Global trends and development of acupuncture for stroke: A review and bibliometric analysis.

The objective of this review is to elaborate on the status, hotspots, and trends of researches on acupuncture for stroke over the past 26 years. Publications about acupuncture for stroke were downloaded from the Web of Science Core Collection, and these papers were published up to December 31, 2022. A bibliometric analysis of acupuncture for stroke was conducted by CiteSpace (6.2.R4) and VOSviewer (1.6.17). In this study, VOSviewer was used for visual analysis of countries, institutions, authors, journals, keywords, and co-cited references. CiteSpace was used to draw a keyword burst map and a co-cited reference burst map. A total of 534 papers were obtained from the Web of Science Core Collection. The number of papers per year showed a rapid upward trend. The most productive country and institution in this field were China (452) and the Fujian University of Traditional Chinese Medicine (43), respectively. Tao Jing had the highest number of articles (34), and EZ Longa was the most popular author (129 co-citations). Neural Regeneration Research (51) was the most productive journal, and Stroke (1346) was the most co-cited journal. An paper written by EZ Longa was the most influential reference, with the highest citation count. The hotspots and frontiers of this area of research were focused on the mechanisms of acupuncture, especially its neural regenerative or neuroprotective effects. This study used CiteSpace and VOSviewer for bibliometric analysis to provide researchers with information on the research status, hotspots, and trends in acupuncture for stroke research over the past 26 years.

Effect of the Deletion of icl1 Gene and icl2 Gene on the Growth Rate of Mycobacterium tuberculosis and the Specific Regulatory Mechanism Involved.

Objective: To explore the effect of the deletion of the icl1 gene and icl2 gene on the growth rate of Mycobacterium tuberculosis (Mtb) and the specific regulatory mechanism involved. Methods: H37Rv was purchased from the Tuberculosis Prevention and Control Institute, and H37Rv was grown in Middlebrook 7H9 broth. Macrophages THP-1 cells were purchased by our researchers from the Cell Bank of the Chinese Academy of Sciences, which were maintained in Roswell Park Memorial Institute (RPMI) 1640 medium supplemented with 10% fetal bovine serum (FBS), at 37°C and 5% CO2. The experiment was divided into 3 groups: the control group (H37Rv infected with THP-1 cells), the icl1/2 deletion group (H37Rv infected with icl1/2 deleted THP-1 cells) and the icl1/2 complementation group (H37Rv infected with icl1/2 deletion, icl1/2 complementary THP-1 cells). Absorbance was measured with a microplate spectrophotometer and the bacterial growth rate was calculated. The colony-forming units (CFU) obtained from the dilution was used to calculate the total number of CFU per milliliter and the percentage of survival of mycobacteria. The protein levels of isocitrate lyase 1 (ICL1), ICL2, p-mTOR and p-Akt were analyzed by Western blot. The CD4+ level was analyzed by flow cytometry. The mRNA expression levels of CCL20, CXCL2, CXCL8, interferon gamma (IFN-γ), interleukin (IL)-17 and IL-22 were analyzed using the quantitative reverse transcription polymerase chain reaction (RT-qPCR) method. Stably transformed monomeric red fluorescent protein (mRFP)-green fluorescent protein (GFP)-LC3 reporter THP-1 cells were used to monitor the aggregation of LC3B in autophagosomes and autophagolysosomes. Results: The Mtb growth rate and CFU of the icl1/2 deletion group were decreased in comparison with the control group (P < .05). When compared with the icl1/2 deletion group, however, the Mtb growth rate and CFU of the icl1/2 complementation group were associated with increased results (P < .05). The protein levels of ICL1 and ICL2 in the icl1/2 deletion group were significantly decreased compared with the control group (P < .05), which were evidently increased in the icl1/2 complementation group when compared with the icl1/2 deletion group (P < .05). In addition, compared with the control group (25.16 ± 2.18), the level of CD4+ appeared to be increased in the icl1/2 deletion group (62.37 ± 5.46) (P < .05), while it was decreased in the icl1/2 complementation group compared with the icl1/2 deletion group (28.33 ± 1.32) (P < .05). The expression levels of chemokine (C-C motif) ligand 20 (CCL20), chemokine (C-X-C motif) ligand 2 (CXCL2), chemokine (C-X-C motif) ligand 8 (CXCL8), IL-17, IFN-γ, and IL-22 mRNA were increased in the icl1/2 deletion group compared with the control group (P < .05), which were significantly decreased in the icl1/2 complementary group compared with the icl1/2 deletion group (P < .05). A comparison between the control group and the icl1/2 deletion group showed that the latter increased the formation of autophagosomes and autophagolysosomes in H37Rv-infected cells (P < .05). However, compared with the icl1/2 deletion group, the icl1/2 complementation group decreased the formation of autophagosomes and autolysosomes in H37Rv-infected cells (P < .05). Moreover, the expression levels of phosphor-mammalian target of rapamycin (p-mTOR) and p-Akt in the icl1/2 deletion group were significantly reduced compared with the control group (P < .05), and were increased in the icl1/2 complementation group compared with the icl1/2 deletion group (P < .05). Conclusion: Loss of icl1/2 was believed to increase the expression of CD4 and CCL20, CXCL8 as well as CXCL2 in the immune system, which increased autophagy. Furthermore, it exerted potential in inhibiting the growth of intracellular Mtb in macrophages.

