bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of Immune Responses in Giant African Snail, Achatina immaculata, against a Two-Round Lipopolysaccharide Challenge
Authors: Wang Xinfeng , Tang Yuzhe , Li Zaiyuan , Wu Qiang , Qiao Xi , Wan Fanghao , Qian Wanqiang , Liu Conghui
Published: July 2023

As one of the 100 most-threatening invasive alien species, the giant African snail (Achatina immaculata) has successfully invaded and established itself in most areas of southern China. Protection against recurrent pathogen infections is vital to biological invasion. Enhanced immune protection has been previously found in other invertebrates, but not in the unique immune system of the giant African snail. In the present study, the survival rate of the giant African snail was recorded following a second infection with lethal doses of Escherichia coli after a previous first injection using lipopolysaccharide (LPS), and the mechanism of immune enhancement was investigated by examining the cellular and transcriptomic response of the giant African snail after two successive stimuli using LPS. Snails injected first with LPS, sterilized physiologic (0.9%) saline (SPS), phosphate-buffered saline (PBS) or untreated (Blank) were rechallenged at 7d with E. coli (Ec), and were named as LPS + Ec, SPS + Ec, PBS + Ec, Ec, and Blank. The log-rank test shows the survival rate of the LPS + Ec group as significantly higher than that of other control groups after the second injection (p < 0.05). By performing cell counting and BrdU labeling on newly generated circulating hemocytes, we found that the total hemocyte count (THC) and the ratio of BrdU-positive cells to total cells increased significantly after primary stimulation with LPS and that they further increased after the second challenge. Then, caspase-3 of apoptosis protease and two antioxidant enzyme activities (CAT and SOD) increased significantly after infection, and were significantly higher in the second response than they had been in the first round. Moreover, transcriptome analysis results showed that 84 differentially expressed genes (DEGs) were expressed at higher levels in both the resting and activating states after the second immune response compared to the levels observed after the first challenge. Among them, some DEGs, including Toll-like receptor 4 (TLR4) and its downstream signaling molecules, were verified using qRT-PCR and were consistent with the transcriptome assay results. Based on gene expression levels, we proposed that these genes related to the TLR signaling cascade participate in enhanced immune protection. All results provide evidence that enhanced immune protection exists in the giant African snail.
Insight into the Potential Mechanisms of Endocrine Disruption by Dietary Phytoestrogens in the Context of the Etiopathogenesis of Endometriosis
Authors: Szukiewicz Dariusz
Published: July 2023

Phytoestrogens (PEs) are estrogen-like nonsteroidal compounds derived from plants (e.g., nuts, seeds, fruits, and vegetables) and fungi that are structurally similar to 17β-estradiol. PEs bind to all types of estrogen receptors, including ERα and ERβ receptors, nuclear receptors, and a membrane-bound estrogen receptor known as the G protein-coupled estrogen receptor (GPER). As endocrine-disrupting chemicals (EDCs) with pro- or antiestrogenic properties, PEs can potentially disrupt the hormonal regulation of homeostasis, resulting in developmental and reproductive abnormalities. However, a lack of PEs in the diet does not result in the development of deficiency symptoms. To properly assess the benefits and risks associated with the use of a PE-rich diet, it is necessary to distinguish between endocrine disruption (endocrine-mediated adverse effects) and nonspecific effects on the endocrine system. Endometriosis is an estrogen-dependent disease of unknown etiopathogenesis, in which tissue similar to the lining of the uterus (the endometrium) grows outside of the uterus with subsequent complications being manifested as a result of local inflammatory reactions. Endometriosis affects 10–15% of women of reproductive age and is associated with chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility. In this review, the endocrine-disruptive actions of PEs are reviewed in the context of endometriosis to determine whether a PE-rich diet has a positive or negative effect on the risk and course of endometriosis.
Biochemical and Structural Insights into a Thiamine Diphosphate-Dependent α-Ketoglutarate Decarboxylase from Cyanobacterium Microcystis aeruginosa NIES-843
Authors: Li Zhi-Min , Hu Ziwei , Wang Xiaoqin , Chen Suhang , Yu Weiyan , Liu Jianping , Li Zhimin
Published: July 2023

α-Ketoglutarate decarboxylase is a crucial enzyme in the tricarboxylic acid cycle of cyanobacteria, catalyzing the non-oxidative decarboxylation of α-ketoglutarate to produce succinate semialdehyde and CO2. The decarboxylation process is reliant on the cofactor of thiamine diphosphate. However, this enzyme’s biochemical and structural properties have not been well characterized. In this work, two α-ketoglutarate decarboxylases encoded by MAE_06010 and MiAbw_01735 genes from Microcystis aeruginosa NIES-843 (MaKGD) and NIES-4325 (MiKGD), respectively, were overexpressed and purified by using an Escherichia coli expression system. It was found that MaKGD exhibited 9.2-fold higher catalytic efficiency than MiKGD, which may be attributed to the absence of glutamate decarboxylase in Microcystis aeruginosa NIES-843. Further biochemical investigation of MaKGD demonstrated that it displayed optimum activity at pH 6.5–7.0 and was most activated by Mg2+. Additionally, MaKGD showed substrate specificity towards α-ketoglutarate. Structural modeling and autodocking results revealed that the active site of MaKGD contained a distinct binding pocket where α-ketoglutarate and thiamine diphosphate interacted with specific amino acid residues via hydrophobic interactions, hydrogen bonds and salt bridges. Furthermore, the mutagenesis study provided strong evidence supporting the importance of certain residues in the catalysis of MaKGD. These findings provide new insights into the structure-function relationships of α-ketoglutarate decarboxylases from cyanobacteria.
Innate and Adaptive Immunity-Related Markers as Predictors of the Short-Term Progression of Subclinical Atherosclerosis in Middle-Aged Patients
Authors: Genkel Vadim , Dolgushin Ilya , Savochkina Albina , Nikushkina Karina , Baturina Irina , Minasova Anna , Sumerkina Veronika , Pykhova Lubov , Kupriyanov Semen , Kuznetsova Alla , Shaposhnik Igor
Published: July 2023

