Transcriptomic and genetic approaches reveal that low-light-induced disease susceptibility is related to cellular oxidative stress in tomato.

The impact of low light intensities on plant disease outbreaks represents a major challenge for global crop security, as it frequently results in significant yield losses. However, the underlying mechanisms of the effect of low light on plant defense are still poorly understood. Here, using an RNA-seq approach, we found that the susceptibility of tomato to Pseudomonas syringae pv. tomato DC3000 (Pst DC3000) under low light was associated with the oxidation-reduction process. Low light conditions exacerbated Pst DC3000-induced reactive oxygen species (ROS) accumulation and protein oxidation. Analysis of gene expression and enzyme activity of ascorbate peroxidase 2 (APX2) and other antioxidant enzymes revealed that these defense responses were significantly induced by Pst DC3000 inoculation under normal light, whereas these genes and their associated enzyme activities were not responsive to pathogen inoculation under low light. Additionally, the reduced ascorbate to dehydroascorbate (AsA/DHA) ratio was lower under low light compared with normal light conditions upon Pst DC3000 inoculation. Furthermore, the apx2 mutants generated by a CRISPR-Cas9 gene-editing approach were more susceptible to Pst DC3000 under low light conditions. Notably, this increased susceptibility could be significantly reduced by exogenous AsA treatment. Collectively, our findings suggest that low-light-induced disease susceptibility is associated with increased cellular oxidative stress in tomato plants. This study sheds light on the intricate relationship between light conditions, oxidative stress, and plant defense responses, and may pave the way for improved crop protection strategies in low light environments.

Plant N-acylethanolamines play a crucial role in defense and its variation in response to elevated CO2 and temperature in tomato.

The ubiquitous lipid-derived molecules N-acylethanolamines (NAEs) have multiple immune functions in mammals, but their roles and mechanisms in plant defense response during changing environment remain largely unclear. Here, we found that exogenous NAE18:0 and NAE18:2 promoted defense against the necrotrophic pathogen Botrytis cinerea but suppressed defense to the hemi-biotrophic pathogen Pseudomonas syringae pv. tomato (Pst) DC3000 in tomato. The knocking-down and overexpression function analysis of the pathogen-responsive NAE synthetic gene PHOSPHOLIPASE Dγ (PLDγ) and hydrolytic gene FATTY ACID AMID HYDROLASE 1 (FAAH1) revealed that the NAE pathway is crucial for plant defense response. Using exogenous applications and SA-abolished NahG plants, we unveiled the antagonistic relationship between NAE and SA in plant defense response. Elevated CO2 and temperature significantly changed the NAE pathway in response to pathogens, while inhibition of the NAE pathway led to the alternation of environment-mediated defense variations against Pst DC3000 in tomato, indicating that NAE pathway is associated with plant defense variations in response to elevated CO2 and temperature. The results herein reveal a new function of NAE in plant defense, and its involvement in environment-mediated defense variation in tomato. These findings shed light on the NAE-based plant defense, which may have relevance to crop disease management in future changing climate.

Melatonin mediates elevated carbon dioxide-induced photosynthesis and thermotolerance in tomato.

Increasing carbon dioxide (CO2 ) promotes photosynthesis and mitigates heat stress-induced deleterious effects on plants, but the regulatory mechanisms remain largely unknown. Here, we found that tomato (Solanum lycopersicum L.) plants treated with high atmospheric CO2 concentrations (600, 800, and 1000 µmol mol-1 ) accumulated increased levels of melatonin (N-acetyl-5-methoxy tryptamine) in their leaves and this response is conserved across many plant species, including Arabidopsis, rice, wheat, mustard, cucumber, watermelon, melon, and hot pepper. Elevated CO2 (eCO2 ; 800 µmol mol-1 ) caused a 6.8-fold increase in leaf melatonin content, and eCO2 -induced melatonin biosynthesis preferentially occurred through chloroplast biosynthetic pathways in tomato plants. Crucially, manipulation of endogenous melatonin levels by genetic means affected the eCO2 -induced accumulation of sugar and starch in tomato leaves. Furthermore, net photosynthetic rate, maximum photochemical efficiency of photosystem II, and transcript levels of chloroplast- and nuclear-encoded photosynthetic genes, such as rbcL, rbcS, rbcA, psaD, petB, and atpA, significantly increased in COMT1 overexpressing (COMT1-OE) tomato plants, but not in melatonin-deficient comt1 mutants at eCO2 conditions. While eCO2 enhanced plant tolerance to heat stress (42°C) in wild-type and COMT1-OE, melatonin deficiency compromised eCO2 -induced thermotolerance in comt1 plants. The expression of heat shock proteins genes increased in COMT1-OE but not in comt1 plants in response to eCO2 under heat stress. Further analysis revealed that eCO2 -induced thermotolerance was closely linked to the melatonin-dependent regulation of reactive oxygen species, redox homeostasis, cellular protein protection, and phytohormone metabolism. This study unveiled a crucial mechanism of elevated CO2 -induced thermotolerance in which melatonin acts as an essential endogenous signaling molecule in tomato plants.

