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In this editorial, we delve into the article and offer valuable insights into a crucial aspect of gastric cancer aetiology. Gastric cancer is a malignancy emanating from the epithelial lining of the gastric mucosa and one of the most prevalent forms of cancer worldwide. The development of gastric cancer is associated with multiple risk factors, including Helicobacter pylori infection, advanced age, a diet rich in salt, and suboptimal eating patterns. Despite notable reductions in morbidity and mortality rates, gastric cancer remains a formidable public health concern, impacting patients' lives. Advanced glycation end products (AGEs) are complex compounds arising from nonenzymatic reactions within living organisms, the accumulation of which is implicated in cellular and tissue damage; thus, the levels are AGEs are correlated with the risk of diverse diseases. The investigation of AGEs is of paramount importance for the treatment of gastric cancer and can provide pivotal insights into disease pathogenesis and preventive and therapeutic strategies. The reduction of AGEs levels and suppression of their accumulation are promising avenues for mitigating the risk of gastric cancer. This approach underscores the need for further research aimed at identifying innovative interventions that can effectively lower the incidence and mortality rates of this malignancy.
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High-voltage Li metal battery (HV-LMB) is one of the most promising energy storage technologies to achieve ultrahigh energy density. Nevertheless, electrolytes reported to date are difficult to simultaneously stabilize the Li metal anode and high-voltage cathode, especially without the assistance of expensive and corrosive high-concentration Li salts. Herein, a dual-interphase-stabilizing (DIS) and safe electrolyte that bypasses the high-concentration Li salt is reported. The electrolyte consists of high-flash-point sulfolane as solvent, molecular-orbital-engineered additives that enable stable B-F rich cathodic interphase, and unique C-F rich organic anodic interphase. The stable cycling of both Li metal anode and 4.75 V-LiCoO2 cathode in the DIS electrolyte (> 500 cycles) is demonstrated. HV-LMB pouch cells of a high energy density (435 Wh kg-1) can sustainably operate for more than 100 cycles. Moreover, the low cost and high thermal stability of the DIS electrolyte offer superior cost-effectiveness and safety for large-scale applications of HV-LMBs in the future.
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PURPOSE: To assess the reproducibility of radiomic features (RFs) extracted from dynamic contrast-enhanced computed tomography (DCE-CT) scans of patients diagnosed with hepatocellular carcinoma (HCC) with regards to inter-observer variability and acquisition timing after contrast injection. The predictive ability of reproducible RFs for differentiating between the degrees of HCC differentiation is also investigated. METHODS: We analyzed a set of DCE-CT scans of 39 patients diagnosed with HCC. Two radiologists independently segmented the scans, and RFs were extracted from each sequence of the DCE-CT scans. The same lesion was segmented across the DCE-CT sequences of each patient's scan. From each lesion, 127 commonly used RFs were extracted. The reproducibility of RFs was assessed with regard to (i) inter-observer variability, by evaluating the reproducibility of RFs between the two radiologists; and (ii) timing of acquisition following contrast injection (inter- and intra-imaging phase). The reproducibility of RFs was assessed using the concordance correlation coefficient (CCC), with a cut-off value of 0.90. Reproducible RFs were used for building XGBoost classification models for the differentiation of HCC differentiation. RESULTS: Inter-observer analyses across the different contrast-enhancement phases showed that the number of reproducible RFs was 29 (22.8%), 52 (40.9%), and 36 (28.3%) for the non-contrast enhanced, late arterial, and portal venous phases, respectively. Intra- and inter-sequence analyses revealed that the number of reproducible RFs ranged between 1 (0.8%) and 47 (37%), inversely related with time interval between the sequences. XGBoost algorithms built using reproducible RFs in each phase were found to be high predictive ability of the degree of HCC tumor differentiation. CONCLUSIONS: The reproducibility of many RFs was significantly impacted by inter-observer variability, and a larger number of RFs were impacted by the difference in the time of acquisition after contrast injection. Our findings highlight the need for quality assessment to ensure that scans are analyzed in the same physiologic imaging phase in quantitative imaging studies, or that phase-wide reproducible RFs are selected. Overall, the study emphasizes the importance of reproducibility and quality control when using RFs as biomarkers for clinical applications.
