bluuebunny/crossref_metadata_2025 huggingface dataset:
Landslide Risk Assessments through Multicriteria Analysis
Authors: Chaabane Fatma Zohra , Lamine Salim , Guettouche Mohamed Said , Bachari Nour El Islam , Hallal Nassim
Published: August 2024

Natural risks comprise a whole range of disasters and dangers, requiring comprehensive management through advanced assessment, forecasting, and warning systems. Our specific focus is on landslides in difficult terrains. The evaluation of landslide risks employs sophisticated multicriteria models, such as the weighted sum GIS approach, which integrates qualitative parameters. Despite the challenges posed by the rugged terrain in Northern Algeria, it is paradoxically home to a dense population attracted by valuable hydro-agricultural resources. The goal of our research is to study landslide risks in these areas, particularly in the Mila region, with the aim of constructing a mathematical model that integrates both hazard and vulnerability considerations. This complex process identifies threats and their determining factors, including geomorphology and socio-economic conditions. We developed two algorithms, the analytic hierarchy process (AHP) and the fuzzy analytic hierarchy process (FAHP), to prioritize criteria and sub-criteria by assigning weights to them, aiming to find the optimal solution. By integrating multi-source data, including satellite images and in situ measurements, into a GIS and applying the two algorithms, we successfully generated landslide susceptibility maps. The FAHP method demonstrated a higher capacity to manage uncertainty and specialist assessment errors. Finally, a comparison between the developed risk map and the observed risk inventory map revealed a strong correlation between the thematic datasets.
The Synergistic Effects of Polyol Pathway-Induced Oxidative and Osmotic Stress in the Aetiology of Diabetic Cataracts
Authors: Thorne Courtney A. , Grey Angus C. , Lim Julie C. , Donaldson Paul J.
Published: August 2024

Cataracts are the world’s leading cause of blindness, and diabetes is the second leading risk factor for cataracts after old age. Despite this, no preventative treatment exists for cataracts. The altered metabolism of excess glucose during hyperglycaemia is known to be the underlying cause of diabetic cataractogenesis, resulting in localised disruptions to fibre cell morphology and cell swelling in the outer cortex of the lens. In rat models of diabetic cataracts, this damage has been shown to result from osmotic stress and oxidative stress due to the accumulation of intracellular sorbitol, the depletion of NADPH which is used to regenerate glutathione, and the generation of fructose metabolites via the polyol pathway. However, differences in lens physiology and the metabolism of glucose in the lenses of different species have prevented the translation of successful treatments in animal models into effective treatments in humans. Here, we review the stresses that arise from hyperglycaemic glucose metabolism and link these to the regionally distinct metabolic and physiological adaptations in the lens that are vulnerable to these stressors, highlighting the evidence that chronic oxidative stress together with osmotic stress underlies the aetiology of human diabetic cortical cataracts. With this information, we also highlight fundamental gaps in the knowledge that could help to inform new avenues of research if effective anti-diabetic cataract therapies are to be developed in the future.
Post-Acute Sequelae and Mitochondrial Aberration in SARS-CoV-2 Infection
Authors: Ward Charles , Schlichtholz Beata
Published: August 2024

This review investigates links between post-acute sequelae of SARS-CoV-2 infection (PASC), post-infection viral persistence, mitochondrial involvement and aberrant innate immune response and cellular metabolism during SARS-CoV-2 infection. Advancement of proteomic and metabolomic studies now allows deeper investigation of alterations to cellular metabolism, autophagic processes and mitochondrial dysfunction caused by SARS-CoV-2 infection, while computational biology and machine learning have advanced methodologies of predicting virus–host gene and protein interactions. Particular focus is given to the interaction between viral genes and proteins with mitochondrial function and that of the innate immune system. Finally, the authors hypothesise that viral persistence may be a function of mitochondrial involvement in the sequestration of viral genetic material. While further work is necessary to understand the mechanisms definitively, a number of studies now point to the resolution of questions regarding the pathogenesis of PASC.
Research Advancements in Salt Tolerance of Cucurbitaceae: From Salt Response to Molecular Mechanisms
Authors: Chen Cuiyun , Yu Wancong , Xu Xinrui , Wang Yiheng , Wang Bo , Xu Shiyong , Lan Qingkuo , Wang Yong
Published: August 2024

Soil salinization severely limits the quality and productivity of economic crops, threatening global food security. Recent advancements have improved our understanding of how plants perceive, signal, and respond to salt stress. The discovery of the Salt Overly Sensitive (SOS) pathway has been crucial in revealing the molecular mechanisms behind plant salinity tolerance. Additionally, extensive research into various plant hormones, transcription factors, and signaling molecules has greatly enhanced our knowledge of plants’ salinity tolerance mechanisms. Cucurbitaceae plants, cherished for their economic value as fruits and vegetables, display sensitivity to salt stress. Despite garnering some attention, research on the salinity tolerance of these plants remains somewhat scattered and disorganized. Consequently, this article offers a review centered on three aspects: the salt response of Cucurbitaceae under stress; physiological and biochemical responses to salt stress; and the current research status of their molecular mechanisms in economically significant crops, like cucumbers, watermelons, melon, and loofahs. Additionally, some measures to improve the salt tolerance of Cucurbitaceae crops are summarized. It aims to provide insights for the in-depth exploration of Cucurbitaceae’s salt response mechanisms, uncovering the roles of salt-resistant genes and fostering the cultivation of novel varieties through molecular biology in the future.
Investigating the Link between Circadian Clock Gene Expressions, Chronotype, Insomnia, and Daytime Sleepiness in Patients with Obstructive Sleep Apnea
Authors: Gabryelska Agata , Turkiewicz Szymon , Gajewski Adrian , Białasiewicz Piotr , Strzelecki Dominik , Chałubiński Maciej , Sochal Marcin
Published: August 2024

