Knockout of Sirt2 alleviates traumatic brain injury in mice

Sirtuin 2(SIRT2) inhibition or Sirt2 knocko ut in animal models protects against the development of neurodegenerative diseases and cerebral ischemia.However,the role of SIRT2 in traumatic brain injury(TBI) remains unclear.In this study,we found that knockout of Sirt2 in a mouse model of TBI reduced brain edema,attenuated dis ruption of the blood-brain barrie r,decreased expression of the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammasome,reduced the activity of ...     

Knockdown of DEAD-box 51 inhibits tumor growth of esophageal squamous cell carcinoma via the PI3K/AKT pathway

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is one of the most prevalent malignancies that seriously threaten people’s health worldwide.DEAD-box helicase 51(DDX51)is a member of the DEAD-box(DDX)RNA helicase family,and drives or inhibits tumor progression in multiple cancer types.AIM To determine whether DDX51 affects the biological behavior of ESCC.METHODS The expression of DDX51 in ESCC tumor tissues and adjacent normal tissues was detected by Immunohistochemistry(IHC)analyses and quantitative PCR(qPCR).We knocked down DDX51 in ESCC cell lines by using a small interfering RNA(siRNA)transfection.The proliferation,apoptosis,and mobility of DDX51 siRNAtransfected cells were detected.The effect of DDX51 on the phosphoinositide 3-kinase(PI3K)/AKT pathway was investigated by western blot analysis.A mouse xenograft model was established to investigate the effects of DDX51 knockdown on ESCC tumor growth.RESULTS DDX51 exhibited high expression in ESCC tissues compared with normal tissues and represented a poor prognosis in patients with ESCC.Knockdown of DDX51 induced inhibition of ESCC cell proliferation and promoted apoptosis.Moreover,DDX51 siRNA-expressing cells also exhibited lower migration and invasion rates.Investigations into the underlying mechanisms suggested that DDX51 knock down induced inactivation of the PI3K/AKT pathway,including decreased phosphorylation levels of phosphate and tensin homolog,PI3K,AKT,and mammalian target of rapamycin.Rescue experiments demonstrated that the AKT activator insulin-like growth factor 1 could reverse the inhibitory effects of DDX51 on ESCC malignant development.Finally,we injected DDX51 siRNA-transfected TE-1 cells into an animal model,which resulted in slower tumor growth.CONCLUSION Our study suggests for the first time that DDX51 promotes cancer cell proliferation by regulating the PI3K/AKT pathway;thus,DDX51 might be a therapeutic target for ESCC.     

Analysis on internal mechanism of zedoary turmeric in treatment of liver cancer based on pharmacodynamic substances and pharmacodynamic groups

Zedoary tumeric (Curcumae Rhizoma, Ezhu in Chinese) has a long history of application and has great potential in the treatment of liver cancer. The anti liver cancer effect of zedoary tumeric depends on the combined action of multiple pharmacodynamic substances. In order to clarify the specific mechanism of zedoary tumeric against liver cancer, this paper first analyzes the mechanism of its single pharmacodynamic substance against liver cancer, and then verifies the joint anti liver cancer mechanism of its "pharmacodynamic group". By searching the research on the anti hepatoma effect of active components of zedoary tumeric in recent years, we found that pharmacodynamic substances, including curcumol, zedoarondiol, curcumenol, curzerenone, curdione, curcumin, germacrone, β-elemene, can act on multi-target and multi-channel to play an anti hepatoma role. For example, curcumin can regulate miR, GLO1, CD133, VEGF, YAP, LIN28B, GPR81, HCAR-1, P53 and PI3K/Akt/mTOR, HSP70/TLR4 and NF-κB. Wnt/TGF/EMT, Nrf2/Keap1, JAK/STAT and other pathways play an anti hepatoma role. Network pharmacological analysis showed that the core targets of the "pharmacodynamic group" for anti-life cancer are AKT1, EGFR, MAPK8, etc, and the core pathways are neuroactive live receiver interaction, nitrogen metabolism, HIF-1 signaling pathway, etc. At the same time, by comparing and analyzing the relationship between the specific mechanisms of pharmacodynamic substance and "pharmacodynamic group", it is found that they have great reference significance in target, pathway, biological function, determination of core pharmacodynamic components, formation of core target protein interaction, in-depth research of single pharmacodynamic substance, increasing curative effect and so on. By analyzing the internal mechanism of zedoary tumeric pharmacodynamic substance and "pharmacodynamic group" in the treatment of liver cancer, this paper intends to provide some ideas and references for the deeper pharmacological research of zedoary tumeric and the relationship between pharmacodynamic substance and "pharmacodynamic group".     

