Obesity is prevalent and linked to cognitive impairment via hippocampal atrophy and insulin resistance. Here, we investigated whether the primary catechin of green tea, epigallocatechin‑3‑gallate (EGCG), could attenuate this neuropathology. Epidemiological analysis of UK Biobank adults with obesity provided an initial clue, showing a positive linear trend between green tea intake and hippocampal volume (p = 0.07). To elucidate the underlying mechanisms, we administered a human‑achievable dose of EGCG (50 mg/kg) to high‑fat diet-fed mice. EGCG treatment significantly reduced body weight and inflammatory signaling while improving insulin sensitivity, attenuating hippocampal atrophy, and mitigating cognitive deficits. Mechanistically, EGCG rescued synaptic structural integrity by suppressing the pro-inflammatory JNK pathway, restoring hippocampal insulin signaling (IRS1/Akt), and stimulating neuronal autophagy through the AMPK/mTOR/ULK1 axis. Together, these data provide translational evidence that EGCG counteracts obesity-linked neurodegeneration by linking metabolic health to hippocampal integrity through the inflammation-insulin-autophagy axis, motivating dietary trials to mitigate cognitive impairment.

BACKGROUND:Caloric restriction (CR) is reported to promote longevity and improve metabolism in different species, such as rodents and flies. However, limited studies have examined the effects of CR on obesity-associated psychiatric disorders and the underlying mechanisms. OBJECTIVES:This study aimed to investigate the effects of CR on obesity-associated anxiety-like behavior in mice fed on a high-fat diet (HFD) and elucidate the underlying mechanisms. METHODS:Male C57BL/6 mice (n = 24) were randomized into the standard diet group and the HFD group (fed on an HFD for 8 wk to induce obesity). The mice in the HFD group (n = 16) were further randomized into the following 2 groups for an additional 4-wk dietary intervention: the HFD group and calorie-restricted HFD (HFCR) group (received 70% of the mean daily food intake in the previous 3 d). Mouse body weight, anxiety-like behaviors, peripheral insulin sensitivity, central insulin signaling, and fecal microbiota were assessed. RESULTS:HFCR effectively mitigated HFD-induced weight gain and insulin resistance, demonstrating significant reductions in final body weight (-28.0%), glucose area under the curve (-30.7%), and homeostasis model assessment of insulin resistance index (-58.8%) compared with the HFD group (P < 0.01). HFCR also significantly reduced anxiety-like behaviors in open-field and elevated plus maze tests (P < 0.05). Mechanistically, HFCR suppressed neuroinflammatory pathways by inhibiting NF-κB activation and c-Jun N-terminal kinase phosphorylation, while concurrently improving central insulin sensitivity via the insulin receptor substrate 1/Akt pathway (P < 0.05). Furthermore, HFCR remodeled the gut microbiota profile and markedly increased fecal short-chain fatty acid concentrations, with acetic acid and propionic acid levels rising by 107.7% and 57.0%, respectively (P < 0.01). CONCLUSIONS:In summary, our data indicate that CR, even without a change in dietary composition, could attenuate HFD-induced anxiety symptoms by modulating the gut microbiota, suppressing neuroinflammation, and regulating the brain insulin signaling pathway in adult male obese mice.

