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Epidermal growth factor receptor 2-positive breast cancer (HER2+ BC) is a highly invasive and malignant type of tumor. Due to its resistance to HER2-targeted therapy, HER2+ BC has a poor prognosis and a tendency for metastasis. Understanding the mechanisms underlying this resistance and developing effective treatments for HER2+ BC are major research challenges. The phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) pathway, which is frequently altered in cancers, plays a critical role in cellular proliferation and drug resistance. This signaling pathway activates various downstream pathways and exhibits complex interactions with other signaling networks. Given the significance of the PI3K/AKT pathway in HER2+ BC, several targeted drugs are currently in development. Multiple drugs have entered clinical trials or gained market approval, bringing new hope for HER2+ BC therapy. However, new drugs and therapies raise concerns related to safety, regulation, and ethics. Populations of different races and disease statuses exhibit varying responses to treatments. Therefore, in this review, we summarize current knowledge on the alteration and biological roles of the PI3K/AKT pathway, as well as its clinical applications and perspectives, providing new insights for advancing targeted therapies in HER2+ BC. [ABSTRACT FROM AUTHOR]

Enterovirus‐D68 (EV‐D68) was first identified in 1962 in pediatric patients with acute respiratory conditions in California, USA (US). From the 1970s to 2005, EV‐D68 was underestimated due to limited data and serotyping methods. In 2014, the United States experienced outbreaks of acute flaccid myelitis (AFM) in children EV‐D68 positive. WIN‐like compounds (pleconaril, pocapavir, and vapendavir) bind to the virus capsid and have been tested against various enteroviruses (EVs) in clinical trials. However, these compounds encountered issues with resistance and adverse effects, which impeded their approval by the Food and Drug Administration (FDA). Presently, the medical field lacks FDA‐approved antiviral treatments or vaccines for EV‐D68. Ongoing research efforts are dedicated to identifying viable therapeutics to address EV‐D68 infections. This review explores the current advancements in antiviral therapies and potential therapeutics to mitigate the significant impact of EV‐D68 infection control. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is a prevalent malignant tumor worldwide, characterized by high malignancy and rapid progression. Most cases are diagnosed at intermediate to advanced stages. Current treatment methods have limited efficacy, resulting in high recurrence rates and poor prognosis. Radical hepatectomy remains the primary treatment for HCC, complemented by radiotherapy, chemotherapy, targeted therapy, and immunotherapy. Despite significant improvement in patient prognosis with radical hepatectomy, the five-year survival rate post-surgery remains low; thus necessitating exploration of more effective therapeutic approaches. Ferroptosis is a recently discovered form of cell death that can modulate the occurrence and development of HCC through various mechanisms. This article aims to elucidate the mechanism of ferroptosis and its impact on HCC development to provide novel insights for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Background: Poly C Binding Protein 1 (PCBP1) belongs to the heterogeneous nuclear ribonucleoprotein family. It is a multifunctional protein that participates in several functional circuits and plays a variety of roles in cellular processes. Although PCBP1 has been identified in several mammals, its function in porcine was unclear. Results: In this study, we cloned the gene of porcine PCBP1 and analyzed its evolutionary relationships among different species. We found porcine PCBP1 protein sequence was similar to that of other animals. The subcellular localization of PCBP1 in porcine kidney cells 15 (PK-15) cells was analyzed by immunofluorescence assay (IFA) and revealed that PCBP1 was mainly localized to the nucleus. Reverse transcription-quantitative PCR (RT-qPCR) was used to compare PCBP1 mRNA levels in different tissues of 30-day-old pigs. Results indicated that PCBP1 was expressed in various tissues and was most abundant in the liver. Finally, the effects of PCBP1 on cell cycle and apoptosis were investigated following its overexpression or knockdown in PK-15 cells. The findings demonstrated that PCBP1 knockdown arrested cell cycle in G0/G1 phase, and enhanced cell apoptosis. Conclusions: Porcine PCBP1 is a highly conserved protein, plays an important role in determining cell fate, and its functions need further study. [ABSTRACT FROM AUTHOR]

