Caffeine intake and anxiety: a meta-analysis

The results from studies on relationship between caffeine intake and risk of anxiety remains controversial, so we conducted a meta-analysis to summarize the evidence about the association between caffeine intake and risk of anxiety. Relevant articles were identified by researching PubMed, Web of Science, Cochrane library, Embase, CNKI, WANFANG DATA, SinoMed and VIP from the inception to December, 2022. Three investigators independently sifted through the literature, extracted the data, and evaluated the quality of the included studies based on predetermined selection criteria and assessed articles with Risk of bias assessment tool for Cochrane systematic reviews and analytical cross-sectional study quality assessment tool from JBI PACES. After assessing the quality of the literature, meta-analysis was performed using Revman 5.4 and Stata 12.0. Data were obtained from eight articles, and 546 participants from 14 studies in eight articles from healthy populations were included in the caffeine-anxiety analyses. As the scales used to assess anxiety vary in the literature, we chose standardized mean difference as the outcome indicator. In terms of overall effect, the results of the meta-analysis showed that caffeine intake increased the risk of anxiety [SMD = 0.94, 95% Cl = (0.28, 1.60), p < 0.05]. After suspecting that dose size might be responsible for the heterogeneity by sensitivity analysis, we performed subgroup analysis according to dose size and found that low-dose caffeine intake moderately increased the risk of anxiety [SMD = 0.61, 95%Cl = (0.42, 0.79), p < 0.05], whereas high-dose caffeine intake had a highly significant increase in the risk of anxiety [SMD = 2.86, 95%Cl = (2.50, 3.22), p < 0.05]. The results confirm that caffeine intake is associated with an elevated risk of anxiety in healthy individuals without psychiatric disorders, especially when the intake dose is greater than 400 mg

TRPM7 Kinase Controls Calcium Responses in Arterial Thrombosis and Stroke in Mice

Objective: TRPM7 (transient receptor potential cation channel, subfamily M, member 7) is a ubiquitously expressed bifunctional protein comprising a transient receptor potential channel segment linked to a cytosolic alpha-type serine/threonine protein kinase domain. TRPM7 forms a constitutively active Mg2+ and Ca2+ permeable channel, which regulates diverse cellular processes in both healthy and diseased conditions, but the physiological role of TRPM7 kinase remains largely unknown. Approach and Results: Here we show that point mutation in TRPM7 kinase domain deleting the kinase activity in mice (Trpm7(R/R)) causes a marked signaling defect in platelets. Trpm7(R/R) platelets showed an impaired PIP2 (phosphatidylinositol-4,5-bisphosphate) metabolism and consequently reduced Ca2+ mobilization in response to stimulation of the major platelet receptors GPVI (glycoprotein VI), CLEC-2 (C-type lectin-like receptor), and PAR (protease-activated receptor). Altered phosphorylation of Syk (spleen tyrosine kinase) and phospholipase C gamma 2 and beta 3 accounted for these global platelet activation defects. In addition, direct activation of STIM1 (stromal interaction molecule 1) with thapsigargin revealed a defective store-operated Ca2+ entry mechanism in the mutant platelets. These defects translated into an impaired platelet aggregate formation under flow and protection of the mice from arterial thrombosis and ischemic stroke in vivo. Conclusions: Our results identify TRPM7 kinase as a key modulator of phospholipase C signaling and store-operated Ca2+ entry in platelets. The protection of Trpm7(R/R) mice from acute ischemic disease without developing intracranial hemorrhage indicates that TRPM7 kinase might be a promising antithrombotic target

Studien über die Rolle von Calcium Kanälen und der Kinase Dömane von transient receptor potential melastatin-like 7 (TRPM7) für die Thrombozytenfunktion

