bluuebunny/crossref_metadata_2025 huggingface dataset:
Nrf2 Pathway in Huntington’s Disease (HD): What Is Its Role?
Authors: Tucci Paolo , Lattanzi Roberta , Severini Cinzia , Saso Luciano
Published: December 2022

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease that occurs worldwide. Despite some progress in understanding the onset of HD, drugs that block or delay symptoms are still not available. In recent years, many treatments have been proposed; among them, nuclear transcriptional factor-2 (Nrf2) enhancer compounds have been proposed as potential therapeutic agents to treat HD. Nrf2 triggers an endogenous antioxidant pathway activated in different neurodegenerative disorders. Probably, the stimulation of Nrf2 during either the early phase or before HD symptoms’ onset, could slow or prevent striatum degeneration. In this review, we present the scientific literature supporting the role of Nrf2 in HD and the potential prophylactic and therapeutic role of this compound.
Overexpression of GmPHR1 Promotes Soybean Yield through Global Regulation of Nutrient Acquisition and Root Development
Authors: Li Yanjun , Ma Wenjing , Zhang Kefei , Wang Xiaoqian , Liu Ran , Tian Yingzhe , Ma Niannian , Zhao Qingsong , Xu Ruineng , Zhong Yongjia , Liao Hong
Published: December 2022

MYB-CC transcription factors (TFs) are essential for plant growth and development. Members of the MYB-CC subfamily with long N terminal domains, such as phosphate starvation response 1 (PHR1) or PHR1-like TFs, have well documented functions, while those with short N terminal domains remain less understood. In this study, we identified a nodule specific MYB-CC transcription factor 1 (GmPHR1) in soybean that is different from other canonical PHR family genes in that GmPHR1 harbors a short N terminal ahead of its MYB-CC domain and was highly induced by rhizobium infection. The overexpression of GmPHR1 dramatically increased the ratio of deformed root hairs, enhanced subsequent soybean nodulation, and promoted soybean growth in pot experiments. The growth promotion effects of GmPHR1 overexpression were further demonstrated in field trails in which two GmPHR1-OE lines yielded 10.78% and 8.19% more than the wild type line. Transcriptome analysis suggested that GmPHR1 overexpression led to global reprogramming, with 749 genes upregulated and 279 genes downregulated, especially for genes involved in MYB transcription factor activities, root growth, and nutrient acquisition. Taken together, we conclude that GmPHR1 is a key gene involved in the global regulation of nodulation, root growth, and nutrient acquisition in soybeans, and is thus a promising candidate gene to target for soybean yield enhancement.
Crosstalk between Resveratrol and Gut Barrier: A Review
Authors: Drabińska Natalia , Jarocka-Cyrta Elżbieta
Published: December 2022

The plant-based nutraceuticals are receiving increasing interest in recent time. The high attraction to the phytochemicals is associated with their anti-inflammatory and antioxidant activities, which can lead to reduced risk of the development of cardiovascular and other non-communicable diseases. One of the most disseminated groups of plant bioactives are phenolic compounds. It was recently hypothesized that phenolic compounds can have the ability to improve the functioning of the gut barrier. The available studies showed that one of the polyphenols, resveratrol, has great potential to improve the integrity of the gut barrier. Very promising results have been obtained with in vitro and animal models. Still, more clinical trials must be performed to evaluate the effect of resveratrol on the gut barrier, especially in individuals with increased intestinal permeability. Moreover, the interplay between phenolic compounds, intestinal microbiota and gut barrier should be carefully evaluated in the future. Therefore, this review offers an overview of the current knowledge about the interaction between polyphenols with a special emphasis on resveratrol and the gut barrier, summarizes the available methods to evaluate the intestinal permeability, discusses the current research gaps and proposes the directions for future studies in this research area.
Novel Genes Involved in Hypertrophic Cardiomyopathy: Data of Transcriptome and Methylome Profiling
Authors: Kiselev Ivan , Kozin Maxim , Baulina Natalia , Pisklova Maria , Danilova Ludmila , Zotov Alexandr , Chumakova Olga , Zateyshchikov Dmitry , Favorova Olga
Published: December 2022

Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease; its pathogenesis is still being intensively studied to explain the reasons for the significant genetic and phenotypic heterogeneity of the disease. To search for new genes involved in HCM development, we analyzed gene expression profiles coupled with DNA methylation profiles in the hypertrophied myocardia of HCM patients. The transcriptome analysis identified significant differences in the levels of 193 genes, most of which were underexpressed in HCM. The methylome analysis revealed 1755 nominally significant differentially methylated positions (DMPs), mostly hypomethylated in HCM. Based on gene ontology enrichment analysis, the majority of biological processes, overrepresented by both differentially expressed genes (DEGs) and DMP-containing genes, are involved in the regulation of locomotion and muscle structure development. The intersection of 193 DEGs and 978 DMP-containing genes pinpointed eight common genes, the expressions of which correlated with the methylation levels of the neighboring DMPs. Half of these genes (AUTS2, BRSK2, PRRT1, and SLC17A7), regulated by the mechanism of DNA methylation, were underexpressed in HCM and were involved in neurogenesis and synapse functioning. Our data, suggesting the involvement of innervation-associated genes in HCM, provide additional insights into disease pathogenesis and expand the field of further research.
Psychedelic-Induced Serotonin 2A Receptor Downregulation Does Not Predict Swim Stress Coping in Mice
Authors: Pędzich Błażej D. , Medrano Mireia , Buckinx An , Smolders Ilse , De Bundel Dimitri
Published: December 2022

