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Background: Hypertrophic scar (HS) is associated with cosmetic defects, mobility, and functional impairments, pruritus, and pain. Previous circRNA microarray analysis identified reduced expression of circRNA_SLC8A1 in HS tissues. Therefore, this study aims to investigate the role of circRNA_SLC8A1 in modulating the abnormal behavior of HS-derived fibroblasts (HSFs) in vitro., Methods: RT-qPCR and FISH assays were used to assess the differential expression and localization of circRNA_SLC8A1 in normal and HS tissues. Following modulation of circRNA_SLC8A1 expression, CCK-8, flow cytometry, Transwell, and wound healing assays were employed to evaluate the effects of circRNA_SLC8A1 on the biological behaviors of HSFs. The Starbase database, dual-luciferase reporter assays, and Ago2-RIP assays were utilized to predict and validate the interaction between circRNA_SLC8A1 and downstream miRNAs., Results: CircRNA_SLC8A1 was found to be downregulated in HS tissues and was primarily localized in the cytoplasm. Overexpression of circRNA_SLC8A1 reduced cell viability, cell invasion, wound healing, and the expression of Vimentin, N-cadherin, Col I, and Col III, while enhancing apoptosis and E-cadherin expression in HSFs. CircRNA_SLC8A1 activates the Nrf2-ARE pathway by competitively binding to miRNA-27a-3p. miRNA-27a-3p and Nrf2 exhibited high and low expression, respectively in HS tissues, with an inverse correlation between their levels. Overexpression of miRNA-27a-3p counteracted the effects of circRNA_SLC8A1 in HSF proliferation, apoptosis, migration, EMT, collagen deposition, and Nrf2-ARE pathway activity., Conclusion: CircRNA_SLC8A1 inhibits the proliferation, migration, EMT, and collagen deposition of HSF through competitive binding with miRNA-27a-3p, thereby activating the Nrf2-ARE pathway. The circRNA_SLC8A1/miRNA-27a-3p/Nrf2-ARE axis may offer a promising molecular target for HS therapy., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Cervical cancer ranks the fourth most prevalent type of cancer worldwide, characterized by a notably low survival rate, particularly in its metastatic stage. Despite 5-aminolevulinic acid photodynamic therapy (ALA-PDT) demonstrating potential anti-tumor effects against cervical cancer, the intricate mechanisms underlying its efficacy necessitate further investigation. Here, the study aims to elucidate the impact of ALA-PDT on the cancer cell viability, invasion and migration, alongside delineating the underlying molecular mechanisms., Methods: Cervical cancer SiHa cells were subjected to ALA and red light irradiation, and we then measured the ALA-PDT's effects on cell functions using various assays. The potential interaction between miR-152-3p and JAK1 was explored through bioinformatics analyses and validated by dual-luciferase reporter assays. Post-transfection with miR-152-3p and JAK1 vectors, cellular functions were re-evaluated. The efficacy of ALA-PDT in tumor suppression was further investigated through tumor transplantation experiment in vivo., Results: ALA-PDT markedly suppressed SiHa cell viability, invasion and migration, impacting critical markers of proliferation, apoptosis, and epithelial-mesenchymal transition(EMT). And these effects were echoed by the inhibition of miR-152-3p. JAK1 was identified as a direct target of miR-152-3p, and ALA-PDT was found to regulate the expression levels of miR-152-3p, consequently influencing the JAK1/STAT1 signaling pathway. Augmentation of miR-152-3p expression and inhibition of the JAK1/STAT1 pathway mitigated the anti-cancer effects of ALA-PDT, whereas JAK1 overexpression diminished these effects. In vivo analyses demonstrated that ALA-PDT suppressed tumor growth and modulated the miR-152-3p/JAK1/STAT1 pathway expression., Conclusions: ALA-PDT inhibits the viability, invasion, and migration of cervical cancer SiHa cells by modulating the miR-152-3p/JAK1/STAT1 axis, offering a promising therapeutic avenue for combating invasive cervical cancer., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest. No conflicting relationship exists for any author., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Zebrafish is a highly advantageous model animal for drug screening and toxicity evaluation thanks to its amenability to optical imaging (i.e., transparency), possession of organ structures similar to humans, and the ease with which disease models can be established. However, current zebrafish drug screening technologies and devices suffer from limitations such as low level of automation and throughput, and low accuracy caused by the heterogeneity among individual zebrafish specimens. To address these issues, we herein develop a high-throughput zebrafish drug screening system. This system is capable of maintaining optimal culturing conditions and simultaneously monitoring and analyzing the movement of 288 zebrafish larvae under various external conditions, such as drug combinations. Moreover, to eliminate the effect of heterogeneity, locomotion of participating zebrafish is assessed and grouped before experiments. It is demonstrated that in contrast to the experimental results without pre-selection, which shows ∼20 % damaged motor function (i.e., degree of attenuation), the drug-induced variations among zebrafish with equivalent mobility reaches ∼80 %. Overall, our high-throughput zebrafish drug screening system overcomes current limitations by improving automation, throughput, and accuracy, resulting in enhanced detection of drug-induced variations in zebrafish motor function., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Aims: This study aimed to investigate the relationship between microglial metabolism and neuroinflammation by examining the impact of citrate accumulation in microglia and its potential regulation through Cs K215 hypoacetylation., Methods: Experimental approaches included assessing Cs enzyme activity through Cs K215Q mutation and investigating the inhibitory effects of hesperidin, a natural flavanone glycoside, on citrate synthase. Microglial phagocytosis and expression of pro-inflammatory cytokines were also examined in relation to Cs K215Q mutation and hesperidin treatment., Results: Cs K215Q mutation and hesperidin exhibited significant inhibitory effects on Cs enzyme activity, microglial citrate accumulation, phagocytosis, and pro-inflammatory cytokine expression. Interestingly, Sirt3 knockdown aggravated microglial pro-inflammatory functions during neuroinflammation, despite its proven role in Cs deacetylation., Conclusion: Cs K215Q mutation and hesperidin effectively inhibited microglial pro-inflammatory functions without reversing the metabolic reprogramming. These findings suggest that targeting Cs K215 hypoacetylation and utilizing hesperidin may hold promise for modulating neuroinflammation in microglia., (© 2023 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Background: Gamma delta (γδ) T cells play dual roles in human tumors, with both antitumor and tumor-promoting functions. However, the role of γδT cells in HPV-infected cervical cancer is still undetermined. Therefore, we aimed to identify γδT cell-related prognostic signatures in the cervical tumor microenvironment., Methods: Single-cell RNA-sequencing (scRNA-seq) data, bulk RNA-seq data, and corresponding clinical information of cervical cancer patients were obtained from the TCGA and GEO databases. The Seurat R package was used for single-cell analysis, and machine learning algorithms were used to screen and construct a γδT cell-related prognostic signature. Real-time quantitative PCR (RT-qPCR) was performed to detect the expression of prognostic signature genes., Results: Single-cell analysis indicated distinct populations of γδT cells between HPV-positive (HPV+) and HPV-negative (HPV-) cervical cancers. A trajectory analysis indicated γδT cells clustered into differential clusters with the pseudotime. High-dimensional Weighted Gene Co-expression Network Analysis (hdWGCNA) identified the key γδT cell-related gene modules. Bulk RNA-seq analysis also demonstrated the heterogeneity of immune cells, and the γδT-score was positively associated with inflammatory response and negatively associated with MYC stemness. Eight γδT cell-related hub genes (GTRGs), including ITGAE, IKZF3, LSP1, NEDD9, CLEC2D, RBPJ, TRBC2, and OXNAD1, were