bluuebunny/crossref_metadata_2025_split huggingface dataset:
The circular RNA hsa_circ_000780 as a potential molecular diagnostic target for gastric cancer
Authors: Song Jian , Yu Shuyong , Zhong Dunjing , Yang Weizhong , Jia Zhen , Yuan Guihong , Li Ping , Zhang Ronglin , Li Yini , Zhong Guobing , Chen Zhaowei 
Published: November 2021

Abstract
Background
The present study aimed to identify a specific circular RNA (circRNA) for early diagnosis of gastric cancer (GC).

Methods
Totally 82 patients with GC, 30 with chronic nonatrophic gastritis and 30 with chronic atrophic gastritis were included in this study. Four of the 82 GC patients were selected for screening. Total RNA from malignant and adjacent tissue samples was extracted, and circRNAs in four patients were screened. According to the screening results, the eight most upregulated and downregulated circRNAs with a statistically significant association with GC were identified by real-time fluorescent quantitative polymerase chain reaction (PCR). Then, the most regulated circRNA was selected for further sensitivity and specificity assessments. CircRNA expression was examined by quantitative reverse transcriptase PCR in 78 GC (21 and 57 early and advanced GC, respectively) and adjacent tissue samples, as well as in gastric fluid samples from 30 patients with chronic nonatrophic gastritis, 30 with chronic atrophic gastritis, and 78 GC.

Results
A total of 445 circRNAs, including 69 upregulated and 376 downregulated circRNAs, showed significantly altered expression in GC tissue samples. Hsa_circ_000780 was significantly downregulated in 80.77% of GC tissue samples, with levels in GC tissue samples correlating with tumor size, tumor stage, T stage, venous invasion, carcinoembryonic antigen amounts, and carbohydrate antigen 19–9 levels. Strikingly, this circRNA was found in the gastric fluid of patients with early and advanced GC.

Conclusions
The present study uncovered a new circRNA expression profile in human GC, with hsa_circ_000780 significantly downregulated in GC tissue and gastric fluid specimens. These findings indicate that hsa_circ_000780 should be considered a novel biomarker for early GC screening.
Repurposed pharmacological agents for the potential treatment of COVID-19: a literature review
Authors: Kröker Alina , Tirzīte Madara 
Published: November 2021

Abstract
Background
The COVID-19 pandemic has affected the world extraordinarily. This disease has a potential to cause a significantly severe course of disease leading to respiratory complications, multiple organ failure and possibly death. In the fight against this pandemic-causing disease, medical professionals around the world are searching for pharmacological agents that could treat and prevent disease progression and mortality. To speed the search of promising treatment options, already existing pharmacological agents are repurposed for the potential treatment of COVID-19 and tested in clinical trials. The aim of this literature review is to investigate the efficacy and safety of repurposed pharmacological agents for the treatment of COVID-19 at different pathophysiologic stages of the disease. For this literature review, online-databases PubMed and Google Scholar were utilised. Keywords “COVID-19”, “SARS-CoV-2”, “pathogenesis”, “drug targets”, “pharmacological treatment”, “cytokine storm”, “coagulopathy” and individual drug names were used. Scientific articles, including reviews, clinical trials, and observational cohorts, were collected and analysed. Furthermore, these articles were examined for references to find more clinical trials testing for the potential treatment of COVID-19. In total, 97 references were used to conduct this research paper.

Results
The most beneficial pharmacological agent for the treatment of COVID-19 are corticosteroids, especially dexamethasone, for the treatment of mechanically ventilated COVID-19 patients. Other promising agents are remdesivir for the treatment of patients with COVID-19 pneumonia requiring minimal supplemental oxygen therapy, and IL-6 receptor antagonist monoclonal antibodies in severe COVID-19. Lopinavir/ritonavir, as well as chloroquine or hydroxychloroquine with or without azithromycin demonstrate the least efficacy in the treatment of COVID-19. The clinical benefits of the treatment of a COVID-19-specific coagulopathy with increased dosing of anticoagulation need further research and confirmation of randomised controlled trials.

