A Plasmopara viticola RXLR effector targets a chloroplast protein PsbP to inhibit ROS production in grapevine

Pathogens secrete a large number of effectors that manipulate host processes to create an environment conducive to pathogen colonization. However, the underlying mechanisms by which Plasmopara viticola effectors manipulate host plant cells remain largely unclear. In this study, we reported that RXLR31154, a P. viticola RXLR effector, was highly expressed during the early stages of P. viticola infection. In our study, stable expression of RXLR31154 in grapevine (Vitis vinifera) and Nicotiana benthamiana promoted leaf colonization by P. viticola and Phytophthora capsici, respectively. By yeast two-hybrid screening, the 23-kDa oxygen-evolving enhancer 2 (VpOEE2 or VpPsbP), encoded by the PsbP gene, in Vitis piasezkii accession Liuba-8 was identified as a host target of RXLR31154. Overexpression of VpPsbP enhanced susceptibility to P. viticola in grapevine and P. capsici in N. benthamiana, and silencing of NbPsbPs, the homologs of PsbP in N. benthamiana, reduced P. capcisi colonization, indicating that PsbP is a susceptibility factor. RXLR31154 and VpPsbP protein were co-localized in the chloroplast. Moreover, VpPsbP reduced H₂O₂ accumulation and activated the ¹O₂ signaling pathway in grapevine. RXLR31154 could stabilize PsbP. Together, our data revealed that RXLR31154 reduces H₂O₂ accumulation and activates the ¹O₂ signaling pathway through stabilizing PsbP, thereby promoting disease.     

Pre treatment with Bacillus subtilis mitigates drought induced photo-oxidative damages in okra by modulating antioxidant system and photochemical activity

Growth promoting potential of Bacillus subtilis (BS) in drought stressed Abelmoschus esculentus (L.) Moench (okra) was assessed by measuring the chlorophyll stability index (CSI), chlorophyll a (Chl-a) fluorescence, leaf osmotic potential and lipid peroxidation by malondialdehyde content, emission of reactive oxygen species (ROS), osmolyte content and the activity of non-enzyme and enzyme antioxidants. BS treatment significantly increased the leaf osmotic potential, osmolyte production and the activity of non-enzyme and enzyme antioxidants under drought stress. BS treatment mitigated the drought-induced reduction in Chl a fluorescence and CSI. Concomitant increase in total sugar, proline, non-enzyme antioxidants [glutathione and ascorbate] and enzyme antioxidants like superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase modulate the intracellular ROS concentration in okra to resist the stress induced oxidative damage in BS treated plants led to fast recovery and less photodamage.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12298-021-00982-8.     

The thermodynamics of thinking: connections between neural activity,energy metabolism and blood flow

Several current functional neuroimaging methods are sensitive to cerebral metabolism and cerebral blood flow (CBF) rather than the underlying neural activity itself. Empirically, the connections between metabolism, flow and neural activity are complex and somewhat counterintuitive: CBF and glycolysis increase more than seems to be needed to provide oxygen and pyruvate for oxidative metabolism, and the oxygen extraction fraction is relatively low in the brain and decreases when oxygen metabolism increases. This work lays a foundation for the idea that this unexpected pattern of physiological changes is consistent with basic thermodynamic considerations related to metabolism. In the context of this thermodynamic framework, the apparent mismatches in metabolic rates and CBF are related to preserving the entropy change of oxidative metabolism, specifically the O₂/CO₂ ratio in the mitochondria. However, the mechanism supporting this CBF response is likely not owing to feedback from a hypothetical O₂ sensor in tissue, but rather is consistent with feed-forward control by signals from both excitatory and inhibitory neural activity. Quantitative predictions of the thermodynamic framework, based on models of O₂ and CO₂ transport and possible neural drivers of CBF control, are in good agreement with a wide range of experimental data, including responses to neural activation, hypercapnia, hypoxia and high-altitude acclimatization.This article is part of the theme issue ‘Key relationships between non-invasive functional neuroimaging and the underlying neuronal activity’.     