selected and validated as a prognostic signature for cervical cancer., Conclusion: We identified γδT cell-related prognostic signatures that can be considered independent factors for survival prediction in cervical cancer., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Early brain injury (EBI) following  subarachnoid hemorrhage (SAH) is characterized by rapid development of neuron apoptosis and dysregulated inflammatory response. Microglia efferocytosis plays a critical role in the clearance of apoptotic cells, attenuation of inflammation, and minimizing brain injury in various pathological conditions. Here, using a mouse SAH model, we aim to investigate whether microglia efferocytosis is involved in post-SAH inflammation and to determine the underlying signaling pathway. We hypothesized that TAM receptors and their ligands regulate this process. To prove our hypothesis, the expression and cellular location of TAM (Tyro3, Axl, and Mertk) receptors and their ligands growth arrest-specific 6 (Gas6) and Protein S (ProS1) were examined by PCR, western blots, and fluorescence immunostaining. Thirty minutes after SAH, mice received an intraventricular injection of recombinant Gas6 (rGas6) or recombinant ProS1 (rPros1) and underwent evaluations of inflammatory mediator expression, neurological deficits, and blood-brain barrier integrity at 24 h. Microglia efferocytosis of apoptotic neurons was analyzed in vivo and in vitro. The potential mechanism was determined by inhibiting or knocking down TAM receptors and Rac1 by specific inhibitors or siRNA. SAH induced upregulation of Axl and its ligand Gas6. The administration of rGas6 but not rPros1 promoted microglia efferocytosis, alleviated inflammation, and ameliorated SAH-induced BBB breakdown and neurological deficits. The beneficial effects of rGas6 were arrogated by inhibiting or knocking down Axl and Rac1. We concluded that rGas6 attenuated the development of early brain injury in mice after SAH by facilitating microglia efferocytosis and preventing inflammatory response, which is partly dependent on activation of Axl and Rac1., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The pathogenesis and progression of endometrial cancer (EC) are associated with epithelial-mesenchymal transition (EMT) and long noncoding RNAs (lncRNAs). In the present study, we aimed to identify an EMT-related lncRNA signature and evaluate its prognostic value in EC. We obtained the expression profile of lncRNAs and clinical information of patients with endometrioid EC from The Cancer Genome Atlas database (N = 401). We identified a signature of 5 EMT-related lncRNAs and calculated the risk score of each patient. Next, we validated the independence of the prognostic value of the EMT-related lncRNA signature. Furthermore, we performed Gene Set Enrichment Analysis to identify potential molecular function and Kyoto Encyclopedia of Genes and Genomes pathways related to the EMT-related lncRNA signature. Tumor microenvironment analysis and immune checkpoint blockade (ICB) response prediction were also assessed. Survival analysis revealed that the high-risk group, based on the EMT-related lncRNA signature, had a poorer prognosis than the low-risk group in the training, testing, and entire sets. The predictive value of the EMT-related lncRNA signature was independent of age, The International Federation of Gynecology and Obstetrics stage, tumor grade, and body mass index. Time-dependent receiver operating characteristic curves also demonstrate the prognostic accuracy of this risk model. Gene Set Enrichment Analysis showed that cytokine-cytokine receptor interaction, glycolysis/gluconeogenesis, and IL-17 signaling pathway were significantly enriched. Furthermore, tumor microenvironment analysis indicated a significant negative correlation between the immune score and EMT-related lncRNA signature risks core, while the low-risk group was more likely to respond to ICB therapy than the high-risk group. A reliable EMT-related lncRNA signature of endometrioid EC was identified that could be utilized as an independent prognostic biomarker to predict patient survival outcomes and provide references for the option of ICB therapy., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Adult granulosa cell tumors (AGCT) mainly secret estrogen, but few androgens. It is rarer to have amenorrhea and hyperandrogenemia as clinical features. Here, we report a rare case of right side AGCTs with amenorrhea and hyperandrogenemia in a 19-year-old female., Patient Concerns: The 19-year-old patient was admitted to our hospital due to amenorrhea for more than 1 year, and discovery of pelvic mass for 4 months. The gynecological ultrasound and computed tomography (CT) cannot define the nature of the mass. Surprisingly, an elevation in testosterone levels was also measured., Diagnosis and Interventions: The present patient underwent laparoscopic right salpingo-oophorectomy and partial omentectomy and biopsy of the peritoneum., Outcomes: After the surgery, the testosterone value was down to normal. The patient menstrual cramps on August 13, 2021. Her clitoris is smaller than the front. Up to August 1, 2022, there was no obvious sign of recurrence., Lessons: Androgen-secreting AGCT is rare. We hope that this case can strengthen gynecologists' early diagnosis and treatment of this disease and improve the prognosis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Repetitive mild traumatic brain injury (rmTBI) is associated with a range of neural changes which is characterized by axonal injury and neuroinflammation. Ketogenic diet (KD) is regarded as a potential therapy for facilitating recovery after moderate-severe traumatic brain injury (TBI). However, its effect on rmTBI has not been fully studied. In this study, we evaluated the anti-neuroinflammation effects of KD after rmTBI in adolescent mice and explored the potential mechanisms. Experimentally, specific pathogen-free (SPF) adolescent male C57BL/6 mice received a sham surgery or repetitive mild controlled cortical impacts consecutively for 7 days. The uninjured mice received the standard diet, and the mice with rmTBI were fed either the standard diet or KD for 7 days. One week later, all mice were subjected to behavioral tests and experimental analysis. Results suggest that KD significantly increased blood beta-hydroxybutyrate (β-HB) levels and improved neurological function. KD also reduced white matter damage, microgliosis, and astrogliosis induced by rmTBI. Aryl hydrocarbon receptor (AHR) signaling pathway, which was mediated by indole-3-acetic acid (3-IAA) from Lactobacillus reuteri (L. reuteri) in gut and activated in microglia and astrocytes after rmTBI, was inhibited by KD. The expression level of the toll-like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88) in inflammatory cells, which mediates the NF-κB pathway, was also attenuated by KD. Taken together, our results indicated that KD can promote recovery following rmTBI in adolescent mice. KD may modulate neuroinflammation by altering L. reuteri in gut and its metabolites. The inhibition of indole/AHR pathway and the downregulation of TLR4/MyD88 may play a role in the beneficial effect of KD against neuroinflammation in rmTBI mice., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Selective activation of the C(sp 3 )-H bond is an important process in organic synthesis, where efficiently activating a specific C(sp 3 )-H bond without causing side reactions remains one of chemistry's great challenges. Here we report that illuminated plasmonic silver metal nanoparticles (NPs) can abstract hydrogen from the C(sp 3 )-H bond of the C α atom of an alkyl aryl ether β-O-4 linkage. The intense electromagnetic near-field generated at the illuminated plasmonic NPs promotes chemisorption of the β-O-4 compound and the transfer of photo-generated hot electrons from the NPs to the adsorbed molecules leads to hydrogen abstraction and direct cleavage of the unreactive ether C β -O bond under moderate reaction conditions (≈90 °C). The plasmon-driven process has certain exceptional features: enabling hydrogen abstraction from a specific C(sp 3 )-H bond, along with precise scission of the targeted C-O bond to form aromatic compounds containing unsaturated, substituted groups in excellent yields., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

