bluuebunny/crossref_metadata_2025 huggingface dataset:
Nigericin Suppresses the Wnt/β-catenin Signaling in Pancreatic Cancer through Targeting pre-miR-374b-PRKCA/HBP1 Axis
Authors: Zhi Qiaoming , Li Wei , Zhu Dongming , Wan Daiwei , Han Ye , Liu Fei , Xu Zhihua , Jiang Min , Xu Ye
Published: August 2020

Background

The polyether antibiotic nigericin has been demonstrated recently to have anti-tumor activity in multiple cancers. But the biochemical basis for its anti-cancer effects has not been fully elucidated. The objective of this study was to investigate the potential mechanisms of nigericin in pancreatic cancer (PC) cells.
Methods

PC cells were exposed to increasing concentrations of nigericin at different time periods, and the corresponding IC50 values were calculated. Then the effects on the biological functions of PC cells were evaluated. Subsequent experiments including the high-throughput RNA sequencing, qRT-PCR, western blot, TOP/FOP-Flash reporter, Co-Immunoprecipitation and luciferase report assays were employed to reveal the potential mechanisms of nigericin. In addition, the inhibitory effects of nigericin on PC cells were also accessed in the subcutaneous tumor model.
Results

The data showed that nigericin was extremely sensitive to PC cells, and could influence the abilities of cell proliferation, colony formation, apoptosis, migration and invasion. The results in vitro implied that nigericin suppressed the Wnt/β-catenin signaling by up-regulating PRKCA and HBP1 mRNA expressions. Furthermore, the dual strands of pre-miR-374b were proved to down-regulate the PRKCA and HBP1 expressions coordinately, and over-expression of pre-miR-374b partly antagonized the suppressing effects of PC cells induced by nigericin. Meanwhile, the inhibitory effects of nigericin on PC cells were also confirmed in mice.
Conclusion

These findings demonstrated that suppressing the Wnt/β-catenin signaling pathway by targeting pre-miR-374b-PRKCA/HBP1 axis might represent a novel molecular mechanism of nigericin in PC. Nigericin remained a candidate for a potential pre-clinical application for PC.
Impact of Four-Dimensional Cone-Beam Computed Tomography on Target Localization for Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Radiotherapy: Reducing Planning Target Volume Margin
Authors: Shimohigashi Yoshinobu , Toya Ryo , Saito Tetsuo , Kono Yumiko , Doi Yasuhiro , Fukugawa Yoshiyuki , Watakabe Takahiro , Matsumoto Tadashi , Kai Yudai , Maruyama Masato , Oya Natsuo
Published: August 2020

Background: Radiotherapy of gastric mucosa-associated lymphoid tissue (MALT) lymphoma should be delivered to the whole stomach with optimal planning target volume (PTV) margins that account for variations in stomach volume, respiratory movement, and patient set-up error. In this study, we evaluated whether the use of four-dimensional cone-beam computed tomography (4D-CBCT) reduces the PTV margin.Methods: Eight patients underwent radiotherapy with 15 fractions of gastric MALT lymphoma using 4D-CBCT. Structures with PTV margins of 5–30 mm (5 mm intervals) from the internal target volume of the stomach defined based on the 4D-CT images were generated. For the target localization, we performed matching based on skin marking (skin matching), bone anatomy (bone matching), and stomach anatomy (4D soft-tissue matching) based on registration between planning CT and 4D-CBCT images from 10 phases. For each patient, we calculated the covering ratio (CR) of the stomach with variable PTV margins, based on the 4D-CBCT images, with a total of 150 phases [CR (%) = (number of covering phases / 150 phases) × 100], for three target localization methods. We compared the CR values of the different target localization methods and defined a minimal PTV margin with an average CR of ≥ 95 % for all patients as optimal.Results: The average CR for all patients increased from 17.9 % to 100 %, 19.6 % to 99.8 %, and 33.8 % to 100 %, in the skin, bone, and 4D soft-tissue matchings, respectively, as the PTV margins increased from 5 to 30 mm. The CR obtained by 4D soft-tissue matching was superior to that obtained by skin (P = 0.013) and bone matching (P = 0.008) for a PTV margin of 15 mm. The optimal PTV margins were 20 mm (average CR: 95.2 %), 25 mm (average CR: 99.1 %), and 15 mm (average CR: 98.0 %) for the skin, bone, and 4D soft-tissue matchings, respectively.Conclusions: This study demonstrates that the use of 4D-CBCT reduces the PTV margin when applying 4D soft-tissue matching, compared to skin and bone matchings. Additionally, bone matching does not reduce the PTV margin as compared with traditional skin matching.
The Effect of Edible Lipids on Atherogenic Index of Plasma: Results From RaNCD Cohort Study
Authors: Sahargahi Badrieh , Pasdar Yahya , Moradinazar Mehdi , Najafi Farid , Darbandi Mitra , Moludi Jalal , Hamzeh Behrooz , Shakiba Ebrahim
Published: August 2020