Phenolic Constituents, Antioxidant and Cytoprotective Activities, Enzyme Inhibition Abilities of Five Fractions from Vaccinium dunalianum Wight.

The bud of Vaccinium dunalianum Wight has been traditionally consumed as health herbal tea by "Yi" people in Yunnan Province, China, which was locally named "Que Zui tea". This paper studied the chemical constituents of five fractions from Vaccinium dunalianum, and their enzyme inhibitory effects of α-glucosidase and pancreatic lipase, antioxidant activity, and cytoprotective effects on H2O2-induced oxidative damage in HepG2 cells. The methanol extract of V. dunalianum was successively partitioned with petroleum ether (PF), chloroform (CF), ethyl acetate (EF), n-butanol (BF), and aqueous (WF) to obtain five fractions. The chemical profiling of the five fractions was analyzed by ultra-high-performance liquid chromatography coupled with a tandem mass spectrometry (UHPLC-MS/MS), and 18 compounds were tentatively identified. Compared to PF, CF, BF and WF, the EF revealed the highest total phenols (TPC) and total flavonoids (TFC), and displayed the strongest enzyme inhibition ability (α-glucosidase and pancreatic lipase) and antioxidant capacity (DPPH, ABTS and FRAP). Furthermore, these five fractions, especially EF, could effectively inhibit reactive oxygen species (ROS) production and cell apoptosis on H2O2-induced oxidative damage protection in HepG2 cells. This inhibitory effect might be caused by the up-regulation of intracellular antioxidant enzyme activity (CAT, SOD, and GSH). The flavonoids and phenolic acids of V. dunalianum might be the bioactive substances responsible for enzyme inhibitory, antioxidant, and cytoprotective activities.

Extracorporeal Shock Wave Therapy Shows Superiority Over Injections for Pain Relief and Grip Strength Recovery in Lateral Epicondylitis: A Systematic Review and Network Meta-analysis.

PURPOSE: To examine the efficacy of extracorporeal shock wave therapy (ESWT) and injection therapies by synthesizing direct and indirect evidence for all pairs of competing therapies for lateral epicondylitis. METHODS: PubMed, EMBASE, and Web of Science databases were searched for all appropriate randomized controlled trials (RCTs), assessing the effect of ESWT or injection therapies. The primary outcome was short-term (≤3 months) and medium-term (>3 months but ≤12 months) pain, while the secondary outcomes were grip strength and patient-reported outcome measures. All outcomes were assessed using standardized mean differences (SMDs) with 95% confidence intervals (CIs) and were ranked using surface under the cumulative ranking curve (SUCRA) probabilities to determine a hierarchy of treatments. Sensitivity analysis was performed to eliminate potential therapeutic effects of normal saline (NS) and exclude trials that included patients with acute lateral epicondylitis (LE). RESULTS: 40 RCTs were included to evaluate ESWT and five different injection therapies, including corticosteroids (CSs), autologous whole blood, platelet-rich plasma (PRP), botulinum toxin A (BoNT-A), and dextrose prolotherapy (DPT). DPT (-.78 [-1.34 to -.21]), ESWT (.57 [-.89 to -.25]), PRP (-.48 [-.85 to -.11]), and BoNT-A (-.43 [-.84 to -.02]) outperformed placebo for short-term pain relief; ESWT (-.44 [-.85 to -.04]) outperformed placebo for medium-term pain relief. DPT was ranked as the most optimal short-term and medium-term pain reliever (SUCRA, 87.3% and 98.6%, respectively). ESWT was ranked as the most optimal short-term and medium-term grip strength recovery (SUCRA; 79.4% and 86.4%, respectively). CONCLUSIONS: DPT and ESWT were the best two treatment options for pain control and ESWT was the best treatment option for grip strength recovery. CSs were not recommended for the treatment of LE. More evidence is required to confirm the superiority in pain control of DPT among all these treatment options on LE. LEVEL OF EVIDENCE: Level I, meta-analysis of Level I randomized controlled trials.