A dataset of street light images is presented. Our dataset consists of ∼350 k images, taken from 140 UMBRELLA nodes installed in the South Gloucestershire region in the UK. Each UMBRELLA node is installed on the pole of a lamppost and is equipped with a Raspberry Pi Camera Module v1 facing upwards towards the sky and lamppost light bulb. Each node collects an image at hourly intervals for 24 h every day. The data collection spans for a period of six months. Each image taken is logged as a single entry in the dataset along with the Global Positioning System (GPS) coordinates of the lamppost. All entries in the dataset have been post-processed and labelled based on the operation of the lamppost, i.e., whether the lamppost is switched ON or OFF. The dataset can be used to train deep neural networks and generate pre-trained models providing feature representations for smart city CCTV applications, smart weather detection algorithms, or street infrastructure monitoring. The dataset can be found at 10.5281/zenodo.6046758., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests., (© 2022 The Authors. Published by Elsevier Inc.)

Rationale: Mucosa-associated lymphoid tissue (MALT) lymphoma accounts for 7%-8% of newly diagnosed lymphomas. The stomach is the most common organ of origin (nearly 50% of MALT lymphomas). Only 2% of MALT lymphomas arise from the female genital tract, and most originated from uterus. We described a rare case of MALT lymphoma primarily arising from the fallopian tube., Patient Concerns: A 26-year-old woman was brought into our gynecological clinic because of a history of irregular menstruation. The transvaginal ultrasonography revealed cystic masses in bilateral adnexa and both of them showed rich vasculature. Laboratory tests showed a high level (455.3 U/mL) of cancer antigen-125 (CA-125)., Interventions: A laparoscopy was performed., Outcomes: Frozen section of the removed specimen revealed acute and chronic inflammation with abundant inflammatory cells infiltrating the mesenchyme. The right fallopian tube was removed. However, the final histological results showed inflammation accompanied by hyperplasia of lymphoid tissue. Immunohistochemistry staining were consistent with MALT lymphoma. The patient received the second surgery to remove the left fallopian tube and also confirmed the same pathology., Lessons: Gynecologists should be aware of cystic masses which showed rich vasculature and high level of CA-125., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Surface-plasmon-mediated phenylacetylide intermediate transfer from the Cu to the Pd surface affords a novel mechanism for transmetalation, enabling wavelength-tunable cross-coupling and homo-coupling reaction pathway control. C-C bond forming Sonogashira coupling and Glaser coupling reactions in O 2 atmosphere are efficiently driven by visible light over heterogeneous Cu and Pd nanoparticles as a mixed catalyst without base or other additives. The reaction pathway can be controlled by switching the excitation wavelength. Shorter wavelengths (400-500 nm) give the Glaser homo-coupling diyne, whereas longer wavelength irradiation (500-940 nm) significantly increases the degree of cross-coupling Sonogashira coupling products. The ratio of the activated intermediates of alkyne to the iodobenzene is wavelength dependent and this regulates transmetalation. This wavelength-tunable reaction pathway is a novel way to optimize the product selectivity in important organic syntheses., (© 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.)

