bluuebunny/crossref_metadata_2025 huggingface dataset:
Coinfection with PEDV and BVDV induces inflammatory bowel disease pathway highly enriched in PK-15 cells
Authors: Cheng Jinghua , Tao Jie , Li Benqiang , Shi Ying , Liu Huili
Published: July 2022

Background

From the 1078 diarrhea stools tested in our survey from 2017 to 2020 in local area of China, PEDV was the key pathogen that was closely related to the death of piglets with diarrhea. In addition, coinfection of PEDV-positive samples with BVDV reached 17.24%. Although BVDV infection in swine is typically subclinical, the effect of PEDV and BVDV coinfection on disease severity and the potential molecular mechanism of coinfection with these two viruses remain unknown.

Methods

In this study, we developed a model of coinfection with porcine epidemic diarrhea virus (PEDV) and bovine viral diarrhea virus (BVDV) in PK15 cells, and a tandem mass tag (TMT) combined with LC–MS/MS proteomic approach was used to identify differential protein expression profiles. Additionally, we performed drug experiments to explore the inflammatory response induced by PEDV or BVDV mono- or coinfection.

Results

A total of 1094, 1538, and 1482 differentially expressed proteins (DEPs) were identified upon PEDV monoinfection, BVDV monoinfection and PEDV/BVDV coinfection, respectively. KEGG pathway analysis revealed that PEDV and BVDV coinfection led to a highly significantly enrichment of the inflammatory bowel disease (IBD) pathway. In addition, the NF-κB signaling pathway was more intensively activated by PEDV and BVDV coinfection, which induced higher production of inflammatory cytokines, than PEDV or BVDV monoinfection.

Conclusions

Our study indicated that cattle pathogens might play synergistic roles in the pathogenesis of porcine diarrhea, which might also improve our understanding of the pathogenesis of multiple infections in diarrhea.
The effect of iron dextran on vitamin D3 metabolism in SD rats
Authors: Qiu Fubin , Li Rui , Gu Siyu , Zhao Yimin , Yang Linxue
Published: July 2022

Background

Iron and vitamin D (VD) is essential to health. Previous studies have shown that iron homeostasis has a potential effect on VD metabolism, but the mechanism is not fully understood.

Objectives

To explore the relationship between VD metabolism and iron metabolism, as well as the regulatory mechanism of iron on VD metabolism.

Methods

40 male rats were fed adaptively for 7 days and randomly divided into control (C, n = 6 normal diet) group and model (M, n = 24 iron deficient diet) by simple randomization, the latter was used to establish iron deficiency anemia (IDA) model. After 6 weeks of feeding, the M group was randomly divided into: iron deficiency group (DFe), low iron group (LFe), medium iron group (MFe) and high iron group (HFe) by block randomization. Different doses of iron dextran (based on iron content (100 g·bw·d)): 0, 1.1, 3.3 and 9.9 mg) were given respectively. After 4 weeks, the rats were anesthetized with 8% chloral hydrate, Blood (collected from the abdominal aorta), liver and kidney tissues were collected. The serum and tissues were separately packed and frozen at -80℃ for testing.

Results

The results showed that the levels of hemoglobin (Hb), red blood cell (RBC), serum iron (SI), liver iron, and kidney iron in DFe group were lower than those in the other four groups, while the levels of total iron-binding capacity (TIBC), transferrin (TF) and transferrin receptor (Tfr) in DFe group were higher than those in other groups; The serum levels of 25-(OH)D3 and 1,25-(OH)2D3 in DFe group were significantly lower than those in C group (P < 0.05). The correlation analysis showed that the levels of 25-(OH)D3 and 1,25-(OH)2D3 were negatively correlated with TIBC, TF and Tfr no correlation with SI. Western blotting, immunofluorescence, and q-PCR results showed that compared with C group, the protein and gene expressions of CYP2R1, CYP27A1, and CYP24A1 in DFe group were down-regulated, and the expression of CYP27B1 protein and gene was up-regulated in DFe group.

Conclusion

Iron may be involved in the metabolism of VD3 by regulating the expression of VD3 hydroxylase, suggesting that appropriate iron supplementation might promote the activation of VD3.
Association of PD-1/PD-L1 expression and Epstein-–Barr virus infection in patients with invasive breast cancer
Authors: Zhang Wei-tong , Zhu Gui-lu , Xu Wu-qin , Zhang Wei , Wang Hui-zhen , Wang Ya-bing , Li Yong-xiang
Published: July 2022

Purpose

Causative factors of breast cancer include infections, such as Epstein–Barr virus (EBV) infection. The aim of this study was to analyze the clinicopathological features of EBV-positive (IBC) and determine if EBV affects programmed cell death receptor 1 (PD-1)/PD ligand 1 (PD-L1) expression in IBC, similar to other EBV-infected tumors with PD-L1/PD-1 expression.

Methods

We collected 140 samples of IBC tissues and 25 samples of adjacent tissues. All patients were followed-up by telephone from the day of surgery to December 2020. Chromogenic in-situ hybridization was performed to evaluate EBV-encoded RNA (EBER). Immunohistochemistry was performed to evaluate PD-L1 and PD-1 expressions. The correlation between PD1/PDL1 expression and clinicopathological features was also analyzed.

