bluuebunny/crossref_metadata_2025 huggingface dataset:
Zoonotic Visceral Leishmaniasis: New Insights on Innate Immune Response by Blood Macrophages and Liver Kupffer Cells to Leishmania infantum Parasites
Authors: Rodrigues Armanda Viana , Valério-Bolas Ana , Alexandre-Pires Graça , Aires Pereira Maria , Nunes Telmo , Ligeiro Dário , Pereira da Fonseca Isabel , Santos-Gomes Gabriela
Published: January 2022

L. infantum is the aetiological agent of zoonotic visceral leishmaniasis (ZVL), a disease that affects humans and dogs. Leishmania parasites are well adapted to aggressive conditions inside the phagolysosome and can control the immune activation of macrophages (MØs). Although MØs are highly active phagocytic cells with the capacity to destroy pathogens, they additionally comprise the host cells for Leishmania infection, replication, and stable establishment in the mammal host. The present study compares, for the first time, the innate immune response to L. infantum infection of two different macrophage lineages: the blood macrophages and the liver macrophages (Kupffer cells, KC). Our findings showed that L. infantum takes advantage of the natural predisposition of blood-MØs to phagocyte pathogens. However, parasites rapidly subvert the mechanisms of MØs immune activation. On the other hand, KCs, which are primed for immune tolerance, are not extensively activated and can overcome the dormancy induced by the parasite, exhibiting a selection of immune mechanisms, such as extracellular trap formation. Altogether, KCs reveal a different pattern of response in contrast with blood-MØs when confronting L. infantum parasites. In addition, KCs response appears to be more efficient in managing parasite infection, thus contributing to the ability of the liver to naturally restrain Leishmania dissemination.
Phenotypic and Molecular Characteristics of the MDR Efflux Pump Gene-Carrying Stenotrophomonas maltophilia Strains Isolated in Warsaw, Poland
Authors: Zając Olga M. , Tyski Stefan , Laudy Agnieszka E.
Published: January 2022

An increase of nosocomial infections caused by Stenotrophomonas maltophilia strains has recently been observed all over the world. The isolation of these bacteria from the blood is of particular concern. In this study we performed the phenotypic and genotypic characterization of 94 S. maltophilia isolates, including isolates from patients hospitalized in a tertiary Warsaw hospital (n = 79) and from outpatients (n = 15). All isolates were found to be susceptible to trimethoprim-sulfamethoxazole and minocycline, while 44/94 isolates demonstrated a reduction in susceptibility to levofloxacin. A large genetic variation was observed among the isolates tested by pulsed-field gel electrophoresis. A clonal relationship with 100% similarity was observed between isolates within two sub-pulsotypes: the first included nine bloodstream isolates and the second involved six. Multilocus sequence typing showed two new sequence types (ST498 and ST499) deposited in public databases for molecular typing. Moreover, the presence of genes encoding ten different efflux pumps from the resistance-nodulation-division family and the ATP-binding cassette family was shown in the majority of the 94 isolates. The obtained knowledge about the prevalence of efflux pump genes in clinical S. maltophilia strains makes it possible to predict the scale of the risk of resistance emergence in strains as a result of gene overexpression.
Association between Fecal Short-Chain Fatty Acid Levels, Diet, and Body Mass Index in Patients with Inflammatory Bowel Disease
Authors: Dąbek-Drobny Agnieszka , Kaczmarczyk Olga , Woźniakiewicz Michał , Paśko Paweł , Dobrowolska-Iwanek Justyna , Woźniakiewicz Aneta , Piątek-Guziewicz Agnieszka , Zagrodzki Paweł , Zwolińska-Wcisło Małgorzata
Published: January 2022

Disturbances in the production of bacterial metabolites in the intestine have been reported in diseases associated with dysbiosis, such as inflammatory bowel diseases (IBDs) that include two conditions: Crohn disease (CD) and ulcerative colitis (UC). Short-chain fatty acids (SCFAs) are the main dietary-fiber-derived bacterial metabolites associated with the course of intestinal inflammation. In this study, we assessed the relationship between body mass index (BMI), the type of diet used, and changes in fecal SCFA levels in patients with IBD. We performed nutritional assessments using a nutritional questionnaire and determined fecal SCFA levels in 43 patients with UC, 18 patients with CD, and 16 controls. Our results revealed that subjects with a BMI > 24.99 kg/m2 had higher levels of isobutyric acid, whereas those with a BMI < 18.5 kg/m2 had lower level of butyric, isovaleric, and propionic acids. Furthermore, we observed higher levels of valeric acid in controls than in IBD patients. We did not reveal a relationship between a specific SCFA and the type of diet, but eating habits appear to be related to the observed changes in the SCFA profile depending on BMI. In conclusion, we demonstrated that BMI is associated with SCFA levels in patients with IBD.
Predicting Current Potential Distribution and the Range Dynamics of Pomacea canaliculata in China under Global Climate Change
Authors: Yin Yingxuan , He Qing , Pan Xiaowen , Liu Qiyong , Wu Yinjuan , Li Xuerong
Published: January 2022

