bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Metabolic Study of Two Contrasting Chinese Cabbage Genotypes under Mild and Severe Drought Stress
Authors: Chen Lin , Shen Yongrui , Yang Wenjing , Pan Qiming , Li Chao , Sun Qingguo , Zeng Qi , Li Baohua , Zhang Lugang
Published: May 2022

Chinese cabbage (Brassica rapa L. ssp. pekinensis) is an important leafy vegetable crop cultivated worldwide. Drought is one of the most important limiting factors for the growth, production and quality of Chinese cabbage due to its weak drought tolerance. In order to deepen the understanding of drought stress response in Chinese cabbage, metabolomics studies were conducted in drought−tolerant (DT) and drought−susceptible (DS) genotypes of Chinese cabbage under water deficit−simulated mild and severe drought stress conditions. A total of 777 metabolites were detected, wherein 90 of them were proposed as the drought−responsive metabolites in Chinese cabbage, with abscisic acid (ABA), serine, choline alfoscerate, and sphingosine as potential representative drought stress biomarkers. We also found that drought−tolerant and drought−susceptible genotypes showed differential metabolic accumulation patterns with contrasting drought response mechanisms. Notably, constitutively high levels of ABA and glutathione were detected in drought−tolerant genotype in all tested and control conditions. In addition, proline, sucrose, γ−aminobutyric acid, and glutathione were also found to be highly correlated to drought tolerance. This study is the first metabolomic study on how Chinese cabbage responds to drought stress, and could provide insights on how to develop and cultivate new drought−resistant varieties.
Molecular Classification and Overcoming Therapy Resistance for Acute Myeloid Leukemia with Adverse Genetic Factors
Authors: Ikeda Daisuke , Chi SungGi , Uchiyama Satoshi , Nakamura Hirotaka , Guo Yong-Mei , Yamauchi Nobuhiko , Yuda Junichiro , Minami Yosuke
Published: May 2022

The European LeukemiaNet (ELN) criteria define the adverse genetic factors of acute myeloid leukemia (AML). AML with adverse genetic factors uniformly shows resistance to standard chemotherapy and is associated with poor prognosis. Here, we focus on the biological background and real-world etiology of these adverse genetic factors and then describe a strategy to overcome the clinical disadvantages in terms of targeting pivotal molecular mechanisms. Different adverse genetic factors often rely on common pathways. KMT2A rearrangement, DEK-NUP214 fusion, and NPM1 mutation are associated with the upregulation of HOX genes. The dominant tyrosine kinase activity of the mutant FLT3 or BCR-ABL1 fusion proteins is transduced by the AKT-mTOR, MAPK-ERK, and STAT5 pathways. Concurrent mutations of ASXL1 and RUNX1 are associated with activated AKT. Both TP53 mutation and mis-expressed MECOM are related to impaired apoptosis. Clinical data suggest that adverse genetic factors can be found in at least one in eight AML patients and appear to accumulate in relapsed/refractory cases. TP53 mutation is associated with particularly poor prognosis. Molecular-targeted therapies focusing on specific genomic abnormalities, such as FLT3, KMT2A, and TP53, have been developed and have demonstrated promising results.
Carbon Metabolism of a Soilborne Mn(II)-Oxidizing Escherichia coli Isolate Implicated as a Pronounced Modulator of Bacterial Mn Oxidation
Authors: Gu Tong , Tong Zhenghu , Zhang Xue , Wang Zhiyong , Zhang Zhen , Hwang Tzann-Shun , Li Lin
Published: May 2022

Mn(II)-oxidizing microorganisms are generally considered the primary driving forces in the biological formation of Mn oxides. However, the mechanistic elucidation of the actuation and regulation of Mn oxidation in soilborne bacteria remains elusive. Here, we performed joint multiple gene-knockout analyses and comparative morphological and physiological determinations to characterize the influence of carbon metabolism on the Mn oxide deposit amount (MnODA) and the Mn oxide formation of a soilborne bacterium, Escherichia coli MB266. Different carbon source substances exhibited significantly varied effects on the MnODA of MB266. A total of 16 carbon metabolism-related genes with significant variant expression levels under Mn supplementation conditions were knocked out in the MB266 genome accordingly, but only little effect on the MnODA of each mutant strain was accounted for. However, a simultaneous four-gene-knockout mutant (namely, MB801) showed an overall remarkable MnODA reduction and an initially delayed Mn oxide formation compared with the wild-type MB266. The assays using scanning/transmission electron microscopy verified that MB801 exhibited not only a delayed Mn-oxide aggregate processing, but also relatively smaller microspherical agglomerations, and presented flocculent deposit Mn oxides compared with normal fibrous and crystalline Mn oxides formed by MB266. Moreover, the Mn oxide aggregate formation was highly related to the intracellular ROS level. Thus, this study demonstrates that carbon metabolism acts as a pronounced modulator of MnODA in MB266, which will provide new insights into the occurrence of Mn oxidation and Mn oxide formation by soilborne bacteria in habitats where Mn(II) naturally occurs.
Antiproliferative Effects of the Aptamer d(GGGT)4 and Its Analogues with an Abasic-Site Mimic Loop on Different Cancer Cells
Authors: Virgilio Antonella , Pecoraro Annalisa , Benigno Daniela , Russo Annapina , Russo Giulia , Esposito Veronica , Galeone Aldo
Published: May 2022

