The role of NAD-dependent deacetylase sirtuin-2 in liver metabolic stress through regulating pyruvate kinase M2 ubiquitination.

NAD-dependent deacetylase Sirt2 is involved in mammalian metabolic activities, matching energy demand with energy production and expenditure, and is relevant to a variety of metabolic diseases. Here, we constructed Sirt2 knockout and adeno-associated virus overexpression mice and found that deletion of hepatic Sirt2 accelerated primary obesity and insulin resistance in mice with concomitant hepatic metabolic dysfunction. However, the key targets of Sirt2 are unknown. We identified the M2 isoform of pyruvate kinase (PKM2) as a key Sirt2 target involved in glycolysis in metabolic stress. Through yeast two-hybrid and mass spectrometry combined with multi-omics analysis, we identified candidate acetylation modification targets of Sirt2 on PKM2 lysine 135 (K135). The Sirt2-mediated deacetylation-ubiquitination switch of PKM2 regulated the development of glycolysis. Here, we found that Sirt2 deficiency led to impaired glucose tolerance and insulin resistance and induced primary obesity. Sirt2 severely disrupted liver function in mice under metabolic stress, exacerbated the metabolic burden on the liver, and affected glucose metabolism. Sirt2 underwent acetylation modification of lysine 135 of PKM2 through a histidine 187 enzyme active site-dependent effect and reduced ubiquitination of the K48 ubiquitin chain of PKM2. Our findings reveal that the hepatic glucose metabolism links nutrient state to whole-body energetics through the rhythmic regulation of Sirt2.

Contrasting nidification behaviors facilitate diversification and colonization of the Music frogs under a changing paleoclimate.

In order to cope with the complexity and variability of the terrestrial environment, amphibians have developed a wide range of reproductive and parental behaviors. Nest building occurs in some anuran species as parental care. Species of the Music frog genus Nidirana are known for their unique courtship behavior and mud nesting in several congeners. However, the evolution of these frogs and their nidification behavior has yet to be studied. With phylogenomic and phylogeographic analyses based on a wide sampling of the genus, we find that Nidirana originated from central-southwestern China and the nidification behavior initially evolved at ca 19.3 Ma but subsequently lost in several descendants. Further population genomic analyses suggest that the nidification species have an older diversification and colonization history, while N. adenopleura complex congeners that do not exhibit nidification behavior have experienced a recent rapid radiation. The presence and loss of the nidification behavior in the Music frogs may be associated with paleoclimatic factors such as temperature and precipitation. This study highlights the nidification behavior as a key evolutionary innovation that has contributed to the diversification of an amphibian group under past climate changes.

Multifunctional iron-apigenin nanocomplex conducting photothermal therapy and triggering augmented immune response for triple negative breast cancer.

Triple negative breast cancer (TNBC) presents a formidable challenge due to its low sensitivity to many chemotherapeutic drugs and a relatively low overall survival rate in clinical practice. Photothermal therapy has recently garnered substantial interest in cancer treatment, owing to its swift therapeutic effectiveness and minimal impact on normal cells. Metal-polyphenol nanostructures have recently garnered significant attention as photothermal transduction agents due to their facile preparation and favorable photothermal properties. In this study, we employed a coordinated approach involving Fe3+ and apigenin, a polyphenol compound, to construct the nanostructure (nFeAPG), with the assistance of ß-CD and DSPE-PEG facilitating the formation of the complex nanostructure. In vitro research demonstrated that the formed nFeAPG could induce cell death by elevating intracellular oxidative stress, inhibiting antioxidative system, and promoting apoptosis and ferroptosis, and near infrared spectrum irradiation further strengthen the therapeutic outcome. In 4T1 tumor bearing mice, nFeAPG could effectively accumulate into tumor site and exhibit commendable control over tumor growth. Futher analysis demonstrated that nFeAPG ameliorated the suppressed immune microenvironment by augmenting the response of DC cells and T cells. This study underscores that nFeAPG encompasses a multifaceted capacity to combat TNBC, holding promise as a compelling therapeutic strategy for TNBC treatment.

O-GlcNAcylation regulates long-chain fatty acid metabolism by inhibiting ACOX1 ubiquitination-dependent degradation.

