bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oral toxicity to high level sodium fluoride causes impairment of autophagy
Authors: Oka Shunichi , Li Xiaoyan , Zhang Fengzhu , Taguchi Chieko , Tewari Nitesh , Kim Il-Shin , Zhong Liangjun , Arikawa Kazumune , Liu Yi , Bhawal Ujjal K. 
Published: August 2020

Abstract
Background: Gingival recession and concomitant alveolar bone resorption are hallmarks of periodontal diseases and excessive fluoride intake has some deleterious effects on teeth, bone and soft tissues. Autophagy is a highly conserved intracellular digestion process that degrades damaged proteins and organelles but the biological roles of autophagy in pathological aspects of oral tissues remain largely unknown. We sought to elucidate the function of autophagy, especially its interplay with apoptosis and oxidative stress, in the oral toxicity induced by exposure to 5 mM sodium fluoride (NaF). Methods: HCEM2 cementoblast cells in culture were exposed to 5 mM NaF for 5 min, after which cell viability and cell apoptosis were assessed using the MTS assay and an Annexin V-FITC/PI apoptosis detection kit, respectively. Real-time quantitative RT-PCR and Western blotting were performed to characterize the mRNA and protein expression levels of markers for autophagy, apoptosis, and oxidative stress. C57BL/6 mice were exposed to 5 mM NaF in their drinking water from 12 to 58 weeks. Micro-computed tomography was used to measure changes in their alveolar bone while immunohistochemistry and immunofluorescence staining was used to evaluate protein expression levels of autophagy, apoptosis, and oxidative stress markers.Results: Cementoblasts exposed to 5 mM NaF had decreased levels of autophagy, as shown by reduced expression levels of ATG5, Beclin1 and LC3-II, elicited excessive apoptosis, which in turn induced oxidative stress and inflammation, as manifested by elevated levels of Bax, cleaved caspase-3, SOD1 and phospho NF-κB. Consistently, the in vivo results verified the findings of the in vitro study and treatment of mice with 5 mM NaF resulted in histological abnormalities in periodontal tissues, induced excessive oxidative stress and apoptosis, and reduced autophagy. These results correlated with the immunofluorescence observations, thus confirming the pivotal role of autophagic flux dysfunction in 5 mM NaF-induced cell death. Micro-computed tomography analysis demonstrated that 5 mM NaF caused a decrease in bone areas of mice compared with controls. Exposure to 5 mM NaF induced RANKL (receptor activator of nuclear factor κB ligand) and cathepsin K expression in periodontal tissues, while ATG5 and Beclin1 expression was abrogated by 5 mM NaF.Conclusion: Taken together, our findings suggest that 5 mM NaF elicits oral toxicity that contributes to excessive apoptosis, oxidative stress, and defective autophagy, which aggravates periodontal tissue damage.
Guidelines Translation for Distress Management in Cancer Patients Based on CAN-IMPLEMENT: Adaptation Part
Authors: Fu Liang , Yang Yang , Hu Yan , Lu Zhenqi , Zhang Xiaoju , Huang Mingzhu , Li Yuanyuan , Zhu Fuzhong , Wang Yang , Huang Zhe 
Published: August 2020