Assessment of inflammation is a promising approach to monitoring the progression of asymptomatic atherosclerosis. The aim of the present study was to investigate the predictive value of innate and adaptive immunity-related markers, in relation to the short-term progression of subclinical atherosclerosis. The study included 183 patients aged 40–64 years who underwent duplex scanning of the carotid and lower limb arteries at two visits with an interval of 12–24 months between examinations. Phenotyping of circulating lymphocytes and monocytes subpopulations were performed through flow cytometry. An increase in the number of circulating TLR4-positive intermediate monocytes (>447.0–467.0 cells/μL) was an independent predictor of the short-term progression of lower limb artery atherosclerosis (p < 0.0001) and polyvascular atherosclerosis (p = 0.003). The assessment of TLR4-positive monocytes significantly improved the prognostic model for the progression of lower limb arterial atherosclerosis (C-index 0.728 (0.642–0.815) versus 0.637 (0.539–0.735); p = 0.038). An increase in the number of circulating TLR4-positive intermediate monocytes was an independent predictor of the short-term progression of lower limb artery and polyvascular atherosclerosis. Their inclusion into models containing conventional risk factors significantly improved their prognostic effectiveness regarding lower limb artery atherosclerosis progression.
Combined Salivary Proteome Profiling and Machine Learning Analysis Provides Insight into Molecular Signature for Autoimmune Liver Diseases Classification
Authors: Guadalupi Giulia , Contini Cristina , Iavarone Federica , Castagnola Massimo , Messana Irene , Faa Gavino , Onali Simona , Chessa Luchino , Vitorino Rui , Amado Francisco , Diaz Giacomo , Manconi Barbara , Cabras Tiziana , Olianas Alessandra
Published: July 2023

Autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) are autoimmune liver diseases that target the liver and have a wide spectrum of presentation. A global overview of quantitative variations on the salivary proteome in presence of these two pathologies is investigated in this study. The acid-insoluble salivary fraction of AIH and PBC patients, and healthy controls (HCs), was analyzed using a gel-based bottom-up proteomic approach combined with a robust machine learning statistical analysis of the dataset. The abundance of Arginase, Junction plakoglobin, Desmoplakin, Hexokinase-3 and Desmocollin-1 decreased, while that of BPI fold-containing family A member 2 increased in AIHp compared to HCs; the abundance of Gelsolin, CD14, Tumor-associated calcium signal transducer 2, Clusterin, Heterogeneous nuclear ribonucleoproteins A2/B1, Cofilin-1 and BPI fold-containing family B member 2 increased in PBCp compared to HCs. The abundance of Hornerin decreased in both AIHp and PBCp with respect to HCs and provided an area under the ROC curve of 0.939. Machine learning analysis confirmed the feasibility of the salivary proteome to discriminate groups of subjects based on AIH or PBC occurrence as previously suggested by our group. The topology-based functional enrichment analysis performed on these potential salivary biomarkers highlights an enrichment of terms mostly related to the immune system, but also with a strong involvement in liver fibrosis process and with antimicrobial activity.
Characterization of Breast Cancer Aggressiveness by Cell Mechanics
Authors: Zbiral Barbara , Weber Andreas , Vivanco Maria dM. , Toca-Herrera José L.
Published: July 2023

In healthy tissues, cells are in mechanical homeostasis. During cancer progression, this equilibrium is disrupted. Cancer cells alter their mechanical phenotype to a softer and more fluid-like one than that of healthy cells. This is connected to cytoskeletal remodeling, changed adhesion properties, faster cell proliferation and increased cell motility. In this work, we investigated the mechanical properties of breast cancer cells representative of different breast cancer subtypes, using MCF-7, tamoxifen-resistant MCF-7, MCF10A and MDA-MB-231 cells. We derived viscoelastic properties from atomic force microscopy force spectroscopy measurements and showed that the mechanical properties of the cells are associated with cancer cell malignancy. MCF10A are the stiffest and least fluid-like cells, while tamoxifen-resistant MCF-7 cells are the softest ones. MCF-7 and MDA-MB-231 show an intermediate mechanical phenotype. Confocal fluorescence microscopy on cytoskeletal elements shows differences in actin network organization, as well as changes in focal adhesion localization. These findings provide further evidence of distinct changes in the mechanical properties of cancer cells compared to healthy cells and add to the present understanding of the complex alterations involved in tumorigenesis.
Blood Plasma Small Non-Coding RNAs as Diagnostic Molecules for the Progesterone-Receptor-Negative Phenotype of Serous Ovarian Tumors
Authors: Timofeeva Angelika V. , Fedorov Ivan S. , Asaturova Aleksandra V. , Sannikova Maya V. , Tregubova Anna V. , Mayboroda Oleg A. , Khabas Grigory N. , Frankevich Vladimir E. , Sukhikh Gennady T.
Published: July 2023

