bluuebunny/crossref_metadata_2025 huggingface dataset:
Sustainable Biomass Lignin-Based Hydrogels: A Review on Properties, Formulation, and Biomedical Applications
Authors: Hachimi Alaoui Chaymaa , Réthoré Gildas , Weiss Pierre , Fatimi Ahmed
Published: August 2023

Different techniques have been developed to overcome the recalcitrant nature of lignocellulosic biomass and extract lignin biopolymer. Lignin has gained considerable interest owing to its attractive properties. These properties may be more beneficial when including lignin in the preparation of highly desired value-added products, including hydrogels. Lignin biopolymer, as one of the three major components of lignocellulosic biomaterials, has attracted significant interest in the biomedical field due to its biocompatibility, biodegradability, and antioxidant and antimicrobial activities. Its valorization by developing new hydrogels has increased in recent years. Furthermore, lignin-based hydrogels have shown great potential for various biomedical applications, and their copolymerization with other polymers and biopolymers further expands their possibilities. In this regard, lignin-based hydrogels can be synthesized by a variety of methods, including but not limited to interpenetrating polymer networks and polymerization, crosslinking copolymerization, crosslinking grafted lignin and monomers, atom transfer radical polymerization, and reversible addition–fragmentation transfer polymerization. As an example, the crosslinking mechanism of lignin–chitosan–poly(vinyl alcohol) (PVA) hydrogel involves active groups of lignin such as hydroxyl, carboxyl, and sulfonic groups that can form hydrogen bonds (with groups in the chemical structures of chitosan and/or PVA) and ionic bonds (with groups in the chemical structures of chitosan and/or PVA). The aim of this review paper is to provide a comprehensive overview of lignin-based hydrogels and their applications, focusing on the preparation and properties of lignin-based hydrogels and the biomedical applications of these hydrogels. In addition, we explore their potential in wound healing, drug delivery systems, and 3D bioprinting, showcasing the unique properties of lignin-based hydrogels that enable their successful utilization in these areas. Finally, we discuss future trends in the field and draw conclusions based on the findings presented.
FXR Maintains the Intestinal Barrier and Stemness by Regulating CYP11A1-Mediated Corticosterone Synthesis in Biliary Obstruction Diseases
Authors: Li Zequn , Dong Haijiang , Bian Suchen , Wu Hao , Song Wenfeng , Jia Xing , Chen Jian , Zhu Xingxin , Zhao Long , Xuan Zefeng , Jin Cheng , Zhou Mengqiao , Zheng Shusen , Song Penghong
Published: August 2023

Biliary obstruction diseases are often complicated by an impaired intestinal barrier, which aggravates liver injury. Treatment of the intestinal barrier is often neglected. To investigate the mechanism by which intestinal bile acid deficiency mediates intestinal barrier dysfunction after biliary obstruction and identify a potential therapeutic modality, we mainly used a bile duct ligation (BDL) mouse model to simulate biliary obstruction and determine the important role of the bile acid receptor FXR in maintaining intestinal barrier function and stemness. Through RNA-seq analysis of BDL and sham mouse crypts and qRT-PCR performed on intestinal epithelial-specific Fxr knockout (FxrΔIEC) and wild-type mouse crypts, we found that FXR might maintain intestinal stemness by regulating CYP11A1 expression. Given the key role of CYP11A1 during glucocorticoid production, we also found that FXR activation could promote intestinal corticosterone (CORT) synthesis by ELISA. Intestinal organoid culture showed that an FXR agonist or corticosterone increased crypt formation and organoid growth. Further animal experiments showed that corticosterone gavage treatment could maintain intestinal barrier function and stemness, decrease LPS translocation, and attenuate liver injury in BDL mice. Our study hopefully provides a new theoretical basis for the prevention of intestinal complications and alleviation of liver injury after biliary obstruction.
Single-Cell Transcriptional Landscape Reveals the Regulatory Network and Its Heterogeneity of Renal Mitochondrial Damages in Diabetic Kidney Disease
Authors: Wu Chenhua , Song Yuhui , Yu Yihong , Xu Qing , Cui Xu , Wang Yurong , Wu Jie , Gu Harvest F.
Published: August 2023

Diabetic kidney disease (DKD) is one of the common chronic microvascular complications of diabetes in which mitochondrial disorder plays an important role in its pathogenesis. The current study delved into the single-cell level transcriptome heterogeneity of mitochondrial homeostasis in db/db mice, an animal model for study of type 2 diabetes and DKD, with single-cell RNA sequencing (scRNA-Seq) and bulk RNA-seq analyses. From the comprehensive dataset comprising 13 meticulously captured and authenticated renal cell types, an unsupervised cluster analysis of mitochondria-related genes within the descending loop of Henle, collecting duct principal cell, endothelial, B cells and macrophage, showed that they had two types of cell subsets, i.e., health-dominant and DKD-dominant clusters. Pseudotime analysis, cell communication and transcription factors forecast resulted in identification of the hub differentially expressed genes between these two clusters and unveiled that the hierarchical regulatory network of receptor-TF-target genes was triggered by mitochondrial degeneration. Furthermore, the collecting duct principal cells were found to be regulated by the decline of Fzd7, which contributed to the impaired cellular proliferation and development, apoptosis and inactive cell cycle, as well as diminished capacity for material transport. Thereby, both scRNA-Seq and bulk RNA-Seq data from the current study elucidate the heterogeneity of mitochondrial disorders among distinct cell types, particularly in the collecting duct principal cells and B cells during the DKD progression and drug administration, which provide novel insights for better understanding the pathogenesis of DKD.
Unraveling the Angiogenic Puzzle: Pre-Treatment sVEGFR1 and sVEGFR2 Levels as Promising Prognostic Indicators in Early-Stage Breast Cancer Patients
Authors: Zarychta Elżbieta , Bielawski Kornel , Wrzeszcz Katarzyna , Rhone Piotr , Ruszkowska-Ciastek Barbara
Published: August 2023

