bluuebunny/crossref_metadata_2025_split huggingface dataset:
A traditional gynecological medicine inhibits ovarian cancer progression and eliminates cancer stem cells via the LRPPRC–OXPHOS axis
Authors: Jiang Ruibin , Chen Zhongjian , Ni Maowei , Li Xia , Ying Hangjie , Fen Jianguo , Wan Danying , Peng Chanjuan , Zhou Wei , Gu Linhui 
Published: July 2023

Abstract
Background
Ovarian cancer (OC) is the most lethal malignant gynecological tumor type for which limited therapeutic targets and drugs are available. Enhanced mitochondrial oxidative phosphorylation (OXPHOS), which enables cell growth, migration, and cancer stem cell maintenance, is a critical driver of disease progression and a potential intervention target of OC. However, the current OXPHOS intervention strategy mainly suppresses the activity of the electron transport chain directly and cannot effectively distinguish normal tissues from cancer tissues, resulting in serious side effects and limited efficacy.

Methods
We screened natural product libraries to investigate potential anti-OC drugs that target OXPHOS. Additionally, LC-MS, qRT-PCR, western-blot, clonogenic assay, Immunohistochemistry, wound scratch assay, and xenograft model was applied to evaluate the anti-tumor mechanism of small molecules obtained by screening in OC.

Results
Gossypol acetic acid (GAA), a widely used gynecological medicine, was screened out from the drug library with the function of suppressing OXPHOS and OC progression by targeting the leucine-rich pentatricopeptide repeat containing (LRPPRC) protein. Mechanically, LRPPRC promotes the synthesis of OXPHOS subunits by binding to RNAs encoded by mitochondrial DNA. GAA binds to LRPPRC directly and induces LRPPRC rapid degradation in a ubiquitin-independent manner. LRPPRC was overexpressed in OC, which is highly correlated with the poor outcomes of OC and could promote the malignant phenotype of OC cells in vitro and in vivo. GAA management inhibits cell growth, clonal formation, and cancer stem cell maintenance in vitro, and suppresses subcutaneous graft tumor growth in vivo.

Conclusions
Our study identified a therapeutic target and provided a corresponding inhibitor for OXPHOS-based OC therapy. GAA inhibits OC progression by suppressing OXPHOS complex synthesis via targeting LRPPRC protein, supporting its potential utility as a natural therapeutic agent for ovarian cancer.
Novel heavily fucosylated glycans as a promising therapeutic target in colorectal cancer
Authors: Tsai Kuei-Yen , Chang Yu-Jia , Huang Chien-Yu , Prince G. M. Shazzad Hossain , Chen Hsin-An , Makondi Precious Takondwa , Shen Ying-Rou , Wei Po-Li 
Published: July 2023

Abstract
Background
Colorectal cancer (CRC) is highly prevalent and lethal globally, and its prognosis remains unsatisfactory. Drug resistance is regarded as the main cause of treatment failure leading to tumor recurrence and metastasis. The overexpression of fucosylated epitopes, which are usually modifications of glycoproteins, was reported to occur in various epithelial cancers. However, the effects of treatments that target these antigens in colorectal cancer remain unclear.

Methods
This study investigated the expression of heavily fucosylated glycans (HFGs) in 30 clinical samples from patients with CRC and other normal human tissues. The complement-dependent cytotoxicity was explored in vitro through treatment with anti-HFG monoclonal antibody (mAb) alone or in combination with chemotherapeutic agents. In vivo inhibitory effects were also examined using a xenograft mouse model.

Results
Immunohistochemistry staining and western blotting revealed that HFG expression was higher in human colorectal cancer tissues than in normal tissues. In DLD-1 and SW1116 cells, which overexpress fucosylated epitopes, anti-HFG mAb produced observable cytotoxic effects, especially when it was combined with chemotherapeutic agents. The xenograft model also demonstrated that anti-HFG mAb had potent and dose-dependent inhibitory effects on colorectal tumor growth.

