bluuebunny/crossref_metadata_2025 huggingface dataset:
Characteristics of a Recombinant Lentinula edodes Ferulic Acid Esterase and Its Adverse Effects on In Vitro Fermentation of Wheat Straw
Authors: Zhang Xiangyu , Lei Xiaowen , Ouyang Kehui , Zhang Wenjing , Liu Chanjuan , Li Yanjiao , Qiu Qinghua , Zang Yitian , Qu Mingren , Pan Ke , Zhao Xianghui
Published: July 2023

Ferulic acid esterases belong to the category of carboxylesterases and possess the capability to enzymatically break down hemicellulose within lignocellulosic substances, thereby liberating ferulic acid. A ferulic acid esterase from Lentinula edodes (LeFae) was expressed using Pichia pastoris, and its characterization and effects on the in vitro fermentation of wheat straw were investigated in this study. The optimal pH and temperature for LeFae were pH 7.0 and 60 °C, respectively. LeFae exhibited a broad temperature and pH adaptability (>60% of the maximum activity at pH 4.0–7.0 and 40–70 °C) and excellent thermal stability. The activity of LeFae was increased by 30.3% with a dosage of Tween 20 at 0.25% (v/v) and exhibited satisfactory resistance to Mn2+ and sodium dodecyl sulfate. LeFae released ferulic acid from wheat straw and exhibited an obvious synergistic effect with cellulase during wheat straw hydrolysis. LeFae severely inhibited the microbial fermentation of wheat straw and reduced the in vitro dry matter digestibility, total volatile fatty acid yield, and 16S rDNA copy numbers of Ruminococcus flavefaciens by 9.6%, 9.9 mM, and 40.1%, respectively. It also increased pH and the concentration of soluble phenols during wheat straw fermentation. Pretreating wheat straw with LeFae did not affect the microbial fermentation of wheat straw but resulted in the leaching of more dissolving sugars. The current results showed that although LeFae can cooperate with cellulase to promote the hydrolysis of wheat straw, its adverse effect on rumen microorganisms when directly fed to ruminants is a problem worthy of consideration.
Selenocysteine Formation by Enterococcus faecium ABMC-05 Follows a Mechanism That Is Not Dependent on Genes selA and selD but on Gene cysK
Authors: Escobar-Ramírez Meyli Claudia , Rodríguez-Serrano Gabriela Mariana , Zúñiga-León Eduardo , García-Montes Mario Adolfo , Pérez-Escalante Emmanuel , González-Olivares Luis Guillermo
Published: July 2023

Lactic acid bacteria (LAB) resist sodium selenite of concentrations greater than 100 mg/L in fermentation media. Selenium affects the growth rate, but once the microorganism absorbs selenium, this element is converted through a complex mechanism into selenocysteine and then into a selenoprotein structure. This study verified the presence of selenocysteine in Enterococcus faecium ABMC-05. The microorganism was cultivated in a medium enriched with a minimum inhibitory concentration of sodium selenite (184 mg/L). The concentration of selenium absorbed and the bioconversion into selenocysteine were determined by inductively coupled plasma optical emission spectrometry (ICP-OES) and reverse-phase high-performance chromatography (RP-HPLC), respectively. The presence of the selD, selA, and cysK genes was determined by amplifying the 16S rDNA through polymerase chain reaction (PCR). The microorganism accumulated inorganic selenium, and part was transformed into selenocysteine. The growth curves were atypical for a lactic acid bacterium with a stationary phase greater than 70 h. Determining the genetic expression showed only the presence of the cysK gene and the absence of the selD and the selA genes. The results demonstrate that this microorganism produces selenocysteine through a mechanism independent of the SelA and SelD pathways in contrast to other LAB.
Functional Foods for Health: The Antioxidant and Anti-Inflammatory Role of Fruits, Vegetables and Culinary Herbs
Authors: Fernandes Ana S. , Ferreira-Pêgo Cíntia , Costa João G.
Published: July 2023

The concept of “functional foods” converges topics such as diet, food, health, and disease [...]
Non-Destructive Detection of the Freshness of Air-Modified Mutton Based on Near-Infrared Spectroscopy
Authors: Jin Peilin , Fu Yifan , Niu Renzhong , Zhang Qi , Zhang Mingyue , Li Zhigang , Zhang Xiaoshuan
Published: July 2023

Monitoring and identifying the freshness levels of meat holds significant importance in the field of food safety as it directly relates to human dietary safety. Traditional packaging methods for lamb meat quality assessment present issues such as cumbersome operations and irreversible damage. This research proposes a quality assessment method for modified atmosphere packaging lamb meat using near-infrared spectroscopy and multi-parameter fusion. Fresh lamb meat quality is taken as the research subject, comparing various physicochemical indicators and near-infrared spectroscopic information under different temperatures (4 °C and 10 °C) and different modified atmosphere packaging combinations. Through precision parameter comparison, rebound and TVB-N values are selected as the modeling parameters. Six spectral preprocessing methods (multi-scatter calibration, MSC; standard normal variate transformation, SNV; normalization; Savitzky–Golay smoothing, SG; Savitzky–Golay 1 derivative, SG-1st; and Savitzky–Golay 2 derivative, SG-2nd), and three feature wavelength selection methods (competitive adaptive reweighted sampling, CARS; successive projections algorithm, SPA; and uninformative variable elimination, UVE) are compared. Partial least squares (PLS) and support vector machine (SVM) are used to construct prediction models for chilled fresh lamb meat quality. The results show that when rebound is used as a parameter, the SG-2nd-SPA-PLSR model has the highest accuracy, with a determination coefficient R2p of 0.94 for the prediction set. When TVB-N is used as a parameter, the MSC-UVE-SVM model has the highest accuracy, with an R2p of 0.95 for the prediction set. In conclusion, the use of near-infrared spectroscopic analysis enables rapid and non-destructive prediction and evaluation of lamb meat freshness, including its textural characteristics and TVB-N content under different modified atmosphere packaging. This study provides a theoretical basis and technical support for further encapsulating the models into portable devices and developing portable near-infrared spectrometers to rapidly determine lamb meat freshness.
ERCC1 and MGMT Methylation as a Predictive Marker of Relapse and FOLFOX Response in Colorectal Cancer Patients from South Tunisia
Authors: Jamai Dhouha , Gargouri Raja , Selmi Boulbaba , Khabir Abdelmajid
Published: July 2023