In this paper, we study the T30923 antiproliferative potential and the contribution of its loop residues in six different human cancer cell lines by preparing five T30923 variants using the single residue replacement approach of loop thymidine with an abasic site mimic (S). G-rich oligonucleotides (GRO) show interesting anticancer properties because of their capability to adopt G-quadruplex structures (G4s), such as the G4 HIV-1 integrase inhibitor T30923. Considering the multi-targeted effects of G4-aptamers and the limited number of cancer cell lines tested, particularly for T30923, it should be important to find a suitable tumor line, in addition to considering that the effects also strictly depend on G4s. CD, NMR and non-denaturating polyacrylamide gel electrophoresis data clearly show that all modified ODNs closely resemble the dimeric structure of parallel G4s’ parent aptamer, keeping the resistance in biological environments substantially unchanged, as shown by nuclease stability assay. The antiproliferative effects of T30923 and its variants are tried in vitro by MTT assays, showing interesting cytotoxic activity, depending on time and dose, for all G4s, especially in MDA-MB-231 cells with a reduction in cell viability approximately up to 30%. Among all derivatives, QS12 results are the most promising, showing more pronounced cytotoxic effects both in MDA-MB-231 and Hela cells, with a decrease in cell viability from 70% to 60%. In summary, the single loop residue S substitution approach may be useful for designing antiproliferative G4s, considering that most of them, characterized by single residue loops, may be able to bind different targets in several cancer cell pathways. Generally, this approach could be of benefit by revealing some minimal functional structures, stimulating further studies aimed at the development of novel anticancer drugs.
Neurotransmitters—Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System
Authors: Teleanu Raluca Ioana , Niculescu Adelina-Gabriela , Roza Eugenia , Vladâcenco Oana , Grumezescu Alexandru Mihai , Teleanu Daniel Mihai
Published: May 2022

Neurotransmitters are molecules that amplify, transmit, and convert signals in cells, having an essential role in information transmission throughout the nervous system. Hundreds of such chemicals have been discovered in the last century, continuing to be identified and studied concerning their action on brain health. These substances have been observed to influence numerous functions, including emotions, thoughts, memories, learning, and movements. Thus, disturbances in neurotransmitters’ homeostasis started being correlated with a plethora of neurological and neurodegenerative disorders. In this respect, the present paper aims to describe the most important neurotransmitters, broadly classified into canonical (e.g., amino acids, monoamines, acetylcholine, purines, soluble gases, neuropeptides) and noncanonical neurotransmitters (e.g., exosomes, steroids, D-aspartic acid), and explain their link with some of the most relevant neurological conditions. Moreover, a brief overview of the recently developed neurotransmitters’ detection methods is offered, followed by several considerations on the modulation of these substances towards restoring homeostasis.
The Functional and Application Possibilities of Starch/Chitosan Polymer Composites Modified by Graphene Oxide
Authors: Krystyjan Magdalena , Khachatryan Gohar , Khachatryan Karen , Konieczna-Molenda Anna , Grzesiakowska Anna , Kuchta-Gładysz Marta , Kawecka Agnieszka , Grzebieniarz Wiktoria , Nowak Nikola
Published: May 2022

This study describes functional properties of bionanocomposites consisting of starch/chitosan/graphene oxide (GO) obtained using the green synthesis method, such as water-barrier and optical properties, as well as the rate of degradation by enzymatic and acid hydrolysis. The toxicity of the composites and their effects on the development of pathogenic microflora during storage of meat food products was also investigated. Although the results showed that the barrier properties of the composites were weak, they were similar to those of biological systems. The studies carried out confirmed the good optical properties of the composites containing chitosan, which makes it possible to use them as active elements of packaging. The susceptibility of starch and chitosan films to enzymatic and acid hydrolyses indicates their relatively high biodegradability. The lack of toxicity and the high barrier against many microorganisms offer great potential for applications in the food industry.
HDACs Gene Family Analysis of Eight Rosaceae Genomes Reveals the Genomic Marker of Cold Stress in Prunus mume
Authors: Meng Juan , Wen Zhenying , Li Mingyu , Cheng Tangren , Zhang Qixiang , Sun Lidan
Published: May 2022

Histone deacetylases (HDACs) play important roles in plant growth, development, and stress response. However, the pattern of how they are expressed in response to cold stress in the ornamental woody plant Prunus mume is poorly understood. Here, we identify 121 RoHDACs from eight Rosaceae plants of which 13 PmHDACs genes are from P. mume. A phylogenetic analysis suggests that the RoHDACs family is classified into three subfamilies, HDA1/RPD3, HD2, and SIR2. We identify 11 segmental duplication gene pairs of RoHDACs and find, via a sequence alignment, that the HDACs gene family, especially the plant-specific HD2 family, has experienced gene expansion and contraction at a recent genome evolution history. Each of the three HDACs subfamilies has its own conserved domains. The expression of PmHDACs in mei is found to be tissue-specific or tissue-wide. RNA-seq data and qRT-PCR experiments in cold treatments suggest that almost all PmHDACs genes—especially PmHDA1/6/14, PmHDT1, and PmSRT1/2—significantly respond to cold stress. Our analysis provides a fundamental insight into the phylogenetic relationship of the HDACs family in Rosaceae plants. Expression profiles of PmHDACs in response to cold stress could provide an important clue to improve the cold hardiness of mei.
KOMPEITO, an Atypical Arabidopsis Rhomboid-Related Gene, Is Required for Callose Accumulation and Pollen Wall Development
Authors: Kanaoka Masahiro M. , Shimizu Kentaro K. , Xie Bo , Urban Sinisa , Freeman Matthew , Hong Zonglie , Okada Kiyotaka
Published: May 2022