Background and Purpose: Sirt5 (Sirtuin 5) desuccinylates multiple metabolic enzymes and plays an important role in maintaining energy homeostasis. The goal of this study was to determine whether Sirt5-mediated desuccinylation restores the energy metabolism and protects brain against subarachnoid hemorrhage (SAH)., Methods: Male C57BL/6 or Sirt5 -/- mice were used. The endovascular perforation SAH model was applied. Protein lysine succinylation in the brain cortex was examined using liquid chromatography-tandem mass spectrometry analysis. The brain metabolism was evaluated by measurement of brain pH as well as ATP and reactive oxygen species level. Neuronal cell death and neurobehavioral deficits were assessed 24 hours after SAH. The expression and desuccinylation activity of Sirt5, lysine succinylation of citrate synthase and ATP synthase subunits were investigated by Western blot, immunohistochemistry, and ELISA in SAH mice and patients. Furthermore, the benefits of resveratrol-mediated Sirt5 activation were investigated., Results: A total of 211 lysine succinylation sites were differentially expressed on 170 proteins in mice brain after SAH. Thirty-nine percent of these succinylated proteins were localized in mitochondria and they are related to energy metabolism. SAH caused a decrease of Sirt5 expression and succinylated citrate synthase as well as the subunits of ATP synthase, subsequently lowered brain pH, reduced ATP and increased reactive oxygen species production, leading to neuronal cell death, and neurological deficits. Knockdown of Sirt5 aggravated SAH-induced effects, mentioned above. Administration of resveratrol resulted in activation of Sirt5. The activation was accompanied both with restoration of the mitochondrial metabolism and alleviation of early brain injury as well as with desuccinylating citrate synthase and ATP synthase., Conclusions: Protein lysine succinylation is a biochemical hallmark of metabolic crisis after SAH, and disruption of lysine succinylation through activation of Sirt5 might be a promising therapeutic strategy for the treatment of SAH.

LncRNA PVT1 has been implicated in numerous pathophysiological processes and diseases, especially cancers. However, the role and mechanism of PVT1 in the tumorigenesis of glioblastoma remain unclear. We investigated the alteration of PVT1 and its key functions in glioblastoma. PVT1 was upregulated and associated with poor prognosis in glioblastoma. We demonstrated that PVT1 silencing suppressed cell proliferation, colony formation, and orthotopic xenograft tumor growth. Mechanistic investigations found that PVT1 interacted with TRIM24 directly and increased its protein stability. PVT1 recruited COPS5 to deubiquitinate TRIM24; reciprocally, PVT1 depletion impaired the interaction between COPS5 and TRIM24, resulting in decreased expression of TRIM24. PVT1 , TRIM24, and COPS5 coordinately contributed to the activation of STAT3 signaling and malignant phenotype of glioblastoma. Collectively, this study elucidates the essential role of PVT1 in the tumorigenesis of glioblastoma, which provides candidacy therapeutic target for glioblastoma treatment., Competing Interests: The authors declare no competing interests., (© 2021 The Authors.)

Abstract: The authors reported 2 cases with proximal anterior cerebral artery (A1) aneurysms, and one was treated with aneurysm clipping, whereas another was treated with coil embolization. The authors suggest both endovascular surgery and aneurysm clipping are good options for A1 aneurysms., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by Mutaz B. Habal, MD.)

A case of multiple occurrences of benign metastasizing leiomyoma in the lung, left thigh, left ilium and pelvis in a 43-year-old woman who underwent twice myomectomy in 1999 and 2004 and had hysterectomy in 2009 was reported. She was complained of chest distress as well as the pain of left hip and back of thigh. Computed tomography, X-ray and positron emission tomography-computed tomography (PET-CT) demonstrated multiple nodules in lung, masses of left thigh and pelvis. Biopsy of these nodules indicated benign metastasizing leiomyomas according to pathologic and immunohistochemical results. The patient received gonadotropin-releasing hormone agonist injection and regular follow-up. Up to now, all the symptoms have been alleviated., (© 2019 Japan Society of Obstetrics and Gynecology.)

Objective: A ketogenic diet (KD) improves cellular metabolism and functional recovery after moderate-to-severe traumatic brain injury. Here, we evaluated the changes of neurochemical metabolites after KD therapy for repetitive mild traumatic brain injury (rmTBI) and its possible role in neurodegeneration., Methods: Postnatal day 35 rats were randomly divided into 3 groups: sham, control, and KD groups. Rats in control and KD groups were given 3 rmTBI by a fluid percussion traumatic brain injury device 24 hours apart. All rats were killed at 7 days after the last injury. The ipsilateral cortex were analyzed with hematoxylin and eosin staining; beta-hydroxybutyrate was measured; conventional magnetic resonance imaging and the dry-wet weight method were used to assess the brain edema; changes of neurochemical metabolites were assessed using the ratio of N-acetylaspartate (NAA)/creatine (Cr), choline compound (Cho)/Cr, and NAA/Cho with magnetic resonance spectroscopy; the effect of KD therapy on neurodegeneration was evaluated with double immunofluorescence staining of Iba-1/beclin-1; behavioral outcome was assessed with beam walk/beam balance tests., Results: KD significantly elevated beta-hydroxybutyrate levels, and there was no brain edema associated with rmTBI and KD therapy; behavioral assessment showed KD therapy significantly improved motor performance; magnetic resonance spectroscopy showed that rmTBI reduced the ratio of NAA/Cr and had no effect on the ratios of Cho/Cr and NAA/Cho whereas KD increased the ratio of NAA/Cr; double immunofluorescence staining showed KD therapy could significantly decrease microglial beclin-1 expression in the ipsilateral cortex., Conclusions: These results suggest the effect of KD on metabolic status and its possible role in preventing neurodegeneration in adolescent rats after rmTBI., (Copyright © 2018 Elsevier Inc. All rights reserved.)

