Functional Materials for Subcellular Targeting Strategies in Cancer Therapy: Progress and Prospects.

Neoadjuvant and adjuvant therapies have made significant progress in cancer treatment. However, tumor adjuvant therapy still faces challenges due to the intrinsic heterogeneity of cancer, genomic instability, and the formation of an immunosuppressive tumor microenvironment. Functional materials possess unique biological properties such as long circulation times, tumor-specific targeting, and immunomodulation. The combination of functional materials with natural substances and nanotechnology has led to the development of smart biomaterials with multiple functions, high biocompatibilities, and negligible immunogenicities, which can be used for precise cancer treatment. Recently, subcellular structure-targeting functional materials have received particular attention in various biomedical applications including the diagnosis, sensing, and imaging of tumors and drug delivery. Subcellular organelle-targeting materials can precisely accumulate therapeutic agents in organelles, considerably reduce the threshold dosages of therapeutic agents, and minimize drug-related side effects. This review provides a systematic and comprehensive overview of the research progress in subcellular organelle-targeted cancer therapy based on functional nanomaterials. Moreover, it explains the challenges and prospects of subcellular organelle-targeting functional materials in precision oncology. The review will serve as an excellent cutting-edge guide for researchers in the field of subcellular organelle-targeted cancer therapy.

A Pyroptosis-Related Gene Signature Predicts Prognosis and Immune Microenvironment for Breast Cancer Based on Computational Biology Techniques.

Breast cancer (BC) is a malignant tumor with high morbidity and mortality, which seriously threatens women's health worldwide. Pyroptosis is closely correlated with immune landscape and the tumorigenesis and development of various cancers. However, studies about pyroptosis and immune microenvironment in BC are limited. Therefore, our study aimed to investigate the potential prognostic value of pyroptosis-related genes (PRGs) and their relationship to immune microenvironment in BC. First, we identified 38 differentially expressed PRGs between BC and normal tissues. Further on, the least absolute shrinkage and selection operator (LASSO) Cox regression and computational biology techniques were applied to construct a four-gene signature based on PRGs and patients in The Cancer Genome Atlas (TCGA) cohort were classified into high- and low-risk groups. Patients in the high-risk group showed significantly lower survival possibilities compared with the low-risk group, which was also verified in an external cohort. Furthermore, the risk model was characterized as an independent factor for predicting the overall survival (OS) of BC patients. What is more important, functional enrichment analyses demonstrated the robust correlation between risk score and immune infiltration, thereby we summarized genetic mutation variation of PRGs, evaluated the relationship between PRGs, different risk group and immune infiltration, tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint blockers (ICB), which indicated that the low-risk group was enriched in higher TMB, more abundant immune cells, and subsequently had a brighter prognosis. Except for that, the lower expression of PRGs such as GZMB, IL18, IRF1, and GZMA represented better survival, which verified the association between pyroptosis and immune landscape. In conclusion, we performed a comprehensive bioinformatics analysis and established a four-PRG signature consisting of GZMB, IL18, IRF1, and GZMA, which could robustly predict the prognosis of BC patients.

The clinical value of miRNA-21 in cervical cancer: A comprehensive investigation based on microarray datasets.

Previous work has demonstrated that the expression of microRNA-21 (miR-21) is implicated in cervical cancer (CC). However, little is known regarding its associations with clinical parameters. We first conducted a meta-analysis using data from Gene Expression Omnibus (GEO) microarrays and The Cancer Genome Atlas (TCGA). Then, enrichment analysis and hub gene screening were performed by bioinformatic methods. Finally, the role of the screened target genes in CC was explored. According to the meta-analysis, the expression of miR-21 in cancer tissues was higher than in adjacent nontumor tissues (P < 0.05). In addition, 46 genes were predicted as potential targets of miR-21. After enrichment analyses, it was detected that these genes were enriched in various cancer pathways, including the phosphatidylinositol signaling system and mammalian target of rapamycin (mTOR) signaling pathway. In this study, bioinformatic tools and meta-analysis validated that miR-21 may function as a highly sensitive and specific marker for the diagnosis of CC, which may provide a novel approach to the diagnosis and treatment of CC.