Despite the advancements in breast cancer (BrC) diagnosis and treatment, a considerable proportion of patients with early-stage disease still experience local recurrence or metastasis. This study aimed to assess the levels of specific angiogenic parameters in the EDTA plasma of BrC patients before and after treatment and to explore their clinical and prognostic significance. The levels of vascular endothelial growth factor A (VEGF-A), soluble form of vascular endothelial growth factor receptor type 1 (sVEGFR1), and soluble form of vascular endothelial growth factor receptor type 2 (sVEGFR2) were measured in 84 early BrC patients, both prior to surgery and within a median time of nine months post-treatment. Prognostic significance was evaluated using Kaplan-Meier survival and Cox regression analyses. Linear regression models were employed to examine the independent impact of selected angiogenic factors on DFS in breast cancer patients. The results of uni- and multivariate analyses indicated that a pre-treatment concentration of sVEGFR1 above 30.99 pg/mL was associated with improved disease-free survival (DFS) (p < 0.0001 for both analyses), while a pre-treatment concentration of sVEGFR2 above 9475.67 pg/mL was associated with an increased risk of BrC relapse (p < 0.0001 for both analyses). Additionally, a post-treatment concentration of sVEGFR2 above 7361.71 pg/mL was associated with better overall survival (OS) based on the Kaplan-Meier survival analysis (p = 0.0141). Furthermore, linear regression models revealed a significant inverse association between pre-treatment levels of sVEGFR1 and the risk of relapse (standardized β −0.2578, p = 0.0499) and a significant positive association of VEGF-A levels with the risk of recurrence (standardized β 0.2958, p = 0.0308). In conclusion, the findings suggest that both pre- and post-treatment levels of sVEGFR1 and sVEGFR2 may hold promise as potential prognostic markers for BrC patients.
Visible-Light-Activated Carbon Dot Photocatalyst for ROS-Mediated Inhibition of Algae Growth
Authors: Song Jun , Xu Zhibin , Li Hao , Chen Yu , Guo Jiaqing
Published: August 2023

The growing occurrence of detrimental algal blooms resulting from industrial and agricultural activities emphasizes the urgency of implementing efficient removal strategies. In this study, we have successfully synthesized stable and biocompatible carbon dots (R-CDs) capable of generating reactive oxygen species (ROS) upon exposure to natural light irradiation. Phaeocystis globosa Scherffel (PGS) was selected as a representative model for conducting anti-algal experiments. Remarkably, in the presence of R-CDs, the complete eradication of harmful algae within a simulated light exposure period of 27 h was achieved. Furthermore, fluorescence lifetime imaging microscopy (FLIM) was first employed to study the physiological processes involved in the oxidative stress induced by PGS when subjected to ROS attack. The findings of this study demonstrate the potential of R-CDs as a highly promising anti-algal agent. This elucidation of the mechanism contributes to a comprehensive understanding of the efficacy and effectiveness of such agents in combating algal growth, further inspiring the development of other anti-algal agents.
The Dual Role of Mesenchymal Stem Cells in Cancer Pathophysiology: Pro-Tumorigenic Effects versus Therapeutic Potential
Authors: Slama Youssef , Ah-Pine Franck , Khettab Mohamed , Arcambal Angelique , Begue Mickael , Dutheil Fabien , Gasque Philippe
Published: August 2023

Mesenchymal stem/stromal cells (MSCs) are multipotent cells involved in numerous physiological events, including organogenesis, the maintenance of tissue homeostasis, regeneration, or tissue repair. MSCs are increasingly recognized as playing a major, dual, and complex role in cancer pathophysiology through their ability to limit or promote tumor progression. Indeed, these cells are known to interact with the tumor microenvironment, modulate the behavior of tumor cells, influence their functions, and promote distant metastasis formation through the secretion of mediators, the regulation of cell–cell interactions, and the modulation of the immune response. This dynamic network can lead to the establishment of immunoprivileged tissue niches or the formation of new tumors through the proliferation/differentiation of MSCs into cancer-associated fibroblasts as well as cancer stem cells. However, MSCs exhibit also therapeutic effects including anti-tumor, anti-proliferative, anti-inflammatory, or anti-oxidative effects. The therapeutic interest in MSCs is currently growing, mainly due to their ability to selectively migrate and penetrate tumor sites, which would make them relevant as vectors for advanced therapies. Therefore, this review aims to provide an overview of the double-edged sword implications of MSCs in tumor processes. The therapeutic potential of MSCs will be reviewed in melanoma and lung cancers.
Connecting Cryptococcal Meningitis and Gut Microbiome
Authors: Ma Yuanyuan , Yang Liang , Jiang Mengna , Zhao Xinyuan , Xue Peng
Published: August 2023