Prognostic and incremental value of computed tomography-based radiomics from tumor and nodal regions in esophageal squamous cell carcinoma

Objective: This study aimed to evaluate the prognostic value of preoperative radiomics and establish an integrated model for esophageal squamous cell cancer(ESCC).Methods: A total of 931 patients were retrospectively enrolled in this study(training cohort, n=624; validation cohort, n=307). Radiomics features were obtained by contrast-enhanced computed tomography(CT) before esophagectomy. A radiomics index was set based on features of tumor and reginal lymph nodes by using the least absolute shri...     

Heparanase-1 is downregulated in chemoradiotherapy orbital rhabdomyosarcoma and relates with tumor growth as well as angiogenesis

AIM:To determine the role of heparanase-1(HPSE-1)in orbital rhabdomyosarcoma(RMS),and to investigate the feasibility of HPSE-1 targeted therapy for RMS.METHODS:Immunohistochemistry was performed to analyze HPSE-1 expression in 51 cases of orbital RMS patients(including 28 cases of embryonal RMS and 23 cases of alveolar RMS),among whom there were 27 treated and 24 untreated with preoperative chemoradiotherapy.In vitro,studies were conducted to examine the effect of HPSE-1 silencing on RMS cell proliferation and tube formation of human umbilical vein endothelial cells(HUVECs).RD cells(an RMS cell line)and HUVECs were infected with HPSE-1 sh RNA lentivirus at a multiplicity of infection(MOI)of 10 and 30 separately.Real-time PCR and Western blot were applied to detect the m RNA and protein expression levels of HPSE-1.Cell viability of treated or control RD cells was evaluated by cell counting kit-8(CCK-8)assay.Matrigel tube formation assay was used to evaluate the effect of HPSE-1 RNAi on the tube formation of HUVECs.RESULTS:Immunohistochemistry showed that the expression rate of HPSE-1 protein was 92.9%in orbital embr yonal RMS and 91.3%in orbital alveolar RMS.Tissue from alveolar orbital RMS did not show relatively stronger staining than that from the embryonal orbital RMS.However,despite the types of RMS,comparing the cases treated chemoradiotherapy with those untreated,we have observed that chemoradiotherapy resulted in weaker staining in patients’tissues.The expression levels of HPSE-1 declined significantly in both the m RNA and protein levels in HPSE-1 sh RNA transfected RD cells.The CCK-8 assay showed that lentivirus-mediated HPSE-1 silencing resulted in significantly reduced RD cells viability in vitro.Silencing HPSE-1 expression also inhibited VEGF-induced tube formation of HUVECs in Matrigel.CONCLUSION:HPSE-1 silencing may be a promising therapy for the inhibition of orbital RMS progression.     

Clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection with fresh or cryopreserved sperm in patients with nonobstructive azoospermia

We performed this study to evaluate the clinical outcomes of microdissection testicular sperm extraction-intracytoplasmic sperm injection(micro-TESE-ICSI)treatment that used fresh or cryopreserved sperm in patients with nonobstructive azoospermia(NOA).A total of 338 NOA patients with 344 consecutive cycles received treatment in the reproductive medicine center of Peking University Third Hospital in Beijing,China,from January 2014 to December 2017.Fresh oocytes and fresh sperm were used in 222 patients with 234 cycles(Group A).Fresh oocytes and cryopreserved sperm were used in 116 patients with 110 cycles(Group B).We compared patient characteristics,embryonic development,and pregnancy outcomes between Groups A and B.There was no statistical difference in the patient characteristics,and no differences were observed with fertilization or quality embryo rates between Groups A and B.The rates of clinical pregnancy and live birth were both higher for Group A than those for Group B(both P<0.05).In conclusion,fresh testicular sperm appears to produce better ICSI outcomes than cryopreserved testicular sperm in patients with NOA.     

