Alzheimer’s disease (AD) is a neurodegenerative disorder that damages health and welfare of the elderly, and there has been no effective therapy for AD until now. It has been proved that tanshinone ...IIA (tan IIA) could alleviate pathological symptoms of AD via improving non-amyloidogenic cleavage of amyloid precursor protein, decreasing the accumulations of p-tau and amyloid-β1–42 (Aβ1–42), and so forth. However, the further biochemical mechanisms of tan IIA are not clear. The experiment was undertaken to explore metabolites of tan IIA in AD rats induced by microinjecting Aβ1-42 in the CA1 region of hippocampus. AD rats were orally administrated with tan IIA at 100 mg/kg weight, and plasma, urine, faeces, kidney, liver and brain were then collected for metabolites analysis by UHPLC-Q-Exactive Qrbitrap mass spectrometry. Consequently, a total of 37 metabolites were positively or putatively identified on the basis of mass fragmentation behavior, accurate mass measurements and retention times. As a result, methylation, hydroxylation, dehydration, decarbonylation, reduction reaction, glucuronidation, glycine linking and their composite reactions were characterized to illuminate metabolic pathways of tan IIA in vivo. Several metabolites presented differences in the distribution of tan IIA between the sham control and the AD model group. Overall, these results provided valuable references for research on metabolites of tan IIA in vivo and its probable active structure for exerting neuroprotection.
Objective:
This study aimed to investigate the possible molecular mechanisms associated with ischemic stroke through the construction of a lncRNA-miRNA-mRNA network. miRNA expression profile in ...GSE55937, mRNA and lncRNA expression profiles in GSE122709, and mRNA expression profile in GSE146882 were downloaded from the NCBI GEO database. After the identification of the differentially expressed miRNA, lncRNA, and mRNA using GSE55937 and GSE122709 in ischemic stroke
vs.
control groups, a protein-protein interaction (PPI) network was constructed. The lncRNA-miRNA, lncRNA-mRNA, and miRNA-mRNA pairs were predicted, and a lncRNA-miRNA-mRNA network was constructed. Additionally, the gene-drug interactions were predicted. Characteristic genes were used to construct a support vector machine (SVM) model and verified using quantitative reverse transcription polymerase chain reaction. In total 38 miRNAs, 115 lncRNAs, and 990 mRNAs were identified between ischemic stroke and control groups. A PPI network with 371 nodes and 2306 interaction relationships was constructed. The constructed lncRNA-miRNA-mRNA network contained 7 mRNAs, 14 lncRNAs, such as SND1-IT1, NAPA-AS1, LINC01001, LUCAT1, and ASAP1-IT2, and 8 miRNAs, such as miR-93-3p and miR-24-3p. The drug action analysis of the seven differential mRNAs included in the lncRNA-miRNA-mRNA network showed that four genes (
GPR17
,
ADORA1
,
OPRM1
and
LPAR3
) were predicted as molecular targets of drugs. The area under the curve of the constructed SVM model was 0.886. The verification results of the relative expression of RNA by qRT-PCR were consistent with the results of bioinformatics analysis.
LPAR3
,
ADORA1
,
GPR17
, and
OPRM1
may serve as therapeutic targets of ischemic stroke. lncRNA-miRNA-mRNA regulatory axis such as SND1-IT1/NAPA-AS1/LINC01001-miR-24-3p-
LPAR3
/
ADORA1
and LUCAT1/ASAP1-IT2-miR-93-3p
-GPR17
may play important roles in the progression of ischemic stroke.
Alzheimer’s disease (AD) is a common neurological disease in the elderly, and the major manifestations are cognitive dysfunction, neuronal loss, and neuropathic lesions in the brain. In the process ...of AD pathogenesis, the inflammatory response plays an indispensable role. The nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome containing NOD, leucine-rich repeat (LRR), and pyran domains is a multi-molecular complex that can detect dangerous signals related to neurological diseases. The assembly of NLRP3 inflammasome promotes the maturation of interleukin-1beta (IL-1β) and IL-18 mediated by caspase-1 in microglia, which leads to neuroinflammation and finally contributes to the occurrence and development of AD. This review aimed to clarify the structure and activating mechanism of NLRP3 inflammasome and its key role in the pathogenesis of AD, summarize the latest findings on the suppression of NLRP3 inflammasome activation for the treatment of AD, as well as indicate that targeting regulation of NLRP3 inflammasome assembly may be a potential strategy for the treatment of AD, providing a theoretical basis for the research of AD.