Fungal pathogens of the Cryptococcus neoformans species complex (C. neoformans SC) are a major cause of fungal meningitis in immunocompromised individuals. As with other melanotic microorganisms associated with human diseases, the cell-wall-associated melanin of C. neoformans SC is a major virulence factor that contributes to its ability to evade host immune responses. The levels of melanin substrate and the regulation of melanin formation could be influenced by the microbiota–gut–brain axis. Moreover, recent studies show that C. neoformans infections cause dysbiosis in the human gut microbiome. In this review, we discuss the potential association between cryptococcal meningitis and the gut microbiome. Additionally, the significant potential of targeting the gut microbiome in the diagnosis and treatment of this debilitating disease is emphasized.
Chlorogenic Acid Alleviates LPS-Induced Inflammation and Oxidative Stress by Modulating CD36/AMPK/PGC-1α in RAW264.7 Macrophages
Authors: Gu Tiantian , Zhang Zhiguo , Liu Jinyu , Chen Li , Tian Yong , Xu Wenwu , Zeng Tao , Wu Weicheng , Lu Lizhi
Published: August 2023

Chlorogenic acid (CGA) is a bioactive substance with anti-inflammatory activities. Clusters of CD36 have been suggested to be widely involved in inflammatory damage. However, the mechanism of CGA protecting against LPS-induced inflammation involving the CD36 regulation is unclear. Here, we demonstrated that CGA protected against LPS-induced cell death and decreased the production of ROS. Moreover, the SOD, CAT, and GSH-Px activities were also upregulated in CGA-treated cells during LPS stimulation. CGA reduced COX-2 and iNOS expression and IL-1β, IL-6, and TNF-α secretion in LPS-stimulated RAW264.7 macrophages. In addition, CGA treatment widely involved in immune-related signaling pathways, including NF-κB signaling, NOD-like receptor signaling, and IL-17 signaling using transcriptomic analysis and CD36 also markedly reduced during CGA pretreatment in LPS-induced RAW264.7 cells. Furthermore, the CD36 inhibitor SSO attenuated inflammation and oxidative stress by enabling activation of the AMPK/PGC-1α cascade. These results indicate that CGA might provide benefits for the regulation of inflammatory diseases by modulating CD36/AMPK/PGC-1α to alleviate oxidative stress.
Overexpression of BoLSU1 and BoLSU2 Confers Tolerance to Sulfur Deficiency in Arabidopsis by Manipulating Glucosinolate Metabolism
Authors: Yang Shuang , Zhou Zihuan , Zhang Tianqi , Zhang Qianqian , Li Rui , Li Jing
Published: August 2023

Sulfur is an essential element for plant growth, development and resistance to environmental stresses. Glucosinolates (GSLs), a group of sulfur rich secondary metabolites found in Brassicaceae plants, are known for their defensive properties against pathogens and herbivores. Due to their integration of a large proportion of total sulfur, their biosynthesis and degradation are closely linked to sulfur metabolism. It has been demonstrated that GSLs can be broken down to release sulfur and facilitate the production of other thio-metabolites when the plant is under stress. However, the regulation of this process is still not fully understood. In this study, we constructed two broccoli LSU (low sulfur responsive) gene overexpressing lines, 35S::BoLSU1 and 35S::BoLSU2, to detect changes in GSL metabolism after sulfur deficiency treatment. The results showed that BoLSU1 and BoLSU2 inhibit the biosynthesis of aliphatic GSLs, while also promoting their degradation and increasing the content of glutathione (GSH), leading to the reallocation of sulfur from the GSL pool to other thio-metabolites such as GSH. Furthermore, this regulation of GSL metabolism mediated by BoLSU1 and BoLSU2 is found to be dependent on myrosinases BGLU28 and BGLU30. Our study provides insight into the physiological role of LSU proteins and their regulation of sulfur metabolism.
IL-31RA and TRPV1 Expression in Atopic Dermatitis Induced with Trinitrochlorobenzene in Nc/Nga Mice
Authors: Lee Seokwoo , Lim Na Yeon , Kang Min Soo , Jeong Yunho , Ahn Jin-Ok , Choi Jung Hoon , Chung Jin-Young
Published: August 2023

Atopic dermatitis (AD) is a common chronic inflammatory skin disease. Interleukin 31 (IL-31), a novel cytokine in AD, causes pruritus, typically characteristic of AD patients. The transient receptor potential vanilloid type 1 (TRPV1) is a cation channel activated by diverse noxious stimuli that has been studied in a variety of pruritic skin diseases. In this study, the AD animal model was generated by administering the hapten, trinitrochlorobenzene (TNCB), to Nc/Nga mice, and the degree of expression of the IL-31 receptor alpha (IL-31RA) and TRPV1 in the skin of these atopic models was evaluated. The Nc/Nga mice were divided into 3 groups: control, TNCB 2-weeks treated, and TNCB 8-weeks treated. After inducing AD, the skin lesions in each group were scored and compared, and the histology of the skin lesions and the IL-31RA and TRPV1 expression for each group were evaluated by analyzing immunohistochemistry. The results show a significant difference in the skin lesion scores between the groups. The immunohistochemistry evaluation highlighted the remarkable expression of IL-31RA and TRPV1 in the nerve fibers of the TNCB 8-weeks-treated group. We thus confirmed that the long-term application of TNCB induced chronic atopic-like dermatitis and that IL-31RA and TRPV1 were overexpressed in the peripheral nerve fibers in this AD model.
The Response Regulator VC1795 of Vibrio Pathogenicity Island-2 Contributes to Intestinal Colonization by Vibrio cholerae
Authors: Yan Junxiang , Liu Qian , Xue Xinke , Li Jinghao , Li Yuehua , Su Yingying , Cao Boyang
Published: August 2023

