PurposeThis study aimed to evaluate the neuroprotective ability of the conditioned medium of stem cells from human exfoliated deciduous teeth (CM-SHED) to prevent glutamate-induced apoptosis of neural progenitors.Materials and methodsNeural progenitors were isolated from two-day-old rat brains, and the conditioned medium was obtained from a mesenchymal stem cell SHED. Four groups were examined: neural progenitor cells cultured in neurobasal medium with (N + ) and without (N-) glutamate and glycine, and neural progenitor cells cultured in CM-SHED with (K + ) and without (K-) glutamate and glycine.ResultsThe expression of GABA A1 receptor (GABAAR1) messenger RNA (mRNA) in neural progenitor measured by real-time quantitative PCR. GABA contents were measured by enzyme-linked immunosorbent assay, whereas the apoptosis markers caspase-3 and 7-aminoactinomycin D were analysed with a Muse® cell analyzer. The viability of neural progenitor cells in the K + group (78.05 %) was higher than the control group N- (73.22 %) and lower in the N + group (68.90 %) than in the control group. The K + group showed the highest GABA content, which significantly differed from that in the other groups, whereas the lowest content was observed in the N + group. The expression level of GABAAR1 mRNA in the K + group was the highest compared to that in the other groups. CM-SHED potently protected the neural progenitors from apoptosis.ConclusionsCM-SHED may effectively prevent glutamate-induced apoptosis of neural progenitors. 相似文献
Anthrax is a zoonotic infection caused by the gram-positive, aerobic, spore-forming bacterium Bacillus anthracis. Depending on the origin of the infection, serious health problems or mortality is possible. The virulence of B. anthracis is reliant on three pathogenic factors, which are secreted upon infection: protective antigen (PA), lethal factor (LF), and edema factor (EF). Systemic illness results from LF and EF entering cells through the formation of a complex with the heptameric form of PA, bound to the membrane of infected cells through its receptor. The currently available anthrax vaccines have multiple drawbacks, and recombinant PA is considered a promising second-generation vaccine candidate. However, the inherent chemical instability of PA through Asn deamidation at multiple sites prevents its use after long-term storage owing to loss of potency. Moreover, there is a distinct possibility of B. anthracis being used as a bioweapon; thus, the developed vaccine should remain efficacious and stable over the long-term. Second-generation anthrax vaccines with appropriate adjuvant formulations for enhanced immunogenicity and safety are desired. In this article, using protein engineering approaches, we have reviewed the stabilization of anthrax vaccine candidates that are currently licensed or under preclinical and clinical trials. We have also proposed a formulation to enhance recombinant PA vaccine potency via adjuvant formulation. 相似文献
The endodontic literature contains a plethora of studies on static and dynamic cyclic fatigue resistance tests performed on a large array of rotary or reciprocating nickel–titanium endodontic instruments. It was the aim of this review to summarize the currently available evidence to point out the different outcomes from static versus dynamic tests and to assess whether cyclic fatigue tests provide useful data and information for clinical practice. An electronic literature research in the database PubMed was performed using appropriate search terms, and the titles and abstract were screened for relevance. Language was restricted to English. The review reveals marked differences between the results obtained in static and dynamic tests, and also, the results for the same instruments assessed either under static or dynamic experimental conditions are widely inconsistent. Between the lowest and the highest value for one and the same pathfinding instrument was a factor of about 123 when cyclic fatigue was assessed either under static or dynamic experimental conditions. Moreover, standard deviations of up to 30% have been reported. Environmental temperature has a 500% impact on the lifetime of instruments. In conclusion, fatigue resistance tests conducted under room temperature should be regarded as having little meaning and the scientific and clinical benefits of fatigue resistance tests are very limited. These data should be provided by the manufacturer of the instruments. 相似文献