Detection of folate receptor-positive circulating tumor cells as a biomarker for diagnosis, prognostication, and therapeutic monitoring in breast cancer.

OBJECTIVES: This study is to explore the clinical significance of folate receptor-positive circulating tumor cells (FR+ CTC) in the early diagnosis and disease progress in patients with breast cancer. METHODS: Folate receptor-positive circulating tumor cells was enriched from peripheral blood of the patients with immunomagnetic separation method and quantitated by folate receptor on the CTC with the ligand-targeted PCR. RESULTS: The levels of FR+ CTC were significantly higher in breast cancer patients compared with healthy controls. Detective rate of FR+ CTC was decreased in 19 of 27 patients underwent the surgery in 2 weeks post-operation compared with pre-operation; statistical analysis showed the difference was significant. We also found that the combination of FR+ CTC, CEA, CA125, and CA153 can significantly improve the diagnostic efficiency for breast cancer. CONCLUSIONS: This study showed the detective rate of FR+ CTC is significantly increased in the patients with breast cancer, and the detective level is associated with disease progress.

Application and prospect of artificial intelligence in digestive endoscopy.

INTRODUCTION: With the progress of science and technology, artificial intelligence represented by deep learning has gradually begun to be applied in the medical field. Artificial intelligence has been applied to benign gastrointestinal lesions, tumors, early cancer, inflammatory bowel disease, gallbladder, pancreas, and other diseases. This review summarizes the latest research results on artificial intelligence in digestive endoscopy and discusses the prospect of artificial intelligence in digestive system diseases. AREAS COVERED: We retrieved relevant documents on artificial intelligence in digestive tract diseases from PubMed and Medline. This review elaborates on the knowledge of computer-aided diagnosis in digestive endoscopy. EXPERT OPINION: Artificial intelligence significantly improves diagnostic accuracy, reduces physicians' workload, and provides a shred of evidence for clinical diagnosis and treatment. Shortly, artificial intelligence will have high application value in the field of medicine.

DNA Methylation and Recurrent Pregnancy Loss: A Mysterious Compass?

Recurrent pregnancy loss (RPL) is a common and severe pathological pregnancy, whose pathogenesis is not fully understood. With the development of epigenetics, the study of DNA methylation, provides a new perspective on the pathogenesis and therapy of RPL. The abnormal DNA methylation of imprinted genes, placenta-specific genes, immune-related genes and sperm DNA may, directly or indirectly, affect embryo implantation, growth and development, leading to the occurrence of RPL. In addition, the unique immune tolerogenic microenvironment formed at the maternal-fetal interface has an irreplaceable effect on the maintenance of pregnancy. In view of these, changes in the cellular components of the maternal-fetal immune microenvironment and the regulation of DNA methylation have attracted a lot of research interest. This review summarizes the research progress of DNA methylation involved in the occurrence of RPL and the regulation of the maternal-fetal immune microenvironment. The review provides insights into the personalized diagnosis and treatment of RPL.

Silencing of lncRNA UCA1 inhibited the pathological progression in PCOS mice through the regulation of PI3K/AKT signaling pathway.

BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common hormonal disorder among reproductive-aged women worldwide, however, the mechanisms and progression of PCOS still unclear due to its heterogeneous nature. Using the human granulosa-like tumor cell line (KGN) and PCOS mice model, we explored the function of lncRNA UCA1 in the pathological progression of PCOS. RESULTS: CCK8 assay and Flow cytometry were used to do the cell cycle, apoptosis and proliferation analysis, the results showed that UCA1 knockdown in KGN cells inhibited cell proliferation by blocking cell cycle progression and promoted cell apoptosis. In the in vivo experiment, the ovary of PCOS mice was injected with lentivirus carrying sh-UCA1, the results showed that knockdown of lncRNA UCA1 attenuated the ovary structural damage, increased the number of granular cells, inhibited serum insulin and testosterone release, and reduced the pro-inflammatory cytokine production. Western blot also revealed that UCA1 knockdown in PCOS mice repressed AKT activation, inhibitor experiment demonstrated that suppression of AKT signaling pathway, inhibited the cell proliferation and promoted apoptosis. CONCLUSIONS: Our study revealed that, in vitro, UCA1 knockdown influenced the apoptosis and proliferation of KGN cells, in vivo, silencing of UCA1 regulated the ovary structural damage, serum insulin release, pro-inflammatory production, and AKT signaling pathway activation, suggesting lncRNA UCA1 plays an important role in the pathological progression of PCOS.