Pomacea canaliculata is one of the 100 worst invasive alien species in the world, which has significant effects and harm to native species, ecological environment, human health, and social economy. Climate change is one of the major causes of species range shifts. With recent climate change, the distribution of P. canaliculata has shifted northward. Understanding the potential distribution under current and future climate conditions will aid in the management of the risk of its invasion and spread. Here, we used species distribution modeling (SDM) methods to predict the potential distribution of P. canaliculata in China, and the jackknife test was used to assess the importance of environmental variables for modeling. Our study found that precipitation of the warmest quarter and maximum temperature in the coldest months played important roles in the distribution of P. canaliculata. With global warming, there will be a trend of expansion and northward movement in the future. This study could provide recommendations for the management and prevention of snail invasion and expansion.
Surfactant Protein-G in Wildtype and 3xTg-AD Mice: Localization in the Forebrain, Age-Dependent Hippocampal Dot-like Deposits and Brain Content
Authors: Meinicke Anton , Härtig Wolfgang , Winter Karsten , Puchta Joana , Mages Bianca , Michalski Dominik , Emmer Alexander , Otto Markus , Hoffmann Karl-Titus , Reimann Willi , Krause Matthias , Schob Stefan
Published: January 2022

The classic surfactant proteins (SPs) A, B, C, and D were discovered in the lungs, where they contribute to host defense and regulate the alveolar surface tension during breathing. Their additional importance for brain physiology was discovered decades later. SP-G, a novel amphiphilic SP, was then identified in the lungs and is mostly linked to inflammation. In the brain, it is also present and significantly elevated after hemorrhage in premature infants and in distinct conditions affecting the cerebrospinal fluid circulation of adults. However, current knowledge on SP-G-expression is limited to ependymal cells and some neurons in the subventricular and superficial cortex. Therefore, we primarily focused on the distribution of SP-G-immunoreactivity (ir) and its spatial relationships with components of the neurovascular unit in murine forebrains. Triple fluorescence labeling elucidated SP-G-co-expressing neurons in the habenula, infundibulum, and hypothalamus. Exploring whether SP-G might play a role in Alzheimer’s disease (AD), 3xTg-AD mice were investigated and displayed age-dependent hippocampal deposits of β-amyloid and hyperphosphorylated tau separately from clustered, SP-G-containing dots with additional Reelin-ir—which was used as established marker for disease progression in this specific context. Semi-quantification of those dots, together with immunoassay-based quantification of intra- and extracellular SP-G, revealed a significant elevation in old 3xTg mice when compared to age-matched wildtype animals. This suggests a role of SP-G for the pathophysiology of AD, but a confirmation with human samples is required.
In Silico, In Vitro, and In Vivo Analysis of Tanshinone IIA and Cryptotanshinone from Salvia miltiorrhiza as Modulators of Cyclooxygenase-2/mPGES-1/Endothelial Prostaglandin EP3 Pathway
Authors: Saviano Anella , De Vita Simona , Chini Maria Giovanna , Marigliano Noemi , Lauro Gianluigi , Casillo Gian Marco , Raucci Federica , Iorizzi Maria , Hofstetter Robert Klaus , Fischer Katrin , Koeberle Andreas , Werz Oliver , Maione Francesco , Bifulco Giuseppe
Published: January 2022

Tanshinone IIA (TIIA) and cryptotanshinone (CRY) from Salvia miltiorrhiza Bunge were investigated for their inhibitory activity against the cyclooxygenase-2 (COX-2)/microsomal prostaglandin E synthase-1 (mPGES-1)/endothelial prostaglandin 3 (EP3) pathway using in silico, in vitro, in vivo, and ex vivo assays. From the analysis of the docking poses, both diterpenoids were able to interact significantly with COX-2, 5-lipoxygenase (5-LO), platelet-activating factor receptor (PAFR), and mPGES-1. This evidence was further corroborated by data obtained from a cell-free assay, where CRY displayed a significant inhibitory potency against mPGES-1 (IC50 = 1.9 ± 0.4 µM) and 5-LO (IC50 = 7.1 µM), while TIIA showed no relevant inhibition of these targets. This was consistent with their activity to increase mice bleeding time (CRY: 2.44 ± 0.13 min, p ≤ 0.001; TIIA: 2.07 ± 0.17 min p ≤ 0.01) and with the capability to modulate mouse clot retraction (CRY: 0.048 ± 0.011 g, p ≤ 0.01; TIIA: 0.068 ± 0.009 g, p ≤ 0.05). For the first time, our results show that TIIA and, in particular, CRY are able to interact significantly with the key proteins involved not only in the onset of inflammation but also in platelet activity (and hyper-reactivity). Future preclinical and clinical investigations, together with this evidence, could provide the scientific basis to consider these compounds as an alternative therapeutic approach for thrombotic- and thromboembolic-based diseases.
HMGB1 Inhibition to Ameliorate Organ Failure and Increase Survival in Trauma
Authors: Yang Zhangsheng , Simovic Milomir O. , Edsall Peter R. , Liu Bin , Cancio Tomas S. , Batchinsky Andriy I. , Cancio Leopoldo C. , Li Yansong
Published: January 2022

Several preclinical and clinical reports have demonstrated that levels of circulating high mobility group box 1 protein (HMGB1) are increased early after trauma and are associated with systemic inflammation and clinical outcomes. However, the mechanisms of the interaction between HMGB1 and inflammatory mediators that lead to the development of remote organ damage after trauma remain obscure. HMGB1 and inflammatory mediators were analyzed in plasma from 54 combat casualties, collected on admission to a military hospital in Iraq, and at 8 and 24 h after admission. In total, 45 (83%) of these patients had traumatic brain injury (TBI). Nine healthy volunteers were enrolled as controls. HMGB1 plasma levels were significantly increased in the first 8 h after admission, and were found to be associated with systemic inflammatory responses, injury severity score, and presence of TBI. These data provided the rationale for designing experiments in rats subjected to blast injury and hemorrhage, to explore the effect of HMGB1 inhibition by CX-01 (2-O, 3-O desulfated heparin). Animals were cannulated, then recovered for 5–7 days before blast injury in a shock tube and volume-controlled hemorrhage. Blast injury and hemorrhage induced an early increase in HMGB1 plasma levels along with severe tissue damage and high mortality. CX-01 inhibited systemic HMGB1 activity, decreased local and systemic inflammatory responses, significantly reduced tissue and organ damage, and tended to increase survival. These data suggest that CX-01 has potential as an adjuvant treatment for traumatic hemorrhage.
Multi-Organ Crosstalk with Endocrine Pancreas: A Focus on How Gut Microbiota Shapes Pancreatic Beta-Cells
Authors: Fernández-Millán Elisa , Guillén Carlos
Published: January 2022

