bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of Gutting Blue Whiting (Micromesistius poutassou, Risso, 1827), in Spanish Supermarkets as an Anisakidosis Safety Measure
Authors: Ahuir-Baraja Ana Elena , Llobat Lola , Garijo Maria Magdalena
Published: April 2021

Anisakidosis is a parasitic zoonotic disease which can cause gastroallergic reactions in humans. In 2010, the European Food Safety Agency estimated that approximately 20,000 cases of anisakiasis had been reported across the world, with Spain having the highest number of infections in Europe. The blue whiting (Micromesistius poutassou, Risso, 1827) is one of the most widely fished species worldwide and represents around 25% of the white fish eaten in Spain. The Spanish Food Safety Authority requires obligatory evisceration of certain fish species before commercialization, but not for blue whiting. Nevertheless, some supermarkets carry this out themselves to prevent human infections and negative customer reactions deriving from the presence of ascaridoid larvae. To assess the effectiveness of eviscerations at supermarkets, a total of 320 blue whiting specimens were examined. The risk of larval migration from the visceral cavity to the musculature in gutted and ungutted fish was also assessed. Our results showed a total prevalence (25%) of ascaridoids in fish gutted at the supermarket, and a direct relationship was found between the presence of larvae in the muscle and time until evisceration. In ungutted fish, the standard length and weight were higher for infected than for non-infected fish. Also, massive infections had a higher prevalence in these larger specimens, in which the viability of larvae was also high. Larval viability was not found to be affected by a 24-h refrigeration period. Anisakis was the most prevalent genus identified in the fish examined. The results indicate that gutting at the supermarket is not an effective method for the total removal of ascaridoid larvae and that additional safety measures are advisable.
The Potential of Grape Pomace Varieties as a Dietary Source of Pectic Substances
Authors: Spinei Mariana , Oroian Mircea
Published: April 2021

Grape pomace is one of the most abundant solid by-products generated during winemaking. A lot of products, such as ethanol, tartrates, citric acid, grape seed oil, hydrocolloids, bioactive compounds and dietary fiber are recovered from grape pomace. Grape pomace represents a major interest in the field of fiber extraction, especially pectin, as an alternative source to conventional ones, such as apple pomace and citrus peels, from which pectin is obtained by acid extraction and precipitation using alcohols. Understanding the structural and functional components of grape pomace will significantly aid in developing efficient extraction of pectin from unconventional sources. In recent years, natural biodegradable polymers, like pectin has invoked a big interest due to versatile properties and diverse applications in food industry and other fields. Thus, pectin extraction from grape pomace could afford a new reason for the decrease of environmental pollution and waste generation. This paper briefly describes the structure and composition of grape pomace of different varieties for the utilization of grape pomace as a source of pectin in food industry.
Management and Prevention of COVID-19 in Pregnancy and Pandemic Obstetric Care: A Review of Current Practices
Authors: Pountoukidou Argyro , Potamiti-Komi Maria , Sarri Vrisiis , Papapanou Michail , Routsi Eleni , Tsiatsiani Anna Maria , Vlahos Nikolaos , Siristatidis Charalampos
Published: April 2021

Constant accumulation of data results in continuous updates of guidelines and recommendations on the proper management of pregnant women with COVID-19. This study aims to summarize the up-to-date information about the prevention and management of suspected/confirmed SARS-CoV-2 infection in obstetric patients and obstetric care during prenatal, intrapartum, and postpartum periods. We conducted a comprehensive literature search in PubMed for relevant English-written full-text reviews. We also included relevant guidelines and recommendations. In women with a low risk for infection and uncomplicated pregnancy, elective and non-urgent appointments should be postponed or completed through telehealth. Vaccination should be discussed and distance and personal hygiene preventive measures should be recommended. Routine ultrasound examinations should be adjusted in order to minimize exposure to the virus. Standardized criteria should evaluate the need for admission. Women with moderate/high-risk for infection should be isolated and tested with RT-PCR. The mode and timing of delivery should follow routine obstetric indications. In case of infection, glucocorticoids are recommended in critically ill pregnant women, after individualized evaluation. During labor and concomitant infection, the duration of the first two stages should be reduced as possible to decrease aerosolization, while minimization of hemorrhage is essential during the third stage. Close maternal monitoring and adequate oxygenation when necessary always remain a prerequisite. Discharge should be considered on the first or second day postpartum, also depending on delivery mode. Breastfeeding with protective equipment is recommended, as its benefits outweigh the risks of neonatal infection. Recommendations are currently based on limited available data. More original studies on infected pregnant women are needed to establish totally evidence-based protocols of care for these patients.
The Findings of SPECT/CT Concerning Bypass Lymph Circulation in Lymphedema Following Breast Cancer Surgery
Authors: Lee Min-Young , Kong Eun-Jung , Lee Dong-Gyu
Published: April 2021

