bluuebunny/crossref_metadata_2025 huggingface dataset:
A Sustainable Option to Reuse Scaly Clays as Geomaterial for Earthworks
Authors: Rosone Marco , Celauro Clara
Published: January 2024

Scaly clays are structurally complex clay formations found throughout the world. Their typical fissured structure, the low shear strength and the high swelling potential often make them unsuitable for earthworks in road and railway infrastructure. This research has attempted to extend the possibilities of using this geomaterial in this field after appropriate lime treatment. A laboratory test programme was carried out to evaluate the response of the treated geomaterial to typical loads acting on road infrastructures. Unconfined and confined compression tests as well as cyclic triaxial tests, in undrained conditions, were carried out to investigate the static and dynamic mechanical behaviour. The results show that lime treatment induces significant improvements in the geomechanical properties and limits the swelling behaviour upon saturation of the geomaterial. Dynamic tests showed that, after only 28 days of curing, the treated scaly clay became insensitive to the damaging cyclic loading caused by vehicular traffic. The collected results show that the scaly clay can be properly used as a subgrade and embankment layer in road and railway construction with limited economic and environmental costs, after accurate treatment with lime. These results are significant for researchers and practitioners to increase sustainability in the construction of linear infrastructures involving excavations in scaly clays and to avoid landfill, which in some cases represented the only option.
Assessing the Impact of a Shallow Geothermal System Operation through Multi-Layer Temperature Monitoring in a Mediterranean Climate
Authors: Aljundi Kamar , Vieira Ana , Lapa José , Figueiredo António , Cardoso Rafaela
Published: January 2024

Shallow Geothermal Energy (SGE) exchanges heat with the ground. In continuous, long-term operation, the initial temperature field can be disturbed, and subsurface thermal changes can be developed. In this paper, the thermal impact of a SGE system under a Mediterranean climate is handled. Temperature monitoring was conducted on 15 investigation boreholes equipped with a total of 92 thermal sensors placed at specific depths. Investigation boreholes were drilled 1–2 m from SGE system borehole heat exchangers installed in a university building. The analysis handles a one-year monitoring period of SGE system operation. Temperature depth profiles, reaching up to 140 m depth, were registered with a 10 min time step, resulting in a large amount of data. Ground thermal conductivity was estimated experimentally and semi-empirically, allowing us to obtain, using a numerical model, the initial undisturbed ground temperature profiles and compare them with the monitored values. Climate data were recorded by the university meteorological station. Globally, the measured and computed data were coherent, and a non-negligible impact of the SGE system operation in the first year was observed. The building orientation as well as the nearby departments had significant impacts on the shallow ground temperature. Maximum ground temperature changes observed at depths higher than 10–20 m, ranging from 2 to 3 °C as observed in different boreholes, indicate that the system is operating efficiently.
Influence of Plasma-Activated Water on Foliar and Fruit Micronutrient Content and Plant Protection Efficiency
Authors: Kuzin Andrei I. , Kashirskaya Natalia Ya. , Solovchenko Alexei E. , Kochkina Anna M. , Stepantsowa Ludmila V. , Krasin Vyacheslav N. , Konchekov Evgeny M. , Lukanin Vladimir I. , Sergeichev Konstantin F. , Gudkova Victoria V. , Khort Dmitry O. , Smirnov Igor G.
Published: January 2024

Foliar fertilizing is very important to supply apple plants with calcium and micronutrients. The most cost-effective approach to this is the application of the fertilizers in tank mixtures with plant protection chemicals. Plasma-activated water (PAW) has great potential for the use in the agriculture. We used two type of PAWs, PAW1 (made using underwater electrical discharge in an aqueous KNO3 solution and includes reactive nitrogen species and platinum nanoparticles) and PAW2 (made using a plasma torch with nitrogen gas makeup and contains reactive nitrogen species but not metals). We studied the impact of two PAW types on the contents of Ca, B, Mn, Fe, and Co in leaves and Ca, Mn, Fe, Zn, and Mo in fruits sprayed with tank mixtures containing the fertilizers. We also tested the efficiency of PAW in the control of apple scab when applied as tank mixtures with plant protection chemicals. The application of the PAWs significantly increased foliar Ca when the PAW was mixed with Ca-containing formulations (spraying PAW1 containing Ca increased leaf Ca by up to 21%, and PAW2 up by to 9% compared to Ca spraying without PAW). The largest fruit Ca increase was in the variant treated with PAW1 with a micronutrient spraying program (up to 143%). The PAW treatments enhanced the baseline mineral contents of the plants even when they were not sprayed with the nutrients. PAW1 mainly increased the nutrient contents of the apple fruits. PAWs have proven to be efficient for the control of apple scab, thereby reducing the demand for fungicides. The scab damage to the leaves and fruits was similar in plants treated with PAWs without fungicides (1.7–1.9% on the leaves and 1.6–1.8% on the fruits) compared to the conventional chemical scab control (0.9% leaves and 0.6% fruits) and was significantly lower than in the untreated control (9.3% on leaves and 11.9 on fruits).
Multimodal Approaches in the Treatment of Chronic Peripheral Neuropathy—Evidence from Germany
Authors: Romeyke Tobias , Stummer Harald
Published: January 2024