Role of methylation-related genes CRYAB and SLC39A11 in the occurrence and development of lung adenocarcinoma.

Background: Previous studies have shown that human crystallin alpha B (CRYAB) is highly expressed in human cancers and associated with poor survival in cancer patients. Here we investigated whether SLC39A11 and CRYAB genes were related to the proliferation and development of lung adenocarcinoma (LUAD) to explore their potential as therapeutic targets and prognostic markers for LUAD. Methods: CRYAB and SLC39A11 genes were identified from The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database. The human lung cancer cell lines A549 and H1975 were cultured, transfected, and subjected to RNA extraction. After genomic DNA removal, the RNA was reverse-transcribed. Differences between 2 groups were compared using t-test. Results: Knockdown of SLC39A11 inhibited the proliferation of LUAD cells in A549 and H1975. Knockdown of CRYAB promoted the increase of LUAD cell clones, while knockdown of SLC39A11 suppressed LUAD cell clones. In both A549 and H1975 cell lines, knockout of CRYAB inhibited the apoptosis of LUAD cells, whereas knockout of SLC39A11 promoted the apoptosis of LUAD cells. In the H1975 cell line, knockout of CRYAB also lowered the proportion of cells in interphase and increased the proportion of mitotic cells, while knockout of SLC39A11 also slowed down the division cycle of tumor cells. Knockdown of CRYAB promoted the migration of LUAD cells in both the A549 cell line and H1975 cell line. In the H1975 cell line, knockout of SLC39A11 also reduced the invasive ability of LUAD cells. Conclusions: CRYAB and SLC39A11 could be used as prognostic indicators and therapeutic targets for LUAD.

Tomato SlMYB15 transcription factor targeted by sly-miR156e-3p positively regulates ABA-mediated cold tolerance.

Cold is a common abiotic stress that seriously affects plant growth and development. MYB transcription factors are regulatory molecules that play important roles in various biological processes. We have previously demonstrated that SlMYB15 positively regulates cold tolerance in tomato. However, the underlying mechanism of SlMYB15-induced cold tolerance remains largely unexplored. Here, cold-induced SlMYB15 was found to be targeted by Solanum lycopersicum (sly)-miR156e-3p, which was decreased by cold stimulus in tomato. Tomato plants overexpressing sly-MIR156e-3p displayed significant enhancement in susceptibility to cold stress, while silencing of sly-miR156e-3p by an artificial microRNA interference strategy caused tomato plants to be more tolerant to cold. Moreover, both overexpression of SlMYB15 and silencing of sly-miR156e-3p increased the accumulation of ABA. SlMYB15 directly binds to the promoter regions of ABA biosynthesis and signalling genes, SlNCED1 and SlABF4, resulting in enhanced cold tolerance. Further experiments showed that SlMYB15 and sly-miR156e-3p also coordinated the cold tolerance of tomato via the reactive oxygen species (ROS) signalling pathway, as reflected by the increased expression of SlRBOH1, enhanced H2O2 and O2•-accumulation, and amplified activity of antioxidant enzymes in SlMYB15-overexpressing and sly-miR156e-3p-silenced plants. Taken together, our results demonstrate that SlMYB15 targeted by sly-miR156e-3p confers higher survivability to cold stress via ABA and ROS signals. This study provides valuable information for breeding improved crop cultivars better equipped with cold tolerance.

BAG9 Confers Thermotolerance by Regulating Cellular Redox Homeostasis and the Stability of Heat Shock Proteins in Solanum lycopersicum.