Type 2 diabetes (T2D) results from impaired beta-cell function and insufficient beta-cell mass compensation in the setting of insulin resistance. Current therapeutic strategies focus their efforts on promoting the maintenance of functional beta-cell mass to ensure appropriate glycemic control. Thus, understanding how beta-cells communicate with metabolic and non-metabolic tissues provides a novel area for investigation and implicates the importance of inter-organ communication in the pathology of metabolic diseases such as T2D. In this review, we provide an overview of secreted factors from diverse organs and tissues that have been shown to impact beta-cell biology. Specifically, we discuss experimental and clinical evidence in support for a role of gut to beta-cell crosstalk, paying particular attention to bacteria-derived factors including short-chain fatty acids, lipopolysaccharide, and factors contained within extracellular vesicles that influence the function and/or the survival of beta cells under normal or diabetogenic conditions.
Early Blockade of CB1 Receptors Ameliorates Schizophrenia-like Alterations in the Neurodevelopmental MAM Model of Schizophrenia
Authors: Stark Tibor , Iannotti Fabio Arturo , Di Martino Serena , Di Bartolomeo Martina , Ruda-Kucerova Jana , Piscitelli Fabiana , Wotjak Carsten T. , D’Addario Claudio , Drago Filippo , Di Marzo Vincenzo , Micale Vincenzo
Published: January 2022

In agreement with the neurodevelopmental hypothesis of schizophrenia, prenatal exposure of Sprague-Dawley rats to the antimitotic agent methylazoxymethanol acetate (MAM) at gestational day 17 produces long-lasting behavioral alterations such as social withdrawal and cognitive impairment in adulthood, mimicking a schizophrenia-like phenotype. These abnormalities were preceded at neonatal age both by the delayed appearance of neonatal reflexes, an index of impaired brain maturation, and by higher 2-arachidonoylglycerol (2-AG) brain levels. Schizophrenia-like deficits were reversed by early treatment [from postnatal day (PND) 2 to PND 8] with the CB1 antagonist/inverse agonist AM251 (0.5 mg/kg/day). By contrast, early CB1 blockade affected the behavioral performance of control rats which was paralleled by enhanced 2-AG content in the prefrontal cortex (PFC). These results suggest that prenatal MAM insult leads to premorbid anomalies at neonatal age via altered tone of the endocannabinoid system, which may be considered as an early marker preceding the development of schizophrenia-like alterations in adulthood.
Research on Optimization of Climate Responsive Indoor Space Design in Residential Buildings
Authors: Li Zhixing , Zou Yukai , Tian Mimi , Ying Yuxi
Published: January 2022

This paper first analyzes the climate characteristics of five typical cities in China, including Harbin, Beijing, Shanghai, Shenzhen and Kunming. Then, based on Grasshopper, Ladybug and Honeybee analysis software, according to the indoor layout of typical residential buildings, this research extracts design parameters such as the depth and width of different rooms and their window-to-wall ratios etc., to establish a climate responsive optimization design process with indoor lighting environment comfort, with heating and cooling demand as the objective functions. Meanwhile, based on Monte Carlo simulation data, ANN (Artificial Neural Network) is used to establish a prediction model to analyze the sensitivity of interior design parameters under different typical cities’ climatic conditions. The study results show that the recommended values for the total width and total depth of indoor units under the climatic conditions of each city are both approximately 14.97 m and 7.88 m. Among them, under the climatic conditions of Harbin and Shenzhen, the design parameters of residential interiors can take the recommended value of UDI optimal or nZEB optimal. While the recommended values of window-to-wall ratios for the north bedroom, master bedroom and living room in Shanghai residential interiors are 0.26, 0.32 and 0.33, respectively. The recommended value of the window-to-wall ratio of the master bedroom in Kunming residences is 0.36, and that of the remaining rooms is between 0.15 and 0.18. The recommended values of window-to-wall ratios for the master bedroom and living room in Beijing residences are 0.41 and 0.59, respectively, and that for the remaining rooms are 0.15. The multi-objective optimization process based on parametric performance simulation used in the study can effectively assist architects in making energy-saving design decisions in the preliminary stage, allowing architects to have a case to follow in the actual design operation process.
Enabling Nature-Based Solutions to Build Back Better—An Environmental Regulatory Impact Analysis of Green Infrastructure in Ontario, Canada
Authors: Anderson Vidya , Gough William A.
Published: January 2022

The application of green infrastructure in the built environment delivers a nature-based solution to address the impacts of climate change. This study presents a qualitative evidence synthesis that evaluates policy instruments which enable the use and implementation of green infrastructure, using Ontario, Canada as a case study. Unpacking the elements of the policy landscape that govern green infrastructure through environmental regulatory impact analysis can inform effective implementation of this nature-based solution and support decision-making in public policy. This environmental regulatory impact analysis is based on a systematic review of existing policy instruments, contextual framing in a continuum of coercion, and identification of alignment with relevant UN SDGs. Enabling widespread usage of green infrastructure in the built environment could be a viable strategy to build back better, localize the UN SDGs, and address multiple climate change impacts.
Recent Advances in Device Engineering and Computational Analysis for Characterization of Cell-Released Cancer Biomarkers
Authors: Abouali Hesam , Hosseini Seied Ali , Purcell Emma , Nagrath Sunitha , Poudineh Mahla
Published: January 2022