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Carcinoma Hepatocelular , Meios de Contraste , Neoplasias Hepáticas , Variações Dependentes do Observador , Tomografia Computadorizada por Raios X , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Feminino , Tomografia Computadorizada por Raios X/métodos , Reprodutibilidade dos Testes , Pessoa de Meia-Idade , Idoso , Adulto , RadiômicaRESUMO
BACKGROUND AND AIMS: Patients with aggressive hepatocellular carcinoma (HCC) have limited therapeutic options. Therefore, a better understanding of HCC pathogenesis is needed to improve treatment. Genomic studies of HCC have improved our understanding of cancer biology. However, the ubiquitomic characteristics of HCC remain poorly understood. We aimed to reveal the ubiquitomic characteristics of HCC and provide clinical feature biomarkers of the aggressive HCC that may be used for diagnosis or therapy in the clinic. APPROACH AND RESULTS: The comprehensive proteomic, phosphoproteomic, and ubiquitomic analyses were performed on tumors and adjacent normal liver tissues from 85 HCC patients. HCCs displayed overexpression of drugable targets CBR1-S151 and CPNE1-S55. COL4A1, LAMC1 and LAMA4 were highly expressed in the DFS poor patients. Phosphoproteomic and ubiquitomic features of HCC revealed crosstalk in metabolism and metastasis. Ubiquitomics predicted diverse prognosis and clarified HCC subtype-specific proteomic signatures. Expression of biomarkers TUBA1A, BHMT2, BHMT, and ACY1 exhibited differential ubiquitination levels and displayed high prognostic risk scores, suggesting that targeting these proteins or their modified forms may be beneficial for future clinical treatment. We validated that TUBA1A K370 deubiquitination drove severe HCC and labeled an aggressive subtype of HCCs. TUBA1A K370 deubiquitination was at least partly attributed to AKT-mediated USP14 activation in HCC. Notably, targeting AKT-USP14-TUBA1A complex promoted TUBA1A degradation and blocked liver tumorigenesis in vivo. CONCLUSIONS: This study expands our knowledge of ubiquitomic signatures, biomarkers, and potential therapeutic targets in HCC.
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BACKGROUND: Fusobacterium nucleatum (F. nucleatum) is one of the key tumorigenic bacteria in colorectal cancer (CRC), yet how F. nucleatum is involved in colorectal cancer carcinogenesis remains unknown. RESULTS: In the present study, we carried out PathSeq analysis on RNA sequencing data from the 430 primary colon adenocarcinomas in TCGA database to assess the relationship between patients' survival and F. nucleatum abundance. Among patients with cecum and ascending colon tumors, we found that F. nucleatum transcriptome abundance is positively correlated with mutation load. We further demonstrated that patients with both high tumoral abundance of F. nucleatum and high mutation load exhibited poorer survival and DNA damage. We furthermore determined that F. nucleatum-conditioned medium (Fn. CM) induces DNA damage in both in vitro and in vivo studies. In addition, two F. nucleatum-secreted mutagens, namely DL-homocystine and allantoic acid, were identified to lead to DNA damage. CONCLUSIONS: Our finding delineates the genotoxicity of F.nucleatum-secreted mutagens, which provides a basis for further work to investigate the role of F. nucleatum in the pathogenicity of CRC.
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Antarctic Bottom Water (AABW), which supplies the lower limb of the thermohaline circulation, originates from dense shelf water (DSW) forming in Antarctic polynyas. Here, combining a long mooring record of DSW measurements with numerical simulations and satellite data, we show that significant correlation exists between interannual variability of DSW production in the Ross Sea polynyas, where DSW contributes between 20-40% of the global AABW production, and the Southern Annular Mode (SAM). The correlation is largest when the Amundsen Sea Low (ASL) is weakened and shifted east of the Ross Sea. During positive SAM phases, enhanced offshore winds and lower air temperatures over the western Ross Sea increase sea ice production and promote DSW formation, with the opposite response during negative SAM phases. These processes ultimately modulate AABW thickness in the open ocean. A projected positive shift of the SAM and eastward displacement of the ASL thus has implications for the future of DSW and AABW formation.