Hyaluronic acid optimises therapeutic effects of hydrogen peroxide‐induced oxidative stress on breast cancer

Distinguishing the multiple effects of reactive oxygen species (ROS) on cancer cells is important to understand their role in tumour biology. On one side, ROS can be oncogenic by promoting hypoxic conditions, genomic instability and tumorigenesis. Conversely, elevated levels of ROS‐induced oxidative stress can induce cancer cell death. This is evidenced by the conflicting results of research using antioxidant therapy, which in some cases promoted tumour growth and metastasis. However, some antioxidative or ROS‐mediated oxidative therapies have also yielded beneficial effects. To better define the effects of oxidative stress, in vitro experiments were conducted on 4T1 and splenic mononuclear cells (MNCs) under hypoxic and normoxic conditions. Furthermore, hydrogen peroxide (H₂O₂; 10–1,000 μM) was used as an ROS source alone or in combination with hyaluronic acid (HA), which is frequently used as drug delivery vehicle. Our result indicated that the treatment of cancer cells with H₂O₂ + HA was significantly more effective than H₂O₂ alone. In addition, treatment with H₂O₂ + HA led to increased apoptosis, decreased proliferation, and multiphase cell cycle arrest in 4T1 cells in a dose‐dependent manner under normoxic or hypoxic conditions. As a result, migratory tendency and the messenger RNA levels of vascular endothelial growth factor, matrix metalloproteinase‐2 (MMP‐2), and MMP‐9 were significantly decreased in 4T1 cells. Of note, HA treatment combined with 100–1,000 μM H₂O₂ caused more damage to MNCs as compared to treatment with lower concentrations (10–50 μM). Based on these results, we propose to administer high‐dose H₂O₂ + HA (100–1000 μM) for intratumoural injection and low doses for systemic administration. Intratumoural route could have toxic and inhibitory effects not only on the tumour but also on residential myeloid cells defending it, whereas systemic treatment could stimulate peripheral immune responses against the tumour. More in vivo research is required to confirm this hypothesis.     

“Take My Bone Away?” Hypoxia and bone: A narrative review

To maintain normal cellular and physiological function, sufficient oxygen is required. Recently, evidence has suggested that hypoxia, either pathological or environmental, may influence bone health. It appears that bone cells are distinctly responsive to hypoxic stimuli; for better or worse, this is still yet to be elucidated. Hypoxia has been shown to offer potentially therapeutic effects for bone by inducing an osteogenic–angiogenic response, although, others have noted excessive osteoclastic bone resorption instead. Much evidence suggests that the hypoxic‐inducible pathway is integral in mediating the changes in bone metabolism. Furthermore, many factors associated with hypoxia including changes in energy metabolism, acid–base balance and the increased generation of reactive oxygen species, are known to influence bone metabolism. This review aims to examine some of the putative mechanisms responsible for hypoxic‐induced alterations of bone metabolism, with regard to osteoclasts and osteoblasts, both positive and negative.     

新生儿首次呼吸前后脐带动静脉血液氧和二氧化碳变化探索呼吸调控机制的初步报告II—同一个新生儿同一时间的脐带动静脉血液氧和二氧化碳分压差值个体化分析*

目的: 为探讨新生儿自主呼吸产生机制,前文已对新生儿出生后自主呼吸开始前脐带动静脉氧气和二氧化碳差值进行了人群组间分析;而本部分则对相关信息进行个体化分析。方法: 在产前经所有胎儿父母签署知情同意书,新生儿出生后还没有呼吸之前在脐带动脉和脐带静脉分别连续逐搏取血,仅有3例同时采集到Pua和Puv血液样本进行血气分析测定,计算分析脐带静脉和脐带动脉的异同和动态变化。结果: 虽然准备了数十产妇,但仅有3例同时采集到Pua和Puv血液样本,同一时间的PuvO₂显著高于PuaO₂（P均<0.01）,平均相差（24.17±7.09） mmHg;而PuvCO₂显著低于PuaCO₂（P均<0.01）,平均相差（-7.67±3.70） mmHg。在同一时间的Puv-uaO₂显著高于Puv-uaCO₂（P<0.05）。结论: 新生儿出生后自主呼吸前,全部氧气供应由脐带静脉运输,只要胎盘开始剥离则新生儿的PuaO₂随时间（心跳次数）逐渐降低,当PuaO₂达到触发呼吸阈值（最低值）诱发第一次吸气开始其自主呼吸。     

