PPIH as a poor prognostic factor increases cell proliferation and m6A RNA methylation in hepatocellular carcinoma.

RNA-binding proteins (RBPs) play a crucial role in the biological processes of liver hepatocellular carcinoma (LIHC). Peptidyl-prolyl cis-trans isomerase H (PPIH), an RBP, possesses prolyl isomerase activity and functions as a protein chaperone. The relationship between PPIH and LIHC has not yet been fully elucidated. This study elucidated potential mechanisms through which PPIH affects the prognosis of LIHC. Bioinformatics analysis and in vitro experiments revealed that PPIH expression was higher in LIHC tissues than in normal tissues. PPIH was identified as an independent prognostic factor, with high PPIH expression being associated with worse prognoses. Moreover, PPIH increased the m6A RNA methylation level and promoted cell proliferation by modulating DNA replication and the expression of cell cycle-related genes in LIHC cells. Bioinformatics analysis also revealed that PPIH expression increased immune cell infiltration and the expression of immune checkpoint proteins. Collectively, these findings indicate that PPIH might promote LIHC progression by enhancing the m6A RNA methylation level, increasing cell proliferation, and altering the tumor immune microenvironment. Our study demonstrates that PPIH, as a poor prognostic factor, may lead to LIHC malignancy through multiple pathways. Further in-depth research on this topic is warranted.

TESC associated with poor prognosis enhances cancer stemness and migratory properties in liver cancer.

Liver cancer stem cells (LCSCs) are responsible for recurrence, metastasis, and drug resistance in liver cancer. However, the genes responsible for inducing LCSCs have not been fully identified. Based on our previous study, we found that tescalcin (TESC), a calcium-binding EF hand protein that plays a crucial role in chromatin remodeling, transcriptional regulation, and epigenetic modifications, was up-regulated in LCSCs of spheroid cultures. By searching the Cancer Genome Atlas, International Cancer Genome Consortium, Human Protein Atlas, and Kaplan-Meier Plotter databases, we found that TESC expression was significantly elevated in liver cancer compared with that in normal liver tissue and was predictive of a decreased overall survival rate. Multivariate Cox analysis revealed TESC to be an independent prognostic factor for survival. High TESC expression was positively associated with cancer stem cell pathways, cancer stem cell surface markers, stemness transcription factors, epithelial-mesenchymal transition (EMT) factors, immune checkpoint proteins, and various cancer-related biological processes in liver cancer. Furthermore, TESC was implicated as promoting cancer stem cell properties through its influence on EMT. We demonstrated that TESC is a novel stemness-related gene that can serve as an independent prognostic factor for liver cancer.

Research integrity in the era of artificial intelligence: Challenges and responses.

The application of artificial intelligence (AI) technologies in scientific research has significantly enhanced efficiency and accuracy but also introduced new forms of academic misconduct, such as data fabrication and text plagiarism using AI algorithms. These practices jeopardize research integrity and can mislead scientific directions. This study addresses these challenges, underscoring the need for the academic community to strengthen ethical norms, enhance researcher qualifications, and establish rigorous review mechanisms. To ensure responsible and transparent research processes, we recommend the following specific key actions: Development and enforcement of comprehensive AI research integrity guidelines that include clear protocols for AI use in data analysis and publication, ensuring transparency and accountability in AI-assisted research. Implementation of mandatory AI ethics and integrity training for researchers, aimed at fostering an in-depth understanding of potential AI misuses and promoting ethical research practices. Establishment of international collaboration frameworks to facilitate the exchange of best practices and development of unified ethical standards for AI in research. Protecting research integrity is paramount for maintaining public trust in science, making these recommendations urgent for the scientific community consideration and action.

Ethical perspective on AI hazards to humans: A review.

This article explores the potential ethical hazards of artificial intelligence (AI) on society from an ethical perspective. We introduce the development and application of AI, emphasizing its potential benefits and possible negative impacts. We particularly examine the application of AI in the medical field and related ethical and legal issues, and analyze potential hazards that may exist in other areas of application, such as autonomous driving, finance, and security. Finally, we offer recommendations to help policymakers, technology companies, and society as a whole address the potential hazards of AI. These recommendations include strengthening regulation and supervision of AI, increasing public understanding and awareness of AI, and actively exploring how to use the advantages of AI to achieve a more just, equal, and sustainable social development. Only by actively exploring the advantages of AI while avoiding its negative impacts can we better respond to future challenges.

T-cell exhaustion and stemness in antitumor immunity: Characteristics, mechanisms, and implications.

