Heat stress suppresses MnSOD expression via p53-Sp1 interaction and induces oxidative stress damage in endothelial cells: Protective effects of MitoQ10 and Pifithrin-α.

Aim: To investigate the mechanism of p53-mediated suppression of heat stress-induced oxidative stress damage by manganese superoxide dismutase (MnSOD) in endothelial cells (ECs). Methods: Primary ECs isolated from mouse aortas were used to examine the effects of heat stress on vascular ECs viability and apoptosis. We measured MnSOD expression, reactive oxygen species (ROS) production, p53 expression, viability, and apoptosis of heat stress-induced ECs. We also tested the protective effects of MitoQ10, a mitochondrial-targeted antioxidant, and Pifithrin-α, a p53 inhibitor, in ECs from a mouse model of heat stroke. Results: Heat stress increased cellular apoptosis, ROS production, and p53 expression, while reducing cellular viability and MnSOD expression in ECs. We also showed that the suppression of MnSOD expression by heat stress in ECs was mediated by interactions between p53 and Sp1. Furthermore, MitoQ10 and Pifithrin-α alleviated heat stress-induced oxidative stress and apoptosis in ECs. Conclusion: Our results revealed that p53-mediated MnSOD downregulation is a key mechanism for heat stress-induced oxidative stress damage in ECs and indicated that MitoQ10 and Pifithrin-α could be potential therapeutic agents for heat stroke.

Multiple intracranial enlarging dissecting aneurysms: a case report.

BACKGROUND: Cases of multiple cerebral aneurysms are rare. In this case report, we describe a male patient with multiple, enlarging, and ruptured aneurysms. The two aneurysms were believed to be dissecting aneurysms. CASE DESCRIPTION: A 47-year-old man presented with left limb paralysis. Magnetic resonance imaging revealed a cerebral infarction. Digital subtraction angiography (DSA) identified an aneurysm and occlusion in the right middle cerebral artery (MCA). The MCA aneurysm was remarkably enlarged on the eighth day after cerebral ischemia and was treated using endovascular techniques. Two weeks after the endovascular treatment, the patient experienced a severe headache and became comatose, and a subarachnoid re-hemorrhage was confirmed. The fourth DSA revealed an enlarging dissecting aneurysm in the posterior cerebral artery. The patient died without further treatment. CONCLUSION: Some dissecting aneurysms rapidly enlarge and rupture.

Heat stress-induced intestinal epithelial cells necroptosis via TLR3-TRIF-RIP3 pathway was dependent on p53.

BACKGROUND: Heatstroke is a life-threatening disease. Present study was aimed to investigate the mechanism in heat induced intestinal epithelial cell death. METHOD: Heat stress in vitro model was established on IEC cells with 42℃ for 2 h. Caspase-8 inhibitor, Caspase-3 inhibitor, RIP3 inhibitor, TLR3 agonist, poly(I:C) and p53 knockdown were used to determine the signaling pathway. Heatstroke in vivo model was established on C57BL/6 mice, with a temperature of 35.5℃±0.5℃ and a relative humidity of 60% ± 5%. The intestine necroptosis and inflammatory cytokines were measured. Pifithrin α (3 mg/kg) and p53 knockout mice were used to evaluate the role of p53. RESULTS: Heat stress-induced reduction of cell viability was remarkable reversed by RIP3 inhibitor. Heat stress induced upregulation of TLR3 and facilitate the formation of TRIF-RIP3 complex. The heat stress induced upregulation of RIP3 and p-RIP3 were normalized by the deletion of p53. Meanwhile, p53 knockout decreased TLR3 expression and blocked the formation of TLR3-TRIF complex. The deletion of p53 blocked the decreased cell viability and restored the activation of RIP3-MLKL signaling after heat stress, however, which were abolished by re-expression of p53 via Tp53 OE. Increased the expression of TLR3 in the p53-deficient cells could not affect the heat stress induced necrotic cell death, which suggests that heat stress induced necroptosis via TLR3-TRIF-RIP3 signaling pathway is dependent on p53. CONCLUSION: Heat stress promoted p53 phosphorylation, then upregulated TLR3 and enhanced the interaction of TRIF-RIP3, which would activate the RIP3-MLKL signaling pathway to mediate necroptosis in intestinal epithelial cells.