5-Aminolevulinic acid photodynamic therapy(ALA-PDT) has been widely used for cervical cancer treatment, but the mechanisms are still not fully delineated. Here we showed that ALA-PDT significantly upregulated HMGB1 while downregulated miR-34a expression levels in cervical cancer tissues, and the percentages of mature DCs(mDCs) were increased in ALA-PDT treated patients' peripheral blood. After treating HPV-positive Hela, SiHa, Caski and HPV-negative C33 A cervical cancer cell lines with ALA-PDT, HPV-positive cells' proliferative ability was significantly inhibited and apoptosis rates were elevated, while no significant changes were found in HPV-negative C33 A cell line. Most importantly, in HPV-positive cells, we found that miR-34a were downregulated in cytoplasm, and both cytoplasm and exosome HMGB1 were significantly elevated comparing to cancer cells without ALA-PDT treatment, and it could be reversed by miR-34a mimic transfection, which indicated that HPV infection and miR-34a downregulation might be vital for ALA-PDT treatment. Based on the HMGB1 is the potential target of miR-34a and an inverse correlation between miR-34a and HMGB1 in ALA-PDT treated cancer tissues, we verified that HMGB1 could be targeted and downregulated by miR-34a mimic, and ALA-PDT promotes HMGB1 secretion by inhibiting miR-34a expression. By co-culturing cervical cancer cell lines with immature DCs(imDCs) in the Transwell systems, we found that ALA-PDT induced HMGB1 exosomes could promote DCs maturation, which could be reversed by silencing HMGB1 in HPV-positive cervical cancer cells. In vivo animal experiments also proved that ALA-PDT inhibited tumor growth in tumor bearing mice, which was reversed by co-transfected with miR-34a mimic or silencing HMGB1 in HPV-positive cells. Hence we concluded that ALA-PDT treatment specifically inhibited HPV-positive cervical cancer cells' proliferative ability, promoted cell apoptosis and modulated DCs maturation by regulating miR-34a mediated HMGB1 exosomes secretion., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Complex mechanisms participate in microglial activation after a traumatic brain injury (TBI). TBI can induce autophagy and apoptosis in neurons and glial cells, and moderate hypothermia plays a protective role in the acute phase of TBI. In the present study, we evaluated the effect of TBI and moderate hypothermia on microglial activation and investigated the possible roles of autophagy/apoptosis and toll-like receptor 4 (TLR4)., Methods: The TBI model was induced with a fluid percussion TBI device. Moderate hypothermia was achieved under general anesthesia by partial immersion in a water bath for 4 h. All rats were killed 24 h after the TBI., Results: Our results showed downregulation of the microglial activation and autophagy, but upregulation of microglial apoptosis, upon post-TBI hypothermia treatment. The expression of TLR4 and downstream myeloid differentiation primary response 88 (MyD88) was attenuated. Moderate hypothermia reduced neural cell death post-TBI., Conclusions: Moderate hypothermia can reduce the number of activated microglia by inhibiting autophagy and promoting apoptosis, probably through a negative modulation between autophagy and apoptosis. Moderate hypothermia may attenuate the pro-inflammatory function of microglia by inhibiting the MyD88-dependent TLR4 signaling pathway.

The pathophysiology of delayed cerebral vasospasm (CVS) after subarachnoid haemorrhage (SAH) is multifaceted and involves endothelial apoptosis and inflammation. Ethyl pyruvate (EP) could attenuate early brain injury following SAH via anti-inflammation and inhibition of the c-Jun N-terminal kinase (JNK) signalling pathway. However, the role of EP in the delayed CVS has yet to be determined. In this study, we examined the effect of EP on endothelial apoptosis and inflammation and explore possible signalling pathways. We found that EP could significantly attenuate the delayed CVS. Possible mechanisms include a decrease in the endothelial cell apoptosis of the basilar artery and alleviation of endothelial inflammation. The JNK signalling pathway may play an important role in the neuroprotective effects of EP on delayed CVS. The results suggest that EP may be a possible therapy for delayed CVS, and the JNK signalling pathway should be targeted for therapeutic purposes in the future., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Objective: We evaluated the role of microglia autophagy in microglia activation after traumatic brain injury (TBI) in rats., Methods: TBI was induced by a fluid percussion TBI device. All rats were killed 24 hours after TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin-eosin staining. Immunohistochemistry and Western blotting of ionized calcium-binding adapter molecule 1 was used to determine changes in microglia activation. Double staining of microtubule-associated protein light chain 3, Beclin-1, and ionized calcium-binding adapter molecule 1 was used to assess changes of microglia autophagy. Enzyme-linked immunosorbent assay of tumor necrosis factor-α and interleukin-1β was used to evaluate changes in inflammatory responses. Terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling staining was used to determine cell death in the ipsilateral hippocampus., Results: At 24 hours after TBI, microglial cells became activated, and the autophagy inhibitor 3-methyladenine (3-MA) further promoted microglia activation. Protein light chain 3- and Beclin-1-positive microglial cells were increased after TBI, whereas 3-MA decreased the number of positive microglial cells, increasing the expression of tumor necrosis factor-α and interleukin-1β; terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling staining demonstrated that 3-MA could increase the number of terminal deoxyribonucleotidyl transferase-mediated deoxyuridine 5'-triphosphate nick-end labeling-positive cells (16.83 ± 0.83 vs. 11 ± 0.82, P < 0.001)., Conclusions: Our data demonstrated that TBI induced microglia activation and microglia autophagy. Inhibition of microglia autophagy with 3-MA increased microglia activation and neural apoptosis. These findings indicate that targeting microglia autophagy may be a therapeutic strategy for TBI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Malignant transformation of an epidermoid cyst is rare. The current report presents a case of a 55-year-old female patient with squamous cell carcinoma arising from a benign epidermoid cyst in the left temporal region and prepontine area. She had undergone subtotal resection of an epidermoid cyst 7 months previously. Preoperative imaging findings included a focal enhancing area adjacent to the lesion. Postoperative computed tomography demonstrated an increase in the size of the enhancing area. The patient underwent removal of the lesion and postoperative histological examination revealed a squamous cell carcinoma possibly arising from the epidermoid cyst. Accurate diagnosis of malignant transformation prior to operation is difficult; however, the possibility of an intracranial epidermoid cyst must be considered if a focally enhancing area is visible. Postoperative histological examinations may be used to determine a definite diagnosis, and accurate diagnosis is important for planning a rational therapeutic strategy.