6-Hydroxydopamine (6-OHDA) is a classic neurotoxin that has been widely used in Parkinson’s disease research. 6-OHDA can increase intracellular reactive oxygen species (ROS) and can cause cell damage, which can be attenuated with (-)-Epigallocatechin-3-gallate (EGCG) treatment. However, the mechanism by which EGCG alters the 6-OHDA toxicity remains unclear; In this study, we found 6-OHDA (25 μM) alone increased intracellular ROS concentration in N27 cells, which was attenuated by pretreating with EGCG (100 μM). We evaluated the intracellular oxidative damage by determining the level of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content. 6-OHDA significantly increased TBARS by 82.7% ( P < .05) and protein carbonyl content by 47.8 ( P < .05), compared to the control. Pretreatment of EGCG decreased TBARS and protein carbonyls by 36.4% ( P < .001) and 27.7% ( P < .05), respectively, compared to 6-OHDA alone treatment. Antioxidant effect was tested with E2-related factor 2 (Nrf2), heme oxygenase-1(HO-1) and peroxisome-proliferator activator receptor γ (PPARγ) expression. 6-OHDA increased Nrf2 expression by 69.6% ( P < .001), HO-1 by 173.3% ( P < .001), and PPARγ by 122.7% ( P < .001), compared with untreatment. EGCG pretreatment stabilized these alterations induced by 6-OHDA. Our results suggested that the neurotoxicity of 6-OHDA in N27 cells was associated with ROS pathway, whereas pretreatment of EGCG suppressed the ROS generation and deactivated the Nrf2/HO-1 and PPARγ expression.

Chronic pain has emerged as a significant public health issue, seriously affecting patients' quality of life and psychological well-being, with a lack of effective pharmacological treatments. Numerous studies have indicated that macrophages play a crucial role in inflammatory pain, and targeting neuro-immune interactions for drug development may represent a promising direction for pain management. Chilobrachys jingzhao (C. jingzhao) is used as a folk medicine of the Li nationality with the efficacy of eliminating swelling, detoxicating, and relieving pain, and the related products are widely used in the market. However, the chemical constituents of C. jingzhao have not been reported, and the pharmacodynamic substance and the precise functional mechanism are unrevealed. Here we isolated a cyclic dipeptide, cyclo(L-Pro-L-Trp) (CPT) from C. jingzhao for the first time. CPT remarkably alleviated formalin-induced inflammatory pain and significantly inhibited inflammatory responses. In vivo, CPT attenuated neutrophil infiltration and plantar tissue edema and suppressed the mRNA expression of pro-inflammatory molecules. In vitro, CPT suppressed inflammation triggered by lipopolysaccharide (LPS) in both RAW 264.7 and iBMDM cells, reducing expressions of inducible nitric oxide synthase (iNOS), superoxide, and pro-inflammatory molecules. A mechanistic study revealed that CPT exerted an anti-inflammatory activity by blocking the mitogen-activated protein kinases (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways, as well as alleviating the ubiquitination of tumor necrosis factor receptor-associated factor 6 (TRAF6). Our results elucidated the pharmacodynamic material basis of C. jingzhao, and CPT can be a promising lead for alleviating inflammation and inflammatory pain.

Parkinson’s disease (PD) is a common neurodegenerative disorder with no cure. Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity. The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A. membranaceus (TFA) and their protective mechanisms. TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in the mouse model of Parkinsonism, by improving behavior performance in the gait analysis and pole test, and inhibiting the decline of tyrosine hydroxylase (TH) positive neurons and TH protein expression in substantia nigra of mice. TFA also prevented 1-methyl-4-phenylpyridinium (MPP+) induced neurotoxicity in SH-SY5Y cells, by increasing GSH and GSH/GSSG ratio, and reducing reactive oxygen species. In addition, the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+ induced downregulation of SLC7A11 and glutathione peroxidase 4 (GPX-4). In conclusion, we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+ induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis, suggesting the use of TFA as a possible food supplement in the prevention of PD.