Vitamin D in gynecological diseases.

BACKGROUND: Most reproductive system studies suggest the protective effects of vitamin D, but vitamin D deficiency and insufficiency are growing global health issues. The present study investigates the association between vitamin D deficiency/insufficiency and gynecologic diseases to identify illness risks at different serum vitamin D levels in Taiwan. METHODS: A total of 7699 female adults aged ≥20 years with results for both serum vitamin D and gynecologic-associated diseases were drawn from the Taiwan MJ cohort. We analyzed the correlation between serum vitamin D levels and results from reproductive system evaluations, including history of dysmenorrhea, results of Pap smear, high-risk human papillomavirus (HPV) infection of the cervix, mammography, and ultrasound of breast and pelvis. RESULTS: Over 80% of participants showed vitamin D deficiency/insufficiency. Participants with abnormal Pap smear results, high-risk HPV infection, and history of dysmenorrhea showed significantly lower levels of serum vitamin D (p < 0.001-0.05). Serum vitamin D deficiency was significantly associated with positive high-risk HPV infection of the cervix (p < 0.05) and dysmenorrhea (p < 0.001). After controlling for age as a confounding variable for each gynecologic disease, level of serum vitamin D was significantly associated with abnormal breast ultrasound (odds ratio = 0.724) and uterus ultrasound (odds ratio = 0.673 - 0.8), and dysmenorrhea (odds ratio = 0.829). CONCLUSION: Associations were found between vitamin D deficiency and endometriosis, uterine myoma, dysmenorrhea, abnormal Pap smear results, and high-risk HPV infection of the cervix. Therefore, vitamin D supplements may present a cost-effective benefit for the prevention and treatment of gynecologic diseases, and thus reduction of healthcare expenditures.

The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19.

Different dietary nutrients have distinct effects, including enhancing immune response activity and supporting mucous membrane integrity. These effects are critical in fighting against pathogenic agents, which cover coronavirus disease 2019 (COVID-19), the coronavirus disease that shuts down globally. Recent researches have shown that micronutrient deficiency is commonly associated with compromised immune responses, respiratory tract infections, or even susceptibility to COVID-19. The relationship between Vit A and infection is its role in mucosal epithelium integrity (skin and mucous membrane), the supplementation could be an option for assisted-treating the SARS-CoV-2 virus and a possible prevention of lung infection. Vit C/ascorbic acid stimulates oxygen radical scavenging activity of the skin and enhances epithelial barrier function. Ascorbic acid alone or with other natural compounds (baicalin and theaflavin) may inhibit the expression of angiotensin-converting enzyme II in human small alveolar epithelial cells and limited the entry of SARS-CoV-2. Vitamin D receptors can be expressed by immune cells, and different immune cells (macrophages, monocytes, dendritic cells, T cells, and B cells) can convert Vit D into its active form 1,25-(OH)2 D. Oral vitamin D intake can be a readily way to restrict the viral infection through downregulation of ACE2 receptor and to attenuate the disease severity by decreasing the frequency of cytokine storm and pulmonary pro-inflammatory response. Vit E supports T-cell mediated functions, optimization of Th1 response, and suppression of Th2 response. Vitamin E supplementation can lower the production of superoxides and may favors the antioxidants and benefit the progress of COVID-19 treatment. Zinc plays an essential role in both innate and adaptive immune systems and cytokine production, and Zinc-dependent viral enzymes to initiate the infectious process have proved the Zinc levels are directly associated with symptoms relieved of COVID-19. Iron is an essential component of enzymes involved in the activation of immune cells, lower iron levels predispose to severe symptoms of SARS-CoV-2, and monitoring the status can predict the disease severity and mortality. Selenium participates in the adaptive immune response by supporting antibody production and development. Deficiency can reduce antibody concentration, decreased cytotoxicity of NK cells, compromised cellular immunity, and an attenuated response to vaccination. The COVID-19 vaccines including three broad categories, protein-based vaccines, gene-based vaccines (mRNA vaccines and DNA vaccines), combination of gene and protein-based vaccines. Micronutrients are involved in immunity from the virus entering the human to innate immune response and adaptive immune response. Micronutrients are indispensable in immune response of vaccination.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Impact of rhizosphere microorganisms on arsenic (As) transformation and accumulation in a traditional Chinese medical plant.