During cancer progression, tumors shed different biomarkers into the bloodstream, including circulating tumor cells (CTCs), extracellular vesicles (EVs), circulating cell-free DNA (cfDNA), and circulating tumor DNA (ctDNA). The analysis of these biomarkers in the blood, known as ‘liquid biopsy’ (LB), is a promising approach for early cancer detection and treatment monitoring, and more recently, as a means for cancer therapy. Previous reviews have discussed the role of CTCs and ctDNA in cancer progression; however, ctDNA and EVs are rapidly evolving with technological advancements and computational analysis and are the subject of enormous recent studies in cancer biomarkers. In this review, first, we introduce these cell-released cancer biomarkers and briefly discuss their clinical significance in cancer diagnosis and treatment monitoring. Second, we present conventional and novel approaches for the isolation, profiling, and characterization of these markers. We then investigate the mathematical and in silico models that are developed to investigate the function of ctDNA and EVs in cancer progression. We convey our views on what is needed to pave the way to translate the emerging technologies and models into the clinic and make the case that optimized next-generation techniques and models are needed to precisely evaluate the clinical relevance of these LB markers.
ATX-101, a Peptide Targeting PCNA, Has Antitumor Efficacy Alone or in Combination with Radiotherapy in Murine Models of Human Glioblastoma
Authors: Gravina Giovanni , Colapietro Alessandro , Mancini Andrea , Rossetti Alessandra , Martellucci Stefano , Ventura Luca , Di Franco Martina , Marampon Francesco , Mattei Vincenzo , Biordi Leda , Otterlei Marit , Festuccia Claudio
Published: January 2022

Cell proliferation requires the orchestrated actions of a myriad of proteins regulating DNA replication, DNA repair and damage tolerance, and cell cycle. Proliferating cell nuclear antigen (PCNA) is a master regulator which interacts with multiple proteins functioning in these processes, and this makes PCNA an attractive target in anticancer therapies. Here, we show that a cell-penetrating peptide containing the AlkB homolog 2 PCNA-interacting motif (APIM), ATX-101, has antitumor activity in a panel of human glioblastoma multiforme (GBM) cell lines and patient-derived glioma-initiating cells (GICs). Their sensitivity to ATX-101 was not related to cellular levels of PCNA, or p53, PTEN, or MGMT status. However, ATX-101 reduced Akt/mTOR and DNA-PKcs signaling, and a correlation between high Akt activation and sensitivity for ATX-101 was found. ATX-101 increased the levels of γH2AX, DNA fragmentation, and apoptosis when combined with radiotherapy (RT). In line with the in vitro results, ATX-101 strongly reduced tumor growth in two subcutaneous xenografts and two orthotopic GBM models, both as a single agent and in combination with RT. The ability of ATX-101 to sensitize cells to RT is promising for further development of this compound for use in GBM.
Potential Role of CXCL13/CXCR5 Signaling in Immune Checkpoint Inhibitor Treatment in Cancer
Authors: Hsieh Ching-Hung , Jian Cheng-Zhe , Lin Liang-In , Low Guan-Sian , Ou Ping-Yun , Hsu Chiun , Ou Da-Liang
Published: January 2022

Immune checkpoint inhibitors (ICIs), including antibodies that target programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), or cytotoxic T lymphocyte antigen 4 (CTLA4), represent some of the most important breakthroughs in new drug development for oncology therapy from the past decade. CXC chemokine ligand 13 (CXCL13) exclusively binds CXC chemokine receptor type 5 (CXCR5), which plays a critical role in immune cell recruitment and activation and the regulation of the adaptive immune response. CXCL13 is a key molecular determinant of the formation of tertiary lymphoid structures (TLSs), which are organized aggregates of T, B, and dendritic cells that participate in the adaptive antitumor immune response. CXCL13 may also serve as a prognostic and predictive factor, and the role played by CXCL13 in some ICI-responsive tumor types has gained intense interest. This review discusses how CXCL13/CXCR5 signaling modulates cancer and immune cells to promote lymphocyte infiltration, activation by tumor antigens, and differentiation to increase the antitumor immune response. We also summarize recent preclinical and clinical evidence regarding the ICI-therapeutic implications of targeting the CXCL13/CXCR5 axis and discuss the potential role of this signaling pathway in cancer immunotherapy.
Radionuclides in Diagnostics and Therapy of Malignant Tumors: New Development
Authors: Tolmachev Vladimir , Vorobyeva Anzhelika
Published: January 2022

The interest in using targeted radiopharmaceuticals in nuclear oncology has increased in recent years and continues to grow [...]
The Decision-Making Process for Palliative Sedation for Patients with Advanced Cancer–Analysis from a Systematic Review of Prospective Studies
Authors: Belar Alazne , Arantzamendi Maria , Menten Johan , Payne Sheila , Hasselaar Jeroen , Centeno Carlos
Published: January 2022