IntroductionThe role of individual nutrients including vitamins and minerals in cognitive function gained increasing attention in recent years. With regard to the association between dietary minerals and cognitive function, the results of human studies are inconclusive. The objective of this study was to explore the association between mineral intake and cognitive function using the data from Shanghai Health and Nutrition Survey (SHNS) in 2018.MethodsIn total, 835 adults were included in a crosssectional study, and completed a three-day dietary record to estimate their average daily intake of minerals. Mini-Mental State Examination (MMSE) was used for the assessment of cognitive function, and logistic regression analyses were performed on participants to examine the association between dietary mineral intake and cognitive performance. The participants were divided into tertiles according to their mineral intake.ResultsParticipants in the second and third tertile of the dietary copper intake had lower rates of low MMSE scores compared to those in the lowest tertile. We found the adjusted OR and 95%CI values were 0.44 (0.21–0.89) and 0.40 (0.16–0.94), respectively. Participants in the second tertile of dietary magnesium intake showed a trend of lower rates of low MMSE score compared to those in the lowest tertile (p = 0.06). The adjusted OR and 95%CI values were 0.35 (0.16–0.72). No significant association were observed between any of the other minerals including iron, zinc, selenium and manganese and cognitive function.DiscussionOur findings suggest that dietary intake of copper and magnesium may have a protective effect on cognitive performance in elderly over 60 years old. To prevent cognitive decline, elderly should get recommended amounts of copper and magnesium from diet or supplements.

Parkinson’s disease (PD) and Alzheimer’s disease (AD) are two of the most common neurodegenerative disorders, characterized by the progressive loss of neurons. These two diseases share common molecular mechanisms, including brain iron accumulation, oxidative stress, protein aggregation, and neuroinflammation. There is no effective therapy to halt the progression of PD or AD. However, accumulating evidence suggests that the consumption of phytochemicals may delay the onset or slow down the progression of neurodegeneration. Phytic acid, is a dihydrogenphosphate ester of inositol. It is stored as phosphorus in plant seeds like cereals, legumes, and nuts. Traditionally, IP6 has been considered an anti-nutritional factor due to its mineral chelating properties, which can reduce mineral absorption. Recent research also indicates its potential benefits for neurodegenerative disorders. In this review, we will summarize the sources and bioavailability of IP6 and its potential neuroprotective roles in preventing or slowing down the progression of PD and AD.

上海中医药大学食品卫生与营养学是一门复合型和应用型专业.本研究以“膳食加工与烹饪”实践课程为例,在胜任力模型支撑下,以意识维度、知识维度和技能维度为出发点,设计和实施课程实践教学策略,旨在提升学生的实践能力,为营养事业的发展输送优质和具有中医特色的人才.

Cinnamon procyanidin oligomers (CPOs) are water-soluble components extracted from cinnamon. This study aims to explore the neuroprotection of B-type CPO (CPO-B) against 1-methyl-4-phenylpyridinium (MPP+)-mediated cytotoxicity and the molecular mechanisms underlying its protection. The results demonstrated that CPO-B showed protection by increasing cell viability, attenuating an intracellular level of reactive oxygen species, downregulating cleaved caspase-3 expression, and upregulating the Bcl-2/Bax ratio. Moreover, CPO-B completely blocked the dephosphorylation of extracellular, signal-regulated kinase 1 and 2 (Erk1/2) caused by MPP+. Treatment with an Erk1/2 inhibitor, SCH772984, significantly abolished the neuroprotection of CPO-B against MPP+. Taken together, we demonstrate that CPO-B from cinnamon bark provided protection against MPP+ in cultured SH-SY5Y cells, and the potential mechanisms may be attributed to its ability to modulate the dysregulation between pro-apoptotic and anti-apoptotic proteins through the Erk1/2 signaling pathway. Our findings suggest that the addition of cinnamon to food or supplements might benefit patients with PD.