Results

EBER was detected in 57 of 140 (40.7%) IBC tissues and not detected in any adjacent tissue (P < 0.05). Clinicopathologic features of patients were consistent with EBV-associated IBC. EBV infection was correlated with the mass size, menopausal status, axillary lymph node metastasis, vascular invasion, Ki-67 index, clinical stage, and estrogen receptor and progesterone receptor expressions (all P < 0.05), but not with the histological type, invasive ductal carcinoma histological grade, or human epidermal growth factor receptor 2 (HER2) expression (all P > 0.05). The positive rate of PD-1/PD-L1 expression was higher in the EBV-positive group than in the EBV-negative group (P < 0.05). The Kaplan–Meier univariate survival analysis showed that EBV was associated with poor disease-free survival and overall survival in patients with IBC. PD-L1/PD-1 expression could predict a poor prognosis.

Conclusions

In this study, clinicopathologic characteristics of patients were consistent with EBV-infected IBC. Patients with EBV-positive breast cancer were more likely to have elevated PD-1/PDL-1 expression compared to those with EBV-negative breast cancer. This finding could serve as a basis to explore therapeutic targets, particularly immunotherapy, for patients with IBC.
Long-term survival of patients with central or > 7 cm T4 N0/1 M0 non-small-cell lung cancer treated with definitive concurrent radiochemotherapy in comparison to trimodality treatment
Authors: Guberina Nika , Pöttgen Christoph , Schuler Martin , Guberina Maja , Stamatis Georgios , Plönes Till , Metzenmacher Martin , Theegarten Dirk , Gauler Thomas , Darwiche Kaid , Aigner Clemens , Eberhardt Wilfried E. E. , Stuschke Martin
Published: July 2022

Abstarct

Background

To examine long-term-survival of cT4 cN0/1 cM0 non-small-cell lung carcinoma (NSCLC) patients undergoing definitive radiochemotherapy (ccRTx/CTx) in comparison to the trimodality treatment, neoadjuvant radiochemotherapy followed by surgery, at a high volume lung cancer center.

Methods

All consecutive patients with histopathologically confirmed NSCLC (cT4 cN0/1 cM0) with a curative-intent-to-treat ccRTx/CTx were included between 01.01.2001 and 01.07.2019. Mediastinal involvement was excluded by systematic EBUS-TBNA or mediastinoscopy. Following updated T4-stage-defining-criteria initial staging was reassessed by an expert-radiologist according to UICC-guidelines [8th edition]. Outcomes were compared with previously reported results from patients of the same institution with identical inclusion criteria, who had been treated with neoadjuvant radiochemotherapy and resection. Factors for treatment selection were documented. Endpoints were overall-survival (OS), progression-free-survival (PFS), and cumulative incidences of isolated loco-regional failures, distant metastases, secondary tumors as well as non-cancer deaths within the first year.

Results

Altogether 46 consecutive patients with histopathologically confirmed NSCLC cT4 cN0/1 cM0 [cN0 in 34 and cN1 in 12 cases] underwent ccRTx/CTx after induction chemotherapy (iCTx). Median follow-up was 133 months. OS-rates at 3-, 5-, and 7-years were 74.9%, 57.4%, and 57.4%, respectively. Absolute OS-rate of ccRTx/CTx at 5 years were within 10% of the trimodality treatment reference group (Log-Rank p = 0.184). The cumulative incidence of loco-regional relapse was higher after iCTx + ccRT/CTx (15.2% vs. 0% at 3 years, p = 0.0012, Gray’s test) while non-cancer deaths in the first year were lower than in the trimodality reference group (0% vs 9.1%, p = 0.0360, Gray’s test). None of the multiple recorded prognostic parameters were significantly associated with survival after iCTx + ccRT/CTx: Propensity score weighting for adjustment of prognostic factors between iCTx + ccRT/CTx and trimodality treatment did not change the results of the comparisons.

Conclusions

Patients with cT4 N0/1 M0 NSCLC have comparable OS with ccRTx/CTx and trimodality treatment. Loco-regional relapses were higher and non-cancer related deaths lower with ccRTx/CTx. Definitive radiochemotherapy is an adequate alternative for patients with an increased risk of surgery-related morbidity.
Chemo-radiotherapy plus durvalumab for loco-regional relapse of resected NSCLC
Authors: Borghetti Paolo , Imbrescia Jessica , Volpi Giulia , Scotti Vieri , Aquilano Michele , Bruni Alessio , Franceschini Davide , Ursino Stefano , Ciammella Patrizia , Piperno Gaia , Taraborrelli Maria , Magrini Stefano Maria
Published: July 2022

Background

tumor recurrence after NSCLC surgical resection is the most common cause of treatment failure that sharply reduces the patient’s life expectancy. The optimal treatment strategy for loco-regional recurrences developing after surgical resection in patients with non–small-cell lung cancer (NSCLC) is not established yet.

This report aims to describe the pattern of relapse, PFS, and OS in patients treated with radio-chemotherapy and durvalumab for loco-regional relapse after surgery.

Methods

 We conducted a multicenter, retrospective study including subjects who underwent surgical resection for NSCLC and were treated with Pacific protocol after loco-regional relapse.

Results

Twenty-four patients met the inclusion criteria. At the time of diagnosis mean age was 65 years (range 47–78), the majority being male (58.3%). The 12-month progression-free survival rate was 68.7%, the 18-month progression-free survival rate was 45.8%, and the 24-month progression-free survival rate was 34.3%. There were three deaths: the 12-month survival rate was 91%, and the 18-month survival rate was 82.8%.

