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1.
Article | IMSEAR | ID: sea-228637

ABSTRACT

Steroid-resistant nephrotic syndrome poses a significant therapeutic challenge in paediatric nephrology. Previously exact cause of steroid-resistant nephrotic syndrome was mostly unknown. Recently, advancements in diagnostic intervention, they are found to be a heterogeneous entity having an immune basis and genetic aetiology. With a better understanding of the pathogenesis of SRNS, leading to the development of novel therapeutic strategies. Novel therapeutic options include extracorporeal therapy, monoclonal antibodies, stem cell therapy, ACTH and galactose. The aim of this study was to provide an overview of emerging therapies for SRNS in paediatric populations.

2.
Chinese Journal of Nephrology ; (12): 225-230, 2024.
Article in Chinese | WPRIM | ID: wpr-1029293

ABSTRACT

IgA nephropathy (IgAN) is currently the most common primary glomerulonephritis worldwide, with 20%-40% of patients progressing to end-stage renal disease within 20 years of diagnosis. At present, the pathogenesis of IgAN is not clear, and clinical treatment is mainly to control the progression, without specific treatment plan. A series of studies on galactose-deficient IgA1 (Gd-IgA1) suggest that the pathogenesis of IgAN involves multiple links. This review summarizes the research progress on the pathogenesis of IgAN, covering the structure characteristics of IgA1, Gd-IgA1 antibodies and Gd-IgA1 immune complexes in IgAN patients, the deposition of Gd-IgA1 immune complexes in the kidneys, kidney damage following the deposition of Gd-IgA1 immune complexes, the role of complement in IgAN, the genomics of IgAN, and mucosal immunity in IgAN, providing clues and insights for further research and clinical treatment.

3.
Int. j. morphol ; 41(3): 825-830, jun. 2023. ilus, tab
Article in English | LILACS | ID: biblio-1514291

ABSTRACT

SUMMARY: The cerebellum is a crucial area of the hindbrain that plays an essential role in balancing, excitement control, and subtle and accurate functions. Studies have shown that long-term use of D-galactose in mice, as with the symptoms of aging, causes morphological and functional disorders in the brain. This study was performed to evaluate the changes in the cerebellum cortex tissue and the measurement of reactive oxygen species (ROS) in the cerebellum following the induction of aging in mice by D-galactose. Accordingly, subjects were randomly assigned into two groups: Normal saline group and Aging group (D-galactose). To create an aging model, D- galactose, and saline solution (sodium chloride 0.9 %) were used. After completing the preparation and passage of the tissue, the cerebellum specimens were cut in 5 microns thickness and then stained with hematoxylin-eosin stain and finally examined under a Nikon microscope. Quantitative variables were analyzed by SPSS software using T-test. In the observations of cerebellum tissue samples, in the aged induced group by D-galactose, the most changes were observed in the Neuron purkinjense (Purkinje cells) layer. In the observations of the cerebellum tissue samples of aging group induced by D-galactose, the most changes were observed in the Neuron purkinjense, and the arrangement and placement of these cells were disorientated. The nucleus positioning was not central, and the Neuron purkinjense induced by aging were seen in different morphological forms. Necrosis, Chromatolysis, and Pyknosis were found. Based on the results, D-galactose (induction of aging) causes pathological changes in the cerebellar cortex, especially in the Neuron purkinjense layer.


El cerebelo es un área crucial del rombencéfalo que desempeña un papel esencial en el equilibrio, el control de la excitación y las funciones sutiles y precisas. Los estudios han demostrado que el uso a largo plazo de D-galactosa en ratones, al igual que con los síntomas del envejecimiento, provoca trastornos morfológicos y funcionales en el cerebro. Este estudio se realizó para evaluar los cambios en el tejido de la corteza del cerebelo y la medición de especies reactivas de oxígeno (ROS) en el cerebelo luego de la inducción del envejecimiento en ratones por D-galactosa. En consecuencia, los sujetos fueron asignados aleatoriamente a dos grupos: grupo de solución salina normal y grupo de envejecimiento (D-galactosa). Para crear un modelo de envejecimiento, se utilizaron D-galactosa y solución salina (cloruro de sodio al 0,9 %). Después de completar la preparación y el paso del tejido, las muestras de cerebelo se cortaron en un grosor de 5 µm y luego se tiñeron con tinción de hematoxilina-eosina y finalmente se examinaron bajo un microscopio Nikon. Las variables cuantitativas se analizaron mediante el software SPSS utilizando la prueba T. En las observaciones de muestras de tejido de cerebelo, en el grupo envejecido inducido por D-galactosa, la mayoría de los cambios se observaron en la capa de neuronas purkinjenses (células de Purkinje). En las observaciones de las muestras de tejido del cerebelo del grupo de envejecimiento inducidas por D-galactosa, la mayoría de los cambios se observaron en las neuronas purkinjenses, y la disposición y ubicación de estas células estaban desorientadas. El posicionamiento del núcleo no era central y las neuronas purkinjenses inducidas por el envejecimiento se observaban en diferentes formas morfológicas. Se encontró necrosis, cromatólisis y picnosis. Según los resultados, la D-galactosa (inducción del envejecimiento) provoca cambios patológicos en la corteza cerebelosa, especialmente en la capa de neuronas purkinjenses.


