Curcumin protects against cigarette smoke-induced cognitive impairment and increased acetylcholinesterase activity in rats

Cigarette smoke, a widely spread habit, is associated with a decline in cognitive function and studies have demonstrated that curcumin (Cur), an Indian spice, possesses a strong neuroprotective potential. Considering the relevance of investigating dietary compounds this study aimed to investigate the effect of Cur on memory and acetylcholinesterase (AChE) activity in brain structures and blood of cigarette smoke-exposed rats. Male Wistar rats were treated with curcumin and cigarette smoke, once a day, 5 days each week, for 30 days. The experimental procedures were divided in two sets of experiments. In the first, the animals were divided into 4 groups: Vehicle (corn oil), Cur 12.5 mg/kg, Cur 25 mg/kg and Cur 50 mg/kg. In the second, the animals were divided into 5 groups: Vehicle (corn oil), Smoke, Smoke plus Cur 12.5 mg/kg, Smoke plus Cur 25 mg/kg and Smoke plus Cur 50 mg/kg. Treatment with Cur significantly prevented the decreased latency and cholinergic alterations in cigarette smoke-exposed rats. These AChE alterations could suggest a role in the memory impairment promoted by cigarette smoke-exposure and point toward the potential of Cur to modulate cholinergic neurotransmission and, consequently, improve cognition deficits induced by smoke. This study suggests that the dietary compound Cur may be involved in cholinergic system modulation and as a consequence exert an effect on learning and memory.     

姜黄素对创面愈合作用的影响及其机制的初步探讨

目的 观察姜黄素(Curcumin,Cur)对大鼠皮肤创面愈合作用的影响及其机制.方法 取30只雄性SD大鼠,用6 mm打孔器在每只大鼠背部制作4个直径为6 mm大小创面模型.每只大鼠的每个创面每天施加不同浓度姜黄素(30、15、0mg/mL)及PBS干预创面的愈合.在术后第1、3、7、10、14 d随机取6只大鼠计算各创面愈合速率,采用免疫组织化学法检测各组中不同时间点各创面中血管内皮生长因子(vascular endothlial growth factor,VEGF)、碱性成纤维细胞生长因子(basic fibroblast growth factor,bFGF)表达量,采用免疫荧光法检测各组中不同时间点各创面中M1型及M2型巨噬细胞含量.结果 溶媒剂对创面愈合未见明显影响;与对照组相比,Cur15组及Cur30组创面愈合明显增快;Cur15组及Cur30组术后第7天和第10天创面VEGF免疫组化平均光密度数值均多于相同时间点Cur0组及PBS组(P＜0.05);Cur15组术后第3、7和10天及Cur30组术后第7天和第10天bFGF免疫组化平均光密度数值均多于相同时间点Cur0组及PBS组(P ＜0.05);Cur15组及Cur30组术后第3和7天创面CD68与诱导型一氧化氮合酶(inducible nitric oxide sythase,iNOS)双阳性细胞百分比均少于相同时间点Cur0组及PBS组(P＜0.05);Cur15组术后第3和7天及Cur30组术后第3、7、10和14天创面CD68与精氨酸酶1(arginase-1,Arg-1)双阳性细胞百分比均多于相同时间点Cur0组及PBS组(P＜0.05).结论 Cur能够明显促进创面愈合,其机制可能与Cur对M1与M2型巨噬细胞的极化调节有关;Cur浓度为15 mg/mL时创面愈合速率最快.     

The inhibitory effects of different curcuminoids on β-amyloid protein, β-amyloid precursor protein and β-site amyloid precursor protein cleaving enzyme 1 in swAPP HEK293 cells

The hallmark of Alzheimer's disease (AD) is the accumulation of β-amyloid protein (Aβ). Aβ is generated from the β-amyloid precursor protein (APP) through the proteolysis of β-site APP cleaving enzyme 1 (BACE1) and γ-secretase. Aβ₄₂ isoform is more easily aggregate and more toxic to neurons than any other Aβ isoforms, thus being regarded as the primary toxic specie in AD. Curcumin mix has potent anti-amyloidogenic effect and shows great promise for AD treatment and prevention. The present study was conducted to examine the effects of curcumin mix and its different curcuminoids including curcumin (Cur), demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) on Aβ₄₂, APP and BACE1. We found that Cur was the most active curcuminoid fraction in suppressing Aβ₄₂ production and the order of inhibitory potency of other curcuminoids was DMC > curcumin mix > BDMC. Cur, but not other curcuminoids, could reduce APP protein expression and none of curcuminoids affected APP mRNA level. BDMC could reduce BACE1 mRNA and protein levels, while DMC only affected BACE1 mRNA expression. Our data indicate that the anti-amyloidogenic effect of Cur may be mediated through the modulation of APP, while the anti-amyloidogenic effect of BDMC may be mediated through the modulation of BACE1.     