Introduction. This study aimed to investigate the relationship between obstructive sleep apnea (OSA), circadian rhythms, and individual sleep–wake preferences, as measured by chronotype, and to assess the association between circadian clock gene expression and subjective sleep-related variables. Methods: A total of 184 individuals were recruited, underwent polysomnography (PSG), and completed questionnaires including a chronotype questionnaire (CQ), insomnia severity index (ISI), and Epworth sleepiness scale (ESS). Blood samples were collected in the evening before and morning after PSG. Gene expression analysis included BMAL1, CLOCK, PER1, CRY1, NPAS2, and NR1D1. Results: In the OSA group, the subjective amplitude (AM score of CQ) positively correlated with all circadian clock genes in the morning (R ≥ 0.230 and p < 0.05 for each one), while the morningness–eveningness (ME score of CQ) was only associated with the evening BMAL1 level (R = 0.192; p = 0.044). In healthy controls, insomnia severity correlated with evening expression of BMAL1, PER1, and CRY1. Conclusions: The findings highlight the complex interplay between OSA, circadian rhythms, and sleep-related variables, suggesting potential determinants of morning chronotype in OSA and implicating disrupted circadian clock function in subjective feelings of energy throughout the day. Further research is warranted to elucidate underlying mechanisms and guide personalized management strategies.
Identification and Expression Analysis of Sulfate Transporter Genes Family and Function Analysis of GmSULTR3;1a from Soybean
Authors: Zhou Jingwen , Dong Yue , Liu Yue , Huang Yifan , Jiang Wenjing , Zheng Xiangmin , Zhang Huimin , Gong Na , Bai Xi
Published: August 2024

Sulfate transporters (SULTRs) are essential for the transport and absorption of sulfate in plants and serve as critical transport proteins within the sulfur metabolism pathway, significantly influencing plant growth, development, and stress adaptation. A bioinformatics analysis of SULTR genes in soybean was performed, resulting in the identification and classification of twenty-eight putative GmSULTRs into four distinct groups. In this study, the characteristics of the 28 GmSULTR genes, including those involved in collinearity, gene structure, protein motifs, cis-elements, tissue expression patterns, and the response to abiotic stress and plant hormone treatments, were systematically analyzed. This study focused on conducting a preliminary functional analysis of the GmSULTR3;1a gene, wherein a high expression level of GmSULTR3;1a in the roots, stems, and leaves was induced by a sulfur deficiency and GmSULTR3;1a improved the salt tolerance. A further functional characterization revealed that GmSULTR3;1a-overexpressing soybean hairy roots had higher SO42−, GSH, and methionine (Met) contents compared with the wild-type (WT) plant. These results demonstrate that the overexpression of GmSULTR3;1a may promote the sulfur assimilation metabolism and increase the content of sulfur-containing amino acids in plants.
S100B Serum Levels in Chronic Heart Failure Patients: A Multifaceted Biomarker Linking Cardiac and Cognitive Dysfunction
Authors: Traub Jan , Schuhmann Michael K. , Sell Roxanne , Frantz Stefan , Störk Stefan , Stoll Guido , Frey Anna
Published: August 2024

S100 calcium-binding protein B (S100B) is a protein primarily known as a biomarker for central nervous system (CNS) injuries, reflecting blood–brain barrier (BBB) permeability and dysfunction. Recently, S100B has also been implicated in cardiovascular diseases, including heart failure (HF). Thus, we investigated serum levels of S100B in 146 chronic HF patients from the Cognition.Matters-HF study and their association with cardiac and cognitive dysfunction. The median S100B level was 33 pg/mL (IQR: 22–47 pg/mL). Higher S100B levels were linked to longer HF duration (p = 0.014) and increased left atrial volume index (p = 0.041), but also with a higher prevalence of mild cognitive impairment (p = 0.023) and lower visual/verbal memory scores (p = 0.006). In a multivariable model, NT-proBNP levels independently predicted S100B (T-value = 2.27, p = 0.026). S100B did not impact mortality (univariable HR (95% CI) 1.00 (0.99–1.01); p = 0.517; multivariable HR (95% CI) 1.01 (1.00–1.03); p = 0.142), likely due to its reflection of acute injury rather than long-term outcomes and the mild HF phenotype in our cohort. These findings underscore S100B’s value in comprehensive disease assessment, reflecting both cardiac dysfunction and potentially related BBB disruption.
Functionalized Magnetic Fe3O4 Nanoparticles for Targeted Methotrexate Delivery in Ovarian Cancer Therapy
Authors: Nowak-Jary Julia , Płóciennik Artur , Machnicka Beata
Published: August 2024

Magnetic Fe3O4 nanoparticles (MNPs) functionalized with (3-aminopropylo)trietoksysilan (APTES) or N-carboxymethylchitosan (CMC) were proposed as nanocarriers of methotrexate (MTX) to target ovarian cancer cell lines. The successful functionalization of the obtained nanostructures was confirmed by FT-IR spectroscopy. The nanoparticles were characterized by transmission electron spectroscopy (TEM) and dynamic light scattering (DLS) techniques. Their potential zeta, magnetization, and hyperthermic properties were also explored. MTX was conjugated with the nanocarriers by ionic bonds or by amide bonds. The drug release kinetics were examined at different pH and temperatures. The MTT assay showed no toxicity of the MNPs[APTES] and MNPs[CMC]. Finally, the cytotoxicity of the nanostructures with MTX attached towards the ovarian cancer cells was measured. The sensitivity and resistance to methotrexate was determined in simplistic 2D and spheroid 3D conditions. The cytotoxicity tests of the tested nanostructures showed similar values for inhibiting the proliferation of ovarian cancer cells as methotrexate in its free form. Conjugating MTX with nanoparticles allows the drug to be directed to the target site using an external magnetic field, reducing overall toxicity. Combining this approach with hyperthermia could enhance the therapeutic effect in vivo compared to free MTX, though further research on advanced 3D models is needed.
GSDMD-Dependent Neutrophil Extracellular Traps Mediate Portal Vein Thrombosis and Associated Fibrosis in Cirrhosis
Authors: Che Ying , Chien Youjung , Zhu Yuli , Huang Xiaoquan , Wu Ling , Ai Yingjie , Jiang Siyu , Li Feng , Chen Shiyao
Published: August 2024