BACKGROUND: Cold as a common environmental stress, causes increased heat production, accelerated metabolism and even affects its production performance. How to improve the adaptability of the animal organism to cold has been an urgent problem. As a key hub of lipid metabolism, the liver can regulate lipid metabolism to maintain energy balance, and O-GlcNAcylation is a kind of important PTMs, which participates in a variety of signaling and mechanism regulation, and at the same time, is very sensitive to changes in stress and nutritional levels, and is the body's "stress receptors" and "nutrient receptors". Therefore, the aim of this experiment was to investigate the effect of cold-induced O-GlcNAcylation on hepatic lipid metabolism, and to explore the potential connection between O-GlcNAcylation and hepatic lipid metabolism. METHODS: To investigate the loss of O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT) and the precise impacts of additional cold-induced circumstances on liver mass, shape, and metabolic profile, C57 mice were used as an animal model. Using the protein interactions approach, the mechanism of O-GlcNAcylation, as well as the degradation pathway of acyl-Coenzyme A oxidase 1 (ACOX1), were clarified. Additional in vitro analyses of oleic acid (OA) and OGT inhibitor tetraoxan (Alloxan) (Sigma, 2244-11-3) on lipid breakdown in AML-12 cells. RESULTS: In C57BL/6 mice, deletion of O-GlcNAcylation disrupted lipid metabolism, caused hepatic edema and fibrosis, and altered mitochondrial apoptosis. This group of modifications was made worse by cold induction. The accumulation of medium- and long-chain fatty acids is a hallmark of lipolysis, which is accelerated by the deletion of O-GlcNAcylation, whereas lipid synthesis is slowed down. The association between ACOX1 and OGT at the K48 gene precludes ubiquitinated degradation.

Effect of chronic cold stress on gut microbial diversity, intestinal inflammation and pyroptosis in mice.

Hypothermia is an essential environmental factor in gastrointestinal diseases, but the main molecular mechanisms of pathogenesis remain unclear. The current study sought to better understand how chronic cold stress affects gut damage and its underlying mechanisms. In this work, to establish chronic cold stress (CS)-induced intestinal injury model, mice were subjected to continuous cold exposure (4 °C) for 3 h per day for 3 weeks. Our results indicated that CS led to gut injury via inducing changes of heat shock proteins 70 (HSP70) and apoptosis-related (caspases-3, Bax and Bcl-2) proteins; enhancing expression of intestinal tight-related (ZO-1 and occludin) proteins; promoting releases of inducible nitric oxide synthase (iNOS), tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), high mobility group box 1 (HMGB1), interleukin1ß (IL-1ß), IL-18 and IL-6 inflammatory mediators in the ileum; and altering gut microbial diversity. Furthermore, persistent cold exposure resulted in the cleavage of pyroptosis-related Gasdermin D (GSDMD) protein by regulating the NLRP3/ASC/caspase-1 and caspase-11 pathway, and activation of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways, which are strongly associated with changes in gut microbiota diversity. Taken together, these investigations provide new insights into the increased risk of intestinal disorders at extremely low temperatures and establish a theoretical foundation for the advancement of novel pharmaceutical interventions targeting cold-related ailments.

A rare case report of infratentorial cisternal angiolipoma with review of literature.

Angiolipomas are slow-growing benign mesenchymal-derived tumors consisting of mature adipocytes and thin-walled blood vessels. While the majority of angiolipomas are found in subcutaneous tissues, rarely there are case reports of intracranial lesions. We present a case of cisternal angiolipoma in a 10-year-old female. She presented with vague symptoms like dizziness without neurological deficits and radiological evaluation confirmed a left-sided infratentorial cisternal partially enhancing mass. She underwent craniotomy and had complete resection of the mass, which was histologically composed of mature adipocytes and blood vessels, consistent with angiolipoma. A review of the literature found only 18 cases of intracranial angiolipoma ever reported with our case representing the first case of infratentorial cisternal region.

Protein O-GlcNAcylation: The sweet hub in liver metabolic flexibility from a (patho)physiological perspective.

