bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unveiling the role of UPF3B in hepatocellular carcinoma: Potential therapeutic target
Authors: Hou Bowen , Shu Min , Liu Chenghao , Du Yunfeng , Xu Cuicui , Jiang Huijiao , Hou Jun , Chen Xueling , Wang Lianghai , Wu Xiangwei 
Published: June 2024

AbstractRNA‐binding proteins can regulate nucleotide metabolism and gene expression. UPF3B regulator of nonsense mediated mRNA decay (UPF3B) exhibits dysfunction in cancers. However, its role in the progression of hepatocellular carcinoma (HCC) is still insufficiently understood. Here, we found that UPF3B was markedly upregulated in HCC samples and associated with adverse prognosis in patients. UPF3B dramatically promoted HCC growth both in vivo and in vitro. Mechanistically, UPF3B was found to bind to PPP2R2C, a regulatory subunit of PP2A, boosting its mRNA degradation and activating the PI3K/AKT/mTOR pathway. E2F transcription factor 6 (E2F6) directly binds to the UPF3B promoter to facilitate its transcription. Together, the E2F6/UPF3B/PPP2R2C axis promotes HCC growth through the PI3K/AKT/mTOR pathway. Hence, it could be a promising therapeutic target for treating HCC.
Zingiber officinale promotes autophagy and apoptosis in human oral cancer through the C/EBP homologous protein
Authors: Kim Hyun‐Ji , Shin Ji‐Ae , Lee Yeong‐Geun , Jin Bohwan , Lee Won Woo , Lee Yosub , Choi Su‐Jung , Han Jung‐Min , Ahn Min‐Hye , Kim Ji‐Hoon , Park Dong‐Guk , Hong Seong‐Doo , Kang Se‐Chan , Cho Sung‐Dae 
Published: June 2024

AbstractThe rhizome of Zingiber officinale (Z. officinale), commonly known as ginger, has been characterized as a potential drug candidate due to its antitumor effects. However, the chemotherapeutic effect of ginger on human oral cancer remains poorly understood. In this study, we examined the effects of an ethanol extract of Z. officinale rhizomes (ZOE) on oral cancer and identified the components responsible for its pharmacological activity. ZOE exerts its inhibitory activity in oral cancer by inducing both autophagy and apoptosis simultaneously. Mechanistically, ZOE‐induced autophagy and apoptosis in oral cancer are attributed to the reactive oxygen species (ROS)‐mediated endoplasmic reticulum stress response. Additionally, we identified two active components of ZOE, 1‐dehydro‐6‐gingerdione and 8‐shogaol, which were sufficient to stimulate autophagy initiation and apoptosis induction by enhancing CHOP expression. These results suggest that ZOE and its two active components induce ROS generation, upregulate CHOP, initiate autophagy and apoptosis, and hold promising therapeutics against human oral cancer.
Methyltransferase like‐14 suppresses growth and metastasis of non‐small‐cell lung cancer by decreasing LINC02747
Authors: Wang Jiemin , Wang Shu , Yang Haopeng , Wang Ruixuan , Shi Kesong , Liu Yueshi , Dou Le , Yu Haiquan 
Published: June 2024

AbstractMultiple epigenetic regulatory mechanisms exert critical roles in tumor development, and understanding the interactions and impact of diverse epigenetic modifications on gene expression in cancer is crucial for the development of precision medicine. We found that methyltransferase‐like 14 (METTL14) was significantly downregulated in non‐small‐cell lung cancer (NSCLC) tissues. Functional experiments demonstrated that overexpression of METTL14 inhibited the proliferation and migration of NSCLC cells both in vivo and in vitro, and the colorimetric m6A quantification assay also showed that knockdown of METTL14 notably reduced global m6A modification levels in NSCLC cells. By using the methylated‐RNA immunoprecipitation‐qPCR and dual‐luciferase reporter assays, we verified that long noncoding RNA LINC02747 was a target of METTL14 and was regulated by METTL14‐mediated m6A modification, and silencing LINC02747 inhibited the malignant progression of NSCLC by modulating the PI3K/Akt and CDK4/Cyclin D1 signaling pathway. Further studies revealed that overexpression of METTL14 promoted m6A methylation and accelerated the decay of LINC02747 mRNA via increased recognition of the “GAACU” binding site by YTHDC2. Additionally, histone demethylase lysine‐specific histone demethylase 5B (KDM5B) mediated the demethylation of histone H3 lysine 4 tri‐methylation (H3K4me3) in the METTL14 promoter region and repressed its transcription. In summary, KDM5B downregulated METTL14 expression at the transcriptional level in a H3K4me3‐dependent manner, while METTL14 modulated LINC02747 expression via m6A modification. Our results demonstrate a synergy of multiple mechanisms in regulating the malignant phenotype of NSCLC, revealing the complex regulation involved in the occurrence and development of cancer.
Integrated bioinformatics analysis reveals the bidirectional effects of TSPAN6 for cisplatin resistance in lung cancer
Authors: Fang Zhihong , Bai Jinmei 
Published: June 2024