Fertilization is a key event for sexually reproducing plants. Pollen–stigma adhesion, which is the first step in male–female interaction during fertilization, requires proper pollen wall patterning. Callose, which is a β-1.3-glucan, is an essential polysaccharide that is required for pollen development and pollen wall formation. Mutations in CALLOSE SYNTHASE 5 (CalS5) disrupt male meiotic callose accumulation; however, how CalS5 activity and callose synthesis are regulated is not fully understood. In this paper, we report the isolation of a kompeito-1 (kom-1) mutant defective in pollen wall patterning and pollen–stigma adhesion in Arabidopsis thaliana. Callose was not accumulated in kom-1 meiocytes or microspores, which was very similar to the cals5 mutant. The KOM gene encoded a member of a subclass of Rhomboid serine protease proteins that lacked active site residues. KOM was localized to the Golgi apparatus, and both KOM and CalS5 genes were highly expressed in meiocytes. A 220 kDa CalS5 protein was detected in wild-type (Col-0) floral buds but was dramatically reduced in kom-1. These results suggested that KOM was required for CalS5 protein accumulation, leading to the regulation of meiocyte-specific callose accumulation and pollen wall formation.
Molecular Regulation of Arbuscular Mycorrhizal Symbiosis
Authors: Ho-Plágaro Tania , García-Garrido José Manuel
Published: May 2022

Plant-microorganism interactions at the rhizosphere level have a major impact on plant growth and plant tolerance and/or resistance to biotic and abiotic stresses. Of particular importance for forestry and agricultural systems is the cooperative and mutualistic interaction between plant roots and arbuscular mycorrhizal (AM) fungi from the phylum Glomeromycotina, since about 80% of terrestrial plant species can form AM symbiosis. The interaction is tightly regulated by both partners at the cellular, molecular and genetic levels, and it is highly dependent on environmental and biological variables. Recent studies have shown how fungal signals and their corresponding host plant receptor-mediated signalling regulate AM symbiosis. Host-generated symbiotic responses have been characterized and the molecular mechanisms enabling the regulation of fungal colonization and symbiosis functionality have been investigated. This review summarizes these and other recent relevant findings focusing on the molecular players and the signalling that regulate AM symbiosis. Future progress and knowledge about the underlying mechanisms for AM symbiosis regulation will be useful to facilitate agro-biotechnological procedures to improve AM colonization and/or efficiency.
Genome-Wide Identification, Classification, Expression and Duplication Analysis of bZIP Family Genes in Juglans regia L.
Authors: Zhang Zhongrong , Quan Shaowen , Niu Jianxin , Guo Caihua , Kang Chao , Liu Jinming , Yuan Xing
Published: May 2022

Basic leucine zipper (bZIP), a conserved transcription factor widely found in eukaryotes, has important regulatory roles in plant growth. To understand the information related to the bZIP gene family in walnut, 88 JrbZIP genes were identified at the genome-wide level and classified into 13 subfamilies (A, B, C, D, E, F, G, H, I, J, K, M, and S) using a bioinformatic approach. The number of exons in JrbZIPs ranged from 1 to 12, the number of amino acids in JrbZIP proteins ranged from 145 to 783, and the isoelectric point ranged from 4.85 to 10.05. The majority of JrbZIP genes were localized in the nucleus. The promoter prediction results indicated that the walnut bZIP gene contains a large number of light-responsive and jasmonate-responsive action elements. The 88 JrbZIP genes were involved in DNA binding and nucleus and RNA biosynthetic processes of three ontological categories, molecular functions, cellular components and biological processes. The codon preference analysis showed that the bZIP gene family has a stronger bias for AGA, AGG, UUG, GCU, GUU, and UCU than other codons. Moreover, the transcriptomic data showed that JrbZIP genes might play an important role in floral bud differentiation. The results of a protein interaction network map and kegg enrichment analysis indicated that bZIP genes were mainly involved in phytohormone signaling, anthocyanin synthesis and flowering regulation. qRT-PCR demonstrated the role of the bZIP gene family in floral bud differentiation. Co-expression network maps were constructed for 29 walnut bZIP genes and 6 flowering genes, and JrCO (a homolog of AtCO) was significantly correlated (p < 0.05) with 13 JrbZIP genes in the level of floral bud differentiation expression, including JrbZIP31 (homolog of AtFD), and JrLFY was significantly and positively correlated with JrbZIP10,11,51,59,67 (p < 0.05), and the above results suggest that bZIP family genes may act together with flowering genes to regulate flower bud differentiation in walnut. This study was the first genome-wide report of the walnut bZIP gene family, which could improve our understanding of walnut bZIP proteins and provide a solid foundation for future cloning and functional analyses of this gene family.
Unraveling the Binding Mechanism of Alzheimer’s Drugs with Irisin: Spectroscopic, Calorimetric, and Computational Approaches
Authors: Waseem Rashid , Shamsi Anas , Khan Tanzeel , Hassan Md. Imtaiyaz , Kazim Syed Naqui , Shahid Mohammad , Islam Asimul
Published: May 2022

