Nasopharyngeal carcinoma (NPC) is a type of malignant tumors commonly found in Southeast Asia and China, with insidious onset and clinical symptoms. N6-methyladenosine (m6A) modification significantly contributes to tumorigenesis and progression by altering RNA secondary structure and influencing RNA-protein binding at the transcriptome level. However, the mechanism and role of abnormal m6A modification in nasopharyngeal carcinoma remain unclear.
The existence of cancer stem cells (CSCs) is considered as a direct reason for the failure of clinic treatment in hepatocellular carcinoma (HCC). Growing evidences have demonstrated that miRNAs play an important role in regulation of stem cell proliferation, differentiation and self-renewal and their aberrances cause the formation of CSCs and eventually result in carcinogenesis. We recently identified miRNA-148b as one of the miRNAs specifically down-regulated in side population (SP) cells of PLC/PRF/5 cell line. However, it remains elusive how miRNA-148b regulates CSC properties in HCC. In the present study, we observed that overexpression or knockdown of miR-148b through lentiviral transfection could affect the proportion of SP cells as well as CSC-related gene expression in HCC cell lines. In addition, miR-148b blocking could stimulate cell proliferation, enhance chemosensitivity, as well as increase cell metastasis and angiogenesis in vitro. More importantly, miR-148b could significantly suppress tumorigenicity in vivo. Further studies revealed that Neuropilin-1 (NRP1), a transmembrane co-receptor involved in tumour initiation, metastasis and angiogenesis, might be the direct target of miRNA-148b. Taking together, our findings define that miR-148b might play a critical role in maintenance of SP cells with CSC properties by targeting NRP1 in HCC. It is the potential to develop a new strategy specifically targeting hepatic CSCs (HCSCs) through restoration of miR-148b expression in future therapy.
Six new compounds, penicitrinols L-O (1-4), penicillenols D1 (9) and D2 (10), together with six known compounds were isolated from the marine--derived fungus Penicillium citrinum.Their structures were elucidated on the basis of comprehensive spectral analysis and chemical methods.All the new compounds were evaluated for their cytotoxic effects on the A-549, HL-60 and SW-620 cell lines by the MTT method.Penicitrinols L (1) and M (2) showed weak cytotoxicities against SW-620 cell line, while penicillenols D1 (9) and D2 (10) showed weak cytotoxicities against A-549 and HL-60 cell lines, respectively.Penicillium citrinum is a rich source of various anticancer compounds. 1Our previous chemical investigation of P. citrinum resulted in the isolation of seven new citrinin derivatives, penicitrinols C-I, 1a,1f two new tumonoic acids (K and L), 1g and a new benzene derivative, 1g which showed different degrees of cytotoxicities against the P388, HL-60 and A-375 cell lines.Our continuing search for bioactive compounds from this organism has further resulted in the isolation of another four new citrinin derivatives, namely, penicitrinols L-O (1-4), along with two new tetramic acid analogues, namely, penicillenols D1 and D2 (9, 10).Additional, six known compounds, including penicitrinol J (5), 2 citrinin (6), 2 dihydrocitrinone (7), 1g 2, 4-dihydroxy-3, 5, 6-trimethylbenzaldehyde (8), 3 penicillenol B1 (11), 4 and penicillenol B2 (12), 4 were purified together.In this paper, we report the isolation, structural elucidation and bioactivities of these metabolites.
Metastasis and recurrence following surgery are major reasons for the high mortality rate and poor prognosis associated with hepatocellular carcinoma (HCC). Cancer stem cells (CSCs) are thought to be able to cause cancer, and to be the primary cause of tumor recurrence and metastasis. The underlying mechanisms of the metastatic potential of CSCs is poorly understood. In the present study, side population (SP) cells were isolated from 4 HCC cell lines, and their self‑renewal and migratory abilities were compared. The results demonstrate that SP cells from different cell lines exhibited similar self‑renewal abilities but different metastatic potentials. Furthermore, the overall proteomes of the SP cells were systematically quantified. This revealed 11 and 19 differentially expressed proteins (DEPs), upregulated and downregulated, respectively, associated with increased metastatic potential. These proteins were involved in the 'regulation of mRNA processing' and 'cytoskeleton organization' biological processes. The majority of the proteins were involved in 'cell proliferation', 'migration' and 'invasion of cancer', and may promote HCC metastasis in a synergistic manner. The AKT and nuclear factor‑κB signaling pathways may contribute to the regulation of HCC metastasis through regulating the DEPs in SP cells. To the best of our knowledge, the present study is the first to demonstrate the overall proteome difference among SP cells from the different HCC cell lines with different metastatic potentials. The present study provides novel information regarding the metastatic potential of CSCs, which will facilitate further investigation of the topic.
