bluuebunny/crossref_metadata_2025 huggingface dataset:
Non-Apoptotic Caspase-3 Activation Mediates Early Synaptic Dysfunction of Indirect Pathway Neurons in the Parkinsonian Striatum
Authors: Fieblinger Tim , Li Chang , Espa Elena , Cenci M. Angela
Published: May 2022

Non-apoptotic caspase-3 activation is critically involved in dendritic spine loss and synaptic dysfunction in Alzheimer’s disease. It is, however, not known whether caspase-3 plays similar roles in other pathologies. Using a mouse model of clinically manifest Parkinson’s disease, we provide the first evidence that caspase-3 is transiently activated in the striatum shortly after the degeneration of nigrostriatal dopaminergic projections. This caspase-3 activation concurs with a rapid loss of dendritic spines and deficits in synaptic long-term depression (LTD) in striatal projection neurons forming the indirect pathway. Interestingly, systemic treatment with a caspase inhibitor prevents both the spine pruning and the deficit of indirect pathway LTD without interfering with the ongoing dopaminergic degeneration. Taken together, our data identify transient and non-apoptotic caspase activation as a critical event in the early plastic changes of indirect pathway neurons following dopamine denervation.
Hypoxia Differently Affects TGF-β2-Induced Epithelial Mesenchymal Transitions in the 2D and 3D Culture of the Human Retinal Pigment Epithelium Cells
Authors: Suzuki Soma , Sato Tatsuya , Watanabe Megumi , Higashide Megumi , Tsugeno Yuri , Umetsu Araya , Furuhashi Masato , Ida Yosuke , Hikage Fumihito , Ohguro Hiroshi
Published: May 2022

The hypoxia associated with the transforming growth factor-β2 (TGF-β2)-induced epithelial mesenchymal transition (EMT) of human retinal pigment epithelium (HRPE) cells is well recognized as the essential underlying mechanism responsible for the development of proliferative retinal diseases. In vitro, three-dimensional (3D) models associated with spontaneous O2 gradients can be used to recapitulate the pathological levels of hypoxia to study the effect of hypoxia on the TGF-β2-induced EMT of HRPE cells in detail, we used two-dimensional-(2D) and 3D-cultured HRPE cells. TGF-β2 and hypoxia significantly and synergistically increased the barrier function of the 2D HRPE monolayers, as evidenced by TEER measurements, the downsizing and stiffening of the 3D HRPE spheroids and the mRNA expression of most of the ECM proteins. A real-time metabolic analysis indicated that TGF-β2 caused a decrease in the maximal capacity of mitochondrial oxidative phosphorylation in the 2D HRPE cells, whereas, in the case of 3D HRPE spheroids, TGF-β2 increased proton leakage. The findings reported herein indicate that the TGF-β2-induced EMT of both the 2D and 3D cultured HRPE cells were greatly modified by hypoxia, but during these EMT processes, the metabolic plasticity was different between 2D and 3D HRPE cells, suggesting that the mechanisms responsible for the EMT of the HRPE cells may be variable during their spatial spreading.
Toll-like Receptor Response to Hepatitis C Virus Infection: A Recent Overview
Authors: Kayesh Mohammad Enamul Hoque , Kohara Michinori , Tsukiyama-Kohara Kyoko
Published: May 2022

Hepatitis C virus (HCV) infection remains a major global health burden, causing chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Toll-like receptors (TLRs) are evolutionarily conserved pattern recognition receptors that detect pathogen-associated molecular patterns and activate downstream signaling to induce proinflammatory cytokine and chemokine production. An increasing number of studies have suggested the importance of TLR responses in the outcome of HCV infection. However, the exact role of innate immune responses, including TLR response, in controlling chronic HCV infection remains to be established. A proper understanding of the TLR response in HCV infection is essential for devising new therapeutic approaches against HCV infection. In this review, we discuss the progress made in our understanding of the host innate immune response to HCV infection, with a particular focus on the TLR response. In addition, we discuss the mechanisms adopted by HCV to avoid immune surveillance mediated by TLRs.
Antitumoral Activity of a CDK9 PROTAC Compound in HER2-Positive Breast Cancer
Authors: Noblejas-López María del Mar , Gandullo-Sánchez Lucía , Galán-Moya Eva M. , López-Rosa Raquel , Tébar-García David , Nieto-Jiménez Cristina , Gómez-Juárez Mónica , Burgos Miguel , Pandiella Atanasio , Ocaña Alberto
Published: May 2022

