The Characteristics of the Influenza Virus Epidemic Around the SARS-CoV-2 Epidemic Period in the Pudong New Area of Shanghai.

OBJECTIVES: The concurrent impact of COVID-19 and influenza on disease burden is a topic of great concern. This discussion delves into the epidemiological characteristics of seasonal influenza activity in Shanghai within the context of the SARS-CoV-2 epidemic. METHODS: From 2017 to 2023, a total of 11,081 patients having influenza-like illness (ILI) were included in this study for influenza virus detection. Reverse transcription polymerase chain reaction (RT-PCR) assays were conducted according to standardised protocols to identify the types and subtypes of influenza viruses. The positivity rate of the influenza virus among the sampled ILI cases served as a surrogate measure for estimating various influenza seasonal characteristics, such as periodicity, duration, peak occurrences, and the prevalent subtypes or lineages. Epidemiological aspects across different years and age groups were subjected to comprehensive analysis. For categorical variables, the Chi-square test or Fisher's exact test was employed, as deemed appropriate. RESULTS: A total of 1553 (14.0%) tested positive for influenza virus pathogens. The highest positivity rate for influenza was observed in adults aged 25-59 years (18.8%), while the lowest rate was recorded in children under 5 years (3.8%). The influenza circulation patterns in Shanghai were characterised: (1) 2 years exhibited semiannual periodicity (2017-2018, 2022-2023); (2) 3 years displayed annual periodicity (2018-2019, 2019-2020, and 2021-2022); and (3) during 2020-2021, epidemic periodicities of seasonal influenza viruses disappeared. In terms of influenza subtypes, four subtypes were identified during 2017-2018. In 2018-2019 and 2019-2020, A/H3N2, A/H1N1, and B/Victoria were circulating. Notably, one case of B/Victoria was detected in 2020-2021. The epidemic period of 2021-2022 was attributed to B/Victoria, and during 2022-2023, the influenza A virus was the dominant circulating strain. CONCLUSIONS: The seasonal epidemic period and the predominant subtype/lineage of influenza viruses around the SARS-CoV-2 epidemic period in Shanghai city are complex. This underscores the necessity for vigilant influenza control strategies amidst the backdrop of other respiratory virus pandemics.

Spatial timing of circulating seasonal influenza A and B viruses in China from 2014 to 2018.

Major outbreaks of influenza virus occurred in China in 2017-2018. To describe the pattern of influenza circulation and timing of seasonal epidemics, we analyzed data from influenza-like illness (ILI) specimens on surveillance wards of sentinel hospitals during 2014-2018. Among 1,890,084 ILI cases, 324,211 (17.2%) tested positive for influenza. Influenza A virus (particularly A/H3N2), which circulates annually, was detected in 62% of cases, compared with influenza B virus in 38% of cases. The detection rate of A/H1N1, A/H3N2, B/Victoria, and B/Yamagata viruses were 3.56%, 7.07%, 2.08%, and 3.45%, respectively. Influenza prevalence was generally stable over the four years analyzed, but obvious outbreaks occurred in 2015-2016 (17.28%) and 2017-2018 (22.67%), with B/Victoria and B/Yamagata contributing to these outbreaks, respectively. In the south, a characteristic peak in infections was detected in the summer (week 23-38), which was not detected in the north. Influenza B was found high frequency in school-age children (5-14 years) with 4.78% of B/Victoria and 6.76% of B/Yamagata. Therefore, the epidemiological characteristics of seasonal influenza were complex in China during 2014-2018, presenting distinctions in region, season, and susceptible population. These findings underline the importance of enhancing year-round influenza surveillance and provide a reference for the timing and variety of influenza vaccination.

Ratanasampil is more effective than flunarizine in relieving migraine.