Objective: The role of autophagy in moderate hypothermia in posttraumatic brain injury (post-TBI) remains elusive. In this study, we evaluated the protective role of autophagy in post-TBI moderate hypothermia., Methods: Adult male Sprague-Dawley rats were randomly divided into 3 groups (n = 36/group): TBI with hypothermia group (sham), TBI with hypothermia and a single intracerebroventricular injection of saline (saline, 5 μL), and TBI with hypothermia and a single intracerebroventricular injection of 3-methyladenine (600 nmol, diluted in 0.9% saline to a final volume of 5 μL). All rats, except those in the behavioral tests, were killed at 24 hours after fluid percussion TBI. Immunohistochemistry staining, western blot, and transmission electron microscopy were performed to assess changes in apoptosis and autophagy after injection of 3-methyladenine. Motor function (beam-walk test) and spatial learning/memory (Morris water maze) were assessed on postoperative days 1-5 and 11-15, respectively., Results: Our results showed downregulation of the expression level of microtubule-associated protein 1 light chain 3 and Beclin-1, aggravation of behavioral outcome, and increase of apoptosis., Conclusion: Our results suggest that the autophagy pathway is involved in the neuroprotective effect of post-TBI hypothermia and negative modulation of apoptosis may be 1 possible mechanism., (Copyright © 2016. Published by Elsevier Inc.)

Cranioplasty (CP) with titanium mesh after standard trauma craniectomy (STC) has been proven to be a favorable technology. According to reflection of temporalis muscle or not, the CP was divided into 2 operation ways. Effect of reflection of temporalis muscle has not been systematically researched. Thirty-nine patients were enrolled to assess the effect of reflection of temporalis muscle during CP after STC. Cranial index of symmetry was adopted to evaluate the aesthetic results, transcranial Doppler was used to assess change of cerebral blood flow (CBF), functional independence measurements were performed to monitor the improvement of neuronal function, and complications associated with CP were also recorded. The results displayed that reflection of temporalis muscle or not had no effect on the anesthetic results. Both operation ways could improve CBF and neuronal function. Cranioplasty with reflection of temporalis muscle could improve CBF and neuronal function more significantly. Furthermore, reflection of temporalis muscle would not increase complications associated with CP. Reflection of temporalis muscle during CP with titanium mesh after STC proves to be an effective and safe operation way.

Introduction: Glial fibrillary acidic protein (GFAP) may serve as a serum marker of traumatic brain injury (TBI) that can be used to monitor biochemical changes in patients and gauge the response to treatment. However, the temporal profile of serum GFAP in the acute period of brain injury and the associated utility for outcome prediction has not been elucidated., Methods: We conducted a prospective longitudinal cohort study of consecutive severe TBI patients in a local tertiary neurotrauma center in Shanghai, China, between March 2011 and September 2014. All patients were monitored and managed with a standardized protocol with inclusion of hypothermia and other intensive care treatments. Serum specimens were collected on admission and then daily for the first 5 days. GFAP levels were measured using enzyme-linked immunosorbent assay techniques. Patient outcome was assessed at 6 months post injury with the Glasgow Outcome Scale and further grouped into death versus survival and unfavorable versus favorable., Results: A total of 67 patients were enrolled in the study. The mean time from injury to admission was 2.6 hours, and the median admission Glasgow Coma Scale score was 6. Compared with healthy subjects, patients with severe TBI had increased GFAP levels on admission and over the subsequent 5 days post injury. Serum GFAP levels showed a gradual reduction from admission to day 3, and then rebounded on day 4 when hypothermia was discontinued with slow rewarming. GFAP levels were significantly higher in patients who died or had an unfavorable outcome across all time points than in those who were alive or had a favorable outcome. Results of receiver operating characteristic curve analysis indicated that serum GFAP at each time point could predict neurological outcome at 6 months. The areas under the curve for GFAP on admission were 0.761 for death and 0.823 for unfavorable outcome, which were higher than those for clinical variables such as age, Glasgow Coma Scale score, and pupil reactions., Conclusions: Serum GFAP levels on admission and during the first 5 days of injury were increased in patients with severe TBI and were predictive of neurological outcome at 6 months.

A number of studies have been done to investigate the role of brain-derived neurotrophic factor (BDNF) in patients with post-traumatic stress disorder (PTSD). In this study we aimed to test the relationship between plasma BDNF levels and PTSD. We solicited 65 subjects having recently experienced road traffic accidents (RTA) conforming to screening criteria. They were given follow-up examinations after one month, three months, and six months. PTSD was diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-R-TR, American Psychiatric Association, 2000) using the Mini International Neuropsychiatric Interview (MINI). All participants were divided into two groups: a group with PTSD and a group without PTSD. There were no significant differences in plasma BDNF levels between the two groups at either the 48h or six-month examination. Within the PTSD group, no significant differences were found in plasma BDNF levels between the two examinations. BDNF levels in those without PTSD showed a higher trend over time after trauma. Higher BDNF levels may be an important protective factor for the prevention of traumatized subjects from developing PTSD., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Multiple mechanisms participated in the cell death after fluid percussion traumatic brain injury (TBI). In the present study, we evaluated the effect on cell death in the injured cortex after fluid percussion TBI and investigated a possible role of autophagy., Methods: TBI model was induced by a fluid percussion TBI device. Moderate hypothermia (32°C) was achieved by partial immersion in a water bath (0°C) under general anesthesia for 4 hours. All rats were killed at 6 or 24 hours after TBI., Results: Cleaved caspase 3 evaluated with Western blotting and terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling-positive cells in injured cortex were significantly increased 6 hours after fluid percussion TBI and were further up-regulated 24 hours after TBI, dramatic up-regulation of Beclin-1 and protein light chain-3 expression levels was also observed. Further up-regulation of biomarkers of autophagy, attenuation of caspase 3 up-regulation and reduction of cell death was observed after 4 hours of hypothermia. Immunofluorescence analysis for cell localization demonstrated that protein light chain-3- and Beclin-1-positive cells included neurons and glial cells in the injured cortex after TBI and hypothermic treatment. By ultrastructural observation, autolysosomes in injured cortex were significantly increased at 6 and 24 hours after TBI and were further up-regulated after TBI hypothermic treatment., Conclusions: These data suggest that hypothermic treatment could attenuate TBI-induced cell death in this fluid percussion TBI model, possibly through activation of autophagy pathway., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Here, we evaluated changes in autophagy after post-traumatic brain injury (TBI) followed by moderate hypothermia in rats. Adult male Sprague-Dawley rats were randomly divided into four groups: sham injury with normothermia group (37 °C); sham injury with hypothermia group (32 °C); TBI with normothermia group (TNG; 37 °C); and TBI with hypothermia group (THG; 32 °C). Injury was induced by a fluid percussion TBI device. Moderate hypothermia (32 °C) was achieved by partial immersion in a water bath (0 °C) under general anesthesia for 4 h. All rats were killed at 24 h after fluid percussion TBI. The ipsilateral hippocampus in all rats was analyzed with hematoxylin and eosin staining; terminal deoxynucleoitidyl transferase-mediated nick end labeling staining was used to determine cell death in ipsilateral hippocampus. Immunohistochemistry and western blotting of microtubule-associated protein light chain 3 (LC3), Beclin-1, as well as transmission electron microscopy performed to assess changes in autophagy. At 24 h after TBI, the cell death index was 27.90 ± 2.36% in TNG and 14.90 ± 1.52% in THG. Expression level of LC3 and Beclin-1 were significantly increased after TBI and were further up-regulated after post-TBI hypothermia. Further, ultrastructural observations showed that there was a marked increase of autophagosomes and autolysosomes in ipsilateral hippocampus after post-TBI hypothermia. Our data demonstrated that moderate hypothermia significantly attenuated cell death and increased autophagy in ipsilateral hippocampus after fluid percussion TBI. In conclusion, autophagy pathway may participate in the neuroprotective effect of post-TBI hypothermia.