Subject(s)
Animals , Male , Mice , Aging , Cerebellum/pathology , Galactose/administration & dosage , Purkinje Cells , Cerebellum/cytology , Reactive Oxygen Species , Models, Animal , Mice, Inbred BALB C
4.
Article in Chinese | WPRIM | ID: wpr-972291

ABSTRACT

ObjectiveTo investigate the mechanism of Lycium barbarum polysaccharides (LBP) in promoting the activation of RAW264.7 macrophages. MethodRAW264.7 macrophages were stimulated with LBP at different concentrations (50, 100, 200 mg·L-1), and those stimulated with lipopolysaccharide (LPS) at 100 μg·L-1 and galactose (Gal) at 100 mg·L-1 as positive controls. After 24 h of LBP stimulation, the cell counting kit-8 (CCK-8) was used to detect the survival rate of RAW264.7 macrophages treated with LBP (0, 50, 100, 200, 400, 800 mg·L-1). The levels of interleukin-6 (IL-6) and interleukin-12 (IL-12) in cell culture supernatant were detected by enzyme-linked immunosorbent assay (ELISA). The protein and mRNA expression of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and nuclear factor κB (NF-κB) in Toll-like receptor 4 (TLR4)/Toll-like receptor 2 (TLR2)/macrophage galactose-type lectin (MGL) pathway of RAW264.7 macrophages was detected by Real-time fluorescence-based quantitative polymerase chain reaction (Real-time PCR) and Western blot. ResultCCK-8 results showed that compared with the results in the blank group, the survival rate of RAW264.7 macrophages decreased in the 400, 800 mg·L-1 LBP groups (P<0.05). ELISA results showed that compared with the blank group, 50 mg·L-1 LBP could promote the secretion of IL-12 in RAW264.7 macrophages (P<0.01). Compared with the blank group, 100 mg·L-1 LBP and 200 mg·L-1 LBP could promote the secretion of IL-6 in RAW264.7 macrophages (P<0.05, P<0.01). Western blot results showed that compared with the blank group, the LBP groups (50, 100, 200 mg·L-1) enhanced protein expression levels of MAPK key molecules (p-p38 MAPK, p-ERK, p-NF-κB, and p-JNK) in TLR4, TLR2, and MGL pathways (P<0.05, P<0.01). Compared with the model group, the 200 mg·L-1 LBP group could promote the expression level of p-NF-κB protein in RAW264.7 macrophages (P<0.01). Real-time PCR results showed that compared with the blank group, the LBP groups (50, 100, and 200 mg·L-1) enhanced the mRNA expression levels of MAPK key molecules (p38 MAPK, ERK, NF-κB, and JNK) in TLR4 and TLR2 pathways (P<0.05, P<0.01). Compared with the model group, the 50 and 200 mg·L-1 LBP groups could promote the mRNA expression levels of JNK and ERK2 in RAW264.7 macrophages (P<0.05, P<0.01). ConclusionLBP can regulate the activation of RAW264.7 macrophages and participate in the immune response through the TLR2/TLR4/MGL pathway.

5.
China Pharmacy ; (12): 413-418, 2023.
Article in Chinese | WPRIM | ID: wpr-962483

ABSTRACT

OBJECTIVE To study the intervention effect and metabolic mechanism of Mongolian medicine Echinops sphaerocephalus extract on D-galactose-induced osteoporosis. METHODS Thirty-six 12-week-old male Wistar rats were selected and randomly divided into blank group, model group, Gushukang group, E. sphaerocephalus high-dose, medium-dose and low- dose groups, with 6 rats in each group. Except for blank group, other groups were intraperitoneally injected with D-galactose at 120 mg/kg per day. After 8 weeks of continuous injection, E. sphaerocephalus high-dose, medium-dose and low-dose groups were given drugs intragastrically at dose of 878, 439, 219.5 mg/kg, respectively. Gushukang group was given Gushukang 105.1 mg/kg intragastrically, once a day, for consecutive 8 weeks. After last administration, blood was collected from the abdominal aorta. Enzyme-linked immunosorbent assay was used to measure the contents of bone metabolism indexes [hydroxyproline (HYP), alkaline phosphatase (ALP)] and oxidative stress indexes [total antioxidant capacity (TAOC), superoxide dismutase (SOD), malondialdehyde (MDA)] in serum of rats. Positron emission tomography/computedtomography (PET/CT) was used to analyze the changes of bone microstructure in right tibia bone. Meanwhile, metabolomic technology was used to study the regulation effect of E. sphaerocephalus on osteoporosis model rats. RESULTS Compared with blank group, HYP, ALP, MDA, ratio of bone surface to bone volume (BS/BV), and trabecular separation (Tb·Sp) in model group were significantly increased (P<0.05), while TAOC, SOD, bone mineral density (BMD), bone volume fraction (BVF), trabecular E-mail:Xpfdc153@163.com thickness (Tb·Th) and trabecular number (Tb·N) were significantly decreased (P<0.05). Compared with model group, above indexes of administration groups were all reversed to different extents. The results of metabonomics study showed that after intervened with the extract of E. sphaerocephalus, 18 metabolites such as arachidonic acid, phenylalanine, tyrosine, tryptophan, isoleucine and uric acid in the serum of rats changed significantly, involving 15 metabolic pathways such as arachidonic acid, phenylalanine and tyrosine, of which arachidonic acid metabolism, phenylalanine metabolism and tyrosine metabolism were the main influencing pathways. CONCLUSIONS E. sphaerocephalus extract can effectively improve D-galactose-induced oxidative stress and the deterioration of bone microstructure, which interferes with metabolic pathways such as arachidonic acid metabolism and amino acid metabolism.