This study aimed to determine whether bypass circulation was present in lymphedema and its effect. This was a retrospective, cross-sectional study. Patients who underwent unilateral breast cancer surgery with axillary lymph node dissection were recruited and underwent single-photon emission tomography/computed tomography (SPECT/CT). SPECT/CT was performed to detect the three-dimensional locations of radio-activated lymph nodes. Patients with radioactivity in anatomical locations other than axillary lymph nodes were classified into a positive group. All patients received complete decongestive therapy (CDT). Exclusion criteria were as follows: History of bilateral breast cancer surgery, cervical lymph node dissection history, and upper extremity amputation. The difference in the upper extremity circumference (cm) was measured at four points: Mid-point of the upper arm, elbow, and 10 and 15 cm below the elbow. Twenty-nine patients were included in this study. Fifteen patients (51.7%) had bypass lymphatic systems on the affected side, six (20.7%) had a bypass lymphatic system with axillary lymph nodes on the unaffected side, and 11 (37.9%) showed new lymphatic drainage. The positive group showed significantly less swelling than the negative group at the mid-arm, elbow, and 15 cm below the elbow. Bypass lymphatic circulation had two patterns: Infraclavicular lymph nodes and supraclavicular and/or cervical lymph nodes. Changes in lymph drainage caused by surgery triggered the activation of the superficial lymphatic drainage system to relieve lymphedema. Superficial lymphatic drainage has a connection through the deltopectoral groove.
Protective Effect of Quercetin on Sodium Iodate-Induced Retinal Apoptosis through the Reactive Oxygen Species-Mediated Mitochondrion-Dependent Pathway
Authors: Chang Yuan-Yen , Lee Yi-Ju , Hsu Min-Yen , Wang Meilin , Tsou Shang-Chun , Chen Ching-Chung , Lin Jer-An , Hsiao Yai-Ping , Lin Hui-Wen
Published: April 2021

Age-related macular degeneration (AMD) leads to gradual central vision loss and is the third leading cause of irreversible blindness worldwide. The underlying mechanisms for this progressive neurodegenerative disease remain unclear and there is currently no preventive treatment for dry AMD. Sodium iodate (NaIO3) has been reported to induce AMD-like retinal pathology in mice. We established a mouse model for AMD to evaluate the effects of quercetin on NaIO3-induced retinal apoptosis, and to investigate the pertinent underlying mechanisms. Our in vitro results indicated that quercetin protected human retinal pigment epithelium (ARPE-19) cells from NaIO3-induced apoptosis by inhibiting reactive oxygen species production and loss of mitochondrial membrane potential as detected by Annexin V-FITC/PI flow cytometry. We also evaluated the relative expression of proteins in the apoptosis pathway. Quercetin downregulated the protein expressions of Bax, cleaved caspase-3, and cleaved PARP and upregulated the expression of Bcl-2 through reduced PI3K and pAKT expressions. Furthermore, our in vivo results indicated that quercetin improved retinal deformation and increased the thickness of both the outer nuclear layer and inner nuclear layer, whereas the expression of caspase-3 was inhibited. Taken together, these results demonstrate that quercetin could protect retinal pigment epithelium and the retina from NaIO3-induced cell apoptosis via reactive oxygen species-mediated mitochondrial dysfunction, involving the PI3K/AKT signaling pathway. This suggests that quercetin has the potential to prevent and delay AMD and other retinal diseases involving NaIO3-mediated apoptosis.
Degraded Arabinogalactans and Their Binding Properties to Cancer-Associated Human Galectins
Authors: Pfeifer Lukas , Baumann Alexander , Petersen Lea Madlen , Höger Bastian , Beitz Eric , Classen Birgit
Published: April 2021

Galectins represent β-galactoside-binding proteins with numerous functions. Due to their role in tumor progression, human galectins-1, -3 and -7 (Gal-1, -3 and -7) are potential targets for cancer therapy. As plant derived glycans might act as galectin inhibitors, we prepared galactans by partial degradation of plant arabinogalactan-proteins. Besides commercially purchased galectins, we produced Gal-1 and -7 in a cell free system and tested binding capacities of the galectins to the galactans by biolayer-interferometry. Results for commercial and cell-free expressed galectins were comparable confirming functionality of the cell-free produced galectins. Our results revealed that galactans from Echinacea purpurea bind to Gal-1 and -7 with KD values of 1–2 µM and to Gal-3 slightly stronger with KD values between 0.36 and 0.70 µM depending on the sensor type. Galactans from the seagrass Zostera marina with higher branching of the galactan and higher content of uronic acids showed stronger binding to Gal-3 (0.08–0.28 µM) compared to galactan from Echinacea. The results contribute to knowledge on interactions between plant polysaccharides and galectins. Arabinogalactan-proteins have been identified as a new source for production of galactans with possible capability to act as galectin inhibitors.
Impact of Stress on Epilepsy: Focus on Neuroinflammation—A Mini Review
Authors: Espinosa-Garcia Claudia , Zeleke Helena , Rojas Asheebo
Published: April 2021

Epilepsy, one of the most common neurological disorders worldwide, is characterized by recurrent seizures and subsequent brain damage. Despite strong evidence supporting a deleterious impact on seizure occurrence and outcome severity, stress is an overlooked component in people with epilepsy. With regard to stressor duration and timing, acute stress can be protective in epileptogenesis, while chronic stress often promotes seizure occurrence in epilepsy patients. Preclinical research suggests that chronic stress promotes neuroinflammation and leads to a depressive state. Depression is the most common psychiatric comorbidity in people with epilepsy, resulting in a poor quality of life. Here, we summarize studies investigating acute and chronic stress as a seizure trigger and an important factor that worsens epilepsy outcomes and psychiatric comorbidities. Mechanistic insight into the impact of stress on epilepsy may create a window of opportunity for future interventions targeting neuroinflammation-related disorders.
Biohybrid Bovine Bone Matrix for Controlled Release of Mesenchymal Stem/Stromal Cell Lyosecretome: A Device for Bone Regeneration
Authors: Bari Elia , Roato Ilaria , Perale Giuseppe , Rossi Filippo , Genova Tullio , Mussano Federico , Ferracini Riccardo , Sorlini Marzio , Torre Maria Luisa , Perteghella Sara
Published: April 2021