Aims
We performed a meta-analysis to indirectly compare the treatment effectiveness of balloon angioplasty and stenting for patients with intracranial arterial stenosis.
Methods
Literature searches ...were performed in well-known databases to identify eligible studies published before January 04, 2021. The incidence of restenosis, transient ischemic attack (TIA), stroke, death, and dissection after balloon angioplasty or stenting were pooled. An indirect comparison of balloon angioplasty vs. stenting was performed, and the ratios of incidence (RIs) with 95% confidence intervals (CIs) were calculated using the random-effects model.
Results
120 studies that recruited 10,107 patients with intracranial arterial stenosis were included. The pooled incidence of restenosis after balloon angioplasty and stenting were 13% (95%CI: 8-17%) and 11% (95%CI: 9-13%), respectively, with no significant difference between them (RI: 1.18; 95%CI: 0.78–1.80;
P
= 0.435). Moreover, the pooled incidence of TIA after balloon angioplasty and stenting was 3% (95%CI: 0–6%) and 4% (95%CI: 3%-5%), and no significant difference was observed (RI: 0.75; 95%CI: 0.01–58.53;
P
= 0.897). The pooled incidence of stroke after balloon angioplasty and stenting was 7% (95%CI: 5–9%) and 8% (95%CI: 7–9%), respectively, and the difference between groups was found to be statistically insignificant (RI: 0.88; 95%CI: 0.64–1.20;
P
= 0.413). Additionally, the pooled incidence of death after balloon angioplasty and stenting was 2% (95%CI: 1–4%) and 2% (95%CI: 1–2%), with no significant difference between groups (RI: 1.00; 95%CI: 0.44–2.27;
P
= 1.000). Finally, the pooled incidence of dissection after balloon angioplasty and stenting was 13% (95%CI: 5–22%) and 3% (95%CI: 2–5%), respectively, and balloon angioplasty was associated with a higher risk of dissection than that with stenting for patients with intracranial arterial stenosis (RI: 4.33; 95%CI: 1.81–10.35;
P
= 0.001).
Conclusion
This study found that the treatment effectiveness of balloon angioplasty and stenting were similar for patients with symptomatic intracranial arterial stenosis.
•ASA inhibited the growth of Fusarium sulphureum.•ASA disturbed the morphological and major cellular changes of F. sulphureum.•ASA reduced Fusarium rot development in muskmelon fruits inoculated with ...F. sulphureum.•ASA reduced neosolaniol accumulation in inoculated muskmelon fruits.•ASA down-regulated Tri genes expressions involved in trichothecenes biosynthesis.
Fusarium rot of muskmelon is a common and frequently-occurring postharvest disease, which leads to quality deterioration and neosolaniol (NEO) contamination. New strategies to control postharvest decay and reduce NEO contamination are of paramount importance. The effects of acetylsalicylic acid (ASA) treatment on the growth of Fusarium sulphureum in vitro, and Fusarium rot development and NEO accumulation in fruits inoculated with F. sulphureum in vivo were investigated. The results showed that ASA inhibited the growth of F. sulphureum, evident morphological and major cellular changes were observed under the microscope. In vivo testing showed that 3.2 mg/mL ASA significantly suppressed Fusarium rot development and NEO accumulation after 6 and 8 d of pathogen inoculation. Meanwhile, Tri gene expressions involved in NEO biosynthesis were down-regulated after treatment. Taken together, ASA treatment not only reduced Fusarium rot development by inhibiting the growth of F. sulphureum, but decreased NEO accumulation by suppressing NEO biosynthesis pathway.
