bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome and Metabolome Profiling Provide Insights into Flavonoid Synthesis in Acanthus ilicifolius Linn
Authors: Wu Zhihua , Wang Zhen , Xie Yaojian , Liu Guo , Shang Xiuhua , Zhan Ni
Published: March 2023

Acanthus ilicifolius is an important medicinal plant in mangrove forests, which is rich in secondary metabolites with various biological activities. In this study, we used transcriptomic analysis to obtain differentially expressed genes in the flavonoid metabolic pathway and metabolomic methods to detect changes in the types and content in the flavonoid metabolic synthesis pathway. The results showed that DEGs were identified in the mature roots vs. leaves comparison (9001 up-regulated and 8910 down-regulated), mature roots vs. stems comparison (5861 up-regulated and 7374 down-regulated), and mature stems vs. leaves comparison (10,837 up-regulated and 11,903 down-regulated). Furthermore, two AiCHS genes and four AiCHI genes were up-regulated in the mature roots vs. stems of mature A. ilicifolius, and were down-regulated in mature stems vs. leaves, which were highly expressed in the A. ilicifolius stems. A total of 215 differential metabolites were found in the roots vs. leaves of mature A. ilicifolius, 173 differential metabolites in the roots vs. stems, and 228 differential metabolites in the stems vs. leaves. The metabolomic results showed that some flavonoids in A. ilicifolius stems were higher than in the roots. A total of 18 flavonoid differential metabolites were detected in the roots, stems, and leaves of mature A. ilicifolius. In mature leaves, quercetin-3-O-glucoside-7-O-rhamnoside, gossypitrin, isoquercitrin, quercetin 3,7-bis-O-β-D-glucoside, and isorhamnetin 3-O-β-(2″-O-acetyl-β-D-glucuronide) were found in a high content, while in mature roots, di-O-methylquercetin and isorhamnetin were the major compounds. The combined analysis of the metabolome and transcriptome revealed that DEGs and differential metabolites were related to flavonoid biosynthesis. This study provides a theoretical basis for analyzing the molecular mechanism of flavonoid synthesis in A. ilicifolius and provides a reference for further research and exploitation of its medicinal value.
Multi-Hazard Susceptibility Assessment Using the Analytical Hierarchy Process in Coastal Regions of South Aegean Volcanic Arc Islands
Authors: Krassakis Pavlos , Karavias Andreas , Nomikou Paraskevi , Karantzalos Konstantinos , Koukouzas Nikolaos , Athinelis Ioannis , Kazana Stavroula , Parcharidis Issaak
Published: March 2023

Coastal environments are highly recognized for their spectacular morphological features and economic activities, such as agriculture, maritime traffic, fishing, and tourism. In the context of climate change and the evolution of physical processes, the occurrence of intense natural phenomena adjacent to populated coastal areas may result in natural hazards, causing human and/or structural losses. As an outcome, scientific interest in researching and assessing multi-hazard susceptibility techniques has increased rapidly in an effort to better understand spatial patterns that are threatening coastal exposed elements, with or without temporal coincidence. The islands of Milos and Thira (Santorini Island) in Greece are prone to natural hazards due to their unique volcano-tectonic setting, the high number of tourist visits annually, and the unplanned expansion of urban fabric within the boundaries of the low-lying coastal zone. The main goal of this research is to analyze the onshore coastal terrain’s susceptibility to natural hazards, identifying regions that are vulnerable to soil erosion, torrential flooding, landslides and tsunamis. Therefore, the objective of this work is the development of a multi-hazard approach to the South Aegean Volcanic Arc (SAVA) islands, integrating them into a superimposed susceptibility map utilizing Multi-Criteria Decision-Making (MCDM) analysis. The illustrated geospatial workflow introduces a promising multi-hazard tool that can be implemented in low-lying coastal regions globally, regardless of their morphometric and manmade characteristics. Consequently, findings indicated that more than 30% of built-up areas, 20% of the transportation network, and 50% of seaports are within the high and very high susceptible zones, in terms of the Extended Low Elevation Coastal Zone (ELECZ). Coastal managers and decision-makers must develop a strategic plan in order to minimize potential economic and natural losses, private property damage, and tourism infrastructure degradation from potential inundation and erosion occurrences, which are likely to increase in the foreseeable future.
Leveraging Deep Convolutional Neural Network for Point Symbol Recognition in Scanned Topographic Maps
Authors: Huang Wenjun , Sun Qun , Yu Anzhu , Guo Wenyue , Xu Qing , Wen Bowei , Xu Li
Published: March 2023

Point symbols on a scanned topographic map (STM) provide crucial geographic information. However, point symbol recognition entails high complexity and uncertainty owing to the stickiness of map elements and singularity of symbol structures. Therefore, extracting point symbols from STMs is challenging. Currently, point symbol recognition is performed primarily through pattern recognition methods that have low accuracy and efficiency. To address this problem, we investigated the potential of a deep learning-based method for point symbol recognition and proposed a deep convolutional neural network (DCNN)-based model for this task. We created point symbol datasets from different sources for training and prediction models. Within this framework, atrous spatial pyramid pooling (ASPP) was adopted to handle the recognition difficulty owing to the differences between point symbols and natural objects. To increase the positioning accuracy, the k-means++ clustering method was used to generate anchor boxes that were more suitable for our point symbol datasets. Additionally, to improve the generalization ability of the model, we designed two data augmentation methods to adapt to symbol recognition. Experiments demonstrated that the deep learning method considerably improved the recognition accuracy and efficiency compared with classical algorithms. The introduction of ASPP in the object detection algorithm resulted in higher mean average precision and intersection over union values, indicating a higher recognition accuracy. It is also demonstrated that data augmentation methods can alleviate the cross-domain problem and improve the rotation robustness. This study contributes to the development of algorithms and the evaluation of geographic elements extracted from STMs.
Biotherapy Using Probiotics as Therapeutic Agents to Restore the Gut Microbiota to Relieve Gastrointestinal Tract Inflammation, IBD, IBS and Prevent Induction of Cancer
Authors: Dahiya Divakar , Nigam Poonam Singh
Published: March 2023

