ] MOF-type and [B3 O3 (py)3 ] COF-type trimers. With this strategy, the coordination-driven assembly of the acs framework occurred concurrently and synergistically with the COF-1-type condensation of pyridine-4-boronic acid into a C3 -symmetric trimeric boroxine molecule. The resulting boroxine-based pacs materials exhibited dramatically enhanced gas-sorption properties as compared to nonpartitioned acs-type materials and are among the most efficient NH3 -sorption materials.
RESUMO
Heavy-metal ions and nitroaromatic substances are highly toxic and harmful to human health and the ecological environment. It is an urgent issue to selectively detect and capture these toxic substances. By introducing the triazole ligand to the π-conjugated aromatic carboxylate system and borrowing the organic template open framework idea, a stable fluorescent framework [Me2NH2]4[Zn6(qptc)3(trz)4]·6H2O (1) (H4qptc = terphenyl-2,5,2'5'-tetracarboxylic acid, trz = 1,2,4-triazole) has been successfully synthesized, which features Zn4(trz)2 chain-based 3D anionic structure with channels filled by [Me2NH2]+ cations. It is worth noting that the material exhibits selective adsorption and recyclable detection of heavy-metal Cr3+ ion in aqueous solutions, which may be the synergy from the metal charge, bond ability of metal ions to carboxylate oxygen atom, and soft-hard acid-base properties. Furthermore, it can selectively sense of 2,4,6-trinitrophenol with a large quenching coefficient Ksv of 2.08 × 106 M-1.
RESUMO
Endotoxic shock is the primary cause of morbidity and mortality in hospital patients, creating an urgent need to explore the mechanisms involved in sepsis. Our previous studies showed that T-cell immunoglobulin- and mucin-domain-containing molecule-4 (Tim-4) attenuated the inflammatory response through regulating the functions of macrophages. However, the mechanism by which Tim-4 does this has not been fully elucidated. In this study, we found that Tim-4 expression was increased in lipopolysaccharide (LPS)-induced endotoxic shock. Interestingly, the survival rate of mice in the Tim-4 overexpression group was higher than that of the control group after LPS administration. To investigate the function of Tim-4 in LPS-induced inflammation, we further demonstrated that Tim-4 attenuated LPS-induced endotoxic shock by inhibiting cytokine production by macrophages. Blocking expression of Tim-4 and nuclear factor-kappa B (NF-κB) signal inhibition showed that Tim-4 inhibited cytokine production via NF-κB signaling pathway. This study indicates that Tim-4 may exert its immune modulation by regulating inflammatory factor secretion and might act as a novel potential target for inflammatory diseases, especially endotoxic shock.
Assuntos
Proteínas de Membrana/metabolismo , Choque Séptico/metabolismo , Animais , Linhagem Celular , Feminino , Interleucina-6/metabolismo , Lipopolissacarídeos , Macrófagos/metabolismo , Proteínas de Membrana/farmacologia , Proteínas de Membrana/uso terapêutico , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Choque Séptico/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
A porous luminescent zinc(II) metal-organic framework (MOF) with a NbO net [Zn2(tptc)(apy)2-x(H2O)x]·H2O (1) (where x ≈ 1, apy = aminopyridine, H4tptc = terphenyl-3,3â³,5,5â³-tetracarboxylic acid), constructed using paddlewheel [Zn2(COO)4] clusters and π-electron-rich terphenyl-tetracarboxylic acid, has been solvothermally synthesized and characterized. Interestingly, the material displays efficient, reversible adsorption of radioactive I2 in vapor and in solution (up to 216 wtâ¯%). The strong affinity for I2 is mainly due to it having large porosity, a conjugated π-electron aromatic system, halogen bonds, and electron-donating aminos. Furthermore, luminescent study indicated that 1 exhibits high sensitivity to electron-deficient nitrobenzene explosives via fluorescence quenching.