Portal vein thrombosis (PVT) is a challenging and controversial complication of cirrhosis. Experimental models that reproduce cirrhotic PVT and effective pharmacological therapies are limited. We aimed to investigate the nature course and mechanisms of PVT in cirrhosis. A novel PVT model was developed via two-step total portal vein ligation in healthy and thioacetamide (TAA)-cirrhotic rats. Circulating and liver-infiltrating neutrophils were isolated from individuals with cirrhosis to examine neutrophil extracellular traps (NETs) and explore their unique characteristics and implications in PVT-associated fibrosis in cirrhosis. We further validated macrophage–myofibroblast transition (MMT) via multiplex immunofluorescence and single-cell sequencing. In the experimental model, cirrhosis promoted PVT development and portal vein intimal thickening. Interestingly, cirrhosis promoted spontaneous resolution of PVT due to instability of thrombus structure, along with pulmonary and intrahepatic clots. NETs-MMT mediate cirrhotic PVT and PVT-associated fibrosis, including fibrotic thrombus remodeling and increased hepatic collagen deposition. Mechanistically, caspase-4-dependent activation of neutrophils and GSDMD mediated the formation of NETs. The extracellular DNA of NETs promoted TGF-β1/Smad3-driven MMT. Inhibiting GSDMD with disulfiram suppressed cirrhotic PVT and prevented associated fibrosis. The cirrhotic PVT model reflected the following three main characteristics of cirrhotic PVT: spontaneous resolution, immunothrombosis, and intimal fibrosis. Targeting NETs with GSDMD inhibitors may serve as a new therapeutic concept to treat cirrhotic PVT.
Mussel-Inspired Injectable Adhesive Hydrogels for Biomedical Applications
Authors: Dou Wenguang , Zeng Xiaojun , Zhu Shuzhuang , Zhu Ye , Liu Hongliang , Li Sidi
Published: August 2024

The impressive adhesive capacity of marine mussels has inspired various fascinating designs in biomedical fields. Mussel-inspired injectable adhesive hydrogels, as a type of promising mussel-inspired material, have attracted much attention due to their minimally invasive property and desirable functions provided by mussel-inspired components. In recent decades, various mussel-inspired injectable adhesive hydrogels have been designed and widely applied in numerous biomedical fields. The rational incorporation of mussel-inspired catechol groups endows the injectable hydrogels with the potential to exhibit many properties, including tissue adhesiveness and self-healing, antimicrobial, and antioxidant capabilities, broadening the applications of injectable hydrogels in biomedical fields. In this review, we first give a brief introduction to the adhesion mechanism of mussels and the characteristics of injectable hydrogels. Further, the typical design strategies of mussel-inspired injectable adhesive hydrogels are summarized. The methodologies for integrating catechol groups into polymers and the crosslinking methods of mussel-inspired hydrogels are discussed in this section. In addition, we systematically overview recent mussel-inspired injectable adhesive hydrogels for biomedical applications, with a focus on how the unique properties of these hydrogels benefit their applications in these fields. The challenges and perspectives of mussel-inspired injectable hydrogels are discussed in the last section. This review may provide new inspiration for the design of novel bioinspired injectable hydrogels and facilitate their application in various biomedical fields.
Multi-Omics Integrative Analysis to Reveal the Impacts of Shewanella algae on the Development and Lifespan of Marine Nematode Litoditis marina
Authors: Xue Yiming , Xue Beining , Zhang Liusuo
Published: August 2024

Understanding how habitat bacteria affect animal development, reproduction, and aging is essential for deciphering animal biology. Our recent study showed that Shewanella algae impaired Litoditis marina development and lifespan, compared with Escherichia coli OP50 feeding; however, the underlying mechanisms remain unclear. Here, multi-omics approaches, including the transcriptome of both L. marina and bacteria, as well as the comparative bacterial metabolome, were utilized to investigate how bacterial food affects animal fitness and physiology. We found that genes related to iron ion binding and oxidoreductase activity pathways, such as agmo-1, cdo-1, haao-1, and tdo-2, were significantly upregulated in L. marina grown on S. algae, while extracellular structural components-related genes were significantly downregulated. Next, we observed that bacterial genes belonging to amino acid metabolism and ubiquinol-8 biosynthesis were repressed, while virulence genes were significantly elevated in S. algae. Furthermore, metabolomic analysis revealed that several toxic metabolites, such as puromycin, were enriched in S. algae, while many nucleotides were significantly enriched in OP50. Moreover, we found that the “two-component system” was enriched in S. algae, whereas “purine metabolism” and “one-carbon pool by folate” were significantly enriched in E. coli OP50. Collectively, our data provide new insights to decipher how diet modulates animal fitness and biology.
Sirtuin 5 (SIRT5) Suppresses Tumor Growth by Regulating Mitochondrial Metabolism and Synaptic Remodeling in Gliomas
Authors: Tang Wanjun , Chen Bo , Leung Gilberto Ka-Kit , Kiang Karrie M.
Published: August 2024

