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1.
Cell Biochem Funct ; 42(1): e3912, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38269519

RESUMO

Irisin is a glycosylated protein formed from the hydrolysis of fibronectin type III domain-containing protein 5 (FNDC5). Recent studies have demonstrated that FNDC5/Irisin is involved in the regulation of glucose and lipid metabolism, it can inhibit inflammation and have neuroprotective effects. However, the effect and mechanism of FNDC5/Irisin on motor neuron-like cell lines (NSC-34) have not been reported. In this study, we used lipopolysaccharide to construct cellular oxidative stress injury models and investigated the potential roles of FNDC5/Irisin on neurons by different cellular and molecular pathways. Taken together, our findings showed that FNDC5/Irisin can protect neurons, and this effect might be associated with Caspase3 and Bax pathways. These results laid the foundation for neuronal protection and clinical translation of FNDC5/Irisin therapy.


Assuntos
Fibronectinas , Neurônios Motores , Proteína X Associada a bcl-2 , Metabolismo dos Lipídeos , Estresse Oxidativo , Fatores de Transcrição
2.
Acta Neurol Scand ; 146(5): 553-561, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36237129

RESUMO

OBJECTIVE: Anti-neurofascin 155 (NF155) antibody has been discovered in chronic demyelinating conditions. However, the positive rate and clinical description were insufficient in acute demyelinating conditions, such as Guillain-Barré syndrome (GBS). This study aimed to explore the positive rate of anti-NF155 antibody in GBS patients and determine whether there were unique clinical characteristics in these patients. MATERIALS & METHODS: Serum anti-NF155 antibody was detected from 94 GBS patients and 50 sex- and age-matched healthy controls using cell-based assay and tissue-based assay with immunostaining of mouse teased sciatic nerve fibers. Clinical characteristics, laboratory data, and electrophysiology examinations were retrospectively collected. RESULTS: Seven of 94 (7.45%) GBS patients were positive for anti-NF155 antibody, and the main IgG subclass was IgG1. Compared with anti-NF155 antibody-negative GBS patients, anti-NF155 antibody-positive GBS patients had a higher GBS disability score at nadirs (p = .010), higher modified Erasmus GBS outcome score (p = .022), higher rate of abnormal compound motor action potential (CMAP) amplitude (p = .002), higher frequency of prolonged F-wave latency (p < .001), lower frequency of abnormal sensory conduction velocity (p < .001) and sensory nerve action potential amplitude (p < .001), more axonal type (p = .040), and poorer therapeutic effect (p = .017). CONCLUSIONS: Anti-NF155 antibody exists in a small portion of GBS patients. Anti-NF155 antibody-positive GBS patients possibly have a more severe clinical course, less sensory nerves involved, higher proportion of axonal type, poorer therapeutic effect, and worse prognosis, but the pathogenicity of the anti-NF155 antibody in GBS needs further study.


Assuntos
Síndrome de Guillain-Barré , Animais , Feminino , Síndrome de Guillain-Barré/diagnóstico , Humanos , Imunoglobulina G , Masculino , Camundongos , Condução Nervosa , Estudos Retrospectivos
3.
Neurol Sci ; 43(4): 2785-2790, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34709479

RESUMO

OBJECTIVE: Myasthenia gravis (MG) is an autoimmune disorder whose main symptoms are muscle weakness and fatigue. Irisin is a novel skeletal muscle-derived myokine participating in several physiological and pathological processes. The initial objective of the project was to explore serum levels of irisin in patients with MG, as well as its correlation with disease severity. METHODS: We retrospectively evaluated serum levels of irisin in 77 MG patients and 57 healthy controls (HCs) by enzyme-linked immunosorbent assay. Further, clinical parameters were measured properly. RESULTS: Serum irisin levels were significantly elevated in MG patients compared with HCs (p < 0.001). Furthermore, serum irisin levels were associated with the myasthenia gravis activities of daily living score in ocular myasthenia gravis (OMG) patients (r = 0.476, p = 0.004), but there was no relationship to be considered of any relevant value in generalized myasthenia gravis (GMG) patients. Acetylcholine receptor antibody-positive MG patients had higher serum irisin levels compared with HCs. Thymoma, endotracheal intubation, or intensive care unit treatments subsequently were not found to have effect on serum levels of irisin, but tendencies of increase were observed in negative ones. CONCLUSIONS: Serum irisin levels were elevated in patients with MG, suggesting its possible involvement in MG. And irisin is expected to be a signal to evaluate the activities of daily living of OMG patients, while its effect needs further study.


