The clinical features and immune responses of asymptomatic individuals infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have not been well described. We studied 37 ...asymptomatic individuals in the Wanzhou District who were diagnosed with RT-PCR-confirmed SARS-CoV-2 infections but without any relevant clinical symptoms in the preceding 14 d and during hospitalization. Asymptomatic individuals were admitted to the government-designated Wanzhou People's Hospital for centralized isolation in accordance with policy
. The median duration of viral shedding in the asymptomatic group was 19 d (interquartile range (IQR), 15-26 d). The asymptomatic group had a significantly longer duration of viral shedding than the symptomatic group (log-rank P = 0.028). The virus-specific IgG levels in the asymptomatic group (median S/CO, 3.4; IQR, 1.6-10.7) were significantly lower (P = 0.005) relative to the symptomatic group (median S/CO, 20.5; IQR, 5.8-38.2) in the acute phase. Of asymptomatic individuals, 93.3% (28/30) and 81.1% (30/37) had reduction in IgG and neutralizing antibody levels, respectively, during the early convalescent phase, as compared to 96.8% (30/31) and 62.2% (23/37) of symptomatic patients. Forty percent of asymptomatic individuals became seronegative and 12.9% of the symptomatic group became negative for IgG in the early convalescent phase. In addition, asymptomatic individuals exhibited lower levels of 18 pro- and anti-inflammatory cytokines. These data suggest that asymptomatic individuals had a weaker immune response to SARS-CoV-2 infection. The reduction in IgG and neutralizing antibody levels in the early convalescent phase might have implications for immunity strategy and serological surveys.
Elevated levels of neutrophils have been associated with poor survival in various cancers, but direct evidence supporting a role for neutrophils in the immunopathogenesis of human cancers is lacking.
...A total of 573 patients with gastric cancer were enrolled in this study. Immunohistochemistry and real-time PCR were performed to analyze the distribution and clinical relevance of neutrophils in different microanatomic regions. The regulation and function of neutrophils were assessed both
and
Increased neutrophil counts in the peripheral blood were associated with poor prognosis in gastric cancer patients. In gastric cancer tissues, neutrophils were enriched predominantly in the invasive margin, and neutrophil levels were a powerful predictor of poor survival in patients with gastric cancer. IL17
neutrophils constitute a large portion of IL17-producing cells in human gastric cancer. Proinflammatory IL17 is a critical mediator of the recruitment of neutrophils into the invasive margin by CXC chemokines. Moreover, neutrophils at the invasive margin were a major source of matrix metalloproteinase-9, a secreted protein that stimulates proangiogenic activity in gastric cancer cells. Accordingly, high levels of infiltrated neutrophils at the invasive margin were positively correlated with angiogenesis progression in patients with gastric cancer.
These data provide direct evidence supporting the pivotal role of neutrophils in gastric cancer progression and reveal a novel immune escape mechanism involving fine-tuned collaborative action between cancer cells and immune cells in the distinct tumor microenvironment.
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We report acute antibody responses to SARS-CoV-2 in 285 patients with COVID-19. Within 19 days after symptom onset, 100% of patients tested positive for antiviral immunoglobulin-G (IgG). ...Seroconversion for IgG and IgM occurred simultaneously or sequentially. Both IgG and IgM titers plateaued within 6 days after seroconversion. Serological testing may be helpful for the diagnosis of suspected patients with negative RT-PCR results and for the identification of asymptomatic infections.
Intervertebral disc degeneration (IDD) is a chronic skeletal muscle degenerative disease, which is considered the main cause of low back pain. It seriously affects the quality of life of patients and ...consequently brings a heavy economic burden to their families and the society. Although IDD is considered a natural process in degenerative lesions, it is mainly caused by aging, trauma, genetic susceptibility and other factors. It is closely related to changes in the tissue structure and function, including the progressive destruction of extracellular matrix, cell aging, cell death of the intervertebral disc (IVD), inflammation, and impairment of tissue biomechanical function. Currently, the treatment of IDD is aimed at alleviating symptoms rather than at targeting pathological changes in the IVD. Furthermore, the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) signaling pathway is closely related to various pathological processes in IDD, and the activation of the MAPK/ERK pathway promotes the degradation of the IVD extracellular matrix, cell aging, apoptosis, and inflammatory responses. It also induces autophagy and oxidative stress that accelerate the IVD process. In our current review, we summarize the latest developments in the negative regulation of IDD after activation of the MAPK/ERK signaling pathway and emphasize on its influence on IDD. Targeting this pathway may become an attractive treatment strategy for IDD in the near future.
