Acupuncture for cerebral ischemia/reperfusion injury Does it reduce the inflammatory reaction?

BACKGROUND： Nuclear factor-κB （NF-κB）, intercellular adhesion molecule-1 （ICAM-1）, and vascular cell adhesion molecule-1 （VCAM-1） in brain tissue can participate in inflammatory reactions after cerebral ischemia. Acupuncture treatment for acute cerebral ischemia produces abnormal protein expression. OBJECTIVE： To investigate the effects of acupuncture on NF-KB, ICAM-1, and VCAM-1 mRNA and protein expression in the brain tissue of rats with cerebral ischemiaJreperfUsion injury. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiments were performed at the Laboratory of Department of Neurosurgery, Xiangya Hospital, Central South University, China between December 2008 and October 2009. MATERIALS： Rabbit anti-NF-KB polyclonal antibody, rabbit anti-ICAM-1 polyclonal antibody, and rabbit anti-VCAM-1 polyclonal antibody were purchased from Santa Cruz Biotechnology, USA. METHODS： A total of 46 healthy, Sprague Dawley rats were randomly assigned to sham surgery （n= 10）, model （n = 12）, acupuncture pretreatment （n = 12）, and acupuncture intervention （n = 12） groups. Models of middle cerebral artery occlusion were established by right common carotid artery ligation. In the acupuncture pretreatment group, rats received acupuncture for 3 consecutive days, and then models were established. In the acupuncture intervention group, rats received acupuncture for 3 consecutive days at Waiguan （SJ 5）, Sanyinjiao （SP 6）, and Dazhui （DU 14） acupoints following model establishment. MAIN OUTCOME MEASURES： Somatosensory asymmetry and forelimb use asymmetry were tested, as well as NF-KB, ICAM-1, and VCAM-1 mRNA and protein expression in the frontal and parietal cortex at 4, 12, 24, 48 and 72 hours following cerebral ischemia/reperfusion injury. RESULTS： Acupuncture improved neurological function and significantly decreased NF-KB, ICAM-1, and VCAM-1 mRNA and protein expression in the frontal and parietal cortex of rats with cerebral ischemia/reperfusion injury （P 〈 0.05）. CONCLUSION： Acupuncture can improve neurological function, potentially via inhibition of NF-κB, ICAM,I, and VCAM-1 mRNA and protein expression in the frontal and parietal cortex of rats with cerebral ischemia/reperfusion injury.

Retrospective analysis of results of treatment for nasopharyngeal carcinoma in Macao

Background： Nasopharyngeal carcinoma （NPC） is a common malignancy in Southeast Asia, however, a full consensus has not yet been reached as to the value of comprehensive treatment for NPC. This study was designed to evaluate the epidemiological characteristics of NPC and their prognostic value, as well as the long-term efficacy of NPC treatment. Patients and methods： A total of 248 patients, with different stages of NPC, were included in this study. Results： The 5-year overall survival （OS） rates for patients in stages I, II, lII and IV were 90.48%, 76.71%, 76.89% and 33.87%, respectively （P=0.000）, while the respective 5-year progression-free survival （PFS） rates were 85.15%, 72.36%, 63.88% and 26.26% （P=0.000）. The respective 5-year OS rates, according to stage, for the group that received radiotherapy combined with chemotherapy and for the group that received radiotherapy only were as follows： stages I and II, 81.67% and 79.59% （P=0.753）; stage III, 79.91% and 70.38% （P=0.143）; stage IV,, 35.22% and 0% （P=0.000）. The respective 5-year PFS rates in these groups were as follows： stages I and II, 75.83% and 74.98% （P=0.814）; stage III, 74.08% and 42.25% （P=0.027）; stage IV,, 27.31% and 0% （P=0.000）. Conclusions： Clinical staging appears to be the most important prognostic factor for NPC. As the stage number increases, both the 5-year OS and PFS significantly decrease. Adding chemotherapy to radiotherapy was not advantageous for patients with stage I or II NPC, however the addition of chemotherapy to radiotherapy significantly improved OS and PFS in patients with stage IV NPC. The addition of chemotherapy improved PFS, but not OS in patients with stage III NPC.

