bluuebunny/crossref_metadata_2025 huggingface dataset:
A Qualitative Exploratory Study of the Political Commitment for Nutrition Programming: A Case Study of Anambra and Kebbi States of Nigeria
Authors: Ezekannagha Oluchi , Drimie Scott , Von Fintel Dieter , Maziya-Dixon Busie , Mbhenyane Xikombiso
Published: February 2024

In Nigeria, varying levels of malnutrition across states present a critical challenge to public health, demanding tailored policy responses. This paper delves into the specific issues and dynamics influencing nutrition programs in the country. Advocating for nutrition-sensitive actions requires analyzing context-specific political commitment. This article presents a case study on two Nigerian states with varying malnutrition profiles to explore the political economy of nutrition. The study used stakeholder analysis, in-depth interviews, and semi-structured interviews through workshops, incorporating the Political Commitment Rapid Assessment Tool. The objective was to measure political commitment, the window of opportunity for action, and stakeholder analysis. The results showed that despite having a significant child malnutrition problem, Kebbi State received a high political commitment to nutrition, with proportions ranging from 0.67 to 1 in each of the six domains measured. On the other hand, Anambra State, where malnutrition was less severe, had varying commitment levels. Institutional commitment was marginally high (0.67), expressed commitment was high (0.71), and budgetary commitment was lower at 0.33. Kebbi had better support for programs dependent on foreign donors than Anambra. Both states need to use media to increase awareness about nutrition issues. When the nutrition situation is severe, foreign donors’ influence grows. In conclusion, there are opportunities for strategic framing and advocacy of the nutrition profile of the states. Local state media can be effective, and institutional coordination committees that include various sectors already facilitate commitment to nutrition actions. However, individual, uncoordinated sectoral action can counterbalance the benefits of these committees. Further possibilities to generate political commitment for nutrition in the states are available. This study not only offers insights into the effectiveness of political strategies in addressing malnutrition but also lays the groundwork for future research and provides actionable recommendations for government policymaking.
Literary Identification of Differentially Hydroxymethylated DNA Regions for Type 2 Diabetes Mellitus: A Scoping Minireview
Authors: Luong Ryan Anh Minh , Guan Weihua , Vue Fue Chee , Dai Jun
Published: February 2024

Type 2 diabetes mellitus (T2DM) is a public health condition where environmental and genetic factors can intersect through hydroxymethylation. It was unclear which blood DNA regions were hydroxymethylated in human T2DM development. We aimed to identify the regions from the literature as designed in the ongoing Twins Discordant for Incident T2DM Study. A scoping review was performed using Medical Subject Headings (MeSH) and keyword methods to search PubMed for studies published in English and before 1 August 2022, following our registered protocol. The keyword and MeSH methods identified 12 and 3 records separately, and the keyword-identified records included all from the MeSH. Only three case-control studies met the criteria for the full-text review, including one MeSH-identified record. Increased global levels of 5-hydroxymethylated cytosine (5hmC) in T2DM patients versus healthy controls in blood or peripheral blood mononuclear cells were consistently reported (p < 0.05 for all). Among candidate DNA regions related to the human SOCS3, SREBF1, and TXNIP genes, only the SOCS3 gene yielded higher 5hmC levels in T2DM patients with high poly-ADP-ribosylation than participants combined from those with low PARylation and healthy controls (p < 0.05). Hydroxymethylation in the SOCS3-related region of blood DNA is promising to investigate for its mediation in the influences of environment on incident T2DM.
Impact of Environment on Pain among the Working Poor: Making Use of Random Forest-Based Stratification Tool to Study the Socioecology of Pain Interference
Authors: Leung Eman , Lee Albert , Liu Yilin , Hung Chi-Tim , Fan Ning , Ching Sam C. C. , Yee Hilary , He Yinan , Xu Richard , Tsang Hector Wing Hong , Guan Jingjing
Published: February 2024

Pain interferes with one’s work and social life and, at a personal level, daily activities, mood, and sleep quality. However, little research has been conducted on pain interference and its socioecological determinants among the working poor. Noting the clinical/policy decision needs and the technical challenges of isolating the intricately interrelated socioecological factors’ unique contributions to pain interference and quantifying the relative contributions of each factor in an interpretable manner to inform clinical and policy decision-making, we deployed a novel random forest algorithm to model and quantify the unique contribution of a diverse ensemble of environmental, sociodemographic, and clinical factors to pain interference. Our analyses revealed that features representing the internal built environment of the working poor, such as the size of the living space, air quality, access to light, architectural design conducive to social connection, and age of the building, were assigned greater statistical importance than other more commonly examined predisposing factors for pain interference, such as age, occupation, the severity and locations of pain, BMI, serum blood sugar, and blood pressure. The findings were discussed in the context of their benefit in informing community pain screening to target residential areas whose built environment contributed most to pain interference and informing the design of intervention programs to minimize pain interference among those who suffered from chronic pain and showed specific characteristics. The findings support the call for good architecture to provide the spirit and value of buildings in city development.
A Time-Identified R-Tree: A Workload-Controllable Dynamic Spatio-Temporal Index Scheme for Streaming Processing
Authors: Peng Weichen , Chen Luo , Ouyang Xue , Xiong Wei
Published: February 2024

