bluuebunny/crossref_metadata_2025 huggingface dataset:
Changes in serum angiogenic factors among patients with acute pain and subacute pain
Authors: Yang Xuewei , Yuan Chunmei , Wang Huanling , Wang Yunxia , Liu Mei , Li Zongjin , Zhang Jun
Published: July 2022

Screening serum biomarkers for acute and subacute pain is important for precise pain management. This study aimed to examine serum levels of angiogenic factors in patients with acute and subacute pain as potential biomarkers. Serum samples were collected from 12 healthy controls, 20 patients with postherpetic neuralgia (PHN), 4 with low back pain (LBP), and 1 with trigeminal neuralgia (TN). Pain intensity in these patients was evaluated using the visual analog scale (VAS). The serum concentrations of 11 angiogenic biomarkers were examined by Milliplex Map Human Angiogenesis Magnetic Bead Panel 2. The pain assessment from VAS showed that all patients showed moderate and severe pain. Among 11 angiogenic factors, osteopontin (OPN), thrombospondin-2 (TSP-2), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble urokinase-type plasminogen activator receptor (suPAR), and soluble epidermal growth factor receptors (sErbB2) were up-regulated and soluble interleukin-6 receptor α (sIL-6Rα) were down-regulated in patients with pain compared to the healthy participants (all P-values were < 0.005). Moreover, a linear regression model showed that the serum OPN concentration was correlated with pain intensity in patients with PHN (P = 0.03). There was no significant difference between the serum concentration of soluble epidermal growth factor receptors, sErbB3, soluble AXL, tenascin, and soluble neuropilin-1 in patients with acute and subacute pain and that of healthy controls. The results of this study provided new valuable insights into our understanding of angiogenic factors that may contribute to as mechanistic biomarkers of pain, and reveal the pathophysiological mechanism of pain.

Clinical Trial Registration:www.chictr.org.cn, identifier ChiCTR2200061775.
Research on the Mechanism of HRP Relieving IPEC-J2 Cells Immunological Stress Based on Transcriptome Sequencing Analysis
Authors: Li Muyang , Chen Lu , Zhao Yiran , Sun Hui , Zhao Lei
Published: July 2022

Early weaning increased the economic benefits of piglets. However, early weaning damages the intestinal barrier of piglets and causes immunological stress. The mechanism by which Hippophae rhamnoides polysaccharide (HRP) alleviates lipopolysaccharide (LPS)-induced intestinal porcine epithelial cells (IPEC-J2) inflammatory damage was investigated using proteomics in our previous studies. In this study we employed RNA-sequencing (RNA-seq) to determine the level and function of differentially expressed genes (DEGs) and further explore the mechanism of the HRP anti-inflammatory and immune process. The differential expression analysis indicated that 3622, 1216, and 2100 DEGs in the IPEC-J2 cells were identified in C vs. L, L vs. H6-L, and C vs. H6-L, respectively. The Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis foundsix identified pathways related to the immune system. Additionally, we used the Science, Technology, Engineering, and Math (STEM) program to categorize the 3,134 DEGs that were differentially expressed in H2-L, H4-L and H6-L into eight possible expression profiles, in which 612 were clustered into two profiles. The accuracy and consistency of RNA-seq data were validated by the results of qRT-PCR of the nuclear factor of kappa light polypeptide gene enhancer in B-cells 2 (NFKB2), MAP kinase interacting serine/threonine kinase 2 (MKNK2), mitogen-activated protein kinase kinase 1 (MAP2K1), mitogen-activated protein kinase kinase kinase 8 (MAP3K8), Ras-related protein R-Ras (RRAS), TNF receptor-associated factor 1 (TRAF1), NF-kappa-B inhibitor alpha (NFKBIA), interleukin 8 (IL8), tumor necrosis factor, alpha-induced protein 3 (TNFAIP3), and transforming growth factor beta-1 (TGFB1). Transcriptome sequencing also indicated that HRP reduced the expression levels of related DEGs and inhibited the activation of the mitogen-activated protein kinase (MAPK)/nuclear factor kappa-B (NF-κB) signaling pathway. Our findings indicate that the application of HRP in piglet diets during the early weaning period can improve intestinal epithelial function and integrity, and relieve intestinal damage, and improve piglet health.
Differentiation Between Granulomatous Lobular Mastitis and Breast Cancer Using Quantitative Parameters on Contrast-Enhanced Ultrasound
Authors: Yin Liang , Agyekum Enock Adjei , Zhang Qing , Pan Lei , Wu Ting , Xiao Xiudi , Qian Xiao-qin
Published: July 2022

Objective

To investigate the Contrast-enhanced ultrasound (CEUS) imaging characteristics of granulomatous lobular mastitis (GLM) and the value of differentiating GLM from breast cancer.

Materials and methods

The study included 30 women with GLM (mean age 36.7 ± 5 years [SD]) and 58 women with breast cancer (mean age 48. ± 8 years [SD]) who were scheduled for ultrasound-guided tissue biopsy. All patients were evaluated with conventional US and CEUS prior to the biopsy. In both groups, the parameters of the quantitative and qualitative analysis of the CEUS were recorded and compared. The receiver-operating-characteristics curves (ROC) were created. Sensitivity, specificity, cut-off, and area under the curve (AUC) values were calculated.

