bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between DRD2 and DRD4 Polymorphisms and Eating Disorders in an Italian Population
Authors: Ceccarini Maria Rachele , Fittipaldi Simona , Ciccacci Cinzia , Granese Erika , Centofanti Federica , Dalla Ragione Laura , Bertelli Matteo , Beccari Tommaso , Botta Annalisa
Published: March 2022

Anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED) are the three most common eating disorders (EDs). Their etiopathogenesis is multifactorial where both the environmental and genetic factors contribute to the disease outcome and severity. Several polymorphisms in genes involved in the dopaminergic pathways seem to be relevant in the susceptibility to EDs, but their role has not been fully elucidated yet. In this study, we have analyzed the association between selected common polymorphisms in the DRD2 and DRD4 genes in a large cohort of Italian patients affected by AN (n = 332), BN (n = 122), and BED (n = 132) compared to healthy controls (CTRs) (n = 172). Allelic and genotypic frequencies have been also correlated with the main psychopathological and clinical comorbidities often observed in patients. Our results showed significant associations of the DRD2-rs6277 single nucleotide polymorphism (SNP) with AN and BN, of the DRD4-rs936461 SNP with BN and BED and of DRD4 120-bp tandem repeat (TR) polymorphism (SS plus LS genotypes) with BED susceptibility. Moreover, genotyping of DRD4 48-bp variable number TR (VNTR) identified the presence of ≥7R alleles as risk factors to develop each type of EDs. The study also showed that ED subjects with a history of drugs abuse were characterized by a significantly higher frequency of the DRD4 rs1800955 TT genotype and DRD4 120-bp TR short-allele. Our findings suggest that specific combinations of variants in the DRD2 and DRD4 genes are predisposing factors not only for EDs but also for some psychopathological features often coupled specifically to AN, BN, and BED. Further functional research studies are needed to better clarify the complex role of these proteins and to develop novel therapeutic compounds based on dopamine modulation.
Comprehensive Transcriptome Analysis Reveals the Role of lncRNA in Fatty Acid Metabolism in the Longissimus Thoracis Muscle of Tibetan Sheep at Different Ages
Authors: Bao Gaoliang , Li Shaobin , Zhao Fangfang , Wang Jiqing , Liu Xiu , Hu Jiang , Shi Bingang , Wen Yuliang , Zhao Li , Luo Yuzhu
Published: March 2022

Long noncoding RNA (lncRNA) plays an important regulatory role in mammalian adipogenesis and lipid metabolism. However, their function in the longissimus thoracis (LT) muscle of fatty acid metabolism of Tibetan sheep remains undefined. In this study, fatty acid and fat content in LT muscle of Tibetan sheep were determined, and RNA sequencing was performed to reveal the temporal regularity of lncRNA expression and the effect of lncRNA-miRNA-mRNA ceRNA regulatory network on lipid metabolism of LT muscle in Tibetan sheep at four growth stages (4-month-old, 4 m; 1.5-year-old, 1.5 y; 3.5-year-old, 3.5 y; 6-year-old, 6 y). The results indicated that the intramuscular fat (IMF) content was highest at 1.5 y. Moreover, the monounsaturated fatty acid (MUFA) content in 1.5 y of Tibetan sheep is significantly higher than those of the other groups (P < 0.05), and it was also rich in a variety of polyunsaturated fatty acids (PUFA). A total of 360 differentially expressed lncRNAs (DE lncRNAs) were identified from contiguous period transcriptome comparative groups of 4 m vs. 1.5 y, 1.5 y vs. 3.5 y, 3.5 y vs. 6 y, and 4 m vs. 6 y, respectively. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis found that the target genes in lncRNA trans-mRNA were significantly related to the protein digestion, absorption, and fatty acid biosynthesis pathways (P < 0.05), which demonstrated that DE lncRNA trans-regulated the target genes, and further regulated the growth and development of the LT muscle and intramuscular fatty acid metabolism in Tibetan sheep. We further analyzed the role of the lncRNA-miRNA-mRNA regulatory network in the lipid metabolism of Tibetan sheep. Additionally, GPD2, LIPE (lipase E hormone-sensitive enzyme), TFDP2, CPT1A, ACACB, ADIPOQ, and other mRNA related to fatty acid and lipid metabolism and the corresponding lncRNA-miRNA regulatory pairs were identified. The enrichment analysis of mRNA in the regulatory network found that the AMPK signaling pathway was the most significantly enriched (P = 0.0000112361). Comprehensive transcriptome analysis found that the LIPE, ADIPOQ, ACACB, and CPT1A that were regulated by lncRNA might change the formation of energy metabolism in Tibetan sheep muscle through the AMPK signaling pathway, and oxidized muscle fibers are transformed into glycolytic muscle fibers, reduced IMF content, and the fatty acid profile also changed.
Effectiveness and Cost-Utility Analysis of Different Doses of Irinotecan Plus Bevacizumab in Patients With Metastatic Colorectal Cancer: A Long-Term and Prospective Cohort Study
Authors: Shi Hon-Yi , Chen Yen-Cheng , Huang Ching-Wen , Li Ching-Chun , Su Wei-Chih , Chang Tsung-Kun , Chen Po-Jung , Yin Tzu-Chieh , Tsai Hsiang-Lin , Wang Jaw-Yuan
Published: March 2022

Objective

Patients with metastatic colorectal cancer (mCRC) had oncological benefits with irinotecan dose escalation of FOLFIRI regimen combined with bevacizumab according to UGT1A1 genotypes in our previous study. In the current study, we performed a quality of life (QOL) outcome evaluation and cost-utility analysis of different irinotecan dose regimens in patients with mCRC.