Serotoninergic psychedelics such as psilocybin have been reported to elicit a long-lasting reduction in depressive symptoms. Although the main target for serotoninergic psychedelics, serotonin type 2A receptor (5-HT2A), has been established, the possible mechanism of the antidepressant action of psychedelics remains unknown. Using the mouse forced swim test model, we examined whether the administration of the synthetic serotoninergic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI) would modulate 5-HT2A receptor levels in the medial prefrontal cortex (mPFC) and revert stress-induced changes in behavior. Mice subjected to swim stress developed a passive stress-coping strategy when tested in the forced swim test 6 days later. This change in behavior was not associated with the hypothesized increase in 5-HT2A receptor-dependent head twitch behaviors or consistent changes in 5-HT2A receptor levels in the mPFC. When DOI was administered 1 day before the forced swim test, a low dose (0.2 mg/kg i.p.) unexpectedly increased immobility while a high dose (2 mg/kg i.p.) had no significant effect on immobility. Nevertheless, DOI evoked a dose-dependent decrease in 5-HT2A levels in the mPFC of mice previously exposed to swim stress. Our findings do not support the hypothesis that the downregulation of 5-HT2A receptors in the mPFC contributes to the antidepressant-like properties of serotoninergic psychedelics.
The Impact of Corticosteroids on Human Airway Smooth Muscle Contractility and Airway Hyperresponsiveness: A Systematic Review
Authors: Calzetta Luigino , Chetta Alfredo , Aiello Marina , Pistocchini Elena , Rogliani Paola
Published: December 2022

Classically, the effects elicited by corticosteroids (CS) are mediated by the binding and activation of cytosolic glucocorticoid receptors (GR). However, several of the non-genomic effects of CS seem to be mediated by putative non-classic membrane receptors characterized by pharmacological properties that are different from those of classic cytosolic GR. Since pre-clinical findings suggest that inhaled CS (ICS) may also regulate the bronchial contractile tone via putative CS membrane-associate receptors, the aim of this review was to systematically report and discuss the impact of CS on human airway smooth muscle (ASM) contractility and airway hyperresponsiveness (AHR). Current evidence indicates that CS have significant genomic/non-genomic beneficial effects on human ASM contractility and AHR, regardless of their anti-inflammatory effects. CS are effective in reducing either the expression, synthesis or activity of α-actin, CD38, inositol phosphate, myosin light chain kinase, and ras homolog family member A in response to several pro-contractile stimuli; overall these effects are mediated by the genomic action of CS. Moreover, CS elicited a strong bronchorelaxant effect via the rapid activation of the Gsα–cyclic-adenosine-monophosphate–protein-kinase-A pathway in hyperresponsive airways. The possibility of modulating the dose of the ICS in a triple ICS/long-acting β2-adrenoceptor agonist/long-acting muscarinic antagonist fixed-dose combination supports the use of a Triple MAintenance and Reliever Therapy (TriMART) in those asthmatic patients at Step 3–5 who may benefit from a sustained bronchodilation and have been suffering from an increased parasympathetic tone.
Mitochondrial Dysfunction and Oxidative Stress in Hereditary Ectopic Calcification Diseases
Authors: Nollet Lukas L. , Vanakker Olivier M.
Published: December 2022

Ectopic calcification (EC) is characterized by an abnormal deposition of calcium phosphate crystals in soft tissues such as blood vessels, skin, and brain parenchyma. EC contributes to significant morbidity and mortality and is considered a major health problem for which no effective treatments currently exist. In recent years, growing emphasis has been placed on the role of mitochondrial dysfunction and oxidative stress in the pathogenesis of EC. Impaired mitochondrial respiration and increased levels of reactive oxygen species can be directly linked to key molecular pathways involved in EC such as adenosine triphosphate homeostasis, DNA damage signaling, and apoptosis. While EC is mainly encountered in common diseases such as diabetes mellitus and chronic kidney disease, studies in rare hereditary EC disorders such as pseudoxanthoma elasticum or Hutchinson–Gilford progeria syndrome have been instrumental in identifying the precise etiopathogenetic mechanisms leading to EC. In this narrative review, we describe the current state of the art regarding the role of mitochondrial dysfunction and oxidative stress in hereditary EC diseases. In-depth knowledge of aberrant mitochondrial metabolism and its local and systemic consequences will benefit the research into novel therapies for both rare and common EC disorders.
Thermo-Transient Receptor Potential Channels: Therapeutic Potential in Gastric Cancer
Authors: Zong Gang-Fan , Deng Rui , Yu Su-Yun , Wang Ai-Yun , Wei Zhong-Hong , Zhao Yang , Lu Yin
Published: December 2022

Over the last decade, researchers have found abnormal expression of transient receptor potential (TRP) channels. In particular, members of the thermally sensitive subclass (thermo-TRPs) are involved in many disease processes. Moreover, they have a vital role in the occurrence and development of gastric cancer (GC). Accordingly, thermo-TRPs constitute a major pharmacological target, and the elucidation of the mechanisms underlying their response to physiological stimuli or drugs is key for notable advances in GC treatment. Therefore, this paper summarizes the existing literature about thermo-TRP protein expression changes that are linked to the incidence and progression of GC. The review also discusses the implication of such association to pathology and cell physiology and identifies potential thermo-TRP protein targets for diagnosis and treatment of GC.
Unveiling the Metal-Dependent Aggregation Properties of the C-terminal Region of Amyloidogenic Intrinsically Disordered Protein Isoforms DPF3b and DPF3a
Authors: Leyder Tanguy , Mignon Julien , Mottet Denis , Michaux Catherine
Published: December 2022

