Autophagy regulates inflammation in intracerebral hemorrhage: Enemy or friend?

Intracerebral hemorrhage (ICH) is the second-largest stroke subtype and has a high mortality and disability rate. Secondary brain injury (SBI) is delayed after ICH. The main contributors to SBI are inflammation, oxidative stress, and excitotoxicity. Harmful substances from blood and hemolysis, such as hemoglobin, thrombin, and iron, induce SBI. When cells suffer stress, a critical protective mechanism called “autophagy” help to maintain the homeostasis of damaged cells, remove harmful substances or damaged organelles, and recycle them. Autophagy plays a critical role in the pathology of ICH, and its function remains controversial. Several lines of evidence demonstrate a pro-survival role for autophagy in ICH by facilitating the removal of damaged proteins and organelles. However, many studies have found that heme and iron can aggravate SBI by enhancing autophagy. Autophagy and inflammation are essential culprits in the progression of brain injury. It is a fascinating hypothesis that autophagy regulates inflammation in ICH-induced SBI. Autophagy could degrade and clear pro-IL-1β and apoptosis-associated speck-like protein containing a CARD (ASC) to antagonize NLRP3-mediated inflammation. In addition, mitophagy can remove endogenous activators of inflammasomes, such as reactive oxygen species (ROS), inflammatory components, and cytokines, in damaged mitochondria. However, many studies support the idea that autophagy activates microglia and aggravates microglial inflammation via the toll-like receptor 4 (TLR4) pathway. In addition, autophagy can promote ICH-induced SBI through inflammasome-dependent NLRP6-mediated inflammation. Moreover, some resident cells in the brain are involved in autophagy in regulating inflammation after ICH. Some compounds or therapeutic targets that regulate inflammation by autophagy may represent promising candidates for the treatment of ICH-induced SBI. In conclusion, the mutual regulation of autophagy and inflammation in ICH is worth exploring. The control of inflammation by autophagy will hopefully prove to be an essential treatment target for ICH

Genomic Mutation Profile of Primary Gastrointestinal Diffuse Large B-Cell Lymphoma.

Primary gastrointestinal diffuse large B-cell lymphoma (GI-DLBCL) is the most common gastrointestinal lymphoma, but its genetic features are poorly understood. We performed whole-exome sequencing of 25 primary tumor samples from patients with GI-DLBCL and 23 matched normal tissue samples. Oncogenic mutations were screened, and the correlations between genetic mutations and clinicopathological characteristics were analyzed. Twenty-five patients with GI-DLBCL were enrolled in the genetic mutation analysis with a median of 184 (range 79-382) protein-altering variants per patient. We identified recurrent oncogenic mutations in GI-DLBCL, including those in TP53, MUC16, B2M, CCND3, HIST1H1C, NEB, and ID3. Compared with nodal DLBCL, GI-DLBCL exhibited an increased mutation frequency of TP53 and reduced mutation frequencies of PIM1, CREBBP, BCL2, KMT2D, and EZH2. Moreover, GI-DLBCL exhibited fewer MYD88 and CD79B mutations than DLBCL in the testis and central nervous system. GI-DLBCLs with HLA-B, MEF2A, RHOA, and NAV3 mutations exhibited a tendency toward a high proliferation index. MUC16 and ETV6 mutations often occurred in tumors with early clinical staging. Our data provide a comprehensive understanding of the landscape of mutations in a small subset of GI-DLBCLs. The genetic mutation profiles of GI-DLBCL differ from those of nodal DLBCL and DLBCL in immune-privileged sites. The different mutated genes are related to the NF-κB and JAK-STAT pathways, and the different pathogenetic mechanisms leading to the development of DLBCL may be influenced by the tissue microenvironment. Differences in genetic alterations might influence the clinicopathological characteristics of GI-DLBCL

Toxicity of single-walled carbon nanotubes on green microalga Chromochloris zofingiensis