RESUMO
Background and objectives: The prognosis of liver failure treated with non-bioartificial liver support systems is poor. Detecting its risk factors and developing relevant prognostic models still represent the top priority to lower its death risk. Methods: All 215 patients with liver failure treated with non-bioartificial liver support system were retrospectively analyzed. Potential prognostic factors were investigated, and the Nomogram and the Random Survival Forests (RSF) models were constructed, respectively. Notably, we evaluated the performance of models and calculated the risk scores to divide patients into low-risk and high-risk groups. Results: In the training set, multifactorial Cox regression analysis showed that etiology, hepatic encephalopathy, total bilirubin, serum alkaline phosphatase, platelets, and MELD score were independent factors of short-term prognosis. The RSF model (AUC: 0.863, 0.792) performed better in prediction than the Nomogram model (AUC: 0.816, 0.756) and MELD (AUC: 0.658, 0.700) in the training and validation groups. On top of that, patients in the low-risk group had a significantly better prognosis than those in the high-risk group. Conclusion: We constructed the RSF model with etiology, hepatic encephalopathy, total bilirubin, serum alkaline phosphatase, platelets, and MELD score, which showed better prognostic power than the Nomogram model and MELD score and could help physicians make optimal treatment decisions.
RESUMO
Several lines of evidence have highlighted the crucial role of mitochondria-based therapy in depression. However, there are still less mitochondrial targets for the depression treatment. TAM41 mitochondrial translocator assembly and maintenance homolog (TAMM41) is a mitochondrial inner membrane protein for maintaining mitochondrial function, which is tightly related to many brain diseases including Alzheimer's diseases and epilepsy. Here, we investigated whether TAMM41 would be a potential target to treat depression. We found that the expression of TAMM41 was markedly lower in corticosterone-induced depression, lipopolysaccharide-induced depression, and depressed patients. Meanwhile, loss of TAMM41 resulted in increased immobility in the forced swim test (FST), tail suspension test (TST), and center time in open field test (OFT), suggesting depressive-like behaviors in mice. Moreover, genetic overexpression of TAMM41 obviously exerted antidepressant-like activities. Mechanistically, proteomics revealed that pacsin1 might be the underlying target of TAMM41. Further data supported that TAMM41 regulated the expression of pacsin1, and its antidepressant-like effect at least partially was attributed to pacsin1. In addition, exosomes containing TAMM41 was sufficient to exhibit antidepressant-like effect, suggesting an alternative strategy to exert the effect of TAMM41. Taken together, the present study demonstrates the antidepressant-like effect of TAMM41 and sheds light on its molecular mechanism. These finding provide new insights into a therapeutic strategy targeting mitochondria in the development of novel antidepressants.
RESUMO
Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems and organs, with pulmonary involvement known to be associated with disease prognosis and mortality. Acute lupus pneumonitis (ALP) resembling miliary tuberculosis (TB) is rare. Here, we present a case of ALP mimicking miliary TB and review the literature. A 19-year-old male student was referred to our hospital with fever. Although the patient met the diagnostic criteria for SLE, diffuse miliary nodules in both lungs were observed on a chest computed tomography scan. A series of tests, including pathological testing of bronchoscopy brushes, T-lymphocyte culture + interferon assay (A + B), tuberculin test, detection of mycobacterium TB DNA, and acid-fast bacilli smear in bronchoalveolar lavage fluid, were unable to confirm the presence of TB infection. We considered the patient to have ALP. After beginning ALP therapy, his symptoms disappeared, and the imaging and hematological results returned to normal. Miliary TB and ALP have similar clinical manifestations and imaging changes, which make diagnosis difficult. This case highlights the need to ensure accurate diagnosis and treatment to improve prognosis.
RESUMO
BACKGROUND: Hippocampal damage caused by status epilepticus (SE) can bring about cognitive decline and emotional disorders, which are common clinical comorbidities in patients with epilepsy. It is therefore imperative to develop a novel therapeutic strategy for protecting hippocampal damage after SE. Mitochondrial dysfunction is one of contributing factors in epilepsy. Given the therapeutic benefits of mitochondrial replenishment by exogenous mitochondria, we hypothesized that transplantation of mitochondria would be capable of ameliorating hippocampal damage following SE. METHODS: Pilocarpine was used to induced SE in mice. SE-generated cognitive decline and emotional disorders were determined using novel object recognition, the tail suspension test, and the open field test. SE-induced hippocampal pathology was assessed by quantifying loss of neurons and activation of microglia and astrocytes. The metabolites underlying mitochondrial transplantation were determined using metabonomics. RESULTS: The results showed that peripheral administration of isolated mitochondria could improve cognitive deficits and depressive and anxiety-like behaviors. Exogenous mitochondria blunted the production of reactive oxygen species, proliferation of microglia and astrocytes, and loss of neurons in the hippocampus. The metabonomic profiles showed that mitochondrial transplantation altered multiple metabolic pathways such as sphingolipid signaling pathway and carbon metabolism. Among potential affected metabolites, mitochondrial transplantation decreased levels of sphingolipid (d18:1/18:0) and methylmalonic acid, and elevated levels of D-fructose-1,6-bisphosphate. CONCLUSION: To the best of our knowledge, these findings provide the first direct experimental evidence that artificial mitochondrial transplantation is capable of ameliorating hippocampal damage following SE. These new findings support mitochondrial transplantation as a promising therapeutic strategy for epilepsy-associated psychiatric and cognitive disorders.
