bluuebunny/crossref_metadata_2025 huggingface dataset:
Sorghum Flour and Sorghum Flour Enriched Bread: Characterizations, Challenges, and Potential Improvements
Authors: Saeed Omer Saeed Hamid , Hong Jing , Zheng Xueling , Khashaba Reham
Published: November 2023

A Sorghum flour (SF) is a leading and prominent food source for humans in African countries. Recently extensive studies have been conducted on Sorghum bread (SB) or sorghum composite bread (SCB), covering various aspects. However, there are many technical challenges in the formation of SF and sorghum composite flour (SCF) that impact the quality of the bread and fail to meet the consumer’s desires and expectations. This review primarily focuses on the characteristics of SF, SCF, SB, and SCB, with discussions encompassing the rheological and morphological properties of the dough, improvement strategies, and bread quality. Moreover, a comprehensive analysis has been conducted to investigate the behavior of SF and SCF along with a discussion of the challenges affecting bread quality and the strategies applied for improvement. The significant demand for nutrients-rich and gluten-free bread indicates that sorghum will become one of the most vital crops worldwide. However, further comprehensive research is highly demanded and necessary for an in-depth understanding of the key features of SF and the resulting bread quality. Such understanding is vital to optimize the utilization of sorghum grain in large-scale bread production.
An Overview of Ingredients Used for Plant-Based Meat Analogue Production and Their Influence on Structural and Textural Properties of the Final Product
Authors: Benković Maja , Jurinjak Tušek Ana , Sokač Cvetnić Tea , Jurina Tamara , Valinger Davor , Gajdoš Kljusurić Jasenka
Published: November 2023

Plant-based meat analogues are food products made from vegetarian or vegan ingredients that are intended to mimic taste, texture and appearance of meat. They are becoming increasingly popular as people look for more sustainable and healthy protein sources. Furthermore, plant-based foods are marketed as foods with a low carbon footprint and represent a contribution of the consumers and the food industry to a cleaner and a climate-change-free Earth. Production processes of plant-based meat analogues often include technologies such as 3D printing, extrusion or shear cell where the ingredients have to be carefully picked because of their influence on structural and textural properties of the final product, and, in consequence, consumer perception and acceptance of the plant-based product. This review paper gives an extensive overview of meat analogue components, which affect the texture and the structure of the final product, discusses the complex interaction of those ingredients and reflects on numerous studies that have been performed in that area, but also emphasizes the need for future research and optimization of the mixture used in plant-based meat analogue production, as well as for optimization of the production process.
Physiological, Photosynthetic, and Transcriptomics Insights into the Influence of Shading on Leafy Sweet Potato
Authors: Jing Xiaojing , Chen Peiru , Jin Xiaojie , Lei Jian , Wang Lianjun , Chai Shasha , Yang Xinsun
Published: November 2023

Leafy sweet potato is a new type of sweet potato, whose leaves and stems are used as green vegetables. However, sweet potato tips can be affected by pre-harvest factors, especially the intensity of light. At present, intercropping, greenhouse planting, and photovoltaic agriculture have become common planting modes for sweet potato. Likewise, they can also cause insufficient light conditions or even low light stress. This research aimed to evaluate the influence of four different shading levels (no shading, 30%, 50%, and 70% shading degree) on the growth profile of sweet potato leaves. The net photosynthetic rate, chlorophyll pigments, carbohydrates, and polyphenol components were determined. Our findings displayed that shading reduced the content of the soluble sugar, starch, and sucrose of leaves, as well as the yield and Pn. The concentrations of Chl a, Chl b, and total Chl were increased and the Chl a/b ratio was decreased for the more efficient interception and absorption of light under shading conditions. In addition, 30% and 50% shading increased the total phenolic, total flavonoids, and chlorogenic acid. Transcriptome analysis indicated that genes related to the antioxidant, secondary metabolism of phenols and flavonoids, photosynthesis, and MAPK signaling pathway were altered in response to shading stresses. We concluded that 30% shading induced a high expression of antioxidant genes, while genes related to the secondary metabolism of phenols and flavonoids were upregulated by 50% shading. And the MAPK signaling pathway was modulated under 70% shading, and most stress-related genes were downregulated. Moreover, the genes involved in photosynthesis, such as chloroplast development, introns splicing, and Chlorophyll synthesis, were upregulated as shading levels increased. This research provides a new theoretical basis for understanding the tolerance and adaptation mechanism of leafy sweet potato in low light environments.
Concurrent Validity and Test–Retest Reliability of the 3-Meter Backward Walk Test in Stroke Survivors
Authors: Kapan Ali , Ristic Milos , Yang Lin , Kranz Gottfried , Waldhör Thomas
Published: November 2023

In the context of evaluating physical function in individuals with stroke, the 3-Meter Backward Walk Test (3MBWT) emerges as a potential tool of interest. The purpose of this study was to assess the test–retest reliability and concurrent validity of the 3MBWT and its correlation with falling incidents. Conducted in a neurological rehabilitation center, 35 ambulatory individuals with stroke were enrolled within a month post-stroke onset. These participants, with a Functional Ambulation Category score of ≥4, underwent the 3MBWT, Functional Gait Assessment (FGA), 10-Meter Walk Test (10MWT), and 6-Minute Walk Test (6MWT) under the supervision of different physiotherapists. The results indicate that the 3MBWT demonstrated high reliability, with an Intraclass Correlation Coefficient of 0.97 (95% CI: 0.95, 0.98). It also showed significant concurrent validity with other established walking tests like the 6MWT (r = −0.78) and 10MWT (r = 0.71), with a moderate correlation with the FGA (r = −0.54). No marked differences in test outcomes were observed between participants based on their fall history. Conclusively, the 3MBWT proves to be highly reliable and agrees well with existing walking function assessments for stroke patients, suggesting its potential as a time-efficient alternative.
Bacterial and Fungal Endophytes of Grapevine Cultivars Growing in Primorsky Krai of Russia
Authors: Aleynova Olga A. , Nityagovsky Nikolay N. , Ananev Alexey A. , Suprun Andrey R. , Ogneva Zlata V. , Dneprovskaya Alina A. , Beresh Alina A. , Dubrovina Alexandra S. , Chebukin Pavel A. , Kiselev Konstantin V.
Published: November 2023