Morphological and Biochemical Features of Cerebellar Cortex After Exposure to Zinc Oxide Nanoparticles: Possible Protective Role of Curcumin

Zinc oxide nanoparticles (ZnONPs) are widely used in the last decades. Therefore, investigation of its neurotoxic effect is important. This work aimed to investigate the potential adverse effects of ZnONPs on rat's cerebellar cortex and the possible neuroprotective role of curcumin (Cur). Forty male albino rats were randomly divided into four equal groups. Two groups were injected with ZnONPs and one group was previously received Cur before ZnONPs. At the end of the experiment, cerebellar tissue samples were prepared for histological, morphometric, immunohistochemical study, and tissue levels of oxidative stress markers and cytokine analysis. cerebellar damage is clearly visible with ZnONPs. Degeneration, loss, disorganization of cerebellar neurons was observed. Histopathological degeneration of Purkinje and granular cells together with loss of Nissl substance, astrocyte gliosis, and affection of cerebellar blood brain barrier were detected. Moreover, an apoptotic marker (caspase‐3) was significantly expressed in Purkinje and granular layers together with elevated gene expression of P53 and COX‐2 in cerebellar tissue of ZnONPs intoxicated group. Astrocyte gliosis and inflammatory markers IL‐1, IL‐6, and TNF‐α were expressed significantly in ZnONPs intoxicated cerebellum. These changes were associated with evidence of cerebellar oxidative stress. Strikingly, treatment with Cur together with ZnONPs recorded morphological improvement, with increased number of Purkinje cells and decreased caspase +ve cells. These findings were confirmed by morphometric and statistical analysis. Cur ameliorates the deterious effect of ZnONPs on the cerebellar cortex through its antioxidant, antiapoptotic, and anti‐inflammatory efficacies. Anat Rec, 2018. © 2018 Wiley Periodicals, Inc.     

High-dose corticosteroids after spinal cord injury reduce neural progenitor cell proliferation

We assessed whether a clinical dose of the anti-inflammatory drug methylprednisolone (MP) given to adult mice acutely after spinal cord injury (SCI) influences spinal cord or hippocampal progenitor cells. Mice underwent a thoracic dorsal hemisection of the spinal cord and received 30 mg/kg MP immediately and 24 h post-lesion. 5-Bromo-2-deoxyuridine (BrdU) was administered after lesion either acutely (1–6 days) or late (22–27 days) to label proliferating cells. Reaction of microglia/macrophages was quantified 7 days post-lesion and proliferation as well as differentiation of neural progenitor cells (NPCs) was analyzed after two survival times (7 days and 28 days). We also tested the influence of MP on microglia and adult NPCs in vitro. MP treatment reduced the number of cells proliferating acutely after SCI in the spinal cord and hippocampus. Besides reducing activation and proliferation of microglia/macrophages in the spinal cord, MP also decreased the number of oligodendrocyte progenitor cells (OPCs). Analysis of acutely BrdU-labeled cells at 28 days post-lesion suggests that proliferation and number of OPCs were changed chronically. Late proliferating cells were no longer influenced by the glucocorticoid regimen. In vitro experiments showed an inhibitory effect of MP on adult spinal cord and hippocampal progenitor cell proliferation. Both cell types express the glucocorticoid and mineralocorticoid receptors allowing a direct effect of MP. Our results show that MP reduces OPC proliferation after SCI either by affecting progenitor cells directly or via its anti-inflammatory effects. These findings open the question to which extent MP treatment limits the repair capacity of endogenous progenitor cells after CNS injury.     

