bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Different Previous Frozen Holding Periods on the Canned Fish Quality
Authors: Villamarín Elena , Martínez Beatriz , Trigo Marcos , Aubourg Santiago P.
Published: November 2023

The combined effects of thermal processing (i.e., sterilisation treatment) and the prior frozen storage time (3 or 6 months at −18 °C) on the quality loss in canned Atlantic horse mackerel (Trachurus trachurus) were determined. Thus, the sterilisation step led to a remarkable (p < 0.05) formation in the canned fish muscle of fluorescent compounds, free fatty acids (FFAs), and trimethylamine and an increase in the L* and b* colour parameters; meanwhile, a decrease (p < 0.05) in the total ω3 FA/total ω6 FA ratio and the a* colour value were detected. The prior frozen storage period led to an increased (p < 0.05) lipid oxidation (peroxide, thiobarbituric acid reactive substance, and fluorescent compound formation) and hydrolysis (FFA formation) development and to increased L* and b* colour values in the corresponding canned samples; additionally, a lower (p < 0.05) polyene index and phospholipid content were observed in canned fish previously subjected to frozen storage. In most indices, physico-chemical changes related to quality loss were found to be higher if the previous storage period was increased. According to the marked effects of the sterilisation step and the prior frozen storage period, the optimisation of such processing conditions is recommended to maximise the quality of canned horse mackerel.
Glycine Enhances Oxidative Stress Tolerance and Biocontrol Efficacy of Sporidiobolus pararoseus against Aspergillus niger Decay of Apples
Authors: Wang Jiaxi , Gao Qian , Fang Tianqi , Shen Yong , Jing Siyuan , Guo Na
Published: November 2023

Apples are deeply loved by people because of their rich nutritional value, but they are susceptible to rotting. The use of antagonistic yeast is a promising method for controlling postharvest fruit diseases, but biocontrol efficacy of yeast will be weakened in environmental stress. In this study, the effects of glycine (Gly) on the oxidative stress tolerance and the biocontrol efficacy of Sporidiobolus pararoseus (S. pararoseus) against Aspergillus niger (A. niger) are discussed. Under the stimulation of H2O2, the yeast cells treated with Gly (1 mM) showed lower ROS content, less mitochondrial impairment and cellular oxidative damage, and the cell survival rate was significantly higher than Gly-untreated yeast. The yeast cells exposed to Gly significantly increased the activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), and the content of glutathione (GSH). Notably, Gly-treated yeast cells had better biocontrol efficacy against A. niger in postharvest apples. The lesion diameter and decay incidence were reduced by 17.67 mm and 79.63% compared to the control, respectively, when S. pararoseus was treated with 1 mM Gly. Moreover, Gly-treated yeast increased the antioxidant enzymes activities and their gene expression were up-regulated in apples. These results indicated that 1 mM Gly not only reduced the oxidative damage of yeast, but also induced resistance-related enzymes of apples under oxidative stress, which contributed to enhancing the biocontrol efficacy of S. pararoseus against A. niger in apples.
Polyphenols in Agricultural Grassland Crops and Their Health-Promoting Activities—A Review
Authors: Verhulst Emily P. , Brunton Nigel P. , Rai Dilip K.
Published: November 2023

Grassland crops are emerging reservoirs of undisturbed, natural antioxidants and phytochemicals, such as phenolic acids and flavonoids. The present review will focus on the most commonly cultivated crops, namely Lolium perenne L, Cichorium intybus L, Plantago lanceolata L. and Trifolium pratense L, which have been recognized for their polyphenolic composition. However, these crops are often undervalued and underutilized, yet have the means of potentially creating novel, value-added food and nutraceutical products. Previous studies relating to these crops have identified them as rich sources of caffeic acid, chlorogenic acid, daidzein, kaempferol, luteolin, and quercetin. The key to harnessing the hidden potential of these species is the recovery, identification, and characterization of the phytochemicals they contain. Considering the upsurge of research studies on alternative plant-based diets for the health of humans and the planet earth, there is a necessity to understand the phytochemical composition and the bioactivity that they possess. This review summarizes recovery methods of phytochemicals from the aforementioned grassland crops and their compositional and functional (antioxidant, anti-cancer, and anti-diabetic) characterization and discusses the potential for grassland crops as an abundant reservoir of health-promoting ingredients which can increase the nutritional composition within novel food innovations or within nutraceuticals.
Microbiome and Genetic Factors in the Pathogenesis of Liver Diseases
Authors: Miteva Dimitrina , Peshevska-Sekulovska Monika , Snegarova Violeta , Peruhova Milena , Vasilev Georgi H. , Vasilev Georgi V. , Sekulovski Metodija , Lazova Snezhina , Gulinac Milena , Tomov Latchezar , Mihova Antoaneta , Velikova Tsvetelina
Published: November 2023