Double-PHD fingers 3 (DPF3) is a BAF-associated human epigenetic regulator, which is increasingly recognised as a major contributor to various pathological contexts, such as cardiac defects, cancer, and neurodegenerative diseases. Recently, we unveiled that its two isoforms (DPF3b and DPF3a) are amyloidogenic intrinsically disordered proteins. DPF3 isoforms differ from their C-terminal region (C-TERb and C-TERa), containing zinc fingers and disordered domains. Herein, we investigated the disorder aggregation properties of C-TER isoforms. In agreement with the predictions, spectroscopy highlighted a lack of a highly ordered structure, especially for C-TERa. Over a few days, both C-TERs were shown to spontaneously assemble into similar antiparallel and parallel β-sheet-rich fibrils. Altered metal homeostasis being a neurodegeneration hallmark, we also assessed the influence of divalent metal cations, namely Cu2+, Mg2+, Ni2+, and Zn2+, on the C-TER aggregation pathway. Circular dichroism revealed that metal binding does not impair the formation of β-sheets, though metal-specific tertiary structure modifications were observed. Through intrinsic and extrinsic fluorescence, we found that metal cations differently affect C-TERb and C-TERa. Cu2+ and Ni2+ have a strong inhibitory effect on the aggregation of both isoforms, whereas Mg2+ impedes C-TERb fibrillation and, on the contrary, enhances that of C-TERa. Upon Zn2+ binding, C-TERb aggregation is also hindered, and the amyloid autofluorescence of C-TERa is remarkably red-shifted. Using electron microscopy, we confirmed that the metal-induced spectral changes are related to the morphological diversity of the aggregates. While metal-treated C-TERb formed breakable and fragmented filaments, C-TERa fibrils retained their flexibility and packing properties in the presence of Mg2+ and Zn2+ cations.
Porphyromonas gingivalis Fimbriae Induce Osteoclastogenesis via Toll-like Receptors in RAW264 Cells
Authors: Suzuki Yuki , Kikuchi Takeshi , Goto Hisashi , Takayanagi Yuhei , Kawamura Shotaro , Sawada Noritaka , Naiki Yoshikazu , Kondo Hisataka , Hayashi Jun-ichiro , Hasegawa Yoshiaki , Mitani Akio
Published: December 2022

The effect of Mfa1 fimbriae of Porphyromonas gingivalis on the progression of bone resorption remains unclear, especially compared with another fimbriae, FimA. We investigated the effect of Mfa1 on osteoclastogenesis together with FimA. We also investigated the role of Toll-like receptors (TLRs) in Mfa1 recognition during osteoclast differentiation. Receptor activator of nuclear factor κβ ligand (RANKL)-prestimulated RAW264 cells were used to examine the effects of purified Mfa1 fimbriae. The number of osteoclasts was examined by tartrate-resistant acid phosphate (TRAP) staining, osteoclast activation was investigated by bone resorption assays, and gene expression of differentiation markers was examined by quantitative real-time PCR. Transfection of Tlr2 and Tlr4 siRNAs into RAW264 cells was also employed and their role in Mfa1 recognition was investigated. Mfa1 effectively induced the formation of TRAP-positive multinucleated cells and activated osteoclasts. Mfa1 also increased gene expression of Acp5, Mmp9, and Ctsk in RANKL-prestimulated RAW264 cells compared with the control. The osteoclastogenesis induced by Mfa1 was significantly decreased in cells transfected with Tlr2 or Tlr4 siRNAs compared with control siRNA. Our results revealed the role of Mfa1 fimbriae in osteoclastogenesis that may contribute to the partial elucidation of the mechanisms of periodontal disease progression and the development of new therapeutic strategies.
Synthesis, Biological Evaluation and Computational Studies of New Hydrazide Derivatives Containing 1,3,4-Oxadiazole as Antitubercular Agents
Authors: Zampieri Daniele , Fortuna Sara , Romano Maurizio , De Logu Alessandro , Cabiddu Gianluigi , Sanna Adriana , Mamolo Maria Grazia
Published: December 2022

To extend our screening for novel antimycobacterial molecules, we have designed, synthesized, and biologically evaluated a library of 14 new hydrazide derivatives containing 1,3,4-oxadiazole core. A variety of mycobacterial strains, including some drug-resistant strains, were tested for antimycobacterial activity. Among the compounds tested, five showed high antimycobacterial activity (MIC values of 8 μg/mL) against M. tuberculosis H37Ra attenuated strain, and two derivatives were effective (MIC of 4 µg/mL) against pyrazinamide-resistant strains. Furthermore, the novel compounds were tested against the fungal C. albicans strain, showing no antimycotic activity, and thus demonstrating a good selectivity profile. Notably, they also exhibited low cytotoxicity against human SH-SY5Y cells. The molecular modeling carried out suggested a plausible mechanism of action towards the active site of the InhA enzyme, which confirmed our hypothesis. In conclusion, the active compounds were predicted in silico for ADME properties, and all proved to be potentially orally absorbed in humans.
IL-1b in the Secretomes of MSCs Seeded on Human Decellularized Allogeneic Bone Promotes Angiogenesis
Authors: Chen Yi-Chun , Fu Yu-Show , Tsai Shang-Wen , Wu Po-Kuei , Chen Chao-Ming , Chen Wei-Ming , Chen Cheng-Fong
Published: December 2022