SmartBone® (SB) is a biohybrid bone substitute advantageously proposed as a class III medical device for bone regeneration in reconstructive surgeries (oral, maxillofacial, orthopedic, and oncology). In the present study, a new strategy to improve SB osteoinductivity was developed. SB scaffolds were loaded with lyosecretome, a freeze-dried formulation of mesenchymal stem cell (MSC)-secretome, containing proteins and extracellular vesicles (EVs). Lyosecretome-loaded SB scaffolds (SBlyo) were prepared using an absorption method. A burst release of proteins and EVs (38% and 50% after 30 min, respectively) was observed, and then proteins were released more slowly with respect to EVs, most likely because they more strongly adsorbed onto the SB surface. In vitro tests were conducted using adipose tissue-derived stromal vascular fraction (SVF) plated on SB or SBlyo. After 14 days, significant cell proliferation improvement was observed on SBlyo with respect to SB, where cells filled the cavities between the native trabeculae. On SB, on the other hand, the process was still present, but tissue formation was less organized at 60 days. On both scaffolds, cells differentiated into osteoblasts and were able to mineralize after 60 days. Nonetheless, SBlyo showed a higher expression of osteoblast markers and a higher quantity of newly formed trabeculae than SB alone. The quantification analysis of the newly formed mineralized tissue and the immunohistochemical studies demonstrated that SBlyo induces bone formation more effectively. This osteoinductive effect is likely due to the osteogenic factors present in the lyosecretome, such as fibronectin, alpha-2-macroglobulin, apolipoprotein A, and TGF-β.
Cardiovascular Outcomes in the Acute Phase of COVID-19
Authors: Nakano Hiroki , Shiina Kazuki , Tomiyama Hirofumi
Published: April 2021

The cumulative number of cases in the current global coronavirus disease 19 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has exceeded 100 million, with the number of deaths caused by the infection having exceeded 2.5 million. Recent reports from most frontline researchers have revealed that SARS-CoV-2 can also cause fatal non-respiratory conditions, such as fatal cardiovascular events. One of the important mechanisms underlying the multiple organ damage that is now known to occur during the acute phase of SARS-CoV-2 infection is impairment of vascular function associated with inhibition of angiotensin-converting enzyme 2. To manage the risk of vascular dysfunction-related complications in patients with COVID-19, it would be pivotal to clearly elucidate the precise mechanisms by which SARS-CoV-2 infects endothelial cells to cause vascular dysfunction. In this review, we summarize the current state of knowledge about the mechanisms involved in the development of vascular dysfunction in the acute phase of COVID-19.
Preparation and Evaluation of a Self-Nanoemulsifying Drug Delivery System Loaded with Heparin Phospholipid Complex
Authors: Qiu Xiao-Lei , Fan Zi-Rui , Liu Yang-Yang , Wang Ding-Fu , Wang Shi-Xin , Li Chun-Xia
Published: April 2021

A self-nanoemulsifying drug delivery system (SNEDDS) was developed to enhance the absorption of heparin after oral administration, in which heparin was compounded with phospholipids to achieve better fat solubility in the form of heparin-phospholipid (HEP-Pc) complex. HEP-Pc complex was prepared using the solvent evaporation method, which increased the solubility of heparin in n-octanol. The successful preparation of HEP-Pc complex was confirmed by differential scanning calorimetry (DSC), Fourier-transform infrared (FT-IR) spectroscopy, NMR, and SEM. A heparin lipid microemulsion (HEP-LM) was prepared by high-pressure homogenization and characterized. HEP-LM can enhance the absorption of heparin after oral administration, significantly prolong activated partial thromboplastin time (APTT) and thrombin time (TT) in mice, and reduce fibrinogen (FIB) content. All these outcomes indicate that HEP-LM has great potential as an oral heparin formulation.
Immunopathology of Atherosclerosis and Related Diseases: Focus on Molecular Biology
Authors: Bezsonov Evgeny , Sobenin Igor , Orekhov Alexander
Published: April 2021

In this Special Issue of the International Journal of Molecular Sciences, we include insightful reviews and research papers on the subject “Immunopathology of Atherosclerosis and Related Diseases: Focus on Molecular Biology”.[...]
Emerging Roles of Exosomes in Huntington’s Disease
Authors: Ananbeh Hanadi , Vodicka Petr , Kupcova Skalnikova Helena
Published: April 2021

Huntington’s disease (HD) is a rare hereditary autosomal dominant neurodegenerative disorder, which is caused by expression of mutant huntingtin protein (mHTT) with an abnormal number of glutamine repeats in its N terminus, and characterized by intracellular mHTT aggregates (inclusions) in the brain. Exosomes are small extracellular vesicles that are secreted generally by all cell types and can be isolated from almost all body fluids such as blood, urine, saliva, and cerebrospinal fluid. Exosomes may participate in the spreading of toxic misfolded proteins across the central nervous system in neurodegenerative diseases. In HD, such propagation of mHTT was observed both in vitro and in vivo. On the other hand, exosomes might carry molecules with neuroprotective effects. In addition, due to their capability to cross blood-brain barrier, exosomes hold great potential as sources of biomarkers available from periphery or carriers of therapeutics into the central nervous system. In this review, we discuss the emerging roles of exosomes in HD pathogenesis, diagnosis, and therapy.
Contribution of Yeast Studies to the Understanding of BCL-2 Family Intracellular Trafficking
Authors: Rouchidane Eyitayo Akandé , Gonin Mathilde , Arokium Hubert , Manon Stéphen
Published: April 2021