POLYDATIN AMELIORATES TRAUMATIC BRAIN INJURY-INDUCED SECONDARY BRAIN INJURY BY INHIBITING NLRP3-INDUCED NEUROINFLAMMATION ASSOCIATED WITH SOD2 ACETYLATION.

ABSTRACT: Traumatic brain injury (TBI) is a kind of disease with high morbidity, mortality, and disability, and its pathogenesis is still unclear. Research shows that nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) activation in neurons and astrocytes is involved in neuroinflammatory cascades after TBI. What is more, polydatin (PD) has been shown to have a protective effect on TBI-induced neuroinflammation, but the mechanisms remain unclear. Here, we speculated that PD could alleviate TBI-induced neuroinflammatory damage through the superoxide dismutase (SOD2)-NLRP3 signal pathway, and SOD2 might regulate NLRP3 inflammasome activation. The model of lateral fluid percussion for in vivo and cell stretching injury for in vitro were established to mimic TBI. NLRP3 chemical inhibitor MCC950, SOD2 inhibitor 2-methoxyestradiol, and PD were administered immediately after TBI. As a result, the expression of SOD2 acetylation (SOD2 Ac-K122), NLRP3, and cleaved caspase-1 were increased after TBI both in vivo and in vitro , and using SOD2 inhibitor 2-methoxyestradiol significantly promoted SOD2 Ac-K122, NLRP3, and cleaved caspase-1 expression, as well as exacerbated mitochondrial ROS (mtROS) accumulation and mitochondrial membrane potential (MMP) collapse in PC12 cells. However, using NLRP3 inhibitor MCC950 significantly inhibited cleaved caspase-1 activation after TBI both in vivo and in vitro ; meanwhile, MCC950 inhibited mtROS accumulation and MMP collapse after TBI. More importantly, PD could inhibit the level of SOD2 Ac-K122, NLRP3, and cleaved caspase-1 and promote the expression of SOD2 after TBI both in vivo and in vitro. Polydatin also inhibited mtROS accumulation and MMP collapse after stretching injury. These results indicated that PD inhibited SOD2 acetylation to alleviate NLRP3 inflammasome activation, thus acting a protective role against TBI neuroinflammation.

Correction: A hybrid GaN/Ga2O3 structure anchored on carbon cloth as a high-performance electrode of supercapacitors.

Correction for 'A hybrid GaN/Ga2O3 structure anchored on carbon cloth as a high-performance electrode of supercapacitors' by Yan-Ling Hu, et al., Dalton Trans., 2022, https://doi.org/10.1039/d2dt02904a.

A hybrid GaN/Ga2O3 structure anchored on carbon cloth as a high-performance electrode of supercapacitors.

A hybrid structure of GaN/Ga2O3 microrods was fabricated on carbon cloth (CC) using a hydrothermal process combined with a high-temperature nitridation followed by an air annealing process. By elevating the post-annealing temperature to 500 °C, both electron density (ND) and specific capacitance (Ca) of the composite electrode were significantly enhanced. Symmetric SCs assembled with GaN/CC-500 showed great potential in both 1 M H2SO4 aqueous solution and a PVA-H2SO4 gel-like electrolyte. The aqueous symmetric GaN/CC-500 SC exhibited an excellent capacitance (1301.20 mF cm-2, 0.5 mA cm-2), high rate capability (75.23% of capacitance retention at 10 mA cm-2), outstanding cycling stability (77.27% of capacitance retention after 20 000 cycles, 10 mA cm-2), and large energy storage capability (27.53 µW h cm-2 of energy density, 0.10 mW cm-2 of power density). All-solid-state symmetric GaN/CC-500 SC also manifested a high capacitance (1183.35 mF cm-2, 0.5 mA cm-2) and good rate capability (53.98% capacitance retention, 10 mA cm-2). The high electrochemical performance of the GaN/CC-500 electrode is attributed to the GaN/Ga2O3 hybrid structure, with α-Ga2O3 providing absorption/redox active sites on the surface, and the heavily oxygen-doped GaN enabling fast electron transport. The microrods with the GaN/Ga2O3 hybrid structure as the active material for solid SCs can deliver an energy density of 0.58 W h kg-1 (3.54 mW h cm-3) with a power density of 154 W kg-1 (0.94 W cm-3). The mechanism identified in this work would be helpful in designing GaN-based energy storage devices with better performances in the future.