Aims: Migraine is a common neurological disorder with high incidence in population. This study aimed to investigate the therapeutic efficacy of Tibetan medicine Ratanasampil (RNSP) and to identify the serum biomarkers for diagnosis and response assessment.Materials and methods: We prospectively recruited 108 migraine patients living at high altitude (2,260 m), including 40 patients for RNSP group, 40 patients for flunarizine (FLZ) group, and 28 patients for placebo group. Serum levels of 5-hydroxytryptamine (5-HT), brain-derived neurotrophic factor (BDNF), calcitonin gene related peptide (CGRP), nerve growth factor (NGF) and ß-endorphin (ß-EP) before and after therapy were measured.Results: In comparison with placebo, both FLZ and RNSP significantly reduced the migraine days, HIT-6 score and verbal rating scale, headache intensity, duration, accompanying symptoms and headache score in four and eight weeks treatment. RNSP showed no significant difference to FLZ in the above parameters after four weeks treatment, but showed significantly better relief after eight weeks treatment. The overall effective rate of RNSP (92.5%) was also significantly higher than FLZ (74.4%, p < 0.05), mainly due to significantly higher ratio of patients with full recovery. The serum levels of biomarkers, including 5-HT, BDNF, NGF and ß-EP, significantly elevated after eight weeks of treatment with RNSP, whereas the level of CGRP significantly decreased. The serum level of 5-HT exhibited significantly bigger percentage changes than other markers.Conclusion: In conclusion, RNSP was more effective than FLZ in relieving migraine after eight weeks continuous treatment. Serum 5-HT, BDNF, CGRP, NGF and ß-EP were effective markers reflecting the response to RNSP and FLZ therapy.

Structures and mechanisms of the Arabidopsis auxin transporter PIN3.

The PIN-FORMED (PIN) protein family of auxin transporters mediates polar auxin transport and has crucial roles in plant growth and development1,2. Here we present cryo-electron microscopy structures of PIN3 from Arabidopsis thaliana in the apo state and in complex with its substrate indole-3-acetic acid and the inhibitor N-1-naphthylphthalamic acid (NPA). A. thaliana PIN3 exists as a homodimer, and its transmembrane helices 1, 2 and 7 in the scaffold domain are involved in dimerization. The dimeric PIN3 forms a large, joint extracellular-facing cavity at the dimer interface while each subunit adopts an inward-facing conformation. The structural and functional analyses, along with computational studies, reveal the structural basis for the recognition of indole-3-acetic acid and NPA and elucidate the molecular mechanism of NPA inhibition on PIN-mediated auxin transport. The PIN3 structures support an elevator-like model for the transport of auxin, whereby the transport domains undergo up-down rigid-body motions and the dimerized scaffold domains remain static.

Comprehensive methylation profile of CSF cfDNA revealed pathogenesis and diagnostic markers for early-onset Parkinson's disease.

Background: Early-onset Parkinson's disease (EOPD) is one uncommon Parkinson's disease subtype with characteristic clinicopathological features. The full epigenomic profile of EOPD is largely unknown. Methods: We performed the first study to investigate the EOPD full methylation profile of cerebrospinal fluid (CSF) cell-free DNA (cfDNA) from 26 EOPD patients and 10 control patients. Results: 2220 differentially methylated genes were identified in EOPD. Hypermethylation far outweighed hypomethylation in gene numbers. Clustering and enrichment analyses identified aberrant neuronal function and immune response. Weighted correlation network analysis demonstrated significant correlation between methylation signatures and clock drawing test (CDT), mini-mental state examination (MMSE), education, working status, alcohol drinking history and Hamilton anxiety scale (HAMA). Several key networking genes in EOPD aberrant methylation were also identified. Conclusions: The methylation profile and signatures of CSF cfDNA were revealed for the first time in EOPD. Aberrant methylation signatures were correlated with education, working status, alcohol drinking history, CDT, MMSE and HAMA.