Vibrio cholerae is an intestinal pathogen that can cause severe diarrheal disease. The disease has afflicted millions of people since the 19th century and has aroused global concern. The Vibrio Pathogenicity Island-2 (VPI-2) is a 57.3 kb region, VC1758–VC1809, which is present in choleragenic V. cholerae. At present, little is known about the function of VC1795 in the VPI-2 of V. cholerae. In this study, the intestinal colonization ability of the ΔVC1795 strain was significantly reduced compared to that of the wild-type strain, and the colonization ability was restored to the wild-type strain after VC1795 gene replacement. This result indicated that the VC1795 gene plays a key role in the intestinal colonization and pathogenicity of V. cholerae. Then, we explored the upstream and downstream regulation mechanisms of the VC1795 gene. Cyclic adenylate receptor protein (CRP) was identified as being located upstream of VC1795 by a DNA pull-down assay and electrophoretic mobility shift assays (EMSAs) and negatively regulating the expression of VC1795. In addition, the results of Chromatin immunoprecipitation followed by sequencing (ChIP-seq), EMSAs, and Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) indicated that VC1795 directly negatively regulates the expression of its downstream gene, VC1794. Furthermore, by using qRT-PCR, we hypothesized that VC1795 indirectly positively regulates the toxin-coregulated pilus (TCP) cluster to influence the colonization ability of V. cholerae in intestinal tracts. In short, our findings support the key regulatory role of VC1795 in bacterial pathogenesis as well as lay the groundwork for the further determination of the complex regulatory network of VC1795 in bacteria.
Sodium Ferrous Citrate and 5-Aminolevulinic Acid Exert a Therapeutic Effect on Endotoxin-Induced Uveitis in Rats
Authors: Otaka Yuya , Kanai Kazutaka , Okada Daiki , Nagai Noriaki , Yamashita Yohei , Ichikawa Yoichiro , Tajima Kazuki
Published: August 2023

The metabolism of 5-aminolevulinic acid (ALA) is more efficient when combined with sodium ferrous citrate (SFC). Our previous study revealed that oral administration of ALA, which has anti-inflammatory properties, and SFC (ALA/SFC) immediately before lipopolysaccharide (LPS) inoculation suppressed endotoxin-induced uveitis (EIU) in rats. However, the therapeutic effect of ALA/SFC post-administration remains unexplored. Hence, this study aimed to evaluate the therapeutic efficacy of ALA/SFC on EIU in rats, which were administered with a gastric gavage of ALA/SFC (100/157 mg/kg) or prednisolone (Pred, 10 mg/kg) after 4 h of LPS inoculation. The treatment groups showed ameliorated clinical scores, inflammatory cells, protein levels in the aqueous humor (AqH), and histopathologic evaluation 24 h after LPS inoculation. Furthermore, the treatment groups had reduced tumor necrosis factor-α, nitric oxide, prostaglandin E2, and interleukin-6 levels in the AqH. ALA/SFC demonstrated an anti-inflammatory effect equivalent to that demonstrated by Pred. These findings indicate that ALA/SFC exerts a therapeutic effect on EIU in rats, indicating its clinical usefulness in uveitis treatment.
Comparison of Tumour-Specific Phenotypes in Human Primary and Expandable Pancreatic Cancer Cell Lines
Authors: Guo Feng , Kan Kejia , Rückert Felix , Rückert Wolfgang , Li Lin , Eberhard Johannes , May Tobias , Sticht Carsten , Dirks Wilhelm G. , Reißfelder Christoph , Pallavi Prama , Keese Michael
Published: August 2023

There is an ongoing need for patient-specific chemotherapy for pancreatic cancer. Tumour cells isolated from human tissues can be used to predict patients’ response to chemotherapy. However, the isolation and maintenance of pancreatic cancer cells is challenging because these cells become highly vulnerable after losing the tumour microenvironment. Therefore, we investigated whether the cells retained their original characteristics after lentiviral transfection and expansion. Three human primary pancreatic cancer cell lines were lentivirally transduced to create expandable (Ex) cells which were then compared with primary (Pri) cells. No obvious differences in the morphology or epithelial–mesenchymal transition (EMT) were observed between the primary and expandable cell lines. The two expandable cell lines showed higher proliferation rates in the 2D and 3D models. All three expandable cell lines showed attenuated migratory ability. Differences in gene expression between primary and expandable cell lines were then compared using RNA-Seq data. Potential target drugs were predicted by differentially expressed genes (DEGs), and differentially expressed pathways (DEPs) related to tumour-specific characteristics such as proliferation, migration, EMT, drug resistance, and reactive oxygen species (ROS) were investigated using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. We found that the two expandable cell lines expressed similar chemosensitivity and redox-regulatory capability to gemcitabine and oxaliplatin in the 2D model as compared to their counterparts. In conclusion, we successfully generated expandable primary pancreatic cancer cell lines using lentiviral transduction. These expandable cells not only retain some tumour-specific biological traits of primary cells but also show an ongoing proliferative capacity, thereby yielding sufficient material for drug response assays, which may provide a patient-specific platform for chemotherapy drug screening.
Improvement of Vascular Insulin Sensitivity by Ranolazine
Authors: Guerra-Ojeda Sol , Jorda Adrian , Aldasoro Constanza , Vila Jose M. , Valles Soraya L. , Arias-Mutis Oscar J , Aldasoro Martin
Published: August 2023