Patients with chronic peripheral neuropathy suffer greatly and their quality of life is often restricted. Drug therapy can be accompanied by undesirable side effects and intolerances, or the hoped-for effect does not materialize. Therefore, in addition to drug therapy, attempts are also made to treat the physical symptoms with complementary procedures. In the case of severe forms, the search for a suitable form of therapy is difficult. Complex treatments can be an innovative way to treat peripheral neuropathy. At the same time, several different therapy methods are carried out at high frequency by a specialized treatment team. This study aimed to provide an overview of possible complementary forms of therapy. The focus was on a comparison of two interdisciplinary complex therapies that are used in severe cases in an acute inpatient care setting in Germany. The six dimensions (energy, sleep, pain, physicality, emotional response and social isolation) of the Nottingham Health Profile (NHP) were used to assess quality of life. Both complex treatments (naturopathic complex therapy/multimodal pain therapy) showed a significant reduction in impairment in all dimensions of the NHP. In addition, a multivariate analysis was carried out to take into account several influencing variables at the same time. At the time of admission to the hospital, the degree of chronicity was recorded for each patient. This allowed statements to be made about the effect of the respective therapy depending on the chronification stage of the patient. It has been shown that patients with acutely exacerbated pain with the highest degree of chronicity also benefit from both complex treatments. The naturopathic complex treatment gives the treatment team more options. Aspects such as nutrition, methods from phytotherapy and traditional Chinese medicine can be integrated into inpatient care. Thus, a patient-centered, holistic therapy can take place. However, an interdisciplinary holistic therapy requires more time for both the practitioner and the patient. This should be taken into account in the health systems in the context of the diagnosis related groups.
Health Screening Strategies for Artisanal and Small-Scale Miners for Tuberculosis, Human Immunodeficiency Virus and Silicosis: A Case of the USAID-Supported Kunda Nqob’iTB Project in Zimbabwe
Authors: Moyo Dingani , Kavenga Fungai , Moyo Florence , Muzvidziwa Orippa , Madziva Godknows , Chigaraza Blessings , Ncube Mpokiseng , Madadangoma Precious , Masvingo Hellen , Muperi Tafadzwa Charity , Mando Tariro Christwish , Ncube Ronald Thulani
Published: January 2024

Artisanal and small-scale mining is characterized by excessive exposure to physical, chemical, ergonomic, psychosocial and biological hazards. There is a high burden of tuberculosis (TB), human immunodeficiency virus (HIV) infections and silicosis among artisanal and small-scale miners (ASMs). The aim of this project report is to describe lessons learned from strategies implemented to reach ASMs with screening services for TB, HIV and silicosis in Zimbabwe through the Kunda-Nqob’i TB (KNTB) project supported by the United States Agency for International Development (USAID). The intervention package for screening ASMs for TB, HIV and silicosis included service provision through two occupational health clinics at two provincial hospitals and a mobile workplace-based screening (WBS) facility at the mining sites. From 1 October 2020 to 30 September 2023, 10,668 ASMs were screened, with a high number of cases of silicosis (21%) and TB (7.4%). There was a high burden of HIV (30%) in ASMs attending the occupational health clinics. The two occupational health clinics screened 3453 ASMs, while the mobile WBS activities screened 7215 ASMs during the period. A total of 370 healthcare workers (doctors/clinical officers, nurses, environmental health technicians and district tuberculosis and Leprosy control officers) were trained on TB and the fundamental diagnostic principles of silicosis. The KNTB project has been successful in reaching out to many ASMs operating in remote and hard-to-reach mining areas. The KNTB project has brought to light the positive health-seeking behavior of ASMs operating in remote areas. The project has brought to the fore the effectiveness of multi-stakeholder engagement and collaboration in reaching out to ASMs in remote areas with health screening services. There is a high burden of TB, HIV and silicosis in ASMs. Screening for TB, HIV and silicosis using workplace-based screening and occupational health clinics is an effective strategy and should be rolled out to all areas with high artisanal and small-scale mining activity.
A New Urban Built-Up Index and Its Application in National Central Cities of China
Authors: Wang Linfeng , Chen Shengbo , Chen Lei , Wang Zibo , Liu Bin , Xu Yucheng
Published: January 2024

Accurately mapping urban built-up areas is critical for monitoring urbanization and development. Previous studies have shown that Night light (NTL) data is effective in characterizing the extent of human activity. But its inherently low spatial resolution and saturation effect limit its application in the construction of urban built-up extraction. In this study, we developed a new index called VNRT (Vegetation, Nighttime Light, Road, and Temperature) to address these challenges and improve the accuracy of built-up area extraction. The VNRT index is the first to fuse the Normalized Difference Vegetation Index (NDVI), NPP-VIIRS Nighttime NTL data, road density data, and land surface temperature (LST) through factor multiplication. To verify the good performance of VNRT in extracting built-up areas, the built-up area ranges of four national central cities in China (Chengdu, Wuhan, Xi’an, and Zhengzhou) in 2019 are extracted by the local optimum thresholding method and compared with the actual validation points. The results show that the spatial distribution of VNRT is highly consistent with the actual built-up area. THE VNRT increases the variability between urban built-up areas and non-built-up areas, and can effectively distinguish some types of land cover that are easily ignored in previous urban indices, such as urban parks and water bodies. The VNRT index had the highest Accuracy (0.97), F1-score (0.94), Kappa coefficient (0.80), and overall accuracy (92%) compared to the two proposed urban indices. Therefore, the VNRT index could improve the identification of urban built-up areas and be an effective tool for long-term monitoring of regional-scale urbanization.
Hormone, Targeted, and Combinational Therapies for Breast Cancers: From Humans to Dogs
Authors: Ke Chiao-Hsu , Lin Chao-Nan , Lin Chen-Si
Published: January 2024