Psychostimulant use disorders remain an unabated public health concern worldwide, but no FDA approved medications are currently available for treatment. Modafinil (MOD), like cocaine, is a dopamine reuptake inhibitor and one of the few drugs evaluated in clinical trials that has shown promise for the treatment of cocaine or methamphetamine use disorders in some patient subpopulations. Recent structure–activity relationship and preclinical studies on a series of MOD analogs have provided insight into modifications of its chemical structure that may lead to advancements in clinical efficacy. Here, we have tested the effects of the clinically available (R)‐enantiomer of MOD on extracellular dopamine levels in the nucleus accumbens shell, a mesolimbic dopaminergic projection field that plays significant roles in various aspects of psychostimulant use disorders, measured in vivo by fast‐scan cyclic voltammetry and by microdialysis in Sprague‐Dawley rats. We have compared these results with those obtained under identical experimental conditions with two novel and enantiopure bis(F) analogs of MOD, JBG1‐048 and JBG1‐049. The results show that (R)‐modafinil (R‐MOD), JBG1‐048, and JBG1‐049, when administered intravenously with cumulative drug‐doses, will block the dopamine transporter and reduce the clearance rate of dopamine, increasing its extracellular levels. Differences among the compounds in their maximum stimulation of dopamine levels, and in their time course of effects were also observed. These data highlight the mechanistic underpinnings of R‐MOD and its bis(F) analogs as pharmacological tools to guide the discovery of novel medications to treat psychostimulant use disorders. 相似文献
Mesenchymal stem cells (MSCs) are highly sensitive to biomechanics of their extracellular environment. Generally, a higher elasticity of culture substrates can drive cells into the osteogenic lineage, whereas low substrate elasticity results in adipogenesis. Applied mechanical loading by cyclic strain is another major variable influencing cell fate. Yet, little is known about the simultaneous effect of both cues. Therefore, the present study investigated the relative importance of both cues on differentiation. MSCs were cultured in an osteogenic and also an adipogenic environment on soft polyacrylamide (PAAm; E = 23 ± 0.3 kPa), stiff PAAm (111 ± 2 kPa), and polydimethylsiloxane (PDMS; E = 1,5 ± 0.07 MPa) either unstrained or with 8% cyclic strain at 1 Hz. Without strain, the relative expression of the early osteogenic marker alkaline phosphatase (ALP) was significantly higher (78%) on PDMS than on both PAAm. With 8% cyclic strain, ALP expression increased for all groups in comparison with unstrained controls. The highest increase was observed for the soft PAAm by 36%. Moreover, relative oil red O (ORO) expression—indicating adipogenesis—was the highest for unstrained soft PAAm. On the other hand, the percentage of ORO positive cells significantly decreased by 57% and 69% for soft and stiff PAAm when strained. In conclusion, biomaterial elasticity and mechanical loading can act simultaneously on cell differentiation. Substrate elasticity is an important factor, regulating the differentiation, but cyclic strain can drive MSCs towards the osteogenesis even on the softest substrate. As such, the osteogenic effect of mechanical loading can overrule the adipogenic effect of soft substrates, thereby acting as an inhibitor. 相似文献
Introduction: In men, lower urinary tract symptoms (LUTS) are primarily attributed to benign prostatic hyperplasia (BPH). Therapeutic options are targeted to relax prostate smooth muscle and/or reduce prostate enlargement.
Areas covered: This article reviews the major preclinical and clinical data on PDE5 inhibitors with a specific focus on tadalafil. It includes details of the role of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) – PDE5 pathway in the LUT organs (bladder and prostate) in addition to the available data on tadalafil in patients with LUTS secondary to BPH with or without erectile dysfunction (ED).
Expert opinion: Preclinical and clinical data have clearly demonstrated that PDE5 inhibitors induce bladder and prostate relaxation, which contributes to the improvement seen in storage symptoms in both animal models of bladder and prostate hypercontractility. Tadalafil is effective both as a monotherapy and add-on therapy in patients with LUTS secondary to BPH. Furthermore, as LUTS-BPH and ED are urological disorders that commonly coexist in aging men, tadalafil is more advantageous than α1-adrenoceptors and should be used as the first option. Tadalafil is a safe and tolerable therapy and unlike α1- adrenoceptors and 5-alpha reductase inhibitors, which can cause sexual dysfunctions, tadalafil improves sexual function. 相似文献