Cyclin-dependent kinases (CDKs) are a broad family of proteins involved in the cell cycle and transcriptional regulation. In this article, we explore the antitumoral activity of a novel proteolysis-targeting chimera (PROTAC) compound against CDK9. Breast cancer cell lines from different subtypes were used. Transcriptomic mapping of CDKs in breast cancer demonstrated that the expression of CDK9 predicted a detrimental outcome in basal-like tumors (HR = 1.51, CI = 1.08–2.11, p = 0.015) and, particularly, in the luminal B subtype with HER2+ expression (HR = 1.82, CI = 1.17–2.82, p = 0.0069). The novel CDK9 PROTAC, THAL-SNS-032, displayed a profound inhibitory activity in MCF7, T47D, and BT474 cells, with less effect in SKBR3, HCC1569, HCC1954, MDA-MB-231, HS578T, and BT549 cells. The three cell lines with HER2 overexpression and no presence of ER, SKBR3, HCC1569, and HCC1954 displayed an EC50 three times higher compared to ER-positive and dual ER/HER2-positive cell lines. BT474-derived trastuzumab-resistant cell lines displayed a particular sensitivity to THAL-SNS-032. Western blot analyses showed that THAL-SNS-032 caused a decrease in CDK9 levels in BT474, BT474-RH, and BT474-TDM1R cells, and a significant increase in apoptosis. Experiments in animals demonstrated an inverse therapeutic index of THAL-SNS-032, with doses in the nontherapeutic and toxic range. The identified toxicity was mainly due to an on-target off-tumor effect of the compound in the gastrointestinal epithelium. In summary, the potent and efficient antitumoral properties of the CDK9 PROTAC THAL-SNS-032 opens the possibility of using this type of compound in breast cancer only if specifically delivered to cancer cells, particularly in ER/HER2-positive and HER2-resistant tumors.
Oxy210, a Semi-Synthetic Oxysterol, Exerts Anti-Inflammatory Effects in Macrophages via Inhibition of Toll-like Receptor (TLR) 4 and TLR2 Signaling and Modulation of Macrophage Polarization
Authors: Wang Feng , Stappenbeck Frank , Tang Liu-Ya , Zhang Ying E. , Hui Simon T. , Lusis Aldons J. , Parhami Farhad
Published: May 2022

Inflammatory responses by the innate and adaptive immune systems protect against infections and are essential to health and survival. Many diseases including atherosclerosis, osteoarthritis, rheumatoid arthritis, psoriasis, and obesity involve persistent chronic inflammation. Currently available anti-inflammatory agents, including non-steroidal anti-inflammatory drugs, steroids, and biologics, are often unsafe for chronic use due to adverse effects. The development of effective non-toxic anti-inflammatory agents for chronic use remains an important research arena. We previously reported that oral administration of Oxy210, a semi-synthetic oxysterol, ameliorates non-alcoholic steatohepatitis (NASH) induced by a high-fat diet in APOE*3-Leiden.CETP humanized mouse model of NASH and inhibits expression of hepatic and circulating levels of inflammatory cytokines. Here, we show that Oxy210 also inhibits diet-induced white adipose tissue inflammation in APOE*3-Leiden.CETP mice, evidenced by the inhibition of adipose tissue expression of IL-6, MCP-1, and CD68 macrophage marker. Oxy210 and related analogs exhibit anti-inflammatory effects in macrophages treated with lipopolysaccharide in vitro, mediated through inhibition of toll-like receptor 4 (TLR4), TLR2, and AP-1 signaling, independent of cyclooxygenase enzymes or steroid receptors. The anti-inflammatory effects of Oxy210 are correlated with the inhibition of macrophage polarization. We propose that Oxy210 and its structural analogs may be attractive candidates for future therapeutic development for targeting inflammatory diseases.
Amyloid Formation in Nanoliter Droplets
Authors: Cheong Da Yeon , Lee Wonseok , Park Insu , Park Jinsung , Lee Gyudo
Published: May 2022

Processes that monitor the nucleation of amyloids and characterize the formation of amyloid fibrils are vital to medicine and pharmacology. In this study, we observe the nucleation and formation of lysozyme amyloid fibrils using a facile microfluidic system to generate nanoliter droplets that can control the flow rate and movement of monomer-in-oil emulsion droplets in a T-junction microchannel. Using a fluorescence assay, we monitor the nucleation and growth process of amyloids based on the volume of droplets. Using the microfluidic system, we demonstrate that the lag phase, which is vital to amyloid nucleation and growth, is reduced at a lower droplet volume. Furthermore, we report a peculiar phenomenon of high amyloid formation at the edge of a bullet-shaped droplet, which is likely due to the high local monomer concentration. Moreover, we discovered that amyloid fibrils synthesized in the nanoliter droplets are shorter and thicker than fibrils synthesized from a bulk solution via the conventional heating method. Herein, a facile procedure to observe and characterize the nucleation and growth of amyloid fibrils using nanoliter droplets is presented, which is beneficial for investigating new features of amyloid fibril formation as an unconventional synthetic method for amyloid fibrils.
Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models
Authors: Wegrzyn David , Juckel Georg , Faissner Andreas
Published: May 2022

Schizophrenia is a grave neuropsychiatric disease which frequently onsets between the end of adolescence and the beginning of adulthood. It is characterized by a variety of neuropsychiatric abnormalities which are categorized into positive, negative and cognitive symptoms. Most therapeutical strategies address the positive symptoms by antagonizing D2-dopamine-receptors (DR). However, negative and cognitive symptoms persist and highly impair the life quality of patients due to their disabling effects. Interestingly, hippocampal deviations are a hallmark of schizophrenia and can be observed in early as well as advanced phases of the disease progression. These alterations are commonly accompanied by a rise in neuronal activity. Therefore, hippocampal formation plays an important role in the manifestation of schizophrenia. Furthermore, studies with animal models revealed a link between environmental risk factors and morphological as well as electrophysiological abnormalities in the hippocampus. Here, we review recent findings on structural and functional hippocampal abnormalities in schizophrenic patients and in schizophrenia animal models, and we give an overview on current experimental approaches that especially target the hippocampus. A better understanding of hippocampal aberrations in schizophrenia might clarify their impact on the manifestation and on the outcome of this severe disease.
Platelet-Derived miR-126-3p Directly Targets AKT2 and Exerts Anti-Tumor Effects in Breast Cancer Cells: Further Insights in Platelet-Cancer Interplay
Authors: Sibilano Matteo , Tullio Valentina , Adorno Gaspare , Savini Isabella , Gasperi Valeria , Catani Maria Valeria
Published: May 2022