The prevalence of Alzheimer’s disease (AD) has been a major health concern for a long time. Despite recent progress, there is still a strong need to develop effective disease-modifying therapies. Several drugs have already been approved to retard the progression of AD-related symptoms; however, there is a need to develop an effective carrier system for the delivery of drugs to combat such diseases. In recent years, various biological macromolecules, including proteins, have been used as carriers for drug delivery. Irisin is a beneficial hormone in such diseases, including AD and related pathologies. Herein, the interaction mechanism of irisin with AD drugs such as memantine, galantamine, and fluoxetine is investigated. Fluorescence studies revealed that the above drugs bind to irisin with significant affinity, with fluoxetine having the highest binding affinity. Isothermal titration calorimetry (ITC) complemented the spontaneous binding of these drugs with irisin, delineating various associated thermodynamic and binding parameters. Molecular docking further validated the fluorescence and ITC results and unfolded the mechanism that hydrogen bonding governs the binding of fluoxetine to irisin with a significant binding score, i.e., −6.3 kcal/mol. We believe that these findings provide a promising solution to fight against AD as well as a platform for further research to utilize irisin in the drug-delivery system for an effective therapeutic strategy.
RNA-Seq Transcriptome Analysis of Differentiated Human Oligodendrocytic MO3.13 Cells Shows Upregulation of Genes Involved in Myogenesis
Authors: Głowacka Aleksandra , Kilańczyk Ewa , Maksymowicz Małgorzata , Zawadzka Małgorzata , Leśniak Wiesława , Filipek Anna
Published: May 2022

In this work, we examined the differentiation of oligodendrocytic MO3.13 cells and changes in their gene expression after treatment with phorbol 12-myristate 13-acetate, PMA, or with RNA polymerase I (Pol I) inhibitor, CX-5461. We found that MO3.13 cells changed their morphology when treated with both agents. Interestingly, CX-5461, but not PMA, induced noticeable changes in the integrity of the nucleoli. Then, we analyzed the p53 transcriptional activity in MO3.13 cells and found that it was increased in both cell populations, but particularly in cells treated with PMA. Interestingly, this high p53 transcriptional activity in PMA-treated cells coincided with a lower level of an unmodified (non-phosphorylated) form of this protein. Since morphological changes in MO3.13 cells after PMA and CX-5461 treatment were evident, suggesting that cells were induced to differentiate, we performed RNA-seq analysis of PMA-treated cells, to reveal the direction of alterations in gene expression. The analysis showed that the largest group of upregulated genes consisted of those involved in myogenesis and K-RAS signaling, rather than those associated with oligodendrocyte lineage progression.
LDHB Overexpression Can Partially Overcome T Cell Inhibition by Lactic Acid
Authors: Decking Sonja-Maria , Bruss Christina , Babl Nathalie , Bittner Sebastian , Klobuch Sebastian , Thomas Simone , Feuerer Markus , Hoffmann Petra , Dettmer Katja , Oefner Peter J. , Renner Kathrin , Kreutz Marina
Published: May 2022

Accelerated glycolysis leads to secretion and accumulation of lactate and protons in the tumor environment and determines the efficacy of adoptive T cell and checkpoint inhibition therapy. Here, we analyzed effects of lactic acid on different human CD4 T cell subsets and aimed to increase CD4 T cell resistance towards lactic acid. In all CD4 T cell subsets analyzed, lactic acid inhibited metabolic activity (glycolysis and respiration), cytokine secretion, and cell proliferation. Overexpression of the lactate-metabolizing isoenzyme LDHB increased cell respiration and mitigated lactic acid effects on intracellular cytokine production. Strikingly, LDHB-overexpressing cells preferentially migrated into HCT116 tumor spheroids and displayed higher expression of cytotoxic effector molecules. We conclude, that LDHB overexpression might be a promising strategy to increase the efficacy of adoptive T cell transfer therapy.
Mechanisms of Natural Extracts of Andrographis paniculata That Target Lipid-Dependent Cancer Pathways: A View from the Signaling Pathway
Authors: Naomi Ruth , Bahari Hasnah , Ong Zhi Yi , Keong Yong Yoke , Embong Hashim , Rajandram Retnagowri , Teoh Soo Huat , Othman Fezah , Hasham Rosnani , Yin Khoo Boon , Kaniappan Priyatharisni , Yazid Muhammad Dain , Zakaria Zainul Amiruddin
Published: May 2022

Andrographis paniculata is a local medicinal plant that is widely cultivated in Malaysia. It is comprised of numerous bioactive compounds that can be isolated using water, ethanol or methanol. Among these compounds, andrographolide has been found to be the major compound and it exhibits varieties of pharmacological activities, including anti-cancer properties, particularly in the lipid-dependent cancer pathway. Lipids act as crucial membrane-building elements, fuel for energy-demanding activities, signaling molecules, and regulators of several cellular functions. Studies have shown that alterations in lipid composition assist cancer cells in changing microenvironments. Thus, compounds that target the lipid pathway might serve as potential anti-cancer therapeutic agents. The purpose of this review is to provide an overview of the medicinal chemistry and pharmacology of A. paniculata and its active compounds in terms of anti-cancer activity, primary mechanism of action, and cellular targets, particularly in the lipid-dependent cancer pathway.
Structural Rearrangements of Carbonic Anhydrase Entrapped in Sol-Gel Magnetite Determined by ATR–FTIR Spectroscopy
Authors: Ivanovski Vladimir , Shapovalova Olga E. , Drozdov Andrey S.
Published: May 2022