Genetic and epigenetic modifications present a major cause of relapse and treatment failure in colorectal cancer. This study aims to appreciate the prognostic and predictive value of ERRC1 and MGMT methylation. We also studied the prognostic impact of the ERCC1 rs11615 polymorphism as well as its expression. Methylation profiles of ERCC1 and MGMT were tested by methylation-specific PCR. A polymorphism of ERCC1 was studied using PCR-RFLP and its expression was examined by immunohistochemistry. ERCC1 was methylated in 44.6% of colorectal adenocarcinoma while MGMT was methylated in 69% of cases. MGMT methylation was strongly associated with lymph node metastasis, lymph invasion, venous invasion, perineural invasion, distant metastasis and relapse. Patients with methylation of both genes were more likely to have a poor prognosis and display chemoresistance. IHC analysis revealed that ERCC1 staining was noted in 52.8% of colorectal adenocarcinoma and inversely related to distant metastasis and cancer recurrence. Kaplan Meier analysis revealed that the worst overall survival was significantly associated with ERCC1 and MGMT methylation while decreased ERCC1 expression and T/T genotype exhibited the best overall survival. The methylation of MGMT, alone or combined with ERCC1, is predictive for poor prognosis, short overall survival and chemotherapy response in colorectal cancer.
EMAST Type of Microsatellite Instability—A Distinct Entity or Blurred Overlap between Stable and MSI Tumors
Authors: Vuković Đerfi Kristina , Salar Anamarija , Cacev Tamara , Kapitanović Sanja
Published: July 2023

Microsatellite instability (MSI) represents an accumulation of frameshifts in short tandem repeats, microsatellites, across the genome due to defective DNA mismatch repair (dMMR). MSI has been associated with distinct clinical, histological, and molecular features of tumors and has proven its prognostic and therapeutic value in different types of cancer. Recently, another type of microsatellite instability named elevated microsatellite alterations at selected tetranucleotide repeats (EMAST) has been reported across many different tumors. EMAST tumors have been associated with chronic inflammation, higher tumor stage, and poor prognosis. Nevertheless, the clinical significance of EMAST and its relation to MSI remains unclear. It has been proposed that EMAST arises as a result of isolated MSH3 dysfunction or as a secondary event in MSI tumors. Even though previous studies have associated EMAST with MSI-low phenotype in tumors, recent studies show a certain degree of overlap between EMAST and MSI-high tumors. However, even in stable tumors, (MSS) frameshifts in microsatellites can be detected as a purely stochastic event, raising the question of whether EMAST truly represents a distinct type of microsatellite instability. Moreover, a significant fraction of patients with MSI tumors do not respond to immunotherapy and it can be speculated that in these tumors, EMAST might act as a modifying factor.
Incorporating Rainfall Forecast Data in X-SLIP Platform to Predict the Triggering of Rainfall-Induced Shallow Landslides in Real Time
Authors: Gatto Michele Placido Antonio
Published: July 2023

Extreme and prolonged rainfall resulting from global warming determines a growing need for reliable Landslide Early Warning Systems (LEWS) to manage the risk of rainfall-induced shallow landslides (also called soil slips). Regional LEWS are typically based on data-driven methods because of their greater computational effectiveness, which is greater than the ones of physically based models (PBMs); however, the latter reproduces the physical mechanism of the modelled phenomena, and their modelling is more accurate. The purpose of this research is to investigate the prediction quality of the simplified PBM SLIP (implemented in the X-SLIP platform) when applied on a regional scale by analysing the stability of rain forecasts. X-SLIP was updated to handle the GRIB files (format for weather forecast). Four real-time predictions were simulated on some towns of the Emilia Apennines (northern Italy) involved in widespread soil slips on 5 April 2013; specifically, maps of factors of safety related to this event were derived assuming that X-SLIP had run 72 h, 48 h, 24 h and 12 h in advance. The results indicated that the predictions with forecasts (depending on the forecast quality) are as accurate as the ones derived with rainfall recordings only (benchmark). Moreover, the proposed method provides a reduced number of false alarms when no landslide was reported to occur in the whole area. X-SLIP with rain forecasts can, therefore, represent an important tool to predict the occurrence of future soil slips at a regional scale.
The Impact of Persistent Noise Exposure under Inflammatory Conditions
Authors: Cho Inja , Kim Jeongmin , Jung Seungho , Kim So Yeon , Kim Eun Jung , Choo Sungji , Kam Eun Hee , Koo Bon-Nyeo
Published: July 2023