Conclusions
As a novel cancer antigen, HFGs are a promising treatment target, and the implementation of anti-HFG mAb treatment for CRC warrants further investigation.
Mitochondrial dysfunction: roles in skeletal muscle atrophy
Authors: Chen Xin , Ji Yanan , Liu Ruiqi , Zhu Xucheng , Wang Kexin , Yang Xiaoming , Liu Boya , Gao Zihui , Huang Yan , Shen Yuntian , Liu Hua , Sun Hualin 
Published: July 2023

AbstractMitochondria play important roles in maintaining cellular homeostasis and skeletal muscle health, and damage to mitochondria can lead to a series of pathophysiological changes. Mitochondrial dysfunction can lead to skeletal muscle atrophy, and its molecular mechanism leading to skeletal muscle atrophy is complex. Understanding the pathogenesis of mitochondrial dysfunction is useful for the prevention and treatment of skeletal muscle atrophy, and finding drugs and methods to target and modulate mitochondrial function are urgent tasks in the prevention and treatment of skeletal muscle atrophy. In this review, we first discussed the roles of normal mitochondria in skeletal muscle. Importantly, we described the effect of mitochondrial dysfunction on skeletal muscle atrophy and the molecular mechanisms involved. Furthermore, the regulatory roles of different signaling pathways (AMPK-SIRT1-PGC-1α, IGF-1-PI3K-Akt-mTOR, FoxOs, JAK-STAT3, TGF-β-Smad2/3 and NF-κB pathways, etc.) and the roles of mitochondrial factors were investigated in mitochondrial dysfunction. Next, we analyzed the manifestations of mitochondrial dysfunction in muscle atrophy caused by different diseases. Finally, we summarized the preventive and therapeutic effects of targeted regulation of mitochondrial function on skeletal muscle atrophy, including drug therapy, exercise and diet, gene therapy, stem cell therapy and physical therapy. This review is of great significance for the holistic understanding of the important role of mitochondria in skeletal muscle, which is helpful for researchers to further understanding the molecular regulatory mechanism of skeletal muscle atrophy, and has an important inspiring role for the development of therapeutic strategies for muscle atrophy targeting mitochondria in the future.
Specific vulnerability of iPSC-derived motor neurons with TDP-43 gene mutation to oxidative stress
Authors: Onda-Ohto Asako , Hasegawa-Ogawa Minami , Matsuno Hiromasa , Shiraishi Tomotaka , Bono Keiko , Hiraki Hiromi , Kanegae Yumi , Iguchi Yasuyuki , Okano Hirotaka James 
Published: July 2023

AbstractAmyotrophic lateral sclerosis (ALS) is a disease that affects motor neurons and has a poor prognosis. We focused on TAR DNA-binding protein 43 kDa (TDP-43), which is a common component of neuronal inclusions in many ALS patients. To analyze the contribution of TDP-43 mutations to ALS in human cells, we first introduced TDP-43 mutations into healthy human iPSCs using CRISPR/Cas9 gene editing technology, induced the differentiation of these cells into motor and sensory neurons, and analyzed factors that are assumed to be altered in or associated with ALS (cell morphology, TDP-43 localization and aggregate formation, cell death, TDP-43 splicing function, etc.). We aimed to clarify the pathological alterations caused solely by TDP-43 mutation, i.e., the changes in human iPSC-derived neurons with TDP-43 mutation compared with those with the same genetic background except TDP-43 mutation. Oxidative stress induced by hydrogen peroxide administration caused the death of TDP-43 mutant-expressing motor neurons but not in sensory neurons, indicating the specific vulnerability of human iPSC-derived motor neurons with TDP-43 mutation to oxidative stress. In our model, we observed aggregate formation in a small fraction of TDP-43 mutant-expressing motor neurons, suggesting that aggregate formation seems to be related to ALS pathology but not the direct cause of cell death. This study provides basic knowledge for elucidating the pathogenesis of ALS and developing treatments for the disease.
Faecalibacterium prausnitzii alleviates inflammatory arthritis and regulates IL-17 production, short chain fatty acids, and the intestinal microbial flora in experimental mouse model for rheumatoid arthritis
Authors: Moon Jeonghyeon , Lee A. Ram , Kim Heejung , Jhun JooYeon , Lee Seon-Yeong , Choi Jeong Won , Jeong Yunju , Park Myeong Soo , Ji Geun Eog , Cho Mi-La , Park Sung-Hwan 
Published: July 2023

Abstract
Background
Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease that leads to joint destruction and functional disability due to the targeting of self-antigens present in the synovium, cartilage, and bone. RA is caused by a number of complex factors, including genetics, environment, dietary habits, and altered intestinal microbial flora. Microorganisms in the gut bind to nod-like receptors and Toll-like receptors to regulate the immune system and produce various metabolites, such as short-chain fatty acids (SCFAs) that interact directly with the host. Faecalibacterium prausnitzii is a representative bacterium that produces butyrate, a well-known immunomodulatory agent in the body, and this microbe exerts anti-inflammatory effects in autoimmune diseases.