Panax notoginseng is an important traditional medicinal plant, but the commercial value is threatened by root-rot disease caused by rhizosphere microbes and a potential health risk caused by plant arsenic (As) accumulation. Whether rhizospheric microbes isolated from P. notoginseng rhizosphere soil could impact As uptake and transport into P. notoginseng is not yet known. Among the three root-rot disease-causing pathogens Fusarium flocciferum (PG 1), Fusarium oxysporum (PG 2), and Fusarium solani (PG 3) and one root-rot disease biocontrol fungus Trichoderma koningiopsis (FC 1) and five biocontrol-exerting bacterial species Bacillus siamensis (BC 1), Delftia acidovorans (BC 2), Brevibacillus formosus (BC 3), Mortierella alpine (BC 4), and Bacillus subtilis (BC 5), one As-resistant pathogen and four biocontrol microorganisms with As-resistant ability were identified. The As-transforming ability of the identified fungi and bacteria was ranked in the order of FC 1 > PG 1 and BC 2 > BC 3 > BC 1, respectively. Then, the As-resistant biocontrol and pathogenic microbes were initiated to colonize the rhizosphere of 1-year-old P. notoginseng seedlings growing in artificially As(V)-contaminated soil to evaluate the impact of microbe inoculation on P. notoginseng As uptake and transport capacity. Concentration of As in P. notoginseng tissues decreased in the order of the sequence stem > root > leaf. Compared to treatment without colonization by microorganism, inoculation with microorganisms increased As root uptake efficiency and root As concentration, especially under treatment of inoculation by BC 2 and PG 1 + BC 2. As transport efficiency from root to stem decreased by inoculation with microorganism, especially under treatment with inoculation of BC 2 and PG 1 + BC 2. However, the impact of microorganism colonization on As stem to leaf transport efficiency was not obvious. In summary, inoculation with rhizosphere microbes may increase As accumulation in P. notoginseng root, especially when using bacteria with high As transformation ability. Therefore, it is necessary to evaluate the As transformation capacity before applying biological control microorganism to the rhizosphere of P. notoginseng.

Moxibustion against Cyclophosphamide-Induced Premature Ovarian Failure in Rats through Inhibiting NLRP3-/Caspase-1-/GSDMD-Dependent Pyroptosis.

Premature ovarian failure (POF) is a clinical term used to describe a condition in which women present with amenorrhoea, hypergonadotropic hypogonadism, and infertility under 40 years old, which are mainly characterized by ovarian granulosa cell inflammation and death. Pyroptosis is a proinflammatory form of programmed cell death. However, the roles of pyroptosis in POF and moxibustion (Mox) on pyroptosis in POF have not been elucidated. The aim of the present study was to investigate the protective effect of moxibustion against cyclophosphamide- (CP-) induced POF and to determine the underlying mechanisms. The results indicated that Mox could decrease the follicle-stimulating hormone (FSH) and luteotropic hormone (LH) and increase estradiol (E2) in serum, which indicated that it could improve ovarian reserve capacity. Mox also ameliorated CP-induced ovarian injury accompanied by decreased levels of interleukin-1ß (IL-1ß), IL-18, and gasdermin D (GSDMD), which are key features of pyroptosis. Further investigation showed that Mox alleviated POF through NLRP3-mediated pyroptosis. On the one hand, Mox directly inhibited TXNIP/NLRP3/caspase-1 signaling-induced pyroptosis, and on the other hand, it indirectly decreased NLRP3, pro-IL-1ß, and pro-IL-18 through inhibiting TLR4/MyD88/NF-κB signaling. Our results show that Mox might be a new therapeutic strategy for the treatment of POF.