The aim of this study was to investigate the impact of noise exposure in an intensive care unit (ICU) environment on the development of postoperative delirium in a mouse model that mimics the ICU environment. Additionally, we aimed to identify the underlying mechanisms contributing to delirium and provide evidence for reducing the risk of delirium. In this study, to mimic an ICU environment, lipopolysaccharide (LPS)-injected sepsis mouse models were exposed to a 75 dB noise condition. Furthermore, we assessed neurobehavioral function and observed the level of neuroinflammatory response and blood–brain barrier (BBB) integrity in the hippocampal region. The LPS-injected sepsis mouse model exposed to noise exhibited increased anxiety-like behavior and cognitive impairment. Moreover, severe neuroinflammation and BBB disruption were detected in the hippocampal region. This study provides insights suggesting that persistent noise exposure under systemic inflammatory conditions may cause cognitive dysfunction and anxiety- like behavior via the mediation of BBB disruption and neuroinflammation. As a result, we suggest that the detailed regulation of noise exposure may be required to prevent the development of postoperative delirium.
Effects of Predation Tags on Growth and Stress Response in Juvenile Rainbow Trout Oncorhynchus mykiss
Authors: Millsap Emma K. , Huysman Nathan , Gravenhof Dylan A. , Fincel Mark J. , Barnes Michael E.
Published: July 2023

Acid-sensitive predation tags have recently been introduced to fisheries management. The objective of this study was to ascertain the impact of these tags on juvenile rainbow trout Oncorhynchus mykiss physiology and growth after implantation. Twenty approximately 13 g rainbow trout were placed into each of five tanks, with ten surgically implanted with dummy acid-sensitive predation tags and ten control fish not subjected to surgical procedures. Glucose, hematocrit, tag-retention, survival, and growth metrics were collected for 30 days post-surgery. Four tagged fish died while no control fish died. Tag retention was 76%, with tags lost in weeks 2, 3, and 4. Control fish were significantly longer and gained significantly more weight at the end of the experiment. Hematocrit levels for the tagged fish dropped significantly over the course of the trial and were 30% lower than those of the untagged control fish at the end of 30 days. Glucose levels were highly variable for both treatments. The results of this study indicate the negative impacts of predation tagging on the physiology of juvenile rainbow trout. Results from predation field trials should be interpreted with caution because the tagged fish are likely at a competitive disadvantage compared to their untagged conspecifics.
Constructed Wetlands as Nature-Based Solutions for Wastewater Treatment in the Hospitality Industry: A Review
Authors: Justino Sara , Calheiros Cristina , Castro Paula , Gonçalves David
Published: July 2023

The hospitality industry is increasing its awareness of how the integration of nature-based solutions can decrease its environmental impact while maintaining or increasing the service level of the sector. Constructed wetlands (CWs) constitute a promising sustainable solution for proper in situ domestic wastewater treatment. This literature review elucidates the status of CWs implementation in the hospitality industry to help foster the exchange of experiences in the field and deliver examples of approaches in different contexts to support future applications of this technology. Most of the studies reported in the literature were conducted in Europe, but studies emanating from Asia and South America are also available. The design of CWs, the horizontal and vertical subsurface flow CWs (HSFCW, VSFCW), and hybrid systems have been reported. The average removal efficiencies of the systems ranged from 83 to 95% for biochemical oxygen demand, 74 to 94% for chemical oxygen demand, 78 to 96% for total suspended solids, 75 to 85% for ammonium, 44 to 85% for ammonia, 50 to 73% for nitrate, 57 to 88% for total Kjeldahl nitrogen, 51 to 58% total nitrogen, and 66 to 99% for total phosphorus. The majority of the systems were implemented as decentralized treatment solutions using HSFCWs, with the second most common design being the hybrid CW systems in order to reduce area requirements, increase treatment efficiency, and prevent clogging. Overall, CWs are a promising sustainable solution which may support access to adequate sanitation worldwide as well as safe wastewater recycling and reuse, leading to more sustainable tourist destinations.
Anxiety, Attachment Styles and Life Satisfaction in the Polish LGBTQ+ Community
Authors: Kardasz Zofia , Gerymski Rafał , Parker Arkadiusz
Published: July 2023

Poland is one of the most discriminatory places in Europe. The political situation, legal policies, and society’s attitude towards people from the LGBTQ+ community in Poland clearly indicate the need to study the mental health and well-being of this group of individuals. Based on Meyer’s minority stress theory, Bowlby’s attachment theory, the Ainsworth attachment framework, Diener’s subjective well-being model, and provided empirical evidence, this study examined the significance of attachment styles and anxiety as predictors of life satisfaction among the Polish LGBTQ+ community. It also explored the differences between LGBTQ+ and heterosexual individuals in the levels of tested variables. A total of 414 participants took part in this study, of whom most study participants were young adults (M = 24.50; SD = 6.94). Of those, 130 participants identified themselves as heterosexual, while 284 declared themselves members of the LGBTQ+ community. The Satisfaction with Life Scale, Plopa’s Attachment Styles Questionnaire, and the State-Trait Anxiety Inventory were used. Data demonstrate that anxiety and attachment styles were significant predictors of life satisfaction in the LGBTQ+ community. Moreover, LGBTQ+ individuals had higher non-secure attachment styles and anxiety scores, and lower life satisfaction scores in comparison to heterosexual individuals. The presented study is the first Polish study to test such relationships in the Polish LGBTQ+ community. It draws attention to lower life satisfaction among study participants representing the LGBTQ+ community in comparison to cisgender heterosexual individuals. This indicates that researchers, clinical specialists and practitioners should try to improve the levels of subjective well-being in Polish LGBTQ+ individuals, for example, through psychoeducational and supportive programs. In addition, the presented results highlight the possible important role of attachment styles in the functioning of the presented group.
Quality of Life in Healthcare Workers during COVID-19—A Longitudinal Study
Authors: Jungmar Ridell Robin , Orvelius Lotti
Published: July 2023