Conclusion
The search for pharmacological treatment of COVID-19 has elicited great controversy. Whereas drugs like chloroquine, hydroxychloroquine, and lopinavir/ritonavir have not shown proven benefit, the agents remdesivir and dexamethasone are recommended for clinical use for the treatment of COVID-19. Further randomised trials for other pharmacological treatment strategies are awaited.
A short primer on lung stereology
Authors: Ochs Matthias , Schipke Julia 
Published: November 2021

AbstractThe intention of this short primer is to raise your appetite for proper quantitative assessment of lung micro-structure. The method of choice for obtaining such data is stereology. Rooted in stochastic geometry, stereology provides simple and efficient tools to obtain quantitative three-dimensional information based on measurements on nearly two-dimensional microscopic sections. In this primer, the basic concepts of stereology and its application to the lung are introduced step by step along the workflow of a stereological study. The integration of stereology in your laboratory work will help to improve its quality. In a broader context, stereology may also be seen as a contribution to good scientific practice.
A comprehensive approach to stool donor screening for faecal microbiota transplantation in China
Authors: He Jianquan , He Xingxiang , Ma Yonghui , Yang Luxi , Fang Haiming , Shang Shu , Xia Huping , Lian Guanghui , Tang Hailing , Wang Qizhi , Wang Junping , Lin Zhihui , Wen Jianbo , Liu Yuedong , Zhai Chunbao , Wang Wen , Jiang Xueliang , Xuan Ji , Liu Morong , Lu Shiyun , Li Xuejun , Wang Han , Ouyang Cong , Cao Man , Lin Aiqiang , Zhang Bangzhou , Wu Depei , Chen Ye , Xiao Chuanxing 
Published: November 2021

Abstract
Background
Faecal microbiota transplantation (FMT) is an effective therapy for recurrent Clostridium difficile infections and chronic gastrointestional infections. However, the risks of FMT and the selection process of suitable donors remain insufficiently characterized. The eligibility rate for screening, underlying microbial basis, and core ethical issues of stool donors for FMT are yet to be elucidated in China.

Results
The potential stool donors were screened from December 2017 to December 2019 with the help of an online survey, clinical assessments, and stool and blood testing. Bioinformatics analyses were performed, and the composition and stability of gut microbiota in stool obtained from eligible donors were dynamically observed using metagenomics. Meanwhile, we build a donor microbial evaluation index (DoMEI) for stool donor screening. In the screening process, we also focused on ethical principles and requirements. Of the 2071 participants, 66 donors were selected via the screening process (3.19% success rate). Although there were significant differences in gut microbiota among donors, we found that the changes in the gut microbiota of the same donor were typically more stable than those between donors over time.

Conclusions
DoMEI provides a potential reference index for regular stool donor re-evaluation. In this retrospective study, we summarised the donor recruitment and screening procedure ensuring the safety and tolerability for FMT in China. Based on the latest advances in this field, we carried out rigorous recommendation and method which can assist stool bank and clinicians to screen eligible stool donor for FMT.
Prognostic value and immunological role of AXL gene in clear cell renal cell carcinoma associated with identifying LncRNA/RBP/AXL mRNA networks
Authors: Wang Yi , Tian Ye , Liu Shouyong , Wang Zengjun , Xing Qianwei 
Published: November 2021

Abstract
Backgrounds
This article aimed to explore the prognostic and immunological roles of AXL gene in clear cell renal cell carcinoma (ccRCC) for overall survival (OS) and to identify the LncRNA/RBP/AXL mRNA networks.

Methods
AXL-related gene expression matrix and clinical data were obtained from The Cancer Genome Atlas (TCGA) dataset and AXL-related pathways were identified by gene set enrichment analysis (GSEA). We performed univariate/multivariate Cox regression analysis to evaluate independent prognostic factors and the relationships between AXL and immunity were also investigated.