Conclusions

In this article, we propose a treatment strategy that might prolong post recurrence survival in patients with good performance status experiencing loco-regional relapse after surgery.
Comparison of MLC positioning deviations using log files and establishment of specific assessment parameters for different accelerators with IMRT and VMAT
Authors: Lin Xiutong , Sun Tao , Liu Xiao , Zhang Guifang , Yin Yong
Published: July 2022

Background and purpose

The study evaluated the differences in leaf positioning deviations by the log files of three advanced accelerators with two delivery techniques, and established specific assessment parameters of leaf positioning deviations for different types of accelerators.

Methods

A total of 420 treatment plans with 5 consecutive treatment log files were collected from the Trilogy, TrueBeam and Halcyon accelerators. Millennium MLC was equipped on the Trilogy and TrueBeam accelerators. A jawless design and dual-layer MLC were adopted on the Halcyon accelerator. 70 IMRT and 70 VMAT plans were selected randomly on each accelerator. The treatment sites of all plans included head and neck, chest, breast, pelvis and other sites. The parsing tasks for 2100 log files were proceeded by SunCheck software from Sun Nuclear Corporation. The maximum leaf root mean square (RMS) errors, 95th percentile errors and percentages of different leaf positioning errors were statistically analyzed. The correlations between these evaluation parameters and accelerator performance parameters (maximum leaf speed, mean leaf speed, gantry and arc angle) were analyzed.

Results

The average maximum leaf RMS errors of the Trilogy in the IMRT and VMAT plans were 0.44 ± 0.09 mm and 0.79 ± 0.07 mm, respectively, which were higher than the TrueBeam's 0.03 ± 0.01 mm, 0.03 ± 0.01 mm and the Halcyon's 0.05 ± 0.01 mm, 0.07 ± 0.01 mm. Similar data results were shown in the 95th percentile error. The maximum leaf RMS errors were strongly correlated with the 95th percentile errors (Pearson index > 0.5). The leaf positioning deviations in VMAT were higher than those in IMRT for all accelerators. In TrueBeam and Halcyon, leaf position errors above 1 mm were not found in IMRT and VMAT plans. The main influencing factor of leaf positioning deviation was the leaf speed, which has no strong correlation with gantry and arc angles.

Conclusions

Compared with the quality assurance guidelines, the MLC positioning deviations tolerances of the three accelerators should be tightened. For both IMRT and VMAT techniques, the 95th percentile error and the maximum RMS error are suggested to be tightened to 1.5 and 1 mm respectively for the Trilogy accelerator. In TrueBeam and Halcyon accelerators, the 95th percentile error and maximum RMS error of 1 and 0.5 mm, respectively, are considered appropriate.
Assessment of dose perturbations for metal stent in photon and proton radiotherapy plans for hepatocellular carcinoma
Authors: Lee Boram , Cho Sungkoo , Park Hee Chul , Kang Sang-Won , Kim Jae-Sung , Chung Jin-Beom
Published: July 2022

Background

The present study aimed to investigate the dosimetric impact of metal stent for photon and proton treatment plans in hepatocellular carcinoma.

Methods

With computed tomography data of a water-equivalent solid phantom, dose perturbation caused by a metal stent included in the photon and proton treatment of hepatocellular carcinoma was evaluated by comparing Eclipse and RayStation treatment planning system (TPS) to a Monte Carlo (MC) based dose calculator. Photon and proton plans were created with anterior–posterior/posterior-anterior (AP/PA) fields using a 6 MV beam and AP/PA fields of a wobbling beam using 150 MeV and a 10 cm ridge filter. The difference in dose distributions and dosimetric parameters were compared depending on the stent's positions (the bile duct (GB) and intestinal tract (GI)) and angles (0°, 45°, and 90°). Additionally, the dose variation in the target volume including the stent was comparatively evaluated through dose volume histogram (DVH) analysis. And the comparison of clinical cases was carried out in the same way.

Results

Percentage differences in the dosimetric parameters calculated by MC ranged from − 7.0 to 3.9% for the photon plan and − 33.7 to 4.3% for the proton plan, depending on the angle at which the GB and GI stents were placed, compared to those without the stent. The maximum difference was observed at the minimum dose (Dmin), which was observed in both photon and proton plans in the GB and GI stents deployed at a 90° incidence angle. The parameter differences were greater in the proton plan than in photon plan. The target volume showed various dose variations depending on positions and angles of stent for both beams. Compared with no-stent, the doses within the target volume containing the GI and GB stents for the photon beam were overestimated in the high-dose area at 0°, nearly equal within 1% at 45°, and underestimated at 90°. These doses to the proton beam were underestimated at all angles, and the amount of underdose to the target volume increased with an increase in the stent angle. However, the difference was significantly greater with the proton plan than the photon plan.

Conclusions

Dose perturbations within the target volume due to the presence of the metal stent were not observed in the TPS calculations for photon and proton beams, but MC was used to confirm that there are dose variations within the target volume. The MC results found that delivery of the treatment beam avoiding the stent was the best method to prevent target volume underdose.
Repair of finger pulp defects using a free second toe pulp flap anastomosed with the palmar vein
Authors: Zhang Xiaoli , Wang Ziyu , Ma Xiaoning , Jin Yanyan , Wang Jingxin , Yu Hang , Li Tong , Xiu Xiaolei
Published: July 2022

Purpose

To evaluate the clinical utility of surgical reconstruction of finger pulp defects using a plantar flap derived from the toes, with vascular anastomosis of the toe-finger artery and the plantar-palmar vein of the finger.