The role of S100B/RAGE-enhanced ADAM17 activation in endothelial glycocalyx shedding after traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) remains one of the main causes for disability and death worldwide. While the primary mechanical injury cannot be avoided, the prevention of secondary injury is the focus of TBI research. Present study aimed to elucidate the effects and mechanisms of S100B and its receptor RAGE on mediating secondary injury after TBI. METHODS: This study established TBI animal model by fluid percussion injury in rats, cell model by stretch-injured in astrocytes, and endothelial injury model with conditioned medium stimulation. Pharmacological intervention was applied to interfere the activities of S100B/RAGE/ADAM17 signaling pathway, respectively. The expressions or contents of S100B, RAGE, syndecan-1 and ADAM17 in brain and serum, as well as in cultured cells and medium, were detected by western blot. The distribution of relative molecules was observed with immunofluorescence. RESULTS: We found that TBI could activate the release of S100B, mostly from astrocytes, and S100B and RAGE could mutually regulate their expression and activation. Most importantly, present study revealed an obvious increase of syndecan-1 in rat serum or in endothelial cultured medium after injury, and a significant decrease in tissue and in cultured endothelial cells, indicating TBI-induced shedding of endothelial glycocalyx. The data further proved that the activation of S100B/RAGE signaling could promote the shedding of endothelial glycocalyx by enhancing the expression, translocation and activity of ADAM17, an important sheddase, in endothelial cells. The damage of endothelial glycocalyx consequently aggravated blood brain barrier (BBB) dysfunction and systemic vascular hyper-permeability, overall resulting in secondary brain and lung injury. CONCLUSIONS: TBI triggers the activation of S100B/RAGE signal pathway. The regulation S100B/RAGE on ADAM17 expression, translocation and activation further promotes the shedding of endothelial glycocalyx, aggravates the dysfunction of BBB, and increases the vascular permeability, leading to secondary brain and lung injury. Present study may open a new corridor for the more in-depth understanding of the molecular processes responsible for cerebral and systemic vascular barrier impairment and secondary injury after TBI.

Predicting early refractoriness of transarterial chemoembolization in patients with hepatocellular carcinoma using a random forest algorithm: A pilot study.

Purpose: To develop and validate a random forest (RF) based predictive model of early refractoriness to transarterial chemoembolization (TACE) in patients with unresectable hepatocellular carcinoma (HCC). Methods: A total of 227 patients with unresectable HCC who initially treated with TACE from three independent institutions were retrospectively included. Following a random split, 158 patients (70%) were assigned to a training cohort and the remaining 69 patients (30%) were assigned to a validation cohort. The process of variables selection was based on the importance variable scores generated by RF algorithm. A RF predictive model incorporating the selected variables was developed, and five-fold cross-validation was performed. The discrimination and calibration of the RF model were measured by a receiver operating characteristic (ROC) curve and the Hosmer-Lemeshow test. Results: The potential variables selected by RF algorithm for developing predictive model of early TACE refractoriness included patients' age, number of tumors, tumor distribution, platelet count (PLT), and neutrophil-to-lymphocyte ratio (NLR). The results showed that the RF predictive model had good discrimination ability, with an area under curve (AUC) of 0.863 in the training cohort and 0.767 in the validation cohort, respectively. In Hosmer-Lemeshow test, the RF model had a satisfactory calibration with P values of 0.538 and 0.068 in training cohort and validation cohort, respectively. Conclusion: The RF algorithm-based model has a good predictive performance in the prediction of early TACE refractoriness, which may easily be deployed in clinical routine and help to determine the optimal patient of care.

Damaged brain accelerates bone healing by releasing small extracellular vesicles that target osteoprogenitors.

Clinical evidence has established that concomitant traumatic brain injury (TBI) accelerates bone healing, but the underlying mechanism is unclear. This study shows that after TBI, injured neurons, mainly those in the hippocampus, release osteogenic microRNA (miRNA)-enriched small extracellular vesicles (sEVs), which targeted osteoprogenitors in bone to stimulate bone formation. We show that miR-328a-3p and miR-150-5p, enriched in the sEVs after TBI, promote osteogenesis by directly targeting the 3'UTR of FOXO4 or CBL, respectively, and hydrogel carrying miR-328a-3p-containing sEVs efficiently repaires bone defects in rats. Importantly, increased fibronectin expression on sEVs surface contributes to targeting of osteoprogenitors in bone by TBI sEVs, thereby implying that modification of the sEVs surface fibronectin could be used in bone-targeted drug delivery. Together, our work unveils a role of central regulation in bone formation and a clear link between injured neurons and osteogenitors, both in animals and clinical settings.

