bluuebunny/crossref_metadata_2025 huggingface dataset:
Different Arbuscular Mycorrhizal Fungi Established by Two Inoculation Methods Improve Growth and Drought Resistance of Cinnamomum Migao Seedlings Differently
Authors: Xiao Xuefeng , Chen Jingzhong , Liao Xiaofeng , Yan Qiuxiao , Liang Gelin , Liu Jiming , Wang Deng , Guan Ruiting
Published: January 2022

Drought stress is one of the greatest obstacles affecting field crop productivity in arid and semi-arid regions, and its severity and frequency are expected to increase due to human-induced changes to the environment and climate. Drought has led to rocky desertification in Karst regions. Cinnamomum migao is a unique, fast-growing medicinal plant of Southwest China that only thrives in Karst regions. Arbuscular mycorrhizal fungi (AMF) symbiosis alleviates drought stress in plants; however, establishment and function of the symbiotic interaction between AMF host plant in relation to the inoculation method remain unclear. Therefore, we conducted an experiment to investigate the effects of AMF species (Glomus etunicatum and Funneliformis mosseae) and two inoculation methods (seed vs. seedling inoculation) under drought stress on C. migao seedlings, and quantified mycorrhizal colonization, AMF spore density, root vigor, relative water content, C. migao growth, antioxidant enzyme activities, and osmotic adjustment. Inoculation with AMF (G. etunicatum and F. mosseae) positively affected the growth and root vigor of Cinnamomum migao under drought stress, regardless of the inoculation method. Additionally, both AMF species markedly upregulated antioxidant enzyme activities and osmotic adjustment substances, regardless of the inoculation method. Our results showed that the collective stimulatory effect of G. etunicatum is more efficient than that of F. mosseae. AMF application could promote afforestation with C. migao to prevent rocky desertification in Karst regions where water is the greatest limiting factor on plant growth and yield.
Distribution of Copy Number Variation in SYT11 Gene and Its Association with Growth Conformation Traits in Chinese Cattle
Authors: Yang Haiyan , Yue Binglin , Yang Yu , Tang Jia , Yang Shuling , Qi Ao , Qu Kaixing , Lan Xianyong , Lei Chuzhao , Wei Zehui , Huang Bizhi , Chen Hong
Published: January 2022

Currently, studies of the SYT11 gene mainly focus on neurological diseases such as schizophrenia and Parkinson’s disease. However, some studies have shown that the C2B domain of SYT11 can interact with RISC components and affect the gene regulation of miRNA, which is important for cell differentiation, proliferation, and apoptosis, and therefore has an impact on muscle growth and development in animals. The whole-genome resequencing data detected a CNV in the SYT11 gene, and this may affect cattle growth traits. In this study, CNV distribution of 672 individuals from four cattle breeds, Yunling, Pinan, Xianan, and Qinchuan, were detected by qPCR. The relationship between CNV, gene expression and growth traits was further investigated. The results showed that the proportion of multiple copy types was the largest in all cattle breeds, but there were some differences among different breeds. The normal type had higher gene expression than the abnormal copy type. The CNVs of the SYT11 gene were significantly correlated with body length, cannon circumference, chest depth, rump length, and forehead size of Yunling cattle, and was significantly correlated with the bodyweight of Xianan cattle, respectively. These data improve our understanding of the effects of CNV on cattle growth traits. Our results suggest that the CNV of SYT11 gene is a protentional molecular marker, which may be used to improve growth traits in Chinese cattle.
Localized Proteasomal Degradation: From the Nucleus to Cell Periphery
Authors: Guo Xing
Published: January 2022

The proteasome is responsible for selective degradation of most cellular proteins. Abundantly present in the cell, proteasomes not only diffuse in the cytoplasm and the nucleus but also associate with the chromatin, cytoskeleton, various membranes and membraneless organelles/condensates. How and why the proteasome gets to these specific subcellular compartments remains poorly understood, although increasing evidence supports the hypothesis that intracellular localization may have profound impacts on the activity, substrate accessibility and stability/integrity of the proteasome. In this short review, I summarize recent advances on the functions, regulations and targeting mechanisms of proteasomes, especially those localized to the nuclear condensates and membrane structures of the cell, and I discuss the biological significance thereof in mediating compartmentalized protein degradation.
Effects of Phytohormone-Producing Rhizobacteria on Casparian Band Formation, Ion Homeostasis and Salt Tolerance of Durum Wheat
Authors: Martynenko Elena , Arkhipova Tatiana , Safronova Vera , Seldimirova Oksana , Galin Ilshat , Akhtyamova Zarina , Veselov Dmitry , Ivanov Ruslan , Kudoyarova Guzel
Published: January 2022

Inoculation with plant growth-promoting rhizobacteria can increase plant salt resistance. We aimed to reveal bacterial effects on the formation of apoplastic barriers and hormone concentration in relation to maintaining ion homeostasis and growth of salt-stressed plants. The rhizosphere of a durum wheat variety was inoculated with cytokinin-producing Bacillus subtilis and auxin-producing Pseudomonas mandelii strains. Plant growth, deposition of lignin and suberin and concentrations of sodium, potassium, phosphorus and hormones were studied in the plants exposed to salinity. Accumulation of sodium inhibited plant growth accompanied by a decline in potassium in roots and phosphorus in shoots of the salt-stressed plants. Inoculation with both bacterial strains resulted in faster appearance of Casparian bands in root endodermis and an increased growth of salt-stressed plants. B. subtilis prevented the decline in both potassium and phosphorus concentrations and increased concentration of cytokinins in salt-stressed plants. P. mandelii decreased the level of sodium accumulation and increased the concentration of auxin. Growth promotion was greater in plants inoculated with B. subtilis. Increased ion homeostasis may be related to the capacity of bacteria to accelerate the formation of Casparian bands preventing uncontrolled diffusion of solutes through the apoplast. We discuss the relative impacts of the decline in Na accumulation and maintenance of K and P content for growth improvement of salt-stressed plants and their possible relation to the changes in hormone concentration in plants.
Therapeutic Options for Systemic Sclerosis: Current and Future Perspectives in Tackling Immune-Mediated Fibrosis
Authors: Papadimitriou Theodoros-Ioannis , van Caam Arjan , van der Kraan Peter M. , Thurlings Rogier M.
Published: January 2022