Hydrolyzed Chicken Extract (ProBeptigen®) on Cognitive Function in Healthy Middle-Aged People: A Randomized Double-Blind Trial.

Cognitive decline is an important issue of global public health. Cognitive aging might begin at middle adulthood, the period particularly vulnerable to stress in lifespan. Essence of chicken (EOC) has consistently demonstrated its beneficial effects on various cognitive domains as nutritional supplementation. This study primarily aimed to examine the cognitive enhancement effects of ProBeptigen® (previously named CMI-168), hydrolyzed peptides extracted from EOC, in healthy middle-aged people under mild stress. Ninety healthy subjects were randomly assigned into the ProBeptigen® or placebo group for eight weeks. Neurocognitive assessment, event-related potentials (ERPs), and blood tests were conducted before, during, and after the treatment. The ProBeptigen® group outperformed placebo group on Logical Memory subtests of Wechsler Memory Scale-third edition (WMS-III) and Spatial Working Memory task in the Cambridge Neuropsychological Test Automated Battery (CANTAB). The anti-inflammatory effects of ProBeptigen® in humans were also confirmed, with progressively declining high-sensitivity C-reactive protein (hs-CRP) levels. Regular dietary supplementation of ProBeptigen® is suggested to improve verbal short- and long-term memory as well as spatial working memory, and reduce inflammation in middle-aged healthy individuals with stress. The effects of ProBeptigen® on cognition warrant further investigation. (NCT03612752).

Green Tea Catechin (-)-Epigallocatechin-3-Gallate (EGCG) Facilitates Fracture Healing.

Green tea drinking can ameliorate postmenopausal osteoporosis by increasing the bone mineral density. (-)-Epigallocatechin-3-gallate (EGCG), the abundant and active compound of tea catechin, was proven to be able to reduce bone loss and ameliorate microarchitecture in female ovariectomized rats. EGCG can also enhance the osteogenic differentiation of murine bone marrow mesenchymal stem cells and inhibit the osteoclastogenesis in RAW264.7 cells by modulation of the receptor activator of nuclear factor-kB (RANK)/RANK ligand (RANKL)/osteoprotegrin (OPG) (RANK/RANKL/OPG) pathway. Our previous study also found that EGCG can promote bone defect healing in the distal femur partially via bone morphogenetic protein-2 (BMP-2). Considering the osteoinduction property of BMP-2, we hypothesized that EGCG could accelerate the bone healing process with an increased expression of BMP-2. In this manuscript, we studied whether the local use of EGCG can facilitate tibial fracture healing. Fifty-six 4-month-old rats were randomly assigned to two groups after being weight-matched: a control group with vehicle treatment (Ctrl) and a study group with 10 µmol/L, 40 µL, EGCG treatment (EGCG). Two days after the operation, the rats were treated daily with EGCG or vehicle by percutaneous local injection for 2 weeks. The application of EGCG enhanced callus formation by increasing the bone volume and subsequently improved the mechanical properties of the tibial bone, including the maximal load, break load, stiffness, and Young's modulus. The results of the histology and BMP-2 immunohistochemistry staining showed that EGCG treatment accelerated the bone matrix formation and produced a stronger expression of BMP-2. Taken together, this study for the first time demonstrated that local treatment of EGCG can accelerate the fracture healing process at least partly via BMP-2.

Astragalin alleviates cerebral ischemia-reperfusion injury by improving anti-oxidant and anti-inflammatory activities and inhibiting apoptosis pathway in rats.