In this study, the biodiversity of endophytic bacteria of cultivated grape varieties from the vineyards of Primorsky Krai, Russia, was analyzed for the first time. Far Eastern grape varieties with a high level of stress resistance are a unique object of research as they are cultivated in cold and humid climates with a short summer season. Grapevine endophytic microorganisms are known as promising agents for the biological control of grapevine diseases and agricultural pests. Using genomic approaches, we analyzed the biodiversity of the endophytic bacteria and fungi in the most common grape varieties of Primorsky Krai, Russia: Vitis vinifera × Vitis amurensis cv. Adele (hybrid No. 82-41 F3), Vitis riparia × V. vinifera cv. Mukuzani (pedigree unknown), two cultivars Vitis labrusca × V. riparia cv. Alfa, and Vitis Elmer Swenson 2-7-13 cv. Prairie Star for the first time. The main representatives of the endophytic microorganisms included 16 classes of bacteria and 21 classes of fungi. The endophytic bacterial community was dominated by Gammaproteobacteria (31–59%), followed by Alphaproteobacteria (9–34%) and, to a lesser extent, by the classes Bacteroidia (9–22%) and Actinobacteria (6–19%). The dominant fungal class was Dothideomycetes (43–77%) in all samples analyzed, with the exception of the grapevine cv. Mukuzani from Makarevich, where Malasseziomycetes was the dominant fungal class. In the samples cv. Alfa and cv. Praire Star, the dominant classes were Tremellomycetes and Microbotriomycetes. A comparative analysis of the endophytic communities of the cultivated grape varieties and the wild grape V. amurensis Rupr. was also carried out. We found that 18–20% of the variance between the endophytic communities accounted for the differences between the cultivated and wild grapevines, while the factors “plant location” and “individual plants” accounted for 50–56% and 3–10% of the variance, respectively. The results of this study can be used to develop new means of biocontrol in vineyards to protect plants from abiotic stresses and pathogens.
Reducing Barriers to COVID-19 Vaccination Uptake: Community Ideas from Urban and Rural Kenya
Authors: Al-Aghbari Ahmed Asa’ad , Naanyu Violet , Luchters Stanley , Irungu Eunice , Baalawy Kawthar , Bärnighausen Till , Mauti Joy
Published: November 2023

Following the rapid development of COVID-19 vaccines, addressing vaccine hesitancy and optimizing uptake have emerged as critical challenges, emphasizing the importance of reducing barriers toward COVID-19 vaccination. This study investigates ideas on ways to reduce barriers to COVID-19 vaccination uptake. It explores methods that can overcome COVID-19 vaccination barriers through qualitative research: interviews and group discussions involving healthcare providers, administration personnel, teachers, and individuals with chronic conditions across urban (Mombasa) and rural (Kilifi) Kenya. Audio-recorded discussions were transcribed and thematically analyzed across locations. Five themes emerged in our results regarding the reduction in barriers to COVID-19 vaccination in the context of Kenya, including awareness campaigns, engaging diverse stakeholders, using various communication techniques, capacity building to increase vaccination centers and trained staff, and lastly, revising relevant government health policies and guidelines. These results indicate the importance of adopting multiple approaches, as no single strategy can boost vaccine acceptance. Moreover, this study provides recommendations for conceiving actionable interventions to potentially boost vaccine demand and maintain routine immunization in Kenya.
Tellegacy: An Intergenerational Wellness and Health Promotion Project to Reduce Social Isolation and Loneliness in Older Adults: A Feasibility Study
Authors: Holloway Jeremy , Sayeed Owais , Jurivich Donald
Published: November 2023

Emerging research demonstrates that social isolation and loneliness are linked to significant physical and mental health conditions. To address these concerns, the Tellegacy program was developed as an intergenerational health-promoting intervention to ameliorate older adult social isolation and loneliness in an effort to increase wellness. The purpose of this study was to reflect on testing of the Tellegacy program as a behavioral intervention. University students trained in goal setting, mindfulness, and listening strategies were paired with 11 older adults in the northern Midwest area via weekly in-person and phone conversations. Oral reminiscence therapies were used and books containing their stories were given to the older adults after participation. Older adults were surveyed using the University of California Los Angeles Loneliness Scale, Satisfaction of Life Scale, and patient health questionnaire-9 (PHQ-9) scale to elucidate the effectiveness of the intervention. Improved scores in loneliness, satisfaction of life, and PHQ-9 demonstrated favorable improvements in older adults. Additional benefits for the student Legacy Builder were revealed from self-reported changes. This suggests the potential benefits of structured encounters between trained students and isolated or lonely older adults. The Tellegacy intergenerational feasibility program warrants further studies to fully demonstrate its impact on health outcomes.
Social Outbreak in Chile, and Its Association with the Effects Biological, Psychological, Social, and Quality of Life
Authors: Parra-Soto Solange , Duran-Aguero Samuel , Vargas-Silva Francisco , Vázquez-Morales Katherine , Pizarro-Mena Rafael
Published: November 2023