New rapid method to detect BCR-ABL fusion genes with multiplex RT-qPCR in one-tube at a time.

Fast identification of BCR-ABL fusion genes is critical for precise diagnosis, risk stratification and therapy scheme selection in leukemia. More convenient methods are needed for quickly detection of the BCR-ABL fusion genes. Multiplex fluorescent reverse transcription quantitative real-time PCR (Multiplex RT-qPCR) methods are developed for detection of the at least 14 subtypes of BCR-ABL fusion genes in one tube at a time by using patients' bone marrow samples. The new Multiplex RT-qPCR method could quickly detect BCR-ABL fusion genes with sensitivity up to 10-106 copies. It can detect the fusion genes in patients' bone marrow samples containing any subtypes of the major bcr (M-bcr) e13a2, e14a2, e13a3 and e14a3, the minor bcr (m-bcr) e1a2 and e1a3, the micro bcr (µ-bcr) e19a2 and e19a3, and the nano bcr (n-bcr) e6a2 and e6a3. The specificity is comparable to the FISH methods. The cutoff for clinical diagnosis of BCR-ABL(+) is also determined by testing in clinical chronic myeloid leukemia samples. This is a new fast method with high sensitivity and specificity for clinical detection of BCR-ABL fusion genes. It will benefit the precise diagnosis, targeted therapy and minimal residual disease (MRD) monitoring in leukemia.

5'/ 3' imbalance strategy to detect ALK fusion genes in circulating tumor RNA from patients with non-small cell lung cancer.

BACKGROUND: Detecting an ALK fusion gene in patients with non-small cell lung cancer (NSCLC) could provide evidence to guide individualized therapy. METHODS: The 5'/3' imbalance strategy for quantitative reverse transcription-PCR (RT-qPCR) was developed to detect ALK fusion genes in circulating tumor RNA (ctRNA) of NSCLC patients. RESULTS: This method was validated in patients with the ALK fusion gene confirmed by next generation sequencing (NGS). The amount of the ALK fusion gene detected by the new method ranged from 33.2 to 987.4, (mean 315.2), in the patients confirmed to have the ALK fusion gene (+). This is much higher than the amount of fusion gene detected in the patients who are negative for the ALK fusion gene (-). The amount detected in the ALK fusion gene (-) samples ranged from 0.36 to 13.04, (mean 4.58). In 188 NSCLC patients, the specificity and sensitivity of the method was compared to that of the FISH method. About 10.64% of the patients showed higher ALK fusion gene expression, and were classified as ALK fusion gene (+). This is identical to the percentage of patients detected by the FISH method to be ALK fusion gene (+). The cutoff value for diagnosis of ALK fusion (+) is 32.9 as determined by this method. CONCLUSIONS: A new RT-PCR method using a 5'/3' imbalance strategy was developed, with high specificity and sensitivity, for detection of the ALK fusion gene in ctRNA of NSCLC patients. This method can rapidly detect ALK fusion genes in patients, which will be helpful for guiding targeted therapy, particularly the individualized usage of TKIs in these patients.

1,25-Dihydroxyvitamin D3 and cisplatin synergistically induce apoptosis and cell cycle arrest in gastric cancer cells.