Materials and Methods

With inverse probability-of-treatment weighting (IPTW) matching on all covariates, 75 patients with dose escalation of irinotecan (study group) and 121 patients with the recommended dose of irinotecan (control group) were recruited between October 2015 and December 2019. The QOL outcome measures were Functional Assessment of Cancer Therapy-Colorectal, Beck Anxiety Inventory, Beck Depression Inventory, and SF-36; cost-utility outcome measures were medical direct costs, quality-adjusted life-years (QALYs), and incremental cost-utility ratios (ICURs).

Results

All mCRC patients exhibited a significant decrease in both emotional wellbeing and depression from pretherapeutic period to posttherapeutic 6th month (P < 0.05); however, from the posttherapeutic 1st year to the 2nd year, improvement in most QOL measures was significantly better in the study group than in the control group (P < 0.05). Over a 2-year time period, the study group had higher total medical direct costs than the control group (US$ 54,742 ± 14,013 vs. US$ 54,608 ± 9,673) and higher average QALYs gained (1.88 vs. 1.65), with an ICUR of US$ 583 per QALY gained.

Conclusion

For patients with mCRC, irinotecan dose escalation appeared cost-effective with considerable QOL improvements during the study period. Further randomized, multi-institutional controlled trials are warranted to corroborate these results.
Reframing How Physical Activity Reduces The Incidence of Clinically-Diagnosed Cancers: Appraising Exercise-Induced Immuno-Modulation As An Integral Mechanism
Authors: Emery Annabelle , Moore Sally , Turner James E. , Campbell John P.
Published: March 2022

Undertaking a high volume of physical activity is associated with reduced risk of a broad range of clinically diagnosed cancers. These findings, which imply that physical activity induces physiological changes that avert or suppress neoplastic activity, are supported by preclinical intervention studies in rodents demonstrating that structured regular exercise commonly represses tumour growth. In Part 1 of this review, we summarise epidemiology and preclinical evidence linking physical activity or regular structured exercise with reduced cancer risk or tumour growth. Despite abundant evidence that physical activity commonly exerts anti-cancer effects, the mechanism(s)-of-action responsible for these beneficial outcomes is undefined and remains subject to ongoing speculation. In Part 2, we outline why altered immune regulation from physical activity - specifically to T cells - is likely an integral mechanism. We do this by first explaining how physical activity appears to modulate the cancer immunoediting process. In doing so, we highlight that augmented elimination of immunogenic cancer cells predominantly leads to the containment of cancers in a ‘precancerous’ or ‘covert’ equilibrium state, thus reducing the incidence of clinically diagnosed cancers among physically active individuals. In seeking to understand how physical activity might augment T cell function to avert cancer outgrowth, in Part 3 we appraise how physical activity affects the determinants of a successful T cell response against immunogenic cancer cells. Using the cancer immunogram as a basis for this evaluation, we assess the effects of physical activity on: (i) general T cell status in blood, (ii) T cell infiltration to tissues, (iii) presence of immune checkpoints associated with T cell exhaustion and anergy, (iv) presence of inflammatory inhibitors of T cells and (v) presence of metabolic inhibitors of T cells. The extent to which physical activity alters these determinants to reduce the risk of clinically diagnosed cancers – and whether physical activity changes these determinants in an interconnected or unrelated manner – is unresolved. Accordingly, we analyse how physical activity might alter each determinant, and we show how these changes may interconnect to explain how physical activity alters T cell regulation to prevent cancer outgrowth.
Applications of Circulating Tumor DNA in Immune Checkpoint Inhibition: Emerging Roles and Future Perspectives
Authors: Lu Chang , Zhang Yi-Chen , Chen Zhi-Hong , Zhou Qing , Wu Yi-Long
Published: March 2022

Immune checkpoint inhibitors (ICIs), especially anti-programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) antibodies, have made dramatic progress in the treatment of lung cancer, especially for patients with cancers not driven by oncogenes. However, responses are limited to a subset of patients, and which subset of patients will optimally benefit from ICI remains unknown. With the advantage of being minimally invasive and dynamic, noninvasive biomarkers are promising candidates to predict response, monitor resistance, and track the evolution of lung cancer during ICI treatment. In this review, we focus on the application of circulating tumor DNA (ctDNA) in plasma in immunotherapy. We examine the potential of pre- and on-treatment features of ctDNA as biomarkers, and following multiparameter analysis, we determine the potential clinical value of integrating predictive liquid biomarkers of ICIs to optimize patient management. We further discuss the role of ctDNA in monitoring treatment resistance, as well as challenges in clinical translation.
WASF2 Serves as a Potential Biomarker and Therapeutic Target in Ovarian Cancer: A Pan-Cancer Analysis
Authors: Yang Xiaofeng , Ding Yuzhen , Sun Lu , Shi Meiting , Zhang Ping , He Andong , Zhang Xiaotan , Huang Zhengrui , Li Ruiman
Published: March 2022

Background

Wiskott-Aldrich syndrome protein family member 2 (WASF2) has been shown to play an important role in many types of cancer. Therefore, it is worthwhile to further study expression profile of WASF2 in human cancer, which provides new molecular clues about the pathogenesis of ovarian cancer.