The Mechanisms of Pei‑yuan‑Tong‑nao Capsule as a Therapeutic Agent against Cerebrovascular Disease

Objective: Pei?Yuan?Tong?Nao (PYTN) capsule has been widely used for the treatment of cerebrovascular disease (CVD), including cerebral ischemia. However, due to the complexity of traditional Chinese Medicine (TCM) and the lack of proper inspection methods, the pharmacological mechanisms of the actions of PYTN capsule on CVD remain ambiguous. In this investigation, a network pharmacology method was used to investigate the mechanism of action of PYTN capsule in the treatment of CVD. Methods: In this method, a chemical similarity ensemble approach was employed to predict putative targets for chemicals derived from PYTN capsule. Results: Thus, a total of 351 compounds and 650 proteins were identified as potential active ingredients and putative CVD?related targets. In addition, two interaction networks were constructed, including a network between putative targets of PYTN capsule and known CVD?related targets, and a network between candidate active compounds and putative CVD?related targets. Conclusion: The mechanism of PYTN capsule in the treatment of CVD was found to be based on three functional modules, namely, antioxidation, anti?inflammation, and antiapoptosis modules through multiple signaling pathways, such as PI3K?Akt, mitogen?activated protein kinase, and TNF signaling pathways. We hope that this work can provide insight into the pharmacological mechanisms of TCMs in the treatment of CVD and provide a basis for further development and the discovery of more effective clinical strategies for the treatment of complicated diseases.     

Orexin Receptor Antagonists as Emerging Treatments for Psychiatric Disorders

Orexins comprise two neuropeptides produced by orexin neurons in the lateral hypothalamus and are released by extensive projections of these neurons throughout the central nervous system. Orexins bind and activate their associated G protein-coupled orexin type 1 receptors(OX1Rs) and OX2Rs and act on numerous physiological processes, such as sleep-wake regulation, feeding, reward,emotion, and motivation. Research on the development of orexin receptor antagonists has dramatically increased with the approval of suvorexant for the treatment of primary insomnia. In the present review, we discuss recent findings on the involvement of the orexin system in the pathophysiology of psychiatric disorders, including sleep disorders,depression, anxiety, and drug addiction. We discuss the actions of orexin receptor antagonists, including selective OX1R antagonists (SORA1s), selective OX2R antagonists(SORA2s), and dual OX1/2R antagonists (DORAs), in the treatment of these disorders based on both preclinical and clinical evidence. SORA2s and DORAs have more pronounced efficacy in the treatment of sleep disorders,whereas SORA1s may be promising for the treatment of anxiety and drug addiction. We also discuss potential challenges and opportunities for the application of orexin receptor antagonists to clinical interventions.     

Different position from traditional left lateral for colonoscopy? A meta-analysis and systematic review of randomized control trials

Background: Colonoscopy requires the intubation of the cecum for screening of colorectal diseases. The conventional position used for colonoscopy is the left lateral position (LLP). However, alternative positions have also been utilized to enhance the success of intubation. Thus, the aim of this study was to perform a meta-analysis of the different positions to determine the effectiveness of the individual positions for successful colonoscopy.Methods: Medline, Embase and Cochrane trials electronic databases were searched for studies on colonoscopy positions. The primary outcome was defined as the cecal intubation rate. Pooled risk ratios (RR) and 95% confidence intervals (CI) for the rates of cecal intubation were estimated. Secondary outcomes such as the cecal intubation time and adenoma detection rate were further analyzed qualitatively.Results: After reviewing 644 identified records, 7 randomized control trials (RCT) studies were included. No significant difference was observed in either comparisons, between the LLP vs. supine position (SP) (RR = 1.01, 95% CI, 0.98 to 1.04,P = 0.55) or the LLP vs. prone position (PP) (RR = 1.02, 95% CI, 0.98 to 1.06,P = 0.27).Conclusions: Amidst available literature, the use of other positions can be considered when performing colonoscopy. These further highlights that the existential practice is based predominantly on familiarity instead of evidence-based-research.     

The role and its mechanism of intermittent fasting in tumors:friend or foe?

Intermittent fasting(IF)is becoming a prevailing topic worldwide,as it can cause changes in the body’s energy metabolism processes,improve health,and affect the progression of many diseases,particularly in the circumstance of oncology.Recent research has shown that IF can alter the energy metabolism of tumor cells,thereby inhibiting tumor growth and improving antitumor immune responses.Furthermore,IF can increase cancer sensitivity to chemotherapy and radiotherapy and reduce the side effects of these traditional anticancer treatments.IF is therefore emerging as a promising approach to clinical cancer treatment.However,the balance between long-term benefits of IF compared with the harm from insufficient caloric intake is not well understood.In this article,we review the role of IF in tumorigenesis and tumor therapy,and discuss some scientific problems that remain to be clarified,which might provide some assistance in the application of IF in clinical tumor therapy.