Endothelial glycocalyx in traumatic brain injury associated coagulopathy: potential mechanisms and impact.

Traumatic brain injury (TBI) remains one of the leading causes of death and disability worldwide; more than 10 million people are hospitalized for TBI every year around the globe. While the primary injury remains unavoidable and not accessible to treatment, the secondary injury which includes oxidative stress, inflammation, excitotoxicity, but also complicating coagulation abnormalities, is potentially avoidable and profoundly affects the therapeutic process and prognosis of TBI patients. The endothelial glycocalyx, the first line of defense against endothelial injury, plays a vital role in maintaining the delicate balance between blood coagulation and anticoagulation. However, this component is highly vulnerable to damage and also difficult to examine. Recent advances in analytical techniques have enabled biochemical, visual, and computational investigation of this vascular component. In this review, we summarize the current knowledge on (i) structure and function of the endothelial glycocalyx, (ii) its potential role in the development of TBI associated coagulopathy, and (iii) the options available at present for detecting and protecting the endothelial glycocalyx.

Polydatin alleviates severe traumatic brain injury induced acute lung injury by inhibiting S100B mediated NETs formation.

Severe traumatic brain injury (sTBI)-induced acute lung injury (sTBI-ALI) is regarded as the most common complication of sTBI that is an independent predictor of poor outcomes in patients with sTBI and strongly increases sTBI mortality. Polydatin (PD) has been shown to have a potential therapeutic effect on sTBI-induced neurons injury and sepsis-induced acute lung injury (ALI), therefore, it is reasonable to believe that PD has a protective effect on sTBI-ALI. Here, to clarify the PD protective effect following sTBI-ALI, a rat brain injury model of lateral fluid percussion was established to mimic sTBI. As a result, sTBI induced ALI, and caused an increasing of wet/dry weight ratio and lung vascular permeability, as well as sTBI promoted oxidative stress response in the lung; sTBI caused inflammatory cytokines release, such as IL-6, IL-1ß, TNF-α and MCP-1; and sTBI promoted NETs formation, mainly including an increasing expression of MPO, NE and CitH3. Simultaneously, sTBI induced a significant increase in the level of S100B; however, when inhibition of S100B, the expression of MPO, NE and CITH3 were significantly inhibited following sTBI. Inhibition of S100B also promoted lung vascular permeability recovery and alleviated oxidative stress response. Furthermore, PD treatmentreduced the pathological lung damage, promoted lung vascular permeability recovery, alleviated oxidative stress response and inflammatory cytokines release; more importantly, PD inhibited the expression of S100B, and NETs formation in the lung following sTBI. These results indicate that PD alleviates sTBI-ALI by inhibiting S100B mediated NETs formation. Thus, PD may be valuable in sTBI-ALI treatment.

Current updates in machine learning in the prediction of therapeutic outcome of hepatocellular carcinoma: what should we know?

With the development of machine learning (ML) algorithms, a growing number of predictive models have been established for predicting the therapeutic outcome of patients with hepatocellular carcinoma (HCC) after various treatment modalities. By using the different combinations of clinical and radiological variables, ML algorithms can simulate human learning to detect hidden patterns within the data and play a critical role in artificial intelligence techniques. Compared to traditional statistical methods, ML methods have greater predictive effects. ML algorithms are widely applied in nearly all steps of model establishment, such as imaging feature extraction, predictive factor classification, and model development. Therefore, this review presents the literature pertaining to ML algorithms and aims to summarize the strengths and limitations of ML, as well as its potential value in prognostic prediction, after various treatment modalities for HCC.

Evaluation of isolated left ventricular noncompaction using cardiac magnetic resonance tissue tracking in global, regional and layer-specific strains.