Results

TTP values in GLM were statistically higher than in breast cancer (mean, 27.63 ± 7.29 vs. 20.10 ± 6.11), but WIS values were lower (mean, 0.16 ± 0.05 vs. 0.28 ± 0.17). Rich vascularity was discovered in 54.45% of breast cancer patients, but only 30.00% of GLM patients had rich vascularity. The AUC for the ROC test was 0.791 and 0.807, respectively. The optimal cut-off value for TTP was 24.5s, and the WIS cut-off value was 0.185dB/s, yielding 73.33% sensitivity, 84.48% specificity, and 86.21% sensitivity, 70% specificity respectively in the diagnosis of GLM. The lesion scores reduced from 4 to 3 with the addition of CEUS for the patients with GLM. However, the scores did not change for the patients with breast cancer.

Conclusion

CEUS could help distinguish GLM from breast cancer by detecting higher TTP and WIS values, potentially influencing clinical decision-making for additional biopsies.
ELOVLs Predict Distinct Prognosis Value and Immunotherapy Efficacy In Patients With Hepatocellular Carcinoma
Authors: Zhang Yu , Pang Shujie , Sun Bo , Zhang Minbo , Jiao Xiaoxiao , Lai Linying , Qian Yiting , Yang Ning , Yang Wenzhuo
Published: July 2022

Background

Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with high prevalence worldwide and poor prognosis. It has been verified that elongation of very-long-chain fatty acids gene family (ELOVLs), a group of genes that responsible for elongation of saturated and polyunsaturated fatty acids, participate in the pathogenesis and development of multiplex disease including cancers. However, the functions and prognosis of ELOVLs in HCC are still indistinguishable.

Methods

First, we searched the mRNA expression and survival data of ELOVLs in patients with HCC via the data of The Cancer Genome Atlas (TCGA). The prognosis value of ELOVLs on HCC was assessed by Kaplan–Meier plotter and Cox regression analysis. reverse transcription quantitative- polymerase chain reaction (RT-qPCR), Western blot (WB), and immunohistochemistry were applied to assess the specific mRNA and protein expression of ELOVLs in HCC clinical specimens of our cohort. Then, the functional enrichment of ELOVL1 especially the pathways relating to the immune was conducted utilizing the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set enrichment analysis (GSEA) analysis. Additionally, TIMER, CIBERSOR, and tumor immune dysfunction and exclusion (TIDE) were employed to evaluate the relationship between ELOVL1 and immune responses. Last, the correlation of ELOVL1 with genome heterogeneity [microsatellite instability (MSI), tumor mutational burden (TMB), mutant-allele tumor heterogeneity (MATH), homologous recombination deficiency (HRD), purity, ploidy, loss of heterozygosity (LOH), and neoantigens] and mutational landscape were also evaluated basing on the date in TCGA.

Results

Significant expression alteration was observed in ELOVLs family at the pan-cancer level. In liver cancer, ELOVL1 and ELOVL3 were strongly associated with poor prognosis of HCC by survival analysis and differential expression analysis. Immunohistochemistry microarray, WB, and RT-qPCR confirmed that ELOVL1 but not ELOVL3 played an important role in HCC. Mechanistically, functional network analysis revealed that ELOVL1 might be involved in the immune response. ELOVL1 could affect immune cell infiltration and immune checkpoint markers such as PD-1 and CTLA4 in HCC. Meanwhile, high expression of ELOVL1 would be insensitive to immunotherapy. Correlation analysis of immunotherapy markers showed that ELOVL1 has been associated with MSI, TMB, and oncogene mutations such as TP53.

Conclusion

ELOVLs play distinct prognostic value in HCC. ELOVL1 could predict the poor prognosis and might be a potential indicator of immunotherapy efficacy in HCC patients.
Influence of Adjuvant Radiotherapy Timing on Survival Outcomes in High-Risk Patients Receiving Neoadjuvant Treatments
Authors: Cao Lu , Xu Cheng , Wang Meng-Di , Qi Wei-Xiang , Cai Gang , Cai Rong , Wang Shu-Bei , Ou Dan , Li Min , Shen Kun-Wei , Chen Jia-Yi
Published: July 2022

Purpose

To determine the relationship between time to radiotherapy (TTR) and survival outcomes in breast cancer (BC) patients treated with neoadjuvant treatments (NATs).

Methods

Continuous non-metastatic BC patients receiving NAT and adjuvant radiotherapy (RT) from 2009 to 2016 were retrospectively reviewed. A multivariable Cox model with restricted cubic splines (RCSs) was used to determine the panoramic relationship between TTR and survival outcomes. Multivariable analysis was used to control for confounding factors between the groups of TTR.

Results

A total of 315 patients were included. The RCS modeling demonstrated a non-linear relationship between TTR and survival outcomes. The lowest risk for distant metastasis-free survival (DMFS) and recurrence-free survival (RFS) was observed at the TTR of 12 weeks, and the lowest risk of BC-specific survival (BCSS) at 10 weeks. TTR was accordingly transformed into categorical variables as ≤10, 11–20, and >20 weeks. Multivariable analysis revealed that the TTR of ≤10 weeks was an independent prognostic factor for worse DMFS (HR = 2.294, 95% CI 1.079–4.881) and RFS (HR = 2.126, 95% CI 1.038–4.356) compared with the TTR of 10–20 weeks, while the is no difference in DMFS, RFS, and BCSS between TTR >20 weeks and TTR of 10–20 weeks.