BACKGROUND: Astragalin (AG), a flavonoid from many traditional herbs and medicinal plants, has been described to exhibit in vitro anti-inflammatory activity. The paper aimed to study the effects of astragalin on anti-inflammatory, anti-oxidative ability and apoptosis signaling pathway in brain tissue of rats with cerebral ischemia-reperfusion injury, and to explore its possible mechanism. METHODS: The rat model of focal cerebral ischemia-reperfusion injury was established by suture method. It was randomly divided into 5 groups, sham operation group, ischemia-reperfusion (I/R) treatment group, and astragalin treatment I / R group (12.5, 25, 50 mg / kg). After 24 h of reperfusion, the neurological deficits of the rats were analyzed and HE staining was performed. The volume of cerebral infarction was calculated by triphenyltetrazolium chloride (TTC) staining, and the apoptosis of nerve cells was detected by TUNEL staining. In addition, the content of malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), glutathione (GSH) assay and glutathione peroxidase (GSH-Px) were measured in rat brain tissue. Western blot analysis was used to determine the expression of related proteins. RESULTS: Compared with I/R group, the neurological deficit score and infarct volume of I/R rats were reduced in the astragalin treatment group. In the astragalin treatment group, MDA and NO levels in I/R rats were reduced, antioxidant enzymes and superoxide dismutase (SOD) activity were increased. In the astragalin treatment group, NF-κB (p65) and cyclooxygenase-2 (COX-2) expression levels were down-regulated, NF-E2-related factor 2 (Nrf2) nucleus and heme oxygenase-1 (HO-1) protein expression levels were up-regulated. In addition, the astragalin treatment can inhibit apoptosis, down-regulate Bax and cleaved caspase-3 expression, up-regulate Bcl-Xl expression. CONCLUSION: The antioxidant properties of astragalin may play an important role in improving cerebral ischemia-reperfusion injury.

Neuroticism modulates neural activities of posterior cingulate cortex and thalamus during psychosocial stress processing.

OBJECTIVE: Individuals with higher neuroticism are vulnerable to stress and are prone to develop depression, however, the neural mechanisms underlying it have not been clarified clearly. METHOD: The Montreal Imaging Stress Task (MIST) was administered to 148 healthy adults during functional magnetic resonance imaging (fMRI). Whole-brain voxel-wise regression analyses were used to detect associations of neuroticism with neural activity involved in perceiving and processing psychosocial stress. In addition, two-sample t-tests were conducted between the high-neurotic and low-neurotic group in order to supplement the results found in regression analyses. RESULTS: Higher neuroticism scores were associated with higher activities in the posterior cingulate cortex (PCC)/precuneus and thalamus (p < 0.05, false discovery rate correction). Moreover, two sample t-tests also revealed that the high-neurotic group had higher neural stress responses in precuneus and bilateral thalamus in comparison to the low-neurotic group (p < 0.05, false discovery rate correction). LIMITATIONS: Our study mainly recruited young adults, which may limit the generalizability of our findings. CONCLUSIONS: Our findings highlight the crucial role of PCC/precuneus and thalamus in the association between neuroticism and stress and may provide insight into the cognitive model of depression.

Assessing the therapeutic potential of Graptopetalum paraguayense on Alzheimer's disease using patient iPSC-derived neurons.

Alzheimer's disease (AD) is the most common type of dementia and also one of the leading causes of death worldwide. However, the underlying mechanisms remain unclear, and currently there is no drug treatment that can prevent or cure AD. Here, we have applied the advantages of using induced pluripotent stem cell (iPSC)-derived neurons (iNs) from AD patients, which are able to offer human-specific drug responsiveness, in order to evaluate therapeutic candidates for AD. Using approach involving an inducible neurogenin-2 transgene, we have established a robust and reproducible protocol for differentiating human iPSCs into glutamatergic neurons. The AD-iN cultures that result have mature phenotypic and physiological properties, together with AD-like biochemical features that include extracellular ß-amyloid (Aß) accumulation and Tau protein phosphorylation. By screening using a gene set enrichment analysis (GSEA) approach, Graptopetalum paraguayense (GP) has been identified as a potential therapeutic agent for AD from among a range of Chinese herbal medicines. We found that administration of a GP extract caused a significantly reduction in the AD-associated phenotypes of the iNs, including decreased levels of extracellular Aß40 and Aß42, as well as reduced Tau protein phosphorylation at positions Ser214 and Ser396. Additionally, the effect of GP was more prominent in AD-iNs compared to non-diseased controls. These findings provide valuable information that suggests moving extracts of GP toward drug development, either for treating AD or as a health supplement to prevent AD. Furthermore, our human iN-based platform promises to be a useful strategy when it is used for AD drug discovery.