Results
The outcomes of us indicated that the AXL mRNA expression was up-regulated in ccRCC samples and high expression of AXL was associated with worse OS in TCGA dataset (P < 0.01). Further external verification results from HPA, UALCAN, ICGC dataset, GSE6344, GSE14994, and qRT-PCR remained consistent (all P < 0.05). AXL was also identified as an independent prognostic factor for ccRCC by univariate/multivariate Cox regression analysis (both P < 0.05). A nomogram including AXL expression and clinicopathological factors was established by us and GSEA results found that elevated AXL expression was associated with the JAK-STAT, P53, WNT, VEGF and MAPK signaling pathways. In terms of immunity, AXL was dramatically linked to tumor microenvironment, immune cells, immune infiltration, immune checkpoint molecules and tumor mutational burden (TMB). As for its potential mechanisms, we also identified several LncRNA/RBP/AXL mRNA axes.

Conclusions
AXL was revealed to play prognostic and immunological roles in ccRCC and LncRNA/RBP/AXL mRNA axes were also identified by us for its potential mechanisms.
Clinicopathological and prognostic significance of speckle-type POZ protein in cancers: a systematic review and meta-analysis
Authors: He Yan , Chen Jun , Peng Xingchen , Xia Yanli , Su Yonglin 
Published: November 2021

Abstract
Background
Controversial findings have been reported in the impact of speckle-type POZ protein (SPOP) on clinicopathological features and prognosis in diverse cancers. We conducted this meta-analysis to confirm whether SPOP was an effective biomarker to predict clinical stage, cancer differentiation and survival.

Methods
We searched studies published before June 2021 through Medline, Embase, the Cochrane library register of controlled trials and Wanfang databases. The corrections of SPOP expression with expression disparity, tumor differentiation, clinical stage and survival were analyzed.

Results
Our meta-analysis found that higher expression of SPOP was significantly associated with earlier clinical stage, well differentiation and better overall survival. Subgroup analysis showed that the SPOP expression of adjacent tissue was significantly higher than that in cancer tissues of prostate and liver. However, renal cancer presented improved expression of SPOP in cancer tissue.

Conclusions
SPOP has the potential function to act as a novel and effective biomarker for cancer diagnosis and prognostic stratification.
PESV represses non-small cell lung cancer cell malignancy through circ_0016760 under hypoxia
Authors: Zhang Hong , Zhang Haojian , Zhu Jiye , Liu Huan , Zhou Qin 
Published: November 2021

Abstract
Background
Non-small cell lung cancer (NSCLC) accounts for more than 80% of lung cancers, which is the most common malignant tumor worldwide. Polypeptide extract from scorpion venom (PESV) has been reported to inhibit NSCLC process. The present study aims to reveal the roles of PESV in NSCLC progression under hypoxia and the inner mechanism.

Methods
The expression levels of circular RNA 0016760 (circ_0016760) and microRNA-29b (miR-29b) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was determined by western blot and immunohistochemistry assays. Cell migration, invasion, proliferation and tube formation were investigated by transwell, cell colony formation, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide and tube formation assays. The impacts between PESV and circ_0016760 overexpression on tumor growth in vivo were investigated by in vivo tumor formation assay.

Results
Circ_0016760 expression was dramatically upregulated in NSCLC tissues and cells, compared with adjacent lung tissues and cells, respectively. PESV treatment downregulated circ_0016760 expression. Circ_0016760 silencing or PESV treatment repressed cell migration, invasion, proliferation and tube formation under hypoxia in NSCLC cells. Circ_0016760 overexpression restored the effects of PESV treatment on NSCLC process under hypoxia. Additionally, circ_0016760 acted as a sponge of miR-29b, and miR-29b bound to HIF1A. Meanwhile, miR-29b inhibitor impaired the influences of circ_0016760 knockdown on NSCLC process under hypoxia. Further, ectopic circ_0016760 expression restrained the effects of PESV exposure on tumor formation in vivo.