The COVID-19 pandemic occurred in 2020, and affected people’s daily life worldwide at work and at home. Healthcare workers are a professional group with heavy workloads, and during the COVID-19 pandemic, their burden increased. The literature from earlier outbreaks describes risks for affected mental health in frontline workers, and the main aim of this study is to examine healthcare workers’ quality of life during the COVID-19 pandemic. In addition, we sought to assess if there was any difference in working at a pandemic ward compared to anon-pandemic ward. In this longitudinal and descriptive study, a total of 147 healthcare workers assessed their perceived health every third month over one year using the RAND-36 health survey. RAND-36 is a general instrument that consists of 36 questions and is widely used for assessing quality of life. The healthcare workers in this study showed reductions in perceived quality of life during the first six months of the COVID-19 pandemic. Healthcare workers on a pandemic ward reported a lower score in RAND-36 compared to healthcare workers on a non-pandemic ward. Registered nurses and licensed practical nurses seemed more negatively affected in their quality of life than physicians. Compared to data from the general Swedish population, healthcare workers in this study had less energy during this period.
Tortoise or Hare? The Associations between Physical Activity Volume and Intensity Distribution and the Risk of All-Cause Mortality: A Large Prospective Analysis of the UK Biobank
Authors: Salway Ruth , Augustin Nicole Helene , Armstrong Miranda Elaine Glynis
Published: July 2023

Analysis methods to determine the optimal combination of volume and intensity of objectively measured physical activity (PA) with prospective outcomes are limited. Participants in UK Biobank were recruited in the UK between 2006 and 2010. We linked the questionnaire and accelerometer with all-cause mortality data from the NHS Information Centre and NHS Central Register up to April 2021. We developed a novel method, extending the penalized spline model of Augustin et al. to a smooth additive Cox model for survival data, and estimated the prospective relationship between intensity distribution and all-cause mortality, adjusting for the overall volume of PA. We followed 84,166 men and women (aged 40–69) for an average of 6.4 years (range 5.3–7.9), with an observed mortality rate of 22.2 deaths per 1000. Survival rates differed by PA volume quartile, with poorer outcomes for the lowest PA volumes. Participants with more sedentary to light intensity PA (<100 milligravities (mg)) and/or less vigorous intensity PA (>250 mg) than average for a given volume of PA, had higher mortality rates than vice versa. Approximate hazard ratios were 0.83 (95% credible interval [CI]: 0.79, 0.88) for an average-risk profile compared to a high-risk profile and 0.80 (95% CI: 0.74, 0.87) for a low-risk profile compared to an average-risk profile. A high- versus low-risk profile has the equivalent of 15 min more slow walking, but 10 min less moderate walking. At low PA volumes, increasing overall volume suggests the most benefit in reducing all-cause mortality risk. However, at higher overall volumes, substituting lighter with more vigorous intensity activity suggests greater benefit.
Targeted Alpha-Particle Therapy: A Review of Current Trials
Authors: Jang Albert , Kendi Ayse T. , Johnson Geoffrey B. , Halfdanarson Thorvardur R. , Sartor Oliver
Published: July 2023

Radiopharmaceuticals are rapidly developing as a field, with the successful use of targeted beta emitters in neuroendocrine tumors and prostate cancer serving as catalysts. Targeted alpha emitters are in current development for several potential oncologic indications. Herein, we review the three most prevalently studied conjugated/chelated alpha emitters (225actinium, 212lead, and 211astatine) and focus on contemporary clinical trials in an effort to more fully appreciate the breadth of the current evaluation. Phase I trials targeting multiple diseases are now underway, and at least one phase III trial (in selected neuroendocrine cancers) is currently in the initial stages of recruitment. Combination trials are now also emerging as alpha emitters are integrated with other therapies in an effort to create solutions for those with advanced cancers. Despite the promise of targeted alpha therapies, many challenges remain. These challenges include the development of reliable supply chains, the need for a better understanding of the relationships between administered dose and absorbed dose in both tissue and tumor and how that predicts outcomes, and the incomplete understanding of potential long-term deleterious effects of the alpha emitters. Progress on multiple fronts is necessary to bring the potential of targeted alpha therapies into the clinic.
Functionalization of Polyhydroxyalkanoates (PHA)-Based Bioplastic with Phloretin for Active Food Packaging: Characterization of Its Mechanical, Antioxidant, and Antimicrobial Activities
Authors: Mirpoor Seyedeh Fatemeh , Patanè Giuseppe Tancredi , Corrado Iolanda , Giosafatto C. Valeria L. , Ginestra Giovanna , Nostro Antonia , Foti Antonino , Gucciardi Pietro G. , Mandalari Giuseppina , Barreca Davide , Gervasi Teresa , Pezzella Cinzia
Published: July 2023

The formulation of eco-friendly biodegradable packaging has received great attention during the last decades as an alternative to traditional widespread petroleum-based food packaging. With this aim, we designed and tested the properties of polyhydroxyalkanoates (PHA)-based bioplastics functionalized with phloretin as far as antioxidant, antimicrobial, and morpho-mechanic features are concerned. Mechanical and hydrophilicity features investigations revealed a mild influence of phloretin on the novel materials as a function of the concentration utilized (5, 7.5, 10, and 20 mg) with variation in FTIR e RAMAN spectra as well as in mechanical properties. Functionalization of PHA-based polymers resulted in the acquisition of the antioxidant activity (in a dose-dependent manner) tested by DPPH, TEAC, FRAR, and chelating assays, and in a decrease in the growth of food-borne pathogens (Listeria monocytogenes ATCC 13932). Finally, apple samples were packed in the functionalized PHA films for 24, 48, and 72 h, observing remarkable effects on the stabilization of apple samples. The results open the possibility to utilize phloretin as a functionalizing agent for bioplastic formulation, especially in relation to food packaging.
Multiple Ways of Nitric Oxide Production in Plants and Its Functional Activity under Abiotic Stress Conditions
Authors: Allagulova Chulpan R. , Lubyanova Alsu R. , Avalbaev Azamat M.
Published: July 2023