Nanoparticles, or particles in size of 1-100 nm, are extensively used in the world in different applications. For instance, single-walled carbon nanotubes (SWCNTs) are commonly used in consumer products, such as biosensors, drug and vaccine delivery transporters, and novel biomaterials. Although nanoparticles do not cause safety concerns to consumers who use nanoparticle-containing products, these small particles are potentially harmful for workers who produce them in factories or in cases of discharge to aquatic ecosystems. SWCNTs do not have a natural analogue, so the effects on health of their disposal remain largely unknown. In this study, we evaluated the effects of SWCNTs on a population of the green microalga Chromochloris zofingiensis and the profile and production of pigments and fatty acids. The alga was incubated with SWCNTs for 6 days in 0 (control), 40, 80, 160, or 320 mg/L concentrations. SWCNTs showed both positive and negative effects on the growth of C. zofingiensis, with a biomass enhancement at low levels (40-160 mg/L) but inhibition at high levels (320 mg/L). By contrast, a decreased accumulation of fatty acids and pigments of C. zofingiensis was observed over the range of the tested concentrations. These results indicate that the markers on the inhibitive toxicity of SWCNTs are increasingly sensitive in the following order: biomass and fatty acids < primary carotenoids < chlorophylls < secondary carotenoids. C. zofingiensis is a suitable microalga for evaluating the ecotoxicological hazards of SWCNTs, especially in terms of pigmentation response.Nanoparticles, or particles in size of 1-100 nm, are extensively used in the world in different applications. For instance, single-walled carbon nanotubes (SWCNTs) are commonly used in consumer products, such as biosensors, drug and vaccine delivery transporters, and novel biomaterials. Although nanoparticles do not cause safety concerns to consumers who use nanoparticle-containing products, these small particles are potentially harmful for workers who produce them in factories or in cases of discharge to aquatic ecosystems. SWCNTs do not have a natural analogue, so the effects on health of their disposal remain largely unknown. In this study, we evaluated the effects of SWCNTs on a population of the green microalga Chromochloris zofingiensis and the profile and production of pigments and fatty acids. The alga was incubated with SWCNTs for 6 days in 0 (control), 40, 80, 160, or 320 mg/L concentrations. SWCNTs showed both positive and negative effects on the growth of C. zofingiensis, with a biomass enhancement at low levels (40-160 mg/L) but inhibition at high levels (320 mg/L). By contrast, a decreased accumulation of fatty acids and pigments of C. zofingiensis was observed over the range of the tested concentrations. These results indicate that the markers on the inhibitive toxicity of SWCNTs are increasingly sensitive in the following order: biomass and fatty acids < primary carotenoids < chlorophylls < secondary carotenoids. C. zofingiensis is a suitable microalga for evaluating the ecotoxicological hazards of SWCNTs, especially in terms of pigmentation response

The complete chloroplast genome of Clematis henryi var. ternata (Ranunculaceae)

The complete chloroplast genome of Clematis henryi var.ternata was determined in this study. The genome was 159,675 base pair (bp) in length, containing a large single-copy (LSC) region of 79,443 bp, a small single-copy region (SSC) of 18,100 bp and a pair of inverted repeats (IRs) of 31,066 bp. It contains 130 unique genes, including 86 protein-coding genes, 36 transfer RNA (tRNA) genes, and eight ribosomal RNA (rRNA) genes. The GC content of the complete chloroplast genome sequence was 38.0%. Phylogenetic analyses using complete chloroplast genomes showed that Clematis henryi var.ternata is most closely related to Clematis guniuensis (NC_050373.1)

Overexpression of SmbHLH148 induced biosynthesis of tanshinones as well as phenolic acids in Salvia miltiorrhiza hairy roots

Phenolic acids and tanshinones are the two important groups of pharmaceutical ingredients presented in&nbsp;Salvia miltiorrhiza&nbsp;Bunge. The bHLH transcription factors could regulate secondary metabolism efficiently in plants. However, there are only some MYCs have been studied on regulation of either phenolic acids or tanshinones biosynthesis. In this study, a bHLH TF named SmbHLH148, which is homologous to AtbHLH148, AtbHLH147 and CubHLH1, was isolated and functionally characterized from&nbsp;S. miltiorrhiza. Transcription of&nbsp;SmbHLH148&nbsp;could be intensely induced by ABA and also be moderately induced by MeJA and GA. SmbHLH148 is present in all the six tissues and mostly expressed in fibrous root and flowers. Subcellular localization analysis found that SmbHLH148 was localized in the nucleus. Overexpression of&nbsp;SmbHLH148&nbsp;significantly increased not only three phenolic acids components accumulation but also three tanshinones content. Content of caffeic acid, rosmarinic acid and salvianolic acid B were reached to 2.87-, 4.00- and 5.99-fold of the control in the ObHLH148-3, respectively. Content of dihydrotanshinone I, cryptotanshinone, and tanshinone I were also present highest in ObHLH148-3, reached 2.5-, 5.04- and 3.97-fold of the control, respectively. Expression analysis of pathway genes of phenolic acids and tanshinones in transgenic lines showed that most of them were obviously upregulated. Moreover, transcription of&nbsp;AREB&nbsp;and&nbsp;JAZs&nbsp;were also induced in&nbsp;SmbHLH148&nbsp;overexpression lines. These results suggested that SmbHLH148 might be taken part in ABA and MeJA signaling and activated almost the whole biosynthetic pathways of phenolic acids and tanshinones, thus the production of phenolic acids and tanshinones were upregulated.</p