The gut microbiota is composed of several microbial strains with diverse and variable compositions in both healthy and sick people. An undisturbed gut microbiota needs to be sustained in order to perform all physiological, metabolic, and immune functions in a normal way to prevent the development of diseases. This article has reviewed the published information on the issue of disruption of the balance of the gut microbiota. This disruption could be for many reasons, such as microbial infection in the gastrointestinal tract, food poisoning, diarrhoea, chemotherapy, malnutrition, lifestyle, and ageing. If this disruption is not restored to normal, it might cause dysbiosis. Eventually, a gut microbiota interrupted by dysbiosis might initiate several health issues, such as inflammation of the gastrointestinal tract, the induction of cancer, and the progression of a variety of diseases such as irritable bowel syndrome and inflammatory bowel disease. This review concluded that biotherapy is a natural way of using probiotic products, whether in form of food, beverages, or supplements, to restore the gut microbiota disrupted by dysbiosis. Metabolites secreted by the ingested probiotics help to relieve gastrointestinal tract inflammation and can avoid the induction of cancer.
Genome-Wide Analysis of Long Non-Coding RNAs Related to UV-B Radiation in the Antarctic Moss Pohlia nutans
Authors: Fang Shuo , Cong Bailin , Zhao Linlin , Liu Chenlin , Zhang Zhaohui , Liu Shenghao
Published: March 2023

Antarctic organisms are consistently suffering from multiple environmental pressures, especially the strong UV radiation caused by the loss of the ozone layer. The mosses and lichens dominate the vegetation of the Antarctic continent, which grow and propagate in these harsh environments. However, the molecular mechanisms and related regulatory networks of these Antarctic plants against UV-B radiation are largely unknown. Here, we used an integrated multi-omics approach to study the regulatory mechanism of long non-coding RNAs (lncRNAs) of an Antarctic moss (Pohlia nutans) in response to UV-B radiation. We identified a total of 5729 lncRNA sequences by transcriptome sequencing, including 1459 differentially expressed lncRNAs (DELs). Through functional annotation, we found that the target genes of DELs were significantly enriched in plant-pathogen interaction and the flavonoid synthesis pathway. In addition, a total of 451 metabolites were detected by metabonomic analysis, and 97 differentially change metabolites (DCMs) were found. Flavonoids account for 20% of the total significantly up-regulated metabolites. In addition, the comprehensive transcriptome and metabolome analyses revealed the co-expression pattern of DELs and DCMs of flavonoids. Our results provide insights into the regulatory network of lncRNA under UV-B radiation and the adaptation of Antarctic moss to the polar environments.
Molecular Profiling of Inflammatory Processes in a Mouse Model of IC/BPS: From the Complete Transcriptome to Major Sex-Related Histological Features of the Urinary Bladder
Authors: Peskar Dominika , Kuret Tadeja , Lakota Katja , Erman Andreja
Published: March 2023

Animal models are invaluable in the research of the pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS), a chronic aseptic urinary bladder disease of unknown etiology that primarily affects women. Here, a mouse model of IC/BPS was induced with multiple low-dose cyclophosphamide (CYP) applications and thoroughly characterized by RNA sequencing, qPCR, Western blot, and immunolabeling to elucidate key inflammatory processes and sex-dependent differences in the bladder inflammatory response. CYP treatment resulted in the upregulation of inflammatory transcripts such as Ccl8, Eda2r, and Vegfd, which are predominantly involved in innate immunity pathways, recapitulating the crucial findings in the bladder transcriptome of IC/BPS patients. The JAK/STAT signaling pathway was analyzed in detail, and the JAK3/STAT3 interaction was found to be most activated in cells of the bladder urothelium and lamina propria. Sex-based data analysis revealed that cell proliferation was more pronounced in male bladders, while innate immunity and tissue remodeling processes were the most distinctive responses of female bladders to CYP treatment. These processes were also reflected in prominent histological changes in the bladder. The study provides an invaluable reference dataset for preclinical research on IC/BPS and an insight into the sex-specific mechanisms involved in the development of IC/BPS pathology, which may explain the more frequent occurrence of this disease in women.
Expression of GADD45G and CAPRIN1 in Human Nucleus Pulposus: Implications for Intervertebral Disc Degeneration
Authors: Kawaguchi Koki , Akeda Koji , Yamada Junichi , Hasegawa Takahiro , Takegami Norihiko , Fujiwara Tatsuhiko , Sudo Akihiro
Published: March 2023