Sirtuin 5 (SIRT5) is increasingly recognized as a key regulator of cellular metabolism, which is commonly dysregulated in cancer cells, resulting in enhanced proliferation and tumor progression. To investigate the clinicopathologic implications of SIRT5 dysregulation in glioblastoma, we performed comprehensive analyses of transcriptomic data and functional verifications using in vitro and in vivo glioblastoma models. We found that higher SIRT5 expression levels were associated with a favorable prognosis in glioma patients. Knockdown of SIRT5 significantly enhanced glioblastoma cell growth. Our data suggest its potential role in regulating mitochondrial metabolism in gliomas. Furthermore, SIRT5 is also significantly correlated with synaptic remodeling pathways. Our findings indicate a tumor-suppressive role for SIRT5 that extends beyond regulating cancer metabolism, by which it may function through modulating neuroplasticity. Understanding these cellular interactions provides nuanced insights into the multifaceted role of SIRT5 and the broader therapeutic implications of this for the development of novel treatment strategies.
Fungal Diversity and Gibberellin Hormones Associated with Long Whips of Smut-Infected Sugarcanes
Authors: Gillani Syeda Wajeeha , Teng Lixiu , Khan Abdullah , Xu Yuzhi , Powell Charles A. , Zhang Muqing
Published: August 2024

Sugarcane smut, caused by the fungus Sporisorium scitamineum (Sydow), significantly affects sugarcane crops worldwide. Infected plants develop whip-like structures known as sori. Significant variations in these whip lengths are commonly observed, but the physiological and molecular differences causing these morphological differences remain poorly documented. To address this, we employed conventional microbe isolation, metagenomic, and metabolomic techniques to investigate smut-infected sugarcane stems and whips of varying lengths. Metagenomics analysis revealed a diverse fungal community in the sugarcane whips, with Sporisorium and Fusarium genera notably present (>1%) in long whips. Isolation techniques confirmed these findings. Ultra-performance liquid chromatography analysis (UHPLC-MS/MS) showed high levels of gibberellin hormones (GA3, GA1, GA4, GA8, and GA7) in long whips, with GA4 and GA7 found exclusively in long whips and stems. Among the prominent genera present within long whips, Fusarium was solely positively correlated with these gibberellin (GA) hormones, with the exception of GA8, which was positively correlated with Sporisorium. KEGG enrichment analysis linked these hormones to pathways like diterpenoid biosynthesis and plant hormone signal transduction. These findings suggest that Fusarium may influence GA production leading to whip elongation. Our study reveals fungal dynamics and gibberellin responses in sugarcane smut whips. Future research will explore the related molecular gibberellin synthesis mechanisms.
Isolation and Characterization of a Novel Phage against Vibrio alginolyticus Belonging to a New Genus
Authors: Gao Jie , Zhu Yuang , Zhang Rui , Xu Juntian , Zhou Runjie , Di Meiqi , Zhang Di , Liang Wenxin , Zhou Xing , Ren Xing , Li Huifang , Yang Yunlan
Published: August 2024

Vibrio alginolyticus causes substantial economic losses in the aquaculture industry. With the rise of multidrug-resistant Vibrio strains, phages present a promising solution. Here, a novel lytic Vibrio phage, vB_ValC_RH2G (RH2G), that efficiently infects the pathogenic strain V. alginolyticus ATCC 17749T, was isolated from mixed wastewater from an aquatic market in Xiamen, China. Transmission electron microscopy revealed that RH2G has the morphology of Siphoviruses, featuring an icosahedral head (73 ± 2 nm diameter) and long noncontractile tail (142 ± 4 nm). A one-step growth experiment showed that RH2G had a short latent period (10 min) and a burst size of 48 phage particles per infected cell. Additionally, RH2G was highly species-specific and was relatively stable at 4–55 °C and pH 4–10. A genomic analysis showed that RH2G has a 116,749 bp double-stranded DNA genome with 43.76% GC content. The intergenomic similarity between the genome sequence of RH2G and other phages recorded in the GenBank database was below 38.8%, suggesting that RH2G represents a new genus. RH2G did not exhibit any virulence or resistance genes. Its rapid lysis capacity, lytic activity, environmental resilience, and genetic safety suggested that RH2G may be a safe candidate for phage therapy in combatting vibriosis in aquaculture settings.
Polθ Inhibitor (ART558) Demonstrates a Synthetic Lethal Effect with PARP and RAD52 Inhibitors in Glioblastoma Cells
Authors: Barszczewska-Pietraszek Gabriela , Czarny Piotr , Drzewiecka Małgorzata , Błaszczyk Maciej , Radek Maciej , Synowiec Ewelina , Wigner-Jeziorska Paulina , Sitarek Przemysław , Szemraj Janusz , Skorski Tomasz , Śliwiński Tomasz
Published: August 2024

DNA repair proteins became the popular targets in research on cancer treatment. In our studies we hypothesized that inhibition of DNA polymerase theta (Polθ) and its combination with Poly (ADP-ribose) polymerase 1 (PARP1) or RAD52 inhibition and the alkylating drug temozolomide (TMZ) has an anticancer effect on glioblastoma cells (GBM21), whereas it has a low impact on normal human astrocytes (NHA). The effect of the compounds was assessed by analysis of cell viability, apoptosis, proliferation, DNA damage and cell cycle distribution, as well as gene expression. The main results show that Polθ inhibition causes a significant decrease in glioblastoma cell viability. It induces apoptosis, which is accompanied by a reduction in cell proliferation and DNA damage. Moreover, the effect was stronger when dual inhibition of Polθ with PARP1 or RAD52 was applied, and it is further enhanced by addition of TMZ. The impact on normal cells is much lower, especially when considering cell viability and DNA damage. In conclusion, we would like to highlight that Polθ inhibition used in combination with PARP1 or RAD52 inhibition has great potential to kill glioblastoma cells, and shows a synthetic lethal effect, while sparing normal astrocytes.
Effect of Single Session of Swedish Massage on Circulating Levels of Interleukin-6 and Insulin-like Growth Factor 1
Authors: Stenbäck Ville , Lehtonen Inka , Mäkelä Kari Antero , Raza Ghulam Shere , Ylinen Venla , Valtonen Rasmus , Hamari Tuomas , Walkowiak Jaroslaw , Tulppo Mikko , Herzig Karl-Heinz
Published: August 2024