The expression level of the progesterone receptor (PGR) plays a crucial role in determining the biological characteristics of serous ovarian carcinoma. Low PGR expression is associated with chemoresistance and a poorer outcome. In this study, our objective was to explore the relationship between tumor progesterone receptor levels and RNA profiles (miRNAs, piwiRNAs, and mRNAs) to understand their biological characteristics and behavior. To achieve this, we employed next-generation sequencing of small non-coding RNAs, quantitative RT-PCR, and immunohistochemistry to analyze both FFPE and frozen tumor samples, as well as blood plasma from patients with benign cystadenoma (BSC), serous borderline tumor (SBT), low-grade serous ovarian carcinoma (LGSOC), and high-grade serous ovarian carcinoma (HGSOC). Our findings revealed significant upregulation of MMP7 and MUC16, along with downregulation of PGR, in LGSOC and HGSOC compared to BSC. We observed significant correlations of PGR expression levels in tumor tissue with the contents of miR-199a-5p, miR-214-3p, miR-424-3p, miR-424-5p, and miR-125b-5p, which potentially target MUC16, MMP7, and MMP9, as well as with the tissue content of miR-16-5p, miR-17-5p, miR-20a-5p, and miR-93-5p, which are associated with the epithelial–mesenchymal transition (EMT) of cells. The levels of EMT-associated miRNAs were significantly correlated with the content of hsa_piR_022437, hsa_piR_009295, hsa_piR_020813, hsa_piR_004307, and hsa_piR_019914 in tumor tissues. We developed two optimal logistic regression models using the quantitation of hsa_piR_020813, miR-16-5p, and hsa_piR_022437 or hsa_piR_004307, hsa_piR_019914, and miR-93-5p in the tumor tissue, which exhibited a significant ability to diagnose the PGR-negative tumor phenotype with 93% sensitivity. Of particular interest, the blood plasma levels of miR-16-5p and hsa_piR_022437 could be used to diagnose the PGR-negative tumor phenotype with 86% sensitivity even before surgery and chemotherapy. This knowledge can help in choosing the most effective treatment strategy for this aggressive type of ovarian cancer, such as neoadjuvant chemotherapy followed by cytoreduction in combination with hyperthermic intraperitoneal chemotherapy and targeted therapy, thus enhancing the treatment’s effectiveness and the patient’s longevity.
Composites of N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide with Polymers: Effect of Crystallinity on Solubility and Stability
Authors: Markeev Vladimir B. , Blynskaya Evgenia V. , Tishkov Sergey V. , Alekseev Konstantin V. , Marakhova Anna I. , Vetcher Alexandre A. , Shishonin Alexander Y.
Published: July 2023

This work aimed to develop and characterize a water-soluble, high-release active pharmaceutical ingredient (API) composite based on the practically water-insoluble API N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3), a substance with antidepressant and anxiolytic action. This allows to ensure the bioavailability of the medicinal product of combined action. Composites obtained by the method of creating amorphous solid dispersions, where polyvinylpyrrolidone (PVP) or Soluplus® was used as a polymer, were studied for crystallinity, stability and the release of API from the composite into purified water. The resulting differential scanning calorimetry (DSC), powder X-ray diffractometry (PXRD), and dissolution test data indicate that the resulting composites are amorphous at 1:15 API: polymer ratios for PVP and 1:5 for Soluplus®, which ensures the solubility of GML-3 in purified water and maintaining the supercritical state in solution.
Oxidative Stress Markers in Human Brain and Placenta May Reveal the Timing of Hypoxic-Ischemic Injury: Evidence from an Immunohistochemical Study
Authors: Baldari Benedetta , De Simone Stefania , Cipolloni Luigi , Frisoni Paolo , Alfieri Letizia , D’Errico Stefano , Fineschi Vittorio , Turillazzi Emanuela , Greco Pantaleo , Vitagliano Amerigo , Scutiero Gennaro , Neri Margherita
Published: July 2023

During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36–42 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE.
Sir2 and Glycerol Underlie the Pro-Longevity Effect of Quercetin during Yeast Chronological Aging
Authors: Abbiati Francesco , Garagnani Stefano Angelo , Orlandi Ivan , Vai Marina
Published: July 2023