The Bcl-2-associated athanogene (BAG) family, a group of co-chaperones that share conservative domains in flora and fauna, is involved in plant growth, development, and stress tolerance. However, the function of tomato BAG genes on thermotolerance remains largely unknown. Herein, we found that the expression of BAG9 was induced during heat stress in tomato plants. Knockout of the BAG9 gene by CRISPR/Cas9 reduced, while its overexpression increased thermotolerance in tomato plants as reflected by the phenotype, photosynthesis rate, and membrane peroxidation. Heat-induced reactive oxygen species and oxidative/oxidized proteins were further increased in bag9 mutants and were normalized in BAG9 overexpressing plants. Furthermore, the activities of antioxidant enzymes, ascorbic acid (AsA)/dehydroascorbic acid (DHA), and reduced glutathione (GSH)/oxidized glutathione (GSSG) were reduced in bag9 mutants and were increased in BAG9 overexpressing plants under heat stress. Additionally, BAG9 interacted with Hsp20 proteins in vitro and in vivo. Accumulation of Hsp proteins induced by heat showed a reduction in bag9 mutants; meanwhile, it was increased in BAG9 overexpressing plants. Thus, BAG9 played a crucial role in response to heat stress by regulating cellular redox homeostasis and the stability of heat shock proteins.

High Nitric Oxide Concentration Inhibits Photosynthetic Pigment Biosynthesis by Promoting the Degradation of Transcription Factor HY5 in Tomato.

Photosynthetic pigments in higher plants, including chlorophyll and carotenoid, are crucial for photosynthesis and photoprotection. Previous studies have shown that nitric oxide (NO) plays a dual role in plant photosynthesis. However, how pigment biosynthesis is suppressed by NO remains unclear. In this study, we generated NO-accumulated gsnor mutants, applied exogenous NO donors, and used a series of methods, including reverse transcription quantitative PCR, immunoblotting, chromatin immunoprecipitation, electrophoretic mobility shift, dual-luciferase, and NO content assays, to explore the regulation of photosynthetic pigment biosynthesis by NO in tomato. We established that both endogenous and exogenous NO inhibited pigment accumulation and photosynthetic capacities. High levels of NO stimulated the degradation of LONG HYPOCOTYL 5 (HY5) protein and further inactivated the transcription of genes encoding protochlorophyllide oxidoreductase C (PORC) and phytoene synthase 2 (PSY2)-two enzymes that catalyze the rate-limiting steps in chlorophyll and carotenoid biosynthesis. Our findings provide a new insight into the mechanism of NO signaling in modulating HY5-mediated photosynthetic pigment biosynthesis at the transcriptional level in tomato plants.

Autophagic pathway contributes to low-nitrogen tolerance by optimizing nitrogen uptake and utilization in tomato.

Autophagy is a primary process involved in the degradation and reuse of redundant or damaged cytoplasmic components in eukaryotes. Autophagy has been demonstrated to facilitate nutrient recycling and remobilization by delivering intracellular materials to the vacuole for degradation in plants under nutrient starvation. However, the role of autophagy in nitrogen (N) uptake and utilization remains unknown. Here, we report that the ATG6-dependent autophagic pathway regulates N utilization in tomato (Solanum lycopersicum) under low-nitrogen (LN) conditions. Autophagy-disrupted mutants exhibited weakened biomass production and N accumulation compared with wild-type (WT), while ATG6 overexpression promoted autophagy and biomass production under LN stress. The N content in atg6 mutants decreased while that in ATG6-overexpressing lines increased due to the control of N transporter gene expression in roots under LN conditions. Furthermore, ATG6-dependent autophagy enhanced N assimilation efficiency and protein production in leaves. Nitrate reductase and nitrite reductase activities and expression were compromised in atg6 mutants but were enhanced in ATG6-overexpressing plants under LN stress. Moreover, ATG6-dependent autophagy increased plant carbon fixation and photosynthetic capacity. The quantum yield of photosystem II, photosynthetic N use efficiency and photosynthetic protein accumulation were compromised in atg6 mutants but were restored in ATG6-overexpressing plants. A WT scion grafted onto atg6 mutant rootstock and an atg6 scion grafted onto WT rootstock both exhibited inhibited LN-induced autophagy and N uptake and utilization. Thus, ATG6-dependent autophagy regulates not only N uptake and utilization as well as carbon assimilation but also nutrient recycling and remobilization in tomato plants experiencing LN stress.