Our genetic background has not changed over the past century, but chronic diseases are on the rise globally. In addition to the genetic component, among the critical factors for many diseases are inhabitants of our intestines (gut microbiota) as a crucial environmental factor. Dysbiosis has been described in liver diseases with different etiologies like non-alcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ALD), viral hepatitis, autoimmune hepatitis (AIH), primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), cirrhosis, hepatocellular carcinoma (HCC). On the other hand, new technologies have increased our understanding of liver disease genetics and treatment options. Genome-wide association studies (GWAS) identify unknown genetic risk factors, positional cloning of unknown genes associated with different diseases, gene tests for single nucleotide variations (SNVs), and next-generation sequencing (NGS) of selected genes or the complete genome. NGS also allowed studying the microbiome and its role in various liver diseases has begun. These genes have proven their effect on microbiome composition in host genome–microbiome association studies. We focus on altering the intestinal microbiota, and supplementing some bacterial metabolites could be considered a potential therapeutic strategy. The literature data promote probiotics/synbiotics role in reducing proinflammatory cytokines such as TNF-α and the interleukins (IL-1, IL-6, IL-8), therefore improving transaminase levels, hepatic steatosis, and NAFLD activity score. However, even though microbial therapy appears to be risk-free, evaluating side effects related to probiotics or synbiotics is imperative. In addition, safety profiles for long-term usage should be researched. Thus, this review focuses on the human microbiome and liver diseases, recent GWASs on liver disease, the gut-liver axis, and the associations with the microbiome and microbiome during/after liver disease therapy.
Antioxidant, Anti-Inflammatory Effects and Ability to Stimulate Wound Healing of a Common-Plantain Extract in Alginate Gel Formulations
Authors: Bâldea Ioana , Lung Ildiko , Opriş Ocsana , Stegarescu Adina , Kacso Irina , Soran Maria-Loredana
Published: November 2023

Our study aimed to investigate the biological effects of a common-plantain (Plantago major L.) extract, encapsulated in alginate, on dermal human fibroblast cultures in vitro, in view of its potential use as a wound healing adjuvant therapy. Common-plantain extracts were obtained by infusion and ultrasound extraction, and their total polyphenolic content and antioxidant capacity were determined by spectrophotometry. The best extract, which was obtained by infusion, was further encapsulated in sodium alginate in two different formulations. Fourier Transform Infrared Spectroscopy (FTIR) was used to demonstrate the existing interactions in the obtained common-plantain extract in the alginate formulations. The encapsulation efficiency was evaluated based on the total polyphenol content. These alginate gel formulations were further used in vitro to determine their biocompatibility and antioxidant and anti-inflammatory effects by spectrophotometry and ELISA, as well as their ability to stimulate fibroblast migration (scratch test assay) at different time points. In addition, the collagen 1 and 3 levels were determined by Western blot analysis. The data showed that the microencapsulated plantain extract formulations induced an antioxidant, anti-inflammatory effect, enhanced collagen production and increased wound closure in the first 8 h of their application. These results are encouraging for the use of this alginate plantain extract formulation as an adjuvant for skin wound healing.
Potential Drug–Drug Interactions and Related Factors among Geriatric Outpatients of a Tertiary Care Hospital
Authors: Wannawichate Tippayavadee , Limpawattana Panita
Published: November 2023

(1) Background: Drug–drug interactions (DDIs) possess the potential to lead to a range of clinically significant consequences in the older population. (2) Aims: To investigate the prevalence and associated factors of DDIs among older patients within an outpatient setting of a university hospital. (3) Methods: This is a descriptive analysis of patients aged ≥65 years, who received a minimum of two medications. The electronic medical records were obtained from the outpatient clinic of a tertiary care hospital between November 2021 and November 2022. The outcomes were analyzed using descriptive and regression analysis. (4) Results: The study enrolled 10,877 patients, with a mean age of 74.3 ± 6.8 years. The prevalence of major DDI was 36.8%. Factors associated with major DDI were age (odds ratio [OR] 1.03), female sex (OR 1.23), polypharmacy (OR 2.27–13.78), metabolic disease (OR 1.89), psychiatric disorder (OR 1.79), cardiovascular disease (OR 1.51), musculoskeletal disease (OR 1.37), central nervous system disease (OR 1.24), and tuberculosis (OR 0.18). There was a significant difference observed in the primary healthcare facilities for emergency medicine (OR 1.72), orthopedics (OR 1.36), internal medicine (OR 1.29), and radiology (OR 0.45). (5) Conclusions: Major DDI was prevalent among older patients receiving care at outpatient settings. Several factors linked to major DDIs were identified. Developing appropriate strategies to improve the prescription process and avoid any missed interactions with geriatric patients is recommended.
Comparison of Resilience, Personal Recovery, and Quality of Life Measures Pre- and Post-Discharge from Inpatient Mental Health Units in Alberta: Analysis of Control Group Data from a Randomized Trial
Authors: Owusu Ernest , Shalaby Reham , Elgendy Hossam , Mao Wanying , Shalaby Nermin , Agyapong Belinda , Nichols Angel , Eboreime Ejemai , Nkire Nnamdi , Lawal Mobolaji A. , Agyapong Vincent I. O.
Published: November 2023

Background: The transition from hospital to community settings for most mental health service users is often hindered by challenges that affect community adjustment and continuity of care. The first few weeks and days after discharge from mental health inpatient units represent a critical phase for many service users. This paper aims to evaluate the changes in the resilience, personal recovery, and quality of life status of individuals with mental health challenges recently discharged from acute mental health care into the community. Methods: Data for this study were collected as part of a pragmatic stepped-wedge cluster-randomized, longitudinal approach in Alberta. A paired sample t-test and Chi-squared/Fisher test were deployed to assess changes from baseline to six weeks in the recovery assessment scale (RAS), brief resilience scale (BRS), and EuroQol-5d (EQ-5D), using an online questionnaire. Results: A total of 306 service users were recruited and 88 completed both baseline and six weeks, giving a response rate of 28.8%. There was no statistically significant change in the level of resilience, recovery and quality of life as measured with the brief resilience scale, recovery assessment scale and EQ-5D from baseline to six weeks (p > 0.05). Conclusions: The study showed that there was neither an improvement nor deterioration in resilience, recovery, or quality of life status of service users six weeks post-discharge from inpatient mental health care. The lack of further progress calls into question whether the support available in the community when patient’s leave inpatient care is adequate to promote full recovery. The results justify investigations into the effectiveness of innovative and cost-effective programs such as peer and text-based supportive interventions for service users discharged from inpatient psychiatric care.
Posttraumatic Growth, Maladaptive Cognitive Schemas and Psychological Distress in Individuals Involved in Road Traffic Accidents—A Conservation of Resources Theory Perspective
Authors: Delcea Cristian , Rad Dana , Toderici Ovidiu Florin , Bululoi Ana Simona
Published: November 2023