Background: The amount and type of lipids consumed has a great impact on serum lipid profile and risk of cardiovascular diseases (CVDs). A novel index named atherogenic index of plasma (AIP) is better predictors of CVD risk factors than lipids alone. This study aimed to investigate the effect of edible oils on AIP. Methods: This cross-sectional study conducted on preliminary phase of Ravansar Non-Communicable Disease (RaNCD) cohort study. The amount of consumption of edible lipids was determined based on validated Food Frequency Questionnaire (FFQ). Lipid profiles including triglyceride (TG), and lipoprotein cholesterol (HDL-C) were measured, and AIP was calculated as log10 (TG/HDL-C).Results: A total of 9996 individuals, 4738(47.4%) were male. The mean of AIP was 0.98±0.6 (range from -1.73 to 4.15) that in females (0.97 ± 0.6) was lower than males (1.10 ± 0.6). After controlling for confounding and affecting variables, the AIP index decreased with increasing consumption of a local oil named Kermanshahi oil [β(CI 95% ): -0.006(-0.008, -0.003)], butter[β(CI 95% ): -0.008(-0.011, -0.005)] and not statistically significant decrease with Hydrogenated or partial hydrogenated oil [β(CI 95% ): -0.008(-0.001, 0.001)] but the AIP index increased with un-hydrogenated oil [β(CI 95% ): 0.001(-0.001, 0.001)]Conclusion: Kermanshahi oil and butter have decreasing effect on AIP, the effect of margarine was neutral, hydrogenated vegetable oil has trace decreasing effect whereas un-hydrogenated vegetable oil has increasing effect on it. So, consumption of Kermanshahi oil may be associated with lower cardiovascular risk.
Influence of GSTT1 and GSTP1 Polymorphisms on Type 2 Diabetes Mellitus and Diabetic Retinopathy Risk in the Chinese Population: A Case Control Study
Authors: Geng Xinqian , Zha Ling , Zhou Taicheng , Xiong Yixin , Xu Fan , Xu Bo , Wang Feiying , Wang Xiaoling , Yang Ke , Yang Ying , Tao Wenyu , Li Yiping
Published: August 2020

Background: Studies have revealed the association of glutathione S-transferases (GSTM1 and GSTT1) deletion (null) polymorphism with the risks of developing type 2 diabetes mellitus (T2DM) and its complications. The present study aimed to investigate the relationship between GSTT1/ GSTP1 gene polymorphisms and the risks of T2DM and diabetic retinopathy (DR) in a Chinese population.Methods: A total of 336 subjects with T2DM and a defined ophthalmologic status were recruited from the Second People’s Hospital of Yunnan Province between June 2014 and October 2016. Seventy-two age-matched healthy controls were also enrolled. Physical examinations and laboratory tests were performed. The frequencies of GSTT1 and GSTP1 genotypes in all participants were determined by PCR and PCR-restriction fragment length polymorphisms (PCR–RFLP), respectively.Results: Compared with healthy controls, the GSTT1-null genotype was significantly more common in diabetic patients with or without DR (all P < 0.05). However, the frequency of the GSTP1 genotype (AA, GA, GG) was comparable between the two groups. Furthermore, neither the GSTP1 nor GSTT1 genetic polymorphism was associated with the development of DR. In the present study, the risk of developing T2DM was significantly higher in subjects carrying the combined heterozygous GSTP1 (AG) and null GSTT1 genotypes (OR=0.40, 95% CI=0.21-0.74, P=0.02).Conclusions: The deletion of the GSTT1 genotype was associated with a higher risk of developing T2DM, whether alone or in combination with GSTP1, indicating that the null genotype of GSTT1 may serve as a potential biomarker for T2DM in the Chinese population, which is helpful for clinicians to make more effective risk-based decisions.
Long Non-Coding RNA SNHG12 Promotes Prostate Tumor Occurrence and Progression via AKT Regulation
Authors: Chen Zheng , Qi Tao , Qin Xiaoping , Wang Jue , Huang Zhangsen , Hu Xiaoyong , Chen Guo , Ju Lijun , Zhuo Yu-min
Published: August 2020

BackgroundIncreasing studies have shown that long noncoding RNAs (lncRNAs) participated in the development of prostate cancer (PCa). The small nucleolar RNA host gene 12 (SNHG12) has been reported to play an important role in the tumorigenesis and progression of PCa, but the functional underlying mechanism has not been studied clearly. MethodsWe detected the expression level of SNHG12 in PCa tissues and matched adjacent normal tissues that were collected from 85 patients. Then, colony formation assays, MTT experiments and flow cytometry were used to examine the effect of SNHG12 on proliferation, cell cycle distribution and apoptosis of DU145 cells. Further, Transwell invasion assay was utilized to assess whether SNHG12 participates in PCa cell invasion and affects the secretion of VEGF secretion in DU145 cells. Western blot analysis was applied to quantify the expression level of apoptosis-related and invasion-related proteins. Finally, we investigated the effect of SNHG12 on tumor growth in vivo. ResultsWe found that SNHG12 expression was upregulated in prostate tumor tissues compared with the matched adjacent normal tissues. SNHG12 knockdown increased the expression of apoptosis-related protein Caspase 3, whereas downregulated the expression of MMP9, which is an invasion-related protein. SNHG12 knockdown inhibited the expression of phosphorylated AKT. In vivo xenograft experiments showed that knockdown of SNHG12 suppressed the PCa growth. ConclusionsThe above-mentioned results revealed that SNHG12 promoted cell proliferation and suppressed apoptosis in PCa cells, which suggests that SNHG12 is probably a novel PCa biomarker and therapy target of PCa.
Physiological Emergence of Amyloid-β During the Acute Cerebral Stress of Mechanical Ventilation Reduces Peri-Hippocampal and Cortical Blood-Brain Barrier Permeability and Neuronal Injury
Authors: Gezalian Michael M , Rajput Padmesh , Sparrow Nicklaus , Mangiacotti Luigi , Koronyo Yosef , Koronyo-Hamaoui Maya , Lahiri Shouri
Published: August 2020

