A novel fusion protein consisting of anti-ANGPTL3 antibody and interleukin-22 ameliorates diabetic nephropathy in mice

IntroductionThe pathogenic mechanisms of diabetic nephropathy (DN) include podocyte injury, inflammatory responses and metabolic disorders. Although the antagonism of Angiopoietin-like protein 3 (ANGPTL3) can alleviate proteinuria symptoms by inhibiting the activation of integrin αvβ3 on the surface of podocytes, it can not impede other pathological processes, such as inflammatory responses and metabolic dysfunction of glucolipid. Interleukin-22 (IL-22) is considered to be a pivotal molecule involved in suppressing inflammatory responses, initiating regenerative repair, and regulating glucolipid metabolism.MethodsGenes encoding the mIL22IgG2aFc and two chains of anti-ANGPTL3 antibody and bifunctional protein were synthesized. Then, the DN mice were treated with intraperitoneal injection of normal saline, anti-ANGPTL3 (20 mg/kg), mIL22Fc (12 mg/kg) or anti-ANGPTL3 /IL22 (25.3 mg/kg) and irrigation of positive drug losartan (20mg/kg/d) twice a week for 8 weeks.ResultsIn this research, a novel bifunctional fusion protein (anti-ANGPTL3/IL22) formed by the fusion of IL-22 with the C-terminus of anti-ANGPTL3 antibody exhibited favorable stability and maintained the biological activity of anti-ANGPTL3 and IL-22, respectively. The fusion protein showed a more pronounced attenuation of proteinuria and improved dysfunction of glucolipid metabolism compared with mIL22Fc or anti-ANGPTL3. Our results also indicated that anti-ANGPTL3/IL22 intervention significantly alleviated renal fibrosis via inhibiting the expression of the inflammatory response-related protein nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) p65 and NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome. Moreover, transcriptome analysis revealed the downregulation of signaling pathways associated with injury and dysfunction of the renal parenchymal cell indicating the possible protective mechanisms of anti-ANGPTL3/IL22 in DN.ConclusionCollectively, anti-ANGPTL3/IL22 bifunctional fusion protein can be a promising novel therapeutic strategy for DN by reducing podocyte injury, ameliorating inflammatory response, and enhancing renal tissue recovery

EVALITA Evaluation of NLP and Speech Tools for Italian - December 17th, 2020

Welcome to EVALITA 2020! EVALITA is the evaluation campaign of Natural Language Processing and Speech Tools for Italian. EVALITA is an initiative of the Italian Association for Computational Linguistics (AILC, http://www.ai-lc.it) and it is endorsed by the Italian Association for Artificial Intelligence (AIxIA, http://www.aixia.it) and the Italian Association for Speech Sciences (AISV, http://www.aisv.it)

Quarkonium measurements in nucleus-nucleus collisions with ALICE

Heavy quarks are produced in the early stages of nucleus-nucleus collisions and can therefore provide important insight into the Quark-Gluon Plasma (QGP). Quarkonia are proposed as crucial probes to study the QGP. The extent of the medium modification for heavy-quark quarkonium production in heavy-ion collisions is measured in terms of a nuclear modification factor $R_{\rm AA}$, defined as the quarkonium yield in heavy-ion collisions divided by the relative quarkonium cross section in pp collisions scaled by the nuclear overlap function. A possible path-length dependent quarkonium dissociation, as well as a contribution of (re-)generation of quarkonia from heavy quarks in the medium, would lead to an azimuthal anisotropy of quarkonium production relative to the reaction plane. In this contribution, the recent ALICE measurements of quarkonium in Pb-Pb collisions at $\sqrt{s_{\rm NN}}$ = 5.02 TeV will be discussed for both mid- and forward rapidity. The dependence of $R_{\rm AA}$ on centrality and $p_{\rm T}$ for J/$\psi$, $\Upsilon$(1S), $\Upsilon$(2S), as well as the J/$\psi$ elliptic flow $v_{2}$ will be shown. The experimental data and the current theoretical model calculations will be also discussed.Heavy quarks are produced in the early stages of nucleus-nucleus collisions and can therefore provide important insight into the Quark–Gluon Plasma (QGP). Quarkonia are proposed as crucial probes to study the QGP. The extent of the medium modification for heavy-quark quarkonium production in heavy-ion collisions is measured in terms of a nuclear modification factor R AA , defined as the quarkonium yield in heavy-ion collisions divided by the relative quarkonium cross section in pp collisions scaled by the nuclear overlap function. A possible path-length dependent quarkonium dissociation, as well as a contribution of (re-)generation of quarkonia from heavy quarks in the medium, would lead to an azimuthal anisotropy of quarkonium production relative to the reaction plane. In this contribution, the recent ALICE measurements of quarkonia in Pb–Pb collisions at sNN=5.02TeV will be discussed for both mid- and forward rapidity. The dependence of R AA on centrality and p T for J/ ψ , ϒ(1S), ϒ(2S), as well as the J/ ψ elliptic flow ν 2 will be shown. Comparisons between the experimental data and the current theoretical model calculations will be also discussed