Assuntos
Epilepsia , Estado Epiléptico , Camundongos , Animais , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/tratamento farmacológico , Epilepsia/tratamento farmacológico , Epilepsia/patologia , Neurônios/metabolismo , Neurônios/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Mitocôndrias/metabolismo , Mitocôndrias/patologiaRESUMO
Propane/propene (C3 H8 /C3 H6 ) separation is essential in the petrochemical industry but challenging because of their similar physical and chemical properties. Adsorptive separation with C3 H8 -selective porous materials can energy-efficiently produce high-purity C3 H6 , which is highly promising for replacing conventional cryogenic distillation but suffers from unsatisfactory performance. Herein, through the precise incorporation of fluorinated functional groups into the confined pore space, a new fluorinated metal-organic framework (FDMOF-2) featuring the unique and strong C3 H8 -trap is successfully constructed. FDMOF-2 exhibits an unprecedented C3 H8 capture capacity of 140 cm3 cm-3 and excellent C3 H8 /C3 H6 (1:1, v/v) selectivity up to 2.18 (298 K and 1 bar), thus setting new benchmarks for all reported porous materials. Single-crystal X-ray diffraction studies reveal that the tailored pore confinement in FDMOF-2 provides stronger and multiple attractive interactions with C3 H8 , enabling excellent binding affinities. Breakthrough experiments demonstrate that C3 H8 can be directly extracted from various C3 H8 /C3 H6 mixtures with FDMOF-2, affording an outstanding C3 H6 production (501 mmol L-1 ) with over 99.99% purity. Benefiting from the robust framework and hydrophobic ligands, the separation performance of FDMOF-2 can be well maintained even under 70% relative humidity conditions.
RESUMO
BACKGROUND: Therapy in the latent period is favorable for retarding the process of epileptogenesis. Recently, we have discovered that the activated sigma-1 receptor (Sig-1R) attenuates the hippocampus pathological injury and memory impairment in the latent period of epileptogenesis. But the molecular mechanism needs further investigation. METHODS: PRE-084 was utilized as a research tool to highly selectively activate Sig-1R in epileptic mice. After the treatment of PRE-084, the pro-inflammatory cytokines, neuropathological traits, and the level of mitochondrial translocator assembly and maintenance 41 homolog (TAMM41) in the hippocampus were examined. The mode in which the Sig-1R interacts with TAMM41 was explored. The role of TAMM41 in the protecting effect of PRE-084 was established. RESULTS: PRE-084 inhibited the growth of pro-inflammatory cytokines, reduced the formation of gliosis, alleviated neuronal damage in the hippocampus, and attenuated memory impairment in the latent period of epileptogenesis. The protein level of TAMM41 decreased in the hippocampi of epileptic mice and increased in the PRE-084-treated mice. The Sig-1R bound with TAMM41 directly, maintaining the stability of TAMM41. Knockdown of TAMM41 reversed the protective effect of PRE-084, and overexpression of TAMM41 exhibited a similar protective action to that of PRE-084. CONCLUSION: We presented the concept of the "sigma-1 receptor-TAMM41 axis" and proposed that augmenting this axis can attenuate neuroinflammation and memory impairment in the process of epileptogenesis.