Conclusion

There exists a non-linear relationship between TTR after surgery and survival outcomes in patients treated with NAT. Early initiation of RT following surgery does not seem to be associated with a better therapeutic outcome. A relatively flexible recommendation of TTR could be adopted in clinical practice.
Ultrasound Image Classification of Thyroid Nodules Based on Deep Learning
Authors: Yang Jingya , Shi Xiaoli , Wang Bing , Qiu Wenjing , Tian Geng , Wang Xudong , Wang Peizhen , Yang Jiasheng
Published: July 2022

A thyroid nodule, which is defined as abnormal growth of thyroid cells, indicates excessive iodine intake, thyroid degeneration, inflammation, and other diseases. Although thyroid nodules are always non-malignant, the malignancy likelihood of a thyroid nodule grows steadily every year. In order to reduce the burden on doctors and avoid unnecessary fine needle aspiration (FNA) and surgical resection, various studies have been done to diagnose thyroid nodules through deep-learning-based image recognition analysis. In this study, to predict the benign and malignant thyroid nodules accurately, a novel deep learning framework is proposed. Five hundred eight ultrasound images were collected from the Third Hospital of Hebei Medical University in China for model training and validation. First, a ResNet18 model, pretrained on ImageNet, was trained by an ultrasound image dataset, and a random sampling of training dataset was applied 10 times to avoid accidental errors. The results show that our model has a good performance, the average area under curve (AUC) of 10 times is 0.997, the average accuracy is 0.984, the average recall is 0.978, the average precision is 0.939, and the average F1 score is 0.957. Second, Gradient-weighted Class Activation Mapping (Grad-CAM) was proposed to highlight sensitive regions in an ultrasound image during the learning process. Grad-CAM is able to extract the sensitive regions and analyze their shape features. Based on the results, there are obvious differences between benign and malignant thyroid nodules; therefore, shape features of the sensitive regions are helpful in diagnosis to a great extent. Overall, the proposed model demonstrated the feasibility of employing deep learning and ultrasound images to estimate benign and malignant thyroid nodules.
Targeting strategies in the treatment of fumarate hydratase deficient renal cell carcinoma
Authors: Lindner Andrea Katharina , Tulchiner Gennadi , Seeber Andreas , Siska Peter J. , Thurnher Martin , Pichler Renate
Published: July 2022

Fumarate hydratase (FH) - deficient renal cell carcinoma (FHdRCC) is a rare aggressive subtype of RCC caused by a germline or sporadic loss-of-function mutation in the FH gene. Here, we summarize how FH deficiency results in the accumulation of fumarate, which in turn leads to activation of hypoxia-inducible factor (HIF) through inhibition of prolyl hydroxylases. HIF promotes tumorigenesis by orchestrating a metabolic switch to glycolysis even under normoxia, a phenomenon well-known as the Warburg effect. HIF activates the transcription of many genes, including vascular endothelial growth factor (VEGF). Crosstalk between HIF and epidermal growth factor receptor (EGFR) has also been described as a tumor-promoting mechanism. In this review we discuss therapeutic options for FHdRCC with a focus on anti-angiogenesis and EGFR-blockade. We also address potential targets that arise within the metabolic escape routes taken by FH-deficient cells for cell growth and survival.
Prediction of clinically significant prostate cancer with a multimodal MRI-based radiomics nomogram
Authors: Jing Guodong , Xing Pengyi , Li Zhihui , Ma Xiaolu , Lu Haidi , Shao Chengwei , Lu Yong , Lu Jianping , Shen Fu
Published: July 2022

Objective

To develop and validate a multimodal MRI-based radiomics nomogram for predicting clinically significant prostate cancer (CS-PCa).

Methods

Patients who underwent radical prostatectomy with pre-biopsy prostate MRI in three different centers were assessed retrospectively. Totally 141 and 60 cases were included in the training and test sets in cohort 1, respectively. Then, 66 and 122 cases were enrolled in cohorts 2 and 3, as external validation sets 1 and 2, respectively. Two different manual segmentation methods were established, including lesion segmentation and whole prostate segmentation on T2WI and DWI scans, respectively. Radiomics features were obtained from the different segmentation methods and selected to construct a radiomics signature. The final nomogram was employed for assessing CS-PCa, combining radiomics signature and PI-RADS. Diagnostic performance was determined by receiver operating characteristic (ROC) curve analysis, net reclassification improvement (NRI) and decision curve analysis (DCA).

Results

Ten features associated with CS-PCa were selected from the model integrating whole prostate (T2WI) + lesion (DWI) for radiomics signature development. The nomogram that combined the radiomics signature with PI-RADS outperformed the subjective evaluation alone according to ROC analysis in all datasets (all p<0.05). NRI and DCA confirmed that the developed nomogram had an improved performance in predicting CS-PCa.

Conclusions

The established nomogram combining a biparametric MRI-based radiomics signature and PI-RADS could be utilized for noninvasive and accurate prediction of CS-PCa.
TOP2A correlates with poor prognosis and affects radioresistance of medulloblastoma
Authors: Zhang Yufeng , Yang Haiyan , Wang Liwen , Zhou Huandi , Zhang Ge , Xiao Zhiqing , Xue Xiaoying
Published: July 2022