Nitric oxide (NO) is an endogenous signaling molecule that plays an important role in plant ontogenesis and responses to different stresses. The most widespread abiotic stress factors limiting significantly plant growth and crop yield are drought, salinity, hypo-, hyperthermia, and an excess of heavy metal (HM) ions. Data on the accumulation of endogenous NO under stress factors and on the alleviation of their negative effects under exogenous NO treatments indicate the perspectives of its practical application to improve stress resistance and plant productivity. This requires fundamental knowledge of the NO metabolism and the mechanisms of its biological action in plants. NO generation occurs in plants by two main alternative mechanisms: oxidative or reductive, in spontaneous or enzymatic reactions. NO participates in plant development by controlling the processes of seed germination, vegetative growth, morphogenesis, flower transition, fruit ripening, and senescence. Under stressful conditions, NO contributes to antioxidant protection, osmotic adjustment, normalization of water balance, regulation of cellular ion homeostasis, maintenance of photosynthetic reactions, and growth processes of plants. NO can exert regulative action by inducing posttranslational modifications (PTMs) of proteins changing the activity of different enzymes or transcriptional factors, modulating the expression of huge amounts of genes, including those related to stress tolerance. This review summarizes the current data concerning molecular mechanisms of NO production and its activity in plants during regulation of their life cycle and adaptation to drought, salinity, temperature stress, and HM ions.
Interplay between Systemic Glycemia and Neuroprotective Activity of Resveratrol in Modulating Astrocyte SIRT1 Response to Neuroinflammation
Authors: Grabowska Anna D. , Wątroba Mateusz , Witkowska Joanna , Mikulska Agnieszka , Sepúlveda Nuno , Szukiewicz Dariusz
Published: July 2023

The flow of substances between the blood and the central nervous system is precisely regulated by the blood–brain barrier (BBB). Its disruption due to unbalanced blood glucose levels (hyper- and hypoglycemia) occurring in metabolic disorders, such as type 2 diabetes, can lead to neuroinflammation, and increase the risk of developing neurodegenerative diseases. One of the most studied natural anti-diabetic, anti-inflammatory, and neuroprotective compounds is resveratrol (RSV). It activates sirtuin 1 (SIRT1), a key metabolism regulator dependent on cell energy status. The aim of this study was to assess the astrocyte SIRT1 response to neuroinflammation and subsequent RSV treatment, depending on systemic glycemia. For this purpose, we used an optimized in vitro model of the BBB consisting of endothelial cells and astrocytes, representing microvascular and brain compartments (MC and BC), in different glycemic backgrounds. Astrocyte-secreted SIRT1 reached the highest concentration in hypo-, the lowest in normo-, and the lowest in hyperglycemic backgrounds. Lipopolysaccharide (LPS)-induced neuroinflammation caused a substantial decrease in SIRT1 in all glycemic backgrounds, as observed earliest in hyperglycemia. RSV partially counterbalanced the effect of LPS on SIRT1 secretion, most remarkably in normoglycemia. Our results suggest that abnormal glycemic states have a worse prognosis for RSV-therapy effectiveness compared to normoglycemia.
Epigenetic Modulation of Inflammatory Pathways in Myometrial Stem Cells and Risk of Uterine Fibroids
Authors: Yang Qiwei , Ali Mohamed , Treviño Lindsey S. , Mas Aymara , Ismail Nahed , Al-Hendy Ayman
Published: July 2023

The period during which tissue and organ development occurs is particularly vulnerable to the influence of environmental exposures. However, the specific mechanisms through which biological pathways are disrupted in response to developmental insults, consequently elevating the risk of hormone-dependent diseases, such as uterine fibroids (UFs), remain poorly understood. Here, we show that developmental exposure to the endocrine-disrupting chemical (EDC), diethylstilbestrol (DES), activates the inflammatory pathways in myometrial stem cells (MMSCs), which are the origin of UFs. Significantly, the secretome of reprogrammed MMSCs enhances the expression of critical inflammation-related genes in differentiated myometrial cells through the paracrine mechanism, which amplifies pro-inflammatory and immune suppression signaling in the myometrium. The expression of reprogrammed inflammatory responsive genes (IRGs) is driven by activated mixed-lineage leukemia protein-1 (MLL1) in MMSCs. The deactivation of MLL reverses the reprogramming of IRG expression. In addition, the inhibition of histone deacetylases (HDACs) also reversed the reprogrammed IRG expression induced by EDC exposure. This work identifies the epigenetic mechanisms of MLL1/HDAC-mediated MMSC reprogramming, and EDC exposure epigenetically targets MMSCs and imparts an IRG expression pattern, which may result in a “hyper-inflammatory phenotype” and an increased hormone-dependent risk of UFs later in life.
Deciphering the Action of Neuraminidase in Glioblastoma Models
Authors: Baeza-Kallee Nathalie , Bergès Raphaël , Hein Victoria , Cabaret Stéphanie , Garcia Jeremy , Gros Abigaëlle , Tabouret Emeline , Tchoghandjian Aurélie , Colin Carole , Figarella-Branger Dominique
Published: July 2023