The World Health Organization has defined collective violence as the instrumental use of violence by people who identify themselves as members of a group against other individuals and have political, economic, or social objectives. In Chile, the “Social Outbreak” was used to describe an episode of collective violence, which began on October 18, 2019, triggered by a multitude of socioeconomic and political factors, with protests and mobilizations in the country’s large and small cities; in central, commercial, and residential areas, that lasted for several months, affecting a large part of the population. The objective of the present study was to associate the social outbreak in Chile with its biological, psychological, and social effects on people’s health and quality of life, as well as its characteristics in terms of exposure, proximity, type, and frequency. This was a cross-sectional study with non-probabilistic national-level sampling, conducted from 28 November 2019, to 3 March 2020. The instrument had four sections. A total of 2651 participants answered the survey; 70.8% were female, and the mean age was 35.2. The main disturbances perceived were protests (70.9%), alarm sounds (68.1%), shooting sounds (59.0%), and tear gas bombs (56.9%). When quantifying the magnitude of these associations, people who had a medium exposure have a higher probability (OR: 1.99, CI: 1.58; 2.50) of suffering three or more biological effects than people that have a low exposure, while people with higher exposition have a 4.09 times higher probability (CI: 3.11; 5.38). A similar pattern was observed regarding psychological effects, although social effects were primarily experienced by those with high exposure. Social networks, TV, and radio were the most used media among people who perceived a greater effect. People who lived, worked, or shopped near the disturbance’s areas show a higher proportion negative effect.
A Cardiopulmonary Exercise Testing for Prescribing High-Intensity Interval Training Sessions with Elastic Resistance
Authors: Duarte Lorena Flores , Gasparini-Neto Victor Hugo , Neves Letícia Nascimento Santos , Nunes Lenice Brum , Leite Richard Diego , de Sousa Nuno Manoel Frade , Carletti Luciana
Published: November 2023

This study aims to analyze the agreement of cardiopulmonary variables between a cardiopulmonary exercise test with elastic resistance (CPxEL) and high-intensity interval exercise with elastic resistance (EL-HIIE). Methods: Twenty-two physically independent participants were recruited. Visit one consisted of conducting a health survey and anthropometric assessment. On visit two, the participants performed CPxEL. After seven days, on visit three, the participants performed EL-HIIE. The CPxEL was carried out on a rubber mat demarcated by lines representing eight stages. The test consisted of alternating back and forth steps against elastic resistance. The increments were performed at a rate of one stage per minute, following a cadence controlled by a metronome calibrated by beats per minute (bpm). The EL-HIIE was performed at the stage corresponding to an intensity of ~85% VO2max, as determined by CPxEL. The EL-HIIE consisted of 10 × 1 min (work):1 min (passive rest), with a cadence of 200 bpm. Cardiopulmonary parameters, heart rate (HR), and oxygen consumption (VO2) were measured during exercise. Bland–Altman was applied to analyze the agreement between the HR and VO2 found in EL-HIIE and the values prescribed by CPxEL (~85–90% VO2max). Results: The HRpeak and VO2peak in the EL-HIIE showed good agreement with the VO2CPxEL and HRCPxEL values, showing an average difference of (−1.7 mL·kg−1·min−1) and (0.3 bpm). Conclusions: The results of the present study demonstrate the agreement of cardiopulmonary variables between the CPxEL and the EL-HIIE. Therefore, for a more specific prescription of EL-HIIE intensity, CPxEL can be used.
Respiratory Parameters as Predictors of Balance and Gait Ability in Patients with Stroke at Discharge
Authors: Park Hee-Yong , Kwon Oh-Yun , Yi Chung-Hwi , Jeon Hye-Seon , Choi Woochol Joseph , Ahn So-Young , Hwang Ui-Jae
Published: November 2023

Pulmonary complications are frequent in stroke, contributing to both mortality and morbidity rates. Respiratory parameters in such patients encompass both pulmonary function and respiratory muscle strength. Identifying respiratory function variables that influence the balance and gait ability of patients with stroke is crucial for enhancing their recovery in these aspects. However, no study has assessed predictions for a comprehensive array of balance and gait abilities in such patients. We aimed to examine whether initial respiratory muscle strength and pulmonary function can predict balance and gait ability at discharge from a rehabilitation program. Thirty-one patients with stroke were included in this prospective observational study. Multiple regression models with a forward selection procedure were employed to identify respiratory parameters (including peak expiratory flow and maximal expiratory pressure) that contributed to the results of balance assessments and gait evaluations at the time of discharge. The peak expiratory flow (PEF) served as a predictor explaining 42.0% of the variance. Similarly, the maximal expiratory pressure (MEP) was a predictor variable explaining 32.0% of the variance. PEF and MEP assessments at the initial stage as predictive factors for both balance and gait ability are important in stroke management.
Advance in Targeted Cancer Therapy and Mechanisms of Resistance
Authors: Tang Patrick Ming-Kuen , Zhang Dongmei
Published: November 2023

Drug resistance remains one of the important clinical challenges, making cancer one of the leading causes of death worldwide [...]
Low Levels of Serum Total Vitamin B12 Are Associated with Worse Metabolic Phenotype in a Large Population of Children, Adolescents and Young Adults, from Underweight to Severe Obesity
Authors: Aureli Alessia , Recupero Rosanna , Mariani Michela , Manco Melania , Carlomagno Francesco , Bocchini Sarah , Nicodemo Mirella , Marchili Maria Rosaria , Cianfarani Stefano , Cappa Marco , Fintini Danilo
Published: November 2023

