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Taspine is a natural product that suppresses P2X4 receptor activity via phosphoinositide 3-kinase inhibition

Nadzirin IB, Fortuny-Gomez A, Ngum N, Richards D, Ali S, Searcey M, et al.

Br J Pharmacol, 2021 Dec;178(24):4859-4872.
PMID: 34398973 DOI: 10.1111/bph.15663

BACKGROUND AND PURPOSE: P2X4 is a ligand-gated cation channel activated by extracellular ATP involved in neuropathic pain, inflammation and arterial tone.
EXPERIMENTAL APPROACH: Natural products were screened against human or mouse P2X4 activity using fura-2 loaded 1321N1 cells for measurement of intracellular Ca2+ responses. Whole-cell currents were measured by patch clamp. Human primary macrophage chemokine release was used to assess effect of taspine on inflammatory cell function. An enzymatic assay was performed to assess the effect of taspine on recombinant PI3-kinase.
KEY RESULTS: A natural product screen identified taspine as an inhibitor of human P2X4 activity. Taspine inhibits human and mouse P2X4-mediated Ca2+ influx in 1321N1 cells expressing receptors but lacked activity at human P2X2, P2X3, P2X2/3 and P2X7 receptors. Taspine inhibited the maximal response at human and mouse P2X4 but effective on ATP potency. Taspine has a slow onset rate (~15 min for half-maximal inhibition), irreversible over 30 min of washout. Taspine inhibits P2X4-mediated Ca2+ signalling in mouse BV-2 microglia cells and human primary macrophage. Taspine inhibited P2X4-mediated CXCL5 secretion in human primary macrophage. Taspine reversed ivermectin-induced potentiation of P2X4 currents in 1321N1 stably expressing cells. The PI3-kinase inhibitor LY294002 mimicked the properties of taspine on P2X4-mediated Ca2+ influx and whole-cell currents. Taspine directly inhibited the enzymatic activity of recombinant PI3-kinase in a competitive manner.
CONCLUSION AND IMPLICATIONS: Taspine is a novel natural product P2X4 receptor inhibitor, mediating its effect through PI3-kinase inhibition rather than receptor antagonism. Taspine can inhibit the pro-inflammatory signalling by P2X4 in human primary macrophage.
Fulltext Long-term impact of oral surgery with or without amoxicillin on the oral microbiome-A prospective cohort study

Menon RK, Gomez A, Brandt BW, Leung YY, Gopinath D, Watt RM, et al.

Sci Rep, 2019 12 10;9(1):18761.
PMID: 31822712 DOI: 10.1038/s41598-019-55056-3

Routine postoperative antibiotic prophylaxis is not recommended for third molar extractions. However, amoxicillin still continues to be used customarily in several clinical practices worldwide to prevent infections. A prospective cohort study was conducted in cohorts who underwent third molar extractions with (group EA, n = 20) or without (group E, n = 20) amoxicillin (250 mg three times daily for 5 days). Further, a control group without amoxicillin and extractions (group C, n = 17) was included. Salivary samples were collected at baseline, 1-, 2-, 3-, 4-weeks and 3 months to assess the bacterial shift and antibiotic resistance gene changes employing 16S rRNA gene sequencing (Illumina-Miseq) and quantitative polymerase chain reaction. A further 6-month follow-up was performed for groups E and EA. Seven operational taxonomic units reported a significant change from baseline to 3 months for group EA (adjusted p 0.05). In conclusion, the salivary microbiome is resilient to an antibiotic challenge by a low-dose regimen of amoxicillin. Further studies evaluating the effect of routinely used higher dose regimens of amoxicillin on gram-negative bacteria and antibiotic resistance genes are warranted.
The distinct associations of ingroup attachment and glorification with responses to the coronavirus pandemic: Evidence from a multilevel investigation in 21 countries

McLamore Q, Syropoulos S, Leidner B, Hirschberger G, van Bezouw MJ, Rovenpor D, et al.