T cells play a crucial role in the regulation of immune response and are integral to the efficacy of cancer immunotherapy. Because immunotherapy has emerged as a promising treatment for cancer, increasing attention has been focused on the differentiation and function of T cells in immune response. In this review, we describe the research progress on T-cell exhaustion and stemness in the field of cancer immunotherapy and summarize advances in potential strategies to intervene and treat chronic infection and cancer by reversing T-cell exhaustion and maintaining and increasing T-cell stemness. Moreover, we discuss therapeutic strategies to overcome T-cell immunodeficiency in the tumor microenvironment and promote continuous breakthroughs in the anticancer activity of T cells.

Macrophages Are a Double-Edged Sword: Molecular Crosstalk between Tumor-Associated Macrophages and Cancer Stem Cells.

Cancer stem cells (CSCs) are a subset of highly tumorigenic cells in tumors. They have enhanced self-renewal properties, are usually chemo-radioresistant, and can promote tumor recurrence and metastasis. They can recruit macrophages into the tumor microenvironment and differentiate them into tumor-associated macrophages (TAMs). TAMs maintain CSC stemness and construct niches that are favorable for CSC survival. However, how CSCs and TAMs interact is not completely understood. An understanding on these mechanisms can provide additional targeting strategies for eliminating CSCs. In this review, we comprehensively summarize the reported mechanisms of crosstalk between CSCs and TAMs and update the related signaling pathways involved in tumor progression. In addition, we discuss potential therapies targeting CSC-TAM interaction, including targeting macrophage recruitment and polarization by CSCs and inhibiting the TAM-induced promotion of CSC stemness. This review also provides the perspective on the major challenge for developing potential therapeutic strategies to overcome CSC-TAM crosstalk.

Alanine-Glyoxylate Aminotransferase Sustains Cancer Stemness Properties through the Upregulation of SOX2 and OCT4 in Hepatocellular Carcinoma Cells.

Liver cancer stem cells (LCSCs) are a small subset of oncogenic cells with a self-renewal ability and drug resistance, and they promote the recurrence and metastasis of hepatocellular carcinoma (HCC). However, the mechanisms regulating LCSCs have not been fully explored. By enriching LCSCs from spheroid cultures and performing transcriptomic analysis, we determined that alanine-glyoxylate aminotransferase (AGXT), which participates in the metabolism of serine and glycine, was significantly upregulated in spheroid cultures, and its function in LCSCs remains unknown. Through the exogenous overexpression or short hairpin RNA knockdown of AGXT in HCC cells, we observed that changes in the AGXT level did not affect the spheroid ability and population of LCSCs. The knockdown of AGXT in LCSCs reduced the number of spheroids and the population of LCSCs; this implies that AGXT is required for the maintenance of cancer stemness rather than as a driver of LCSCs. Mechanistically, AGXT may sustain the self-renewal potential of LCSCs by upregulating the expression of SRY-box transcription factor 2 (SOX2) and octamer-binding transcription factor 4 (OCT4), two well-known master regulators of cancer stemness. Taken together, our study demonstrates the role of AGXT in supporting LCSCs; thus, AGXT merits further exploration.

Potential of E3 Ubiquitin Ligases in Cancer Immunity: Opportunities and Challenges.

Cancer immunotherapies, including immune checkpoint inhibitors and immune pathway-targeted therapies, are promising clinical strategies for treating cancer. However, drug resistance and adverse reactions remain the main challenges for immunotherapy management. The future direction of immunotherapy is mainly to reduce side effects and improve the treatment response rate by finding new targets and new methods of combination therapy. Ubiquitination plays a crucial role in regulating the degradation of immune checkpoints and the activation of immune-related pathways. Some drugs that target E3 ubiquitin ligases have exhibited beneficial effects in preclinical and clinical antitumor treatments. In this review, we discuss mechanisms through which E3 ligases regulate tumor immune checkpoints and immune-related pathways as well as the opportunities and challenges for integrating E3 ligases targeting drugs into cancer immunotherapy.

[Clinical observation on acupuncture combined with microorganism pharmaceutical preparations for treatment of irritable bowel syndrome of constipation type].

OBJECTIVE: To explore the best program for treatment of irritable bowel syndrome (IBS) of constipation type. METHODS: Ninety-five cases of IBS were randomly divided into 3 groups. Group A (n = 30) were treated by acupuncture combined with microorganism pharmaceutical preparations, group B (n = 35) by oral administration of medicine for loosening the bowel to relieve constipation plus microorganism pharmaceutical preparations, and group C (n = 30) by simple acupuncture. RESULTS: The total effective rates were 90.0%, 77.2% and 66.7%, in the group A, B and C, respectively, with a very significant differences as the group A compared with those in the groups B, C (P < 0.01), and with no significant difference as the group B compared with that of the group C (P > 0. 05). The intestinal available bacteria, bilidobacteria and lactobacillus, increased and enteric bacilli decreased in varying degrees in the 3 groups. CONCLUSION: Acupuncture combined with microorganism pharmaceutical preparations has a better therapeutic effect on irritable bowel syndrome of constipation type.