Background Among patients with coronavirus disease 2019 (COVID-19), the cases of a significant proportion of patients are severe. A viral nucleic acid test is used for the diagnosis of COVID-19, and ...some hematological indicators have been used in the auxiliary diagnosis and identification of the severity of COVID-19. Regarding body fluid samples, except for being used for nucleic acid testing, the relationship between COVID-19 and routine body fluid parameters is not known. Our aim was to investigate the value of urine biochemical parameters in the prediction of the severity of COVID-19. Methods A total of 119 patients with COVID-19 were enrolled at Renmin Hospital of Wuhan University. According to the severity of COVID-19, the patients were divided into three groups (moderate 67, severe 42 and critical 10), and 45 healthy persons were enrolled in the same period as healthy controls. The relationship between the results of urine biochemical parameters and the severity of COVID-19 was analyzed. Results The positive rates of urine occult blood (BLOOD) and proteinuria (PRO) were higher in COVID-19 patients than in healthy controls (p < 0.05); the urine specific gravity (SG) value was lower in patients than in healthy controls (p < 0.05), and the urine potential of hydrogen (pH) value was higher in patients than in healthy controls (p < 0.01). The positive rates of urine glucose (GLU-U) and PRO in the severe and critical groups were higher than those in the moderate group (p < 0.01 and p < 0.05, respectively); other biochemical parameters of urine were not associated with the severity of COVID-19. Conclusions Some urine biochemical parameters are different between patients with severe acute respiratory syndrome (SARS)-CoV-2 and healthy controls, and GLU-U and PRO may be helpful for the differentiation of COVID-19 severity.
Gastrodia elata Blume (G. elata) is a famous restorative food in East Asia. It can be used as an auxiliary reagent in hepatocellular carcinoma (HCC) treatment. Previous studies unveiled that G. elata ...exhibited immunomodulatory activities. To explore the active ingredients contributing to its immunomodulatory activities, gastrodin, vanillin, and parishin B were purified from G. elata and their anti-HCC effects were assessed in vivo. Among these compounds, only gastrodin was capable of repressing transplanted H22 ascitic hepatic tumor cell growth in vivo with low toxicity. Further investigations were designed to explore the effects of gastrodin on the immune system of tumor-bearing mice and potential molecular mechanisms underlying these effects. Our data showed that gastrodin ameliorated tumor cell transplantation-induced activation of endogenous pro-apoptotic pathway in CD4+ T cells and abnormalities in serum cytokine profiles in host animals. These events enhanced cytotoxic activities of natural killer and CD8+ T cells against H22 hepatic cancer cells. Gastrodin administration specifically upregulated mRNA levels of several nuclear factor κB (NF-κB) responsive genes in CD4+ T cells but not in CD8+ T cells. Chromatin immunoprecipitation assay showed that gastrodin increased the association of NF-κB p65 subunit to the promoter regions of IL-2 and Bcl-2 encoding genes in CD4+ T cells. Our investigations demonstrated that gastrodin is the main active ingredient contributing to the anticancer immunomodulatory properties of G. elata. Promoting NF-κB-mediated gene transcription in CD4+ T cells is implicated in its immunomodulatory activity.
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•Gastrodin stimulates anticancer immune response.•Gastrodin represses tumor transplantation-induced CD4+ T cell apoptosis.•Gastrodin activates NF-κB activity in CD4+ T cells.
(1) Background: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide with limited treatment satisfaction. Finding new therapeutic targets has remained a major challenge. ...Ferroptosis is an iron-dependent cell death program that plays a regulatory role in HBV infection and HCC development. It is necessary to classify the roles of ferroptosis or ferroptosis-related genes (FRGs) in HBV-related HCC progression. (2) Methods: We conducted a matched case-control study from the TCGA database, retrospectively collecting demographic data and common clinical indicators from all subjects. The Kaplan-Meier curve, univariate and multivariate cox regression analysis of the FRGs were used to explore the risk factors for HBV-related HCC. The CIBERSORT algorithm and TIDE algorithm were executed to evaluate the functions of FRGs in the tumor-immune environment. (3) Results: A total of 145 HBV-positive HCC patients and 266 HBV-negative HCC patients were enrolled in our study. Four ferroptosis related genes (FANCD2, CS, CISD1 and SLC1A5) were positively correlated with the progression of HBV-related HCC. Among them, SLC1A5 was an independent risk factor for HBV-related HCC, and correlated with poor prognosis, advanced progression and an immunosuppression microenvironment. (4) Conclusions: Here, we revealed that a ferroptosis-related gene, SLC1A5, may be an excellent predictor of HBV-related HCC and may provide insight into the development of innovative possible therapeutic techniques.