Methods
In this study, F. prausnitzii was administered in a mouse model of RA, to investigate RA pathology and changes in the intestinal microbial flora. Using collagen-induced arthritic mice, which is a representative animal model of RA, we administered F. prausnitzii orally for 7 weeks.

Results
The arthritis score and joint tissue damage were decreased in the mice administered F. prausnitzii compared with the vehicle-treated group. In addition, administration of F. prausnitzii reduced the abundance of systemic immune cells that secrete the pro-inflammatory cytokine IL-17 and induced changes in SCFA concentrations and the intestinal microbial flora composition. It also resulted in decreased lactate and acetate concentrations, an increased butyrate concentration, and altered compositions of bacteria known to exacerbate or improve RA.

Conclusion
These results suggest that F. prausnitzii exerts a therapeutic effect on RA by regulation of IL-17 producing cells. In addition, F. prausnitzii modify the microbial flora composition and short chain fatty acids in experimental RA mouse model.
Bioactivities of Garcinia kola enzymatic hydrolysates at different enzyme–substrate ratios
Authors: Salami Salmat Adenike , Osukoya Olukemi Adetutu , Adewale Olusola Bolaji , Odekanyin Oludele , Obafemi Tajudeen Olabisi , Kuku Adenike 
Published: July 2023

AbstractNatural products, such as enzymatic hydrolysates and bioactive peptides from dietary sources, are safe alternatives to synthetic compounds linked to various deleterious effects. The purpose of this study is to determine the in vitro bioactivities (antioxidant and anti-inflammatory activities) of Garcinia kola seeds enzymatic hydrolysates (GKPHs) at different enzyme (pepsin)-substrate ratios. G. kola protein, isolated by alkaline solubilization and acid precipitation, was hydrolyzed with pepsin at varying enzyme–substrate (E:S) ratios. The antioxidant parameters investigated include 1,1-diphenyl-2-picrylhydrazyl (DPPH)-radical scavenging, hydrogen peroxide scavenging and ferrous ion (Fe2+) chelating activities. For anti-inflammatory properties, membrane stabilization and protein denaturation activities tests were used. GKPH produced at 1:32 had the highest degree of hydrolysis (66.27 ± 4.21%). All GKPHs had excellent in vitro anti-inflammatory properties. However, only enzymatic hydrolysates produced at 1:16 (E:S) ratio chelated iron (II) and as well had the highest percentage hemolysis inhibition of 84.45 ± 0.007%, percentage protein denaturation inhibition of 53.36 ± 0.01% at maximum concentration and exhibited highest DPPH scavenging activity (87.24 ± 0.10%). The enzymatic hydrolysates had excellent solubility, emulsifying and foaming properties. It could be deduced from this study that pepsin at a ratio of 1:16 of G. kola protein produced the most effective enzymatic hydrolysates in terms of their antioxidant and anti-inflammatory activities. G. kola pepsin enzymatic hydrolysates, thus, have potential in development as functional foods and as therapeutics pharmaceutical industries in the management of diseases associated with oxidative stress and inflammation owing to their excellent functional, antioxidant and anti-inflammatory properties.
Potential of Y. lipolytica epoxide hydrolase for efficient production of enantiopure (R)-1,2-octanediol
Authors: Godase Vijaya P. , Kumar V. Ravi , Kumar Ameeta Ravi 
Published: July 2023