Among the surrounding cells influencing tumor biology, platelets are recognized as novel players as they release microvesicles (MVs) that, once delivered to cancer cells, modulate signaling pathways related to cell growth and dissemination. We have previously shown that physiological delivery of platelet MVs enriched in miR-126 exerted anti-tumor effects in different breast cancer (BC) cell lines. Here, we seek further insight by identifying AKT2 kinase as a novel miR-126-3p direct target, as assessed by bioinformatic analysis and validated by luciferase assay. Both ectopic expression and platelet MV-mediated delivery of miR-126-3p downregulated AKT2 expression, thus suppressing proliferating and invading properties, in either triple negative (BT549 cells) or less aggressive Luminal A (MCF-7 cells) BC subtypes. Accordingly, as shown by bioinformatic analysis, both high miR-126 and low AKT2 levels were associated with favorable long-term prognosis in BC patients. Our results, together with the literature data, indicate that miR-126-3p exerts suppressor activity by specifically targeting components of the PIK3/AKT signaling cascade. Therefore, management of platelet-derived MV production and selective delivery of miR-126-3p to tumor cells may represent a useful tool in multimodal therapeutic approaches in BC patients.
MicroPET Imaging Assessment of Brain Tau and Amyloid Deposition in 6 × Tg Alzheimer’s Disease Model Mice
Authors: Kang ShinWoo , Kim Jinho , Lee Sang-Yoon , Okamura Nobuyuki , Chang Keun-A
Published: May 2022

Alzheimer’s disease (AD) is characterized by the deposition of extracellular amyloid plaques and intracellular accumulation of neurofibrillary tangles (NFT). Amyloid beta (Aβ) and tau imaging are widely used for diagnosing and monitoring AD in clinical settings. We evaluated the pathology of a recently developed 6 × Tg − AD (6 × Tg) mouse model by crossbreeding 5 × FAD mice with mice expressing mutant (P301L) tau protein using micro-positron emission tomography (PET) image analysis. PET studies were performed in these 6 × Tg mice using [18F]Flutemetamol, which is an amyloid PET radiotracer; [18F]THK5351 and [18F]MK6240, which are tau PET radiotracers; moreover, [18F]DPA714, which is a translocator protein (TSPO) radiotracer, and comparisons were made with age-matched mice of their respective parental strains. We compared group differences in standardized uptake value ratio (SUVR), kinetic parameters, biodistribution, and histopathology. [18F]Flutemetamol images showed prominent cortical uptake and matched well with 6E10 staining images from 2-month-old 6 × Tg mice. [18F]Flutemetamol images showed a significant correlation with [18F]DPA714 in the cortex and hippocampus. [18F]THK5351 images revealed prominent hippocampal uptake and matched well with AT8 immunostaining images in 4-month-old 6 × Tg mice. Moreover, [18F]THK5351 images were confirmed using [18F]MK6240, which revealed significant correlations in the cortex and hippocampus. Uptake of [18F]THK5351 or [18F]MK6240 was highly correlated with [18F]Flutemetamol in 4-month-old 6 × Tg mice. In conclusion, PET imaging revealed significant age-related uptake of Aβ, tau, and TSPO in 6 × Tg mice, which was highly correlated with age-dependent pathology.
Role of miRNAs in Human T Cell Leukemia Virus Type 1 Induced T Cell Leukemia: A Literature Review and Bioinformatics Approach
Authors: Machado Caio Bezerra , da Cunha Leidivan Sousa , Maués Jersey Heitor da Silva , Pessoa Flávia Melo Cunha de Pinho , de Oliveira Marcelo Braga , Ribeiro Rodrigo Monteiro , Lopes Germison Silva , de Moraes Filho Manoel Odorico , de Moraes Maria Elisabete Amaral , Khayat André Salim , Moreira-Nunes Caroline Aquino
Published: May 2022

Human T cell leukemia virus type 1 (HTLV-1) was identified as the first pathogenic human retrovirus and is estimated to infect 5 to 10 million individuals worldwide. Unlike other retroviruses, there is no effective therapy to prevent the onset of the most alarming diseases caused by HTLV-1, and the more severe cases manifest as the malignant phenotype of adult T cell leukemia (ATL). MicroRNA (miRNA) dysfunction is a common feature of leukemogenesis, and it is no different in ATL cases. Therefore, we sought to analyze studies that reported deregulated miRNA expression in HTLV-1 infected cells and patients’ samples to understand how this deregulation could induce malignancy. Through in silico analysis, we identified 12 miRNAs that stood out in the prediction of targets, and we performed functional annotation of the genes linked to these 12 miRNAs that appeared to have a major biological interaction. A total of 90 genes were enriched in 14 KEGG pathways with significant values, including TP53, WNT, MAPK, TGF-β, and Ras signaling pathways. These miRNAs and gene interactions are discussed in further detail for elucidation of how they may act as probable drivers for ATL onset, and while our data provide solid starting points for comprehension of miRNAs’ roles in HTLV-1 infection, continuous effort in oncologic research is still needed to improve our understanding of HTLV-1 induced leukemia.
Tunneling Nanotube-Mediated Communication: A Mechanism of Intercellular Nucleic Acid Transfer
Authors: Driscoll Julia , Gondaliya Piyush , Patel Tushar
Published: May 2022