Vitamin B12 (or cobalamin) is an essential vitamin for DNA synthesis, fatty acid and protein metabolism as well as other metabolic pathways fundamental to the integrity of cells and tissues in humans. It is derived from the diet and mostly stored in the liver. Its deficiency has been associated with metabolic derangements, i.e., obesity, glucose intolerance, increased lipogenesis and metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH). However, data with regard to body weight across the whole spectrum (from underweight to severe obesity) in children and young individuals are scarce. The present study aims to describe the association between serum total vitamin B12 and body mass index (BMI) ranging from underweight to severe obesity in a large population of children, adolescents and young adults. This study also investigates associations with visceral adiposity, glucose and lipid metabolism and liver dysfunction. A cross-sectional, single-centre study was conducted at the Paediatrics and Endocrinology units of the ”Bambino Gesù Children Hospital”, a tertiary referral institution for eating disorders. Clinical charts were reviewed and 601 patients aged from 5 to 25 years were enrolled in order to analyse anthropometric, auxological, clinical, biochemical and liver ultrasound data using robust statistical approaches. Analyses were adjusted for potential confounders. A reduction in serum total B12 levels was associated with a linear increase in body weight, as expressed by WHO BMI SDS (r = −0.31, p < 0.001, BCa 95% −0.38, −0.24). Lower B12 levels were associated with higher waist circumference but only in pubertal girls (r = −0.33, p = 0.008, BCa 95% −0.53, −0.11). Hepatic insulin resistance was higher in males with lower B12 levels (B = −0.003 (−0.007, −0.0001), p = 0.039), but not in females, whereas whole-body insulin resistance was unaffected. Serum lipid profiles (total, HDL and LDL cholesterol and triglycerides) were not influenced by serum cobalamin levels. However, lower cobalamin levels were associated with higher grading of ultrasound-scored hepatic steatosis (ptrend = 0.035). Lastly, both AST and ALT showed a significant and direct correlation with total B12 levels in underweight (r = 0.22 and 0.24, p = 0.002 and <0.001, respectively) and severely obese subjects (r = 0.24 and 0.32, p = 0.002 and <0.001). In conclusion lower vitamin B12 levels are associated with higher body weight, adiposity and with worse metabolic health in a large population of children, adolescents and young adults.
Novel CRYGC Mutation in Conserved Ultraviolet-Protective Tryptophan (p.Trp131Arg) Is Linked to Autosomal Dominant Congenital Cataract
Authors: Delas Flora , Koller Samuel , Feil Silke , Dacheva Ivanka , Gerth-Kahlert Christina , Berger Wolfgang
Published: November 2023

Congenital cataract (CC), the most prevalent cause of childhood blindness and amblyopia, necessitates prompt and precise genetic diagnosis. The objective of this study is to identify the underlying genetic cause in a Swiss patient with isolated CC. Whole exome sequencing (WES) and copy number variation (CNV) analysis were conducted for variant identification in a patient born with a total binocular CC without a family history of CC. Sanger Sequencing was used to confirm the variant and segregation analysis was used to screen the non-affected parents. The first de novo missense mutation at c.391T>C was identified in exon 3 of CRYGC on chromosome 2 causing the substitution of a highly conserved Tryptophan to an Arginine located at p.Trp131Arg. Previous studies exhibit significant changes in the tertiary structure of the crystallin family in the following variant locus, making CRYGC prone to aggregation aggravated by photodamage resulting in cataract. The variant can be classified as pathogenic according to the American College of Medical Genetics and Genomics (ACMG) criteria (PP3 + PM1 + PM2 + PS2; scoring 10 points). The identification of this novel variant expands the existing knowledge on the range of variants found in the CRYGC gene and contributes to a better comprehension of cataract heterogeneity.
Hub Genes in Stable QTLs Orchestrate the Accumulation of Cottonseed Oil in Upland Cotton via Catalyzing Key Steps of Lipid-Related Pathways
Authors: Alam Beena , Liu Ruixian , Gong Juwu , Li Junwen , Yan Haoliang , Ge Qun , Xiao Xianghui , Pan Jingtao , Shang Haihong , Shi Yuzhen , Yuan Youlu , Gong Wankui
Published: November 2023

Upland cotton is the fifth-largest oil crop in the world, with an average supply of nearly 20% of vegetable oil production. Cottonseed oil is also an ideal alternative raw material to be efficiently converted into biodiesel. However, the improvement in kernel oil content (KOC) of cottonseed has not received sufficient attention from researchers for a long time, due to the fact that the main product of cotton planting is fiber. Previous studies have tagged QTLs and identified individual candidate genes that regulate KOC of cottonseed. The regulatory mechanism of oil metabolism and accumulation of cottonseed are still elusive. In the current study, two high-density genetic maps (HDGMs), which were constructed based on a recombinant inbred line (RIL) population consisting of 231 individuals, were used to identify KOC QTLs. A total of forty-three stable QTLs were detected via these two HDGM strategies. Bioinformatic analysis of all the genes harbored in the marker intervals of the stable QTLs revealed that a total of fifty-one genes were involved in the pathways related to lipid biosynthesis. Functional analysis via coexpression network and RNA-seq revealed that the hub genes in the co-expression network that also catalyze the key steps of fatty acid synthesis, lipid metabolism and oil body formation pathways (ACX4, LACS4, KCR1, and SQD1) could jointly orchestrate oil accumulation in cottonseed. This study will strengthen our understanding of oil metabolism and accumulation in cottonseed and contribute to KOC improvement in cottonseed in the future, enhancing the security and stability of worldwide food supply.
Therapeutic Potential of Resveratrol for Glioma: A Systematic Review and Meta-Analysis of Animal Model Studies
Authors: Luís Ângelo , Marcelino Helena , Domingues Fernanda , Pereira Luísa , Cascalheira José Francisco
Published: November 2023