We used cardiac magnetic resonance tissue tracking (CMR-TT) to quantitatively analyze the global, regional and layer-specific strain of isolated left ventricular noncompaction (ILVNC). Combined with late gadolinium enhancement (LGE), we initially explored the effect of focal myocardial fibrosis on myocardial strain. CMR was performed in 63 patients with ILVNC and 52 patients without ILVNC (i.e., the control group). The ILVNC group was divided into an LGE(+) group (29 patients) and an LGE(-) group (34 patients) according to the presence or absence of late gadalinum enhancement (LGE). CVI42 software was used to measure global and regional (basal, middle, apical) radial strain (RS), circumferential strain (CS), longitudinal strain (LS), subendocardial LS and subepicardial LS. The basal-apical strain gradient was defined as the apical mean strain minus the basal mean strain. We then compared differences between these strain parameters. The subendocardial-subepicardial LS gradient was defined as the maximum subendocardial LS minus the subepicardial LS. Compared with the control group, the global and regional RS, CS, LS and the subendocardial, subepicardial LS of the ILVNC group were significantly diminished (P < 0.01). Compared with the LGE(-) group, the global and regional RS, CS, LS and the subendocardial, subepicardial LS of the LGE(+) group were significantly diminished (P < 0.05). In the ILVNC group, the basal-apical CS and LS gradient, and the subendocardial-subepicardial LS gradient were significantly lower than those in the control group (P < 0.01). There were significant differences in myocardial strain between patients with and without ILVNC. ILVNC revealed a specific pattern in terms of strain change. The myocardial strain of the cardiac apex and endocardium was significantly lower than that of the cardiac base and epicardium, respectively. Myocardial strain reduction was more significant in ILVNC patients with focal myocardial fibrosis.

Motion-corrected free-breathing late gadolinium enhancement combined with a gadolinium contrast agent with a high relaxation rate: an optimized cardiovascular magnetic resonance examination protocol.

OBJECTIVE: This prospective study investigated the feasibility of an optimized cardiovascular magnetic resonance (CMR) examination protocol using the motion-corrected (MOCO), balanced steady-state free precession (bSSFP), phase-sensitive inversion recovery (PSIR) sequence combined with a gadolinium contrast agent with a high relaxation rate in patients who cannot hold their breath. METHODS: Fifty-one patients with heart disease underwent CMR examinations twice and these were performed with different late gadolinium enhancement (LGE) imaging sequences (fast low-angle shot [FLASH] sequence vs. MOCO sequence) and different gadolinium contrast agents (gadopentetate dimeglumine vs. gadobenate dimeglumine) with a 48-hour interval. LGE image quality, total time spent in the whole study, and time taken to perform LGE imaging were compared for the two CMR examinations. RESULTS: LGE images with the MOCO bSSFP PSIR sequence showed significantly higher image quality compared with those with the segmented FLASH PSIR sequence. There was a significant difference between the total scan time for the two examinations and different LGE sequences. CONCLUSIONS: The MOCO bSSFP PSIR sequence effectively improves the quality of LGE images. Changing the CMR scanning protocol by combining the MOCO bSSFP PSIR sequence with a gadolinium contrast agent with a high relaxation rate effectively shortens the scan time.Clinical trial registration number: ChiCTR-ROC-17013978.

Preventing necroptosis by scavenging ROS production alleviates heat stress-induced intestinal injury.

Background: Worldwide heat stroke incidence has increased in recent years and is associated with high morbidity and mortality. Therefore, it is critical to identify mechanisms that mediate heat stroke. Previous studies suggested that damage to the small intestine may be a major factor in heat stroke-related morbidity and mortality. However, the mechanism underlying heat stroke related small intestine injury remains unclear.Methods: To explore how heat stroke promotes intestinal damage, we applied two well established models: mouse and IEC-6 cells heat stress (HS) to mimic heat stroke both in vivo and in vitro. The percentages of viability and cell death were assessed by WST-1 and LDH release assays. Induction of HS-induced cell death was analyzed by flow cytometry with Annexin V-FITC/PI staining. Flow cytometry was used to analyze HS-induced mitochondrial superoxide with MitoSOX staining. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) levels were detected by ELISA. Flow cytometry was used to analyze HS-induced mitochondrial depolarization (low ΔΨm) with JC-1 staining. Histopathology changes in the ileum were detected by H&E staining.The ileum ultrastructure was observed by transmission electron microscopy (TEM). RIPK1, RIPK3, phosphorylated MLKL, and MLKL levels were detected by Western blot. RIPK1-RIPK3 complexes were measured by immunoprecipitation assay.Results: HS increased both necrotic cell rate and RIPK1, RIPK3, and phosphorylated MLKL expression levels in IEC-6 cells. These increased expression levels promoted higher RIPK1-RIPK3 complex formation, leading to necrosome formation both in vivo and in vitro. Moreover, HS caused dyshomeostasis, an oxidative stress response, and mitochondrial damage, along with small intestinal tissue injury and cell death. However, IEC-6 cells or mice pretreated with the RIPK1 activity chemical inhibitor Nec-1 or RIPK3 activity chemical inhibitor GSK'872 significantly reversed these phenomena and promoted balance in oxidative stress response homeostasis. More importantly, the reactive oxygen species (ROS) scavenger N-acetyl-L-cysteine (NAC) pretreatment significantly inhibited HS-induced RIPK1/RIPK3-dependent necroptosis formation both in vivo and in vitro, suggesting that preventing necroptosis via scavenging ROS production might alleviate HS-induced small intestinal tissue injury and cell death.Conclusion: This study provides strong evidence that HS causes damage to both the small intestine and intestinal epithelial cells, scavenging ROS production can significantly alleviate such RIPK1/RIPK3-dependent necroptosis, mediating HS-induced intestinal damage both in vitro and in vivo. These findings provide a clear target for future mechanism-based therapeutic strategies for patients diagnosed with heat stroke.