不同介入时间和不同疗程高压氧治疗对脑出血模型大鼠动物学行为及促血管新生因子表达的影响

摘要 目的：探讨不同介入时间和不同疗程高压氧治疗对脑出血大鼠动物学行为及促血管新生因子表达的影响。方法：240只SD大鼠随机分为假手术组、脑出血组、高压氧组,每组各80只。采用胶原酶诱导建立脑出血大鼠模型,建模成功后根据高压氧介入时间分为6 h介入组、1 d介入组、2 d介入组、3 d介入组等亚组。分别治疗1周、2周、3周、4周,采用Longa评分法、平衡木评分法、Berderson评分法评估大鼠动物学行为,采用qRT-PCR检测大鼠脑组织血管内皮生长因子（VEGF）、缺氧诱导因子-1α（HIF-1α）mRNA表达。结果：不同介入时间、不同疗程,脑出血组、高压氧组脑出血大鼠动物学行为评分、脑组织VEGF mRNA与HIF-1α mRNA表达均高于假手术组（P<0.05）。治疗1周、2周、3周、4周,不同介入时间高压氧组脑出血大鼠动物学行为评分低于脑出血组,脑组织VEGF mRNA、HIF-1α mRNA表达高于脑出血组（P<0.05）。高压氧介入时间越早,治疗疗程越长,脑出血大鼠动物学行为评分越低,脑组织VEGF mRNA、HIF-1α mRNA表达越高,差异均有统计学意义（P<0.05）。结论：高压氧治疗能够改善脑出血大鼠动物学行为、促进促血管新生因子表达,且以脑出血后6 h介入、疗程4周效果最佳。     

The protective effect of sulforaphane against oxidative stress in granulosa cells of patients with polycystic ovary syndrome (PCOS) through activation of AMPK/AKT/NRF2 signaling pathway

Increased production of reactive oxygen species (ROS) in granulosa cells (GCs) causes oxidative stress (OS) and plays a role in pathogenesis of polycystic ovary syndrome (PCOS). Sulforaphane (SFN) has received a great deal of attention as potent antioxidant because of its ability to induce expression of antioxidant enzymes through nuclear factor (erythroid-derived 2)-like 2 (NRF2) signaling pathway. Therefore, the present study was done to investigate the protective effect of SFN against OS in granulosa-lutein cells (GLCs) of patients with PCOS through activation of AMP-activated protein kinase (AMPK)/AKT/NRF2 signaling pathway. GLCs were isolated from patients with PCOS and healthy fertile women, as control group, during egg retrieval procedure. Level of intracellular ROS and apoptosis was determined in the isolated cells. For investigating the protective effect of SFN against ROS production and apoptosis in GLCs, the cells were cultured for 24 h in the presence or absence of SFN. Finally, expression of AMPK, AKT, and NRF2 proteins and genes was evaluated by western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), respectively. The results indicated the increased ROS and apoptosis levels in GLCs isolated from patients with PCOS compared to the control group. Addition of SFN to culture medium of GLCs of patients with PCOS reduced intracellular ROS and apoptosis levels, and increased expression of AMPK, AKT, and NRF2 proteins and genes. Our findings demonstrated the protective effect of SFN against OS by lowering level of ROS and apoptosis possibly through activation of AMPK, AKT, and NRF2 proteins and genes expression.     

Elevated angiotensin II induces platelet apoptosis through promoting oxidative stress in an AT1R-dependent manner during sepsis

Thrombocytopenia is independently related with increased mortality in severe septic patients. Renin-angiotensin system (RAS) is elevated in septic subjects; accumulating studies show that angiotensin II (Ang II) stimulate the intrinsic apoptosis pathway by promoting reactive oxygen species (ROS) production. However, the mechanisms underlying the relationship of platelet apoptosis and RAS system in sepsis have not been fully elucidated. The present study aimed to elucidate whether the RAS was involved in the pathogenesis of sepsis-associated thrombocytopenia and explore the underlying mechanisms. We found that elevated plasma Ang II was associated with decreased platelet count in both patients with sepsis and experimental animals exposed to lipopolysaccharide (LPS). Besides, Ang II treatment induced platelet apoptosis in a concentration-dependent manner in primary isolated platelets, which was blocked by angiotensin II type 1 receptor (AT1R) antagonist losartan, but not by angiotensin II type 2 receptor (AT2R) antagonist PD123319. Moreover, inhibiting AT1R by losartan attenuated LPS-induced platelet apoptosis and alleviated sepsis-associated thrombocytopenia. Furthermore, Ang II treatment induced oxidative stress level in a concentration-dependent manner in primary isolated platelets, which was partially reversed by the AT1R antagonist losartan. The present study demonstrated that elevated Ang II directly stimulated platelet apoptosis through promoting oxidative stress in an AT1R-dependent manner in sepsis-associated thrombocytopenia. The results would helpful for understanding the role of RAS system in sepsis-associated thrombocytopenia.