Vascular dementia is the second dementing illness after Alzheimer's disease and caused by reduced blood flow to the brain, and affects cognitive abilities. Our previous study found that auricular ...electrical stimulation (ES) improved motor and learning impairment, and this phenomenon related with nicotinic acetylcholine receptor (nAChR) expressed cells. However, the underlying mechanism was not clear. In the present study, we investigated the effects of auricular ES on cortical blood flow (CBF) and acetylcholine (ACh) - nAChRs expressed cells.
Vascular dementia rat animal model was established by permanent occlusions of common carotid arteries with 6-0 nylon suture filament. At 21 day after surgery, motor impairment was confirmed by rotarod test. 15-Hz auricular ES were applied to the ears for 20 min and CBF was recorded at the mean time. The brains were immediately dissected for immunohistochemical stain and western blot analysis.
Our results showed that 15-Hz auricular ES rapidly elevated CBF in the middle cerebral artery. The numbers of nAChR α4 immuno-positive cells and western blot levels were significally increased by 15-Hz auricular ES in the hippocampal CA2 output cortex. The numbers of choline acetyltransferase (ChAT) - a key enzyme for biosynthesis of ACh - immuno-positive cells and western blot levels had no significant differences.
The present data suggested that the 15-Hz auricular ES for 20 min rapidly elevated cortical blood flow, promoted the expression of nAChR α4, and would be beneficial for the treatment of Alzheimer type and vascular type dementia.
The functions of anorexigenic neurons secreting proopiomelanocortin (POMC)/alpha-melanocyte-stimulating hormone (α-MSH) of the melanocortin system in the hypothalamus in vertebrates are energy ...homeostasis, food intake, and body weight regulation. However, the mechanisms remain elusive. This article reports on zebrafish that have been genetically engineered to produce α-MSH mutants, α-MSH−7aa and α-MSH−8aa, selectively lacking 7 and 8 amino acids within the α-MSH region, but retaining most of the other normal melanocortin-signaling (Pomc-derived) peptides. The α-MSH mutants exhibited hyperphagic phenotypes leading to body weight gain, as observed in human patients and mammalian models. The actions of several genes regulating appetite in zebrafish are similar to those in mammals when analyzed using gene expression analysis. These include four selected orexigenic genes: Promelanin-concentrating hormone (pmch), agouti-related protein 2 (agrp2), neuropeptide Y (npy), and hypothalamic hypocretin/orexin (hcrt). We also study five selected anorexigenic genes: Brain-derived neurotrophic factor (bdnf), single-minded homolog 1-a (sim1a), corticotropin-releasing hormone b (crhb), thyrotropin-releasing hormone (trh), and prohormone convertase 2 (pcsk2). The orexigenic actions of α-MSH mutants are rescued completely after hindbrain ventricle injection with a synthetic analog of α-MSH and a melanocortin receptor agonist, Melanotan II. We evaluate the adverse effects of MSH depletion on energy balance using the Alamar Blue metabolic rate assay. Our results show that α-MSH is a key regulator of POMC signaling in appetite regulation and energy expenditure, suggesting that it might be a potential therapeutic target for treating human obesity.
Higher soluble CD4 (sCD4) levels in serum have been detected in patients of infectious and chronic inflammatory diseases. However, how and why sCD4 is produced remains poorly understood. We establish ...sensitive ELISA and WB assays for sCD4 detection in conditioned medium of in vitro cell culture system and serum of chronic inflammatory patients. Serum samples from patients with systemic lupus erythematosus (SLE) (n = 79), rheumatoid arthritis (RA) (n = 59), ankylosing spondylitis (AS) (n = 25), gout (n = 31), and normal controls (n = 99) were analyzed using ELISA for sCD4 detection. Results from each assay were analyzed by the Kruskal-Wallis test. Dunn's multiple comparison post-test was then applied between groups. We confirm that cells expressing exogenous CD4 produce sCD4 in a constitutive and PMA-induced manner. Importantly, sCD4 production in a heterologous expression system is inhibited by GM6001 and TAPI-0, suggesting receptor shedding by matrix metalloproteinase (MMP)-like proteinases. Moreover, similar findings are recapitulated in human primary CD4(+) T cells. Finally, we show that serum sCD4 levels are increased in patients of chronic inflammatory diseases including RA and SLE, but not in those with gout. Intriguingly, sCD4 levels in RA patients are correlated positively with the disease activities and higher sCD4 levels seem to associate with poor prognosis. Taken together, we conclude that CD4 is shed from cell surface by a MMP-like sheddase and sCD4 level is closely related with the inflammatory condition in certain chronic diseases. Hence, sCD4 might be considered an important parameter for RA disease progression with potential diagnostic importance.