Background: Prior published data show that short-term mechanical ventilation contributes to pathological hallmarks of Alzheimer’s Disease (AD) by increasing cerebral accumulation of the amyloid-β1-40 (Aβ1-40) peptide and neuroinflammation while unexpectedly decreasing blood-brain barrier permeability. In this study, we hypothesized that the acute cerebral immunochallenge of mechanical ventilation promotes physiological emergence of Aβ1-40 to regions of acute vascular disruption, resulting in reduced neuronal injury.Methods: Immunohistology was used to assess the regional relationship between cerebral Aβ1-40 accumulation, acute vascular disruption, and neuronal inflammation and apoptosis as measured by cleaved caspase-3 (CC3) expression from mechanically ventilated double transgenic AD-model (ADtg) mice and compared to mechanically ventilated wild-type (WT) controls.Results: There was significantly decreased expression of CC3 in regions of cortical and hippocampal Aβ1-40 accumulation in mechanically ventilated ADtg animals (p=0.0224). In contrast, CC3 expression was significantly increased in cortical and hippocampal regions of mechanically ventilated WT controls (p=0.0260). Aβ1-40 accumulation occurred in regions of acute vascular disruption in a characteristic banding pattern and reduced blood-brain barrier permeability. The banding pattern was significantly increased in ADtg mice subjected to mechanical ventilation compared to non-mechanically ventilated ADtg mice (p=0.0002). Additionally, no evidence of irreversible neurological injury is seen in mechanically ventilated ADtg and WT mice, as demonstrated by the absence of TUNEL positive staining. Conclusions: This study provides first evidence that acute short-term mechanical ventilation-induced cerebral immunochallenge promotes physiological emergence of Aβ1-40 to reduce blood-brain barrier permeability and neuronal injury. While it is expected that sustained or long-term activation of this normally protective pathway leads to dysregulated Aβ1-40 accumulation, neurodegeneration, and cognitive impairment, these data suggest that a window of opportunity may exist within which implementation of timely interventions may limit cognition-relevant cerebral injury.
Plasma thiol redox status as indicator of acute kidney injury
Authors: Boekhoud Lisanne , Koeze Jacqueline , Slikke Elisabeth C. van der , Bourgonje Arno R. , Moser Jill , Zijlstra Jan G , Kobold Anneke C. Muller , Bulthuis Marian L.C. , Meurs Matijs van , Goor Harry van , Bouma Hjalmar R.
Published: August 2020

Introduction: Acute kidney injury (AKI) is associated with the abrupt loss of kidney function resulting in increased morbidity and mortality. Oxidative stress plays an important role in the pathophysiology of AKI. Free thiols (R-SH, sulfhydryl groups) are crucial components of the extracellular antioxidant machinery and reliably reflect systemic oxidative stress. Lower levels of thiols represent higher levels of oxidative stress. In this study, we hypothesized that plasma free thiols are associated with AKI upon admission to the intensive care unit (ICU). Methods: In this study, 301 critically ill patients were included for analysis. Plasma samples were taken upon admission. Plasma levels of albumin-adjusted plasma free thiols were determined and correlated with AKI stage upon ICU admission. Results: Albumin-adjusted plasma free thiols were significantly lower in patients with AKI (n=43, median [interquartile range] 7.28 µmol/g [3.52,8.95]) compared to patients without AKI (8.50 µmol/g [5.82, 11.28]; p < 0.05) upon admission to the ICU. Higher age (B = -0.72, p < 0.001), higher levels of neutrophil gelatinase-associated lipocalin (B = -0.002, p < 0.05), creatinine (B = -0.01, p < 0.05) and lower serum albumin (B = 0.47, p < 0.001) were associated with lower free thiol levels. Further, albumin-adjusted free thiol levels were significantly reduced in patients with sepsis (8.30 [5.52-10.64] µmol/g) compared to patients without sepsis (6.95 [3.72-8.92] µmol/g; p < 0.05). Conclusion: Albumin-adjusted plasma free thiols were significantly reduced in patients with AKI and patients with sepsis compared with patients without AKI and sepsis. Together, these data suggest that free thiol levels are mainly reduced in sepsis-associated AKI.
Corticosteroid use in COVID-19 patients: A systematic review and meta-analysis on clinical outcomes
Authors: Hoekstra Eva M. , Neumann Katinka M.I. , Boot Pauline C. , Paassen Judith van , Arbous Sesmu M.
Published: August 2020