Platelet activation and aggregation are essential processes for the sealing of injured vessel walls and preventing blood loss. Under pathological conditions, however, platelet aggregation can lead to uncontrolled thrombus formation, resulting in irreversible vessel occlusion. Therefore, precise regulation of platelet activation is required to ensure efficient platelet plug formation and wound sealing but also to prevent uncontrolled thrombus formation. Rapid elevations in the intracellular levels of cations are a core signaling event during platelet activation. In this thesis, the roles of Ca2+ and Mg2+ channels in the regulation of platelet function were investigated. Orai1, the major store-operated calcium (SOC) channel in platelets, is not only vital for diverse signaling pathways, but may also regulate receptor-operated calcium entry (ROCE). The coupling between the Orai1 signalosome and canonical transient receptor potential channel (TRPC) isoforms has been suggested as an essential step in the activation of store-operated calcium entry (SOCE) and ROCE in human platelets. However, the functional significance of the biochemical interaction between Orai and TRPC isoforms still remains to be answered. In the first part of this thesis, the functional crosstalk between Orai1 and TRPC6 was addressed. Orai1-mediated SOCE was found to enhance the activity of phospholipases (PL) C and D, to increase diacylglycerol (DAG) production and finally to regulate TRPC6-mediated ROCE via DAG, indicating that the regulation of TRPC6 channel activity seems to be independent of the physical interaction with Orai1. Furthermore, Orai1 and TRPC6 double deficiency led to a reduced Ca2+ store content and basal cytoplasmic Ca2+ concentrations, but surprisingly also enhanced ATP secretion, which may enhance Ca2+ influx via P2X1 and compensate for the severe Ca2+ deficits seen in double mutant platelets. In addition, Orai1 and TRPC6 were not essential for G protein-coupled receptor (GPCR)-mediated platelet activation, aggregation and thrombus formation. Transient receptor potential melastatin-like 7 (TRPM7) contains a cytosolic serine/threonine protein kinase. To date, a few in vitro substrates of the TRPM7 kinase have been identified, however, the physiological role of the kinase remains unknown. In the second part of this thesis, mice with a point mutation which blocks the catalytic activity of the TRPM7 kinase (Trpm7KI) were used to study the role of the TRPM7 kinase in platelet function. In Trpm7KI platelets phosphatidylinositol-4,5-bisphosphate (PIP2) metabolism and Ca2+ mobilization were severely impaired upon glycoprotein (GP) VI activation, indicating that the TRPM7 kinase regulates PLC function. This signaling defect in Trpm7KI platelets resulted in impaired aggregate formation under flow and protected animals from arterial thrombosis and ischemic brain infarction. Altogether, these results highlight the kinase domain of TRPM7 as a pivotal signaling moiety implicated in the pathogenesis of thrombosis and cerebrovascular events.Die Aktivierung und Aggregation von Thrombozyten sind zwei elementare Prozesse für das Abdichten verletzter Gefäßwände und damit zur Verhinderung von exzessivem Blutverlust. Unter pathologischen Bedingungen kann die Thrombozytenaggregation jedoch zur unkontrollierten Thrombusbildung und