The Antibiotics Degradation and Its Mechanisms during the Livestock Manure Anaerobic Digestion.

Antibiotics are administered to livestock at subtherapeutic levels to promote growth, and their degradation in manure is slow. High antibiotic concentrations can inhibit bacterial activity. Livestock excretes antibiotics via feces and urine, leading to their accumulation in manure. This can result in the propagation of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Anaerobic digestion (AD) manure treatment technologies are gaining popularity due to their ability to mitigate organic matter pollution and pathogens, and produce methane-rich biogas as renewable energy. AD is influenced by multiple factors, including temperature, pH, total solids (TS), substrate type, organic loading rate (OLR), hydraulic retention time (HRT), intermediate substrates, and pre-treatments. Temperature plays a critical role, and thermophilic AD has been found to be more effective in reducing ARGs in manure compared to mesophilic AD, as evidenced by numerous studies. This review paper investigates the fundamental principles of process parameters affecting the degradation of ARGs in anaerobic digestion. The management of waste to mitigate antibiotic resistance in microorganisms presents a significant challenge, highlighting the need for effective waste management technologies. As the prevalence of antibiotic resistance continues to rise, urgent implementation of effective treatment strategies is necessary.

Norcantharidin induces ferroptosis via the suppression of NRF2/HO-1 signaling in ovarian cancer cells.

Increasing evidence has indicated a crucial role of ferroptosis in ovarian cancer (OC). Norcantharidin (NCTD), a normethyl compound of cantharidin, is extensively used in clinical practice as an optional anticancer drug. However, whether NCTD leads to ferroptosis in OC has not been previously explored, at least to the best of our knowledge. In the present study, the effect of NCTD on SKOV3 and OVCAR-3 cells was evaluated. The experimental data of the present study revealed that NCTD significantly suppressed SKOV3 and OVCAR-3 cell viability in a concentration- and time-dependent manner. The results of Cell Counting Kit-8 assay revealed that NCTD treatment decreased SKOV3 and OVCAR-3 cell viability. In comparison, pre-incubation with ferrostatin-1 (Fer-1) significantly reversed the NCTD-induced reduction in SKOV3 and OVCAR-3 cell viability; however, no changes in cell viability were observed when the SKOV3 and OVCAR-3 cells were treated with NCTD, in combination with the apoptosis inhibitor, Z-VAD-FMK, the ferroptosis inhibitor, necrostatin-1, and the autophagy inhibitor, 3-methyladenine. Additionally, it was observed that NCTD markedly enhanced reactive oxygen species production and malondialdehyde and ferrous ion levels in the SKOV3 and OVCAR-3 cells; however, pre-incubation with Fer-1 abolished these effects. Flow cytometry also demonstrated a significant increase in cell death following treatment of the SKOV3 and OVCAR-3 cells with NCTD; however, pre-incubation with Fer-1 also reversed these effects. In vivo experiments demonstrated that NCTD significantly reduced tumor volume and weight. More importantly, it was revealed that nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase 1 (HO-1), glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (xCT) expression levels were significantly decreased following NCTD treatment. Collectively, NCTD may represent a potent anticancer agent in OC cells, and NCTD-induced ferroptotic cell death may be achieved by inhibiting the NRF2/HO-1/GPX4/xCT axis.

NDRG2 inhibits pyruvate carboxylase-mediated anaplerosis and combines with glutamine blockade to inhibit the proliferation of glioma cells.