This study simulates and discusses the behavior of low-rise buildings on liquefiable ground with different ground water table levels during earthquakes via centrifuge modeling. The test results ...reveal that lowering the water table can effectively limit the settlement of structures on liquefiable ground. However, this also reduces the seismic isolation effect of soil liquefaction. As the water table is lowered, the acceleration amplification in structures increases slightly. In addition to this, the effect of reinforcing the first floor slab was studied and the results show that such reinforcement can generate a significant anti-liquefaction effect in areas with a high water table. Engineers can use this combination of improvement methods to achieve better designs.
•The results of dynamic centrifuge tests are used to clarify the anti-liquefaction effect of the concerned methods.•The anti-liquefaction effect of lowering the ground water table is explained by the concept of the cyclic stress ratio.•Several notes on anti-liquefaction design are proposed as a reference for practical engineers.
Nanocomposites of high-density polyethylene (HDPE) modified with 0.2 phr graphene-zinc oxide (GN-ZnO) exhibited optimal mechanical properties and thermal stability. Two other nano-materials—GN and ...nano-ZnO—were also used to compare them with GN-ZnO. Increasing the content of GN-ZnO gradually enhanced the antibacterial and barrier properties, but the addition of 0.3 phr GN-ZnO led to agglomeration that caused defects in the nanocomposites. Herein, we investigated the antibacterial and barrier properties of HDPE nanocomposites infused with different nanoparticles (GN, ZnO, GN-ZnO) of varying concentrations. HDPE and the nanoparticles were melt-blended together in a Haake-Buchler Rheomixer to produce a new environment-friendly nano-material with improved physical and chemical properties. The following characterizations were conducted: tensile test, thermogravimetric analysis, morphology, differential scanning calorimetry, X-ray diffraction, antibacterial test, and oxygen and water vapor permeation test. The results showed that the crystallinity of HDPE was affected with the addition of GN-ZnO, and the nanocomposites had effective antibacterial capacity, strong mechanical properties, high thermal stability, and excellent barrier performance. This type of HDPE nanocomposites reinforced with GN-ZnO would be attractive for packaging industries.
With its pathophysiological characteristics strongly similar to patients with tardive dyskinesia (TD), haloperidol (HP)-induced neurotoxicity and orofacial dyskinesia (OD) in animal models have long ...been used to study human TD. This study aimed to explore the potential protective effects of betaine (BT), a vital biochemical compound present in plants, microorganisms, animals, and various dietary sources. The study focused on investigating the impact of BT on haloperidol (HP)-induced orofacial dyskinesia (OD) in rats, as well as the underlying neuroprotective mechanisms. To induce the development of OD, which is characterized by increased vacuous chewing movement (VCM) and tongue protrusion (TP), rats were administered HP (1 mg/kg i.p.) for 21 consecutive days. BT was administered intraperitoneally (i.p.) at doses of 30 and 100 mg/kg, 60 min later, for 21 successive days. On the 21st day, after evaluating OD behavior, the rats were sacrificed, and various measurements were taken to assess the nitrosative and oxidative status, antioxidant capacity, mitochondrial function, neuroinflammation, and apoptotic markers in the striatum. The results demonstrated that (1) HP induced OD development, and (2) BT was found to prevent most of the HP-induced OD; decrease oxidative stress levels; increase anti-oxidation power; prevent mitochondrial dysfunction; and reduce the levels of neuroinflammatory and apoptotic markers in the striatum. Our results demonstrate that the neuroprotective effects of BT against HP-induced OD are credited to its antioxidant prevention of mitochondrial dysfunction, anti-neuroinflammatory effects, and anti-apoptotic effects, suggesting that BT may be a novel therapeutic candidate in delaying or treating human TD in clinical settings. However, further studies will be warranted to extrapolate preclinical findings into clinical studies for a better understanding of the role of BT.
Eighteen 4-t-octylphenol-degrading bacteria were isolated and screened for the presence of degradative genes by polymerase chain reaction method using four designed primer sets. The primer sets were ...designed to amplify specific fragments from multicomponent phenol hydroxylase, single component monooxygenase, catechol 1,2-dioxygenase and catechol 2,3-dioxygenase genes. Seventeen of the 18 isolates exhibited the presence of a 232bp amplicon that shared 61–92% identity to known multicomponent phenol hydroxylase gene sequences from short and/or medium-chain alkylphenol-degrading strains. Twelve of the 18 isolates were positive for a 324bp region that exhibited 78–95% identity to the closest published catechol 1,2-dioxygenase gene sequences. The two strains, Pseudomonas putida TX2 and Pseudomonas sp. TX1, contained catechol 1,2-dioxygenase genes also have catechol 2,3-dioxygenase genes. Our result revealed that most of the isolated bacteria are able to degrade long-chain alkylphenols via multicomponent phenol hydroxylase and the ortho-cleavage pathway.