Background. The involvement of patients in decision making about their healthcare plans is being emphasized. In the context of palliative sedation, it is unclear how these decisions are made and who are involved in. The aim of the study is to understand how this decision-making is taken. Method. Information from a systematic review on clinical aspects of palliative sedation prospective studies were included. PubMed, CINAHL, Cochrane, MEDLINE, and EMBASE were searched (January 2014–December 2019). Data extraction and analysis regarded: (a) When and by whom the decision-making process is initiated; (b) patient involvement; (c) family involvement and (d) healthcare involvement. Results. Data about decision making were reported in 8/10 included articles. Palliative sedation was reported in 1137 patients (only 16 of them were non-cancer). Palliative sedation was introduced by the palliative care team during the disease process, at admission, or when patients experienced refractory symptoms. Only two studies explicitly mentioned the involvement of patients in decision making. Co-decision between families and the regular health care professionals was usual, and the health care professionals involved had been working in palliative care services. Conclusion. Patient participation in decision making appeared to be compromised by limited physical or cognitive capacity and family participation is described. The possibility of palliative sedation should be discussed earlier in the disease process.
AKT Isoforms Interplay in High-Grade Serous Ovarian Cancer Prognosis and Characterization
Authors: Azzalini Eros , Tierno Domenico , Bartoletti Michele , Barbazza Renzo , Giorda Giorgio , Puglisi Fabio , Cecere Sabrina Chiara , Losito Nunzia Simona , Russo Daniela , Stanta Giorgio , Canzonieri Vincenzo , Bonin Serena
Published: January 2022

High-grade serous ovarian cancer (HGSOC) is among the deadliest gynecological malignancies. The acquired resistance to platinum-based therapies and the intrinsic heterogeneity of the disease contribute to the low survival rate. To improve patients’ outcomes, new combinatorial approaches able to target different tumor vulnerabilities and enhance the efficacy of the current therapies are required. AKT inhibitors are promising antineoplastic agents able to act in synergy with PARP inhibitors, but the spectrum of patients who can benefit from this combination is unclear, since the role of the three different isoforms of AKT is still unknown. Here, we study the expression of AKT isoforms on a retrospective cohort of archive tissue by RT-droplet digital PCR (ddPCR) analyzing their association with the clinicopathological features of patients. Based on AKT1/AKT2 and AKT1/AKT3 ratios, we define four AKT classes which were related to patients’ survival, tumor morphology and BRCA1 expression. Moreover, our results show that high AKT3 expression levels were frequently associated with tumors having classic features, a low number of mitoses and the presence of psammoma bodies. Overall, our study obtains new insights on AKT isoforms and their associations with the clinicopathological features of HGSOC patients. These evidences could help to better define the subsets of patients who can benefit from AKT and PARP inhibitors therapy in future clinical trials.
Complement Factor D Is a Novel Biomarker and Putative Therapeutic Target in Cutaneous Squamous Cell Carcinoma
Authors: Rahmati Nezhad Pegah , Riihilä Pilvi , Knuutila Jaakko S. , Viiklepp Kristina , Peltonen Sirkku , Kallajoki Markku , Meri Seppo , Nissinen Liisa , Kähäri Veli-Matti
Published: January 2022

Cutaneous squamous cell carcinoma (cSCC) is the most prevalent metastatic skin cancer. Previous studies have demonstrated the autocrine role of complement components in cSCC progression. We have investigated factor D (FD), the key enzyme of the alternative complement pathway, in the development of cSCC. RT-qPCR analysis of cSCC cell lines and normal human epidermal keratinocytes (NHEKs) demonstrated significant up-regulation of FD mRNA in cSCC cells compared to NHEKs. Western blot analysis also showed more abundant FD production by cSCC cell lines. Significantly higher FD mRNA levels were noted in cSCC tumors than in normal skin. Strong tumor cell-associated FD immunolabeling was detected in the invasive margin of human cSCC xenografts. More intense tumor cell-specific immunostaining for FD was seen in the tumor edge in primary and metastatic cSCCs, in metastases, and in recessive dystrophic epidermolysis bullosa-associated cSCCs, compared with cSCC in situ, actinic keratosis and normal skin. FD production by cSCC cells was dependent on p38 mitogen-activated protein kinase activity, and it was induced by interferon-γ and interleukin-1β. Blocking FD activity by Danicopan inhibited activation of extracellular signal-regulated kinase 1/2 and attenuated proliferation of cSCC cells. These results identify FD as a novel putative biomarker and therapeutic target for cSCC progression.
Metabolomic Phenotyping of Gliomas: What Can We Get with Simplified Protocol for Intact Tissue Analysis?
Authors: Goryńska Paulina Zofia , Chmara Kamila , Kupcewicz Bogumiła , Goryński Krzysztof , Jaroch Karol , Paczkowski Dariusz , Furtak Jacek , Harat Marek , Bojko Barbara
Published: January 2022

Glioblastoma multiforme is one of the most malignant neoplasms among humans in their third and fourth decades of life, which is evidenced by short patient survival times and rapid tumor-cell proliferation after radiation and chemotherapy. At present, the diagnosis of gliomas and decisions related to therapeutic strategies are based on genetic testing and histological analysis of the tumor, with molecular biomarkers still being sought to complement the diagnostic panel. This work aims to enable the metabolomic characterization of cancer tissue and the discovery of potential biomarkers via high-resolution mass spectrometry coupled to liquid chromatography and a solvent-free sampling protocol that uses a microprobe to extract metabolites directly from intact tumors. The metabolomic analyses were performed independently from genetic and histological testing and at a later time. Despite the small cohort analyzed in this study, the results indicated that the proposed method is able to identify metabolites associated with different malignancy grades of glioma, as well as IDH and 1p19q codeletion mutations. A comparison of the constellation of identified metabolites and the results of standard tests indicated the validity of using the characterization of one comprehensive tumor phenotype as a reflection of all diagnostically meaningful information. Due to its simplicity, the proposed analytical approach was verified as being compatible with a surgical environment and applicable for large-scale studies.
Systemic Mobilization of Breast Cancer Resistance Protein in Response to Oncogenic Stress
Authors: Szczygieł Małgorzata , Markiewicz Marcin , Szafraniec Milena Julia , Hojda Agnieszka , Fiedor Leszek , Urbanska Krystyna
Published: January 2022