Conclusion
Circ_0016760 overexpression counteracted PESV-induced repression of NSCLC cell malignancy and angiogenesis under hypoxia through miR-29b/HIF1A axis.
Let-7a induces metabolic reprogramming in breast cancer cells via targeting mitochondrial encoded ND4
Authors: Sharma Praveen , Sharma Vibhuti , Ahluwalia Tarunveer Singh , Dogra Nilambra , Kumar Santosh , Singh Sandeep 
Published: November 2021

Abstract
Background and objectives
MicroRNA (miRNA) that translocate from the nucleus to mitochondria are referred to as mitochondrial microRNA (mitomiR). Albeit mitomiRs have been shown to modulate gene expression, their functional impact within mitochondria is unknown. The main objective of this study is to investigate whether the mitochondrial genome is regulated by miR present inside the mitochondria.

Methods and results
Here, we report mitomiR let-7a regulates mitochondrial transcription in breast cancer cells and reprogram the metabolism accordingly. These effects were mediated through the interaction of let-7a with mtDNA, as studied by RNA pull-down assays, altering the activity of Complex I in a cell line-specific manner. Our study, for the first time, identifies the role of mitomiR (let-7a) in regulating the mitochondrial genome by transcriptional repression and its contribution to regulating mitochondrial metabolism of breast cancer cells.

Conclusion
These findings uncover a novel mechanism by which mitomiR regulates mitochondrial transcription.
TMED3/RPS15A Axis promotes the development and progression of osteosarcoma
Authors: Xu Wei , Li Yifan , Ye Xiaojian , Ji Yunhan , Chen Yu , Zhang Xiangyang , Li Zhikun 
Published: November 2021

Abstract
Background
Osteosarcoma is a primary malignant tumor that mainly affects children and young adults. Transmembrane emp24 trafficking protein 3 (TMED3) may be involved in the regulation of malignant cancer behaviors. However, the role of TMED3 in osteosarcoma remains mysterious. In this study, the potential biological function and underlying mechanism of TMED3 in progression of osteosarcoma was elaborated.

Methods
The expression of TMED3 in osteosarcoma was analyzed by immunohistochemical staining. The biological function of TMED3 in osteosarcoma was determined through loss-of-function assays in vitro. The effect of TMED3 downregulation on osteosarcoma was further explored by xenograft tumor model. The molecular mechanism of the regulation of TMED3 on osteosarcoma was determined by gene expression profile analysis.

Results
The expression of TMED3 in osteosarcoma tissues was significantly greater than that in matched adjacent normal tissues. Knockdown of TMED3 inhibited the progression of osteosarcoma by suppressing proliferation, impeding migration and enhancing apoptosis in vitro. We further validated that knockdown of TMED3 inhibited osteosarcoma generation in vivo. Additionally, ribosomal protein S15A (RPS15A) was determined as a potential downstream target for TMED3 involved in the progression of osteosarcoma. Further investigations elucidated that the simultaneous knockdown of RPS15A and TMED3 intensified the inhibitory effects on osteosarcoma cells. Importantly, knockdown of RPS15A alleviated the promotion effects of TMED3 overexpression in osteosarcoma cells.

Conclusions
In summary, these findings emphasized the importance of TMED3/RPS15A axis in promoting tumor progression, which may be a promising candidate for molecular therapy of osteosarcoma.
NEDD4L-induced ubiquitination mediating UBE2T degradation inhibits progression of lung adenocarcinoma via PI3K-AKT signaling
Authors: Chen Yongbing , Hong Haihua , Wang Qingqing , Li Junqiang , Zhang Wenfeng , Chen Tingting , Li Pu 
Published: November 2021

Abstract
Background
A number of studies have indicated that Ubiquitin-conjugating enzyme E2T (UBE2T), as an oncogene, promotes progression and metastasis of lung cancer, including lung adenocarcinoma (LUAD), but it is completely unknown whether and how UBE2T is ubiquitylated and degraded, and by which E3 ligase. NEDD4L plays a critical role in the regulation of cellular processes of various cancers, most of which is attributed to its E3 ubiquitin ligase function. However, the relationship between NEDD4L and UBE2T in LUAD has not been elucidated.