Breast cancer (BC) is the most frequent cancer in women. In female dogs, canine mammary gland tumor (CMT) is also the leading neoplasm. Comparative oncology indicates similar tumor behaviors between human BCs (HBCs) and CMTs. Therefore, this review summarizes the current research in hormone and targeted therapies and describes the future prospects for HBCs and CMTs. For hormone receptor-expressing BCs, the first medical intervention is hormone therapy. Monoclonal antibodies against Her2 are proposed for the treatment of Her2+ BCs. However, the major obstacle in hormone therapy or monoclonal antibodies is drug resistance. Therefore, increasing alternatives have been developed to overcome these difficulties. We systemically reviewed publications that reported inhibitors targeting certain molecules in BC cells. The various treatment choices for humans decrease mortality in females with BC. However, the development of hormone or targeted therapies in veterinary medicine is still limited. Even though some clinical trials have been proposed, severe side effects and insufficient case numbers might restrict further explorations. This difficulty highlights the urgent need to develop updated hormone/targeted therapy or novel immunotherapies. Therefore, exploring new therapies to provide more precise use in dogs with CMTs will be the focus of future research. Furthermore, due to the similarities shared by humans and dogs, well-planned prospective clinical trials on the use of combinational or novel immunotherapies in dogs with CMTs to obtain solid results for both humans and dogs can be reasonably anticipated in the future.
Melatonin Alleviates Lipopolysaccharide-Induced Abnormal Pregnancy through MTNR1B Regulation of m6A
Authors: Zhao Shisu , Dong Yanjun , Li Yuanyuan , Wang Zixu , Chen Yaoxing , Dong Yulan
Published: January 2024

Pregnancy is a highly intricate and delicate process, where inflammation during early stages may lead to pregnancy loss or defective implantation. Melatonin, primarily produced by the pineal gland, exerts several pharmacological effects. N6-methyladenosine (m6A) is the most prevalent mRNA modification in eukaryotes. This study aimed to investigate the association between melatonin and m6A during pregnancy and elucidate the underlying protective mechanism of melatonin. Melatonin was found to alleviate lipopolysaccharide (LPS)-induced reductions in the number of implantation sites. Additionally, it mitigated the activation of inflammation, autophagy, and apoptosis pathways, thereby protecting the pregnancy process in mice. The study also revealed that melatonin regulates uterine m6A methylation levels and counteracts abnormal changes in m6A modification of various genes following LPS stimulation. Furthermore, melatonin was shown to regulate m6A methylation through melatonin receptor 1B (MTNR1B) and subsequently modulate inflammation, autophagy, and apoptosis through m6A. In conclusion, our study demonstrates that melatonin protects pregnancy by influencing inflammation, autophagy, and apoptosis pathways in an m6A-dependent manner via MTNR1B. These findings provide valuable insights into the mechanisms underlying melatonin’s protective effects during pregnancy and may have implications for potential therapeutic strategies in managing pregnancy-related complications.
amer1 Regulates Zebrafish Craniofacial Development by Interacting with the Wnt/β-Catenin Pathway
Authors: Sun Le , Ping Lu , Fan Xinmiao , Fan Yue , Zhang Bo , Chen Xiaowei
Published: January 2024

Microtia-atresia is a rare type of congenital craniofacial malformation causing severe damage to the appearance and hearing ability of affected individuals. The genetic factors associated with microtia-atresia have not yet been determined. The AMER1 gene has been identified as potentially pathogenic for microtia-atresia in two twin families. An amer1 mosaic knockdown zebrafish model was constructed using CRISPR/Cas9. The phenotype and the development process of cranial neural crest cells of the knockdown zebrafish were examined. Components of the Wnt/β-catenin pathway were examined by qPCR, Western blotting, and immunofluorescence assay. IWR-1-endo, a reversible inhibitor of the Wnt/β-catenin pathway, was applied to rescue the abnormal phenotype. The present study showed that the development of mandibular cartilage in zebrafish was severely compromised by amer1 knockdown using CRISPR/Cas9. Specifically, amer1 knockdown was found to affect the proliferation and apoptosis of cranial neural crest cells, as well as their differentiation to chondrocytes. Mechanistically, amer1 exerted an antagonistic effect on the Wnt/β-catenin pathway. The application of IWR-1-endo could partially rescue the abnormal phenotype. We demonstrated that amer1 was essential for the craniofacial development of zebrafish by interacting with the Wnt/β-catenin pathway. These findings provide important insight into the role of amer1 in zebrafish mandibular development and the pathology of microtia-atresia caused by AMER1 gene mutations in humans.
Fluorescent Ligand Equilibrium Displacement: A High-Throughput Method for Identification of FMN Riboswitch-Binding Small Molecules
Authors: Tidwell Elizabeth D. , Kilde Ingrid R. , Leskaj Suada , Koutmos Markos
Published: January 2024