δ-Aminolevulinic acid dehydratase (ALAD) is a key enzyme of the cytoplasmic heme biosynthesis pathway. The primary structure of the ALAD gene, the multimeric structure of the ALAD/hemB protein, and ALAD expression during the annual reproductive cycle were studied in the cold-water marine sponge Halisarca dujardinii. The results implicated the GATA-1 transcription factor and DNA methylation in regulating ALAD expression. Re-aggregation of sponge cells was accompanied by a decrease in ALAD expression and a change in the cell content of an active ALAD/hemB form. Further study of heme biosynthesis and the role of ALAD/hemB in morphogenesis of basal animals may provide new opportunities for treating pathologies in higher animals. [ABSTRACT FROM AUTHOR]

Portal vein tumor thrombosis (PVTT), a common complication of advanced hepatocellular carcinoma (HCC), remains the bottleneck of the treatments. Liver cancer cells potentially experienced multi-steps during PVTT process, including cancer cells leave from cancer nest, migrate in extracellular matrix, invade the vascular barrier, and colonize in the portal vein. Accumulated evidences have revealed numerous of molecular mechanisms including genetic and epigenetic regulation, cancer stem cells, immunosuppressive microenvironment, hypoxia, et al. contributed to the PVTT formation. In this review, we discuss state-of-the-art PVTT research on the potential molecular mechanisms and experimental models. In addition, we summarize PVTT-associated clinical trials and current treatments for PVTT and suppose perspectives exploring the molecular mechanisms and improving PVTT-related treatment for the future. [ABSTRACT FROM AUTHOR]

Long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and development of endometrial carcinoma (EC). Here, using RNA sequencing analysis, we systemically screened and identified the lncRNA eukaryotic translation initiation factor 1A, X‐linked (EIF1AX)‐AS1, which is aberrantly downregulated in clinical EC tissues and closely correlated with tumor type. EIF1AX‐AS1 markedly inhibited EC cell proliferation and promoted apoptosis in vitro and in vivo. Mechanistically, EIF1AX‐AS1 interacts with EIF1AX mRNA and poly C binding protein 1 (PCBP1), which promote EIF1AX mRNA degradation. Intriguingly, by interacting with internal ribosome entry site‐related protein Y‐box binding protein 1 (YBX‐1), EIF1AX promotes c‐Myc translation through the internal ribosome entry site pathway. c‐Myc promotes EIF1AX transcription and thus forms a feed‐forward loop to regulate EC cell proliferation. Taken together, these data reveal new insights into the biology driving EC proliferation and highlights the potential of lncRNAs as biomarkers for prognosis and future therapeutic targets for cancer. [ABSTRACT FROM AUTHOR]

Pigs play an important role in agriculture and biomedicine. The globally developing swine industry must address the challenges presented by swine-origin viruses, including ASFV (African swine fever virus), PRRSV (porcine reproductive and respiratory syndrome virus), PEDV (porcine epidemic diarrhea virus), PRV (pseudorabies virus), CSFV (classical swine fever virus), TGEV (transmissible gastroenteritis virus), et al. Despite sustained efforts by many government authorities, these viruses are still widespread. Currently, gene-editing technology has been successfully used to generate antiviral pigs, which offers the possibility for increasing animal disease tolerance and improving animal economic traits in the future. Here, we summarized the current advance in knowledge regarding the host factors in virus infection and the current status of genetically modified pigs that are resistant to virus infection in the world. There has not been any report on PEDV-resistant pigs, ASFV-resistant pigs, and PRV-resistant pigs owing to the poor understanding of the key host factors in virus infection. Furthermore, we summarized the remaining problems in producing virus-resistant pigs, and proposed several potential methods to solve them. Using genome-wide CRISPR/Cas9 library screening to explore the key host receptors in virus infection may be a feasible method. At the same time, exploring the key amino acids of host factors in virus infection with library screening based on ABEs and CBEs (Bes) may provide creative insight into producing antiviral pigs in the future. [ABSTRACT FROM AUTHOR]