Enzymatically active nanocomposites are a perspective class of bioactive materials that finds their application in numerous fields of science and technology ranging from biosensors and therapeutic agents to industrial catalysts. Key properties of such systems are their stability and activity under various conditions, the problems that are addressed in any research devoted to this class of materials. Understanding the principles that govern these properties is critical to the development of the field, especially when it comes to a new class of bioactive systems. Recently, a new class of enzymatically doped magnetite-based sol-gel systems emerged and paved the way for a variety of potent bioactive magnetic materials with improved thermal stability. Such systems already showed themself as perspective industrial and therapeutic agents, but are still under intense investigation and many aspects are still unclear. Here we made a first attempt to describe the interaction of biomolecules with magnetite-based sol-gel materials and to investigate facets of protein structure rearrangements occurring within the pores of magnetite sol-gel matrix using ATR Fourier-transform infrared spectroscopy.
Dysregulated Retinoic Acid Signaling in the Pathogenesis of Pseudoexfoliation Syndrome
Authors: Zenkel Matthias , Hoja Ursula , Gießl Andreas , Berner Daniel , Hohberger Bettina , Weller Julia M. , König Loretta , Hübner Lisa , Ostermann Thomas A. , Gusek-Schneider Gabriele C. , Kruse Friedrich E. , Pasutto Francesca , Schlötzer-Schrehardt Ursula
Published: May 2022

Pseudoexfoliation (PEX) syndrome, a stress-induced fibrotic matrix process, is the most common recognizable cause of open-angle glaucoma worldwide. The recent identification of PEX-associated gene variants uncovered the vitamin A metabolic pathway as a factor influencing the risk of disease. In this study, we analyzed the role of the retinoic acid (RA) signaling pathway in the PEX-associated matrix metabolism and evaluated its targeting as a potential candidate for an anti-fibrotic intervention. We provided evidence that decreased expression levels of RA pathway components and diminished RA signaling activity occur in an antagonistic crosstalk with TGF-β1/Smad signaling in ocular tissues and cells from PEX patients when compared with age-matched controls. Genetic and pharmacologic modes of RA pathway inhibition induced the expression and production of PEX-associated matrix components by disease-relevant cell culture models in vitro. Conversely, RA signaling pathway activation by natural and synthetic retinoids was able to suppress PEX-associated matrix production and formation of microfibrillar networks via antagonization of Smad-dependent TGF-β1 signaling. The findings indicate that deficient RA signaling in conjunction with hyperactivated TGF-β1/Smad signaling is a driver of PEX-associated fibrosis, and that restoration of RA signaling may be a promising strategy for anti-fibrotic intervention in patients with PEX syndrome and glaucoma.
Sedoheptulose Kinase SHPK Expression in Glioblastoma: Emerging Role of the Nonoxidative Pentose Phosphate Pathway in Tumor Proliferation
Authors: Franceschi Sara , Lessi Francesca , Morelli Mariangela , Menicagli Michele , Pasqualetti Francesco , Aretini Paolo , Mazzanti Chiara
Published: May 2022

Glioblastoma (GBM) is the most common form of malignant brain cancer and is considered the deadliest human cancer. Because of poor outcomes in this disease, there is an urgent need for progress in understanding the molecular mechanisms of GBM therapeutic resistance, as well as novel and innovative therapies for cancer prevention and treatment. The pentose phosphate pathway (PPP) is a metabolic pathway complementary to glycolysis, and several PPP enzymes have already been demonstrated as potential targets in cancer therapy. In this work, we aimed to evaluate the role of sedoheptulose kinase (SHPK), a key regulator of carbon flux that catalyzes the phosphorylation of sedoheptulose in the nonoxidative arm of the PPP. SHPK expression was investigated in patients with GBM using microarray data. SHPK was also overexpressed in GBM cells, and functional studies were conducted. SHPK expression in GBM shows a significant correlation with histology, prognosis, and survival. In particular, its increased expression is associated with a worse prognosis. Furthermore, its overexpression in GBM cells confirms an increase in cell proliferation. This work highlights for the first time the importance of SHPK in GBM for tumor progression and proposes this enzyme and the nonoxidative PPP as possible therapeutic targets.
Disruption of Redox Homeostasis by Alterations in Nitric Oxide Synthase Activity and Tetrahydrobiopterin along with Melanoma Progression
Authors: Soares Jaqueline Pereira Moura , Gonçalves Diego Assis , de Sousa Ricardo Xisto , Mouro Margareth Gori , Higa Elisa M. S. , Sperandio Letícia Paulino , Vitoriano Carolina Moraes , Rosa Elisa Bachir Santa , Santos Fernanda Oliveira dos , de Queiroz Gustavo Nery , Yamaguchi Roberta Sessa Stilhano , Pereira Gustavo , Icimoto Marcelo Yudi , Melo Fabiana Henriques Machado de
Published: May 2022

Cutaneous melanoma emerges from the malignant transformation of melanocytes and is the most aggressive type of skin cancer. The progression can occur in different stages: radial growth phase (RGP), vertical growth phase (VGP), and metastasis. Reactive oxygen species contribute to all phases of melanomagenesis through the modulation of oncogenic signaling pathways. Tetrahydrobiopterin (BH4) is an important cofactor for NOS coupling, and an uncoupled enzyme is a source of superoxide anion (O2•−) rather than nitric oxide (NO), altering the redox homeostasis and contributing to melanoma progression. In the present work, we showed that the BH4 amount varies between different cell lines corresponding to distinct stages of melanoma progression; however, they all presented higher O2•− levels and lower NO levels compared to melanocytes. Our results showed increased NOS expression in melanoma cells, contributing to NOS uncoupling. BH4 supplementation of RGP cells, and the DAHP treatment of metastatic melanoma cells reduced cell growth. Finally, Western blot analysis indicated that both treatments act on the PI3K/AKT and MAPK pathways of these melanoma cells in different ways. Disruption of cellular redox homeostasis by the altered BH4 concentration can be explored as a therapeutic strategy according to the stage of melanoma.
Gamma Secretase Inhibitors as Potential Therapeutic Targets for Notch Signaling in Uterine Leiomyosarcoma
Authors: Abedin Yasmin , Gabrilovich Sofia , Alpert Emily , Rego Erica , Begum Salma , Zhao Qingshi , Heller Debra , Einstein Mark H. , Douglas Nataki C.
Published: May 2022

