bluuebunny/crossref_metadata_2025 huggingface dataset:
Vachellia farnesiana Pods or a Polyphenolic Extract Derived from Them Exert Immunomodulatory, Metabolic, Renoprotective, and Prebiotic Effects in Mice Fed a High-Fat Diet
Authors: Delgadillo-Puga Claudia , Sánchez-Castillo Dulce R. , Cariño-Cervantes Yonatan Y. , Torre-Villalvazo Ivan , Tovar-Palacio Claudia , Vásquez-Reyes Sarai , Furuzawa-Carballeda Janette , Acevedo-Carabantes Joshua Ayork , Camacho-Corona María del Rayo , Guzmán-Mar Jorge Luis , Cisneros-Zevallos Luis , Tovar Armando R. , Rebollar-Vega Rosa , Hernández-Montes Georgina , Ulloa-Aguirre Alfredo , Palacios-Gonzalez Berenice , Noriega Lilia G.
Published: April 2023

Obesity causes systemic inflammation, hepatic and renal damage, as well as gut microbiota dysbiosis. Alternative vegetable sources rich in polyphenols are known to prevent or delay the progression of metabolic abnormalities during obesity. Vachellia farnesiana (VF) is a potent source of polyphenols with antioxidant and anti-inflammatory activities with potential anti-obesity effects. We performed an in vivo preventive or an interventional experimental study in mice and in vitro experiments with different cell types. In the preventive study, male C57BL/6 mice were fed with a Control diet, a high-fat diet, or a high-fat diet containing either 0.1% methyl gallate, 10% powdered VFP, or 0.5%, 1%, or 2% of a polyphenolic extract (PE) derived from VFP (Vachellia farnesiana pods) for 14 weeks. In the intervention study, two groups of mice were fed for 14 weeks with a high-fat diet and then one switched to a high-fat diet with 10% powdered VFP for ten additional weeks. In the in vitro studies, we evaluated the effect of a VFPE (Vachellia farnesiana polyphenolic extract) on glucose-stimulated insulin secretion in INS-1E cells or of naringenin or methyl gallate on mitochondrial activity in primary hepatocytes and C2C12 myotubes. VFP or a VFPE increased whole-body energy expenditure and mitochondrial activity in skeletal muscle; prevented insulin resistance, hepatic steatosis, and kidney damage; exerted immunomodulatory effects; and reshaped fecal gut microbiota composition in mice fed a high-fat diet. VFPE decreased insulin secretion in INS-1E cells, and its isolated compounds naringenin and methyl gallate increased mitochondrial activity in primary hepatocytes and C2C12 myotubes. In conclusion VFP or a VFPE prevented systemic inflammation, insulin resistance, and hepatic and renal damage in mice fed a high-fat diet associated with increased energy expenditure, improved mitochondrial function, and reduction in insulin secretion.
Characteristics and Application of a Novel Cold-Adapted and Salt-Tolerant Protease EK4-1 Produced by an Arctic Bacterium Mesonia algae K4-1
Authors: Rao Hailian , Huan Ran , Chen Yidan , Xiao Xun , Li Wenzhao , He Hailun
Published: April 2023

Mesonia algae K4-1 from the Arctic secretes a novel cold-adapted and salt-tolerant protease EK4-1. It has the highest sequence similarity with Stearolysin, an M4 family protease from Geobacillus stearothermophilus, with only 45% sequence identity, and is a novel M4 family protease. Ek4-1 has a low optimal catalytic temperature (40 °C) and is stable at low temperatures. Moreover, EK4-1 is still active in 4 mol/L NaCl solution and is tolerant to surfactants, oxidizing agents and organic solvents; furthermore, it prefers the hydrolysis of peptide bonds at the P1’ position as the hydrophobic residues, such as Leu, Phe and Val, and amino acids with a long side chain, such as Phe and Tyr. Mn2+and Mg2+ significantly promoted enzyme activity, while Fe3+, Co+, Zn2+ and Cu2+ significantly inhibited enzyme activity. Amino acid composition analysis showed that EK4-1 had more small-side-chain amino acids and fewer large-side-chain amino acids. Compared with a thermophilic protease Stearolysin, the cold-adapted protease EK4-1 contains more random coils (48.07%) and a larger active pocket (727.42 Å3). In addition, the acidic amino acid content of protease EK4-1 was higher than that of the basic amino acid, which might be related to the salt tolerance of protease. Compared with the homologous proteases EB62 and E423, the cold-adapted protease EK4-1 was more efficient in the proteolysis of grass carp skin, salmon skin and casein at a low temperature, and produced a large number of antioxidant peptides, with DPPH, ·OH and ROO· scavenging activities. Therefore, cold-adapted and salt-tolerant protease EK4-1 offers wide application prospects in the cosmetic and detergent industries.
Poly-D,L-Lactic Acid Stimulates Angiogenesis and Collagen Synthesis in Aged Animal Skin
Authors: Oh Seyeon , Seo Suk Bae , Kim Gunpoong , Batsukh Sosorburam , Son Kuk Hui , Byun Kyunghee
Published: April 2023