Gliomas are aggressive malignant brain tumors, with poor prognosis despite available therapies, raising the necessity for finding new compounds with therapeutic action. Numerous preclinical investigations evaluating resveratrol’s anti-tumor impact in animal models of glioma have been reported; however, the variety of experimental circumstances and results have prevented conclusive findings about resveratrol’s effectiveness. Several databases were searched during May 2023, ten publications were identified, satisfying the inclusion criteria, that assess the effects of resveratrol in murine glioma-bearing xenografts. To determine the efficacy of resveratrol, tumor volume and animal counts were retrieved, and the data were then subjected to a random effects meta-analysis. The influence of different experimental conditions and publication bias on resveratrol efficacy were evaluated. Comparing treated to untreated groups, resveratrol administration decreased the tumor volume. Overall, the effect’s weighted standardized difference in means was −2.046 (95%CI: −3.156 to −0.936; p-value < 0.001). The efficacy of the treatment was observed for animals inoculated with both human glioblastoma or rat glioma cells and for different modes of resveratrol administration. The combined administration of resveratrol and temozolomide was more effective than temozolomide alone. Reducing publication bias did not change the effectiveness of resveratrol treatment. The findings suggest that resveratrol slows the development of tumors in animal glioma models.
Allogenic Bone Graft in Dentistry: A Review of Current Trends and Developments
Authors: Ciszyński Michał , Dominiak Sebastian , Dominiak Marzena , Gedrange Tomasz , Hadzik Jakub
Published: November 2023

In an effort to prepare non-autologous bone graft or biomaterial that would possess characteristics comparable to autologous bone, many different allogenic bone derivatives have been created. Although different existing processing methods aim to achieve the very same results, the specific parameters applied during different stages material preparation can result in significant differences in the material’s mechanical and biological properties The properties, including osteoconductive, osteoinductive, and even osteogenic potential, can differ vastly depending on particular preparation and storage techniques used. Osteogenic properties, which have long been thought to be characteristic to autogenic bone grafts only, now seem to also be achievable in allogenic materials due to the possibility to seed the host’s stem cells on a graft before its implantation. In this article, we aim to review the available literature on allogenic bone and its derivatives as well as the influence of different preparation methods on its performance.
Evaluation of the Continuous Positive Airway Pressure Effect on Neurotrophins’ Gene Expression and Protein Levels
Authors: Gabryelska Agata , Turkiewicz Szymon , Ditmer Marta , Gajewski Adrian , Białasiewicz Piotr , Strzelecki Dominik , Chałubiński Maciej , Sochal Marcin
Published: November 2023

Neurotrophins (NT) might be associated with the pathophysiology of obstructive sleep apnea (OSA) due to concurrent intermittent hypoxia and sleep fragmentation. Such a relationship could have implications for the health and overall well-being of patients; however, the literature on this subject is sparse. This study investigated the alterations in the serum protein concentration and the mRNA expression of the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NTF3), and neurotrophin-4 (NTF4) proteins following a single night of continuous positive airway pressure (CPAP) therapy. This study group consisted of 30 patients with OSA. Venous blood was collected twice after a diagnostic polysomnography (PSG) and PSG with CPAP treatment. Gene expression was assessed with a quantitative real-time polymerase chain reaction. An enzyme-linked immunosorbent assay was used to determine the protein concentrations. After CPAP treatment, BDNF, proBDNF, GDNF, and NTF4 protein levels decreased (p = 0.002, p = 0.003, p = 0.047, and p = 0.009, respectively), while NTF3 increased (p = 0.001). Sleep latency was correlated with ΔPSG + CPAP/PSG gene expression for BDNF (R = 0.387, p = 0.038), NTF3 (R = 0.440, p = 0.019), and NTF4 (R = 0.424, p = 0.025). OSA severity parameters were not associated with protein levels or gene expressions. CPAP therapy could have an impact on the posttranscriptional stages of NT synthesis. The expression of different NTs appears to be connected with sleep architecture but not with OSA severity.
Identification of Anti-Neuroinflammatory Bioactive Compounds in Essential Oils and Aqueous Distillation Residues Obtained from Commercial Varieties of Cannabis sativa L.
Authors: Barbalace Maria Cristina , Freschi Michela , Rinaldi Irene , Mazzara Eugenia , Maraldi Tullia , Malaguti Marco , Prata Cecilia , Maggi Filippo , Petrelli Riccardo , Hrelia Silvana , Angeloni Cristina
Published: November 2023