Massage therapy increases muscle blood flow and heat, relieving pain, improving immune function, and increasing vagal activity. The mechanisms are unclear. Muscles release cytokines and other peptides called myokines. These myokines exert their effects on different tissues and organs in para-, auto-, and endocrine fashion. The aim of this intervention study was to investigate if massage therapy affects circulating myokine levels. A total of 46 healthy, normal-weight subjects (15 men) aged 18–35 were recruited. Forty-five minutes of massage Swedish therapy was applied to the back and hamstrings. Blood samples via cannula were taken at the baseline, during the massage (30 min), end of the massage (45 min), and 30 min and 1 h after the massage. Interleukin 6 (IL-6) and insulin-like growth factor 1 (IGF-1) were measured as surrogate markers by ELISAs. There was a significant increase in IL-6 from 1.09 pg/mL to 1.85 pg/mL over time (Wilks’ Lambda Value 0.545, p < 0.000; repeated measures ANOVA). Pair-wise comparisons showed a significant increase after 1 h of massage. No significant increase was observed in IGF-1 levels. The change in myokine levels was not correlated with muscle mass (p = 0.16, 0.74). The increase in IL-6 suggests that there might be anti-inflammatory effects, affecting glucose and lipid metabolism pathways via IL-6 signaling to muscles, fat tissue, and the liver.
Enhancing Colorectal Cancer Immunotherapy: The Pivotal Role of Ferroptosis in Modulating the Tumor Microenvironment
Authors: Li Yanqing , Cheng Xiaofei
Published: August 2024

Colorectal cancer (CRC) represents a significant challenge in oncology, with increasing incidence and mortality rates worldwide, particularly among younger adults. Despite advancements in treatment modalities, the urgent need for more effective therapies persists. Immunotherapy has emerged as a beacon of hope, offering the potential for improved outcomes and quality of life. This review delves into the critical interplay between ferroptosis, an iron-dependent form of regulated cell death, and immunotherapy within the CRC context. Ferroptosis’s influence extends beyond tumor cell fate, reshaping the tumor microenvironment (TME) to enhance immunotherapy’s efficacy. Investigations into Ferroptosis-related Genes (OFRGs) reveal their pivotal role in modulating immune cell infiltration and TME composition, closely correlating with tumor responsiveness to immunotherapy. The integration of ferroptosis inducers with immunotherapeutic strategies, particularly through novel approaches like ferrotherapy and targeted co-delivery systems, showcases promising avenues for augmenting treatment efficacy. Furthermore, the expression patterns of OFRGs offer novel prognostic tools, potentially guiding personalized and precision therapy in CRC. This review underscores the emerging paradigm of leveraging ferroptosis to bolster immunotherapy’s impact, highlighting the need for further research to translate these insights into clinical advancements. Through a deeper understanding of the ferroptosis-immunotherapy nexus, new therapeutic strategies can be developed, promising enhanced efficacy and broader applicability in CRC treatment, ultimately improving patient outcomes and quality of life in the face of this formidable disease.
Rabies Virus Regulates Inflammatory Response in BV-2 Cells through Activation of Myd88 and NF-κB Signaling Pathways via TLR7
Authors: Xie Yuan , Chi Yinglin , Tao Xiaoyan , Yu Pengcheng , Liu Qian , Zhang Minghui , Yang Nuo , Liu Shuqing , Zhu Wuyang
Published: August 2024

Rabies is a fatal neurological infectious disease caused by rabies virus (RABV), which invades the central nervous system (CNS). RABV with varying virulence regulates chemokine expression, and the mechanisms of signaling pathway activation remains to be elucidated. The relationship between Toll-like receptors (TLRs) and immune response induced by RABV has not been fully clarified. Here, we investigated the role of TLR7 in the immune response induced by RABV, and one-way analysis of variance (ANOVA) was employed to evaluate the data. We found that different RABV strains (SC16, HN10, CVS-11) significantly increased CCL2, CXCL10 and IL-6 production. Blocking assays indicated that the TLR7 inhibitor reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). The activation of the Myd88 pathway in BV-2 cells stimulated by RABV was TLR7-dependent, whereas the inhibition of Myd88 activity reduced the expression of CCL2, CXCL10 and IL-6 (p < 0.01). Meanwhile, the RABV stimulation of BV-2 cells resulted in TRL7-mediated activation of NF-κB and induced the nuclear translocation of NF-κB p65. CCL2, CXCL10 and IL-6 release was attenuated by the specific NF-κB inhibitor used (p < 0.01). The findings above demonstrate that RABV-induced expression of CCL2, CXCL10 and IL-6 involves Myd88 and NF-κB pathways via the TLR7 signal.
Electroporation Delivery of Cas9 sgRNA Ribonucleoprotein-Mediated Genome Editing in Sheep IVF Zygotes
Authors: Pi Wenhui , Feng Guangyu , Liu Minghui , Nie Cunxi , Chen Cheng , Wang Jingjing , Wang Limin , Wan Pengcheng , Liu Changbin , Liu Yi , Zhou Ping
Published: August 2024