Tunneling nanotubes (TNTs) are thin, F-actin-based membranous protrusions that connect distant cells and can provide e a novel mechanism for intercellular communication. By establishing cytoplasmic continuity between interconnected cells, TNTs enable the bidirectional transfer of nuclear and cytoplasmic cargo, including organelles, nucleic acids, drugs, and pathogenic molecules. TNT-mediated nucleic acid transfer provides a unique opportunity for donor cells to directly alter the genome, transcriptome, and metabolome of recipient cells. TNTs have been reported to transport DNA, mitochondrial DNA, mRNA, viral RNA, and non-coding RNAs, such as miRNA and siRNA. This mechanism of transfer is observed in physiological as well as pathological conditions, and has been implicated in the progression of disease. Herein, we provide a concise overview of TNTs’ structure, mechanisms of biogenesis, and the functional effects of TNT-mediated intercellular transfer of nucleic acid cargo. Furthermore, we highlight the potential translational applications of TNT-mediated nucleic acid transfer in cancer, immunity, and neurological diseases.
Nitric Oxide Mobilizes Intracellular Zn2+ via the GC/cGMP/PKG Signaling Pathway and Stimulates Adipocyte Differentiation
Authors: Chen Chien-Wei , Chen Luen-Kui , Huang Tai-Ying , Yang De-Ming , Liu Shui-Yu , Tsai Pei-Jiun , Chen Tien-Hua , Lin Heng-Fu , Juan Chi-Chang
Published: May 2022

Plasma and tissue zinc ion levels are associated with the development of obesity. Previous studies have suggested that zinc ions may regulate adipocyte metabolism and that nitric oxide (NO) plays a pivotal role in the regulation of adipocyte physiology. Our previous study showed that chronic NO deficiency causes a significant decrease in adipose tissue mass in rats. Studies also suggested that zinc ions play an important modulatory role in regulating NO function. This study aims to explore the role of zinc ions in NO-regulated adipocyte differentiation. We hypothesized that NO could increase intracellular Zn2+ level and then stimulate adipocyte differentiation. ZnCl2 and the NO donor, NONOate, were used to explore the effects of Zn2+ and NO on adipocyte differentiation. Regulatory mechanisms of NO on intracellular Zn2+ mobilization were determined by detection. Then, Zn2+-selective chelator TPEN was used to clarify the role of intracellular Zn2+ on NO-regulated adipocyte differentiation. Furthermore, the relationship between adipocyte size, Zn2+ level, and NOS expression in human subcutaneous fat tissue was elucidated. Results showed that both ZnCl2 and NO stimulated adipocyte differentiation in a dose-dependent manner. NO stimulated intracellular Zn2+ mobilization in adipocytes through the guanylate cyclase (GC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, and NO-stimulated adipocyte differentiation was Zn2+-dependent. In human subcutaneous adipose tissue, adipocyte size was negatively correlated with expression of eNOS. In conclusion, NO treatment stimulates intracellular Zn2+ mobilization through the GC/cGMP/PKG pathway, subsequently stimulating adipocyte differentiation.
Phase-Separated Subcellular Compartmentation and Related Human Diseases
Authors: Zhang Lin , Wang Shubo , Wang Wenmeng , Shi Jinming , Stovall Daniel B. , Li Dangdang , Sui Guangchao
Published: May 2022

In live cells, proteins and nucleic acids can associate together through multivalent interactions, and form relatively isolated phases that undertake designated biological functions and activities. In the past decade, liquid–liquid phase separation (LLPS) has gradually been recognized as a general mechanism for the intracellular organization of biomolecules. LLPS regulates the assembly and composition of dozens of membraneless organelles and condensates in cells. Due to the altered physiological conditions or genetic mutations, phase-separated condensates may undergo aberrant formation, maturation or gelation that contributes to the onset and progression of various diseases, including neurodegenerative disorders and cancers. In this review, we summarize the properties of different membraneless organelles and condensates, and discuss multiple phase separation-regulated biological processes. Based on the dysregulation and mutations of several key regulatory proteins and signaling pathways, we also exemplify how aberrantly regulated LLPS may contribute to human diseases.
Oxygen Binding by Co(II) Complexes with Oxime-Containing Schiff Bases in Solution
Authors: Pająk Marek , Woźniczka Magdalena , Lichawska Marta E. , Czerwiński Bartłomiej , Włodarczyk Jakub , Fichna Jakub
Published: May 2022

The present work describes the complexation properties of two oxime-containing Schiff bases (used as ligands), viz. 2-hydroxyimino-N′-[1-(2-pyridyl)ethylidene]propanohydrazone (Hpop) and 2-hydroxyimino-N′-[(pyridine-2-yl)methylidene]propanohydrazone (Hpoa), with Co(II) ions in DMSO/water solution. Volumetric (oxygenation) studies were carried out to determine the uptake of molecular oxygen O2 in the formation of the complexes Co(II)-Hpop and Co(II)-Hpoa. The acquired data can be useful in the development of oxygen bioinorganic complexes of metal ions with Schiff base ligands in solution. Their properties allow them to be used as synthetic oxygen transporters. Moreover, the binding of dioxygen could play an important role in the research of catalytic activity by such systems.
An Integrated Approach Reveals DNA Damage and Proteotoxic Stress as Main Effects of Proton Radiation in S. cerevisiae
Authors: Vanderwaeren Laura , Dok Rüveyda , Voordeckers Karin , Vandemaele Laura , Verstrepen Kevin J. , Nuyts Sandra
Published: May 2022