RESUMO
The strategic goals of the United Nations and the Aichi Targets for biodiversity conservation have not been met. Instead, biodiversity has continued to rapidly decrease, especially in developing countries. Setting a new global biodiversity framework requires clarifying future priorities and strategies to bridge challenges and provide representative solutions. Hyper-arid, arid, and semi-arid lands (herein, arid lands) form about one third of the Earth's terrestrial surface. Arid lands contain unique biological and cultural diversity, and biodiversity loss in arid lands can have a disproportionate impact on these ecosystems due to low redundancy and a high risk of trophic cascades. They contain unique biological and cultural diversity and host many endemic species, including wild relatives of key crop plants. Yet extensive agriculture, unsustainable use, and global climate change are causing an irrecoverable damage to arid lands, with far-reaching consequences to the species, ground-water resources, ecosystem productivity, and ultimately the communities' dependant on these systems. However, adequate research and effective policies to protect arid land biodiversity and sustainability are lacking because a large proportion of arid areas are in developing countries, and the unique diversity in these systems is frequently overlooked. Developing new priorities for global arid lands and mechanisms to prevent unsustainable development must become part of public discourse and form the basis for conservation efforts. The current situation demands the combined efforts of researchers, practitioners, policymakers, and local communities to adopt a socio-ecological approach for achieving sustainable development (SDGs) in arid lands. Applying these initiatives globally is imperative to conserve arid lands biodiversity and the critical ecological services they provide for future generations. This perspective provides a framework for conserving biodiversity in arid lands for all stakeholders that will have a tangible impact on sustainable development, nature, and human well-being.
Assuntos
Conservação dos Recursos Naturais , Ecossistema , Humanos , Biodiversidade , Agricultura , Mudança ClimáticaRESUMO
Adsorption separation technology using adsorbents is promising as an alternative to the energy-demanding cryogenic distillation of natural gas (CH4/N2) separation. Although a few adsorbents, such as metal-organic frameworks (MOFs), with high performance for CH4/N2 separation, have been reported, it is still challenging to target the desired adsorbents for the actual CH4/N2 separation under humid conditions because the adsorption capacity and selectivity of the adsorbents might be mainly dampened by water vapor. Except for the high CH4 uptake and CH4/N2 selectivity, the adsorption material should simultaneously have excellent stability against moisture and relatively low-water absorption affinity. Here, we tuned the ligands and metal sites of reticular MOFs, Zn-benzene-1,4-dicarboxylic acid-1,4-diazabicyclo[2.2.2]octane (Zn-BDC-DABCO) (DMOF), affording a series of isostructural MOFs (DMOF-N, DMOF-A1, DMOF-A2, and DMOF-A3). Because of the finely engineered pore size and introduced aromatic rings in the functional DMOF, gas sorption results reveal that the materials show improved performance with a benchmark CH4 uptake of 37 cm3/g and a high CH4/N2 adsorption selectivity of 7.2 for DMOF-A2 at 298 K and 1.0 bar. Moisture stability experiments show that DMOF-A2 is a robust MOF with low water vapor capacity even at â¼40% relative humidity (RH) because of the presence of more hydrophobic aromatic rings. Breakthrough experiments verify the excellent CH4/N2 separation performances of DMOF-A2 under high humidity.
RESUMO
Metal-organic frameworks (MOFs) have attracted significant research interest for supercapacitor applications due to their high-tunable conductivity and their structure's pore size. In this work, we report a facile one-step hydrothermal method to synthesize nickel-based metal-organic frameworks (MOF) using organic linker 4,4'-biphenyl dicarboxylic acid (BPDC) for high-performance supercapacitors. The pore size of the Ni-BPDC-MOF nanostructure is tuned through different synthesization temperatures. Among them, the sample synthesized at 180 °C exhibits a nanoplate morphology with a specific surface area of 311.99 m2·g-1, a pore size distribution of 1-40 nm and an average diameter of ~29.2 nm. A high specific capacitance of 488 F·g-1 has been obtained at a current density of 1.0 A·g-1 in a 3 M KOH aqueous electrolyte. The electrode shows reliable cycling stability, with 85% retention after 2000 cycles. The hydrothermal process Ni-BPDC-MOF may provide a simple and efficient method to synthesize high-performance hybrid MOF composites for future electrochemical energy storage applications.