Many kinds of spatio-temporal data in our daily lives, such as the trajectory data of moving objects, stream natively. Streaming systems exhibit significant advantages in processing streaming data due to their distributed architecture, high throughput, and real-time performance. The use of streaming processing techniques for spatio-temporal data applications is a promising research direction. However, due to the strong dynamic nature of data in streaming processing systems, traditional spatio-temporal indexing techniques based on relatively static data cannot be used directly in stream-processing environments. It is necessary to study and design new spatio-temporal indexing strategies. Hence, we propose a workload-controllable dynamic spatio-temporal index based on the R-tree. In order to restrict memory usage, we formulate an INSERT and batch-REMOVE (I&BR) method and append a collection mechanism to the traditional R-tree. To improve the updating performance, we propose a time-identified R-tree (TIR). Moreover, we propose a distributed system prototype called a time-identified R-tree farm (TIRF). Experiments show that the TIR could work in a scenario with a controllable usage of memory and a stable response time. The throughput of the TIRF could reach 1 million points per second. The performance of a range search in the TIRF is many times better than in PostgreSQL, which is a widely used database system for spatio-temporal applications.
Study on Spatio-Temporal Patterns of Commuting under Adverse Weather Events: Case Study of Typhoon In-Fa
Authors: Ji Tao , Huang Xian , Shao Jinliang , Zhu Yunqiang , Deng Shejun , Yu Shijun , Liao Huajun
Published: February 2024

This study focuses on the main urban area of Yangzhou City and conducts a quantitative comparative analysis of traffic accessibility during normal weather and extreme precipitation conditions (typhoon) based on GPS trajectories of buses. From both temporal and spatial dimensions, it comprehensively examines the impact of extreme precipitation on bus travel speed, travel time, and the commuting range of residents in the main urban area of Yangzhou City. (1) Through the mining and analysis of multi-source heterogeneous big data (bus GPS trajectory data, bus network data, rainfall remote sensing data, and road network data), it is found that the rainstorm weather greatly affects the average speed and travel time of buses. In addition, when the intensity of heavy rainfall increases (decreases), the average bus speed and travel time exhibit varying degrees of spatio-temporal change. During the morning and evening rush hour commuting period of rainstorm weather, there are obvious differences in the accessibility change in each typical traffic community in the main urban area of Yangzhou city. In total, 90% of the overall accessibility change value is concentrated around −5 min~5 min, and the change range is concentrated around −25~10%. (2) To extract the four primary traffic districts (Lotus Pond, Slender West Lake, Jinghua City, and Wanda Plaza), we collected Points of Interest (POI) data from Amap and Baidu heat map, and a combination analysis of the employment–residence ratio model and proximity methods was employed. The result show that the rainstorm weather superimposed on the morning peak hour has different degrees of impact on the average speed of the above-mentioned traffic zones, with the most obvious impact on the Lotus Pond and the smallest impact on Wanda Plaza. Under the rainstorm weather, the traffic commute in the main urban area of Yangzhou in the morning and evening peak hour is basically normal. The results of this paper can help to quantify the impact of typhoon-rainstorm weather events on traffic commuting in order to provide a scientific basis for the traffic management department to effectively prevent traffic jams, ensure the reliability of the road network, and allow the traffic management department to more effectively manage urban traffic.
Joint CB1 and NGF Receptor Activation Suppresses TRPM8 Activation in Etoposide-Resistant Retinoblastoma Cells
Authors: Ludwiczak Szymon , Reinhard Jacqueline , Reinach Peter S. , Li Aruna , Oronowicz Jakub , Yousf Aisha , Kakkassery Vinodh , Mergler Stefan
Published: February 2024

In childhood, retinoblastoma (RB) is the most common primary tumor in the eye. Long term therapeutic management with etoposide of this life-threatening condition may have diminishing effectiveness since RB cells can develop cytostatic resistance to this drug. To determine whether changes in receptor-mediated control of Ca2+ signaling are associated with resistance development, fluorescence calcium imaging, semi-quantitative RT-qPCR analyses, and trypan blue dye exclusion staining patterns are compared in WERI-ETOR (etoposide-insensitive) and WERI-Rb1 (etoposide-sensitive) cells. The cannabinoid receptor agonist 1 (CNR1) WIN55,212-2 (40 µM), or the transient receptor potential melastatin 8 (TRPM8) agonist icilin (40 µM) elicit similar large Ca2+ transients in both cell line types. On the other hand, NGF (100 ng/mL) induces larger rises in WERI-ETOR cells than in WERI-Rb1 cells, and its lethality is larger in WERI-Rb1 cells than in WERI-ETOR cells. NGF and WIN55,212-2 induced additive Ca2+ transients in both cell types. However, following pretreatment with both NGF and WIN55,212-2, TRPM8 gene expression declines and icilin-induced Ca2+ transients are completely blocked only in WERI-ETOR cells. Furthermore, CNR1 gene expression levels are larger in WERI-ETOR cells than those in WERI-Rb1 cells. Therefore, the development of etoposide insensitivity may be associated with rises in CNR1 gene expression, which in turn suppress TRPM8 gene expression through crosstalk.
miRNAs Related to Immune Checkpoint Inhibitor Response: A Systematic Review
Authors: García-Giménez José Luis , Saadi Wiam , Ortega Angel L. , Lahoz Agustin , Suay Guillermo , Carretero Julián , Pereda Javier , Fatmi Ahlam , Pallardó Federico V. , Mena-Molla Salvador
Published: February 2024