Angiogenesis plays an important role in the development of bone and bone regeneration to provide the required molecules. Mesenchymal stem cells (MSCs) are pluripotent, self-renewing, and spindle-shaped cells, which can differentiate into multiple lineages such as chondrocytes, osteocytes, and adipocytes. MSCs derived from bone marrow (BMMSCs), adipose tissue (ADMSCs), and Wharton’s jelly (UCMSCs) are popular in the field of tissue regeneration. MSCs have been proposed that can promote bone regeneration by enhancing vascularization. In this study, the angiogenic potential of secretomes of undifferentiated and osteo-differentiated BMMSCs, ADMSCs, and UCMSCs seeded on human decellularized allogeneic bone were compared. Human umbilical vein endothelial cells (HUVECs) were treated with MSC secretomes. Cell growth, cell migration, and angiogenesis of HUVECs were analyzed by MTT, wound healing, and tube formation assays. Angiogenic gene expression levels of MSCs were evaluated using real-time quantitative PCR. Antibody neutralization was performed to validate the candidate target. Our study demonstrates that the angiogenic gene expression profile is tissue-dependent and the angiogenic ability of secretomes is independent of the state of differentiation. We also explore that IL-1b is important for MSC angiogenic potential. Taken together, this study proves that IL-1b in the secretomes plays a vital role in angiogenesis.
Cross-Regulation between Autophagy and Apoptosis Induced by Vitamin E and Lactobacillus Plantarum through Beclin-1 Network
Authors: Alhusaini Ahlam M. , Alhumaidan Sara A. , Alharbi Ghaida M. , Alzahrani Eman A. , Sarawi Wedad S. , Alomar Hatun A. , Alanazi Abeer M. , Mattar Dareen S. , Hasan Iman H.
Published: December 2022

Autophagy and apoptosis are two important regulatory mechanisms for how the body can respond to diseases. This study was designed to investigate the protective actions of vitamin E (Vit-E) and lactobacillus plantarum (Lac-B) against mercuric chloride (HgCl2)-induced kidney injury. Thirty albino rats were divided into five groups: group 1 served as the normal group; rats in group 2 received high doses of HgCl2; rats in groups 3, 4 and 5 were given Vit-E, Lac-B and the combination of Vit-E and Lac-B, respectively along with HgCl2 for two weeks. HgCl2 provoked renal injury, manifested by elevation in serum urea, urea nitrogen and creatinine. Kidney levels of oxidative stress and inflammation were markedly increased post HgCl2 administration. Moreover, HgCl2 significantly elevated the gene expression levels of VCAM-1 and cystatin C, while podocin was downregulated. Additionally, it markedly decreased the protein expression of Beclin-1 and Bcl-2. Histopathological examination revealed massive degeneration with congested blood vessels following HgCl2 administration. Treatment with Vit-E or/and Lac-B restored the normal levels of the previously mentioned parameters, as well as improved the morphology of kidney tissues. Both Vit-E and Lac-B provided a protective effect against HgCl2-induced kidney damage by regulating autophagy and apoptosis.
Increased Number of Mucosal-Associated Invariant T Cells Is Associated with the Inhibition of Nonalcoholic Fatty Liver Disease in High Fat Diet–Fed Mice
Authors: Kishi Haruka , Usui Isao , Jojima Teruo , Fujisaka Shiho , Wakamatsu Sho , Mizunuma-Inoue Yuiko , Niitani Takafumi , Sakurai Shintaro , Iijima Toshie , Tomaru Takuya , Tobe Kazuyuki , Aso Yoshimasa
Published: December 2022

Nonalcoholic fatty liver disease (NAFLD) is an emerging worldwide health concern. The disease may involve immune cells including T cells, but little is known about the role(s) of the innate-like T cells in the liver. Furthermore, the most abundant innate-like T cells in the human liver are mucosal-associated invariant T (MAIT) cells, but the involvement of MAIT cells in NAFLD remains largely unexplored because of their paucity in mice. In this study, we used a novel mouse line, Vα19, in which the number of MAIT cells is equivalent to or greater than that in humans. Compared with the control mice, Vα19 mice fed a high-fat diet (HFD) exhibited a reduction in lipid accumulation, NAFLD activity score, and transcripts relevant to lipogenesis. In addition, serum triglyceride and non-esterified fatty acids were lower in Vα19 mice fed normal chow or HFD. In contrast, the Vα19 mice showed little or no change in glucose tolerance, insulin sensitivity, inflammation in adipose tissues, or intestinal permeability compared with the controls, irrespective of diet. These results suggest that the presence of MAIT cells is associated with reduced lipogenesis and lipid accumulation in the liver; however, further studies are needed to clarify the role of MAIT cells in hepatic lipid metabolism.
Acarbose Protects Glucolipotoxicity-Induced Diabetic Nephropathy by Inhibiting Ras Expression in High-Fat Diet-Fed db/db Mice
Authors: Hung Tung-Wei , Yu Meng-Hsun , Yang Tsung-Yuan , Yang Mon-Yuan , Chen Jia-Yu , Chan Kuei-Chuan , Wang Chau-Jong
Published: December 2022

Diabetic nephropathy (DN) exacerbates renal tissue damage and is a major cause of end-stage renal disease. Reactive oxygen species play a vital role in hyperglycemia-induced renal injury. This study examined whether the oral hypoglycemic drug acarbose (Ab) could attenuate the progression of DN in type 2 diabetes mellitus mice. In this study, 50 mg/kg body weight of Ab was administered to high-fat diet (HFD)-fed db/db mice. Their body weight was recorded every week, and the serum glucose concentration was monitored every 2 weeks. Following their euthanasia, the kidneys of mice were analyzed through hematoxylin and eosin, periodic acid Schiff, Masson’s trichrome, and immunohistochemistry (IHC) staining. The results revealed that Ab stabilized the plasma glucose and indirectly improved the insulin sensitivity and renal functional biomarkers in diabetic mice. In addition, diabetes-induced glomerular hypertrophy, the saccharide accumulation, and formation of collagen fiber were reduced in diabetic mice receiving Ab. Although the dosages of Ab cannot decrease the blood sugar in db/db mice, our results indicate that Ab alleviates glucolipotoxicity-induced DN by inhibiting kidney fibrosis-related proteins through the Ras/ERK pathway.
Longevity-Associated Variant of BPIFB4 Confers Neuroprotection in the STHdh Cell Model of Huntington Disease
Authors: Cattaneo Monica , Maciag Anna , Milella Maria Serena , Ciaglia Elena , Bruno Antonino , Puca Annibale Alessandro
Published: December 2022