Development of a Point-of-Care Test Based on Selenium Nanoparticles for Heart-Type Fatty Acid-Binding Proteins in Human Plasma and Blood.

Purpose: A rapid, convenient, cost-effective in-home test method for identifying heart-type fatty acid-binding protein (H-FABP) in plasma and blood by a lateral-flow immunoassay (LFIA) based on selenium nanoparticles (SeNPs) was developed. Methods: SeNPs were synthesized by using L-ascorbic acid to reduce seleninic acid at room temperature and conjugated with an anti-H-FABP monoclonal antibody. The limit of detection, specificity, and stability were measured, and clinical samples were analyzed. Results: The SeNPs were spherical with a diameter of 39.48 ± 3.72 nm and were conjugated successfully with an anti-H-FABP antibody, resulting in a total diameter of 46.52 ± 2.95 nm. The kit was designed for the determination of H-FABP in plasma specimens and whole blood specimens. The limit of detection was 1 ng/mL in plasma and blood, and the results could be determined within 10 min. No cross-reaction occurred with cardiac troponin I, creatine kinase-MB or myoglobin. The kits were stored at 40 °C for up to 30 days without significant loss of activity. The sensitivity was determined to be 100%, the specificity 96.67%, and the overall coincidence rate 97.83%. Conclusion: This SeNP assay kit can conveniently, rapidly, and sensitively detect H-FABP in plasma or blood with a readout of a simple color change visible to the naked eye with no special device, and can be used as an auxiliary means for the early screening of AMI. Clinical Trial Registration: Plasma and blood samples were used under approval from the Experimental Animal Ethics committee of the Joint National Laboratory for Antibody Drug Engineering, Henan University. The clinical trial registration number was HUSOM-2019-047.

Phytonanotechnology applications in modern agriculture.

With the rapidly changing global climate, the agricultural systems are confronted with more unpredictable and harsh environmental conditions than before which lead to compromised food production. Thus, to ensure safer and sustainable crop production, the use of advanced nanotechnological approaches in plants (phytonanotechnology) is of great significance. In this review, we summarize recent advances in phytonanotechnology in agricultural systems that can assist to meet ever-growing demands of food sustainability. The application of phytonanotechnology can change traditional agricultural systems, allowing the target-specific delivery of biomolecules (such as nucleotides and proteins) and cater the organized release of agrochemicals (such as pesticides and fertilizers). An amended comprehension of the communications between crops and nanoparticles (NPs) can improve the production of crops by enhancing tolerance towards environmental stresses and optimizing the utilization of nutrients. Besides, approaches like nanoliposomes, nanoemulsions, edible coatings, and other kinds of NPs offer numerous selections in the postharvest preservation of crops for minimizing food spoilage and thus establishing phtonanotechnology as a sustainable tool to architect modern agricultural practices.

Effects and safety of acne vulgaris with external application of herbal medicines: A protocol for systematic review and meta analysis.

BACKGROUND: Acne vulgaris (AV) is a common dermatologic disease. The morbidity is increasing annually. External application of herbal medicines (EAHM) has been pervasively used in the therapy of AV. EAHM , as the traditional Chinese therapy, is widely applied in clinical trials for AV. The aim of this review is to systematically evaluate the efficacy and safety of EAHM in the therapy for AV. METHODS: We will conduct an electronic search of 13 databases from their inception to May, 2020, including PubMed, EMBASE, MEDLINE, Web of Science, Cochrane Library, SpringerLink, WHO International Clinical Trials Registry Platform, Wanfang China database, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, as well as China's Conference Papers Database and China Dissertation database. Other valid search strategies will also be retrieved to complete this review. All randomized controlled trials in which EAHM was used for the treatment of AV will be adopted. Two researchers will select eligible studies respectively according to a predefined protocol. Methodological quality will be assessed with Cochrane risk of bias by means of RevMan V.5.3.5 software. RESULTS: This systematic view will present a high-quality synthesis based on current evidence of EAHM intervention for AV patients. CONCLUSION: The summary of our systematic view will provide evidence to judge whether EAHM is an effective and safe intervention for AV patients.

The HY5 and MYB15 transcription factors positively regulate cold tolerance in tomato via the CBF pathway.