O-GlcNAcylation is a dynamic, reversible and atypical O-glycosylation that regulates various cellular physiological processes via conformation, stabilisation, localisation, chaperone interaction or activity of target proteins. The O-GlcNAcylation cycle is precisely controlled by collaboration between O-GlcNAc transferase and O-GlcNAcase. Uridine-diphosphate-N-acetylglucosamine, the sole donor of O-GlcNAcylation produced by the hexosamine biosynthesis pathway, is controlled by the input of glucose, glutamine, acetyl coenzyme A and uridine triphosphate, making it a sensor of the fluctuation of molecules, making O-GlcNAcylation a pivotal nutrient sensor for the metabolism of carbohydrates, amino acids, lipids and nucleotides. O-GlcNAcylation, particularly prevalent in liver, is the core hub for controlling systemic glucose homeostasis due to its nutritional sensitivity and precise spatiotemporal regulation of insulin signal transduction. The pathology of various liver diseases has highlighted hepatic metabolic disorder and dysfunction, and abnormal O-GlcNAcylation also plays a specific pathological role in these processes. Therefore, this review describes the unique features of O-GlcNAcylation and its dynamic homeostasis maintenance. Additionally, it explains the underlying nutritional sensitivity of O-GlcNAcylation and discusses its mechanism of spatiotemporal modulation of insulin signal transduction and liver metabolic homeostasis during the fasting and feeding cycle. This review emphasises the pathophysiological implications of O-GlcNAcylation in nonalcoholic fatty liver disease, nonalcoholic steatohepatitis and hepatic fibrosis, and focuses on the adverse effects of hyper O-GlcNAcylation on liver cancer progression and metabolic reprogramming.

Spontaneous pseudoaneurysm of the superficial temporal artery in neurofibromatosis type 1: illustrative case.

BACKGROUND: A pseudoaneurysm of the superficial temporal artery is an uncommon clinical entity that has largely been linked with direct traumatic causes. Neurofibromatosis type 1 (NF1)-related vasculopathy is a rare cause of idiopathic arterial bleeding in the craniofacial region. OBSERVATIONS: A 46-year-old male with clinical features of NF1 presented to the hospital with an enlarging and tender right temporal mass without a history of trauma. Computed tomography angiography suggested the development of a pseudoaneurysm, and surgery was performed to resect the mass. Histopathological examinations showed focal interruption of the epithelium layer and elastic lamina, well-demarcated thickening of the smooth muscle layers of the arterial wall, supporting the diagnosis of pseudoaneurysm. LESSONS: NF1-associated vasculopathy is likely the predisposing factor for the development of a superficial temporal artery pseudoaneurysm.

Effects of metformin on Sonic hedgehog subgroup medulloblastoma progression: In vitro and in vivo studies.

Metformin is a first-line drug for type 2 diabetes, and its anticancer effects have also been widely studied in recent years. The Sonic hedgehog (Shh) signaling pathway is involved in the initiation and progression of medulloblastoma. In order to develop a new treatment strategy for medulloblastoma (MB), this study investigated the inhibitory effect of metformin on MB and the underlying mechanism of metformin on the Shh signaling pathway. The effect of metformin on proliferation was evaluated by the cell counting kit-8 (CCK-8) test and colony formation experiment. The effect of metformin on metastasis was assessed by the scratch-wound assay and transwell invasion assay. Cell cycle and apoptosis were evaluated by flow cytometry, and the associated proteins were examined by western blotting. The mRNA and protein expression levels related to the Shh pathway were measured by quantitative PCR, western blotting, and immunofluorescence staining. The xenograft murine model was carried out to evaluate the anticancer effect of metformin on medulloblastoma in vivo. Metformin inhibited proliferation and metastasis of the Shh subgroup MB cell line, and the inhibitory effect on proliferation was related to apoptosis and the block of the cell cycle at the G0/G1 phase. Animal experiments showed that metformin inhibits medulloblastoma growth in vivo. Moreover, metformin decreased mRNA and protein expression levels of the Shh pathway, and this effect was reversed by the AMP-activated protein kinase (AMPK) siRNA. Furthermore, the pro-apoptotic and cell cycle arrest effects of metformin on Daoy cells could be reversed by the Shh pathway activators. Our findings demonstrated that metformin could inhibit medulloblastoma progression in vitro and in vivo, and this effect was associated with AMPK-mediated inhibition of the Shh signaling pathway in vitro studies.

RNA binding motif protein 3 (RBM3) promotes protein kinase B (AKT) activation to enhance glucose metabolism and reduce apoptosis in skeletal muscle of mice under acute cold exposure.

