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1.
《Saudi Dental Journal》2022,34(7):565-571
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   
2.
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   
3.
4.
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   
5.
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   
6.
目的 分析儿童周期性呕吐综合征(CVS)临床表现、辅助检查、治疗及预后,以期提高对儿童周期性呕吐综合征的认识和诊治水平。方法 回顾性分析重庆医科大学附属儿童医院消化科2008年1月至2019年12月住院且符合儿童功能性胃肠病ROME Ⅳ诊断标准的141例CVS患儿临床资料及随访结果。结果 141例患儿中男65 例、女76例,发病年龄中位数5.5岁(≤15岁5月龄),诊断年龄中位数8.3岁(11月龄至15岁8月龄),首次发病至确诊病程平均2.3年(3个月至11.3年),平均住院4次。其中60.28%(85/141)有明确诱因,感染与饮食不当最常见。所有病例均有呕吐,发作持续时间中位数为5 d(2~14 d),平均每日呕吐发作约15次,间歇期中位数38 d(5 d至6 个月)。其他症状包括腹痛(72.34%,102/141)、恶心(46.81%,66/141)、头晕(30.50%,43/141)、发热(26.24%,37/141)、头痛(19.86%,28/141)、便秘(19.15%,27/141)。所有病例急性期均予以补液等对症支持治疗,发作间期予以赛庚啶、普萘洛尔、西比灵等药物预防治疗,88例随访1~10年,81例(92%)治疗有效,9例仍有头痛表现(其中1例外院诊断偏头痛),13例有腹痛表现。结论 CVS是儿童呕吐的常见病因之一,各年龄段均可发病,无明显性别差异,发作前通常有诱因且临床诊断常有延迟;CVS可反复发作,除呕吐外常有其他消化道或自主神经紊乱相关症状;对于发作频率高、持续时间长的患儿预防应用赛庚啶、普萘洛尔、西比灵等药物多数有效;该组CVS患儿流行病学、临床表现及疗效与其他地区相似,但随访偏头痛、腹痛发生率明显低于国外数据。  相似文献   
7.
通过考察阿萨伊油、醇提物和水提物等拆分组分对虚热及虚寒证小鼠的温度趋向性动物行为学表征,环核苷酸及代谢水平等内在生化指标的影响,探讨阿萨伊各拆分组分的寒热药性特点以及寒凉的物质基础。将昆明种雄性小鼠随机分为空白组、虚热模型组、虚热+阿萨伊冻干原粉组、虚热+阿萨伊油组、虚热+阿萨伊醇提物组、虚热+阿萨伊水提物组、虚寒模型组、虚寒+肉桂组、虚寒+阿萨伊冻干原粉组、虚寒+阿萨伊油组、虚寒+阿萨伊醇提物组、虚寒+阿萨伊水提物组共12个组。虚热组小鼠每天下午灌胃给予甲状腺片溶液160 mg·kg-1,虚寒组小鼠给予氢化可的松溶液25 mg·kg-1,连续14 d,各给药组灌胃相关药物,实验结束后测定动物温度趋向性、环核苷酸及代谢水平等相关指标。阿萨伊醇提物同阿萨伊原粉一致,表现出对虚热模型小鼠的调整作用;阿萨伊油及其水提物同肉桂一致,表现出对虚寒模型小鼠的调整作用。该研究基于中药性味可拆分理论,采用同类比较异类反证的方法证明了阿萨伊醇提物性偏凉,油及其水提物性偏温的特征,并明确了醇提物为阿萨伊性凉的物质基础。  相似文献   
8.
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   
9.
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   

10.
目的 探讨肝动脉介入栓塞术治疗肝血管瘤患者的疗效及血清甘氨酰脯氨酸二肽氨基肽酶(GPDA)、高尔基体蛋白73(GP73)和β2-微球蛋白(β2-MG)水平的变化。方法 2017年1月~2019年1月我院肝病科收治的60例肝血管瘤患者被随机分为介入手术组30例和开腹肝切除术组30例,分别接受经肝动脉介入栓塞术或开腹肝切除术。术后,随访半年。采用ELISA法检测血清GPDA、GP73、β2-MG水平及肿瘤坏死因子-α(TNF-α)、肿瘤特异性生长因子(TSGF)和甲胎蛋白(AFP)水平。结果 介入手术组手术时间和术后住院时间分别为(84.7±21.9) min和(6.7±1.3)d,均显著短于开腹肝切除术组【分别为(126.8±60.5)min和(9.6±5.8)d,P<0.05】,术中出血量为(110.7±13.5)mL,显著少于开腹肝切除术组【(315.5±17.8)mL,P<0.05】;在术后1 w,介入手术组血清GPDA、GP73、β2-MG、TNF-α、TSGF和AFP水平分别为(62.6±9.8)U/L、(64.3±6.7)μg/L、(1.4±0.5)mg/L、(1.3±0.5)mg/L、(35.5±4.3)U/mL和(2.5±0.6)mg/L,均显著低于开腹肝切除术组【分别为(86.4±11.5)U/L、(112.2±9.3)μg/L,(2.3±0.9)mg/L,(2.1±1.2)mg/L,(61.3±9.8)U/mL和(4.7±0.8)mg/L,P<0.05】;介入手术组并发症发生率为13.3%,显著低于开腹肝切除术组(30.0%,P<0.05);在术后随访6 m,介入手术组总有效率为93.3%,显著高于开腹肝切除术组(80.0%,P<0.05)。结论 采用肝动脉介入栓塞术治疗肝血管瘤患者疗效较好,且可降低血清GPDA、GP73、β2-MG、TNF-α和TSGF水平,明显改善围术期手术相关指标,减少并发症的发生,具有较高的临床安全性。  相似文献   
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