Lay abstract Early-onset Parkinson's disease (EOPD), a progressive disease of the nervous system marked by tremor, muscular rigidity and slow and imprecise movement, is generally found in people under the age of 40 years. In this study, we performed methylation test on cerebrospinal fluid (CSF). The test showed that specific CSF methylation profiles could be used to help EOPD diagnosis. A subset of differentially methylated genes were also identified, which could also be used as markers for EOPD diagnosis. In future, we will validate the methylation test in blood and try to find blood-based diagnostic markers to facilitate the diagnosis of EOPD by a single blood draw.

Transmission of Severe Acute Respiratory Syndrome Coronavirus 2 to Close Contacts, China, January-February 2020.

We estimated the symptomatic, PCR-confirmed secondary attack rate (SAR) for 2,382 close contacts of 476 symptomatic persons with coronavirus disease in Yichang, Hubei Province, China, identified during January 23-February 25, 2020. The SAR among all close contacts was 6.5%; among close contacts who lived with an index case-patient, the SAR was 10.8%; among close-contact spouses of index case-patients, the SAR was 15.9%. The SAR varied by close contact age, from 3.0% for those <18 years of age to 12.5% for those >60 years of age. Multilevel logistic regression showed that factors significantly associated with increased SAR were living together, being a spouse, and being >60 years of age. Multilevel regression did not support SAR differing significantly by whether the most recent contact occurred before or after the index case-patient's onset of illness (p = 0.66). The relatively high SAR for coronavirus disease suggests relatively high virus transmissibility.

Depression and Related Factors in Patients with Parkinson's Disease at High Altitude.

PURPOSE: Depression seems to aggravate progression of Parkinson's disease (PD). Hypoxia stress may be one of the pathogenic factors leading to PD. We investigated the characteristics of PD and factors related to Parkinson's disease depression (PDD) at high altitude (mean altitude ≥2300 m). PATIENTS AND METHODS: Totally 221 PD patients of three different nationalities (Han, Hui, and Tibetan) were recruited in a high-altitude hospital. Depression was present in 55.6% of them. Patient data were examined, including demographic information, medical history, disease duration and family history. Psychopathological characteristics and motor signs were assessed by the Hamilton Depression scale (HAMD) and scales for motor and non-motor symptoms in the Unified Parkinson's Disease Rating Scale (UPDRS). Progression of PD was evaluated by the modified Hoehn and Yahr (H-Y) staging system. RESULTS: Mean age (47.1% men) was 68.25±13.67 years old, with disease duration of 4.18±5.13 years and median H-Y scores 2.07±0.97 points. Among three different nationalities, PD rate was 69.2% in Han nationals, 17.6% in Hui nationals and 13.1% in Tibetans of 221 PD patients. Compared with the non-depressed PD group, female, no-smoking and living alone rates, and dysphagia, pain, H-Y stage, ADL, UPDRS-I, UPDRS-III, HAMA, and PSQI scores were significantly increased in the PDD group, while MMSE scores were significantly decreased (P<0.05 or P<0.01). PD patients of Han and Hui nationalities had increased depression rates compared with Tibetan individuals (P<0.05). Compared with the mild depression group, the moderate and severe depression groups had significantly increased salivation, dysphagia, H-Y stage, UPDRS-I, UPDRS-III, HAMA, and PSQI scores (P<0.05 or P<0.01). Living alone rates and ADL scores were increased in the severe depression group (P<0.05). Logistic regression analysis showed that living alone (OR=19.833, 95% CI: 2.758-142.624, P<0.01), UPDRS-III score (OR=1.079, 95% CI: 1.009-1.153, P<0.05), and PSQI score (OR=1.538, 95% CI: 1.347-1.755, P<0.001) were risk factors for PDD. Male gender (OR=0.292, 95% CI: 0.112-0.763, P<0.05) was a protective factor in PDD. CONCLUSION: PDD is associated with gender, ethnicity, loneliness, non-motor symptoms (NMSs), motor symptoms, and disease severity, and depression severity. Living alone, dyskinesia, and sleep disorder are risk factors for PDD at high altitude. A relative protection against depression was observed in the Tibetan population.

Influenza Vaccine Effectiveness in Mainland China: A Systematic Review and Meta-Analysis.