Ranolazine (RN) is a drug used in the treatment of chronic coronary ischemia. Different clinical trials have shown that RN behaves as an anti-diabetic drug by lowering blood glucose and glycosylated hemoglobin (HbA1c) levels. However, RN has not been shown to improve insulin (IN) sensitivity. Our study investigates the possible facilitating effects of RN on the actions of IN in the rabbit aorta. IN induced vasodilation of the abdominal aorta in a concentration-dependent manner, and this dilatory effect was due to the phosphorylation of endothelial nitric oxide synthase (eNOS) and the formation of nitric oxide (NO). On the other hand, IN facilitated the vasodilator effects of acetylcholine but not the vasodilation induced by sodium nitroprusside. RN facilitated all the vasodilatory effects of IN. In addition, IN decreased the vasoconstrictor effects of adrenergic nerve stimulation and exogenous noradrenaline. Both effects were in turn facilitated by RN. The joint effect of RN with IN induced a significant increase in the ratio of p-eNOS/eNOS and pAKT/AKT. In conclusion, RN facilitated the vasodilator effects of IN, both direct and induced, on the adrenergic system. Therefore, RN increases vascular sensitivity to IN, thus decreasing tissue resistance to the hormone, a key mechanism in the development of type II diabetes.
Could the Oxidation of α1-Antitrypsin Prevent the Binding of Human Neutrophil Elastase in COVID-19 Patients?
Authors: D’Amato Maura , Campagnoli Monica , Iadarola Paolo , Bignami Paola Margherita , Fumagalli Marco , Chiarelli Laurent Roberto , Stelitano Giovanni , Meloni Federica , Linciano Pasquale , Collina Simona , Pietrocola Giampiero , Vertui Valentina , Aliberti Anna , Fossali Tommaso , Viglio Simona
Published: August 2023

Human neutrophil elastase (HNE) is involved in SARS-CoV-2 virulence and plays a pivotal role in lung infection of patients infected by COVID-19. In healthy individuals, HNE activity is balanced by α1-antitrypsin (AAT). This is a 52 kDa glycoprotein, mainly produced and secreted by hepatocytes, that specifically inhibits HNE by blocking its activity through the formation of a stable complex (HNE–AAT) in which the two proteins are covalently bound. The lack of this complex, together with the detection of HNE activity in BALf/plasma samples of COVID-19 patients, leads us to hypothesize that potential functional deficiencies should necessarily be attributed to possible structural modifications of AAT. These could greatly diminish its ability to inhibit neutrophil elastase, thus reducing lung protection. The aim of this work was to explore the oxidation state of AAT in BALf/plasma samples from these patients so as to understand whether the deficient inhibitory activity of AAT was somehow related to possible conformational changes caused by the presence of abnormally oxidized residues.
Deletion of the chd7 Hinders Oligodendrocyte Progenitor Cell Development and Myelination in Zebrafish
Authors: Shi Lingyu , Wang Zongyi , Li Yujiao , Song Zheng , Yin Wu , Hu Bing
Published: August 2023

CHD7, an encoding ATP-dependent chromodomain helicase DNA-binding protein 7, has been identified as the causative gene involved in CHARGE syndrome (Coloboma of the eye, Heart defects, Atresia choanae, Retardation of growth and/or development, Genital abnormalities and Ear abnormalities). Although studies in rodent models have expanded our understanding of CHD7, its role in oligodendrocyte (OL) differentiation and myelination in zebrafish is still unclear. In this study, we generated a chd7-knockout strain with CRISPR/Cas9 in zebrafish. We observed that knockout (KO) of chd7 intensely impeded the oligodendrocyte progenitor cells’ (OPCs) migration and myelin formation due to massive expression of chd7 in oilg2+ cells, which might provoke upregulation of the MAPK signal pathway. Thus, our study demonstrates that chd7 is critical to oligodendrocyte migration and myelination during early development in zebrafish and describes a mechanism potentially associated with CHARGE syndrome.
Perspectives on Saponins: Food Functionality and Applications
Authors: Timilsena Yakindra Prasad , Phosanam Arissara , Stockmann Regine
Published: August 2023

Saponins are a diverse group of naturally occurring plant secondary metabolites present in a wide range of foods ranging from grains, pulses, and green leaves to sea creatures. They consist of a hydrophilic sugar moiety linked to a lipophilic aglycone, resulting in an amphiphilic nature and unique functional properties. Their amphiphilic structures enable saponins to exhibit surface-active properties, resulting in stable foams and complexes with various molecules. In the context of food applications, saponins are utilized as natural emulsifiers, foaming agents, and stabilizers. They contribute to texture and stability in food products and have potential health benefits, including cholesterol-lowering and anticancer effects. Saponins possess additional bioactivities that make them valuable in the pharmaceutical industry as anti-inflammatory, antimicrobial, antiviral, and antiparasitic agents to name a few. Saponins can demonstrate cytotoxic activity against cancer cell lines and can also act as adjuvants, enhancing the immune response to vaccines. Their ability to form stable complexes with drugs further expands their potential in drug delivery systems. However, challenges such as bitterness, cytotoxicity, and instability under certain conditions need to be addressed for effective utilization of saponins in foods and related applications. In this paper, we have reviewed the chemistry, functionality, and application aspects of saponins from various plant sources, and have summarized the regulatory aspects of the food-based application of quillaja saponins. Further research to explore the full potential of saponins in improving food quality and human health has been suggested. It is expected that this article will be a useful resource for researchers in food, feed, pharmaceuticals, and material science.
Mechanistic Insights into the Roles of the IL-17/IL-17R Families in Pancreatic Cancer
Authors: Chen Zheng , Qiao Shuangying , Yang Liu , Sun Meiheng , Li Boyue , Lu Aiping , Li Fangfei
Published: August 2023