Systemic sclerosis (SSc) is a severe auto-immune, rheumatic disease, characterized by excessive fibrosis of the skin and visceral organs. SSc is accompanied by high morbidity and mortality rates, and unfortunately, few disease-modifying therapies are currently available. Inflammation, vasculopathy, and fibrosis are the key hallmarks of SSc pathology. In this narrative review, we examine the relationship between inflammation and fibrosis and provide an overview of the efficacy of current and novel treatment options in diminishing SSc-related fibrosis based on selected clinical trials. To do this, we first discuss inflammatory pathways of both the innate and acquired immune systems that are associated with SSc pathophysiology. Secondly, we review evidence supporting the use of first-line therapies in SSc patients. In addition, T cell-, B cell-, and cytokine-specific treatments that have been utilized in SSc are explored. Finally, the potential effectiveness of tyrosine kinase inhibitors and other novel therapeutic approaches in reducing fibrosis is highlighted.
Phytochemically Derived Zingerone Nanoparticles Inhibit Cell Proliferation, Invasion and Metastasis in Human Oral Squamous Cell Carcinoma
Authors: Yang Cheng-Mei , Chu Tian-Huei , Tsai Kuo-Wang , Hsieh Shuchen , Kung Mei-Lang
Published: January 2022

Due to its aggressiveness and high mortality rate, oral cancer still represents a tough challenge for current cancer therapeutics. Similar to other carcinomas, cancerous invasion and metastasis are the most important prognostic factors and the main obstacles to therapy for human oral squamous cell carcinoma (OSCC). Fortunately, with the rise of the nanotechnical era and innovative nanomaterial fabrication, nanomaterials are widely used in biomedicine, cancer therapeutics, and chemoprevention. Recently, phytochemical substances have attracted increasing interest as adjuvants to conventional cancer therapy. The ginger phenolic compound zingerone, a multitarget pharmacological and bioactive phytochemical, possesses potent anti-inflammatory, antioxidant, and anticancer activities. In our previous study, we generated phytochemically derived zingerone nanoparticles (NPs), and documented their superior antitumorigenic effect on human hepatoma cells. In the present study, we further investigated the effects of zingerone NPs on inhibiting the invasiveness and metastasis of human OSCC cell lines. Zingerone NPs elicited significant cytotoxicity in three OSCC cell lines compared to zingerone. Moreover, the lower dose of zingerone NPs (25 µM) markedly inhibited colony formation and colony survival by at least five-fold compared to zingerone treatment. Additionally, zingerone NPs significantly attenuated cell motility and invasiveness. In terms of the signaling mechanism, we determined that the zingerone NP-mediated downregulation of Akt signaling played an important role in the inhibition of cell viability and cell motility. Zingerone NPs inhibited matrix metalloproteinase (MMP) activity, which was highly correlated with the attenuation of cell migration and cell invasion. By further detecting the roles of zingerone NPs in epithelial–mesenchymal transition (EMT), we observed that zingerone NPs substantially altered the levels of EMT-related markers by decreasing the levels of the mesenchymal markers, N-cadherin and vimentin, rather than the epithelial proteins, ZO-1 and E-cadherin, compared with zingerone. In conclusion, as novel and efficient phytochemically derived nanoparticles, zingerone NPs may serve as a potent adjuvant to protect against cell invasion and metastasis, which will provide a beneficial strategy for future applications in chemoprevention and conventional therapeutics in OSCC treatment.
Impact of Adalimumab Treatment on Interleukin-17 and Interleukin-17 Receptor Expression in Skin and Synovium of Psoriatic Arthritis Patients with Mild Psoriasis
Authors: Bolt Janne W. , van Kuijk Arno W. , Teunissen Marcel B. M. , van der Coelen Dennis , Aarrass Saïda , Gerlag Daniëlle M. , Tak Paul P. , van de Sande Marleen G. , Lebre Maria C. , van Baarsen Lisa G. M.
Published: January 2022