Assuntos
Atividades Cotidianas , Fibronectinas , Miastenia Gravis , Autoanticorpos/sangue , Fibronectinas/sangue , Humanos , Miastenia Gravis/sangue , Miastenia Gravis/diagnóstico , Receptores Colinérgicos/imunologia , Estudos Retrospectivos
4.
Clin Exp Immunol ; 206(2): 208-215, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34428306

RESUMO

Irisin is a novel hormone-like myokine that plays an important role in central nervous system (CNS) diseases, such as cerebral ischaemia and Alzheimer's disease. However, irisin is rarely investigated in multiple sclerosis (MS), a typical inflammatory demyelinating disease of the CNS, and in experimental autoimmune encephalomyelitis (EAE), a typical model of MS. We determined the levels of irisin in the serum and cerebrospinal fluid in patients with MS. The expression and histological distribution of irisin were determined in EAE. Serum irisin levels in patients with MS and in EAE mice were increased, and the levels of FNDC5/irisin mRNA were decreased in the spinal cord and brain regardless of the onset, peak or chronic phase of EAE. Immunofluorescence staining showed co-localization of irisin and neurones. The levels of irisin fluctuated with disease progression in MS and EAE. Irisin may be involved in the pathological process of MS/EAE.


Assuntos
Encefalomielite Autoimune Experimental , Fibronectinas , Regulação da Expressão Gênica , Esclerose Múltipla , Adulto , Animais , Feminino , Humanos , Masculino , Camundongos , Encefalomielite Autoimune Experimental/líquido cefalorraquidiano , Encefalomielite Autoimune Experimental/imunologia , Fibronectinas/líquido cefalorraquidiano , Fibronectinas/imunologia , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/imunologia
5.
Clin Exp Immunol ; 206(1): 1-11, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33998675

RESUMO

Anti-neurofascin-155 (NF155) antibodies have been observed in two cases with neuromyelitis optica spectrum disorders (NMOSD). This study investigated the prevalence of anti-NF155 antibodies in patients with NMOSD and the clinical features of anti-NF155 antibody-positive patients. Sera from 129 patients with NMOSD were screened with anti-NF155 antibodies by cell-based assay (CBA) and re-examined using immunostaining of teased mouse sciatic nerve fibres. Fifty-six patients with multiple sclerosis (MS) and 50 healthy controls (HC) were also enrolled for detecting anti-NF155 antibodies. A total of 12.40% (16 of 129) of patients with NMOSD were positive for anti-NF155 antibodies confirmed by both CBA and immunostaining. Immunoglobulin (Ig) G1 was the predominant subclass. However, none of 56 MS patients or 50 HC were positive for anti-NF155 antibodies. Anti-NF155 antibody-positive NMOSD patients had a higher proportion of co-existing with autoimmune diseases (p < 0.001) and higher positive rates of serum non-organ-specific autoantibodies, including anti-SSA antibodies (p < 0.001), anti-SSB antibodies (p = 0.008), anti-Ro-52 antibodies (p < 0.001) and rheumatoid factor (p < 0.001). Five anti-NF155 antibody-positive NMOSD patients who took part in the nerve conduction study showed mildly abnormal results. Differences in some nerve conduction study parameters were observed between anti-NF155 antibody-positive and negative patients. Anti-NF155 antibodies occurred in a small proportion of NMOSD patients. Anti-NF155 antibody-positive NMOSD patients tended to co-exist with autoimmune diseases.


Assuntos
Autoanticorpos , Moléculas de Adesão Celular , Fatores de Crescimento Neural , Neuromielite Óptica/sangue , Neuromielite Óptica/imunologia , Adulto , Idoso , Autoanticorpos/sangue , Autoanticorpos/imunologia , Moléculas de Adesão Celular/sangue , Moléculas de Adesão Celular/imunologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Crescimento Neural/sangue , Fatores de Crescimento Neural/imunologia , Neuromielite Óptica/epidemiologia , Prevalência
6.
Fish Shellfish Immunol ; 105: 244-252, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32693160