BCL-2 family members are major regulators of apoptotic cell death in mammals. They form an intricate regulatory network that ultimately regulates the release of apoptogenic factors from mitochondria to the cytosol. The ectopic expression of mammalian BCL-2 family members in the yeast Saccharomyces cerevisiae, which lacks BCL-2 homologs, has been long established as a useful addition to the available models to study their function and regulation. In yeast, individual proteins can be studied independently from the whole interaction network, thus providing insight into the molecular mechanisms underlying their function in a living context. Furthermore, one can take advantage of the powerful tools available in yeast to probe intracellular trafficking processes such as mitochondrial sorting and interactions/exchanges between mitochondria and other compartments, such as the endoplasmic reticulum that are largely conserved between yeast and mammals. Yeast molecular genetics thus allows the investigation of the role of these processes on the dynamic equilibrium of BCL-2 family members between mitochondria and extramitochondrial compartments. Here we propose a model of dynamic regulation of BCL-2 family member localization, based on available evidence from ectopic expression in yeast.
Differential Regulation of Ca2+-Activated Cl− Channel TMEM16A Splice Variants by Membrane PI(4,5)P2
Authors: Ko Woori , Suh Byung-Chang
Published: April 2021

TMEM16A is a Ca2+-activated Cl− channel that controls broad cellular processes ranging from mucus secretion to signal transduction and neuronal excitability. Recent studies have reported that membrane phospholipid phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is an important cofactor that allosterically regulates TMEM16A channel activity. However, the detailed regulatory actions of PIP2 in splice variants of TMEM16A remain unclear. Here, we demonstrated that the attenuation of membrane phosphoinositide levels selectively inhibited the current amplitude of the TMEM16A(ac) isoform by decreasing the slow, but not instantaneous, Cl− currents, which are independent of the membrane potential and specific to PI(4,5)P2 depletion. The attenuation of endogenous PI(4,5)P2 levels by the activation of Danio rerio voltage-sensitive phosphatase (Dr-VSP) decreased the Cl− currents of TMEM16A(ac) but not the TMEM16A(a) isoform, which was abolished by the co-expression of PIP 5-kinase type-1γ (PIPKIγ). Using the rapamycin-inducible dimerization of exogenous phosphoinositide phosphatases, we further revealed that the stimulatory effects of phosphoinositide on TMEM16A(ac) channels were similar in various membrane potentials and specific to PI(4,5)P2, not PI4P and PI(3,4,5)P3. Finally, we also confirmed that PI(4,5)P2 resynthesis is essential for TMEM16A(ac) recovery from Dr-VSP-induced current inhibition. Our data demonstrate that membrane PI(4,5)P2 selectively modulates the gating of the TMEM16A(ac) channel in an agonistic manner, which leads to the upregulation of TMEM16A(ac) functions in physiological conditions.
OsARF11 Promotes Growth, Meristem, Seed, and Vein Formation during Rice Plant Development
Authors: Sims Katherine , Abedi-Samakush Fatemeh , Szulc Nicole , Macias Honti Monika Gyongyi , Mattsson Jim
Published: April 2021

The plant hormone auxin acts as a mediator providing positional instructions in a range of developmental processes. Studies in Arabidopsis thaliana L. show that auxin acts in large part via activation of Auxin Response Factors (ARFs) that in turn regulate the expression of downstream genes. The rice (Oryza sativa L.) gene OsARF11 is of interest because of its expression in developing rice organs and its high sequence similarity with MONOPTEROS/ARF5, a gene with prominent roles in A. thaliana development. We have assessed the phenotype of homozygous insertion mutants in the OsARF11 gene and found that in relation to wildtype, osarf11 seedlings produced fewer and shorter roots as well as shorter and less wide leaves. Leaves developed fewer veins and larger areoles. Mature osarf11 plants had a reduced root system, fewer branches per panicle, fewer grains per panicle and fewer filled seeds. Mutants had a reduced sensitivity to auxin-mediated callus formation and inhibition of root elongation, and phenylboronic acid (PBA)-mediated inhibition of vein formation. Taken together, our results implicate OsARF11 in auxin-mediated growth of multiple organs and leaf veins. OsARF11 also appears to play a central role in the formation of lateral root, panicle branch, and grain meristems.
The Cancer Stem Cell Niche in Ovarian Cancer and Its Impact on Immune Surveillance
Authors: Jain Srishti , Annett Stephanie L. , Morgan Maria P. , Robson Tracy
Published: April 2021

Ovarian cancer is an aggressive gynaecological cancer with extremely poor prognosis, due to late diagnosis as well as the development of chemoresistance after first-line therapy. Research advances have found stem-like cells present in ovarian tumours, which exist in a dynamic niche and persist through therapy. The stem cell niche interacts extensively with the immune and non-immune components of the tumour microenvironment. Significant pathways associated with the cancer stem cell niche have been identified which interfere with the immune component of the tumour microenvironment, leading to immune surveillance evasion, dysfunction and suppression. This review aims to summarise current evidence-based knowledge on the cancer stem cell niche within the ovarian cancer tumour microenvironment and its effect on immune surveillance. Furthermore, the review seeks to understand the clinical consequences of this dynamic interaction by highlighting current therapies which target these processes.
Decursinol Angelate Arrest Melanoma Cell Proliferation by Initiating Cell Death and Tumor Shrinkage via Induction of Apoptosis
Authors: Chang Sukkum , Khan Imran , Kim Chang , Park Seon , Choi Dong , Lee Heejin , Hwang Buyng , Kang Sun , Park Jae
Published: April 2021