Marked cellular changes occur in human intervertebral disc (IVD) degeneration during disc degeneration with biochemical changes. Genome-wide analysis of the DNA methylation profile has identified 220 differentially methylated loci associated with human IVD degeneration. Among these, two cell-cycle–associated genes, growth arrest and DNA damage 45 gamma (GADD45G) and cytoplasmic activation/proliferation-associated protein-1 (CAPRIN1), were focused on. The expression of GADD45G and CAPRIN1 in human IVDs remains unknown. We aimed to examine the expression of GADD45G and CAPRIN1 in human nucleus pulposus (NP) cells and evaluate those in human NP tissues in the early and advanced stages of degeneration according to Pfirrmann magnetic resonance imaging (MRI) and histological classifications. Human NP cells were cultured as monolayers after isolation from NP tissues by sequential enzyme digestion. Total RNA was isolated, and the mRNA expression of GADD45G and CAPRIN1 was quantified using real-time polymerase chain reaction. To examine the effects of pro-inflammatory cytokines on mRNA expression, human NP cells were cultured in the presence of IL-1β. Protein expression was evaluated using Western blotting and immunohistochemistry. GADD45G and CAPRIN1 expression was identified in human NP cells at both mRNA and protein levels. The percentage of cells immunopositive for GADD45G and CAPRIN1 significantly increased according to the Pfirrmann grade. A significant correlation between the histological degeneration score and the percentage of GADD45G-immunopositive cells was identified, but not with that of CAPRIN1-immunopositive cells. The expression of cell-cycle-associated proteins (GADD45G and CAPRIN1) was enhanced in human NP cells at an advanced stage of degeneration, suggesting that it may be regulated during the progression of IVD degeneration to maintain the integrity of human NP tissues by controlling cell proliferation and apoptosis under epigenetic alteration.
Antiplatelet Effect of Daphnetin Is Regulated by cPLA2-Mediated Thromboxane A2 Generation in Mice
Authors: Chaudhary Preeti Kumari , Kim Sanggu , Kim Soochong
Published: March 2023

Coumarin derivatives have been recognized for their antithrombotic, anti-inflammatory, and antioxidant properties, and daphnetin is one of the natural coumarin derivatives isolated from Daphne Koreana Nakai. Although the pharmacological value of daphnetin is well documented in diverse biological activities, its antithrombotic effect has not been studied to date. Here, we characterized the role and underlying mechanism of daphnetin in the regulation of platelet activation using murine platelets. In order to check the effect of daphnetin on platelet function, we first measured the effect of daphnetin on platelet aggregation and secretion. Collagen-induced platelet aggregation and dense granule secretion were partially inhibited by daphnetin. Interestingly, 2-MeSADP-induced secondary waves of aggregation and secretion were completely inhibited by daphnetin. It is known that 2-MeSADP-induced secretion and the resultant secondary wave of aggregation are mediated by the positive feedback effect of thromboxane A2 (TxA2) generation, suggesting the important role of daphnetin on TxA2 generation in platelets. Consistently, daphnetin did not affect the 2-MeSADP-induced platelet aggregation in aspirinated platelets where the contribution of TxA2 generation was blocked. Additionally, platelet aggregation and secretion induced by a low concentration of thrombin, which is affected by the positive feedback effect of TxA2 generation, were partially inhibited in the presence of daphnetin. Importantly, 2-MeSADP- and thrombin-induced TxA2 generation was significantly inhibited in the presence of daphnetin, confirming the role of daphnetin on TxA2 generation. Finally, daphnetin significantly inhibited 2-MeSADP-induced cytosolic phospholipase A2 (cPLA2) and ERK phosphorylation in non-aspirinated platelets. Only cPLA2 phosphorylation, not ERK phosphorylation, was significantly inhibited by daphnetin in aspirinated platelets. In conclusion, daphnetin plays a critical role in platelet function by inhibiting TxA2 generation through the regulation of cPLA2 phosphorylation.
Asymmetric Organocatalytic Mannich Reaction in the Synthesis of Hybrid Isoindolinone-Pyrazole and Isoindolinone-Aminal from Functionalized α-Amidosulfone
Authors: Di Mola Antonia , De Piano Felice , Serusi Lorenzo , Pierri Giovanni , Palombi Laura , Massa Antonio
Published: March 2023

The investigation of the reactivity of an α-amido sulfone derived from 2-formyl benzoate under organocatalytic conditions in the presence of acetylacetone allowed the synthesis of a new heterocyclic hybrid isoindolinone-pyrazole with high enantiomeric excess. Dibenzylamine was also used as a nucleophile to afford an isoindolinone with aminal substituent in 3-position in suitable selectivity. The use of Takemoto’s bifunctional organocatalyst not only led to observed enantioselectivity but was also important in accomplishing the cyclization step in both cases. Notably, this catalytic system proved to be particularly effective in comparison to widely used phase transfer catalysts.
Interaction of SARS-CoV-2 Nucleocapsid Protein and Human RNA Helicases DDX1 and DDX3X Modulates Their Activities on Double-Stranded RNA
Authors: Lodola Camilla , Secchi Massimiliano , Sinigiani Virginia , De Palma Antonella , Rossi Rossana , Perico Davide , Mauri Pier Luigi , Maga Giovanni
Published: March 2023