folglich zum irreversiblen Gefäßverschluss führen. Daher ist eine präzise Regulation der Thrombozytenaktivierung wichtig, um effizient Gefäßverletzungen zu schließen aber gleichzeitig eine unkontrollierte Thrombusbildung zu verhindern. Schnelle Veränderungen der zytoplasmatischen Konztentration von Kationen stellen ein Kernelement der Signaltransduktion während der Plättchenaktivierung dar. In dieser Arbeit wurden die Rolle von Ca2+ und Mg2+ Kanälen in der Regulation der Thrombozytenfunktion untersucht. Orai1, der bedeutendste store-operated calcium (SOC) Kanal in Thrombozyten, ist nicht nur entscheidend für verschiedene Signalwege, sondern reguliert möglicherweise auch receptor-operated calcium entry (ROCE). Die Kopplung zwischen dem Orai1-Signalkomplex und canonical transient receptor potential channel (TRPC) Isoformen wurde als entscheidender Schritt in der Aktivierung in der Aktivierung von store-operated calcium entry (SOCE) und ROCE in humanen Thrombozyten vermutet. Die Frage nach der funktionellen Relevanz der Interaktion zwischen Orai und TRPC Isoformen blieb jedoch unbeantwortet. Im ersten Teil dieser Arbeit wurde der funktionelle Crosstalk zwischen Orai1 und TRPC6 adressiert. Hierbei zeigte sich, das Orai1-vermittelter SOCE die Aktivität der Phosholipasen (PL) C und D steigert, die Diacylglycerol (DAG) Produktion verstärkt und schließlich TRPC6-vermittelten ROCE via DAG reguliert, was darauf hindeutet, dass die Regulation der TRPC6 Kanalaktivität unabhängig von einer direkten Interaktion mit Orai1 zu sein scheint. Darüber hinaus führte die Doppeldefizienz von Orai1 und TRPC6 zu verringerten Ca2+ Konzentrationen in intrazellulären Ca2+-Speichern und im Zytoplasma der Thrombozyten. Überraschenderweise war auch die ATP-Sekretion erhöht, was eventuell den Ca2+-Einstrom durch P2X1 verstärkt und möglicherweise das starke Ca2+-Defizit in den doppeldefizienten Thrombozyten kompensiert. Außerdem wurde gezeigt, dass Orai1 und TRPC6 nicht für die Aktivierung und Aggregation von Thrombozyten sowie für die Thrombusbildung mittlels G protein-gekoppelter Rezeptoren (GPCR) benötigt werden. Transient receptor potential melastatin-like 7 (TRPM7) enthält eine zytosolische Serin/Threonin-Kinase Domain. Bislang wurden zwar wenige in vitro Substrate der TRPM7 Kinase identifiziert, jedoch ist die physiologische Rolle dieser Kinase immer noch unbekannt. Im zweiten Teil dieser Arbeit wurden Mäuse mit einer Punktmutation, welche die katalytische Aktivität der TRPM7 Kinase blockiert (Trpm7KI) eingesetzt um die Rolle der TRPM7 Kinase für die Funktion von Thrombozyten zu untersuchen. In Trpm7KI Thrombozyten war der Metabolismus von phosphatidylinositol-4,5-bisphosphat (PIP2) und die Ca2+-Mobilisierung nach Aktivierung des Rezeptors Glykoprotein (GP) VI schwer beeinträchtigt, was darauf hindeutet, dass die Aktivität der TRPM7 Kinase die Funktion der PLC reguliert. Aus diesem Signaltransduktionsdefekt in Trpm7KI Thrombozyten resultierte eine verringerte Aggregatbildung unter Flussbedingungen und ein Schutz der Tiere vor arteriellen Thrombosen und ischämischem Schlaganfall. Zusammenfassend heben diese Ergebnisse die Kinasedomäne von TRPM7 als einen ausschlaggebenden Bestandteil in Signalkaskaden hervor und implizieren eine Rolle dieser Domäne in der Pathogenese von ischämischen Kardio- und zerebrovaskulären Erkrankungen