Background and Aims
The mechanism underlying HCC metastasis remains unclear, many oncogenes are known to regulate this process. However, the role of alternative splicing (AS) in pro‐metastatic HCC is ...poorly understood.
Approach and Results
By performing RNA sequencing on nine pairs of primary HCC tissues with extrahepatic metastasis (EHMH) and nine pairs of metastasis‐free HCC (MFH) tissues, we depicted the AS landscape in HCC and found a higher frequency of AS events in EHMH compared with MFH. Moreover, 28 differentially expressed splicing regulators were identified in EHMH compared with MFH. Among these, DEAD‐box RNA helicase 17 (DDX17) was significantly up‐regulated in EHMH and was strongly associated with patient outcome. Functional studies indicated that DDX17 knockout inhibited the degradation of the extracellular matrix, and diminished the invasive ability of HCC cells. A significant reduction in lung metastasis induced by DDX17 deficiency was also demonstrated in a diethylnitrosamine‐induced DDX17HKO mouse model. Mechanistically, high DDX17 induced intron 3 retention of PXN‐AS1 and produced a transcript (termed PXN‐AS1‐IR3). The transcript PXN‐AS1‐IR3 acted as an important promoter of HCC metastasis by inducing MYC transcription activation via recruiting the complex of testis expressed 10 and p300 to the MYC enhancer region, which led to transcriptional activation of several metastasis‐associated downstream genes. Finally, the PXN‐AS1‐IR3 level was significantly higher in serum and HCC tissues with extrahepatic metastasis.
Conclusions
DDX17 and PXN‐AS1‐IR3 act as important metastatic promoters by modulating MYC signaling, suggesting that DDX17 and PXN‐AS1‐IR3 may be potential prognostic markers for metastatic HCC.
Chemoresistance conferred by leukemia propagating cells (LPCs) in a therapy‐induced niche (TI‐niche) within the bone marrow is one of the main obstacles in leukemia treatment. Effective approaches to ...circumvent the TI‐niche protection and to eliminate the resident LPCs remain to be exploited. Here, developed is a niche‐targeted nanosystem using leukemic cell membrane‐coated mesoporous silica nanoparticles (DAazo@CMSN) for co‐delivering daunorubicin for leukemia cell chemotherapy and a TGFβRII neutralizing antibody (aTGFβRII) to block niche signaling. DAazo@CMSN effectively targets the TI‐niche. Through an azobenzene‐based hypoxia‐responsive linker, sequential delivery of the two active molecules overcomes niche‐mediated chemoresistance, attenuates systemic burden, and prolongs survival in a mouse model of leukemia. This work demonstrates a proof‐of‐principle for biomimetic and microenvironment‐activated multiplexed nanoparticulate drug delivery strategies for overcoming therapy‐induced chemoresistance in leukemia.
A biomimetic, hypoxia‐responsive nanosystem for daunorubicin and TGFβRII neutralizing antibody (aTGFβRII) co‐delivery (DAazo@CMSN) is developed with bone marrow niche targeting and sequential release capacity. This co‐delivery system exhibits potent efficacy in overcoming the therapy‐induced niche‐mediated chemoresistance in a mouse model of acute lymphoblastic leukemia.
The diverse expression pattern of CD36 reflects its multiple cellular functions. However, the roles of CD36 in colorectal cancer (CRC) remain unknown. Here, we discover that CD36 expression is ...progressively decreased from adenomas to carcinomas. CD36 loss predicts poor survival of CRC patients. In CRC cells, CD36 acts as a tumor suppressor and inhibits aerobic glycolysis in vitro and in vivo. Mechanically, CD36-Glypcian 4 (GPC4) interaction could promote the proteasome-dependent ubiquitination of GPC4, followed by inhibition of β-catenin/c-myc signaling and suppression of downstream glycolytic target genes GLUT1, HK2, PKM2 and LDHA. Moreover, disruption of CD36 in inflammation-induced CRC model as well as Apc
mice model significantly increased colorectal tumorigenesis. Our results reveal a CD36-GPC4-β-catenin-c-myc signaling axis that regulates glycolysis in CRC development and may provide an intervention strategy for CRC prevention.