RESUMO

Barrier-to-autointegration factor (BAF) is a highly conserved DNA binding protein that participates in a variety of biological processes such as transcription, epigenetic regulation and antiviral immunity in vertebrates. However, the function of BAF is poorly understood in crustaceans. In this study, we identified a barrier-to-autointegration factor (CqBAF) from red claw crayfish Cherax quadricarinatus, which was responsive to white spot syndrome virus (WSSV) infection. The full-length cDNA sequence of CqBAF was 544 bp, including an open reading frame of 273 bp encoding 90 amino acids, a 107 bp of 5'-Untranslated Regions (5'-UTR) and a 164 bp of 3'-UTR. Gene expression analysis showed that CqBAF was distributed in all tissues examined with the highest expression in the crayfish haematopietic tissue (Hpt), which protein expression was also significantly up-regulated by WSSV infection in Hpt cells. Furthermore, the transcripts of both an immediate early gene IE1 and a late envelope protein gene VP28 of WSSV were clearly reduced in Hpt cells after gene silencing of CqBAF. Importantly, the promoter activity of two immediate early genes of WSSV, including WSV051 and IE1, was strongly enhanced by the increased phosphorylation of CqBAF, which also facilitated the accumulation of CqBAF protein in the cytoplasm of Sf9 cells. Taken together, these data suggest that CqBAF is likely to increase the replication of WSSV by promoting the transcription of viral immediate early genes, probably regulated by phosphorylation of CqBAF, which sheds new light on the molecular mechanism of WSSV infection.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/imunologia , Decápodes/genética , Decápodes/imunologia , Regulação da Expressão Gênica/imunologia , Imunidade Inata/genética , Vírus da Síndrome da Mancha Branca 1/fisiologia , Sequência de Aminoácidos , Animais , Proteínas de Artrópodes/química , Proteínas de Artrópodes/genética , Proteínas de Artrópodes/imunologia , Astacoidea , Sequência de Bases , Proteínas de Ligação a DNA/química , Perfilação da Expressão Gênica , Filogenia , Alinhamento de Sequência
7.
BMC Neurol ; 20(1): 307, 2020 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-32814555

RESUMO

BACKGROUND: Interleukin 36 (IL-36), as a gradually recognized cytokine, is involved in the occurrence and evolution of autoimmune diseases. Nevertheless, the relationship between myasthenia gravis (MG) and IL-36 is rarely reported. METHODS: We evaluated the serum levels of IL-36 (IL-36α, IL-36ß and IL-36γ) by enzyme-linked immunosorbent assay (ELISA). Further, clinical parameters in 97 MG patients and 49 healthy controls (HCs) were carefully measured. RESULTS: Serum IL-36γ levels were significantly elevated in the MG patients compared with the HCs (p < 0.0001). Compared to those in remission, patients in the acute phase exhibited higher levels of IL-36α and IL-36γ (p = 0.038 and p = 0.011, respectively). Furthermore, patients with generalized MG (GMG) exhibited markedly higher serum IL-36γ levels than those with ocular MG (OMG) (p = 0.003). CONCLUSIONS: The serum levels of IL-36γ in patients with MG were increased and positively correlated with disease severity and may thus have potential as a serological MG marker.


Assuntos
Biomarcadores/sangue , Interleucina-1/sangue , Miastenia Gravis/sangue , Miastenia Gravis/imunologia , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Adulto Jovem
8.
Neurol Sci ; 41(10): 2859-2866, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32328833

RESUMO

BACKGROUND AND OBJECTIVE: Autoimmune longitudinal extensive transverse myelitis (LETM) is often combined with connective tissue disorders (CTD). The purpose of this study was to compare the clinical characteristics of autoimmune LETM with and without CTD. METHODS: Ninety-two patients diagnosed with autoimmune LETM were enrolled from our clinical database and divided into two groups depending on whether they had a concomitant diagnosis of CTD. Differences in clinical, serological, and imaging characteristics between the two groups were evaluated and compared. RESULTS: Fifty-nine LETM patients without CTD and 33 LETM patients with CTD were included. LETM patients with CTD had higher Kurtzke Expanded Disability Status Scale at nadir and more severe sensory dysfunction (p < 0.05) than those without CTD. It was also found that LETM patients with CTD, compared with those without CTD, had elevated levels of immune inflammation markers such as IgG, IgA, and globulins (p < 0.05). These abovementioned characteristics were more prominent in patients with aquaporin-4 antibodies (AQP4-ab) than in those without them. In addition, the most common type of CTD in LETM was Sjögren syndrome (SS), which was usually diagnosed at the time of LETM or later. CONCLUSION: LETM patients with CTD, especially those with AQP4-ab, had greater sensory dysfunction and higher levels of inflammatory markers than did LETM patients without CTD. Multicenter cooperation and long-term follow-up are necessary to further study the inherent implications and prognosis of the disease.