Interleukin (IL)-17 and tumor necrosis factor-alpha (TNF)-α are key players in psoriatic arthritis (PsA) pathogenesis. While both cytokines can be therapeutically targeted with beneficial clinical outcome, it is unclear whether inhibiting one cytokine will affect the other at sites of inflammation. If both act independently, this might provide a rationale for dual or combined inhibition of both cytokines. Here, we evaluated the effect of TNF blockade in PsA patients on IL-17 levels in both skin and synovial tissue biopsies. PsA patients with mild psoriatic skin lesions were randomized to receive either adalimumab or placebo for four weeks. Synovial and skin biopsies were obtained at weeks zero and four. Skin from healthy donors (HDs) was used for comparison. Expression of IL-17A, IL-17F, IL-17RA and IL-17RC was assessed by immunohistochemistry and analyzed with digital image analysis. We found relatively low levels of IL-17 and its receptors in the skin of PsA patients compared to HD, and only IL-17F in the dermis of lesional psoriatic skin was significantly higher compared to HD skin (p = 0.0002). Histologically IL-17A, IL-17F, IL-17RA and IL-17RC in skin and synovial tissue were not downregulated by adalimumab treatment. Thus, in this cohort of PsA patients with mild psoriasis, TNF blockade did not affect the protein levels of IL-17 cytokines and its receptors in skin and synovium, despite reduced cellular inflammation and improved clinical outcome for joint involvement.
Treatment with Pulsed Extremely Low Frequency Electromagnetic Field (PELF-EMF) Exhibit Anti-Inflammatory and Neuroprotective Effect in Compression Spinal Cord Injury Model
Authors: Goldshmit Yona , Shalom Moshe , Ruban Angela
Published: January 2022

Background: Spinal cord injury (SCI) pathology includes both primary and secondary events. The primary injury includes the original traumatic event, and the secondary injury, beginning immediately after the initial injury, involves progressive neuroinflammation, neuronal excitotoxicity, gliosis, and degeneration. Currently, there is no effective neuroprotective treatment for SCI. However, an accumulating body of data suggests that PELF-EMF has beneficial therapeutic effects on neurotrauma. The purpose of this study was to test the efficacy of the PELF-EMF SEQEX device using a compression SCI mouse model. Methods: C57BL/6 mice were exposed to PELF-EMF for 4 h on a daily basis for two months, beginning 2 h after a mild-moderate compression SCI. Results: The PELF-EMF treatment significantly diminished inflammatory cell infiltration and astrocyte activation by reducing Iba1, F4/80, CD68+ cells, and GAFP at the lesion borders, and increased pro-survival signaling, such as BDNF, on the neuronal cells. Moreover, the treatment exhibited a neuroprotective effect by reducing the demyelination of the axons of the white matter at the lesion’s center. Conclusions: Treatment with SEQEX demonstrated significant anti-inflammatory and neuroprotective effects. Considering our results, this safe and effective rehabilitative device, already available on the market, may provide a major therapeutic asset in the treatment of SCI.
Asymmetric Interaction of Neuropeptidase Activities between Cortico-Limbic Structures, Plasma and Cardiovascular Function after Unilateral Dopamine Depletions of the Nigrostriatal System
Authors: Banegas Inmaculada , Prieto Isabel , Segarra Ana Belén , Vives Francisco , Martínez-Cañamero Magdalena , Durán Raquel , Luna Juan de Dios , de Gasparo Marc , Domínguez-Vías Germán , Ramírez-Sánchez Manuel
Published: January 2022

In emotional processing, dopamine (DA) plays an essential role, and its deterioration involves important consequences. Under physiological conditions, dopamine exhibits brain asymmetry and coexists with various neuropeptides that can coordinate the processing of brain functions. Brain asymmetry can extend into a broader concept of asymmetric neurovisceral integration, including behavior. The study of the activity of neuropeptide regulatory enzymes (neuropeptidases, NPs) is illustrative. We have observed that the left and right brain areas interact intra- and inter-hemispherically, as well as with peripheral tissues or with physiological parameters such as blood pressure or with behaviors such as turning preference. To obtain data that reflect this integrative behavior, we simultaneously analyzed the impact of left or right brain DA depletion on the activity of various NPs in corticolimbic regions of the left and right hemispheres, such as the medial prefrontal cortex, amygdala and hippocampus, as well as on the plasma activity of the same aminopeptidase activities (APs) and on systolic blood pressure (SBP). Intra- and inter-hemispheric interactions as well as the interactions of NPs from the left or right hemispheres were analyzed with the same plasma APs and the SBP obtained from sham and from left or right lesioned rats. The results demonstrate a complex profile depending on the hemisphere considered. They definitively confirm an asymmetric neurovisceral integration and reveal a higher level of inter-hemispheric corticolimbic interactions including with SBP after left dopamine depletion.
Tempol Preserves Endothelial Progenitor Cells in Male Mice with Ambient Fine Particulate Matter Exposure
Authors: Liu Xuanyou , Wang Aimin , Chen Zhiheng , Cui Yuqi , Hao Hong , Domeier Timothy L. , Sun Qinghua , Liu Zhenguo
Published: January 2022

Ambient fine particulate matter (PM) exposure associates with an increased risk of cardiovascular diseases (CVDs). Major sex differences between males and females exist in epidemiology, pathophysiology, and outcome of CVDs. Endothelial progenitor cells (EPCs) play a vital role in the development and progression of CVDs. PM exposure-induced reduction of EPCs is observed in male, not female, mice with increased reactive oxygen species (ROS) production and oxidative stress. The lung is considered an important source of ROS in mice with PM exposure. The aim of the present study was to investigate the sex differences in pulmonary superoxide dismutase (SOD) expression and ROS production, and to test the effect of SOD mimic Tempol on the populations of EPCs in mice with PM exposure. Both male and female C57BL/6 mice (8–10 weeks) were exposed to intranasal PM or vehicle for 6 weeks. Flow cytometry analysis demonstrated that PM exposure significantly decreased the levels of EPCs (CD34+/CD133+) in both blood and bone marrow with increased ROS production in males, but not in females. ELISA analysis showed higher levels of serum IL-6 and IL-1βin males than in females. Pulmonary expression of the antioxidant enzyme SOD1 was significantly decreased in males after PM exposure, but not in females. Administration of the SOD mimic Tempol in male mice with PM exposure attenuated the production of ROS and inflammatory cytokines, and preserved EPC levels. These data indicated that PM exposure-induced reduction of EPC population in male mice may be due to decreased expression of pulmonary SOD1 in male mice.
A Polydopamine-Coated Gold Nanoparticles Quenching Quantum Dots-Based Dual-Readout Lateral Flow Immunoassay for Sensitive Detection of Carbendazim in Agriproducts
Authors: Mao Xinxin , Wang Yulong , Jiang Lan , Zhang Hanxiaoya , Zhao Yun , Liu Pengyan , Liu Juanjuan , Hammock Bruce D. , Zhang Cunzheng
Published: January 2022