The main danger of cold stress to animals in cold regions is systemic metabolic changes and protein synthesis inhibition. RBM3, an exceptional cold shock protein, is rapidly upregulated in response to hypothermia to resist the adverse effects of cold stress. However, the mechanism of the protective effect and the rapid upregulation of RBM3 remains unclear. O-GlcNAcylation, an atypical O-glycosylation, is precisely regulated only by O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) and participates in the signal transduction of multiple cellular stress responses as a "stress and nutrition receptor." Therefore, our study aimed to explore the mechanism of RBM3 regulating glucose metabolism and promoting survival in skeletal muscle under acute cold exposure. Meanwhile, our study verifies whether O-GlcNAcylation mediated by OGT rapidly upregulates RBM3. The blood and skeletal muscle of mice were collected at the end of cold exposure treatment for 0, 2, and 4 h. Changes in levels of RBM3, AKT, glycolysis apoptosis, and OGT were measured. The results show that acute cold exposure upregulated RBM3, OGT, and AKT phosphorylation and increased energy consumption, which enhanced glycolysis and prevent apoptosis. In the 32 °C mild hypothermia model in vitro, overexpression of RBM3 enhanced AKT phosphorylation. Meanwhile, inactivation of AKT by wortmannin resulted in increased apoptosis and decreased glucose metabolism in skeletal muscle under acute cold exposure. In addition, OGT-mediated O-GlcNAcylation of p65 was confirmed in mouse myoblast cell line (C2C12) cells at mild hypothermia. O-GlcNAcylation level affected p65 activity and nuclear translocation. Compared with wild type (WT) mice, RBM3 and p65 phosphorylation were decreased in specific skeletal muscle Ogt (KO) mice, whereas AKT phosphorylation, glycolysis, and apoptosis were increased. Taken together, O-GlcNAcylation of p65 upregulates RBM3 to promote AKT phosphorylation, enhance glucose metabolism, and reduce apoptosis in skeletal muscle of mice under acute cold exposure.

RBM3 is an outstanding cold shock protein with multiple physiological functions beyond hypothermia.

RNA-binding motif protein 3 (RBM3), an outstanding cold shock protein, is rapidly upregulated to ensure homeostasis and survival in a cold environment, which is an important physiological mechanism in response to cold stress. Meanwhile, RBM3 has multiple physiological functions and participates in the regulation of various cellular physiological processes, such as antiapoptosis, circadian rhythm, cell cycle, reproduction, and tumogenesis. The structure, conservation, and tissue distribution of RBM3 in human are demonstrated in this review. Herein, the multiple physiological functions of RBM3 were summarized based on recent research advances. Meanwhile, the cytoprotective mechanism of RBM3 during stress under various adverse conditions and its regulation of transcription were discussed. In addition, the neuroprotection of RBM3 and its oncogenic role and controversy in various cancers were investigated in our review.

Cold Stress Induced Liver Injury of Mice through Activated NLRP3/Caspase-1/GSDMD Pyroptosis Signaling Pathway.

The body needs to generate heat to ensure basic life activities when exposed to cold temperatures. The liver, as the largest glycogen storage organ in the body and main heat-producing organ at rest, may play a role in chronic cold exposure. Recent studies suggested that pyroptosis plays a crucial role in liver diseases. However, the role of pyroptosis in cold stress-induced liver injury is not clear. Hence, in this study, we attempted to investigate the effects of chronic cold exposure on liver function, apoptosis, oxidative stress and inflammation in mice by establishing a mouse model of chronic cold exposure, and to investigate whether pyroptosis pathways are involved in the process of chronic cold exposure. In vivo, our results show that inflammatory cell infiltration and other pathological changes in liver cells and the activity of liver enzyme evidently increased in the serum and liver of cold-exposed mice, suggesting cold stress may result in liver injury. Remarkably, increased expression of heat shock protein 70 (HSP70) and HSP90 proteins proved the cold stress model is successfully constructed. Then, elevated levels of apoptosis, inflammation, oxidative stress and pyroptosis related proteins and mRNAs, such as cysteinyl aspartate specific proteinase-3 (Caspase-3), inducible nitric oxide synthase (iNOS), nuclear factor erythroid2-related factor 2 (Nrf2) and gasdermins D (GSDMD), confirmed that cold exposure activated apoptosis, oxidative stress and pyroptosis, and released inflammation cytokines. Meanwhile, in vitro, we got similar results as in vivo. Further, adding an NLR family pyrin domain containing 3 (NLRP3) inhibitors found that suppression expression of NLRP3 results in the essential proteins of pyroptosis and antioxidant evidently reduced, and adding GSDMD inhibitor found that suppression expression of GSDMD accompanies with the level of Nrf2 and heme oxygenase-1 (HO-1) obviously reduced. In summary, these findings provide a new understanding of the underlying mechanisms of the cold stress response, which can inform the development of new strategies to combat the effects of hypothermia.