Ser46 phosphorylation of p53 is an essential event in prolyl-isomerase Pin1-mediated p53-independent apoptosis in response to heat stress.

Heat stroke has increased in frequency worldwide in recent years and continues to have a high morbidity and mortality. Identification of the mechanisms mediating heat stoke is important and necessary. Our preliminary study revealed heat stress (HS)-induced apoptosis of vascular endothelial cells was associated with reactive oxygen species (ROS)-induced p53 translocation into mitochondria. Previous studies have suggested the prolyl-isomerase Pin1 regulates p53 functioning through specific binding to p53 phosphorylation sites. Based on these studies, we presumed Pin1 is a key intermediate in regulation of mitochondrial p53 translocation through a HS-induced ROS-p53 transcription-independent apoptosis pathway. In this context, we revealed p53 had a crucial role in a HS-induced mitochondrial apoptotic pathway, where p53 protein rapidly translocated into mitochondria in endothelial cells both in vitro and in vivo. In particular, HS caused an increase in p53 phosphorylation at Ser46 that facilitated interactions with phosphorylation-dependent prolyl-isomerase Pin1, which has a key role in promoting HS-induced localization of p53 to mitochondria. Furthermore, we also found ROS production was a critical mediator in HS-induced Pin1/p53 signaling and was involved in regulating mitochondrial apoptosis pathway activation. Therefore, we have contributed to our profound understanding of the mechanism underlying HS-induced endothelial dysfunction in an effort to reduce the mortality and morbidity of heat stroke.

Microwave-Hydrothermal Treated Grape Peel as an Efficient Biosorbent for Methylene Blue Removal.

Biosorption using agricultural wastes has been proven as a low cost and efficient way for wastewater treatment. Herein, grape peel treated by microwave- and conventional-hydrothermal processes was used as low cost biosorbent to remove methylene blue (MB) from aqueous solutions. The adsorption parameters including the initial pH value, dosage of biosorbents, contact time, and initial MB concentration were investigated to find the optimum adsorption conditions. The biosorbent obtained by microwave-hydrothermal treatment only for 3 min at 180 °C (microwave-hydrothermal treated grape peel, MGP) showed faster kinetics and higher adsorption capability than that produced by a conventional-hydrothermal process (hydrothermal treated grape peel, HGP) with a duration time of 16 h. The maximum adsorption capability of MGP under the optimum conditions (pH = 11, a dosage of 2.50 g/L) as determined with the Langmuir model reached 215.7 mg/g, which was among the best values achieved so far on biosorbents. These results demonstrated that the grape peel treated by a quick microwave-hydrothermal process can be a very promising low cost and efficient biosorbent for organic dye removal from aqueous solutions.

[Role of cytoplasmic p53-mediated suppression of autophagy in heat stress-induced injury of cultured mouse aortic endothelial cells].