姜黄素减轻小鼠深部组织压力性损伤

目的评价姜黄素(Cur)对缺血-再灌注所致小鼠深部组织压力性损伤(DTPI)创面愈合的影响。方法将小鼠随机分为对照组(Con)、模型组(Mod)、姜黄素4和8 mg/kg干预组(Cur 4,Cur 8),每组10只。磁铁压迫法构建深部组织损伤模型,每隔48 h于创面注射姜黄素,拍照观察伤口愈合情况。HE染色观察伤口愈合病理改变,realtime PCR检测肿瘤坏死因子(TNF-α)、白介素-6(IL-6)、白介素-10(IL-10)、血管内皮生长因子(VEGF-α)、转化生长因子-β(TGF-β)的mRNA表达;Western blot检测VEGF-α、TGF-β、Stat3、p-Stat3蛋白的表达。结果与对照组相比,模型组伤口逐渐恶化,病理学改变明显。与模型组相比,Cur 8组伤口愈合明显加快(P<0.05);Cur 8组炎性细胞浸润减少,新生血管密度增多。Cur 8组TNF-α、IL-6的mRNA表达量均低于模型组,IL-10、VEGF-α和TGF-β表达量均高于模型组(P<0.05);Cur 8组VEGF-α、TGF-β、p-Stat3蛋白表达水平均高于模型组(P<0.05)。结论姜黄素可减轻小鼠缺血-再灌注所致的DTPI,其机制可能与抑制炎性反应及促进血管再生有关。     

丙戊酸钠联合甲强龙对大鼠脊髓损伤的影响及其机制

目的:探讨丙戊酸钠(VAP)联合甲强龙(MP)在大鼠脊髓损伤(SCI)后神经功能恢复中的作用及其机制。方法:选取8～10周龄雄性健康SD大鼠60只,按照数字表法随机分为假手术组、SCI组、VAP组、MP组和VAP+MP组,每组12只;各组大鼠再按照数字表法随机分为A组、B组2个亚组,每组6只。假手术组仅暴露脊髓、不做S...     

Cur(Que)min: A neuroactive permutation of Curcumin and Quercetin for treating spinal cord injury

Among Spinal Cord Injury (SCI) intervention the administration of high-dose high-potency steroidal drugs such as methylprednisolone or dexamethasone is used to reduce the inflammation associated with primary injury and prevention of the subsequent secondary injury. The administration of steroids has several side-effects that jeopardize their use and therefore safer chemical neuro-entities are required. Natural compounds such as curcumin (anti-oxidant) and quercetin (anti-inflammatory) have been investigated as alternative neuroactive, but are not as potent as the steroids. Hence, they are required in very high doses which may lead to significant toxicity causing an increase in cellular levels of reactive oxygen species, active iron chelation, inhibiting the activity of the cytochrome P450 enzymes such as glutathione-S-transferase and UDP-glucuronosyltransferase. A reduction in the dose of these neuroactives is possible with the administration of a ‘chemically-variant’ permutation with additive or synergistic therapeutic benefits. Therefore, we hypothesize that curcumin and quercetin, both natural polyphenolic flavonoids, can “additively and synergistically” improve the physiological outcome after traumatic SCI when used in combination and termed ‘Cur(Que)min’ – thereby decreasing the dose levels and hence reducing the inherent high dose-cytotoxicity of the individual neuroactives. This hypothesis provides the first-account of a curcumin–quercetin combination for SCI intervention theorizing the possible biomolecular-mechanism that may provide the scientific community with a novel neuroprotective and neurotherapeutic treatment option for SCI.     

Dietary curcumin supplementation counteracts reduction in levels of molecules involved in energy homeostasis after brain trauma