Uterine leiomyosarcoma (uLMS) is a rare and aggressive cancer with few effective therapeutics. The Notch signaling pathway is evolutionarily conserved with oncogenic properties, but it has not been well studied in uLMS. The purpose of our study was to determine expression of Notch family genes and proteins and to investigate the therapeutic effect of γ-secretase inhibitors (GSIs), indirect inhibitors of Notch signaling, in uLMS. We determined expression of Notch genes and proteins in benign uterine smooth muscle tissue, fibroids, and uLMS samples by immunostaining and in two uLMS cell lines, SK-UT-1B (uterine primary) and SK-LMS-1 (vulvar metastasis) by RT-PCR, Western blot and immunostaining. We exposed our cell lines to GSIs, DAPT and MK-0752, and measured expression of HES1, a downstream effector of Notch. Notch proteins were differentially expressed in uLMS. Expression of NOTCH3 and NOTCH4 was higher in uLMS samples than in benign uterine smooth muscle and fibroids. Expression of NOTCH4 was higher in SK-LMS-1 compared to SK-UT-1B. Exposure of SK-UT-1B and SK-LMS-1 to DAPT and MK-0752 decreased expression of HES1 and decreased uLMS cell viability in a dose- and time-dependent manner that was unique to each GSI. Our findings suggest that GSIs are potential therapeutics for uLMS, albeit with limited efficacy.
Comparative Antimicrobial Activity of Silver Nanoparticles Obtained by Wet Chemical Reduction and Solvothermal Methods
Authors: Marinescu Liliana , Ficai Denisa , Ficai Anton , Oprea Ovidiu , Nicoara Adrian Ionut , Vasile Bogdan Stefan , Boanta Laura , Marin Alexandru , Andronescu Ecaterina , Holban Alina-Maria
Published: May 2022

The synthesis of nanoparticles from noble metals has received high attention from researchers due to their unique properties and their wide range of applications. Silver nanoparticles (AgNPs), in particular, show a remarkable inhibitory effect against microorganisms and viruses. Various methods have been developed to obtain AgNPs, however the stability of such nanostructures over time is still challenging. Researchers attempt to obtain particular shapes and sizes in order to tailor AgNPs properties for specific areas, such as biochemistry, biology, agriculture, electronics, medicine, and industry. The aim of this study was to design AgNPs with improved antimicrobial characteristics and stability. Two different wet chemical routes were considered: synthesis being performed (i) reduction method at room temperatures and (ii) solvothermal method at high temperature. Here, we show that the antimicrobial properties of the obtained AgNPs, are influenced by their synthesis route, which impact on the size and shape of the structures. This work analyses and compares the antimicrobial properties of the obtained AgNPs, based on their structure, sizes and morphologies which are influenced, in turn, not only by the type or quantities of precursors used but also by the temperature of the reaction. Generally, AgNPs obtained by solvothermal, at raised temperature, registered better antimicrobial activity as compared to NPs obtained by reduction method at room temperature.
Metformin Inhibits Lipid Droplets Fusion and Growth via Reduction in Cidec and Its Regulatory Factors in Rat Adipose-Derived Stem Cells
Authors: Yang Lijing , Jia Xiaowei , Fang Dongliang , Cheng Yuan , Zhai Zhaoyi , Deng Wenyang , Du Baopu , Lu Tao , Wang Lulu , Yang Chun , Gao Yan
Published: May 2022

Metformin is still being investigated due to its potential use as a therapeutic agent for managing overweight or obesity. However, the underlying mechanisms are not fully understood. Inhibiting the adipogenesis of adipocyte precursors may be a new therapeutic opportunity for obesity treatments. It is still not fully elucidated whether adipogenesis is also involved in the weight loss mechanisms by metformin. We therefore used adipose-derived stem cells (ADSCs) from inguinal and epididymal fat pads to investigate the effects and mechanisms of metformin on adipogenesis in vitro. Our results demonstrate the similar effect of metformin inhibition on lipid accumulation, lipid droplets fusion, and growth in adipose-derived stem cells from epididymal fat pads (Epi-ADSCs) and adipose-derived stem cells from inguinal fat pads (Ing-ADSCs) cultures. We identified that cell death-inducing DFFA-like effector c (Cidec), Perilipin1, and ras-related protein 8a (Rab8a) expression increased ADSCs differentiation. In addition, we found that metformin inhibits lipid droplets fusion and growth by decreasing the expression of Cidec, Perilipin1, and Rab8a. Activation of AMPK pathway signaling in part involves metformin inhibition on Cidec, Perilipin1, and Rab8a expression. Collectively, our study reveals that metformin inhibits lipid storage, fusion, and growth of lipid droplets via reduction in Cidec and its regulatory factors in ADSCs cultures. Our study supports the development of clinical trials on metformin-based therapy for patients with overweight and obesity.
The Effects of Acidosis on eNOS in the Systemic Vasculature: A Focus on Early Postnatal Ontogenesis
Authors: Gaynullina Dina K. , Tarasova Olga S. , Shvetsova Anastasia A. , Borzykh Anna A. , Schubert Rudolf
Published: May 2022