Protocol to assess fatal embolism risks from human stem cells

Summary: Here, we present a protocol to identify the pro-embolic sub-population of human adipose-derived multipotent stromal cells (ADSCs) and predict fatal embolism risks from ADSC infusion. We describe steps for the collection, processing, and classification of ADSC single-cell RNA-seq data. We then detail the development of a mathematical model for predicting ADSC embolic risk. This protocol allows for the development of prediction models to enhance the assessment of cell quality and advance the clinical applications of stem cells.For complete details on the use and execution of this protocol, please refer to Yan et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics

Genome-Wide Identification of GASA Gene Family in Ten Cucurbitaceae Species and Expression Analysis in Cucumber

Gibberellic acid-stimulated in Arabidopsis (GASA), a unique small molecular protein of plants, plays an essential role in plant growth and development. The GASA family genes have been identified and studied in many plants. However, the identification of GASA gene family in Cucurbitaceae species has not been reported yet. Therefore, in this study, based on the available genome information on the Cucurbitaceae species, the GASA family genes in 10 Cucurbitaceae species including cucumber (Cucumis sativus), watermelon (Citrullus lanatus), melon (Cucumis melo), pumpkin (Cucurbita moschata), wax gourd (Benincasa hispida), sponge gourd (Luffa cylindrica), bottle gourd (Lagenaria siceraria), bitter gourd (Momordica charantia), chayote (Sechium edule), and snake gourd (Trichosanthes anguina) were identified with bioinformatics methods. To understand the molecular functions of GASA genes, the expression pattern analysis of cucumber GASA family genes in different tissues and stress responses were also analyzed. The results showed that a total of 114 GASA genes were identified in the 10 Cucurbitaceae species, which were divided into three subfamilies. Synteny analysis of GASA genes among cucumber, Arabidopsis and rice showed that nine cucumber GASA genes were colinear with 12 Arabidopsis GASA genes, and six cucumber GASA genes were colinear with six rice GASA genes. The cis-acting elements analysis implied that the cucumber GASA genes contained many cis-elements associated with stress and hormone response. Tissue-specific expression analysis of cucumber GASA family genes revealed that only the CsaV3_2G029490 gene was lowly or not expressed in all tissues, the CsaV3_3G041480 gene was highly expressed in all tissues, and the other seven GASA genes showed tissue-specific expression patterns. Furthermore, nine cucumber GASA family genes exhibited different degrees of regulatory response under GA, abiotic and biotic stresses. Two cucumber GASA genes, CsaV3_3G042060 and CsaV3_3G041480, were differentially expressed under multiple biotic and abiotic stresses, which indicated that these two GASA genes play important roles in the growth and development of cucumber

Deep eutectic solvents functionalized polymers for easily and efficiently promoting biocatalysis

Biocompatible and magnetic polymers of poly(vinyl pyrrolidone deep eutectic solvent, VP DES) were investigated to determine whether they could efficiently adsorb L-asparaginase, which is an important enzyme inhibiting the growth of certain tumor cells. A series of poly(VP DES)s were successfully obtained, and that based on VP-malonic acid (VP/MA molar ratio of 1:1) was found to be the best for L-asparaginase adsorption. In addition, L-asparaginase was easily separated with biocompatible poly (VP-MA DES) from Escherichia coli extracts under a magnetic field with a high specific activity toward the hydrolysis of L-asparagine, as determined by the Nessler reaction method. Based on this work, poly(VP-MA DES)s seem ideal carriers via adsorption for the delivery of specific enzyme for the biocatalysis. (C) 2019 Elsevier Inc. All rights reserved