In this study, a fluorometric and colorimetric dual-readout lateral flow immunoassay (LFIA) using antibody functionalized polydopamine-coated gold nanoparticles (Au@PDAs) as a probe was developed for the detection of carbendazim (CBD). Colloidal gold nanoparticles (AuNPs) were coated with polydopamines (PDA) by the oxidation of dopamine to synthesize Au@PDA nanoparticles. The Au@PDA nanoparticles mediated ZnCdSe/ZnS quantum dots (QDs) fluorescence quenching and recovery, resulting in a reverse fluorescence enhancement detection format of CBD. The CBD detection was obtained by the competition between the CBD and the immobilized antigen for Au@PDAs labelled antibody binding, resulting in a significant fluorescence increase and colorimetry decrease corresponded to the concentration of CBD. Dual readout modes were incorporated into the LFIA using the colorimetry signal under natural light and the fluorescence signal under UV light. The cut-off value in the mode of the colorimetric signal and fluorometric signal for CBD detection was 0.5 μg/mL and 0.0156 μg/mL, respectively. The sensitivity of LFIA of the fluorescence mode was 32 times higher than that of the colorimetry mode. There was negligible cross reactivity obtained by using LFIA for the determination of thiabendazole, benomyl, thiophanate-methyl, and thiophanate-ethyl. Consistent and satisfactory results have been achieved by comparing the results of Au@PDAs-QDs-LFIA and liquid chromatography-tandem mass spectrometry (LC—MS/MS) testing spiked cucumber and strawberry samples, indicating good reliability of the Au@PDAs-QDs-LFIA.
Malignant Melanoma-Derived Exosomes Induce Endothelial Damage and Glial Activation on a Human BBB Chip Model
Authors: Wang Peng , Wu Yunsong , Chen Wenwen , Zhang Min , Qin Jianhua
Published: February 2022

Malignant melanoma is a type of highly aggressive tumor, which has a strong ability to metastasize to brain, and 60–70% of patients die from the spread of the tumor into the central nervous system. Exosomes are a type of nano-sized vesicle secreted by most living cells, and accumulated studies have reported that they play crucial roles in brain tumor metastasis, such as breast cancer and lung cancer. However, it is unclear whether exosomes also participate in the brain metastasis of malignant melanoma. Here, we established a human blood–brain barrier (BBB) model by co-culturing human brain microvascular endothelial cells, astrocytes and microglial cells under a biomimetic condition, and used this model to explore the potential roles of exosomes derived from malignant melanoma in modulating BBB integrity. Our findings showed that malignant melanoma-derived exosomes disrupted BBB integrity and induced glial activation on the BBB chip. Transcriptome analyses revealed dys-regulation of autophagy and immune responses following tumor exosome treatment. These studies indicated malignant melanoma cells might modulate BBB integrity via exosomes, and verified the feasibility of a BBB chip as an ideal platform for studies of brain metastasis of tumors in vitro.
Concordance of Alzheimer’s Disease Subtypes Produced from Different Representative Morphological Measures: A Comparative Study
Authors: Zhang Baiwen , Lin Lan , Liu Lingyu , Shen Xiaoqi , Wu Shuicai
Published: January 2022

Background: Gray matter (GM) density and cortical thickness (CT) obtained from structural magnetic resonance imaging are representative GM morphological measures that have been commonly used in Alzheimer’s disease (AD) subtype research. However, how the two measures affect the definition of AD subtypes remains unclear. Methods: A total of 180 AD patients from the ADNI database were used to identify AD subgroups. The subtypes were identified via a data-driven strategy based on the density features and CT features, respectively. Then, the similarity between the two features in AD subtype definition was analyzed. Results: Four distinct subtypes were discovered by both density and CT features: diffuse atrophy AD, minimal atrophy AD (MAD), left temporal dominant atrophy AD (LTAD), and occipital sparing AD. The matched subtypes exhibited relatively high similarity in atrophy patterns and neuropsychological and neuropathological characteristics. They differed only in MAD and LTAD regarding the carrying of apolipoprotein E ε2. Conclusions: The results verified that different representative morphological GM measurement methods could produce similar AD subtypes. Meanwhile, the influences of apolipoprotein E genotype, asymmetric disease progression, and their interactions should be considered and included in the AD subtype definition. This study provides a valuable reference for selecting features in future studies of AD subtypes.
The Association between Modifiable Lifestyle Behaviors and Depression among Asian Americans with Chronic Hepatitis B by Medication Status
Authors: Zhu Lin , Lu Wenyue , Gamoso Winterlyn , Tan Yin , Johnson Cicely , Ma Grace X.
Published: January 2022