Angiogenesis promotes rejuvenation in multiple organs, including the skin. Heat shock protein 90 (HSP90), hypoxia-inducible factor-1 alpha (HIF-1α), and vascular endothelial growth factor (VEGF) are proangiogenic factors that stimulate the activities of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and extracellular signal-regulated kinase 1/2 (ERK1/2). Poly-D,L-lactic acid (PDLLA), polynucleotide (PN), and calcium hydroxyapatite (CaHA) are dermal fillers that stimulate the synthesis of dermal collagen. However, it is not yet known whether these compounds promote angiogenesis, which leads to skin rejuvenation. Here, we evaluated whether PDLLA, PN, and CaHA stimulate angiogenesis and skin rejuvenation using H2O2-treated senescent macrophages and endothelial cells as an in vitro model for skin aging, and we used young and aged C57BL/6 mice as an in vivo model. Angiogenesis was evaluated via endothelial cell migration length, proliferation, and tube formation after conditioned media (CM) from senescent macrophages was treated with PDLLA, PN, or CaHA. Western blot showed decreased expression levels of HSP90, HIF-1α, and VEGF in senescent macrophages, but higher expression levels of these factors were found after treatment with PDLLA, PN, or CaHA. In addition, after exposure to CM from senescent macrophages treated with PDLLA, PN, or CaHA, senescent endothelial cells expressed higher levels of VEGF receptor 2 (VEGFR2), PI3K, phosphorylated AKT (pAKT), and phosphorylated ERK1/2 (pERK1/2) and demonstrated greater capacities for cell migration, cell proliferation, and tube formation. Based on the levels of 4-hydroxy-2-nonenal, the oxidative stress level was lower in the skin of aged mice injected with PDLLA, PN, or CaHA, while the tumor growth factor (TGF)-β1, TGF-β2, and TGF-β3 expression levels; the density of collagen fibers; and the skin elasticity were higher in the skin of aged mice injected with PDLLA, PN, or CaHA. These effects were greater in PDLLA than in PN or CaHA. In conclusion, our results are consistent with the hypothesis that PDLLA stimulates angiogenesis, leading to the rejuvenation of aged skin. Our study is the first to show that PDLLA, PN, or CaHA can result in angiogenesis in the aged skin, possibly by increasing the levels of HSP90, HIF-1α, and VEGF and increasing collagen synthesis.
Association between Taxonomic Composition of Gut Microbiota and Host Single Nucleotide Polymorphisms in Crohn’s Disease Patients from Russia
Authors: Markelova Maria , Senina Anastasia , Khusnutdinova Dilyara , Siniagina Maria , Kupriyanova Elena , Shakirova Gulnaz , Odintsova Alfiya , Abdulkhakov Rustam , Kolesnikova Irina , Shagaleeva Olga , Lyamina Svetlana , Abdulkhakov Sayar , Zakharzhevskaya Natalia , Grigoryeva Tatiana
Published: April 2023

Crohn’s disease (CD) is a chronic relapsing inflammatory bowel disease of unknown etiology. Genetic predisposition and dysbiotic gut microbiota are important factors in the pathogenesis of CD. In this study, we analyzed the taxonomic composition of the gut microbiota and genotypes of 24 single nucleotide polymorphisms (SNP) associated with the risk of CD. The studied cohorts included 96 CD patients and 24 healthy volunteers from Russia. Statistically significant differences were found in the allele frequencies for 8 SNPs and taxonomic composition of the gut microbiota in CD patients compared with controls. In addition, two types of gut microbiota communities were identified in CD patients. The main distinguishing driver of bacterial families for the first community type are Bacteroidaceae and unclassified members of the Clostridiales order, and the second type is characterized by increased abundance of Streptococcaceae and Enterobacteriaceae. Differences in the allele frequencies of the rs9858542 (BSN), rs3816769 (STAT3), and rs1793004 (NELL1) were also found between groups of CD patients with different types of microbiota communities. These findings confirm the complex multifactorial nature of CD.
Domain Localization by Graphene Oxide in Supported Lipid Bilayers
Authors: Tero Ryugo , Hagiwara Yoshi , Saito Shun
Published: April 2023

The gel-phase domains in a binary supported lipid bilayer (SLB) comprising dioleoylphosphatidylcholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC) were localized on graphene oxide (GO) deposited on a SiO2/Si substrate. We investigated the distribution of the gel-phase domains and the liquid crystalline (Lα) phase regions in DOPC+DPPC-SLB on thermally oxidized SiO2/Si substrates with GO flakes to understand the mechanism of the domain localization on GO. Fluorescence microscopy and atomic force microscopy revealed that the gel-phase domains preferably distributed on GO flakes, whereas the fraction of the Lα-phase increased on the bare SiO2 surface which was not covered with the GO flakes. The gel-phase domain was condensed on GO more effectively at the lower cooling rate. We propose that nucleation of the gel-phase domain preferentially occurred on GO, whose surface has amphiphilic property, during the gel-phase domain formation. The domains of the liquid ordered (Lo) phase were also condensed on GO in a ternary bilayer containing cholesterol that was phase-separated to the Lo phase and the liquid disordered phase. Rigid domains segregates on GO during their formation process, leaving fluid components to the surrounding region of GO.
Soybean (Glycine max L.) Lipoxygenase 1 (LOX 1) Is Modulated by Nitric Oxide and Hydrogen Sulfide: An In Vitro Approach
Authors: González-Gordo Salvador , López-Jaramillo Javier , Palma José M. , Corpas Francisco J.
Published: April 2023