Methods

We used a series of bioinformatics methods to comprehensively analyze the relationship between WASF2 and prognosis, tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), and tried to find the potential biological processes of WASF2 in ovarian cancer. Biological behaviors of ovarian cancer cells were investigated through CCK8 assay, scratch test and transwell assay. We also compared WASF2 expression between epithelial ovarian cancer tissues and normal ovarian tissues by using immunohistochemical staining.

Results

In the present study, we found that WASF2 was abnormally expressed across the diverse cancer and significantly correlated with overall survival (OS) and progression-free interval (PFI). More importantly, the WASF2 expression level also significantly related to the TME. Our results also showed that the expression of WASF2 was closely related to immune infiltration and immune-related genes. In addition, WASF2 expression was associated with TMB, MSI, and antitumor drugs sensitivity across various cancer types. Functional bioinformatics analysis demonstrated that the WASF2 might be involved in several signaling pathways and biological processes of ovarian cancer. A risk factor model was found to be predictive for OS in ovarian cancer based on the expression of WASF2. Moreover, in vitro experiments, it was demonstrated that the proliferative, migratory and invasive capacity of ovarian cancer cells was significantly inhibited due to WASF2 knockdown. Finally, the immunohistochemistry data confirmed that WASF2 were highly expressed in ovarian cancer.

Conclusions

Our study demonstrated that WASF2 expression was associated with a poor prognosis and may be involved in the development of ovarian cancer, which might be explored as a potential prognostic marker and new targeted treatments.
Pan-Cancer Analysis Based on EPOR Expression With Potential Value in Prognosis and Tumor Immunity in 33 Tumors
Authors: Zhang Yajing , Wang Senyu , Han Songtao , Feng Yangchun
Published: March 2022

Background

Erythropoietin receptor (EPOR), a member of the cytokine class I receptor family, mediates erythropoietin (EPO)-induced erythroblast proliferation and differentiation, but its significance goes beyond that. The expression and prognosis of EPOR in cancer remain unclear.

Methods

This study intended to perform a pan-cancer analysis of EPOR by bioinformatics methods. Several databases such as GTEx, TCGA, CCLE, and others were used to explore the overall situation of EPOR expression, and the correlation of EPOR expression with prognosis, microRNAs (miRNAs), immune infiltration, tumor microenvironment, immune checkpoint genes, chemokines, tumor mutation burden (TMB), microsatellite instability (MSI), methyltransferases, and DNA mismatch repair (MMR) genes in 33 tumors was analyzed. In addition, we compared the promoter methylation levels of EPOR in cancer tissues with those in normal tissues and performed protein–protein interaction network, gene–disease network, and genetic alteration analyses of EPOR, and finally enrichment analysis of EPOR-interacting proteins, co-expressed genes, and differentially expressed genes.

Results

The TCGA database showed that EPOR expression was upregulated in BLCA, CHOL, HNSC, KIRC, LIHC, STAD, and THCA and downregulated in LUAD and LUSC. After combining the GTEx database, EPOR expression was found to be downregulated in 18 cancer tissues and upregulated in 6 cancer tissues. The CCLE database showed that EPOR expression was highest in LAML cell lines and lowest in HNSC cell lines. Survival analysis showed that high EPOR expression was positively correlated with OS in LUAD and PAAD and negatively correlated with OS in COAD, KIRC, and MESO. Moreover, EPOR had a good prognostic ability for COAD, LUAD, MESO, and PAAD and also influenced progression-free survival, disease-specific survival, disease-free survival, and progression-free interval in specific tumors. Further, EPOR was found to play a non-negligible role in tumor immunity, and a correlation of EPOR with miRNAs, TMB, MSI, and MMR genes and methyltransferases was confirmed to some extent. In addition, the enrichment analysis revealed that EPOR is involved in multiple cancer-related pathways.

Conclusion

The general situation of EPOR expression in cancer provided a valuable clinical reference. EPOR may be target gene of hsa-miR-575, etc. A pan-cancer analysis of panoramic schema revealed that EPOR not only may play an important role in mediating EPO-induced erythroblast proliferation and differentiation but also has potential value in tumor immunity and is expected to be a prognostic marker for specific cancers.
Safety of Rapid Daratumumab Infusion: A Retrospective, Multicenter, Real-Life Analysis on 134 Patients With Multiple Myeloma
Authors: Bonello Francesca , Rocchi Serena , Barilà Gregorio , Sandrone Michela , Talarico Marco , Zamagni Elena , Scaldaferri Matilde , Vedovato Susanna , Bertiond Cecilia , Pavan Laura , Bringhen Sara , Cattel Francesco , Zambello Renato , Cavo Michele , Mina Roberto
Published: March 2022

Background

The anti-CD38 monoclonal antibody daratumumab is the backbone of most anti-multiple myeloma (MM) regimens. To mitigate the risk of infusion-related reactions (IRRs), intravenous daratumumab administration requires 7 hours for the first infusion and 3.5-4 hours thereafter, thus making daratumumab-containing regimens burdensome for patients and health care resources. Preliminary data suggest that a rapid (90-minute) infusion of daratumumab is safe and does not increase IRRs. The rapid schedule was adopted by our centers since 2019.

Methods

We conducted an observational multi-center, real-life study to assess the safety of rapid daratumumab infusion protocol from the third administration in relapsed MM patients receiving daratumumab alone or in combination with lenalidomide-dexamethasone or bortezomib-dexamethasone. The primary endpoint was the safety of the rapid infusion protocol, particularly in terms of IRRs.