Asian Americans are disproportionately affected by chronic hepatitis B (CHB), with incidence and mortality rates well above those experienced by non-Hispanic white populations. The goal of this study was to examine the association between depression and modifiable lifestyle behaviors among Asian Americans with CHB, with a comparison between those on hepatitis medication and those not on medication. In total, 313 Asian Americans with CHB were recruited through outpatient clinics and community-based organizations to participate in an in-person baseline assessment. We collected data on participants’ sociodemographic characteristics, health-related behaviors, depression symptoms, and modifiable lifestyle behaviors. Bivariate analyses (two sample t-test and chi-square test of independence) and multivariable logistic regression were conducted. We found a high prevalence of depression among individuals living with CHB (41.81% among those not on antiviral medication and 39.71% among those on medication). Multivariate logistic regression results showed that Chinese ethnicity (vs. Vietnamese) and lack of physical activity were significantly associated with a higher risk of mild/severe depression, regardless of medication status. However, the protective effect of physical activity was strong for those on antiviral medication. Furthermore, being employed was significantly associated with a lower risk for depression among Asian Americans on medication, while younger age and being currently married were significantly associated with lower risk of depression among those not on medication. Our findings highlight the significance of physical activity among Asian Americans with CHB, especially for those on antiviral medication. Future prospective research efforts are needed to better identify the potential behavioral mechanisms of depression and provide insights for the psychopharmacological management in this vulnerable population.
Personalization of Repetitive Transcranial Magnetic Stimulation for the Treatment of Chronic Subjective Tinnitus
Authors: Schoisswohl Stefan , Langguth Berthold , Hebel Tobias , Vielsmeier Veronika , Abdelnaim Mohamed A. , Schecklmann Martin
Published: February 2022

Background: Personalization of repetitive transcranial magnetic stimulation (rTMS) for tinnitus might be capable to overcome the heterogeneity of treatment responses. The assessment of loudness changes after short rTMS protocols in test sessions has been proposed as a strategy to identify the best protocol for the daily treatment application. However, the therapeutic advantages of this approach are currently not clear. The present study was designed to further investigate the feasibility and clinical efficacy of personalized rTMS as compared to a standardized rTMS protocol used for tinnitus. Methods: RTMS personalization was conducted via test sessions and reliable, sham-superior responses respectively short-term reductions in tinnitus loudness following active rTMS protocols (1, 10, 20 Hz, each 200 pulses) applied over the left and right temporal cortex. Twenty pulses at a frequency of 0.1 Hz served as a control condition (sham). In case of a response, patients were randomly allocated to ten treatment sessions of either personalized rTMS (2000 pulses with the site and frequency producing the most pronounced loudness reduction during test sessions) or standard rTMS (1 Hz, 2000 pulses left temporal cortex). Those participants who did not show a response during the test sessions received the standard protocol as well. Results: The study was terminated prematurely after 22 patients (instead of 50 planned) as the number of test session responders was much lower than expected (27% instead of 50%). Statistical evaluation of changes in metric tinnitus variables and treatment responses indicated only numerical, but not statistical superiority for personalized rTMS compared to standard treatment. Conclusions: The current stage of investigation does not allow for a clear conclusion about the therapeutic advantages of personalized rTMS for tinnitus based on test session responses. The feasibility of this approach is primarily limited by the low test session response rate.
Neuroimaging Applications for Diagnosis and Therapy of Pathologies in the Central and Peripheral Nervous System
Authors: Middei Silvia
Published: February 2022

Imaging in neurosciences allows for the visual representation of micro- and macro-components of the central (CNS) and peripheral (PNS) nervous systems with the intent of investigating their morphology and function, to provide diagnosis and prognosis of neurological diseases and to monitor responses to treatments [...]
Announcement for “2021 Buildings Outstanding Reviewer Awards” Winners
Authors:   Editorial Office
Published: January 2022

Peer review is an essential part of the publication process and is important in ensuring that Buildings maintains high-quality standards for its published papers [...]
Spatial Immunology in Liver Metastases from Colorectal Carcinoma according to the Histologic Growth Pattern
Authors: Garcia-Vicién Gemma , Mezheyeuski Artur , Micke Patrick , Ruiz Núria , Ruffinelli José Carlos , Mils Kristel , Bañuls María , Molina Natàlia , Losa Ferran , Lladó Laura , Molleví David G.
Published: January 2022

Colorectal cancer liver metastases (CRC-LM) present differential histologic growth patterns (HGP) that determine the interaction between immune and tumor cells. We explored the spatial distribution of lymphocytic infiltrates in CRC-LM in the context of the HGP using multispectral digital pathology. We did not find statistically significant differences of immune cell densities in the central regions of desmoplastic (dHGP) and non-desmoplastic (ndHGP) metastases. The spatial evaluation reported that dHGP-metastases displayed higher infiltration by CD8+ and CD20+ cells in peripheral regions as well as CD4+ and CD45RO+ cells in ndHGP-metastases. However, the reactive stroma regions at the invasive margin (IM) of ndHGP-metastases displayed higher density of CD4+, CD20+, and CD45RO+ cells. The antitumor status of the TIL infiltrates measured as CD8/CD4 reported higher values in the IM of encapsulated metastases up to 400 μm towards the tumor center (p < 0.05). Remarkably, the IM of dHGP-metastases was characterized by higher infiltration of CD8+ cells in the epithelial compartment parameter assessed with the ratio CD8epithelial/CD8stromal, suggesting anti-tumoral activity in the encapsulating lesions. Taking together, the amount of CD8+ cells is comparable in the IM of both HGP metastases types. However, in dHGP-metastases some cytotoxic cells reach the tumor nests while remaining retained in the stromal areas in ndHGP-metastases.
Epigenetic Approaches to Overcome Fluoropyrimidines Resistance in Solid Tumors
Authors: Grumetti Laura , Lombardi Rita , Iannelli Federica , Pucci Biagio , Avallone Antonio , Di Gennaro Elena , Budillon Alfredo
Published: January 2022