BACKGROUND:Parkinson's disease (PD) is a common neurodegenerative disorder. Cinnamon procyanidin oligomers (CPOs) are flavonoids with many claimed health benefits. OBJECTIVE:This study aimed to elucidate the neuroprotection of A-type CPOs (CPO-A) and the underlying mechanisms in cultured cell and animal models of PD. METHODS:Thirty male mice (C57BL/6, 9-wk old) were assigned to 3 groups (n = 10), and were given daily gavage of saline [control and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) groups] or CPO-A (150 mg/kg, CPO-A group) during days 1-15 and daily intraperitoneal injections of saline (control group) or MPTP (20 mg/kg; MPTP and MPTP + CPO-A groups) during days 11-15. After the motor behavior test, all mice were killed on day 16 to collect the substantia nigra (SN) for assaying the neuroprotective effects of CPO-A. SH-SY5Y cells were treated with 12.5 μM CPO-A for 2 h or 3 activators of stress-related kinases (5-25 μM) for 12-48 h followed by 1 mM 1-methyl-4-phenylpyridinium (MPP+) for assays of viability, morphology, and stress status. RESULTS:Compared with the control, the MPTP treatment decreased (P < 0.05) locomotor activity by 21%, and tyrosine hydroxylase (TH) positive neurons by 55% and Th mRNA concentration by 51% in the SN. The CPO-A treatment attenuated or restored (P < 0.05) these changes and inhibited (P < 0.05) the MPTP-induced activation of P38 mitogen-activated protein kinase (P38MAPK) and P53, along with the downstream expression of BCL-2 associated X protein (BAX) in the SN. In SH-SY5Y cells, the CPO-A treatment blocked (P < 0.01) the MPP+-induced accumulation of intracellular reactive oxygen species and neurotoxicity. However, this protection was abolished (P < 0.05) by activators of the P38MAPK/P53/BAX pathway. CONCLUSION:CPO-A protected against MPP+-induced cytotoxicity in SH-SY5Y cells and MPTP-induced neurotoxicity in mice by regulating the P38MAPK/P53/BAX signaling. Our findings reveal a novel role and mechanism of a food flavonoid CPO-A in preventing neurodegeneration.

Oxidative stress, iron dysregulation, and inflammation have been implicated in the pathogenesis of Parkinson's disease (PD). Considering the entwined relationship among these factors, epigallocatechin gallate (EGCG) may be a good candidate for PD treatment due to its protective effects against those factors. The objective of this study is to determine whether EGCG protects N27 dopaminergic neuronal cells from H2O2 - and TNFα- induced neurotoxicity. Seven treatments were included: control, H2O2, TNFα, FeSO4, H2O2 + EGCG, TNFα + EGCG, FeSO4 + EGCG. Cells were pretreated with 10 μM EGCG, followed by 50 μM H2O2, 30 ng/ml TNFα or 50 μM FeSO4. Neuroprotective effects of EGCG were assessed by cell viability assay, caspase-3 activity, intracellular reactive oxygen species (ROS) generation, and iron related protein expressions. Caspase-3 activity was increased to 2.8 fold (P < 0.001) and 1.5 fold (P < 0.01) with H2O2 and TNFα treatment; However, EGCG pretreatment significantly decreased the caspase activity by 50.2% (P < 0.001) and 30.1% (P < 0.05). Similarly, cell viability was reduced to 69.2% (P < 0.01) and 89% (P < 0.01) by H2O2 and TNFα, which was partially blocked by EGCG pretreatment. Also, EGCG significantly (P < 0.001) protected against H2O2- induced ROS in a time dependent manner. In addition, both H2O2 and TNFα significantly (P < 0.05) upregulated hepcidin expression and marginally reduced ferroportin (Fpn) expression unlike iron treatment alone. Collectively, our results show that EGCG protects against both TNFα- and H2O2- induced neuronal apoptosis. The observed neuroprotection may be through the inhibition of oxidative stress and inflammation which is possibly mediated mainly by hepcidin and partially by Fpn.

医学英语,作为公共英语的扩展和延伸,是针对医学院校学生开设的专业领域的英语教学.它与中医英语一起,组成了中医药院校专门用途英语(ESP)不可分割的一部分,其目的是让医学生在公共英语的基础上掌握医学领域的英语听说读写译能力[1].随着我国大学英语教学的不断发展和教学改革,越来越多的高等中医药院校意识到医学英语在中医药人才培养过程中的重要性.中医药院校学生不仅需要掌握扎实的中医医学知识,还需要掌握现代医学知识和技能,了解世界最新的医学进展.很多医学教育工作者指出想要培养高素质医学人才,中医药院校必须强化和发展医学英语教学,使医学生能利用英语这一语言工具获取专业信息,拓展专业能力,把握最新医疗进展,进行教学医疗科研等相关活动[2].

