Knockdown of astrocyte elevated gene-1 inhibits proliferation and enhancing chemo-sensitivity to cisplatin or doxorubicin in neuroblastoma cells

<p>Abstract</p> <p>Background</p> <p><it>Astrocyte elevated gene-1 </it>(<it>AEG</it>-<it>1</it>) was originally characterized as a HIV-1-inducible gene in primary human fetal astrocyte. Recent studies highlight a potential role of <it>AEG-1 </it>in promoting tumor progression and metastasis. The aim of this study was to investigate if <it>AEG-1 </it>serves as a potential therapeutic target of human neuroblastoma.</p> <p>Methods</p> <p>We employed RNA interference to reduce <it>AEG-1 </it>expression in human neuroblastoma cell lines and analyzed their phenotypic changes.</p> <p>Results</p> <p>We found that the knockdown of <it>AEG-1 </it>expression in human neuroblastoma cells significantly inhibited cell proliferation and apoptosis. The specific downregulation induced cell arrest in the G₀/G₁phase of cell cycle. In the present study, we also observed a significant enhancement of chemo-sensitivity to cisplatin and doxorubicin by knockdown of <it>AEG-1</it>.</p> <p>Conclusion</p> <p>Our study suggests that overexpressed <it>AEG-1 </it>enhance the tumorogenic properties of neuroblastoma cells. The inhibition of <it>AEG-1 </it>expression could be a new adjuvant therapy for neuroblastoma.</p

Genetic and Antigenic Characterization of an Influenza A(H3N2) Outbreak in Cambodia and the Greater Mekong Subregion during the COVID-19 Pandemic, 2020

Introduction of non-pharmaceutical interventions to control COVID-19 in early 2020 coincided with a global decrease in active influenza circulation. However, between July and November 2020, an influenza A(H3N2) epidemic occurred in Cambodia and in other neighboring countries in the Greater Mekong Subregion in Southeast Asia. We characterized the genetic and antigenic evolution of A(H3N2) in Cambodia and found that the 2020 epidemic comprised genetically and antigenically similar viruses of Clade3C2a1b/131K/94N, but they were distinct from the WHO recommended influenza A(H3N2) vaccine virus components for 2020-2021 Northern Hemisphere season. Phylogenetic analysis revealed multiple virus migration events between Cambodia and bordering countries, with Laos PDR and Vietnam also reporting similar A(H3N2) epidemics immediately following the Cambodia outbreak: however, there was limited circulation of these viruses elsewhere globally. In February 2021, a virus from the Cambodian outbreak was recommended by WHO as the prototype virus for inclusion in the 2021-2022 Northern Hemisphere influenza vaccine. IMPORTANCE The 2019 coronavirus disease (COVID-19) pandemic has significantly altered the circulation patterns of respiratory diseases worldwide and disrupted continued surveillance in many countries. Introduction of control measures in early 2020 against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has resulted in a remarkable reduction in the circulation of many respiratory diseases. Influenza activity has remained at historically low levels globally since March 2020, even when increased influenza testing was performed in some countries. Maintenance of the influenza surveillance system in Cambodia in 2020 allowed for the detection and response to an influenza A(H3N2) outbreak in late 2020, resulting in the inclusion of this virus in the 2021-2022 Northern Hemisphere influenza vaccine

Expression and Correlation of Complement C3 and C4 in Serum and Maternal-Fetal Interface in Patients with Unexplained Recurrent Spontaneous Abortion: A Prospective Cohort Study

Background: In this study, we sought to detect the expression of complement C3 and C4 in serum and maternal-fetal interface in patients with unexplained recurrent spontaneous abortion, and analyze their correlation, in order to explore the clinical significance and role of C3 and C4 in unexplained recurrent spontaneous abortion. Methods: In a prospective cohort study, products of conception of 20 women who underwent curettage due to unexplained recurrent spontaneous abortion in the Department of Obstetrics and Gynecology at the Sichuan Provincial People’s Hospital from December 2021 to December 2022 were chosen as the case group, and 23 healthy early-pregnancy women who underwent elective abortion due to personal reasons during the same period were chosen as the control group. Serum samples before curettage and decidual tissues samples after curettage were collected. C3 and C4 levels in serum samples were detected by immunoturbidimetry, and semi-quantitative scoring analysis was performed after immunohistochemical staining of decidual tissues samples. The correlation between C3 and C4 in serum and decidual tissues was analyzed. Results: The levels of C3 and C4 in serum and decidual tissues in the case group were significantly higher than those in the control group, and the differences were statistically significant (p 0.05). There was no significant correlation between C3 in serum and C3 in decidual tissues, nor between C4 in serum and C4 in decidual tissues in the case group (p > 0.05). Conclusions: The levels of C3 and C4 in serum and decidual tissues in the case group were higher than those in the healthy, normal early pregnancy women. This implies that elevated levels of activated C3 and C4 may be related to the pathogenesis of unexplained recurrent miscarriage. C3 and C4 can be used as early diagnostic criteria for recurrent miscarriage. There is a positive correlation between C3 in serum and C4 in serum in the case group, indicating that different pathways of complement activation may be involved in the pathogenic process of unexplained recurrent miscarriage

Human seasonal influenza under COVID-19 and the potential consequences of influenza lineage elimination.