Influenza endangers human health but can be prevented in part by vaccination. Assessing influenza vaccine effectiveness (VE) provides scientific evidence for developing influenza vaccination policy. We conducted a systematic review and meta-analysis of studies that evaluated influenza VE in mainland China. We searched six relevant databases as of 30 August 2019 to identify studies and used Review Manager 5.3 software to analyze the included studies. The Newcastle-Ottawa scale was used to assess the risk of publication bias. We identified 1408 publications, and after removing duplicates and screening full texts, we included 21 studies in the analyses. Studies were conducted in Beijing, Guangzhou, Suzhou, and Zhejiang province from the 2010/11 influenza season through the 2017/18 influenza season. Overall influenza VE for laboratory confirmed influenza was 36% (95% CI: 25-46%). In the subgroup analysis, VE was 45% (95% CI: 18-64%) for children 6-35 months who received one dose of influenza vaccine, and 57% (95% CI: 50-64%) who received two doses. VE was 47% (95% CI: 39-54%) for children 6 months to 8 years, and 18% (95% CI: 0-33%) for adults ≥60 years. For inpatients, VE was 21% (95% CI: -11-44%). We conclude that influenza vaccines that were used in mainland China had a moderate effectiveness, with VE being higher among children than the elderly. Influenza VE should be continuously monitored in mainland China to provide evidence for policy making and improving uptake of the influenza vaccine.

Barriers to influenza vaccination among different populations in Shanghai.

BACKGROUND: Seasonal influenza vaccination coverage remains low in most areas of China. Its influencing factors and barriers in various populations receiving influenza vaccinations need to be well understood to promote vaccination. METHODS: A cross-sectional survey was conducted with residents in 48 communities. Vaccination status in the 2018-2019 influenza season and reasons for or against vaccination were surveyed. The potential factors influencing vaccination uptake were determined using bivariate logistic regression. RESULTS: In total, 1301 of the 11053 respondents received an influenza vaccine during the 2018-2019 season with a coverage rate of 11.8% (95% CI, 11.2-12.4). The vaccine coverage was highest among children (26.6%, 95%CI: 24.8-28.5), followed by adults (8.2%, 95%CI: 7.4-9.0) and elderly people (7.3%, 95%CI: 6.5-8.1) (p < .001). Those with chronic underlying conditions all had higher vaccine coverage than did those without for different groups (p < .001). Among the three groups, the most common reason for being unvaccinated was worrying about the side effects (45.0%), believing they were healthy and did not need to get vaccinated (42.2%), and lack of influenza vaccine awareness (48.3%). Low education level and lack of awareness were identified as predictors of low coverage rate. CONCLUSION: Influenza vaccination coverage is low among different populations in Shanghai. Our study highlights the need for appropriate influenza vaccination strategies and programmes targeting different populations.

Evidence for pre-symptomatic transmission of coronavirus disease 2019 (COVID-19) in China.

BACKGROUND: Between mid-January and early February, provinces of mainland China outside the epicentre in Hubei province were on high alert for importations and transmission of COVID-19. Many properties of COVID-19 infection and transmission were still not yet established. METHODS: We collated and analysed data on 449 of the earliest COVID-19 cases detected outside Hubei province to make inferences about transmission dynamics and severity of infection. We analysed 64 clusters to make inferences on serial interval and potential role of pre-symptomatic transmission. RESULTS: We estimated an epidemic doubling time of 5.3 days (95% confidence interval (CI): 4.3, 6.7) and a median incubation period of 4.6 days (95% CI: 4.0, 5.2). We estimated a serial interval distribution with mean 5.7 days (95% CI: 4.7, 6.8) and standard deviation 3.5 days, and effective reproductive number was 1.98 (95% CI: 1.68, 2.35). We estimated that 32/80 (40%) of transmission events were likely to have occurred prior to symptoms onset in primary cases. Secondary cases in clusters had less severe illness on average than cluster primary cases. CONCLUSIONS: The majority of transmissions are occurring around illness onset in an infected person, and pre-symptomatic transmission does play a role. Detection of milder infections among the secondary cases may be more reflective of true disease severity.