The members of the cytokine interleukin 17 (IL-17) family, along with their receptors (IL-17R), are vital players in a range of inflammatory diseases and cancer. Although generally regarded as proinflammatory, the effects they exhibit on cancer progression are a double-edged sword, with both antitumor and protumor activities being discovered. There is growing evidence that the IL-17 signaling pathways have significant impacts on the tumor microenvironment (TME), immune response, and inflammation in various types of cancer, including pancreatic cancer. However, the detailed mechanistic functions of the IL-17/IL-17R families in pancreatic cancer were rarely systematically elucidated. This review considers the role of the IL-17/IL-17R families in inflammation and tumor immunity and elaborates on the mechanistic functions and correlations of these members with pathogenesis, progression, and chemoresistance in pancreatic cancer. By summarizing the advanced findings on the role of IL-17/IL17R family members and IL-17 signaling pathways at the molecular level, cellular level, and disease level in pancreatic cancer, this review provides an in-depth discussion on the potential of IL-17/IL-17R as prognostic markers and therapeutic targets in pancreatic cancer.
TMT-Based Quantitative Proteomics Analysis Reveals Differentially Expressed Proteins between Different Sources of hMSCs
Authors: Naudot Marie , Le Ber Julie , Marcelo Paulo
Published: August 2023

Mesenchymal stem cells (MSCs) are an attractive therapeutic tool for tissue engineering and regenerative medicine owing to their regenerative and trophic properties. The best-known and most widely used are bone marrow MSCs, which are currently being harvested and developed from a wide range of adult and perinatal tissues. MSCs from different sources are believed to have different secretion potentials and production, which may influence their therapeutic effects. To confirm this, we performed a quantitative proteomic analysis based on the TMT technique of MSCs from three different sources: Wharton’s jelly (WJ), dental pulp (DP), and bone marrow (BM). Our analysis focused on MSC biological properties of interest for tissue engineering. We identified a total of 611 differentially expressed human proteins. WJ-MSCs showed the greatest variation compared with the other sources. WJ produced more extracellular matrix (ECM) proteins and ECM-affiliated proteins and proteins related to the inflammatory and immune response processes. BM-MSCs expressed more proteins involved in osteogenic, adipogenic, neuronal, or muscular differentiation and proteins involved in paracrine communication. Compared to the other sources, DP-MSCs overexpressed proteins involved in the exocytosis process. The results obtained confirm the existence of differences between WJ, DP, and BM-MSCs and the need to select the MSC origin according to the therapeutic objective sought.
Global Models of Smart Cities and Potential IoT Applications: A Review
Authors: Hassebo Ahmed , Tealab Mohamed
Published: August 2023

As the world becomes increasingly urbanized, the development of smart cities and the deployment of IoT applications will play an essential role in addressing urban challenges and shaping sustainable and resilient urban environments. However, there are also challenges to overcome, including privacy and security concerns, and interoperability issues. Addressing these challenges requires collaboration between governments, industry stakeholders, and citizens to ensure the responsible and equitable implementation of IoT technologies in smart cities. The IoT offers a vast array of possibilities for smart city applications, enabling the integration of various devices, sensors, and networks to collect and analyze data in real time. These applications span across different sectors, including transportation, energy management, waste management, public safety, healthcare, and more. By leveraging IoT technologies, cities can optimize their infrastructure, enhance resource allocation, and improve the quality of life for their citizens. In this paper, eight smart city global models have been proposed to guide the development and implementation of IoT applications in smart cities. These models provide frameworks and standards for city planners and stakeholders to design and deploy IoT solutions effectively. We provide a detailed evaluation of these models based on nine smart city evaluation metrics. The challenges to implement smart cities have been mentioned, and recommendations have been stated to overcome these challenges.
Bolstering Cognitive and Locomotor Function in Post-Stroke Dementia Using Human–Robotic Interactive Gait Training
Authors: Kim Yunhwan , Park Chanhee , Yoon Buhyun , You Joshua (Sung) H.
Published: August 2023

Studies have reported inconclusive results regarding the effectiveness and clinical indications of the exclusive use of human–robotic interactive gait training (HIT) in patients with post-stroke dementia (PSD). This study aimed to compare the effects of human–robotic interactive gait training (HIT) and conventional physiotherapy (CPT) on cognitive and sensorimotor functions, trunk balance and coordination, dynamic and static balance, and activities related to daily living performance in patients with PSD. Forty-eight patients with PSD who received 60-minute therapy sessions three times per week for 6 weeks were assigned to either the CPT (n = 25) or HIT (n = 23) group. The clinical outcomes included the scores of the mini-mental state examination (MMSE), Fugl–Meyer assessment (FMA), trunk impairment scale (TIS), Berg balance scale (BBS), and modified Barthel index (MBI). Friedman tests were conducted at p < 0.05. The Friedman tests showed that HIT had superior effects to CPT in relation to MMSE, FMA, and TIS (p < 0.05), but not in relation to BBS and MBI (p > 0.05). Our results provide promising clinical evidence that HIT significantly improves cognitive and sensorimotor recovery functions, as well as trunk balance and coordination, in patients with PSD who cannot concurrently perform dual cognitive–locomotor tasks.
Cardiac POCUS in Pediatric Emergency Medicine: A Narrative Review
Authors: Scheier Eric
Published: August 2023