Background In the current SARS-CoV-2 pandemic, there has been worldwide debate on the use of corticosteroids in COVID-19. In a recent RCT (RECOVERY trial), a reduced 28-day mortality in patients requiring oxygen therapy or mechanical ventilation evaluating the effect of dexamethasone was shown. Their results have led to considering amendments in guidelines or actually already recommending corticosteroid use in COVID-19. However, the supposed effect of corticosteroids on mortality and viral clearance remains unclear and a clear evidence-based therapeutic strategy is still lacking.Objectives The aim of this systematic review and meta-analysis was to evaluate the effect of corticosteroids on mortality, viral clearance and secondary outcomes in COVID-19 patients.Data source, study eligibility, participants, interventionsA systematic literature search was performed across Medline/PubMed, Embase, and Web of Science from 1st of December 2019 until 10th of July 2020, according to the PRISMA guidelines. RCTs and cohort studies reporting in English, on ≥15 adult COVID-19 patients, treated with any type of corticosteroid therapy were included. Studies on pregnant women, reviews and with a NOS (Newcastle Ottawa Scale for validity assessment of observational studies) score of ≤4 were excluded.Results Twenty-two articles were included, covering 9,760 patients. In eight studies, the effect of corticosteroid use was quantified. The pooled estimate of the observational studies supported the positive effect on mortality of corticosteroid therapy in COVID-19 as reported in the RECOVERY trial, in respiratory compromised COVID-19 patients, i.e. oxygen or mechanical ventilation dependent or with ARDS. The overall pooled estimate (observational studies and the RCT) showed reduced mortality in the corticosteroid group (relative risk 0.55 [95% CI 0.27-0.83]). Furthermore, mechanical ventilation rate seemed lower in corticosteroid treated COVID-19 patients, though no definite conclusions could be drawn because of a low number of studies. With regard to potential side effects of corticosteroids, the effect on viral clearance duration was ambiguous, i.e. prolonged in 4 of 9 and without effect in 5 of 9 studies.Conclusions It appears safe with respect to viral clearance to administer corticosteroids in respiratory compromised COVID-19 patients with possible improvement in mortality and conflicting effects on viral clearance.
Systematic Construction and Validation of an RNA Binding Proteins-Based Signature for Prognostic Prediction in Gastric Cancer
Authors: Zhang Yi , Wang Yuzhi , Li Chengwen , Jiang Tianhua
Published: August 2020

Background: Gastric cancer (GC) is one of the most common cancers with high incidence and mortality worldwide. Recently, RNA-binding proteins (RBPs) have drawn more and more attention for its role in cancer pathophysiology. In this study, we aim to explore the function and clinical implication of RBPs in GC. Methods: RNA sequencing data along with the corresponding clinical information of GC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Differentially expressed RNA-binding proteins (DERBPs) between tumor and normal tissues were identified by ‘limma’ package. Functional enrichment analysis and the protein-protein interaction (PPI) network were harnessed to explore the function and interaction of DERBPs. Next, Univariate and multiple Cox regression were applied to screen prognosis-related hub RBPs and to construct a signature for BC. Meanwhile, a nomogram was built based on the same RBPs. Results: A total of 296 DERBPs were found, and most of them mainly related to post-transcriptional regulation of RNA and ribonucleoprotein. A PPI network of DERBPs was constructed, consisting of 262 nodes and 2567 edges. A prognostic signature was built depended on seven prognosis-related hub RBPs that could divide GC patients into high- and low-risk groups. Survival analysis showed that the high-risk group had a worse prognosis compared to the low-risk group and the time-dependent receiver operating characteristic (ROC) curves suggested that the signature existed moderate predictive capacities of survival for GC patients. Similar results were obtained from another independent set GSE84437, confirming the robustness of signature. Calibration plots reported good consistency between overall survival (OS) prediction by nomogram and actual observation. Conclusion: The findings of this study would provide evidence of the effect of RBPs on GC as well as offering novel potential biomarkers in prognosis prediction and clinical decision for GC patients.
Montelukast in Hospitalized Patients Diagnosed with COVID-19
Authors: Khan Ahsan , Misdary Christian , Yegya-Raman Nikhil , Kim Sinae , Narayanan Navaneeth , Siddiqui Sheraz , Salgame Padmini , Radbel Jared , De Groote Frank , Michel Carl , Mehnert Janice , Hernandez Caleb , Braciale Thomas , Malhotra Jyoti , Gentile Michael A. , Jabbour Salma K.
Published: August 2020

Background Several therapeutic agents have been assessed for the treatment of COVID-19, but few approaches have been proven efficacious. Because leukotriene receptor antagonists such as montelukast have been shown to reduce both cytokine release and lung inflammation in preclinical models of viral influenza and acute respiratory distress syndrome, we hypothesized that therapy with montelukast would reduce clinical deterioration as measured by the COVID-19 Ordinal Scale.Methods We performed a retrospective analysis of COVID-19 confirmed hospitalized patients treated with or without montelukast. We used “clinical deterioration” as the primary endpoint, a binary outcome defined as any increase in the Ordinal Scale value from Day 1 to Day 3 of hospital stay, as these data were uniformly available for all admitted patients before hospital discharge. Rates of clinical deterioration between the montelukast and non-montelukast groups were compared using the Fisher’s exact test. Univariate logistic regression was also used to assess the association between montelukast use and clinical deterioration.Results A total of 92 patients were analyzed, 30 received montelukast at the discretion of the treating physician and 62 patients who did not receive montelukast. Patients receiving montelukast experienced significantly fewer events of clinical deterioration compared to patients not receiving montelukast (10% vs 32%, p = 0.022). Sensitivity analysis among those without asthma showed a trend toward fewer clinical deterioration events in the montelukast group than non-montelukast groups (11% vs 33%, p = 0.077). Sensitivity analysis among those who did not receive azithromycin showed fewer clinical deterioration events in the montelukast group vs. non-montelukast groups (8% vs 32%, p = 0.030).Conclusions Our findings suggest that montelukast associates with a reduction in clinical deterioration for COVID-19 confirmed patients as measured on the COVID-19 Ordinal Scale. Montelukast may have activity in COVID-19 infection, and future efforts should evaluate this potential therapy.
The proteomic characteristics of airway mucus from critical ill COVID-19 patients
Authors: Zhang Zili , Wang Tao , Liu Fei , Zhu Airu , Gu Guoping , Luo Jieping , Xu Jingyi , Zhao Jincun , Li Yiming , Liu Xiaoqing , Zhong Nanshan , Lu Wenju
Published: August 2020