Proton radiotherapy (PRT) has the potential to reduce the normal tissue toxicity associated with conventional photon-based radiotherapy (X-ray therapy, XRT) because the active dose can be more directly targeted to a tumor. Although this dosimetric advantage of PRT is well known, the molecular mechanisms affected by PRT remain largely elusive. Here, we combined the molecular toolbox of the eukaryotic model Saccharomyces cerevisiae with a systems biology approach to investigate the physiological effects of PRT compared to XRT. Our data show that the DNA damage response and protein stress response are the major molecular mechanisms activated after both PRT and XRT. However, RNA-Seq revealed that PRT treatment evoked a stronger activation of genes involved in the response to proteotoxic stress, highlighting the molecular differences between PRT and XRT. Moreover, inhibition of the proteasome resulted in decreased survival in combination with PRT compared to XRT, not only further confirming that protons induced a stronger proteotoxic stress response, but also hinting at the potential of using proteasome inhibitors in combination with proton radiotherapy in clinical settings.
Dynamic Changes in Seed Germination under Low-Temperature Stress in Maize
Authors: Meng Aiju , Wen Daxing , Zhang Chunqing
Published: May 2022

Low-temperature stress delays seed germination in maize. Different maize inbred lines display various low-temperature resistance, but the dynamic changes in seed germination under low-temperature stress in maize remain unknown, especially at the transcriptome level. In this study, low-temperature-resistant maize (RM) inbred line 04Qun0522-1-1 had a significantly faster germination speed than low-temperature-sensitive maize (SM) line B283-1 under low-temperature stress. Moreover, the total antioxidant capacity, superoxide dismutase, and peroxidase activities were notably higher in the RM line than in the SM line from 3 to 6 d. In contrast, the SM line showed significantly higher malondialdehyde (MDA) content than the RM line at 6 d. Gene ontology (GO) enrichment analysis showed that in 2dvs0d, both SM and RM lines displayed the downregulation of ribosome-related genes. Moreover, photosystem II and heat shock protein binding-related genes were also downregulated in the SM line. In 4dvs2d, the RM line showed a higher degree of upregulation of the ribosome and peroxidase (POD)-related genes than the SM line. In 6dvs4d, POD-related genes were continuously upregulated in both SM and RM lines, but the degree of upregulation of the genes was higher in the SM line than in the RM line. Moreover, vitamin B6-related genes were specifically upregulated in the RM line. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that in 6dvs4d, phenylpropanoid biosynthesis was the most significantly enriched pathway in both SM and RM lines. Moreover, phenylpropanoid biosynthesis was also enriched in the RM line in 4dvs2d. More than half of the differentially expressed genes (DEGs) in phenylpropanoid biosynthesis were peroxidase, and the DEGs were similar to the GO enrichment analysis. The results provide new insights into maize seed germination in response to low-temperature stress.
Metabolic Syndrome and Male Fertility: Beyond Heart Consequences of a Complex Cardiometabolic Endocrinopathy
Authors: Salvio Gianmaria , Ciarloni Alessandro , Cutini Melissa , delli Muti Nicola , Finocchi Federica , Perrone Michele , Rossi Silvia , Balercia Giancarlo
Published: May 2022

Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). Male infertility is another common condition which accounts for about 50% of cases of couple infertility worldwide. Interestingly, male infertility and MetS shares several risk factors (e.g., smoking, ageing, physical inactivity, and excessive alcohol consumption), leading to reactive oxygen species (ROS) production and increased oxidative stress (OS), and resulting in endothelial dysfunction and altered semen quality. Thus, the present narrative review aims to discuss the pathophysiological mechanisms which link male infertility and MetS and to investigate the latest available evidence on the reproductive consequences of MetS.
The Anticancer Activity Conferred by the Mud Crab Antimicrobial Peptide Scyreprocin through Apoptosis and Membrane Disruption
Authors: Yang Ying , Chen Hui-Yun , Hao Hua , Wang Ke-Jian
Published: May 2022

Scyreprocin is an antimicrobial peptide first identified in the mud crab Scylla paramamosain. Herein, we showed that its recombinant product (rScyreprocin) could significantly inhibit the growth of human lung cancer NCI-H460 cells (H460), but showed no cytotoxicity to human lung fibroblasts (HFL1). rScyreprocin was a membrane-active peptide that firstly induced the generation of reactive oxygen species (ROS) in H460, and led to endoplasmic reticulum stress and Ca2+ release, which resulted in mitochondrial dysfunction and subsequently activation of caspase-3 cascades, and ultimately led to apoptosis. The comprehensive results indicated that rScyreprocin exerted anticancer activity by disrupting cell membrane and inducing apoptosis. The in vivo efficacy test demonstrated that intratumoral injection of rScyreprocin significantly inhibited the growth of H460 xenografts, which was close to that of the cisplatin (inhibition rate: 69.94% vs. 80.76%). Therefore, rScyreprocin is expected to become a promising candidate for the treatment of lung cancer.
Regulation of Neuroinflammatory Signaling by PPARγ Agonist in Mouse Model of Diabetes
Authors: Piątkowska-Chmiel Iwona , Herbet Mariola , Gawrońska-Grzywacz Monika , Dudka Jarosław
Published: May 2022

Many relevant studies, as well as clinical practice, confirm that untreated diabetes predisposes the development of neuroinflammation and cognitive impairment. Having regard for the fact that PPARγ are widely distributed in the brain and PPARγ ligands may regulate the inflammatory process, the anti-inflammatory potential of the PPARγ agonist, pioglitazone, was assessed in a mouse model of neuroinflammation related with diabetes. In this regard, the biochemical and molecular indicators of neuroinflammation were determined in the hippocampus and prefrontal cortex of diabetes mice. The levels of cytokines (IL-1β, IL-6, and TNF) and the expression of genes (Tnfrsf1a and Cav1) were measured. In addition, behavioral tests such as the open field test, the hole-board test, and the novel object recognition test were conducted. A 14-day treatment with pioglitazone significantly decreased IL-6 and TNFα levels in the prefrontal cortex and led to the downregulation of Tnfrsf1a expression and the upregulation of Cav1 expression in both brain regions of diabetic mice. Pioglitazone, by targeting neuroinflammatory signaling, improved memory and exploratory activity in behavioral tests. The present study provided a potential theoretical basis and therapeutic target for the treatment of neuroinflammation associated with diabetes. Pioglitazone may provide a promising therapeutic strategy in diabetes patients with muffled of behavioral activity.
Decision-Making Model for Reinforcing Digital Transformation Strategies Based on Artificial Intelligence Technology
Authors: Kim Kyungtae , Kim Boyoung
Published: May 2022