Hydrogen sulfide (H2S) and nitric oxide (NO) are two relevant signal molecules that can affect protein function throughout post-translational modifications (PTMs) such as persulfidation, S-nitrosation, metal-nitrosylation, and nitration. Lipoxygenases (LOXs) are a group of non-heme iron enzymes involved in a wide range of plant physiological functions including seed germination, plant growth and development, and fruit ripening and senescence. Likewise, LOXs are also involved in the mechanisms of response to diverse environmental stresses. Using purified soybean (Glycine max L.) lipoxygenase type 1 (LOX 1) and nitrosocysteine (CysNO) and sodium hydrosulfide (NaHS) as NO and H2S donors, respectively, the present study reveals that both compounds negatively affect LOX activity, suggesting that S-nitrosation and persulfidation are involved. Mass spectrometric analysis of nitrated soybean LOX 1 using a peroxynitrite (ONOO−) donor enabled us to identify that, among the thirty-five tyrosine residues present in this enzyme, only Y214 was exclusively nitrated by ONOO−. The nitration of Y214 seems to affect its interaction with W500, a residue involved in the substrate binding site. The analysis of the structure 3PZW demonstrates the existence of several tunnels that directly communicate the surface of the protein with different internal cysteines, thus making feasible their potential persulfidation, especially C429 and C127. On the other hand, the CysNO molecule, which is hydrophilic and bulkier than H2S, can somehow be accommodated throughout the tunnel until it reaches C127, thus facilitating its nitrosation. Overall, a large number of potential persulfidation targets and the ease by which H2S can reach them through the diffuse tunneling network could be behind their efficient inhibition.
In Silico Investigation of Selected Pesticides and Their Determination in Agricultural Products Using QuEChERS Methodology and HPLC-DAD
Authors: Petrović Stefan , Arsić Biljana , Zlatanović Ivana , Milićević Jelena , Glišić Sanja , Mitić Milan , Đurović-Pejčev Rada , Stojanović Gordana
Published: April 2023

In this study, we considered some pesticides as active substances within formulations for the protection of plant-based food in the Republic of Serbia in silico, because these pesticides have not often been investigated in this way previously, and in an analytical way, because there are not very many available fast, cheap, and easy methods for their determination in real agricultural samples. Seven pesticides were detected in selected agricultural products (tomatoes, cucumbers, peppers, and grapes) using the QuEChERS methodology and HPLC-DAD. Standard curves for the investigated pesticides (chlorantraniliprole, methomyl, metalaxyl, thiacloprid, acetamiprid, emamectin benzoate, and cymoxanil) show good linearity, with R2 values from 0.9785 to 0.9996. The HPLC-DAD method is fast, and these pesticides can be determined in real spiked samples in less than 15 min. We further characterized the pesticides we found in food based on physicochemical properties and molecular descriptors to predict the absorption, distribution, metabolism, elimination, and toxicity (ADMET) of the compounds. We summarized the data supporting their effects on humans using various computational tools to determine their potential adverse effects. The results of our prediction study show that all of the selected pesticides considered in this study have good oral bioavailability, and those with high toxicity, therefore, could be harmful to human health. Chlorantraniliprole was shown in a molecular docking study as a good starting point for a new Alzheimer’s disease drug candidate.
Do GWAS-Identified Risk Variants for Chronic Lymphocytic Leukemia Influence Overall Patient Survival and Disease Progression?
Authors: Cabrera-Serrano Antonio José , Sánchez-Maldonado José Manuel , ter Horst Rob , Macauda Angelica , García-Martín Paloma , Benavente Yolanda , Landi Stefano , Clay-Gilmour Alyssa , Niazi Yasmeen , Espinet Blanca , Rodríguez-Sevilla Juan José , Pérez Eva María , Maffei Rossana , Blanco Gonzalo , Giaccherini Matteo , Cerhan James R. , Marasca Roberto , López-Nevot Miguel Ángel , Chen-Liang Tzu , Thomsen Hauke , Gámez Irene , Campa Daniele , Moreno Víctor , de Sanjosé Silvia , Marcos-Gragera Rafael , García-Álvarez María , Dierssen-Sotos Trinidad , Jerez Andrés , Butrym Aleksandra , Norman Aaron D. , Luppi Mario , Slager Susan L. , Hemminki Kari , Li Yang , Berndt Sonja I. , Casabonne Delphine , Alcoceba Miguel , Puiggros Anna , Netea Mihai G. , Försti Asta , Canzian Federico , Sainz Juan
Published: April 2023

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults worldwide. Although genome-wide association studies (GWAS) have uncovered the germline genetic component underlying CLL susceptibility, the potential use of GWAS-identified risk variants to predict disease progression and patient survival remains unexplored. Here, we evaluated whether 41 GWAS-identified risk variants for CLL could influence overall survival (OS) and disease progression, defined as time to first treatment (TTFT) in a cohort of 1039 CLL cases ascertained through the CRuCIAL consortium. Although this is the largest study assessing the effect of GWAS-identified susceptibility variants for CLL on OS, we only found a weak association of ten single nucleotide polymorphisms (SNPs) with OS (p < 0.05) that did not remain significant after correction for multiple testing. In line with these results, polygenic risk scores (PRSs) built with these SNPs in the CRuCIAL cohort showed a modest association with OS and a low capacity to predict patient survival, with an area under the receiver operating characteristic curve (AUROC) of 0.57. Similarly, seven SNPs were associated with TTFT (p < 0.05); however, these did not reach the multiple testing significance threshold, and the meta-analysis with previous published data did not confirm any of the associations. As expected, PRSs built with these SNPs showed reduced accuracy in prediction of disease progression (AUROC = 0.62). These results suggest that susceptibility variants for CLL do not impact overall survival and disease progression in CLL patients.
Tributyrin Intake Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm in LDLR-/- Mice
Authors: Lin Chih-Pei , Huang Po-Hsun , Chen Chi-Yu , Tzeng I-Shiang , Wu Meng-Yu , Chen Jia-Shiong , Chen Jaw-Wen , Lin Shing-Jong
Published: April 2023