Background: Parkinson disease (PD) is a neurodegenerative disorder that has been associated with many factors, including oxidative stress, inflammation, and iron accumulation. The antioxidant, anti-inflammatory, and iron-chelating properties of epigallocatechin gallate (EGCG), a major polyphenol in green tea, may offer protection against PD.Objective: We sought to determine the neurorescue effects of EGCG and the role of iron in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD.Methods: We evaluated the neurorescue effect of EGCG (25 mg/kg, 7 d, oral administration) against MPTP-induced (20 mg/kg, 3 d, intraperitoneal injection) neurodegeneration in C57 male black mice. Thirty mice weighing ∼25 g were divided into 3 groups: control, MPTP, and MPTP + EGCG. The neurorescue effect of EGCG was assessed with the use of motor behavior tests, neurotransmitter analysis, oxidative stress indicators, and iron-related protein expression.Results: Compared with the control group, MPTP treatment shortened the mice's latency to fall from the rotarod by 16% (P < 0.05), decreased the striatal dopamine concentration by 58% (P < 0.001) and dihydroxyphenylacetic acid by 35% (P < 0.05), and increased serum protein carbonyls by 71% (P = 0.07). However, EGCG rescued MPTP-induced neurotoxicity by increasing the rotational latency by 17% (P < 0.05) to a value similar to the control group. Striatal dopamine concentrations were 40% higher in the MPTP + EGCG group than in the MPTP group (P < 0.05), but the values were significantly lower than in the control group. Compared with the MPTP and control groups, mice in the MPTP + EGCG group had higher substantia nigra ferroportin expression (44% and 35%, respectively) (P < 0.05) but not hepcidin and divalent metal transporter 1 expression.Conclusion: Overall, our study demonstrated that EGCG regulated the iron-export protein ferroportin in substantia nigra, reduced oxidative stress, and exerted a neurorescue effect against MPTP-induced functional and neurochemical deficits in mice.

Objective To investigate the students' perception and effectiveness of the flipped class model in bilingual education in special population nutrition class.Method Two classes of Shanghai University of Traditional Chinese Medicine were exposed to either the flipped class model or the traditional class model.In the flipped class model,the students were provided a wealth of teaching resources such as short videos before class.In addition,a series of pedagogical approaches were used to develop the students' cognitive ability.The questionnaire survey and class quiz were employed to evaluate the students' perception and effectiveness of the flipped class model.Results The students in the experimental group have significant higher scores in professional vocabulary section [(23.10 ± 0.71) vs.(21.10 ± 0.67)],listening and speaking section [(21.20 ± 0.78) vs.(19.00 ± 0.74)],essay questions section [(37.80 ± 0.96) vs.(34.40 ± 1.15)],and total test scores [(82.20 ± 1.50) vs.(74.50 ± 1.52)] than did the students in the control group.In addition,the flipped class model ignites the students' learning interest,reduces the learning anxiety,and develops their learning autonomy.Conclusion The flipped class model is a highly effective means that promotes the student centered active learning.This study provides reference for implementation of the flipped class model in Chinese medical bilingual education.

Background . Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD). However, the precise mechanism underlying abnormal iron accumulation in PD is not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator in both systemic and cellular iron homeostasis. Objective . We investigated the role of hepcidin in 6-hydroxydopamine (6-OHDA) induced apoptosis in a cell culture model of PD. Methods . We downregulated hepcidin using siRNA interference in N27 dopaminergic neuronal cells and made a comparison with control siRNA transfected cells to investigate the role of hepcidin in 6-OHDA induced neurodegeneration. Results . Hepcidin knockdown (32.3%,P<0.0001) upregulated ferroportin 1 expression and significantly (P<0.05) decreased intracellular iron by 25%. Hepcidin knockdown also reduced 6-OHDA induced caspase-3 activity by 42% (P<0.05) and DNA fragmentation by 29% (P=0.086) and increased cell viability by 22% (P<0.05). In addition, hepcidin knockdown significantly attenuated 6-OHDA induced protein carbonyls by 52% (P<0.05) and intracellular iron by 28% (P<0.01), indicating the role of hepcidin in oxidative stress. Conclusions . Our results demonstrate that hepcidin knockdown protected N27 cells from 6-OHDA induced apoptosis and that hepcidin plays a major role in reducing cellular iron burden and oxidative damage by possibly regulating cellular iron export mediated by ferroportin 1.