The advent of immune checkpoint inhibitors (ICIs) has represented a breakthrough in the treatment of many cancers, although a high number of patients fail to respond to ICIs, which is partially due to the ability of tumor cells to evade immune system surveillance. Non-coding microRNAs (miRNAs) have been shown to modulate the immune evasion of tumor cells, and there is thus growing interest in elucidating whether these miRNAs could be targetable or proposed as novel biomarkers for prognosis and treatment response to ICIs. We therefore performed an extensive literature analysis to evaluate the clinical utility of miRNAs with a confirmed direct relationship with treatment response to ICIs. As a result of this systematic review, we have stratified the miRNA landscape into (i) miRNAs whose levels directly modulate response to ICIs, (ii) miRNAs whose expression is modulated by ICIs, and (iii) miRNAs that directly elicit toxic effects or participate in immune-related adverse events (irAEs) caused by ICIs.
Special Issue on Biotechnological Applications of Oxidoreductases
Authors: Baratto Maria Camilla , Pogni Rebecca
Published: February 2024

This Special Issue was launched in conjunction with the 10th edition of the OxiZymes meeting in Siena (Italy) in 2022 [...]
Fluorescence-Based Protein Stability Monitoring—A Review
Authors: Gooran Negin , Kopra Kari
Published: February 2024

Proteins are large biomolecules with a specific structure that is composed of one or more long amino acid chains. Correct protein structures are directly linked to their correct function, and many environmental factors can have either positive or negative effects on this structure. Thus, there is a clear need for methods enabling the study of proteins, their correct folding, and components affecting protein stability. There is a significant number of label-free methods to study protein stability. In this review, we provide a general overview of these methods, but the main focus is on fluorescence-based low-instrument and -expertise-demand techniques. Different aspects related to thermal shift assays (TSAs), also called differential scanning fluorimetry (DSF) or ThermoFluor, are introduced and compared to isothermal chemical denaturation (ICD). Finally, we discuss the challenges and comparative aspects related to these methods, as well as future opportunities and assay development directions.
The Lack of TRPA1 Ion Channel Does Not Affect the Chronic Stress-Induced Activation of the Locus Ceruleus
Authors: Milicic Milica , Gaszner Balázs , Berta Gergely , Pintér Erika , Kormos Viktória
Published: February 2024

We have previously proven the involvement of transient receptor potential ankyrin 1 (TRPA1) in stress adaptation. A lack of TRPA1 affects both urocortin 1 (member of the corticotropin-releasing hormone (CRH) family) content of the Edinger–Westphal nucleus. The noradrenergic locus ceruleus (LC) is also an important player in mood control. We aimed at investigating whether the TRPA1 is expressed in the LC, and to test if the response to chronic variable mild stress (CVMS) is affected by a lack of TRPA1. The TRPA1 expression was examined via RNAscope in situ hybridization. We investigated TRPA1 knockout and wildtype mice using the CVMS model of depression. Tyrosine hydroxylase (TH) and FOSB double immunofluorescence were used to test the functional neuromorphological changes in the LC. No TRPA1 expression was detected in the LC. The TH content was not affected by CVMS exposure. The CVMS-induced FOSB immunosignal did not co-localize with the TH neurons. TRPA1 is not expressed in the LC. A lack of functional TRPA1 receptor neither directly nor indirectly affects the TH content of LC neurons under CVMS.
Comparative Analysis of Chloroplast Pan-Genomes and Transcriptomics Reveals Cold Adaptation in Medicago sativa
Authors: Zhang Tianxiang , Chen Xiuhua , Yan Wei , Li Manman , Huang Wangqi , Liu Qian , Li Yanan , Guo Changhong , Shu Yongjun
Published: February 2024

Alfalfa (Medicago sativa) is a perennial forage legume that is widely distributed all over the world; therefore, it has an extremely complex genetic background. Though population structure and phylogenetic studies have been conducted on a large group of alfalfa nuclear genomes, information about the chloroplast genomes is still lacking. Chloroplast genomes are generally considered to be conservative and play an important role in population diversity analysis and species adaptation in plants. Here, 231 complete alfalfa chloroplast genomes were successfully assembled from 359 alfalfa resequencing data, on the basis of which the alfalfa chloroplast pan-genome was constructed. We investigated the genetic variations of the alfalfa chloroplast genome through comparative genomic, genetic diversity, phylogenetic, population genetic structure, and haplotype analysis. Meanwhile, the expression of alfalfa chloroplast genes under cold stress was explored through transcriptome analysis. As a result, chloroplast genomes of 231 alfalfa lack an IR region, and the size of the chloroplast genome ranges from 125,192 bp to 126,105 bp. Using population structure, haplotypes, and construction of a phylogenetic tree, it was found that alfalfa populations could be divided into four groups, and multiple highly variable regions were found in the alfalfa chloroplast genome. Transcriptome analysis showed that tRNA genes were significantly up-regulated in the cold-sensitive varieties, while rps7, rpl32, and ndhB were down-regulated, and the editing efficiency of ycf1, ycf2, and ndhF was decreased in the cold-tolerant varieties, which may be due to the fact that chloroplasts store nutrients through photosynthesis to resist cold. The huge number of genetic variants in this study provide powerful resources for molecular markers.
Clinical Characteristics and Local Histopathological Modulators of Endometriosis and Its Progression
Authors: Istrate-Ofiţeru Anca-Maria , Mogoantă Carmen Aurelia , Zorilă George-Lucian , Roşu Gabriela-Camelia , Drăguşin Roxana Cristina , Berbecaru Elena-Iuliana-Anamaria , Zorilă Marian Valentin , Comănescu Cristina Maria , Mogoantă Stelian-Ștefăniță , Vaduva Constantin-Cristian , Brătilă Elvira , Iliescu Dominic Gabriel
Published: February 2024