Methods
The relationship between NEDD4L and UBE2T in LUAD tissues and cells was found by bioinformatic analyses and immunoblotting. Cell counting kit-8, colony formation assay, half-life analysis and the in vivo ubiquitylation assay, generation of xenograft model were performed to determine how NEDD4L regulates UBE2T and its downstream signaling pathway in vitro and in vivo.

Results
Bioinformatic analyses found that NEDD4L, as a potential correlation E3 ligase of UBE2T, was negatively correlated with UBE2T in LUAD. Consistently, UBE2T protein half-life was shortened or extended by NEDD4L overexpression or depletion, respectively. NEDD4L inhibited LUAD cell progression in vitro and in vivo via inducing the ubiquitination-mediated UBE2T degradation, which repressed PI3K-AKT signaling. Similarly, NEDD4L predicted a better patient survival, whereas UBE2T predicted a worse survival.

Conclusions
Collectively, our results reveal that NEDD4L is a novel E3 ligase of UBE2T, which can inhibit PI3K-AKT signaling by targeting for UBE2T ubiquitination and degradation, resulting in repression of LUAD cell progression.
To explore immune synergistic function of Quercetin in inhibiting breast cancer cells
Authors: Qiu Dan , Yan Xianxin , Xiao Xinqin , Zhang Guijuan , Wang Yanqiu , Cao Jingyu , Ma Ruirui , Hong Shouyi , Ma Min 
Published: November 2021

AbstractBackgroundThe precancerous disease of breast cancer is an inevitable stage in the tumorigenesis and development of breast neoplasms. Quercetin (Que) has shown great potential in breast cancer treatment by inhibiting cell proliferation and regulating T cell function. γδ T cells are a class of nontraditional T cells that have long attracted attention due to their potential in immunotherapy. In this study, we revealed the immunomodulatory function of Que through regulation of the JAK/STAT1 signaling pathway, which was followed by the synergistic killing of breast cancer cells.MethodsIn the experimental design, we first screened target genes with or without Que treatment, and we intersected the Que target with the disease target by functional enrichment analysis. Second, MCF-10A, MCF-10AT, MCF-7 and MDA-MB-231 breast cancer cell lines were treated with Que for 0 h, 24 h and 48 h. Then, we observed the expression of its subsets by coculturing Que and γδ T cells and coculturing Que and γδ T cells with breast tumor cells to investigate their synergistic killing effect on tumor cells. Finally, Western blotting was used to reveal the changes in proteins related to the JAK/STAT1 signaling pathway after Que treatment in MCF-10AT and MCF-7 cells for 48 h.ResultsThe pathway affected by Que treatment was the JAK/STAT1 signaling pathway and was associated with precancerous breast cancer, as shown by network pharmacology analysis. Que induced apoptosis of MCF-10AT, MCF-7 and MDA-MB-231 cells in a time- and concentration-dependent manner (P < 0.05). Most importantly, Que promoted the differentiation of γδ T cells into the Vδ2 T cell subpopulation. The best ratio of effector cells to target cells (E/T) was 10:1, the killing percentages of γδ T cells against MCF-10A, MCF-10AT, MCF-7, and MDA-MB-231 were 61.44 ± 4.70, 55.52 ± 3.10, 53.94 ± 2.74, and 53.28 ± 1.73 (P = 0.114, P = 0.486,andP = 0.343, respectively), and the strongest killing effect on precancerous breast cancer cells and breast cancer cells was found when the Que concentration was 5 μM and the E/T ratio was 10:1 (64.94 ± 3.61, 64.96 ± 5.45, 55.59 ± 5.98, and 59.04 ± 5.67, respectively). In addition, our results showed that Que increased the protein levels of IFNγ-R, p-JAK2 and p-STAT1 while decreasing the protein levels of PD-L1 (P < 0.0001).ConclusionsIn conclusion, Que plays a synergistic role in killing breast cancer cells and promoting apoptosis by regulating the expression of IFNγ-R, p-JAK2, p-STAT1 and PD-L1 in the JAK/STAT1 signaling pathway and promoting the regulation of γδ T cells. Que may be a potential drug for the prevention of precancerous breast cancer and adjuvant treatment of breast cancer.