The nucleocapsid protein Np of SARS-CoV-2 is involved in the replication, transcription, and packaging of the viral genome, but it also plays a role in the modulation of the host cell innate immunity and inflammation response. Ectopic expression of Np alone was able to induce significant changes in the proteome of human cells. The cellular RNA helicase DDX1 was among the proteins whose levels were increased by Np expression. DDX1 and its related helicase DDX3X were found to physically interact with Np and to increase 2- to 4-fold its affinity for double-stranded RNA in a helicase-independent manner. Conversely, Np inhibited the RNA helicase activity of both proteins. These functional interactions among Np and DDX1 and DDX3X highlight novel possible roles played by these host RNA helicases in the viral life cycle.
Exploration of the Antioxidant Effect of Spermidine on the Ovary and Screening and Identification of Differentially Expressed Proteins
Authors: Jiang Dongmei , Guo Yongni , Niu Chunyang , Long Shiyun , Jiang Yilong , Wang Zelong , Wang Xin , Sun Qian , Ling Weikang , An Xiaoguang , Ji Chengweng , Zhao Hua , Kang Bo
Published: March 2023

Spermidine is a naturally occurring polyamine compound that has many biological functions, such as inducing autophagy and anti-inflammatory and anti-aging effects. Spermidine can affect follicular development and thus protect ovarian function. In this study, ICR mice were fed exogenous spermidine drinking water for three months to explore the regulation of ovarian function by spermidine. The results showed that the number of atretic follicles in the ovaries of spermidine-treated mice was significantly lower than that in the control group. Antioxidant enzyme activities (SOD, CAT, T-AOC) significantly increased, and MDA levels significantly decreased. The expression of autophagy protein (Beclin 1 and microtubule-associated protein 1 light chain 3 LC3 II/I) significantly increased, and the expression of the polyubiquitin-binding protein p62/SQSTM 1 significantly decreased. Moreover, we found 424 differentially expressed proteins (DEPs) were upregulated, and 257 were downregulated using proteomic sequencing. Gene Ontology and KEGG analyses showed that these DEPs were mainly involved in lipid metabolism, oxidative metabolism and hormone production pathways. In conclusion, spermidine protects ovarian function by reducing the number of atresia follicles and regulating the level of autophagy protein, antioxidant enzyme activity, and polyamine metabolism in mice.
SCL14 Inhibits the Functions of the NAC043–MYB61 Signaling Cascade to Reduce the Lignin Content in Autotetraploid Populus hopeiensis
Authors: Wu Jian , Kong Bo , Zhou Qing , Sun Qian , Sang Yaru , Zhao Yifan , Yuan Tongqi , Zhang Pingdong
Published: March 2023

Whole-genome duplication often results in a reduction in the lignin content in autopolyploid plants compared with their diploid counterparts. However, the regulatory mechanism underlying variation in the lignin content in autopolyploid plants remains unclear. Here, we characterize the molecular regulatory mechanism underlying variation in the lignin content after the doubling of homologous chromosomes in Populus hopeiensis. The results showed that the lignin content of autotetraploid stems was significantly lower than that of its isogenic diploid progenitor throughout development. Thirty-six differentially expressed genes involved in lignin biosynthesis were identified and characterized by RNA sequencing analysis. The expression of lignin monomer synthase genes, such as PAL, COMT, HCT, and POD, was significantly down-regulated in tetraploids compared with diploids. Moreover, 32 transcription factors, including MYB61, NAC043, and SCL14, were found to be involved in the regulatory network of lignin biosynthesis through weighted gene co-expression network analysis. We inferred that SCL14, a key repressor encoding the DELLA protein GAI in the gibberellin (GA) signaling pathway, might inhibit the NAC043–MYB61 signaling functions cascade in lignin biosynthesis, which results in a reduction in the lignin content. Our findings reveal a conserved mechanism in which GA regulates lignin synthesis after whole-genome duplication; these results have implications for manipulating lignin production.
Whole Genome Resequencing Revealed the Effect of Helicase yqhH Gene on Regulating Bacillus thuringiensis LLP29 against Ultraviolet Radiation Stress
Authors: Ma Weibo , Guan Xiong , Miao Ying , Zhang Lingling
Published: March 2023

Bacillus thuringiensis (Bt) is a widely used microbial pesticide. However, its duration of effectiveness is greatly shortened due to the irradiation of ultraviolet rays, which seriously hinders the application of Bt preparations. Therefore, it is of great importance to study the resistance mechanism of Bt to UV at the molecular level to improve the UV-resistance of Bt strains. In order to know the functional genes in the UV resistance, the genome of UV-induced mutant Bt LLP29-M19 was re-sequenced and compared with the original strain Bt LLP29. It was shown that there were 1318 SNPs, 31 InDels, and 206 SV between the mutant strain and the original strain Bt LLP29 after UV irradiation, which were then analyzed for gene annotation. Additionally, a mutated gene named yqhH, a member of helicase superfamily II, was detected as an important candidate. Then, yqhH was expressed and purified successfully. Through the result of the enzymatic activity in vitro, yqhH was found to have ATP hydrolase and helicase activities. In order to further verify its function, the yqhH gene was knocked out and complemented by homologous recombinant gene knockout technology. The survival rate of the knockout mutant strain Bt LLP29-ΔyqhH was significantly lower than that of the original strain Bt LLP29 and the back-complemented strain Bt LLP29-ΔyqhH-R after treated with UV. Meanwhile, the total helicase activity was not significantly different on whether Bt carried yqhH or not. All of these greatly enrich important molecular mechanisms of Bt when it is in UV stress.
Novel Rigidochromic and Anti-Kasha Dual Emission Fluorophores Based on D-π-A Dyads as the Promising Materials for Potential Applications Ranging from Optoelectronics and Optical Sensing to Biophotonics and Medicine
Authors: Lermontova Svetlana A. , Arsenyev Maxim V. , Cherkasov Anton V. , Fukin Georgy K. , Afanasyev Andrey V. , Yudintsev Andrey V. , Grigoryev Ilya S. , Ladilina Elena Yu. , Lyubova Tatyana S. , Shilyagina Natalia Yu. , Balalaeva Irina V. , Klapshina Larisa G. , Piskunov Alexandr V.
Published: March 2023