Endometriosis (E) and adenomyosis (A) are associated with a wide spectrum of symptoms and may present various histopathological transformations, such as the presence of hyperplasia, atypia, and malignant transformation occurring under the influence of local inflammatory, vascular and hormonal factors and by the alteration of tumor suppressor proteins and the inhibition of cell apoptosis, with an increased degree of lesion proliferation. Material and methods: This retrospective study included 243 patients from whom tissue with E/A or normal control uterine tissue was harvested and stained by histochemical and classical immunohistochemical staining. We assessed the symptomatology of the patients, the structure of the ectopic epithelium and the presence of neovascularization, hormone receptors, inflammatory cells and oncoproteins involved in lesion development. Atypical areas were analyzed using multiple immunolabeling techniques. Results: The cytokeratin (CK) CK7+/CK20− expression profile was present in E foci and differentiated them from digestive metastases. The neovascularization marker cluster of differentiation (CD) 34+ was increased, especially in areas with malignant transformation of E or A foci. T:CD3+ lymphocytes, B:CD20+ lymphocytes, CD68+ macrophages and tryptase+ mast cells were abundant, especially in cases associated with malignant transformation, being markers of the proinflammatory microenvironment. In addition, we found a significantly increased cell division index (Ki67+), with transformation and inactivation of tumor suppressor genes p53, B-cell lymphoma 2 (BCL-2) and Phosphatase and tensin homolog (PTEN) in areas with E/A-transformed malignancy. Conclusions: Proinflammatory/vascular/hormonal changes trigger E/A progression and the onset of cellular atypia and malignant transformation, exacerbating symptoms, especially local pain and vaginal bleeding. These triggers may represent future therapeutic targets.
Senotherapeutics to Counteract Senescent Cells Are Prominent Topics in the Context of Anti-Ageing Strategies
Authors: Calabrò Anna , Accardi Giulia , Aiello Anna , Caruso Calogero , Galimberti Damiano , Candore Giuseppina
Published: February 2024

Cellular senescence is implicated in ageing and associated with a broad spectrum of age-related diseases. Importantly, a cell can initiate the senescence program irrespective of the organism’s age. Various stress signals, including those defined as ageing hallmarks and alterations leading to cancer development, oncogene activation, or loss of cancer-suppressive functions, can trigger cellular senescence. The primary outcome of these alterations is the activation of nuclear factor (NF)-κB, thereby inducing the senescence-associated secretory phenotype (SASP). Proinflammatory cytokines and chemokines, components of this phenotype, contribute to chronic systemic sterile inflammation, commonly referred to as inflamm-ageing. This inflammation is linked to age-related diseases (ARDs), frailty, and increased mortality in older individuals. Additionally, senescent cells (SCs) accumulate in multiple tissues with age and are believed to underlie the organism functional decline, as demonstrated by models. An escalating effort has been dedicated to identify senotherapeutics that selectively target SCs by inducing apoptosis; these drugs are termed senolytics. Concurrently, small molecules that suppress senescent phenotypes without causing cell death are known as senomorphics. Both natural and synthetic senotherapeutics, along with immunotherapies employing immune cell-mediated clearance of SCs, currently represent the most promising strategies to combat ageing and ARDs. Indeed, it is fascinating to observe that information regarding the immune reaction to SCs indicates that regulation by specific lymphocyte subsets, elevated in the oldest centenarians, plays a role in attaining extreme longevity. Regardless, the application of methods already utilized in cancer treatment, such as CAR cells and monoclonal antibodies, broadens the spectrum of potential approaches to be utilized.
Extracts of Sideritis scardica and Clinopodium vulgare Alleviate Cognitive Impairments in Scopolamine-Induced Rat Dementia
Authors: Lazarova Maria , Tsvetanova Elina , Georgieva Almira , Stefanova Miroslava , Uzunova Diamara , Denev Petko , Vassileva Valya , Tasheva Krasimira
Published: February 2024

Sideritis scardica Griseb. and Clinopodium vulgare L., belonging to the Lamiaceae family, are rich in terpenoids and phenolics and exhibit various pharmacological effects, including antioxidant, anti-inflammatory and anti-cancer activities. While the memory-enhancing impacts of S. scardica are well documented, the cognitive benefits of C. vulgare remain unexplored. This study assessed the potential effect of C. vulgare on learning and memory in healthy and scopolamine (Sco)-induced memory-impaired male Wistar rats, comparing it with the effects of S. scardica. Over a 21-day period, rats orally received extracts of cultivated S. scardica (200 mg/kg) and C. vulgare (100 mg/kg), either individually or in combination, with administration starting 10 days before and continuing 11 days simultaneously with Sco injection at a dose of 2 mg/kg intraperitoneally. The results showed that both extracts effectively mitigated Sco-induced memory impairment. Their combination significantly improved recognition memory and maintained monoaminergic function. S. scardica excelled in preserving spatial working memory, while C. vulgare exhibited comparable retention of recognition memory, robust antioxidant activity and acetylcholinesterase inhibitory activity. The extracts alleviated Sco-induced downregulation of p-CREB/BDNF signaling, suggesting neuroprotective mechanisms. The extract combination positively affected most of the Sco-induced impairments, underscoring the potential for further investigation of these extracts for therapeutic development.
Paradigm Shift: A Comprehensive Review of Ovarian Cancer Management in an Era of Advancements
Authors: Tavares Valéria , Marques Inês Soares , Melo Inês Guerra de , Assis Joana , Pereira Deolinda , Medeiros Rui
Published: February 2024