Abstract
Background
Almost all cancer patients experience some level of distress, which has significantly reduced their quality of life. Nowadays evidence-based practice in various fields of health care is increasing, and it has played an important role. This study aimed to clarify the theme of guideline adaptation, integrate relevant clinical practice guidelines on distress management in cancer patients, and develop the Cancer-related Distress Management Guidelines.
Methods
A Guideline Adaptation and Implementation Planning Resource (CAN-IMPLEMENT) was used as the research framework, which include three phases. Here the Adaptation Part (Phase 1) was reported: adaptation of relevant clinical practice guidelines on the distress management in cancer patients to form the Cancer-related Distress Management Guidelines.
Results
The physical symptom distress score (0.61 ± 0.58) was almost equal to the psychological symptom distress score (0.61 ± 0.70) among cancer patients in Shanghai. A work plan for the adaptation of Cancer-related Distress Management Guidelines was developed. Two clinical practice guidelines related to distress management in cancer patents were included after searching, screening, assessment and selection. The domain scores of the draft the Cancer-related Distress Management Guidelines on Appraisal of Guidelines for Research and Evaluation II (AGREE II) were 80.00% (scope and purpose), 82.78% (stakeholder involvement), 87.50% (rigour of development), 73.89% (clarity and presentation), 73.75% (applicability), 87.50% (editorial independence) respectively. The scores of most recommendations on feasibility, appropriateness, meaningfulness and effectiveness were 90.0% or higher. The final guidelines included 13 recommendations.
Conclusions
The psychological symptoms and physical symptoms were both worthy of attention in cancer patients. The quality of the draft the Cancer-related Distress Management Guidelines was well-accepted based on two included guidelines. Most recommendations received positive and constructive feedback on feasibility, appropriateness, meaningfulness and effectiveness. The final guidelines was formed based on the revision of the first draft guidelines.
Clinical scoring for the failure of non-invasive ventilation in acute respiratory failure patients in the Emergency Department.
Authors: liengswangwong Wijittra , Yuksen Chaiyaporn Mahidol , Thepkong Tipanun , Nakasint Pornita , Jenpanitpong Chetsadakon 
Published: August 2020

Abstract
Background Non-invasive mechanical ventilation (NIV) has become an alternative to an invasive artificial airway for the management of acute respiratory failure (ARF). NIV failure causes delayed intubation, which eventually has been associated with increased morbidity and mortality. This study aimed to develop the clinical scoring system of NIV failure in ARF patients. Methods This study was a diagnostic, retrospectively cross-sectional, and exploratory model at the Emergency Medicine Department in Ramathibodi Hospital between February 2017 and December 2017. We included all of the acute respiratory failure patients aged >18 years and received non-invasive ventilation (NIV). Clinical factors associated with NIV failure were recorded. The predictive model and prediction score for NIV failure were developed by multivariable logistic regression analysis. Result A total of 329 acute respiratory failure patients have received NIV success (N = 237) and failure (N = 92). This study showed that NIV failure was associated with heart rate > 110 bpm, systolic BP < 110 mmHg, SpO2 < 90%, arterial pH < 7.30 and serum lactate. The clinical scores were classified into three groups: low, moderate, and high. Conclusion We suggested that the novel clinical scoring of the NIV failure in this study may use as a good predictor for NIV failure in the emergency room.
HSPA4 knockdown retarded progression and development of colorectal cancer
Authors: Zhang Mingliang , Dai Weigang , Li Zhanyu , Tang Liang , Chen Jianhui , Chen Chuangqi 
Published: August 2020

Abstract
Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of cancer death. The heat shock 70kDa protein 4 (HSPA4) participate in progression and development of cancers. However, the cellular functions, potential molecular mechanisms of HSPA4 in CRC are still largely unknown. Methods: In this study, qRT-PCR and Western Blot were used to identify the constructed HSPA4 knockdown cell lines, which was further used to construct mouse xenotransplantation models. Effects of HSPA4 knockdown on cell proliferation, apoptotic, cell cycle and migration of CRC were examined using Celigo cell counting assay, Flow cytometry, wound healing assay and Transwell assay, respectively. In addition, Human Apoptosis Antibody Array was performed to explore downstream molecular mechanism of HSPA4 in CRC cells. Results: HSPA4 was overexpressed in CRC, which was positively associated with lymphatic metastasis (N value), number of Lymph node. In addition, high expression of HSPA4 predicted poor prognosis of patients with CRC. Furthermore, HSPA4 knockdown inhibit proliferation, migration, promote apoptosis, and arrest cell cycle of CRC cells in vitro. Moreover, in vivo results supported HSPA4 knockdown inhibit tumor growth. Additionally, the induction of apoptosis of CRC cells by HSPA4 knockdown required the participation of a series of apoptosis-related proteins. The downregulation of HSPA4 promoted the progression of CRC cells, which resulted in alterations of PI3K/Akt, CCND1 and CDK6 in downstream signaling pathways. Conclusions: In sum, the downregulation of HSPA4 promoted CRC and may be a potential target for molecular therapy.
Multivariate Analysis of Early Surgical Management Factors Affecting Posttraumatic Penoscrotal Avulsion Injury: A Level I Trauma Center Study
Authors: KIM MIN JI , Lee Dong Hwan , Park Dong HA , Lee Il Jae 
Published: August 2020