Assuntos
Mielite Transversa , Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Tecido Conjuntivo , Humanos , Imageamento por Ressonância Magnética , Mielite Transversa/complicações , Mielite Transversa/diagnóstico , Estudos Retrospectivos
9.
BMC Neurol ; 19(1): 185, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31382910

RESUMO

BACKGROUND: Interleukin 36 (IL-36) cytokines belong to the IL-1 family and play an important role in some autoimmune diseases. However, the relationship between IL-36 and neuromyelitis optica spectrum disorders (NMOSD) remains unclear. METHODS: We determined serum IL-36α, IL-36ß and IL-36γ levels and assessed correlations with clinical characteristics in 50 NMOSD patients and 30 healthy controls (HC). RESULTS: The concentrations of serum IL-36ß and IL-36γ were significantly higher in patients with NMOSD than in HCs and decreased during remission. Serum IL-36ß levels were positively correlated with the annual relapse rate (ARR), spinal cord lesion length and Expanded Disability Status Scale (EDSS) scores. CONCLUSIONS: Serum IL-36ß and IL-36γ levels were related to disease activity in NMOSD patients and may be important biomarkers of NMOSD.


Assuntos
Biomarcadores/sangue , Interleucina-1/sangue , Interleucina-1/imunologia , Neuromielite Óptica/sangue , Neuromielite Óptica/imunologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
10.
BMC Neurol ; 18(1): 177, 2018 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-30355349

RESUMO

BACKGROUND: Neuromyelitis optica spectrum disorders (NMOSD) often coexist with connective tissue disorders (CTD). The aim of this study was to investigate and compare the features of NMOSD with and without CTD. METHODS: NMOSD patients with (n = 18) and without CTD (n = 39) were enrolled, and the clinical, laboratory, and magnetic resonance imaging (MRI) features of the two groups were assessed. RESULTS: Most of the demographic and clinical features examined were similar between NMOSD patients with and without CTD. Serum immunoglobulin G (IgG), percentage of γ-globulin and seropositivity for several other autoantibodies were significantly elevated in NMOSD patients with CTD (P < 0.05). NMOSD with CTD was marked by longer spinal cord lesions and a lower frequency of short transverse myelitis (TM) than NMOSD without CTD (P < 0.05). NMOSD with CTD also featured more T1 hypointensity and T2 bright spotty lesions (BSLs) on MRI than NMOSD without CTD (P = 0.001 and 0.011, respectively). There were no other differences in laboratory, MRI and clinical characteristics between different NMOSD subtypes. CONCLUSIONS: A few characteristics differed between NMOSD with and without CTD. NMOSD patients with CTD had higher serum IgG, longer spinal cord lesions, a lower frequency of short TM and more T1 hypointensity and T2 BSLs on spinal MRI than NMOSD patients without CTD.


Assuntos
Doenças do Tecido Conjuntivo/complicações , Neuromielite Óptica/complicações , Adulto , Idoso , Doenças do Tecido Conjuntivo/imunologia , Doenças do Tecido Conjuntivo/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neuromielite Óptica/imunologia , Neuromielite Óptica/patologia
11.
Fish Shellfish Immunol ; 57: 213-221, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27544268

RESUMO

It is well-known that anti-lipopolysacchride factors (ALFs) are involved in the recognition and elimination of invading pathogens. In this study, the full-length ALF cDNA sequence of the red claw crayfish Cherax quadricarinatus (termed CqALF) was cloned from a suppression subtractive hybridization library constructed using red claw crayfish hematopoietic tissue cell (Hpt cell) cultures following challenge with white spot syndrome virus (WSSV). The full-length cDNA sequence of CqALF was 863 bp, and the open reading frame encoded 123 amino acids with a signal peptide in the N-terminus and a conserved LPS-binding domain. Unlike most ALFs, which are highly expressed in haemocytes, high expression levels of CqALF were detected in epithelium, the stomach and eyestalks, while lower expression was detected in Hpt, nerves, the heart, muscle tissue, gonads, haemocytes, intestines, gills and the hepatopancreas. To further explore the biological activities of CqALF, mature recombinant CqALF protein (rCqALF) was expressed and purified using a eukaryotic expression system, and an antimicrobial activity test was carried out. rCqALF clearly exerted antiviral activity, as evidenced by the severe disruption of the envelope of intact WSSV virions following co-incubation of virions with rCqALF. Additionally, pre-incubation of WSSV with rCqALF resulted in both a significant reduction in WSSV replication in red claw crayfish Hpt cell cultures and an increased survival rate among animals. Furthermore, rCqALF was effective against both Gram-negative bacteria and Gram-positive bacteria, particularly Shigella flexneri and Staphylococcus aureus. A membrane integrity assay suggested that rCqALF was unlikely to disrupt bacterial membrane integrity compared to cecropin P1. Taken together, these data suggest that CqALF may play an important role in immune defence in the crustacean C. quadricarinatus.


Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Proteínas de Artrópodes/genética , Astacoidea/genética , Sequência de Aminoácidos , Animais , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/metabolismo , Proteínas de Artrópodes/química , Proteínas de Artrópodes/metabolismo , Astacoidea/microbiologia , Astacoidea/virologia , Sequência de Bases , Candida albicans/fisiologia , Clonagem Molecular , DNA Complementar/genética , DNA Complementar/metabolismo , Bactérias Gram-Negativas/fisiologia , Bactérias Gram-Positivas/fisiologia , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Alinhamento de Sequência , Vírus da Síndrome da Mancha Branca 1/fisiologia
12.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(12): 1491-1495, 2016 Dec.
Artigo em Zh | MEDLINE | ID: mdl-30650296

RESUMO

Objective To explore the effect of Wenshen Yangxue Recipe (WYR) on inhibin-ac- tivin-follistatin (INH-ACT-FS) system and gonadal hormone level in anovulatory rats. Methods Anovula- tory rat model was established in 76 rats (9 days old) by subcutaneous injecting testosterone propionate (1. 25 mg/0. 05 mL for each rat) from the nape. Totally 58 successfully modeled rats were divided into 5 groups according to random digit table, i.e., the model group (n =10), the Western medicine (WM) group (n =12), high, middle, and low dose WYR groups (n =12). Besides, another ten 22-day old rats were recruited as a normal group. Distilled water was daily administered to rats in the normal group and the model group by gastrogavage. Clomiphene citrate (0. 58 mg/100 g) was daily administered to rats in the WM group for 5 successive days. WYR at 5. 2, 2. 6, 1. 3 mg/100 g was daily administered to rats in high, middle, and low dose WYR groups for 21 successive days. Levels of follicular stimulating hormone (FSH) , luteinizing hormone (LH) , estradiol (E2) , progesterone (P) , and prolactin (PRL) were detected using radioimmunoassay. Contents of inhibin (INH) , activin (ACT) , and follistatin (FS) were measured using ELISA. Results Compared with the normal group, serum levels of FSH and LH increased, and P level decreased in the model group (P <0. 05) ; INH level decreased and FS level increased in the model group (P<0. 05). Compared with the model group, serum FSH level decreased in the WM group and 3 WYR groups, P level decreased in the WM group (P <0. 05); INH increased and FS levels decreased in the WM group and 3 WYR groups; ACT level increased in the high dose WYR group, with statistical differ- ence (P <0. 05). Conclusion WYR promoted follicular development possibly through regulating INH- ACT-FS system and gonadal hormone level.


Assuntos
Anovulação , Medicamentos de Ervas Chinesas , Folistatina , Inibinas , Ativinas , Animais , Anovulação/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Feminino , Hormônio Foliculoestimulante , Folistatina/efeitos dos fármacos , Inibinas/efeitos dos fármacos , Hormônio Luteinizante , Ratos
13.
Zhongguo Zhong Yao Za Zhi ; 39(22): 4405-10, 2014 Nov.
Artigo em Zh | MEDLINE | ID: mdl-25850276

RESUMO

OBJECTIVE: To observe the protective effects of the Huanglian Jiedu decoction aqueous extract and its active fraction, which consists of total alkaloids, total flavonoids and total iridoid, on the thalamus of cerebral ischemia in rats. METHOD: The rat model of middle cerebral artery occlusion (MCAO) was chosen. Male SD rats were randomly divided into sham-operation group, model group, aqueous extract group (800 mg x kg(-1)), total alkaloids group(44 mg x kg(-1)), total flavonoids group (50 mg x kg(-1)) and the total iridoid group (80 mg x kg(-1)). The rats were administered the appropriate drugs intragastrically once a day, for 7 days after surgery. An equivalent volume of saline was given in the sham surgery and model groups. The HE staining was adopted to observe the pathological changes. Determination of Glu and gamma-GABA in thalamus were detected by HPLC with fluorescence detection. The expression of GAD65 was examined with immunohistochemistry and double staining with uorescent-conjugated antibodies against GFAP and Cx43 was chosen in this study. RESULT: The neurons degenerated in MCAO rats after cerebral ischemia 7 d. The content of Glu, gamma-GABA decreased (P < 0.05), the expression of GAD65 reduced (P < 0.05) and the expression of GFAP and Cx43 increased (P < 0.01) in thalamus of rats compared with sham-operation group. Huanglian Jiedu decoction aqueous extract, total alkaloids, total flavonoids and total iridoid reduced the degeneration of neurons. Total flavonoids could promote the expression of GAD65 (P < 0.05) and decrease the expression of GFAP and Cx43 (P < 0.01) in thalamus compared with model group while it could also increased the content of Glu,gamma-GA BA to normal levels. Compared with model group, Huanglian Jiedu decoction aqueous extract, total alkaloids and total iridoid could raise the expression of Cx43, and Huanglian Jiedu decoction aqueous extract could also increase the expression of GAD65 (P < 0.05). The expression of GFAP in Huanglian Jiedu decoction aqueous extract group, total alkaloids group and total iridoid group were not different compared with model group while the content of gamma-GABA decreased (P < 0.05) compared with sham-operation group. CONCLUSION: The degeneration of nerve cells, the reduction of neurotransmitter amino acids content, the aberrant activation of astrocytes and the abnormal expression of GFAP and Cx43 will appear in thalamus of MCAO rats after ischemia. Huanglian Jiedu decoction total flavonoids could relieve the injury of nerve cell through inhibiting the abnormal activation of astrocytes and regulating the expression of GFAP and GAD65.