Although fluoropyrimidines were introduced as anticancer agents over 60 years ago, they are still the backbone of many combination chemotherapy regimens for the treatment of solid cancers. Like other chemotherapeutic agents, the therapeutic efficacy of fluoropyrimidines can be affected by drug resistance and severe toxicities; thus, novel therapeutic approaches are required to potentiate their efficacy and overcome drug resistance. In the last 20 years, the deregulation of epigenetic mechanisms has been shown to contribute to cancer hallmarks. Histone modifications play an important role in directing the transcriptional machinery and therefore represent interesting druggable targets. In this review, we focused on histone deacetylase inhibitors (HDACis) that can increase antitumor efficacy and overcome resistance to fluoropyrimidines by targeting specific genes or proteins. Our preclinical data showed a strong synergistic interaction between HDACi and fluoropyrimidines in different cancer models, but the clinical studies did not seem to confirm these observations. Most likely, the introduction of increasingly complex preclinical models, both in vitro and in vivo, cannot recapitulate human complexity; however, our analysis of clinical studies revealed that most of them were designed without a mechanistic approach and, importantly, without careful patient selection.
Potential Involvement of NSD1, KRT24 and ACACA in the Genetic Predisposition to Colorectal Cancer
Authors: Quintana Isabel , Mur Pilar , Terradas Mariona , García-Mulero Sandra , Aiza Gemma , Navarro Matilde , Piñol Virginia , Brunet Joan , Moreno Victor , Sanz-Pamplona Rebeca , Capellá Gabriel , Valle Laura
Published: January 2022

The ALFRED (Allelic Loss Featuring Rare Damaging) in silico method was developed to identify cancer predisposition genes through the identification of somatic second hits. By applying ALFRED to ~10,000 tumor exomes, 49 candidate genes were identified. We aimed to assess the causal association of the identified genes with colorectal cancer (CRC) predisposition. Of the 49 genes, NSD1, HDAC10, KRT24, ACACA and TP63 were selected based on specific criteria relevant for hereditary CRC genes. Gene sequencing was performed in 736 patients with familial/early onset CRC or polyposis without germline pathogenic variants in known genes. Twelve (predicted) damaging variants in 18 patients were identified. A gene-based burden test in 1596 familial/early-onset CRC patients, 271 polyposis patients, 543 TCGA CRC patients and >134,000 controls (gnomAD, non-cancer), revealed no clear association with CRC for any of the studied genes. Nevertheless, (non-significant) over-representation of disruptive variants in NSD1, KRT24 and ACACA in CRC patients compared to controls was observed. A somatic second hit was identified in one of 20 tumors tested, corresponding to an NSD1 carrier. In conclusion, most genes identified through the ALFRED in silico method were not relevant for CRC predisposition, although a possible association was detected for NSD1, KRT24 and ACACA.
Targeting Cell Cycle Checkpoint Kinases to Overcome Intrinsic Radioresistance in Brain Tumor Cells
Authors: Vlatkovic Tijana , Veldwijk Marlon R. , Giordano Frank A. , Herskind Carsten
Published: January 2022

Radiation therapy is an important part of the standard of care treatment of brain tumors. However, the efficacy of radiation therapy is limited by the radioresistance of tumor cells, a phenomenon held responsible for the dismal prognosis of the most aggressive brain tumor types. A promising approach to radiosensitization of tumors is the inhibition of cell cycle checkpoint control responsible for cell cycle progression and the maintenance of genomic integrity. Inhibition of the kinases involved in these control mechanisms can abolish cell cycle checkpoints and DNA damage repair and thus increase the sensitivity of tumor cells to radiation and chemotherapy. Here, we discuss preclinical progress in molecular targeting of ATM, ATR, CHK1, CHK2, and WEE1, checkpoint kinases in the treatment of brain tumors, and review current clinical phase I-II trials.
Direct Oral Anticoagulants Are Associated with Superior Survival Outcomes than Warfarin in Patients with Head and Neck Cancers
Authors: Lee Chien-Lin , Chen Wei-Shan , Wee Yinshen , Wang Ching-Shuen , Chen Wei-Chih , Chiu Tai-Jan , Wang Yu-Ming , Wu Ching-Nung , Yang Yao-Hsu , Luo Sheng-Dean , Wu Shao-Chun
Published: January 2022