Traumatic brain injury (TBI) is followed by an energy crisis that compromises the capacity of the brain to cope with challenges, and often reduces cognitive ability. New research indicates that events that regulate energy homeostasis crucially impact synaptic function and this can compromise the capacity of the brain to respond to challenges during the acute and chronic phases of TBI. The goal of the present study is to determine the influence of the phenolic yellow curry pigment curcumin on molecular systems involved with the monitoring, balance, and transduction of cellular energy, in the hippocampus of animals exposed to mild fluid percussion injury (FPI). Young adult rats were exposed to a regular diet (RD) without or with 500 ppm curcumin (Cur) for four weeks, before an FPI was performed. The rats were assigned to four groups: RD/Sham, Cur/Sham, RD/FPI, and Cur/FPI. We found that FPI decreased the levels of AMP-activated protein kinase (AMPK), ubiquitous mitochondrial creatine kinase (uMtCK) and cytochrome c oxidase II (COX-II) in RD/FPI rats as compared to the RD/sham rats. The curcumin diet counteracted the effects of FPI and elevated the levels of AMPK, uMtCK, COX-II in Cur/FPI rats as compared to RD/sham rats. In addition, in the Cur/sham rats, AMPK and uMtCK increased compared to the RD/sham. Results show the potential of curcumin to regulate molecules involved in energy homeostasis following TBI. These studies may foster a new line of therapeutic treatments for TBI patients by endogenous upregulation of molecules important for functional recovery.     

Curcumin improves the recovery of motor function and reduces spinal cord edema in a rat acute spinal cord injury model by inhibiting the JAK/STAT signaling pathway

Curcumin, a yellow pigment extracted from Carcuma longa, has been demonstrated to have extensive pharmacological activity in various studies, and it exhibits protective effects on injuries involving a number of human organs. The present study was designed to evaluate the potential effect and underlying mechanism of curcumin on the motor function and spinal cord edema in a rat acute spinal cord injury (SCI) model. The SCI model was induced by a heavy object falling. At 30 min after the SCI was successfully induced, the animals were intraperitoneally given 40 mg/kg curcumin. The Basso, Beattie and Bresnahan scores showed that curcumin moderately improved the recovery of the motor function in the injured rats, and hematoxylin–eosin staining demonstrated the role of this compound in reducing the hemorrhage, edema and neutrophil infiltration of the traumatic spinal cord. Furthermore, curcumin also inhibited the SCI-associated aquaporin – 4 (AQP4) overexpression and glial fibrillary acidic protein (GFAP) and repressed the unusual activation of the JAK/STAT signaling pathway. In conclusion, our data demonstrate that curcumin exhibits a moderately protective effect on spinal cord injury, and this effect might be related to the inhibition of overexpressed AQP4 and GFAP and the activated JAK/STAT signaling pathway. Curcumin may have potential for use as a therapeutic option for spinal cord injuries.     

JNK/MCP-1信号通路在姜黄素抗糖尿病神经病理性疼痛中的作用

 目的:观察JNK/MCP-1通路在姜黄素抗大鼠糖尿病神经病理性疼痛（DNP）中的作用及机制。方法:雄性SD大鼠诱导为2型糖尿病神经病理性痛大鼠（DNP）模型,将其随机分为6组（n=27）： DNP组、姜黄素组（Cur组）、溶剂对照组（DSC组）、JNK抑制剂组 (DJ组)、JNK抑制剂溶剂对照组(DJS组)、姜黄素+单核细胞趋化蛋白 1 (MCP-1)激动剂组（DM组）。另取27只正常大鼠为正常对照组（C组）,给药后3 d、7 d、14 d时测定机械缩足痛阈和热缩足潜伏期,并在同一时点取脊髓腰膨大及L4~6背根神经节（DRG）,用免疫印迹法测定脊髓和DRG中p-JNK水平,用ELISA测定脊髓和DRG中的MCP-1含量。结果:与DNP组相比,在给药后的7 d、14 d Cur组、DJ组、DM组p-JNK的表达明显下降（P<0.05）;与C组相比,链脲佐菌素给药后其它6组MCP-1含量出现明显下降;与DNP组相比,在给药后的7 d、14 d Cur组、DJ组MCP-1出现明显上升,而DM组出现进一步下降（P<0.05）。结论: DNP大鼠脊髓和DRG中的p-JNK、MCP-1表达明显升高,姜黄素减轻2型糖尿病大鼠神经病理性疼痛的机制可能与JNK/MCP-1信号通路有关。     