Background: The pandemic of the coronavirus disease 2019 (COVID-19) has brought a global public health crisis. However, the pathogenesis underlying COVID-19 are barely understood. Methods: In this study, we performed proteomic analyses of airway mucus obtained by bronchoscopy from severe COVID-19 patients. In total, 2351 and 2073 proteins were identified and quantified in COVID-19 patients and healthy controls, respectively. Results: Among them, 92 differentiated expressed proteins (DEPs) (46 up-regulated and 46 down-regulated) were found with a fold change > 1.5 or < 0.67 and a p-value < 0.05, and 375 proteins were uniquely present in airway mucus from COVID-19 patients. Pathway and network enrichment analyses revealed that the 92 DEPs were mostly associated with metabolic, complement and coagulation cascades, lysosome, and cholesterol metabolism pathways, and the 375 COVID-19 only proteins were mainly enriched in amino acid degradation (Valine, Leucine and Isoleucine degradation), amino acid metabolism (beta-Alanine, Tryptophan, Cysteine and Methionine metabolism), oxidative phosphorylation, phagosome, and cholesterol metabolism pathways. Conclusions: This study aims to provide fundamental data for elucidating proteomic changes of COVID-19, which may implicate further investigation of molecular targets directing at specific therapy.
Alteration of Gut Microbiota in type 2 Diabetes Complicated with Cholelithiasis Patients
Authors: Chen Jiajia , Yan Linlin , Ma Xingfan , Yuan Ping , Zhao Fan , Han Zihan , Liu Jingshan , Wang Wenbo , Zhou Donghai , Zhao Hongyu , Feng Nan , Huang Dandan , Hu Shoukui , Gu Jin
Published: August 2020

Background: Epidemiological studies showed that diabetes patients are more prone to developing cholelithiasis. Although composition of gut microbiota in type 2 diabetes or cholelithiasis have been studied respectively, the underlying role of gut microbiota in developing from diabetes to cholelithiasis remains unclear. By 16S rRNA gene sequencing, the gut microbial composition of 33 healthy subjects, 53 type 2 diabetes, 31 cholelithiasis and 32 type 2 diabetes complicated with cholelithiasis patients were studied. Results: Microbial diversity significantly decreased in type 2 diabetes complicated with cholelithiasis patients. In type 2 diabetes patients, phylum Proteobacteria class Gammaproteobacteria and order Lactobacillales were significantly increased. In cholelithiasis patients, phylum Bacteroidetes, class Bacteroidia order Bacteroidales family Bacteroidaceae and genus Bacteroides were significantly increased. There were also significant increases of phylum Proteobacteria, class Gammaproteobacteria order Lactobacillales family Lactobacillaceae and genus Lactobacillus in type 2 diabetes complicated with cholelithiasis patients accompanied by elevated serum triglyceride and total bile acids. Conclusions: The results show similar but more intricate gut microbiota dysbiosis in type 2 diabetes complicated with cholelithiasis compared with type 2 diabetes, which might partially explain the mechanism of type 2 diabetes as the risk factor of cholelithiasis from the perspective of gut microbiota.
Effects of Securigera Securidaca Seed Extract, Alone and in combination with Glibenclamide, on Circulating Levels of Pro-Angiogenic/Anti-Angiogenic Biomarkers in Hyperglycemic Rats
Authors: Alizadeh-Fanalou Shahin , Babaei Mohammad , Bahreini Elham
Published: August 2020

Background: Many diabetic patients use herbal medicines in addition to their mainstream treatments. Plants contain a well-known and unknown set of compounds that may exacerbate or improve diabetes complications. Thus, the side effects of these herbs should be known before prescribing. The aim of the study is to investigate the effects of hydroalcoholic extract of Securigera securidaca (L.) Degen & Dorfl (S. securidaca) seed (HESS) on angiogenesis/anti-angiogenesis balance in Streptozotocin (STZ)-induced diabetic rats, alone and in combination with glibenclamide. Methods: The groups involved in this animal study included diabetic and healthy control groups, groups treated with three doses of HESS, group treated with glibenclamide, and groups received combination therapy. Serum samples were taken and analyzed for the levels of angiogenic/ anti-angiogenic biomarkers.Results: Induction of diabetes increased serum levels of angiogenic agents and decreased circulating anti-angiogenic factors. The herbal extract, even with the highest dose, had little effects on the blood levels of the tested biomarkers except with TGF-β. Glibenclamide was more effective than the highest dose of HESS in preventing the increase in serum levels of angiogenic factors and in inhibiting the decrease in anti-angiogenic agents in diabetic rats. Combination therapy with the highest dose of HESS partly enhanced the glibenclamide effects.Conclusions: Although glibenclamide was more effective than the highest dose of HESS used in this study in preventing changes in serum concentrations of angiogenic/ anti-angiogenic biomarkers in the diabetic animals, this study show that S. securidaca has no side effects on diabetes complications caused by vascular disorders and neovascularization, and still it can be used as a herbal supplement with the standard drug.
Phase II Study of Definitive Chemoradiation Therapy Using S-1 for Esophageal Squamous Cell Carcinoma Patients --- the ESO-Shanghai 7 Trial Protocol
Authors: Tseng Ihsuan , Chen Yun , Zhu Zhengfei , Zhao Weixin , Liu Qi , Zhang Junhua , Deng Jiaying , Ai Dashan , Lu Saiquan , Jia Huixun , Zhao Kuaile
Published: August 2020