Due to the rapid proliferation, cancer cells have increased anabolic biosynthesis, which requires anaplerosis to replenish precursor intermediates. The major anaplerotic sources are pyruvate and glutamine, which require the catalysis of pyruvate carboxylase (PC) and glutaminase (GLS) respectively. In GLS-suppressed cancer cells, the PC-mediated pathway for anaplerosis is crucial to maintain cell growth and proliferation. Here, we investigated the regulatory role and molecular mechanism of N-myc downstream-regulated gene 2 (NDRG2) in PC and PC-mediated anaplerosis. NDRG2 interacted with PC and induced the degradation of PC in glutamine-deprived cells. NDRG2 also inhibited the activity of PC and PC-mediated anaplerosis. As a result, NDRG2 significantly inhibited the malignant growth and proliferation of glioma cells in combination with a glutamine antagonist. In addition, NDRG2 more significantly inhibited the protein level of PC in isocitrate dehydrogenase 1 (R132H)-mutant glioma cells than in wild-type glioma cells. These findings indicate that the molecular mechanism of NDRG2 inhibits PC-mediated anaplerosis and collaborates with glutamine antagonist to inhibit the malignant proliferation of glioma cells, thus providing a theoretical and experimental basis for targeting anaplerosis in glioma therapy.

Effects of supplementing with Humulus scandens on the growth performance and gut microbiota in piglets.

AIMS: This study was conducted to evaluate the effects of feeding Humulus scandens (Hu) on growth performance and gut microbiota in piglets. METHODS AND RESULTS: A total of 120 piglets were allocated to four dietary treatments (1) CON, basal diet; (2) T1, basal diet + 2.0% Hu; (3) T2, basal diet + 2.8% Hu and (4) T3, basal diet + 3.6% Hu. The results showed that dietary H. scandens supplementation increased the final body weight and average daily gain. Furthermore, H. scandens supplementation in T1 groups increased the content of total protein, globulin and IgG in serum and the apparent digestibility of crude protein. Gut microbiota analysis showed that H. scandens treatment in T1 groups increased the abundances of Lactobacillus, Ruminococcaceae, Enterococcus and Pseudomonas in cecum content. CONCLUSIONS: These findings suggested that dietary H. scandens supplementation improved the growth performance, immunological function and nutrient apparent digestibility as well as modulating the gut microbiota in piglets. SIGNIFICANCE AND IMPACT OF THE STUDY: This study contributed to developing new feed resources and might provide an alternative strategy for growth promotion in piglets.

The Differential Responses of Coastal Diatoms to Ocean Acidification and Warming: A Comparison Between Thalassiosira sp. and Nitzschia closterium f.minutissima.

Marine diatoms are one of the marine phytoplankton functional groups, with high species diversity, playing important roles in the marine food web and carbon sequestration. In order to evaluate the species-specific responses of coastal diatoms to the combined effects of future ocean acidification (OA) and warming on the coastal diatoms, we conducted a semi-continuous incubation on the large centric diatom Thalassiosira sp. (~30 µm) and small pennate diatom Nitzschia closterium f.minutissima (~15 µm). A full factorial combination of two temperature levels (15 and 20°C) and pCO2 (400 and 1,000 ppm) was examined. The results suggest that changes in temperature played a more important role in regulating the physiology of Thalassiosira sp. and N. closterium f.minutissima than CO2. For Thalassiosira sp., elevated temperature significantly reduced the cellular particulate organic carbon (POC), particulate organic nitrogen (PON), particulate organic phosphate (POP), biogenic silica (BSi), chlorophyll a (Chl a), and protein contents, and the C:N ratio. CO2 only had significant effects on the growth rate and the protein content. However, for the smaller pennate diatom N. closterium f.minutissima, the growth rate, POC production rate, and the C:P ratio significantly increased with an elevated temperature, whereas the cellular POP and BSi contents significantly decreased. CO2 had significant effects on the POC production rate, cellular BSi, POC, and PON contents, the C:P, Si:C, N:P, and Si:P ratios, and sinking rate. The interaction between OA and warming showed mostly antagonistic effects on the physiology of both species. Overall, by comparison between the two species, CO2 played a more significant role in regulating the growth rate and sinking rate of the large centric diatom Thalassiosira sp., whereas had more significant effects on the elemental compositions of the smaller pennate diatom N. closterium f.minutissima. These results suggest differential sensitivities of different diatom species with different sizes and morphology to the changes in CO2/temperature regimes and their interactions.