Today we see an increasing demand for new fluorescent materials exhibiting various sensory abilities due to their broad applicability ranging from the construction of flexible devices to bioimaging. In this paper, we report on the new fluorescent pigments AntTCNE, PyrTCNE, and PerTCNE which consist of 3–5 fused aromatic rings substituted with tricyanoethylene fragments forming D-π-A diad. Our studies reveal that all three compounds exhibit pronounced rigidochromic properties, i.e., strong sensitivity of their fluorescence to the viscosity of the local environment. We also demonstrate that our new pigments belong to a very rare type of organic fluorophores which do not obey the well-known empirical Kasha’rule stating that photoluminescence transition always occurs from the lowest excited state of an emitting molecule. This rare spectral feature of our pigments is accompanied by an even rarer capability of spectrally and temporally well-resolved anti-Kasha dual emission (DE) from both higher and lowest electronic states in non-polar solvents. We show that among three new pigments, PerTCNE has significant potential as the medium-bandgap non-fullerene electron acceptor. Such materials are now highly demanded for indoor low-power electronics and portable devices for the Internet-of-Things. Additionally, we demonstrate that PyrTCNE has been successfully used as a structural unit in template assembling of the new cyanoarylporphyrazine framework with 4 D-π-A dyads framing this macrocycle (Pyr4CN4Pz). Similarly to its structural unit, Pyr4CN4Pz is also the anti-Kasha fluorophore, exhibiting intensive DE in viscous non-polar medium and polymer films, which strongly depends on the polarity of the local environment. Moreover, our studies showed high photodynamic activity of this new tetrapyrrole macrocycle which is combined with its unique sensory capacities (strong sensitivity of its fluorescent properties to the local environmental stimuli such as viscosity and polarity. Thus, Pyr4CN4Pz can be considered the first unique photosensitizer that potentially enables the real-time combination of photodynamic therapy and double-sensory approaches which is very important for modern biomedicine.
Molecular Anatomy of the EML4-ALK Fusion Protein for the Development of Novel Anticancer Drugs
Authors: Cheon So Yeong , Kwon Sunghark
Published: March 2023

The EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene in non-small-cell lung cancer (NSCLC) was first identified in 2007. As the EML4-ALK fusion protein promotes carcinogenesis in lung cells, much attention has been paid to it, leading to the development of therapies for patients with NSCLC. These therapies include ALK tyrosine kinase inhibitors and heat shock protein 90 inhibitors. However, detailed information on the entire structure and function of the EML4-ALK protein remains deficient, and there are many obstacles to overcome in the development of novel anticancer agents. In this review, we describe the respective partial structures of EML4 and ALK that are known to date. In addition to their structures, noteworthy structural features and launched inhibitors of the EML4-ALK protein are summarized. Furthermore, based on the structural features and inhibitor-binding modes, we discuss strategies for the development of novel inhibitors targeting the EML4-ALK protein.
Sarcoma: Molecular Pathology, Diagnostics, and Therapeutics
Authors: Miwa Shinji , Yamamoto Norio , Tsuchiya Hiroyuki
Published: March 2023

Although the incidence of sarcomas accounts for less than 1% of all malignancies, they are classified into more than 50 different subtypes with different biological behaviours [...]
Aconitum carmichaelii Debx. Attenuates Heart Failure through Inhibiting Inflammation and Abnormal Vascular Remodeling
Authors: Xing Ziwei , Chen Junren , Yu Tingting , Li Xu , Dong Wei , Peng Cheng , Li Dan
Published: March 2023

Heart failure (HF) is the most common complication following myocardial infarction, closely associated with ventricular remodeling. Aconitum carmichaelii Debx., a traditional Chinese herb, possesses therapeutic effects on HF and related cardiac diseases. However, its effects and mechanisms on HF-associated cardiac diseases are still unclear. In the present study, a water extraction of toasted Aconitum carmichaelii Debx. (WETA) was verified using UPLC-Q/TOF-MS. The heart function of HF rats was assessed by echocardiography and strain analysis, and myocardial injury was measured by serum levels of CK-MB, cTnT, and cTnI. The pathological changes of cardiac tissues were evaluated by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and Masson’s trichrome staining. Additionally, the levels of inflammation-related genes and proteins and components related to vascular remodeling were detected by RT-qPCR, Western blot, and immunofluorescence. WETA significantly inhibited the changes in echocardiographic parameters and the increase in heart weight, cardiac infarction size, the myonecrosis, edema, and infiltration of inflammatory cells, collagen deposition in heart tissues, and also mitigated the elevated serum levels of CK-MB, cTnT, and cTnI in ISO-induced rats. Additionally, WETA suppressed the expressions of inflammatory genes, including IL-1β, IL-6, and TNF-α and vascular injury-related genes, such as VCAM1, ICAM1, ANP, BNP, and MHC in heart tissues of ISO-induced HF rats, which were further confirmed by Western blotting and immunofluorescence. In summary, the myocardial protective effect of WETA was conferred through inhibiting inflammatory responses and abnormal vascular remodeling in ISO-treated rats.
Isolation and NMR Scaling Factors for the Structure Determination of Lobatolide H, a Flexible Sesquiterpene from Neurolaena lobata
Authors: Kovács Tibor , Lajter Ildikó , Kúsz Norbert , Schelz Zsuzsanna , Bózsity-Faragó Noémi , Borbás Anikó , Zupkó István , Krupitza Georg , Frisch Richard , Hohmann Judit , Vasas Andrea , Mándi Attila
Published: March 2023