Abstract
Background To conduct an accurate evaluation of patients presenting with posttraumatic penoscrotal injuries, and to formulate a treatment algorithm based on this assessment. Methods We conducted a retrospective chart review study. Patients with penoscrotal defects admitted to our level Ⅰ trauma center from 2017 to 2019 were evaluated. The Braden scale score was used for wound evaluation and the Korean patient classification system (KPCS) was used for assessment of severity. Univariate and multivariate analyses were performed for potential risk factors associated with early surgical management. Results In total, there were 58 male patients, and the average Braden scale score was 12.08 ± 2.54, with the scrotum (36.20%), and the penile shaft (32.76%) being popular sites for injuries. The wounds requiring surgical treatment were 20.68% (n=12), with local flaps (33.33%) being most commonly used. The significant predictors of advanced wounds which required surgical treatment were old age (p=0.026, Odds Ratio [OR] 8.238), orthopedic combined injuries (p=0.044, OR 1.088), intubation (p=0.018, OR 9.625), restrain (p=0.036, OR 0.157) and blood transfusion (p<0.001, OR 2.462).Conclusion In multiple trauma patients, penoscrotal defects caused by high-speed trauma are an important matter of concern. Specifically, patients with combined skeletal injuries or requiring respiratory care were prone to advanced wounds. We proposed a five-category algorithm to manage such patients, which included severity of the patient’s condition, respiration, hemodynamic status, comorbidity, and immobilization. Additionally, inter-departmental cooperation and active intervention by plastic surgeons is needed for the comprehensive treatment of such injuries. Trial registration This study was performed in line with the principles of the Declaration of Helsinki. The study and all its protocols were approved by the institutional review board of Ajou Medical Center (approval no. AJIRB-MED-MDB-17-254). The need for informed consent was waived by the institutional review board of our hospital due to the retrospective design of the study.
Global transcriptional regulation by cell-free sup of S. Typhimurium peptide transporter mutant leads to inhibition of intraspecies biofilm initiation
Authors: Chandra Kasturi , Muralidhara Prerana , Kamanna Sathisha , Tatu Utpal , Chakravortty Dipshikha 
Published: August 2020

Abstract
Salmonella is a genus of widely spread Gram negative, facultative anaerobic bacteria, which is known to cause ¼th of the diarrhoeal morbidity and mortality globally. It causes typhoid fever and gastroenteritis by gaining access to the host gut through contaminated food and water. Salmonella utilizes its biofilm lifestyle to strongly resist antibiotics and persist in the host. Although the biofilm removal or dispersal have been studied widely, the inhibition of initiation Salmonella biofilm has not been studied much. This study was conducted to determine the anti-biofilm property of the cell-free supernatant obtained from a carbon-starvation inducible proline peptide transporter mutant (ΔyjiY) strain. Our study shows that Salmonella ΔyjiY culture supernatant inhibits biofilm initiation by regulating biofilm associated transcriptional network. This work demonstrates that highly abundant proteases like ecotin, HslV and GrpE cleave the protein aggregates, whereas global transcription regulators H-NS, FlgM regulate expression of SPIs and flagellar genes. Relatively low abundance of flavoredoxin, glutaredoxin, thiol peroxidase etc. leads to accumulation of ROS within the biofilm, and subsequent toxicity. This work further suggests that targeting these oxidative stress relieving proteins might be a good druggable choice to reduce Salmonella biofilm.
Rhodanine-3-Acetamide Derivatives as Aldose and Aldehyde Reductase Inhibitors to Treat Diabetic Complications; Synthesis, Biological Evaluation and Molecular Docking Studies
Authors: Bacha Mohsinul Mulk , Nadeem Humaira , Rehman Shafiq Ur , Sarwar Sadia , Imran Aqeel , Zaib Sumera , Arif Muazzam , Iqbal Jamshed 
Published: August 2020