AbstractCisplatin‐based chemotherapy is frequently employed as the primary therapeutic approach for advanced lung cancer. Nevertheless, a significant proportion of patients may develop resistance to cisplatin, leading to diminished efficacy of chemotherapy. Through analysis of Gene Expression Omnibus databases, TSPAN6 has been identified as a key factor in conferring resistance to cisplatin, attributed to its activation of the NF‐κB signaling pathway. Knockdown of TSPAN6 using siRNA resulted in decreased expression levels of NF‐κB in A549 cells. This indicates that TSPAN6 may have dual effects on lung cancer cisplatin resistance and could serve as a promising therapeutic target for individuals with cisplatin resistance.
Dental antibiotic policies, stewardship, and implementation in India: A policy document analysis
Authors: Bhuvaraghan Aarthi , King Rebecca , Walley John , Thiruvenkatachari Badri , Aggarwal Vishal R. 
Published: June 2024

AbstractObjectivesDental antibiotic stewardship is crucial in low‐ and middle‐income countries where the burden of antimicrobial resistance (AMR) is high and antibiotic misuse is common. Given that India is the most populous country, the largest antibiotic consumer and has a large dental prescriber population, this study investigated the extent to which current Indian policy and practice for dental antibiotic prescribing and stewardship aligns with the global policy and best practice.MethodsThe READ approach was used to identify and extract data and synthesize the findings. Policy documents on dental antimicrobial stewardship were identified using a systematic search strategy involving nine medical and grey literature databases (Medline, Global Health, Web of Science, Cochrane, CINAHL, Eldis, Global Index Medicus, Proquest and Opengrey), targeted websites (government organizations and dental regulatory bodies) and contact with experts. Framework analysis was used to code extracted data into themes related to dental antimicrobial stewardship.ResultsOf the 3039 records screened, 25 documents were included in the final analysis. The analysis showed a lack of guidelines or toolkits for appropriate antibiotic prescribing in dentistry in India. The treatment guidelines for antimicrobial use in common syndromes published by the Indian Council of Medical Research had no section or content for dental practitioners. Furthermore, the undergraduate dental curriculum developed by the Dental Council of India (DCI), included little content on appropriate antibiotic prescribing and no mention of AMR or stewardship. There were no educational resources either for dental practitioners or patients in the documents.ConclusionThis document analysis showed that there was little or no mention of dental antibiotic prescribing guidelines in key policy documents such as the National Action Plan on AMR. In addition, contradictory and subjective information provided in some policy documents could encourage dentists and other health professionals such as general practitioners to prescribe antibiotics for common dental conditions for which they are contra‐indicated. There is an urgent need to develop relevant guidelines and include these in Indian policy documents on AMR particularly the National Action Plan on AMR.
Effects of cerebellar repetitive transcranial magnetic stimulation plus physiotherapy in spinocerebellar ataxias – A randomized clinical trial
Authors: Grobe‐Einsler Marcus , Bork Friederike , Faikus Aline , Hurlemann René , Kaut Oliver 
Published: June 2024

AbstractBackgroundIn absence of drug therapy options, standard treatment for spinocerebellar ataxia consists of symptomatic physiotherapy and speech therapy. New therapeutic options are urgently needed. Transcranial magnetic stimulation is a promising therapeutic option, but applicability is limited by lengthy duration of stimulation protocols.MethodsIn this randomized sham controlled clinical trial, patients were assigned to verum (n = 15) or sham (n = 18) cerebellar transcranial magnetic stimulation. To yield best possible treatment effects, both intervention groups received intensified physiotherapy for the duration of the study.ResultsAtaxia severity was reduced by 1.6 points on the Scale for assessment and Rating of Ataxia among patients in the verum group (p < 0.001). Clinical improvement was significantly larger in the verum group, compared to the sham group (p < 0.01). The treatment effect was mainly carried by improved appendicular coordination. Patients in the verum group also significantly improved in the 8 Meter Walk Test (p < 0.05) and PATA rate (p < 0.01).ConclusionsCerebellar rTMS ameliorates ataxia severity in patient with spinocerebellar ataxia. Condensing treatment duration to only 5 days without reduction of treatment effects facilitates applicability and therefore broadens availability to larger patient populations.
Volume loss in the left anterior‐superior subunit of the hypothalamus in amyotrophic lateral sclerosis
Authors: Ghaderi Sadegh , Fatehi Farzad , Kalra Sanjay , Mohammadi Sana , Zemorshidi Fariba , Ramezani Mahtab , Hesami Omid , Pezeshgi Saharnaz , Batouli Seyed Amir Hossein 
Published: June 2024