Results

A total of 134 MM patients were enrolled. IRRs occurred in 7 (5%) patients and were mostly mild (6/7 of grade 1-2), with only 1 patient experiencing a grade 3 IRR. Due to the IRRs, 5 (3.7%) patients discontinued the rapid infusions and resumed daratumumab at the standard infusion rate, while 1 patient permanently discontinued daratumumab. In 4/7 patients (57%), IRRs occurred while resuming rapid daratumumab infusions after a temporary interruption (2-4 months). No other adverse event was considered related to the rapid infusion protocol.

Conclusions

Our findings confirmed the safety of rapid daratumumab infusions starting from the third administration. In case of prolonged daratumumab interruption, it is advisable to resume infusions at the standard rate (3.5 hours) before switching to the rapid infusion.
Cause of Death Among Patients With Thyroid Cancer: A Population-Based Study
Authors: Wang Qian , Zeng Zhen , Nan Junjie , Zheng Yongqiang , Liu Huanbing
Published: March 2022

Background

Over the last decades, the number of patients diagnosed with thyroid carcinoma has been increasing, highlighting the importance of comprehensively evaluating causes of death among these patients. This study aimed to comprehensively characterize the risk of death and causes of death in patients with thyroid carcinoma.

Methods

A total of 183,641 patients diagnosed with an index thyroid tumor were identified from the Surveillance, Epidemiology, and End Result database (1975–2016). Standardized mortality rates (SMRs) for non-cancer deaths were calculated to evaluate mortality risk and to compare mortality risks with the cancer-free US population. Cumulative mortality rates were calculated to explore the factors associated with higher risk of deaths.

Results

There were 22,386 deaths recorded during follow-up, of which only 31.0% were due to thyroid cancer and 46.4% due to non-cancer causes. Non-cancer mortality risk among patients with thyroid cancer was nearly 1.6-fold (SMR=1.59) that of the general population. Cardiovascular diseases were the leading cause of non-cancer deaths, accounting for 21.3% of all deaths in thyroid cancer patients. Non-cancer causes were the dominant cause of death in thyroid cancer survivors as of the third year post-diagnosis. We found that males with thyroid cancer had a higher risk of all-cause mortality compared with females. The risk of suicide was highest in the first post-diagnostic year (<1 year: SMR=1.51). The long-term risk of Alzheimer’s disease was notably increased in thyroid cancer patients (>5 years: SMR=8.27).

Conclusion

Non-cancer comorbidities have become the major risks of death in patients with thyroid tumor in the US, as opposed to death from the tumor itself. Clinicians and researchers should be aware of these risk trends in order to conduct timely intervention strategies.
Integrative Neuromuscular Training in Adolescents and Children Treated for Cancer (INTERACT): Study Protocol for a Multicenter, Two-Arm Parallel-Group Randomized Controlled Superiority Trial
Authors: Schmidt-Andersen Peter , Fridh Martin Kaj , Müller Klaus Gottlob , Anna Pouplier  , Hjalgrim Lisa Lyngsie , Faigenbaum Avery D. , Schmiegelow Kjeld , Hasle Henrik , Lykkedegn Sine , Zhang He , Christensen Jan , Larsen Hanne Bækgaard
Published: March 2022

Background

Improved survival rates for children and adolescents diagnosed with cancer call for novel strategies for reducing short- and long-term treatment-related side effects. These include the physical and metabolic sequelae that are exacerbated by sedentary behavior and treatment-induced toxicities. We aim to investigate the effect of an integrative neuromuscular training intervention during the first 6 months of anti-cancer treatment primarily on muscle strength, and secondarily on exercise capacity, physical function, markers of metabolic syndrome, dysmetabolism, and health-related quality of life during and after ended treatment.

Methods

One hundred and twenty-seven children and adolescents, newly diagnosed with malignant and benign neoplasia, aged 6–17 years, and treated with chemotherapy or radiation will be randomized to either the intervention or the control arm of the study. The intervention group will, in addition to usual care, be offered a combination of 6 months of supervised physical exercise (integrative neuromuscular training) and home-based exercise. The active control group will, in addition to usual care, receive information along an unsupervised written home-based training program. All participants, including parents, will receive information about the importance of physical exercise during the course of cancer treatment, at the start of treatment, and in 5 monthly sessions. The primary outcome is measured in terms of isometric quadriceps muscle strength. Secondary outcomes include muscle strength and endurance, markers of metabolic syndrome and dysmetabolism, exercise capacity, physical function and activity, days of hospitalization, and health-related quality of life. Assessment will be conducted at treatment initiation (baseline), at 3 and 6 months after inclusion, and 1 month and 1 year after ended treatment. The primary endpoint for lower-body muscle strength is at 6 months after treatment initiation. The effects of the intervention will be evaluated through a constrained linear mixed model.

Discussion

This national randomized controlled study has the potential to provide new knowledge concerning the short- and long-term effects of a novel, inclusive approach for youth exercise programming (integrative neuromuscular exercise) in children and adolescents during anti-cancer treatment. Using a pragmatic, low-cost, and time-efficient training design, this intervention can be easily adapted to both hospital and home settings.