RESUMO
Memory impairment and emotional disorder are two common clinical comorbidities in patients with epilepsy. It is imperative to develop a novel therapeutic agent or a strategy. 6-Chloro-7,8-dihydroxy-3-methyl-1-(3-methylphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine (SKF83959) is a dopamine-1 receptor agonist and sigma-1 receptor allosteric modulator, which displays the neuron-protective and anti-neuroinflammation activity. We examined the effect of SKF83959 on the memory impairment and emotional disorder in the latent period of epilepsy using the mice post-status epilepticus model. We found that SKF83959 ameliorated memory impairment and depressive-like mood, alleviated the neuron damage and the formation of gliosis in hippocampus, suppressed the rise of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-1ß, and induced nitric oxide synthase in the latent period of epilepsy. Additionally, SKF83959 significantly inhibited the activity of calcineurin and glycogen synthase kinase-3ß. All of these protective actions were reversed by BD1047 (a sigma-1 receptor antagonist). In addition, the intra-hippocampus injection of ketoconazole (a dehydroepiandrosterone synthesis inhibitor) also reversed the protective activity of SKF83959. Thus, we concluded that SKF83959 ameliorated the memory impairment and depressive-like mood in epilepsy via allosterically activating the sigma-1 receptor and subsequently inhibiting the calcineurin/glycogen synthase kinase-3ß pathway.
Assuntos
Calcineurina , Epilepsia , Ratos , Animais , Camundongos , Regulação Alostérica , Ratos Sprague-Dawley , Agonistas de Dopamina/farmacologia , Epilepsia/tratamento farmacológico , Quinases da Glicogênio Sintase , Receptor Sigma-1RESUMO
Astrocytes play important roles in the development of depression. As a promising target for antidepressant development, sigma-1 receptor (Sig-1R) is reported to promote activation of astrocyte in chronic stress-induced depression in our previous study. However, astrocytes are hyper-activated in inflammation-induced depression, raising concerns of whether stimulation of astrocytic Sig-1R would exert antidepressant-like effect in inflammation-induced depression. Here we reported that specific stimulation of astrocytic Sig-1R using adeno-associated virus (AAV) significantly attenuated lipopolysaccharide (LPS)- induced depressive-like behavior in the forced swim test (FST), tail suspension test (TST), sucrose preference test, and improved the memory function in novel object recognition test. Besides, specific stimulation of astrocytic Sig-1R decreased the activation of astrocyte and microglia, as well as increased brain-derived neurotrophic factor (BDNF) in LPS-induced depression. In primary cultured astrocytes, overexpression of Sig-1R also reduced the expression of IL-1ß, TNF-α, iNOS during inflammation-treated astrocyte. Taken together, the results suggest that specific stimulation of astrocytic Sig-1R ameliorates inflammation-induced depressive-like behavior, providing the evidence that astrocytic Sig-1R could represent a reliable therapeutic target for depression.
Assuntos
Astrócitos/metabolismo , Comportamento Animal/fisiologia , Depressão , Inflamação , Receptores sigma/metabolismo , Animais , Células Cultivadas , Depressão/etiologia , Depressão/metabolismo , Depressão/fisiopatologia , Modelos Animais de Doenças , Inflamação/induzido quimicamente , Inflamação/complicações , Lipopolissacarídeos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Receptor Sigma-1RESUMO
BACKGROUND: Obesity is known as a common risk factor for osteoporosis and type 2 diabetes mellitus (T2DM). Perirenal fat, surrounding the kidneys, has been reported to be unique in anatomy and biological functions. This study aimed to explore the relationship between perirenal fat and bone metabolism in patients with T2DM. METHODS: A total of 234 patients with T2DM were recruited from September 2019 to December 2019 in the cross-sectional study. The biochemical parameters and bone turnover markers (BTMs) were determined in all participants. Perirenal fat thickness (PrFT) was performed by ultrasounds via a duplex Doppler apparatus. Associations between PrFT and bone metabolism index were determined via correlation analysis and regression models. RESULTS: The PrFT was significantly correlated with ß-C-terminal telopeptides of type I collagen (ß-CTX) (r = -0.14, P < 0.036), parathyroid hormone (iPTH) (r = -0.18, P ≤ 0.006), and 25 hydroxyvitamin D (25-OH-D) (r = -0.14, P = 0.001). Multivariate analysis confirmed that the association of PrFT and ß-CTX (ß = -0.136, P = 0.042) was independent of other variables. CONCLUSION: This study showed a negative and independent association between PrFT and ß-CTX in subjects with T2DM, suggesting a possible role of PrFT in bone metabolism. Follow-up studies and further research are necessary to validate the associations and to elucidate the underlying mechanisms.