bluuebunny/crossref_metadata_2025_split huggingface dataset:
NCAPG promotes the proliferation of hepatocellular carcinoma through the CKII-dependent regulation of PTEN
Authors: Zhang Rongguiyi , Ai Jiyuan , Wang Jiakun , sun Chi , Lu Hongcheng , He Aoxiao , Li Min , Liao Yuting , Lei Jun , Zhou Fan , Wu Linquan , Liao Wenjun 
Published: July 2022

Abstract
Background
NCAPG, non-SMC subunit in the concentrate I complex, might promote the proliferation of hepatocellular carcinoma (HCC), but the mechanism is unclear. The aim of this study was to explore how NCAPG affects PTEN to influence the proliferation of HCC.

Methods
Western blotting, qRT-PCR and immunohistochemistry were used to detect NCAPG expression in HCC tissues. The effect of NCAPG on the proliferation of HCC cell lines was evaluated using an EdU incorporation assay, a Cell Counting Kit-8 assay and Fluorescence in situ hybridization (FISH). BALB/c-nu/nu mice were used for the in vivo proliferation experiment. Transcriptome sequencing was used to determine the relationship between NCAPG and PTEN. Immunocoprecipitation-mass spectrometry (IP-MS), proteomic sequencing and Co-immunoprecipitation (CO-IP) were used to identify and examine the interaction between the NCAPG and CKII proteins.

Results
We confirmed that NCAPG was abnormally overexpressed in HCC and promoted the proliferation of HCC cells. Transcriptome sequencing revealed that NCAPG inhibited the transcription of PTEN and promoted the activation of the PI3K-AKT pathway. We found a close association between NCAPG and CKII through proteomic sequencing; their interaction was confirmed by Co-IP. There was a positive correlation between NCAPG and CKII that promoted the phosphorylation of PTEN and thus inhibited its transcription and functions. We also proved that CKII was the key factor in the induction of proliferation by NCAPG.

Conclusion
We revealed the mechanism by which NCAPG regulates the proliferation of HCC: NCAPG inhibits PTEN through its interaction with CKII, and then activates the PI3K-AKT pathway to promote the proliferation of HCC.
Forkhead Box S1 mediates epithelial-mesenchymal transition through the Wnt/β-catenin signaling pathway to regulate colorectal cancer progression
Authors: Zhang Liang , Ren Chuan-fu , Yang Zhi , Gong Long-bo , Wang Chao , Feng Min , Guan Wen-xian 
Published: July 2022

Abstract
Background
Recent studies have shown that the fox family plays a vital role in tumorigenesis and progression. Forkhead Box S1 (FOXS1), as a newly identified subfamily of the FOX family, is overexpressed in certain types of malignant tumors and closely associated with patient's prognosis. However, the role and mechanism of the FOXS1 in colorectal cancer (CRC) remain unclear.

Method
FOXS1 level in CRC tissues and cell lines was analyzed by western blot and quantitative real-time polymerase chain reaction (qRT-PCR). Immunohistochemistry (IHC) was used to detect the relationship between FOXS1 expression and clinicopathological features in 136 patients in our unit. The expression of FOXS1 was knocked down in CRC cells using small interfering RNA (siRNA) technology. Cell proliferation was assessed by CCK8 assay, colony formation, and 5-Ethynyl-20-deoxyuridine (EdU) incorporation assay. Flow cytometry detected apoptosis and wound healing, and Transwell assays determined cell migration and invasion. Western blotting was used to detect the levels of proteins associated with the Wnt/β-catenin signaling pathway. Then, we used short hairpin RNA (shRNA) to knock down FOXS1 to see the effect of FOXS1 on the proliferation, migration, invasion, and metastasis of CRC cells in vivo. Finally, we investigated the impact of Wnt activator LiCl on the proliferation, migration, invasion, and metastasis of CRC cells after FOXS1 knockdown.

Result
Compared to those in normal groups, FOXS1 overexpressed in CRC tissues and CRC cells (P < 0.05). Upregulation of FOXS1 association with poor prognosis of CRC patients. si-FOXS1 induced apoptosis and inhibited proliferation, migration, invasion, the epithelial-mesenchymal transition (EMT), and the Wnt/β-catenin signaling pathway in vitro; sh-FOXS1 inhibited the volume and weight of subcutaneous xenografts and the number of lung metastases in vivo. LiCl, an activator of Wnt signaling, partially reversed the effect of FOXS1 overexpression on CRC cells.