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A majority of flexible and wearable electronics require high operational voltage that is conventionally achieved by serial connection of battery unit cells using external wires. However, this inevitably decreases the energy density of the battery module and may cause additional safety hazards. Herein, a bipolar textile composite electrode (BTCE) that enables internal tandem-stacking configuration to yield high-voltage (6 to 12 V class) solid-state lithium metal batteries (SSLMBs) is reported. BTCE is comprised of a nickel-coated poly(ethylene terephthalate) fabric (NiPET) core layer, a cathode coated on one side of the NiPET, and a Li metal anode coated on the other side of the NiPET. Stacking BTCEs with solid-state electrolytes alternatively leads to the extension of output voltage and decreased usage of inert package materials, which in turn significantly boosts the energy density of the battery. More importantly, the BTCE-based SSLMB possesses remarkable capacity retention per cycle of over 99.98% over cycling. The composite structure of BTCE also enables outstanding flexibility; the battery keeps stable charge/discharge characteristics over thousands of bending and folding. BTCE shows great promise for future safe, high-energy-density, and flexible SSLMBs for a wide range of flexible and wearable electronics.
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Flexible solid-state lithium metal batteries (SSLMBs) are highly desirable for future wearable electronics because of their high energy density and safety. However, flexible SSLMBs face serious challenges not only in regulating the Li plating/stripping behaviors but also in enabling the mechanical flexibility of the cell. Both challenges are largely associated with the interfacial gaps between the solid electrolytes and the electrodes. Here, a UV-permeable and flexible composited Li metal anode (UVp-Li), which possesses a unique light-penetrating interwoven structure similar to textiles is reported. UVp-Li allows one-step bonding of the cathode, anode, and solid electrolyte via an in situ UV-initiated polymerization method to achieve the gapless SSLMBs. The gapless structure not only effectively stabilizes the plating/stripping of Li metal during cycling, but also ensures the integrity of the cell during mechanical bending. UVp-Li symmetric cell presents a stable cycling over 1000 h at 0.5 mA cm-2. LiFePO4||UVp-Li full cells (areal capacity ranging from 0.5 to 3 mAh cm-2) show outstanding capacity retention of over 84% after 500 charge/discharge cycles at room temperature. Large pouch cells using high-loading cathodes maintain stable electrochemical performance during 1000 times of dynamic bending.
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Aim: A bibliometric analysis and evaluation of research on non-Helicobacter pylori Helicobacter species (NHPHs) is essential to determining future research directions. Materials & methods: A comprehensive search was carried out using predetermined search terms within the Web of Science Core Collection (WoSCC) to gather publications spanning from 1993 to 2023. VOSviewer and Citespace were employed for data analysis and visualization. Results: 308 publications on NHPHs were included. Among these, gastric NHPHs received more publications and attention compared with enterohepatic NHPHs. Key findings included the identification of most productive countries, institutions, journals, authors, keywords, research trends and notable perspectives in the field. Conclusion: The article guides further research and clinical applications on NHPHs.
[Box: see text].