Clinical Trial Registration

ClinicalTrials.gov(NCT04706676), first released January 5, 2021.
Berberine: A Review of its Pharmacokinetics Properties and Therapeutic Potentials in Diverse Vascular Diseases
Authors: Ai Xiaopeng , Yu Peiling , Peng Lixia , Luo Liuling , Liu Jia , Li Shengqian , Lai Xianrong , Luan Fei , Meng Xianli
Published: March 2022

Traditional Chinese medicine plays a significant role in the treatment of various diseases and has attracted increasing attention for clinical applications. Vascular diseases affecting vasculature in the heart, cerebrovascular disease, atherosclerosis, and diabetic complications have compromised quality of life for affected individuals and increase the burden on health care services. Berberine, a naturally occurring isoquinoline alkaloid form Rhizoma coptidis, is widely used in China as a folk medicine for its antibacterial and anti-inflammatory properties. Promisingly, an increasing number of studies have identified several cellular and molecular targets for berberine, indicating its potential as an alternative therapeutic strategy for vascular diseases, as well as providing novel evidence that supports the therapeutic potential of berberine to combat vascular diseases. The purpose of this review is to comprehensively and systematically describe the evidence for berberine as a therapeutic agent in vascular diseases, including its pharmacological effects, molecular mechanisms, and pharmacokinetics. According to data published so far, berberine shows remarkable anti-inflammatory, antioxidant, antiapoptotic, and antiautophagic activity via the regulation of multiple signaling pathways, including AMP-activated protein kinase (AMPK), nuclear factor κB (NF-κB), mitogen-activated protein kinase silent information regulator 1 (SIRT-1), hypoxia-inducible factor 1α (HIF-1α), vascular endothelial growth factor phosphoinositide 3-kinase (PI3K), protein kinase B (Akt), janus kinase 2 (JAK-2), Ca2+ channels, and endoplasmic reticulum stress. Moreover, we discuss the existing limitations of berberine in the treatment of vascular diseases, and give corresponding measures. In addition, we propose some research perspectives and challenges, and provide a solid evidence base from which further studies can excavate novel effective drugs from Chinese medicine monomers.
Urolithin A Promotes Angiogenesis and Tissue Regeneration in a Full-Thickness Cutaneous Wound Model
Authors: Feng Zhen-hua , Chen Jia , Yuan Pu-tao , Ji Zhong-yin , Tao Si-yue , Zheng Lin , Wei Xiao-an , Zheng Ze-yu , Zheng Bing-jie , Chen Bin , Chen Jian , Zhao Feng-dong
Published: March 2022

The treatment of chronic wound is an important topic of current clinical issue. Neovascularization plays a crucial role in skin wound healing by delivering fresh nutrients and oxygen to the wound area. The aim of this study was to investigate the mechanisms of urolithin A (UA) in angiogenesis during wound healing. The results of in vitro experiments showed that treatment with UA (5–20 μM) promoted the proliferation, migration, and angiogenic capacity of HUVECs. Furthermore, we investigated the effect of UA in vivo using a full-thickness skin wound model. Subsequently, we found that UA promoted the regeneration of new blood vessels, which is consistent with the results of accelerated angiogenesis in vitro experiments. After UA treatment, the blood vessels in the wound are rapidly formed, and the deposition and remodeling process of the collagen matrix is also accelerated, which ultimately promotes the effective wound healing. Mechanistic studies have shown that UA promotes angiogenesis by inhibiting the PI3K/AKT pathway. Our study provides evidence that UA can promote angiogenesis and skin regeneration in chronic wounds, especially ischemic wounds.
Fengreqing Oral Liquid Exerts Anti-Inflammatory Effects by Promoting Apoptosis and Inhibiting PI3K/AKT and NF-κB Signaling Pathways
Authors: Rao Zhili , Li Xiangyu , Zhang Xia , Zeng Jiuseng , Wang Baojun , Yang Ruocong , Zeng Nan
Published: March 2022

Fengreqing oral liquid (FOL), a Chinese patent drug frequently used in clinical practice in China, is effective in treating inflammatory diseases of the upper respiratory tract such as colds and flu. However, its anti-inflammatory effects and mechanisms remain to be elucidated. In this study, the anti-inflammatory effects of FOL and its mechanisms on PI3K/AKT and NF-κB signaling pathways in LPS-induced RAW264.7 cells were explored, as well as the regulatory effect of FOL on apoptosis. In addition, the potential of FOL for the treatment of acute lung injury was explored in LPS-induced ALI mice. The results showed that treatment with FOL significantly reduced the levels of interleukin 1β (IL-1β), interleukin 6 (IL-6), nitric oxide (NO), and tumor necrosis factor α (TNF-α) in the supernatant of LPS-induced RAW264.7 cells, and also significantly reduced the phosphorylated protein levels of PI3K and AKT in the PI3K/AKT signaling pathway and also protein levels of NF-κB p50, phosphorylated NF-κB p65, and IκBα in the NF-κB signaling pathway. In addition, the results showed that FOL induced apoptosis in LPS-induced RAW264.7 cells at the level of 80%–90%, and significantly increased the protein expression levels of the pro-apoptotic Bax and cleaved-caspase-3. In LPS-induced ALI mice, FOL administration showed inhibition of IL-1β, IL-6, and TNF-α in Bronchoalveolar lavage fluid (BALF) and decreased protein expression levels of PI3K, AKT, NF-κB p50, and NF-κB p65, and elevated protein expression levels of Bax and cleaved-caspase-3 significantly. These results suggest that FOL may exert anti-inflammatory effects by inhibiting the PI3K/AKT signaling pathway to promote apoptosis and leading to attenuated activation of the NF-κB signaling pathway.
Adverse Drug Reactions of Antihypertensives and CYP3A5*3 Polymorphism Among Chronic Kidney Disease Patients
Authors: Lee Fei Yee , Islahudin Farida , Abdul Gafor Abdul Halim , Wong Hin-Seng , Bavanandan Sunita , Mohd Saffian Shamin , Md Redzuan Adyani , Makmor-Bakry Mohd
Published: March 2022