Abdominal aortic aneurysm (AAA) is a multifactorial cardiovascular disease with a high risk of death, and it occurs in the infrarenal aorta with vascular dilatation. High blood pressure acts on the aortic wall, resulting in rupture and causing life-threatening intra-abdominal hemorrhage. Vascular smooth muscle cell (VSMC) dysregulation and extracellular matrix (ECM) degradation, especially elastin breaks, contribute to structural changes in the aortic wall. The pathogenesis of AAA includes the occurrence of oxidative stress, inflammatory cell infiltration, elastic fiber fragmentation, VSMC apoptosis, and phenotypic transformation. Tributyrin (TB) is decomposed by intestinal lipase and has a function similar to that of butyrate. Whether TB has a protective effect against AAA remains uncertain. In the present study, we established an AAA murine model by angiotensin II (AngII) induction in low-density lipoprotein receptor knockout (LDLR-/-) mice and investigated the effects of orally administered TB on the AAA size, ratio of macrophage infiltration, levels of matrix metalloproteinase (MMP) expression, and epigenetic regulation. TB attenuates AngII-induced AAA size and decreases elastin fragmentation, macrophage infiltration, and MMP expression in the medial layer of the aorta and reduces the levels of SBP (systolic blood pressure, p < 0.001) and MMP-2 (p < 0.02) in the serum. TB reduces the AngII-stimulated expression levels of MMP2 (p < 0.05), MMP9 (p < 0.05), MMP12, and MMP14 in human aortic smooth muscle cells (HASMCs). Moreover, TB and valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, suppress AngII receptor type 1 (AT1R, p < 0.05) activation and increase the expression of acetyl histone H3 by HDAC activity inhibition (p < 0.05). Our findings suggest that TB exerts its protective effect by suppressing the activation of HDAC to attenuate the AngII-induced AT1R signaling cascade.
Ferulic Acid: A Review of Pharmacology, Toxicology, and Therapeutic Effects on Pulmonary Diseases
Authors: Zhai Yiman , Wang Tingyu , Fu Yunmei , Yu Tong , Ding Yan , Nie Hongguang
Published: April 2023

Ferulic acid (FA), a prevalent dietary phytochemical, has many pharmacological effects, including anti-oxidation and anti-inflammation effects, and has been widely used in the pharmaceutical, food, and cosmetics industries. Many studies have shown that FA can significantly downregulate the expression of reactive oxygen species and activate nuclear factor erythroid-2-related factor-2/heme oxygenase-1 signaling, exerting anti-oxidative effects. The anti-inflammatory effect of FA is mainly related to the p38 mitogen-activated protein kinase and nuclear factor-kappaB signaling pathways. FA has demonstrated potential clinical applications in the treatment of pulmonary diseases. The transforming growth factor-β1/small mothers against decapentaplegic 3 signaling pathway can be blocked by FA, thereby alleviating pulmonary fibrosis. Moreover, in the context of asthma, the T helper cell 1/2 imbalance is restored by FA. Furthermore, FA ameliorates acute lung injury by inhibiting nuclear factor-kappaB and mitogen-activated protein kinase pathways via toll-like receptor 4, consequently decreasing the expression of downstream inflammatory mediators. Additionally, there is a moderate neuraminidase inhibitory activity showing a tendency to reduce the interleukin-8 level in response to influenza virus infections. Although the application of FA has broad prospects, more preclinical mechanism-based research should be carried out to test these applications in clinical settings. This review not only covers the literature on the pharmacological effects and mechanisms of FA, but also discusses the therapeutic role and toxicology of FA in several pulmonary diseases.
Evaluation of Autonomic Nervous System Dysfunction in Childhood Obesity and Prader–Willi Syndrome
Authors: Richer Lawrence P. , Tan Qiming , Butler Merlin G. , Avedzi Hayford M. , DeLorey Darren S. , Peng Ye , Tun Hein M. , Sharma Arya M. , Ainsley Steven , Orsso Camila E. , Triador Lucila , Freemark Michael , Haqq Andrea M.
Published: April 2023

The autonomic nervous system (ANS) may play a role in the distribution of body fat and the development of obesity and its complications. Features of individuals with Prader–Willi syndrome (PWS) impacted by PWS molecular genetic classes suggest alterations in ANS function; however, these have been rarely studied and presented with conflicting results. The aim of this study was to investigate if the ANS function is altered in PWS. In this case-control study, we assessed ANS function in 20 subjects with PWS (6 males/14 females; median age 10.5 years) and 27 body mass index (BMI) z-score-matched controls (19 males/8 females; median age 12.8 years). Standardized non-invasive measures of cardiac baroreflex function, heart rate, blood pressure, heart rate variability, quantitative sudomotor axon reflex tests, and a symptom questionnaire were completed. The increase in heart rate in response to head-up tilt testing was blunted (p < 0.01) in PWS compared to controls. Besides a lower heart rate ratio with Valsalva in PWS (p < 0.01), no significant differences were observed in other measures of cardiac function or sweat production. Findings suggest possible altered sympathetic function in PWS.
The Apelinergic System in Pregnancy
Authors: Pécheux Océane , Correia-Branco Ana , Cohen Marie , Martinez de Tejada Begoῆa
Published: April 2023

The apelinergic system is a highly conserved pleiotropic system. It comprises the apelin receptor apelin peptide jejunum (APJ) and its two peptide ligands, Elabela/Toddler (ELA) and apelin, which have different spatiotemporal localizations. This system has been implicated in the regulation of the adipoinsular axis, in cardiovascular and central nervous systems, in carcinogenesis, and in pregnancy in humans. During pregnancy, the apelinergic system is essential for embryo cardiogenesis and vasculogenesis and for placental development and function. It may also play a role in the initiation of labor. The apelinergic system seems to be involved in the development of placenta-related pregnancy complications, such as preeclampsia (PE) and intrauterine growth restriction, but an improvement in PE-like symptoms and birth weight has been described in murine models after the exogenous administration of apelin or ELA. Although the expression of ELA, apelin, and APJ is altered in human PE placenta, data related to their circulating levels are inconsistent. This article reviews current knowledge about the roles of the apelinergic system in pregnancy and its pathophysiological roles in placenta-related complications in pregnancy. We also discuss the challenges in translating the actors of the apelinergic system into a marker or target for therapeutic interventions in obstetrics.
Molecular Advances in Microbial Metabolism
Authors: Martínez-Espinosa Rosa María , Pire Carmen
Published: April 2023