Absorbable Artificial Dura Versus Nonabsorbable Artificial Dura in Decompressive Craniectomy for Severe Traumatic Brain Injury: A Retrospective Cohort Study in Two Centers.

Background: Severe traumatic brain injury (TBI) patients usually need decompressive craniectomy (DC) to decrease intracranial pressure. Duraplasty is an important step in DC with various dura substitute choices. This study aims to compare absorbable dura with nonabsorbable dura in duraplasty for severe TBI patients. Methods: One hundred and three severe TBI patients who underwent DC and dura repair were included in this study. Thirty-nine cases used absorbable artificial dura (DuraMax) and 64 cases used nonabsorbable artificial dura (NormalGEN). Postoperative complications, mortality and Karnofsky Performance Scale (KPS) score in one year were compared in both groups. Results: Absorbable dura group had higher complication rates in transcalvarial cerebral herniation (TCH) (43.59% in absorbable dura group vs. 17.19% in nonabsorbable dura group, P = 0.003) and CSF leakage (15.38% in absorbable dura group vs. 1.56% in nonabsorbable dura group, P = 0.021). But severity of TCH described with hernial distance and herniation volume demonstrated no difference in both groups. There was no statistically significant difference in rates of postoperative intracranial infection, hematoma progression, secondary operation, hydrocephalus, subdural hygroma and seizure in both groups. KPS score in absorbable dura group (37.95 ± 28.58) was statistically higher than nonabsorbable dura group (49.05 ± 24.85) in one year after operation (P = 0.040), while no difference was found in the rate of functional independence (KPS ≥ 70). Besides, among all patients in this study, TCH patients had a higher mortality rate (P = 0.008), lower KPS scores (P < 0.001) and lower functionally independent rate (P = 0.049) in one year after surgery than patients without TCH. Conclusions: In terms of artificial biological dura, nonabsorbable dura is superior to absorbable dura in treatment of severe TBI patients with DC. Suturable nonabsorbable dura has fewer complications of TCH and CFS leakage, and manifest lower mortality and better prognosis. Postoperative TCH is an important complication in severe TBI which usually leads to a poor prognosis.

Integrated metabolism and epigenetic modifications in the macrophages of mice in responses to cold stress.

The negative effects of low temperature can readily induce a variety of diseases. We sought to understand the reasons why cold stress induces disease by studying the mechanisms of fine-tuning in macrophages following cold exposure. We found that cold stress triggers increased macrophage activation accompanied by metabolic reprogramming of aerobic glycolysis. The discovery, by genome-wide RNA sequencing, of defective mitochondria in mice macrophages following cold exposure indicated that mitochondrial defects may contribute to this process. In addition, changes in metabolism drive the differentiation of macrophages by affecting histone modifications. Finally, we showed that histone acetylation and lactylation are modulators of macrophage differentiation following cold exposure. Collectively, metabolism-related epigenetic modifications are essential for the differentiation of macrophages in cold-stressed mice, and the regulation of metabolism may be crucial for alleviating the harm induced by cold stress.

O-GlcNAcylation: The Underestimated Emerging Regulators of Skeletal Muscle Physiology.

O-GlcNAcylation is a highly dynamic, reversible and atypical glycosylation that regulates the activity, biological function, stability, sublocation and interaction of target proteins. O-GlcNAcylation receives and coordinates different signal inputs as an intracellular integrator similar to the nutrient sensor and stress receptor, which target multiple substrates with spatio-temporal analysis specifically to maintain cellular homeostasis and normal physiological functions. Our review gives a brief description of O-GlcNAcylation and its only two processing enzymes and HBP flux, which will help to better understand its physiological characteristics of sensing nutrition and environmental cues. This nutritional and stress-sensitive properties of O-GlcNAcylation allow it to participate in the precise regulation of skeletal muscle metabolism. This review discusses the mechanism of O-GlcNAcylation to alleviate metabolic disorders and the controversy about the insulin resistance of skeletal muscle. The level of global O-GlcNAcylation is precisely controlled and maintained in the "optimal zone", and its abnormal changes is a potential factor in the pathogenesis of cancer, neurodegeneration, diabetes and diabetic complications. Although the essential role of O-GlcNAcylation in skeletal muscle physiology has been widely studied and recognized, it still is underestimated and overlooked. This review highlights the latest progress and potential mechanisms of O-GlcNAcylation in the regulation of skeletal muscle contraction and structural properties.