The breast cancer resistance protein (BCRP or ABCG2) involved in cancer multidrug resistance (MDR), transports many hydrophobic compounds, including a number of anti-cancer drugs. Our comprehensive study using a mouse model reveals that a subcutaneously growing tumor strongly affects the expression of BCRP in the host’s normal organs on both the transcriptional and translational level. Additionally, the efflux of BCRP substrates is markedly enhanced. The levels of BCRP and its transcript in normal tissues distant from the tumor site correlate with tumor growth and the levels of cytokines in the peripheral blood. Thus, oncogenic stress causes transient systemic upregulation of BCRP in the host’s normal tissues and organs, which is possibly mediated via cytokines. Because BCRP upregulation takes place in many organs as early as the initial stages of tumor development, it reveals a most basic mechanism that may be responsible for the induction of primary MDR. We hypothesize that such effects are not tumor-specific responses, but rather constitute a more universal defense strategy. The xenobiotic transporters are systemically mobilized due to various stresses, seemingly in a pre-emptive manner so that the body can be quickly and efficiently detoxified. Our findings shed new light on the biology of cancer and on the complexity of cancer–host interactions and are highly relevant to cancer therapies as well as to the design of new generations of therapeutics and personalized medicine.
Afatinib Treatment Alone or with Bevacizumab in a Real-World Cohort of Non-Small Cell Lung Cancer Patients with Epidermal Growth Factor Receptor Mutation
Authors: Kuo Chih-Hsi Scott , Chiu Tzu-Hsuan , Tung Pi-Hung , Huang Chi-Hsien , Ju Jia-Shiuan , Huang Allen Chung-Cheng , Wang Chin-Chou , Ko Ho-Wen , Hsu Ping-Chih , Fang Yueh-Fu , Guo Yi-Ke , Yang Cheng-Ta
Published: January 2022

Background: Treatment outcome between afatinib alone or with bevacizumab in non-small cell lung cancer (NSCLC) patient with epidermal growth factor receptor (EGFR) mutation remains insufficiently reported. Methods: A total of 405 advanced NSCLC patients with sensitizing-EGFR mutation receiving first-line single-agent afatinib or with bevacizumab were grouped and propensity score-matched. Progression-free survival (PFS), overall survival (OS) and secondary T790M mutation were analyzed. Results: In the original cohort, 367 (90.6%) patients received afatinib treatment alone and 38 (9.4%) patients received afatinib plus bevacizumab. Patients who received bevacizumab combination were significantly younger (54.6 ± 10.9 vs. 63.9 ± 11.5; p < 0.001) compared to the afatinib alone group. After propensity score matching, the afatinib alone and afatinib plus bevacizumab groups contained 118 and 34 patients, respectively. A non-significantly higher objective response was noted in the afatinib plus bevacizumab group (82.4% vs. 67.8%; p = 0.133). In the propensity score-matched cohort, a bevacizumab add-on offered no increased PFS (16.1 vs. 15.0 months; p = 0.500), risk reduction of progression (HR 0.85 [95% CI, 0.52–1.40]; p = 0.528), OS benefit (32.1 vs. 42.0 months; p = 0.700), nor risk reduction of death (HR 0.85 [95% CI, 0.42–1.74] p = 0.660) compared to the single-agent afatinib. The secondary T790M rate in afatinib plus bevacizumab and afatinib alone groups was similar (56.3% vs. 49.4%, p = 0.794). Multivariate analysis demonstrated that EGFR L858R (OR 0.51 [95% CI, 0.26–0.97]; p = 0.044), EGFR uncommon mutation (OR 0.14 [95% CI, 0.02–0.64]; p = 0.021), and PFS longer than 12 months (OR 2.71 [95% CI, 1.39–5.41]; p = 0.004) were independent predictors of secondary T790M positivity. Conclusion: Bevacizumab treatment showed moderate efficacy in real-world, afatinib-treated NSCLC patients with EGFR-sensitizing mutation.
The Overall Quality of Life and Oncological Outcomes Following Radical Hysterectomy in Cervical Cancer Survivors Results from a Large Long-Term Single-Institution Study
Authors: Stanca Mihai , Căpîlna Dan Mihai , Trâmbițaș Cristian , Căpîlna Mihai Emil
Published: January 2022

(1) Background: Cervical cancer patients have been found to have worse quality of life (QoL) scores due to cancer treatment, not only when compared to the general population, but also when compared to other gynecological cancer survivors. In Eastern European developing countries, the health care system often cannot afford the uppermost standardized treatment for these patients. In the absence of a comparable study in our country, the authors’ aim for this retrospective cross-sectional observational study was to evaluate the overall survival (OS) and the QoL o cervical cancer survivors; (2) Methods: 430 patients were analyzed. The first objective is to evaluate the OS rates of patients with cervical cancer stages IA2 to IIB undergoing radical hysterectomy (RH) +/− neoadjuvant or adjuvant radiotherapy +/− chemoradiotherapy treatment combinations. The second objective is to assess their QoL, using two standardized questionnaires issued by the European Organisation for Research and Treatment of Cancer (EORTC), namely QLQ-C30 and QLQ-CX24. (3) Results: The mean age of the participants was 51 years (22–76) and the average follow-up time was 65 months (2–128). At the time of the analysis, 308 out of 430 patients were alive, with a mean five-year OS of 72.4%. The multivariate Cox regression analysis identified stage IIB, parametrial invasion, and the lymph node metastases as independent prognostic risk factors negatively impacting the OS. Of the 308 patients still alive at the time of the analysis, 208 (68%) answered the QoL questionnaires. The QLQ-C30 shows a good long-term Global QoL of 64.6 (median), good functioning scores, and a decent symptom scale value. However, the EORTC QLQ-CX24 showed high values of cervical cancer-specific symptoms, namely: lymphedema, peripheral neuropathy, severe menopausal symptoms, and distorted body-image perception. The results also indicate a significant decline in the quality of sexual life with a low sexual enjoyment and decreased level of sexual activities. (4) Conclusion: Despite a good OS, in this setting of patients, cervical cancer survivors have a modest QoL and sexual function. Our study may provide a comparison for future randomized, controlled trials in Eastern European countries needing to confirm these results.
Optical Coherence Tomography Identifies Visual Pathway Involvement Earlier than Visual Function Tests in Children with MRI-Verified Optic Pathway Gliomas
Authors: Arnljots Urszula , Nilsson Maria , Sandvik Ulrika , Myrberg Ida Hed , Munoz Daniel Martin , Blomgren Klas , Hellgren Kerstin
Published: January 2022