Road traffic accidents can have profound psychological impacts on the individuals involved, encompassing both negative distress and positive growth. This study, guided by the conservation of resources (COR) theory, investigates the intricate relationship between posttraumatic growth (PTG), maladaptive cognitive schemas, and psychological distress in individuals involved in road traffic accidents. PTG reflects an individual’s ability to derive positive changes from adversity, while maladaptive schemas represent negative cognitive patterns. Using a 122 sample of individuals involved in road traffic accidents, we examined direct and indirect effects within this complex network. Our findings reveal significant direct effects of PTG on psychological distress (β = 0.101, p = 0.02). Particularly noteworthy are the indirect effects mediated by cognitive schemas, emphasizing the role of impaired autonomy and perceived performance deficiencies (β = 0.102, p = 0.05). This suggests that individuals involved in road traffic accidents experiencing higher PTG levels may indirectly experience greater psychological distress through these maladaptive cognitive schemas. This study not only advances our understanding of the psychological consequences of road traffic accidents but also aligns with self-determination theory, emphasizing autonomy and competence as fundamental needs. Individuals involved in road traffic accidents may undergo profound shifts in perspective following the trauma, which our results support. Recognizing the nuanced relationship between PTG, maladaptive cognitive schemas, and psychological distress is crucial for tailoring interventions and support systems for individuals involved in traffic accidents. As PTG can coexist with distress, interventions should foster adaptive growth while addressing maladaptive schemas to promote resilience in the face of traumatic events.
How Much Dialogic Coordination Practices Matter to Healthcare Professionals—A Delphi Approach towards a Tool for Identification and Measurement
Authors: Santos-Cebrián Mónica , Morales-Moya Miguel-Ángel , De-Pablos-Heredero Carmen , Pacheco-Olivares María-del-Rosario
Published: November 2023

The study of coordination practices in health policy is a central aspect. The need for further research has been recently highlighted because of COVID-19. In this sense, dialogic practices (DP) have been identified but not validated yet. The purpose of this study is to develop and validate a DP questionnaire for healthcare teams. Items were identified based on a literature review, and the content validation was carried out by means of a Delphi study. A total of 10 experts assessed the clarity and appropriateness of the items and their corresponding measurement scales. After two rounds, a high level of consensus was reached, with agreement of 90% or higher on all items, and a high degree of stability and concordance in the results. This study resulted in a questionnaire consisting of four items, one for each identified DP initially proposed to the experts, as no other practices were revealed. From a practical perspective, the validation of these items constitutes a methodological innovation that responds to the call in the literature to open new avenues for comparative studies, and the possibility of generalising the findings and bringing together different approaches to the problem of coordination, which is key in health policy where unforeseen situations emerge.
Validation of the Portuguese Version of the Scleroderma Health Assessment Questionnaire
Authors: Genrinho Inês , Ferreira Pedro L. , Santiago Tânia , Carones Adriana , Mazeda Carolina , Barcelos Anabela , Beirão Tiago , Costa Flávio , Santos Inês , Couto Maura , Rato Maria , Terroso Georgina , Monteiro Paulo
Published: November 2023

The Health Assessment Questionnaire Disability Index (HAQ-DI) was completed with five visual analog scales to assess systemic sclerosis (SSc) called Scleroderma HAQ (SHAQ). We performed a validation of the European Portuguese version of SHAQ for patients with SSc. Patients with different forms of SSc from five Hospital Centers were invited. The reliability of the Portuguese SHAQ was evaluated by internal consistency and by test–retest reliability. Content validity was checked by two rheumatologists and by a panel of patients. Construct validity was assessed by structural validity and by known-groups hypothesis tests. Criterion validity was addressed with selected dimensions from the UCLA GIT 2.0, the SF-36v2, and the EuroQoL EQ-5D-5L. A total of 102 SSc patients agreed to participate, 31 of which answered to the retest. HAQ-DI demonstrated high internal consistency reliability (α = 0.866) and SHAQ also showed high test–retest reliability (ICC 0.61–0.95). We evidenced the unidimensionality of all VASs. HAQ-DI scores were worse in males, patients older than 65 years, and individuals with a diffuse form of SSc. Criterion validity was mainly evidenced through the correlation between the HAQ-DI and SF-36v2 physical summary measure (r = −0.688) and EQ-5D-5L index score (r = −0.723). Likewise, the SHAQ overall disease severity VAS was also correlated with SF-36v2 physical summary measure (r = −0.628). Mental score correlations were smaller. With the exception of the Raynaud’s VAS, all the other VASs correlated well with similar clinical variables. This paper provides evidence to demonstrate how reliable and valid the European Portuguese version of SHAQ is, to be used in SSc patients to assess the clinical severity under the perspective of patients.
Corporate Digital Transformation and M&A Efficiency: Evidence Based on Chinese Listed Companies
Authors: Ren Gui , Huo Zhenxian , Wang Jingjing , Liu Xihe
Published: November 2023

