The effects of ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate on the production of 1,3-propanediol from crude glycerol by microbial consortium

Bioprocess and Biosystems Engineering - Ionic liquids (ILs) as “green” solvents have been widely used owing to their excellent properties, e.g., for biodiesel production. Crude glycerol...     

Characterization of Cre recombinase mouse lines enabling cell type-specific targeting of postnatal intervertebral discs

Cre/loxP technology is an important tool for studying cell type-specific gene functions. Cre recombinase mouse lines, including Agc1-CreER^T2, Col2a1-Cre; Col2a1-CreER^T2, Shh-Cre, Shh-CreER^T2, and Osx-Cre, have been proven to be valuable tools to elucidate the biology of long bones, yet the information for their activity in postnatal intervertebral disc (IVD) tissues was very limited. In this study, we used R26-mTmG fluorescent reporter to systematically analyze cell specificity and targeting efficiency of these six mouse lines in IVD tissues at postnatal growing and adult stages. We found that Agc1-CreER^T2 is effective to direct recombination in all components of IVDs, including annulus fibrosus (AF), nucleus pulposus (NP), and cartilaginous endplate (CEP), upon tamoxifen induction at either 2 weeks or 2 months of ages. Moreover, Col2a1-Cre targets most of the cells in IVDs, except for some cells in the outer AF (OAF) and NP. In contrast, the activity of Col2a1-CreER^T2 is mainly limited to the IAF of IVD tissues at either stage of tamoxifen injection. Similarly, Shh-Cre directs recombination specifically in all NP cells, whereas Shh-CreER^T2 is active only in a few NP cells when tamoxifen is administered at either stage. Finally, Osx-Cre targets cells in the CEP, but not in the NP or AF of IVDs tissues at these two stages. Thus, our data demonstrated that all these Cre lines can direct recombination in IVD tissues at postnatal stages with different cell type specificity and/or targeting efficiency, and can, therefore, serve as valuable tools to dissect cell type-specific gene functions in IVD development and homeostasis.     

Lyoniresinol 3α-O-β-D-Glucopyranoside-Mediated Hypoglycaemia and Its Influence on Apoptosis-Regulatory Protein Expression in the Injured Kidneys of Streptozotocin-Induced Mice

Averrhoa carambola L. (Oxalidaceae) root (ACLR) has a long history of use in traditional Chinese medicine for treating diabetes and diabetic nephropathy (DN). (±)-Lyoniresinol 3α-O-β-D-glucopyranoside (LGP1, LGP2) were two chiral lignan glucosides that were isolated from the ACLR. The purpose of this study was to investigate the effect of LGP1 and LGP2-mediated hypoglycaemia on renal injury in streptozotocin (STZ)-induced diabetic mice. STZ-induced diabetic mice were administrated LGP1 and LGP2 orally (20, 40, 80 mg/kg body weight/d) for 14 days. Hyperglycaemia and the expression of related proteins such as nuclear factor-κB (NF-κB), caspase-3, -8, -9, and Bcl-associated X protein (Bax) were markedly decreased by LGP1 treatment. However, LGP2 treatment had no hypoglycaemic activity. Diabetes-dependent alterations in the kidney such as glomerular hypertrophy, excessive extracellular matrix amassing, and glomerular and tubular basement membrane thickening were improved after 14 days of LGP1 treatment. B cell lymphoma Leukaemia-2 (Bcl-2) expression was reduced in the STZ-induced diabetic mouse kidneys but was enhanced by LGP1 treatment. These findings suggest that LGP1 treatment may inhibit diabetic nephropathy progression and may regulate several pharmacological targets for treating or preventing diabetic nephropathy.     

Viral tegument proteins restrict cGAS-DNA phase separation to mediate immune evasion

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五株乳酸菌和三株芽孢杆菌的生物学特性和功能

【背景】乳酸菌和芽孢杆菌是应用于生产最多的益生菌,但不同菌株间的生长特性均不相同,因此了解菌株的生物学特性具有重要意义。【目的】研究菌株的生物学特性,能合理地开发和利用菌株,以保证菌株生产应用的安全性。【方法】活化后鉴定5株乳酸菌和3株芽孢杆菌并对其形态进行观察,探究菌株的生长曲线、产酸能力及最适生长条件,测定菌株的抑菌活性和产酶性能,同时探究菌株的益生性和安全性。【结果】五株乳酸菌分别编号鉴定为干酪乳杆菌R1、副干酪乳杆菌R2、香肠乳杆菌R3、福莱乳杆菌R4和唾液乳杆菌R5;3株芽孢杆菌分别编号命名为贝莱斯芽孢杆菌Y1、枯草芽孢杆菌Y2和地衣芽孢杆菌Y3。八株菌形态结构均不相同但都为杆状,均在2–10 h为对数生长期,18–24 h为稳定期,培养24 h时乳酸菌和芽孢杆菌的活菌数均保持在10⁹和10⁸ CFU/mL,最适生长温度为37.0℃。乳酸菌具有较强的产酸能力和抑菌活性,芽孢杆菌有较强的产酶性,在人工胃液中都有较强的耐受性。八株菌都无溶血活性、无毒力基因、对抗生素都保持中度敏感以上;其中唾液乳杆菌有四环素耐药基因,但对四环素抗性为中度敏感。【结论】八株菌生长繁殖速度快,乳酸菌产酸能力和抑菌活性较强,芽孢杆菌具有较强的产酶性能,在体外具有较好的益生性和安全性,可应用于生产实践。     

DYRK1A inhibition suppresses STAT3/EGFR/Met signalling and sensitizes EGFR wild‐type NSCLC cells to AZD9291