A new flexible germacranolide (1, lobatolide H) was isolated from the aerial parts of Neurolaena lobata. The structure elucidation was performed by classical NMR experiments and DFT NMR calculations. Altogether, 80 theoretical level combinations with existing 13C NMR scaling factors were tested, and the best performing ones were applied on 1. 1H and 13C NMR scaling factors were also developed for two combinations utilizing known exomethylene containing derivatives, and the results were complemented by homonuclear coupling constant (JHH) and TDDFT-ECD calculations to elucidate the stereochemistry of 1. Lobatolide H possessed remarkable antiproliferative activity against human cervical tumor cell lines with different HPV status (SiHa and C33A), induced cell cycle disturbance and exhibited a substantial antimigratory effect in SiHa cells.
Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells
Authors: Voulgaridou Georgia-Persephoni , Theologidis Vasileios , Venetikidou Maria , Tsochantaridis Ilias , Tsolou Avgi , Koffa Maria , Panayiotidis Mihalis I. , Pappa Aglaia
Published: March 2023

Aldehyde dehydrogenase 3A1 (ALDH3A1) oxidizes medium-chain aldehydes to their corresponding carboxylic acids. It is expressed at high rates in the human cornea, where it has been characterized as a multi-functional protein displaying various cytoprotective modes of action. Previous studies identified its association with the DNA damage response (DDR) pathway. Here, we utilized a stable transfected HCE-2 (human corneal epithelium) cell line expressing ALDH3A1, to investigate the molecular mechanisms underlying the cytoprotective role(s) of ALDH3A1. Our data revealed morphological differences among the ALDH3A1-expressing and the mock-transfected HCE-2 cells accompanied by differential expression of E-cadherin. Similarly, the ALDH3A1/HCE-2 cells demonstrated higher mobility, reduced proliferation, upregulation of ZEB1, and downregulation of CDK3, and p57. The expression of ALDH3A1 also affected cell cycle progression by inducing the sequestration of HCE-2 cells at the G2/M phase. Following 16 h cell treatments with either H2O2 or etoposide, a significantly lower percentage of ALDH3A1/HCE-2 cells were apoptotic compared to the respective treated mock/HCE-2 cells. Interestingly, the protective effect of ALDH3A1 expression under these oxidative and genotoxic conditions was accompanied by a reduced formation of γ-H2AX foci and higher levels of total and phospho (Ser15) p53. Finally, ALDH3A1 was found to be localized both in the cytoplasm and the nucleus of transfected HCE-2 cells. Its cellular compartmentalization was not affected by oxidant treatment, while the mechanism by which ALDH3A1 translocates to the nucleus remains unknown. In conclusion, ALDH3A1 protects cells from both apoptosis and DNA damage by interacting with key homeostatic mechanisms associated with cellular morphology, cell cycle, and DDR.
Systematic Selection Signature Analysis of Chinese Gamecocks Based on Genomic and Transcriptomic Data
Authors: Ren Xufang , Guan Zi , Zhao Xiurong , Zhang Xinye , Wen Junhui , Cheng Huan , Zhang Yalan , Cheng Xue , Liu Yuchen , Ning Zhonghua , Qu Lujiang
Published: March 2023

Selection pressures driven by natural causes or human interference are key factors causing genome variants and signatures of selection in specific regions of the genome. Gamecocks were bred for cockfighting, presenting pea-combs, larger body sizes, stronger limbs, and higher levels of aggression than other chickens. In this study, we aimed to explore the genomic differences between Chinese gamecocks and commercial, indigenous, foreign, and cultivated breeds by detecting the regions or sites under natural or artificial selection using genome-wide association studies (GWAS), genome-wide selective sweeps based on the genetic differentiation index (FST), and transcriptome analyses. Ten genes were identified using GWAS and FST: gga-mir-6608-1, SOX5, DGKB, ISPD, IGF2BP1, AGMO, MEOX2, GIP, DLG5, and KCNMA1. The ten candidate genes were mainly associated with muscle and skeletal development, glucose metabolism, and the pea-comb phenotype. Enrichment analysis results showed that the differentially expressed genes between the Luxi (LX) gamecock and Rhode Island Red (RIR) chicken were mainly related to muscle development and neuroactive-related pathways. This study will help to understand the genetic basis and evolution of Chinese gamecocks and support the further use of gamecocks as an excellent breeding material from a genetic perspective.
Immune Activation Following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study
Authors: Titmuss E. , Milne K. , Jones M. , Ng T. , Topham J. , Brown S. , Schaeffer D. , Kalloger S. , Wilson D. , Corbett R. , Williamson L. , Mungall K. , Mungall A. , Holt R. , Nelson B. , Jones S. , Laskin J. , Lim H. , Marra M.
Published: March 2023

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual’s cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies.
Progress of Section “Biochemistry” in 2022
Authors: Supuran Claudiu T.
Published: March 2023

Of more than 16,400 papers published in 2022 in International Journal of Molecular Sciences [...]
CDDO-Me Abrogates Aberrant Mitochondrial Elongation in Clasmatodendritic Degeneration by Regulating NF-κB-PDI-Mediated S-Nitrosylation of DRP1
Authors: Lee Duk-Shin , Kim Tae-Hyun , Park Hana , Kim Ji-Eun
Published: March 2023