Assuntos
Astrócitos/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Substâncias Protetoras/farmacologia , Tálamo/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley
14.
Inflammation ; 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38761250

RESUMO

Abnormal activation of microglia, the resident macrophages in the central nervous system, plays an important role in the pathogenesis of multiple sclerosis (MS). The immune responsive gene 1(IRG1)/itaconate axis is involved in regulating microglia-mediated neuroinflammation. 4-Octyl itaconate (4-OI), a derivative of itaconate, plays a crucial immunomodulatory role in macrophages. This study investigated the effects and mechanisms of action of 4-OI on experimental autoimmune encephalomyelitis (EAE) and inflammatory BV2 microglia. In an EAE mouse model, clinical evaluation was conducted during the disease course. Hematoxylin and eosin staining was performed to assess inflammatory infiltration and Luxol Fast Blue was used to visualize pathological damage. Quantitative real-time polymerase chain reaction, western blotting and immunofluorescence were used to evaluate inflammatory response and microglial function status in EAE mice. BV2 microglia were used to further investigate the effects and mechanisms of action of 4-OI in vitro. 4-OI significantly alleviated the clinical symptoms of EAE, the inflammatory infiltration, and demyelination; reduced the levels of inflammatory factors; and inhibited the classical activation of microglia in the spinal cord. 4-OI successfully suppressed the classical activation of BV2 microglia and decreased the levels of inflammatory factors by activating the Nrf2/HO-1 signaling pathway. Furthermore, 4-OI downregulated IRG1 expression in both EAE mice and inflammatory BV2 microglia. 4-OI attenuates the microglia-mediated neuroinflammation and has promising therapeutic effects in MS.

15.
Huan Jing Ke Xue ; 45(5): 2962-2970, 2024 May 08.
Artigo em Zh | MEDLINE | ID: mdl-38629557

RESUMO

The sediment and soil in the Juma River channel pose a risk of pollution to the downstream ecological environment of Beijing and Xiong'an New Area. To address this issue, sediments and soil samples were collected along the river from the source to the Zhangfang outlet. The samples were further divided into three types:main stream sediment (29 samples), riverbank soil (27 samples), and farmland soil (26 samples). Enrichment factor analysis and the potential ecological risk index were employed to investigate the ecological risk. The results showed that the average concentrations of Cd, Hg, Pb, Zn, and Cu in the river sediment and soil in the study area were higher than those in the Baiyangdian Lake sediment and the surface soil of Hebei Province, whereas the concentrations of As, Cr, and Ni were relatively lower. The ranking of heavy metal pollution levels from high to low were Cd > Hg > Pb > Zn > Cu > Cr > Ni > As. The comprehensive ecological risk index showed that farmland soil and riverbank soil were mainly at a slight risk, followed by a moderate risk. The potential ecological risk of the main stream sediment was mainly moderate, severe, and extremely severe, accounting for 35.5%, 24.1%, and 24.1%, respectively, and the main contributing factors of the risk were Cd and Hg. The results of multivariate statistical analysis indicated that the main pollution sources of Cd, Pb, Zn, and Cu were industrial and mining activities. Cr, Ni, and As were mainly controlled by the weathering of the parent rock, and As was also influenced by agricultural activities. Hg was controlled by composite pollution sources such as industrial and mining activities, parent rock weathering, and atmospheric dust fall. Overall, the risk of heavy metal in the soil of the research area was generally at a slight level. However, there was a significant enrichment of Cd and other heavy metal in the sediment of the Taiyu-Sigezhuang-Pengtou River. This river section should be the focus of environmental monitoring, river dredging, and governance.