Annual epidemics of seasonal influenza cause hundreds of thousands of deaths, high levels of morbidity, and substantial economic loss. Yet, global influenza circulation has been heavily suppressed by public health measures and travel restrictions since the onset of the COVID-19 pandemic. Notably, the influenza B/Yamagata lineage has not been conclusively detected since April 2020, and A(H3N2), A(H1N1), and B/Victoria viruses have since circulated with considerably less genetic diversity. Travel restrictions have largely confined regional outbreaks of A(H3N2) to South and Southeast Asia, B/Victoria to China, and A(H1N1) to West Africa. Seasonal influenza transmission lineages continue to perish globally, except in these select hotspots, which will likely seed future epidemics. Waning population immunity and sporadic case detection will further challenge influenza vaccine strain selection and epidemic control. We offer a perspective on the potential short- and long-term evolutionary dynamics of seasonal influenza and discuss potential consequences and mitigation strategies as global travel gradually returns to pre-pandemic levels

COVID-19 Breakthrough Infections in Vaccinated Kidney Transplant Recipients

Coronavirus disease 2019 (COVID-19) is associated with increased morbidity and mortality among kidney transplant recipients (KTRs). The administration of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is the only reliable strategy to prevent COVID-19 and alleviate the severity of COVID-19 in this particular population. The aim of this article was to evaluate the clinical protection by vaccines (breakthrough infections, deaths, and hospitalizations) in KTRs. There were 135 KTRs with COVID-19 breakthrough infections for whom patient-level data were available in PubMed and Web of Science. There was a male predominance (61.4%), 97 were given the standard vaccination regimen, and 38 received three or four doses of the vaccine. The median age was 59.0 (IQR: 49.0–69.0) years. A total of 67 patients were hospitalized, and 10 patients died. In 72.6% of cases, triple-maintenance immunosuppression was employed. The deceased patients were older than the survivors (p p p p < 0.05). Among 16,820 fully vaccinated or boosted KTRs from 14 centers, there were 633 breakthrough infections (3.58%) and 73 associated deaths (0.41%). The center-level breakthrough infection rates varied from 0.21% to 9.29%. These findings highlight the need for booster doses for KTRs. However, more research is needed to define the long-term effectiveness and immunogenicity of booster doses and to identify methods to boost the protective response to vaccination in these immunocompromised patients

BastionHub: a universal platform for integrating and analyzing substrates secreted by Gram-negative bacteria

Gram-negative bacteria utilize secretion systems to export substrates into their surrounding environment or directly into neighboring cells. These substrates are proteins that function to promote bacterial survival: by facilitating nutrient collection, disabling competitor species or, for pathogens, to disable host defenses. Following a rapid development of computational techniques, a growing number of substrates have been discovered and subsequently validated by wet lab experiments. To date, several online databases have been developed to catalogue these substrates but they have limited user options for in-depth analysis, and typically focus on a single type of secreted substrate. We therefore developed a universal platform, BastionHub, that incorporates extensive functional modules to facilitate substrate analysis and integrates the five major Gram-negative secreted substrate types (i.e. from types I–IV and VI secretion systems). To our knowledge, BastionHub is not only the most comprehensive online database available, it is also the first to incorporate substrates secreted by type I or type II secretion systems. By providing the most up-to-date details of secreted substrates and state-of-the-art prediction and visualized relationship analysis tools, BastionHub will be an important platform that can assist biologists in uncovering novel substrates and formulating new hypotheses

Off-season RSV epidemics in Australia after easing of COVID-19 restrictions

Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection (ARI) with the most severe disease in the young and elderly1,2. Non-pharmaceutical interventions (NPIs) and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia, where during 2020 the normal winter epidemics were notably absent3–6. However, in late 2020, unprecedented widespread RSV outbreaks occurred, beginning in spring, and extending into summer across two widely separated states of Australia, Western Australia (WA) and New South Wales (NSW) including the Australian Capital Territory (ACT). Genome sequencing revealed a significant reduction in RSV genetic diversity following COVID-19 emergence except for two genetically distinct RSV-A clades. These clades circulated cryptically, likely localized for several months prior to an epidemic surge in cases upon relaxation of COVID-19 control measures. The NSW/ACT clade subsequently spread to the neighbouring state of Victoria (VIC) and caused extensive outbreaks and hospitalisations in early 2021. These findings highlight the need for continued surveillance and sequencing of RSV and other respiratory viruses during and after the COVID-19 pandemic as mitigation measures introduced may result in unusual seasonality, along with larger or more severe outbreaks in the future

Off-season RSV epidemics in Australia after easing of COVID-19 restrictions

Human respiratory syncytial virus (RSV) is an important cause of acute respiratory infection with the most severe disease in the young and elderly. Non-pharmaceutical interventions and travel restrictions for controlling COVID-19 have impacted the circulation of most respiratory viruses including RSV globally, particularly in Australia, where during 2020 the normal winter epidemics were notably absent. However, in late 2020, unprecedented widespread RSV outbreaks occurred, beginning in spring, and extending into summer across two widely separated regions of the Australian continent, New South Wales (NSW) and Australian Capital Territory (ACT) in the east, and Western Australia. Through genomic sequencing we reveal a major reduction in RSV genetic diversity following COVID-19 emergence with two genetically distinct RSV-A clades circulating cryptically, likely localised for several months prior to an epidemic surge in cases upon relaxation of COVID-19 control measures. The NSW/ACT clade subsequently spread to the neighbouring state of Victoria and to cause extensive outbreaks and hospitalisations in early 2021. These findings highlight the need for continued surveillance and sequencing of RSV and other respiratory viruses during and after the COVID-19 pandemic, as mitigation measures may disrupt seasonal patterns, causing larger or more severe outbreaks