Radiotherapy remains the standard treatment for medulloblastoma (MB), and the radioresistance contributes to tumor recurrence and poor clinical outcomes. Nuclear DNA topoisomerase II-alpha (TOP2A) is a key catalytic enzyme that initiates DNA replication, and studies have shown that TOP2A is closely related to the therapeutic effects of radiation. In this study, we found that TOP2A was significantly upregulated in MB, and high expression of TOP2A related to poor prognosis of MB patients. Knockdown of TOP2A inhibited MB cell proliferation, migration, and invasion, whereas overexpression of TOP2A enhanced the proliferative and invasive ability of MB cells. Moreover, si-TOP2A transfection in combination with irradiation (IR) significantly reduced the tumorigenicity of MB cells, compared with those transfected with si-TOP2A alone. Cell survival curve analysis revealed that the survival fraction of MB cells was significantly reduced upon TOP2A downregulation and that si-TOP2A-transfected cells had decreased D0, Dq, and SF2 values, indicating that TOP2A knockdown suppresses the resistance to radiotherapy in MB cells. In addition, western blot analysis demonstrated that the activity of Wnt/β-catenin signaling pathway was inhibited after TOP2A downregulation alone or in combination with IR treatment, whereas overexpression of TOP2A exhibited the opposite effects. Gene set enrichment analysis also revealed that Wnt/β-catenin signaling pathway is enriched in TOP2A high-expression phenotypes. Collectively, these data indicate that high expression of TOP2A leads to poor prognosis of MB, and downregulation of TOP2A inhibits the malignant behaviour as well as the radioresistance of MB cells. The Wnt/β-catenin signaling pathway may be involved in the molecular mechanisms of TOP2A mediated reduced tumorigenicity and radioresistance of MB cells.
Clinical potential of the Hippo-YAP pathway in bladder cancer
Authors: Cheng Xin , Lou Kecheng , Ding Liang , Zou Xiaofeng , Huang Ruohui , Xu Gang , Zou Junrong , Zhang Guoxi
Published: July 2022

Bladder cancer (BC) is one of the world’s most frequent cancers. Surgery coupled with adjuvant platinum-based chemotherapy is the current standard of therapy for BC. However, a high proportion of patients progressed to chemotherapy-resistant or even neoplasm recurrence. Hence, identifying novel treatment targets is critical for clinical treatment. Current studies indicated that the Hippo-YAP pathway plays a crucial in regulating the survival of cancer stem cells (CSCs), which is related to the progression and reoccurrence of a variety of cancers. In this review, we summarize the evidence that Hippo-YAP mediates the occurrence, progression and chemotherapy resistance in BC, as well as the role of the Hippo-YAP pathway in regulating bladder cancer stem-like cells (BCSCs). Finally, the clinical potential of Hippo-YAP in the treatment of BC was prospected.
Immune Checkpoint Inhibitors in the Treatment of Patients With Cancer and Preexisting Psoriasis: A Systematic Review and Meta-Analysis of Observational Studies
Authors: Yu Yixuan , Zhou Yang , Zhang Xu , Tan Kexin , Zheng Jiabin , Li Jia , Cui Huijuan
Published: July 2022

Background

Immunotherapies represented by immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment. A large part of the population has both cancer and psoriasis but is usually excluded from ICI clinical trials because of the dysregulated activation of the immune system. This is the first study to evaluate the safety and efficacy of ICI therapy in patients with cancer and preexisting psoriasis.

Methods

PubMed, EMBASE, Cochrane, and MEDLINE databases were searched from inception through February 2022. Observational studies on patients with cancer and confirmed psoriasis before ICI initiation were included. Outcomes included the incidence of psoriasis flares, de novo immune-related adverse events (irAEs), discontinuation rate due to flare/de novo irAEs, and efficacy of ICI therapy. Clinical manifestations, management, and outcomes for adverse events (AEs) were systematically reviewed. All pooled analyses were based on a random-effects model using Stata software. Meta-regression and subgroup analyses were performed to identify sources of heterogeneity.

Results

Twelve studies involving 191 patients were included. The pooled incidence of psoriasis flares was 45.0% (95% CI: 31.1%-58.9%, I2 = 71.7%) and 44.9% (95% CI: 29.0%–60.7%, I2 = 71.8%) for de novo irAEs. The tumor type, psoriasis subtype, ICI class, and country were the main sources of heterogeneity. Grade 3–4 flares occurred in 10.8% (95% CI: 5.3%–16.3%) of patients, and about 16.6% (95% CI: 10.7%–22.5%) of patients experienced grade 3–4 de novo irAEs. The estimated incidence of ICI discontinuation due to AE was 18.5% (95% CI: 6.1%–30.8%, I2 = 68.7%). The median times to develop flare and de novo irAEs were 44 and 63 days, respectively. Endocrinopathies and colitis were the most common de novo irAEs. Conventional therapy is effective for most AEs. The estimated objective response rate (ORR) of ICIs was 38.1% (95% CI: 11.8%–64.3%, I2 = 81.7%), and the disease control rate (DCR) was 64.5% (95% CI: 55.3%–73.8%, I2 = 0).

Conclusions

The flare of patients with cancer and preexisting psoriasis treated with ICI therapy is frequent, but the incidence of de novo irAEs and the efficacy of ICI therapy are comparable to those of the general population. Most AEs are mild and manageable with conventional therapy, which required discontinuation of ICI therapy in 18.5%.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022320646
Effects of glycolysis and polyamine predation on intestinal epithelial barrier in colorectal cancer
Authors: Wang Yu , He Huan , Chen Jingwen , Song Zijing , Pan Xuediao , Lan Tian , Wang Guixiang
Published: July 2022