Residual hemifacial spasm (HFS) after microvascular decompression (MVD) is common, and the factors associated with residual HFS are still controversial. In the present study, we analyzed the outcome of 212 patients with hemifacial spasm after a single microvascular decompression and evaluated the prognostic factors involved in residual hemifacial spasm. Based on our study, possible prognostic factors included indentation of the root exit zone (REZ), preoperative illness duration, and preoperative psychological state. We suggest that MVD should be performed as early as possible for it may decrease the rate of residual HFS. Preoperative assessment of psychological state in HFS patients is a timely intervention that should be implemented to minimize the residual HFS.

Intracranial arachnoid cysts are rare cystic-appearing intracranial masses. In rarer cases, the arachnoid cysts originate from brain parenchyma, which is defined as intracerebral arachnoid cyst. Here, we present a patient younger than 2 years with massive intracranial arachnoid cysts (one of which was intracerebral arachnoid cyst), whose clinical symptoms included megacephaly and limb weakness. Ommaya reservoir implantation and repeated aspiration of the intracerebral cyst fluid were performed. The symptoms gradually improved, and the intracerebral arachnoid cyst gradually disappeared during 13 months of follow-up. The case highlights the potential of Ommaya reservoir implantation in the treatment of intracerebral arachnoid cyst, especially for young patients. We also reviewed the published literatures concerning the rare condition, including the mechanisms for its pathogenesis and enlargement.

Spontaneous resolution of chronic subdural hematoma (CSDH) is rare, especially for the nontraumatic cases. Here, we present 1 case of a 70-year-old female patient with spontaneous resolution of CSDH. She was chronically anticoagulated after percutaneous coronary intervention. Moreover, she denied previous mild head trauma and bleeding episodes. For personal reasons, she declined surgery. Treatment just included mannitol, which was used to alleviate the symptoms. Intermittent computed tomography showed gradually resolution of CSDH. Spontaneous resolution of nontraumatic CSDH is rare, with different mechanisms and computed tomography characteristics compared with that of traumatic CSDH. Dimerized plasmin fragment D in venous blood may be more sensitive in the judgment of types of CSDH.

Moyamoya disease patients with subarachnoid hemorrhage and cerebral infarction are rare, especially when the subarachnoid hemorrhage is nonaneurysmal. Here, we present one 48-year-old male patient with moyamoya disease identified with digital subtraction angiography. His initial symptoms are associated with increased intracranial pressure. Subsequent computed tomography demonstrated subarachnoid hemorrhage and cerebral infarction. Digital subtraction angiography showed no obvious aneurysms. We assume that subarachnoid hemorrhage is associated with the rupture of the moyamoya vessels and transdural anastomotic vessels. The cerebral infarction can be also explained by hemodynamic mechanisms. We should pay more attention to the recurrent hemorrhagic stroke.

Objective: The objective of this study was to retrospectively review the postoperative seizure outcome in patients with short duration of epilepsy associated with cavernous malformations and analyze the effect of surgical methods on seizure outcome in such population., Methods: 36 patients with short duration of epilepsy (shorter than 12 months) associated with cavernous malformations in temporal or frontal lobe underwent microsurgical resection. The patients were retrospectively divided into two groups: Group A (21 patients) with complete removal of hemosiderin rim and Group B (15 patients) with partial removal of hemosiderin rim. Clinical follow-up was achieved with telephone correspondence or outpatient assessment. The seizure outcome was based on Engel's classification., Results: After a mean follow-up period of 18 months, 77.8% of the patients (28/36) were classified into Engel class I, including 19 patients (90.5%) in the complete removal of hemosiderin rim group (Group A) and 9 patients (60%) in the partial removal of hemosiderin rim group (Group B). Seizure outcome was significantly better in Group A. There was no mortality and all the postoperative neurological deficits were recovered at the time of follow-up., Conclusion: The analysis of the seizure outcome demonstrate patients with short duration of epilepsy associated with cavernous malformations could benefit greatly from complete resection of hemosiderin rim and cavernous malformations., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Rupture of traumatic pseudoaneurysms of the middle meningeal artery (MMA) usually causes extradural hematoma. In rare cases, it may be a possible cause of intraparenchymal hematoma. We present 2 cases of intraparenchymal hematoma caused by rupture of traumatic pseudoaneurysms of MMA. Both patients had definite medical history of head trauma. Imaging examinations indicated temporal hematoma or frontal hematoma caused by rupture of pseudoaneurysm of MMA. After surgical management, both the patients had a favorable prognosis. The formation of the traumatic pseudoaneurysms, imaging findings, and the management were discussed, and we conclude that in the management of traumatic intraparenchymal hematoma, possibility of traumatic pseudoaneurysms must be considered. Surgery may be the prior choice for the treatment of traumatic pseudoaneurysms.