Giant Pediatric Supratentorial Tumor: Clinical Feature and Surgical Strategy.

Purpose: To analyze the clinical character of giant pediatric supratentorial tumor (GPST) and explore prognostic factors. Materials and Methods: We analyzed the clinical data comprising of 35 cases of GPST from a single center between January 2015 and December 2020. The tumor volume was measured by 3D slicer software based on preoperative magnetic resonance imaging (MRI). Glasgow Outcome Scale (GOS) was used to evaluate the short-term prognosis. Result: The tumor volume varied from 27.3 to 632.8 ml (mean volume 129.8 ml/ median volume 82.8 ml). Postoperative histopathological types include ependymoma, pilocytic astrocytoma, choroid plexus papilloma (CPP), craniopharyngioma, primitive neuroectoderm tumor (PNET), choroid plexus carcinoma (CPC), immature teratoma, atypical teratoid rhabdoid tumor (AT/RT), anaplastic astrocytoma, and gangliocytoma. Tumors in children younger than 3 years and tumors located at the hemispheres appeared to be larger than their respective counterparts, though no statistical significance was found. A patient with giant immature teratoma died during the operation because of excessive bleeding. Postoperative complications include cerebrospinal fluid subgaleal collection/effusion, infection, neurological deficits, and seizures. The mean GOS score of patients with GPST in 6 months is 3.43 ± 1.12, and 83% of patients (29/35) showed improvement. Favorable GPST characteristics to indicated better GOS included small tumor (≤100 ml) (p = 0.029), low-grade (WHO I-II) (p = 0.001), and gross total resection (GTR) (p = 0.015). WHO grade was highly correlated with GOS score (correlation coefficient = -0.625, p < 0.001). GTR and tumor volume were also correlated (correlation coefficient = -0.428, p = 0.010). Conclusion: The prognosis of GPST is highly correlated with the histopathological type. Smaller tumors are more likely to achieve GTR and might lead to a higher GOS score. Early diagnosis and GTR of the tumor are important for GPST management.

Rigid Neuroendoscopy Assisted Hematoma Resection Reduces the Recurrence Rate of Chronic Subdural Hematoma With Mixed Density: A Retrospective Analytic Cohort Study.

Background: The mixed density hematoma (MDH) has a high recurrence rate in chronic subdural hematoma (CSDH). This study adopted rigid neuroendoscopy assisted hematoma resection to evacuate CSDH and investigated its efficacy as compared with the traditional burr-hole craniostomy (BHC) in CSDH with mixed density. Methods: A retrospective cohort study was conducted at two centers between January 2015 and December 2020. The data of 124 patients who underwent BHC for CSDH with mixed density were collected and analyzed. A total of 41 patients underwent rigid neuroendoscopy assisted hematoma resection (neuroendoscopy group) and 83 patients were treated by the traditional BHC (control group). Follow-ups were conducted 6 months after the surgery. Results: There was no significant difference in the baseline characteristics and preoperative CT features between the two groups (p > 0.05). The neuroendoscopy group had a lower recurrence rate than the control group (p = 0.043). Besides the neuroendoscopy group had a higher rate of hematoma evacuation (p < 0.001), less pneumocephalus volume (p < 0.001), shorter hospital stay (p < 0.001) and better Markwalder score (p < 0.001) than the control group within 24-48 h after operation. However, there was no significant difference between the two groups in the incidence of pneumocephalus, Markwalder score (at discharge and 6 months after surgery) and mortality. Moreover, the operation time was longer in the neuroendoscopy group (p < 0.001). Conclusions: When compared with the traditional BHC, rigid neuroendoscopy assisted hematoma resection can better reduce the recurrence rate of CSDH with mixed density. Also, it surpassed the results obtained from BHC in reducing the volume of pneumocephalus, improving hematoma evacuation rate, promoting short-term neurological recovery, and shortening hospital stays.

