The study aimed to investigate the effect of the CD200R1 gene deletion on microglia activation and nigrostriatal dopamine neuron loss in the Parkinson's disease (PD) process. The CRISPR-Cas9 technology was applied to construct the CD200R1^-/- mice. The primary microglia cells of wild-type and CD200R1^-/- mice were cultured and treated with bacterial lipopolysaccharide (LPS). Microglia phagocytosis level was assessed by a fluorescent microsphere phagocytosis assay. PD mouse model was prepared by nigral stereotaxic injection of recombinant adeno-associated virus vector carrying human α-synuclein (α-syn). The changes in the motor behavior of the mice with both genotypes were evaluated by cylinder test, open field test, and rotarod test. Immunohistochemical staining was used to assess the loss of dopamine neurons in substantia nigra. Immunofluorescence staining was used to detect the expression level of CD68 (a key molecule involved in phagocytosis) in microglia. The results showed that CD200R1 deletion markedly enhanced LPS-induced phagocytosis in vitro by the microglial cells. In the mouse model of PD, CD200R1 deletion exacerbated motor behavior impairment and dopamine neuron loss in substantia nigra. Fluorescence intensity analysis results revealed a significant increase in CD68 expression in microglia located in the substantia nigra of CD200R1^-/- mice. The above results suggest that CD200R1 deletion may further activates microglia by promoting microglial phagocytosis, leading to increased loss of the nigrostriatal dopamine neurons in the PD model mice. Therefore, targeting CD200R1 could potentially serve as a novel therapeutic target for the treatment of early-stage PD.
Animals ; Microglia/physiology* ; Mice ; Phagocytosis ; Parkinson Disease/genetics* ; Disease Models, Animal ; Receptors, Cell Surface/physiology* ; Dopaminergic Neurons/pathology* ; Antigens, CD/metabolism* ; Gene Deletion ; Substantia Nigra ; Mice, Inbred C57BL ; Mice, Knockout ; Cells, Cultured ; Male ; alpha-Synuclein ; CD68 Molecule ; Orexin Receptors

The current study aimed to clarify the roles of apolipoprotein A5 (ApoA5) and milk fat globule-epidermal growth factor 8 (Mfge8) in regulating myocardial lipid deposition and the regulatory relationship between them. The serum levels of ApoA5 and Mfge8 in obese and healthy people were compared, and the obesity mouse model induced by the high-fat diet (HFD) was established. In addition, primary cardiomyocytes were purified and identified from the hearts of suckling mice. The 0.8 mmol/L sodium palmitate treatment was used to establish the lipid deposition cardiomyocyte model in vitro. ApoA5-overexpressing adenovirus was used to observe its effects on cardiac function and lipids. The expressions of the fatty acid uptake-related molecules and Mfge8 on transcription or translation levels were detected. Co-immunoprecipitation was used to verify the interaction between ApoA5 and Mfge8 proteins. Immunofluorescence was used to observe the co-localization of Mfge8 protein with ApoA5 or lysosome-associated membrane protein 2 (LAMP2). Recombinant rMfge8 was added to cardiomyocytes to investigate the regulatory mechanism of ApoA5 on Mfge8. The results showed that participants in the simple obesity group had a significant decrease in serum ApoA5 levels (P < 0.05) and a significant increase in Mfge8 levels (P < 0.05) in comparison with the healthy control group. The adenovirus treatment successfully overexpressed ApoA5 in HFD-fed obese mice and palmitic acid-induced lipid deposition cardiomyocytes, respectively. ApoA5 reduced the weight of HFD-fed obese mice (P < 0.05), shortened left ventricular isovolumic relaxation time (IVRT), increased left ventricular ejection fraction (LVEF), and significantly reduced plasma levels of triglycerides (TG) and cholesterol (CHOL) (P < 0.05). In myocardial tissue and cardiomyocytes, the overexpression of ApoA5 significantly reduced the deposition of TG (P < 0.05), transcription of fatty acid translocase (FAT/CD36) (P < 0.05), fatty acid-binding protein (FABP) (P < 0.05), and fatty acid transport protein (FATP) (P < 0.05), and protein expression of Mfge8 (P < 0.05), while the transcription levels of Mfge8 were not significantly altered (P > 0.05). In vitro, the Mfge8 protein was captured using ApoA5 as bait protein, indicating a direct interaction between them. Overexpression of ApoA5 led to an increase in co-localization of Mfge8 with ApoA5 or LAMP2 in cardiomyocytes under lipid deposition status. On this basis, exogenous added recombinant rMfge8 counteracted the improvement of lipid deposition in cardiomyocytes by ApoA5. The above results indicate that the overexpression of ApoA5 can reduce fatty acid uptake in myocardial cells under lipid deposition status by regulating the content and cellular localization of Mfge8 protein, thereby significantly reducing myocardial lipid deposition and improving cardiac diastolic and systolic function.
Animals ; Humans ; Mice ; Myocytes, Cardiac/metabolism* ; Obesity/physiopathology* ; Male ; Apolipoprotein A-V/blood* ; Lipid Metabolism/physiology* ; Milk Proteins/blood* ; Myocardium/metabolism* ; Diet, High-Fat ; Antigens, Surface/physiology* ; Mice, Inbred C57BL ; Cells, Cultured ; Female