Huntington’s disease (HD) is caused by the production of mutant Huntingtin (mHTT), characterized by long polyglutamine repeats with toxic effects. There are currently no clinically validated therapeutic agents that slow or halt HD progression, resulting in a significant clinical unmet need. The striatum-derived STHdh cell line, generated from mHTT knock-in mouse embryos (STHdhQ111/Q111), represents a useful model to study mechanisms behind pathogenesis of HD and to investigate potential new therapeutic targets. Indeed, these cells show susceptibility to nucleolar stress, activated DNA damage response and apoptotic signals, and elevated levels of H3K9me3 that all together concur in the progressive HD pathogenesis. We have previously shown that the adeno-associated viral vector-mediated delivery of the longevity-associated variant (LAV) of BPIFB4 prevents HD progression in a mouse model of HD. Here, we show that LAV-BPIFB4 stably infected in STHdhQ111/Q111 cells reduces (i) nucleolar stress and DNA damage through the improvement of DNA repair machinery, (ii) apoptosis, through the inhibition of the caspase 3 death signaling, and (iii) the levels of H3K9me3, by accelerating the histone clearance, via the ubiquitin–proteasome pathway. These findings pave the way to propose LAV-BPIFB4 as a promising target for innovative therapeutic strategies in HD.
Role of Ceramides and Lysosomes in Extracellular Vesicle Biogenesis, Cargo Sorting and Release
Authors: Horbay Rostyslav , Hamraghani Ali , Ermini Leonardo , Holcik Sophie , Beug Shawn T. , Yeganeh Behzad
Published: December 2022

Cells have the ability to communicate with their immediate and distant neighbors through the release of extracellular vesicles (EVs). EVs facilitate intercellular signaling through the packaging of specific cargo in all type of cells, and perturbations of EV biogenesis, sorting, release and uptake is the basis of a number of disorders. In this review, we summarize recent advances of the complex roles of the sphingolipid ceramide and lysosomes in the journey of EV biogenesis to uptake.
Expression and Characterization of Monomeric Recombinant Isocitrate Dehydrogenases from Corynebacterium glutamicum and Azotobacter vinelandii for NADPH Regeneration
Authors: Lee Hun-Dong , Yoo Su-Kyoung , Yoo Ho-Seok , Yun Chul-Ho , Kim Geun-Joong
Published: December 2022

The enzymatic transformation of various chemicals, especially using NADPH-dependent hydroxylase, into more soluble and/or high value-added products has steadily garnered increasing attention. However, the industrial application of these NADPH-dependent hydroxylases has been limited due to the high cost of the cofactor NADPH. As an alternative, enzymatic NADPH-regeneration systems have been developed and are frequently used in various fields. Here, we expressed and compared two recombinant isocitrate dehydrogenases (IDHs) from Corynebacterium glutamicum and Azotobacter vinelandii in Escherichia coli. Both enzymes were hyper-expressed in the soluble fraction of E. coli and were single-step purified to apparent homogeneity with yields of more than 850 mg/L. These enzymes also functioned well when paired with NADPH consumption systems. Specifically, NADPH was regenerated from NADP+ when an NADPH-consuming cytochrome P450 BM3 from Bacillus megaterium was incorporated. Therefore, both enzymes could be used as alternatives to the commonly used regeneration system for NADPH. These enzymes also have promising potential as genetic fusion partners with NADPH-dependent enzymes due to the monomeric nature of their quaternary structure, thereby resulting in self-sufficient biocatalysts via NADPH regeneration in a single polypeptide with NADPH-dependent activity.
Radiomic Features Applied to Contrast Enhancement Spectral Mammography: Possibility to Predict Breast Cancer Molecular Subtypes in a Non-Invasive Manner
Authors: Nicosia Luca , Bozzini Anna Carla , Ballerini Daniela , Palma Simone , Pesapane Filippo , Raimondi Sara , Gaeta Aurora , Bellerba Federica , Origgi Daniela , De Marco Paolo , Castiglione Minischetti Giuseppe , Sangalli Claudia , Meneghetti Lorenza , Curigliano Giuseppe , Cassano Enrico
Published: December 2022

We aimed to investigate the association between the radiomic features of contrast-enhanced spectral mammography (CESM) images and a specific receptor pattern of breast neoplasms. In this single-center retrospective study, we selected patients with neoplastic breast lesions who underwent CESM before a biopsy and surgical assessment between January 2013 and February 2022. Radiomic analysis was performed on regions of interest selected from recombined CESM images. The association between the features and each evaluated endpoint (ER, PR, Ki-67, HER2+, triple negative, G2–G3 expressions) was investigated through univariate logistic regression. Among the significant and highly correlated radiomic features, we selected only the one most associated with the endpoint. From a group of 321 patients, we enrolled 205 malignant breast lesions. The median age at the exam was 50 years (interquartile range (IQR) 45–58). NGLDM_Contrast was the only feature that was positively associated with both ER and PR expression (p-values = 0.01). NGLDM_Coarseness was negatively associated with Ki-67 expression (p-value = 0.02). Five features SHAPE Volume(mL), SHAPE_Volume(vx), GLRLM_RLNU, NGLDM_Busyness and GLZLM_GLNU were all positively and significantly associated with HER2+; however, all of them were highly correlated. Radiomic features of CESM images could be helpful to predict particular molecular subtypes before a biopsy.
Identification of Agents That Ameliorate Hyperphosphatemia-Suppressed Myogenin Expression Involved in the Nrf2/p62 Pathway in C2C12 Skeletal Muscle Cells
Authors: Hsieh Li Shu-Man , Liu Shu-Ting , Chang Yung-Lung , Chen Gunng-Shinng , Huang Shih-Ming
Published: December 2022