The protective effects of taurine on oxidative stress, cytoplasmic free-Ca2+ and apoptosis of pufferfish (Takifugu obscurus) under low temperature stress.

The present study was aimed to investigate the low temperature toxicity and its protection by taurine in pufferfish. The experimental basal diets supplemented with taurine at the rates of 250 (control), 550, 850, 1140, 1430, 1740 mg kg-1 were fed to fish for 8 weeks. The results showed that fish fed diet with taurine had significantly improved weight gain and specific growth rate. After the feeding trial, the fish were then exposed to low temperature stress. The results showed that low temperature stress could induce reactive oxygen species (ROS) generation, disturb the cytoplasm Ca2+ homeostasis, and lead to oxidative stress and apoptosis. Compared with the control group, dietary taurine supplementation groups increased antioxidant enzyme genes such as manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and catalase (CAT), heat shock proteins (HSP70) and complement C3 (C3) mRNA levels under low temperature stress. Meanwhile, dietary taurine supplementation groups reduced ROS generation, and stabilized the cytoplasm Ca2+ under low temperature stress. Furthermore, dietary taurine supplementation groups reduced apoptosis via decreasing caspase-3 activity. This is the first report to demonstrate the mechanisms of taurine against low temperature stress in fish.

Protective effect of Nelumbo nucifera extracts on beta amyloid protein induced apoptosis in PC12 cells, in vitro model of Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia in the elderly. ß-Amyloid (Aß) has been proposed to play a role in the pathogenesis of AD. Deposits of insoluble Aß are found in the brains of patients with AD and are one of the pathological hallmarks of the disease, but the underlying signaling pathways are poorly understood. In order to develop antidementia agents with potential therapeutic value, we examined the inhibitory effect of the Nelumbo nucifera seed embryo extracts on to the aggregated amyloid ß peptide (agg Aß1-40)-induced damage of differentiated PC-12 cells (dPC-12), a well-known cell model for AD. In the present study, seed embryos of N. nucifera were extracted with 70% methanol in water and then separated into hexane, ethyl acetate, n-butanol, and water layers. Among them, only the n-butanol layer showed strong activity and was therefore subjected to separation on Sephadex LH-20 chromatography. Two fractions showing potent activity were found to significantly inhibit Aß1-40 toxicity on dPC-12 cells in increasing order of concentration (10-50 µg/mL). Further purification and characterization of these active fractions identified them to be flavonoids such as rutin, orientin, isoorientin, isoquercetrin, and hyperoside. 2,2-Diphenyl-1-picrylhydrazyl hydrate scavenging activity of the extracts was also carried out to ascertain the possible mechanism of the activity.

Growth performance and protective effect of vitamin E on oxidative stress pufferfish (Takifugu obscurus) following by ammonia stress.

This study was conducted to determine the effects of vitamin E on growth performance, biochemical parameters, and antioxidant capacity of pufferfish (Takifugu obscurus) exposed to ammonia stress. The experimental basal diets supplemented with vitamin E at the rates of 2.31 (control), 21.84, 40.23, 83.64, 158.93, and 311.64 mg kg-1 dry weight were fed to fish for 60 days. After the feeding trial, the fish were exposed to 100 mg L-1 ammonia-nitrogen for 48 h. The results shown that the vitamin E group significantly improved weight gain, specific growth rate, and the expression levels of growth hormone receptors and insulin-like growth factor. Fish fed with the vitamin E-supplemented diets could increase plasma alkaline phosphatase activities and decrease plasma glutamicoxalacetic transaminase and glutamic-pyruvic transaminase activities. The relative expression levels of heat shock proteins (40.23-311.64 mg kg-1 vitamin E diet group), manganese superoxide dismutase (83.64-158.93 mg kg-1 vitamin E diet group), catalase (40.23-311.64 mg kg-1 vitamin E diet group), and glutathione reductase (40.23-311.64 mg kg-1 vitamin E diet group) were upregulated. On the other hand, the decreased level of reactive oxygen species (ROS) was observed in the 83.64-311.64 mg kg-1 vitamin E additive group. These results showed that vitamin E might have a potentially useful role as an effective antioxidant to improve resistance in pufferfish.