6.
Article in Chinese | WPRIM | ID: wpr-964936

ABSTRACT

Background Imidacloprid is a neonicotinoid insecticide that is widely used in agricultural production, with a high detection rate in human biological samples. Previous studies have shown a high correlation between imidacloprid exposure and liver injury, but the specific mechanism is still unknown. Objective To observe potential toxic effects of HepG2 cells and its perturbation of non-targeted metabolic profile after imidacloprid exposure, and to explore possible molecular mechanisms of hepatotoxicity of imidacloprid by analyzing invovlved biological processes and signaling pathways. Methods HepG2 cell suspension was prepared and seeded in a 96-well plate, which was divided into blank control group, dimethyl sulfoxide (DMSO) solvent control group and imidacloprid exposure groups with multiple concentrations. Each group was set with 5 parallel samples. The viability of HepG2 cells viability were determined after 8 h of exposure to different concentrationsof imidacloprid (1, 2.5, 5, 7.5, 10 mmol·L−1), and the dose-effect relationship was analyzed. A proper concentration (3 mmol·L−1 with 80% viability) was chosen for imidacloprid exposure, non-targeted metabolomic analysis was applied to the cultivated HepG2 cells using UHPLC-Q-TOF/MS technology, the differential metabolites between groups were screened, and the bioprocess and related signaling pathways of their enrichment were annotated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Results Compared to the other two groups, the survival rates of HepG2 cells in the imidacloprid exposure groups decreased. A survival rate of about 86% of HepG2 cells was found in HepG2 cells exposed to 2.5 mmol·L−1 imidacloprid exposure. The non-targeted metabolomics studies showed that 61 metabolites were significantly affected in HepG2 cells after 3 mmol·L−1 imidacloprid exposure, including creatine (variable importance in projection VIP=1.11, P<0.001), arginine (VIP=1.47, P=0.048), taurine (VIP=4.28, P=0.001), and α-D-glucose (VIP=1.90, P=0.006). The differential metabolites enriched in bioprocess and related signaling pathways were mainly directed to mTOR signaling pathways (P<0.001), arginine and proline metabolism (P=0.002), and galactose metabolism (P=0.015). Conclusion Imidacloprid exposure can significantly inhibit the survival rate of HepG2 cells, and interfere with the mTOR signaling pathway, arginine and proline metabolism, galactose metabolism, and so on.

7.
Chinese Journal of Biotechnology ; (12): 1107-1118, 2023.
Article in Chinese | WPRIM | ID: wpr-970426

ABSTRACT

L-arabinose isomerase (L-AI) is the key enzyme that isomerizes D-galactose to D-tagatose. In this study, to improve the activity of L-arabinose isomerase on D-galactose and its conversion rate in biotransformation, an L-arabinose isomerase from Lactobacillus fermentum CGMCC2921 was recombinantly expressed and applied in biotransformation. Moreover, its substrate binding pocket was rationally designed to improve the affinity and catalytic activity on D-galactose. We show that the conversion of D-galactose by variant F279I was increased 1.4 times that of the wild-type enzyme. The Km and kcat values of the double mutant M185A/F279I obtained by superimposed mutation were 530.8 mmol/L and 19.9 s-1, respectively, and the catalytic efficiency was increased 8.2 times that of the wild type. When 400 g/L lactose was used as the substrate, the conversion rate of M185A/F279I reached a high level of 22.8%, which shows great application potential for the enzymatic production of tagatose from lactose.


Subject(s)
Galactose/metabolism , Limosilactobacillus fermentum/genetics , Lactose , Hexoses/metabolism , Aldose-Ketose Isomerases/genetics , Hydrogen-Ion Concentration
8.
Article in Chinese | WPRIM | ID: wpr-965565

ABSTRACT

Objective To explore the effect and mechanism of Bajitianwan on preventing D-galactose (D-gal)-induced osteoblast bone loss. Methods Osteoblasts isolated from 24 h old Wistar rats were injured by D-gal and intervened with Bajitianwan extract. The osteoblastic proliferation and differentiation were determined by MTT and alkaline phosphatase (ALP), respectively. The cell reactive oxygen species (ROS) levels were detected by DCFH-DA fluorescent probes. The expression of cellular oxidation-related protein nuclear factor erythroid 2-related factor 2 (Nrf2), phosphorylated protein kinase B (p-AKT), protein kinase B (AKT), heme oxygenase-1 (HO-1), and NADPH quinone oxidoreductase 1 (NQO1) were detected by Western blotting. The intranuclear expression of Nrf2 protein was measured by immunofluorescence. Results Bajitianwan extract had significantly increased the osteoblastic proliferation and differentiation, and significantly reduced the intracellular ROS level. Bajitianwan extract had activated the PI3K/AKT pathway via activating the phosphorylation of AKT in osteoblasts, and promoted NQO1 and HO-1 expression. In addition, Bajitianwan had significantly promoted the expression of Nrf2 in the nucleus of osteoblasts, activating Nrf2 signaling pathway, and further promoted bone formation. Conclusion This study confirmed that Bajitianwan could prevent D-gal injured osteoblastic bone loss for the first time. The mechanism might be related to the regulation of oxidative stress associated PI3K/AKT and Nrf2 signaling pathway.

9.
Chinese Journal of Neurology ; (12): 1034-1043, 2023.
Article in Chinese | WPRIM | ID: wpr-994929

ABSTRACT

Objective:To summarize the clinical manifestations, gene variations, diagnosis and treatment of 3 cases with SLC35A2 variations characterized by congenital glycosylation disorder Ⅱm (CDG Ⅱm). Methods:A total of 3 patients admitted to the Department of Pediatrics of Xiangya Hospital of Central South University in China from 2018 to 2020 were examined in detail. The studies till January 2022 were searched with key words of "congenital disorders of glycosylation Ⅱm", " SLC35A2" and "CDG Ⅱm" in both English and Chinese in the databases of China National Knowledge Infrast Ructure (CNKI), Wanfang, Online Mendelian Inheritance in Man and PubMed, and the clinical manifestations, genetic variation, treatments and prognosis of patients with SLC35A2 mutation were summarized. Results:The patients all presented with intractable infantile spasm and global developmental delay, onset in infancy. A variety of antiepileptic treatments had temporary and partial efficacy. Otherwise, proband 2 and 3 presented with abnormal glutamic-pyruvic transaminase and increased platelets. Funduscopy showed dysplasia of the retinal pigment epithelium in both eyes, and they both received D-galactose treatment. A total of 22 relevant case reports, including 99 patients, were collected. The 99 patients all were heterozygous mutations, and a total of 75 different variation sites were reported. The clinical manifestations were characterized by global developmental delay or mental retardation ( n=89), epileptic seizure ( n=75), hypotonia ( n=57), facial deformity ( n=57), skeletal abnormality ( n=50), visual impairment ( n=42), elevated glutamic-pyruvic transaminase ( n=31), gastrointestinal symptoms ( n=28), skin deformity ( n=26), microcephaly ( n=23) and congenital heart disease ( n=12). Craniocerebral magnetic resonance imaging may be normal in the early stage. With age, magnetic resonance imaging may show abnormal white matter signals, brain atrophy, dysplasia of corpus callosum, delayed myelination, enlargement of lateral ventricle, brain stem atrophy and so on. Studies have shown that galactose treatment may be effective. Conclusions:SLC35A2 variants lead to CDG Ⅱm, whose clinical manifestations mainly include epileptic encephalopathy and global developmental delay. Multiple antiepileptic therapies can temporarily or partially control seizures, while oral galactose may improve the clinical symptoms, showing its prospect as a dietary therapy.