Abstract
In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2.
LncRNA PCDHB17P promotes metastasis and angiogenesis of breast cancer through a miR-145-3p/MELK/NF- κ B feedback loop
Authors: Zhu Li , Zhang Yan-Jun , Wang Bin , Yang Li , Zheng Yi-Qiong , Sun Lin-De , Tian Lin , Chen Tao , Wang Jian Dong 
Published: August 2020

Abstract
Background: Breast cancer is one of the most common life-threatening cancers, mainly due to its aggressiveness and metastasis. Accumulating evidence indicates that long non-coding RNAs (lncRNAs) participate in the development and progression of breast cancer. Nevertheless, the function and expression level of lncRNAs in breast cancer are still not fully understood.Methods: TCGA data was utilized to screen out lncRNAs dysregulated in breast cancer. The expression level of genes were analyzed and measured by RT-qPCR. The effects of PCDHB17P in breast cancer were determined in vitro and in vivo. Bioinformatics analysis was applied to predict the target between genes in breast cancer and verified via luciferase reporter assays, RNA Immunoprecipitation (RIP) and Chromatin immunoprecipitation (ChIP).Results: LncRNA PCDHB17P was up-expressed in human breast cancer tissues and cell lines. Knockdown of PCDHB17P remarkably suppressed migration and invasion as well as tube formation ability of breast cancer cells. MiR-145-3p was significantly decree ased in breast cancer samples, which was negatively correlated to the expression of PCDHB17P. In addition, we identified MELK was a direct target gene of miR-145-3p, which was higher expressed in breast cancer tissues than that in adjacent normal tissues. Mechanistic investigation indicated that PCDHB17P acted as a cancer-promoting competing endogenous RNA (ceRNA) by binding miR-145-3p and upregulating MELK. Interestingly, MELK could in turn increase the promoter activity and expression of PCDHB17P via NF-κB, thus forming a positive feedback loop that drives the metastasis and angiogenesis of breast cancer.Conclusions: Our research demonstrated that the constitutive activation of PCDHB17P/miR-145-3p/MELK /NF-κB feedback loop promotes the metastasis and angiogenesis of breast cancer, suggested that this lncRNA might be a promising prognostic biomarker and therapeutic target for breast cancer.
Bioinformatics Analysis of the Regulatory lncRNA-miRNA-mRNA Network in Patients with Neuropathic Pain
Authors: Zhang Huai-Gen , Liu Li , Song Zhi-Ping , Zhang Da-Ying 
Published: August 2020

Abstract
Background: Neuropathic pain (NP) is the main form of chronic pain, caused by damage to the nervous system and dysfunction. Methods: Here, we explore the key molecules involved in the development of NP condition via identification of lncRNA-miRNA-mRNA expression pattern of patients with NP. We identified differentially expressed miRNAs, lncRNA and mRNA through a comprehensive analysis strategy. Subsequently, we used bioinformatics approach to perform pathway enrichment analysis on DEGs and protein-protein interaction analysis. Combined with the three datasets, the lncRNA-miRNA-mRNA network was constructed. It will then be used as targets for drug prediction. Results: The results showed that a total of 8,251 DEGs (4,193 upregulated and 4,058 downregulated) were identified from the three microarray datasets, 959 DEmiRs (455 upregulated and 504 downregulated), 2,848 DElncs (1,324 upregulated and 1,524 downregulated). GO analysis showed that DEGs are mainly enriched in blood circulation, regulation of membrane potential and regulation of ion transmembrane transport. KEGG results showed that DEGs are enriched in neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway and MAPK signaling pathway. When the correlation is set to above 0.8, a total of 31 lncRNAs, 36 miRNAs and 24 mRNAs were screened in the lncRNA-miRNA-mRNAs network. The results of drug prediction indicated the targeted drugs mainly include INDOMETHACIN, GLUTAMIC ACID and PIRACETAM. Conclusion: The lncRNA-miRNA-mRNA network has been carried out a comprehensive biological information analysis and predicted the potential therapeutic application of drugs in patients with NP. The corresponding data has a certain reference for studying the pathological mechanism of NP.
RIP3 mediates TCN-induced necroptosis through activating mitochondrial metabolism and ROS production in apoptosis-resistant cancer cells
Authors: Zhao Xu , Quan Jing , Tan Yue , Liu Ying , Liao Chaoliang , Li Zhenzhen , Liao Weihua , Liu Jikai , Cao Ya , Luo Xiangjian 
Published: August 2020