Colorectal cancer (CRC) is the second most lethal cancer and the third most common cancer in the world, and its prognosis is severely affected by high intestinal mucosal permeability and increasing tumor burden. Studies have shown that the expression of hypoxia induce factor 1α (HIF1α) is up-regulated in a variety of tumor tissues, which is related to multiple metabolic reprogramming of tumor cells. However, the role of HIF1α in CRC tumor growth, tumor polyamine metabolism and intestinal mucosal barrier damage has not been studied. Here, we constructed different types of CRC tumor-bearing mice models by inoculating HCT116 cells with different levels of HIF1α expression (knockdown, wild type, overexpression) in the armpits of mice to explore the upstream and downstream regulators of HIF1α, the effects of HIF1α on the growth of CRC, and the CRC polyamine metabolism and its effect on the intestinal mucosal barrier. We found that with the increase of HIF1 gene expression, tumor growth was promoted and intestinal mucosal permeability was increased. The expression of glycolysis-related proteins was up-regulated, the rate-limiting enzyme ODC of polyamine synthesis was decreased, and the transfer protein of polyamine was increased. HPLC showed that the polyamine content in the tumor tissue of the overexpression group HIF1α OE was higher than that of the wild group HIF1α (+/+), and higher than that of the knockdown group HIF1α (-/-), but the content of polyamines in intestinal mucosa was the opposite. After supplementation of exogenous polyamines, the content of polyamines in intestinal mucosa and tumor tissue increased, and the damage of intestinal mucosa was alleviated. In conclusion, upon activation of the MYC/HIF1 pathway, tumor glycolysis is enhanced, tumors require more energy and endogenous polyamine synthesis is reduced. Therefore, in order to meet its growth needs, tumor will rob polyamines in the intestinal mucosa, resulting in intestinal mucosal epithelial barrier dysfunction.
The Role of Imaging Biomarkers to Guide Pharmacological Interventions Targeting Tumor Hypoxia
Authors: Gallez Bernard
Published: July 2022

Hypoxia is a common feature of solid tumors that contributes to angiogenesis, invasiveness, metastasis, altered metabolism and genomic instability. As hypoxia is a major actor in tumor progression and resistance to radiotherapy, chemotherapy and immunotherapy, multiple approaches have emerged to target tumor hypoxia. It includes among others pharmacological interventions designed to alleviate tumor hypoxia at the time of radiation therapy, prodrugs that are selectively activated in hypoxic cells or inhibitors of molecular targets involved in hypoxic cell survival (i.e., hypoxia inducible factors HIFs, PI3K/AKT/mTOR pathway, unfolded protein response). While numerous strategies were successful in pre-clinical models, their translation in the clinical practice has been disappointing so far. This therapeutic failure often results from the absence of appropriate stratification of patients that could benefit from targeted interventions. Companion diagnostics may help at different levels of the research and development, and in matching a patient to a specific intervention targeting hypoxia. In this review, we discuss the relative merits of the existing hypoxia biomarkers, their current status and the challenges for their future validation as companion diagnostics adapted to the nature of the intervention.
Photodynamic Effects of Thuja occidentalis on Lung Cancer Cells
Authors: Loonat Ayesha , Chandran Rahul , Pellow Janice , Abrahamse Heidi
Published: July 2022

The global incidence and mortality rates resulting from lung cancer encapsulate a need to identify more effective treatment protocols. Photodynamic therapy (PDT) and homeopathy offer possible anticancer therapies as part of a multi-disciplinary approach. Studies have identified the anticancer effects of Thuja occidentalis L. plant extracts. The aim of this study was to investigate the effects of Thuja occidentalis (TO) homeopathic mother tincture and TO mediated PDT (TO-PDT) on A549 lung cancer cells. Commercially available A549 cells were pre-treated with TO, or laser irradiation at 660 nm, or the combined treatment (TO-PDT). Cells were analyzed morphologically by inverted light microscopy and Hoechst stain; and biochemically by lactate dehydrogenase (LDH), adenosine triphosphate (ATP), and trypan blue assays. Cells treated with TO and TO-PDT demonstrated morphological changes in the cell and cell nuclei indicative of cell death. These groups exhibited a dose dependent increase in LDH release and a decrease in ATP levels and cell viability indicating its cytotoxic and antiproliferative potential. Furthermore, at the same doses, TO when photoactivated in PDT induced enhanced anticancer responses thereby surpassing the effects of treatment with the tincture alone. Results demonstrate how the direct cytotoxic effects of TO can be improved when administered as a photosensitizer in PDT to promote cancer cell death.
Alternative adenosine Receptor activation: The netrin-Adora2b link
Authors: Yuan Xiaoyi , Mills Tingting , Doursout Marie-Francoise , Evans Scott E. , Vidal Melo Marcos F. , Eltzschig Holger K.
Published: July 2022

During hypoxia or inflammation, extracellular adenosine levels are elevated. Studies using pharmacologic approaches or genetic animal models pertinent to extracellular adenosine signaling implicate this pathway in attenuating hypoxia-associated inflammation. There are four distinct adenosine receptors. Of these, it is not surprising that the Adora2b adenosine receptor functions as an endogenous feedback loop to control hypoxia-associated inflammation. First, Adora2b activation requires higher adenosine concentrations compared to other adenosine receptors, similar to those achieved during hypoxic inflammation. Second, Adora2b is transcriptionally induced during hypoxia or inflammation by hypoxia-inducible transcription factor HIF1A. Studies seeking an alternative adenosine receptor activation mechanism have linked netrin-1 with Adora2b. Netrin-1 was originally discovered as a neuronal guidance molecule but also functions as an immune-modulatory signaling molecule. Similar to Adora2b, netrin-1 is induced by HIF1A, and has been shown to enhance Adora2b signaling. Studies of acute respiratory distress syndrome (ARDS), intestinal inflammation, myocardial or hepatic ischemia and reperfusion implicate the netrin-Adora2b link in tissue protection. In this review, we will discuss the potential molecular linkage between netrin-1 and Adora2b, and explore studies demonstrating interactions between netrin-1 and Adora2b in attenuating tissue inflammation.
Stick-Slip Dynamics in a Granular Material With Varying Grain Angularity
Authors: Kozlowski Ryan , Zheng Hu , Daniels Karen E. , Socolar Joshua E. S.
Published: July 2022