DYRK1A is considered a potential cancer therapeutic target, but the role of DYRK1A in NSCLC oncogenesis and treatment requires further investigation. In our study, high DYRK1A expression was observed in tumour samples from patients with lung cancer compared with normal lung tissues, and the high levels of DYRK1A were related to a reduced survival time in patients with lung cancer. Meanwhile, the DYRK1A inhibitor harmine could suppress the proliferation of NSCLC cells compared to that of the control. As DYRK1A suppression might be effective in treating NSCLC, we next explored the possible specific molecular mechanisms that were involved. We showed that DYRK1A suppression by siRNA could suppress the levels of EGFR and Met in NSCLC cells. Furthermore, DYRK1A siRNA could inhibit the expression and nuclear translocation of STAT3. Meanwhile, harmine could also regulate the STAT3/EGFR/Met signalling pathway in human NSCLC cells. AZD9291 is effective to treat NSCLC patients with EGFR‐sensitivity mutation and T790 M resistance mutation, but the clinical efficacy in patients with wild‐type EGFR remains modest. We showed that DYRK1A repression could enhance the anti‐cancer effect of AZD9291 by inducing apoptosis and suppressing cell proliferation in EGFR wild‐type NSCLC cells. In addition, harmine could enhance the anti‐NSCLC activity of AZD9291 by modulating STAT3 pathway. Finally, harmine could enhance the anti‐cancer activity of AZD9291 in primary NSCLC cells. Collectively, targeting DYRK1A might be an attractive target for AZD9291 sensitization in EGFR wild‐type NSCLC patients.     

A Double‐Edged Sword: Complement Component 3 in Toxoplasma gondii Infection

Sprague Dawley rats and Kunming (KM) mice are artificially infected with type II Toxoplasma gondii strain Prugniaud (Pru) to generate toxoplasmosis, which is a fatal disease mediated by T. gondii invasion of the central nervous system (CNS) by unknown mechanisms. The aim is to explore the mechanism of differential susceptibility of mice and rats to T. gondii infection. Therefore, a strategy of isobaric tags for relative and absolute quantitation (iTRAQ) is established to identify differentially expressed proteins (DEPs) in the rats’ and the mice's brains compared to the healthy groups. In KM mice, which is susceptible to T. gondii infection, complement component 3 (C3) is upregulated and the tight junction (TJ) pathway shows a disorder. It is presumed that T. gondii‐stimulated C3 disrupts the TJ of the blood–brain barrier in the CNS. This effect allows more T. gondii passing to the brain through the intercellular space.     

Perivascular adipose tissue‐derived stromal cells contribute to vascular remodeling during aging

Aging is an independent risk factor for vascular diseases. Perivascular adipose tissue (PVAT), an active component of the vasculature, contributes to vascular dysfunction during aging. Identification of underlying cell types and their changes during aging may provide meaningful insights regarding the clinical relevance of aging‐related vascular diseases. Here, we take advantage of single‐cell RNA sequence to characterize the resident stromal cells in the PVAT (PVASCs) and identified different clusters between young and aged PVASCs. Bioinformatics analysis revealed decreased endothelial and brown adipogenic differentiation capacities of PVASCs during aging, which contributed to neointimal hyperplasia after perivascular delivery to ligated carotid arteries. Mechanistically, in vitro and in vivo studies both suggested that aging‐induced loss of peroxisome proliferator‐activated receptor‐γ coactivator‐1 α (PGC1α) was a key regulator of decreased brown adipogenic differentiation in senescent PVASCs. We further demonstrated the existence of human PVASCs (hPVASCs) and overexpression of PGC1α improved hPVASC delivery‐induced vascular remodeling. Our finding emphasizes that differentiation capacities of PVASCs alter during aging and loss of PGC1α in aged PVASCs contributes to vascular remodeling via decreased brown adipogenic differentiation.     

5,2′‐dibromo‐2,4′,5′‐trihydroxydiphenylmethanone attenuates LPS‐induced inflammation and ROS production in EA.hy926 cells via HMBOX1 induction

Inflammation and reactive oxygen species (ROS) are important factors in the pathogenesis of atherosclerosis (AS). 5,2′‐dibromo‐2,4′,5′‐trihydroxydiphenylmethanone (TDD), possess anti‐atherogenic properties; however, its underlying mechanism of action remains unclear. Therefore, we sought to understand the therapeutic molecular mechanism of TDD in inflammatory response and oxidative stress in EA.hy926 cells. Microarray analysis revealed that the expression of homeobox containing 1 (HMBOX1) was dramatically upregulated in TDD‐treated EA.hy926 cells. According to the gene ontology (GO) analysis of microarray data, TDD significantly influenced the response to lipopolysaccharide (LPS); it suppressed the LPS‐induced adhesion of monocytes to EA.hy926 cells. Simultaneously, TDD dose‐dependently inhibited the production or expression of IL‐6, IL‐1β, MCP‐1, TNF‐α, VCAM‐1, ICAM‐1 and E‐selectin as well as ROS in LPS‐stimulated EA.hy926 cells. HMBOX1 knockdown using RNA interference attenuated the anti‐inflammatory and anti‐oxidative effects of TDD. Furthermore, TDD inhibited LPS‐induced NF‐κB and MAPK activation in EA.hy926 cells, but this effect was abolished by HMBOX1 knockdown. Overall, these results demonstrate that TDD activates HMBOX1, which is an inducible protective mechanism that inhibits LPS‐induced inflammation and ROS production in EA.hy926 cells by the subsequent inhibition of redox‐sensitive NF‐κB and MAPK activation. Our study suggested that TDD may be a potential novel agent for treating endothelial cells dysfunction in AS.