In order to help enterprises to achieve high-quality development and improve the capital market regulatory policies by supporting with more factual basis from China, this paper conducts research on clarifying impact mechanism of digital transformation on M&A efficiency of listed companies. Taking the mergers and acquisitions of listed companies from 2007 to 2021 as a research sample, the influence mechanism of the digital transformation degree of companies on their M&A efficiency was studied. The research results show that the digital transformation of listed companies will improve their M&A efficiency. Digital transformation will reduce the degree of mispricing stocks of M&A companies, curb conflicts between managers and agents of M&A companies, and improve their M&A efficiency. Further research finds that the promotion effect of digital transformation on M&A efficiency is more significant in non-state-owned companies, with a higher degree of financing constraint and high analyst attention. In the future, regulatory authorities should actively promote the digital transformation of listed companies, curb mispricing and management agency problems in the capital market with digital governance, and improve the efficiency of mergers and acquisitions in the capital market. This paper not only provides a more factual basis on concrete case from China but also enriches the related empirical analysis on corporate digital transformation and M&A efficiency.
Early Flood Monitoring and Forecasting System Using a Hybrid Machine Learning-Based Approach
Authors: Koutsovili Eleni-Ioanna , Tzoraki Ourania , Theodossiou Nicolaos , Tsekouras George E.
Published: November 2023

The occurrence of flash floods in urban catchments within the Mediterranean climate zone has witnessed a substantial rise due to climate change, underscoring the urgent need for early-warning systems. This paper examines the implementation of an early flood monitoring and forecasting system (EMFS) to predict the critical overflow level of a small urban stream on Lesvos Island, Greece, which has a history of severe flash flood incidents requiring rapid response. The system is supported by a network of telemetric stations that measure meteorological and hydrometric parameters in real time, with a time step accuracy of 15 min. The collected data are fed into the physical Hydrologic Engineering Center’s Hydrologic Modeling System (HEC-HMS), which simulates the stream’s discharge. Considering the HEC-HMS’s estimated outflow and other hydro-meteorological parameters, the EMFS uses long short-term memory (LSTM) neural networks to enhance the accuracy of flood prediction. In particular, LSTMs are employed to analyze the real-time data from the telemetric stations and make multi-step predictions of the critical water level. Hydrological time series data are utilized to train and validate the LSTM models for short-term leading times of 15 min, 30 min, 45 min, and 1 h. By combining the predictions obtained by the HEC-HMS with those of the LSTMs, the EMFS can produce accurate flood forecasts. The results indicate that the proposed methodology yields trustworthy behavior in enhancing the overall resilience of the area against flash floods.
Prdx6 Regulates Nlrp3 Inflammasome Activation-Driven Inflammatory Response in Lens Epithelial Cells
Authors: Chhunchha Bhavana , Kumar Rakesh , Kubo Eri , Thakur Priyanka , Singh Dhirendra P.
Published: November 2023

The continuum of antioxidant response dysregulation in aging/oxidative stress-driven Nlrp3 inflammasome activation-mediated inflammatory response is associated with age-related diseases. Peroxiredoxin (Prdx) 6 is a key antioxidant that provides cytoprotection by regulating redox homeostasis. Herein, using lens epithelial cells (LECs) derived from the targeted inactivation of Prdx6 gene and aging lenses, we present molecular evidence that Prdx6-deficiency causes oxidative-driven Nlrp3 inflammasome activation, resulting in pyroptosis in aging/redox active cells wherein Prdx6 availability offsets the inflammatory process. We observed that Prdx6−/− and aging LECs harboring accumulated reactive oxygen species (ROS) showed augmented activation of Nlrp3 and bioactive inflammatory components, like Caspase-1, IL-1β, ASC and Gasdermin-D. Similar to lipopolysaccharide treatment, oxidative exposure led to further ROS amplification with increased activation of the Nlrp3 inflammasome pathway. Mechanistically, we found that oxidative stress enhanced Kruppel-like factor 9 (Klf9) expression in aging/Prdx6−/− mLECs, leading to a Klf9-dependent increase in Nlrp3 transcription, while the elimination of ROS by the delivery of Prdx6 or by silencing Klf9 prevented the inflammatory response. Altogether, our data identify the biological significance of Prdx6 as an intrinsic checkpoint for regulating the cellular health of aging or redox active LECs and provide opportunities to develop antioxidant-based therapeutic(s) to prevent oxidative/aging-related diseases linked to aberrant Nlrp3 inflammasome activation.
Graft–Host Interaction and Its Effect on Wound Repair Using Mouse Models
Authors: Garcia Nicole , Rahman Md Mostafizur , Arellano Carlos Luis , Banakh Ilia , Yung-Chih Chen , Peter Karlheinz , Cleland Heather , Lo Cheng Hean , Akbarzadeh Shiva
Published: November 2023