Climate change, global pollution due to plastics, greenhouse gasses, or heavy metals among other pollutants, as well as limited natural sources due to unsustainable lifestyles and consumption patterns, are revealing the need for more research to understand ecosystems, biodiversity, and global concerns from the microscale to the macroscale [...]
Clinical and Genetic Characteristics of Calvarial Doughnut Lesions with Bone Fragility in Three Families with a Reccurent SGMS2 Gene Variant
Authors: Merkuryeva Elena , Markova Tatiana , Tyurin Anton , Valeeva Diana , Kenis Vladimir , Sumina Maria , Sorokin Igor , Shchagina Olga , Skoblov Mikhail , Nefedova Maria , Khusainova Rita , Zakharova Ekaterina , Dadali Elena , Kutsev Sergey
Published: April 2023

Calvarial doughnut lesions (CDL) with bone fragility with or without spondylometaphyseal dysplasia (MIM: #126550) is a rare autosomal dominant skeletal disorder characterized by low bone mineral density, spinal and peripheral fractures, and specific sclerotic lesions of the cranial bones. In the current classification of skeletal disorders, the disease is included in the group of bone fragility disorders along with osteogenesis imperfecta. The disease is caused by pathogenic variants in the SGMS2 gene, the protein product of which is sphingomyelin synthase 2, which primarily contributes to sphingomyelin (SM) synthesis—the main lipid component of the plasma membrane essential for bone mineralization. To date, 15 patients from eight families with CDL with bone fragility have been described in the literature, and a recurrent variant c.148C>T (p.Arg50Ter) in the SGMS2 gene has been identified, which was found in patients from six families. We diagnosed the disease in 11 more patients from three unrelated families, caused by the same heterozygous nonsense variant c.148C>T (p.Arg50Ter) in the SGMS2 gene. Our results show wide interfamilial and intrafamilial phenotypic variability in patients with a detected recurrent variant in the SGMS2 gene, the presence of which must be taken into consideration in the diagnosis of the disease. The primary analysis of this variant will contribute to optimal molecular genetic diagnostics, which can reduce diagnostic costs and time.
The Role of Microbiota-Derived Metabolites in Colorectal Cancer
Authors: Duizer Coco , de Zoete Marcel R.
Published: April 2023

The impact of bacterial members of the microbiota on the development of colorectal cancer (CRC) has become clear in recent years. However, exactly how bacteria contribute to the development of cancer is often still up for debate. The impact of bacteria-derived metabolites, which can influence the development of CRC either in a promoting or inhibiting manner, is undeniable. Here, we discuss the effects of the most well-studied bacteria-derived metabolites associated with CRC, including secondary bile acids, short-chain fatty acids, trimethylamine-N-oxide and indoles. We show that the effects of individual metabolites on CRC development are often nuanced and dose- and location-dependent. In the coming years, the array of metabolites involved in CRC development will undoubtedly increase further, which will emphasize the need to focus on causation and mechanisms and the clearly defined roles of bacterial species within the microbiota.
Novel Salinity-Tolerant Third-Generation Hybrid Rice Developed via CRISPR/Cas9-Mediated Gene Editing
Authors: Sheng Xiabing , Ai Zhiyong , Tan Yanning , Hu Yuanyi , Guo Xiayu , Liu Xiaolin , Sun Zhizhong , Yu Dong , Chen Jin , Tang Ning , Duan Meijuan , Yuan Dingyang
Published: April 2023

Climate change has caused high salinity in many fields, particularly in the mud flats in coastal regions. The resulting salinity has become one of the most significant abiotic stresses affecting the world’s rice crop productivity. Developing elite cultivars with novel salinity-tolerance traits is regarded as the most cost-effective and environmentally friendly approach for utilizing saline-alkali land. To develop a highly efficient green strategy and create novel rice germplasms for salt-tolerant rice breeding, this study aimed to improve rice salinity tolerance by combining targeted CRISPR/Cas9-mediated editing of the OsRR22 gene with heterosis utilization. The novel alleles of the genic male-sterility (GMS) and elite restorer line (733Srr22-T1447-1 and HZrr22-T1349-3) produced 110 and 1 bp deletions at the third exon of OsRR22 and conferred a high level of salinity tolerance. Homozygous transgene-free progeny were identified via segregation in the T2 generation, with osrr22 showing similar agronomic performance to wild-type (733S and HZ). Furthermore, these two osrr22 lines were used to develop a new promising third-generation hybrid rice line with novel salinity tolerance. Overall, the results demonstrate that combining CRISPR/Cas9 targeted gene editing with the “third-generation hybrid rice system” approach allows for the efficient development of novel hybrid rice varieties that exhibit a high level of salinity tolerance, thereby ensuring improved cultivar stability and enhanced rice productivity.
Uremic Toxin Indoxyl Sulfate Promotes Macrophage-Associated Low-Grade Inflammation and Epithelial Cell Senescence
Authors: Ribeiro Andrea , Liu Feiyue , Srebrzynski Matthias , Rother Simone , Adamowicz Karina , Wadowska Marta , Steiger Stefanie , Anders Hans-Joachim , Schmaderer Christoph , Koziel Joanna , Lech Maciej
Published: April 2023