Quercetin (QUER) is a natural polyphenolic compound endowed with beneficial properties for human health, with anti-aging effects. However, although this flavonoid is commercially available as a nutraceutical, target molecules/pathways underlying its pro-longevity potential have yet to be fully clarified. Here, we investigated QUER activity in yeast chronological aging, the established model for simulating the aging of postmitotic quiescent mammalian cells. We found that QUER supplementation at the onset of chronological aging, namely at the diauxic shift, significantly increases chronological lifespan (CLS). Consistent with the antioxidant properties of QUER, this extension takes place in concert with a decrease in oxidative stress. In addition, QUER triggers substantial changes in carbon metabolism. Specifically, it promotes an enhancement of a pro-longevity anabolic metabolism toward gluconeogenesis due to improved catabolism of C2 by-products of yeast fermentation and glycerol. The former is attributable to the Sir2-dependent activity of phosphoenolpyruvate carboxykinase and the latter to the L-glycerol 3-phosphate pathway. Such a combined increased supply of gluconeogenesis leads to an increase in the reserve carbohydrate trehalose, ensuring CLS extension. Moreover, QUER supplementation to chronologically aging cells in water alone amplifies their long-lived phenotype. This is associated with intracellular glycerol catabolism and trehalose increase, further indicating a QUER-specific influence on carbon metabolism that results in CLS extension.
Roles and Preliminary Mechanism of Tobacco cis-Abienol in Inducing Tomato Resistance against Bacterial Wilt
Authors: Sun Yuqing , Gui Zuqing , Yan Ning , Wang Qian , Zhang Zhongfeng , Zhang Hongbo , Sun Feifei , Han Xiao , Du Yongmei
Published: July 2023

Bacterial wilt negatively impacts the yield and quality of tomatoes. cis-Abienol, a labdane diterpenoid abundantly produced in the trichome secretion of Nicotiana spp., can induce bacterial wilt resistance in plants; however, study on its practical application and acting mechanism is very limited. This study established the application conditions of cis-abienol for inducing tomato bacterial wilt resistance by pot-inoculation experiments and investigated the underlying mechanism by determining the physio-biochemical indexes and transcriptomic changes. The results showed that applying cis-abienol to the roots was the most effective approach for inducing tomato bacterial wilt resistance. The optimal concentration was 60 μg/mL, and 2–3 consecutive applications with 3–6 days intervals were sufficient to induce the bacterial wilt resistance of tomato plants. cis-Abienol could enhance the antioxidant enzyme activity and stimulate the defensive signal transduction in tomato roots, leading to the upregulation of genes involved in the mitogen-activated protein kinase cascade. It also upregulated the expression of JAZ genes and increased the content of jasmonic acid (JA) and salicylic acid (SA), which control the expression of flavonoid biosynthetic genes and the content of phytoalexins in tomato roots. cis-Abienol-induced resistance mainly depends on the JA signalling pathway, and the SA signalling pathway is also involved in this process. This study established the feasibility of applying the plant-derived terpenoid cis-abienol to induce plant bacterial wilt resistance, which is of great value for developing eco-friendly bactericides.
Lipophilic Studies and In Silico ADME Profiling of Biologically Active 2-Aminothiazol-4(5H)-one Derivatives
Authors: Redka Małgorzata , Baumgart Szymon , Kupczyk Daria , Kosmalski Tomasz , Studzińska Renata
Published: July 2023

Pseudothiohydantoin derivatives have a wide range of biological activities and are widely used in the development of new pharmaceuticals. Lipophilicity is a basic, but very important parameter in the design of potential drugs, as it determines solubility in lipids, nonpolar solvents, and makes it possible to predict the ADME profile. The aim of this study was to evaluate the lipophilicity of 28 pseudothiohydantoin derivatives showing the inhibition of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) using chromatographic methods. Experimentally, lipophilicity was determined by reverse phase thin layer chromatography (RP-TLC) and reverse phase high-performance liquid chromatography (RP-HPLC). In both methods, methanol was used as the organic modifier of the mobile phase. For each 2-aminothiazol-4(5H)-one derivative, a relationship was observed between the structure of the compound and the values of the lipophilicity parameters (log kw, RM0). Experimental lipophilicity values were compared with computer calculated partition coefficient (logP) values. A total of 27 of the 28 tested compounds had a lipophilicity value < 5, which therefore met the condition of Lipinski’s rule. In addition, the in silico ADME assay showed favorable absorption, distribution, metabolism, and excretion parameters for most of the pseudothiohydantoin derivatives tested. The study of lipophilicity and the ADME analysis indicate that the tested compounds are good potential drug candidates.
Adlercreutzia equolifaciens Is an Anti-Inflammatory Commensal Bacterium with Decreased Abundance in Gut Microbiota of Patients with Metabolic Liver Disease
Authors: Oñate Florian Plaza , Chamignon Célia , Burz Sebastian D. , Lapaque Nicolas , Monnoye Magali , Philippe Catherine , Bredel Maxime , Chêne Laurent , Farin William , Paillarse Jean-Michel , Boursier Jérome , Ratziu Vlad , Mousset Pierre-Yves , Doré Joël , Gérard Philippe , Blottière Hervé M.
Published: July 2023

Non-alcoholic fatty liver disease (NAFLD) affects about 20–40% of the adult population in high-income countries and is now a leading indication for liver transplantation and can lead to hepatocellular carcinoma. The link between gut microbiota dysbiosis and NAFLD is now clearly established. Through analyses of the gut microbiota with shotgun metagenomics, we observe that compared to healthy controls, Adlercreutzia equolifaciens is depleted in patients with liver diseases such as NAFLD. Its abundance also decreases as the disease progresses and eventually disappears in the last stages indicating a strong association with disease severity. Moreover, we show that A. equolifaciens possesses anti-inflammatory properties, both in vitro and in vivo in a humanized mouse model of NAFLD. Therefore, our results demonstrate a link between NAFLD and the severity of liver disease and the presence of A. equolifaciens and its anti-inflammatory actions. Counterbalancing dysbiosis with this bacterium may be a promising live biotherapeutic strategy for liver diseases.
Progenitor Cells Play a Role in Reinstatement of Ethanol Seeking in Adult Male and Female Ethanol Dependent Rats
Authors: Nonoguchi Hannah A. , Jin Michael , Narreddy Rajitha , Kouo Timothy Wee Shang , Nayak Mahasweta , Trenet Wulfran , Mandyam Chitra D.
Published: July 2023