Autologous skin grafting has been commonly used in clinics for decades to close large wounds, yet the cellular and molecular interactions between the wound bed and the graft that mediates the wound repair are not fully understood. The aim of this study was to better understand the molecular changes in the wound triggered by autologous and synthetic grafting. Defining the wound changes at the molecular level during grafting sets the basis to test other engineered skin grafts by design. In this study, a full-thickness skin graft (SKH-1 hairless) mouse model was established. An autologous full-thickness skin graft (FTSG) or an acellular fully synthetic Biodegradable Temporising Matrix (BTM) was grafted. The wound bed/grafts were analysed at histological, RNA, and protein levels during the inflammation (day 1), proliferation (day 5), and remodelling (day 21) phases of wound repair. The results showed that in this mouse model, similar to others, inflammatory marker levels, including Il-6, Cxcl-1, and Cxcl-5/6, were raised within a day post-wounding. Autologous grafting reduced the expression of these inflammatory markers. This was different from the wounds grafted with synthetic dermal grafts, in which Cxcl-1 and Cxcl-5/6 remained significantly high up to 21 days post-grafting. Autologous skin grafting reduced wound contraction compared to wounds that were left to spontaneously repair. Synthetic grafts contracted significantly more than FTSG by day 21. The observed wound contraction in synthetic grafts was most likely mediated at least partly by myofibroblasts. It is possible that high TGF-β1 levels in days 1–21 were the driving force behind myofibroblast abundance in synthetic grafts, although no evidence of TGF-β1-mediated Connective Tissue Growth Factor (CTGF) upregulation was observed.
Characterization of VvmiR166s-Target Modules and Their Interaction Pathways in Modulation of Gibberellic-Acid-Induced Grape Seedless Berries
Authors: Bai Yunhe , Wang Zhuangwei , Luo Linjia , Xuan Xuxian , Tang Wei , Qu Ziyang , Dong Tianyu , Qi Ziyang , Yu Mucheng , Wu Weimin , Fang Jinggui , Wang Chen
Published: November 2023

Exogenous GA is widely used to efficiently induce grape seedless berry development for significantly improving berry quality. Recently, we found that VvmiR166s are important regulators of response to GA in grapes, but its roles in GA-induced seedless grape berry development remain elusive. Here, the precise sequences of VvmiR166s and their targets VvREV, VvHB15 and VvHOX32 were determined in grape cv. ‘Rosario Bianco’, and the cleavage interactions of VvmiR166s-VvHB15/VvHOX32/VvREV modules and the variations in their cleavage roles were confirmed in grape berries. Exogenous GA treatment significantly induced a change in their expression correlations from positive to negative between VvmiR166s and their target genes at the seeds during the stone-hardening stages (32 DAF–46 DAF) in grape berries, indicating exogenous GA change action modes of VvmiR166s on their targets in this process, in which exogenous GA mainly enhanced the negative regulatory roles of VvmiR166s on VvHB15 among all three VvmiR166s-target pairs. The transient OE-VvmiR166a-h/OE-VvHB15 in tobacco confirmed that out of the VvmiR166 family, VvmiR166h/a/b might be the main factors in modulating lignin synthesis through inhibiting VvHB15, of which VvmiR166h-VvHB15-NtPAL4/NtCCR1/NtCCR2/NtCCoAMT5/NtCOMT1 and VvmiR166a/b-VvHB15-NtCAD1 are the potential key regulatory modules in lignin synthesis. Together with the GA-induced expression modes of VvmiR166s-VvHB15 and genes related to lignin synthesis in grape berries, we revealed that GA might repress lignin synthesis mainly by repressing VvCAD1/VvCCR2/VvPAL2/VvPAL3/Vv4CL/VvLac7 levels via mediating VvmiR166s-VvHB15 modules in GA-induced grape seedless berries. Our findings present a novel insight into the roles of VvmiR66s that are responsive to GA in repressing the lignin synthesis of grape seedless berries, with different lignin-synthesis-enzyme-dependent action pathways in diverse plants, which have important implications for the molecular breeding of high-quality seedless grape berries.
Fe2O3/Ni Nanocomposite Electrocatalyst on Cellulose for Hydrogen Evolution Reaction and Oxygen Evolution Reaction
Authors: Thangarasu Sadhasivam , Baby Nimisha , Bhosale Mrunal , Lee Jaeman , Jeong Changseong , Oh Tae-Hwan
Published: November 2023

A key challenge in the development of sustainable water-splitting (WS) systems is the formulation of electrodes by efficient combinations of electrocatalyst and binder materials. Cellulose, a biopolymer, can be considered an excellent dispersing agent and binder that can replace high-cost synthetic polymers to construct low-cost electrodes. Herein, a novel electrocatalyst was fabricated by combining Fe2O3 and Ni on microcrystalline cellulose (MCC) without the use of any additional binder. Structural characterization techniques confirmed the formation of the Fe2O3–Ni nanocomposite. Microstructural studies confirmed the homogeneity of the ~50 nm-sized Fe2O3–Ni on MCC. The WS performance, which involves the hydrogen evolution reaction (HER) and the oxygen evolution reaction (OER), was evaluated using a 1 M KOH electrolyte solution. The Fe2O3–Ni nanocomposite on MCC displayed an efficient performance toward lowering the overpotential in both the HER (163 mV @ 10 mA cm−2) and OER (360 mV @ 10 mA cm−2). These results demonstrate that MCC facilitated the cohesive binding of electrocatalyst materials and attachment to the substrate surface. In the future, modified cellulose-based structures (such as functionalized gels and those dissolved in various media) can be used as efficient binder materials and alternative options for preparing electrodes for WS applications.
Beta-Hydroxyisovaleryl-Shikonin Eradicates Epithelial Cell Adhesion Molecule-Positive Liver Cancer Stem Cells by Suppressing dUTP Pyrophosphatase Expression
Authors: Asahina Yoshiro , Takatori Hajime , Nio Kouki , Okada Hikari , Hayashi Takehiro , Hayashi Tomoyuki , Hashiba Tomomi , Suda Tsuyoshi , Nishitani Masaki , Sugimoto Saiho , Honda Masao , Kaneko Shuichi , Yamashita Taro
Published: November 2023