The activity of many vasomotor signaling pathways strongly depends on extracellular/intracellular pH. Nitric oxide (NO) is one of the most important vasodilators produced by the endothelium. In this review, we present evidence that in most vascular beds of mature mammalian organisms metabolic or respiratory acidosis increases functional endothelial NO-synthase (eNOS) activity, despite the observation that direct effects of low pH on eNOS enzymatic activity are inhibitory. This can be explained by the fact that acidosis increases the activity of signaling pathways that positively regulate eNOS activity. The role of NO in the regulation of vascular tone is greater in early postnatal ontogenesis compared to adulthood. Importantly, in early postnatal ontogenesis acidosis also augments functional eNOS activity and its contribution to the regulation of arterial contractility. Therefore, the effect of acidosis on total peripheral resistance in neonates may be stronger than in adults and can be one of the reasons for an undesirable decrease in blood pressure during neonatal asphyxia. The latter, however, should be proven in future studies.
Zinc(II) Complexes with Dimethyl 2,2′-Bipyridine-4,5-dicarboxylate: Structure, Antimicrobial Activity and DNA/BSA Binding Study
Authors: Andrejević Tina P. , Aleksic Ivana , Kljun Jakob , Pantović Bojana V. , Milivojevic Dusan , Vojnovic Sandra , Turel Iztok , Djuran Miloš I. , Glišić Biljana Đ.
Published: May 2022

Two zinc(II) complexes with dimethyl 2,2′-bipyridine-4,5-dicarboxylate (py-2py) of the general formula [Zn(py-2py)X2], X = Cl− (1) and Br− (2) were synthesized and characterized by NMR, IR and UV-Vis spectroscopy and single-crystal X-ray diffraction analysis. Complexes 1 and 2 are isostructural and adopt a slightly distorted tetrahedral geometry with values of tetrahedral indices τ4 and τ’4 in the range of 0.80–0.85. The complexes were evaluated for their in vitro antimicrobial activity against two bacterial (Pseudomonas aeruginosa and Staphylococcus aureus) and two fungal strains (Candida albicans and Candida parapsilosis), while their cytotoxicity was tested on the normal human lung fibroblast cell line (MRC-5) and the model organism Caenorhabditis elegans. Complex 1 showed moderate activity against both Candida strains. However, this complex was twofold more cytotoxic compared to complex 2. The complexes tested had no effect on the survival rate of C. elegans. Complex 2 showed the ability to inhibit filamentation of C. albicans, while complex 1 was more effective than complex 2 in inhibiting biofilm formation. The interactions of complexes 1 and 2 with calf thymus DNA (ct-DNA) and bovine serum albumin (BSA) were studied to evaluate their binding affinity toward these biomolecules.
Effects of Habitat Fragmentation on the Population Structure and Genetic Diversity of Erythroneurini in the Typical Karst Rocky Ecosystem, Southwest China
Authors: Chen Xiaoxiao , Jiang Jia , Zhang Ni , Yang Xiao , Chi Yongkuan , Song Yuehua
Published: May 2022

Karst rocky desertification is one of the main causes of habitat fragmentation in Southwest China. Guizhou Province is located in the center of the karst area in southern China and is a typical karst ecological environment fragile area. Many studies have shown that habitat fragmentation is the main factor leading to the loss of biodiversity and species extinction, and it is also one of the important factors that threaten the survival of natural organisms. This study initially explored the habitat fragmentation degree, species diversity, and genetic diversity of leafhoppers in three typical karst areas in Guizhou. The study was combined with the general situation of the study area, understanding the main factors affecting habitat fragmentation, and putting forward reasonable protection suggestions for species resources. Based on satellite imagery, field survey collection, molecular sequencing data, and related index measurement methods, we measured the habitat fragmentation degree, species diversity index, and genetic diversity index of Erythroneurine leafhoppers of Shibing Yuntai Mountain Nature Reserve, Bijie Salaxi Demonstration Zone, Zhenfeng-Huajiang Demonstration Zone. Moreover, we compared the differences in the three study areas, carried out correlation analysis with relevant environmental factors, and discussed the main factors that formed the results. The results of the study show that the species diversity and genetic diversity of Erythroneurine leafhoppers in the study areas are affected by habitat fragmentation, and the weaker the degree of habitat fragmentation in the region, the higher the species diversity and genetic diversity, which is specifically manifested in species, quantity, and gene-flow. Understanding the status of biodiversity in karst areas is conducive to the sustainable development of biological resources. In order to better protect the diversity of such insects and their host plants and other biological diversity, combined with the background of the research area, we propose corresponding protection measures for reference.
Differences in Diagnosis and Management of Hypertensive Urgencies and Emergencies According to Italian Doctors from Different Departments Who Deal With Acute Increase in Blood Pressure—Data from Gear (Gestione Dell’emergenza e Urgenza in ARea Critica) Study
Authors: Saladini Francesca , Mancusi Costantino , Bertacchini Fabio , Spannella Francesco , Maloberti Alessandro , Giavarini Alessandra , Rosticci Martina , Bruno Rosa Maria , Pucci Giacomo , Grassi Davide , Pengo Martino , Muiesan Maria Lorenza
Published: May 2022