Female and male glial fibrillary acidic protein-thymidine kinase (GFAP-TK) transgenic rats were made ethanol dependent via a six-week chronic intermittent ethanol vapor (CIE) and ethanol drinking (ED) procedure. During the last week of CIE, a subset of male and female TK rats was fed valcyte to ablate dividing progenitor cells and continued the diet until the end of this study. Following week six, all CIE rats experienced two weeks of forced abstinence from CIE-ED, after which they experienced relapse to drinking, extinction, and reinstatement of ethanol seeking sessions. CIE increased ED in female and male rats, with females having higher ethanol consumption during CIE and relapse sessions compared with males. In both sexes, valcyte reduced the levels of Ki-67-labeled progenitor cells in the subgranular zone of the dentate gyrus and did not alter the levels in the medial prefrontal cortex (mPFC). Valcyte increased ED during relapse, increased lever responses during extinction and, interestingly, enhanced latency to extinguish ethanol-seeking behaviors in males. Valcyte reduced the reinstatement of ethanol-seeking behaviors triggered by ethanol cues in females and males. Reduced seeking by valcyte was associated with the normalization of cytokines and chemokines in plasma isolated from trunk blood, indicating a role for progenitor cells in peripheral inflammatory responses. Reduced seeking by valcyte was associated with increases in tight junction protein claudin-5 and oligodendrogenesis in the dentate gyrus and reduction in microglial activity in the dentate gyrus and mPFC in females and males, demonstrating a role for progenitor cells in the dentate gyrus in dependence-induced endothelial and microglial dysfunction. These data suggest that progenitor cells born during withdrawal and abstinence from CIE in the dentate gyrus are aberrant and could play a role in strengthening ethanol memories triggered by ethanol cues via central and peripheral immune responses.
Identification of a Putative CFSH Receptor Inhibiting IAG Expression in Crabs
Authors: Liu Fang , Huang Lin , Liu An , Jiang Qingling , Huang Huiyang , Ye Haihui
Published: July 2023

The crustacean female sex hormone (CFSH) is a neurohormone peculiar to crustaceans that plays a vital role in sexual differentiation. This includes the preservation and establishment of secondary female sexual traits, as well as the inhibition of insulin-like androgenic gland factor (IAG) expression in the androgenic gland (AG). There have been no reports of CFSH receptors in crustaceans up to this point. In this study, we identified a candidate CFSH receptor from the mud crab Scylla paramamosain (named Sp-SEFIR) via protein interaction experiments and biological function experiments. Results of GST pull-down assays indicated that Sp-SEFIR could combine with Sp-CFSH. Findings of in vitro and in vivo interference investigations exhibited that knockdown of Sp-SEFIR could significantly induce Sp-IAG and Sp-STAT expression in the AG. In brief, Sp-SEFIR is a potential CFSH receptor in S. paramamosain, and Sp-CFSH controls Sp-IAG production through the CFSH-SEFIR-STAT-IAG axis.
Radotinib Decreases Prion Propagation and Prolongs Survival Times in Models of Prion Disease
Authors: Choi Yeong-Gon , Jang Byungki , Park Jeong-Ho , Choi Min-Woo , Lee Gong Yeal , Cho Dae Jin , Kim Hong Youp , Lim Hae Kyoung , Lee Won Jae , Choi Eun-Kyoung , Kim Yong-Sun
Published: July 2023

The conversion of cellular prion protein (PrPC) into pathogenic prion isoforms (PrPSc) and the mutation of PRNP are definite causes of prion diseases. Unfortunately, without exception, prion diseases are untreatable and fatal neurodegenerative disorders; therefore, one area of research focuses on identifying medicines that can delay the progression of these diseases. According to the concept of drug repositioning, we investigated the efficacy of the c-Abl tyrosine kinase inhibitor radotinib, which is a drug that is approved for the treatment of chronic myeloid leukemia, in the treatment of disease progression in prion models, including prion-infected cell models, Tga20 and hamster cerebellar slice culture models, and 263K scrapie-infected hamster models. Radotinib inhibited PrPSc deposition in neuronal ZW13-2 cells that were infected with the 22L or 139A scrapie strains and in cerebellar slice cultures that were infected with the 22L or 263K scrapie strains. Interestingly, hamsters that were intraperitoneally injected with the 263K scrapie strain and intragastrically treated with radotinib (100 mg/kg) exhibited prolonged survival times (159 ± 28.6 days) compared to nontreated hamsters (135 ± 9.9 days) as well as reduced PrPSc deposition and ameliorated pathology. However, intraperitoneal injection of radotinib exerted a smaller effect on the survival rate of the hamsters. Additionally, we found that different concentrations of radotinib (60, 100, and 200 mg/kg) had similar effects on survival time, but this effect was not observed after treatment with a low dose (30 mg/kg) of radotinib. Interestingly, when radotinib was administered 4 or 8 weeks after prion inoculation, the treated hamsters survived longer than the vehicle-treated hamsters. Additionally, a pharmacokinetic assay revealed that radotinib effectively crossed the blood–brain barrier. Based on our findings, we suggest that radotinib is a new candidate anti-prion drug that could possibly be used to treat prion diseases and promote the remission of symptoms.
Cripto Is Targeted by miR-1a-3p in a Mouse Model of Heart Development
Authors: Angrisano Tiziana , Varrone Francesca , Ragozzino Elvira , Fico Annalisa , Minchiotti Gabriella , Brancaccio Mariarita
Published: July 2023