MIIP inhibits clear cell renal cell carcinoma proliferation and angiogenesis via negative modulation of the HIF-2α-CYR61 axis.

OBJECTIVE: In various cancers, migration and invasion inhibitory protein (MIIP) is expressed at low level and is involved in cancer pathogenesis. Herein, we sought to explore the function of MIIP in clear cell renal cell carcinoma (ccRCC). METHODS: CCK-8, colony formation, cell cycle, and endothelial cell tube formation assays were performed to evaluate the roles of MIIP in ccRCC proliferation and angiogenesis. To explore the underlying mechanism, we conducted RNA-sequencing, GSEA, qRT-PCR, Western blot, ELISA, cell transfection, coimmunoprecipitation, and ubiquitination assays in ccRCC cell lines. Furthermore, xenograft tumor growth in nude mice, and Ki-67 and CD31 staining in xenograft tissues were examined. Finally, the association of MIIP expression with clinical pathology and the expression status of HIF-2α and cysteine-rich 61 (CYR61) were further analyzed in human RCC tissues through Western blot and immunohistochemistry. RESULTS: Both in vitro and in vivo functional experiments indicated that forced expression of MIIP inhibited ccRCC proliferation and angiogenesis, whereas silencing MIIP either in normal HK-2 cells or in ccRCC cells had the opposite effect (P < 0.05). Mechanistically, CYR61 was identified as a gene significantly downregulated by MIIP overexpression, and was required for the suppressive role of MIIP in ccRCC. MIIP was found to promote HSP90 acetylation and thus impair its chaperone function toward HIF-2α. Consequently, RACK1 binds HIF-2α and causes its ubiquitination and proteasomal degradation, thus decreasing the transcription of its target, CYR61. Finally, analyses of clinical samples demonstrated that MIIP is significantly downregulated in cancer vs. normal tissues in RCC cases, and its expression is negatively associated with histological grade, metastasis, the prognosis of patients with RCC, and the expression of HIF-2α and CYR61 (P < 0.05). CONCLUSIONS: MIIP is a novel tumor suppressor in ccRCC via negative regulation of HIF-2α-CYR61 axis.

P53/miR-154 Pathway Regulates the Epithelial-Mesenchymal Transition in Glioblastoma Multiforme Cells by Targeting TCF12.

PURPOSE: Glioblastoma multiforme (GBM) is an aggressive brain tumor with a rather short survival time. Mutation of p53 has been observed and reported to play critical roles in the progression of GBM. However, the pathological mechanisms are still unclear. This study was designed to identify the role of miR-154 in mediating the biological functions of p53 in glioblastoma multiforme. METHODS: In the current study, the expression of miR-154 in GBM tissue samples and cell lines with wt-p53 or mutant p53 was evaluated. The functions of miR-154 in tumor migration, invasion and epithelial-mesenchymal transition were analyzed in vitro. A luciferase reporter assay was used to identify the target of miR-154. RESULTS: We found that expression of miR-154 was much lower in patient tissues with mutant p53. Further study revealed that p53 was a transcription factor of miR-154 and that the R273H mutation led to its inactivation. In addition, overexpression of miR-154 remarkably suppressed cell migration, invasion and EMT in vitro and tumor growth in vivo. Moreover, TCF12 was proven to be a direct target of miR-154, and the tumor suppressive effect of miR-154 was reversed by TCF12. CONCLUSION: Overall, miR-154, which was regulated by wt-p53, inhibited migration, invasion and EMT of GBM cells by targeting TCF12, indicating that miR-154 may act as a biomarker and that the p53/miR-154/TCF12 pathway could be a potential therapeutic target for GBM.

Clinical Value of 3D-Printed Navigation Technology Combined with Neuroendoscopy for Intracerebral Hemorrhage.

Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke with high morbidity and mortality. Rapid and massive bleeding may compress the brain tissue, causing space-occupying and pathological effects, such as reduced local cerebral blood flow, acidosis, and inflammatory and immune responses. Although the development of minimally invasive technique provides a new option for the treatment of ICH, their application is limited due to the difficulty in achieving accurate puncture localization under the guidance of the marks on CT. We selected 30 patients treated with neuroendoscopic surgery guided by 3D-printed navigation technology (experimental group) and 30 patients treated with neuroendoscopic surgery guided by hand-painted on the patient's body surface according to the marks on CT (control group). Our results showed that patients in the experimental group had a lower number of intraoperative punctures, shorter operation time, less intraoperative blood loss, higher hematoma clearance rate, and smaller volume of perihematomal edema than the patients in the control group. Moreover, patients in the experimental group had higher Glasgow Coma Scale score at discharge, shorter postoperative hospitalization time and ICU stay, and a lower rate of postoperative complications, despite the lack of statistically significant differences. In addition, no statistically significant differences were observed in mortality and Glasgow Outcome Scale score between the two groups. In conclusion, 3D-printed navigation technology used for the neuroendoscopic hematoma removal is a more reliable and less invasive approach in the treatment of ICH. This technique has great application prospects and deserves promotion in the future clinical practice.

[Isolation, identification and heavy metals biosorption of a lead and cadmium-tolerant strain].

Adding biological passivation agent during composting is one of the most effective ways to reduce the toxicity of heavy metals in contaminated livestock manure. To further improve biological passivation, we obtained a strain with high-heavy metal compounds tolerance to passivate heavy-metal contaminated manure and to characterize heavy-metal biosorption. High-tolerance microorganisms for lead and cadmium were isolated and screened from swine manure composting samples. The strain was identified by its morphology and molecular biology. After the influence of different pH, temperature and salt concentrations on growth of the strain were investigated, the optimal growth conditions were obtained for further analysis of its biosorption characteristics of lead and cadmium. The bacterium with tolerance to lead and cadmium termed SC19 was obtained, whose lead resistance was 600 mg/L and cadmium resistance was 120 mg/L. The isolate was further identified as Cedecea sp., and then its optimum pH was 7.0, temperature was 37 °C, and salt concentration was 0.5%. Lead removal was highest after 30 min of adsorption by the SC19 strain cultured for the stationary phase 36 h, and the maximum removal rate and biosorption capacity of lead were 60.7% and 329.13 mg/g, respectively. Meanwhile, cadmium removal was highest after 30 min of adsorption by the strain cultured for the logarithmic phase 8 h, and the maximum removal rate and biosorption capacity of cadmium were 51.0% and 126.19 mg/g, respectively. Fourier Transform InfraRed (FT-IR) results revealed that the biosorption process mainly happened on the surface of SC19 cell and many active groups on the cell surface could chelate the Pb²âº and Cd²âº. By comprehensive comparison, it was showed that strain SC19 shared a certain capacity of Pb²âº and Cd²âº biosorption, and the bacterium provided precious microbial germplasm resources for biological passivation of heavy metal contaminated manure.

PIF1 Affects the Proliferation and Apoptosis of Cervical Cancer Cells by Influencing TERT.

INTRODUCTION: Cervical cancer is a common malignancy in female and it is a serious disease threatening women's lives. We aimed to explore whether PIF1 helicase expression could affect cell proliferation and apoptosis, and whether its mechanisms were related to the expression and activity of TERT. METHODS: Western blot analysis was used to detect the expressions of PIF1 and TERT in End1/E6E7, Hela, SiHa, Ca-Ski and C-33A cells and apoptosis-related proteins (Bax, Bcl-2 and Caspase-3). RT-qPCR and Western blot analysis determined the expressions of PIF1 and TERT after transfection. After transfection or cycloastragenol (CAG) treatment, the proliferation, apoptosis, cell cycle and telomerase TERT activity were analyzed by CCK-8 assay, flow cytometry analysis and ELISA assay. Co-immunoprecipitation assay was used to verify the interactions between PIF1 and TERT. RESULTS: The expressions of PIF1 and TERT in End1/E6E7, Hela, SiHa, Ca-Ski and C-33A cells were increased. As PIF1 and TERT expressions in C-33A cells showed the minimum increase, C-33A cells were chosen for the next study. PIF1 interference inhibited the proliferation, decreased the ratio of G2/M phase and promoted apoptosis of transfected cells, and PIF1 interference promoted the expressions of Bax and Caspase-3 and suppressed the Bcl-2 expression. Furthermore, PIF1 interference down-regulated the telomerase activity. The effect of PIF1 overexpression was opposite to that of PIF1 interference. Co-immunoprecipitation assay demonstrated that PIF1 could combine with TERT. CAG treatment effectively reversed the effect of PIF1 interference on proliferation, cycle and apoptosis of C-33A cells transfected with shRNA-PIF1. Moreover, CAG treatment increased the expressions of PIF1 and TERT. DISCUSSION: PIF1 helicase could promote the proliferation and suppress the apoptosis of cervical cancer cells by down-regulating the activity of telomerase TERT.