10.
Digital Chinese Medicine ; (4): 328-340, 2023.
Article in English | WPRIM | ID: wpr-997736

ABSTRACT

Objective@#To investigate the metabolic trajectory of kidney aging and the effects of Polygonatum sibiricum polysaccharides (PSP) against kidney aging in D-galactose (D-gal)-induced aging mice, based on ultra-performance liquid chromatography/Q-Exactive Orbitrap mass spectrometry (UPLC-Q-Exactive MS/MS). @*Methods@#A total of 36 C57 BL/6J mice were randomly allocated to six groups: control (CON), model (MOD), PSP low-dose (PSP-L), PSP medium-dose (PSP-M), PSP high-dose (PSP-H), and positive drug ascorbic acid (VC) groups. To create models of aging mice, D-gal was intraperitoneally administered to all other groups of mice except the CON group. After modeling, the appropriate Chinese medicine [PSP-L: 150 mg/(kg·d), PSP-M: 300 mg/(kg·d), PSP-H: 600 mg/(kg·d)] or positive drug [ascorbic acid, 300 mg/(kg·d)] was administered for intervention. Key markers of renal function in urine and serum of mice in each group, such as creatinine (Crea), urea nitrogen (BUN), and uric acid (UA) levels, as well as key indicators of oxidative stress in serum and kidney, including superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione peroxidase (GSH-Px) were determined to validate the successful establishment of kidney aging models and to estimate the effects of PSP. Hematoxylin and eosin (HE), periodic acid Schiff (PAS), and β-galactosidase staining were used to assess the renal pathological changes. The metabolic profiles of serum, kidney, and urine samples from CON, MOD, and PSP-H groups were analyzed by UPLC-Q-Exactive MS/MS, and pattern recognition methods were used to outline the metabolic trajectory of kidney aging and to identify the characteristic metabolites. @*Results@#Age-related alterations in renal histopathology and impaired renal function in mice were also associated with oxidative stress indicators. Following the injection of PSP [PSP-H: 600 mg/(kg·d)], the pathological indices associated with aging were adjusted to normal levels, renal function and oxidative stress were improved in aging mice, and renal pathological damage was markedly improved. Meanwhile, the potential biomarkers were identified by UPLC-Q-Exactive MS/MS analysis and were further analyzed to form related metabolic pathways, with P < 0.05 as a threshold. The results showed that purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms were the main metabolic pathways associated with aging. After administration of PSP, these pathological indices returned to normal levels, and biomarkers related to the aging process, such as adenosine monophosphate (AMP), tryptophan, and 5-hydroxytryptophan, also demonstrated, to some degree, reverse regulation (promoting synthesis). @*Conclusion@#Metabolomics methods based on UPLC-Q-Exactive MS/MS and multivariate statistical analysis can be adopted to establish metabolic profiles in aging mice. PSP has been shown to protect against kidney aging by interfering with the purine, sphingolipid, glycerophospholipid, tryptophan, and riboflavin metabolisms in the kidney.

11.
Article in Chinese | WPRIM | ID: wpr-1015651

ABSTRACT

Multiple organs are physiologically and pathologically interconnected during aging, and the brain plays a central role in this process. There is a direct two-way communication between the brain and the gut called “brain-gut interaction”, which is of great significance for the study of aging, and the molecular mechanism remains to be further studied. The aim of this study is to explore the mechanism of aging in the context of brain-gut interaction. The results of general physical signs of mice showed that the amount of exercise decreased, body weight and food intake decreased significantly in aged mice (P < 0. 001, P<0. 05). The thymus index of aged mice was significantly lower than that of normal mice (P< 0. 05), and the thymic pathological results showed that the thymic cortex of aging mice was thinner, the boundary between medulla and cortex was blurred, and the cells were loosely arranged. Metabolomics analysis revealed 317 differential metabolites in feces and 100 differential metabolites in hippocampus. The results of microbiome showed that Bacteroidetes and Firmicutes were the dominant phyla of gut microbiota. Bacteroidetes showed an upward trend and Firmicutes showed a downward trend after aging. KEGG pathway results showed that 26 metabolic pathways were related to the study of aging, among which galactose metabolism, ABC transporter and purine metabolism were of great significance for the brain-gut interaction. The results of Spearman correlation analysis of the three groups showed that the types of metabolites involved were mainly lipids and lipid-like molecules and organic acids and derivatives, and the gut microbiota involved were mainly Bacteroidetes and Firmicutes. In conclusion, the present study demonstrated that the synergistic changes between brain and gut in aging mice were related to the mechanism of aging, which provided new insights into the mechanism of aging process.