RGD-FasL Induces Apoptosis of Pituitary Adenoma Cells

This study was to investigate the cytotoxic effects on pituitary adenoma cell lines GH3/MMQ/AtT20 induced by RGD-FasL and the underlying mechanism. Fas/DcR3 mRNAs were detected by RT-PCR and their surface expressions were measured by flow cytometry. Cytotoxicity exerted by RGD-FasL on tumor cells was measured with MTT assay and the induced apoptosis was determined by agarose gel electrophoresis. The cell cycle and apoptosis was assessed by flow cytometry with PI staining. The expressions of caspase8/9/3, Bcl-2, RANKL and JNK2 were detected by Western blotting. Approximately 13.7% of GH3 cells, 25.5% of MMQ cells, 22.2% of AtT20 cells express Fas, while 23.9% of GH3 cells, 24.1% of MMQ cells, 4.6% of AtT20 cells express DcR3. The cytotoxic effects of FasL/RGD-FasL on tumor cells were all taken in a dose-dependent manner. Cell lines MMQ/AtT20 showed the same sensitivity to RGD-FasL as to FasL, while cell line GH3 was less sensitive to RGD-FasL. The cell cycle analysis indicated that RGD-FasL could inhibit cells in G0/G1 phase and G2/M phase. In MMQ and AtT20 cells treated with RGD-FasL, the AI was not significantly different from that treated with FasL, while in GH3 cells treated with RGD-FasL, the AI was lower than that treated with FasL. The expressions of caspase-8/9/3, RANKL and JNK2 were increased while that of Bcl-2 was decreased after treatment with RGD-FasL, suggesting that RGD-FasL induces apoptosis through caspase activation. We concluded that RGD-FasL could possibly be considered as a novel therapeutical candidate for the treatment of pituitary adenomas. Cellular ＆ Molecular Immunology.

Therapeutic implications of exosomes in the treatment of radiation injury

Radiotherapy is one of the main cancer treatments,but it may damage normal tissue and cause various side effects.At present,radioprotective agents used in clinics have side effects such as nausea,vomiting,diarrhea and hypotension,which limit their clinical application.It has been found that exosomes play an indispensable role in radiation injury.Exosomes are lipid bilayer vesicles that carry various bioactive substances,such as proteins,lipids and microRNA(miRNA),that play a key role in cell-to-cell communication and affect tissue injury and repair.In addition,studies have shown that radiation can increase the uptake of exosomes in cells and affect the composition and secretion of exosomes.Here,we review the existing studies and discuss the effects of radiation on exosomes and the role of exosomes in radiation injury,aiming to provide new insights for the treatment of radiation injury.

Discrepancies and error evaluation metrics for machine learning interatomic potentials

Machine learning interatomic potentials(MLIPs)are a promising technique for atomic modeling.While small errors are widely reported for MLIPs,an open concern is whether MLIPs can accurately reproduce atomistic dynamics and related physical properties in molecular dynamics(MD)simulations.In this study,we examine the state-of-the-art MLIPs and uncover several discrepancies related to atom dynamics,defects,and rare events(REs),compared to ab initio methods.We find that low averaged errors by current MLIP testing are insufficient,and develop quantitative metrics that better indicate the accurate prediction of atomic dynamics by MLIPs.The MLIPs optimized by the RE-based evaluation metrics are demonstrated to have improved prediction in multiple properties.The identified errors,the evaluation metrics,and the proposed process of developing such metrics are general to MLIPs,thus providing valuable guidance for future testing and improvements of accurate and reliable MLIPs for atomistic modeling.

PC4 serves as a negative regulator of skin wound healing in mice

Background:Human positive cofactor 4(PC4)was initially characterized as a multifunctional transcriptional cofactor,but its role in skin wound healing is still unclear.The purpose of this study was to explore the role of PC4 in skin wound healing through PC4 knock-in mouse model.Methods:A PC4 knock-in mouse model(PC4^(+/+))with a dorsal full-thickness wound was used to investigate the biological functions of PC4 in skin wound healing.Quantitative PCR,Western blot analysis and immunohistochemistry were performed to evaluate the expression of PC4;Sirius red staining and immunofluorescence were performed to explore the change of collagen deposition and angiogenesis.Proliferation and apoptosis were detected using Ki67 staining and TUNEL assay.Primary dermal fibroblasts were isolated from mouse skin to perform cell scratch experiments,cck-8 assay and colony formation assay.Results:The PC4^(+/+)mice were fertile and did not display overt abnormalities but showed an obvious delay in cutaneous healing of dorsal skin.Histological staining showed insufficient re-epithelialization,decreased angiogenesis and collagen deposition,increased apoptosis and decreased cell proliferation in PC4^(+/+)skin.Our data also showed decreased migration rate and proliferation ability in cultured primary fibroblasts from PC4^(+/+)mice in vitro.Conclusions:This study suggests that PC4 might serve as a negative regulator of skin wound healing in mice.