The effect of traditional Tibetan guozhuang dance on vascular health in elderly individuals living at high altitudes.

To evaluate the effect of dance on vascular-related factors and cerebral hemodynamics in elderly individuals in Qinghai-Tibetan plateau regions (mean altitude ≥2,300 m). Thirty elderly individuals, who practiced traditional Tibetan Guozhuang dance or did not, were enrolled, respectively. Serum PGC-1α, HCY, FSTL-1, VEGF and HIF-1α were measured by ELISA assays. Carotid artery stenosis and plaque, IMT, extracranial internal carotid artery stenosis and cerebral arteriosclerosis were evaluated using CUS and TCD. Body weight, BMI, heart rate, systolic pressure, and diastolic pressure, serum BGS, TC, LDL, HIF-1α, VEGF, and HCY in the dance group were significantly lower than the no-dance group. FSTL-1 levels, SO2 and SO2/heart rate ratio in the dance group were significantly higher than the no-dance group. Incidence of extracranial internal carotid artery stenosis, carotid stenosis and plaque in the dance group was significantly lower than the no-dance group. IMT was a significant positive correlation between PGC-1α and HCY in the no-dance group. Elderly individuals who regularly practiced Tibetan dance had improved blood vessel functionality and cerebral hemodynamic at high altitudes.

Characteristics of Seasonal Influenza Virus Activity in a Subtropical City in China, 2013-2019.

BACKGROUND: To optimize seasonal influenza vaccination programs in regions with potentially complicated seasonal patterns, the epidemiological characteristics of seasonal influenza activity in a subtropical city of China were explored. MATERIALS AND METHODS: Influenza virus data of patients with influenza-like illness (ILI) during 2013-2019 were collected from two sentinel hospitals in a subtropical region of China, Yichang city. The influenza virus positive rate among sampled ILI cases served as a proxy to estimate influenza seasonal characteristics, including periodicity, duration, peaks, and predominant subtypes/lineages. Epidemiological features of different years, seasons and age groups were analyzed, and vaccine mismatches were identified. RESULTS: In total, 8693 ILI cases were included; 1439 (16.6%) were laboratory-confirmed influenza cases. The influenza A positive rate (10.6%) was higher than the influenza B positive rate (5.9%). There were three influenza circulation patterns in Yichang: (1) annual periodicity (in 2013-2014, 2015-2016 and 2018-2019), (2) semiannual periodicity (in 2014-2015), and (3) year-round periodicity (in 2016-2017 and 2017-2018). Summer epidemics existed in two of the six years and were dominated by influenza A/H3N2. Winter and spring epidemics occurred in five of the six years, and A/H1N1, A/H3N2, B/Victoria, and B/Yamagata were codominant. During the study period, the predominant lineages, B/Victoria in 2015-16 and B/Yamagata in 2017-2018, were both mismatched with the influenza B component of the trivalent vaccine. Children 5-14 years old (26.4%) and individuals over 60 years old (16.9%) had the highest influenza positive rates. CONCLUSIONS: The seasonal epidemic period and the predominant subtype/lineage of influenza viruses in Yichang city are complex. Influenza vaccination timing and strategies need to be optimized according to the local features of influenza virus activity.

A centipede toxin causes rapid desensitization of nociceptor TRPV1 ion channel.

The nociceptive transient receptor potential vanilloid 1 (TRPV1) ion channel is a polymodal receptor for multiple painful stimuli, hence actively pursued as a target for analgesic drugs. We identified a small peptide toxin RhTx2 from the Chinese red-headed centipede that strongly modulates TRPV1 activities. RhTx2, a 31-amino-acid peptide, is similar to a TRPV1-activating toxin RhTx we have previously discovered but with four extra amino acids at the N terminus. We observed that, like RhTx, RhTx2 activated TRPV1, but RhTx2 rapidly desensitized the channel upon prolonged exposure. Desensitization was achieved by reducing both the open probability and the single-channel conductance. RhTx2 is not only a tool to study the desensitization mechanism of TRPV1, but also a promising starting molecule for developing novel analgesics.