In this study, we investigated the impact of the uremic toxin indoxyl sulfate on macrophages and tubular epithelial cells and its role in modulating the response to lipopolysaccharide (LPS). Indoxyl sulfate accumulates in the blood of patients with chronic kidney disease (CKD) and is a predictor of overall and cardiovascular morbidity/mortality. To simulate the uremic condition, primary macrophages and tubular epithelial cells were incubated with indoxyl sulfate at low concentrations as well as concentrations found in uremic patients, both alone and upon LPS challenge. The results showed that indoxyl sulfate alone induced the release of reactive oxygen species and low-grade inflammation in macrophages. Moreover, combined with LPS (proinflammatory conditions), indoxyl sulfate significantly increased TNF-α, CCL2, and IL-10 release but did not significantly affect the polarization of macrophages. Pre-treatment with indoxyl sulfate following LPS challenge induced the expression of aryl hydrocarbon receptor (Ahr) and NADPH oxidase 4 (Nox4) which generate reactive oxygen species (ROS). Further, experiments with tubular epithelial cells revealed that indoxyl sulfate might induce senescence in parenchymal cells and therefore participate in the progression of inflammaging. In conclusion, this study provides evidence that indoxyl sulfate provokes low-grade inflammation, modulates macrophage function, and enhances the inflammatory response associated with LPS. Finally, indoxyl sulfate signaling contributes to the senescence of tubular epithelial cells during injury.
Influence of Leptin on the Secretion of Growth Hormone in Ewes under Different Photoperiodic Conditions
Authors: Wójcik Maciej , Krawczyńska Agata , Zieba Dorota Anna , Antushevich Hanna , Herman Andrzej Przemysław
Published: April 2023

Leptin is an adipokine with a pleiotropic impact on many physiological processes, including hypothalamic-pituitary-somatotropic (HPS) axis activity, which plays a key role in regulating mammalian metabolism. Leptin insensitivity/resistance is a pathological condition in humans, but in seasonal animals, it is a physiological adaptation. Therefore, these animals represent a promising model for studying this phenomenon. This study aimed to determine the influence of leptin on the activity of the HPS axis. Two in vivo experiments performed during short- and long-day photoperiods were conducted on 12 ewes per experiment, and the ewes were divided randomly into 2 groups. The arcuate nucleus, paraventricular nucleus, anterior pituitary (AP) tissues, and blood were collected. The concentration of growth hormone (GH) was measured in the blood, and the relative expression of GHRH, SST, GHRHR, SSTR1, SSTR2, SSTR3, SSTR5, LEPR, and GH was measured in the collected brain structures. The study showed that the photoperiod, and therefore leptin sensitivity, plays an important role in regulating HPS axis activity in the seasonal ewe. However, leptin influences the release of GH in a season-dependent manner, and its effect seems to be targeted at the posttranscriptional stages of GH secretion.
Biological Assay to Determine Gonadotropin Potency: From In Vivo to In Vitro Sustainable Method
Authors: Nevelli Francesco , Palmese Angelo , Gleixner Ralf , Peroglio Flavio , D’Acunto Cosimo-Walter , Dadone Aurora , D’Hooghe Thomas , Lispi Monica
Published: April 2023

Various preparations of follicle-stimulating hormone (FSH) are commercially available; however, they differ in glycoforms composition and purity owing to their respective sources. Additional chemical/physical changes can also be introduced during manufacturing and can impact their biological activity (biopotency), which is routinely assessed using an in vivo bioassay (Steelman–Pohley). This study aimed to determine whether an in vitro bioassay could assess biopotency by distinguishing between r-hFSH chemical/physical variants with similar ability to the in vivo bioassay. The specific activity (units of biological activity per mg of product) of variants of r-hFSH generated through enrichment (acidic/basic), stress (oxidative/acidic pH) and enzymatic treatment (desialylation and desialylation/degalactosylation) was compared using the in vivo and in vitro bioassays. The in vitro bioassay reliably detected potential chemical/physical modifications in r-hFSH variants that may impact biopotency. Overall, the methods demonstrated a comparable ability to detect changes in specific activities due to chemical/physical differences in r-hFSH variants. These data indicate that the in vitro bioassay is suitable to replace the in vivo bioassay.
Molecular Evolution of Histone Methylation Modification Families in the Plant Kingdom and Their Genome-Wide Analysis in Barley
Authors: An Bingzhuang , Cai Haiya , Li Bo , Zhang Shuo , He Yonggang , Wang Rong , Jiao Chunhai , Guo Ying , Xu Le , Xu Yanhao
Published: April 2023

In this study, based on the OneKP database and through comparative genetic analysis, we found that HMT and HDM may originate from Chromista and are highly conserved in green plants, and that during the evolution from algae to land plants, histone methylation modifications gradually became complex and diverse, which is more conducive to the adaptation of plants to complex and variable environments. We also characterized the number of members, genetic similarity, and phylogeny of HMT and HDM families in barley using the barley pangenome and the Tibetan Lasa Goumang genome. The results showed that HMT and HDM were highly conserved in the domestication of barley, but there were some differences in the Lasa Goumang SDG subfamily. Expression analysis showed that HvHMTs and HvHDMs were highly expressed in specific tissues and had complex expression patterns under multiple stress treatments. In summary, the amplification and variation of HMT and HDM facilitate plant adaptation to complex terrestrial environments, while they are highly conserved in barley and play an important role in barley growth and development with abiotic stresses. In brief, our findings provide a novel perspective on the origin and evolutionary history of plant HvHMTs and HvHDMs, and lay a foundation for further investigation of their functions in barley.
Topical Treatment for Retinal Degenerative Pathologies: A Systematic Review
Authors: Samoilă Lăcrămioara , Voștinaru Oliviu , Dinte Elena , Bodoki Andreea Elena , Iacob Bogdan-Cezar , Bodoki Ede , Samoilă Ovidiu
Published: April 2023