Parkinson's disease (PD) is a neurodegenerative disorder that has been associated with oxidative stress, inflammation, and iron accumulation. (−)‐Epigallocatechin gallate (EGCG) is the major polyphenol in green tea that has antioxidant, anti‐inflammatory and iron chelating properties. In the present study, we determined the neurorescue effect of EGCG (25mg/kg, oral administration) against 1‐methyl‐4‐phenyl‐1,2,3,6‐ tetrahydropyridine (MPTP, 20mg/kg, IP) induced neurodegeneration. The neurorescue effect of EGCG was assessed by motor behavior tests, neurotransmitter analysis, oxidative stress indicators, and iron related protein expressions. MPTP treatment shortened mice's latency to fall from the rotating rod by 16.3% (P<0.05), decreased striatal dopamine by 58.4% (P<0.001) and DOPAC concentrations by 35.4% (P<0.05), and increased serum protein carbonyls by 67.5% (p<0.05). However, EGCG post treatment (daily for 7d after MPTP treatment) significantly rescued MPTP induced neurotoxicity by increasing the rotational latency by 18% (P<0.05), and increasing dopamine by 41.5% (P<0.05). However, increase in DOPAC and reduction in serum protein carbonyl concentrations was marginally different but not significant. In addition, western blot shows neither MPTP nor EGCCG post treatment affects divalent metal transporter 1(DMT 1) expression. However, EGCG slightly down regulated hepcidin expression and significantly upregulated ferroportin expression in the substantia nigra, indicating that the protection of EGCG is associated with regulation of iron efflux but not influx. Collectively, our results show that EGCG rescued dopaminergic neurons after MPTP treatment and the protective mechanism might be associated with alleviating nigral iron burden and reducing oxidative stress.

Several factors including oxidative stress, iron dysregulation, and inflammation have been implicated in the pathogenesis of Parkinson's disease (PD). Considering the entwined relationship among these factors, (−)‐Epigallocatechin gallate (EGCG) may be a good candidate for PD treatment due to its antioxidant, iron chelating and anti‐inflammatory properties. The objective of this study is to determine whether EGCG protects immortalized rat mesencephalic cells from hydrogen peroxide (H2O2) and TNF alpha induced apoptosis. We chose 50µM H2O2 and 30ng/ml TNF alpha in experiments based on our preliminary data. Our results show that caspase‐3 activity was increased to 2.8 fold (P<0.001) and 1.5 fold (P<0.01) with H2O2 and TNF alpha treatment; however, EGCG pretreatment significantly decreased the caspase activity by 50% (P<0.001) and 31% (P<0.05). Cell viability was reduced to 69.16% (P<0.01) and 89% (P<0.01) by H2O2 and TNF alpha, which is almost completely blocked by EGCG pretreatment. In addition, 10µM EGCG pretreatment also significantly protected against H2O2 induced reactive oxygen species in a time dependent manner. TNF alpha or ferrous iron up‐regulated hepcidin and down‐regulated ferroportin expression, and EGCG pretreatment reversed this effect, indicating EGCG can normalize iron overload by altering iron influx and efflux mechanisms. Collectively, our results show that EGCG protects against both TNF alpha and H2O2 induced neuronal apoptosis. The observed neuroprotection may be through the inhibition of oxidative stress and inflammation which is possibly mediated by iron regulated proteins hepcidin and ferroportin.

