bluuebunny/crossref_metadata_2025_split huggingface dataset:
Silencing of LINC01279 is activated apoptosis and autophagy in lung cancer by regulating FAK/ERK via SIN3A
Authors: Su Wenmei , Wu Jiancong , Huang Xiaobi , Li Xiaofang , Zhou Honglian , Chen Xiaorao , Chen Yongyang , Huang Jian , Huang Hanqing , Huang Zhong , Chen Guoan , Zhang Jian , Yang Zhixiong 
Published: September 2021

Abstract
Background: In human lung adenocarcinoma (LUAD) tissues, Long noncoding RNA LINC01279 is significantly upregulated. However, the functions of LINC01279 in LUAD is yet to be clarified.Methods: In situ hybridization was employed to investigate the difference between expression of LINC01279 in LUAD and in normal tissues. The result of in situ hybridization is verified by qRT-PCR. Cytoplasmic and nuclear experiments showed that LINC01279 was mainly located in the cytoplasm of lung cancer cells. The loss of function experiment showed that LINC01279 could inhibit the proliferation, colony formation, invasion and migration of lung cancer cells. The interaction between SIN3A and LINC01279 was confirmed by RIP test. At the same time, through western bolt, we found that LINC01279 plays a key role in the regulation of apoptosis and autophagy in lung adenocarcinoma.Results: Our study confirmed that LINC01279 was upregulated in LUAD tissues, the knocking-down of which significantly inhibited the growth of LUAD cancer cells both in vitro and in vivo. Mechanistic investigations revealed that LINC01279 could directly interact with SIN3A and modulate the FAK and ERK protein expression in the cytoplasm. Moreover, the proteins of PARP and LC3B, P62, Beclin-1, respectively related with apoptosis and autophagy, were changed after LINC01279 siRNA. Conclusions: Taken together, our research found that LINC01279 which is significantly up-regulated in LUAD tissues and cell lines, and promotes the changes of FAK and ERK proteins in downstream pathways by combining with SIN3A, promotes the proliferation of LUAD cells, and inhibits apoptosis and autophagy. The results of this work illustrated how LINC01279 is part of a regulatory network that contributes to the oncogenesis of LUAD and proposed LINC01279 could be a potential target for LUAD diagnosis and treatment.
ThermomiR-377-3p-induced Suppression of Cirbp Expression Is Required for Effective Elimination of Cancer Cells and Cancer Stem-like Cells by Hyperthermia
Authors: Lin Tao-Yan , Jia Jun-Shuang , Luo Wei-Ren , Xiao Sheng-Jun , Lin Xiao-Lin , Yang Jie , Xia Jia-Wei , Zhou Chen , Zhou Zhi-Hao , Lin Shu-Jun , Li Qi-Wen , Shen Hong-Fen , Le Yei , Yang Zhi-Zhi , Yang Wen-Qing , Chen Lin-Bei , Xue Shu-Wen , Li Yong-Long , Wei Fang , Xiao-Xiang Rong , Luo Xiao-Jun , Zhao Bing-Xia , Huang Wen-Hua , Sun Yan , Xiao Dong 
Published: September 2021

Abstract
In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold-inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). Our results firstly revealed that hyperthermia significantly attenuated the stemness property of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)-like population. Moreover, hyperthermia substantially improved the sensitivity of radiation-resistant NPC cells and CSC-like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti-tumor-killing activity of hyperthermia against NPC cells and CSC-like cells, whereas ectopic expression of Cirbp compromised tumor-killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377–3p improved the sensitivity of NPC cells and cancer stem-like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp nearly completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377–3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.
Impact of Exogenous Application of Salicylic Acid and Hydrogen Peroxide on Essential Nutrients and Silymarin in Silybum Marianum (L.) Gaertn Grown at Two Different Altitudes of Balochistan Under Cadmium Stress
Authors: Nizar Mereen , Shaukat Kanval , Zahra Noreen , Samad Abdul , Hafeez Mohammad Bilal , Gul Shamim 
Published: September 2021