Hyperphosphatemia can occur as a result of reduced phosphate (Pi) excretion in cases of kidney dysfunction, which can induce muscle wasting and suppress myogenic differentiation. Higher Pi suppresses myogenic differentiation and promotes muscle atrophy through canonical (oxidative stress-mediated) and noncanonical (p62-mediated) activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling. However, the crosstalk between myogenin and Nrf2/p62 and potential drug(s) for the regulation of myogenin expression needed to be addressed. In this study, we further identified that myogenin may negatively regulate Nrf2 and p62 protein levels in the mouse C2C12 muscle cell line. In the drug screening analysis, we identified N-acetylcysteine, metformin, phenformin, berberine, 4-chloro-3-ethylphenol, cilostazol, and cilomilast as ameliorating the induction of Nrf2 and p62 expression and reduction in myogenin expression that occur due to high Pi. We further elucidated that doxorubicin and hydrogen peroxide reduced the amount of myogenin protein mediated through the Kelch-like ECH-associated protein 1/Nrf2 pathway, differently from the mechanism of high Pi. The dual functional roles of L-ascorbic acid (L-AA) were found to be dependent on the working concentration, where concentrations below 1 mM L-AA reversed the effect of high Pi on myogenin and those above 1 mM L-AA had a similar effect of high Pi on myogenin when used alone. L-AA exacerbated the effect of hydrogen peroxide on myogenin protein and had no further effect of doxorubicin on myogenin protein. In summary, our results further our understanding of the crosstalk between myogenin and Nrf2, with the identification and verification of several potential drugs that can be applied in rescuing the decline of myogenin due to high Pi in muscle cells.
Comprehensive Analysis of Betula platyphylla Suk. PIF Gene Family and Their Potential Functions in Growth and Development
Authors: Chen Aihua , Huang Peng , Guo Shanshan , Liu Sige , Hu Xiaoqing , Liu Xuemei
Published: December 2022

Phytochrome-interacting factors (PIFs) are transcription factors with the basic helix–loop–helix (bHLH) domain. As integration factors between different signal pathways, members of the PIF protein family regulate many aspects of plant growth and development, such as seed germination, photomorphogenesis, thermomorphogenesis, rhythm regulation, flowering response, stomatal development, and stress responses. Our previous studies have shown that the BpSPL2 gene may regulate plants’ adventitious root development through PIF genes. Within the Betula platyphylla genome, we identified eight PIF (BpPIFs) genes. We analysed and named them based on a phylogenetic tree, gene structures, and conserved motifs. Synteny analysis indicated that transposition or segmental duplication events played a minor role in the expansion of BpPIFs. The comparative syntenic analysis combined with phylogenetic analysis provided a deep insight into the phylogenetic relationships of BpPIF genes, suggesting that BpPIF proteins are closer to PtPIF than to AtPIF. The analysis of cis-acting elements in promoter regions of BpPIF genes indicated that various elements were related to light, abiotic stress, and plant hormone responsiveness. In addition, we found that these promoters have the transcription factor of B. platyphylla SPL2 (BpSPL2) binding motif GTAC. Expression analysis demonstrated that BpPIF genes, especially BpPIF4, BpPIF9b, and BpPIF10, might be the potential target genes of BpSPL2 in the process of adventitious root formation. Besides providing a comprehensive understanding of the BpPIF family, we propose a hypothetical gene network regulatory model for adventitious root formation.
The PI3K/Akt Pathway in Meta-Inflammation
Authors: Acosta-Martinez Maricedes , Cabail Maria Zulema
Published: December 2022

Obesity is a global epidemic representing a serious public health burden as it is a major risk factor for the development of cardiovascular disease, stroke and all-cause mortality. Chronic low-grade systemic inflammation, also known as meta-inflammation, is thought to underly obesity’s negative health consequences, which include insulin resistance and the development of type 2 diabetes. Meta-inflammation is characterized by the accumulation of immune cells in adipose tissue, a deregulation in the synthesis and release of adipokines and a pronounced increase in the production of proinflammatory factors. In this state, the infiltration of macrophages and their metabolic activation contributes to complex paracrine and autocrine signaling, which sustains a proinflammatory microenvironment. A key signaling pathway mediating the response of macrophages and adipocytes to a microenvironment of excessive nutrients is the phosphoinositide 3-kinase (PI3K)/Akt pathway. This multifaceted network not only transduces metabolic information but also regulates macrophages’ intracellular changes, which are responsible for their phenotypic switch towards a more proinflammatory state. In the present review, we discuss how the crosstalk between macrophages and adipocytes contributes to meta-inflammation and provide an overview on the involvement of the PI3K/Akt signaling pathway, and how its impairment contributes to the development of insulin resistance.
Key Genetic Components of Fibrosis in Diabetic Nephropathy: An Updated Systematic Review and Meta-Analysis
Authors: Tziastoudi Maria , Theoharides Theoharis C. , Nikolaou Evdokia , Efthymiadi Maria , Eleftheriadis Theodoros , Stefanidis Ioannis
Published: December 2022