12.
Dement. neuropsychol ; 16(2): 228-236, Apr.-June 2022. tab, graf, il. color
Article in English | LILACS | ID: biblio-1384665

ABSTRACT

ABSTRACT. Alzheimer's dementia (AD) is a neurodegenerative disease. The mechanism of oxidative stress in AD is due to amyloid beta (Aβ) protein that aggregates to form plaques, which further triggers chronic inflammation and neuronal apoptosis. Purple sweet potato extract with the main content of anthocyanins is a potential antioxidant with a direct target on the amyloid cascade hypothesis. Objective: The research objective was to determine the role of purple sweet potato water extract as an antioxidant and anti-inflammatory in preventing apoptosis in order to provide a neuroprotective effect in d-galactose-induced rats. Methods: A total of 100 male Wistar rats with randomized posttest-only control group design that met the eligibility criteria were included in this study. The treatment group was given 200 mg/kg BW/day of purple sweet potato water extract on days 1-70. d-galactose induction was administered in the treatment and control groups on days 15-70. Results: The independent t-test showed that the mean tumor necrosis factor-α (TNF-α) levels in the treatment group (735.36±139.74) was significantly lower than that in the control group (896.77±152.52). The p53 and glial fibrillary acidic protein (GFAP) expressions of astrocyte cells in the treatment group were significantly lower than that in the control group. The brain-derived neurotrophic factor (BDNF) levels in the treatment group (498.13±121.47) were higher than that in the control (391.93±140.28), and there was a significant increase in spatial working memory in the treatment group (72.01±10.22) than the control (59.77±11.87). Conclusions: The neuroprotective effect of purple sweet potato extract is due to d-galactose induction resulting from decrease in TNF-α levels, p53 expression, and GFAP expression and increase in BDNF levels and spatial working memory.


RESUMO. A doença de Alzheimer (DA) é uma doença neurodegenerativa. O mecanismo de estresse oxidativo na DA ocorre devido à proteína beta amilóide que se agrega para formar placas que desencadeiam inflamação crônica e apoptose neuronal. O extrato de batata-doce roxa composto principalmente por antocianinas é um potencial antioxidante com efeito direto sobre a hipótese da cascata amilóide. Objetivo: O objetivo da pesquisa foi determinar o papel do extrato aquoso de batata-doce roxa como antioxidante e anti-inflamatório na prevenção da apoptose, para proporcionar um efeito neuroprotetor em ratos induzidos por D-galactose. Métodos: Grupo controle randomizado pós-teste com 100 ratos Wistar machos que preencheram os critérios de elegibilidade. O grupo de tratamento recebeu 200mg/kg de peso corporal/dia de extrato aquoso de batata-doce roxa nos dias 1-70. A indução de D-galactose foi testada nos grupos de tratamento e controle nos dias 15-70. Resultados: O teste t independente mostrou que a média dos níveis de TNF-α no grupo de tratamento (735,36±139,74) foi significativamente menor do que no grupo controle (896,77±152,52). A expressão de p53 e a expressão de GFAP de células de astrócitos foram significativamente menores no grupo de tratamento do que no grupo controle. Os níveis de BDNF no grupo de tratamento (498,13±121,47) foram maiores que no grupo controle (391,93±140,28) e houve um aumento significativo da memória de trabalho espacial no grupo de tratamento (72,01±10,22) em relação ao controle (59,77±11,87). Conclusões: O efeito neuroprotetor do extrato de batata-doce roxa é devido à indução de D-galactose pela diminuição dos níveis de TNF-α, expressão de p53 e expressão de GFAP, aumentando assim os níveis de BDNF e memória espacial.


Subject(s)
Animals , Rats , Inhibitor of Apoptosis Proteins , Ipomoea batatas
13.
Article in Chinese | WPRIM | ID: wpr-933382

ABSTRACT

Objective:To investigate the effects and potential mechanism of vitamin D supplementation on testicular function in aging rats induced by D-galactose.Methods:The aging rats were induced by D-galactose with subcutaneous injection. The animals were randomly divided into 6 groups: aging rats (DG), aging rats with low-dose vitamin D supplementation (LD), aging rats with high-dose vitamin D supplementation (HD), normal control rats(NC), normal rats with low-dose vitamin D supplementation(LN), normal rats with high-dose vitamin D supplementation (HN). The body weight, testicular weight, serum testosterone concentrations and sperm quality of the rats in each group were measured. The testis morphological changes were detected using light microscopy. The activity of superoxide dismutase (SOD) and level of malondialdehyde(MDA) were determined with spectrophotometer. The expression levels of Nrf2, GCLC, SOD2 and VDR in testis were detected by western blot.Results:At baseline, compared with NC group, testicular weight, serum testosterone level, SOD activity, Nrf2, GCLC and SOD2 expression levels were significantly decreased in DG group, while MDA level was significantly increased. After vitamin D supplementation, testicular weight, testosterone levels and SOD activity in both of HD and LD groups were significantly increased, while the MDA level was significantly decreased. The expression levels of Nrf2, GCLC, SOD2 and VDR were significantly increased.Conclusion:Vitamin D supplementation may enhance the testicular antioxidant capacity through activating Nrf2-ARE signaling pathway, and improve the testicular function in D-galactose-induced aging rats.

14.
Article in Chinese | WPRIM | ID: wpr-924058

ABSTRACT

Objective To study the effect of traditional Chinese medicine, Syngnathus on learning and memory impairment induced by D-galactose in aging mice and its mechanism of action. Methods HPLC was used to determine the content of DHA, the active ingredient in anti-learning and memory impairment in Syngnathus. The aging mouse model was prepared by intraperitoneal injection of D-galactose (D-gal). Morris water maze test and Western blot were used to detect the ability of learning and memory, biochemical indicators and protein expression related to oxidative damage in the hippocampus, and to explore the protective effect and mechanism of Syngnathus on learning and memory impairment in aging mice. Results HPLC results showed that the DHA content in Syngnathus was 7.761 3 mg/g (calculated as crude drug), accounting for about 47% of the total composition. Morris water maze results showed that Syngnathus could reduce the escape latency of learning and memory-impaired aging mice and increase the target quadrant swimming time, the proportion of swimming distance and the number of times of crossing the platform, and improve the learning and memory impairment of mice. In addition, Syngnathus can activate the AKT/FOXO1/SOD2 signaling pathway in the hippocampus of aging mice with learning and memory impairment, promote the expression of oxidative stress pathway-related proteins, and improve the learning and memory impairment in aging mice by reducing the degree of oxidative damage in the hippocampus of aging mice. Conclusion This study found that Syngnathus is rich in DHA, which has the effect of improving learning and memory impairment induced by D-galactose in aging mice, and preliminarily clarified that its mechanism of action is related to anti-oxidation. Experimental evidence is provided.