Cancer stem cells (CSCs) have been known to be implicated in tumorigenesis, metastasis, and drug resistance in oral squamous cell carcinomas (OSCC). In this study, we aimed to investigate whether ...magnolol, a polyphenolic component derived from Magnolia officinalis, exhibited the anti-CSCs properties.
The cytotoxicity of magnolol was tested using normal gingival epithelioid SG cells and sphere-forming OSCC-CSCs isolated from SAS, OECM1, and GNM cells. Secondary sphere-forming ability, the proportion of ALDH1 positive cells, Transwell migration, and invasion capacities were examined as well. The chemosensitive effects of magnolol were investigated using MTT, secondary sphere-forming, and invasion assays.
Magnolol exerted a higher cytotoxicity of OSCC-CSCs and cancer stemness features, including self-renewal ability, the expression CSC marker, migration, and invasion capacities were all downregulated in magnolol-treated OSCC-CSCs. Moreover, administration of magnolol potentiated the effect of cisplatin, including a decrease in cell viability, self-renewal, and invasion activities. In addition, we observed that the secretion of IL-6 and phosphorylation of Stat3 were decreased in OSCC-CSCs treated with magnolol.
Our data suggest that magnolol is able to target CSCs and suppress the cancer stemness properties, at least in part, via IL-6/Stat3 signaling. Besides, a dietary supplement of magnolol may function as an adjunct to cisplatin treatment.
Gout is strongly associated with the incidence of atherosclerotic events, including stroke and myocardial infarction. Considering the increased prevalence of stroke in the population with gout, the ...aim of this study was to evaluate the effects of benzbromarone, a uricosuric agent, on the incidence of stroke in the population with gout. We used data from the Taiwanese National Health Insurance Registration Database (NHIRD). The benzbromarone user cohort included 15,143 patients; each patient was age- and sex-matched with one non-user randomly selected from the population with gout. Cox proportional hazard regression analysis was conducted to estimate the effects of benzbromarone on the incidence of stroke in the population with gout. The incidence of stroke was significantly lower in benzbromarone users than in benzbromarone non-users. The HR for the incidence of stroke was lower in male benzbromarone users than in non-users. An analysis of three age groups (<40, 40-59, and ≥60 years) indicated that the HRs in those aged 40-59 years and ≥60 years were significantly lower among benzbromarone users than non-users. In the population with gout, the incidence of stroke was lower in benzbromarone users than in benzbromarone non-users.
Previous studies reported that long noncoding RNA (lncRNA) ZFPM2‐AS1 is upregulated in renal cell carcinoma (RCC). However, the biological role of lncRNA ZFPM2‐AS1 in RCC has not been explored. In ...this study, we investigated the role of lncRNA ZFPM2‐AS1 in the progression of RCC. Quantitative real‐time polymerase chain reaction was used for gene expression analysis, and functional assays including Cell Counting Kit‐8 assay, flow cytometry‐based apoptosis assay and transwell migration assays were performed to examine the malignant phenotypes. The functional interaction between ZFPM2‐AS1 or miR‐130A‐3P and their targets was detected by dual‐luciferase reporter assay. We found that the expressions of ZFPM2‐AS1 and ESCO2 were upregulated in RCC tissues and cells, whereas miR‐130a‐3p was downregulated. The expression level of ZFPM2‐AS1 is significantly associated with advanced TNM, distant metastasis, lymphatic metastasis, and a poor overall survival in RCC patients. Silencing ZFPM2‐AS1 in RCC cells suppressed cell proliferation, invasion, and migration, and induced cell apoptosis. ZFPM2‐AS1 interacted with miR‐130A‐3P and negatively regulated its expression in RCC cells. We further showed that ESCO2 was a downstream target of miR‐130a‐3p. Both miR‐130a‐3p inhibitor and ESCO2 overexpression could rescue the inhibitory effects of ZFPM2‐AS1 knockdown in RCC cells. Together, our study demonstrates that ZFPM2‐AS1 plays an oncogenic role in RCC progression via the miR‐130a‐3p/ESCO2 axis.
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