A novel actinomycete strain, designated S2‐4
T
, was isolated from a mangrove soil sample, and a polyphasic approach was employed to determine its taxonomic position. Phylogenetic analysis based on ...16S rRNA gene indicated that strain S2‐4
T
formed a unique clade next to that harboring
Pseudonocardia dioxanivorans
CB1190
T
, which shared the highest sequence similarity (98.20%) with the new isolate. Phylogenetic analysis based on core genes of genomic sequences displayed a different scenario, exhibiting closer phylogenetic relationship of strain S2-4
T
with several species with 16S rRNA gene sequence similarities ranging from 96.95 to 98.06%, which was confirmed by the phylogenetic tree reconstructed based on genomic sequences. Further, substantial differences between the genotypic properties of strain S2-4
T
and its closest neighbors, including digital DNA–DNA hybridization, average nucleotide identity, and distribution patterns of biosynthetic gene clusters (BGC), indicated the taxonomic position of strain S2-4
T
as a novel species of the genus
Pseudonocardia
. Accordingly, strain S2-4
T
was observed to show a different distribution pattern of a predicted BGC encoding ectoine by comparative genomic analysis, which could be strongly linked to its unique habitat distinct from where its close neighbors were isolated. The major cellular fatty acids were
iso
-C
15:0
, C
21:0
, and
iso
-C
16:0
. The predominant menaquinone was MK-8(H
4
). The polar lipids were composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidyl-N-monomethylethanolamine, phosphatidylcholine, phosphatidylinositol, phosphatidylinositol mannosides, and two unidentified glycolipids. Here, we propose a novel species of the genus
Pseudonocardia
:
Pseudonocardia humida
sp. nov. with the type strain S2-4
T
(= JCM 34291
T
= CGMCC 4.7706
T
).
Chinese medicine Xuebijing (XBJ) has proven to be effective in the treatment of mild coronavirus disease 2019 (COVID-19) cases. But the bioactive compounds and potential mechanisms of XBJ for ...COVID-19 prevention and treatment are unclear. This study aimed to examine the potential effector mechanisms of XBJ on COVID-19 based on network pharmacology.
We searched Chinese and international papers to obtain the active ingredients of XBJ. Then, we compiled COVID-19 disease targets from the GeneCards gene database and via literature searches. Next, we used the SwissTargetPrediction database to predict XBJ's effector targets and map them to the abovementioned COVID-19 disease targets in order to obtain potential therapeutic targets of XBJ. Cytoscape software version 3.7.0 was used to construct a "XBJ active-compound-potential-effector target" network and protein-protein interaction (PPI) network, and then to carry out network topology analysis of potential targets. We used the ClueGO and CluePedia plugins in Cytoscape to conduct gene ontology (GO) biological process (BP) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment analysis of XBJ's effector targets. We used AutoDock vina and PyMOL software for molecular docking.
We obtained 144 potential COVID-19 effector targets of XBJ. Fourteen of these targets-glyceraldehyde 3-phosphate dehydrogenase (
), albumin (
), tumor necrosis factor (
), epidermal growth factor receptor (
), mitogen-activated protein kinase 1 (
), Caspase-3 (
), signal transducer and activator of transcription 3 (
),
, prostaglandin-endoperoxide synthase 2 (
),
, interleukin-2 (
), estrogen receptor 1 (
), and
had degree values > 40 and therefore could be considered key targets. They participated in extracellular signal-regulated kinase 1 and 2 (
,
) cascade, the T-cell receptor signaling pathway, activation of
activity, cellular response to lipopolysaccharide, and other inflammation- and immune-related BPs. XBJ exerted its therapeutic effects through the renin-angiotensin system (RAS), nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB),
, phosphatidylinositol-4, 5-bisphosphate 3-kinase (
)-protein kinase B (
)-vascular endothelial growth factor (VEGF), toll-like receptor (TLR), TNF, and inflammatory-mediator regulation of transient receptor potential (TRP) signaling pathways to ultimately construct a "drug-ingredient-target-pathway" effector network. The molecular docking results showed that the core 18 effective ingredients had a docking score of less than - 4.0 with those top 10 targets.
The active ingredients of XBJ regulated different genes, acted on different pathways, and synergistically produced anti-inflammatory and immune-regulatory effects, which fully demonstrated the synergistic effects of different components on multiple targets and pathways. Our study demonstrated that key ingredients and their targets have potential binding activity, the existing studies on the pharmacological mechanisms of XBJ in the treatment of sepsis and severe pneumonia, could explain the effector mechanism of XBJ in COVID-19 treatment, and those provided a preliminary examination of the potential effector mechanism in this disease.