Abstract
Cadmium (Cd+2) is a potentially toxic element that inhibits growth and development of several species of plants along with Silybum marianum (L.) Gaertn which is an essential medicinal plant belonging to family Asteraceae. The exogenous application with 0.25µM Salicylic acid (SA) and 10µM hydrogen peroxide (H2O2) to ameliorate harmful effects of cadmium (500 µM) on milk thistle were studied that were grown at two different ecological zones of Balochistan province of Pakistan i.e. Quetta (Qta) and Turbat (Tbt). The design of experiment was Randomized Complete Block Design (RCBD) with three replicates. Application of SA and H2O2, priming (P), Foliar spray (FS) and combinational treatments (P+FS) were highly helpful in alleviating the negative role of cadmium toxicity. The essential nutrients i.e. nitrate (NO3-), calcium (Ca2+) and potassium (K) were affected by Cd+2 induced toxicity however, the substantial role of SA and H2O2 widely helped to reduce the cadmium stress and boosted up the plant nutrients content. In a nutshell, exogenous treatments of SA and H2O2 enhanced the yield potential along with highest silymarin contents in milk thistle seeds which is of prime significance for its medicinal importance in treatment of liver diseases. The data obtained in this study highly recommend the priming and foliar spray of SA and H2O2 on milk thistle plants, as the best solution to alleviative the cadmium toxicity which will ultimately leads to better growth and yield of the plants.
Thioacetamide promotes osteoclast transformation of bone marrow macrophages by influencing PI3K/AKT pathways
Authors: Jin Xiaoli , Li Yang , Yang Yayang , Shen Hao , Chen Jin , Xu Bin , Xu Jian 
Published: September 2021

Abstract
Background
Osteoclast cell increase is a major risk factor for osteoporosis and degenerative bone and joint diseases. Thioacetamide (TAA) can lead to many types of liver and kidney damage, but less attention has been paid to the association of TAA with bone damage. In this work, we investigated the effects of TAA on the osteoclastogenesis and differentiation of bone marrow macrophages (BMMs).
Methods
Bone marrow mononuclear macrophages of SD rat suckling mice were taken for primary culture. CCK-8 was used to detect the toxic effects of TAA on BMMs, and flow cytometry was used to detect the effects of TAA on the cell cycle, cell viability, apoptosis and intracytoplasmic Ca2+ concentration of BMMs. TRAP immunohistochemistry and fluorescence staining were used to detect the effect of TAA on osteoclast differentiation of BMMs. Western Blot was used to detect the expression level of PI3K/AKT pathway and osteoclast-specific proteins (TRAP and Cts-K).
Results
The results suggested that TAA inhibited the proliferation of BMMs, while enhancing osteoclastogenesis at 0.5 mg/mL and 1 mg/mL as assayed by TRAP staining, and BMMs could differentiate into osteoclast-like cells with overexpression of cathepsin K and TRAP proteins after TAA treatment. Western blot results showed that TAA can activate the expression levels of P-PI3K, P-AKT, P-P38, and P-JNK, accompanied by apoptosis of BMM cells and increase of intracellular Ca2+.
Conclusion
TAA may induce osteoclast formation in BMMs by activating the expression of PI3K/AKT pathway proteins, which is comparable to the classic osteoclast differentiation inducer RANKL. This suggests that we may find a cheap osteoclast inducer.
Cross-talk of different dimensional methylation modification patterns alters tumor microenvironment infiltration and immunotherapy response in renal cancer
Authors: Qin Xin , Pan Ling , Yan Lei , Fang Zhiqing , Fan Yidong 
Published: September 2021

Abstract
Background

Different dimensional methylation modifications, including DNA, RNA and histone methylation, are mediated by different functional regulators and play an indispensable role in tumor progression. However, the cross-talk and underlying mechanisms of these modification patterns in tumorigenesis, tumor microenvironment (TME) disorder and aberrant immune response are still unknown.
Methods

We summarized the 9 most common types of modifications from different dimensions and revealed transcriptional and genetic alterations of 104 modification regulators in clean cell renal cell carcinoma (ccRCC) patients. Next, we constructed a prognosis-correlation network to further explore their interactions and identified distinct methylation modification patterns by using unsupervised clustering algorithm. Lastly, we constructed a methylation modification regulator score (MMR Score) model to quantify the characterizations of different modification patterns for individual patients, and validated its predictive value to immunotherapy response.
Results