Abstract
Background: Resisting cell death is one of the hallmarks of cancer. Necroptosis is a form of non-caspase dependent necrotic cell death mediated by receptor-interacting protein kinase-1/3 (RIP1/3), which represents another mode of programmed cell death besides apoptosis. Growing evidence supports that RIP3 has emerged as a critical regulator of necroptosis and can be activated by several stimuli to trigger necroptotic cell death in a RIP1-independent manner. RIP3 also acts as an energy metabolism regulator associated with switching cell death from apoptosis to necroptosis. Natural products provide a unique source for the discovery of innovative leading compounds and drugs, which exhibits promising anticancer activities through inducing cell death and enhancing chemotherapeutic sensitivity. Trichothecin (TCN) is a sesquiterpenoid originating from an endophytic fungus of the herbal plant Maytenus hookeri Loes and shows potent anti-tumor bioactivity. However, the underlying mechanism is not fully understood.Methods: Cell permeability assay and transmission electron microscopy were applied to identify the death pattern induced by TCN in apoptotic-resistant cancer cells. We used Seahorse extracellular flux analyzer to examine the cellular oxygen consumption rate (OCR) and flow cytometry to detect mitochondrial reactive oxygen species (ROS) content. Xenograft animal experiment was performed to assess the effect of TCN synergized with cisplatin to enhance chemotherapeutic sensitivity of tumor cells. Results: Our current findings revealed that RIP3 mediated TCN-induced necroptosis through activating mitochondria energy metabolism and ROS production in apoptotic-resistant cancer cells. RIP3 might be involved in sensitizing tumor cells to chemotherapy induced by TCN. Conclusions: Activating RIP3 to induce necroptosis through reprogramming mitochondrial energy metabolism and ROS production contributes to the anti-tumor activity of TCN. Moreover, TCN could be exploited for therapeutic gain through up-regulating RIP3 to sensitize cancer chemotherapy.
Coupling of the atmosphere and sediment melts across the Archean-Proterozoic transition
Authors: Liebmann Janne , Spencer Christopher , Kirkland Christopher , Bucholz Claire , Xia Xiao-Ping , Martin Laure , Kitchen Nami , Shumlyanskyy Leonid 
Published: August 2020

Abstract
The Archean-Proterozoic transition marks a time of fundamental geologic, biologic, and atmospheric changes to the Earth system, including oxygenation of the atmosphere (termed the Great Oxygenation Event; GOE), and the emergence of continents above sea-level. The impacts of the GOE on Earth’s surface environment are imprinted on the geologic record, including the attenuation of mass-independent fractionation of sulfur isotopes (S-MIF). Temporally overlapping geologic and geochemical observations (e.g. a change in oxygen isotope ratio of sediment melts) imply the widespread subaerial emergence of continents was coeval with atmospheric oxygenation. Here we present triple sulfur isotope ratios in pyrite and oxygen isotope ratios in garnet and zircon in a global suite of Archean and Proterozoic sediment-derived granitoids. These crustal melts record an increase in average 18O/16O isotope ratio and a disappearance of S-MIF in the Paleoproterozoic. The coupled behaviour of sulfur and oxygen isotope signatures imply a potential causal link between the emergence of continents and atmospheric oxygenation at ~2.3 Ga.