Recent quarkonium measurements with ALICE

Quarkonium production is one of the essential probes for studying the properties of the quark-gluon plasma (QGP) created in relativistic heavy-ion collisions. The suppression of J/ψ due to color screening in the medium was initially proposed as direct evidence of QGP formation. The J/ψ in heavy-ion collisions is affected by the (re-)generation of uncorrelated charm-anticharm (cc‾) quark pairs in the medium as well as the underlying cold nuclear matter effects. The heavier quarkonium states ϒ, the re-(generated) effect is found significantly smaller than J/ψ since the density of uncorrelated beauty-antibeauty (bb‾) quark pairs in the medium is much smaller than cc‾ pairs. Both the J/ψ and ϒ can be used as the probes to study the quark mass dependent (re-)generation effect. In this contribution, the recent measurements of J/ψ and ϒ production in various collision systems performed by the ALICE are shown. The measured quarkonium production cross-section, the nuclear modification factor RpA, RAA, and the flow coefficient v2 are discussed. Results are compared with the model calculations

Research progress on SIRT1 and sepsis.

SIRT1, a member of the sirtuin family, belongs to the NAD + -dependent class III histone deacetylase. SIRT1 can regulate gene expression by catalyzing non-histone and histone lysine residues deacetylation. SIRT1 also plays important roles in glucose and lipid metabolism, cell aging, tumorigenesis and inflammation. Recent studies indicate that SIRT1 can inhibit the inflammatory responses via regulating several inflammatory signaling pathways. It is closely related to the occurrence and development of sepsis and other inflammatory diseases. Research has been done on relevant signaling pathways of SIRT1 as well as its target genes during inflammation. SIRT1 is a hot spot in uncontrolled inflammatory response research. This article focuses on the role of SIRT1 in inflammation, especially its targets and involved signaling pathways in sepsis, and tries to provide more convincing evidence for the clinical treatment of sepsis and other inflammatory diseases

Recent advances in hypertrophic scar

Hypertrophic scars (HTS) are predominant diseases after burn and trauma, which cause severe physiological and psychological problems. HTS have been researched for decades, and our knowledge about the mechanisms of HTS formation process has been increasing. However, the effects of currently available prevention and treatment strategies are limited. In this review, we summarize currently known mechanisms and recent studies of HTS, including extracellular matrix, matrix metalloproteinases, fibroblasts, myofibroblasts and their contraction ability, keratinocytes, growth factors, inflammatory and immune response, and stem cell treatment, hoping for a better understanding of HTS generation, development and effective translation to treatment strategies

Loureirin B Inhibits Hypertrophic Scar Formation via Inhibition of the TGF-β1-ERK/JNK Pathway

Background/Aims: Our previous study confirmed that Loureirin B (LB) can inhibit hypertrophic scar formation. However, the mechanism of LB-mediated inhibition of scar formation is still unknown. Methods: Immunohistochemistry was used to detect expression of Col1, FN and TGF-β1 in skin and scar tissue. Fibroblasts were stimulated with TGF-β1 to mimic scar formation. LB or MAPK inhibitors were used to study the pathways involved in the process. Western blotting was used to evaluate the expression of p-JNK, p-ERK, p-p38, Col1 and FN. The contractile capacity of fibroblasts was evaluated using a gel contraction assay. Tissues were cultured ex vivo with LB to further investigate the participation of ERK and JNK in the LB-mediated inhibition of scar formation. Results: FN and Col1 were up regulated in hypertrophic scars. LB down regulated p-ERK and p-JNK in TGF-β1-stimulated fibroblasts, while levels of phosphorylated p38 did not change. The down regulation of p-ERK and p-JNK was associated with a reduction of Col1 and FN. Similarly, inhibition of ERK and JNK down regulated the expression of Col1 and FN in TGF-β1-stimulated fibroblasts. LB down regulated protein levels of p-ERK and p-JNK in cultured hypertrophic scar tissue ex vivo. Conclusions: This study suggests that LB can inhibit scar formation through the ERK/JNK pathway