Firms’ digital environment changes and industrial competitions have evolved quickly since the Fourth Industrial Revolution and the COVID-19 pandemic. Many companies are propelling company-wide digital transformation strategies based on artificial intelligence (AI) technology for the digital innovation of organizations and businesses. This study aims to define the factors affecting digital transformation strategies and present a decision-making model required for digital transformation strategies based on the definition. It also reviews previous AI technology and digital transformation strategies and draws influence factors. The research model drew four evaluation areas, such as subject, environment, resource, and mechanism, and 16 evaluation factors through the SERM model. After the factors were reviewed through the Delphi methods, a questionnaire survey was conducted targeting experts with over 10 years of work experience in the digital strategy field. The study results were produced by comparing the data’s importance using an Analytic Hierarchy Process (AHP) on each group. According to the analysis, the subject was the most critical factor, and the CEO (top management) was more vital than the core talent or technical development organization. The importance was shown in the order of resource, mechanism and environment, following subject. It was ascertained that there were differences of importance in industrial competition and market digitalization in the demander and provider groups.
No Evidence of Bacterial Symbionts Influencing Host Specificity in Aphis gossypii Glover (Hemiptera: Aphididae)
Authors: Guo Hao , Yang Fengying , Meng Min , Feng Jingjing , Yang Qinglan , Wang Yongmo
Published: May 2022

The cotton-melon aphid, Aphis gossypii Glover, is a polyphagous insect pest with many host-specialized biotypes, such as the Cucurbitaceae- and Malvaceae-specialized (CU and MA) biotypes. Bacterial symbionts were reported to determine the host range in some aphids. Whether this is the case in A. gossypii remains unknown. Here, we tested the host specificity of the CU and MA biotypes, compared the host specificity between the wingless and winged morph within the same biotype, and analyzed the composition of the bacterial symbionts. The reproduction of the CU and MA biotypes reduced by 66.67% and 82.79%, respectively, on non-native hosts, compared with on native hosts. The composition of bacterial symbionts was not significantly different between the CU and MA biotypes, with a Buchnera abundance >95% in both biotypes. Meanwhile, the winged morph produced significantly more nymphs than the wingless morph on non-native hosts, and the Buchnera abundance in the winged morph was only about 10% of that in the wingless morph. There seemed to be a relationship between the Buchnera abundance and host specificity. We regulated the Buchnera abundance by temperature and antibiotics, but did not find that a low Buchnera abundance resulted in the high reproduction on non-native hosts. We conclude that the host specificity of A. gossypii is not controlled by specific bacterial symbionts or by Buchnera abundance.
Association of Circulating IgE and CML Levels with In-Stent Restenosis in Type 2 Diabetic Patients with Stable Coronary Artery Disease
Authors: Liu Jingmeng , Chen Qiujing , Lu Lin , Jin Qi , Bao Yangyang , Ling Tianyou , Lin Changjian , Ding Fenghua , Wang Xiaoqun , Shen Weifeng , Shen Ying , Dai Yang , Wu Liqun
Published: May 2022

Background: We investigated whether serum levels of immunoglobin (Ig) E and Nε-carboxymethyl-lysine (CML) are related to in-stent restenosis (ISR) in patients with stable coronary artery disease and type 2 diabetes mellitus (T2DM). Methods: Serum levels of IgE and CML were measured in 196 ISR patients and 220 non-ISR patients with stable angina and T2DM who received angiographic follow-up 12 months after percutaneous coronary intervention (PCI) with third-generation drug-eluting stent (DES) implantation for de novo lesions. Multivariate logistic regression analysis was performed to assess the association between IgE or CML and ISR. Results: Both IgE and CML levels were higher in patients with ISR compared with non-ISR patients (IgE: 187.10 (63.75–489.65) vs. 80.25 (30.65–202.50), p < 0.001; CML: 203.26 (164.50–266.84) vs. 174.26 (130.85–215.56), p < 0.001). The rate of ISR increased stepwise with increasing tertiles of IgE and CML levels (p for all trends < 0.001), and IgE correlated significantly with CML. After adjusting for potential confounders, IgE and CML levels remained independently associated with ISR. Moreover, IgE and CML levels improved the predictive capability of traditional risk factors for ISR, and there existed an interaction between IgE and CML in relation to ISR (p for interaction < 0.01). Conclusion: Elevated circulating IgE and CML levels confer an increased risk for ISR after DES-based PCI in type 2 diabetic patients with stable coronary artery disease.
Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome in Women: Effects of Lifestyle Modifications
Authors: Guagnano Maria Teresa , D'Ardes Damiano , Ilaria Rossi , Santilli Francesca , Schiavone Cosima , Bucci Marco , Cipollone Francesco
Published: May 2022

