Innate immune imprints in SARS-CoV-2 Omicron variant infection convalescents.

SARS-CoV-2 Omicron variant infection generally gives rise to asymptomatic to moderate COVID-19 in vaccinated people. The immune cells can be reprogrammed or "imprinted" by vaccination and infections to generate protective immunity against subsequent challenges. Considering the immune imprint in Omicron infection is unclear, here we delineate the innate immune landscape of human Omicron infection via single-cell RNA sequencing, surface proteome profiling, and plasma cytokine quantification. We found that monocyte responses predominated in immune imprints of Omicron convalescents, with IL-1ß-associated and interferon (IFN)-responsive signatures with mild and moderate symptoms, respectively. Low-density neutrophils increased and exhibited IL-1ß-associated and IFN-responsive signatures similarly. Mild convalescents had increased blood IL-1ß, CCL4, IL-9 levels and PI3+ neutrophils, indicating a bias to IL-1ß responsiveness, while moderate convalescents had increased blood CXCL10 and IFN-responsive monocytes, suggesting durative IFN responses. Therefore, IL-1ß- or IFN-responsiveness of myeloid cells may indicate the disease severity of Omicron infection and mediate post-COVID conditions.

Autophagy is involved in the neuroprotective effect of nicotiflorin.

ETHNOPHARMACOLOGICAL RELEVANCE: Nicotiflorin is a flavonoid glycoside derived from the traditional Chinese medicine FlosCarthami, dried petals of Carthamus tinctorius L., and has been confirmed to be a promising novel drug candidate for ischemic stroke. Yet, the exact role of nicotiflorin in cerebral I/R injury is uncharacterized and the possible mechanisms have not been clearly expounded. AIM OF THE STUDY: The present study was designed to determine the effect of nicotiflorin on cerebral ischemia/reperfusion (I/R) injury and its relationship with autophagy. MATERIALS AND METHODS: Middle cerebral artery occlusion (MCAO) in rats and oxygen-glucose deprivation and reintroduction (OGD/R) in SH-SY5Y cells were established in in vivo and in vitro models, respectively. The severity of MCAO was assessed by brain infarct size, neurological scores and survival rate. The severity of OGD/R was evaluated by cell viability, lactate dehydrogenase (LDH) release and cell apoptosis. The level of autophagy was evaluated both in vivo and in vitro. Autophagosomes were observed using transmission electron microscopy and autophagic flux was measured using mRFP-GFP-tandem fluorescent LC3 adenovirus. Autophagy-related proteins (LC3-II/I, SQSTM1, beclin-1, Phospho-mTOR/mTOR) were measured by immunoblot. Autophagy-related mRNA levels (Becn1, Atg7) were detected by Real-Time PCR. Inhibition of autophagy was implemented by 3-Methyladenine (3-MA) or chloroquine in vitro. RESULTS: In vivo, nicotiflorin treatment alleviated brain damage and neurological deficit while it dramatically increased 72 h survival rate in rats. In vitro, nicotiflorin treatment also ameliorated the severity of OGD/R. Moreover, nicotiflorin treatment increased ischemic penumbra autophagy (autophagosomes, BECN1, LC3-II/I ratio, SQSTM1, Phospho-mTOR/mTOR, Atg7). In vitro, nicotiflorin likewise enhanced autophagy and promoted autophagy flux. Furthermore, the blockade of autophagy by 3-MA or chloroquine disabled the efficacic of nicotiflorin in preventing cell damage upon OGD/R insult. CONCLUSION: These findings suggest that autophagy plays a significant role in the protective effect of nicotiflorin against ischemic stroke.

Long non-coding RNA LNC01133 promotes the tumorigenesis of ovarian cancer by sponging miR-126.

BACKGROUND: Ovarian cancer (OC) is the gynecologic malignancy with the highest mortality rate (70%), and it is urgent to find out a powerful prognostic marker for OC patients. LncRNAs are recently thought to be oncogenes in various cancers, and its expression levels are validated that can be inhibited by miRNAs. There are several studies indicating that sponging miRNAs will contribute to the tumorigenesis of cancers. METHODS: In the present study, bioinformatics analysis is used to explore the potential oncogene and its target miRNAs; QRT-PCR is performed to count the expression level of several genes; Flow cytometric analysis is conducted to assess the apoptosis rate of several cell lines; Western blot assays are used to evaluate the expression levels of several proteins; Cells proliferation, migration and invasion abilities are detected by CCK-8 assay, Wound scratch assay and Transwell invasion assay, respectively. In vivo experiments are performed to assess the influence of LNC01133 on the formation of tumor. RESULTS: We found LNC01133 was related to poor survival of OC patients, and identified that LNC01133 had significant influence on OC cells' apoptosis, proliferation, migration and invasion abilities. Furthermore, we observed miR-126 could target LNC01133 and decreased the expression level of LNC01133 in OC cells. Therefore, we sponged miR-126 to further study the molecular mechanism of OC tumorigenesis, and found an elevation in proliferation, migration and invasion abilities of OC cells, which suggested that miR-126 could serve as a powerful prognostic marker for OC patients, and had great clinical significance on OC diagnosis and treatment. CONCLUSION: We found LNC01133 was an oncogene in OC, which is targeted by miR-126. miR-126 served as a powerful prognostic marker for OC patients because of its ability of promoting OC tumorigenesis after sponging.