Low iron bioavailability (IBA) is a major contributor of iron deficiency anemia, a most prevalent nutritional deficiency around the world. In vitro IBA is commonly measured using simulated gastrointestinal digestion, caco‐2 cell uptake and followed by ferritin response measurement. This method is cumbersome since it takes more than 24 hours and needs an expensive kit to measure ferritin concentrations. Hence, our objective was to develop a high throughput and cost effective method to assess IBA in large number of samples in a short period of time. In this new method, the quenching of calcein fluorescence in a caco‐2 cell model by food iron following in vitro digestion is used as an index of IBA. The meals we used were similar to the ones that were used in human studies. IBA assessed in this method was compared with published human absorption data and measured ferritin responses. Similar to human absorption data, IBA was enhanced by ascorbic acid, and was reduced by bran, phytate, and tea. A high correlation was found between published human absorption data and the IBA we tested (r=0.90; p=0.04). Our data was also highly correlated with the data obtained using traditional ferritin method (r=0.92; p<0.01). In conclusion, our method does not only reliably predict human iron absorption, but also is a more cost effective and faster one compared to the widely used ferritin method. However, future studies are needed for more comparisons with human studies.

Elevated brain iron levels have been implicated in the pathogenesis of Parkinson’s disease (PD), however the underlying mechanisms are not clear. Hepcidin, a hormone primarily produced by hepatocytes, acts as a key regulator of cellular iron homeostasis. To investigate hepcidin’s role in 6‐hydroxydopamine (6‐OHDA) induced neurodegeneration, we down regulated hepcidin (32.3% P<0.0001) using siRNA interference technique in N27 dopaminergic neuronal cells and compared with a negative control. Our results show that hepcidin knockdown upregulated ferroportin expression and decreased intracellular free iron as measured with calcein fluorescence quenching method, by 35% and 24% in control and 6‐OHDA treatments. In addition, hepcidin knockdown protected 6‐OHDA induced apoptosis by attenuating oxidative damage. 6‐OHDA increased protein carbonyls by 146.4% (p<0.05), caspase‐3 activity by 154.6% (p<0.001) and DNA fragmentation by 54.3% (p<0.01), whereas hepcidin knockdown almost completely blocked the 6‐OHDA induced protein carbonyls, caspase‐3 activation and DNA fragmentation. Collectively, our results show that hepcidin plays a key role in reducing cellular iron burden and oxidative damage by possibly regulating iron export mediated by ferroprotin. This hepcidin dependent iron regulation in dopaminergic degeneration may provide a novel therapeutic strategy for slowing down the progression of PD.

OBJECTIVE:To investigate the chemopreventive effect and mechanisms of epigallocatechin-3-gallate (EGCG) and folic acid on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced gastrointestinal cancer in rats, and to investigate and compare the combinatorial effects of EGCG and folic acid on the chemoprevention of gastrointestinal carcinogenesis.METHODS:A total of 159 healthy male Wistar rats were randomly divided into seven groups to have the MNNG in drink (group M), MNNG in drink and EGCG in the feed (group ME), MNNG in drink and folic acid in the feed (group MF), MNNG in drink and EGCG + folic acid in the feed (group MEF), EGCG in the feed (group E), folic acid in the feed (group F) or normal feed (group C), respectively. At 44 weeks, all the rats were killed and assessed for the presence of gastrointestinal tumor. The occurrence of cancer was evaluated by histology. Ki-67 in cancerous tissues and in situ apoptosis were determined by immunohistochemical staining or terminal deoxyribonucleotide transferase-mediated nick-end labeling (TUNEL) assay, respectively.RESULTS:The experiment was completed in 157 rats (98.74%). As compared with group M, the tumor incidence of group MEF decreased significantly (P = 0.011). Ki-67 expression in cancerous tissues of group ME and MEF also decreased significantly (P = 0.038, P = 0.009), while apoptosis of group ME, MF and MEF increased significantly (P = 0.000, P = 0.003, P = 0.000).CONCLUSION:EGCG combined with folic acid has an obvious chemopreventive effect on gastrointestinal carcinogenesis induced by MNNG in rats.