Glioblastoma (GBM) contains cancer stem cells (CSC) that are resistant to treatment. GBM CSC expresses glycolipids recognized by the A2B5 antibody. A2B5, induced by the enzyme ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyl transferase 3 (ST8Sia3), plays a crucial role in the proliferation, migration, clonogenicity and tumorigenesis of GBM CSC. Our aim was to characterize the resulting effects of neuraminidase that removes A2B5 in order to target GBM CSC. To this end, we set up a GBM organotypic slice model; quantified A2B5 expression by flow cytometry in U87-MG, U87-ST8Sia3 and GBM CSC lines, treated or not by neuraminidase; performed RNAseq and DNA methylation profiling; and analyzed the ganglioside expression by liquid chromatography–mass spectrometry in these cell lines, treated or not with neuraminidase. Results demonstrated that neuraminidase decreased A2B5 expression, tumor size and regrowth after surgical removal in the organotypic slice model but did not induce a distinct transcriptomic or epigenetic signature in GBM CSC lines. RNAseq analysis revealed that OLIG2, CHI3L1, TIMP3, TNFAIP2, and TNFAIP6 transcripts were significantly overexpressed in U87-ST8Sia3 compared to U87-MG. RT-qPCR confirmed these results and demonstrated that neuraminidase decreased gene expression in GBM CSC lines. Moreover, neuraminidase drastically reduced ganglioside expression in GBM CSC lines. Neuraminidase, by its pleiotropic action, is an attractive local treatment against GBM.
Bradykinin Metabolism and Drug-Induced Angioedema
Authors: Smolinska Sylwia , Antolín-Amérigo Darío , Popescu Florin-Dan
Published: July 2023

Bradykinin (BK) metabolism and its receptors play a central role in drug-induced angioedema (AE) without urticaria through increased vascular permeability. Many cardiovascular and diabetic drugs may cause BK-mediated AE. Angiotensin-converting enzyme inhibitors (ACEIs) and neprilysin inhibitors impair BK catabolism. Dipeptidyl peptidase-IV (DPP-IV) inhibitors reduce the breakdown of BK and substance P (SP). Moreover, angiotensin receptor blockers, thrombolytic agents, and statins may also induce BK-mediated AE. Understanding pathophysiological mechanisms is crucial for preventing and treating drug-induced AE.
Phospho-RNA-Seq Highlights Specific Small RNA Profiles in Plasma Extracellular Vesicles
Authors: Solaguren-Beascoa Maria , Gámez-Valero Ana , Escaramís Georgia , Herrero-Lorenzo Marina , Ortiz Ana M. , Minguet Carla , Gonzalo Ricardo , Bravo Maria Isabel , Costa Montserrat , Martí Eulàlia
Published: July 2023

Small RNAs (sRNAs) are bioactive molecules that can be detected in biofluids, reflecting physiological and pathological states. In plasma, sRNAs are found within extracellular vesicles (EVs) and in extravesicular compartments, offering potential sources of highly sensitive biomarkers. Deep sequencing strategies to profile sRNAs favor the detection of microRNAs (miRNAs), the best-known class of sRNAs. Phospho-RNA-seq, through the enzymatic treatment of sRNAs with T4 polynucleotide kinase (T4-PNK), has been recently developed to increase the detection of thousands of previously inaccessible RNAs. In this study, we investigated the value of phospho-RNA-seq on both the EVs and extravesicular plasma subfractions. Phospho-RNA-seq increased the proportion of sRNAs used for alignment and highlighted the diversity of the sRNA transcriptome. Unsupervised clustering analysis using sRNA counts matrices correctly classified the EVs and extravesicular samples only in the T4-PNK treated samples, indicating that phospho-RNA-seq stresses the features of sRNAs in each plasma subfraction. Furthermore, T4-PNK treatment emphasized specific miRNA variants differing in the 5′-end (5′-isomiRs) and certain types of tRNA fragments in each plasma fraction. Phospho-RNA-seq increased the number of tissue-specific messenger RNA (mRNA) fragments in the EVs compared with the extravesicular fraction, suggesting that phospho-RNA-seq favors the discovery of tissue-specific sRNAs in EVs. Overall, the present data emphasizes the value of phospho-RNA-seq in uncovering RNA-based biomarkers in EVs.
Suppression of TGFβ-Induced Interleukin-6 Secretion by Sinulariolide from Soft Corals through Attenuation of the p38–NF-kB Pathway in Carcinoma Cells
Authors: Yang Jenq-Lin , Lin Weng-Ling , Tai Shun-Ban , Ciou Yi-Siang , Chung Chih-Ling , Chen Jih-Jung , Liu Pei-Feng , Lin Ming-Wei , Chen Chun-Lin
Published: July 2023

Sinulariolide (SC-1) is a natural product extracted from the cultured-type soft coral Sinularia flexibilis and possesses anti-inflammation, anti-proliferative, and anti-migratory in several types of cancer cells. However, the molecular pathway behind its effects on inflammation remains poorly understood. Since inflammatory cytokines such as TGFβ, TNFα, IL-1, IL-6, and IL-8 activate transcription factors such as Smads, NF-κB, STAT3, Snail, Twist, and Zeb that drive the epithelial-to-mesenchymal transition (EMT), in this study, we focus on the investigation in effects of SC-1 on TGFβ-induced interleukin-6 (IL-6) releases in an in vitro cell culture model. We showed that both intracellular IL-6 expression and secretion were stimulated by TGFβ and associated with strong upregulation of IL-6 mRNA and increased transcription in A549 cells. SC-1 blocked TGFβ-induced secretion of IL-6 while showing no effect on the induction of fibronectin and plasminogen activator inhibitor-1 genes, indicating that SC-1 interferes with only a subset of TGFβ activities. In addition, SC-1 inhibits TGFβ-induced IL-6 by suppressing p38 MAPK signaling and subsequently inhibits NF-κB and its nuclear translocation without affecting the canonical Smad pathway and receptor turnover. Overall, these data suggest that p38 may involve in the inhibition of SC-1 in IL-6 release, thus illustrating an inhibitory effect for SC-1 in the suppression of inflammation, EMT phenotype, and tumorigenesis.
Evaluation of Novel Enhancer Compounds in Gentamicin-Mediated Readthrough of Nonsense Mutations in Rett Syndrome
Authors: Wong Keit Men , Wegener Eike , Baradaran-Heravi Alireza , Huppke Brenda , Gärtner Jutta , Huppke Peter
Published: July 2023