Humans ; Consensus ; East Asian People ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Hepatitis B/virology* ; Hepatitis B Antibodies ; Hepatitis B Surface Antigens ; Hepatitis B virus/physiology* ; Virus Activation ; Latent Infection/virology*

Animals ; Antigens, Surface/genetics* ; Cell Communication/genetics* ; Copulation/physiology* ; Fallopian Tubes/metabolism* ; Female ; Fertilization/genetics* ; GPI-Linked Proteins/genetics* ; Gene Expression Regulation ; Genes, Reporter ; Green Fluorescent Proteins/metabolism* ; Litter Size ; Luminescent Proteins/metabolism* ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/metabolism* ; Reproduction/genetics* ; Signal Transduction ; Sperm Count ; Sperm Motility/genetics* ; Spermatozoa/metabolism* ; Uterus/metabolism*

PURPOSEMacrophages are known to be important for healing numerous injured tissues depending on their functional phenotypes in response to different stimuli. The objective of this study was to reveal macrophage phenotypic changes involved in exercise-induced skeletal muscle injury and regeneration.

METHODSAdult male Sprague-Dawley rats experienced one session of downhill running (16° decline, 16 m/min) for 90 min. After exercise the blood and soleus muscles were collected at 0 h, 6 h, 12 h, 1 d, 2 d, 3 d, 1 w and 2 w after exercise, separately.

RESULTSIt was showed that CD68 M1 macrophages mainly infiltrated into muscle necrotic sites at 1-3 d, while CD163 M2 macrophages were present in muscles from 0 h to 2 weeks after exercise. Using transmission electron microscopy, we observed activated satellite cells 1 d after exercise. Th1-associated transcripts of iNOS and Ccl2 were inhibited post exercise, while COX-2 mRNA was dramatically increased 12 h after running (p < 0.01). M2 phenotype marker Arg-1 increased 12 h and 3 d (p < 0.05, p < 0.01) after exercise, and Clec10a and Mrc2 were up-regulated in muscles 12 h following exercise (p < 0.05, p < 0.05).

CONCLUSIONThe data demonstrate the dynamic patterns of macrophage phenotype in skeletal muscle upon eccentric exercise stimuli, and M1 and M2 phenotypes perform different functions during exercise-induced skeletal muscle injury and recovery.

Animals ; Antigens, CD ; analysis ; Antigens, Differentiation, Myelomonocytic ; analysis ; Macrophages ; physiology ; Male ; Muscle, Skeletal ; injuries ; pathology ; Myoglobin ; blood ; Phenotype ; Physical Conditioning, Animal ; Rats ; Rats, Sprague-Dawley ; Receptors, Cell Surface ; analysis

The incidence of HBV infection in lymphoma patients is much higher than that in the general normal population. HBV reactivation caused by treatment is one of the common complications in considerable amount of lymphoma patients, which can induce fatal fulminating hepatitis in severe cases. The HBV reactivation in lymphoma patients is related to multiple factors, such as age, sex, HBV infectious state, HBV genotypes and gene mutations, and antitumor drugs. It's necessary to strengthen monitoring, prevention and treatment to HBV reactivation in the process of dealing with lymphoma. This review focuses on the epidemiological characteristics of lymphoma and HBV, as well as the risk factors, morbidity, pathogenesis, clinical feature, suggestion on prevention and treatment of HBV reactivation.
Antineoplastic Agents ; therapeutic use ; Hepatitis B ; complications ; drug therapy ; prevention & control ; Hepatitis B Surface Antigens ; Hepatitis B virus ; drug effects ; physiology ; Humans ; Lymphoma ; drug therapy ; virology ; Risk Factors ; Virus Activation ; drug effects

Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual's HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.
Antiviral Agents/therapeutic use ; Autoimmune Diseases/complications/pathology ; Hematopoietic Stem Cell Transplantation ; Hepatitis B/complications/drug therapy ; Hepatitis B Core Antigens/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/*physiology ; Humans ; Immunosuppressive Agents/therapeutic use ; Organ Transplantation ; Virus Activation/*physiology