Chronic kidney disease (CKD) patients may be more susceptible to adverse drug reactions (ADRs), given their complex medication regimen and altered physiological state driven by a decline in kidney function. This study aimed to describe the relationship between CYP3A5*3 polymorphism and the ADR of antihypertensive drugs in CKD patients. This retrospective, multi-center, observational cohort study was performed among adult CKD patients with a follow-up period of up to 3 years. ADRs were detected through medical records. CYP3A5*3 genotyping was performed using the direct sequencing method. From the 200 patients recruited in this study, 33 (16.5%) were found to have ADRs related to antihypertensive drugs, with 40 ADRs reported. The most frequent ADR recorded was hyperkalemia (n = 8, 20.0%), followed by bradycardia, hypotension, and dizziness, with 6 cases (15.0%) each. The most common suspected agents were angiotensin II receptor blockers (n = 11, 27.5%), followed by angiotensin-converting enzyme inhibitors (n = 9, 22.5%). The CYP3A5*3 polymorphism was not found to be associated with antihypertensive-related ADR across the genetic models tested, despite adjustment for other possible factors through multiple logistic regression (p > 0.05). After adjusting for possible confounding factors, the factors associated with antihypertensive-related ADR were anemia (adjusted odds ratio [aOR] 5.438, 95% confidence interval [CI]: 2.002, 14.288) and poor medication adherence (aOR 3.512, 95% CI: 1.470, 8.388). In conclusion, the CYP3A5*3 polymorphism was not found to be associated with ADRs related to antihypertensives in CKD patients, which requires further verification by larger studies.
Network Pharmacology Identifies Therapeutic Targets and the Mechanisms of Glutathione Action in Ferroptosis Occurring in Oral Cancer
Authors: Huang Chen , Zhan Lei
Published: March 2022

Oral cancer (OC) is one of the most pernicious cancers with increasing incidence and mortality worldwide. Surgery is the primary approach for the treatment of early-stage OC, which reduces the quality of life of the patients. Therefore, there is an urgent need to discover novel treatments for OC. Targeting ferroptosis to induce cell death through the modulation of lipid oxidation has been used as a new approach to treat many cancers. Glutathione (GSH) is a coenzyme factor of GSH peroxidase 4, and it carries potential applicability in treating OC. By using network pharmacology and molecular docking followed by systematic bioinformatic analysis, we aimed to study GSH-targeting ferroptosis to treat OC. We identified 14 core molecular targets, namely, EGFR, PTGS2, HIF1A, VEGFA, TFRC, SLC2A1, CAV1, CDKN2A, SLC3A2, IFNG, NOX4, DDIT4, CA9, and DUSP1, involved in ferroptosis that were targeted by GSH for OC treatment. Functional characterization of these molecular targets showed their importance in the control of cell apoptosis, cell proliferation, and immune responses through various kinase activities such as the mitogen-activated protein kinase activity (e.g., ERK1 and ERK2 cascades) and modulation of TOR signaling (e.g., the HIF-1 signaling pathway). Molecular docking further revealed the direct binding of GSH with EGFR, PTGS2, and HIF1A proteins. These findings provide a novel insight into the targets of GSH in ferroptosis as well as possible molecular mechanisms involved, suggesting the possible use of GSH as a combined therapy for treating OC.
Measuring the Competitive Advantage of Countries Along the Belt and Road From the Perspective of Complex Social Networks
Authors: Wang Yanni , Chen Wen , Jiang Chuke , Xing Lizhi
Published: March 2022

For the Belt and Road Initiative, “extensive consultation, joint contribution and shared benefits” is the basic principle, and the competitiveness heterogeneity is an important condition for cooperation. Based on the complex network theory, this paper constructs a complex network model of global value chain (GVC) division of labor system by using the Multi-Regional Input-output (MRIO) table, and reveals the variation trend of competitiveness of industrial sectors and economies on the GVC network by the National Competitive Advantage Index (NCAI). The results verify the effectiveness of BRI, and help countries along the B&R route to explore their comparative advantages and cooperation prospects with other countries. The research also provides a direction and reference for China to better implement the Initiative.
Numerical Simulation of Mechanical Properties of Irregular Columnar Jointed Rock Mass
Authors: Yan Long , Xiang Zhipeng , Xu Weiya , Wang Rubin , Ji Hua
Published: March 2022

Columnar jointed rock masses (CJRM) are characterized by significant anisotropy. The mechanical properties of CJRM are complicated by the presence of columnar joints. In this paper, based on the Voronoi random graph generation algorithm, the irregular CJRM numerical model is established, in which columns are simulated by solid elements while joints are simulated by contact surface elements. Uniaxial compression tests on irregular CJRM are then conducted by using FLAC3D to investigate the deformation and strength characteristics, and failure modes. Results indicate that irregular CJRM exhibit strong anisotropy under uniaxial compression, and the compressive strength varies with joint angle in a typical U-shape curve. Failure modes can be classified as three categories: splitting failure along loading direction, shear-sliding failure along columnar joint, and combined failure of column fracturing and joint splitting. The numerical results are then compared with the experimental results. It demonstrates the effectiveness and reliability of applying numerical simulation to investigations on mechanical properties and failure mechanism of irregular CJRM. The results of this study provide helpful information for the design and construction of the project involving CJRM.
Is the Natural Instinct to Oviposit in Mated Female Oriental Fruit Fly, Bactrocera dorsalis More of a Brain-Independent Act?
Authors: Vyas Meenal , Parepally Saravan Kumar , Kamala Jayanthi Pagadala Damodaram
Published: March 2022