Background: Diagnosis and treatment of hypertension emergency (HE) and urgency (HU) may vary according to the physicians involved and the setting of the treatment. The aim of this study was to investigate differences in management of HE and HU according to the work setting of the physicians. Methods: The young investigators of the Italian Society of Hypertension developed a 23-item questionnaire spread by email invitation to the members of Italian Scientific societies involved in the field of emergency medicine and hypertension. Results: Six-hundred and sixty-five questionnaires were collected. No differences emerged for the correct definitions of HE and HU or for the investigation of possible drugs that may be responsible for an acute increase in BP. The techniques used to assess BP values (p < 0.004) and the sizes of cuffs available were different according to the setting. Cardiologists more frequently defined epistaxis (55.2% p = 0.012) and conjunctival hemorrhages (70.7%, p < 0.0001) as possible presentation of HE, and rarely considered dyspnea (67.2% p = 0.014) or chest pain (72.4%, p = 0.001). Intensive care (IC) unit doctors were more familiar with lung ultrasound (50% p = 0.004). With regard to therapy, cardiologists reported the lowest prescription of i.v. labetalol (39.6%, p = 0.003) and the highest of s.l. nifedipine (43.1% p < 0.001). After discharge, almost all categories of physicians required home BP assessment or referral to a general practitioner, whereas hypertensive center evaluation or ambulatory BP monitoring were less frequently suggested. Conclusion: Management and treatment of HE and HU may be different according to the doctor’s specialty. Educational initiatives should be done to standardize treatment protocols and to improve medical knowledge.
Coded DNN Watermark: Robustness against Pruning Models Using Constant Weight Code
Authors: Yasui Tatsuya , Tanaka Takuro , Malik Asad , Kuribayashi Minoru
Published: May 2022

Deep Neural Network (DNN) watermarking techniques are increasingly being used to protect the intellectual property of DNN models. Basically, DNN watermarking is a technique to insert side information into the DNN model without significantly degrading the performance of its original task. A pruning attack is a threat to DNN watermarking, wherein the less important neurons in the model are pruned to make it faster and more compact. As a result, removing the watermark from the DNN model is possible. This study investigates a channel coding approach to protect DNN watermarking against pruning attacks. The channel model differs completely from conventional models involving digital images. Determining the suitable encoding methods for DNN watermarking remains an open problem. Herein, we presented a novel encoding approach using constant weight codes to protect the DNN watermarking against pruning attacks. The experimental results confirmed that the robustness against pruning attacks could be controlled by carefully setting two thresholds for binary symbols in the codeword.
Endosurgical aspects of diagnosis and treatment of strangulated inguinal hernias (a brief literature review)
Authors:   Federal State Budgetary Educational Institution of Higher Professional Education «I.I. Mechnikov Northwestern State Medical University» of the Ministry of Health of the Russian Federation, Radzhabov Bekhruz Elboevich , Levin Leonid Alexandrovich ,   Federal State Budgetary Educational Institution of Higher Education «I.I. Mechnikov Northwestern State Medical University» of the Ministry of Health of the Russian Federation
Published: May 2022

Inguinal hernias are among the most common surgical diseases, 10–15 % of which are complicated by strangulation. Emergent surgery in such cases are associated with a high frequency of hernia recurrence (up to 30 %), and difficulties in diagnosing hernial strangulation lead to a long delay in operations and dramatically increase postoperative mortality up to 4–12 %. The review of the literature in the historical perspective reflects the use of videolaparoscopic techniques with diagnostic and therapeutic purposes for acute hernial incarceration. The experience of diagnostic videolaparoscopy for strangulated hernias of all kinds of localization accumulated in the world practice indicates a very high sensitivity of the method that allows recognizing hernial strangulation, differentiating it from other diseases, verifying organs that have undergone incarceration, and assessing their viability. However, targeted studies of the diagnostic capabilities of videolaparoscopy for strangulated hernias have not been conducted. By 2009, 7 articles had been published in the world press on the treatment of strangulated inguinal hernias by laparoscopic (TAPP) or endosurgical (TEP) methods. A meta-analysis of these publications showed that laparoscopic hernioplasty for strangulated hernias is a performable operation with acceptable results. Further studies have identified a number of physiological and socio-economic advantages of endosurgical operations compared to open methods of prosthetic hernioplasty. However, such operations remain the lot of a narrow circle of specialists. To date, there are no randomized trials or systematic reviews on hernioplasty techniques for TARR and TER in patients with strangulated inguinal hernias. The question about optimal method of eliminating a strangulated inguinal hernia is not covered in modern literature and is still pending.
Processing of a «difficult» duodenal stump in an original way
Authors:   Federal State Medical University of the Chita State Medical Academy of the Ministry of Health of the Russian Federation, Bogomolov Nikolai Ivanovich , Goncharov Andrei Gennadievich ,   Federal State Budgetary Institution Chita State Medical Academy of the Ministry of Health of the Russian Federation, Kashafeeva Alla Anatolyevna ,   Federal State Budgetary Institution Chita State Medical Academy of the Ministry of Health of the Russian Federation
Published: May 2022

Treatment of the «difficult» stump of the duodenum occurs during peptic ulcer surgery. More than 340 methods of its suturing are known. When processing the «difficult» duodenal stump in the examples presented in the paper, the author’s method was used (patent No. 2696656 dated 08/05/2019).
Comparison of farming in Germany and Russia
Authors:   Belgorod State Agrarian University, Maysky village, Kovaleva E.V. , Gugulyan K.A. ,   Belgorod State Agrarian University, Maysky village
Published: May 2022

Agriculture in Germany takes an important place in the development of the country, as it provides the population with basic food. However, the main functions of agriculture include secondary tasks - protection of the natural foundations of life, preservation of attractive landscapes for residential areas, and provision industry with agricultural raw materials. The transformation of the agricultural sector of the economy has predetermined the formation and development of new forms of management, such as farming, which in modern economic relations acquire a rather high value. The main features of farming for the production of fruit and berry crops in the south of Germany in Mösbach village were considered in this paper. The main problems of farming in Russia were analyzed here as well.