Non-alcoholic fatty liver disease (NAFLD) is the most widespread liver disease, characterized by fatty acids liver accumulation and subsequent fibrosis. NAFLD prevalence ranges from 80% to 90% in obese subjects and is estimated to be around 50% in patients with metabolic syndrome. In this clinical scenario, diet and lifestyle modifications can play an important role. There are several imaging techniques that can accurately diagnose fatty liver. Recently, ultrasound has acquired a leading role in the diagnosis and follow-up of fatty liver disease. Furthermore, elastosonography represents a valid alternative to liver biopsy. Shear wave elastosonography evaluates the elastic and mechanical properties of liver tissue. The aim is to evaluate the effects of lifestyle and nutritional interventions and a loss of body weight during hepatic steatosis through ultrasonographic and elastosonographic techniques. Thirty-two female subjects with metabolic syndrome were subjected to clinical, anthropometric, and laboratory assessments, as well as abdominal ultrasonographic/elastosonographic measurements taken from enrollment time (T0) and after 3 months (T1) of lifestyle modifications. After 3 months of lifestyle changes, significant weight loss was observed, with a marked improvement in all adiposity indices. The laboratory parameters at T1 showed significant decreases in total and LDL cholesterol, triglycerides, basal blood glucose, 120 min glycaemia, basal insulin and HOMA Index (p < 0.001). A similar improvement was observed at T1 for steatosis degree (p < 0.01) and elastosonographic measurements (Kpa p < 0.001). The linear regression analysis of the baseline conditions documented that the size of the liver positively correlated with body weight, BMI, neck and waist circumferences, waist to height ratio (WhtR), insulin and HOMA Index, fat mass and visceral fat, and steatosis grade. After 3 months, the liver size showed improvement with positive correlations to all previous variables. Hepatic stiffness (Kpa) positively correlated with neck circumference, visceral fat, and ALT, with basal insulin, gamma-GT, and AST, and with waist circumference, WhtR, and fat mass. The degree of steatosis was positively correlated with more variables and with greater statistical significance at T1 with respect to T0. Particularly, the positive correlations between the degree of steatosis and neck circumference (p < 0.001), HOMA Index, and triglycerides (p < 0.001) appeared to be very significant. NAFLD management in women with metabolic syndrome should be focused on lifestyle modifications. Moreover, liver involvement and improvement at follow-up could be evaluated in a non-invasive manner through ultrasonographic and elastosonographic techniques.
The Effect of Hyperlipidemia on the Course of Diabetic Retinopathy—Literature Review
Authors: Bryl Anna , Mrugacz Małgorzata , Falkowski Mariusz , Zorena Katarzyna
Published: May 2022

Diabetes mellitus is a very important social issue, and its retinal complications continue to be one of the major causes of blindness worldwide. The effect of glucose level on the development of retinal retinopathy has been the subject of numerous studies and is well understood. Hypertension and hyperlipidemia have been known to be important risk factors in the development of diabetes complications. However, the mechanisms of this effect have not been fully explained and raise a good deal of controversy. The latest research results suggest that some lipoproteins are closely correlated with the incidence of diabetic retinopathy and that by exerting an impact on their level the disease course can be modulated. Moreover, pharmacotherapy which reduces the level of lipids, particularly by means of statins and fibrate, has been shown to alleviate diabetic retinopathy. Therefore, we have decided to review the latest literature on diabetic retinopathy with respect to the impact of hyperlipidemia and possible preventive measures
Complications Risk Assessment and Imaging Findings of Thermal Ablation Treatment in Liver Cancers: What the Radiologist Should Expect
Authors: Granata Vincenza , Fusco Roberta , De Muzio Federica , Cutolo Carmen , Setola Sergio Venanzio , Simonetti Igino , Dell’Aversana Federica , Grassi Francesca , Bruno Federico , Belli Andrea , Patrone Renato , Pilone Vincenzo , Petrillo Antonella , Izzo Francesco
Published: May 2022

One of the major fields of application of ablation treatment is liver tumors. With respect to HCC, ablation treatments are considered as upfront treatments in patients with early-stage disease, while in colorectal liver metastases (CLM), they can be employed as an upfront treatment or in association with surgical resection. The main prognostic feature of ablation is the tumor size, since the goal of the treatment is the necrosis of all viable tumor tissue with an adequate tumor-free margin. Radiofrequency ablation (RFA) and microwave ablation (MWA) are the most employed ablation techniques. Ablation therapies in HCC and liver metastases have presented a challenge to radiologists, who need to assess response to determine complication-related treatment. Complications, defined as any unexpected variation from a procedural course, and adverse events, defined as any actual or potential injury related to the treatment, could occur either during the procedure or afterwards. To date, RFA and MWA have shown no statistically significant differences in mortality rates or major or minor complications. To reduce the rate of major complications, patient selection and risk assessment are essential. To determine the right cost-benefit ratio for the ablation method to be used, it is necessary to identify patients at high risk of infections, coagulation disorders and previous abdominal surgery interventions. Based on risk assessment, during the procedure as part of surveillance, the radiologists should pay attention to several complications, such as vascular, biliary, mechanical and infectious. Multiphase CT is an imaging tool chosen in emergency settings. The radiologist should report technical success, treatment efficacy, and complications. The complications should be assessed according to well-defined classification systems, and these complications should be categorized consistently according to severity and time of occurrence.
Maternal and Neonatal Outcomes of Women Conceived Less Than 6 Months after First Trimester Dilation and Curettage
Authors: Margaliot Kalifa Tal , Lang Ben Nun Eyal , Sela Hen Y. , Khatib Fayez , Grisaru-Granovsky Sorina , Rottenstreich Misgav
Published: May 2022