The induction of C-repeat binding factors (CBFs) is crucial for plant survival at low temperatures. Therefore, understanding the mechanisms that regulate CBF transcription is vital for the future development of crops with increased cold tolerance. Here, we provide evidence for the existence of a LONG HYPOCOTYL 5 (HY5)-MYB15-CBFs transcriptional cascade that plays a crucial role in the cold response in tomato. The exposure of tomato plants to cold (4°C) increased the levels of HY5, MYB15 and CBFs transcripts. Moreover, mutations in HY5 or MYB15 decreased the levels of CBF transcripts. In contrast, overexpression of HY5 or MYB15 increased CBF transcript abundance. Crucially, the HY5 transcription factor activated the expression of MYB15 by directly binding to the promoter region, while both HY5 and MYB15 activated the expression of CBF1, CBF2 and CBF3. Taken together, these data show that HY5 can directly regulate CBF transcript levels, and also influence CBF expression indirectly via MYB15. The coordinated action of HY5 and MYB15 allows precise regulation of CBF expression and subsequent cold tolerance. These findings provide an improved understanding of the molecular mechanisms affording transcriptional regulation of CBFs, which can be exploited in the future to enhance cold tolerance in crops.

Light-induced HY5 Functions as a Systemic Signal to Coordinate the Photoprotective Response to Light Fluctuation.

Optimizing the photoprotection of different leaves as a whole is important for plants to adapt to fluctuations in ambient light conditions. However, the molecular basis of this leaf-to-leaf communication is poorly understood. Here, we used a range of techniques, including grafting, chlorophyll fluorescence, revers transcription quantitative PCR, immunoblotting, chromatin immunoprecipitation, and electrophoretic mobility shift assays, to explore the complexities of leaf-to-leaf light signal transmission and activation of the photoprotective response to light fluctuation in tomato (Solanum lycopersicum). We established that light perception in the top leaves attenuated the photoinhibition of both PSII and PSI by triggering photoprotection pathways in the bottom leaves. Local light promoted the accumulation and movement of LONG HYPOCOTYL5 from the sunlit local leaves to the systemic leaves, priming the photoprotective response of the latter to light fluctuation. By directly activating the transcription of PROTON GRADIENT REGULATION5 and VIOLAXANTHIN DE-EPOXIDASE, LONG HYPOCOTYL5 induced cyclic electron flow, the xanthophyll cycle, and energy-dependent quenching. Our findings reveal a systemic signaling pathway and provide insight into an elaborate regulatory network, demonstrating a pre-emptive advantage in terms of the activation of photoprotection and, hence, the ability to survive in a fluctuating light environment.

[Effects of electroacupuncture at "Baihui" and "Yongquan" on the levels of synaptic plasticity related proteins postsynaptic density-95 and synaptophysin in hippocampus of APP/PS1 mice].

OBJECTIVE: From the perspective of ß-amyloid (Aß) toxicity and synaptic plasticity, the mechanism of electroacupuncture to improve learning and memory ability in the early pathological stages of Alzheimer's disease was explored. METHODS: Twelve male amyloid-protein precursor (APP)/γ-secretase (PS1) double transgenic AD mice were randomly and equally divided into electroacupuncture (EA) group and model group, and other 6 male C57BL/6 mice were used as the normal group. EA (1 Hz/50 Hz, 0.5 mA) was applied to "Baihui" (GV20) and bilateral "Yongquan"(KI1) for 15 min, once every other day for 6 weeks. Immunofluorescence was used to observe the positive expression of Aß in the left hippocampus. Immunohistochemistry was used to observe the positive expression of postsynaptic density-95 (PSD-95) in the left hippocampus. Western blot was used to detect the expression of PSD-95 and synaptophysin (SYN)in the right hippocampus. RESULTS: Immunofluorescence results showed that extracellular Aß was seen in the model group and electroacupuncture group, but no senile plaques were seen. Compared with the normal group, the expression level of Aß in the hippocampus of the model group increased significantly (P<0.01). Compared with the model group, the expression of Aß in the hippocampus of the EA group decreased (P<0.05). Immunohistochemical results showed that compared with the normal group, the PSD-95 positive expression in the model group was decreased(P<0.05). Compared with the model group, the expression of PSD-95 in the EA group was increased (P<0.05). Western blot results showed that compared with the normal group, the expression levels of PSD-95 and SYN in the hippocampus of the model group were decreased (P<0.05, P<0.01). Compared with the model group, the expression levels of PSD-95 and SYN in the EA group were increased (P<0.05，P <0.01). CONCLUSION: EA can reduce the expression of Aß in the hippocampus of APP/PS1 mice and increase the expression of PSD-95 and SYN, which may contribute to its effect in improving the synaptic plasticity.