Increasing clinical evidence supports the use of direct oral anticoagulants (DOACs) as a potential new therapeutic option for patients suffering from cancer-associated thromboembolism. However, the clinical impact of DOACs compared with traditional anticoagulants on the survival of patients with head and neck cancer has not been well studied. A total of 1025 patients diagnosed as having head and neck cancer, including 92 DOAC users, 113 warfarin users, and 820 nonusers of anticoagulants, were selected from the Chang Gung Research Database between January 2001 and December 2019. The patients were matched using the propensity-score method. The survival rates were estimated among the three groups using the Kaplan–Meier method. The protective effects and side effects of the two anticoagulants were compared using the chi-square test. The death rate (18 patients, 19.57%) in patients using DOACs was significantly lower than that in patients using warfarin (68 patients, 60.18%) and those not using any anticoagulant (403 patients, 49.15%). DOAC users had significantly better disease-specific survival (DSS) than warfarin users (p = 0.019) and those who did not use any anticoagulant (p = 0.03). Further, DOAC users had significantly higher overall survival (OS) rates than warfarin users and those who did not use any anticoagulant (p = 0.003). Patients with oropharyngeal and laryngeal cancer and DOAC users had a significantly lower hazard ratio for survival, whereas patients with American Joint Committee on Cancer stage IV disease and those receiving multidisciplinary treatment (e.g., surgery with radiotherapy or concurrent radiochemotherapy) had a significantly higher hazard ratio for survival. Among them, patients with laryngeal cancer (HR = 0.47, 95% CI = 0.26–0.86, p = 0.0134) and DOAC users (HR = 0.53, 95% CI = 0.29–0.98, p = 0.042) had the lowest hazard ratio from DSS analysis. Similarly, patients with laryngeal cancer (HR = 0.48, 95% CI = 0.30–0.76, p = 0.0018) and DOAC users (HR = 0.58, 95% CI = 0.36–0.93, p = 0.0251) had the lowest hazard ratio from OS analysis. As for the protective effects or side effects of anticoagulants, there were no significant differences in the occurrence rate of bleeding or ischemic events between DOAC and warfarin users. In our study, DOACs were found to be better than warfarin in terms of survival in patients with head and neck cancer. As regards thromboembolism prevention and side effects, DOACs were comparable to warfarin in our patients. DOACs can be a treatment choice or prophylaxis for tumor emboli in head and neck cancer patients and they might be a better choice than traditional anticoagulants according to the results of our study.
Editorial on Special Issue “Advances and Novel Treatment Options in Metastatic Melanoma”
Authors: Carè Alessandra , Del Bufalo Donatella , Facchiano Antonio
Published: January 2022

Investigating mechanisms controlling melanoma setup, development and progression is currently an extremely hot and rapidly evolving topic [...]
Radiomics Features of the Spleen as Surrogates for CT-Based Lymphoma Diagnosis and Subtype Differentiation
Authors: Enke Johanna S. , Moltz Jan H. , D'Anastasi Melvin , Kunz Wolfgang G. , Schmidt Christian , Maurus Stefan , Mühlberg Alexander , Katzmann Alexander , Sühling Michael , Hahn Horst , Nörenberg Dominik , Huber Thomas
Published: January 2022

The spleen is often involved in malignant lymphoma, which manifests on CT as either splenomegaly or focal, hypodense lymphoma lesions. This study aimed to investigate the diagnostic value of radiomics features of the spleen in classifying malignant lymphoma against non-lymphoma as well as the determination of malignant lymphoma subtypes in the case of disease presence—in particular Hodgkin lymphoma (HL), diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma (MCL), and follicular lymphoma (FL). Spleen segmentations of 326 patients (139 female, median age 54.1 +/− 18.7 years) were generated and 1317 radiomics features per patient were extracted. For subtype classification, we created four different binary differentiation tasks and addressed them with a Random Forest classifier using 10-fold cross-validation. To detect the most relevant features, permutation importance was analyzed. Classifier results using all features were: malignant lymphoma vs. non-lymphoma AUC = 0.86 (p < 0.01); HL vs. NHL AUC = 0.75 (p < 0.01); DLBCL vs. other NHL AUC = 0.65 (p < 0.01); MCL vs. FL AUC = 0.67 (p < 0.01). Classifying malignant lymphoma vs. non-lymphoma was also possible using only shape features AUC = 0.77 (p < 0.01), with the most important feature being sphericity. Based on only shape features, a significant AUC could be achieved for all tasks, however, best results were achieved combining shape and textural features. This study demonstrates the value of splenic imaging and radiomic analysis in the diagnostic process in malignant lymphoma detection and subtype classification.
Synthesis of Biotinylated PAMAM G3 Dendrimers Substituted with R-Glycidol and Celecoxib/Simvastatin as Repurposed Drugs and Evaluation of Their Increased Additive Cytotoxicity for Cancer Cell Lines
Authors: Wróbel Konrad , Wołowiec Stanisław , Markowicz Joanna , Wałajtys-Rode Elżbieta , Uram Łukasz
Published: January 2022

Recent achievement in anticancer therapy considers the application of repurposed drugs in optimal combinations with the use of specific carriers for their targeted delivery. As a result, new optimized medications with reduced side effects can be obtained. In this study, two known anticancer drugs, celecoxib and/or simvastatin, were conjugated covalently with PAMAM G3 dendrimer and tested in vitro against human squamous carcinoma (SCC-15-15) and glioblastoma (U-118 MG) cells, as well as normal human fibroblasts (BJ). The obtained conjugates were also substituted with biotin and R-glycidol to increase their affinity for cancer cells and were characterized with NMR spectroscopy and dynamic light scattering technique. Conjugates furnished with two celecoxib and four simvastatin residues revealed the very high effectiveness and dramatically decreased the SCC-15 and U-118 MG cell viability at very low concentrations with IC50 equal to about 3 µM. Its action was 20–50-fold stronger than that of either drug alone or as a mixture. Combined conjugate revealed also additive action since it was 2–8-fold more effective than conjugates with either single drug. The combined conjugate revealed rather low specificity since it was also highly cytotoxic for BJ cells. Despite this, it may be concluded that biotinylated and R-glycidylated PAMAM G3 dendrimers substituted with both celecoxib and simvastatin can be considered as a new perspective anticancer agent, effective in therapy of malignant, incurable glioblastomas.
Efficient Reduction of Cr (VI) to Cr (III) over a TiO2-Supported Palladium Catalyst Using Formic Acid as a Reductant
Authors: Qin Chengxin , Pan Ganen , Zhang Yingxue , Ding Fangjun , Qu Jianyu , Xu Xingliang , Su Xiurong
Published: January 2022