What physiological and neuro-molecular changes control the female oviposition behavior post-mating in insects? The molecular changes that occur in a gravid female insect are difficult to dissect out considering the distinct behavioral patterns displayed by different insect groups. To understand the role of the brain center in Oriental fruit fly, Bactrocera dorsalis oviposition, egg-laying behavior was analyzed in γ-octalactone exposed, decapitated mated B. dorsalis females. Interestingly, the females displayed a possible urge to oviposit, which suggests a natural instinct to pass on the gene pool. Expression analysis of certain genes involved in oviposition behavior was also carried out in these insects to explore the molecular aspects of such behavior. This study tries to assess the involvement of brain center in egg-laying and also explore the role of certain neurotransmitter-related receptors in decapitated B. dorsalis oviposition behavior. Our results indicate that B. dorsalis oviposition behavior could potentially have a bypass route of neuronal control devoid of the brain. The study reported here establishes that decapitation in gravid females fails to abolish their ability to sense ovipositional cues and also to oviposit.
Dietary Nitrate Supplementation Is Not Helpful for Endurance Performance at Simulated Altitude Even When Combined With Intermittent Normobaric Hypoxic Training
Authors: Sousa Ana , Viana João L. , Milheiro Jaime , Reis Vítor M. , Millet Grégoire P.
Published: March 2022

Introduction

Training intensity and nutrition may influence adaptations to training performed in hypoxia and consequently performance outcomes at altitude. This study investigates if performance at simulated altitude is improved to a larger extent when high-intensity interval training is performed in normobaric hypoxia and if this is potentiated when combined with chronic dietary nitrate (NO3−) supplementation.

Methods

Thirty endurance-trained male participants were allocated to one of three groups: hypoxia (13% FiO2) + NO3−; hypoxia + placebo; and normoxia (20.9% FiO2) + placebo. All performed 12 cycling sessions (eight sessions of 2*6 × 1 min at severe intensity with 1 min recovery and four sessions of 4*6*10 s all-out with 20 s recovery) during a 4-week period (three sessions/week) with supplementation administered 3–2.5 h before each session. An incremental exhaustion test, a severe intensity exercise bout to exhaustion (Tlim) and a 3 min all-out test (3AOT) in hypoxia (FiO2 = 13%) with pulmonary oxygen uptake (V˙O2), V˙O2 kinetics, and changes in vastus lateralis local O2 saturation (SmO2) measured were completed by each participant before and after training.

Results

In all tests, performance improved to the same extent in hypoxia and normoxia, except for SmO2 after Tlim (p = 0.04, d = 0.82) and 3AOT (p = 0.03, d = 1.43) which were lower in the two hypoxic groups compared with the normoxic one. Dietary NO3− supplementation did not bring any additional benefits.

Conclusion

Performance at simulated altitude was not improved to a larger extent when high-intensity interval training was undertaken in normobaric hypoxic conditions, when compared with normoxic training. Additionally, dietary NO3− supplementation was ineffective in further enhancing endurance performance at simulated altitude.
Purinergic and Adenosinergic Signaling in Pancreatobiliary Diseases
Authors: Faraoni Erika Y. , Ju Cynthia , Robson Simon C. , Eltzschig Holger K. , Bailey-Lundberg Jennifer M.
Published: March 2022

Adenosine 5'-triphosphate (ATP), other nucleotides, and the nucleoside analogue, adenosine, all have the capacity to modulate cellular signaling pathways. The cellular processes linked to extracellular purinergic signaling are crucial in the initiation, evolution, and resolution of inflammation. Injured or dying cells in the pancreatobiliary tract secrete or release ATP, which results in sustained purinergic signaling mediated through ATP type-2 purinergic receptors (P2R). This process can result in chronic inflammation, fibrosis, and tumor development. In contrast, signaling via the extracellular nucleoside derivative adenosine via type-1 purinergic receptors (P1R) is largely anti-inflammatory, promoting healing. Failure to resolve inflammation, as in the context of primary sclerosing cholangitis or chronic pancreatitis, is a risk factor for parenchymal and end-organ scarring with the associated risk of pancreatobiliary malignancies. Emerging immunotherapeutic strategies suggest that targeting purinergic and adenosinergic signaling can impact the growth and invasive properties of cancer cells, potentiate anti-tumor immunity, and also block angiogenesis. In this review, we dissect out implications of disordered purinergic responses in scar formation, end-organ injury, and in tumor development. We conclude by addressing promising opportunities for modulation of purinergic/adenosinergic signaling in the prevention and treatment of pancreatobiliary diseases, inclusive of cancer.
Iconography of Beans and Related Legumes Following the Columbian Exchange
Authors: Myers James R. , Formiga Alice K. , Janick Jules
Published: March 2022