姜黄素对gp120所致大鼠学习记忆障碍的作用及机制研究

目的:探讨姜黄素改善HIV-1包膜糖蛋白gp120所致大鼠学习记忆障碍的作用及机制.方法:用gp120侧脑室灌注制备拟艾滋痴呆症动物模型,并用水迷宫实验观察侧脑室灌注gp120造成的大鼠认知功能的障碍. SD大鼠随机分为6组:对照组、假手术组、模型组、姜黄素低、中和高剂量治疗组.除对照组、假手术组外其余4组侧脑室缓慢注射5 μL的gp120,连续3 d.第4天开始,姜黄素低、中、高剂量治疗组分别给予50 mg/(kg·d)、100 mg/(kg·d)、200 mg/(kg·d)的姜黄素灌胃,对照组、假手术组和模型组大鼠用双蒸水灌胃,连续灌胃14 d.然后各组大鼠进行水迷宫测试,并分组进行NMDA2B受体免疫组化染色.结果:50 ng/d的gp120侧脑室灌注3 d,可制备拟艾滋痴呆症动物模型. Morris水迷宫可见模型组大鼠逃避潜伏期与对照组相比明显延长(P<0.05),姜黄素低、中、高剂量治疗组大鼠的逃避潜伏期与模型组相比缩短,其中姜黄素低剂量组效果更好(P<0.05).免疫组化结果显示模型组大鼠海马内N-甲基天冬氨酸受体(NMDA2B)的表达与对照组相比有所降低(P<0.01),姜黄素各剂量治疗组NMDA2B受体的表达与模型组相比有所上调.结论:gp120侧脑室灌注可制备拟艾滋痴呆症动物模型,姜黄素具有改善侧脑室灌注gp120所致大鼠学习记忆障碍的作用,其机制可能与对抗NMDA2B受体表达下调有关.     

MP‐AzeFlu is more effective than fluticasone propionate for the treatment of allergic rhinitis in children

The objective was to evaluate the efficacy of MP‐AzeFlu (Dymista^®) vs fluticasone propionate (FP), (both 1 spray/nostril bid), in children with allergic rhinitis (AR). MP‐AzeFlu combines azelastine hydrochloride, FP and a novel formulation in a single spray. Children were randomized in a 3 : 1 ratio to MP‐AzeFlu or FP in this open‐label, 3‐month study. Efficacy was assessed in children aged ≥ 6 to <12 years (MP‐AzeFlu: n = 264; FP: n = 89), using a 4‐point symptom severity rating scale from 0 to 3 (0 = no symptoms; 3 = severe symptoms). Over the 3‐month period, MP‐AzeFlu‐treated children experienced significantly greater symptom relief than FP‐treated children (Diff: ?0.14; 95% CI: ?0.28, ?0.01; P = 0.04), noted from the first day (particularly the first 7 days) and sustained for 90 days. More MP‐AzeFlu children achieved symptom‐free or mild symptom severity status, and did so up to 16 days faster than FP. MP‐AzeFlu provides significantly greater, more rapid and clinically relevant symptom relief than FP in children with AR.     

Preparation and in vitro release of curcumin sustained-release microspheres北大核心

BACKGROUND: Curcumin can inhibit inflammation and promote axonal growth, but it has a short half-life and a fast clearance rate. OBJECTIVE: To prepare curcumin sustained-release microspheres to release curcumin slowly and continuously. METHODS: Curcumin sustained-release microspheres were synthesized by O/W emulsification volatilization method using polylactic acid-glycolic acid copolymer as raw material. The preset drug loading rates were 10% and 20%, respectively, and set as No. 1 and No. 2 microspheres. The curcumin sustained release microspheres were synthesized by O/W emulsification volatilization method using L-lactic acid-polycaprolactone copolymer as raw material. The preset drug loading rates were 10% and 20%, respectively, and the microspheres were set as No. 3 and No. 4. The surface morphology of the microspheres was observed by scanning electron microscopy, and the drug loading and encapsulation efficiency of the microspheres were determined by high performance liquid chromatography. Four groups of microspheres were immersed in PBS release solution containing 1% sodium dodecyl sulfate, and the sustained release of curcumin microspheres was detected under simulated physiological environment. RESULTS AND CONCLUSION: (1) Scanning electron microscopy showed that the particle size and morphology of No. 3 and No. 4 curcumin microspheres were better than those of No. 1 and No. 2 curcumin microspheres. (2) The encapsulation rate of No. 3 microspheres was higher than that of the other three groups (P < 0.05, P < 0.01), and there was no significant difference in the encapsulation rate of No. 1, 2 and 4 microspheres (P > 0.05). (3) The drug loading rates of No. 2, 3 and 4 microspheres were higher than that of No. 1 microsphere (P < 0.01), and the drug loading rates of No. 2 and 4 microspheres were higher than that of No. 3 microsphere (P < 0.01). (4) The in vitro release of No. 3 curcumin sustained-release microspheres lasted for 14 days, and the release of the other three kinds of microspheres lasted for 21 days. The cumulative release rate of No. 1 and No. 3 was higher than that of No. 2 and No. 4, and the curcumin release concentration of No. 3 was higher than that of No. 1. (5) The results showed that slow-release effect of the curcumin sustained-release microspheres with a preset loading rate of 10% prepared by L-lactic acid-polycaprolactone copolymer best meets the Zero order release requirements. © 2022, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