Advances in the treatment of malignant and inflammatory diseases have developed over time, with increasing use of chemotherapeutic and immunosuppressive agents of a range of drug classes with varying mechanism and potency in their effects on the immune system. These advances have been met with the challenge of increased risk of hepatitis B virus (HBV) reactivation in susceptible individuals. The magnitude of risk of HBV reactivation is associated with the individual's HBV serological status and the potency and duration of immunosuppression. Individuals with chronic hepatitis B (CHB) and previously infected but serologically cleared HBV infection are both susceptible to HBV reactivation. HBV reactivation in the setting of immunosuppression is a potentially life threatening condition leading to liver failure and death in extreme cases. It is important to recognize that HBV reactivation in the setting of immunosuppression is potentially preventable. Therefore, identification of patients at risk of HBV reactivation and institution of prophylactic antiviral therapy prior to initiation of immunosuppression is essential.
Antiviral Agents/therapeutic use ; Autoimmune Diseases/complications/pathology ; Hematopoietic Stem Cell Transplantation ; Hepatitis B/complications/drug therapy ; Hepatitis B Core Antigens/blood ; Hepatitis B Surface Antigens/blood ; Hepatitis B virus/*physiology ; Humans ; Immunosuppressive Agents/therapeutic use ; Organ Transplantation ; Virus Activation/*physiology

To examine levels of M-type phospholipase A2 receptor (PLA2R) and its antibody in the patients with hepatitis B virus-associated membranous nephropathy (HBV-MN), and to explore the correlation of PLA2R with laboratory parameters and pathological characteristics.
 Methods: A total of 49 adult patients with biopsy-proved HBV-MN were enrolled in this study. Levels of anti-PLA2R antibody in serum and PLA2R in renal tissue were detected. Patients were assigned into two groups: a positive PLA2R group and a negative PLA2R group. Differences in laboratory parameters and pathological characteristics were compared between the two groups.
 Results: Of 49 patients with HBV-MN, 17 had positive PLA2R expression in renal tissues. In the positive PLA2R group, 10 patients were positive for serum anti-PLA2R antibody. Patients with positive PLA2R expression in renal tissues showed higher levels of 24 hour urinary protein [(4.6±3.9) g/d], serum HbsAg (70.5%) and renal HbsAg expression (71%), while lower level of serum albumin [(24.1±7.5) g/L] than those of the negative group.
 Conclusion: PLA2R is expressed in the renal tissues and serum anti-PLA2R antibody can be detected in some HBV-MN patients. Positive PLA2R expression in renal tissue might be related to HbsAg deposition in serum and renal tissues. Patients with positive PLA2R expression in renal tissue have more severe glomerular sclerosis.
Adult ; Antibodies ; Autoantibodies ; genetics ; physiology ; Biopsy ; Glomerulonephritis, Membranous ; complications ; etiology ; genetics ; Hepatitis B ; complications ; Hepatitis B Surface Antigens ; adverse effects ; Hepatitis B virus ; Humans ; Kidney ; blood supply ; chemistry ; physiopathology ; Kidney Diseases ; etiology ; genetics ; physiopathology ; Male ; Prognosis ; Proteinuria ; epidemiology ; genetics ; Receptors, Phospholipase A2 ; blood ; physiology ; Serum Albumin ; genetics

OBJECTIVES: To examine the sex-specific factors associated with being unaware of one's hepatitis B virus surface antigen (HBsAg) seropositivity status in a large, HBsAg-positive population of Koreans. METHODS: In total, 1197 subjects aged 19 years or older who were HBsAg-positive according to data from the 2007-2012 Korea National Health and Nutrition Examination Survey were included. Subjects were considered unaware of their HBsAg seropositivity status if they answered that they had no knowledge of being previously infected by the hepatitis B virus (HBV) or diagnosed with HBV hepatitis. Multivariate Poisson regression models with robust variance estimate were used to assess the significance of the variables using weighted frequencies. RESULTS: The majority (77.8%) of HbsAg-positive Korean adults (females, 81.9%; males, 74.6%) were unaware of their HBsAg seropositivity status. We found that sex (female: prevalence ratio [PR] 1.19), household income (low: PR, 1.15), marital status (never married: PR, 1.18), self-rated health (moderate: PR, 1.14; good: PR, 1.12), and alcohol use (at least 2-3 times/wk: PR, 1.21) were associated with being unaware. In females, age (50 to 59 years: PR, 1.29; > or =70 years: PR, 1.30), household income (low: PR, 1.37; middle-low: PR, 1.24), and marital status (never married: PR, 1.33) were associated with being unaware. In males, self-rated health (moderate: PR, 1.14; good: PR, 1.21) and alcohol use (at least 2-3 times/wk: PR, 1.21) were associated with being unaware. CONCLUSIONS: Factors related to the socioeconomic status of females and the health-related behaviors of males were found to be associated with being unaware of one's HBsAg seropositivity status.
Adult ; Aged ; Alcohol Drinking ; Asian Continental Ancestry Group ; Awareness/*physiology ; Body Mass Index ; Female ; Health Status ; Hepatitis B/*diagnosis/epidemiology/virology ; Hepatitis B Surface Antigens/*blood ; Hepatitis B virus/*metabolism ; Humans ; Income ; Male ; Middle Aged ; Nutrition Surveys ; Poisson Distribution ; Prevalence ; Republic of Korea/epidemiology ; Sex Factors ; Young Adult