Inflammatory myofibroblastic tumor (IMT) is a rare tumor with an indolent course. It is less often reported as a second tumor that occurs after treatment of malignant tumors in pediatric patients. ...Here, we report a case of IMT following Wilms tumor (WT), and conduct a literature review concerning IMTs and WT to evaluate the diagnostic possibility of IMT as a second tumor. The coexistence of the 2 tumors may cause confusion as to whether they share genetic links or that IMTs may appear as late effects of the treatment of WT.
Background
Hepatocellular carcinoma (HCC) is a prevalent malignancy with poor prognosis. As a cell adhesion molecule, poliovirus receptor (PVR/CD155) is abnormally overexpressed in tumour cells, and ...related to tumour proliferation and invasion. However, the potential role and mechanism of CD155 have not yet been elucidated in HCC.
Methods
Immunohistochemistry, RT‐PCR and Western blot assays were used to determine CD155 expression in HCC cell lines and tissues. Cell Counting Kit‐8 and colony formation assays were used to examine cell proliferation. Transwell and wound healing assays were used to evaluate cell migration and invasion. Cell apoptosis and cycle distribution were assessed by flow cytometry. Cox regression and Kaplan–Meier analyses were performed to explore the clinical significance of CD155. The role of CD155 in vivo was evaluated by establishing liver orthotropic xenograft mice model. RNA sequencing, bioinformatics analysis and co‐immunoprecipitation assay were used to explore the downstream signalling pathway of CD155.
Results
CD155 was upregulated in HCC tissues and represented a promising prognostic indicator for HCC patients (n = 189) undergoing curative resection. High CD155 expression enhanced cell proliferation, migration and invasion, and contributed to cell survival in HCC. CD155 overexpression also induced epithelial–mesenchymal transition in HCC cells. CD155 function in HCC involved SRC/p38 MAPK signalling pathway. CD155 interacted with SRC homology‐2 domain of SRC and promoted SRC activation, further inhibiting the downstream p38 MAPK signalling pathway in HCC.
Conclusions
CD155 promotes HCC progression via the SRC/p38 MAPK signalling pathway. CD155 may represent a predictor for poor postsurgery prognosis in HCC patients.
CD155 is highly expressed in hepatocellular carcinoma (HCC) tissues, and its overexpression predicts poor postsurgery prognosis in HCC patients.
CD155 promotes HCC progression via its cell‐intrinsic role in regulating cell proliferation, migration, invasion and epithelial–mesenchymal transition (EMT).
CD155 enhances SRC activation through interacting with SH2 domain of SRC, further inhibiting the downstream p38 MAPK signalling pathway in HCC.
Abstract
Interferon-α2b (IFN-α2b) is a highly active cytokine that belongs to the interferon-α (IFN-α) family. IFN-α2b has beneficial antiviral, antitumour, antiparasitic and immunomodulatory ...activities. Direct and indirect antiproliferative effects of IFN-α2b have been found to occur via multiple pathways, mainly the JAK-STAT pathway, in certain cancers. This article reviews mechanistic studies and clinical trials on IFN-α2b. Potential regulators of the function of IFN-α2b were also reviewed, which could be utilized to relieve the poor response to IFN-α2b. IFN-α2b can function not only by enhancing the systematic immune response but also by directly killing tumour cells. Different parts of JAK-STAT pathway activated by IFN-α2b, such as interferon alpha and beta receptors (IFNARs), Janus kinases (JAKs) and IFN‐stimulated gene factor 3 (ISGF3), might serve as potential target for enhancing the pharmacological action of IFN-α2b. Despite some issues that remain to be solved, based on current evidence, IFN-α2b can inhibit disease progression and improve the survival of patients with certain types of malignant tumours. More efforts should be made to address potential adverse effects and complications.
Phenol oxidases (POs) catalyze the oxidation of dopa and dopamine to melanin, which is crucial for cuticle formation and innate immune maintenance in insects. Although, Laccase 2, a member of the PO ...family, has been reported to be a requirement for melanin-mediated cuticle tanning in the development stages of some insects, whether it participates in cuticle construction and other physiological processes during the metamorphosis of mosquito pupae is unclear.