Conclusion
FOXS1 could function as an oncogene and promote CRC cell proliferation, migration, invasion and metastasis through the Wnt/βcatenin signaling pathway, FOXS1 may be a potential target for CRC treatment.
Establishment of a piglet model for peritoneal metastasis of ovarian cancer
Authors: Lee Eun Ji , Park Soo Jin , Seol Aeran , Lim Hyunji , Park Sumin , Ahn Ji Yeon , Lim Jeong Mook , Kim Hee Seung ,   the KoRIA Trial Group, Park Ji Won , Song Gwonhwa , Ham Jiyen , Park Sunwoo , Yim Ga Won , Shim Seung-Hyuk , Kang Beong-Cheol , Chang Suk Joon , Lim Whasun , Lee Jung Chan 
Published: July 2022

Abstract
Background
A piglet model for peritoneal metastasis (PM) of ovarian cancer was developed. It will contribute to establishing innovative chemotherapeutical and surgical strategies without any limitation on rodent models.

Methods
A total of 12 four- to five-week-old piglets of 7 to 8 kg were used. Two phases of ovarian cancer cell injections were performed with laparoscopic surgery.
In phase I trial, 5.0 × 106 SK-OV-3 cells in 0.1 ml suspension were inoculated into the omentum, peritoneum, and uterine horns of two piglets twice with a one-week interval. In the phase II trial, 5.0 × 106 SNU-008 cells in 0.1 ml suspension were injected only into uterine horns within the same time frame because tumor implantation after inoculation of SK-OV-3 cells was not observed at the omentum or peritoneum in the phase I trial. Modified peritoneal cancer index (PCI) score was used to monitor tumorigenesis up to 4 weeks after inoculation. Tumor tissues disseminated in the peritoneum 4 weeks after injection were used for histological examination with hematoxylin and eosin (H&E) and paired-box gene 8 (PAX-8) staining.

Results
In the phase I trial, two piglets showed PM with modified PCI scores of 5 and 4 at 3 weeks after the first inoculation, which increased to 14 and 15 after 4 weeks, respectively. In the phase II trial, PM was detected in eight of ten piglets, which showed modified PCI scores of 6 to 12 at 4 weeks after the first inoculation. The overall incidence of PM from the total of 12 piglets after inoculation was 75%. Immunohistochemical H&E and PAX-8 staining confirmed metastatic tumors.

Conclusions
This study provides strong evidence that piglets can be employed as a model for PM by inoculating ovarian cancer cell lines from humans. Using two cell lines, the PM rate is 75%.
Short and long-term effects of robot-assisted therapy on upper limb motor function and activity of daily living in patients post-stroke: a meta-analysis of randomized controlled trials
Authors: Zhang Liping , Jia Gongwei , Ma Jingxi , Wang Sanrong , Cheng Li 
Published: July 2022

Abstract
Objective
To investigate the effect of robot-assisted therapy (RAT) on upper limb motor control and activity function in poststroke patients compared with that of non-robotic therapy.

Methods
We searched PubMed, EMBASE, Cochrane Library, Google Scholar and Scopus. Randomized controlled trials published from 2010 to nowadays comparing the effect of RAT and control treatment on upper limb function of poststroke patients aged 18 or older were included. Researchers extracted all relevant data from the included studies, assessed the heterogeneity with inconsistency statistics (I2 statistics), evaluated the risk of bias of individual studies and performed data analysis.

Result
Forty-six studies were included. Meta-analysis showed that the outcome of the Fugl-Meyer Upper Extremity assessment (FM-UE) (SMD = 0.20, P = 0.001) and activity function post intervention was significantly higher (SMD = 0.32, P < 0.001) in the RAT group than in the control group. Differences in outcomes of the FM-UE and activity function between the RAT group and control group were observed at the end of treatment and were not found at the follow-up. Additionally, the outcomes of the FM-UE (SMD = 0.15, P = 0.005) and activity function (SMD = 0.32, P = 0.002) were significantly different between the RAT and control groups only with a total training time of more than 15 h. Moreover, the differences in outcomes of FM-UE and activity post intervention were not significant when the arm robots were applied to patients with severe impairments (FM-UE: SMD = 0.14, P = 0.08; activity: SMD = 0.21, P = 0.06) or when patients were provided with patient-passive training (FM-UE: SMD = − 0.09, P = 0.85; activity: SMD = 0.70, P = 0.16).