We investigated the interactions between different dimensional modifications and identified critical negative regulated nodes in the prognosis-correlation network. Our clustering results revealed that, different from other cancers, immune activity in ccRCC not only depended on the abundance of immune cells, but also the infiltration of stromal cells. The MMR Score for the quantification of each patient can act as an effective biomarker to predict clinical outcomes. Patients with high MMR Score were more likely to experience a therapeutic advantage and clinical benefits from immunotherapy.
Conclusions

This work revealed that cross-talk of different modifications could lead to the complexity and heterogeneity of individual TME. The integrated quantification of individual modification patterns can better guide clinical personalized cancer treatments.
Evaluation of Anti-Malaria Potency of Wild and Genetically Modified Enterobacter Cloacae Expressing Effector Proteins in Anopheles Stephensi
Authors: Dehghan Hossein , Mosa-Kazemi Seyed Hassan , Yakhchali Bagher , Maleki-Ravasan Naseh , Vatandoost Hassan , Oshaghi Mohammad 
Published: September 2021

Abstract
Background: Malaria is one of the most lethal infectious diseases in tropical and subtropical areas of the world. To fight the disease, paratransgenesis using symbiotic bacteria offers a sustainable and environmentally-friendly strategy. Here we evaluated the disruption of malaria transmission in the Anopheles stephensi-Plasmodium berghei assemblage, using wild and modified insect gut bacterium, Enterobacter cloacae.Methods: The assay was carried out using E. cloacae dissolvens wild-type (WT) and its three engineered strains expressing GFP-defensin (GFP-D), scorpine-HasA (S-HasA), and HasA, The 3-5 day-old female mosquitoes were supplemented overnight with the studied bacteria [1×109cells/mL of 5% (wt/vol), fructose and red dye (1/50 ml)] soaked on cotton-wool. Each group of sugar-fed mosquitoes was then starved for 4-6 hours and fed on a P. berghei–infected mouse for 20 min in the dark at 17-20°C. The blood-fed mosquitoes were kept at 19±1°C and RH 80±5, and parasite infection was measured by midgut dissection and oocyst counting 10 days post-infection (dpi). Results: Both wild-type and genetically modified bacterial strains significantly (P< 0.0001) disrupted the P. berghei development in the An. stephensi midgut, in comparison with the control group. The mean parasite inhibition of E. cloacaeWT, E. cloacaeHasA, E. cloacaeS-HasA, and E. cloacaeGFP-D was measured as 72, 86, 92.5 and 92.8 respectively. Conclusions: The wild and modified E. cloacae might abolish oocyst development by providing a physical barrier or by excretion of intrinsic effector molecules. These findings reinforce the case for the use of either wild or genetically modified E. cloacae bacteria as a powerful tool to combat malaria.
Not All Dual Users of Cigarettes and E-vapor Products Are the Same: Biomarkers and Tobacco Use Behavior in Subpopulations of Dual Users From the PATH Wave 1 Data
Authors: Lizhnyak Pavel N. , Noggle Richard B. , Wei Lai , Edmiston Jeffery , Becker Elizabeth , Black Ryan A. , Sarkar Mohamadi 
Published: September 2021

Abstract
Introduction: Dual users of cigarettes and e-vapor products (EVP) are often considered as a homogenous group even though multiple subgroups may exist. We examined biomarkers of exposure (BOE) and biomarkers of potential harm (BOPH) to differentiate between subgroups of dual users based on PATH Study Wave 1 (2013-2014) data.Methods: We segmented adult dual users (n=970) into four subgroups based on the number of days of product used in past 30 days – frequent dual users of both products (FreqDU, n=169), frequent smokers who vape infrequently (SMVP, n=678), frequent vapers who smoke infrequently (VPSM, n=57), and infrequent dual users of both products (InfreqDU, n=66). Eighteen BOEs (representing exposure to TSNAs, nicotine, heavy metals, PAHs, and volatile organic compounds), and four BOPHs (representing inflammation and oxidative stress) were analyzed within the subgroups, versus exclusive daily cigarette smokers (ESM, n=2,442) and exclusive daily e-cigarette users (EVP, n=169).Results: Levels of many BOEs and BOPHs were higher among SMVP relative to FreqDU, VPSM and InfreqDU. Compared to ESM, many BOEs were significantly lower in VPSM (15/18) and InfreqDU (17/18), and some BOEs were higher among SMVP (4/18). InfreqDU showed significantly lower levels of 2/18 BOEs than EVP, and lower levels of 2/4 BOPHs than ESM.Conclusions: Overall, the levels of BOEs and BOPHs in dual users are associated with frequency of cigarette smoking. Our findings indicate that not all dual users are the same, and tobacco product use frequency should be considered when categorizing dual users.
Comparison of the Diagnostic Efficacy of 68Ga-FAPI-04 PET/MRI and 18F-FDG PET/CT in Patients With Pancreatic Cancer
Authors: Zhang Zeyu , Jia Guorong , Pan Guixia , Cao Kai , Yang Qinqin , Meng Hongyu , Yang Jian , Zhang Lu , Wang Tao , Cheng Chao , Zuo Changjing 
Published: September 2021