Purpose of this Review: The cardiac point of care ultrasound (POCUS) is among the most impactful examinations in the evaluation of an ill child. This paper will review the English-language literature on cardiac POCUS in the pediatric emergency department (PED), the adult emergency literature with relevance to pediatric emergency, and other pediatric cardiac studies outside pediatric emergency with relevance to PED detection of potentially emergent pediatric cardiac pathology. Recent findings: Pediatric emergency physicians can reliably detect decreased left-sided systolic function and pericardial effusion using POCUS. Case reports show that pediatric emergency physicians have detected right-sided outflow tract obstruction, aortic root dilatation, and congenital cardiac disease using POCUS. Training for pediatric cardiac POCUS competency is feasible, and cardiac POCUS does not increase the burden on cardiology resources to the PED. Summary: While cardiac pathology in children is relatively rare, pediatric cardiac POCUS can incorporate a broad curriculum beyond systolic function and the presence of pericardial fluid. Further research should assess pediatric emergency physician performance in the identification of a broader range of cardiac pathology.
The Effect of Telemedicine in Glycemic Control in Adult Patients with Diabetes during the COVID-19 Era—A Systematic Review
Authors: Sotomayor Fiorella , Hernandez Reynier , Malek Rana , Parimi Nehu , Spanakis Elias K.
Published: August 2023

Telemedicine can be an effective tool for managing chronic diseases. The disruption in traditional diabetes care resulting from the COVID-19 pandemic led to global interest in telemedicine. With this manuscript, we evaluated the use of telemedicine for the management of diabetes during the pandemic and its impact on glycemic control, focusing on retrospective and prospective studies which included adult, non-pregnant patients with diabetes. We evaluated whether there was an improvement in HbA1c, time in range (TIR), glucose management indicator (GMI), mean glucose values, hypoglycemic episodes, time below range (TBR), or hospitalizations for hypoglycemia/DKA, depending on the available information provided. This review article highlights the benefits of telemedicine during the global state of emergency, which altered the standard of healthcare delivery. Across the studies reported in this review, telemedicine was shown to be an effective tool for the management of diabetes, illustrating its potential to be the new standard of care. Although these improvements may be confounded by potential extraneous factors present during the pandemic, telemedicine was shown to positively impact glycemic control. Overall, this article highlights the benefits of telemedicine on glycemic control during the global state of emergency, which altered the standard of care. With the rollback of COVID-19 restrictions, and a return to the office, this article emphasizes the necessity to study how telemedicine can be best utilized for diabetes management when compared to the traditional standard of care.
Urological Complications in Radical Surgery for Cervical Cancer: A Comparative Meta-Analysis before and after LACC Trial
Authors: Bruno Valentina , Chiofalo Benito , Logoteta Alessandra , Brandolino Gabriella , Savone Delia , Russo Mario , Sperduti Isabella , Mancini Emanuela , Fabrizi Luana , Anceschi Umberto , Vizza Enrico
Published: August 2023

Background: After the LACC trial publication in 2018, the minimally invasive approach (MIS) has severely decreased in favor of open surgery: MIS radical hysterectomy was associated with worse oncological outcomes than open surgery, but urological complications were never extensively explored in pre- versus post-LACC eras, even if they had a great impact on post-operative QoL. The purpose of this meta-analysis is to compare functional and organic urological complication rates before and after LACC trial. Methods: An independent search of the literature was conducted 4 years before and after the LACC trial and 50 studies were included. Results: The overall rate of urologic complications was higher in pre-LACC studies while no differences were found for organic urological complications. Conversely, the overall risk of dysfunctional urological complications showed a higher rate in the pre-LACC era. This is probably related to a sudden shift to open surgery, with potential lower thermal damage to the urinary tract autonomic nervous fibers. Conclusions: This meta-analysis showed that the incidence of urological complications in radical cervical cancer surgery was higher before the LACC trial, potentially due to the shift to open surgery. Nevertheless, further studies are needed to shed light on the connection between minimally invasive surgery and urological damage.
Periosteal Dry Needling for Carpometacarpal Osteoarthritis: A Prospective Case Series
Authors: Staehli Wiser Anna , Dunning James , Charlebois Casey , Bliton Paul , Mourad Firas
Published: August 2023

Background: Carpometacarpal (CMC) osteoarthritis (OA) of the thumb is a painful condition that affects over 15% of individuals above the age of 30 and up to 30% of post-menopausal women. Dry needling (DN) has been found to reduce pain and disability in a variety of neuromusculoskeletal conditions; however, DN in the management of CMC OA has not been well studied. Methods: Consecutive patients with clinical and radiographic evidence of CMC OA were treated with DN. The primary outcome measure was pain using the Numerical Pain Rating Scale (NPRS) at 12 weeks. Secondary outcome measures were the Upper Extremity Functional Index (UEFI-20) and the Global Rating of Change (GROC) scale. Outcome measures were collected at baseline, 4 weeks, 8 weeks, and 12 weeks. Results: Nine patients were treated for six sessions of periosteal DN over 3 weeks. Compared to baseline, statistically significant and clinically meaningful improvements were observed in thumb pain (NPRS mean difference: 2.6; p = 0.029) and function (UEFI-20 mean difference: 21.3; p = 0.012) at 12 weeks. Conclusion: Statistically significant and clinically meaningful within-group improvements in thumb pain and function were observed at 12 weeks following six sessions of periosteal DN treatment. DN may be a useful intervention in the management of patients with CMC OA of the thumb.
Intraoperative Fluorescent Ureter Visualization in Complex Laparoscopic or Robotic-Assisted Gynecologic Surgery
Authors: Kim Jiyoun , Jang Yoon , Choi Su Hyeon , Jung Yong Wook , Kim Mi-La , Yun Bo Seong , Seong Seok Ju , Jun Hye Sun
Published: August 2023