Rett syndrome (RTT), a severe X-linked neurodevelopmental disorder, is primarily caused by mutations in the methyl CpG binding protein 2 gene (MECP2). Over 35% RTT patients carry nonsense mutation in MECP2, making it a suitable candidate disease for nonsense suppression therapy. In our previous study, gentamicin was found to induce readthrough of MECP2 nonsense mutations with modest efficiency. Given the recent discovery of readthrough enhancers, CDX compounds, we herein evaluated the potentiation effect of CDX5-1, CDX5-288, and CDX6-180 on gentamicin-mediated readthrough efficiency in transfected HeLa cell lines bearing the four most common MECP2 nonsense mutations. We showed that all three CDX compounds potentiated gentamicin-mediated readthrough and increased full-length MeCP2 protein levels in cells expressing the R168X, R255X, R270X, and R294X nonsense mutations. Among all three CDX compounds, CDX5-288 was the most potent enhancer and enabled the use of reduced doses of gentamicin, thus mitigating the toxicity. Furthermore, we successfully demonstrated the upregulation of full-length Mecp2 protein expression in fibroblasts derived from Mecp2R255X/Y mice through combinatorial treatment. Taken together, findings demonstrate the feasibility of this combinatorial approach to nonsense suppression therapy for a subset of RTT patients.
T Cells in Colorectal Cancer: Unravelling the Function of Different T Cell Subsets in the Tumor Microenvironment
Authors: Zheng Ziwen , Wieder Thomas , Mauerer Bernhard , Schäfer Luisa , Kesselring Rebecca , Braumüller Heidi
Published: July 2023

Therapeutic options for metastatic colorectal cancer (mCRC) are very limited, and the prognosis using combination therapy with a chemotherapeutic drug and a targeted agent, e.g., epidermal growth factor receptor or tyrosine kinase, remains poor. Therefore, mCRC is associated with a poor median overall survival (mOS) of only 25–30 months. Current immunotherapies with checkpoint inhibitor blockade (ICB) have led to a substantial change in the treatment of several cancers, such as melanoma and non-small cell lung cancer. In CRC, ICB has only limited effects, except in patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) tumors, which comprise about 15% of sporadic CRC patients and about 4% of patients with metastatic CRC. The vast majority of sporadic CRCs are microsatellite-stable (MSS) tumors with low levels of infiltrating immune cells, in which immunotherapy has no clinical benefit so far. Immunotherapy with checkpoint inhibitors requires the presence of infiltrating T cells into the tumor microenvironment (TME). This makes T cells the most important effector cells in the TME, as evidenced by the establishment of the immunoscore—a method to estimate the prognosis of CRC patients. The microenvironment of a tumor contains several types of T cells that are anti-tumorigenic, such as CD8+ T cells or pro-tumorigenic, such as regulatory T cells (Tregs) or T helper 17 (Th17) cells. However, even CD8+ T cells show marked heterogeneity, e.g., they can become exhausted, enter a state of hyporesponsiveness or become dysfunctional and express high levels of checkpoint molecules, the targets for ICB. To kill cancer cells, CD8+ T cells need the recognition of the MHC class I, which is often downregulated on colorectal cancer cells. In this case, a population of unconventional T cells with a γδ T cell receptor can overcome the limitations of the conventional CD8+ T cells with an αβT cell receptor. γδ T cells recognize antigens in an MHC-independent manner, thus acting as a bridge between innate and adaptive immunity. Here, we discuss the effects of different T cell subsets in colorectal cancer with a special emphasis on γδ T cells and the possibility of using them in CAR-T cell therapy. We explain T cell exclusion in microsatellite-stable colorectal cancer and the possibilities to overcome this exclusion to enable immunotherapy even in these “cold” tumors.
Perfect Complementarity Mechanism for Aphid Control: Oligonucleotide Insecticide Macsan-11 Selectively Causes High Mortality Rate for Macrosiphoniella sanborni Gillette
Authors: Puzanova Yelizaveta , Novikov Ilya , Bilyk Anastasiya , Sharmagiy Alexander , Plugatar Yuri , Oberemok Volodymyr
Published: July 2023