Abstract
PurposeTo assess the diagnostic performance of 68Ga-FAPI-04 (68Ga-FAPI) PET/MR for primary as well as metastatic lesions in pancreatic cancer patients and to compare the results with those of 18F-FDG PET/CT.MethodsProspectively, we evaluated 31 patients suspected to have pancreatic malignancy. Within one week, each patient underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/MR. Comparisons of the detection abilities and the standardized uptake values (SUVs) for primary tumors, lymph nodes, as well as hepatic metastases were conducted for the two imaging approaches.ResultsTwenty-eight pancreatic cancer patients and three pancreatitis ones were enrolled. 68Ga-FAPI and 18F-FDG exhibited equivalent (100%) detection rates for primary tumors. The SUVs of primary tumors on 68Ga-FAPI PET were markedly higher than those on 18F-FDG (p < 0.05). Fifteen pancreatic cancer patients were accompanied by pancreatic parenchymal uptake, whereas 18F-FDG PET images showed parenchymal uptake in 3 patients only (53.57% vs. 10.71%, p < 0.001). The number of positive lymph nodes detected was higher for 68Ga-FAPI than for 18F-FDG PET (31 vs. 26), led to N upstaging in 27.27% (3/11) of patients, however, the difference was not statistically significant (p = 0.053). 18F-FDG PET was able to detect more liver metastases than 68Ga-FAPI, and 68Ga-FAPI uptake of metastatic tumors was significantly lower than 18F-FDG (6.13 ± 1.63 vs. 8.09 ± 1.68, p < 0.001). In larger liver metastatic lesions, 68Ga-FAPI tended to distribute around the periphery of the lesions. In addition, multiple sequence MR imaging was helpful for finding more micrometastases.Conclusion68Ga-FAPI PET demonstrated equivalent detection rate with 18F-FDG for primary tumors of pancreatic cancer, and its percentage of pancreatic parenchymal uptake caused by inflammation was higher. It might be better in the detection of suspicious lymph node metastases. The MR multiple sequence imaging of integrated PET/MR was helpful for detecting tiny liver metastases.
Caffeine, Coffee, Tea and Risk of Rheumatoid Arthritis: Systematic Review and Dose- Response Meta-analysis of Prospective Cohort Studies
Authors: Asoudeh Farzaneh , Dashti Fatemeh , Jayedi Ahmad , Hemmati Amirhossein , Fadel Abdulmannan , Mohammadi Hamed 
Published: September 2021

Abstract
Objective: Prospective cohort studies on coffee, tea and caffeine in relation to the risk of rheumatoid arthritis (RA) have shown conflicting results. The aim of this study was to conduct a dose–response meta-analysis of cohort studies on the association between dietary caffeine, different types of coffee and tea consumption and the risk of RA.Methods: PubMed/Medline, Scopus and EMBASE were searched up to July 2021 to identify relevant studies that had considered different types of coffee (caffeinated or decaffeinated), tea or caffeine exposure with RA as the main, or one of the, outcome(s). Two authors independently screened 742 publications. Finally, 5 prospective cohort studies were included in our meta-analysis. Pooled relative risks (RRs) were calculated by using a fixed-effects model. We also performed linear and non-linear dose-response analyses to examine the dose-response relations. Results: Comparing extreme categories, we found a positive, significant association between coffee (RR: 1.30; 95% CI: 1.04-1.62; I2 = 0%, n = 5) and decaffeinated coffee (RR: 1.89; 95% CI: 1.35-2.65; I2 =38.1%, n =3) consumption and risk of RA. One additional cup of coffee consumed per day was associated with an increased risk of RA by 6% (95% CI: 1.02-1.10; I2 = 0%;). This increase in the risk of RA for one cup/d of decaffeinated coffee was 11% 95% CI: 1.05-1.18; I2 = 38). No significant association was observed between caffeinated coffee, tea or caffeine intake and the risk of RA.Conclusion: We found that a higher intake of coffee and decaffeinated coffee was associated with increased risk of RA. No significant association between caffeinated coffee, tea or caffeine intake and the risk of RA was observed.
Deubiquitinase USP9X loss Sensitizes Cancer Cells to mTOR Inhibitors through p62 Dysregulation
Authors: Roldán-Romero Juan M. , Santos Maria , Lanillos Javier , Maroto Pablo , Anguera Georgia , Calsina Bruna , Martinez-Montes Angel , Monteagudo María , Mellid Sara , Leandro-García Luis J. , Montero-Conde Cristina , Cascón Alberto , Roncador Giovanna , Coloma Javier , Robledo Mercedes , Rodriguez-Antona Cristina 
Published: September 2021