Neuroinflammation, which is mainly triggered by microglia, is a key contributor to multiple neurodegenerative diseases. Natural products, and in particular Cannabis sativa L., due to its richness in phytochemical components, represent ideal candidates to counteract neuroinflammation. We previously characterized different C. sativa commercial varieties which showed significantly different chemical profiles. On these bases, the aim of this study was to evaluate essential oils and aqueous distillation residues from the inflorescences of three different hemp varieties for their anti-neuroinflammatory activity in BV-2 microglial cells. Cells were pretreated with aqueous residues or essential oils and then activated with LPS. Unlike essential oils, aqueous residues showed negligible effects in terms of anti-inflammatory activity. Among the essential oils, the one obtained from ‘Gorilla Glue’ was the most effective in inhibiting pro-inflammatory mediators and in upregulating anti-inflammatory ones through the modulation of the p38 MAPK/NF-κB pathway. Moreover, the sesquiterpenes (E)-caryophyllene, α-humulene, and caryophyllene oxide were identified as the main contributors to the essential oils’ anti-inflammatory activity. To our knowledge, the anti-neuroinflammatory activity of α-humulene has not been previously described. In conclusion, our work shows that C. sativa essential oils characterized by high levels of sesquiterpenes can be promising candidates in the prevention/counteraction of neuroinflammation.
Alterations in Intratumoral Immune Response before and during Early-On Nivolumab Treatment for Unresectable Advanced or Recurrent Gastric Cancer
Authors: Sato Yasuyoshi , Yamashita Hiroharu , Kobayashi Yukari , Nagaoka Koji , Hisayoshi Tetsuro , Kawahara Takuya , Kuroda Akihiro , Saito Noriyuki , Iwata Ryohei , Okumura Yasuhiro , Yagi Koichi , Aiko Susumu , Nomura Sachiyo , Kakimi Kazuhiro , Seto Yasuyuki
Published: November 2023

We investigated the tumor immune response in gastric cancer patients receiving third-line nivolumab monotherapy to identify immune-related biomarkers for better patient selection. Nineteen patients (10 males, median age 67 years) who received nivolumab as a third- or later-line therapy were enrolled. We analyzed the tumor immune response in durable clinical benefit (DCB) and non-DCB patients. Pre-treatment and early-on-treatment tumor transcriptomes were examined, and gene expression profiles, immunograms, and T cell receptor (TCR) repertoire were analyzed. DCB was observed in 15.8% of patients, with comparable secondary endpoints (ORR; objective response rate, OS; overall survival, PFS; progression-free survival) to previous trials. The immunograms of individual subjects displayed no significant changes before or early in the treatment, except for the regulatory T cell (Treg) score. Moreover, there were no consistent alterations observed among cases experiencing DCB. The intratumoral immune response was suppressed by previous treatments in most third- or later-line nivolumab recipients. TCR repertoire analysis revealed newly emerged clonotypes in early-on-treatment tumors, but clonal replacement did not impact efficacy. High T cell/Treg ratios and a low UV-radiation-response gene signature were linked to DCB and treatment response. This study emphasizes the tumor immune response’s importance in nivolumab efficacy for gastric cancer. High T cell/Treg ratios and specific gene expression signatures show promise as potential biomarkers for treatment response. The tumor-infiltrating immune response was compromised by prior treatments in third-line therapy, implying that, to enhance immunotherapeutic outcomes, commencing treatment at an earlier stage might be preferable. Larger cohort validation is crucial to optimize immune-checkpoint inhibitors in gastric cancer treatment.
Using an RNA Aptamer to Inhibit the Action of Effector Proteins of Plant Pathogens
Authors: Abdeeva Inna A. , Maloshenok Liliya G. , Pogorelko Gennady V. , Bruskin Sergey A.
Published: November 2023

In previous work, we experimentally demonstrated the possibility of using RNA aptamers to inhibit endogenous protein expression and their function within plant cells In the current work, we show that our proposed method is suitable for inhibiting the functions of exogenous, foreign proteins delivered into the plant via various mechanisms, including pathogen proteins. Stringent experimentation produced robust RNA aptamers that are able to bind to the recombinant HopU1 effector protein of P. syringae bacteria. This research uses genetic engineering methods to constitutively express/transcribe HopU1 RNA aptamers in transgenic A. thaliana. Our findings support the hypothesis that HopU1 aptamers can actively interfere with the function of the HopU1 protein and thereby increase resistance to phytopathogens of the genus P. syringae pv. tomato DC 3000.
Reproductive Immunology and Pregnancy 3.0
Authors: Szukiewicz Dariusz
Published: November 2023

This Special Issue, the third dedicated to reproductive immunology and pregnancy, is another review of the latest trends in research topics in this field [...]
The Effects of Natural Product-Derived Extracts for Longitudinal Bone Growth: An Overview of In Vivo Experiments
Authors: Lim Dong Wook , Lee Changho
Published: November 2023

Approximately 80% of children with short stature are classified as having Idiopathic Short Stature (ISS). While growth hormone (GH) treatment received FDA approval in the United States in 2003, its long-term impact on final height remains debated. Other treatments, like aromatase inhibitors, metformin, and insulin-like growth factor-1 (IGF-1), have been explored, but there is no established standard treatment for ISS. In South Korea and other Asian countries, East Asian Traditional Medicine (EATM) is sometimes employed by parents to potentially enhance their children’s height growth, often involving herbal medicines. One such product, Astragalus membranaceus extract mixture HT042, claims to promote height growth in children and has gained approval from the Korean Food and Drug Administration (KFDA). Research suggests that HT042 supplementation can increase height growth in children without skeletal maturation, possibly by elevating serum IGF-1 and IGF-binding protein-3 levels. Preclinical studies also indicate the potential benefits of natural products, including of EATM therapies for ISS. The purpose of this review is to offer an overview of bone growth factors related to ISS and to investigate the potential of natural products, including herbal preparations, as alternative treatments for managing ISS symptoms, based on their known efficacy in in vivo studies.
The Subtype Selectivity in Search of Potent Hypotensive Agents among 5,5-Dimethylhydantoin Derived α1-Adrenoceptors Antagonists
Authors: Kaczor Aneta , Knutelska Joanna , Kucwaj-Brysz Katarzyna , Zygmunt Małgorzata , Żesławska Ewa , Siwek Agata , Bednarski Marek , Podlewska Sabina , Jastrzębska-Więsek Magdalena , Nitek Wojciech , Sapa Jacek , Handzlik Jadwiga
Published: November 2023