AbstractBackground and ObjectiveAmyotrophic lateral sclerosis (ALS) causes motor neuron loss and progressive paralysis. While traditionally viewed as motor neuron disease (MND), ALS also affects non‐motor regions, such as the hypothalamus. This study aimed to quantify the hypothalamic subregion volumes in patients with ALS versus healthy controls (HCs) and examine their associations with demographic and clinical features.MethodsForty‐eight participants (24 ALS patients and 24 HCs) underwent structural MRI. A deep convolutional neural network was used for the automated segmentation of the hypothalamic subunits, including the anterior‐superior (a‐sHyp), anterior‐inferior (a‐iHyp), superior tuberal (supTub), inferior tuberal (infTub), and posterior (posHyp). The neural network was validated using FreeSurfer v7.4.1, with individual head size variations normalized using total intracranial volume (TIV) normalization. Statistical analyses were performed for comparisons using independent sample t‐tests. Correlations were calculated using Pearson's and Spearman's tests (p < 0.05). The standard mean difference (SMD) was used to compare the mean differences between parametric variables.ResultsThe volume of the left a‐sHyp hypothalamic subunit was significantly lower in ALS patients than in HCs (p = 0.023, SMD = ‐0.681). No significant correlation was found between the volume of the hypothalamic subunits, body mass index (BMI), and ALSFRS‐R in patients with ALS. However, right a‐sHyp (r = 0.420, p = 0.041) was correlated with disease duration, whereas right supTub (r = −0.471, p = 0.020) and left postHyp (r = −0.406, p = 0.049) were negatively correlated with age. There was no significant difference in the volume of hypothalamic subunits between males and females, and no significant difference was found between patients with revised ALS Functional Rating Scale (ALSFRS‐R) scores ≤41 and >41 and those with a disease duration of 9 months or less.Discussion and ConclusionThe main finding suggests atrophy of the left a‐sHyp hypothalamic subunit in patients with ALS, which is supported by previous research as an extra‐motor neuroimaging finding for ALS.
Identification and validation of COL6A1 as a novel target for tumor electric field therapy in glioblastoma
Authors: Chen Junyi , Liu Yuyang , Lan Jinxin , Liu Hongyu , Tang Qingyun , Li Ze , Qiu Xiaoguang , Hu Wentao , Xie Jiaxin , Feng Yaping , Qin Lilin , Zhang Xin , Liu Jialin , Chen Ling 
Published: June 2024

AbstractBackgroundGlioblastoma multiforme (GBM) is the most aggressive primary brain malignancy. Novel therapeutic modalities like tumor electric field therapy (TEFT) have shown promise, but underlying mechanisms remain unclear. The extracellular matrix (ECM) is implicated in GBM progression, warranting investigation into TEFT‐ECM interplay.MethodsT98G cells were treated with TEFT (200 kHz, 2.2 V/m) for 72 h. Collagen type VI alpha 1 (COL6A1) was identified as hub gene via comprehensive bioinformatic analysis based on RNA sequencing (RNA‐seq) and public glioma datasets. TEFT intervention models were established using T98G and Ln229 cell lines. Pre‐TEFT and post‐TEFT GBM tissues were collected for further validation. Focal adhesion pathway activity was assessed by western blot. Functional partners of COL6A1 were identified and validated by co‐localization and survival analysis.ResultsTEFT altered ECM‐related gene expression in T98G cells, including the hub gene COL6A1. COL6A1 was upregulated in GBM and associated with poor prognosis. Muti‐database GBM single‐cell analysis revealed high‐COL6A1 expression predominantly in malignant cell subpopulations. Differential expression and functional enrichment analyses suggested COL6A1 might be involved in ECM organization and focal adhesion. Western blot (WB), immunofluorescence (IF), and co‐immunoprecipitation (Co‐IP) experiments revealed that TEFT significantly inhibited expression of COL6A1, hindering its interaction with ITGA5, consequently suppressing the FAK/Paxillin/AKT pathway activity. These results suggested that TEFT might exert its antitumor effects by downregulating COL6A1 and thereby inhibiting the activity of the focal adhesion pathway.ConclusionTEFT could remodel the ECM of GBM cells by downregulating COL6A1 expression and inhibiting focal adhesion pathway. COL6A1 could interact with ITGA5 and activate the focal adhesion pathway, suggesting that it might be a potential therapeutic target mediating the antitumor effects of TEFT.
Epilepsy alters brain networks in patients with insular glioma
Authors: He Qifeng , Yang Zuocheng , Xue BoWen , Song Xinyu , Zhang Chuanhao , Yin ChuanDong , Li Zhenye , Deng Zhenghai , Sun Shengjun , Qiao Hui , Xie Jian , Hou Zonggang 
Published: June 2024