This study investigates whether optical coherence tomography (OCT) could add useful information in the examination of children with optic pathway glioma (OPG) at high risk of developing vision loss. For this purpose, the relationship between ganglion cell-inner plexiform layer (GC-IPL) thickness and visual function, evaluated with tests of visual acuity (VA) and visual field (VF), as well as tumor site according to magnetic resonance imaging (MRI), were examined in a geographically defined group of children with OPG. Methods: Children aged <18 years with OPG underwent ophthalmic examination including VA, VF (Zeiss HFA perimetry) and OCT imaging (Zeiss Cirrus HD-OCT). Results: Out of 51 patients included, 45 provided 77 eyes with MRI-verified OPG, and 19 patients provided 25 eyes without OPG. Significant correlations were found between GC-IPL, VF and VA (p < 0.001). The GC-IPL pattern loss corresponded in 95% to VF defects and in 92% to MRI findings. Conclusions: Our study indicates that GC-IPL measures could serve as an early marker of vision-threatening changes related to OPG and as a valuable link between MRI and visual function tests. Thinning of GC-IPL and differences in topography between eyes are strong indicators of and predictive of vision loss related to OPG.
Correction: Kwok et al. Targeting the p53 Pathway in CLL: State of the Art and Future Perspectives. Cancers 2021, 13, 4681
Authors: Kwok Marwan , Agathanggelou Angelo , Davies Nicholas , Stankovic Tatjana
Published: January 2022

The authors wish to make the following corrections to their paper [1] [...]
Pathophysiological Integration of Metabolic Reprogramming in Breast Cancer
Authors: Corchado-Cobos Roberto , García-Sancha Natalia , Mendiburu-Eliçabe Marina , Gómez-Vecino Aurora , Jiménez-Navas Alejandro , Pérez-Baena Manuel Jesús , Holgado-Madruga Marina , Mao Jian-Hua , Cañueto Javier , Castillo-Lluva Sonia , Pérez-Losada Jesús
Published: January 2022

Metabolic changes that facilitate tumor growth are one of the hallmarks of cancer. The triggers of these metabolic changes are located in the tumor parenchymal cells, where oncogenic mutations induce an imperative need to proliferate and cause tumor initiation and progression. Cancer cells undergo significant metabolic reorganization during disease progression that is tailored to their energy demands and fluctuating environmental conditions. Oxidative stress plays an essential role as a trigger under such conditions. These metabolic changes are the consequence of the interaction between tumor cells and stromal myofibroblasts. The metabolic changes in tumor cells include protein anabolism and the synthesis of cell membranes and nucleic acids, which all facilitate cell proliferation. They are linked to catabolism and autophagy in stromal myofibroblasts, causing the release of nutrients for the cells of the tumor parenchyma. Metabolic changes lead to an interstitium deficient in nutrients, such as glucose and amino acids, and acidification by lactic acid. Together with hypoxia, they produce functional changes in other cells of the tumor stroma, such as many immune subpopulations and endothelial cells, which lead to tumor growth. Thus, immune cells favor tissue growth through changes in immunosuppression. This review considers some of the metabolic changes described in breast cancer.
Efficacy and Safety of Trans-Arterial Yttrium-90 Radioembolization in Patients with Unresectable Liver-Dominant Metastatic or Primary Hepatic Soft Tissue Sarcomas
Authors: Testa Stefano , Bui Nam Q. , Wang David S. , Louie John D. , Sze Daniel Y. , Ganjoo Kristen N.
Published: January 2022

Patients with liver-dominant metastatic or primary hepatic soft tissue sarcomas (STS) have poor prognosis. Surgery can prolong survival, but most patients are not surgical candidates, and treatment response is limited with systemic chemotherapy. Liver-directed therapies have been increasingly employed in this setting, and Yttrium-90 trans-arterial radioembolization (TARE) is an understudied yet promising treatment option. This is a retrospective analysis of 35 patients with metastatic or primary hepatic STS who underwent TARE at a single institution between 2006 and 2020. The primary outcomes that were measured were overall survival (OS), liver progression-free survival (LPFS), and radiologic tumor response. Clinical and biochemical toxicities were assessed 3 months after the procedure. Median OS was 20 months (95% CI: 13.9–26.1 months), while median LPFS was 9 months (95% CI: 6.2–11.8 months). The objective response rate was 56.7%, and the disease control rate was 80.0% by mRECIST at 3 months. The following correlated with better OS post-TARE: liver disease control (DC) at 6 months (median OS: 40 vs. 17 months, p = 0.007); LPFS ≥ 9 months (median OS: 50 vs. 8 months, p < 0.0001); ECOG status 0–1 vs. 2 (median OS: 22 vs. 6 months, p = 0.042); CTP class A vs. B (median OS: 22 vs. 6 months, p = 0.018); and TACE post-progression (median OS: 99 vs. 16 months, p = 0.003). The absence of metastases at diagnosis was correlated with higher median LPFS (7 vs. 1 months, p = 0.036). Two grade 4 (5.7%) and ten grade 3 (28.6%) laboratory toxicities were identified at 3 months. There was one case of radioembolization-induced liver disease and two cases of radiation-induced peptic ulcer disease. We concluded that TARE could be an effective and safe treatment option for patients with metastatic or primary hepatic STS with good tumor response rates, low incidence of severe toxicity, and longer survival in patients with liver disease control post-TARE.
Noble-Metal-Based Catalytic Oxidation Technology Trends for Volatile Organic Compound (VOC) Removal
Authors: Kim Hyo-Sik , Kim Hyun-Ji , Kim Ji-Hyeon , Kim Jin-Ho , Kang Suk-Hwan , Ryu Jae-Hong , Park No-Kuk , Yun Dae-Sik , Bae Jong-Wook
Published: January 2022