Cancer stem cells (CSCs) play an essential role in tumorigenesis, chemoresistance, and metastasis. Previously, we demonstrated that the development of hepatocellular carcinoma (HCC) is dictated by a subset of epithelial cell adhesion molecule-positive (EpCAM+) liver CSCs with the activation of Wnt signaling. In this study, we evaluated the expression of dUTP pyrophosphatase (dUTPase), which plays a central role in the development of chemoresistance to 5-fluorouracil, in EpCAM+ HCC cells. We further evaluated the effect of beta-hydroxyisovaleryl-shikonin (β-HIVS), an ATP-noncompetitive inhibitor of protein tyrosine kinases, on HCC CSCs. EpCAM and dUTPase were expressed in hepatoblasts in human fetal liver, hepatic progenitors in adult cirrhotic liver, and a subset of HCC cells. Sorted EpCAM+ CSCs from HCC cell lines showed abundant nuclear accumulation of dUTPase compared with EpCAM-negative cells. Furthermore, treatment with the Wnt signaling activator BIO increased EpCAM and dUTPase expression. In contrast, β-HIVS treatment decreased dUTPase expression. β-HIVS treatment decreased the population of EpCAM+ liver CSCs in a dose-dependent manner in vitro and suppressed tumor growth in vivo compared with the control vehicle. Taken together, our data suggest that dUTPase could be a good target to eradicate liver CSCs resistant to 5-fluorouracil. β-HIVS is a small molecule that could decrease dUTPase expression and target EpCAM+ liver CSCs.
Epidermal Growth Factor Receptors in Vascular Endothelial Cells Contribute to Functional Hyperemia in the Brain
Authors: Ferris Hannah R. , Stine Nathan C. , Hill-Eubanks David C. , Nelson Mark T. , Wellman George C. , Koide Masayo
Published: November 2023

Functional hyperemia—activity-dependent increases in local blood perfusion—underlies the on-demand delivery of blood to regions of enhanced neuronal activity, a process that is crucial for brain health. Importantly, functional hyperemia deficits have been linked to multiple dementia risk factors, including aging, chronic hypertension, and cerebral small vessel disease (cSVD). We previously reported crippled functional hyperemia in a mouse model of genetic cSVD that was likely caused by depletion of phosphatidylinositol 4,5-bisphosphate (PIP2) in capillary endothelial cells (EC) downstream of impaired epidermal growth factor receptor (EGFR) signaling. Here, using EC-specific EGFR-knockout (KO) mice, we directly examined the role of endothelial EGFR signaling in functional hyperemia, assessed by measuring increases in cerebral blood flow in response to contralateral whisker stimulation using laser Doppler flowmetry. Molecular characterizations showed that EGFR expression was dramatically decreased in freshly isolated capillaries from EC-EGFR-KO mice, as expected. Notably, whisker stimulation-induced functional hyperemia was significantly impaired in these mice, an effect that was rescued by administration of PIP2, but not by the EGFR ligand, HB-EGF. These data suggest that the deletion of the EGFR specifically in ECs attenuates functional hyperemia, likely via depleting PIP2 and subsequently incapacitating Kir2.1 channel functionality in capillary ECs. Thus, our study underscores the role of endothelial EGFR signaling in functional hyperemia of the brain.
A Berberine-Loaded Bletilla striata Polysaccharide Hydrogel as a New Medical Dressing for Diabetic Wound Healing
Authors: Hu Zhengbo , Zhao Kai , Chen Xingcan , Zhou Mingyuan , Chen Yuchi , Ye Xiaoqing , Zhou Fangmei , Ding Zhishan , Zhu Bingqi
Published: November 2023

The healing process of a diabetic wound (DW) is often impeded by a series of interrelated factors, including severe infection, persistent inflammation, and excessive oxidative stress. Therefore, it is particularly crucial to develop a medical dressing that can address these issues simultaneously. To this end, different ratios of Bletilla striata polysaccharide (BSP) and berberine (BER) were physically blended with Carbomer 940 (CBM940) to develop a composite hydrogel as a medical dressing. The BSP/BER hydrogel was characterized using SEM, FTIR, rheological testing and other techniques. The anti-inflammatory, antioxidant, and antibacterial properties of the hydrogel were evaluated using cell and bacterial models in vitro. A DW model of ICR mice was established to evaluate the effect of the hydrogel on DW healing in vivo. The hydrogel exhibited excellent biocompatibility and remarkable antibacterial, anti-inflammatory, and antioxidant properties. In addition, animal experiments showed that the BSP/BER hydrogel significantly accelerated wound healing in DW mice. Among the different formulations, the LBSP/BER hydrogel (2% BSP, mBER:mBSP = 1:40) demonstrated the most remarkable efficacy. In conclusion, the BSP/BER hydrogel developed exhibited immense properties and great potential as a medical dressing for the repair of DW, addressing a crucial need in clinical practice.
Nanoscale Bilirubin Analysis in Translational Research and Precision Medicine by the Recombinant Protein HUG
Authors: Sist Paola , Tramer Federica , Bandiera Antonella , Urbani Ranieri , Redenšek Trampuž Sara , Dolžan Vita , Passamonti Sabina
Published: November 2023