Ovarian cancer (OC) is the female genital malignancy with the highest lethality. Patients present a poor prognosis mainly due to the late clinical presentation allied with the common acquisition of chemoresistance and a high rate of tumour recurrence. Effective screening, accurate diagnosis, and personalised multidisciplinary treatments are crucial for improving patients’ survival and quality of life. This comprehensive narrative review aims to describe the current knowledge on the aetiology, prevention, diagnosis, and treatment of OC, highlighting the latest significant advancements and future directions. Traditionally, OC treatment involves the combination of cytoreductive surgery and platinum-based chemotherapy. Although more therapeutical approaches have been developed, the lack of established predictive biomarkers to guide disease management has led to only marginal improvements in progression-free survival (PFS) while patients face an increasing level of toxicity. Fortunately, because of a better overall understanding of ovarian tumourigenesis and advancements in the disease’s (epi)genetic and molecular profiling, a paradigm shift has emerged with the identification of new disease biomarkers and the proposal of targeted therapeutic approaches to postpone disease recurrence and decrease side effects, while increasing patients’ survival. Despite this progress, several challenges in disease management, including disease heterogeneity and drug resistance, still need to be overcome.
Identification of miR-30c-5p microRNA in Serum as a Candidate Biomarker to Diagnose Endometriosis
Authors: Chico-Sordo Lucía , Ruiz-Martínez Tamara , Toribio Mónica , González-Martín Roberto , Spagnolo Emanuela , Domínguez Francisco , Hernández Alicia , García-Velasco Juan A.
Published: February 2024

The diagnosis of endometriosis by laparoscopy is delayed until advanced stages. In recent years, microRNAs have emerged as novel biomarkers for different diseases. These molecules are small non-coding RNA sequences involved in the regulation of gene expression and can be detected in peripheral blood. Our aim was to identify candidate serum microRNAs associated with endometriosis and their role as minimally invasive biomarkers. Serum samples were obtained from 159 women, of whom 77 were diagnosed with endometriosis by laparoscopy and 82 were healthy women. First, a preliminary study identified 29 differentially expressed microRNAs between the two study groups. Next, nine of the differentially expressed microRNAs in the preliminary analysis were evaluated in a new cohort of 67 women with endometriosis and 72 healthy women. Upon validation by quantitative real-time PCR technique, the circulating level of miR-30c-5p was significantly higher in the endometriosis group compared with the healthy women group. The area under the curve value of miR-30c-5p was 0.8437, demonstrating its diagnostic potential even when serum samples registered an acceptable limit of hemolysis. Dysregulation of this microRNA was associated with molecular pathways related to cancer and neuronal processes. We concluded that miR-30c-5p is a potential minimally invasive biomarker of endometriosis, with higher expression in the group of women with endometriosis diagnosed by laparoscopy.
Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway
Authors: Kuo Fu-Chen , Tsai Hsin-Yi , Cheng Bi-Ling , Tsai Kuen-Jang , Chen Ping-Chen , Huang Yaw-Bin , Liu Chung-Jung , Wu Deng-Chyang , Wu Meng-Chieh , Huang Bin , Lin Ming-Wei
Published: February 2024

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and the lack of a standard treatment protocol related to this condition, the investigation of the mechanisms underlying melanoma progression is crucial to achieve advancements in the relevant gynecological surgery and treatment. Mitochondrial transfer between adjacent cells in the tumor microenvironment regulates tumor progression. This study investigated the effects of endothelial mitochondria on the growth of melanoma cells and the activation of specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from endothelial cells (ECs) and transplanted into B16F10 melanoma cells, resulting in the upregulation of proteins associated with tumor growth. Furthermore, enhanced antioxidation and mitochondrial homeostasis mediated by the Sirt1-PGC-1α-Nrf2-HO-1 pathway were observed, along with the inhibition of apoptotic protein caspase-3. Finally, the transplantation of endothelial mitochondria into B16F10 cells promoted tumor growth and increased M2-type macrophages through Nrf2/HO-1-mediated pathways in a xenograft animal model. In summary, the introduction of exogenous mitochondria from ECs into melanoma cells promoted tumor growth, indicating the role of mitochondrial transfer by stromal cells in modulating a tumor’s phenotype. These results provide valuable insights into the role of mitochondrial transfer and provide potential targets for gynecological melanoma treatment.
Protective Effect of the Novel Melatonin Analogue Containing Donepezil Fragment on Memory Impairment via MT/ERK/CREB Signaling in the Hippocampus in a Rat Model of Pinealectomy and Subsequent Aβ1-42 Infusion
Authors: Tchekalarova Jana , Ivanova Petya , Krushovlieva Desislava , Kortenska Lidia , Angelova Violina T.
Published: February 2024

A reduction in melatonin function contributes to the acceleration of Alzheimer’s disease (AD), and understanding the molecular processes of melatonin-related signaling is critical for intervention in AD progression. Recently, we synthesized a series of melatonin analogues with donepezil fragments and tested them in silico and in vitro. In this study, one of the most potent compounds, 3c, was evaluated in a rat model of pinealectomy (pin) followed by icvAβ1-42 infusion. Melatonin was used as the reference drug. Treatment with melatonin and 3c (10 mg/kg, i.p. for 14 days) had a beneficial effect on memory decline and the concomitant increase in hippocampal Aβ1-42 and pTAU in the pin+icvAβ1-42 rats. Melatonin supplementation facilitated non-amyloidogenic signaling via non-receptor (histone deacetylase sirtuin 1, SIRT1) and receptor-related signaling (MT/ERK/CREB). The hybrid 3c analogue up-regulated the MT1A and MT2B receptors, pERK and pCREB. Our results strongly support the hypothesis that melatonin-related analogues may become a promising drug candidate for Alzheimer’s disease therapy.
Gut Symptoms, Gut Dysbiosis and Gut-Derived Toxins in ALS
Authors: Lee Aven , Henderson Robert , Aylward James , McCombe Pamela
Published: February 2024