Clasmatodendrosis is a kind of astroglial degeneration pattern which facilitates excessive autophagy. Although abnormal mitochondrial elongation is relevant to this astroglial degeneration, the underlying mechanisms of aberrant mitochondrial dynamics are still incompletely understood. Protein disulfide isomerase (PDI) is an oxidoreductase in the endoplasmic reticulum (ER). Since PDI expression is downregulated in clasmatodendritic astrocytes, PDI may be involved in aberrant mitochondrial elongation in clasmatodendritic astrocytes. In the present study, 26% of CA1 astrocytes showed clasmatodendritic degeneration in chronic epilepsy rats. 2-cyano-3,12-dioxo-oleana-1,9(11)-dien-28-oic acid methyl ester (CDDO-Me; bardoxolone methyl or RTA 402) and SN50 (a nuclear factor-κB (NF-κB) inhibitor) ameliorated the fraction of clasmatodendritic astrocytes to 6.8 and 8.1% in CA1 astrocytes, accompanied by the decreases in lysosomal-associated membrane protein 1 (LAMP1) expression and microtubule-associated protein 1A/1B light-chain 3 (LC3)-II/LC3-I ratio, indicating the reduced autophagy flux. Furthermore, CDDO-Me and SN50 reduced NF-κB S529 fluorescent intensity to 0.6- and 0.57-fold of vehicle-treated animal level, respectively. CDDO-Me and SN50 facilitated mitochondrial fission in CA1 astrocytes, independent of dynamin-related protein 1 (DRP1) S616 phosphorylation. In chronic epilepsy rats, total PDI protein, S-nitrosylated PDI (SNO-PDI), and SNO-DRP1 levels were 0.35-, 0.34- and 0.45-fold of control level, respectively, in the CA1 region and increased CDDO-Me and SN50. Furthermore, PDI knockdown resulted in mitochondrial elongation in intact CA1 astrocytes under physiological condition, while it did not evoke clasmatodendrosis. Therefore, our findings suggest that NF-κB-mediated PDI inhibition may play an important role in clasmatodendrosis via aberrant mitochondrial elongation.
Current Knowledge on Chemosensory-Related Candidate Molecules Potentially Involved in Tick Olfaction via Haller’s Organ
Authors: Gebremedhin Mebrahtu Berhe , Xu Zhengmao , Kuang Ceyan , Shumuye Nigus Abebe , Cao Jie , Zhou Yongzhi , Zhang Houshuang , Zhou Jinlin
Published: March 2023

Ticks are obligatory hematophagous ectoparasites and vectors of many animal and human pathogens. Chemosensation plays a significant role in tick communication with their environment, including seeking out blood meal hosts. Studies on the structure and function of Haller’s organ and its components have improved our understanding regarding tick olfaction and its chemical ecology. Compared with the knowledge on insect olfaction, less is known about the molecular basis of olfaction in ticks. This review focused on the chemosensory-related candidate molecules likely involved in tick olfaction. Members of the ionotropic receptor family and a new class of odorant-binding proteins are now known to be involved in tick olfaction, which appear to differ from that of insects. These candidate molecules are more closely related to those of mites and spiders than to other arthropods. The amino acid sequences of candidate niemann–pick type C2 and microplusin-like proteins in ticks exhibit features indicating their potential role as binding proteins. In the future, more comprehensive pertinent research considering the existing shortcomings will be required to fully understand the molecular basis of tick olfactory chemoreception. This information may contribute to the development of new molecular-based control mechanisms to reduce tick populations and related disease transmission.
Comparison of Needle Knife versus Scissors Forceps for Colorectal Endoscopic Submucosal Dissection: A Prospective Randomized Study
Authors: Yachida Tatsuo , Kobara Hideki , Kozuka Kazuhiro , Nakatani Kaho , Tada Naoya , Matsui Takanori , Chiyo Taiga , Kobayashi Nobuya , Fujihara Shintaro , Nishiyama Noriko , Kondo Akihiro , Ando Yasuhisa , Okano Keiichi , Nonaka Wakako , Ishikawa Kaori , Masugata Hisashi , Masaki Tsutomu
Published: March 2023

Background and Aim: To evaluate the efficacy and safety of a grasping-type knife, called Clutch Cutter (CC), for colorectal endoscopic submucosal dissection (C-ESD). Methods: This was a randomized prospective study. Patients who underwent C-ESD for colorectal neoplasms >20 mm and <50 mm in size were enrolled, dividing into two groups: ESD using needle type of dual knife alone (D-group) and circumferential incision using dual knife followed by submucosal dissection using CC (CC-group). The primary outcome was the self-completion rate. The secondary outcomes were intraoperative complication rate, procedure time, and en bloc resection rate. Results: A total of 45 patients were allocated to the D-group and 43 to the CC-group were allocated. The self-completion rate was higher in the CC-group (87% [39/45] vs. 98% [42/43]). All of the six patients with an incomplete procedure in the D-group were completely resected with CC use. The intraoperative complication rate was not significant in either group (D vs. CC: 2% vs. 0%). The mean procedure time was significantly shorter in the D-group than that in the CC-group (62.0 vs. 81.1 min; p = 0.0036). The en bloc resection rate was 100% in the D-group and 98% in the CC-group. Conclusions: While dual knife use is superior to CC in terms of time efficiency, the use of CC may be a safe and efficacious option for achieving complete C-ESD.
Complement Binding Anti-HLA Antibodies and the Survival of Kidney Transplantation
Authors: Muñoz-Herrera Claudia , Gutiérrez-Bautista Juan , López-Nevot Miguel
Published: March 2023