AbstractAimsWe intend to elucidate the alterations of cerebral networks in patients with insular glioma‐related epilepsy (GRE) based on resting‐state functional magnetic resonance images.MethodsWe collected 62 insular glioma patients, who were subsequently categorized into glioma‐related epilepsy (GRE) and glioma with no epilepsy (GnE) groups, and recruited 16 healthy individuals matched to the patient's age and gender to form the healthy control (HC) group. Graph theoretical analysis was applied to reveal differences in sensorimotor, default mode, visual, and executive networks among different subgroups.ResultsNo significant alterations in functional connectivity were found in either hemisphere insular glioma. Using graph theoretical analysis, differences were found in visual, sensorimotor, and default mode networks (p < 0.05). When the glioma located in the left hemisphere, the degree centrality was reduced in the GE group compared to the GnE group. When the glioma located in the right insula, the degree centrality, nodal efficiency, nodal local efficiency, and nodal clustering coefficient of the GE group were lower than those of the GnE group.ConclusionThe impact of insular glioma itself and GRE on the brain network is widespread. The networks altered by insular GRE differ depending on the hemisphere location. GRE reduces the nodal properties of brain networks than that in insular glioma.
GIP attenuates neuronal oxidative stress by regulating glucose uptake in spinal cord injury of rat
Authors: Guo Beibei , Qi Mengwei , Luo Xiaoqian , Guo Longyu , Xu Man , Zhang Yufang , Li Zhen , Li Mingxuan , Wu Ronghua , Guan Tuchen , Liu Mei , Liu Yan 
Published: June 2024

AbstractAimGlucose‐dependent insulinotropic polypeptide (GIP) is a ligand of glucose‐dependent insulinotropic polypeptide receptor (GIPR) that plays an important role in the digestive system. In recent years, GIP has been regarded as a hormone‐like peptide to regulate the local metabolic environment. In this study, we investigated the antioxidant role of GIP on the neuron and explored the possible mechanism.MethodsCell counting Kit‐8 (CCK‐8) was used to measure cell survival. TdT‐mediated dUTP Nick‐End Labeling (TUNEL) was used to detect apoptosis in vitro and in vivo. Reactive oxygen species (ROS) levels were probed with 2', 7'‐Dichloro dihydrofluorescein diacetate (DCFH‐DA), and glucose intake was detected with 2‐NBDG. Immunofluorescence staining and western blot were used to evaluate the protein level in cells and tissues. Hematoxylin‐eosin (HE) staining, immunofluorescence staining and tract‐tracing were used to observe the morphology of the injured spinal cord. Basso‐Beattie‐Bresnahan (BBB) assay was used to evaluate functional recovery after spinal cord injury.ResultsGIP reduced the ROS level and protected cells from apoptosis in cultured neurons and injured spinal cord. GIP facilitated wound healing and functional recovery of the injured spinal cord. GIP significantly improved the glucose uptake of cultured neurons. Meanwhile, inhibition of glucose uptake significantly attenuated the antioxidant effect of GIP. GIP increased glucose transporter 3 (GLUT3) expression via up‐regulating the level of hypoxia‐inducible factor 1α (HIF‐1α) in an Akt‐dependent manner.ConclusionGIP increases GLUT3 expression and promotes glucose intake in neurons, which exerts an antioxidant effect and protects neuronal cells from oxidative stress both in vitro and in vivo.
Advances of the MAPK pathway in the treatment of spinal cord injury
Authors: Huang Shixue , Zhang Yinuo , Shu Haoming , Liu Wei , Zhou Xin , Zhou Xuhui 
Published: June 2024