Abstract
BackgroundMutations in MTOR and TSC1/2 can only explain part of variability in mTOR inhibitor response. Here, we performed a comprehensive molecular characterization of tumors with high sensitivity to these drugs to uncover novel mechanisms of response.MethodsChromophobe renal cell carcinoma (chRCC) tumors were analyzed by whole-exome sequencing. Rapamycin sensitivity, expression of mTOR pathway effectors, ubiquitylome analyses to identify USP9X substrates, p62 immunoprecipitation and autophagy assessment through immunofluorescence assays for p62 and LC3 were performed in USP9X depleted HeLa and 786-O cells for mechanistic investigation. ResultsWhole-exome sequencing of chRCC patients with high mTOR inhibitor sensitivity, uncovered USP9X deubiquitinase as the only mutated gene shared by these tumors. The clonal characteristics of the mutations, revealed by studying multiple primary and metastatic samples, together with the low USP9X mutation rate in unselected chRCC series, implied a causal link between USP9X and mTOR inhibitor sensitivity. The high sensitivity was recapitulated in vitro, and while no direct effect on mTORC1 was detected, an unbiased ubiquitylome analysis revealed p62 as a direct USP9X target. Bortezomib treatment, which also led to p62 ubiquitination, increased rapamycin effect. Finally, immunofluorescence assays for p62 and LC3 confirmed dysregulated autophagy in USP9X depleted cells, supporting a synthetic lethal interaction between rapamycin-induced autophagy via mTOR-axis and USP9X loss.ConclusionsOur study uncovers USP9X as a potential novel marker of sensitivity to mTOR inhibitors and suggests the inhibition of this gene as a clinically exploitable strategy able to increase sensitivity to these drugs through a novel p62 regulatory mechanism.
Enhanced Simultaneous Photocatalytic Removal of SO2 and CO2 Using Powder and Coated Zeolites-Supported TiO2 Under Concentrated Sunlight Irradiation
Authors: Razavi Zahra , Mirghaffari Nourollah , Soleimani Mohsen 
Published: September 2021

Abstract
Single-step process for simultaneous removal of gaseous pollutants is more advantageous than multi-steps one. In this study, the efficiency of a novel synthetic zeolite (Ze) prepared from stone cutting sludge and a natural zeolite (clinoptilolite, Cp) as the supports of TiO2 photocatalyst were examined for the separate and simultaneous removal of SO2 and CO2 under solar irradiation using a parabolic trough collector (PTC). The composites exhibited a higher efficiency than raw zeolites and TiO2 for the removal of both gases. The maximum removal of SO2 by TiO2-Ze and TiO2-Cp under sunlight was 41.9 % and 56.2 % that enhanced to 53.4 % and 78.8 %, respectively in the presence of CO2. Correspondingly, it was 61.8 % and 68.7 % for single CO2 removal that increased to 74.2 % and 79.0 % in the binary gas stream. This behavior could be due to the enhanced simultaneous SO2 oxidation and CO2 reduction. The performance of coated composite for SO2 was higher than of powder one (54.3% vs. 41.9%) and for CO2 removal was almost close together (58.9% vs. 61.2%). This work promises the application of photocatalytic co-removal of SO2 and CO2 by using synthetic and natural zeolite under solar irradiation.