Experiments, simulations, and theoretical treatments of granular materials typically feature circular or elliptical grains. However, grains found in natural systems often have flat faces that introduce local rotational constraints; these rotational constraints have been shown to affect, for example, the jamming transition, discontinuous shear thickening, and ordered states in colloids and thermalized grains. In this work, we experimentally investigate the effects of grain angularity on stick-slip dynamics. A weighted slider is pulled by a spring over a gravity-packed granular bed composed of polygonal grains with varying angularity. We find that packings of triangular or square grains have higher shear strengths than packings of pentagons, hexagons, heptagons, or disks. Additionally, as the number of sides increases, sticking periods, during which the slider remains motionless while the spring force on it increases, become shorter on average, with the material yielding at smaller applied stresses. Lastly, we find that dilation of the medium during sticking periods tends to be larger for grains with higher angularity, in part because of the presence of stilt-like columnar structures that prop the slider up. We report on measurements of the pulling force on the slider, particle dynamics during slip events, and properties of force-bearing contact networks identified via photoelasticity. Our findings indicate that high angularity of grains (pentagons, squares, triangles) leads to differences in grain-scale flow and macroscopic stick-slip dynamics of bulk granular materials. Our experiments also indicate a continuous change in dynamics with decreasing angularity as the circular grain limit is approached.
Study on Proteomics-Based Aortic Dissection Molecular Markers Using iTRAQ Combined With Label Free Techniques
Authors: Deng Ting , Liu Yongguang , Gael Akindavyi , Fu Xiaohua , Deng Xiaofang , Liu Yunfeng , Wu Yizhang , Wu Yingzhi , Wang Huimin , Deng Yuying , Lai Jun , Fu Qiang
Published: July 2022

Background: Aortic dissection refers to the separation of aortic media and extension along the long axis to form the true and false chambers of the aortic wall. 65–70% of the patients died of cardiac tamponade, arrhythmia, dissection rupture, etc. At present, echocardiography, computed tomography angiography (CTA), etc. are the main diagnosis tools for aortic dissection. To date, there is no rapid serum molecular marker that can be used for differential diagnosis and risk assessment.

Objectives: To screen serum molecular markers systematically amid aortic dissection and acute coronary syndrome and to preliminarily identify the pathogenesis of acute aortic dissection.

Methods: Related disputes cases of all hospitals were statistically analyzed for the AAD medical disputes ratio, early death ratio and misdiagnosis ratio from the database of Guangdong Province Medical Disputes Coordination Committee from 2013 to 2017. Serum and Aortic tissues samples were respectively quantified by iTRAQ and label-free analysis, further validated by ELISA and protein verified by immunofluorescence and Western blot from AAD and control patients enrolled from the Zhujiang Hospital of Southern Medical University and Guangdong Province people's Hospital from 2016 to 2018.

Results: AAD cases ratio accounted for 15.29% in all 150 cardiovascular disputes, 59.26% in all cardiovascular death less than 24 h, and 88.89% in the patients who remained undiagnosed at the time of death, 84 proteins (66 and 18 upregulated and downregulated, respectively) were identified by iTRAQ and 16 proteins (9 and 7 upregulated and downregulated, respectively) by Label-free. Nine proteins (Lumican, FGL1, PI16, MMP9, FBN1, MMP2, VWF, MMRN1, and PF4) related to the pathogenesis of aortic dissection were identified by David /Ease and String techniques as candidate biomarkers for verification test. Four proteins (Lumican, FGL1, PI16, and MMP9) were found to be statistically different after ELISA verification. The expression of FGL1, PI16, and MMP9 proteins was pathologically significantly increased except for Lumican. Histologically, TGF-β1, α-SMA, and Collagen1 were also significantly higher in the aortic group.

Conclusion: Lumican, FGL1, PI16, and MMP9 may be potential biomarkers in AAD patients, and the Lumican-mediated TGF-β1 pathway is likely to be involved in the pathogenesis of aortic dissection.
How Does Our Knowledge on the Na+/H+ Exchanger NHE1 Obtained by Biochemical and Molecular Analyses Keep up With Its Recent Structure Determination?
Authors: Poet Mallorie , Doyen Denis , Van Obberghen Emmanuel , Jarretou Gisèle , Bouret Yann , Counillon Laurent
Published: July 2022

Na+/H+ exchangers are membrane transporters conserved in all living systems and therefore are assumed to be amongst the most ancestral molecular devices that equipped the first protocells. Following the cloning and sequencing of its gene, the mammalian NHE1, that regulates pH and volume in all cells, has been thoroughly scrutinized by molecular and biochemical analyses. Those gave a series of crucial clues concerning its topology, dimeric organization, pharmacological profile, regulation, and the role of key amino acids. Recently thanks to cryogenic Electron Microscopy (Cryo-EM) the long-awaited molecular structures have been revealed. With this information in mind we will challenge the robustness of the earlier conclusions and highlight how the new information enriches our understanding of this key cellular player. At the mechanistic level, we will pinpoint how the NHE1 3D structures reveal that the previously identified amino acids and regions are organized to coordinate transported cations, and shape the allosteric transition that makes NHE1 able to sense intracellular pH and be regulated by signaling pathways.
Evidence that resistin acts on the mechanical responses of the mouse gastric fundus
Authors: Idrizaj Eglantina , Garella Rachele , Nistri Silvia , Squecco Roberta , Baccari Maria Caterina
Published: July 2022