15.
Zhongguo Zhong Yao Za Zhi ; (24): 2074-2081, 2022.
Article in Chinese | WPRIM | ID: wpr-928147

ABSTRACT

The present study investigated the mechanism of the Tibetan patent medicine Ershiwuwei Shanhu Pills(ESP) in alleviating Alzheimer's disease in mice via Akt/mTOR/GSK-3β signaling pathway. BALB/c mice were randomly assigned into a blank control group, a model group, low(200 mg·kg~(-1)), medium(400 mg·kg~(-1)) and high(800 mg·kg~(-1)) dose groups of ESP, and donepezil hydrochloride group. Except the blank control group, the other groups were given 20 mg·kg~(-1) aluminum chloride by gavage and 120 mg·kg~(-1) D-galactose by intraperitoneal injection for 56 days to establish Alzheimer's disease model. Morris water maze was used to detect the learning and memory ability of mice. The level of p-tau protein in mouse hippocampus and the levels of superoxide dismutase(SOD), malondialdehyde(MDA), catalase(CAT), and total antioxidant capacity(T-AOC) in hippocampus and serum were detected. Hematoxylin-eosin staining and Nissl staining were performed for the pathological observation of whole brain in mice. TdT-mediated dUTP nick-end labeling(TUNEL) staining was employed for the observation of apoptosis in mouse cortex. Western blot was adopted to detect the protein levels of p-mTOR, p-Akt, and GSK-3β in the hippocampus. Compared with the model group, the ESP groups showcased alleviated pathological damage of the whole brain, decreased TUNEL positive cells, reduced level of p-tau protein in hippocampus, and risen SOD, CAT, and T-AOC levels and declined MDA level in hippocampus and serum. Furthermore, the ESP groups had up-regulated protein levels of p-mTOR and p-Akt while down-regulated protein level of GSK-3β in hippocampus. Therefore, ESP can alleviate the learning and memory decline and oxidative damage in mice with Alzheimer's disease induced by D-galactose combined with aluminum chloride, which may be related to Akt/mTOR/GSK-3β signaling pathway.


Subject(s)
Animals , Mice , Aluminum Chloride/adverse effects , Alzheimer Disease/drug therapy , Galactose/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Hippocampus/metabolism , Mice, Inbred BALB C , Plant Extracts , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Superoxide Dismutase/metabolism , TOR Serine-Threonine Kinases/metabolism , tau Proteins
16.
Organ Transplantation ; (6): 583-2022.
Article in Chinese | WPRIM | ID: wpr-941478

ABSTRACT

IgA nephropathy (IgAN) is one of the common primary glomerulonephritis, which is also an important risk factor for end-stage renal disease. Kidney transplantation is the optimal treatment for end-stage renal disease induced by IgAN, whereas there is still a risk of recurrence of IgAN after kidney transplantation. At present, research progress upon IgAN recurrence after kidney transplantation is relatively lacking. The pathogenesis of IgAN recurrence remains elusive, and its pathological manifestations are not specific. The diagnosis of IgAN recurrence still depends on renal biopsy. Besides, no effective prevention and treatment are available for recurrent IgAN. In this article, research progress on IgAN recurrence after kidney transplantation was illustrated from the perspectives of pathogenesis, diagnosis, risk factors and treatment, aiming to provide reference for clinical prevention and treatment of IgAN recurrence after kidney transplantation and improve clinical prognosis of kidney transplant recipients.

17.
Organ Transplantation ; (6): 626-2022.
Article in Chinese | WPRIM | ID: wpr-941484

ABSTRACT

Objective To evaluate the effect and mechanism of terminal fucosylation inhibitor 2-deoxy-D-galactose (2-D-gal) on ciclosporin (CsA)-induced renal epithelial-mesenchymal transition (EMT). Methods Fifteen male C57BL/6 mice aged 8-10 weeks were randomly and evenly divided into the control group (Ctrl group), CsA group and CsA+2-D-gal group (n=5). The expression levels of fucosyltransferase 1 (FUT1), EMT-associated proteins including E-cadherin, Vimentin, α-smooth muscle actin (α-SMA) in the kidney tissues of the Ctrl and CsA groups were detected by Western blot. The expression levels of terminal fucose in the kidney tissues of Ctrl and CsA groups were determined by immunofluorescence. The renal fibrosis of mice in each group was evaluated by Masson staining. The blood urea nitrogen and serum creatinine levels of mice in each group were detected. The in vitro EMT model of renal tubular epithelial cell HK2 was induced by CsA. HK2 cells were stimulated with 0, 2.5, 5.0 and 10.0 μmol/L CsA for 24 h, respectively. In addition, HK2 cells were divided into the Ctrl, 2-D-gal, CsA and CsA+2-D-gal groups. The morphology of HK2 cells after stimulation with different concentrations of CsA and in each group was observed. The expression levels of FUT1, E-cadherin, Vimentin and α-SMA in HK2 cells after stimulation with different concentrations of CsA and in each group were detected by Western blot. The expression level of terminal fucose in HK2 cells of the Ctrl and CsA groups was measured by immunofluorescence. Results Compared with the Ctrl group, the relative expression of E-cadherin protein was down-regulated, those of FUT1, Vimentin and α-SMA proteins were up-regulated (all P < 0.05), and that of terminal fucose in the mouse kidney tissues was up-regulated in the CsA group. Compared with the Ctrl group, the blood urea nitrogen and serum creatinine levels in the CsA and CsA+2-D-gal groups were up-regulated (all P < 0.05). Compared with the CsA group, the blood urea nitrogen and serum creatinine levels in the CsA+2-D-gal group were down-regulated (both P < 0.05). Compared with the Ctrl group, the collagen fiber deposition was increased and the relative expression of α-SMA protein was up-regulated in the mouse kidney tissues of CsA and CsA+2-D-gal groups (all P < 0.05). Compared with the CsA group, the collagen fiber deposition was decreased and the relative expression of α-SMA protein in the mouse kidney tissues was down-regulated in the CsA+2-D-gal group (both P < 0.05). With the increase of CsA concentration, the morphology of HK2 cells gradually became longer and thinner from original normal cobblestone shape, the relative expression levels of FUT1, Vimentin and α-SMA protein in HK2 cells were up-regulated, and that of E-cadherin protein was down-regulated in a concentration-dependent manner. Compared with the Ctrl group, the expression level of terminal fucose of HK2 cells was up-regulated in the CsA group. After CsA treatment combined with 2-D-gal intervention, the morphology of HK2 cells in the CsA+2-D-gal group was restored to resemble that of normal HK2 cells. Compared with the CsA group, the relative expression of E-cadherin protein in HK2 cells was up-regulated, whereas those of Vimentin and α-SMA proteins were down-regulated in the CsA+2-D-gal group (all P < 0.05). Conclusions CsA may induce EMT both in vivo and in vitro, and the terminal fucosylation is increased. 2-D-gal may inhibit CsA-induced EMT by suppressing the terminal fucosylation.