Mori cortex prevents kidney damage through inhibiting expression of inflammatory factors in the glomerulus in streptozocin-induced diabetic rats.

OBJECTIVES: It has been widely reported that Mori cortex extract (MCE) is used for the treatment of diabetes mellitus in traditional medicine. The present study was designed to investigate its mechanism of action in the treatment of diabetic nephropathy (DN). We assessed whether MCE preventive treatment ameliorates kidney damage in high-fat diet and streptozotocin (STZ)-induced type 2 diabetic rats. MATERIALS AND METHODS: Rats were fed a high-fat diet and injected with STZ. MCE was given to rats daily at 10 g/kg. Fasting blood glucose (FBG) and postprandial plasma glucose were measured. Blood and urine biochemical parameters, renal tissue morphology, and inflammation were investigated. RESULTS: Prevention with MCE significantly decreased FBG and homoeostasis model assessment (HOMA) of IR (HOMA-IR) levels and increased insulin levels in diabetic rats. MCE prevention significantly decreased levels of KW/BW, BUN, Cr, and 24 hr urinary protein. MCE inhibited glomerular basement membrane thickening, tubular epithelial cell hypertrophy, and glomerular capillary dilation. MCE also prevented the disappearance of bowman's space and renal tubular lumen and decreased collagen deposition in rat kidney. Moreover, MCE reduced the levels of inflammatory factors (MCP-1 and TNF-α) and fibrosis factors (collagen IV and fibronectin). CONCLUSION: MCE prevents DN through inhibition of inflammation and fibrosis in a rat model. It might provide a safe and effective way to prevent DN.

A study of mild cognitive impairment in veterans: role of hypertension and other confounding factors.

INTRODUCTION: Hypertension has shown to be an important risk factor for the decline in cognitive function. Aim of our study is to investigate the presence of cognitive impairment of the elders with hypertension and other confounding factors. METHODS: This study was conducted on 400 veterans who were matched one-to-one with the confounding factors for assessing the presence of mild cognitive impairment using both MMSE and Montreal Cognitive Assessment (MoCA). The 13 related factors of patient data were studied. RESULTS: The prevalence rate of cognitive impairment was 29.25%. Age (OR 2.679, 95%CI 1.663-6.875), sleep impairment (OR 1.117, 95%CI 1.754-7.422), uncontrolled hypertension (OR 1.522, 95%CI 1.968-4.454), type 2 diabetes (OR 2.464, 95%CI 1.232-4.931), and hyperlipidaemia (OR 1.411, 95%CI 1.221-8.988) are the risk factors for the cognitive deterioration, while the protective factors are high level of education (OR 0.032, 95%CI 0.007-0.149) and regular exercise (OR 0.307, 95%CI 0.115-0.818). DISCUSSION: Because some vascular disease risk factors, such as hypertension, can be treated effectively, cognitive decline related to these risk factors, and vascular disease per se, may be prevented or its course modified through more aggressive treatment and improved compliance.

Neuropeptide Y induces secretion of high-mobility group box 1 protein in mouse macrophage via PKC/ERK dependent pathway.

Despite increasing evidence highlighting the role of NPY in the modulation of inflammatory reaction, surprisingly little is known about the direct effects of NPY on the release of proinflammatory mediators. In the present work, we have evaluated the effects of NPY on the release of TNF-α, IL-1ß, IL-6 and HMGB1 mediators in peritoneal macrophages. Our results demonstrate for the first time that NPY can directly induce active HMGB1 release and cytoplasmic translocation, while the production of TNF-α, IL-1ß and IL-6 is not affected. PKC and ERK pathway inhibitors can abolish the promotive effect of NPY on HMGB1 secretion. Thus, our results indicate that NPY might impact on the innate immune system by directly potentiating the HMGB1 release from the macrophage.