Resistin, among its several actions, has been reported to exert central anorexigenic effects in rodents. Some adipokines which centrally modulate food intake have also been reported to affect the activity of gastric smooth muscle, whose motor responses represent a source of peripheral signals implicated in the control of the hunger-satiety cycle through the gut-brain axis. On this basis, in the present experiments, we investigated whether resistin too could affect the mechanical responses in the mouse longitudinal gastric fundal strips. Electrical field stimulation (EFS) elicited tetrodotoxin- and atropine-sensitive contractile responses. Resistin reduced the amplitude of the EFS-induced contractile responses. This effect was no longer detected in the presence of L-NNA, a nitric oxide (NO) synthesis inhibitor. Resistin did not influence the direct muscular response to methacholine. In the presence of carbachol and guanethidine, EFS elicited inhibitory responses whose amplitude was increased by resistin. L-NNA abolished the inhibitory responses evoked by EFS, indicating their nitrergic nature. In the presence of L-NNA, resistin did not have any effect on the EFS-evoked inhibitory responses. Western blot and immunofluorescence analysis revealed a significant increase in neuronal nitric oxide synthase (nNOS) expression in neurons of the myenteric plexus following resistin exposure. In conclusion, the present results offer the first evidence that resistin acts on the gastric fundus, likely through a modulatory action on the nitrergic neurotransmission.
The Quantitative Associations Between Near Infrared Spectroscopic Cerebrovascular Metrics and Cerebral Blood Flow: A Scoping Review of the Human and Animal Literature
Authors: Gomez Alwyn , Sainbhi Amanjyot Singh , Froese Logan , Batson Carleen , Slack Trevor , Stein Kevin Y. , Cordingley Dean M. , Mathieu Francois , Zeiler Frederick A.
Published: July 2022

Cerebral blood flow (CBF) is an important physiologic parameter that is vital for proper cerebral function and recovery. Current widely accepted methods of measuring CBF are cumbersome, invasive, or have poor spatial or temporal resolution. Near infrared spectroscopy (NIRS) based measures of cerebrovascular physiology may provide a means of non-invasively, topographically, and continuously measuring CBF. We performed a systematically conducted scoping review of the available literature examining the quantitative relationship between NIRS-based cerebrovascular metrics and CBF. We found that continuous-wave NIRS (CW-NIRS) was the most examined modality with dynamic contrast enhanced NIRS (DCE-NIRS) being the next most common. Fewer studies assessed diffuse correlation spectroscopy (DCS) and frequency resolved NIRS (FR-NIRS). We did not find studies examining the relationship between time-resolved NIRS (TR-NIRS) based metrics and CBF. Studies were most frequently conducted in humans and animal studies mostly utilized large animal models. The identified studies almost exclusively used a Pearson correlation analysis. Much of the literature supported a positive linear relationship between changes in CW-NIRS based metrics, particularly regional cerebral oxygen saturation (rSO2), and changes in CBF. Linear relationships were also identified between other NIRS based modalities and CBF, however, further validation is needed.
Highly Overexpressed AtC3H18 Impairs Microgametogenesis via Promoting the Continuous Assembly of mRNP Granules
Authors: Xu Liai , Liu Tingting , Xiong Xingpeng , Shen Xiuping , Huang Li , Yu Youjian , Cao Jiashu
Published: July 2022

Plant CCCH zinc-finger proteins form a large family of regulatory proteins function in many aspects of plant growth, development and environmental responses. Despite increasing reports indicate that many CCCH zinc-finger proteins exhibit similar subcellular localization of being localized in cytoplasmic foci, the underlying molecular mechanism and the connection between this specific localization pattern and protein functions remain largely elusive. Here, we identified another cytoplasmic foci-localized CCCH zinc-finger protein, AtC3H18, in Arabidopsis thaliana. AtC3H18 is predominantly expressed in developing pollen during microgametogenesis. Although atc3h18 mutants did not show any abnormal phenotype, possibly due to redundant gene(s), aberrant AtC3H18 expression levels caused by overexpression resulted in the assembly of AtC3H18-positive granules in a dose-dependent manner, which in turn led to male sterility phenotype, highlighting the importance of fine-tuned AtC3H18 expression. Further analyzes demonstrated that AtC3H18-positive granules are messenger ribonucleoprotein (mRNP) granules, since they can exhibit liquid-like physical properties, and are associated with another two mRNP granules known as processing bodies (PBs) and stress granules (SGs), reservoirs of translationally inhibited mRNAs. Moreover, the assembly of AtC3H18-positive granules depends on mRNA availability. Combined with our previous findings on the AtC3H18 homologous genes in Brassica campestris, we concluded that appropriate expression level of AtC3H18 during microgametogenesis is essential for normal pollen development, and we also speculated that AtC3H18 may act as a key component of mRNP granules to modulate pollen mRNAs by regulating the assembly/disassembly of mRNP granules, thereby affecting pollen development.
Glycogen synthase kinases in model and crop plants – From negative regulators of brassinosteroid signaling to multifaceted hubs of various signaling pathways and modulators of plant reproduction and yield
Authors: Zolkiewicz Karolina , Gruszka Damian
Published: July 2022