18.
Article in Chinese | WPRIM | ID: wpr-940626

ABSTRACT

ObjectiveTo observe the effect of polysaccharides from root, stem, leaf and fruit of Schisandra chinensis on exercise endurance in the aging mice induced by D-galactose. MethodMale ICR mice were randomly assigned into six groups: blank control group, model group, root polysaccharide group, stem polysaccharide group, leaf polysaccharide group and fruit polysaccharide group. The mice were administrated with distilled water or root, stem, leaf and fruit polysaccharide (total sugar content of 35 mg·kg-1) by gavage. Thirty minutes after the administration, the blank control group was subcutaneously injected with normal saline, and the other groups with D-galactose (300 mg·kg-1), once daily for 6 weeks. The anti-fatigue effects were evaluated by rotarod test, forelimb grip strength test, and weight-loaded swimming test. The fatigue and oxidation indicators such as blood urea nitrogen (BUN), serum lactic acid (LD), lactic dehydrogenase (LDH), creatine kinase (CK), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), and reactive oxygen species (ROS) were measured by chemical colorimetry. The protein levels of pro-apoptotic protein B cell lymphoma-2 (Bcl-2)-associated X protein (Bax), anti-apoptotic Bcl-2 and cleaved cysteinyl aspartate-specific protease-3 (cleaved Caspase-3) in mouse skeletal muscle were detected by Western blot. ResultIn the rotarod test, the time on rod was shorter in the model group than in the blank control group (P<0.01) and the root, stem and fruit polysaccharide groups (P<0.01). In the forelimb grip strength test, the forelimb grip strength in the model group was lower than that in the blank control group (P<0.01) and the root, stem, leaf and fruit polysaccharide groups (P<0.01). In the weight-loaded swimming test, the weight-loaded swimming time in the model group was shorter than that in the blank control group (P<0.01) and the root, stem, leaf and fruit polysaccharide groups (P<0.01). Compared with those in the blank control group, the BUN, LD, LDH and CK levels significantly increased in the model group (P<0.05, P<0.01). The increases in BUN and LDH levels were decreased by the root, stem and fruit polysaccharides (P<0.05, P<0.01) and those in LD and CK by the root, stem, leaf and fruit polysaccharides (P<0.05, P<0.01). Compared with the blank control group, the model group showed decreased SOD and GSH-Px activities (P<0.01) and increased MDA and ROS content (P<0.01). Compared with the model group, the root, stem, and fruit polysaccharide increased the SOD activity (P<0.05, P<0.01) and decreased ROS content (P<0.01). The root and stem polysaccharides decreased the MDA content (P<0.01) and increased the GSH-Px activity (P<0.05, P<0.01). Compared with the blank control group, the model group showed up-regulated protein levels of Bax and cleaved Caspase-3 and down-regulated protein level of Bcl-2 (P<0.01). Compared with the model group, the root, and stem polysaccharides down-regulated the protein levels of cleaved Caspase-3 (P<0.05) and up-regulated protein level of Bcl-2 (P<0.01). ConclusionThe polysaccharides from the root, stem, leaf, and fruit of S. chinensis have anti-fatigue effect in D-galactose-induced aging mice. The polysaccharides may exert such effect by improving the antioxidant capacity and inhibiting the apoptosis of skeletal muscle cells.