Weakly-supervised temporal action localization aims to localize action instances in videos with only video-level action labels. Existing methods mainly embrace a localization-by-classification pipeline that optimizes the snippet-level prediction with a video classification loss. However, this formulation suffers from the discrepancy between classification and detection, resulting in inaccurate separation of foreground and background (F&B) snippets. To alleviate this problem, we propose to explore the underlying structure among the snippets by resorting to unsupervised snippet clustering, rather than heavily relying on the video classification loss. Specifically, we propose a novel clustering-based F&B separation algorithm. It comprises two core components: a snippet clustering component that groups the snippets into multiple latent clusters and a cluster classification component that further classifies the cluster as foreground or background. As there are no ground-truth labels to train these two components, we introduce a unified self-labeling mechanism based on optimal transport to produce high-quality pseudo-labels that match several plausible prior distributions. This ensures that the cluster assignments of the snippets can be accurately associated with their F&B labels, thereby boosting the F&B separation. We evaluate our method on three benchmarks: THUMOS14, ActivityNet v1.2 and v1.3. Our method achieves promising performance on all three benchmarks while being significantly more lightweight than previous methods. Code is available at https://github.com/Qinying-Liu/CASE
Weakly-supervised temporal action localization (WTAL) intends to detect action instances with only weak supervision, \eg, video-level labels. The current~\textit{de facto} pipeline locates action instances by thresholding and grouping continuous high-score regions on temporal class activation sequences. In this route, the capacity of the model to recognize the relationships between adjacent snippets is of vital importance which determines the quality of the action boundaries. However, it is error-prone since the variations between adjacent snippets are typically subtle, and unfortunately this is overlooked in the literature. To tackle the issue, we propose a novel WTAL approach named Convex Combination Consistency between Neighbors (C$^3$BN). C$^3$BN consists of two key ingredients: a micro data augmentation strategy that increases the diversity in-between adjacent snippets by convex combination of adjacent snippets, and a macro-micro consistency regularization that enforces the model to be invariant to the transformations~\textit{w.r.t.} video semantics, snippet predictions, and snippet representations. Consequently, fine-grained patterns in-between adjacent snippets are enforced to be explored, thereby resulting in a more robust action boundary localization. Experimental results demonstrate the effectiveness of C$^3$BN on top of various baselines for WTAL with video-level and point-level supervisions. Code is at https://github.com/Qinying-Liu/C3BN.
Penicitrinine A, a novel alkaloid with a unique spiro skeleton, was isolated from a marine-derived fungus Penicillium citrinum. In this study, the isolation, structure and biosynthetic pathway elucidation of the new compound were described. This new compound showed anti-proliferative activity on multiple tumor types. Among them, the human malignant melanoma cell A-375 was confirmed to be the most sensitive. Morphologic evaluation, apoptosis rate analysis, Western blot and real-time quantitative PCR (RT-qPCR) results showed penicitrinine A could significantly induce A-375 cell apoptosis by decreasing the expression of Bcl-2 and increasing the expression of Bax. Moreover, we investigated the anti-metastatic effects of penicitrinine A in A-375 cells by wound healing assay, trans-well assay, Western blot and RT-qPCR. The results showed penicitrinine A significantly suppressed metastatic activity of A-375 cells by regulating the expression of MMP-9 and its specific inhibitor TIMP-1. These findings suggested that penicitrinine A might serve as a potential antitumor agent, which could inhibit the proliferation and metastasis of tumor cells.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)