The utilization of electroporation for delivering CRISPR/Cas9 system components has enabled efficient gene editing in mammalian zygotes, facilitating the development of genome-edited animals. In this study, our research focused on targeting the ACTG1 and MSTN genes in sheep, revealing a threshold phenomenon in electroporation with a voltage tolerance in sheep in vitro fertilization (IVF) zygotes. Various poring voltages near 40 V and pulse durations were examined for electroporating sheep zygotes. The study concluded that stronger electric fields required shorter pulse durations to achieve the optimal conditions for high gene mutation rates and reasonable blastocyst development. This investigation also assessed the quality of Cas9/sgRNA ribonucleoprotein complexes (Cas9 RNPs) and their influence on genome editing efficiency in sheep early embryos. It was highlighted that pre-complexation of Cas9 proteins with single-guide RNA (sgRNA) before electroporation was essential for achieving a high mutation rate. The use of suitable electroporation parameters for sheep IVF zygotes led to significantly high mutation rates and heterozygote ratios. By delivering Cas9 RNPs and single-stranded oligodeoxynucleotides (ssODNs) to zygotes through electroporation, targeting the MSTN (Myostatin) gene, a knock-in efficiency of 26% was achieved. The successful generation of MSTN-modified lambs was demonstrated by delivering Cas9 RNPs into IVF zygotes via electroporation.
Novel Copper (II) Complexes with Fluorine-Containing Reduced Schiff Base Ligands Showing Marked Cytotoxicity in the HepG2 Cancer Cell Line
Authors: Oboňová Bianka , Valentová Jindra , Litecká Miroslava , Pašková Ľudmila , Hricovíniová Jana , Bilková Andrea , Bilka František , Horváth Branislav , Habala Ladislav
Published: August 2024

Several novel copper (II) complexes of reduced Schiff bases containing fluoride substituents were prepared and structurally characterized by single-crystal X-ray diffraction. The complexes exhibited diverse structures, with the central atom in distorted tetrahedral geometry. The biological effects of the products were evaluated, specifically their cytotoxicity, antimicrobial, and antiurease activities, as well as affinity for albumin (BSA) and DNA (ct-DNA). The complexes showed marked cytotoxic activities in the HepG2 hepatocellular carcinoma cell line, considerably higher than the standard cisplatin. The cytotoxicity depended significantly on the substitution pattern. The best activity was observed in the complex with a trifluoromethyl group in position 4 of the benzene ring—the dichloro[(±)-trans-N,N′-bis-(4-trifluoromethylbenzyl)-cyclohexane-1,2-diamine]copper (II) complex, whose activity (IC50 28.7 μM) was higher than that of the free ligand and markedly better than the activity of the standard cisplatin (IC50 336.8 μM). The same complex also showed the highest antimicrobial effect in vitro. The affinity of the complexes towards bovine serum albumin (BSA) and calf thymus DNA (ct-DNA) was established as well, indicating only marginal differences between the complexes. In addition, all complexes were shown to be excellent inhibitors of the enzyme urease, with the IC50 values in the lower micromolar region.
CuO Nanoparticles Reduce Toxicity and Enhance Bioaccumulation of Cadmium and Lead in the Cells of the Microalgae Desmodesmus communis
Authors: Chebotaryova Svetlana P. , Baranchikov Peter A. , Zakharova Olga V. , Kozlova Tatiana A. , Maltsev Yevhen I. , Kulikovskiy Maxim S. , Grigoriev Gregory V. , Gusev Alexander A.
Published: August 2024

The removal of pollutants, including heavy metals, from the aquatic environment is an urgent problem worldwide. Actively developing nanotechnology areas is becoming increasingly important for solving problems in the field of the remediation of aquatic ecosystems. In particular, methods for removing pollutants using nanoparticles (NPs) are proposed, which raises the question of the effect of a combination of NPs and heavy metals on living organisms. In this work, we investigated the role of CuO-NPs in changing the toxicity of Cd and Pb salts, as well as the bioaccumulation of these elements in a culture of the microalga Desmodesmus communis. It was found that CuO-NPs at concentrations of 10, 100, and 1000 µg L−1 had no effect on the viability of microalgae cells. On the 14th day of the experiment, Cd at a concentration of 1 mg L−1 reduced the viability index by 30% and, when combined with CuO-NPs, by 25%, i.e., CuO-NPs slightly reduced the toxic effect of Cd. At the same time, in this experiment, when CuO-NPs and Cd were used together, the level of oxidative stress increased, including on the first day in mixtures with 1 mg L−1 Cd. Under the influence of Pb, the cell viability index decreased by 70% by the end of the experiment, regardless of the metal concentration. The presence of CuO-NPs slightly reduced the toxicity of Pb in terms of viability and reactive oxygen species (ROS). At the same time, unlike Cd, Pb without NPs caused ROS production on the first day, whereas the addition of CuO-NPs completely detoxified Pb at the beginning and had a dose-dependent effect on mixtures at the end of the experiment. Also, the introduction of CuO-NPs slightly reduced the negative effect of Pb on pigment synthesis. As a molecular mechanism of the observed effects, we prioritized the provocation of oxidative stress by nanoparticles and related gene expression and biochemical reactions of algae cells. Analysis of the effect of CuO-NPs on the Cd and Pb content in microalgae cells showed increased accumulation of heavy metals. Thus, when algae were cultured in an environment with Cd and CuO-NPs, the Cd content per cell increased 4.2 times compared to the variant where cells were cultured only with Cd. In the case of Pb, the increase in its content per one cell increased 6.2 times when microalgae were cultured in an environment containing CuO-NPs. Thus, we found that CuO-NPs reduce the toxic effects of Cd and Pb, as well as significantly enhance the bioaccumulation of these toxic elements in the cells of D. communis microalgae. The results obtained can form the basis of technology for the nanobioremediation of aquatic ecosystems from heavy metals using microalgae.
Protective Mechanisms of Vaginal Lactobacilli against Sexually Transmitted Viral Infections
Authors: Avitabile Elisa , Menotti Laura , Croatti Vanessa , Giordani Barbara , Parolin Carola , Vitali Beatrice
Published: August 2024