Br J Soc Psychol, 2023 Apr;62(2):992-1012.
PMID: 36507575 DOI: 10.1111/bjso.12614

While public health crises such as the coronavirus pandemic transcend national borders, practical efforts to combat them are often instantiated at the national level. Thus, national group identities may play key roles in shaping compliance with and support for preventative measures (e.g., hygiene and lockdowns). Using data from 25,159 participants across representative samples from 21 nations, we investigated how different modalities of ingroup identification (attachment and glorification) are linked with reactions to the coronavirus pandemic (compliance and support for lockdown restrictions). We also examined the extent to which the associations of attachment and glorification with responses to the coronavirus pandemic are mediated through trust in information about the coronavirus pandemic from scientific and government sources. Multilevel models suggested that attachment, but not glorification, was associated with increased trust in science and compliance with federal COVID-19 guidelines. However, while both attachment and glorification were associated with trust in government and support for lockdown restrictions, glorification was more strongly associated with trust in government information than attachment. These results suggest that both attachment and glorification can be useful for promoting public health, although glorification's role, while potentially stronger, is restricted to pathways through trust in government information.
Fulltext Author Correction: A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic

Wang K, Goldenberg A, Dorison CA, Miller JK, Uusberg A, Lerner JS, et al.

Nat Hum Behav, 2022 Sep;6(9):1318-1319.
PMID: 36002766 DOI: 10.1038/s41562-022-01441-4
Fulltext A multi-country test of brief reappraisal interventions on emotions during the COVID-19 pandemic

Wang K, Goldenberg A, Dorison CA, Miller JK, Uusberg A, Lerner JS, et al.

Nat Hum Behav, 2021 Aug;5(8):1089-1110.
PMID: 34341554 DOI: 10.1038/s41562-021-01173-x

The COVID-19 pandemic has increased negative emotions and decreased positive emotions globally. Left unchecked, these emotional changes might have a wide array of adverse impacts. To reduce negative emotions and increase positive emotions, we tested the effectiveness of reappraisal, an emotion-regulation strategy that modifies how one thinks about a situation. Participants from 87 countries and regions (n = 21,644) were randomly assigned to one of two brief reappraisal interventions (reconstrual or repurposing) or one of two control conditions (active or passive). Results revealed that both reappraisal interventions (vesus both control conditions) consistently reduced negative emotions and increased positive emotions across different measures. Reconstrual and repurposing interventions had similar effects. Importantly, planned exploratory analyses indicated that reappraisal interventions did not reduce intentions to practice preventive health behaviours. The findings demonstrate the viability of creating scalable, low-cost interventions for use around the world. PROTOCOL REGISTRATION: The stage 1 protocol for this Registered Report was accepted in principle on 12 May 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.c.4878591.v1.
Fulltext In COVID-19 Health Messaging, Loss Framing Increases Anxiety with Little-to-No Concomitant Benefits: Experimental Evidence from 84 Countries

Dorison CA, Lerner JS, Heller BH, Rothman AJ, Kawachi II, Wang K, et al.

Affect Sci, 2022 Sep;3(3):577-602.
PMID: 36185503 DOI: 10.1007/s42761-022-00128-3

The COVID-19 pandemic (and its aftermath) highlights a critical need to communicate health information effectively to the global public. Given that subtle differences in information framing can have meaningful effects on behavior, behavioral science research highlights a pressing question: Is it more effective to frame COVID-19 health messages in terms of potential losses (e.g., "If you do not practice these steps, you can endanger yourself and others") or potential gains (e.g., "If you practice these steps, you can protect yourself and others")? Collecting data in 48 languages from 15,929 participants in 84 countries, we experimentally tested the effects of message framing on COVID-19-related judgments, intentions, and feelings. Loss- (vs. gain-) framed messages increased self-reported anxiety among participants cross-nationally with little-to-no impact on policy attitudes, behavioral intentions, or information seeking relevant to pandemic risks. These results were consistent across 84 countries, three variations of the message framing wording, and 560 data processing and analytic choices. Thus, results provide an empirical answer to a global communication question and highlight the emotional toll of loss-framed messages. Critically, this work demonstrates the importance of considering unintended affective consequences when evaluating nudge-style interventions.