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Bibliometria , Infecções por Helicobacter , Helicobacter , Humanos , Infecções por Helicobacter/microbiologia , Helicobacter/isolamento & purificação , Helicobacter/genética , Helicobacter/classificação , Helicobacter pylori/isolamento & purificação , Publicações/estatística & dados numéricosRESUMO
Background: Post-hepatectomy liver failure (PHLF) is still a predominant cause of hepatectomy-related mortality. However, it is difficult to evaluate the remnant liver functional reserve accurately before surgery to prevent PHLF. In this study, we aimed to explore the role of gadoxetate disodium-enhanced magnetic resonance imaging (MRI) in evaluating remnant liver functional reserve. Methods: For this cross-sectional study, the sample retrospectively included 56 patients undergoing liver resections of at least three segments between June 2019 and September 2022 at The General Hospital of the Western Theater Command. Pre-surgery assessments involved liver computer tomography (CT), an indocyanine green (ICG) clearance test, the Child-Pugh scoring system, and liver function serum biochemical indicators. Each patient underwent a gadoxetate disodium-enhanced MRI before the hepatectomy, and we measured the remnant hepatocellular uptake index (rHUI) as well as the standard remnant hepatocellular uptake index (SrHUI). We examined the diagnostic utility of rHUI, SrHUI, indocyanine green retention rate of 15 minutes (ICG R15), and Albumin for PHLF. Receiver operating characteristics (ROC) analyses were used to measure the preoperative liver function parameters (namely, rHUI, SrHUI, ICG R15, and Albumin) for predicting PHLF. The areas under the curve (AUCs) were calculated and compared between different preoperative liver function parameters using the Wilson/Brown method. The Pearson or Spearman correlation coefficient was used for correlation analysis between ICG R15, Albumin, and rHUI and between ICG R15, Albumin, and SrHUI, respectively. Results: Twelve patients (21.43%) had complications of PHLF. We found significant differences in rHUI, SrHUI, ICG R15, and Albumin between the non-PHLF and PHLF groups. The pooled r between ICG R15 and rHUI was -0.591 [95% confidence interval (CI): -0.740 to -0.389, P<0.001], and between ICG R15 and SrHUI was -0.534 (95% CI: -0.703 to -0.308, P<0.001). The area under the curve (AUC) values of rHUI, SrHUI, ICG R15, and Ablumin were 0.871 (sensitivity 81.82%; specificity 91.67%), 0.878 (sensitivity 79.55%; specificity 83.33%), 0.835 (sensitivity 99.73%; specificity 66.67%), and 0.782 (sensitivity 88.64%; specificity 58.33%), respectively. Conclusions: We found that the rHUI and SrHUI calculated using the gadoxetate disodium-enhanced MRI reflected a combination of remnant hepatocyte function and liver volume, and these were useful as a quantitative assessment indicator of remnant liver functional reserve and can be a better predictor of PHLF after major hepatic resection.
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BACKGROUND: The prognostic value of traditional clinical indicators for locally recurrent nasopharyngeal carcinoma is limited because of their inability to reflect intratumor heterogeneity. We aimed to develop a radiomic signature to reveal tumor immune heterogeneity and predict survival in locally recurrent nasopharyngeal carcinoma. METHODS: This multicenter, retrospective study included 921 patients with locally recurrent nasopharyngeal carcinoma. A machine learning signature and nomogram based on pretreatment magnetic resonance imaging features were developed for predicting overall survival in a training cohort and validated in 2 independent cohorts. A clinical nomogram and an integrated nomogram were constructed for comparison. Nomogram performance was evaluated by concordance index and receiver operating characteristic curve analysis. Accordingly, patients were classified into risk groups. The biological characteristics and immune infiltration of the signature were explored by RNA-sequencing analysis. RESULTS: The machine learning signature and nomogram demonstrated comparable prognostic ability to a clinical nomogram, achieving concordance indexes of 0.729, 0.718, and 0.731 in the training, internal, and external validation cohorts, respectively. Integration of the signature and clinical variables statistically improved the predictive performance. The proposed signature effectively distinguished patients between risk groups with statistically distinct overall survival rates. Subgroup analysis indicated the recommendation of local salvage treatments for low-risk patients. Exploratory RNA-sequencing analysis revealed differences in interferon response and lymphocyte infiltration between risk groups. CONCLUSIONS: A magnetic resonance imaging-based radiomic signature predicted overall survival more accurately. The proposed signature associated with tumor immune heterogeneity may serve as a valuable tool to facilitate prognostic stratification and guide individualized management for locally recurrent nasopharyngeal carcinoma patients.