Role of Thioredoxin-1 and its inducers in human health and diseases.

Thioredoxin-1 (Trx-1) is a small redox-active protein normally found in mammalian cells that responds to the changing redox environment by contributing electrons or regulating related proteins. There is growing evidence that Trx-1 has multiple functions, including cytoprotective, anti-apoptotic, antioxidant and anti-inflammatory effects. To date, researchers have found that Trx-1 deficiency leads to severe damage in various disease models, such as atherosclerosis, cerebral ischemia, diabetes and tumors. Conversely, activation of Trx-1 has a protective effect against these diseases. Accordingly, a variety of Trx-1 inducers have been widely used in the clinic with significant therapeutic value. In this paper, we summarize the pathogenesis of Trx-1 involvement in the above-mentioned diseases and describe the protective effects of Trx-1 inducers on them.

OGT upregulates myogenic IL-6 by mediating O-GlcNAcylation of p65 in mouse skeletal muscle under cold exposure.

Cold exposure is an unavoidable and severe challenge for people and animals residing in cold regions of the world, and may lead to hypothermia, drastic changes in systemic metabolism, and inhibition of protein synthesis. O-linked-N-acetylglucoseaminylation (O-GlcNAcylation) directly regulates the activity and function of target proteins involved in multiple biological processes by acting as a stress receptor and nutrient sensor. Therefore, our study aimed to examine whether O-GlcNAcylation affected myogenic IL-6 expression, regulation of energy metabolism, and promotion of survival in mouse skeletal muscle under acute cold exposure conditions. Total protein was extracted from C2C12 cells that had been cultured at 32°C for 3, 6, 9, and 12 h. Western blot analysis showed that mild hypothermia enhanced O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA) expression. Furthermore, global OGT-dependent glycosylation and interleukin-6 (IL-6) levels peaked 3 h after induction of mild hypothermia. Enhanced activation of the NF-κB pathway was also observed in response to mild hypothermia. Alloxan and Thiamet G were used to reduce and increase global OGT glycosylation levels in C2C12 cells, respectively. Increased O-GlcNAcylation was associated with significant upregulation of IL-6 expression, as well as enhanced activity and nuclear translocation of p65, while decreased O-GlcNAcylation had the opposite effect. In addition, increased O-GlcNAcylation was associated with significantly increased glucose metabolism, and OGT-mediated O-GlcNAcylation of p65. We generated skeletal muscle-specific OGT knockout mice and exposed them to cold at 4°C for 3 h per day for 1 week. OGT deficiency attenuated the O-GlcNAcylation, activity, and nuclear translocation of p65, resulting in downregulation of IL-6 in mouse skeletal muscle of mice exposed to cold conditions. Taken together, our data suggested that O-GlcNAcylation of p65 enhanced p65 activity and nuclear translocation leading to the upregulation of IL-6, which maintained energy homeostasis and promotes cell survival in mouse skeletal muscle during cold exposure.

Procyanidin B2 alleviates liver injury caused by cold stimulation through Sonic hedgehog signalling and autophagy.

Procyanidin B2 (PB2), a naturally occurring flavonoid abundant in a wide range of fruits, has been shown to exert antioxidant, anti-inflammatory and anticancer properties. However, the role of PB2 in the prevention of cold stimulation (CS)-induced liver injury. The present study was undertaken to determine the effects of PB2 on liver injury induced by cold stimulation and its potential molecular mechanisms. The present study results showed that treatment with PB2 significantly reduced CS-induced liver injury by alleviating histopathological changes and serum levels of alanine transaminase and aspartate transaminase. Moreover, treatment with PB2 inhibited secretion of inflammatory cytokines and oxidative stress in cold-stimulated mice. PB2 reduced cold stimulation-induced inflammation by inhibiting TLR4/NF-κB and Txnip/NLRP3 signalling. Treatment with PB2 reduced oxidative stress by activating Nrf-2/Keap1, AMPK/GSK3ß signalling pathways and autophagy. Furthermore, simultaneous application of Shh pathway inhibitor cyclopamine proved that PB2 targets the Hh pathway. More importantly, co-treatment with PB2 and cyclopamine showed better efficacy than monotherapy. In conclusion, our findings provide new evidence that PB2 has protective potential against CS-induced liver injury, which might be closely linked to the inhibition of Shh signalling pathway.