Melanoma is known to aggressively metastasize and is one of the prominent causes of skin cancer mortality. This study was designed to assess the molecular mechanism of decursinol angelate (DA) against murine melanoma cell line (B16F10 cells). Treatment of DA resulted in growth inhibition and cell cycle arrest at G0/G1 (p < 0.001) phase, evaluated through immunoblotting. Moreover, autophagy-related proteins such as ATG-5 (p < 0.0001), ATG-7 (p < 0.0001), beclin-1 (p < 0.0001) and transition of LC3-I to LC3-II (p < 0.0001) were markedly decreased, indicating autophagosome inhibition. Additionally, DA treatment triggered apoptotic events which were corroborated by the occurrence of distorted nuclei, elevated reactive oxygen species (ROS) levels and reduction in the mitochondrial membrane potential. Subsequently, there was an increase in the expression of pro-apoptotic protein Bax in a dose-dependent manner, with the corresponding downregulation of Bcl-2 expression and cytochrome C expression following 24 h DA treatment in A375.SM and B16F10 cells. We substantiated our results for apoptotic occurrence through flow cytometry in B16F10 cells. Furthermore, we treated B16F10 cells with N-acetyl-L-cysteine (NAC). NAC treatment upregulated ATG-5 (p < 0.0001), beclin-1 (p < 0.0001) and LC3-I to LC3-II (p < 0.0001) conversion, which was inhibited in the DA treatment group. We also noticed a systematic upregulation of important markers for progression of G1 cell phase such as CDK-2 (p < 0.029), CDK-4 (p < 0.036), cyclin D1 (p < 0.0003) and cyclin E (p < 0.020) upon NAC treatment. In addition, we also observed a significant fold reduction (p < 0.05) in ROS fluorescent intensity and the expression of Bax (p < 0.0001), cytochrome C (p < 0.0001), cleaved caspase-9 (p > 0.010) and cleaved caspase-3 (p < 0.0001). NAC treatment was able to ameliorate DA-induced apoptosis and cell cycle arrest to support our finding. Our in vivo xenograft model also revealed similar findings, such as downregulation of CDK-2 (p < 0.0001) and CDK-4 (p < 0.0142) and upregulation of Bax (p < 0.0001), cytochrome C (p < 0.0001), cleaved caspase 3 (p < 0.0001) and cleaved caspase 9 (p < 0.0001). In summary, our study revealed that DA is an effective treatment against B16F10 melanoma cells and xenograft mice model.
Deficiency of NEIL3 Enhances the Chemotherapy Resistance of Prostate Cancer
Authors: Wang Yiwei , Xu Liuyue , Shi Shanshan , Wu Sha , Meng Ruijie , Chen Huifang , Jiang Zhenyou
Published: April 2021

Acquired treatment resistance is an important cause of death in prostate cancer, and this study aimed to explore the mechanisms of chemotherapy resistance in prostate cancer. We employed castration-resistant prostate cancer (CRPC), neuroendocrine prostate cancer (NEPC), and chemotherapy-resistant prostate cancer datasets to screen for potential target genes. The Cancer Genome Atlas (TCGA) was used to detect the correlation between the target genes and prognosis and clinical characteristics. Nei endonuclease VIII-like 3 (NEIL3) knockdown cell lines were constructed with RNA interference. Prostate cancer cells were treated with enzalutamide for the androgen deprivation therapy (ADT) model, and with docetaxel and cisplatin for the chemotherapy model. Apoptosis and the cell cycle were examined using flow cytometry. RNA sequencing and western blotting were performed in the knockdown Duke University 145 (DU145) cell line to explore the possible mechanisms. The TCGA dataset demonstrated that high NEIL3 was associated with a high T stage and Gleason score, and indicated a possibility of lymph node metastasis, but a good prognosis. The cell therapy models showed that the loss of NEIL3 could promote the chemotherapy resistance (but not ADT resistance) of prostate cancer (PCa). Flow cytometry revealed that the loss of NEIL3 in PCa could inhibit cell apoptosis and cell cycle arrest under cisplatin treatment. RNA sequencing showed that the knockdown of NEIL3 changes the expression of neuroendocrine-related genes. Further western blotting revealed that the loss of NEIL3 could significantly promote the phosphorylation of ATR serine/threonine kinase (ATR) and ATM serine/threonine kinase (ATM) under chemotherapy, thus initiating downstream pathways related to DNA repair. In summary, the loss of NEIL3 promotes chemotherapy resistance in prostate cancer, and NEIL3 may serve as a diagnostic marker for chemotherapy-resistant patients.
Monomethyl Auristatin E Grafted-Liposomes to Target Prostate Tumor Cell Lines
Authors: Abawi Ariana , Wang Xiaoyi , Bompard Julien , Bérot Anna , Andretto Valentina , Gudimard Leslie , Devillard Chloé , Petiot Emma , Joseph Benoit , Lollo Giovanna , Granjon Thierry , Girard-Egrot Agnès , Maniti Ofelia
Published: April 2021