Bilirubin is a toxicological biomarker for hemolysis and liver diseases. The current automated diazo method used in clinical chemistry has limited applicability in rodent models and cannot be used in small animals relevant to toxicology, microphysiological systems, cell cultures, and kinetic studies. Here, we present a versatile fluorometric method for nanoscale analysis of bilirubin based on its highly specific binding to the recombinant bifunctional protein HELP–UnaG (HUG). The assay is sensitive (LoQ = 1.1 nM), accurate (4.5% relative standard error), and remarkably robust, allowing analysis at pH 7.4–9.5, T = 25–37 °C, in various buffers, and in the presence of 0.4–4 mg × L−1 serum albumin or 30% DMSO. It allows repeated measurements of bilirubinemia in murine models and small animals, fostering the 3Rs principle. The assay determines bilirubin in human plasma with a relative standard error of 6.7% at values that correlate and agree with the standard diazo method. Furthermore, it detects differences in human bilirubinemia related to sex and UGT1A1 polymorphisms, thus demonstrating its suitability for the uniform assessment of bilirubin at the nanoscale in translational and precision medicine.
Sequence Variant Analysis of the APOCII Locus among an Arab Cohort
Authors: Al-Bustan Suzanne A. , Alrashid Maryam H. , Al-Serri Ahmad E. , Annice Babitha G. , Bahbahani Hussain M.
Published: November 2023

Apolipoprotein CII (ApocII) plays a key role in regulating lipoprotein lipase (LPL) in lipid metabolism and transport. Numerous polymorphisms within APOCII are reportedly associated with type 2 diabetes mellitus (T2DM), dyslipidemia, and aberrant plasma lipid levels. Few studies have investigated sequence variants at APOCII loci and their association with metabolic disorders. This study aimed to identify and characterize genetic variants by sequencing the full APOCII locus and its flanking sequences in a sample of the Kuwaiti Arab population, including patients with T2DM, hypertriglyceridemia, non-Arab patients with T2DM, and healthy Arab controls. A total of 52 variants were identified in the noncoding sequences: 45 single nucleotide polymorphisms, wherein five were novel, and seven insertion deletions. The minor allele frequency (MAF) of the 47 previously reported variants was similar to the global MAF and to that reported in major populations. Sequence variant analysis predicted a conserved role for APOCII with a potential role for rs5120 in T2DM and rs7133873 as an informative ethnicity marker. This study adds to the ongoing research that attempts to identify ethnicity-specific variants in the apolipoprotein gene loci and associated LPL genes to elucidate the molecular mechanisms of metabolic disorders.
TWIST1 Upregulation Is a Potential Target for Reversing Resistance to the CDK4/6 Inhibitor in Metastatic Luminal Breast Cancer Cells
Authors: Cordani Nicoletta , Mologni Luca , Piazza Rocco , Tettamanti Pietro , Cogliati Viola , Mauri Mario , Villa Matteo , Malighetti Federica , Di Bella Camillo , Jaconi Marta , Cerrito Maria Grazia , Cavaletti Guido , Lavitrano Marialuisa , Cazzaniga Marina Elena
Published: November 2023

Cyclin-dependent kinase (CDK) 4/6 inhibitors have significantly improved progression-free survival in hormone-receptor-positive (HR+), human-epidermal-growth-factor-receptor-type-2-negative (HER2−) metastatic luminal breast cancer (mLBC). Several studies have shown that in patients with endocrine-sensitive or endocrine-resistant LBC, the addition of CDK4/6 inhibitors to endocrine therapy significantly prolongs progression-free survival. However, the percentage of patients who are unresponsive or refractory to these therapies is as high as 40%, and no reliable and reproducible biomarkers have been validated to select a priori responders or refractory patients. The selection of mutant clones in the target oncoprotein is the main cause of resistance. Other mechanisms such as oncogene amplification/overexpression or mutations in other pathways have been described in several models. In this study, we focused on palbociclib, a selective CDK4/6 inhibitor. We generated a human MCF-7 luminal breast cancer cell line that was able to survive and proliferate at different concentrations of palbociclib and also showed cross-resistance to abemaciclib. The resistant cell line was characterized via RNA sequencing and was found to strongly activate the epithelial-to-mesenchymal transition. Among the top deregulated genes, we found a dramatic downregulation of the CDK4 inhibitor CDKN2B and an upregulation of the TWIST1 transcription factor. TWIST1 was further validated as a target for the reversal of palbociclib resistance. This study provides new relevant information about the mechanisms of resistance to CDK4/6 inhibitors and suggests potential new markers for patients’ follow-up care during treatment.
YKL-40 and the Cellular Metabolic Profile in Parkinson’s Disease
Authors: Gevezova Maria , Kazakova Maria , Trenova Anastasia , Sarafian Victoria
Published: November 2023

Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. A growing body of evidence suggests that mitochondrial dysfunction and inflammation play a crucial role as a pathogenetic mechanism in PD. The glycoprotein YKL-40 (CHI3L1) is a potential biomarker involved in inflammation and tumor processes. The aim of the present study was to investigate the metabolic profile of PBMCs from PD patients and to search for a possible relationship between cellular bioenergetics and YKL-40. The study included 18 naïve PD patients and an age-matched control group (HC, n = 7). Patients were diagnosed according to the MDS-PD, the UPDRS, and the Hoen–Yahr scales. Mitochondrial activity was measured by a metabolic analyzer on isolated PBMCs from PD patients. Gene (qPCR) and protein (ELISA) expression levels of YKL40 were investigated. New data are reported revealing changes in the mitochondrial activity and YKL-40 levels in PD patients. Bioenergetic parameters showed increased respiratory reserve capacity in PD compared to HC. The protein levels of YKL-40 were threefold higher in PD. We found a correlation between the YKL-40 protein levels and basal respiration and between YKL-40 and ATP production. These observations suggest an interplay between YKL-40 and mitochondrial function in PD. We assume that the YKL-40 gene and protein levels in combination with changes in mitochondrial function might serve as an additional tool to monitor the clinical course of PD.
Yeast Hydrolysate Inhibits Lipid Accumulation via Regulation of Lipid Accumulation-Related Genes in a Drosophila Model of High-Sugar Diet-Induced Obesity
Authors: Kim Nari , Ahn Yejin , Ko Kayoung , Kim Boyun , Han Kisoo , Suh Hyung Joo , Jung Jewon , Hong Ki-Bae
Published: November 2023