Conclusion
RAT has the significant immediate benefits for motor control and activity function of hemiparetic upper limb in patients after stroke compared with controls, but there is no evidence to support its long-term additional benefits. The superiority of RAT in improving motor control and activity function is limited by the amount of training time and the patients' active participation.
Comprehensive profiling and characterization of cellular microRNAs in response to coxsackievirus A10 infection in bronchial epithelial cells
Authors: Hu Yajie , Wang Lan , Zhong Mingmei , Zhao Wei , Wang Yujue , Song Jie , Zhang Yunhui 
Published: July 2022

AbstractCoxsackievirus A10 (CV-A10), the causative agent of hand, foot, and mouth disease (HFMD), caused a series of outbreaks in recent years and often leads to neurological impairment, but a clear understanding of the disease pathogenesis and host response remains elusive. Cellular microRNAs (miRNAs), a large family of non-coding RNA molecules, have been reported to be key regulators in viral pathogenesis and virus-host interactions. However, the role of host cellular miRNAs defensing against CV-A10 infection is still obscure. To address this issue, we systematically analyzed miRNA expression profiles in CV-A10-infected 16HBE cells by high-throughput sequencing methods in this study. It allowed us to successfully identify 312 and 278 miRNAs with differential expression at 12 h and 24 h post-CV-A10 infection, respectively. Among these, 4 miRNAs and their target genes were analyzed by RT-qPCR, which confirmed the sequencing data. Gene target prediction and enrichment analysis revealed that the predicted targets of these miRNAs were significantly enriched in numerous cellular processes, especially in regulation of basic physical process, host immune response and neurological impairment. And the integrated network was built to further indicate the regulatory roles of miRNAs in host-CV-A10 interactions. Consequently, our findings could provide a beneficial basis for further studies on the regulatory roles of miRNAs relevant to the host immune responses and neuropathogenesis caused by CV-A10 infection.
Percutaneous endoscopic interlaminar discectomy via inner border of inferior pedicle approach for downmigrated disc herniation: a retrospective study
Authors: Huang Huiyu , Hu Haigang , Lin Xu , Wu Chao , Tan Lun 
Published: July 2022

Abstract
Objective
To evaluate the efficacy and feasibility of percutaneous endoscopic interlaminar discectomy (PEID) via the inner border of the inferior pedicle approach for downmigrated disc herniation.

Methods
Seventeen patients who had downmigrated disc herniation were included in this study from May 2020 to February 2021. After PEID via the inner border of the inferior pedicle approach, a retrospective study was conducted on all patients. Radiologic findings were investigated, and based on the level of migration seen on preoperative magnetic resonance imaging (MRI), participants were divided into two types (high-grade and low-grade migrations). Preoperative, 1st post-operative day, 3rd post-operative month, and the final follow-up visual analogue scale (VAS) assessments for back and leg pain and preoperative, 3rd post-operative month, and the final follow-up Oswestry disability index (ODI) evaluations were performed. The clinical effects at the final follow-up were assessed by the modified MacNab criterion.

Results
All patients successfully completed surgery. There were 10 males and 7 females in the group. These patients were 42 years old on average (range, 25–68 years). Four and 13 patients had downmigrated disc herniation with high-grade and low-grade, respectively, on MRI. The mean follow-up duration was 10.47 ± 1.84 months (range, 8–14 months). The mean VAS score for back and leg improved from 5.18 ± 0.81 preoperatively to 1.35 ± 0.49 at the final follow-up (P < 0.05) and 6.94 ± 0.66 preoperatively to 1.47 ± 0.51 at the final follow-up (P < 0.05), respectively. The mean ODI score improved from 48.00 ± 3.64 preoperatively to 18.71 ± 1.31 at the final follow-up (P < 0.05). According to the modified MacNab criterion, 15 patients (88.2%) obtained excellent, while the rest 2 patients (11.8%) reported good outcomes.

Conclusion
PEID via the inner border of the inferior pedicle approach could be a good alternative option for the treatment of downmigrated disc herniation.
Dysregulation and prometastatic function of glycosyltransferase C1GALT1 modulated by cHP1BP3/ miR-1-3p axis in bladder cancer
Authors: Tan Zengqi , Jiang Yazhuo , Liang Liang , Wu Jinpeng , Cao Lin , Zhou Xiaoman , Song Zhihui , Ye Zhenyu , Zhao Ziyan , Feng Hui , Dong Zewen , Lin Shuai , Zhou Zhangjian , Wang Yili , Li Xiang , Guan Feng 
Published: July 2022

Abstract
Background
Abnormal glycosylation in a variety of cancer types is involved in tumor progression and chemoresistance. Glycosyltransferase C1GALT1, the key enzyme in conversion of Tn antigen to T antigen, is involved in both physiological and pathological conditions. However, the mechanisms of C1GALT1 in enhancing oncogenic phenotypes and its regulatory effects via non-coding RNA are unclear.