[Effects of microbial agents on bacterial community composition during swine manure composting]. / å¾®ç”Ÿç‰©èŒå‰‚å¯¹çŒªç²ªå †è‚¥ä¸­ç»†èŒç¾¤è½ç»“æž„çš„å½±å“.

The process of swine manure and wheat straw aerobic composting was examined, with exogenous microbial agents being added in treatment group. The physicochemical properties were measured by conventional methods, and bacterial community characteristics were investigated by high throughput sequencing analysis. Exogenous microbial agents increased high-temperature duration, reduced pH value at the end of fermentation stage, augmented total nitrogen content, reduced C/N ratio. Results from principal component analysis showed that microbial agents affected the stability of bacterial community during composting. At the phylum level, the relative abundance of Firmicutes, Proteobacteria, and Chloroflexi was higher in the treatment group. At the class level, the relative abundance of Clostridia, Alphaproteobacteria, and Gammaproteobacteria in the treatment group were higher at the mesophilic and thermophilic phases. At the family level, Peptostreptococcaceae, Clostridiaceae_1, and Halanaerobiaceae of the Clostridia and Micromonosporaceae in the treatment group were higher at the mesophilic and thermophilic phases. Halocella was significantly positively correlated with exogenous microbial agents, while Ammoniibacillus was significantly negatively correlated with it. It suggested that microbial agents significantly changed the physicochemical properties and bacterial community structure during swine composting.

Combined Aberrant Expression of NDRG2 and LDHA Predicts Hepatocellular Carcinoma Prognosis and Mediates the Anti-tumor Effect of Gemcitabine.

The Warburg effect is one of the important hallmarks of cancer. The activation of oncogene and inactivation of tumor suppressor gene contribute to the enhancement of glycolytic enzymes and the Warburg effect. The N-myc downstream regulated gene 2 (NDRG2) is a tumor suppressor gene and is frequently lost in various types of cancer. However, little is known about glycolytic function and therapeutic value of NDRG2 in hepatocellular carcinoma (HCC). In this study, we found that NDRG2 and lactate dehydrogenase A (LDHA) were aberrantly expressed in HCC and were closely related to the Warburg effect. The correlation between NDRG2 and LDHA expression predicted HCC prognosis and the clinical response to chemotherapy. NDRG2 expression was significantly decreased while LDHA expression was increased in HCC specimens. NDRG2 and LDHA expression was significantly correlated with differentiation status, vascular invasion, and TNM stage of HCC. NDRG2 inhibited LDHA expression, the Warburg effect and the growth of HCC cells. Furthermore, NDRG2 mediated gemcitabine-induced inhibition of LDHA expression and the Warburg effect in HCC cells. Taken together, our data suggest that NDRG2 plays an important role in inhibiting the Warburg effect and the malignant growth of HCC via LDHA. NDRG2 combined with LDHA might be powerful prognostic biomarkers and targets for chemotherapy treatment of HCC.

Neuregulin1 attenuates cognitive deficits and hippocampal CA1 neuronal apoptosis partly via ErbB4 receptor in a rat model of chronic cerebral hypoperfusion.