Novel nanomedicines have been engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or short half-life. Lipid-based carriers such as liposomes represent one of the most advanced classes of drug delivery systems. A Monomethyl Auristatin E (MMAE) warhead was grafted on a lipid derivative and integrated in fusogenic liposomes, following the model of antibody drug conjugates. By modulating the liposome composition, we designed a set of particles characterized by different membrane fluidities as a key parameter to obtain selective uptake from fibroblast or prostate tumor cells. Only the fluid liposomes made of palmitoyl-oleoyl-phosphatidylcholine and dioleoyl-phosphatidylethanolamine, integrating the MMAE-lipid derivative, showed an effect on prostate tumor PC-3 and LNCaP cell viability. On the other hand, they exhibited negligible effects on the fibroblast NIH-3T3 cells, which only interacted with rigid liposomes. Therefore, fluid liposomes grafted with MMAE represent an interesting example of drug carriers, as they can be easily engineered to promote liposome fusion with the target membrane and ensure drug selectivity.
Dysregulated Immunological Functionome and Dysfunctional Metabolic Pathway Recognized for the Pathogenesis of Borderline Ovarian Tumors by Integrative Polygenic Analytics
Authors: Chang Chia-Ming , Li Yao-Feng , Lin Hsin-Chung , Lu Kai-Hsi , Lin Tzu-Wei , Liu Li-Chun , Su Kuo-Min , Chang Cheng-Chang
Published: April 2021

The pathogenesis and molecular mechanisms of ovarian low malignant potential (LMP) tumors or borderline ovarian tumors (BOTs) have not been fully elucidated to date. Surgery remains the cornerstone of treatment for this disease, and diagnosis is mainly made by histopathology to date. However, there is no integrated analysis investigating the tumorigenesis of BOTs with open experimental data. Therefore, we first utilized a functionome-based speculative model from the aggregated obtainable datasets to explore the expression profiling data among all BOTs and two major subtypes of BOTs, serous BOTs (SBOTs) and mucinous BOTs (MBOTs), by analyzing the functional regularity patterns and clustering the separate gene sets. We next prospected and assembled the association between these targeted biomolecular functions and their related genes. Our research found that BOTs can be accurately recognized by gene expression profiles by means of integrative polygenic analytics among all BOTs, SBOTs, and MBOTs; the results exhibited the top 41 common dysregulated biomolecular functions, which were sorted into four major categories: immune and inflammatory response-related functions, cell membrane- and transporter-related functions, cell cycle- and signaling-related functions, and cell metabolism-related functions, which were the key elements involved in its pathogenesis. In contrast to previous research, we identified 19 representative genes from the above classified categories (IL6, CCR2 for immune and inflammatory response-related functions; IFNG, ATP1B1, GAS6, and PSEN1 for cell membrane- and transporter-related functions; CTNNB1, GATA3, and IL1B for cell cycle- and signaling-related functions; and AKT1, SIRT1, IL4, PDGFB, MAPK3, SRC, TWIST1, TGFB1, ADIPOQ, and PPARGC1A for cell metabolism-related functions) that were relevant in the cause and development of BOTs. We also noticed that a dysfunctional pathway of galactose catabolism had taken place among all BOTs, SBOTs, and MBOTs from the analyzed gene set databases of canonical pathways. With the help of immunostaining, we verified significantly higher performance of interleukin 6 (IL6) and galactose-1-phosphate uridylyltransferase (GALT) among BOTs than the controls. In conclusion, a bioinformatic platform of gene-set integrative molecular functionomes and biophysiological pathways was constructed in this study to interpret the complicated pathogenic pathways of BOTs, and these important findings demonstrated the dysregulated immunological functionome and dysfunctional metabolic pathway as potential roles during the tumorigenesis of BOTs and may be helpful for the diagnosis and therapy of BOTs in the future.
500 Meters Is a Result of 6-Minute Walk Test Which Differentiates Patients with High and Low Risk of Postoperative Complications after Lobectomy—A Validation Study
Authors: Marjanski Tomasz , Wnuk Damian , Dziedzic Robert , Ostrowski Marcin , Sawicka Wioletta , Rzyman Witold
Published: April 2021

The 6-min walk test (6MWT) is a simple method of identifying patients with a high risk of postoperative complications. In this study, we internally validated the previously obtained threshold value of 500 m in the 6MWT as differentiating populations with a high and a low risk of postoperative complications after a lobectomy. Between November 2011 and November 2016, 624 patients who underwent a lobectomy and performed the 6MWT preoperatively entered this study. We compared the complication rates of two groups of patients—those who walked more than and those who walked less than 500 m. The patients who did not reach the distance of 500 m in the 6MWT were older (70 vs. 63 years p < 0.001), had worse pulmonary function tests (FEV1% 84 vs. 88 p = 0.041) and had a higher Charlson Comorbidity Index (p < 0.001). The patients who had a worse result in the 6MWT had a higher complication rate (52% vs. 42% p = 0.019; OR: 1.501 95% CI: 1.066–2.114) and a longer median postoperative hospital stay (7 vs. 6 days p = 0.010). In a multivariate analysis, the result of the 6MWT and pack-years proved to independently influence the risk of postoperative complications. This internal validation study confirms that 500 m is a result of the 6MWT which differentiates patients with a higher risk of postoperative complications and a prolonged hospital stay after a lobectomy.
The Anatomical Conditions of the Alveolar Process of the Anterior Maxilla in Terms of Immediate Implantation—Radiological Retrospective Case Series Study
Authors: Wychowański Piotr , Starzyńska Anna , Osiak Martyna , Kowalski Jan , Jereczek-Fossa Barbara Alicja , Seklecka Blanka , Morawiec Tadeusz , Adamska Paulina , Woliński Jarosław
Published: April 2021