The Critical Role of IL-10 in the Antineuroinflammatory and Antioxidative Effects of Rheum tanguticum on Activated Microglia.

Rheum tanguticum Maxim. ex Balf. (Rt), a traditional Tibetan medicine, is known to exert various bioactivities, including anti-inflammatory and antioxidative activities. The present study was conducted to investigate anti-inflammatory and antioxidative effects of Rt on activated microglia. Rt (10 µg/ml) significantly inhibited the mean protein level of interleukin-1ß (IL-1ß) in the organotypic hippocampal slice cultures following treatment with chromogranin A (CGA, 10 nM) and pancreastatin (10 nM), endogenous microglial activators present in senile plaques. Rt also significantly inhibited the expression and production of inflammatory and oxidative molecules, including IL-1ß, tumor necrosis factor-α, and nitric oxide, by cultured microglia after treatment with CGA. These effects of Rt are considered to be mediated by the secretion of interleukin-10 (IL-10) from microglia, because neutralizing antibodies against IL-10 significantly canceled these effects. To explore the causative components of Rt responsible for inducing the secretion of IL-10, the effects of seven components of Rt on the IL-10 expression in microglia were examined. Among them, aloe-emodin (10 µM) and (+)-catechin (30 µM) were able to induce the secretion of IL-10 from cultured microglia. Therefore, aloe-emodin and (+)-catechin are deemed responsible for the antineuroinflammatory and antioxidative effects of Rt through the secretion of IL-10 from microglia. Accordingly, Rt is considered potentially useful for the treatment of AD.

Brazilian Green Propolis Prevents Cognitive Decline into Mild Cognitive Impairment in Elderly People Living at High Altitude.

BACKGROUND: Systemic inflammation is known as a risk factor of cognitive decline. OBJECTIVE: To investigate the effects of propolis on cognitive decline and systemic inflammation in elderly people living at high altitude. METHODS: Sixty participants (average 72.8 years) living at altitude (2,260 meters) were randomized to receive propolis (0.83 g, n = 30) or placebo (n = 30) for 24 months. Cognitive outcomes were assessed using MMSE and serum cytokine levels were measured for 24 months in a double-blind study. RESULTS: MMSE scores were 26.17 at baseline and 23.87 at 24 months in placebo group. Compared to placebo group, improvements of MMSE scores were significant in propolis-treated subjects (p = 0.007) with a response emerging over time (time points×group interaction, p = 0.016). In addition, the serum IL-1ß and IL-6 levels were significantly different across treatments (p < 0.0001) showing upward and downward trends in placebo- and propolis-treated subjects, respectively (p < 0.0001). Serum levels of TNF-α were not significantly different across treatment (p = 0.0528) but with a response emerging over time (time points×group interaction, p = 0.016). In contrast, serum levels of TGFß1 were significantly different across treatments (p < 0.0001) showing downward and upward trends in placebo- and propolis-treated subjects, respectively. Serum levels of IL-10 were significant for the effect of groups (p = 0.0411). Furthermore, MMSE scores correlated with the decrease in IL-1ß and the increase in TGFß1 in serum. CONCLUSION: Elderly people living at high altitude developed to MCI in 24 months with exacerbation of systemic inflammation. Ingestion of propolis (>12 months) protected against cognitive decline after systemic inflammation was reduced.

The Neuroprotective Effects of Brazilian Green Propolis on Neurodegenerative Damage in Human Neuronal SH-SY5Y Cells.