Methods

Between April 2018 and November 2020, 29 patients with finger pulp defects underwent treatment via the transplantation of pulp tissue from the second toe, with the plantar vein of the toe and the palmar vein of the finger being anastomosed during this procedure. In addition, an anastomosis of the toe and finger artery and nerve was conducted, with a flap size of 1.0 cm * 0.8 cm–2.3 cm * 4.0 cm being used for such repair. Donor tissue sites were closed without introducing deformities or other complications.

Results

In all patients in the present study, flap tissues survived and did not exhibit evidence of vascular crisis over a mean 16.8-month follow-up period (range 8–24 months). After successful skin flap grafting, they exhibited good elasticity and a soft texture. At three months post-surgery, some patients reported partial recovery of touch sensation in the transplanted tissue, while pain recovery was evident in some patients at 4–6 months post-surgery. No deformities or other complications were observed at the donor site, and the ability of patients to walk normally was not impaired.

Conclusion

The anastomosis of toe plantar flaps with the palmar vein can facilitate the repair of finger pulp injuries without the need to dissect the dorsal vein of the toe, allowing for the suturing of donor tissue sites without causing any deformities or other complications. This surgical approach can easily be conducted with satisfactory clinical outcomes.
Ozone induces autophagy by activating PPARγ/mTOR in rat chondrocytes treated with IL-1β
Authors: Sun Panpan , Xu Weicheng , Zhao Xu , Zhang Cong , Lin Xiaowen , Gong Moxuan , Fu Zhijian
Published: July 2022

Background

Osteoarthritis (OA) is the main cause of older pain and disability. Intra-articular injections of ozone (O3) commonly have been found to have antioxidative and anti-inflammatory effects to reduce pain and improve function in knee osteoarthritis. It has been reported that reduced autophagy in chondrocytes plays an important role in the development of OA. This study aimed to probe the role of O3 on the autophagy in chondrocytes treated with IL-1β.

Methods

Primary chondrocytes were isolated from Wistar rats cartilage within 3 days. The OA chondrocytes model was induced via treatment with IL-1β for 24 h. Then the cells were treated with O3 and GW9662, the inhibitor of PPARγ. Cell viability was assessed by CCK-8. Further, the cells subjected to Western blot analysis, qRT-PCR and immunofluorescence assay. The numbers of autophagosomes were observed via transmission electron microscopy.

Results

30 μg/ml O3 improved the viability of chondrocytes treated with IL-1β. The decreased level of autophagy proteins and the numbers of autophagosomes improved in IL-1β-treated chondrocytes with O3 via activating PPARγ/mTOR. In addition, the qRT-PCR results showed that O3 decreased the levels of IL-6, TNF-α and MMP-3, MMP-13 in chondrocytes treated with IL-1β.

Conclusions

30 μg/ml O3 improved autophagy via activating PPARγ/mTOR signaling and suppressing inflammation in chondrocytes treated with IL-1β.
In reply to the letter to the editor regarding “Comparison of a twin interlocking derotation and compression screw cephalomedullary nail (InterTAN) with a single screw derotation cephalomedullary nail (proximal femoral nail antirotation): a systematic review and meta-analysis for intertrochanteric fractures”
Authors: Nherera Leo , Trueman Paul , Horner Alan , Watson Tracy , Johnstone Alan J.
Published: July 2022

Background

Intertrochanteric hip fractures are common and devastating injuries, especially for the elderly. Surgical treatment is the optimal strategy for managing intertrochanteric fractures as it allows early rehabilitation and functional recovery. The relative effects of internal fixation strategies for intertrochanteric fracture after operation remain limited to relatively small studies which create uncertainty in attempts to establish evidence-based best practice.

Methods

We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) and observational studies to assess the clinical effectiveness of two commonly used intramedullary devices: a twin-screw integrated cephalomedullary nail (InterTAN) versus a single-screw cephalomedullary nail (proximal femoral nail antirotation) in patients with intertrochanteric fractures. The following outcomes were considered: revisions, implant-related failures, non-unions, pain, Harris hip score and intra-operative outcomes. Odds ratios or mean differences with 95% confidence intervals in brackets are reported.

Results

Six studies met the inclusion criteria: two randomised controlled trials and four observational studies enrolling 970 patients with a mean age of 77 years and 64% of patients being female. There was a statistically significant difference (p value < 0.05) for revisions OR 0.27 (0.13–0.56), implant-related failures OR 0.16 (0.09–0.27) and proportion of patients complaining of pain OR 0.50 (0.34–0.74). There was no difference in non-unions and Harris hip score (p value > 0.05). There was a significant difference in blood loss and fluoroscopy usage in favour of PFNA, while no difference in operating times was observed between the two devices.