Glycogen synthase kinases, also known as SHAGGY-like Kinases (GSKs/SKs), are highly conserved serine/threonine protein kinases present both in animals and plants. Plant genomes contain multiple homologs of theGSK3genes which participate in various biological processes. Plant GSKs/SKs, and their best known representative inArabidopsis thaliana –Brassinosteroid Insentisive2 (BIN2/SK21) in particular, were first identified as components of the brassinosteroid (BR) signaling pathway. As phytohormones, BRs regulate a wide range of physiological processes in plants – from germination, cell division, elongation and differentiation to leaf senescence, and response to environmental stresses. The GSKs/SKs proteins belong to a group of several highly conserved components of the BR signaling which evolved early during evolution of this molecular relay. However, recent reports indicated that the GSKs/SKs proteins are also implicated in signaling pathways of other phytohormones and stress-response processes. As a consequence, the GSKs/SKs proteins became hubs of various signaling pathways and modulators of plant development and reproduction. Thus, it is very important to understand molecular mechanisms regulating activity of the GSKs/SKs proteins, but also to get insights into role of the GSKs/SKs proteins in modulation of stability and activity of various substrate proteins which participate in the numerous signaling pathways. Although elucidation of these aspects is still in progress, this review presents a comprehensive and detailed description of these processes and their implications for regulation of development, stress response, and reproduction of model and crop species. The GSKs/SKs proteins and their activity are modulated through phosphorylation and de-phosphorylation reactions which are regulated by various proteins. Importantly, both phosphorylations and de-phosphorylations may have positive and negative effects on the activity of the GSKs/SKs proteins. Additionally, the activity of the GSKs/SKs proteins is positively regulated by reactive oxygen species, whereas it is negatively regulated through ubiquitylation, deacetylation, and nitric oxide-mediated nitrosylation. On the other hand, the GSKs/SKs proteins interact with proteins representing various signaling pathways, and on the basis of the complicated network of interactions the GSKs/SKs proteins differentially regulate various physiological, developmental, stress response, and yield-related processes.
When Employees Experience Low Levels of Job Autonomy, Fair Procedures Buffer Unfair Outcomes
Authors: Versteegt Lisanne , van Dijke Marius , van Ruysseveldt Joris , van den Bos Kees
Published: July 2022

Organizations play a key role in maintaining employee wellbeing. Some research suggests that one way to protect employee wellbeing is to treat them fairly (procedural justice), especially when fair job outcomes (distributive justice) cannot be ensured. Yet, previous studies have not consistently found this interaction effect between distributive and procedural justice. This study investigates job autonomy as a boundary condition to the Distributive Justice × Procedural Justice effect on wellbeing outcomes. To test our hypothesized three-way interaction between distributive justice, procedural justice, and job autonomy, we collected cross-sectional data among Dutch employees in two studies. We used validated self-report measures of our core constructs to test our hypothesis on two employee wellbeing indicators: job satisfaction and emotional exhaustion. Results show a significant three-way interaction effect on both job satisfaction and emotional exhaustion in Study 1 (N = 411), and a significant three-way interaction effect on emotional exhaustion in Study 2 (N = 1117). Simple slopes analyses of the significant three-way interactions showed that distributive justice and procedural justice interact to predict wellbeing outcomes among employees with low job autonomy. Among employees with high job autonomy, distributive justice and procedural justice do not interact to predict wellbeing. The results contribute to the employee wellbeing literature by showing that job autonomy is a boundary condition to the Distributive Justice × Procedural Justice effect on wellbeing outcomes. We discuss other implications of our findings for the workplace and the ramifications for employees with low and high job autonomy.
The influence of ceremonial settings on mystical and challenging experiences occasioned by ayahuasca: A survey among ritualistic and religious ayahuasca users
Authors: Pontual Alexandre Augusto de Deus , Tófoli Luís Fernando , Corradi-Webster Clarissa Mendonça , van Oorsouw Kim , Delgado Alicia Raquel Osuna , Ramaekers Johannes G.
Published: July 2022

Recent studies have recognized the importance of non-pharmacological factors such as setting to induce or promote mystical experiences or challenging experiences among ayahuasca users. This study aimed to evaluate the association between the setting in which ayahuasca is consumed and the intensity of mystical and challenging experiences considering three ayahuasca using traditions (União do Vegetal, Santo Daime and neo-shamanic groups). A cross-sectional analysis was performed on survey data collected online from 2,751 participants. The Setting Questionnaire for the Ayahuasca Experience (SQAE) was used to evaluate six dimensions of the setting characteristics. The Mystical Experience Questionnaire (MEQ) and the Challenging Experience Questionnaire (CEQ) were used to quantify the psychedelic experience. Ratings on every SQAE setting dimension were negatively correlated with ratings of the CEQ (r values between 0.21 and 0.36) for all ayahuasca using traditions. Regression analysis revealed that ratings on four SQAE dimensions (Social, Comfort, Infrastructure and Decoration) explained 41% of the variance in CEQ ratings. Associations between SQAE and MEQ ratings were relatively weak and confined to the dimensions Leadership and Comfort, explaining 14% of the variance in MEQ ratings. Ratings of Social context were higher among members of União do Vegetal compared to Santo Daime and neo-shamanic members. Ratings of Infrastructure, Comfort and Decoration were more consistently correlated with MEQ in the neoshamanic tradition compared to the other traditions. This study shows that the setting is an important moderator of a challenging experience under ayahuasca. Maximizing the quality of the setting in which ayahuasca is taken will reduce the chance of a challenging experience while contributing positively to a mystical experience. The present findings can be considered when designing rituals and the (social) environment of ayahuasca ceremonies, and indicate that the SQAE questionnaire can be employed to monitor the influence of ceremonial settings on the ayahuasca experience.