The healthy cervicovaginal microbiota is dominated by various Lactobacillus species, which support a condition of eubiosis. Among their many functions, vaginal lactobacilli contribute to the maintenance of an acidic pH, produce antimicrobial compounds, and modulate the host immune response to protect against vaginal bacterial and fungal infections. Increasing evidence suggests that these beneficial bacteria may also confer protection against sexually transmitted infections (STIs) caused by viruses such as human papillomavirus (HPV), human immunodeficiency virus (HIV) and herpes simplex virus (HSV). Viral STIs pose a substantial public health burden globally, causing a range of infectious diseases with potentially severe consequences. Understanding the molecular mechanisms by which lactobacilli exert their protective effects against viral STIs is paramount for the development of novel preventive and therapeutic strategies. This review aims to provide more recent insights into the intricate interactions between lactobacilli and viral STIs, exploring their impact on the vaginal microenvironment, host immune response, viral infectivity and pathogenesis, and highlighting their potential implications for public health interventions and clinical management strategies.
Quantitative Characterization of the Impact of Protein–Protein Interactions on Ligand–Protein Binding: A Multi-Chain Dynamics Perturbation Analysis Method
Authors: Li Lu , Li Hao , Su Ting , Ming Dengming
Published: August 2024

Many protein–protein interactions (PPIs) affect the ways in which small molecules bind to their constituent proteins, which can impact drug efficacy and regulatory mechanisms. While recent advances have improved our ability to independently predict both PPIs and ligand–protein interactions (LPIs), a comprehensive understanding of how PPIs affect LPIs is still lacking. Here, we examined 63 pairs of ligand–protein complexes in a benchmark dataset for protein–protein docking studies and quantified six typical effects of PPIs on LPIs. A multi-chain dynamics perturbation analysis method, called mcDPA, was developed to model these effects and used to predict small-molecule binding regions in protein–protein complexes. Our results illustrated that the mcDPA can capture the impact of PPI on LPI to varying degrees, with six similar changes in its predicted ligand-binding region. The calculations showed that 52% of the examined complexes had prediction accuracy at or above 50%, and 55% of the predictions had a recall of not less than 50%. When applied to 33 FDA-approved protein–protein-complex-targeting drugs, these numbers improved to 60% and 57% for the same accuracy and recall rates, respectively. The method developed in this study may help to design drug–target interactions in complex environments, such as in the case of protein–protein interactions.
Anticancer Activity and Mechanism of Action of Couroupita guianensis Bark Decoction in Gastric Adenocarcinoma Cancer Cell Line
Authors: Pisanti Simona , Penna Serena , Sposito Silvia , Esposito Tiziana , Mencherini Teresa , Celano Rita , Re Tania , Aquino Rita Patrizia , Martinelli Rosanna
Published: August 2024

Couroupita guianensis, a medicinal plant autochthonal to South America and South India, is widely used in the ethnomedicine of the indigenous peoples of these regions thanks to its alleged antimicrobial, anti-inflammatory, antioxidant and wound-healing properties. The majority of studies have mainly analyzed organic extracts of the Indian plant’s flowers and leaves, with limited research on its bark decoction, traditionally used in Amazonian shamanic medicine. In this study, we investigated the anticancer effects of the bark decoction and its main fractions obtained through chromatographic separation, as well as the underlying molecular mechanisms in AGS gastric cancer cells. Viability, cell proliferation, cell cycle, apoptosis and protein expression related to these processes were evaluated. Both the bark decoction and fraction III significantly inhibited cell viability, and the cytotoxic effect was linked to cell cycle blockade and the induction of apoptosis also through an engulfment of the autophagic flux. Increased expression or activation of the key proteins (p53, p21, cdk2, Bak, caspases, pAMPK, pAkt, beclin, p62 and LC3BII) involved in these processes was observed. The results obtained confirmed an important anticancer effect of C. guianensis bark decoction, providing scientific validation for its use in traditional medicine and highlighting its potential as a therapeutic agent against gastric cancer.
Human Beta Defensin-2 mRNA and Proteasome Subunit β Type 8 mRNA Analysis, Useful in Differentiating Skin Biopsies from Atopic Dermatitis and Psoriasis Vulgaris Patients
Authors: Terlikowska-Brzósko Agnieszka , Galus Ryszard , Murawski Piotr , Niderla-Bielińska Justyna , Młynarczuk-Biały Izabela , Paluchowska Elwira , Owczarek Witold
Published: August 2024