Conclusions

Our meta-analysis suggests that a twin-screw integrated cephalomedullary nail (InterTAN) is clinically more effective when compared to a single-screw cephalomedullary nail proximal femoral nail antirotation resulting in fewer complications, fewer revisions and fewer patients complaining of pain. No difference has been established regarding non-unions and Harris hip score. Intra-operative outcomes favour PFNA with less blood loss and fluoroscopy usage. Further studies are warranted to explore the cost-effectiveness of these and other implants in managing patients with intertrochanteric fractures.
Crosstalk of organelles in Parkinson’s disease – MiT family transcription factors as central players in signaling pathways connecting mitochondria and lysosomes
Authors: Lang Martin , Pramstaller Peter P. , Pichler Irene
Published: July 2022

Living organisms constantly need to adapt to their surrounding environment and have evolved sophisticated mechanisms to deal with stress. Mitochondria and lysosomes are central organelles in the response to energy and nutrient availability within a cell and act through interconnected mechanisms. However, when such processes become overwhelmed, it can lead to pathologies. Parkinson’s disease (PD) is a common neurodegenerative disorder (NDD) characterized by proteinaceous intracellular inclusions and progressive loss of dopaminergic neurons, which causes motor and non-motor symptoms. Genetic and environmental factors may contribute to the disease etiology. Mitochondrial dysfunction has long been recognized as a hallmark of PD pathogenesis, and several aspects of mitochondrial biology are impaired in PD patients and models. In addition, defects of the autophagy-lysosomal pathway have extensively been observed in cell and animal models as well as PD patients’ brains, where constitutive autophagy is indispensable for adaptation to stress and energy deficiency. Genetic and molecular studies have shown that the functions of mitochondria and lysosomal compartments are tightly linked and influence each other. Connections between these organelles are constituted among others by mitophagy, organellar dynamics and cellular signaling cascades, such as calcium (Ca2+) and mTOR (mammalian target of rapamycin) signaling and the activation of transcription factors. Members of the Microphthalmia-associated transcription factor family (MiT), including MITF, TFE3 and TFEB, play a central role in regulating cellular homeostasis in response to metabolic pressure and are considered master regulators of lysosomal biogenesis. As such, they are part of the interconnection between mitochondria and lysosome functions and therefore represent attractive targets for therapeutic approaches against NDD, including PD. The activation of MiT transcription factors through genetic and pharmacological approaches have shown encouraging results at ameliorating PD-related phenotypes in in vitro and in vivo models. In this review, we summarize the relationship between mitochondrial and autophagy-lysosomal functions in the context of PD etiology and focus on the role of the MiT pathway and its potential as pharmacological target against PD.
Exploring immunotherapy in colorectal cancer
Authors: Weng Junyong , Li Shanbao , Zhu Zhonglin , Liu Qi , Zhang Ruoxin , Yang Yufei , Li Xinxiang
Published: July 2022

Chemotherapy combined with or without targeted therapy is the fundamental treatment for metastatic colorectal cancer (mCRC). Due to the adverse effects of chemotherapeutic drugs and the biological characteristics of the tumor cells, it is difficult to make breakthroughs in traditional strategies. The immune checkpoint blockades (ICB) therapy has made significant progress in the treatment of advanced malignant tumors, and patients who benefit from this therapy may obtain a long-lasting response. Unfortunately, immunotherapy is only effective in a limited number of patients with microsatellite instability—high (MSI-H), and segment initial responders can subsequently develop acquired resistance. From September 4, 2014, the first anti-PD-1/PD-L1 drug Pembrolizumab was approved by the FDA for the second-line treatment of advanced malignant melanoma. Subsequently, it was approved for mCRC second-line treatment in 2017. Immunotherapy has rapidly developed in the past 7 years. The in-depth research of the ICB treatment indicated that the mechanism of colorectal cancer immune-resistance has become gradually clear, and new predictive biomarkers are constantly emerging. Clinical trials examining the effect of immune checkpoints are actively carried out, in order to produce long-lasting effects for mCRC patients. This review summarizes the treatment strategies for mCRC patients, discusses the mechanism and application of ICB in mCRC treatment, outlines the potential markers of the ICB efficacy, lists the key results of the clinical trials, and collects the recent basic research results, in order to provide a theoretical basis and practical direction for immunotherapy strategies.
Super-enhancer profiling identifies novel critical and targetable cancer survival gene LYL1 in pediatric acute myeloid leukemia
Authors: Fang Fang , Lu Jun , Sang Xu , Tao Yan-Fang , Wang Jian-Wei , Zhang Zi-Mu , Zhang Yong-Ping , Li Xiao-Lu , Xie Yi , Wu Shui-Yan , Chu Xin-Ran , Li Gen , Wu Di , Chen Yan-Ling , Yu Juan-Juan , Jia Si-qi , Feng Chen-xi , Tian Yuan-Yuan , Li Zhi-Heng , Ling Jing , Hu Shao-Yan , Pan Jian
Published: July 2022

Background

Acute myeloid leukemia (AML) is a myeloid neoplasm makes up 7.6% of hematopoietic malignancies. Super-enhancers (SEs) represent a special group of enhancers, which have been reported in multiple cell types. In this study, we explored super-enhancer profiling through ChIP-Seq analysis of AML samples and AML cell lines, followed by functional analysis.

Methods

ChIP-seq analysis for H3K27ac was performed in 11 AML samples, 7 T-ALL samples, 8 B-ALL samples, and in NB4 cell line. Genes and pathways affected by GNE-987 treatment were identified by gene expression analysis using RNA-seq. One of the genes associated with super-enhancer and affected by GNE-987 treatment was LYL1 basic helix-loop-helix family member (LYL1). shRNA mediated gene interference was used to down-regulate the expression of LYL1 in AML cell lines, and knockdown efficiency was detected by RT-qPCR and western blotting. The effect of knockdown on the growth of AML cell lines was evaluated by CCK-8. Western blotting was used to detect PARP cleavage, and flow cytometry were used to determine the effect of knockdown on apoptosis of AML cells.