Volatile organic compounds (VOCs) are toxic and are considered the most important sources for the formation of photochemical smog, secondary organic aerosols (SOAs), and ozone. These can also greatly affect the environment and human health. For this reason, VOCs are removed by applying various technologies or reused after recovery. Catalytic oxidation for VOCs removal is widely applied in the industry and is regarded as an efficient and economical method compared to other VOCs removal technologies. Currently, a large amount of VOCs are generated in industries with solvent-based processes, and the ratio of aromatic compounds is high. This paper covers recent catalytic developments in VOC combustion over noble-metal-based catalysts. In addition, this report introduces recent trends in the development of the catalytic mechanisms of VOC combustion and the deactivation of catalysts, such as coke formation, poisoning, sintering, and catalyst regeneration. Since VOC oxidation by noble metal catalysts depends on the support of and mixing catalysts, an appropriate catalyst should be used according to reaction characteristics. Moreover, noble metal catalysts are used together with non-noble metals and play a role in the activity of other catalysts. Therefore, further elucidation of their function and catalytic mechanism in VOC removal is required.
Recent Developments in Advanced Oxidation Processes for Organics-Polluted Soil Reclamation
Authors: Calenciuc Crina , Fdez-Sanromán Antía , Lama Gabriela , Annamalai Sivasankar , Sanromán Angeles , Pazos Marta
Published: January 2022

Soil pollution has become a substantial environmental problem which is amplified by overpopulation in different regions. In this review, the state of the art regarding the use of Advanced Oxidation Processes (AOPs) for soil remediation is presented. This review aims to provide an outline of recent technologies developed for the decontamination of polluted soils by using AOPs. Depending on the decontamination process, these techniques have been presented in three categories: the Fenton process, sulfate radicals process, and coupled processes. The review presents the achievements of, and includes some reflections on, the status of these emerging technologies, the mechanisms, and influential factors. At the present, more investigation and development actions are still desirable to bring them to real full-scale implementation.
Dielectric Barrier Discharge Plasma-Assisted Catalytic CO2 Hydrogenation: Synergy of Catalyst and Plasma
Authors: Gao Xingyuan , Liang Jinglong , Wu Liqing , Wu Lixia , Kawi Sibudjing
Published: January 2022

CO2 hydrogenation is an effective way to convert CO2 to value-added chemicals (e.g., CH4 and CH3OH). As a thermal catalytic process, it suffers from dissatisfactory catalytic performances (low conversion/selectivity and poor stability) and high energy input. By utilizing the dielectric barrier discharge (DBD) technology, the catalyst and plasma could generate a synergy, activating the whole process in a mild condition, and enhancing the conversion efficiency of CO2 and selectivity of targeted product. In this review, a comprehensive summary of the applications of DBD plasma in catalytic CO2 hydrogenation is provided in detail. Moreover, the state-of-the-art design of the reactor and optimization of reaction parameters are discussed. Furthermore, several mechanisms based on simulations and experiments are provided. In the end, the existing challenges of this hybrid system and corresponding solutions are proposed.
Mixed Metal Oxides of M1 MoVNbTeOx and TiO2 as Composite Catalyst for Oxidative Dehydrogenation of Ethane
Authors: Chen Yuxin , Dang Dan , Yan Binhang , Cheng Yi
Published: January 2022

Composite catalysts of mixed metal oxides were prepared by mixing a phase-pure M1 MoVNbTeOx with anatase-phase TiO2. Two methods were used to prepare the composite catalysts (the simple physically mixed or sol-gel method) for the improvement of the catalytic performance in the oxidative dehydrogenation of ethane (ODHE) process. The results showed that TiO2 particles with a smaller particle size were well dispersed on the M1 surface for the sol-gel method, which presented an excellent activity for ODHE. At the same operating condition (i.e., the contact time of 7.55 gcat·h/molC2H6 and the reaction temperature of 400 °C), the M1-TiO2-SM and M1-TiO2-PM achieved the space time yields of 0.67 and 0.52 kgC2H4/kgcat/h, respectively, which were about ~76% and ~35% more than that of M1 catalyst (0.38 kgC2H4/kgcat/h), respectively. The BET, ICP, XRD, TEM, SEM, H2-TPR, C2H6-TPSR, and XPS techniques were applied to characterize the catalysts. It was noted that the introduction of TiO2 raised the V5+ abundance on the catalyst surface as well as the reactivity of active oxygen species, which made contribution to the promotion of the catalytic performance. The surface morphology and crystal structure of used catalysts of either M1-TiO2-SM or M1-TiO2-PM remained stable as each fresh catalyst after 24 h time-on-stream tests.