Cr (VI) has been considered to be a harmful environmental pollutant due to its toxicity, mobility and strong oxidation. It has become challenging to remove Cr (VI) from wastewater. In this work, a series of supported palladium-based catalysts were synthesized via a facile wet chemical reduction method. Among all the as-synthesized catalysts, Pd/TiO2 (P25) showed the optimized catalytic activity for the reduction of Cr (VI) to Cr (III) using formic acid (HCOOH) as the reductant. More than 99% of K2Cr2O7 (50 mg/L) was reduced completely within 30 min at 25 °C. The structural properties of the Pd/TiO2 catalyst (such as particle size, hydrophilicity and stability) and the synergistic effect of metal and support played significant roles in the reduction of Cr (VI) to Cr (III). Meanwhile, several pivotal parameters such as Cr (VI) concentration, catalyst loading, HCOOH concentration and temperature were investigated in detail. Furthermore, this catalyst was also active for the reduction of nitro compounds with HCOOH as the reductant at room temperature. Finally, the reasonable reaction mechanism of the Pd/TiO2/HCOOH system for the reduction of Cr (VI) to Cr (III) was put forward.
Hybrid Organic–Inorganic Membranes for Photocatalytic Water Remediation
Authors: Mendes-Felipe Cristian , Veloso-Fernández Antonio , Vilas-Vilela José Luis , Ruiz-Rubio Leire
Published: January 2022

Mismanagement, pollution and excessive use have depleted the world’s water resources, producing a shortage that in some territories is extreme. In this context, the need for potable water prompts the development of new and more efficient wastewater treatment systems to overcome shortages by recovering and reusing contaminated water. Among the water treatment methods, membrane technology is considered one of the most promising. Besides, photocatalytic degradation has become an attractive and efficient technology for water and wastewater treatment. However, the use of unsupported catalysts has as its main impediment their separation from the water once treated. With this, providing the membranes with this photocatalyzed degradation capacity can improve the application of photocatalysts, since in many cases their application improves their recovery and reuse. This review describes the general photocatalytic processes of the main inorganic nanoparticles used as fillers in hybrid polymeric membranes. In addition, the most recent hybrid organic–inorganic membranes are reviewed. Finally, the membranes formed by metal–organic frameworks that can be considered one of the newest and most versatile developments are described.
Property Prediction of Ag-Filled Isotropic Conductive Adhesive through the Analysis of Its Curing and Decomposition Kinetics
Authors: Jiang Han , Zhou Minbo , Zhang Xinping
Published: February 2022

In this study, various thermal analyses were carried out on a self-developed and commerce-oriented Ag-filled isotropic conductive adhesive (ICA) and its unfilled matrix resin through which glass transition temperature (Tg) and thermal endurance could be quantitatively predicted. An autocatalyzed kinetic model was used to describe the curing reaction, which was proven to be in good consistency with the experimental data. The activation energies for the curing reaction of the ICA and the matrix resin were determined to be 68.1 kJ/mol and 72.9 kJ/mol, respectively, which means that the reaction of the ICA was easier to occur than its unfilled matrix resin. As a result, the time–temperature profile could be calculated for any Tg requested based on the kinetic model of curing and the DiBenedetto equation. Further, the thermal decomposition stability of the ICA and its unfilled matrix resin were also studied. The activation energies for the thermal decomposition of the ICA and the matrix resin were calculated to be 134.1 kJ/mol and 152.7 kJ/mol, respectively, using the Ozawa–Flynn–Wall method, which means that the decomposition of ICA was easier to occur. The service life of the resin system at a specific temperature could therefore be calculated with their activation energy. The addition of micro-scale Ag flakes did not change the curing and decomposition mechanisms by much.
The Role of Ionizing Radiation for Diagnosis and Treatment against COVID-19: Evidence and Considerations
Authors: Chalkia Marina , Arkoudis Nikolaos-Achilleas , Maragkoudakis Emmanouil , Rallis Stamatis , Tremi Ioanna , Georgakilas Alexandros G. , Kouloulias Vassilis , Efstathopoulos Efstathios , Platoni Kalliopi
Published: January 2022

The Coronavirus disease 2019 (COVID-19) pandemic continues to spread worldwide with over 260 million people infected and more than 5 million deaths, numbers that are escalating on a daily basis. Frontline health workers and scientists diligently fight to alleviate life-threatening symptoms and control the spread of the disease. There is an urgent need for better triage of patients, especially in third world countries, in order to decrease the pressure induced on healthcare facilities. In the struggle to treat life-threatening COVID-19 pneumonia, scientists have debated the clinical use of ionizing radiation (IR). The historical literature dating back to the 1940s contains many reports of successful treatment of pneumonia with IR. In this work, we critically review the literature for the use of IR for both diagnostic and treatment purposes. We identify details including the computed tomography (CT) scanning considerations, the radiobiological basis of IR anti-inflammatory effects, the supportive evidence for low dose radiation therapy (LDRT), and the risks of radiation-induced cancer and cardiac disease associated with LDRT. In this paper, we address concerns regarding the effective management of COVID-19 patients and potential avenues that could provide empirical evidence for the fight against the disease.