AbstractSpinal cord injury (SCI) represents a complex pathology within the central nervous system (CNS), leading to severe sensory and motor impairments. It activates various signaling pathways, notably the mitogen‐activated protein kinase (MAPK) pathway. Present treatment approaches primarily focus on symptomatic relief, lacking efficacy in addressing the underlying pathophysiological mechanisms. Emerging research underscores the significance of the MAPK pathway in neuronal differentiation, growth, survival, axonal regeneration, and inflammatory responses post‐SCI. Modulating this pathway post‐injury has shown promise in attenuating inflammation, minimizing apoptosis, alleviating neuropathic pain, and fostering neural regeneration. Given its pivotal role, the MAPK pathway emerges as a potential therapeutic target in SCI management. This review synthesizes current knowledge on SCI pathology, delineates the MAPK pathway's characteristics, and explores its dual roles in SCI pathology and therapeutic interventions. Furthermore, it addresses the existing challenges in MAPK research in the context of SCI, proposing solutions to overcome these hurdles. Our aim is to offer a comprehensive reference for future research on the MAPK pathway and SCI, laying the groundwork for targeted therapeutic strategies.
Alterations in cortical thickness and volumes of subcortical structures in pediatric patients with complete spinal cord injury
Authors: Wang Ling , Yang Beining , Zheng Weimin , Liang Tengfei , Chen Xin , Chen Qian , Du Jubao , Lu Jie , Li Baowei , Chen Nan 
Published: June 2024

AbstractAimsTo study the changes in cortical thickness and subcortical gray matter structures in children with complete spinal cord injury (CSCI), reveal the possible causes of dysfunction beyond sensory motor dysfunction after CSCI, and provide a possible neural basis for corresponding functional intervention training.MethodsThirty‐seven pediatric CSCI patients and 34 age‐, gender‐matched healthy children as healthy controls (HCs) were recruited. The 3D high‐resolution T1‐weighted structural images of all subjects were obtained using a 3.0 Tesla MRI system. Statistical differences between pediatric CSCI patients and HCs in cortical thickness and volumes of subcortical gray matter structures were evaluated. Then, correlation analyses were performed to analyze the correlation between the imaging indicators and clinical characteristics.ResultsCompared with HCs, pediatric CSCI patients showed decreased cortical thickness in the right precentral gyrus, superior temporal gyrus, and posterior segment of the lateral sulcus, while increased cortical thickness in the right lingual gyrus and inferior occipital gyrus. The volume of the right thalamus in pediatric CSCI patients was significantly smaller than that in HCs. No significant correlation was found between the imaging indicators and the injury duration, sensory scores, and motor scores of pediatric CSCI patients.ConclusionsThese findings demonstrated that the brain structural reorganizations of pediatric CSCI occurred not only in sensory motor areas but also in cognitive and visual related brain regions, which may suggest that the visual processing, cognitive abnormalities, and related early intervention therapy also deserve greater attention beyond sensory motor rehabilitation training in pediatric CSCI patients.
The role of spinal neurons targeted by corticospinal neurons in central poststroke neuropathic pain
Authors: Fan Fenqqi , Yin Tianze , Wu Biwu , Zheng Jiajun , Deng Jiaojiao , Wu Gang , Hu Shukun 
Published: June 2024

AbstractBackgroundCentral poststroke pain (CPSP) is one of the primary sequelae following stroke, yet its underlying mechanisms are poorly understood.MethodsBy lesioning the lateral thalamic nuclei, we first established a CPSP model that exhibits mechanical and thermal hypersensitivity. Innocuous mechanical stimuli following the thalamic lesion evoked robust neural activation in somatosensory corticospinal neurons (CSNs), as well as in the deep dorsal horn, where low threshold mechanosensory afferents terminate. In this study, we used viral‐based mapping and intersectional functional manipulations to decipher the role of somatosensory CSNs and their spinal targets in the CPSP pathophysiology.ResultsWe first mapped the post‐synaptic spinal targets of lumbar innervating CSNs using an anterograde trans‐synaptic AAV1‐based strategy and showed these spinal interneurons were activated by innocuous tactile stimuli post‐thalamic lesion. Functionally, tetanus toxin‐based chronic inactivation of spinal neurons targeted by CSNs prevented the development of CPSP. Consistently, transient chemogenetic silencing of these neurons alleviated established mechanical pain hypersensitivity and innocuous tactile stimuli evoked aversion linked to the CPSP. In contrast, chemogenetic activation of these neurons was insufficient to induce robust mechanical allodynia typically observed in the CPSP.ConclusionThe CSNs and their spinal targets are required but insufficient for the establishment of CPSP hypersensitivity. Our study provided novel insights into the neural mechanisms underlying CPSP and potential therapeutic interventions to treat refractory central neuropathic pain conditions.