Antibiotic resistance remains a pressing global concern, with most antibiotics targeting the bacterial ribosome or a limited range of proteins. One class of underexplored antibiotic targets is bacterial riboswitches, structured RNA elements that regulate key biosynthetic pathways by binding a specific ligand. We developed a methodology termed Fluorescent Ligand Equilibrium Displacement (FLED) to rapidly discover small molecules that bind the flavin mononucleotide (FMN) riboswitch. FLED leverages intrinsically fluorescent FMN and the quenching effect on RNA binding to create a label-free, in vitro method to identify compounds that can bind the apo population of riboswitch in a system at equilibrium. The response difference between known riboswitch ligands and controls demonstrates the robustness of the method for high-throughput screening. An existing drug discovery library that was screened using FLED resulted in a final hit rate of 0.67%. The concentration response of each hit was determined and revealed a variety of approximate effective concentration values. Our preliminary screening data support the use of FLED to identify small molecules for medicinal chemistry development as FMN riboswitch-targeted antibiotic compounds. This robust, label-free, and cell-free method offers a strong alternative to other riboswitch screening methods and can be adapted to a variety of laboratory setups.
Mitochondria: An Emerging Unavoidable Link in the Pathogenesis of Periodontitis Caused by Porphyromonas gingivalis
Authors: Luo Shiyin , Xu Tong , Zheng Qifan , Jiang Aijia , Zhao Jiahui , Ying Yue , Liu Nan , Pan Yaping , Zhang Dongmei
Published: January 2024

Porphyromonas gingivalis (P. gingivalis) is a key pathogen of periodontitis. Increasing evidence shows that P. gingivalis signals to mitochondria in periodontal cells, including gingival epithelial cells, gingival fibroblast cells, immune cells, etc. Mitochondrial dysfunction affects the cellular state and participates in periodontal inflammatory response through the aberrant release of mitochondrial contents. In the current review, it was summarized that P. gingivalis induced mitochondrial dysfunction by altering the mitochondrial metabolic state, unbalancing mitochondrial quality control, prompting mitochondrial reactive oxygen species (ROS) production, and regulating mitochondria-mediated apoptosis. This review outlines the impacts of P. gingivalis and its virulence factors on the mitochondrial function of periodontal cells and their role in periodontitis.
Shotgun Metagenomics Reveals Minor Micro“bee”omes Diversity Defining Differences between Larvae and Pupae Brood Combs
Authors: Smutin Daniil , Taldaev Amir , Lebedev Egor , Adonin Leonid
Published: January 2024

Bees represent not only a valuable asset in agriculture, but also serve as a model organism within contemporary microbiology. The metagenomic composition of the bee superorganism has been substantially characterized. Nevertheless, traditional cultural methods served as the approach to studying brood combs in the past. Indeed, the comb microbiome may contribute to determining larval caste differentiation and hive immunity. To further this understanding, we conducted a shotgun sequencing analysis of the brood comb microbiome. While we found certain similarities regarding species diversity, it exhibits significant differentiation from all previously described hive metagenomes. Many microbiome members maintain a relatively constant ratio, yet taxa with the highest abundance level tend to be ephemeral. More than 90% of classified metagenomes were Gammaproteobacteria, Bacilli and Actinobacteria genetic signatures. Jaccard dissimilarity between samples based on bacteria genus classifications hesitate from 0.63 to 0.77, which for shotgun sequencing indicates a high consistency in bacterial composition. Concurrently, we identified antagonistic relationships between certain bacterial clusters. The presence of genes related to antibiotic synthesis and antibiotic resistance suggests potential mechanisms underlying the stability of comb microbiomes. Differences between pupal and larval combs emerge in the total metagenome, while taxa with the highest abundance remained consistent. All this suggests that a key role in the functioning of the comb microbiome is played by minor biodiversity, the function of which remains to be established experimentally.
Mouse Model of Nitrogen Mustard Ocular Surface Injury Characterization and Sphingolipid Signaling
Authors: Basu Sandip K. , Prislovsky Amanda , Lenchik Nataliya , Stephenson Daniel J. , Agarwal Rajesh , Chalfant Charles E. , Mandal Nawajes
Published: January 2024

Vesicating chemicals like sulfur mustard (SM) or nitrogen mustard (NM) can cause devastating damage to the eyes, skin, and lungs. Eyes, being the most sensitive, have complicated pathologies that can manifest immediately after exposure (acute) and last for years (chronic). No FDA-approved drug is available to be used as medical counter measures (MCMs) against such injuries. Understanding the pathological mechanisms in acute and chronic response of the eye is essential for developing effective MCMs. Here, we report the clinical and histopathological characterization of a mouse model of NM-induced ocular surface injury (entire surface) developed by treating the eye with 2% (w/v) NM solution for 5 min. Unlike the existing models of specific injury, our model showed severe ocular inflammation, including the eyelids, structural deformity of the corneal epithelium and stroma, and diminished visual and retinal functions. We also observed alterations of the inflammatory markers and their expression at different phases of the injury, along with an activation of acidic sphingomyelinase (aSMase), causing an increase in bioactive sphingolipid ceramide and a reduction in sphingomyelin levels. This novel ocular surface mouse model recapitulated the injuries reported in human, rabbit, and murine SM or NM injury models. NM exposure of the entire ocular surface in mice, which is similar to accidental or deliberate exposure in humans, showed severe ocular inflammation and caused irreversible alterations to the corneal structure and significant vision loss. It also showed an intricate interplay between inflammatory markers over the injury period and alteration in sphingolipid homeostasis in the early acute phase.
Resveratrol for the Management of Human Health: How Far Have We Come? A Systematic Review of Resveratrol Clinical Trials to Highlight Gaps and Opportunities
Authors: Brown Karen , Theofanous Despoina , Britton Robert G. , Aburido Grandezza , Pepper Coral , Sri Undru Shanthi , Howells Lynne
Published: January 2024