The relationship between carotid atherosclerosis (AS) and levels of serum cathepsin K (CatK) and cystatin C (CysC) on patients with ischemic cerebral vascular disease (ICVD) was explored. In total, ...266 patients with ICVD who were admitted in our hospital were enrolled. According to the results of carotid ultrasound, they were randomly divided into plaque group (n = 133) and control group (n = 133). According to atherosclerotic plaque type distribution, the plaque group was divided into stable plaque group and unstable group. The relationship between levels of serum CatK and CysC of two groups and carotid AS indicator (such as intima-media thickness (IMT)) were analyzed with Spearman’s correlation. Spearman’s correlation analysis showed that IMT level was positively correlated with stability of carotid atherosclerotic plaque (P < 0.05). The level of serum CatK in plaque group was significantly higher than control group, and the level of serum CysC in plaque group was significantly lower than control group (P < 0.05); the level of serum CatK in unstable plaque group was significantly higher than stable plaque group, and the level of serum CysC in unstable plaque group was significantly lower than stable plaque group (P < 0.05). Serum CatK and IMT levels were positively correlated, and serum CysC and CatK levels were negatively correlated (P < 0.05). CatK and CysC levels may be used as serum markers for predicting carotid AS plaque instability, providing a new observational index for prevention and treatment of ICVD caused by carotid AS plaque.
Alzheimer’s disease (AD) is a chronic, neurodegenerative disorder that affects the central nervous system and is found predominantly in elderly populations. As amyloid b protein (Ab) is one of the ...key players responsible for the pathogenesis of AD, we sought to investigate the protective effects of fisetin in an Ab1-42-induced rat model of AD. In this model, the protective effects of fisetin on learning and memory impairment induced by Ab1-42 were determined via the Morris water maze and passive avoidance test. Furthermore, the antioxidant activity, anti-inflammation, and apoptosis effect of fisetin were investigated using biochemical and immunohistochemical methods. The results showed that intragastric (i.g.) administration of fisetin (100, 50, and 25 mg/kg) improved previous learning and memory impairments in Ab1-42-treated rats. Hippocampal tissue from these fisetin-treated rats revealed that the activities of total superoxide dismutase (T-SOD) and glutathione peroxidase (GSH-Px) were markedly enhanced, and that the levels of malondialdehyde (MDA) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) were significantly reduced. Meanwhile, fisetin also significantly attenuated Ab1-42-induced cholinergic dysfunction such as elevated the activity of choline acetyltransferase (ChAT) and reduced the activity of acetylcholine esterase (AChE). In addition, hippocampal tissue obtained from fisetin-treated rats revealed a reversal of Ab1-42-induced effects on apoptotic pathway protein (caspase-3) expression and inflammatory response of glial fibrillary acidic protein (GFAP). This indicated that the amount of degenerating hippocampal neurons with apoptotic features was dramatically reduced after treatment with fisetin. Collectively, these findings suggest that fisetin has potential as a treatment agent for Alzheimer’s disease and that its effects occur through several mechanisms, including inhibition of oxidative stress, adjustments to previous cholinergic dysfunction, anti-inflammatory actions, and decreased apoptotic activity.
•The objective of this experiment was to assess the role of lactogenic immunity in protecting piglets against the effects of PEDV by quantifying virus shedding in feces and piglet growth, ...thermoregulation, and survival in the presence (PEDV exposed sows) or absence (PEDV negative sows) of PEDV antibody in colostrum and milk.•The presence of lactogenic antibody markedly affected the outcome of PEDV infection in neonates, including less PEDV shedding in feces, better thermostability (p=0.0001), higher rate of growth, and higher rate of survivability.•Therefore, maintenance of sufficient levels of lactogenic immunity will be the cornerstone for the prevention of PED in endemically-infected herds.