Methods
Abnormal expression of C1GALT1 and its products T antigen in human bladder cancer (BLCA) were evaluated with BLCA tissue, plasma samples and cell lines. Effects of C1GALT1 on migratory ability and proliferation were assessed in YTS-1 cells by transwell, CCK8 and colony formation assay in vitro and by mouse subcutaneous xenograft and trans-splenic metastasis models in vivo. Dysregulated circular RNAs (circRNAs) and microRNAs (miRNAs) were profiled in 3 pairs of bladder cancer tissues by RNA-seq. Effects of miR-1-3p and cHP1BP3 (circRNA derived from HP1BP3) on modulating C1GALT1 expression were investigated by target prediction program, correlation analysis and luciferase reporter assay. Functional roles of miR-1-3p and cHP1BP3 on migratory ability and proliferation in BLCA were also investigated by in vitro and in vivo experiments. Additionally, glycoproteomic analysis was employed to identify the target glycoproteins of C1GALT1.

Results
In this study, we demonstrated upregulation of C1GALT1 and its product T antigen in BLCA. C1GALT1 silencing suppressed migratory ability and proliferation of BLCA YTS-1 cells in vitro and in vivo. Subsets of circRNAs and miRNAs were dysregulated in BLCA tissues. miR-1-3p, which is reduced in BLCA tissues, inhibited transcription of C1GALT1 by binding directly to its 3′-untranslated region (3′-UTR). miR-1-3p overexpression resulted in decreased migratory ability and proliferation of YTS-1 cells. cHP1BP3 was upregulated in BLCA tissues, and served as an miR-1-3p “sponge”. cHP1BP3 was shown to modulate migratory ability, proliferation, and colony formation of YTS-1 cells, and displayed tumor-suppressing activity in BLCA. Target glycoproteins of C1GALT1, including integrins and MUC16, were identified.

Conclusions
This study reveals the pro-metastatic and proliferative function of upregulated glycosyltransferase C1GLAT1, and provides preliminary data on mechanisms underlying dysregulation of C1GALT1 via miR-1-3p / cHP1BP3 axis in BLCA.
Prognostic meaning of right ventricular function and output reserve in patients with systemic sclerosis
Authors: Xanthouli Panagiota , Miazgowski Julia , Benjamin Nicola , Gordjani Ojan , Egenlauf Benjamin , Harutyunova Satenik , Seeger Rebekka , Marra Alberto M. , Blank Norbert , Lorenz Hanns-Martin , Grünig Ekkehard , Eichstaedt Christina A. 
Published: July 2022

Abstract
Background
The objective of this study was to investigate the prognostic impact of right ventricular (RV) function at rest and during exercise in patients with systemic sclerosis (SSc) presenting for a screening for pulmonary hypertension (PH).

Methods
In this study, data from SSc patients who underwent routinely performed examinations for PH screening including echocardiography and right heart catheterization at rest and during exercise were analysed. Uni- and multivariable analyses were performed to identify prognostic parameters.

Results
Out of 280 SSc patients screened for PH, 225 were included in the analysis (81.3% female, mean age 58.1±13.0 years, 68% limited cutaneous SSc, WHO-FC II–III 74%, 24 manifest PH). During the observation period of 3.2±2.7 (median 2.6) years 35 patients died. Tricuspid annular plane systolic excursion (TAPSE) at rest <18 mm (p=0.001), RV output reserve as increase of cardiac index (CI) during exercise <2 l/min (p<0.0001), RV pulmonary vascular reserve (Δ mean pulmonary artery pressure/Δ cardiac output) ≥3 mmHg/l/min (p<0.0001), peak CI <5.5 l/min/m2 (p=0.001), pulmonary arterial compliance <2 ml/mmHg (p=0.002), TAPSE/systolic pulmonary arterial pressure (sPAP) ratio ≤0.6 ml/mmHg (p<0.0001) and echocardiographic qualitative RV function at rest (p<0.0001) significantly predicted worse survival. In the multivariable analysis TAPSE/sPAP ratio and diffusion capacity for carbon monoxide ≤65% were identified as independent prognostic predictors and had 75% sensitivity and 69% specificity to predict future development of pulmonary vascular disease (PVD) during follow-up.