Common bean (Phaseolus vulgaris L.), maize, and squash were described by explorers as early as 1492. The illustration of common bean recognized as the first in Europe is in Fuchs’ Di Historias Stirpium, published in 1542 and a half-century after beans were observed in the Caribbean. Besides herbals and herbarium specimens, the sources of information on the introduction of New World crops are paintings and illustrations. Two early sources of images of maize and squash are the Grandes Heures d’Anne de Bretagne and the Loggia di Amore e Psiche in the Villa Farnesina, Rome. The former was illustrated between 1507 and 1508 and has an image identified as the common bean. The Villa Farnesina Loggia was decorated in 1515–1518, with festoons containing three instances of bean pods. Our first objective was to evaluate these images to determine whether they represented depictions of common bean earlier than the illustration by Fuchs. Neither image appears to be a common bean based on a combination of botanical characters and size. Folio 194 of the Grandes Heures d’Anne de Bretagne is most likely a Vigna species in the Ceratotropis subgenus. In the Loggia, one set of pods appears to be a species in the Mimosoideae subfamily and the second and third sets of pods most closely resemble Canavalia gladiata. Neither image likely represents common beans and are probably Old-World species. Secondly, illustrations of common beans from ten early herbals were analyzed for traits that are characteristic of the centers of domestication and races of common beans. Our objective was to characterize the diversity observed among herbals and determine whether beans from both centers of domestication were present. We potentially identified both Middle American, race Mesoamerica and Andean, race Nueva Granada types. We posit that both Middle American and Andean types were in the Caribbean at the time of the Columbian exchange and that beans from both centers were informally introduced into Europe early on. This review of 16th-century manuscripts and illustrations has provided some answers to the questions of what and when common beans reached Europe and provide new hypotheses for researchers studying the origins, diversity, and distribution of this crop.
How Does the Implicit Awareness of Consumers Influence the Effectiveness of Public Service Announcements? A Functional Near-Infrared Spectroscopy Study
Authors: Fu Jialin , Li Xihang , Zhao Xi , Zhang Keyi , Cui Nan
Published: March 2022

A large number of scholars have conducted detailed studies on the effectiveness of commercial advertising by using neuroimaging methods, but only a few scholars have used this method to study the effectiveness of public service announcements (PSAs). To research the relationship between the effectiveness of PSAs and the audience’s implicit awareness, functional near-infrared spectroscopy (fNIRS) was employed to record the neural activity data of participants in this study. The results showed that there was a correlation between activation of dorsolateral prefrontal cortex (dlPFC) and the effectiveness of PSAs; The activation of the dlPFC could also be used as an indicator to represent the appeal of advertising content. The results means that neuroimaging tool can also be used to investigate the effectiveness of PSAs, not just commercial advertisements and a few PSAs study, and that neural activity can predict and improve the effectiveness of PSAs before they are released.
Text Materialities, Affordances, and the Embodied Turn in the Study of Reading
Authors: Hillesund Terje , Schilhab Theresa , Mangen Anne
Published: March 2022

Digital texts have for decades been a challenge for reading research, creating a range of questions about reading and a need for new theories and concepts. In this paper, we focus on materialities of texts and suggest an embodied, enacted, and extended approach to the research on digital reading. We refer to findings showing that cognitive activities in reading are grounded in bodily and social experiences, and we explore the cognitive role of the body in reading, claiming that–influenced by tacit knowledge and the task at hand–textual meaning is enacted through a mental and physical engagement with text. Further, applying the concept of affordances, we examine how digital technologies have induced new ways of physically handling and mentally interpreting text, indicating that brain, body, text, and technologies are integrated parts of an extended process of reading. The aim of the paper is to encourage empirical research on the interplay between body (including brain), text, and text materialities, a focus we argue will deepen our understand of the current transformation of reading.
The Use of Non-verbal Displays in Framing COVID-19 Disinformation in Europe: An Exploratory Account
Authors: Dumitrescu Delia , Trpkovic Mina
Published: March 2022

While online disinformation practices have grown exponentially over the past decade, the COVID-19 pandemic provides arguably the best opportunity to date to study such communications at a cross-national level. Using the data provided by the International Fact-Checking Network (IFCN), we examine the strategic uses of non-verbal and verbal arguments to push disinformation through social media and websites during the first wave of lockdowns in 2020 across 16 European countries. Our paper extends the work by Brennen et al. (2021) on the use of visuals in COVID-19 misinformation claims by investigating the use of facial emotional expressions and body pose depictions in conjunction with framing elements such as problems identified and attribution of responsibility in the construction of disinformation messages. Our European-wide comparative analysis of 174 messages indexed by the IFCN during the months of April and May 2020 helps provide a rounder understanding of the use of non-verbal devices in advancing COVID-19 disinformation across the continent, and can provide the basis for a framework for further study of the strategic use of non-verbal devices in COVID-19 disinformation world-wide.
Exploring the Antecedents and Outcomes of Entrepreneurial Well-Being: Empirical Evidence From Iranian Rural Entrepreneurs
Authors: Karimi Saeid , Reisi Sima
Published: March 2022

Studies regarding rural entrepreneurs in developing countries and, specifically, their well-being have not been sufficiently developed in the literature. The present study was an attempt to fill this gap and to examine important antecedents and outcomes associated with entrepreneurial well-being among a sample of 102 Iranian rural entrepreneurs. This research established a theoretical research model that highlighted the relationships among job fit, entrepreneurial passion, well-being, and persistence. The results of structural equation modeling supported the hypothesized model. In particular, the results indicated that higher job fit was associated with higher levels of entrepreneurial well-being through an entrepreneurial passion mechanism. Moreover, the results supported the hypothesized serial mediating effect. In other words, a high level of job fit enhances entrepreneurial persistence through a high level of entrepreneurial passion and well-being. This study provides significant input to policymakers and practitioners in their efforts to promote the antecedents and outcomes of well-being among rural entrepreneurs.