Facile and large-scale synthesis of curcumin/PVA hydrogel: effectively kill bacteria and accelerate cutaneous wound healing in the rat

The complicated synthesis procedure and limited preparation size of hydrogel inhibit its clinical application. Therefore, a facile preparation method for large-size hydrogel is required. In this study, a series of curcumin (Cur)/polyvinyl alcohol (PVA) hydrogel in a large size with different Cur concentrations is prepared by a facile physical-chemical crosslinking. The physicochemical properties, antibacterial performance and accelerating wound healing ability are evaluated with the aim of attaining a novel and effective wound dressing. The results show that the as-prepared hydrogel with the optimal Cur to PVA volume ratio of 1:5 (20% Cur/PVA) exhibits the best antibacterial abilities to E. coli (85.6%) and S. aureus (97%) than other hydrogels. When the volume ratio of Cur to PVA is 1:10 (10% Cur/PVA), the hydrogel can significantly accelerate the wound healing in rats, and successfully reconstruct intact and thickened epidermis during 14 day of healing of impaired wounds after histological examination. In one word, the present approach can shed new light on designing new type of hydrogels with promising applications in wound dressing.     

MnTBAP对脊髓损伤大鼠脂质过氧化和运动功能的影响

目的观察脊髓损伤(SCI)后锰卟啉(MnTBAP)对损伤早期脂质过氧化反应、活性氧水平和伤后4W内运动功能的影响,探讨MnTBAP对脊髓继发性损伤的保护作用。方法用钳夹法制备大鼠SCI模型,分为假手术组、损伤组、MnTBAP治疗组和甲基强的松龙(MP)治疗组。损伤组术后立即腹腔注射生理盐水,MnTBAP组伤后立即腹腔注射MnTBAP(10mg/kg体重),MP组伤后立即腹腔注射MP(100mg/kg)。经1、6、12、24h,取SCI段标本,用于测定损伤段脊髓超氧化物歧化酶(SOD)、脂质过氧化产物丙二醛(MDA)和活性氧水平(ROS),经1、7、14、21、28d,进行斜板试验,评价运动功能。结果与假手术组相比,损伤组伤段脊髓组织SOD显著减少(均<0.01),MDA和ROS显著增加(均<0.01);与损伤组相比,MnTBAP治疗组伤段脊髓组织SOD水平显著增加(均<0.01),相反,MDA和ROS水平显著减少(均<0.01),其作用和MP相当;斜板试验结果观察,除1d组外,MnTBAP治疗组斜板角度与损伤组相比明显增加(均<0.01)。结论 MnTBAP有效抑制SCI早期受损脊髓脂质过氧化反应和活性氧水平,改善SCI大鼠运动功能,对继发性SCI具有保护作用。     

Nanoparticle-mediated local delivery of methylprednisolone after spinal cord injury

Systemic administration of a high-dose of Methylprednisolone (MP) can reduce neurological deficits after acute spinal cord injury (SCI). However, the use of high-dose MP in treating acute SCI is controversial due to significant dose related side effects and relatively modest improvements in neurological function. Here, using a rat model of SCI, we compare the efficacy of controlled, nanoparticle-enabled local delivery of MP to the injured spinal cord with systemic delivery of MP, and a single local injection of MP without nanoparticles. Based on histological and behavioral data, we report that local, sustained delivery of MP via nanoparticles is significantly more effective than systemic delivery. Relative to systemic delivery, MP-nanoparticle therapy significantly reduced lesion volume and improved behavioral outcomes. Nanoparticle-enabled delivery of MP presents an effective method for introducing MP locally after SCI and significantly enhances therapeutic effectiveness compared to bare MP administered either systemically or locally.     