Electroacupuncture Ameliorates Cognitive Impairment by Inhibiting the JNK Signaling Pathway in a Mouse Model of Alzheimer's Disease.

Electroacupuncture (EA) has become popular for its adjustable strength and frequency and easy quantification in the clinic and has demonstrated therapeutic potential for Alzheimer's disease (AD). However, the mechanism remains unknown. Abnormally activated c-Jun N-terminal kinase (JNK) has been closely related to the pathological process of AD. The aim of this study was to investigate the effect of EA on cognitive impairment and the role of the JNK signaling pathway in AD model amyloid precursor protein (APP)/presenilin 1 (PS1) mice. The memory and learning ability of each group was assessed using the Morris Water Maze (MWM). Immunofluorescence, immunohistochemistry and Western blot were performed to measure the expression of APP, JNK, phosphorylated (P-)JNK, mitogen-activated protein kinase 4 (MKK4), MKK7, c-Jun and caspase-3 in hippocampal tissue samples in APP/PS1 mice after EA intervention. Obvious cognitive deficits were observed in the AD model APP/PS1 mice in the MWM test and were associated with JNK signaling pathway activation and APP upregulation. Four weeks of EA significantly ameliorated the cognitive impairments and inhibited JNK signaling pathway activation and APP upregulation. Taken together, the findings demonstrated that EA can reverse cognitive deficits and substantially lower the burden of APP in AD model APP/PS1 mice, at least partially through inhibiting the JNK signaling pathway and regulating apoptosis signals. Therefore, EA may offer an effective alternative therapeutic approach for AD.

Molecular Mechanisms of Autophagy Regulation in Plants and Their Applications in Agriculture.

Autophagy is a highly conserved cellular process for the degradation and recycling of unnecessary cytoplasmic components in eukaryotes. Various studies have shown that autophagy plays a crucial role in plant growth, productivity, and survival. The extensive functions of plant autophagy have been revealed in numerous frontier studies, particularly those regarding growth adjustment, stress tolerance, the identification of related genes, and the involvement of metabolic pathways. However, elucidation of the molecular regulation of plant autophagy, particularly the upstream signaling elements, is still lagging. In this review, we summarize recent progress in research on the molecular mechanisms of autophagy regulation, including the roles of protein kinases, phytohormones, second messengers, and transcriptional and epigenetic control, as well as the relationship between autophagy and the 26S proteasome in model plants and crop species. We also discuss future research directions for the potential application of autophagy in agriculture.

The effects of acupuncture on cognitive impairment of vascular dementia patients: Protocol for a systematic review and meta-analysis.

BACKGROUND: Vascular dementia (VaD) is the second prevalent dementia worldwide attributable to cognitive impairments. Acupuncture has been applied in clinic as a therapeutic modality to treat VaD. This systematic review and meta-analysis aims to evaluate current evidence to explore the effectiveness and safety of acupuncture treatment to cognitive impairment of VaD. METHODS: Randomized controlled trials will be searched restricted to their inception from January 1, 2000 to September 15, 2019. The following literature databases will be searched, including 4 English databases: PubMed, Excerpta Medica Database, the Cochrane Library, Medline, and 4 Chinese databases, namely the China National Knowledge Infrastructure Database, the Wanfang Database, the Chinese Scientific Journal Database, and the Chinese BioMedical Literature Database. After the selection and extraction of eligible studies, a meta-analysis will be undertaken to assess the efficacy and safety of acupuncture on VaD. The Review Manager Software V.5.3.5 will be employed for meta-analysis to assess the risk of bias, data synthesis, and subgroup analysis. RESULTS: The systematic review and meta-analysis will be carried out to evaluate the efficacy and safety of acupuncture in the treatment of VaD, further provide an evidence-based synthesis for clinical and research applications. CONCLUSIONS: The summary of our systematic review will determine whether acupuncture intervention to VaD is safe and well-tolerated in global status.

Effects and safety of herbal medicines on patients with overactive bladder: A protocol for a systematic view and meta-analysis.