Resveratrol has long been proposed as being beneficial to human health across multiple morbidities, yet there is currently no conclusive clinical evidence to advocate its recommendation in any healthcare setting. A large cohort with high-quality clinical data and clearly defined biomarkers or endpoints are required to draw meaningful conclusions. This systematic review compiles every clinical trial conducted using a defined dose of resveratrol in a purified form across multiple morbidities to highlight the current ‘state-of-play’ and knowledge gaps, informing future trial designs to facilitate the realisation of resveratrol’s potential benefits to human health. Over the last 20 years, there have been almost 200 studies evaluating resveratrol across at least 24 indications, including cancer, menopause symptoms, diabetes, metabolic syndrome, and cardiovascular disease. There are currently no consensus treatment regimens for any given condition or endpoint, beyond the fact that resveratrol is generally well-tolerated at a dose of up to 1 g/day. Additionally, resveratrol consistently reduces inflammatory markers and improves aspects of a dysregulated metabolism. In conclusion, over the last 20 years, the increasing weight of clinical evidence suggests resveratrol can benefit human health, but more large, high-quality clinical trials are required to transition this intriguing compound from health food shops to the clinic.
Svx Peptidases of Phytopathogenic Pectolytic Bacteria: Structural, Catalytic and Phytoimmune Properties
Authors: Tendiuk Natalia , Diakonova Anastasiya , Petrova Olga , Mukhametzyanov Timur , Makshakova Olga , Gorshkov Vladimir
Published: January 2024

Svx proteins are virulence factors secreted by phytopathogenic bacteria of the Pectobacterium genus into the host plant cell wall. Svx-encoding genes are present in almost all species of the soft rot Pectobacteriaceae (Pectobacterium and Dickeya genera). The Svx of P. atrosepticum (Pba) has been shown to be a gluzincin metallopeptidase that presumably targets plant extensins, proteins that contribute to plant cell wall rigidity and participate in cell signaling. However, the particular “output” of the Pba Svx action in terms of plant-pathogen interactions and plant immune responses remained unknown. The Svx proteins are largely unexplored in Dickeya species, even though some of them have genes encoding two Svx homologs. Therefore, our study aims to compare the structural and catalytic properties of the Svx proteins of Pba and D. solani (Dso) and to test the phytoimmune properties of these proteins. Two assayed Dso Svx proteins, similar to Pba Svx, were gluzincin metallopeptidases with conservative tertiary structures. The two domains of the Svx proteins form electronegative clefts where the active centers of the peptidase domains are located. All three assayed Svx proteins possessed phytoimmunosuppressory properties and induced ethylene-mediated plant susceptible responses that play a decisive role in Pba-caused disease.
Accumulation of Polyphenols and Associated Gene Expression in Hairy Roots of Salvia viridis Exposed to Methyl Jasmonate
Authors: Grzegorczyk-Karolak Izabela , Krzemińska Marta , Grąbkowska Renata , Gomulski Jan , Żekanowski Cezary , Gaweda-Walerych Katarzyna
Published: January 2024

Methyl jasmonate (MJA), a signaling molecule in stress pathways, can be used to induce secondary metabolite synthesis in plants. The present study examines its effects on the growth of Salvia viridis hairy roots, and the accumulation of bioactive compounds, and correlates it with the expression of genes involved in the phenylpropanoid pathway. To our knowledge, this study represents the first exploration of elicitation in S. viridis culture and the first comprehensive analysis of MJA’s influence on such a wide array of genes within the polyphenol metabolic pathway in the Salvia genus. Plants were treated with 50 and 100 µM MJA, and samples were collected at intervals of one, three, five, and seven days post-elicitation. HPLC analysis revealed that MJA stimulated the accumulation of all tested compounds, with a 30% increase (38.65 mg/g dry weight) in total polyphenol content (TPC) on day five. Quantitative real-time polymerase chain reaction (RT-PCR) analysis demonstrated a significant increase in the expression of the phenylpropanoid pathway genes—TAT (tyrosine aminotransferase), HPPR (4-hydroxyphenylpyruvate reductase), PAL (phenylalanine ammonia-lyase), C4H (cinnamic acid 4-hydroxylase), 4CL (4-coumarate-CoA ligase), and RAS (rosmarinic acid synthase)—following MJA treatment. For the majority of the genes, this increase was observed after the first day of treatment. Importantly, our present results confirm strong correlations of the analyzed gene expression with polyphenol biosynthesis. These findings support the notion that hairy roots provide a promising biotechnological framework for augmenting polyphenol production. Additionally, the combination of elicitor treatment and transgenic technology emerges as a viable strategy to enhance the biosynthesis of these valuable metabolites.
Inferring Drug Set and Identifying the Mechanism of Drugs for PC3
Authors: Kim Shinuk
Published: January 2024