Many pathogenetic mechanisms have been proposed for amyotrophic lateral sclerosis (ALS). Recently, there have been emerging suggestions of a possible role for the gut microbiota. Gut microbiota have a range of functions and could influence ALS by several mechanisms. Here, we review the possible role of gut-derived neurotoxins/excitotoxins. We review the evidence of gut symptoms and gut dysbiosis in ALS. We then examine a possible role for gut-derived toxins by reviewing the evidence that these molecules are toxic to the central nervous system, evidence of their association with ALS, the existence of biochemical pathways by which these molecules could be produced by the gut microbiota and existence of mechanisms of transport from the gut to the blood and brain. We then present evidence that there are increased levels of these toxins in the blood of some ALS patients. We review the effects of therapies that attempt to alter the gut microbiota or ameliorate the biochemical effects of gut toxins. It is possible that gut dysbiosis contributes to elevated levels of toxins and that these could potentially contribute to ALS pathogenesis, but more work is required.
Construction of a g-C3N4/Bi(OH)3 Heterojunction for the Enhancement of Visible Light Photocatalytic Antibacterial Activity
Authors: Feng Jian , Wang Li , Xiao Bo , Ran Xia , Wang Caiying , Zhu Jinming , Liu Zuoji , Li Chaozhong , Cui Xinai , Li Rong , Feng Guangwei , Dai Zeqin
Published: February 2024

Photocatalytic technology has been recently conducted to remove microbial contamination due to its unique features of nontoxic by-products, low cost, negligible microbial resistance and broad-spectrum elimination capacity. Herein, a novel two dimensional (2D) g-C3N4/Bi(OH)3 (CNB) heterojunction was fabricated byincorporating Bi(OH)3 (BOH) nanoparticles with g-C3N4 (CN) nanosheets. This CNB heterojunction exhibited high photocatalytic antibacterial efficiency (99.3%) against Escherichia coli (E. coli) under visible light irradiation, which was 4.3 and 3.4 times that of BOH (23.0%) and CN (28.0%), respectively. The increase in specific surface area, ultra-thin layered structure, construction of a heterojunction and enhancement of visible light absorption were conducive to facilitating the separation and transfer of photoinduced charge carriers. Live/dead cell staining, sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) assays and scanning electron microscopy (SEM) have been implemented to investigate the damage to the cell membrane and the leakage of the intracellular protein in the photocatalytic antibacterial process. The e−, h+ and O2•− were the active species involved in this process. This study proposed an appropriate photocatalyst for efficient treatment of bacterial contamination.
Rosavin Alleviates LPS-Induced Acute Lung Injure by Modulating the TLR-4/NF-κB/MAPK Singnaling Pathways
Authors: Liu Qiao-Hui , Zhang Ke , Feng Shu-Shu , Zhang Li-Juan , Li Shun-Ying , Wang Hang-Yu , Wang Jin-Hui
Published: February 2024

Acute lung injury (ALI) is a serious inflammatory disease with high morbidity and mortality. Rosavin is an anti-inflammatory and antioxidant phenylpropanoid and glucoside, which is isolated from Rhodiola rosea L. However, its potential molecular mechanisms and whether it has protective effects against lipopolysaccharide (LPS)-induced ALI remain to be elucidated. To assess the in vitro anti-inflammatory effects and anti-lung injury activity of rosavin, RAW264.7 and A549 cells were stimulated using 1 μg/mL LPS. Rosavin attenuated LPS-induced activation of the TLR-4/NF-κB signaling pathway in RAW264.7 cells and inhibited LPS-induced release of inflammatory factors in A549 cells. A mouse model of acute lung injury was constructed by intraperitoneal injection of 5 mg/kg LPS to observe the therapeutic effect of rosavin. Transcriptomics analysis and Western blot assays were utilized to verify the molecular mechanism, rosavin (20, 40, and 80 mg/kg) dose-dependently ameliorated histopathological alterations, reduced the levels of inflammatory factors, and inhibited the TLR-4/NF-κB/MAPK signaling pathway and apoptosis activation. Rosavin is a promising therapeutic candidate for acute lung injury by inhibiting the TLR-4/NF-κB/MAPK pathway.
Untargeted Metabolomic Analyses and Antilipidemic Effects of Citrus Physiological Premature Fruit Drop
Authors: Wang Chao , Peng Mingfang , Gao Zhipeng , Han Qi , Fu Fuhua , Li Gaoyang , Su Donglin , Huang Lvhong , Guo Jiajing , Shan Yang
Published: February 2024