16.
Arterioscler Thromb Vasc Biol ; 32(11): 2694-701, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22922960

RESUMO

OBJECTIVE: The function of the endothelial cell (EC)-enriched Rho family guanine nucleotide exchange factor, facio-genital dysplasia-5 (FGD5), is poorly understood. We sought to determine whether FGD5 regulates endothelial cytoskeletal reorganization and angiogenesis. METHODS AND RESULTS: We observed that FGD5 is expressed in primary human EC isolated from sites across the vasculature. Inhibition of FGD5 expression using RNA interference decreased the protein by ≈70%. In 3-dimensional vascular endothelial growth factor-stimulated angiogenesis in vitro, FGD5-deficient endothelial sprout protrusion was markedly blunted versus nonsilenced controls. FGD5 knockdown impaired adhesion to fibronectin and collagen IV and remodeling of matrix adhesion complexes. Similarly, monolayer electric impedance was decreased, and impedance increased at a slower rate after seeding FGD5-deficient cells versus controls, reflecting decreased EC spreading. Further, FGD5 plays a role in cell survival, because expression of cleaved caspase-3 was increased in FGD5-deficient EC after loss of cell-matrix contacts, and proapoptotic tumor necrosis factor-α stimulation elicited EC with subdiploid DNA content among FGD5-deficient EC. Mechanistically, the phosphatidylinositol 3-kinase/Akt pathway that regulates both adhesive and survival signal transduction pathways requires FGD5. Vascular endothelial growth factor-stimulated Akt phosphorylation and downstream forkhead box protein-O1 inactivation is inhibited by FGD5 loss. CONCLUSIONS: FGD5 regulates endothelial adhesion, survival, and angiogenesis by modulating phosphatidylinositol 3-kinase signaling.


Assuntos
Adesão Celular , Colágeno Tipo IV/metabolismo , Fibronectinas/metabolismo , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Apoptose , Caspase 3/metabolismo , Sobrevivência Celular , Células Cultivadas , Citoesqueleto/metabolismo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Humanos , Neovascularização Fisiológica , Fosfatidilinositol 3-Quinase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interferência de RNA , Transdução de Sinais , Fatores de Tempo , Transfecção , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Clin Neurol Neurosurg ; 229: 107720, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37084652

RESUMO

OBJECTIVE: The anterior choroidal artery territory (AChA) infarction has a high rate of progression and poor functional prognosis. The aim of the study is to search for fast and convenient biomarkers to forecast the early progression of acute AChA infarction. METHODS: We respectively collected 51 acute AChA infarction patients, and compared the laboratorial index between early progressive and non-progressive acute AChA infarction patients. The receiver-operating characteristics curve (ROC) analysis was used to determine the discriminant efficacy of indicators that had statistical significance. RESULTS: The white blood cell, neutrophil, monocyte, white blood cell to high-density lipoprotein cholesterol ratio, neutrophil to high-density lipoprotein cholesterol ratio (NHR), monocyte to high-density lipoprotein cholesterol ratio, monocyte to lymphocyte ratio, neutrophil to lymphocyte ratio (NLR), and hypersensitive C-reaction protein in acute AChA infarction are significantly higher than healthy controls (P < 0.05). The NHR (P = 0.020) and NLR (P = 0.006) are remarkably higher in acute AChA infarction patients with early progression than non-progression. The area under the ROC curve of NHR, NLR, the combine of NHR and NLR are 0.689 (P = 0.011), 0.723 (P = 0.003), 0.751 (P < 0.001), respectively. But there are no significant differences in efficiency between NHR and NLR and their combined marker in predicting progression (P > 0.05). CONCLUSION: NHR and NLR may be significant predictors of early progressive patients with acute AChA infarction, and the combination of NHR and NLR could be a preferable prognostic marker for AChA infarction with early progressive course in acute stage.


Assuntos
Linfócitos , Neutrófilos , Humanos , Prognóstico , Biomarcadores , Infarto , Infarto Cerebral , Lipoproteínas HDL , Colesterol , Artérias , Estudos Retrospectivos , Curva ROC
18.
Front Public Health ; 11: 1168792, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37397753

RESUMO

Objective: Frailty increases adverse clinical outcomes in older patients with cardio-cerebral vascular disease (CCVD). The aim of this study was to investigate the prevalence of frailty and pre-frailty in older adults with CCVD in China and the factors associated with it. Research design and methods: In this cross-sectional study, we used data from the fourth Sample Survey of Aged Population in Urban and Rural China. We used the frailty index for frailty and pre-frailty assessment, and the diagnosis of CCVD in older adults was self-reported. Results: A total of 53,668 older patients with CCVD were enrolled in the study. The age-standardized prevalence of frailty and pre-frailty in older patients with CCVD was 22.6% (95% CI 22.3-23.0%) and 60.1% (95% CI 59.7-60.5%). Multinomial logistic regression analyses showed that being female, increasing age, rural residence, illiteracy, widowhood, ethnic minority, living alone, no health screening during the last year, hospitalization during the last year, difficult financial status, comorbid chronic conditions, and disability in activities of daily living were associated with frailty and pre-frailty in older patients with CCVD. Conclusion: CCVD is strongly associated with frailty and pre-frailty in older Chinese people, and assessment of frailty should become routine in the management of older CCVD patients. Appropriate public health prevention strategies should be developed based on identified risk factors for frailty in older CCVD patients, which can help prevent, ameliorate or reverse the development of frailty in CCVD in the older population.