Neuregulin1 (NRG1) is an effective neuroprotectant. Previously we demonstrated that the expression of hippocampal NRG1/ErbB4 gradually decreased and correlates with neuronal apoptosis during chronic cerebral hypoperfusion (CCH). Here we aimed to further investigate the protective role of NRG1 in CCH. AG1478, an ErbB4 inhibitor, was used to explore the involvement of ErbB4 receptors in NRG1's action. Permanent bilateral common carotid artery occlusion (2VO) or sham operation was performed in Sprague-Dawley rats. NRG1 (100 µM) and AG1478 (50 mM) was administered intraventricularly. Eight weeks post-surgery, cognitive impairment was analyzed using Morris water maze (MWM) and radial arm water maze (RAWM) tests, followed by histological assessment of the survival and apoptosis of hippocampal CA1 neurons using NeuN and TUNEL immunostaining respectively. Expression of apoptosis-related proteins and ErbB4 activation (pErbB4/ErbB4) was evaluated by Western blotting. The results showed that NRG1 significantly improved the performances in MWM (spatial learning and memory) and RAWM (spatial working and reference memory), attenuated hippocampal CA1 neuronal loss and apoptosis, upregulated the expression of pErbB4/ErbB4 and the anti-apoptotic protein Bcl-2, and downregulated the expression of pro-apoptotic proteins of Cleaved (Cl)-caspase3 and Bax. In addition, the protective effects of NRG1 could be partly abolished by AG1478. Taken together, our study suggested that NRG1 ameliorates cognitive impairment and neuronal apoptosis partly via ErbB4 receptors in rats with CCH.

Effect of PTEN loss on metabolic reprogramming in prostate cancer cells.

The tumor suppressor gene PTEN is one of the most often deleted genes in human prostate cancer. Loss of PTEN is an important event in prostate carcinogenesis. Metabolic reprogramming induced by PTEN loss fuels malignant growth and proliferation of prostate cancer cells. Targeted metabolomics analysis was used to investigate the effects of PTEN loss on intracellular metabolic pathways in prostate cancer cells. DU-145 cells were transfected with PTEN siRNAs (siRNA-1 and siRNA-2) for 48 h, and endogenous PTEN expression was monitored by western blotting. Changes in intracellular metabolites were determined by liquid chromatography-tandem mass chromatography (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS). Most intracellular metabolites involved in glycolysis and glutaminolysis were increased in PTEN knockdown prostate cancer cells. In addition, most intracellular metabolites involved in fatty acid de novo synthesis, fatty acid beta oxidation and branched chain amino acid catabolism were also increased in PTEN knockdown prostate cancer cells. These results revealed that PTEN loss induced the metabolic reprogramming of prostate cancer cells and promoted the malignant proliferation of prostate cancer cells. The present metabolomics analysis indicates that tumor suppressor gene PTEN mutation or deletion can induce metabolic reprogramming in prostate cancer cells and tumorigenesis by altering the metabolic flux of glycolysis, glutaminolysis, fatty acid metabolism and branched chain amino acid catabolism pathways. Metabolic reprogramming is one of the contributors to PTEN-loss driven prostate cancer.

Loss of Sfrp2 contributes to the neurological disorders related with morphine withdrawal via Wnt/ß-catenin signaling.