Renal fibrosis (RF) constitutes the common end-point of all kinds of chronic kidney disease (CKD), regardless of the initial cause of disease. The aim of the present study was to identify the key players of fibrosis in the context of diabetic nephropathy (DN). A systematic review and meta-analysis of all available genetic association studies regarding the genes that are included in signaling pathways related to RF were performed. The evaluated studies were published in English and they were included in PubMed and the GWAS Catalog. After an extensive literature review and search of the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, eight signaling pathways related to RF were selected and all available genetic association studies of these genes were meta-analyzed. ACE, AGT, EDN1, EPO, FLT4, GREM1, IL1B, IL6, IL10, IL12RB1, NOS3, TGFB1, IGF2/INS/TH cluster, and VEGFA were highlighted as the key genetic components driving the fibrosis process in DN. The present systematic review and meta-analysis indicate, as key players of fibrosis in DN, sixteen genes. However, the results should be interpreted with caution because the number of studies was relatively small.
Association of the FCN2 Gene Promoter Region Polymorphisms with Very Low Birthweight in Preterm Neonates
Authors: Szala-Poździej Agnieszka , Świerzko Anna S. , Gajek Gabriela , Kufelnicka-Babout Maja , Chojnacka Karolina , Kobiela Paulina , Jarych Dariusz , Sobczuk Katarzyna , Mazela Jan , Domżalska-Popadiuk Iwona , Kalinka Jarosław , Sekine Hideharu , Matsushita Misao , Cedzyński Maciej
Published: December 2022

Single nucleotide polymorphisms (SNPs) localised to the promoter region of the FCN2 gene are known to influence the concentration of ficolin-2 in human serum and therefore potentially have clinical associations. We investigated the relationships between SNPs at positions −986 (A > G), −602 (G > A), −64 (A > C) and −4 (A > G) and clinical complications in 501 preterms. Major alleles at positions −986 and −64 and A/A homozygosity for both polymorphisms were less frequent among babies with very low birthweight (VLBW, ≤1500 g) compared with the reference group (OR = 0.24, p = 0.0029; and OR = 0.49, p = 0.024, respectively for A/A genotypes). A lower frequency of G/G homozygosity at position −4 was associated with gestational age <33 weeks and VLBW (OR = 0.38, p = 0.047; and OR = 0.07, p = 0.0034, respectively). The AGAG haplotype was protective for VLBW (OR = 0.6, p = 0.0369), whilst the GGCA haplotype had the opposite effect (OR = 2.95, p = 0.0249). The latter association was independent of gestational age. The AGAG/GGAA diplotype favoured both shorter gestational age and VLBW (OR = 1.82, p = 0.0234 and OR = 1.95, p = 0.0434, respectively). In contrast, AGAG homozygosity was protective for lower body mass (OR = 0.09, p = 0.0155). Our data demonstrate that some FCN2 variants associated with relatively low ficolin-2 increase the risk of VLBW and suggest that ficolin-2 is an important factor for fetal development/intrauterine growth.
Role of Acrostyle Cuticular Proteins in the Retention of an Aphid Salivary Effector
Authors: Deshoux Maëlle , Monsion Baptiste , Pichon Elodie , Jiménez Jaime , Moreno Aránzazu , Cayrol Bastien , Thébaud Gaël , Mugford Sam T. , Hogenhout Saskia A. , Blanc Stéphane , Fereres Alberto , Uzest Marilyne
Published: December 2022

To avoid the activation of plant defenses and ensure sustained feeding, aphids are assumed to use their mouthparts to deliver effectors into plant cells. A recent study has shown that effectors detected near feeding sites are differentially distributed in plant tissues. However, the precise process of effector delivery into specific plant compartments is unknown. The acrostyle, a cuticular organ located at the tip of maxillary stylets that transiently binds plant viruses via its stylin proteins, may participate in this specific delivery process. Here, we demonstrate that Mp10, a saliva effector released into the plant cytoplasm during aphid probing, binds to the acrostyles of Acyrthosiphon pisum and Myzus persicae. The effector probably interacts with Stylin-03 as a lowered Mp10-binding to the acrostyle was observed upon RNAi-mediated reduction in Stylin-03 production. In addition, Stylin-03 and Stylin-01 RNAi aphids exhibited changes in their feeding behavior as evidenced by electrical penetration graph experiments showing longer aphid probing behaviors associated with watery saliva release into the cytoplasm of plant cells. Taken together, these data demonstrate that the acrostyle also has effector binding capacity and supports its role in the delivery of aphid effectors into plant cells.
Mesenchymal Stem Cells in Burn Wound Management
Authors: Surowiecka Agnieszka , Chrapusta Anna , Klimeczek-Chrapusta Maria , Korzeniowski Tomasz , Drukała Justyna , Strużyna Jerzy
Published: December 2022

Mesenchymal stem cells have a known regenerative potential and are used in many indications. They secrete many growth factors, including for fibroblasts (FGF), endothelium (VEGF), as well as 14 anti-inflammatory cytokines, and they stimulate tissue regeneration, promoting the secretion of proteins and glycosaminoglycans of extracellular matrices, such as collagen I, II, III, and V, elastin, and also metalloproteinases. They secrete exosomes that contain proteins, nucleic acids, lipids, and enzymes. In addition, they show the activity of inactivating free radicals. The aim of this study was an attempt to collect the existing literature on the use of stem cells in the treatment of a burn wound. There were 81 studies included in the analysis. The studies differed in terms of the design, burn wound model, source of stem cells, and methods of cellular therapy application. No major side effects were reported, and cellular therapy reduced the healing time of the burn wound. Few case reports on human models did not report any serious adverse events. However, due to the heterogeneity of the evidence, cellular therapy in burn wound treatment remains an experimental method.
Assessment of Pristine Carbon Nanotubes Toxicity in Rodent Models
Authors: Witkowska Marta , Florek Ewa , Mrówczyński Radosław
Published: December 2022