Results

We identified a total of 200 genes which were commonly associated with super-enhancers in ≧10 AML samples, and were found enriched in regulation of transcription. Using the BRD4 inhibitor GNE-987, we assessed the dependence of AML cells on transcriptional activation for growth and found GNE-987 treatment predominantly inhibits cell growth in AML cells. Moreover, 20 candidate genes were selected by super-enhancer profile and gene expression profile and among which LYL1 was observed to promote cell growth and survival in human AML cells.

Conclusions

In summary, we identified 200 common super-enhancer-associated genes in AML samples, and a series of those genes are cancer genes. We also found GNE-987 treatment downregulates the expression of super-enhancer-associated genes in AML cells, including the expression of LYL1. Further functional analysis indicated that LYL1 is required for AML cell growth and survival. These findings promote understanding of AML pathophysiology and elucidated an important role of LYL1 in AML progression.
Selective block of sensory neuronal T-type/Cav3.2 activity mitigates neuropathic pain behavior in a rat model of osteoarthritis pain
Authors: Itson-Zoske Brandon , Shin Seung Min , Xu Hao , Qiu Chensheng , Fan Fan , Hogan Quinn H. , Yu Hongwei
Published: July 2022

Background

Peripheral and central nociceptive sensitization is a critical pathogenetic component in osteoarthritis (OA) chronic pain. T-type calcium channel 3.2 (CaV3.2) regulates neuronal excitability and plays important roles in pain processing. We previously identified that enhanced T-type/CaV3.2 activity in the primary sensory neurons (PSNs) of dorsal root ganglia (DRG) is associated with neuropathic pain behavior in a rat model of monosodium iodoacetate (MIA)-induced knee OA. PSN-specific T-type/CaV3.2 may therefore represent an important mediator in OA painful neuropathy. Here, we test the hypothesis that the T-type/CaV3.2 channels in PSNs can be rationally targeted for pain relief in MIA-OA.

Methods

MIA model of knee OA was induced in male and female rats by a single injection of 2 mg MIA into intra-knee articular cavity. Two weeks after induction of knee MIA-OA pain, recombinant adeno-associated viruses (AAV)-encoding potent CaV3.2 inhibitory peptide aptamer 2 (CaV3.2iPA2) that have been characterized in our previous study were delivered into the ipsilateral lumbar 4/5 DRG. Effectiveness of DRG-CaV3.2iPA2 treatment on evoked (mechanical and thermal) and spontaneous (conditioned place preference) pain behavior, as well as weight-bearing asymmetry measured by Incapacitance tester, in the arthritic limbs of MIA rats were evaluated. AAV-mediated transgene expression in DRG was determined by immunohistochemistry.

Results

AAV-mediated expression of CaV3.2iPA2 selective in the DRG-PSNs produced significant and comparable mitigations of evoked and spontaneous pain behavior, as well as normalization of weight-bearing asymmetry in both male and female MIA-OA rats. Analgesia of DRG-AAV-CaV3.2iPA1, another potent CaV3.2 inhibitory peptide, was also observed. Whole-cell current-clamp recordings showed that AAV-mediated CaV3.2iPA2 expression normalized hyperexcitability of the PSNs dissociated from the DRG of MIA animals, suggesting that CaV3.2iPA2 attenuated pain behavior by reversing MIA-induced neuronal hyperexcitability.

Conclusions

Together, our results add therapeutic support that T-type/CaV3.2 in primary sensory pathways contributes to MIA-OA pain pathogenesis and that CaV3.2iPAs are promising analgesic leads that, combined with AAV-targeted delivery in anatomically segmental sensory ganglia, have the potential for further development as a peripheral selective T-type/CaV3.2-targeting strategy in mitigating chronic MIA-OA pain behavior. Validation of the therapeutic potential of this strategy in other OA models may be valuable in future study.
Cross-cultural adaptation and validation of the rapid assessment of physical activity questionnaire (RAPA) in Hungarian elderly over 50 years
Authors: Miszory Erika Viktória , Makai Alexandra , Pakai Annamária , Járomi Melinda
Published: July 2022

Background

Reliable and valid instruments are needed to estimate physical activity levels. The aim was to culturally adapt the “Rapid Assessment of Physical Activity” (RAPA) into Hungarian and to investigate the validity and reliability of this adapted version in the elderly over 50 years.

Methods

In our cross-sectional study 222 subjects were recruited in Hungary between December 2020 and January 2021(age 61.1 ± 7.9 years, 28% male). Criterion validity of RAPA and International Physical Activity Questionnaire (IPAQ)—Hungarian long version was tested by Spearman’s rank correlation. The examination of repeatability was based on a group of 32 people, and on the one-week test–retest reliability approach, and in addition to this during the statistical analysis intra-class correlation coefficient was calculated. To examine the sensitivity and specificity of the RAPA, negative and positive physical activity values were calculated from the results of the long version of the IPAQ and the RAPA. We tested 4 hypotheses (3 validity, 1 reliability). We considered acceptable validity and reliability if > 75% of hypotheses were confirmed. Results: All of the hypotheses (100%) were confirmed. Based on results of the validity testing of the newly adapted questionnaire was showed a moderate correlation between the examined measurement tools (R = 0.542, p < 0.001). The test–retest results of the questionnaire (N = 32, R = 0.988, p < 0.001) showed strong association.