BACKGROUND: Overactive bladder (OAB) is a common disease in the urinary system. The morbidity is increasing annually. Herbal medicines have been pervasively used in the therapy of OAB. However, systematic review or meta-analysis has not been found to assess the effects and safety of herbal medicines in curing OAB at present. Hence, the systematic review is conducted to scientifically and methodically evaluate the value of its effectiveness and safety of herbal medicines on OAB. METHODS: We will collect all randomized controlled trials (RCTs) to assess the effectiveness and safety of herbal medicines on OAB. The RCTs will be searched from the electronic databases, including 7 English databases, consisting of PubMed, Excerpta Medica Database (EMBASE), MEDLINE, Web of Science, Cochrane Library, SpringerLink, and WHO International Clinical Trials Registry Platform (ICTRP), and 4 Chinese databases, namely Wanfang Chinese database, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), and Chinese Scientific Journal Database (VIP), others valid search strategy will be adopted. All the RCTs will be assessed from the databases establishment to July 2019. We will perform the meta-analysis of RCTs when the dissertation is appropriate. We will conduct an assessment including data synthesis, bias risk, and subgroup analysis by means of Review Manager software (RevMan) V.5.3.5 software while the setting condition is met. RESULTS: This systematic view and meta-analysis will generate a summary based on the current relevant research to calculate the effects and safety of herbal medicines in promoting the therapy of OAB. Furthermore, it will provide a high-quality synthesis for participants who use herbal medicine to cure OAB. CONCLUSION: The summary of our systematic view will verify whether herbal medicines intervention could be an effective and safety approach in curing OAB.

Electroacupuncture Mitigates Hippocampal Cognitive Impairments by Reducing BACE1 Deposition and Activating PKA in APP/PS1 Double Transgenic Mice.

Increased amyloid-ß (Aß) plaque deposition is thought to be the main cause of Alzheimer's disease (AD). ß-Site amyloid precursor protein cleaving enzyme 1 (BACE1) is the key protein involved in Aß peptide generation. Excessive expression of BACE1 might cause overproduction of neurotoxins in the central nervous system. Previous studies indicated that BACE1 initially cleaves the amyloid precursor protein (APP) and may subsequently interfere with physiological functions of proteins such as PKA, which is recognized to be closely associated with long-term potentiation (LTP) level and can effectively ameliorate cognitive impairments. Therefore, revealing the underlying mechanism of BACE1 in the pathogenesis of AD might have a significant impact on the future development of therapeutic agents targeting dementia. This study examined the effects of electroacupuncture (EA) stimulation on BACE1, APP, and p-PKA protein levels in hippocampal tissue samples. Memory and learning abilities were assessed using the Morris water maze test after EA intervention. Immunofluorescence, immunohistochemistry, and western blot were employed to assess the distribution patterns and expression levels of BACE1, APP, and p-PKA, respectively. The results showed the downregulation of BACE1 and APP and the activation of PKA by EA. In summary, EA treatment might reduce BACE1 deposition in APP/PS1 transgenic mice and regulate PKA and its associated substrates, such as LTP to change memory and learning abilities.

Effects of acupuncture on patients with Alzheimer's disease: Protocol for a systematic review and meta-analysis.

BACKGROUND: Alzheimer's disease (AD) is the leading progressive neurodegenerative disease worldwide, accompanied with nonreversible cognitive impairments. Acupuncture, as the traditional Chinese technique, is widely applied in clinical trials for AD. The aim of this review is to evaluate the efficacy and safety of acupuncture in the aspect of antidementia. METHODS: Randomized controlled trials (RCTs) related to acupuncture treatment targeting AD will be collected. We will search the following 4 databases of electronic English resources, including PubMed, Embase, MEDLINE, Web of Science, and 4 Chinese databases, namely CNKI, CBM, VIP, and Wanfang database. All the RCTs will be searched from their inception to November 2018. After screening the studies, a meta-analysis of RCTs will be carried out. Subsequently, the assessment of bias risk, data synthesis, subgroup analysis will be conducted using RevMan V.5.3.5 software if the setting condition is met. RESULTS: This systematic view and meta-analysis will assess the efficacy and safety of acupuncture intervention on AD patients, which is fundamentally based on current published evidence, and provide a high-quality synthesis for clinical practitioners of treating AD with acupuncture, CONCLUSION:: The summary of our systematic view will determine whether acupuncture intervention could be an efficient and feasible approach to the treatment of AD patients.