Increasingly globally prevalent obesity and related metabolic disorders have underscored the demand for safe and natural therapeutic approaches, given the limitations of weight loss drugs and surgeries. This study compared the phytochemical composition and antioxidant activity of five different varieties of citrus physiological premature fruit drop (CPFD). Untargeted metabolomics was employed to identify variations in metabolites among different CPFDs, and their antilipidemic effects in vitro were assessed. The results showed that Citrus aurantium L. ‘Daidai’ physiological premature fruit drop (DDPD) and Citrus aurantium ‘Changshan-huyou’ physiological premature fruit drop (HYPD) exhibited higher levels of phytochemicals and stronger antioxidant activity. There were 97 differential metabolites identified in DDPD and HYPD, including phenylpropanoids, flavonoids, alkaloids, organic acids, terpenes, and lipids. Additionally, DDPD and HYPD demonstrated potential antilipidemic effects against oleic acid (OA)-induced steatosis in HepG2 hepatocytes and 3T3-L1 adipocytes. In conclusion, our findings reveal the outstanding antioxidant activity and antilipidemic effects of CPFD, indicating its potential use as a natural antioxidant and health supplement and promoting the high-value utilization of this resource.
The XCL1-Mediated DNA Vaccine Targeting Type 1 Conventional Dendritic Cells Combined with Gemcitabine and Anti-PD1 Antibody Induces Potent Antitumor Immunity in a Mouse Lung Cancer Model
Authors: Zhang Ke , Wuri Qimuge , Cai Zongyu , Qu Xueli , Zhang Shiqi , Wu Hui , Wu Jiaxin , Wang Chu , Yu Xianghui , Kong Wei , Zhang Haihong
Published: February 2024

With the advent of cancer immunotherapy, there is a growing interest in vaccine development as a means to activate the cellular immune system against cancer. Despite the promise of DNA vaccines in this regard, their effectiveness is hindered by poor immunogenicity, leading to modest therapeutic outcomes across various cancers. The role of Type 1 conventional dendritic cells (cDC1), capable of cross-presenting vaccine antigens to activate CD8+T cells, emerges as crucial for the antitumor function of DNA vaccines. To address the limitations of DNA vaccines, a promising approach involves targeting antigens to cDC1 through the fusion of XCL1, a ligand specific to the receptor XCR1 on the surface of cDC1. Here, female C57BL/6 mice were selected for tumor inoculation and immunotherapy. Additionally, recognizing the complexity of cancer, this study explored the use of combination therapies, particularly the combination of cDC1-targeted DNA vaccine with the chemotherapy drug Gemcitabine (Gem) and the anti-PD1 antibody in a mouse lung cancer model. The study’s findings indicate that fusion antigens with XCL1 effectively enhance both the immunogenicity and antitumor effects of DNA vaccines. Moreover, the combination of the cDC1-targeted DNA vaccine with Gemcitabine and anti-PD1 antibody in the mouse lung cancer model demonstrates an improved antitumor effect, leading to the prolonged survival of mice. In conclusion, this research provides important support for the clinical investigation of cDC1-targeting DNA vaccines in combination with other therapies.
Fuch’s Endothelial Corneal Dystrophy in Cataract Patients Is Associated with Elevated Levels of Inflammatory Chemokines, but Not Growth Factors, in the Aqueous Humor
Authors: Fiolka Rafał , Wylęgała Edward , Toborek Michał , Szkodny Dominika , Czuba Zenon , Wylęgała Adam
Published: February 2024

The study investigated a profile of chemokines and growth factors in the aqueous humor (AH) of eyes with Fuch’s endothelial corneal dystrophy (FECD) and cataracts in comparison with cataract patients as a control group. A total of 52 AH samples (26 FECD + cataract and 26 cataract/control) were collected before cataract surgery. None of the patients had any clinically apparent inflammation at the time of AH collection. The AH levels of MCP-1 (CCL2), MIP-1α (CCL3), MIP-1β(CCL4), RANTES (CCL5), eotaxin (CCL11), IP-10 (CXCL10), FGF basic, G-CSF, GM-CSF, PDGF-bb, and VEGF were compared between the groups. The analyses were performed using the Bio-Plex 200 System from Bio-Rad. Among the studied parameters, the AH levels of RANTES, eotaxin, and IP-10 significantly increased in the FECD + cataract eyes, compared with the cataract controls (p < 0.05). Elevated levels of the RANTES, Eotaxin, and IP-10 indicate more intense inflammation in the eyes of patients in the FECD + cataract group. Moreover, these factors exhibit potential as predictive biomarkers for early detection of FECD in cataract patients. The discovery of elevated concentrations of biochemical markers in a patient, who has not yet received a clinical diagnosis, may suggest the need for heightened observation of the other eye to monitor the potential development of FECD.
Transcriptomic Analysis Provides Insights into Candidate Genes and Molecular Pathways Involved in Growth of Mytilus coruscus Larvae
Authors: Xu Minhui , Li Zhong , Liang Xinjie , Li Jiji , Ye Yingying , Qi Pengzhi , Yan Xiaojun
Published: February 2024