During cardiac differentiation, numerous factors contribute to the development of the heart. Understanding the molecular mechanisms underlying cardiac development will help combat cardiovascular disorders, among the leading causes of morbidity and mortality worldwide. Among the main mechanisms, we indeed find Cripto. Cripto is found in both the syncytiotrophoblast of ampullary pregnancies and the inner cell mass along the primitive streak as the second epithelial–mesenchymal transformation event occurs to form the mesoderm and the developing myocardium. At the same time, it is now known that cardiac signaling pathways are intimately intertwined with the expression of myomiRNAs, including miR-1. This miR-1 is one of the muscle-specific miRs; aberrant expression of miR-1 plays an essential role in cardiac diseases. Given this scenario, our study aimed to evaluate the inverse correlation between Cripto and miR-1 during heart development. We used in vitro models of the heart, represented by embryoid bodies (EBs) and embryonic carcinoma cell lines derived from an embryo-derived teratocarcinoma in mice (P19 cells), respectively. First, through a luciferase assay, we demonstrated that Cripto is a target of miR-1. Following this result, we observed that as the days of differentiation increased, the Cripto gene expression decreased, while the level of miR-1 increased; furthermore, after silencing miR-1 in P19 cells, there was an increase in Cripto expression. Moreover, inducing damage with a cobra cardiotoxin (CTX) in post-differentiation cells, we noted a decreased miR-1 expression and increased Cripto. Finally, in mouse cardiac biopsies, we observed by monitoring gene expression the distribution of Cripto and miR-1 in the right and left ventricles. These results allowed us to detect an inverse correlation between miR-1 and Cripto that could represent a new pharmacological target for identifying new therapies.
Dissecting the Structural Dynamics of Authentic Cholesteryl Ester Transfer Protein for the Discovery of Potential Lead Compounds: A Theoretical Study
Authors: Zhao Yizhen , Hao Dongxiao , Zhao Yifan , Zhang Shengli , Zhang Lei , Yang Zhiwei
Published: July 2023

Current structural and functional investigations of cholesteryl ester transfer protein (CETP) inhibitor design are nearly entirely based on a fully active mutation (CETPMutant) constructed for protein crystallization, limiting the study of the dynamic structural features of authentic CETP involved in lipid transport under physiological conditions. In this study, we conducted comprehensive molecular dynamics (MD) simulations of both authentic CETP (CETPAuthentic) and CETPMutant. Considering the structural differences between the N- and C-terminal domains of CETPAuthentic and CETPMutant, and their crucial roles in lipid transfer, we identified the two domains as binding pockets of the ligands for virtual screening to discover potential lead compounds targeting CETP. Our results revealed that CETPAuthentic displays greater flexibility and pronounced curvature compared to CETPMutant. Employing virtual screening and MD simulation strategies, we found that ZINC000006242926 has a higher binding affinity for the N- and C-termini, leading to reduced N- and C-opening sizes, disruption of the continuous tunnel, and increased curvature of CETP. In conclusion, CETPAuthentic facilitates the formation of a continuous tunnel in the “neck” region, while CETPMutant does not exhibit such characteristics. The ligand ZINC000006242926 screened for binding to the N- and C-termini induces structural changes in the CETP unfavorable to lipid transport. This study sheds new light on the relationship between the structural and functional mechanisms of CETP. Furthermore, it provides novel ideas for the precise regulation of CETP functions.
Distinct Clades of Protein Phosphatase 2A Regulatory B’/B56 Subunits Engage in Different Physiological Processes
Authors: Heidari Behzad , Nemie-Feyissa Dugassa , Lillo Cathrine
Published: July 2023

Protein phosphatase 2A (PP2A) is a strongly conserved and major protein phosphatase in all eukaryotes. The canonical PP2A complex consists of a catalytic (C), scaffolding (A), and regulatory (B) subunit. Plants have three groups of evolutionary distinct B subunits: B55, B’ (B56), and B’’. Here, the Arabidopsis B’ group is reviewed and compared with other eukaryotes. Members of the B’α/B’β clade are especially important for chromatid cohesion, and dephosphorylation of transcription factors that mediate brassinosteroid (BR) signaling in the nucleus. Other B’ subunits interact with proteins at the cell membrane to dampen BR signaling or harness immune responses. The transition from vegetative to reproductive phase is influenced differentially by distinct B’ subunits; B’α and B’β being of little importance, whereas others (B’γ, B’ζ, B’η, B’θ, B’κ) promote transition to flowering. Interestingly, the latter B’ subunits have three motifs in a conserved manner, i.e., two docking sites for protein phosphatase 1 (PP1), and a POLO consensus phosphorylation site between these motifs. This supports the view that a conserved PP1-PP2A dephosphorelay is important in a variety of signaling contexts throughout eukaryotes. A profound understanding of these regulators may help in designing future crops and understand environmental issues.
Emerging Two-Dimensional Materials for Electromagnetic Interference Shielding Application
Authors: Kumari Suman , Dalal Jasvir , Kumar Vibhor , Kumar Anand , Ohlan Anil
Published: July 2023