Background: Concurrent chemoradiotherapy (CCRT) is a standard treatment for inoperable locally advanced esophageal carcinoma. However, there exists a group of patients who are intolerable to intravenous chemotherapy for the old age or with serious comorbidities. S-1 is an oral fluorouracil derivative with well tolerance than 5-fluorouracil. The ESO-Shanghai 7 trial aimed to access the safety and efficacy of S-1 combined with radiotherapy for esophageal squamous cell carcinoma (ESCC) patients who are elderly or with serious comorbidities.Methods: 105 ESCC patients with old age or serious comorbidities will be enrolled in this prospective, single-arm phase 2 clinical trial. Patients will receive S-1 orally at a dose of 40 mg (BSA ≤ 1.6 m2) or 50 mg (BSA >1.6 m2) twice daily for 28 days. The concurrent radiotherapy dose is 61.2 Gy delivered in 34 fractions. The primary endpoints are 3-yr local control and number and grade of participants with adverse events, and the secondary endpoint is overall survival. Discussion: The aim of this phase 2 trial is to determine the tolerance and efficacy of S-1 concurrent with radiotherapy for ESCC patients with old age or serious comorbidities. A very promising 3-yr local control should beat least 60% from the clinical point of view.Trial registration: ClinicalTrials.gov, NCT01831531. Registered 29 March 2013, https://clinicaltrials.gov/ct2/show/NCT01831531?term=NCT01831531&draw=2&rank=1
Advantages of Surgical Implantation Impella 5.5 SmartAssist in the Management of Acute Post-Infarction Ventricular Septal Defect with Cardiogenic Shock
Authors: Madjarov Jeko , Katz Michael G , Madzharov Svetozar , Fazal Shahood , Robicsek francis
Published: August 2020

ABSTRACT Background: Despite advances in surgical techniques and aggressive therapy of post-infarction ventricular septal defect (VSD) with cardiogenic shock, the overall morbidity and mortality is frustratingly high. The Impella 5.5 SmartAssist (Abiomed, Danvers, MA) is a surgically implanted temporary device, recently approved by the FDA for treatment of patients in cardiogenic shock, and may fill a technological gap for perioperative patients who require acute circulatory support. Case presentation: We report our initial experience with trans-aortic implantation of the Impella 5.5 SmartAssist for two patients with post myocardial infarction VSD in the setting of cardiogenic shock. First patient had a posterior VSD with a left to right shunt (Qp/Qs ratio of 3.3), right ventricle dysfunction, severe pulmonary arterial hypertension, and severe mitral valve regurgitation. Second patient was admitted for massive MI with large anterior VSD (Qp/Qs ratio of 2.8). Under cardiopulmonary bypass with cardioplegic arrest both patients underwent urgent VSD closure with trans-aortic implantation of the Impella. Minimal postoperative support was required. Patients were discharged on postoperative day 10 and 14 and remained well three months later. Follow-up echocardiogram showed no residual shunt. Conclusions: Early surgical implantation of Impella 5.5 SmartAssist can prevent multiorgan dysfunction and stabilize the patients in cardiogenic shock with post-myocardial infarction VSD.
Clinicopathology and Outcomes of Small Bowel Metastases: A Retrospective Study of 31 Consecutive Cases
Authors: Liao Yu-Tso , Lin Been-Ren , Lai I-Rue , Chen Chiung-Nien , Liang Jin-Tung , Lin Ming-Tsan
Published: August 2020

BACKGROUND

The small bowel (SB) is a rare site for distant metastasis. Few recent studies have systematically reported on the clinicopathology and outcomes of SB metastasis. This study aimed to describe the clinicopathology and outcomes of SB metastasis.
METHODS

A retrospective study involving patients diagnosed with SB metastasis at a single medical center between January 2009 and December 2019 was conducted. Patients with secondary SB cancer with direct invasion or peritoneal carcinomatosis by a primary tumor were excluded. The demographic characteristics of the patients, clinical patterns of primary cancer and SB metastasis, and outcomes were analyzed.
RESULTS

During the 10-year period, we identified 31 patients eligible for analysis. The female:male ratio was 8:24, and the median patient age was 63.5 years. Metastasis of lung cancer to the SB was noted most frequently. Most patients presented with abdominal pain, gastrointestinal bleeding, or abnormal imaging findings. The interval between primary cancer and SB metastasis was 19.2 months. Sole SB metastasis was noted in 20 patients (64.5%). Twenty-two (70.1%) patients underwent surgical intervention. The median survival was 6.6 months.
Conclusions

Distant metastasis of other primary cancers to the SB is noted extremely rarely. The presence of SB metastasis indicated extremely poor prognosis. Surgery plays an important role in ameliorating critical symptoms However, surgery does not confer survival benefits.
Multiparametric MRI and 18F-DCFPyL PET/CT for Detection of Locally Recurrent Prostate Cancer After Low dose Rate Brachytherapy
Authors: Walker Stephanie M. , Fernandez Martina , Roy Soumyajit , Mena Esther , Sackett Jonathan , Mease Ronnie , Merino Maria , Pomper Martin , Salerno Kilian , Schott Erica , Wood Bradford , Pinto Peter , Lindenberg Liza , Choyke Peter , Citrin Deborah , Turkbey Baris
Published: August 2020