In order to find new hypotensive drugs possessing higher activity and better selectivity, a new series of fifteen 5,5-dimethylhydantoin derivatives (1–15) was designed. Three-step syntheses, consisting of N-alkylations using standard procedures as well as microwaves, were carried out. Crystal structures were determined for compounds 7–9. All of the synthesized 5,5-dimethylhydantoins were tested for their affinity to α1-adrenergic receptors (α1-AR) using both in vitro and in silico methods. Most of them displayed higher affinity (Ki < 127.9 nM) to α1-adrenoceptor than urapidil in radioligand binding assay. Docking to two subtypes of adrenergic receptors, α1A and α1B, was conducted. Selected compounds were tested for their activity towards two α1-AR subtypes. All of them showed intrinsic antagonistic activity. Moreover, for two compounds (1 and 5), which possess o-methoxyphenylpiperazine fragments, strong activity (IC50 < 100 nM) was observed. Some representatives (3 and 5), which contain alkyl linker, proved selectivity towards α1A-AR, while two compounds with 2-hydroxypropyl linker (11 and 13) to α1B-AR. Finally, hypotensive activity was examined in rats. The most active compound (5) proved not only a lower effective dose than urapidil but also a stronger effect than prazosin.
A Comparative Study on the Mechanism of Delayed-Type Hypersensitivity Mediated by the Recombinant Mycobacterium tuberculosis Fusion Protein ESAT6-CFP10 and Purified Protein Derivative
Authors: Guo Xiaonan , Du Weixin , Li Junli , Dong Jiaxin , Shen Xiaobing , Su Cheng , Zhao Aihua , Wu Yongge , Xu Miao
Published: November 2023

While purified protein derivative (PPD) is commonly used as skin diagnostic reagent for tuberculosis (TB) infection, it cannot distinguish effectively Bacillus Calmette–Guérin (BCG) vaccination from Mycobacterium tuberculosis (MTB) complex and nontuberculous mycobacteria infection. The new skin reagent ESAT6-CFP10 (EC) has favorable sensitivity and specificity, which can overcome limitations associated with PPD. At present, EC skin test reactions are mainly characterized by erythema, while PPD mainly causes induration. We conducted a comparative study on the potential differences between EC-induced erythema and PPD-induced induration using a guinea pig model. The size of EC-dependent erythema was similar to that of PPD-induced induration, and an inflammatory response characterized by the infiltration of monocytes, macrophages and lymphocytes, as well as tissue damage, appeared at the injection site. The lymphocytes included CD4+ T and CD8+ T cells, which released IFN-γ as the main cytokine. Both EC erythema and PPD induration could lead to increased levels of acute-phase proteins, and the differential pathways were similar, thus indicating that the main induced immune pathways were similar. The above results indicated that erythema produced by EC could generate the main delayed-type hypersensitivity (DTH) response characteristic of PPD induration, thereby suggesting that erythema might also have a certain diagnostic significance and provide a possible theoretical basis for its use as a diagnostic indicator for detecting MTB infection.
Nervous Necrosis Virus Modulation of European Sea Bass (Dicentrarchus labrax, L.) Immune Genes and Transcriptome towards Establishment of Virus Carrier State
Authors: Toubanaki Dimitra K. , Efstathiou Antonia , Tzortzatos Odysseas-Panagiotis , Valsamidis Michail-Aggelos , Papaharisis Leonidas , Bakopoulos Vasileios , Karagouni Evdokia
Published: November 2023

Viral infections of teleost fish have great environmental and economic implications in aquaculture. Nervous necrosis virus (NNV) is a pathogen affecting more than 120 different species, causing high mortality and morbidity. Herein, we studied the course of NNV experimental infection of D. labrax, focusing on survivors which indicated viral carrier state. To determine the carrier state of D. labrax head kidney, we performed a gene expression analysis of selected immune-related genes and we profiled its transcriptome 14 days post infection (dpi). All tested genes showed clear differentiations in expression levels while most of them were up-regulated 14 dpi suggesting that their role is not limited in early antiviral responses, but they are also implicated in disease persistence. To gain a better understanding of the fish that survived the acute infection but still maintained a high viral load, we studied the differential expression of 124 up-regulated and 48 down-regulated genes in D. labrax head kidney, at 14 dpi. Concluding, the NNV virus persistent profile was assessed in D. labrax, where immune-related gene modification was intense (14 dpi) and the head kidney transcriptome profile at this time point offered a glimpse into host attempts to control the infection in asymptomatic carriers.
Bioactive Compounds and Their Influence on Postnatal Neurogenesis
Authors: Mattova Simona , Simko Patrik , Urbanska Nicol , Kiskova Terezia
Published: November 2023