The association between the phenotype and the expression profile of Anopheles sinensis Laccase 2 (AsLac2) was assessed from pupation to adult eclosion. Individuals showing an expression deficiency of AsLac2 that was produced by RNAi and their phenotypic defects and physiological characterizations were compared in detail with the controls.
During the dominant expression period, knockdown of AsLac2 in pupae caused the cuticle to be unpigmented, and produced thin and very soft cuticles, which further impeded the eclosion rate of adults as well as their fitness. Moreover, melanization immune responses in the pupae were sharply decreased, leading to poor resistance to microorganism infection. Both the high conservation among Laccase 2 homologs and a very similar genomic synteny of the neighborhood in Anopheles genus implies a conservative function in the pupal stage.
To our knowledge, this is the first study to report the serious phenotypic defects in mosquito pupae caused by the dysfunction of Laccase 2. Our findings strongly suggest that Laccase 2 is crucial for Anopheles cuticle construction and melanization immune responses to pathogen infections during pupal metamorphosis. This irreplaceability provides valuable information on the application of Lacccase 2 and/or other key genes in the melanin metabolism pathway for developing mosquito control strategies.
Angiosarcomas account for a mere 2–3% of adult soft tissue sarcomas, with an overall poor outcome. Depending on the primary site, angiosarcomas have distinct prognosis. Primary hepatic angiosarcomas ...(PHAs) are much rare tumors, with worse prognosis compared with other angiosarcomas. PHA is reported to be associated with vinyl chloride, but the majority of patients were still with unknown etiology. As PHA lacks specific symptoms, signs, or images, pathological diagnosis is necessary. The review summarizes 25 articles published from January 2000 to December 2012, including 64 cases of PHA with detailed information. Survival curves are estimated using the Kaplan–Meier method by SPSS 21.0. We find that the median survival time is 5 months; local excision alone or combination with adjuvant therapy is the optimal choice, with median survival time of 17 months. In addition, liver transplant is abandoned for high recurrence rate; emergent transcatheter arterial embolization is thought to be an efficient method for controlling intra‐abdominal bleeding; and transcatheter arterial chemoembolization and chemotherapy may be helpful in improving survival.
Ionic liquids have been widely used to improve the efficiency and stability of perovskite solar cells (PSCs), and are generally believed to passivate defects on the grain boundaries of perovskites. ...However, few studies have focused on the relevant effects of ionic liquids on intragrain defects in perovskites which have been shown to be critical for the performance of PSCs. In this work, the effect of ionic liquid 1-hexyl-3-methylimidazolium iodide (HMII) on intragrain defects of formamidinium lead iodide (FAPbI3) perovskite is investigated. Abundant {111}c intragrain planar defects in pure FAPbI3 grains are found to be significantly reduced by the addition of the ionic liquid HMII, shown by using ultra-low-dose selected area electron diffraction. As a result, longer charge carrier lifetimes, higher photoluminescence quantum yield, better charge carrier transport properties, lower Urbach energy, and current-voltage hysteresis are achieved, and the champion power conversion efficiency of 24.09% is demonstrated. These observations suggest that ionic liquids significantly improve device performance resulting from the elimination of {111}c intragrain planar defects.
Keloids are benign fibroproliferative diseases with abnormally proliferated bulges beyond the edge of the skin lesions, and they are characterized by uncontrolled fibroblast proliferation and ...excessive extracellular matrix deposition in the dermis. However, the definite mechanisms that increase fibroblast proliferation and collagen deposition in keloids remain unclear. Thrombospondin 1 (TSP1) has been suggested to play an important role in wound healing and fibrotic disorders, but its role in keloids is unknown. In this study, we aimed to clarify the specific role of TSP1 in keloids and explore the potential mechanism. Our results demonstrated that TSP1 was highly expressed in keloid lesions compared to normal skin. Knockdown of TSP1 in keloid fibroblasts decreased cell proliferation and collagen I deposition. Exogenous TSP1 treatment increased cell proliferation and collagen I deposition in normal fibroblasts. We further investigated the underlying mechanism and found that TSP1 promoted fibroblast proliferation and extracellular matrix deposition by upregulating the IL6/JAK2/STAT3 pathway. Moreover, we verified that TSP1 expression was positively correlated with IL6/STAT3 signalling activity in keloids. Taken together, our findings indicate that TSP1 promotes keloid development via the IL6/JAK2/STAT3 signalling pathway and blocking TSP1 may represent a potential strategy for keloid therapy.
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