Graphene is the first two-dimensional material that becomes the center material in various research areas of material science, chemistry, condensed matter, and engineering due to its advantageous properties, including larger specific area, lower density, outstanding electrical conductivity, and ease of processability. These properties attracted the attention of material researchers that resulted in a large number of publications on EMI shielding in a short time and play a central role in addressing the problems and challenges faced in this modern era of electronics by electromagnetic interference. After the popularity of graphene, the community of material researchers investigated other two-dimensional materials like MXenes, hexagonal boron nitride, black phosphorous, transition metal dichalcogenides, and layered double hydroxides, to additionally enhance the EMI shielding response of materials. The present article conscientiously reviews the current progress in EMI shielding materials in reference to two-dimensional materials and addresses the future challenges and research directions to achieve the goals.
Brainstem Modulates Parkinsonism-Induced Orofacial Sensorimotor Dysfunctions
Authors: Nascimento Glauce Crivelaro , Jacob Gabrielle , Milan Bruna Araujo , Leal-Luiz Gabrielli , Malzone Bruno Lima , Vivanco-Estela Airam Nicole , Escobar-Espinal Daniela , Dias Fernando José , Del-Bel Elaine
Published: July 2023

Parkinson’s Disease (PD), treated with the dopamine precursor l-3,4-dihydroxyphenylalanine (L-DOPA), displays motor and non-motor orofacial manifestations. We investigated the pathophysiologic mechanisms of the lateral pterygoid muscles (LPMs) and the trigeminal system related to PD-induced orofacial manifestations. A PD rat model was produced by unilateral injection of 6-hydroxydopamine into the medial forebrain bundle. Abnormal involuntary movements (dyskinesia) and nociceptive responses were determined. We analyzed the immunodetection of Fos-B and microglia/astrocytes in trigeminal and facial nuclei and morphological markers in the LPMs. Hyperalgesia response was increased in hemiparkinsonian and dyskinetic rats. Hemiparkinsonism increased slow skeletal myosin fibers in the LPMs, while in the dyskinetic ones, these fibers decreased in the contralateral side of the lesion. Bilateral increased glycolytic metabolism and an inflammatory muscle profile were detected in dyskinetic rats. There was increased Fos-B expression in the spinal nucleus of lesioned rats and in the motor and facial nucleus in L-DOPA-induced dyskinetic rats in the contralateral side of the lesion. Glial cells were increased in the facial nucleus on the contralateral side of the lesion. Overall, spinal trigeminal nucleus activation may be associated with orofacial sensorial impairment in Parkinsonian rats, while a fatigue profile on LPMs is suggested in L-DOPA-induced dyskinesia when the motor and facial nucleus are activated.
Tuta absoluta-Specific DNA in Domestic and Synanthropic Vertebrate Insectivore Feces
Authors: Janssen Dirk , González-Miras Emilio , Rodríguez Estefanía
Published: July 2023

The ecology of greenhouse pests generally involves parasitoid or predatory insects. However, we investigated whether the leaf miner Tuta absoluta (Meyrick, 1917) (Lepidoptera: Gelechiidae) is part of the diet of domestic and synanthropic vertebrate animals, such as birds, reptiles, and mammals, and that take part in an ecosystem that contains a high density of tomato greenhouses. Feces from domesticated partridges, common quails, and chickens, as well as from wild lizards were collected within tomato greenhouses, and fecal pellets from bats, swallows, common swifts, and house martins living in the vicinity of tomato greenhouses were collected outside. The efficiencies of three different DNA extraction methods were compared on bird, reptile, and mammal stool samples, and the DNA extracts were analyzed using probe real-time PCR for the presence of T. absoluta DNA. The results showed that bats fed on the pest, which was also part of the diet of several bird species: partridges and common quails kept within tomato greenhouses and swallows and common swifts living outside but in the vicinity of tomato greenhouses. In addition, fecal samples of three lizard species living near tomato crops also tested positive for T. absoluta DNA. The results suggest that aerial foraging bats and insectivorous birds are part of ecosystems that involve leaf miners and tomato greenhouses.
Mathematical Model for the Biological Control of the Coffee Berry Borer Hypothenemus hampei through Ant Predation
Authors: Trujillo-Salazar Carlos Andrés , Olivar-Tost Gerard , Sotelo-Castelblanco Deissy Milena
Published: July 2023