Drug repurposing is a strategy for discovering new applications of existing drugs for use in various diseases. Despite the use of structured networks in drug research, it is still unclear how drugs interact with one another or with genes. Prostate adenocarcinoma is the second leading cause of cancer mortality in the United States, with an estimated incidence of 288,300 new cases and 34,700 deaths in 2023. In our study, we used integrative information from genes, pathways, and drugs for machine learning methods such as clustering, feature selection, and enrichment pathway analysis. We investigated how drugs affect drugs and how drugs affect genes in human pancreatic cancer cell lines that were derived from bone metastases of grade IV prostate cancer. Finally, we identified significant drug interactions within or between clusters, such as estradiol-rosiglitazone, estradiol-diclofenac, troglitazone-rosiglitazone, celecoxib-rofecoxib, celecoxib-diclofenac, and sodium phenylbutyrate-valproic acid.
Membrane Transporter of Serotonin and Hypercholesterolemia in Children
Authors: Sadykova Dinara , Nigmatullina Razina , Salakhova Karina , Slastnikova Evgeniia , Galimova Liliya , Khaliullina Chulpan , Valeeva Ildaria
Published: January 2024

The serotonin membrane transporter is one of the main mechanisms of plasma serotonin concentration regulation. Serotonin plays an important role in the pathogenesis of various cardiovascular diseases, stimulating the proliferation of smooth muscle cells, key cells in the process of hypertrophic vascular remodeling. Vascular remodeling is one of the leading prognostically unfavorable factors of atherosclerosis, the main manifestation of familial hypercholesterolemia. Familial hypercholesterolemia is one of the most common genetically determined lipid metabolism disorders and occurs in 1 in 313 people. The aim of our study was to investigate the levels of plasma and platelet serotonin, 5-hydroxyindoleacetic acid, and membrane transporter in a cross-sectional study of two pediatric groups, including patients with familial hypercholesterolemia and the control group, which consisted of apparently healthy children without cardiovascular diseases. The study involved 116 children aged 5 to 17 years old. The proportion of boys was 50% (58/116) and the average age of the children was 10.5 years (CI 2.8–18.1). The concentrations of serotonin in blood plasma and platelets and 5-hydroxyindoleacetic acid were higher in children with familial hypercholesterolemia than in the controls. The concentration of the serotonin transporter in platelets in healthy children, compared with the main group, was 1.3 times higher. A positive correlation was revealed between the level of serotonin (5-HT and PWV: ρ = 0.6, p < 0.001), its transporter (SERT and PWV: ρ = 0.5, p < 0.001), and the main indicators of arterial vascular stiffness. Our study revealed the relationship between high serotonin and SERT concentrations and markers of arterial stiffness. The results we obtained suggest the involvement of serotonin and SERT in the process of vascular remodeling in familial hypercholesterolemia in children.
Functional Characterization of Circadian Nuclear Receptors REV-ERBα and REV-ERBβ in Human Osteosarcoma Cell Cultures
Authors: Cho Hana , Yun Ahee , Kim Joohee , Park Eunjeong , Jung Jong-Wha , Chung Sooyoung , Son Gi Hoon
Published: January 2024

REV-ERBα and its paralog, REV-ERBβ, encoded by NR1D1 and NR1D2 genes, are key nuclear receptors that link the circadian timing system and metabolic homeostasis. Since heme is an endogenous ligand, REV-ERBs have been considered key components of the circadian molecular clock and can be pharmacologically targeted to treat various circadian rhythm-related diseases, such as cardiometabolic, inflammatory, and neuropsychiatric diseases, as well as cancer. REV-ERBs are believed to be functionally redundant and compensatory, although they often affect the expression of gene subsets in an isoform-specific manner. Therefore, this study aimed to identify the redundant and distinct roles of each isoform in controlling its target genes by comparing the transcriptome profiles of a panel of mutant U2OS human osteosarcoma cells in which either NR1D1 or NR1D2 was ablated. Indeed, our transcriptomic analyses revealed that most REV-ERB-regulated genes are controlled by redundant or even additive actions. However, the RNA expression profiles of each single mutant cell line also provide strong evidence for isoform-dependent actions. For example, REV-ERBα is more responsible for regulating the NF-κΒ signaling pathway, whereas a group of extracellular matrix components requires REV-ERBβ to maintain their expression. We found that REV-ERBs have isoform-selective functions in the regulation of certain circadian output pathways despite their overlapping roles in the circadian molecular clock. Thus, the development of isoform-selective REV-ERB modulators can help treat metabolic disturbances and certain types of cancer.
Damage-Associated Molecular Patterns, a Class of Potential Psoriasis Drug Targets
Authors: Gao Yaqi , Gong Bishuang , Chen Zhenxing , Song Jierong , Xu Na , Weng Zhuangfeng
Published: January 2024

Psoriasis is a chronic skin disorder that involves both innate and adaptive immune responses in its pathogenesis. Local tissue damage is a hallmark feature of psoriasis and other autoimmune diseases. In psoriasis, damage-associated molecular patterns (DAMPs) released by damaged local tissue act as danger signals and trigger inflammatory responses by recruiting and activating immune cells. They also stimulate the release of pro-inflammatory cytokines and chemokines, which exacerbate the inflammatory response and contribute to disease progression. Recent studies have highlighted the role of DAMPs as key regulators of immune responses involved in the initiation and maintenance of psoriatic inflammation. This review summarizes the current understanding of the immune mechanism of psoriasis, focusing on several important DAMPs and their mechanisms of action. We also discussed the potential of DAMPs as diagnostic and therapeutic targets for psoriasis, offering new insights into the development of more effective treatments for this challenging skin disease.
The Specificities of Lysophosphatidic Acid Acyltransferase and Fatty Acid Desaturase Determine the High Content of Myristic and Myristoleic Acids in Cyanobacterium sp. IPPAS B-1200
Authors: Starikov Alexander Y. , Sidorov Roman A. , Mironov Kirill S. , Los Dmitry A.
Published: January 2024