This paper presents a task allocation-oriented framework to enable efficient in-network processing and cost-effective multi-hop resource sharing for dynamic multi-hop multimedia wireless sensor networks with low node mobility, e.g., pedestrian speeds. The proposed system incorporates a fast task reallocation algorithm to quickly recover from possible network service disruptions, such as node or link failures. An evolutional self-learning mechanism based on a genetic algorithm continuously adapts the system parameters in order to meet the desired application delay requirements, while also achieving a sufficiently long network lifetime. Since the algorithm runtime incurs considerable time delay while updating task assignments, we introduce an adaptive window size to limit the delay periods and ensure an up-to-date solution based on node mobility patterns and device processing capabilities. To the best of our knowledge, this is the first study that yields multi-objective task allocation in a mobile multi-hop wireless environment under dynamic conditions. Simulations are performed in various settings, and the results show considerable performance improvement in extending network lifetime compared to heuristic mechanisms. Furthermore, the proposed framework provides noticeable reduction in the frequency of missing application deadlines.

Six patients with central neurocytoma were retrospectively examined, including diagnosis and treatment process as well as postoperative complications. Clinical follow-ups were performed through telephone calls or outpatient service. Of the 6 patients, a total of 5 patients had 1 or more postoperative complications. The postoperative complications included hydrocephalus, basal ganglia edema, epidural hematoma of the operated region and the remote region, and intracranial infection; 5 patients underwent the cortical fistulization approach and 1 underwent the longitudinal fissure-corpus callosum approach. The neoplasms of 3 patients were totally resected and those of the other 3 patients were subtotally resected. Preoperative accurate diagnosis of central neurocytoma is of great importance for the drawing up of the operation strategy; in addition to magnetic resonance imaging and computed tomography, digital subtraction angiography and magnetic resonance spectroscopy could be helpful for the preoperative diagnosis of central neurocytoma. Subtotal resection of the lesion and the longitudinal fissure-corpus callosum approach may be useful for the reduction of postoperative complications.

Intracranial chondromas are rare benign tumors, which usually originate from skull base synchondrosis. In rarer cases, intracranial chondromas originate from the cerebral parenchyma without meningeal attachment, which is defined as intracerebral chondroma. In this paper, an 18-year-old male patient with intracerebral chondroma is presented. There are only 5 cases of intracerebral chondromas without meningeal attachment published in the literature. According to the clinical data, the intracerebral chondromas are hard hyaline cartilage, irregular lobulated grayish-white mass macroscopically and consist of mature hyaline chondrocyte microscopically. Total removal is the best treatment method for intracerebral chondroma.

Context: Smoke inhalation injury is the leading cause of acute respiratory failure in critical burn victims. Advances in the treatment of smoke inhalation injury have been limited in the past years. To further explore the pathogenesis, stable and practical animal models are necessary., Objective: To develop a rat model of smoke inhalation injury., Materials and Methods: The smoke composition including the particulate matters, irritant gases, chemical carcinogens was measured. The blood gas values, pro-inflammatory and protein concentration in bronchoalveolar lavage fluid and lung wet to dry weight ratio were assayed. Pathological evaluations of pulmonary were performed at 24 h, 96 h, 7 days and 28 days post-injury. Masson-Goldner trichrome staining was performed on day 7 and 28 post-injury, along with the measurement of hydroxyproline and collagen I and III., Results: In our present animal model, smoke inhalation caused a significant hypoxemia and CO poisoning. A surge of pro-inflammatory response and microvascular hyperpermeability with neutrophils accumulations were also found in our animal model. At 24 h post-smoke inhalation, the hematoxylin and eosin results exhibited that there were inflammatory exudates and diffuse hemorrhage in the lung tissue with significant edema. With the time going, the lung injuries appeared at alveolar collapse and alveolar septum thickening, which indicated that smoke inhalation further induced damage to lung parenchyma. Specially, the markedly collagen deposition appeared at 28 days post-injury indicated that pulmonary fibrosis happened., Discussion and Conclusion: In conclusion, this rat smoke inhalation injury model induced by our novel self-made smoke generator could be used for acute and chronic lung injury experiments.

Acute lung injury (ALI) is a serious illness, the incidence and mortality of which are very high. Free radicals, such as hydroxyl radicals (OH) and peroxynitrite (ONOO(-)), are considered to be the final causative molecules in the pathogenesis of ALI. Hydrogen, a new antioxidant, can selectively reduce OH and ONOO(-). In the present study, we investigated the hypothesis that hydrogen inhalation could ameliorate ALI induced by intra-tracheal lipopolysaccharide (LPS, 5mg/kg body weight). Mice were randomized into three groups: sham group (physiological saline+2% hydrogen mixed gas), control group (LPS+normal air) and experiment group (LPS+2% hydrogen mixed gas). Bronchoalveolar lavage fluid (BALF) was performed to determine the total protein concentrations and pro-inflammatory cytokines. Lung tissues were assayed for oxidative stress variables, wet/dry (W/D) ratio, histological, immunohistochemistry and Western blotting examinations. Our experiments exhibited that hydrogen improved the survival rate of mice and induced a decrease in lung W/D ratio. In addition, hydrogen decreased malonaldehyde and nitrotyrosine content, inhibited myeloperoxidase and maintained superoxide dismutase activity in lung tissues and associated with a decrease in the expression of TNF-α, IL-1β, IL-6 and total protein concentrations in the BALF. Hydrogen further attenuated histopathological alterations and mitigated lung cell apoptosis. Importantly, hydrogen inhibited the activation of P-JNK, and also reversed changes in Bax, Bcl-xl and caspase-3. In conclusion, our data demonstrated that hydrogen inhalation ameliorated LPS-induced ALI and it may be exerting its protective role by preventing the activation of ROS-JNK-caspase-3 pathway., (Copyright © 2011 Elsevier B.V. All rights reserved.)