The feasibility and the level of difficulty of immediate flapless implantation depend largely on the residual alveolar bone. The purpose of the study was to determine how often immediate flapless implantation in the anterior maxilla is feasible and assess the difficulty level using cone-beam computed tomography (CBCT) scans. A radiological retrospective case series study was conducted. In total, 1200 CBCT scans from 300 consecutive patients were analyzed with dedicated planning software. Immediate flapless implants were possible in 78.33% of cases. Drilling direction was either through the apex or the palatal slope. Bimodal was conducted in 9% of the cases; only through the apex in 13.08% of the cases and in 56.25% only in the slope. In 21.67%, immediate flapless implants were excluded. The feasibility and degree of difficulty differed statistically to the disadvantage of the lateral incisors compared to the central incisors. Drilling direction caused that BASE classification reflects the difficulty level of immediate implantation. CBCT is a helpful diagnostic tool for assessing the feasibility of immediate flapless implants due to the residual bone shape and volume. BASE classification helps to determine a challenge level that may also facilitate communication and result in comparison. The alveolar bone condition allows for immediate flapless implants in most cases in the aesthetic region of the maxilla, but they should be performed by an experienced specialist with regard to the bone and soft tissue quality.
Hepatocellular Carcinoma Recurrence after Hepatitis C Virus Therapy with Direct-Acting Antivirals. A Systematic Review and Meta-Analysis
Authors: Frazzoni Leonardo , Sikandar Usama , Metelli Flavio , Sadalla Sinan , Mazzella Giuseppe , Bazzoli Franco , Fuccio Lorenzo , Azzaroli Francesco
Published: April 2021

Background: Hepatocellular carcinoma (HCC) is a major cause of morbidity and mortality among patients with cirrhosis. The risk of HCC recurrence after a complete response among patients treated with direct-acting antivirals (DAAs) has not been fully elucidated yet. Aim: To assess the risk of HCC recurrence after DAA therapy for hepatitis C virus (HCV). Methods: A systematic review across PubMed, Scopus and Scholar up to November 2020, including full-text studies that assessed the pattern of HCC recurrence after DAA therapy for HCV. Random-effect meta-analysis and univariable metaregression were applied to obtain pooled estimates for proportions and relative risk (RR) and variables influential for the outcome, respectively. Results: Thirty-one studies with 2957 patients were included. Overall, 30% (CI, 26–34%) of the patients with a history of HCC experienced HCC recurrence after DAA therapy, at mean time intervals ranging from 4 to 21 months. This result increased when going from European studies (23%, CI, 17–28%) to US studies (34%, CI, 30–38%), to Egyptian studies (37%, CI, 27–47%), and to Asian studies (33%, CI, 27–40%). Sixty-eight percent (CI, 45–91%) of recurrent HCCs developed within 6 months of follow-up since DAA treatment, among the eight studies providing stratified data. Among the studies providing head-to-head comparisons, the HCC recurrence risk was significantly lower after DAA therapy than IFN (RR, 0.64; CI, 0.51–0.81), and after DAA therapy than no intervention (RR, 0.68; CI, 0.49–0.94). Conclusions: The recurrence of HCC after DAA is not negligible, being higher soon after the end of treatment and among non-European countries. DAA therapy seems to reduce the risk of HCC recurrence compared to an IFN regimen and no intervention.
Awake Bruxism—Single-Point Self-Report versus Ecological Momentary Assessment
Authors: Emodi-Perlman Alona , Manfredini Daniele , Shalev Tamar , Yevdayev Ilanit , Frideman-Rubin Pessia , Bracci Alessandro , Arnias-Winocur Orit , Eli Ilana
Published: April 2021

Assessment of awake bruxism (AB) is problematic due to the inability to use continuous recordings during daytime activities. Recently, a new semi-instrumental approach was suggested, namely, ecological momentary assessment (EMA), via the use of a smartphone application. With the application, subjects are requested to report, at least 12 times per day, the status of their masticatory muscle activity (relaxed muscles, muscle bracing without tooth contact, teeth contact, teeth clenching, or teeth grinding). The aim of the present study was to test the association between a single observation point self-report and EMA assessment of AB. The most frequent condition recorded by the EMA was relaxed muscles (ca. 60%) and the least frequent was teeth grinding (less than 1%). The relaxed muscle condition also showed the lowest coefficient of variance over a seven-day period of report. Additionally, only the relaxed muscles and the muscle bracing conditions presented an acceptable ability to assess AB-positive and AB-negative subjects, as defined by single-point self-report questions. The combination between self-report and EMA may have the potential to promote our ability to assess AB. We suggest to re-consider the conditions of teeth contact and teeth grinding while using EMA to evaluate AB.
Postoperative Olfaction Alteration Following Laparoscopic Bariatric Surgery
Authors: Pisarska-Adamczyk Magdalena , Tylec Piotr , Gajewska Natalia , Wierzbicka Julia , Przęczek Krzysztof , Małczak Piotr , Wysocki Michał , Pędziwiatr Michał , Wierdak Mateusz , Major Piotr
Published: April 2021