The cyanobacterial strain Cyanobacterium sp. IPPAS B-1200 isolated from Lake Balkhash is characterized by high relative amounts of myristic (30%) and myristoleic (10%) acids. The remaining fatty acids (FAs) are represented mainly by palmitic (20%) and palmitoleic (40%) acids. We expressed the genes for lysophosphatidic acid acyltransferase (LPAAT; EC 2.3.1.51) and Δ9 fatty acid desaturase (FAD; EC 1.14.19.1) from Cyanobacterium sp. IPPAS B-1200 in Synechococcus elongatus PCC 7942, which synthesizes myristic and myristoleic acids at the level of 0.5–1% and produces mainly palmitic (~60%) and palmitoleic (35%) acids. S. elongatus cells that expressed foreign LPAAT synthesized myristic acid at 26%, but did not produce myristoleic acid, suggesting that Δ9-FAD of S. elongatus cannot desaturate FAs with chain lengths less than C16. Synechococcus cells that co-expressed LPAAT and Δ9-FAD of Cyanobacterium synthesized up to 45% palmitoleic and 9% myristoleic acid, suggesting that Δ9-FAD of Cyanobacterium is capable of desaturating saturated acyl chains of any length.
Anti-Inflammatory Effect of Fermented Cabbage Extract Containing Nitric Oxide Metabolites with Silica
Authors: Lee Yun-Seong , Ji Byeong-Jun , Pae Hyun-Ock , Cheon Mu-Weon , Xu Guangpeng , Chun Hyun-Soo , Kim Sooah
Published: January 2024

The aim of this study was to evaluate the anti-inflammatory effect of fermented cabbage extract (FC) containing nitric oxide metabolites with silica (FCS) on 1-fluoro-2,4-dinitrofluorobenzene (DNFB)-induced atopic dermatitis (AD) in BALB/c mice. Atopic dermatitis-like allergic contact dermatitis was induced by DNFB challenge in the ear after DNFB sensitization on the dorsal skin of mice. FCS alleviated the severity of atopic dermatitis-like skin lesions. In addition, epidermis thickness of the ear and penetration of inflammatory cells in atopic dermatitis-like skin lesions were decreased after topical application of FCS. The serum levels of TNF-α and IL-4 were measured in atopic dermatitis mice using ELISA kits, which were observed to be significantly decreased after topical application of FCS. This study demonstrates that the FCS can be used as a potential therapeutic for the treatment and prevention of AD.
Identification of One O-Methyltransferase Gene Involved in Methylated Flavonoid Biosynthesis Related to the UV-B Irradiation Response in Euphorbia lathyris
Authors: Zhao Wanli , Huang Long , Xu Shu , Wu Junzhi , Wang Fan , Li Pirui , Li Linwei , Tian Mei , Feng Xu , Chen Yu
Published: January 2024

Flavonoids are ubiquitous polyphenolic compounds that play a vital role in plants’ defense response and medicinal efficacy. UV-B radiation is a vital environmental regulator governing flavonoid biosynthesis in plants. Many plants rapidly biosynthesize flavonoids as a response to UV-B stress conditions. Here, we investigated the effects of flavonoid biosynthesis via UV-B irradiation in Euphorbia lathyris. We found that exposure of the E. lathyris callus to UV-B radiation sharply increased the level of one O-methyltransferase (ElOMT1) transcript and led to the biosynthesis of several methylated flavonoids. The methyltransferase ElOMT1 was expressed heterologously in E. coli, and we tested the catalytic activity of recombinant ElOMT1 with possible substrates, including caffeic acid, baicalin, and luteolin, in vitro. ElOMT1 could efficiently methylate when the hydroxyl groups were contained in the core nucleus of the flavonoid. This molecular characterization identifies a methyltransferase responsible for the chemical modification of the core flavonoid structure through methylation and helps reveal the mechanism of methylated flavonoid biosynthesis in Euphorbiaceae. This study identifies the O-methyltransferase that responds to UV-B irradiation and helps shed light on the mechanism of flavonoid biosynthesis in Euphorbia lathyris.
Potential Antioxidant and Anti-Inflammatory Properties of Polyphenolic Compounds from Cirsium japonicum Extract
Authors: Kim Hun Hwan , Jeong Se Hyo , Park Min Yeong , Bhosale Pritam Bhagwan , Abusaliya Abuyaseer , Kim Hyun Wook , Seong Je Kyung , Kim Dong Il , Lee Sang Joon , Park Kwang Il , Kim Gon Sup
Published: January 2024