Conclusion

RAPA showed fair to moderate validity and strong test–retest reliability similar to other studies. Based on our study’s results the RAPA is a valid and reliable questionnaire to measure the elderly Hungarian population’s physical activity.
Video analysis of 100 matches in male semi-professional football reveals a heading rate of 5.7 headings per field player and match
Authors: Weber Johannes , Ernstberger Andreas , Reinsberger Claus , Popp Daniel , Nerlich Michael , Alt Volker , Krutsch Werner
Published: July 2022

Introduction

Heading is an integral part of football and frequent media reports and previous studies about potential danger of heading and head trauma in football fuelled discussions. Epidemiological data and video analyses regarding headings situation and associated head injuries are still missing in male adult professional football.

Methods

In a prospective cohort study in the male fourth German football league, 100 official matches of the 2015–2016 season were assessed by video analysis and a standardized protocol. Heading situations and concomitant circumstances as well as incidents with a propensity of injury (critical incidents) were analyzed. Critical incidents (CI) and seasonal reported head injuries were cross-referenced.

Results

Overall, 11,514 headings were analysed in detail. Video analysis yielded a mean of 5.7 headings per player and match (SD: 1.2; range 0–15). Heading was predominantly performed with the frontal part of the head (76.8%), and nearly two thirds of all headings occurred during defending (65.8%). 71.0% of all headings occured during tacklings, of which 71.9% involved body contact with the opponent player. Video analysis yielded 31 CI on the head due to heading (incidence: 1.02 per 1000 h match exposure and player). 29 CI occurred during heading duels (odds ratio: 5.91), 30 CI with body contact (odds ratio: 28.8) and 6 CI with elbow contact (odds ratio: 6.13).

Conclusion

Heading frequency in male semi-professional football could be determined with a rate of 5.7 headings per match and field player. Cross referencing CI and seasonal reported head injuries revealed a very low number of reported head injuries.
Physical activity during pregnancy: a systematic review for the assessment of current evidence with future recommendations
Authors: Cilar Budler Leona , Budler Marko
Published: July 2022

Background

Physical activity is essential to maternal and infant health. Healthcare professionals should inform pregnant women about benefits of physical activity to prevent possible health issues. Those recommendations should elaborate on relevant contemporary evidence. The aim of this study was to review evidence-based recommendations for physical activity during pregnancy.

Methods

A systematic search, analysis and synthesis of conducted randomised controlled trials (RCTs) was conducted from October 2021 to June 2022 in following databases: PubMed, CINAHL, ScienceDirect and Web of Science. Literature was searched using inclusion and exclusion criteria and following PRISMA recommendations.

Results

Benefits for pregnant-women health and well-being were reported while performing aerobic exercise, lumbar stabilization and stretching exercise, water exercise, nerve and tendon-slip exercise, resistance training and strength training. For all exercise modalities it is recommended to perform moderate intensity activities during the whole time of pregnancy.

Conclusions

This systematic literature review supplements current knowledge on physical activity of pregnant women. Exercise interventions are listed and suggested in an integrative model with physical-fitness components to contextualize and promote physical activity among pregnant women.
Effects of maximal-versus submaximal-intent resistance training on functional capacity and strength in community-dwelling older adults: a systematic review and meta-analysis
Authors: Pearson Liam T. , Behm David G. , Goodall Stuart , Mason Rachel , Stuart Samuel , Barry Gill
Published: July 2022

The objective of this systematic review is to investigate the effects of different methods of resistance training (RT) on functional capacity in older adults. A systematic literature search was conducted using PubMed, SPORTDiscus, Web of Science, CINAHL, Cochrane CENTRAL, ClinicalTrials.gov databases, from inception to December 2021. Eligibility criteria consisted of randomised control trials (RCT’s) involving maximal-intent resistance training (MIRT), where participants (aged 60+) had specific instruction to move ‘as fast as possible’ during the concentric phase of the exercise. Twelve studies were included within the meta-analysis. Divided into functional capacity and strength-related outcomes; Improvements were evident for timed-up-and-go (p = 0.001, SMD: − 1.74 [95% CI − 2.79, − 0.69]) and knee extension one-repetition maximum (1RM) (p = 0.01, SMD: − 1.21, [95% CI − 2.17, − 0.25]), both in favour of MIRT, as well as in 30 s sit-to-stand in favour of T-STR (p = 0.04, SMD: 3.10 [95% CI 0.07, 6.14]). No statistical significance was found for combined functional capacity outcomes (p = 0.17, SMD: − 0.84, [95% CI − 2.04, 0.37]), with near-significance observed in strength-related outcomes (p = 0.06. SMD: − 0.57, [95% CI − 1.16, 0.02]) favouring MIRT. Heterogeneity for FC-outcomes was observed as Tau2 = 4.83; Chi = 276.19, df = 14, I2 = 95%, and for strength-outcomes Tau2 = 1.290; Chi = 109.65, df = 115, I2 = 86%. Additionally, MIRT elicited substantial clinically meaningful improvements (CMI) in Short Physical Performance Battery (SPPB) scores but fell short of CMI in 400 m walk test by 0.6 s. In conclusion, this systematic review highlights the lack of sufficient and quality evidence for maximal- versus submaximal-intent resistance training on functional capacity and strength in community-dwelling older adults. Study limitations revolved around lack of research, low quality (“low” PEDro score), and largely due to the fact many comparison studies did not match their loads lifted (1500 kg vs. 500 kg), making comparisons not possible.
Characterization of polymorphic microsatellite markers for the Japanese endangered land snail Mandarina
Authors: Nishida Shu , Mimura Kotaro , Mori Hideaki , Chiba Satoshi
Published: July 2022

Objective

Mandarina is an endangered land snail genus of the oceanic Ogasawara archipelago. On Chichijima Island, the largest inhabited island in Ogasawara, this genus is almost extinct in the wild due to predation by invasive species. Although ex situ conservation programs started in 2010, genetic diversity and population structure remain unclear due to a lack of genetic markers with sufficient genetic variation. In this study, we designed polymorphic microsatellite markers of Mandarina to enable genetic analysis and to develop appropriate conservation plans.