Apigenin Restricts FMDV Infection and Inhibits Viral IRES Driven Translational Activity

Foot-and-mouth disease (FMD) is a highly contagious disease of domestic and wild ruminants that is caused by FMD virus (FMDV). FMD outbreaks have occurred in livestock-containing regions worldwide. Apigenin, which is a flavonoid naturally existing in plant, possesses various pharmacological effects, including anti-inflammatory, anticancer, antioxidant and antiviral activities. Results show that apigenin can inhibit FMDV-mediated cytopathogenic effect and FMDV replication in vitro. Further studies demonstrate the following: (i) apigenin inhibits FMDV infection at the viral post-entry stage; (ii) apigenin does not exhibit direct extracellular virucidal activity; and (iii) apigenin interferes with the translational activity of FMDV driven by internal ribosome entry site. Studies on applying apigein in vivo are required for drug development and further identification of potential drug targets against FDMV infection

Cyclin-dependent Kinase 1 (CDK1) in Pacific white shrimp (Litopenaeus vannamei): Molecular characterization and its role in response to cold stress

Cyclin-dependent kinases (CDKs) are a large family of proteins exerting different regulatory functions in eukaryotic cells, including control over the cell cycle and gene transcription. CDK1 controls the cell cycle and promotes cell proliferation by regulating the initiation and transition of the G2/M phase. Similar to mammals, CDK1 has also been characterized in arthropods; however, its functions and physiological importance in crustaceans remain unknown. Our pervious transcriptomic data indicated that CDK1 was a candidate cold-stress response gene in the Pacific white shrimp (Litopenaeus vannamei). Therefore, in the present study, the full-length sequence of CDK1 (LvCDK1) was obtained from L. vannamei containing a conserved PSTAIRE sequence and ATP-binding region. The expression of LvCDK1 is tissue-specific, with relatively higher in the hepatopancreas. The in situ hybridization (ISH) signals for LvCDK1 were present in the distal zone of hepatopancreas and mainly located in the cytoplasm and nucleus. The expression of LvCDK1 in hepatopancreatic was sensitive to environmental temperature. Furthermore, under cold stress, knockdown of LvCDK1 led to increased mortality in shrimp. Our study provides the first evidence of LvCDK1 responding to cold stress in shrimps. This mechanism for modifying the transcriptional roles of LvCDK1 may show new light on the molecular regulation of crustaceans in response to cold stress

Shrub Diversity and Niche Characteristics in the Initial Stage of Reconstruction of Low-Efficiency Cupressus funebris Stands

The upper reaches of the Yangtze River are a very important ecological barrier in China, but the ecological benefits of large-scale Cupressus funebris Endl.plantations are low. This study investigated 12 plantations of different compositions and densities, including two densities of Cinnamomum septentrionale Hand.-Mazz. (Cs), Alnus cremastogyne Burk. (Ac), and Toona sinensis (A. Juss.) Roem. (Ts), and mixed plantations of Cs + Ac (CA), Ts + Cs (TC), Ts + Ac (TA), and Ac + Ts + Cs (ATC) and the cutting-blank (CB), and, at the same time, the unreconstructed pure C. funebris (Cf) forest was set as the control. We aimed to explore the influence mechanism of upper tree composition and density on shrub diversity, as well as the relationship between shrub diversity and niche. Our research results are as follows: (1) Among all the patterns, the TA, CA, and TC patterns are the most conducive to improving the diversity of shrubs. The composition and density of different trees have a great influence on the diversity of shrubs. (2) Niche is closely related to the diversity of shrubs. In the patterns of low niche overlap between dominant shrubs, the diversity of shrubs is greater. These results contribute to a deeper understanding of the relationship between the diversity of overstory and shrubs, and reveals the relationship between niche and diversity

Additional file 1: Table S1. of Isolation and full-genome sequencing of Seneca Valley virus in piglets from China, 2016

List of primers used in the study. (DOCX 19 kb

Regulation of “Right Ankle Dorsiflexion” Motor Imagery on Brain Function of Spinal Cord Injury: A FOCA-Based Prospective Study

Background: Motor dysfunction is the main functional disability after spinal cord injury (SCI), seriously affecting the life and work of patients. In addition to spinal cord damage, the brain undergoes structural and functional plastic changes. This study explored brain function remodeling in patients with SCI and the effect of right ankle dorsiflexion motor imagery task on brain function. Methods: This prospective study enrolled 11 patients with SCI and dyskinesia of the right lower limb and 12 healthy subjects at the General Hospital of Western Theater Command PLA (January 2015 to December 2016). They underwent functional magnetic resonance imaging (fMRI) in the resting state and the “right ankle dorsiflexion” motor imagery task state. Four-dimensional (spatiotemporal) concordance (FOCA) of local neuronal activity was used for fMRI image analysis. The differences between SCI patients and healthy subjects were compared using the two-sample t-test. Results: In the resting state, compared with healthy subjects, patients with SCI showed decreased FOCA in the left putamen, right caudate nucleus, and right superior occipital gyrus and increased FOCA in the left precentral gyrus. In the right ankle dorsiflexion motor imagery task state, FOCAs in the right inferior temporal gyrus and left inferior parietal lobule were decreased in patients with SCI. Conclusions: After SCI, a series of changes in the structure and function of the brain occur. Research on brain plasticity after SCI might help explore the central mechanisms underlying functional recovery after treatments, providing more therapeutic strategies for SCI