BackgroundThe initiation of atherosclerosis (AS) is attributed to the dysfunction of endothelial cells (ECs) via the inhibition of g protein-coupled estrogen receptor (GPER). In the current study, we assessed the potential of Ginsenoside Rb1 (Rb1) to attenuate the dysfunction of ECs via GPER-mediated PI3K/Akt pathway.Material/MethodsAS was induced in rabbits and then the AS rabbits were treated with Rb1. Thereafter, the ECs were isolated from AS and healthy rabbits, and treated with Rb1. The effect of Rb1 on blood lipid levels in AS rabbits and on apoptosis, inflammatory response, and GPER/PI3K/Akt axis activity in ECs was detected. Furthermore, the activities of GPER and PI3K were modulated to verify the key role of the axis in the anti-AS effect of Rb1.ResultsThe levels of total cholesterol, low-density lipoprotein (LDL), and triglyceride in AS rabbits were suppressed by Rb1 while the high-density lipoprotein (HDL) level was increased. In in vitro assays, Rb1 administration inhibited apoptosis process and the production of pro-inflammation cytokines in AS ECs. The expression levels of GPER, p-PI3K, and p-Akt were upregulated by Rb1, associated with the increased level of Bcl-2 and reduced level of Bax. When the activity of GPER was inhibited by GP-15 in AS ECs, the treatment effect of Rb1 was blocked. However, the activation of PI3K could restore the protective effect of Rb1 after the inhibition of GPER.ConclusionsThe anti-AS potential of Rb1 was exerted by restoring the regular function of ECs via the activation of GPER-mediated PI3K/Akt signaling.
Background
Acute bacterial meningitis (ABM) is a serious health issue in Yemen where civil war, which continues unabated, has crippled the healthcare system. We conducted a nationwide retrospective observational study in Yemeni sentinel hospitals to identify the prevalence, aetiology, vaccination coverage and spatio-temporal pattern of ABM in children aged <5 years before and during the civil war, 2014–20.
Methods
Cerebrospinal fluid samples were collected from hospitalized children and were analysed macroscopically for appearance and microscopically by Gram stain and white blood cell count. Culture and latex agglutination tests were performed. Data on the prevalence of and vaccination coverage for ABM were obtained from the Ministry of Health. Joinpoint regression was used to assess the annual percent change (APC) of ABM prevalence and vaccination coverage. Pearson's correlation was used to evaluate the association between ABM prevalence and vaccination coverage.
Results
In total, 11 339 hospitalized children had suspected cases of ABM (prevalence, 40.07/100 000 of the whole Yemeni population) and 2.6% (293/11 339) of suspected ABM cases were confirmed (prevalence, 1.04/100 000 of the whole Yemeni population). The dominant pathogens were Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae type b (Hib). The civil war reduced the Hib and pneumococcal vaccination coverage (APC = –1.92), reaching its lowest (79.5%) in 2018. The prevalence of suspected ABM increased (APC = 3.46), reaching its maximum (6.08/100 000 of the whole Yemeni population) in 2019. The conflict inversely correlated with the ABM prevalence and vaccination coverage (Pearson correlation coefficient (r), –0.69 to –0.53). Ta'izz region, which was severely affected by the civil war, had the highest prevalence of suspected ABM (120.90/100 000 of the whole Yemeni population) and lowest vaccination coverage (60%).
Conclusions
The civil war had a negative impact on vaccination coverage and coincided with increasing prevalence of ABM in Yemen. Streptococcus pneumoniae is the dominant causative pathogen.
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