Background and purpose: Both multiparametric magnetic resonance imaging (mpMRI) and prostate specific membrane antigen (PSMA)-targeting positron emission tomography (PET) imaging have shown promise in early localization of prostate cancer (PCa) recurrence after primary external beam radiotherapy. Detecting recurrence after brachytherapy for PCa using MRI is significantly hampered by susceptibility artifacts secondary to brachy seeds. Here, we compare the efficacy of 18F-DCFPyL (2-(3-{1-carboxy-5-[(6-18F-fluoro-pyridine-3-carbonyl)-amino]-pentyl}-ureido)-pentanedioic acid) PET/CT versus mpMRI for detecting sites of local recurrence after low dose rate (LDR) brachytherapy for prostate cancer. Materials and methods: A total of 155 patients with a history of recurrent PCa who underwent mpMRI at 3 Tesla and 18F-DCFPyL PET/CT were retrospectively reviewed. Patients who underwent LDR brachytherapy for PCa and had subsequent biochemical recurrence (BCR) followed by mpMRI and 18F-DCFPyL PET/CT were included in this study. mpMRI was performed on a 3T scanner with endorectal and surface coils and images were prospectively read by a single expert radiologist. The 18F-DCFPyL PET/CT scan was prospectively interpreted by one of two nuclear medicine physicians. Patients underwent targeted biopsy when deemed clinically necessary and specimens were interpreted by an expert GU pathologist. Positivity rates (PR) from mpMRI and 18F-DCFPyL PET/CT were compared, and pathology results were used to calculate the positive predictive value (PPV) of each imaging modality for detecting PCa recurrence.Results: 14 patients who underwent LDR brachytherapy and had subsequent biochemical failure were imaged with mpMRI and 18F-DCFPyL PET/CT. 17 lesions were identified on at least one imaging modality. The PR for detection of intraprostatic lesions was 71% (10/14) for PET/CT and 64.3% (9/14) for mpMRI. 18F-DCFPyL PET/CT identified pelvic and extra-pelvic lymph nodes in 8 (57%) patients, while mpMRI noted positive lymph node findings in only 2 (14%) patients. A total of 14 lesions corresponding to 8 patients were targeted for biopsy and in these, 18F-DCFPyL PET/CT performed better than mpMRI for the detection of local recurrence with a PPV of 81.8% vs. 66.7%. For the detection of intraprostatic lesions, 18F-DCFPyL PET/CT and mpMRI had a PPV of 87.5% and 71.4%, respectively. Conclusion: Our findings suggest that 18F-DCFPyL PET/CT detects local and regional recurrent PCa after LDR brachytherapy at a higher rate than mpMRI and has a much higher detection rate of suspicious pelvic lymph nodes. Further studies are needed to validate these findings in larger cohorts.
Molecular Characterization of AEBP1 at Transcriptional Level in Glioma
Authors: Wang Kuanyu , Huang Ruoyu , Wang Zhiliang , Tong Xuezhi , Wu Chenxing
Published: August 2020

Background: Glioma is the most common malignant tumor of brain in adult patients. The standardized treatment protocol was based on surgical therapy, supplemented with radiotherapy and chemotherapy. However, the prognosis was still unsatisfied. The chemoresistance is one of the most important reason for the poor prognosis of glioma patients. It has confirmed that glioma stem cell (GSC) are one of the reasons for chemoresistance.Methods: In this study three datasets (GSE23806, COSMIC, TCGA) was used to perform the analysis to search for the key genes related to GSC, temozolomide (TMZ) resistance and prognosis. The key gene for further research was selected by reviewing the previous studies. The selected gene was investigated the relation between expression levels and clinical characteristics in both TCGA and CGGA dataset. The bioinformatics analysis was performed by Gene ontology (GO) analysis. The survival analysis was performed by Kaplan–Meier survival analysis. Results: AE binding protein 1 (AEBP1) was selected for further analysis. AEBP1 was overexpressed in GSCs and TMZ resistance cells. In both TCGA and CGGA dataset, the results showed that the expression level of AEBP1 was increased in glioblastoma (GBM) samples, IDH wild-type samples and MGMT promoter unmethylated samples. Meanwhile, AEBP1 expression was positive related with several GSC markers. GO analysis showed that AEBP1 were related with immune response, cell adhesion, apoptotic process, inflammatory response, positive regulation of cell proliferation, angiogenesis, response to drug and response to hypoxia. The survival analysis showed that the overexpressed level of AEBP1 was correlated with short survival time in both glioma and GBM patients. Conclusion: In summary, AEBP1 was related with GSC induced TMZ resistance. Our study showed that AEBP1 might be an oncogene and a new effective therapeutic target for the treatment of glioma.
MSC-derived miR-181b Overexpressing Exosomes Enhanced Osteointegration by Enhancing M2 Polarization of Macrophages via Targeting the PRKCD/AKT Pathway
Authors: Liu Wei , Yu Muyu , Chen Feng , Xie Dong , Wang Longqing , Ye Cheng , Zhu Qi , Shao Mingzhe , Yang Lili
Published: August 2020