Abstract
Background
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel β-coronavirus, causes severe pneumonia and has spread throughout the globe rapidly. The disease associated ...with SARS-CoV-2 infection is named coronavirus disease 2019 (COVID-19). To date, real-time reverse-transcription polymerase chain reaction (RT-PCR) is the only test able to confirm this infection. However, the accuracy of RT-PCR depends on several factors; variations in these factors might significantly lower the sensitivity of detection.
Methods
In this study, we developed a peptide-based luminescent immunoassay that detected immunoglobulin (Ig)G and IgM. The assay cutoff value was determined by evaluating the sera from healthy and infected patients for pathogens other than SARS-CoV-2.
Results
To evaluate assay performance, we detected IgG and IgM in the sera from confirmed patients. The positive rate of IgG and IgM was 71.4% and 57.2%, respectively.
Conclusions
Therefore, combining our immunoassay with real-time RT-PCR might enhance the diagnostic accuracy of COVID-19.
A peptide-based magnetic chemiluminescence enzyme immunoassay for the detection of SARS-CoV-2 antibodies was developed; 71.4% (197 of 276) and 57.2% (158 of 276) of the COVID-19 inpatients were positive for IgG and IgM against SARS-CoV-2.
Abstract
Background
Coronavirus disease 2019 (COVID-19) is a global pandemic with no licensed vaccine or specific antiviral agents for therapy. Little is known about the longitudinal dynamics of ...severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific neutralizing antibodies (NAbs) in patients with COVID-19.
Methods
Blood samples (n = 173) were collected from 30 patients with COVID-19 over a 3-month period after symptom onset and analyzed for SARS-CoV-2–specific NAbs using the lentiviral pseudotype assay, coincident with the levels of IgG and proinflammatory cytokines.
Results
SARS-CoV-2–specific NAb titers were low for the first 7–10 days after symptom onset and increased after 2–3 weeks. The median peak time for NAbs was 33 days (interquartile range IQR, 24–59 days) after symptom onset. NAb titers in 93.3% (28/30) of the patients declined gradually over the 3-month study period, with a median decrease of 34.8% (IQR, 19.6–42.4%). NAb titers increased over time in parallel with the rise in immunoglobulin G (IgG) antibody levels, correlating well at week 3 (r = 0.41, P < .05). The NAb titers also demonstrated a significant positive correlation with levels of plasma proinflammatory cytokines, including stem cell factor (SCF), TNF-related apoptosis-inducing ligand (TRAIL), and macrophage colony-stimulating factor (M-CSF).
Conclusions
These data provide useful information regarding dynamic changes in NAbs in patients with COVID-19 during the acute and convalescent phases.
Objective
Few studies have explored the clinical features in children infected with SARS‐CoV‐2 and other common respiratory viruses, including respiratory syncytial virus (RSV), Influenza virus (IV), ...and adenovirus (ADV). Herein, we reported the clinical characteristics and cytokine profiling in children with COVID‐19 or other acute respiratory tract infections (ARTI).
Methods
We enrolled 20 hospitalized children confirmed as COVID‐19 positive, 58 patients with ARTI, and 20 age and sex‐matched healthy children. The clinical information and blood test results were collected. A total of 27 cytokines and chemokines were measured and analyzed.
Results
The median age in the COVID‐19 positive group was 14.5 years, which was higher than that of the ARTI groups. Around one‐third of patients in the COVID‐19 group experienced moderate fever, with a peak temperature of 38.27°C. None of the patients displayed wheezing or dyspnea. In addition, patients in the COVID‐19 group had lower white blood cells, platelet counts as well as a neutrophil‐lymphocyte ratio. Lower serum concentrations of 14 out of 27 cytokines were observed in the COVID‐19 group than in healthy individuals. Seven cytokines (IL‐1Ra, IL‐1β, IL‐9, IL‐10, TNF‐α, MIP‐1α, and VEGF) changed serum concentration in COVID‐19 compared with other ARTI groups.
Conclusion
Patients with COVID‐19 were older and showed milder symptoms and a favorable prognosis than ARTI caused by RSV, IV, and ADV. There was a low grade or constrained innate immune reaction in children with mild COVID‐19.
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