Results

Twenty-three polymorphic microsatellite markers were identified from the genomic DNA of wild samples of Mandarina mandarina. We assessed the genetic diversity of each marker. In 16 markers, neither linkage disequilibrium nor deviation from Hardy–Weinberg equilibrium was detected. These 16 markers were tested for multiplex PCR using low-density DNA extracted non-lethally from captive samples of M. mandarina, M. chichijimana and M. suenoae. Of the 16 markers, 15, 12 and 9 were usable for multiplex PCR, respectively. Genetic analysis using these microsatellite loci will be an important resource for the conservation of Mandarina.
Persistently elevated β-human chorionic gonadotropin level after vacuum-assisted uterine aspiration: a case report
Authors: Sinha Annika , Patterson Betsy
Published: July 2022

Background

Urothelial carcinoma of the bladder accounts for nearly 90% of all bladder cancers. Risk factors include cigarette smoke, chronic cystitis, and human papilloma virus infection. It is commonly diagnosed by hematuria, obstructive voiding, and irritative symptoms. Despite the prevalence of urothelial carcinoma, elevation of β-human chorionic gonadotropin in the setting of these malignancies is not common. This case report informs gynecologic practitioners to consider urologic causes of β-human chorionic gonadotropin elevation even in the setting of recent spontaneous abortion and details comprehensive review of diagnostic testing in the setting of β-human chorionic gonadotropin elevation.

Case presentation

A 49-year-old, non-Hispanic Caucasian woman, former smoker, with a history of polycystic ovary syndrome, high-risk human chorionic gonadotropin infection, and hypertension, underwent vacuum-assisted aspiration for significant vaginal bleeding in the setting of incomplete abortion. Fetal tissue was confirmed pathologically. Human chorionic gonadotropin levels decreased to 12.5 mU/mL and were no longer followed due to resumption of menses. Five months later during routine preoperative evaluation for orthopedic surgery, her human chorionic gonadotropin level was found to be elevated. She was also noted to have persistent asymptomatic hematuria. She completed an extensive gynecologic and urologic work-up, including hysteroscopy, dilation and curettage, methotrexate therapy, computerized tomographic imaging, and cystoscopy to finally arrive at the diagnosis of urothelial carcinoma.

Conclusions

Only a rare subset of urothelial carcinomas secretes β-human chorionic gonadotropin. Therefore, diagnosis of urothelial carcinoma is typically achieved by urine cytology with cystoscopic biopsy. Although rare, urothelial carcinoma should be considered in patients with risk factors presenting with persistently elevated beta-human chorionic gonadotropin.
Macrophage-derived apoptotic vesicles regulate fate commitment of mesenchymal stem cells via miR155
Authors: Zhu Yuan , Zhang Xiao , Yang Kunkun , Shao Yuzi , Gu Ranli , Liu Xuenan , Liu Hao , Liu Yunsong , Zhou Yongsheng
Published: July 2022

Background

In tissue engineering, mesenchymal stem cells (MSCs) are common seed cells because of abundant sources, strong proliferation ability and immunomodulatory function. Numerous researches have demonstrated that MSC-macrophage crosstalk played a key role in the tissue engineering. Macrophages could regulate the differentiation of MSCs via different molecular mechanisms, including extracellular vesicles. Apoptotic macrophages could generate large amounts of apoptotic vesicles (apoVs). ApoVs are rich in proteins, RNA (microRNAs, mRNAs, ncRNAs, etc.) and lipids, and are a key intercellular communication mediator that can exert different regulatory effects on recipient cells. MiRNAs account for about half of the total RNAs of extracellular vesicles, and play important roles in biological processes such as cell proliferation and differentiation, whereas the functions of macrophage-derived apoVs remain largely unknown. There was no research to clarify the role of macrophage-derived apoVs in MSC fate choices. In this study, we aimed to characterize macrophage-derived apoVs, and investigate the roles of macrophage-derived apoVs in the fate commitment of MSCs.

Methods

We characterized macrophage-derived apoVs, and investigated their role in MSC osteogenesis and adipogenesis in vitro and in vivo. Furthermore, we performed microRNA loss- and gain-of-function experiments and western blot to determine the molecular mechanism.

Results

Macrophages could produce a large number of apoVs after apoptosis. MSCs could uptake apoVs. Then, we found that macrophage-derived apoVs inhibited osteogenesis and promoted adipogenesis of MSCs in vitro and in vivo. In mechanism, apoVs were enriched for microRNA155 (miR155), and apoVs regulated osteogenesis and adipogenesis of MSCs by delivering miR155. Besides, miR155 regulated osteogenesis and adipogenesis of MSCs cultured with macrophage-derived apoVs via the SMAD2 signaling pathway.

Conclusions

Macrophage-derived apoVs could regulate the osteogenesis and adipogenesis of MSCs through delivering miR155, which provided novel insights for MSC-mediated tissue engineering.