Burn ointment (BO) is a clinically useful medicine for the treatment of burns and scalds. However, there is no enough scientific evidence to report the effect of BO on wound healing and its analgesic ...and anti-inflammatory efficacy. The aim of this work was to evaluate the anti-inflammatory and analgesic efficacy of BO and to reveal the potential wound healing properties and related mechanisms of BO. In this work, the content of active ingredients of BO was determined by high-performance liquid chromatography (HPLC). Two animal models of inflammation were used to study its anti-inflammatory activity, and a hot plate method was used to evaluate its analgesic effect. In addition, mouse incision and rat burn models were used to investigate the effect of BO on the anti-inflammatory and wound healing mechanisms. The results showed that BO was safe for topical application, and BO could significantly inhibit auricular swelling in mice and paw swelling in rats and significantly prolong the latency period of paw licking in the hot plate experiment in mice. It can also accelerate wound healing and repair scars by promoting the formation of new epithelial tissues in rat burn models. In addition, BO significantly downregulated the serum level of TNF-α and significantly increased the serum levels of VEGF and TGF-β1. Also, BO promoted the expression of collagen I and increased the ratio in p-PI3K/PI3K, p-AKT/AKT, and p-mTOR/mTOR pathways. Our results demonstrate the safety and efficacy of BO and suggest that activation of the PI3K/AKT/mTOR signaling pathway may play an important role in the promotion of wound healing by BO.
N6-methyladenosine(m
6
A) is one of the most abundant modifications of mammalian cellular RNAs. m
6
A regulates various biological functions in epitranscriptomic ways, including RNA stability, decay, ...splicing, translation and nuclear export. Recent studies have indicated the growing importance of m
6
A modification in precancerous disease, influencing viral replication, immune escape, and carcinogenesis. Here, we review the role of m
6
A modification in HBV/HCV infection, NAFLD and liver fibrosis, and its function in liver disease pathogenesis. Our review will provide a new sight for the innovative treatment strategy for precancerous liver disease.
•TSFC induces HCC cell apoptosis in vitro and in vivo.•TSFC suppresses NF-κB activity in HCC cells.•TSFC exhibits low toxic effects to tumor-bearing mice.
Salvia chinensia Benth (S. chinensia) is a ...medical plant that has been traditionally applied for centuries in the treatment of malignant diseases including hepatocellular carcinoma (HCC). However, the scientific basis underlying its anti-HCC activity has not been fully established. In this study, the chemical profiles of total flavonoids from S. chinensia (TFSC) were explored. Thirteen compounds which constituted the major components of TFSC were separated and identified. Flow cytometry analysis and caspase activity assays showed that TFSC dose-dependently induced HepG2 and Huh-7 HCC cell apoptosis. TFSC was also shown to substantially suppress NF-κB activity in HCC cells. Moreover, TFSC significantly repressed transplanted murine H22 ascitic hepatic cancer cell growth in vivo. Further studies revealed that TFSC induced HCC cell apoptosis and inhibited expressional levels of NF-κB responsive genes in transplanted tumor tissues. In addition, the toxic impact of TFSC on tumor-bearing mice was undetectable. These results indicate that TFSC induces HCC cell apoptosis both in vitro and in vivo. The suppression of cellular NF-κB activity is implicated in the TFSC-mediated HCC cell apoptosis.
Objectives:
The longitudinal characterization and risk of poor outcomes related to cytokine overproduction in critical coronavirus disease 2019 (COVID-19) patients with hyperinflammation in ...bronchoalveolar lavage requires further investigation.