Morphine administration is a medical problem characterized by compulsive opioid use that causes terrible negative consequences. The exact mechanisms of morphine-induced dependence and morphine withdrawal symptoms remain unclear. Recent studies have revealed that the upregulation of Wnt/ß-catenin signaling plays important roles in morphine exposure and morphine withdrawal. Secreted frizzled-related protein 2 (Sfrp2) can prevent the activation of Wnt/ß-catenin signaling by competing with the Frizzled receptor for Wnt ligands. We conducted this study aimed to evaluate the effect of iatrogenic trauma induced by stereotactic surgery and the protective effect of stereotaxic Sfrp2 injection on morphine withdrawal symptoms in Male Sprague Dawley (SD) rats. Many techniques including western blot analysis and immunoprecipitation were used. Anxiety-related behaviors, morphine withdrawal syndrome, and dendritic spines were also examined in male SD rats after morphine treatment and stereotaxic injection of Sfrp2. Western blot results suggested that Wnt signaling was activated in the nucleus accumbens of SD rats suffering from morphine withdrawal and that Sfrp2 attenuated the overexpression of Wnt signaling. Similarly, the withdrawal-like symptoms of morphine dependent rats were abrogated by intracerebral Sfrp2 injection. The iatrogenic trauma induced by stereotactic surgery showed no influence on the Wnt signaling and withdrawal-like symptoms. Moreover, the results of Golgi-cox staining and DiI staining indicated that the damage on proximal spine density caused by morphine treatment was restored by intracerebral Sfrp2 injection. Together, the data presented here indicated that Sfrp2 abrogated the neurological disorders and loss of proximal spine related with morphine withdrawal via Wnt/ß-catenin signaling.

MiR-7-5p suppresses stemness and enhances temozolomide sensitivity of drug-resistant glioblastoma cells by targeting Yin Yang 1.

Glioblastoma multiforme (GBM) is the most malignant tumor of the central nervous system, and chemoresistance blunts the effect of temozolomide (TMZ) in the treatment of GBM. Clarifying the underlying mechanism of chemoresistance might yield novel strategies to improve the patients' response to chemotherapeutics. Mounting evidence indicates that microRNAs (miRNAs) are involved in chemoresistance and tumorigenesis. At present, miR-7-5p has been recognized as a tumor suppressor involved in multiple cancers. However, the biological effects of miR-7-5p in TMZ resistance have not been illuminated. In this study, we used RNA sequencing and high-throughput screening techniques, which revealed that miR-7-5p is significantly downregulated in TMZ resistant LN229 cells (LN229/TMZ-R) compared to control cells (LN229), and low miR-7-5p expression was correlated with recurrence in GBM patients. Ectopic overexpression of miR-7-5p sensitized LN229/TMZ-R cells to TMZ and suppressed the stemness of glioblastoma stem cells (GSCs). Further experiments demonstrated that miR-7-5p exerts its role by directly targeting the 3'-untranslated region of Yin Yang 1 (YY1). Our findings suggest that combinational use of miR-7-5p and TMZ might be a promising therapeutic strategy to increase the long-term drug response in GBM patients.

Propoxyphene Mediates Oxyhemoglobin-Induced Injury in Rat Cortical Neurons Through Up-Regulation of Active-ß-Catenin.

Wnt/ß-catenin signaling is involved in various biological processes, including the development of the central nervous system. The dysfunction of mitochondria has been shown to participate in the progress of subarachnoid hemorrhage (SAH). Traumatic subarachnoid hemorrhage (tSAH) is a serious complication in acute craniocerebral trauma. Opioids can activate the canonical Wnt/ß-catenin signaling pathway. c-Myc, a downstream protein of Wnt/ß-catenin signaling, contributes to the fusion of mitochondria. Here, we investigated the protective roles of Propoxyphene (Pro) against Oxyhemoglobin (OxyHb)-induced primary cultured neuron apoptosis. The data indicated that Pro rescued active-ß-catenin from OxyHb-induced decline. Furthermore, Pro attenuated OxyHb-induced apoptosis and fission of mitochondria in primary cortical neurons. However, the protective effects were abrogated under active-ß-catenin-deficient conditions. Together, the data presented here showed that Pro, a weak opioid analgesic drug, attenuates OxyHb-induced mitochondria-dependent apoptosis in an active-ß-catenin-c-Myc-dependent manner.

GSK-3ß Inhibitor Alsterpaullone Attenuates MPP+-Induced Cell Damage in a c-Myc-Dependent Manner in SH-SY5Y Cells.