Carbon nanotubes are increasingly used in nanomedicine and material chemistry research, mostly because of their small size over a large surface area. Due to their properties, they are very attractive candidates for use in medicine and as drug carriers, contrast agents, biological platforms, and so forth. Carbon nanotubes (CNTs) may affect many organs, directly or indirectly, so there is a need for toxic effects evaluation. The main mechanisms of toxicity include oxidative stress, inflammation, the ability to damage DNA and cell membrane, as well as necrosis and apoptosis. The research concerning CNTs focuses on different animal models, functionalization, ways of administration, concentrations, times of exposure, and a variety of properties, which have a significant effect on toxicity. The impact of pristine CNTs on toxicity in rodent models is being increasingly studied. However, it is immensely difficult to compare obtained results since there are no standardized tests. This review summarizes the toxicity issues of pristine CNTs in rodent models, as they are often the preferred model for human disease studies, in different organ systems, while considering the various factors that affect them. Regardless, the results showed that the majority of toxicological studies using rodent models revealed some toxic effects. Even with different properties, carbon nanotubes were able to generate inflammation, fibrosis, or biochemical changes in different organs. The problem is that there are only a small amount of long-term toxicity studies, which makes it impossible to obtain a good understanding of later effects. This article will give a greater overview of the situation on toxicity in many organs. It will allow researchers to look at the toxicity of carbon nanotubes in a broader context and help to identify studies that are missing to properly assess toxicity.
Synthesis of Silver Nanoparticles and Detection of Glucose via Chemical Reduction with Nanocellulose as Carrier and Stabilizer
Authors: Zhang Zhiguo , Yang Guihua , He Ming , Qi Letian , Li Xincai , Chen Jiachuan
Published: December 2022

The application of silver nanoparticles (AgNPs) in antibacterial materials, glucose detection, etc., is of broad interest for researchers around the world. Nanocellulose with many excellent properties can be used as a carrier and stabilizer to assist in the synthesis of AgNPs. In this study, cellulose nanofibrils (CNFs) and cellulose nanocrystals (CNCs) were used to assist in the synthesis of AgNPs under the reduction of glucose and detection of glucose concentration under different conditions. Transmission electron microscopy (TEM) analysis showed that the AgNPs in the nanocellulose-AgNPs (NC-AgNPs) system were roughly spherical and randomly distributed on the nanocellulose. In the whole reaction system, when the concentration of nanocellulose is 0.11 mg/mL, the concentration of silver ammonia solution is 0.6 mM, and the mixing time is 2.5 h, according to the UV-Vis analysis, the absorbance of CNF-AgNPs at 425 nm exhibited a good linear relationship (R2 = 0.9945) with the glucose concentration range (5–50 μM), while the absorbance of CNC-AgNPs at 420 nm showed a good linear relationship (R2 = 0.9956) with the glucose concentration range (5–35 μM). The synthesis of NC-AgNPs can be further developed into a sensor with higher sensitivity and higher stability for detecting glucose concentration and a material with antibacterial effects.
Regulation of Apoptosis and Oxidative Stress by Oral Boswellia Serrata Gum Resin Extract in a Rat Model of Endometriosis
Authors: D’Amico Ramona , Impellizzeri Daniela , Cordaro Marika , Siracusa Rosalba , Interdonato Livia , Crupi Rosalia , Gugliandolo Enrico , Macrì Francesco , Di Paola Davide , Peritore Alessio Filippo , Fusco Roberta , Cuzzocrea Salvatore , Di Paola Rosanna
Published: December 2022

Endometriosis (EMS) is a gynecological disease characterized by inflammation, oxidative stress, and apoptosis dysregulation. This study aims to evaluate the effect of Boswellia serrata gum resin extract (BS) on the endometriotic lesions in a rat model of endometriosis. We divided female rats into three groups, including Sham, EMS, EMS + BS. In the EMS and EMS + BS groups, pathology was induced and after 7 days by the abdominal high-frequency ultrasound (hfUS) analysis the presence of the endometriotic lesions was confirmed. Subsequently, the EMS + BS group was administered with BS (100 mg/Kg) daily for another 7 days. At the end of the experiment, the hfUS analysis was repeated and the animals were sacrificed to evaluate the size and histoarchitecture of the endometriotic implants. Pelvic ultrasound showed increased size of the endometriotic lesions in the Endo group, while BS administration reduced the lesion size. The macroscopic analysis confirmed the reduced area and volume of the endometriotic lesions of the EMS + BS group. The histological analysis showed reduced characteristic of ectopic stroma and glands in the animals treated with BS. Western blot analyses were conducted to evaluate the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. BS increases the expression of Nfr2 in the nucleus and the expression of its downstream antioxidant proteins NQO-1 and HO-1. Moreover, it reduced lipid peroxidation and increased glutathione (GSH) levels, and glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities. BS administration also restored the impaired apoptotic pathway in the lesions by reducing Bcl-2 expression and increasing Bax and cleaved caspase 9 levels. The BS apoptotic effect was also confirmed by the cleavage of PARP, another specific marker of apoptosis, and by the TUNEL assay. Our results show that BS administration resulted in an effective and coordinated suppression of Endo owing to its antioxidant and antiapoptotic activities.