Background: Many patients suffer from implant loosening after the implantation of titanium alloy caused by immune response to the foreign bodies and this could inhibit osteogenesis, which could possibly give rise to poor osteointegration and there is currently no appropriate solution in clinical practice. Exosomes overexpressing miRNA has been proven to be a suitable candidate for solving this problem. In this study, we explored whether miR-181b could exert beneficial effect on promoting M2 macrophage polarization, thus inhibiting inflammation as well as promoting osteogenesis and elaborated the underlying mechanism in vitro. Furthermore, we aimed to find whether exosomes overexpressing miR-181b (Exo-181b) could enhance osteointegration in vivo.Methods: In vitro and in vivo studies were carried out for assessing the anti-inflammatory and pro-osteogenesis effect of miR-181b. In vitro, ELISA was applied for the detection of the inflammation factors levels including IL-6, TNF-α, as well as IL-10 and the percentage of M1 or M2 polarization was determined by flow cytometry. Also, qRT-PCR was used for the detection of the relative gene expression of the CCR7, CD206, Arg-1, iNOS, VEGF and BMP-2 genes. Western blotting was applied for detecting the protein expression of PRKCD, AKT and p-AKT. In vivo, we established air pouch model for evaluating the effect of Exo-181b on macrophage polarization and distal femoral bone defect model was established for determining the osteointegration effect of Exo-181b by MicroCT, sequential fluorescent labeling and histological analysis. Results: In vitro, we firstly verified that miR-181b significantly enhanced M2 polarization and inhibited inflammation by suppressing PRKCD and activating p-AKT. Then, in vivo, we verified that Exo-181b enhanced M2 polarization, reduced the inflammatory response and enhanced osteointegration. Conclusions: MiR-181b could suppress inflammatory response by regulating the PRKCD/AKT signaling pathway and promoting M2 polarization, which further promoting osteogenesis of hBMSC in vitro and Exo-181b could promote osteointegration in vivo.
Adaptability and Resilience in Aging Adults (ARIAA): A Pilot and Feasibility Study in Chronic Low Back Pain
Authors: Lysne Paige E , Palit Shreela , Morais Calia A , DeMonte Lucas C , Lakdawala Maria , Sibille Kimberly T , Bartley Emily J
Published: August 2020

Background: Chronic low back pain (cLBP) is the leading cause of disability among older adults and one of the top reasons for seeking healthcare, resulting in significant decrements in physical functioning. Because older adults are among the fastest growing cohorts in the United States, both the incidence and burden of cLBP are expected to increase considerably, rendering geriatric pain management a top health priority. Resilience is defined as a process allowing individuals to adapt and recover from adverse and stressful conditions and it has been highlighted as a crucial factor in positive health-related functioning. While a growing body of literature supports the use of resilience-based interventions in chronic pain, research examining their effectiveness in older adults with cLBP remains limited.Methods: In this article, we describe the rationale and design of the Adaptability and Resilience in Aging Adults (ARIAA) study, a single-arm intervention in which 50 participants (ages >60 years) with cLBP will be recruited to participate in a 7-week group-based program aimed at enhancing psychological resilience. Intervention sessions will target positive psychology concepts (e.g., positive affect, pain acceptance, hopeful thinking, pain self-efficacy) and cognitive-behavioral techniques that have established benefits in pain management. Primary study outcomes include intervention feasibility and acceptability as measured by treatment engagement, intervention credibility and satisfaction, ability to meet recruitment and retention metrics, and the feasibility of questionnaire and home activity completion. Outcomes will be assessed at baseline, immediately at post-treatment, and at the 3-month follow-up period. Discussion: This study will establish the feasibility and acceptability of a novel intervention aimed at enhancing positive, psychological functioning and resilience in older adults with cLBP. Achievement of these aims will provide a rich platform for future intervention research targeting improvements in pain and disability among geriatric populations and will serve as a foundation for a fully powered trial to examine treatment efficacy of the proposed intervention.Trial Registration: Clinicaltrials.gov, identifier NCT04068922. Registered 28 August 2019, https://clinicaltrials.gov/ct2/show/NCT04068922
Management of dentine hypersensitivity through Propolis – A Scoping Review
Authors: Allana Raheel , Abrar Syed Kashif , Siddiqui Saaduddin , Allana Asad , Iqbal Ammara , Fatima
Published: August 2020

Objective: To evaluate the effect of propolis (a natural herb) against dentine hypersensitivity and to compare their effect with the controls.Methodology: Two databases were selected and searched for the relevant articles published up to 2019. Clinical trials involving propolis with other desensitizing agents and comparing it with controls were included involving patients that possess dentine hypersensitivity along with the extracted teeth. Nine clinical trials from 1999 to 2019 met the criteria involving 169 patients who had sensitivity and 214 extracted teeth were included in this scoping review.Results: Propolis was found to have a better desensitizing results than the controls, except Recaldent ™ which showed better results than Porpolis. Conclusion: Our results support the assertion that propolis is a good option which occludes the dentinal tubules and can relieve the symptoms of dentine hypersensitivity. However more clinical trials and high quality studies are needed to confirm its results in a better way.
Firm-level immunity to COVID-19 induced uncertainty
Authors: Narang Sahil , Rawat Savita , Pradhan Rudra Prakash
Published: August 2020

The paper investigates the stock market response to COVID-19 induced financial uncertainty and the role of pre-shock firm-specific characteristics in shaping such stock market behaviour using a sample of S&P BSE 500 companies. Initially, the stock market experiences a significant downfall due to COVID-19 induced uncertainty; although, the market appears to rebound after a major setback. Downfall and recovery are quite surprising as downfall happened when cases were extremely small in number and there was no nation-wide lockdown announcement yet. Recovery happened when strict lockdowns were enforced and cases were rising significantly. Stock market reaction were heterogeneous among industries and various firm characteristics. On closer analysis, we find that some firms are more resilient to COVID-19 shock than others. Our analysis reveals that the most affected were small-sized, high beta, loser, and low-profitability firms as indicated by univariate analysis. The multivariate analysis finds momentum, profitability, beta, market capitalization, age, and book-to-market ratio to be the major determinants of cross-sectional CARs during downfall & recovery period. The study provides evidence of the negative reaction to COVID-19 induced uncertainty and subsequent recovery. We concludes that pre-COVID firm-specific factors play an essential role in explaining the variation in the stock market reaction to COVID-19 induced uncertainty.