Growth is a fundamental aspect of aquaculture breeding programs, pivotal for successful cultivation. Understanding the mechanisms that govern growth and development differences across various stages can significantly boost seedling production of economically valuable species, thereby enhancing aquaculture efficiency and advancing the aquaculture industry. Mytilus coruscus, a commercially vital marine bivalve, underscores this importance. To decipher the intricate molecular mechanisms dictating growth and developmental disparities in marine shellfish, we conducted transcriptome sequencing and meticulously analyzed gene expression variations and molecular pathways linked to growth traits in M. coruscus. This study delved into the molecular and gene expression variations across five larval development stages, with a specific focus on scrutinizing the differential expression patterns of growth-associated genes using RNA sequencing and quantitative real-time PCR analysis. A substantial number of genes—36,044 differentially expressed genes (DEGs)—exhibited significant differential expression between consecutive developmental stages. These DEGs were then categorized into multiple pathways (Q value < 0.05), including crucial pathways such as the spliceosome, vascular smooth muscle contraction, DNA replication, and apoptosis, among others. In addition, we identified two pivotal signaling pathways—the Hedgehog (Hh) signaling pathway and the TGF-beta (TGF-β) signaling pathway—associated with the growth and development of M. coruscus larvae. Ten key growth-related genes were pinpointed, each playing crucial roles in molecular function and the regulation of growth traits in M. coruscus. These genes and pathways associated with growth provide deep insights into the molecular basis of physiological adaptation, metabolic processes, and growth variability in marine bivalves.
Calcium, Phosphorus, and Vitamin D Levels in a Series of Cystic Fibrosis Patients: A Cross-Sectional Study
Authors: Escobedo-Monge Marlene Fabiola , Marcos-Temprano Marianela , Parodi-Román Joaquín , Escobedo-Monge María Antonieta , Alonso-Vicente Carmen , Torres-Hinojal María Carmen , Marugán-Miguelsanz José Manuel
Published: February 2024

Cystic fibrosis (CF) is a monogenic disease with different types of mutations that mainly affect the respiratory-digestive system. Calcium (Ca), phosphorus (P), and vitamin D (Vit-D) are essential nutrients for maintaining adequate growth and development, as well as key components in crucial metabolic pathways. Proper diagnosis, treatment, and response are decisive components of precision medicine. Therefore, we conducted a cross-sectional study to evaluate Ca, P, and Vit-D levels along with health and nutritional indicators, regarding their non-skeletal functions, in a series of CF patients. Anthropometric and clinical evaluation, biochemical analysis, dietary survey, and respiratory and pancreatic status were performed. Even though the results showed that all patients had normal dietary and serum Ca levels, 47% of patients had deficient Vit-D intake, 53% of patients had hypovitaminosis D, 35% had insufficient Vit-D levels, 18% had hypophosphatemia, 76% had elevated alkaline phosphate levels, 29% had hypercalciuria, and 65% had hyperphosphaturia. There were no significant differences between homozygous and compound heterozygous patients. Ca, P, and Vit-D levels were associated with body mass index; body composition; physical activity; diet; growth hormones; and the immune, liver, and kidney systems. We suggest a periodically evaluation of Ca and P losses.
Infertility Improvement after Medical Weight Loss in Women and Men: A Review of the Literature
Authors: Pavli Polina , Triantafyllidou Olga , Kapantais Efthymios , Vlahos Nikolaos F. , Valsamakis Georgios
Published: February 2024

Infertility is a modern health problem. Obesity is another expanding health issue associated with chronic diseases among which infertility is also included. This review will focus on the effects of weight loss by medical therapy on fertility regarding reproductive hormonal profile, ovulation rates, time to pregnancy, implantation rates, pregnancy rates, normal embryo development, and live birth rates. We comprised medicine already used for weight loss, such as orlistat and metformin, and emerging medical treatments, such as Glucagon-Like Peptide-1 receptor agonists (GLP-1 RA). Their use is not recommended during a planned pregnancy, and they should be discontinued in such cases. The main outcomes of this literature review are the following: modest weight loss after medication and the duration of the treatment are important factors for fertility improvement. The fecundity outcomes upon which medical-induced weight loss provides significant results are the female reproductive hormonal profile, menstrual cyclicity, ovulation and conception rates, and pregnancy rates. Regarding the male reproductive system, the fertility outcomes that feature significant alterations after medically induced weight loss are as follows: the male reproductive hormonal profile, sperm motility, movement and morphology, weight of reproductive organs, and sexual function. The newer promising GLP-1 RAs show expectations regarding fertility improvement, as they have evidenced encouraging effects on improving ovulation rates and regulating the menstrual cycle. However, more human studies are needed to confirm this. Future research should aim to provide answers about whether medical weight loss therapies affect fertility indirectly through weight loss or by a possible direct action on the reproductive system.
Searching for Frataxin Function: Exploring the Analogy with Nqo15, the Frataxin-like Protein of Respiratory Complex I from Thermus thermophilus
Authors: Doni Davide , Cavallari Eva , Noguera Martin Ezequiel , Gentili Hernan Gustavo , Cavion Federica , Parisi Gustavo , Fornasari Maria Silvina , Sartori Geppo , Santos Javier , Bellanda Massimo , Carbonera Donatella , Costantini Paola , Bortolus Marco
Published: February 2024

Nqo15 is a subunit of respiratory complex I of the bacterium Thermus thermophilus, with strong structural similarity to human frataxin (FXN), a protein involved in the mitochondrial disease Friedreich’s ataxia (FRDA). Recently, we showed that the expression of recombinant Nqo15 can ameliorate the respiratory phenotype of FRDA patients’ cells, and this prompted us to further characterize both the Nqo15 solution’s behavior and its potential functional overlap with FXN, using a combination of in silico and in vitro techniques. We studied the analogy of Nqo15 and FXN by performing extensive database searches based on sequence and structure. Nqo15’s folding and flexibility were investigated by combining nuclear magnetic resonance (NMR), circular dichroism, and coarse-grained molecular dynamics simulations. Nqo15’s iron-binding properties were studied using NMR, fluorescence, and specific assays and its desulfurase activation by biochemical assays. We found that the recombinant Nqo15 isolated from complex I is monomeric, stable, folded in solution, and highly dynamic. Nqo15 does not share the iron-binding properties of FXN or its desulfurase activation function.