Pharmacogenomics: a new paradigm to personalize treatments in nephrology patients

Although notable progress has been made in the therapeutic management of patients with chronic kidney disease in both conservative and renal replacement treatments (dialysis and transplantation), the occurrence of medication‐related problems (lack of efficacy, adverse drug reactions) still represents a key clinical issue. Recent evidence suggests that adverse drug reactions are major causes of death and hospital admission in Europe and the United States. The reasons for these conditions are represented by environmental/non‐genetic and genetic factors responsible for the great inter‐patient variability in drugs metabolism, disposition and therapeutic targets. Over the years several genetic settings have been linked, using pharmacogenetic approaches, to the effects and toxicity of many agents used in clinical nephrology. However, these strategies, analysing single gene or candidate pathways, do not represent the gold standard, being the overall pharmacological effects of medications and not typically monogenic traits. Therefore, to identify multi‐genetic influence on drug response, researchers and clinicians from different fields of medicine and pharmacology have started to perform pharmacogenomic studies employing innovative whole genomic high‐throughput technologies. However, to date, only few pharmacogenomics reports have been published in nephrology underlying the need to enhance the number of projects and to increase the research budget for this important research field. In the future we would expect that, applying the knowledge about an individual's inherited response to drugs, nephrologists will be able to prescribe medications based on each person's genetic make‐up, to monitor carefully the efficacy/toxicity of a given drug and to modify the dosage or number of medications to obtain predefined clinical outcomes.     

姜黄素诱导永生化人HaCaT细胞凋亡

目的 探讨姜黄素对人永生化上皮细胞凋亡的诱导作用.方法 应用细胞计数、流式细胞术、琼脂糖凝胶电泳、Hoechst33258染色、苏木素-伊红(HE)染色和透射电镜检测经姜黄素诱导处理后人永生化上皮HaCaT细胞的凋亡.结果经7.5mg/L姜黄素诱导处理后,人永生化上皮HaCaT细胞的增殖活动受到明显的抑制,细胞生长抑制率达83.03%;细胞周期检测出现亚二倍体(亚G1期)细胞峰值,细胞凋亡率达13.1%,并发生G2/M期阻滞;琼脂糖凝胶电泳出现细胞凋亡典型的DNA"梯状"条带;细胞核经Hoechst33258染色出现浓染致密的固缩形态和颗粒状荧光;光镜和电镜观察结果显示,姜黄素处理组细胞体积缩小,细胞核固缩,染色质凝聚,线粒体肿胀,有凋亡小体形成等显著的凋亡特征.结论姜黄素对人永生化上皮HaCaT细胞凋亡有显著的诱导作用,从而为进一步研究表皮细胞衰老、凋亡机理提供了重要基础和研究依据.     

Targets and dimensions of social comparison among people with spinal cord injury and other health problems

The present research examined comparison targets and comparison dimensions among two Spanish samples of individuals facing serious illnesses and diseases. In Study 1, 90 older patients (mean age 66.36) with various age‐related diseases, particularly cardiovascular diseases and diabetes, indicated that they compared themselves most often with others with the same disease, next with others with another disease and least with people without health problems. They compared themselves more often on their mental state, symptoms and physical activities than on their social activities. Social comparison orientation (SCO) as an individual difference characteristic was associated with more frequent comparisons with particularly similar targets, and with more frequent comparisons of one's symptoms and physical activities. Neuroticism was correlated only with more comparisons of one's symptoms. Study 2 was conducted in a sample of 70 relatively young patients (mean age 43.97) with spinal cord injury (SCI). Overall, they compared themselves more often with others than the participants in Study 1, and they compared themselves to a similar extent with people with SCI as with people with another disease and with people without health problems. While they felt on average better off than people with other diseases and other people with SCI, people with SCI felt on average worse off than people without health problems. They compared themselves more often on physical activities than on any other dimension. Higher levels of stress and uncertainty were associated with more frequent comparisons with people without SCI, and with more frequent comparisons of one's mental state, one's symptoms and one's future perspectives. The discussion focuses on the theoretical relevance of the results for social comparison theory, and on the practical relevance of the findings for interventions.