Introduction: Bariatric surgery is an effective method of treatment for morbid obesity that is known to change nutritional habits. Proper nutrition has an impact on postoperative recovery and outcomes. Diet preferences depend on flavour and olfaction stimuli. Some studies show long-term changes in the sense of smell after bariatric surgery, but little research has addressed olfactory function shortly after surgery. Observations of olfactory changes that occur immediately after bariatric surgery may lead to improvements in postoperative care. Aim: The aim of this study is to investigate the impact of bariatric surgery on olfactory changes in the short postoperative period. Material and methods: This is a prospective study of patients undergoing laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) between April 2018 and December 2018. The control group consists of patients who underwent various non-oncological elective surgical procedures. Patients’ olfaction was tested qualitatively and quantitatively the day before and 24 h after surgery. Sniffin Sticks test consists of three subtests: odor threshold, discrimination, and identification. Results: The study enrolled 83 patients (LSG = 39; LRYGB = 14; control = 30). Mean scores in the threshold subtest differed significantly in the bariatric group, 9.3 ± 3.9 before the surgery and 8.2 ± 3.0 a day after the surgery (p = 0.032). There were no significant differences between scores from the discrimination subtest, identification subtest and the mean total scores in the bariatric group. There was no observed change in the intensity of the smell in the control group. Analyzing the results of patients undergoing LSG and LRYGB separately, we only showed significant differences in the case of LSG. Mean score from the 1st test (9.12 ± 3.97 vs. 7.75 ± 2.98; p = 0.0339) and mean total score (32.83 ± 5.45 vs. 30.67 ± 4.88; p = 0.0173) differ between repetitive measurements in LSG patients. Conclusions: Our study shows deterioration of odor threshold in the bariatric surgery group compared to the control group 24 h after surgery. However, this change occurred only in patients undergoing LSG.
Robotic Completion Thyroidectomy via the Bilateral Axillo-Breast Approach
Authors: Kwak JungHak , Kim Su-jin , Xu Zhen , Lee Keunchul , Ahn Jong-hyuk , Yu Hyeong Won , Chai Young Jun , Choi June Young , Lee Kyu Eun
Published: April 2021

Background: Bilateral axillo-breast approach (BABA) robotic thyroidectomy has been successfully performed for thyroid cancer patients with excellent cosmetic results. Completion thyroidectomy is sometimes necessary after thyroid lobectomy, and whether it has a higher complication rate than the primary operation due to the presence of adhesions remains controversial. The aim of this study was to evaluate surgical outcomes, including operation time and postoperative complications, in patients who underwent BABA robotic completion thyroidectomy. Methods: From Jan 2012 to Aug 2020, 33 consecutive patients underwent BABA robotic completion thyroidectomy for a thyroid malignancy after BABA robotic thyroid lobectomy. The procedures were divided into five steps: (1) robot setting and surgical draping, (2) flap dissection, (3) robot docking, (4) thyroidectomy, and (5) closure. Clinicopathological characteristics, operation time, and postoperative complications were reviewed. Results: The total operation time was shorter for completion thyroidectomy than for the initial operation (164.8 ± 31.7 min vs. 179.8 ± 27.1 min, p = 0.043). Among the robotic thyroidectomy steps, the duration of the thyroidectomy step was shorter than that of the initial operation (69.6 ± 20.9 min vs. 83.0 ± 19.5 min, p = 0.009. One patient (1/33, 3.0%) needed hematoma evacuation under the flap area immediately after surgery. Three patients (3/33, 9.1%) showed transient hypoparathyroidism, and one patient (1/33, 3.0%) had permanent hypoparathyroidism. Two patients (2/33, 6.1%) showed transient vocal cord palsy and recovered within 3 months following the completion thyroidectomy. There were no cases of open conversion, tracheal injury, flap injury or wound infection. Conclusions: BABA robotic completion thyroidectomy could be performed safely without completion-related complication.
Predictors of Single Bronchodilation Treatment Response for COPD: An Observational Study with the Trace Database Cohort
Authors: Hernández Laura Carrasco , Eraso Candela Caballero , Ruiz-Duque Borja , Arranz María Abad , Martín Eduardo Márquez , Calero Acuña Carmen , Lopez-Campos Jose Luis
Published: April 2021

Chronic obstructive pulmonary disease (COPD) patients constitute a heterogeneous population in terms of treatment response. Our objective was to identify possible predictive factors of response to treatment with single bronchodilation monotherapy in patients diagnosed with COPD. The Time-based Register and Analysis of COPD Endpoints (TRACE; clinicaltrials.gov NCT03485690) is a prospective cohort of COPD patients who have been attending annual visits since 2012. Patients who were kept on a single bronchodilator during the first year of follow-up were selected. The responders were defined according to all of the following variables: any improvement in morning post-dose forced expiratory volume in 1 s or deterioration <100 mL, no change or improvement in dyspnea score, and no occurrence of exacerbations. Significant and plausible variables were analyzed using a proportional hazard Cox regression for single bronchodilator responders. We analyzed 764 cases, of whom 128 (16.8%) were receiving monotherapy with one bronchodilator. Of these, 85 patients (66.4%) were responders. Factors affecting responder status were: female gender (hazard ratio (HR) 0.276; 95% confidence interval (CI) 0.089–0.858), dyslipidemia (HR 0.436; 95%CI 0.202–0.939), not performing regular exercise (HR 0.523; 95%CI 0.254–1.076), active smoking (HR 0.413; 95%CI 0.186–0.920), and treatment adherence (HR 2.527; 95%CI 1.271–5.027). The factors associated with a single bronchodilation response are mainly non-pharmacological interventions and comorbidities.