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Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Recidiva Local de Neoplasia , Nomogramas , Radiômica , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aprendizado de Máquina , Imageamento por Ressonância Magnética , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/diagnóstico por imagem , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/patologia , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
The prevalence of drug-resistant bacteria presents a significant challenge to the antibiotic treatment of Helicobacter pylori (H. pylori), while traditional antimicrobial agents often suffer from shortcomings such as poor gastric retention, inadequate alleviation of inflammation, and significant adverse effects on the gut microbiota. Here, a selenized chitosan (CS-Se) modified bismuth-based metal-organic framework (Bi-MOF@CS-Se) nanodrug is reported that can target mucin through the charge interaction of the outer CS-Se layer to achieve mucosal adhesion and gastric retention. Additionally, the Bi-MOF@CS-Se can respond to gastric acid and pepsin degradation, and the exposed Bi-MOF exhibits excellent antibacterial properties against standard H. pylori as well as clinical antibiotic-resistant strains. Remarkably, the Bi-MOF@CS-Se effectively alleviates inflammation and excessive oxidative stress by regulating the expression of inflammatory factors and the production of reactive oxygen species (ROS), thereby exerting therapeutic effects against H. pylori infection. Importantly, this Bi-MOF@CS-Se nanodrug does not affect the homeostasis of gut microbiota, providing a promising strategy for efficient and safe treatment of H. pylori infection.
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Microbioma Gastrointestinal , Helicobacter pylori , Inflamação , Estruturas Metalorgânicas , Helicobacter pylori/efeitos dos fármacos , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Animais , Inflamação/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Quitosana/química , Antibacterianos/farmacologia , Antibacterianos/química , Espécies Reativas de Oxigênio/metabolismo , CamundongosRESUMO
The acquisition of stable and high-areal-capacity S cathodes over 10 mA h cm-2 is a critical and indispensable step to realize the high energy density configuration. However, increasing the areal capacity of S cathodes often deteriorates the specific capacity and stability due to the aggravated dissolution of S and diffusion of solvable polysulfides in the thick electrode. Herein, the design of a freestanding composite cathode that leverages 3D covalent binding sites and chemical adsorption environment to offer dissolution-limiting and diffusion-blocking functions of S species is reported. By employing this architecture, the coin cell exhibits excellent cycling stability and an exceptional specific capacity of 1444.3 mA h g-1 (13 mA h cm-2), and the pouch cell configuration manifests a noteworthy areal capacity exceeding 11 mA h cm-2. This performance is coupled with excellent flexibility, demonstrated through consecutive bending cycle tests, even at a sulfur loading of 9.00 mg cm-2. This study lays the foundation for the development of flexible Li-S batteries with increased loading capacities and exceptional performance.
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Liver fibrosis is a chronic liver disease characterized by a progressive wound healing response caused by chronic liver injury. Currently, there are no approved clinical treatments for liver fibrosis. Sevelamer is used clinically to treat hyperphosphatemia and has shown potential therapeutic effects on liver diseases. However, there have been few studies evaluating the therapeutic effects of sevelamer on liver fibrosis, and the specific mechanisms are still unclear. In this study, we investigated the antifibrotic effects of sevelamer-induced low inorganic phosphate (Pi) stress in vitro and in vivo and analyzed the detailed mechanisms. We found that low Pi stress could inhibit the proliferation of activated hepatic stellate cells (HSCs) by promoting apoptosis, effectively suppressing the migration and epithelial-mesenchymal transition (EMT) of hepatic stellate cells. Additionally, low Pi stress significantly increased the antioxidant stress response. It is worth noting that low Pi stress indirectly inhibited the activation and migration of HSCs by suppressing transforming growth factor ß (TGF-ß) expression in macrophages. In a rat model of liver fibrosis, oral administration of sevelamer significantly decreased blood phosphorus levels, improved liver function, reduced liver inflammation, and increased the antioxidant stress response in the liver. Our study revealed that the key mechanism by which sevelamer inhibited liver fibrosis involved binding to gastrointestinal phosphate, resulting in a decrease in blood phosphorus levels, the downregulation of TGF-ß expression in macrophages, and the inhibition of HSC migration and fibrosis-related protein expression. Therefore, our results suggest that sevelamer-induced low Pi stress can attenuate hepatic stellate cell activation and inhibit the progression of liver fibrosis, making it a potential option for the treatment of liver fibrosis and other refractory chronic liver diseases.