Background: Antibody-mediated rejection (AMR) is one of the most important challenges in the context of renal transplantation, because the binding of de novo donor-specific antibodies (dnDSA) to the kidney graft triggers the activation of the complement, which in turn leads to loss of transplant. In this context, the objective of this study was to evaluate the association between complement-fixing dnDSA antibodies and graft loss as well as the possible association between non-complement-fixing antibodies and transplanted organ survival in kidney transplant recipients. Methods: Our study included a cohort of 245 transplant patients over a 5-year period at Virgen de las Nieves University Hospital (HUVN) in Granada, Spain. Results: dnDSA was observed in 26 patients. Of these patients, 17 had non-complement-fixing dnDSA and 9 had complement-fixing dnDSA. Conclusions: Our study demonstrated a significant association between the frequency of rejection and renal graft loss and the presence of C1q-binding dnDSA. Our results show the importance of the individualization of dnDSA, classifying them according to their ability to activate the complement, and suggest that the detection of complement-binding capacity by dnDSA could be used as a prognostic marker to predict AMR outcome and graft survival in kidney transplant patients who develop dnDSA.
Primary Proximal ACL Repair: A Biomechanical Evaluation of Different Arthroscopic Suture Configurations
Authors: Rosslenbroich Steffen B. , Achtnich Andrea , Brodkorb Cathrin , Kösters Clemens , Kreis Carolin , Metzlaff Sebastian , Schliemann Benedikt , Petersen Wolf
Published: March 2023

Purpose: Several suture techniques have been described in the past for direct ACL repair with poor healing capacity and a high re-rupture rate. Therefore, we investigated a refixation technique for acute primary proximal ACL repair. The purpose of this study is to compare the biomechanical properties of different suture configurations using a knotless anchor. Methods: In this study, 35 fresh-frozen porcine knees underwent proximal ACL refixation. First, in 10 porcine femora, the biomechanical properties of the knotless anchor, without the ligament attached, were tested. Then, three different suture configurations were evaluated to reattach the remaining ACL. Using a material testing machine, the structural properties were evaluated for cyclic loading followed by loading to failure. Results: The ultimate failure load of the knotless anchor was 198, 76 N ± 23, 4 N significantly higher than all of the tested ACL suture configurations. Comparing the different configurations, the modified Kessler–Bunnell suture showed significant superior ultimate failure load, with 81, 2 N ± 15, 6 N compared to the twofold and single sutures (50, 5 N ± 14 N and 37, 5 ± 3, 8 N). In cyclic loading, there was no significant difference noted for the different configurations in terms of stiffness and elongation. Conclusions: The results of this in vitro study show that when performing ACL suture using a knotless anchor, a modified Kessler–Bunnell suture provides superior biomechanical properties than a single and a twofold suture. Within this construct, no failure at the bone–anchor interface was seen. Clinical relevance: Since primary suture repair techniques of ACL tears have been abandoned because of inconsistent results, ACL reconstruction remains the gold standard of treating ACL tears. However, with the latest improvements in surgical techniques, instrumentation, hardware and imaging, primary ACL suture repair might be a treatment option for a select group of patients. By establishing an arthroscopic technique in which proximal ACL avulsion can be reattached, the original ACL can be preserved by using a knotless anchor and a threefold suture configuration. Nevertheless, this technique provides an inferior ultimate failure load compared to graft techniques, so a careful rehabilitation program must be followed if using this technique in vivo.
Ketoprofen-Based Polymer-Drug Nanoparticles Provide Anti-Inflammatory Properties to HA/Collagen Hydrogels
Authors: Halfter Norbert , Espinosa-Cano Eva , Pontes-Quero Gloria María , Ramírez-Jiménez Rosa Ana , Heinemann Christiane , Möller Stephanie , Schnabelrauch Matthias , Wiesmann Hans-Peter , Hintze Vera , Aguilar Maria Rosa
Published: March 2023

Current limitations of wound dressings for treating chronic wounds require the development of novel approaches. One of these is the immune-centered approach, which aims to restore the pro-regenerative and anti-inflammatory properties of macrophages. Under inflammatory conditions, ketoprofen nanoparticles (KT NPs) can reduce pro-inflammatory markers of macrophages and increase anti-inflammatory cytokines. To assess their suitability as part of wound dressings, these NPs were combined with hyaluronan (HA)/collagen-based hydro- (HGs) and cryogels (CGs). Different HA and NP concentrations and loading techniques for NP incorporation were used. The NP release, gel morphology, and mechanical properties were studied. Generally, colonialization of the gels with macrophages resulted in high cell viability and proliferation. Furthermore, direct contact of the NPs to the cells reduced the level of nitric oxide (NO). The formation of multinucleated cells on the gels was low and further decreased by the NPs. For the HGs that produced the highest reduction in NO, extended ELISA studies showed reduced levels of the pro-inflammatory markers PGE2, IL-12 p40, TNF-α, and IL-6. Thus, HA/collagen-based gels containing KT NPs may represent a novel therapeutic approach for treating chronic wounds. Whether effects observed in vitro translate into a favorable profile on skin regeneration in vivo will require rigorous testing.