AbstractThe recombinant Yleh from a tropical marine yeast Yarrowia lipolytica NCIM 3589 exhibited a high epoxide hydrolase activity of 9.34 ± 1.80 µmol min-1 mg-1 protein towards 1,2-epoxyoctane (EO), at pH 8.0 and 30 °C. The reaction product was identified as 1,2-Octanediol (OD) by GC-MS using EO and H2O18 as substrate, affirming the functionality of Yleh as an epoxide hydrolase. For EO, the Km, Vmax, and kcat/Km values were 0.43 ± 0.017 mM, 0.042 ± 0.003 mM min-1, and 467.17 ± 39.43 mM-1 min-1, respectively. To optimize the reaction conditions for conversion of racemic EO by Yleh catalyst to enantiopure (R)-1,2-octanediol, initially, Response Surface Methodology was employed. Under optimized reaction conditions of 15 mM EO, 150 µg purified Yleh at 30 °C a maximal diol production of 7.11 mM was attained in a short span of 65 min with a yield of 47.4%. Green technology using deep eutectic solvents for the hydrophobic substrate (EO) were tested as co-solvents in Yleh catalyzed EO hydrolysis. Choline chloride-Glycerol, produced 9.08 mM OD with an increased OD yield of 60.5%. Thus, results showed that deep eutectic solvents could be a promising solvent for Yleh-catalyzed reactions making Yleh a potential biocatalyst for the biosynthesis of enantiopure synthons.
Predicting diagnostic biomarkers associated with immune infiltration in Crohn's disease based on machine learning and bioinformatics
Authors: Bao Wenhui , Wang Lin , Liu Xiaoxiao , Li Ming 
Published: July 2023

Abstract
Objective
The objective of this study is to investigate potential biomarkers of Crohn's disease (CD) and the pathological importance of infiltration of associated immune cells in disease development using machine learning.

Methods
Three publicly accessible CD gene expression profiles were obtained from the GEO database. Inflammatory tissue samples were selected and differentiated between colonic and ileal tissues. To determine the differentially expressed genes (DEGs) between CD and healthy controls, the larger sample size was merged as a training unit. The function of DEGs was comprehended through disease enrichment (DO) and gene set enrichment analysis (GSEA) on DEGs. Promising biomarkers were identified using the support vector machine-recursive feature elimination and lasso regression models. To further clarify the efficacy of potential biomarkers as diagnostic genes, the area under the ROC curve was observed in the validation group. Additionally, using the CIBERSORT approach, immune cell fractions from CD patients were examined and linked with potential biomarkers.

Results
Thirty-four DEGs were identified in colon tissue, of which 26 were up-regulated and 8 were down-regulated. In ileal tissues, 50 up-regulated and 50 down-regulated DEGs were observed. Disease enrichment of colon and ileal DEGs primarily focused on immunity, inflammatory bowel disease, and related pathways. CXCL1, S100A8, REG3A, and DEFA6 in colon tissue and LCN2 and NAT8 in ileum tissue demonstrated excellent diagnostic value and could be employed as CD gene biomarkers using machine learning methods in conjunction with external dataset validation. In comparison to controls, antigen processing and presentation, chemokine signaling pathway, cytokine–cytokine receptor interactions, and natural killer cell-mediated cytotoxicity were activated in colonic tissues. Cytokine–cytokine receptor interactions, NOD-like receptor signaling pathways, and toll-like receptor signaling pathways were activated in ileal tissues. NAT8 was found to be associated with CD8 T cells, while CXCL1, S100A8, REG3A, LCN2, and DEFA6 were associated with neutrophils, indicating that immune cell infiltration in CD is closely connected.

Conclusion
CXCL1, S100A8, REG3A, and DEFA6 in colonic tissue and LCN2 and NAT8 in ileal tissue can be employed as CD biomarkers. Additionally, immune cell infiltration is crucial for CD development.
Geolocation of a demersal fish (Pacific cod) in a high-latitude island chain (Aleutian Islands, Alaska)
Authors: Nielsen Julie K. , Bryan David R. , Rand Kimberly M. , Arostegui Martin C. , Braun Camrin D. , Galuardi Benjamin , McDermott Susanne F. 
Published: July 2023

Abstract
Background
Fish geolocation methods are most effective when they are customized to account for species behavior and study area characteristics. Here, we provide an example of customizing a hidden Markov model (HMM) for reconstructing movement pathways of a high-latitude demersal fish species in a remote island chain using Pop-up Satellite Archival Tag (PSAT) data. Adult Pacific cod were tagged with PSATs while occupying winter spawning grounds in the Aleutian Islands in February 2019. We adapted a demersal fish application of the HMM to (1) add light-based longitude to the data likelihood model, (2) account for possible off-bottom behavior of demersal fishes in the maximum daily depth likelihood, and (3) modify the model framework to accommodate convoluted island topography in the study area. A simulation study was conducted to explore the two primary modifications to the model framework, reflecting boundary for the movement kernel and the Viterbi method of pathway reconstruction, under known conditions.