The topical administration of medicines is the preferred route in ocular therapy, at least for the anterior segment of the eye. However, the eye’s inherent functional and biological barriers all work against the active pharmaceutical ingredient (API) to efficiently reach the targeted retinal structures. The main objective of this article is to offer a systematic review of the scientific literature in recent years, focusing on the latest developments of topical treatment intended for retinal degenerative diseases. Database search returned 102 clinical studies, focused on topical treatment for age macular degeneration, macular edemas (in diabetic retinopathy, surgery related or in retinal dystrophies) or glaucoma. After the exclusion of low-powered studies and those combining vitreo-retinal surgery, 35 articles remained for analysis. Currently, the topical treatment of retinal degenerative diseases is limited by the difficulty to deliver effective drug concentrations to the posterior eye structures. However, in the case of drug classes like NSAIDs, the presence of certain molecular and metabolic features for specific representatives makes the topical administration currently feasible in several clinical contexts. For other drug classes, either a fine-tuning of the API’s pharmacokinetic profile or the use of more advanced formulation strategies, such as rationally designed nanostructured drugs and vehicles, crystalline polymorphs or supramolecular complexes, could bring the much awaited breakthrough for a more predictable and controlled delivery towards the retinal structures and could eventually be employed in the future for the development of more effective ways of delivering drugs to the posterior eye, with the ultimate goal of improving their clinical efficacy.
The Histone Deacetylases Hst1 and Rpd3 Integrate De Novo NAD+ Metabolism with Phosphate Sensing in Saccharomyces cerevisiae
Authors: Groth Benjamin , Lee Yi-Ching , Huang Chi-Chun , McDaniel Matilda , Huang Katie , Lee Lan-Hsuan , Lin Su-Ju
Published: April 2023

Nicotinamide adenine dinucleotide (NAD+) is a critical cofactor essential for various cellular processes. Abnormalities in NAD+ metabolism have also been associated with a number of metabolic disorders. The regulation and interconnection of NAD+ metabolic pathways are not yet completely understood. By employing an NAD+ intermediate-specific genetic system established in the model organism S. cerevisiae, we show that histone deacetylases (HDACs) Hst1 and Rpd3 link the regulation of the de novo NAD+ metabolism-mediating BNA genes with certain aspects of the phosphate (Pi)-sensing PHO pathway. Our genetic and gene expression studies suggest that the Bas1–Pho2 and Pho2–Pho4 transcription activator complexes play a role in this co-regulation. Our results suggest a model in which competition for Pho2 usage between the BNA-activating Bas1–Pho2 complex and the PHO-activating Pho2–Pho4 complex helps balance de novo activity with PHO activity in response to NAD+ or phosphate depletion. Interestingly, both the Bas1–Pho2 and Pho2–Pho4 complexes appear to also regulate the expression of the salvage-mediating PNC1 gene negatively. These results suggest a mechanism for the inverse regulation between the NAD+ salvage pathways and the de novo pathway observed in our genetic models. Our findings help provide a molecular basis for the complex interplay of two different aspects of cellular metabolism.
Operational Performance Analysis of the Public Transport System over Time
Authors: Cazuza de Sousa Júnior José Nauri , Dias Teresa Galvão , Nunes de Azevedo Filho Mário Angelo
Published: April 2023

The public transport system is responsible for the displacement of a large part of the population, particularly in developing countries. This fact makes it relevant to evaluate the performance of public transport to provide an efficient and effective service. The purpose of this study is to conduct a performance evaluation of the public transport operation in the Metropolitan Region of Fortaleza (MRF), in the State of Ceará, Brazil. The analysis is based on DEA and the Malmquist index, based on three inputs (total operating time, fleet age, and the mileage traveled) and two outputs (fare revenue and number of passengers). Data were obtained through automated fare collection systems (AFCs) that were implemented in the MRF. Although there were no major fluctuations in performance during the analyzed period, the results indicate that the system’s performance declined in certain years. In addition, the analysis enables a better understanding of route performance, considering the operating company or the area of operation, which helps to diagnose and comprehend the operation more effectively. By analyzing the operational performance over time, the proposed approach provides an additional contribution by offering a comprehensive overview to the involved stakeholders, fostering decision-making processes based on evidence.
Modelling of Climate Change’s Impact on Prunus armeniaca L.’s Flowering Time
Authors: Korsakova Svetlana , Korzin Vadim , Plugatar Yuri , Kazak Anatoliy , Gorina Valentina , Korzina Natalia , Khokhlov Sergey , Makoveichuk Krystina
Published: April 2023

This study presents the results of the development of numerical models for predicting the timing of apricot flowering, including using experimental data on the emergence of plants from a state of deep dormancy. The best results of approximation of the process of accumulation of the necessary cooling in the autumn–winter period were obtained using the sigmoidal function. Models that take into account the combined effect of temperature and photoperiod on the processes of spring development showed a high accuracy of the process of accumulation of thermal units. Based on the results of testing, two models were selected with an accuracy of 3.0 days for the start of flowering and the absence of a systematic bias, which can be considered a good quality assessment These models describe well the interannual variability of apricot flowering dates and can be used to predict these dates. The discrepancy is no more than 2–4 days in 87–89% of cases. Estimates of the timing of flowering and the end of deep dormancy are very important for increasing the profitability of fruit production in the South of Russia without incurring additional costs, by minimizing the risks associated with irrational crop placement and the selection of varieties without taking into account the specifics of climate change. When constructing a system of protective measures and dates of treatments, it is also necessary to take into account the calendar dates of the shift in the development of plants.
Productivity Index in Clinical Andrology: Research Directions on High-Impact Topics and in Particular on Male Infertility
Authors: Crafa Andrea , Calogero Aldo Eugenio , Cannarella Rossella , Condorelli Rosita Angela , Aversa Antonio , La Vignera Sandro
Published: April 2023