The increasing frequency of processed food consumption has led to the higher ingestion of sugar, increasing the risk of chronic diseases, such as obesity. Yeast hydrolysates (YHs) inhibit body fat accumulation. However, the action mechanism of YH in relation to high-sugar diet-induced obesity is still unclear. Therefore, this study aimed to evaluate the biological effects of YH on lipid accumulation and verify behavioral changes and carbohydrate metabolic gene regulation in high-sugar diet-fed fruit flies. Adult male flies (Drosophila melanogaster; 2–5 days old) were exposed to 20% sucrose for obesity induction. In high-sugar-fed Drosophila, the effect of YH was compared with that of yeast extract. The effects of YH on body conditions and lipid droplet size were quantified and analyzed. Behavioral factors were evaluated by analyzing circadian rhythm patterns and neurotransmitter content, and a molecular approach was used to analyze the expression of metabolism-related genes. Dietary supplementation with YH did not reduce total sugar content, but significantly decreased the triglyceride (TG) levels in Drosophila. A behavioral analysis showed that the total number of night-time activities increased significantly with YH treatment in a dose-dependent manner. In addition, YH effectively regulated the gene expression of insulin-like peptides related to carbohydrate metabolism as well as genes related to lipogenesis. The TG content was significantly reduced at a YH concentration of 0.5%, confirming that the active compound in YH effectively suppresses fat accumulation. These findings support that YH is a potential anti-obesity food material via regulating carbohydrate metabolism in Drosophila.
A Network Pharmacology Prediction and Molecular Docking-Based Strategy to Explore the Potential Pharmacological Mechanism of Astragalus membranaceus for Glioma
Authors: Feng Yu , Zhu Peng , Wu Dong , Deng Wenbin
Published: November 2023

Glioma treatment in traditional Chinese medicine has a lengthy history. Astragalus membranaceus, a traditional Chinese herb that is frequently utilized in therapeutic practice, is a component of many Traditional Chinese Medicine formulas that have been documented to have anti-glioma properties. Uncertainty persists regarding the molecular mechanism behind the therapeutic effects. Based on results from network pharmacology and molecular docking, we thoroughly identified the molecular pathways of Astragalus membranaceus’ anti-glioma activities in this study. According to the findings of the enrichment analysis, 14 active compounds and 343 targets were eliminated from the screening process. These targets were mainly found in the pathways in cancer, neuroactive ligand–receptor interaction, protein phosphorylation, inflammatory response, positive regulation of phosphorylation, and inflammatory mediator regulation of Transient Receptor Potential (TRP) channels. The results of molecular docking showed that the active substances isoflavanone and 1,7-Dihydroxy-3,9-dimethoxy pterocarpene have strong binding affinities for the respective targets ESR2 and PTGS2. In accordance with the findings of our investigation, Astragalus membranaceus active compounds exhibit a multicomponent and multitarget synergistic therapeutic impact on glioma by actively targeting several targets in various pathways. Additionally, we propose that 1,7-Dihydroxy-3,9-dimethoxy pterocarpene and isoflavanone may be the main active ingredients in the therapy of glioma.
Unraveling Connective Tissue Growth Factor as a Therapeutic Target and Assessing Kahweol as a Potential Drug Candidate in Triple-Negative Breast Cancer Treatment
Authors: Lee Jeong Hee , Kim Jongsu , Kim Hong Sook , Kang Young Jin
Published: November 2023

Triple-negative breast cancer (TNBC) is characterized by aggressive behavior and limited treatment options, necessitating the identification of novel therapeutic targets. In this study, we investigated the clinical significance of connective tissue growth factor (CTGF) as a prognostic marker and explored the potential therapeutic effects of kahweol, a coffee diterpene molecule, in TNBC treatment. Initially, through a survival analysis on breast cancer patients from The Cancer Genome Atlas (TCGA) database, we found that CTGF exhibited significant prognostic effects exclusively in TNBC patients. To gain mechanistic insights, we performed the functional annotation and gene set enrichment analyses, revealing the involvement of CTGF in migratory pathways relevant to TNBC treatment. Subsequently, in vitro experiments using MDA-MB 231 cells, a representative TNBC cell line, demonstrated that recombinant CTGF (rCTGF) administration enhanced cell motility, whereas CTGF knockdown using CTGF siRNA resulted in reduced motility. Notably, rCTGF restored kahweol-reduced cell motility, providing compelling evidence for the role of CTGF in mediating kahweol’s effects. At the molecular level, kahweol downregulated the protein expression of CTGF as well as critical signaling molecules, such as p-ERK, p-P38, p-PI3K/AKT, and p-FAK, associated with cell motility. In summary, our findings propose CTGF as a potential prognostic marker for guiding TNBC treatment and suggest kahweol as a promising antitumor compound capable of regulating CTGF expression to suppress cell motility in TNBC. These insights hold promise for the development of targeted therapies and improved clinical outcomes for TNBC patients.