Objective: To evaluate the maternal and neonatal outcomes of pregnancies conceived ≤6 months after first trimester (<14 weeks) dilation and curettage (D&C). Methods: A retrospective computerized database study of women who conceived ≤6 months following a missed abortion and delivered in a single tertiary medical center between 2016 and 2021. The maternal and neonatal outcomes of women who had D&C were compared to those of women who had non-medical or spontaneous miscarriages. The primary outcome of this study was the rate of preterm birth (<37 weeks). Secondary outcomes were adverse maternal and neonatal outcomes. Univariate analysis was followed by multiple logistic regression models; adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated. Results: During the study period, 1773 women met the inclusion criteria; of those, 1087 (61.3%) women gave birth following D&C. We found no differences between the study groups in any maternal or neonatal parameter examined including preterm birth (PTB), miscarriage to pregnancy interval, fertility treatments, hypertension disorders of pregnancy, placental complications, mode of delivery and neonatal birth weights. This was confirmed on a multivariate analysis as well [aOR 1.74 (0.89–3.40), p = 0.11] for preterm birth. Conclusion: Watchful waiting or the medical treatment of a first trimester missed abortion present no more risks than D&C to pregnancies conceived within six months of the index miscarriage. Further studies in other settings to strengthen these findings are needed.
Telomere Lengths and Serum Proteasome Concentrations in Patients with Type 1 Diabetes and Different Severities of Diabetic Retinopathy in Latvia and Lithuania
Authors: Svikle Zane , Pahirko Leonora , Zariņa Līga , Baumane Kristīne , Kardonaite Deimante , Radzeviciene Lina , Daugintyte-Petrusiene Laura , Balciuniene Vilma Jurate , Verkauskiene Rasa , Tiščuka Angeļina , Rovite Vita , Sjakste Nikolajs , Sokolovska Jelizaveta
Published: May 2022

The aim of the study was to compare telomere lengths and circulating proteasome concentrations in patients with different stages of diabetic retinopathy and type 1 diabetes in Latvia and Lithuania. Methods. Patients with no diabetic retinopathy and with non-proliferative diabetic retinopathy were included in the NDR/NPDR group (n = 187). Patients with proliferative diabetic retinopathy and status post laser-photocoagulation were included int the PDR/LPC group (n = 119). Telomeres were evaluated by real-time quantitative polymerase chain reaction. Proteasome concentration was measured by ELISA. Results. Telomeres were longer in PDR/LPC (ΔCT 0.21 (0.12–0.28)) vs. NDR/NPDR (ΔCT 0.18 (0.1–0.28)), p = 0.036. In NDR/NPDR, telomeres were correlated negatively with age (R = −0.17, p = 0.019), BMI (R = −0.21, p = 0.004), waist/hip ratio (R = −0.21, p = 0.005), total cholesterol (R = −0.18, p = 0.021), and low-density cholesterol (R = −0.20, p = 0.010), and positively with estimated glomerular filtration rate (eGFR) (R = 0.28, p < 0.001). None of the above correlations were observed in PRD/LPC. Proteasome concentrations were lower in PDR/LPC (130 (90–210) ng/mL) vs. NDR/NPDR (150 (100–240) ng/mL), p = 0.024. This correlated negatively with eGFR (R = −0.17, p = 0.025) in the NDR/NPDR group and positively with age (R = 0.23, p = 0.014) and systolic blood pressure (R = 0.20, p = 0.032) in the PRD/LPC group. Telomere lengths did not correlate with proteasome concentrations. Conclusion. Longer telomeres and lower circulating proteasome concentrations are observed in patients with type 1 diabetes and advanced diabetic retinopathy.
Clinical Implications of Multi-Drug Resistant Organisms’ Gastrointestinal Colonization in an Internal Medicine Ward: The Pandora’s Box
Authors: Para Ombretta , Caruso Lorenzo , Blasi Eleonora , Pestelli Caterina , Pestelli Giulia , Guidi Stefano , Fedi Giacomo , Giarretta Igor , Maggi Fabrizio , Ciarambino Tiziana , Nozzoli Carlo , Dentali Francesco
Published: May 2022

Background: Multi-drug resistant organisms (MDRO) are an emerging health problem with an important impact on clinical outcome in Intensive Care Units (ICUs) and immunocompromised patients. Conversely, the role of MDRO colonization in Internal Medicine is less clear. The objective of our study is to evaluate the clinical impact (namely sepsis development, in-hospital and 30-days mortality, and re-hospitalization) of MDRO colonization in Internal Medicine. Methods: Patients admitted to our Internal Medicine Unit between January 2019 and March 2020 were potentially includible. Outcomes in patients with a positive rectal swab for MDRO (RS+) and in patients without a RS+ were compared. Results of the multivariate analyses were expressed as Odds Ratios (ORs) and the corresponding 95% Confidence Interval (CI). Results: In a cohort of 2147 patients, 77 patients with RS+ were consecutively identified; 377 patients with a rectal swab negative for MDRO were randomly selected from the same cohort (five for each patient with RS+). At the multivariate analysis, RS+ was associated with an increased risk of sepsis development during hospitalization (OR 4.18; 95% CI, 1.99–8.78) and with death or re-hospitalization at 30 days (OR 4.79; 95% CI, 2.79–8.23), whereas RS+ did not appear to be associated with death during hospitalization or need for ICU transfer. Conclusions: Our results suggest for the first time a prognostic role for RS+ in Internal Medicine. Thus, assessment of rectal swab at hospital admission appears useful even in this setting. However, larger prospective studies and a cost–benefit analysis are needed to confirm our preliminary findings.