Purpose: Andrological diseases have an important social and economic impact as they cause a serious impairment of the quality of life of the affected patient. Epidemiologically, the impact of these disorders is progressively increasing, as demonstrated by the ever-growing prevalence of male infertility. This evidence justifies the rapid development of research in andrology that the scientific community has undertaken in recent decades. This study aims to evaluate the productivity index of the main andrological topics studied and reported in the literature. Methods: The total number of published articles was extracted from the Scopus database by entering the following keywords and mesh terms: “Male Infertility”, “Erectile Dysfunction”, “Premature Ejaculation”, “Male Hypogonadism”, “Testicular Tumors”, “Prostate Cancer”, “Prostatic hyperplasia”, “Prostate hyperplasia”, “Prostatitis”, “Prostate inflammation”, and “Male Accessory Gland Infections”. Furthermore, a list of the top 50 researchers sorted by productivity was created for each topic. For male infertility, a further search was performed by combining the search term “male infertility” with the above-mentioned terms. Thus, a list of the top 30 authors in order of productivity was also extracted. The graphs were created using Excel. Results and Conclusions: As could be expected, we observed that prostate cancer and male infertility were the two most investigated topics, followed by benign prostatic hyperplasia and erectile dysfunction, whose prevalence is set to increase given the progressive aging of the population. Less investigated is the inflammation of the accessory sexual glands. In conclusion, this study provides a ranking of the main andrological topics investigated in the literature, also presenting the top list of the most productive authors for each one.
Combination of Intracardiac Echocardiography and Contact Force Sensing for Left Ventricular Papillary Muscle Arrhythmias
Authors: Chen Tongshuai , Chang Lujie , Rong Bing , Zhang Kai , Fan Guanqi , Kong Jing , Ling Mingying , Kong Qingyu , Maduray Kellina , Zhao Cuifen , Zhong Jingquan
Published: April 2023

Objectives: The catheter ablation of ventricular arrhythmias (VAs) arising from the left ventricular (LV) papillary muscles (PMs) is challenging. This study sought to address whether the combination of intracardiac echocardiography (ICE) and contact force sensing (CFS) can improve the acute and long-term ablation outcomes of left ventricular papillary muscle arrhythmias. Methods and Results: From May 2015 to August 2022, a total of thirty-three patients underwent catheter ablation for LV PM arrhythmias: VAs were located in anterolateral PMs in 11 and posteromedial PMs in 22. A combination of intracardiac echocardiography (ICE) and contact force sensing (CFS) was used in 21 of the 33 procedures. A mean of 6.93 ± 4.91 for lesions was used per patient, comparable between the CFS/ICE and no ICE/CFS (4.90 ± 2.23 vs. 10.17 ± 5.89; p = 0.011). The mean CF achieved in the ICE/CFS group was 7.52 ± 3.31 g. Less X-ray time was used in the combination group (CFS/ICE: 165.67 ± 47.80 S vs. no ICE/CFS: 365.00 ± 183.73 S; p < 0.001). An acute success rate of 100% was achieved for the ICE/CFS group (n = 22) and 66.67% for the no ICE/CFS group (n = 8). VA recurrence at the 11.21 ± 7.21-month follow-up was 14.2% for the ICE/CFS group and 50% for the no ICE/CFS group (p = 0.04). No severe complications occurred in all patients. Conclusions: The combination of intracardiac echocardiography (ICE) and contact force sensing (CFS) could provide precise geometries of cardiac endocavitary structures and accurate contact information for the catheter during ablation, which improved acute and long-term ablation outcomes. The routine adoption of this strategy should be considered to improve the outcomes of LV PM VA ablation.
Arterial Elastance: A Predictor of Hypotension Due to Anesthesia Induction
Authors: Aktas Yildirim Serap , Sarikaya Zeynep Tugce , Dogan Lerzan , Ulugol Halim , Gucyetmez Bulent , Toraman Fevzi
Published: April 2023

Background: Hypotension is common after anesthesia induction and may have adverse outcomes. The aim of this study was to investigate whether arterial elastance (Ea) is a predictor of post-induction hypotension. Methods: Between January and June 2022, the hemodynamic parameters of 85 patients who underwent major surgery under general anesthesia were prospectively evaluated. The noncalibrated pulse contour device MostCare (Vytech, Vygon, Padua, Italy) was used to measure hemodynamic parameters before and after anesthesia induction. The duration of the measurements was determined from one minute before induction to 10 min after induction. Hypotension was defined as a greater than 30% decrease in mean arterial pressure from the pre-induction value and/or systolic arterial pressure of less than 90 mmHg. The patients were divided into post-induction hypotension (−) and (+) groups. For the likelihood of post-induction hypotension, a multivariate regression model was used by adding significantly different pre-induction parameters to the post-induction hypotension group. Results: The incidence of post-induction hypotension was 37.6%. The cut-off value of the pre-induction Ea for the prediction of post-induction hypotension was ≥1.08 mmHg m−2mL−1 (0.71 [0.59–0.82]). In the multivariate regression model, the likelihood of postinduction hypotension was 3.5-fold (1.4–9.1), increased by only an Ea ≥ 1.08 mmHg m−2mL−1. Conclusion: Pre-induction Ea showed excellent predictability of hypotension during anesthetic induction and identified patients at risk of general anesthesia induction-related hypotension.