Coffee is a relevant agricultural product in the global economy, with the amount and quality of the bean being seriously affected by the coffee berry borer Hypothenemus hampei (Ferrari), CBB, its principal pest. One of the ways to deal with this beetle is through biological control agents, like ants (Hymenoptera: Formicidae), some of which are characterized by naturally inhabiting coffee plantations and feeding on CBB in all their life stages. Our paper considers a predator–prey interaction between these two insects through a novel mathematical model based on ordinary differential equations, where the state variables correspond to adult CBBs, immature CBBs, and ants from one species, without specifying whether preying on the CBB is among their feeding habits, in both adult and immature stages. Through this new mathematical model, we could qualitatively predict the different dynamics present in the system as some meaningful parameters were varied, filling the existing gap in the literature and envisioning ways to manage pests. Mathematically, the system’s equilibrium points were determined, and its stability was studied through qualitative theory. Bifurcation theory and numerical simulations were applied to illustrate the stability of the results, which were interpreted as conditions of the coexistence of the species, as well as conditions for eradicating the pest, at least theoretically, through biocontrol action in combination with other actions focused on eliminating only adult CBBs.
Complete Transthoracic Echocardiography for the Assessment and Guidance of Percutaneous Atrial Septal Defect Closure in Adults without Balloon Sizing: An Observed Study with a 10-Year Follow-Up
Authors: Xie Lin-Feng , Lin Yong , Chen Mei-Fang , Zhang Gui-Can
Published: July 2023

Objectives: This study aims to determine if complete transthoracic echocardiography (TTE)-guided percutaneous atrial septal defect (ASD) closure without balloon sizing could be safe and efficacious in adult patients. Methods: A total of 551 patients with ASDs were enrolled in this study, of which 438 patients underwent percutaneous ASD closure. Patients who received TTE-guided percutaneous ASD closure were classified into group T, and those who underwent a procedure that was guided by transesophageal echocardiography (TEE) were classified into group E. The clinical characteristics and the outcomes of the patients were analyzed. Results: The characteristics were comparable at baseline, except for the body mass index (BMI) (21.6 ± 5.3 vs. 23.8 ± 7.1, p < 0.001) between group T and group E. No significant difference was observed between the two groups regarding in-hospital outcomes, except for the duration of the procedure (29.8 ± 15.3 min vs. 41.5 ± 20.4 min), the length of stay in the hospital (2.1 ± 2.3 d vs. 2.9 ± 2.6 d), and hospital costs (USD 6233.3 ± 312.4 vs. USD 6673.7 ± 446.9). There were no significant differences in the incidences of long-term complications, cardiac chamber sizes, and tricuspid regurgitation severity between the patients in the two groups during the 10-year follow-up period. Conclusion: TTE may be as safe and efficacious as TEE for the assessment and guidance of percutaneous ASD closure without balloon sizing in adult patients with lower BMIs who are commonly found in East Asia.
Obesity-Related Atrial Fibrillation: Cardiac Manifestation of a Systemic Disease
Authors: Limpitikul Worawan B. , Das Saumya
Published: July 2023

Atrial fibrillation (AF) is the most common arrhythmia worldwide and is associated with increased morbidity and mortality. The mechanisms underlying AF are complex and multifactorial. Although it is well known that obesity is a strong risk factor for AF, the mechanisms underlying obesity-related AF are not completely understood. Current evidence proposes that in addition to overall hemodynamic changes due to increased body weight, excess adiposity raises systemic inflammation and oxidative stress, which lead to adverse atrial remodeling. This remodeling includes atrial fibrosis, atrial dilation, decreased electrical conduction between atrial myocytes, and altered ionic currents, making atrial tissue more vulnerable to both the initiation and maintenance of AF. However, much remains to be learned about the mechanistic links between obesity and AF. This knowledge will power the development of novel diagnostic tools and treatment options that will help combat the rise of the global AF burden among the obesity epidemic.
Longitudinal Trends in Severe Dyslipidemia in the Czech Population: The Czech MONICA and Czech Post-MONICA Study
Authors: Cífková Renata , Bruthans Jan , Wohlfahrt Peter , Hrubeš Krajčoviechová Alena , Šulc Pavel , Jozífová Marie , Eremiášová Lenka , Pudil Jan , Linhart Aleš , Widimský Jiří , Filipovský Jan , Mayer Otto , Poledne Rudolf , Stávek Petr , Lánská Věra , Strilchuk Larysa
Published: July 2023

Background: Severe hypercholesterolemia is associated with an increase in the risk of developing atherosclerotic cardiovascular disease. The aim of this analysis was to assess longitudinal trends in severe dyslipidemia (defined as total cholesterol > 8 mmol/L or LDL-cholesterol > 5 mmol/L) in a representative population sample of the Czech Republic and to analyze the longitudinal trends in the basic characteristics of individuals with severe dyslipidemia. Methods: Seven independent cross-sectional surveys were organized in the Czech Republic to screen for major cardiovascular risk factors (from 1985 to 2015–2018). A total of 20,443 randomly selected individuals aged 25–64 years were examined. Results: The overall prevalence of severe dyslipidemia was 6.6%, with a significant downward trend from the fifth survey onwards (2000/2001). Over the study period of 30+ years, the individuals with severe dyslipidemia became older, increased in BMI, and did not change their smoking habits. Total cholesterol and non-HDL-cholesterol decreased significantly in both sexes throughout the duration of the study. Conclusions: Despite a significant improvement in lipids in the Czech Republic from 1985, substantially contributing to the decline in cardiovascular mortality, the number of individuals with severe dyslipidemia remained high, and in most cases, they were newly detected during our screening examinations and were thus untreated.