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Células Estreladas do Fígado , Hepatopatias , Ratos , Animais , Sevelamer/efeitos adversos , Antioxidantes/farmacologia , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Fígado/metabolismo , Hepatopatias/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fósforo/metabolismo , Fósforo/farmacologia , Fósforo/uso terapêutico , Fator de Crescimento Transformador beta1/metabolismoAssuntos
Histerectomia , Laparoscopia , Umbigo , Humanos , Laparoscopia/métodos , Feminino , Histerectomia/métodos , Umbigo/cirurgia , Adulto , Pessoa de Meia-IdadeRESUMO
Helicobacter pylori (H. pylori) is a major risk factor of gastric cancer (GC). The SUMO-activating enzyme SAE1(SUMO-activating enzyme subunit 1), which is indispensable for protein SUMOylation, involves in human tumorigenesis. In this study, we used the TIMER and TCGA database to explore the SAE1 expression in GC and normal tissues and Kaplan-Meier Plotter platform for survival analysis of GC patients. GC tissue microarray and gastric samples from patients who underwent endoscopic treatment were employed to detect the SAE1expression. Our results showed that SAE1 was overexpressed in GC tissues and higher SAE1 expression was associated with worse clinical characteristics of GC patients. Cell and animal models showed that H. pylori infection upregulated SAE1, SUMO1, and SUMO2/3 protein expression. Functional assays suggested that suppression of SAE1 attenuated epithelial-mesenchymal transition (EMT) biomarkers and cell proliferation abilities induced by H. pylori. Cell and animal models of ROS inhibition in H. pylori showed that ROS could mediate the H. pylori-induced upregulation of SAE1, SUMO1, and SUMO2/3 protein. RNA sequencing was performed and suggested that knockdown of SAE1 could exert an impact on IGF-1 expression. General, increased SUMOylation modification is involved in H. pylori-induced GC.
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Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Animais , Humanos , Regulação para Cima/genética , Neoplasias Gástricas/patologia , Helicobacter pylori/genética , Helicobacter pylori/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transformação Celular Neoplásica , Infecções por Helicobacter/complicações , Infecções por Helicobacter/genética , Infecções por Helicobacter/metabolismo , Enzimas Ativadoras de Ubiquitina/genética , Enzimas Ativadoras de Ubiquitina/metabolismoRESUMO
Contrast-enhanced computed tomography scans (CECT) are routinely used in the evaluation of different clinical scenarios, including the detection and characterization of hepatocellular carcinoma (HCC). Quantitative medical image analysis has been an exponentially growing scientific field. A number of studies reported on the effects of variations in the contrast enhancement phase on the reproducibility of quantitative imaging features extracted from CT scans. The identification and labeling of phase enhancement is a time-consuming task, with a current need for an accurate automated labeling algorithm to identify the enhancement phase of CT scans. In this study, we investigated the ability of machine learning algorithms to label the phases in a dataset of 59 HCC patients scanned with a dynamic contrast-enhanced CT protocol. The ground truth labels were provided by expert radiologists. Regions of interest were defined within the aorta, the portal vein, and the liver. Mean density values were extracted from those regions of interest and used for machine learning modeling. Models were evaluated using accuracy, the area under the curve (AUC), and Matthew's correlation coefficient (MCC). We tested the algorithms on an external dataset (76 patients). Our results indicate that several supervised learning algorithms (logistic regression, random forest, etc.) performed similarly, and our developed algorithms can accurately classify the phase of contrast enhancement.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Aprendizado de Máquina , AlgoritmosRESUMO