Cirsium japonicum is a medicinal plant that has been used due to its beneficial properties. However, extensive information regarding its therapeutic potential is scarce in the scientific literature. The antioxidant and anti-inflammatory potential of polyphenols derived from the Cirsium japonicum extracts (CJE) was systematically analyzed. High-performance liquid chromatography (HPLC) with mass spectrometry (MS) was used to examine the compounds in CJE. A total of six peaks of polyphenol compounds were identified in the extract, and their MS data were also confirmed. These bioactive compounds were subjected to ultrafiltration with LC analysis to assess their potential for targeting cyclooxygenase-2 (COX2) and DPPH. The outcomes showed which primary compounds had the highest affinity for binding both COX2 and DPPH. This suggests that components that showed excellent binding ability to DPPH and COX2 can be considered significant active substances. Additionally, in vitro analysis of CJE was carried out in macrophage cells after inducing inflammation with lipopolysaccharide (LPS). As a result, it downregulated the expression of two critical pro-inflammatory cytokines, COX2 and inducible nitric oxide synthase (iNOS). In addition, we found a solid binding ability through the molecular docking analysis of the selected compounds with inflammatory mediators. In conclusion, we identified polyphenolic compounds in CJE extract and confirmed their potential antioxidant and anti-inflammatory effects. These results may provide primary data for the application of CJE in the food and pharmaceutical industries with further analysis.
The Use of Nitrosative Stress Molecules as Potential Diagnostic Biomarkers in Multiple Sclerosis
Authors: Räuber Saskia , Förster Moritz , Schüller Julia , Willison Alice , Golombeck Kristin S. , Schroeter Christina B. , Oeztuerk Menekse , Jansen Robin , Huntemann Niklas , Nelke Christopher , Korsen Melanie , Fischer Katinka , Kerkhoff Ruth , Leven Yana , Kirschner Patricia , Kölsche Tristan , Nikolov Petyo , Mehsin Mohammed , Marae Gelenar , Kokott Alma , Pul Duygu , Schulten Julius , Vogel Niklas , Ingwersen Jens , Ruck Tobias , Pawlitzki Marc , Meuth Sven G. , Melzer Nico , Kremer David
Published: January 2024

Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) of still unclear etiology. In recent years, the search for biomarkers facilitating its diagnosis, prognosis, therapy response, and other parameters has gained increasing attention. In this regard, in a previous meta-analysis comprising 22 studies, we found that MS is associated with higher nitrite/nitrate (NOx) levels in the cerebrospinal fluid (CSF) compared to patients with non-inflammatory other neurological diseases (NIOND). However, many of the included studies did not distinguish between the different clinical subtypes of MS, included pre-treated patients, and inclusion criteria varied. As a follow-up to our meta-analysis, we therefore aimed to analyze the serum and CSF NOx levels in clinically well-defined cohorts of treatment-naïve MS patients compared to patients with somatic symptom disorder. To this end, we analyzed the serum and CSF levels of NOx in 117 patients (71 relapsing–remitting (RR) MS, 16 primary progressive (PP) MS, and 30 somatic symptom disorder). We found that RRMS and PPMS patients had higher serum NOx levels compared to somatic symptom disorder patients. This difference remained significant in the subgroup of MRZ-negative RRMS patients. In conclusion, the measurement of NOx in the serum might indeed be a valuable tool in supporting MS diagnosis.
The Relationship between the Brain-Derived Neurotrophic Factor Gene Polymorphism (Val66Met) and Substance Use Disorder and Relapse
Authors: Strońska-Pluta Aleksandra , Suchanecka Aleksandra , Chmielowiec Krzysztof , Chmielowiec Jolanta , Boroń Agnieszka , Masiak Jolanta , Sipak-Szmigiel Olimpia , Recław Remigiusz , Grzywacz Anna
Published: January 2024

Substance addiction is a neuropsychiatric disorder characterized by a recurring desire to continue using a substance despite harmful consequences. Brain-derived neurotrophic factor (BDNF) is a protein that plays a role in the activity-dependent remodeling of neural function in adult nervous systems. This study analyzed the association of the rs6265 polymorphism of the BDNF gene in a group of patients addicted to psychoactive substances who were participating in addiction treatment for the first time, in a group of post-relapse psychoactive substance abusers and in a control group. The study also assessed personality and anxiety in all study groups. Statistically significant differences in the frequency of genotypes and alleles were found between all study groups. Compared to the control, both study groups had statistically significantly higher scores for trait and state anxiety. Addicted patients in both groups also had higher scores on the Neuroticism and Openness scales and lower scores on the Extraversion and Agreeableness scales. The results of this study provide further evidence that personality traits, anxiety and the rs6265 polymorphism of the BDNF gene may be risk factors for susceptibility to addiction to psychoactive substances. In addition, they can be a predictor of addiction relapse, but further extensive studies are required to confirm these findings.
Spice Up Your Kidney: A Review on the Effects of Capsaicin in Renal Physiology and Disease
Authors: Musolino Michela , D’Agostino Mario , Zicarelli Mariateresa , Andreucci Michele , Coppolino Giuseppe , Bolignano Davide
Published: January 2024

Capsaicin, the organic compound which attributes the spicy flavor and taste of red peppers and chili peppers, has been extensively studied for centuries as a potential natural remedy for the treatment of several illnesses. Indeed, this compound exerts well-known systemic pleiotropic effects and may thus bring important benefits against various pathological conditions like neuropathic pain, rhinitis, itching, or chronic inflammation. Yet, little is known about the possible biological activity of capsaicin at the kidney level, as this aspect has only been addressed by sparse experimental investigations. In this paper, we aimed to review the available evidence focusing specifically on the effects of capsaicin on renal physiology, as well as its potential benefits for the treatment of various kidney disorders. Capsaicin may indeed modulate various aspects of renal function and renal nervous activity. On the other hand, the observed experimental benefits in preventing acute kidney injury, slowing down the progression of diabetic and chronic kidney disease, ameliorating hypertension, and even delaying renal cancer growth may set the stage for future human trials of capsaicin administration as an adjuvant or preventive therapy for different, difficult-to-treat renal diseases.