Effect of dietary astaxanthin on the growth performance, non-specific immunity, and antioxidant capacity of pufferfish (Takifugu obscurus) under high temperature stress.

The present study was conducted to investigate the effects of astaxanthin on growth performance, biochemical parameters, ROS production, and immune-related gene expressions of the pufferfish (Takifugu obscurus) under high temperature stress. The experimental basal diets supplemented with astaxanthin at the rates of 0 (control), 20, 40, 80, 160, and 320 mg kg-1 were fed to fish for 8 weeks. The results showed that the fish fed diet with 80, 160, and 320 mg kg-1 astaxanthin significantly improved weight gain and specific growth rate. Furthermore, fish fed the moderate dietary astaxanthin increased plasma alkaline phosphatase activities, and decrease plasma aspartate aminotransferase and alanine aminotransferase activities. After the feeding trial, the fish were exposed to high temperature stress for 48 h. The results shown that astaxanthin could suppress ROS production induced by high temperature stress. Meanwhile, compared with the control group, the astaxanthin groups increased SOD, CAT, and HSP70 mRNA levels under high temperature stress. These results showed that the basal diet supplemented with 80-320 mg kg-1 astaxanthin could enhance growth, nonspecific immune responses, and antioxidant defense system and improve resistance against high temperature stress in pufferfish.

Untargeted Proteomics and Systems-Based Mechanistic Investigation of Artesunate in Human Bronchial Epithelial Cells.

The antimalarial drug artesunate is a semisynthetic derivative of artemisinin, the principal active component of a medicinal plant Artemisia annua. It is hypothesized to attenuate allergic asthma via inhibition of multiple signaling pathways. We used a comprehensive approach to elucidate the mechanism of action of artesunate by designing a novel biotinylated dihydroartemisinin (BDHA) to identify cellular protein targets of this anti-inflammatory drug. By adopting an untargeted proteomics approach, we demonstrated that artesunate may exert its protective anti-inflammatory effects via direct interaction with multiple proteins, most importantly with a number of mitochondrial enzymes related to glucose and energy metabolism, along with mRNA and gene expression, ribosomal regulation, stress responses, and structural proteins. In addition, the modulatory effects of artesunate on various cellular transcription factors were investigated using a transcription factor array, which revealed that artesunate can simultaneously modulate multiple nuclear transcription factors related to several major pro- and anti-inflammatory signaling cascades in human bronchial epithelial cells. Artesunate significantly enhanced nuclear levels of nuclear factor erythroid-2-related factor 2 (Nrf2), a key promoter of antioxidant mechanisms, which is inhibited by the Kelch-like ECH-associated protein 1 (Keap1). Our results demonstrate that, like other electrophilic Nrf2 regulators, artesunate activates this system via direct molecular interaction/modification of Keap1, freeing Nrf2 for transcriptional activity. Altogether, the molecular interactions and modulation of nuclear transcription factors provide invaluable insights into the broad pharmacological actions of artesunate in inflammatory lung diseases and related inflammatory disorders.

A Safety Study on Honghua Injection Based on Literature / 中国中医药信息杂志

Objective To conduct a comprehensive evaluation on safety of Honghua Injection through adopting the method of the evidence-based method;To provide reference for clinical reasonable application of Honghua Injection. Methods Computers were used to retrieve some Chinese databases, such as China Biology Medicine, China National Knowledge Infrastructure, Wangfang Database and VIP database. At the same time, other search methods were employed, up to July 2013, including all research types about Honghua Injection. The adverse reactions in the reports of published literature were analyzed by description and statistical analysis. Results Sixty-nine researches on Honghua Injection were included. The total cases of adverse drug reaction (ADR) were 1111, among which male cases were 568 (51%), and female cases were 543 (49%). Thirty-six (52%) papers described ADR of Honghua Injection in detail, and thirty-three (48%) papers just mentioned ADR or did not describe ADR in detail. Skin, skin accessories damage and pathological changes in circulatory system were main contents of ADR. In terms of original diseases, diseases of circulatory system play an important role. Solvent medium was largely in line with its product specification requirements. Most ADR appeared when the drug was used for the first time, from 5 minutes to 5 days. Conclusion The current published literature data show that severe ADR does not happen after the intervention of Honghua Injection.