Conclusions
This study demonstrates that assessment of RV function at rest and during exercise may provide crucial information to identify SSc patients who are at a high risk of poor outcome and for the development of PH and/or PVD.
The association between diabetes and obesity with Dengue infections
Authors: Sekaran S. D. , Liew Z. M. , Yam H. C. , Raju C. S. 
Published: July 2022

AbstractDengue, an arboviral disease is a global threat to public health as the number of Dengue cases increases through the decades and this trend is predicted to continue. Non-communicable diseases such as diabetes and obesity are also on an upward trend. Moreover, past clinical studies have shown comorbidities worsen the clinical manifestation of especially Severe Dengue. However, discussion regarding the underlying mechanisms regarding the association between these comorbidities and dengue are lacking. The hallmark of Severe Dengue is plasma leakage which is due to several factors including presence of pro-inflammatory cytokines and dysregulation of endothelial barrier protein expression. The key factors of diabetes affecting endothelial functions are Th1 skewed responses and junctional-related proteins expression. Additionally, obesity alters the lipid metabolism and immune response causing increased viral replication and inflammation. The similarity between diabetes and obesity individuals is in having chronic inflammation resulting in endothelial dysfunction. This review outlines the roles of diabetes and obesity in severe dengue and gives some insights into the plausible mechanisms of comorbidities in Severe Dengue.
An incidental finding of retroperitoneal paraganglioma during the coronavirus disease 2019 pandemic: a case report
Authors: Ben Hamida K. , Slimane M. , Mlouka A. , Boujelbene N. , Essghaier S. , Rahal K. 
Published: July 2022

Abstract
Background
Extra-adrenal paraganglioma of the retroperitoneum is a very rare neoplasm arising from cells of the primitive neural crest. Although paragangliomas are considered benign and are often found incidentally, they have the potential to metastasize.

Case presentation
We report the case of a 68-year-old Caucasian woman with an incidental diagnosis of retroperitoneal paraganglioma that was discovered on chest computed tomography performed for high suspicion of coronavirus disease 2019 pneumonia. The patient showed no metastasis and was successfully treated by complete surgical removal of the tumor.

Conclusion
As the diagnosis of paragangliomas is often delayed because of absent clinical symptoms, they represent a significant diagnostic challenge. Although surgery may exacerbate coronavirus disease 2019 infection, surgical resection of this tumor is prioritized, given its malignancy potential, and it must be performed as soon as no infection is detected.
Neuropharmacological Study of Posaconazole for Glioblastoma: A Phase 0 Clinical Trial Protocol
Authors: Bhanja Debarati , Neighbors Jeffrey , Connor James , Zadeh Gelareh , Mansouri Alireza 
Published: July 2022

BACKGROUND:
Glioblastoma (GBM) is the most common malignant primary brain tumor with a universally poor prognosis. GBMs express elevated levels of hexokinase 2 (HK2), catalyzing the critical step in glycolysis and influencing several oncogenic pathways. Previous preclinical work has suggested a role for repurposed posaconazole (PCZ) in downregulating HK2 activity, reducing lactate and pyruvate production, interfering with tumor cell metabolism, and increasing mouse survival.

OBJECTIVE:
To establish brain tumor penetrance, neuropharmacokinetic profile, and mechanistic effect on tumor cell metabolism of PCZ in adults with GBM.

METHODS:
This is an open label, nonrandomized, parallel arm trial involving patients with GBM. Cohorts will receive PCZ (intervention, n = 5) or will not receive PCZ (control, n = 5), followed by tumor resection and microdialysis catheter placement. Dialysate, plasma, and tumor samples will be analyzed for lactate and pyruvate concentrations. Tumor samples will also be assessed for PCZ concentration, HK2 expression, angiogenesis, and apoptosis. PCZ's neuropharmacokinetics will be determined based on the concentration vs time profile and area under the curve 0 to 24 hours of PCZ concentration in the brain interstitium.

EXPECTED OUTCOMES:
(1) Increased PCZ concentration in contrast-enhancing brain regions compared with nonenhancing regions; (2) inverse correlation between lactate/pyruvate and PCZ concentrations in dialysate samples from treated patients, over time; and (3) decreased HK2 activity in PCZ-treated tumor samples.

DISCUSSION:
A successful trial will support the decision to proceed to advanced phase trials. Any tumor penetration by PCZ, with concomitant effect on glycolysis, warrants further in-depth analysis, as therapeutic options for these deadly tumors are currently limited.