(1): Atopic dermatitis and psoriasis vulgaris are chronic, inflammatory diseases. Clinical presentation usually leads to a proper diagnosis, but sometimes neither clinical examination nor histopathological evaluation can be conclusive. Therefore, we aimed to build up a novel diagnostic tool and check it for accuracy. The main objective of our work was to differentiate between healthy skin (C), atopic dermatitis (AD) and psoriasis vulgaris (PV) biopsies on the base of involucrin (IVL) and human β-defensin-2 (hBD-2) concentrations and their mRNA, as well as mRNA for TPP2 and PSMB8. (2): ELISA for IVL and hBD-2 proteins and Real-time PCR for the relative expression of mRNA for: IVL (IVL mRNA), hBD-2 (hBD-2 mRNA), PSMB8 (PSMB8 mRNA) and TPP2 (TPP2 mRNA), isolated from skin biopsies taken from AD and PV patients and healthy volunteers were performed. (3): hBD-2 mRNA and PSMB8 mRNA correlated with some parameters of clinical assessment of inflammatory disease severity. hBD-2 mRNA expression, exclusively, was sufficient to distinguish inflammatory skin biopsies from the healthy ones. (4): hBD-2 mRNA and PSMB8 mRNA analysis were the most valuable parameters in differentiating AD and PV biopsies.
Localization of Piezo 1 and Piezo 2 in Lateral Line System and Inner Ear of Zebrafish (Danio rerio)
Authors: Aragona Marialuisa , Mhalhel Kamel , Pansera Lidia , Montalbano Giuseppe , Guerrera Maria Cristina , Levanti Maria , Laurà Rosaria , Abbate Francesco , Vega José A. , Germanà Antonino
Published: August 2024

Piezo proteins have been identified as mechanosensitive ion channels involved in mechanotransduction. Several ion channel dysfunctions may be associated with diseases (including deafness and pain); thus, studying them is critical to understand their role in mechanosensitive disorders and to establish new therapeutic strategies. The current study investigated for the first time the expression patterns of Piezo proteins in zebrafish octavolateralis mechanosensory organs. Piezo 1 and 2 were immunoreactive in the sensory epithelia of the lateral line system and the inner ear. Piezo 1 (28.7 ± 1.55 cells) and Piezo 2 (28.8 ± 3.31 cells) immunopositive neuromast cells were identified based on their ultrastructural features, and their overlapping immunoreactivity to the s100p specific marker (28.6 ± 1.62 cells), as sensory cells. These findings are in favor of Piezo proteins’ potential role in sensory cell activation, while their expression on mantle cells reflects their implication in the maintenance and regeneration of the neuromast during cell turnover. In the inner ear, Piezo proteins’ colocalization with BDNF introduces their potential implication in neuronal plasticity and regenerative events, typical of zebrafish mechanosensory epithelia. Assessing these proteins in zebrafish could open up new scenarios for the roles of these important ionic membrane channels, for example in treating impairments of sensory systems.
The Accordion Zebrafish tq206 Mutant in the Assessment of a Novel Pharmaceutical Approach to Brody Myopathy
Authors: Akyürek Eylem Emek , Greco Francesca , Tesoriero Chiara , Dalla Barba Francesco , Carotti Marcello , Gorni Giulia , Sandonà Dorianna , Vettori Andrea , Sacchetto Roberta
Published: August 2024

Brody disease (BD) is an “ultra-rare” human genetic disorder of skeletal muscle function due to defects in the atp2a1 gene causing deficiency of the SERCA protein, isoform1. The main clinical signs are exercise-induced stiffness and delayed muscular relaxation after physical exercises, even mild ones. No mouse model nor specific therapies exist for Brody myopathy, which is therefore considered an orphan disease. Bovine congenital pseudomyotonia (PMT) is a muscular disorder characterized by an impairment of muscle relaxation and is the only mammalian model of human BD. The pathogenetic mechanism underlying bovine PMT has been recently clarified. These findings prompted us to purpose a potential pharmacological approach addressing a specific population of BD patients who exhibit reduced expression but still exhibit activity of the SERCA1 pump. Preclinical research involving in vivo studies is essential and necessary before clinical trials can be pursued and SERCA protein shows a high degree of conservation among species. So far, the only animal models available to study BD in vivo are a group of zebrafish mutant lines known as accordion zebrafish (acc). In this paper, we focused on a comprehensive characterization of the “acctq206” zebrafish variant. Our aim was to use this mutant line as an experimental animal model for testing the novel therapeutic approach for BD.
Disturbed Complement Receptor Expression Pattern of B Cells Is Enhanced by Toll-like Receptor CD180 Ligation in Diffuse Cutaneous Systemic Sclerosis
Authors: Erdő-Bonyár Szabina , Rapp Judit , Subicz Rovéna , Böröcz Katalin , Szinger Dávid , Filipánits Kristóf , Minier Tünde , Kumánovics Gábor , Czirják László , Berki Tímea , Simon Diána
Published: August 2024

Autoantibody production is a hallmark of systemic sclerosis (SSc) and the most extensively studied role of B cells in the pathogenesis of the disease. However, the potential involvement of innate immune molecules in B-cell dysfunction in SSc is less understood. B-cell activation is an early event in the pathogenesis of SSc and is influenced by complement receptors (CRs) and Toll-like receptors (TLRs), shaping antibody responses. CR2 and CR1 modulate B-cell activation, and the roles of CR3 and CR4 are associated with autoimmune conditions. We investigated the expression of CRs in B cells from patients with the more severe form of the disease, diffuse cutaneous SSc (dcSSc), and the effect of TLR CD180 ligation on their expression. We found no significant difference in the basal expression of CD21 and CD11c in B cells between dcSSc and healthy controls (HCs). However, reduced basal CD11b expression in B cells in dcSSc compared to HCs, accompanied by a decrease in CD35 and an increase in CD11c expression following CD180 ligation may promote plasma cell formation and autoantibody production. Additionally, we searched for correlations between dcSSc-associated anti-DNA topoisomerase I (Scl-70) autoantibody, anti-citrate synthase (CS) natural autoantibody and complement component 3 (C3) levels and found a negative correlation between C3 and anti-CS autoantibody in dcSSc but not in HCs, supporting the hypothesis that natural autoantibodies could activate the complement system contributing to tissue injury in SSc.