Assuntos
Fragilidade , Doenças Vasculares , Idoso , Humanos , Feminino , Masculino , Fragilidade/epidemiologia , Idoso Fragilizado , Estudos Transversais , Atividades Cotidianas , Prevalência , Etnicidade , Grupos Minoritários , China/epidemiologia
19.
Front Public Health ; 11: 1136135, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36935664

RESUMO

Objective: There are few studies on the prevalence and factors associated with frailty and pre-frailty in older adults with asthma worldwide. The aim of this study was to examine the epidemiological status and factors associated with frailty and pre-frailty in older adults with asthma in China. Research design and methods: Data were obtained from the Sample Survey of Aged Population in Urban and Rural China in 2015, a nationwide cross-sectional survey covering 224,142 older people aged 60 years or older in 31 provinces/autonomous regions/municipalities in mainland China. We performed frailty and pre-frailty assessments using the frailty index, and the diagnosis of asthma in the older adults was self-reported based on the history of the physician's diagnosis. Results: Nine thousand four hundred sixteen older adults with asthma were included in the study. The age-sex standardized prevalence of frailty and pre-frailty in Chinese older adults with asthma was 35.8% (95% CI 34.8%-36.7%) and 54.5% (95% CI 53.5%-55.5%). Multinomial logistic regression analysis showed that increased age, female, illiteracy, living alone, poor economic status, ADL disability, comorbid chronic diseases, previous hospitalization in the past year, and residence in northern China were associated with frailty and pre-frailty in older adults with asthma. Conclusion: The prevalence of frailty and pre-frailty in Chinese older adults with asthma is very high, and assessment of frailty should become routine in the management of older adults with asthma. Appropriate public health prevention strategies based on identified risk factors for frailty in older adults with asthma should be developed to reduce the burden of frailty in Chinese older adults with asthma.


Assuntos
Asma , Fragilidade , Humanos , Feminino , Idoso , Fragilidade/epidemiologia , Estudos Transversais , Asma/epidemiologia , China/epidemiologia , Fatores de Risco
20.
Front Public Health ; 11: 1110648, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37554734

RESUMO

Objective: Frailty increases poor clinical outcomes in older adults, the aim of this study was to investigate the prevalence and factors associated with frailty and pre-frailty in older adults in China. Research design and methods: Data were obtained from the Sample Survey of the Aged Population in Urban and Rural China in 2015, which was a cross-sectional study involving a nationally representative sample of older adults aged 60 years or older from 31 provinces/autonomous regions/municipalities in mainland China. The frailty index (FI) based on 33 potential deficits was used to classify individuals as robust (FI < 0.12), pre-frail (FI ≧0.12 and <0.25) and frail (FI ≥0.25). Results: A total of 208,386 older people were included in the study, and the age-sex standardised prevalence of frailty and pre-frailty among older adults in China was 9.5% (95% CI 9.4-9.7) and 46.1% (45.9-46.3) respectively. The prevalence of frailty and pre-frailty was higher in female than in male older adults, higher in rural than in urban older adults, and higher in northern China than in southern China. The multinomial analysis revealed similar risk factors for frailty and pre-frailty, including increased age, being female, living in a rural area, low educational attainment, poor marital status, living alone, difficult financial status, poor access to medical reimbursement, and living in northern China. Conclusion: Frailty and pre-frailty are very common among older adults in China and differ significantly between southern and northern China, men and women, and rural and urban areas. Appropriate public health prevention strategies should be developed based on identified risk factors in frail and pre-frail populations. The management of frailty and pre-frailty should be optimised according to regional and gender differences in prevalence and associated factors, such as strengthening the integrated management of chronic diseases, increasing reimbursement rates for medical costs, and focusing on vulnerable groups such as the disabled, economically disadvantaged, living alone and those with low literacy levels, in order to reduce the burden of frailty among older adults in China.


Assuntos
Fragilidade , Idoso , Humanos , Masculino , Feminino , Fragilidade/epidemiologia , Idoso Fragilizado , Estudos Transversais , Prevalência , China/epidemiologia
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