OBJECTIVE: To explore the association of cytoplasmic p53 with autophagy and apoptosis of primary aortic endothelial cells (MAECs) exposed to heat stress. METHODS: Cultured mouse MAECs were exposed to heat stress induced by incubation at 43 ℃ for 2 h, with the cells in routine culture condition (37 ℃, 5% CO2) as the control group. All the cells were further incubated for 1, 3, 6 or 9 h at 37 ℃ before treatment with the autophagy inhibitor 3-MA (5 mmol/L), the autophagy inducer rapamycin (20 µmol/L), or the p53 inhibitor PFT (10 µmol/L) for 1 h. After the treatments, the cell viability was measured with CCK8 method, cell apoptosis analyzed by flow cytometry, and the mitochondrial membrane potential detected with flow cytometry with JC-1 staining; the subcellular localization of p53 and the autophagy- associated protein LC3-Ⅱ was detected with immunofluorescence staining, and their protein expressions were analyzed using Western blotting. RESULTS: Compared with the control cells, MAECs exposed to heat stress showed significantly decreased viability (P < 0.05). At 6 h after the exposure, the cells exhibited significantly decreased mitochondrial membrane potential with increased apoptotic rate (P < 0.05). The cytoplasmic fraction of p53 expression decreased and its mitochondrial fraction increased gradually with time within 6 h after heat stress. Treatment with 3- MA further decreased the mitochondrial membrane potential and significantly increased the apoptotic rate of the exposed cells (P < 0.05), while rapamycin obviously reversed these heat stress-induced cell injuries (P < 0.05). PFT significantly enhanced the expression of LC3-Ⅱ and also inhibited heat stress-induced mitochondrial membrane potential reduction and cell apoptosis (P < 0.05). CONCLUSIONS: Heat stress induces mitochondrial damage and apoptosis in MAECs possibly in relation with mitochondrial translocation of cytoplasmic p53 to result in autophagy inhibition.

Heat stress induces intestinal injury through lysosome- and mitochondria-dependent pathway in vivo and in vitro.

Damage to the small intestine secondary to heat stroke is a major factor in heat stroke-related morbidity and mortality. However, the underlying mechanisms by which heat stroke causes small intestinal lesions and dysfunction remain unclear. To explore the pathogenesis of small intestinal tissue and epithelial cell injury, the SW480 cell heat stress model and the mice heat stroke model were established to mimic heat stroke. Morphologic changes in intestinal tissue and increased TUNEL-positive index were induced by heat stress in vivo. Heat stress activated the lysosomal-mitochondrial apoptotic pathway in SW480 cells, increasing intracellular reactive oxygen species and causing lysosomal membrane permeabilization with subsequent release of cathepsin B to the cytosol, mitochondrial depolarization, and cytochrome C release to cytosol. An increase in the Bax/Bcl2 ratio, caspase-9 and caspase-3 were observed. N-Acetyl-L-Cysteine was shown to inhibit ROS generation, suppress permeabilization of lysosomal membranes, decrease levels of cathepsin B and cytochrome C in the cytosol, and inhibit Bax/Bcl2 ratio, caspase-9 and caspase-3 activity both in vitro and in vivo. Mitochondrial damage was alleviated when the models were pre-treated with CA-074 Me both in vitro and in vivo, decreasing cathepsin B and cytochrome C levels in the cytosol, Bax/Bcl2 ratio, caspase-9 and caspase-3 activity. In our models, heat stress-induced apoptosis of small intestinal tissue and epithelial cells through accumulation of ROS and activation of the lysosomal-mitochondrial apoptotic pathway involved the release of cathepsin B. These findings may offer potentially pharmaceutical targets and strategies to repair intestinal injury caused by heat stroke.

Dormant micro arteriovenous malformations lead to recurrent cerebral haemorrhage.

INTRODUCTION: Some micro arteriovenous malformations (AVMs) located in deep brain are undetectable. How to choose a proper timing to detect these AVMs remains unclear. CASE DESCRIPTION: A 21-year-old male patient was admitted to our center for intraventricular haematoma. Digital subtraction angiographies (DSAs) were performed one week and one month respectively after his haemorrhage, but no positive results were obtained. The patient was hospitalized for re-haemorrhage six years later. A micro AVM with two diffused niduses was detected and embolised three months after his re-haemorrhage. The patient recovered without any neurological deficit. DISCUSSION AND EVALUATION: Compressive effects of haematoma and spontaneous obliteration of AVMs might play pivotal roles in negative DSA results. CONCLUSIONS: Strategic and timely use of DSA could identify some dormant re-haemorrhagic AVMs.