The contribution of lactogenic antibody to the protection of piglets against porcine epidemic diarrhea virus (PEDV) was evaluated. Pregnant multiparous sows and their litters were allocated to one of 3 treatment groups: Group 1–6 serum antibody-negative sows and a subset (n=11) of their piglets. Group 2–8 serum antibody-positive sows and their 91 piglets. Piglets were orally inoculated with PEDV at 4 (Group 1) or 2 (Group 2) days of age. Group 3–2 PEDV serum antibody-negative sows and 22 piglets, provided a baseline for piglet survivability and growth rate. Piglets were monitored daily for clinical signs, body weight, and body temperature through day post-inoculation (DPI) 12 (Groups 2 and 3) or 14 (Group 1). Serum and mammary secretions were tested for PEDV IgG, IgA, and virus-neutralizing antibody. Feces were tested by PEDV real-time, reverse transcriptase PCR (rRT-PCR). Piglets on sows without (Group 1) or with (Group 2) anti-PEDV antibody showed significantly different responses to PEDV infection in virus shedding (p<0.05), thermoregulation (p<0.05), growth rate (p<0.05), and survivability (p<0.0001). Specifically, Group 1 piglets shed more virus on DPIs 1 to 5, were hypothermic at all sampling points except DPIs 9, 11, and 12, gained weight more slowly, and exhibited lower survivability than Group 2 piglets. Within Group 2 litters, significant differences were found in virus shedding (p<0.05), and body temperature (p<0.05), but not in piglet survival rate. The number of sows and litters in Group 2 was insufficient to derive the relationship between specific levels of lactogenic antibody (FFN, IgA, and IgG) and the amelioration of clinical effects. However, when combined with previous PEDV literature, it can be concluded that the optimal protection to piglets will be provided by dams able to deliver sufficient lactogenic immunity, both humoral and cellular, to their offspring.
The contribution of circulating antibody to the protection of naïve piglets against porcine epidemic diarrhea virus (PEDV) was evaluated using a passive antibody transfer model. Piglets (n = 62) ...derived from 6 sows were assigned to one of 6 different treatments using a randomized block design which provided for allocation of all treatments to all sows' litters. Each treatment was designed to achieve a different level of circulating anti-PEDV antibody via intraperitoneally administration of concentrated serum antibody. Piglets were orally inoculated with PEDV (USA/IN/2013/19338E, 1 x 103 TCID50 per piglet) 24 hours later and then monitored for 14 days. Piglets remained with their dam throughout the experiment. Sow milk samples, piglet fecal samples, and data on piglet clinical signs, body weight, and body temperature were collected daily. Fecal samples were tested by PEDV real-time reverse transcriptase PCR. Serum, colostrum, and milk were tested for PEDV IgG, IgA, and virus-neutralizing antibody. The data were evaluated for the effects of systemic PEDV antibody levels on growth, body temperature, fecal shedding, survival, and antibody response. The analysis showed that circulating antibody partially ameliorated the effect of PEDV infection. Specifically, antibody-positive groups returned to normal body temperature faster and demonstrated a higher rate of survivability than piglets without PEDV antibody. When combined with previous literature on PEDV, it can be concluded that both systemic antibodies and maternal secretory IgA in milk contribute to the protection of the neonatal pig against PEDV infections. Overall, the results of this experiment suggested that passively administered circulating antibodies contributed to the protection of neonatal piglets against PEDV infection.
Objective: To explore the effect of a probiotic compound preparation composed of Bifidobacterium longum BB536 and Bifidobacterium lactis HN019 on dysbiosis of murine gut microbiota induced by ...ceftriaxone sodium. Methods: Ceftriaxone sodium (2 mg/g) was given to mice for 5 days to construct intestinal flora dysbiosis model mice and then they were randomly divided into model group, low-dose (2×105 CFU/g), medium-dose (4×105 CFU/g) and high-dose (1.2×106 CFU/g) groups of probiotic compound preparations. In addition, normal mice were set as the control group. From the 6th day, each dose group was administered with the corresponding dose of probiotic compound preparation, the control group and model group were administered with equal volume of normal saline for 30 days. After the gavage, the mice feces were collected to count the intestinal flora and 16S rDNA high-throughput sequencing was performed to analyze the diversity and structure of the flora. The levels of IL-2, IL-6, IL-1β and TNF-α in serum were measure
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