Since postnatal neurogenesis was revealed to have significant implications for cognition and neurological health, researchers have been increasingly exploring the impact of natural compounds on this process, aiming to uncover strategies for enhancing brain plasticity. This review provides an overview of postnatal neurogenesis, neurogenic zones, and disorders characterized by suppressed neurogenesis and neurogenesis-stimulating bioactive compounds. Examining recent studies, this review underscores the multifaceted effects of natural compounds on postnatal neurogenesis. In essence, understanding the interplay between postnatal neurogenesis and natural compounds could bring novel insights into brain health interventions. Exploiting the therapeutic abilities of these compounds may unlock innovative approaches to enhance cognitive function, mitigate neurodegenerative diseases, and promote overall brain well-being.
Molecular Cloning, Expression Analysis, and Functional Analysis of Nine IbSWEETs in Ipomoea batatas (L.) Lam
Authors: Huang Jingli , Fu Xuezhen , Li Wenyan , Ni Zhongwang , Zhao Yanwen , Zhang Pinggang , Wang Aiqin , Xiao Dong , Zhan Jie , He Longfei
Published: November 2023

Sugar Will Eventually be Exported Transporter (SWEET) genes play an important regulatory role in plants’ growth and development, stress response, and sugar metabolism, but there are few reports on the role of SWEET proteins in sweet potato. In this study, nine IbSWEET genes were obtained via PCR amplification from the cDNA of sweet potato. Phylogenetic analysis showed that nine IbSWEETs separately belong to four clades (Clade I~IV) and contain two MtN3/saliva domains or PQ-loop superfamily and six~seven transmembrane domains. Protein interaction prediction showed that seven SWEETs interact with other proteins, and SWEETs interact with each other (SWEET1 and SWEET12; SWEET2 and SWEET17) to form heterodimers. qRT-PCR analysis showed that IbSWEETs were tissue-specific, and IbSWEET1b was highly expressed during root growth and development. In addition to high expression in leaves, IbSWEET15 was also highly expressed during root expansion, and IbSWEET7, 10a, 10b, and 12 showed higher expression in the leaves. The expression of SWEETs showed a significant positive/negative correlation with the content of soluble sugar and starch in storage roots. Under abiotic stress treatment, IbSWEET7 showed a strong response to PEG treatment, while IbSWEET10a, 10b, and 12 responded significantly to 4 °C treatment and, also, at 1 h after ABA, to NaCl treatment. A yeast mutant complementation assay showed that IbSWEET7 had fructose, mannose, and glucose transport activity; IbSWEET15 had glucose transport activity and weaker sucrose transport activity; and all nine IbSWEETs could transport 2-deoxyglucose. These results provide a basis for further elucidating the functions of SWEET genes and promoting molecular breeding in sweet potato.
Nutrient Solution Flowing Environment Affects Metabolite Synthesis Inducing Root Thigmomorphogenesis of Lettuce (Lactuca sativa L.) in Hydroponics
Authors: Baiyin Bateer , Xiang Yue , Hu Jiangtao , Tagawa Kotaro , Son Jung Eek , Yamada Satoshi , Yang Qichang
Published: November 2023

The principal difference between hydroponics and other substrate cultivation methods is the flowing liquid hydroponic cultivation substrate. Our previous studies have revealed that a suitable flowing environment of nutrient solution promoted root development and plant growth, while an excess flow environment was unfavorable for plants. To explain the thigmomorphogenetic response of excess flow-induced metabolic changes, six groups of lettuce (Lactuca sativa L.), including two flow conditions and three time periods, were grown. Compared with the plants without flow, the plants with flow showed decreased root fresh weight, total root length, root surface area, and root volume but increased average root diameter and root density. The roots with flow had more upregulated metabolites than those without flow, suggesting that the flow may trigger metabolic synthesis and activity. Seventy-nine common differential metabolites among six groups were screened, and enrichment analysis showed the most significant enrichment in the arginine biosynthesis pathway. Arginine was present in all the groups and exhibited greater concentrations in roots with flow than without flow. It can be speculated from the results that a high-flowing environment of nutrient solution promotes arginine synthesis, resulting in changes in root morphology. The findings provide insights on root thigmomorphogenesis affected by its growing conditions and help understand how plants respond to environmental mechanical forces.
Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats
Authors: Derkach Kira V. , Lebedev Ivan A. , Morina Irina Yu. , Bakhtyukov Andrey A. , Pechalnova Alena S. , Sorokoumov Viktor N. , Kuznetsova Veronica S. , Romanova Irina V. , Shpakov Alexander O.
Published: November 2023

Gonadotropins, including human chorionic gonadotropin (hCG), are used to induce ovulation, but they have a number of side effects, including ovarian hyperstimulation syndrome (OHSS). A possible alternative is allosteric luteinizing hormone (LH)/hCG receptor agonists, including the compound TP4/2 we developed, which remains active when administered orally. The aim was to study the effectiveness of TP4/2 (orally, 40 mg/kg) as an ovulation inducer in FSH-stimulated immature female rats, compared with hCG (s.c., 15 IU/rat). TP4/2 stimulated progesterone production and corpus luteum formation; time-dependently increased the ovarian expression of steroidogenic genes (Star, Cyp11a1, Cyp17a1) and genes involved in ovulation regulation (Adamts-1, Cox-2, Egr-1, Mt-1); and increased the content of metalloproteinase ADAMTS-1 in the ovaries. These effects were similar to those of hCG, although in some cases they were less pronounced. TP4/2, in contrast to hCG, maintained normal LH levels and increased the ovarian expression of the LH/hCG receptor gene, indicating preservation of ovarian sensitivity to LH, and did not cause a sustained increase in expression of vascular endothelial growth factor-A involved in OHSS. Thus, TP4/2 is an effective ovulation inducer that, unlike hCG, has a lower risk of OHSS and ovarian LH resistance due to its moderate stimulating effect on steroidogenesis.