19.
Article in Chinese | WPRIM | ID: wpr-940831

ABSTRACT

ObjectiveThe effect of modified Shengjiangsan on immunoglobulin A (IgA) nephropathy was observed. The microRNA-148b (miRNA-148b), interleukin 6 (IL-6), core 1 beta 1,3-galactosyltransferase (C1GALT1), molecular chaperone Cosmc (core1β3-Gal-T-specific molecular chaperone C1GALT1C1), and galactose-deficient IgA1 (Gd-IGA1) in serum and kidney tissues of IgA nephropathy rats were detected to explore the underlying mechanism. The result is expected to lay a scientific basis for clinical application of modified Shengjiangsan in the treatment of IgA nephropathy. MethodA total of 42 SPF male SD rats were randomized into the normal group (8rats) and modeling group (34 rats) with the random number table method. After one week of adaptive feeding, rats for modeling were given bovine serum albumin (BSA, gavage), lipopolysaccharide (LPS, injection into tail vein), carbon tetrachloride (CCl4, subcutaneous injection), and castor oil to induce IgA nephropathy. After modeling, two rats were randomly selected to test the modeling outcome. Then the model rats were classified into the model group, low-dose Chinese medicine group (modified Shengjiangsan,6.27 g·kg-1), high-dose Chinese medicine group (modified Shengjiangsan,12.54 g·kg-1), and benazepril group (10 mg·kg-1) with the random number table method, 8 in each group. The administration (gavage, once a day) lasted 4 weeks. The 24-h urinary total protein (24 h-UTP) was detected at the end of the 1st, 9th, and 13th week of the experiment. At the 14th week, after anesthesia, femoral artery blood was collected and centrifugated. The supernatant was collected to detect albumin (ALB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN). The expression levels of IL-6 and Gd-IGA1 were determined by enzyme-linked immunosorbent assay (ELISA). Based on hematoxylin-eosin (HE)/Masson/periodic Schiff-methenamine silver (PASM) staining, the pathological changes of renal tissues were observed. Ultrastructural changes of glomeruli were observed by transmission electron microscopy. The expression of miRNA-148b, IL-6, C1GALT1, and C1GALT1C1 was detected by immunohistochemistry. The mesangial area of the glomeruli was observed by immunofluorescence. Real-time polymerase chain reaction (Real-time PCR) was employed to determine the mRNA levels of mirNA-148b, IL-6, C1GALT1, and C1GALT1C1, and Western blot was used to detect the protein levels of IL-6, C1GALT1, and C1GALT1C1. ResultCompared with normal group, the model group showed increase in the content of 24 h-UTP, SCr, ALT, IL-6, and GD-IGA1 (P<0.05), decrease in ALB content (P<0.05). Moreover, rats in the model group demonstrated hyperplasia of glomerular mesangial cells, thickening of mesangial area, podocyte foot process effacement, and a large number of granular IgA immune complex in the mesangial area. In addition, the model group showed increase in the expression of IL-6 in mesangial area and podocytes, decrease in the expression of C1GALT1 and C1GALT1C1 in mesangial area and podocytes, enhanced expression of IL-6 mRNA and miRNA-148b (P<0.01), weakened expression of C1GALT1 mRNA and C1GALT1C1 mRNA (P<0.01), rise of IL-6 protein expression (P<0.01), and reduction in the protein expression of C1GALT1 and C1GALT1C1 (P<0.01). Compared with the model group, modified Shengjiangsan decreased the content of 24 h-UTP, SCr, ALT, IL-6, and Gd-IGA1 (P<0.05) and increased the content of ALB (P<0.05, P<0.01). Moreover, with the treatment of this Chinese medicine, the pathological damage was significantly alleviated and the deposition of IgA immune complex in basement membrane was reduced. The expression of IL-6 in the mesangial area and podocytes of rats was decreased, and the expression of C1GALT1 and C1GALT1C1 in the mesangial area and podocytes of rats was increased. Moreover, the expression of IL-6 mRNA and miRNA-148b was decreased (P<0.01), and the expression of C1GALT1 mRNA and C1GALT1C1 mRNA was increased (P<0.01). The protein expression of IL-6 was decreased (P<0.05, P<0.01), and the protein expression of C1GALT1 and C1GALT1C1 was enhanced (P<0.05, P<0.01). The Chinese medicine group showed obvious dose-effect trend. ConclusionModified Shengjiangsan may reduce the expression of miRNA-148b and IL-6 in serum and kidney tissue of IgA nephropathy rats, restore the expression of C1GALT1 and C1GALT1C1, and decrease the generation of Gd-IGA1, so as to reduce renal pathological damage and proteinuria, protect the kidney protection, and finally delay the disease progression. Moreover, the effect is enhanced with the rise of dose.

20.
Chinese Journal of Geriatrics ; (12): 1512-1517, 2022.
Article in Chinese | WPRIM | ID: wpr-993763

ABSTRACT

Objective:To investigate the protective effect of hyperbaric oxygen therapy(HBOT)on myocardial fibrosis and oxidative stress induced by D-galactose(D-gal)in senescent model mice and its possible mechanism.Methods:Three-month-old male Kunming mice(n=27)were randomized into control, D-gal, and D-gal + HBOT groups.The control group received subcutaneous sterilized saline(5 ml · kg -1· d -1)for 8 weeks; the remaining 2 groups received subcutaneous D-gal(200 mg · kg -1· d -1)for 8 weeks. The D-gal + HBOT group underwent HBOT intervention at week 7~8.At the end of the experiment, the histopathological changes were analyzed by hematoxylin-eosin(HE)staining, and the fibrosis changes were analyzed by Masson staining and Sirius red staining.Oxidative stress kit was used to detect catalase(CAT), total superoxide dismutase(T-SOD)activity and malon-di-aldehyde(MDA)content in serum of mice.Western blotting was used to detect the expression levels of the aging-related proteins p53 and p16 in mouse heart tissue, the heart-function-related proteins atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP), and the oxidative stress-related protein superoxide dismutase 1(SOD1), superoxide dismutase 2(SOD2)and catalase(CAT). Results:Cardiac morphologic staining indicated that as compared with the control group, mice of D-gal group exhibited features of senescence and the increased fibrosis area, and senescence and fibrosis were obviously improved after HBOT intervention as compared with the D-gal group.The findings of the oxidative stress kit measurement indicated that as compared with the control group, the D-gal group had markedly decreased activities of CAT and T-SOD, significantly increased MDA content in the serum.After HBOT treatment, as compared with d-gal group, serum CAT and T-SOD activities were increased, while MDA content was decreased( F=126.85, 32.89, 157.50, all P<0.05).Furthermore, as compared with the control group, the D-gal group had obviously increased contents of p53, p16, ANP and BNP, while the content of CAT, SOD1 and SOD2 were obviously decreased.After HBOT intervention, as compared with the D-gal group, the contents of p53, p16, ANP、BNP were reduced, while the content of CAT, SOD1 and SOD2 were increased( F=36.37, 14.81, 23.28, 58.41, 12.79, 80.08, 6.63, all P<0.05). Conclusions:HBOT intervention could protects against cardiac injury in aging mice, which may be related to attenuating myocardial fibrosis, inducing the expression of antioxidant enzymes, and reducing oxidative stress.

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