BACKGROUND: Gastric cancer has attracted widespread attention on social media due to its high incidence and severity. The Bilibili, TikTok, and YouTube video-sharing platforms have received considerable interest among general health consumers. Nevertheless, it remains unclear whether the information in videos on these platforms is of satisfactory content and quality. METHODS: A total of 300 eligible videos related to gastric cancer were screened from three video-sharing platforms, Bilibili, TikTok, and YouTube, for assessment and analysis. First, the basic information presented in the videos was recorded. Next, we identified the source and content type of each video. Then, the Global Quality Scale (GQS), Journal of the American Medical Association (JAMA), and Modified DISCERN were used to assess the educational content and quality of each video. A comparative analysis was undertaken of the videos procured from these three sources. RESULTS: We identified six categories of uploaders of the 300 videos: 159 videos (53%) were uploaded by health professionals, 21 videos (7%) by users in science communications, 29 videos (9.67%) by general users, 27 videos (9%) from news agencies, 63 videos (12%) by nonprofit organizations, and one video (0.33%) by a for-profit organization. In terms of the content types of the 300 videos, we identified five distinct categories. There were 48 videos (16%) on early signals, 12 videos (4%) on late symptoms, 40 videos (13.33%) on etiologies and causations, 160 videos (53.33%) on scientific introductions, and 40 videos (13.33%) on treatment methods. The overall quality of the videos was evaluated by the GQS, JAMA, and Modified DISCERN and was found to be medium, with scores of 2.6/5, 2.41/4, and 2.71/5 points, respectively. CONCLUSIONS: This innovative study demonstrates that videos on social media platforms can help the public learn about early signals, late symptoms, treatment methods, etiologies and causations, and scientific introductions of gastric cancer. However, both the content and quality of uploaded recordings are inadequate currently. More efforts should be made to enhance the content and quality of videos on gastric cancer and to increase public awareness.
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Mídias Sociais , Neoplasias Gástricas , Estados Unidos , Humanos , Neoplasias Gástricas/diagnóstico , Comunicação , Escolaridade , Pessoal de Saúde , Reprodutibilidade dos Testes , Gravação em Vídeo , Disseminação de InformaçãoRESUMO
Dysregulation of wild-type p53 turnover is a key cause of hepatocellular carcinoma (HCC), yet its mechanism remains poorly understood. Here, we report that WD repeat and SOCS box containing protein 2 (WSB2), an E3 ubiquitin ligase, is an independent adverse prognostic factor in HCC patients. WSB2 drives HCC tumorigenesis and lung metastasis in vitro and in vivo. Mechanistically, WSB2 is a new p53 destabilizer that promotes K48-linked p53 polyubiquitination at the Lys291 and Lys292 sites in HCC cells, leading to p53 proteasomal degradation. Degradation of p53 causes IGFBP3-dependent AKT/mTOR signaling activation. Furthermore, WSB2 was found to bind to the p53 tetramerization domain via its SOCS box domain. Targeting mTOR with everolimus, an oral drug, significantly blocked WSB2-triggered HCC tumorigenesis and metastasis in vivo. In clinical samples, high expression of WSB2 was associated with low wild-type p53 expression and high p-mTOR expression. These findings demonstrate that WSB2 is overexpressed and degrades wild-type p53 and then activates the IGFBP3-AKT/mTOR axis, leading to HCC tumorigenesis and lung metastasis, which indicates that targeting mTOR could be a new therapeutic strategy for HCC patients with high WSB2 expression and wild-type p53.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Carcinogênese , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/uso terapêutico , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/genéticaRESUMO
The role of N6-methyladenosine (m6A) modification of host mRNA during bacterial infection is unclear. Here, we show that Helicobacter pylori infection upregulates host m6A methylases and increases m6A levels in gastric epithelial cells. Reducing m6A methylase activity via hemizygotic deletion of methylase-encoding gene Mettl3 in mice, or via small interfering RNAs targeting m6A methylases, enhances H. pylori colonization. We identify LOX-1 mRNA as a key m6A-regulated target during H. pylori infection. m6A modification destabilizes LOX-1 mRNA and reduces LOX-1 protein levels. LOX-1 acts as a membrane receptor for H. pylori catalase and contributes to bacterial adhesion. Pharmacological inhibition of LOX-1, or genetic ablation of Lox-1, reduces H. pylori colonization. Moreover, deletion of the bacterial catalase gene decreases adhesion of H. pylori to human gastric sections. Our results indicate that m6A modification of host LOX-1 mRNA contributes to protection against H. pylori infection by downregulating LOX-1 and thus reducing H. pylori adhesion.