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] plays an anticancer role in multiple types of cancer and potentiates the cytotoxic effects of several common chemotherapeutic agents. The hypercalcemia caused by 1,25(OH)2D3 alone or resistance to cisplatin weaken the anticancer effects of vitamin D. Thus, in this study, we aimed to investigate the synergistic effects of 1,25(OH)2D3 and cisplatin on the apoptosis and cell cycle progression of gastric cancer cells. BGC-823 human gastric cancer cells were treated with 1,25(OH)2D3 or cisplatin alone, or a combination of both agents. Cell apoptosis was assessed by TUNEL assay and flow cytometry. The expression of the apoptosis-related proteins, poly(ADP-ribose) polymerase (PARP), Bax, Bcl-2, caspase-3 and caspase-8, was examined using immunoblot analysis. ERK and AKT phosphorylation were examined by immunoblot analysis. The cell cycle distribution was determined by propidium iodide staining and flow cytometric analysis. p21 and p27 protein expression was also examined using immunoblot analysis. Our results revealed that co-treatment with 1,25(OH)2D3 enhanced cisplatin-induced apoptosis and upregulated the expression of Bax, and promoted the cleavage of PARP and caspase-3. The phosphorylation levels of ERK and AKT were reduced following combined treatment with 1,25(OH)2D3 and cisplatin. The percentage of cells in the G0/G1 phase was greater in the cells treated with the combined treatment than in those treated with either 1,25(OH)2D3 or cisplatin alone. p21 and p27 expression was upregulated following co-treatment with both agents. The results of this study suggest that 1,25(OH)2D3 potentiates cisplatin-mediated cell growth inhibition and cell apoptosis, which involves the upregulation of Bax, a decrease in ERK and AKT phosphorylation levels, and increased p21 and p27 levels.

Tumor-suppressive effects of 1, 25-dihydroxyvitamin D3 in gastric cancer cells.

BACKGROUNDS/AIMS: It has been previously demonstrated that vitamin D acts as a prognostic indicator of gastric cancer and may be correlated with the incidence risk of gastric cancer. However, the effect of 1,25-dihydroxyvitamin D3 on the apoptosis of human gastric cancer cells is unclear. The aim of this study was to determine whether 1,25-dihydroxyvitamin D3 induced the cellular apoptosis of BGC-823 gastric cancer cells and to determine the potential mechanism of action. METHODOLOGY: We demonstrate that 1,25-dihydroxyvitamin D3 induced the apoptosis of gastric cancer cells via the processing of PARP and cleavage of caspase 3. Additionally, an increase in BAX expression and a decrease in ERK1/2 and AKT phosphorylation were associated with 1,25-dihydroxyvitamin D3-induced apoptosis. The mRNA expression levels of VDR, CYP24A1, and p21 were increased significantly following 1,25-dihydroxyvitamin D3 treatment. CONCLUSIONS: These findings suggest that 1,25-dihydroxyvitamin D3 exerts tumor-suppressive effects on BGC-823 human gastric cancer cells.

[Effect of chronic Toxoplasma infection on the spatial learning and memory capability in mice].

OBJECTIVE: To investigate the effect of chronic infection of Toxoplasma gondii on the spatial learning and memory capability in mice. METHODS: Toxoplasma tachyzoites (RH strain) were reanimated at 37 degrees C after 15 days' storage at -20 degrees C, and injected intraperitoneally to mice of the experimental group each with 7.7 x 10(5). Normal saline was given to the control group, 0.5 ml per mouse. Two months later, all mice were tested in the Morris Water Maze. Smears of the mice brain homogenate and pathological sections were examined. RESULTS: (1) The density of cysts in the brain homogenate was 15/HP, and there was no evident pathological change in the hippocampus and adjacent areas of mice in the brain in the experimental mice. (2) Latency to platform, cumulative distance to the platform, total distance traveled in both experimental and control groups decreased significantly with the increase of training days (P < 0.01). The latency and cumulative distance in experimental group were significantly longer than that of the control group (P < 0.01). (3) The searching strategy of mice in the experimental group was significantly different from that of the control group. CONCLUSION: Toxoplasma tachyzoites can induce chronic infection in mice and the infection can damage at some extent the spatial learning and memory capability of mice.