Results
Geolocation was performed on satellite-transmitted and detailed archival data sets from 6 adult Pacific cod at liberty for 21–277 days. Migration from winter spawning to summer foraging areas (range 60–395 km) was detected for the 4 tagged fish that were at liberty for more than 90 days. Light-based longitude was the primary geolocation variable for detecting migrations with precision (root mean square error) estimates of 0.56 degrees during winter and 1.3 degrees during the summer. Simulation studies confirmed the effectiveness of model framework modifications and generated guidelines for use in specific applications.

Conclusions
This study demonstrates that post-spawning migrations of Pacific cod in the Aleutian Islands can be detected and characterized using PSAT data. Initial insights into migrations, summer foraging areas, and associated development of appropriate analysis tools will support future Pacific cod movement studies in the Aleutian Islands as well as other regions of Alaska. The adaptations to the HMM presented here will benefit current and future research on demersal fish in other regions as well as fish species that occupy areas with convoluted shorelines or island chain topography.
The identity of Fuegian and Patagonian “dogs” among indigenous peoples in southernmost South America
Authors: Jaksic Fabian M. , Castro Sergio A. 
Published: July 2023

Abstract
Background
By using a historical approach we attempt to answer the question of whether the “dogs” of Fuegian and Patagonian peoples are a domesticated dog (Canis lupus familiaris) or a tamed or domesticated Culpeo “fox” (Lycalopex culpaeus), or a cross breed.

Methods and results
We reviewed historical chronicles and current scientific papers, and clarified several rather confusing concepts, providing disambiguation for terms such as Magellanic region, Patagonia, and Tierra del Fuego; Fuegian and Patagonian peoples; and Fuegian and Patagonian dogs. We conclude that these dogs belong to two different canid varieties: The smaller domestic dog typical of the “canoe-indians” (Chonos, Kawesqar, and Yahgan peoples) and the larger tamed or domesticated Culpeo “fox" typical of the “foot indians” (Aonikenk, Manek'enk, and Selk’nam peoples, thus proposing the use of Fuegian and Patagonian dog, respectively.

Discussion
We think that the original Fuegian dog was indeed a Canis lupus familiaris brought along by the natives after the Bering’s crossing and that the Patagonian dog was a tame Culpeo fox Lycalopex culpaeus, which was progressively replaced by the more gregarious, human friendly, and colorful domestic dogs brought by European explorers, adventurers, colonizers, and settlers of Patagonia and Tierra del Fuego during the mid to late 1800s. The possibility that the Patagonian dog was a cross between domestic dog and Culpeo “fox” cannot be ruled out, but the only specimen genetically analyzed was closest to being the latter and not a hybrid.
Prediction of measles patients using machine learning classifiers: a comparative study
Authors: Gyebi Robert , Okyere Gabriel Asare , Nakua Emmanuel Kwaku , Aseidu-Bekoe Franklin , Nti Jane Serwaa Akoto , Ansah Emmanuel Owusu , Opoku Felix Agyemang 
Published: July 2023

Abstract
Background
Measles has high primary reproductive number, extremely infectious and ranked second to malaria in terms of disease burden in Ghana. Owing to the disease’s high infectious rate, making early diagnosis based on an accurate system can help limit the spread of the disease. Studies have been conducted to derive models to serve as preliminary tools for early detection. However, these derived models are based on traditional methods, which may be limited in terms of model sensitivity and prediction power. This study focuses on comparing the performance of five machine learning classification techniques with a traditional method for predicting measles patients in Ghana. The study was an analytical cross-sectional design of suspected measles cases in Ghana.

Results
The performance of six classifiers were compared and the random forest (RF) model demonstrated better performance among other models. The RF model achieved the highest sensitivity (0.88) specificity (0.96), ROC (0.92) and total accuracy (0.92).

Conclusions
Our findings showed that, despite all the six methods had good performance in classifying measles patients, the RF model outperformed all the other classifiers in terms of different criteria in prediction accuracy. Accordingly, this approach is an effective classifier for predicting measles in the early stage.