Mitochondrial dysfunction plays significant roles in the pathogenesis of Parkinson's Disease (PD). The inactivation of c-Myc, a down-stream gene of Wnt/ß-catenin signaling, may contribute to the mitochondria dysfunction. Inhibition of glycogen synthase kinase 3ß (GSK-3ß) with Alsterpaullone (Als) can activate the down-stream events of Wnt signaling. Here, we investigated the protective roles of Als against MPP+-induced cell apoptosis in SH-SY5Y cells. The data showed that Als effectively rescued c-Myc from the MPP+-induced decline via Wnt signaling. Furthermore, Als protected SH-SY5Y cells from the MPP+-induced mitochondrial fission and cell apoptosis. However, the protective roles of Als were lost under ß-catenin-deficient conditions. These findings indicate that Als, a GSK-3ß inhibitor, attenuated the MPP+-induced mitochondria-dependent apoptotic via up-regulation of the Wnt signaling.

Two novel mutations in the ANTXR2 gene in a Chinese patient suffering from hyaline fibromatosis syndrome: A case report.

Hyaline fibromatosis syndrome (HFS; MIM 228600) is a rare autosomal recessive disorder characterized by the abnormal growth of hyalinized fibrous tissue at subcutaneous regions on the scalp, ears and neck. The disease is caused by either a homozygous or compound heterozygous mutation of the anthrax toxin receptor 2 (ANTXR2) gene. The present study describes a patient with HFS confirmed by clinical examination as well as histopathological and genetic analyses. Numerous painless and variable­sized subcutaneous nodules were observed on the scalp, ear, trunk and four extremities of the patient. With increasing age, the number and size of the nodules gradually increased in the patient. The patient additionally presented with severe gingival thickening and developed pearly papules on the ears, back and penis foreskin. Biopsies of ear nodules revealed that the tumor was located in the dermis, and no marked alterations were observed in the epidermis compared with healthy patients. Spindle­shaped or round tumor cells were revealed to be immersed in the eosinophilic hyaline ground substance. Furthermore, a skeletal X­ray of the patient revealed multiple low­density imaging on the right distal humerus. Compound heterozygous mutations in the ANTXR2 gene were identified in the patient: c.470_472del in exon 5 and c.1073 delC in exon 13. c.470_472del were revealed to be inherited from his mother and father, respectively. These two mutations, c.470_472del and c.1073 delC, to the best of our knowledge, have not previously been identified. Identification of the mutations in ANTXR2 may make prenatal diagnosis of HFS possible during future pregnancies.

Computed Tomography Angiography Spot Sign as an Indicator for Ultra-Early Stereotactic Aspiration of Intracerebral Hemorrhage.

BACKGROUND: Ultra-early surgical clot removal relieves mechanical compression on adjacent normal brain tissue and limits the toxic effects of a hematoma, which might improve the outcomes in patients with intracerebral hemorrhage (ICH); however, hematoma expansion frequently occurs within 20 hours after the ictus, and this limits the use of ultra-early surgery. Computed tomography angiography spot sign was recently validated as an important predictor of hematoma expansion in patients with ICH. METHODS: Fifty-nine patients with ICH and negative spot sign who received ultra-early stereotactic aspiration (<6 hours after ictus; n = 32 [Ultra-early group]) or routine stereotactic aspiration (≥6 hours after ictus; n = 27 [Routine group]) were included in retrospective analysis. RESULTS: The percentage of rebleeding was not significantly different between the 2 groups. Perihematoma edema 7 days after surgery in the Ultra-early group was significantly less frequent than that in the Routine group. For long-term outcomes, the proportion of patient fatalities and Glasgow Outcome Scale score were not significantly different between the 2 groups; however, for patients with severe symptoms, the rate of good neurological outcome in the Ultra-early group was higher than that in the Routine group. CONCLUSIONS: Ultra-early stereotactic aspiration might decrease the volume of perihematoma edema and improve the functional outcomes to some extent, without increasing the recurrence of ICH and patient fatalities. Our findings suggest that using negative spot sign as an indicator for performing ultra-early stereotactic aspiration could be a safe and effective protocol for ICH patients.