This study aimed to demonstrate the feasibility of ureteral navigation using intraoperative indocyanine green (ICG) and near-infrared fluorescence (NIRF) imaging during complex laparoscopic or robot-assisted gynecologic surgery (LRAGS). Twenty-six patients at high risk of ureteral injury with complex pelvic pathology (CPP) due to pelvic organ prolapse (POP), multiple myomas, large intraligamentary or cervical myoma, severe pelvic adhesions, or cervical atresia underwent LRAGS. All patients underwent cystoscopic intraureteral ICG instillation before LRAGS and ureteral navigation under NIRF imaging intraoperatively. Both ureteral pathways were identified from the pelvic brim downwards through NIRF imaging in all patients, even though some were not visualized under the white light mode. The fluorescent ureters were visualized immediately after the beginning of surgery and typically lasted for >5 h during surgery. There were no cases of iatrogenic ureteral injury. The hemoglobin decrement was 1.47 ± 1.13 g/dL, and no transfusion was required. In our study, both ureters in all patients were identified with ICG-NIRF imaging during LRAGS, and these techniques made surgeries easier and safer. Despite the CPP, there was no ureteral injury or transfusion following surgery. Further prospective studies are needed to introduce intraoperative ureteral guidelines for ICG-NIRF imaging during LRAGS with CPP.
Impact of the Allergic Therapeutic Adherence in Children with Allergic Rhinitis and ADHD: A Pilot Study
Authors: Gambadauro Antonella , Foti Randazzese Simone , Currò Arianna , Galletta Francesca , Crisafulli Giuseppe , Caminiti Lucia , Germanò Eva , Di Rosa Gabriella , Nicotera Antonio Gennaro , Manti Sara
Published: August 2023

Background: Allergic rhinitis (AR) is the most common chronic allergic disease in children. Several studies have shown an association between attention deficit hyperactivity disorder (ADHD) and allergies, especially AR. Patients with ADHD usually have poor therapeutic adherence, and untreated AR symptoms may worsen the quality of life of patients. Methods: The aim of our study was to analyse therapeutic adherence in patients with ADHD and AR and estimate the impact of the adherence on ADHD symptoms. Total Nasal Symptoms Score (TNSS), Paediatric or Adolescent Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ 6–12 years; ARQLQ 13–17 years), Swanson, Nolan, and Pelham version IV scale (SNAP-IV), and Medication Assessment Questionnaire (MGL MAQ) were recorded. Results: In the AR-ADHD group, a positive correlation between TNSS and SNAP-IV subscales was found: worse AR symptoms were related to a negative effect on ADHD scores. AR-ADHD patients with better ADHD therapeutic adherence showed higher AR symptoms and higher oppositional defiant disorder scores in the SNAP-IV questionnaire. Conclusions: Our results suggest that better adherence to AR therapy (oral antihistamines and/or intranasal corticosteroids, INCS) is associated with a reduction in inattention symptoms in children with ADHD. This data could prove to be fundamental for the psychic outcome of these patients.
Biochar Enhances Soil Resource Availability and Suppresses Microbial Metabolism Genes in the Rhizosphere of Wheat
Authors: Gong Xin , Li Sixian , Wu Zelu , Alhaj Hamoud Yousef , Shaghaleh Hiba , Kalkhajeh Yusef Kianpoor , Si Chenxiao , Zhu Lin , Ma Chao
Published: August 2023

Despite the well-documented role of biochar in promoting soil quality and crop productivity, the underlying biological mechanisms remain poorly understood. Here, we explored the effects of straw biochar on soil microbiome in the rhizosphere from wheat using metagenomic sequencing. Our results showed that straw return decreased the yields of wheat, while the straw biochar return increased the wheat yields. Further, both the richness and community composition confirmed different effects of the straw return and straw biochar return. The straw biochar return also resulted in greater rhizosphere effects from wheat, represented by resource availability, including soil organic carbon, soil total nitrogen, available phosphorus, and available potassium. The rhizosphere effects from wheat, represented by microbial metabolism genes involved in carbon, nitrogen, phosphorus, and potassium cycling, however, were decreased by straw biochar returning. In addition, the rhizosphere effects from nitrogen content and the nitrogen cycling genes showed negative relationships with wheat yields. Together, these results revealed that straw biochar enhanced soil resource availability but suppressed microbial metabolism genes in the rhizosphere from wheat, supporting the idea that straw biochar serves as a nutrient pool for crops.
Existence of Solutions for Planar Kirchhoff–Choquard Problems
Authors: Niu Rui , Wu Tianxing
Published: August 2023

In this article, we are interested in the study of the following Kirchhoff–Choquard equations: −a+b∫R2|∇u|2dxΔu+V(x)u=λ(ln|x|∗u2)u+f(u),x∈R2, where λ>0,a>0,b>0, V and f are continuous functions with some appropriate assumptions. We prove that when the parameter λ is sufficiently small, the above problem has a mountain pass solution, a least energy solution and a ground state solution by applying the variational methods and building some subtle inequalities.