Oxidative stress and synapse dysfunction are the major neurodegenerative damage correlated to cognitive impairment in Alzheimer's disease (AD). We have found that Brazilian green propolis (propolis) improves the cognitive functions of mild cognitive impairment patients living at high altitude; however, mechanism underlying the effects of propolis is unknown. In the present study, we investigated the effects of propolis on oxidative stress, expression of brain-derived neurotrophic factor (BDNF), and activity-regulated cytoskeleton-associated protein (Arc), the critical factors of synapse efficacy, using human neuroblastoma SH-SY5Y cells. Pretreatment with propolis significantly ameliorated the hydrogen peroxide- (H2O2-) induced cytotoxicity in SH-SY5Y cells. Furthermore, propolis significantly reduced the H2O2-generated reactive oxygen species (ROS) derived from mitochondria and 8-oxo-2'-deoxyguanosine (8-oxo-dG, the DNA oxidative damage marker) but significantly reversed the fibrillar ß-amyloid and IL-1ß-impaired BDNF-induced Arc expression in SH-SY5Y cells. Furthermore, propolis significantly upregulated BDNF mRNA expression in time- and dose-dependent manners. In addition, propolis induced Arc mRNA and protein expression via phosphoinositide-3 kinase (PI3K). These observations strongly suggest that propolis protects from the neurodegenerative damage in neurons through the properties of various antioxidants. The present study provides a potential molecular mechanism of Brazilian green propolis in prevention of cognitive impairment in AD as well as aging.

Nutrients, Microglia Aging, and Brain Aging.

As the life expectancy continues to increase, the cognitive decline associated with Alzheimer's disease (AD) becomes a big major issue in the world. After cellular activation upon systemic inflammation, microglia, the resident immune cells in the brain, start to release proinflammatory mediators to trigger neuroinflammation. We have found that chronic systemic inflammatory challenges induce differential age-dependent microglial responses, which are in line with the impairment of learning and memory, even in middle-aged animals. We thus raise the concept of "microglia aging." This concept is based on the fact that microglia are the key contributor to the acceleration of cognitive decline, which is the major sign of brain aging. On the other hand, inflammation induces oxidative stress and DNA damage, which leads to the overproduction of reactive oxygen species by the numerous types of cells, including macrophages and microglia. Oxidative stress-damaged cells successively produce larger amounts of inflammatory mediators to promote microglia aging. Nutrients are necessary for maintaining general health, including the health of brain. The intake of antioxidant nutrients reduces both systemic inflammation and neuroinflammation and thus reduces cognitive decline during aging. We herein review our microglia aging concept and discuss systemic inflammation and microglia aging. We propose that a nutritional approach to controlling microglia aging will open a new window for healthy brain aging.

The Neuroprotective Effects of Ratanasampil on Oxidative Stress-Mediated Neuronal Damage in Human Neuronal SH-SY5Y Cells.

We previously found that Ratanasampil (RNSP), a traditional Tibetan medicine, improves the cognitive function of mild-to-moderate AD patients living at high altitude, as well as learning and memory in an AD mouse model (Tg2576); however, mechanism underlying the effects of RNSP is unknown. In the present study, we investigated the effects and molecular mechanisms of RNSP on oxidative stress-induced neuronal toxicity using human neuroblastoma SH-SY5Y cells. Pretreatment with RNSP significantly ameliorated the hydrogen peroxide- (H2O2-) induced cytotoxicity of SH-SY5Y cells in a dose-dependent manner (up to 60 µg/mL). Furthermore, RNSP significantly reduced the H2O2-induced upregulation of 8-oxo-2'-deoxyguanosine (8-oxo-dG, the oxidative DNA damage marker) but significantly reversed the expression of repressor element-1 silencing transcription factor (REST) from H2O2 associated (100 µM) downregulation. Moreover, RNSP significantly attenuated the H2O2-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase 1/2 (ERK 1/2) in SH-SY5Y cells. These observations strongly suggest that RNSP may protect the oxidative stress-induced neuronal damage that occurs through the properties of various antioxidants and inhibit the activation of MAPKs. We thus provide the principle molecular mechanisms of the effects of RNSP and indicate its role in the prevention and clinical management of AD.