Macrosiphoniella sanborni is a widespread pest of Chrysanthemum morifolium that causes significant damage to world floriculture. Chemical insecticides and biological methods of control have a number of disadvantages that can be improved by using oligonucleotide insecticides. In this article, we present, for the first time, the results of using oligonucleotide insecticides, for which the target sequence is an internal transcribed spacer (ITS) in a polycistronic rRNA transcript. The mortality of wingless aphid individuals after a Macsan-11 treatment was recorded at a level of 67.15 ± 3.32% 7 days after a single treatment with a solution at a concentration of 100 ng/μL and 97.38 ± 2.49% 7 days after a double treatment with a solution of the same concentration and a daily interval. The contact use of the control oligonucleotide (ACTG)2ACT-11. as well as the oligonucleotide insecticides Macsan-11(3′) and Macsan-11(5′) was not accompanied by insect mortality. Given the high variability in the internal transcribed spacer, which has proven to be a promising target for the action of oligonucleotide insecticides, it is possible to create selective preparations. This study showed the prospects of ribosomal insect pest genes as targets for the action of olinscides, and also demonstrated the high specificity of such insecticidal agents.
The Influence of Pedo-Climatic Conditions on the Micromorphological, Phytochemical Features, and Biological Properties of Leaves of Saponaria sicula Raf
Authors: Cornara Laura , Malaspina Paola , Betuzzi Federica , Di Gristina Emilio , D’Arrigo Manuela , Ingegneri Mariarosaria , Trombetta Domenico , Smeriglio Antonella
Published: July 2023

Saponaria sicula Raf. grows in Sicily, Sardinia, and Algeria on limestone cliffs and volcanic sands 1300–2500 m above sea level. The aim of the present study was to investigate how the pedo-climatic conditions influence the micromorphological, phytochemical, and biological properties of Sicilian S. sicula leaves collected in the Madonie Mountains (SsM) and on Etna Mt (SsE). Micromorphological investigations revealed that leaves from SsM had a higher amount of calcium oxalate druses in the mesophyll and a more intense blue–green staining with Toluidine blue O, indicating a higher content of polyphenols. These data were confirmed by phytochemical analyses carried out on hydroalcoholic extracts, which showed a higher content of total phenols (8.56 ± 0.57 g GAE/100 g DE) and flavonoids (6.09 ± 0.17 g RE/100 g DE) in SsM. Sixty-four compounds were identified by LC-DAD-ESI-MS analysis with propelargonidin dimer as the most abundant compound (10.49% and 10.19% in SsM and SsE, respectively). The higher polyphenol content of SsM leaves matches also with their biological activity, identifying SsM extract as the strongest plant complex (IC50 2.75–477.30 µg/mL). In conclusion, the present study experimentally demonstrates that not only climatic differences but also soil characteristics affect the micromorphological, phytochemical, and biological features of this plant species.
Overview of Updated Control Tactics for Western Flower Thrips
Authors: Rodríguez Daniel , Coy-Barrera Ericsson
Published: July 2023

Frankliniella occidentalis Pergande (Thysanoptera: Thripidae), broadly known as Western flower thrips (WFT), are currently one of the most critical pests worldwide in field and greenhouse crops, and their management is full of yet unsolved challenges derived from their high reproductive potential, cryptic habit, and ability to disperse. The control of this pest relies widely on chemical control, despite the propensity of the species to develop resistance. However, significant advances have been produced through biological and ethological control. Although there has recently been a remarkable amount of new information regarding the management of this pest worldwide, there is no critical analysis of recent developments and advances in the attractive control tactics for WFT, constituting the present compilation’s aim. Hence, this narrative review provides an overview of effective control strategies for managing thrips populations. By understanding the pest’s biology, implementing monitoring techniques, accurately identifying the species, and employing appropriate control measures, farmers and researchers can mitigate the WFT impact on agricultural production and promote sustainable pest management practices.
Effect of Aging on Intraventricular Kinetic Energy and Energy Dissipation
Authors: Mele Donato , Beccari Riccardo , Pedrizzetti Gianni
Published: July 2023

In recent years, analysis of kinetic energy (KE) and the rate of kinetic energy dissipation (KED) or energy loss (EL) within the cardiac chambers, obtained by cardiac imaging techniques, has gained increasing attention. Thus, there is a need to clarify the effect of physiological variables, specifically aging, on these energetic measures. To elucidate this aspect, we reviewed the literature on this topic. Overall, cardiac magnetic resonance and echocardiographic studies published so far indicate that aging affects the energetics of left and right intraventricular blood flow, although not all energy measures during the cardiac cycle seem to be affected by age in the same way. Current studies, however, have limitations. Additional large, multicenter investigations are needed to test the effect of physiological variables on intraventricular KE and KED/EL measures.
Dietary Intervention Improves Gastrointestinal Symptoms after Treatment of Cancer in the Pelvic Organs
Authors: Borre Mette , Fassov Janne , Poulsen Jakob , Christensen Peter , Laurberg Søren , Drewes Asbjørn , Krogh Klaus
Published: July 2023

Gastrointestinal (GI) symptoms are common in patients receiving radiotherapy, chemotherapy, and/or surgery for cancer in the pelvic organs. The aim of the present prospective cohort study was to report the efficacy of dietary intervention in patients with chronic GI sequelae to treatment of cancer in pelvic organs and insufficient symptomatic effect of medical treatment. Eighty-eight patients were offered specialist dietitian guidance. Gastrointestinal symptoms and quality of life were assessed before and after intervention by validated questionnaires. The main dietary interventions were low-fat diet (n = 44; 50%), modification of dietary fiber content (n = 19; 33%), dietary restrictions with a low-FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides, and polyols) diet (n = 18; 20%), gluten-free diet (n = 1; 1%), and other dietary advice (n = 6; 7%). Compared to baseline, dietary intervention improved quality of life (EQ5D scale) (p < 0.01), bowel function for the last four weeks (p < 0.02), stool frequency (p < 0.03), constipation (p < 0.05), incomplete rectal emptying at defecation (p < 0.02), and performing usual activities (p < 0.0). In conclusion, this observational study using tailored dietary intervention showed that symptoms can be reduced and quality of life can be improved in patients with chronic GI sequelae following treatment of cancer in the pelvic organs not responding sufficiently to medical treatment.