Methods:
We enrolled two critically ill patients with comorbidities diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) detected by RT-PCR during hospitalization. Clinical characteristics, longitudinal immunological, and biochemical parameters of each critical COVID-19 case were collected.
Main Results:
The clinical characteristics and laboratory results of each case demonstrated critical symptoms of COVID-19 with poor outcomes. Both nasopharyngeal swabs and bronchoalveolar lavage fluid (BALF) samples tested positive for SARS-CoV-2. Two patients received targeted treatments against pathogen infection and inflammation in addition to interventional therapies, except for Patient 2, who received an additional artificial liver system treatment. Hyperinflammation with a dominantly high level of IL-6 was observed in BALF samples from both critical cases with decreased T cell populations. High levels of cytokines and pathological parameters were successively maintained in Patient 1, but rapidly reduced at the late treatment stage in Patient 2. The outcome of Patient 1 is death, whereas the outcome of Patient 2 is recovery.
Conclusions:
This case report suggests that a high risk of poor outcomes was related to a heavily hyperinflammatory milieu in both the blood and lungs of critical COVID-19 patients. The artificial liver intervention on cytokines overproduction might be beneficial for the recovery of critical COVID-19 patients as a reliable therapy that can be coordinated with targeted treatments, which ought to be further tested in adequately designed and powered clinical trials.
Deep Hashing has achieved great success in large-scale image retrieval due to binary code’s storage and computation efficiency. However, its learning paradigm under real-world environments is less ...studied, and most existing approaches are developed in the closed scenario, e.g., simple and unchanging semantics. When images of new classes emerge, they have to retrain the model on all history training datasets, but the constant data uploading makes this impractical. This paper proposes a novel method, called continual deep semantic hashing (CDSH), for learning binary codes of multi-label images with increasing classes. The CDSH consists of two hashing networks. One learns to hash the increasing semantics of data, i.e., label, into the semantic codes and accumulates label-code pairs as long-term knowledge, incorporating empirically verified loss and designed special regularization to ensure encoding old labels unchanged. The other learns to map images to the corresponding semantic code from a probabilistic view and solid knowledge via retaining history exemplar samples and projecting model gradients. We theoretically prove this improves the probability of old data’s code unchanged after the model is updated. Extensive experiments on four widely used image datasets demonstrate that the CDSH method can continually learn hash functions and yield state-of-the-art retrieval performance.
•The code drift is a key problem in continual hash learning for image retrieval.•The two-step hash learning is a useful architecture for continual hash learning.•Keeping label-code pairs can capture the similarities between old and new data.•The combination of different losses can alleviate the code drift of the hashing.•The gradient projection improves the probability of code of old data unchanged.
Deep supervised hashing techniques have exhibited remarkable efficiency in cross-modal retrieval tasks, because they enable the transformation of data from different modalities into compact binary ...codes that preserve semantic similarity structures. Nonetheless, existing methods often rely on pairwise or triplet relationships within known (or in-distribution) semantics during training, failing to capture the comprehensive ranking information inherent in web data that encompasses diverse concepts. In addition, these methods are vulnerable to out-of-distribution (OOD) semantic data when applied in realistic scenarios, resulting in suboptimal performance. In this paper, we propose ranking distribution preserving hashing (RDPH) to address these problems. We present a novel ranking loss, a differentiable surrogate that maximizes the NDCG metric for cross-modal retrieval. This loss incorporates two target ranking distributions derived from the ideal NDCG scores of samples and the cosine similarity of features. These distributions encourage RDPH to generate hash codes that approximate the desired inter-modal and intra-modal ranking distributions. To enhance the robustness of the hash codes against OOD data, RDPH leverages the CLIP paradigm to acquire OOD-resilient intermediate representations. Besides, we utilize the outlier exposure strategy to enhance the discriminative ability of OOD for hash codes under supervision by constructing auxiliary pseudo-OOD data from known data in feature space. Experiments on three datasets demonstrate that the proposed method achieves state-of-the-art performance on regular retrieval tasks and good results on simulated real-world retrieval tasks.
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