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1.
Front Mol Neurosci ; 15: 812479, 2022.
Article in English | MEDLINE | ID: covidwho-1686515

ABSTRACT

The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.

2.
Int Health ; 2021 Nov 29.
Article in English | MEDLINE | ID: covidwho-1545985

ABSTRACT

BACKGROUND: Knowing the spatiotemporal pattern of the early geographic spread of coronavirus disease 2019 (COVID-19) would inform the preparedness for a possible recurrence of COVID-19. METHODS: We ascertained the number of confirmed cases during the early spread of COVID-19 during the Wuhan outbreak in 2020 and the Nanjing outbreak in 2021. RESULTS: We observed a speeding-up pattern of geographic spread, in particular to cities of no particular orientation then outflowing to commercial cities during the first month of both the Wuhan and Nanjing outbreaks. CONCLUSION: Re-emergence of COVID-19 indicates it is becoming endemic, with new outbreaks and a risk of increased transmission remaining a challenge to local public health institutions. Social distancing and lockdowns should continue in response to any potential widespread and focal outbreaks.

3.
Acta Pharmacol Sin ; 42(12): 2155-2172, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1209738

ABSTRACT

LianhuaQingwen capsule, prepared from an herbal combination, is officially recommended as treatment for COVID-19 in China. Of the serial pharmacokinetic investigations we designed to facilitate identifying LianhuaQingwen compounds that are likely to be therapeutically important, the current investigation focused on the component Glycyrrhiza uralensis roots (Gancao). Besides its function in COVID-19 treatment, Gancao is able to induce pseudoaldosteronism by inhibiting renal 11ß-HSD2. Systemic and colon-luminal exposure to Gancao compounds were characterized in volunteers receiving LianhuaQingwen and by in vitro metabolism studies. Access of Gancao compounds to 11ß-HSD2 was characterized using human/rat, in vitro transport, and plasma protein binding studies, while 11ß-HSD2 inhibition was assessed using human kidney microsomes. LianhuaQingwen contained a total of 41 Gancao constituents (0.01-8.56 µmol/day). Although glycyrrhizin (1), licorice saponin G2 (2), and liquiritin/liquiritin apioside (21/22) were the major Gancao constituents in LianhuaQingwen, their poor intestinal absorption and access to colonic microbiota resulted in significant levels of their respective deglycosylated metabolites glycyrrhetic acid (8), 24-hydroxyglycyrrhetic acid (M2D; a new Gancao metabolite), and liquiritigenin (27) in human plasma and feces after dosing. These circulating metabolites were glucuronized/sulfated in the liver and then excreted into bile. Hepatic oxidation of 8 also yielded M2D. Circulating 8 and M2D, having good membrane permeability, could access (via passive tubular reabsorption) and inhibit renal 11ß-HSD2. Collectively, 1 and 2 were metabolically activated to the pseudoaldosterogenic compounds 8 and M2D. This investigation, together with such investigations of other components, has implications for precisely defining therapeutic benefit of LianhuaQingwen and conditions for its safe use.


Subject(s)
Antiviral Agents/pharmacokinetics , COVID-19/drug therapy , Drugs, Chinese Herbal/pharmacokinetics , Phytochemicals/pharmacokinetics , 11-beta-Hydroxysteroid Dehydrogenase Type 2/antagonists & inhibitors , 11-beta-Hydroxysteroid Dehydrogenase Type 2/metabolism , Administration, Oral , Animals , Antiviral Agents/administration & dosage , Antiviral Agents/adverse effects , Biological Availability , Biotransformation , Capsules , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/adverse effects , Female , Glycyrrhiza/adverse effects , HEK293 Cells , Humans , Liddle Syndrome/chemically induced , Liddle Syndrome/enzymology , Male , Patient Safety , Phytochemicals/administration & dosage , Phytochemicals/adverse effects , Rats, Sprague-Dawley , Risk Assessment
4.
Preprint in English | bioRxiv | ID: ppbiorxiv-439088

ABSTRACT

Angiotensin-converting enzyme-2 (ACE2) has been recognized as an entry receptor of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into the host cells while bats has been suspected as natural host of SARS-CoV-2. However, the detail of intermediate host or the route of transmission of SARS-CoV-2 is still unclear. In this study, we analyze the conservation of ACE2 gene in 11 laboratory and wild animals that live in close proximity either with Bats or human and further investigated its RNA and protein expression pattern in wild bats, mice and tree shrew. We verified that the wild-bats and mice were belonged to Hipposideros pomona and Rattus norvegicus, respectively. ACE2 gene is highly conserved among all 11 animals species at the DNA level. Phylogenetic analysis based on the ACE2 nucleotide sequences revealed that wild bat and Tree shrew were forming a cluster close to human. We further report that ACE2 RNA expression pattern is highly species-specific in different tissues of different animals. Most notably, we found that the expression pattern of ACE2 RNA and protein are very different in each animal species. In summary, our results suggested that ACE2 gene is highly conserved among all 11 animals species. However, different relative expression pattern of ACE2 RNA and protein in each animal species is interesting. Further research is needed to clarify the possible connection between different relative expression pattern of ACE2 RNA and protein in different laboratory and wild animal species and the susceptibility to SARS-CoV-2 infection.

5.
Acta Pharmacol Sin ; 43(1): 64-75, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1142428

ABSTRACT

Coronavirus disease 2019 (COVID-19) broke out in December 2019. Due its high morbility and mortality, it is necessary to summarize the clinical characteristics of COVID-19 patients to provide more theoretical basis for future treatment. In the current study, we conducted a retrospective analysis of the clinical characteristics of COVID-19 patients and explored the risk factors for the severity of illness. A total of 101 COVID-19 patients hospitalized in Leishenshan Hospital (Wuhan, China) was classified into three sub-types: moderate (n = 47), severe (n = 36), and critical (n = 18); their clinical data were collected from the Electronic Medical Record. We showed that among the 101 COVID-19 patients, the median age was 62 years (IQR 51-74); 50 (49.5%) patients were accompanied by hypertension, while 25 (24.8%) and 22 (21.8%) patients suffered from diabetes and heart diseases, respectively, with complications. All patients were from Wuhan who had a definite history of exposure to the epidemic area. Multivariate logistic regression analysis revealed that older age, diabetes, chronic liver disease, percentage of neutrophils (N%) > 75%, CRP > 4 mg/L, D-dimer > 0.55 mg/L, IL-2R > 710 U/mL, IL-8 > 62 pg/mL, and IL-10 > 9.1 pg/mL were independent variables associated with severe COVID-19. In conclusion, we have identified the independent risk factors for the severity of COVID-19 pneumonia, including older age, diabetes, chronic liver disease, higher levels of N%, CRP, D-dimer, IL-2R, IL-8, and IL-10, providing evidence for more accurate risk prediction.


Subject(s)
COVID-19/pathology , Aged , COVID-19/metabolism , China , Female , Hospitalization , Humans , Interleukin-10/metabolism , Male , Middle Aged , Neutrophils/metabolism , Neutrophils/pathology , Retrospective Studies , Risk Factors , Severity of Illness Index
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