Background Gastric cancer (GC) is considered one of the most lethal malignancies worldwide, which is accompanied by a poor prognosis. Although reports regarding the importance of cancer stem cell (CSC) markers in gastric cancer progression have rapidly developed over the last few decades, their clinicopathological and prognostic values in gastric cancer still remain inconclusive. Therefore, the current meta-analysis aimed to quantitatively re-evaluate the association of CSC markers expression, overall and individually, with GC patients’ clinical and survival outcomes. Methods Literature databases including PubMed, Scopus, ISI Web of Science, and Embase were searched to identify the eligible articles. Hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were recorded or calculated to determine the relationships between CSC markers expression positivity and overall survival (OS), disease-free survival (DFS)/relapse-free survival (RFS), disease-specific survival (DSS)/ cancer-specific survival (CSS), and clinicopathological features. Results We initially retrieved 4,425 articles, of which a total of 66 articles with 89 studies were considered as eligible for this meta-analysis, comprising of 11,274 GC patients. Overall data analyses indicated that the overexpression of CSC markers is associated with TNM stage (OR = 2.19, 95% CI 1.84–2.61, P = 0.013), lymph node metastasis (OR = 1.76, 95% CI 1.54–2.02, P < 0.001), worse OS (HR = 1.65, 95% CI 1.54–1.77, P < 0.001), poor CSS/DSS (HR = 1.69, 95% CI 1.33–2.15, P < 0.001), and unfavorable DFS/RFS (HR = 2.35, 95% CI 1.90–2.89, P < 0.001) in GC patients. However, CSC markers expression was found to be slightly linked to tumor differentiation (OR = 1.25, 95% CI 1.01–1.55, P = 0.035). Sub-analysis demonstrated a significant positive relationship between most of the individual markers, specially Gli-1, Oct-4, CD44, CD44V6, and CD133, and clinical outcomes as well as the reduced survival, whereas overexpression of Lgr-5, Nanog, and sonic hedgehog (Shh) was not found to be related to the majority of clinical outcomes in GC patients. Conclusion The expression of CSC markers is mostly associated with worse outcomes in patients with GC, both overall and individual. The detection of a combined panel of CSC markers might be appropriate as a prognostic stratification marker to predict tumor aggressiveness and poor prognosis in patients with GC, which probably results in identifying novel potential targets for therapeutic approaches.

An efficient and safe delivery system for the transfection of CRISPR plasmid (p/CRISPR) into target cells can open new avenues for the treatment of various diseases. Herein, we design a novel nonvehicle by integrating an arginine-disulfide linker with low-molecular-weight PEI (PEI1.8k) for the delivery of p/CRISPR. These PEI1.8k-Arg nanoparticles facilitate the plasmid release and improve both membrane permeability and nuclear localization, thereby exhibiting higher transfection efficiency compared to native PEI1.8k in the delivery of nanocomplexes composed of PEI1.8k-Arg and p/CRISPR into conventional cells (HEK 293T). This nanovehicle is also able to transfect p/CRISPR in a wide variety of cells, including hard-to-transfect primary cells (HUVECs), cancer cells (HeLa), and neuronal cells (PC-12) with nearly 5–10 times higher efficiency compared to the polymeric gold standard transfection agent. Furthermore, the PEI1.8k-Arg nanoparticles can edit the GFP gene in the HEK 293T-GFP reporter cell line by delivering all possible forms of CRISPR/Cas9 system (e.g. plasmid encoding Cas9 and sgRNA targeting GFP, and Cas9/sgRNA ribonucleoproteins (RNPs) as well as Cas9 expression plasmid and in vitro-prepared sgRNA) into HEK 293T-GFP cells. The successful delivery of p/CRISPR into local brain tissue is also another remarkable capability of these nanoparticles. In view of all the exceptional benefits of this safe nanocarrier, it is expected to break new ground in the field of gene editing, particularly for therapeutic purposes.

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Background: Non-coding RNAs are a cluster of RNAs that do not encode functional proteins, and involve infrastructural and regulatory types, which transfer RNAs (tRNAs) belong to former and small RNAs (sRNA) to the latter one. Recently, tRNA-derived small RNAs (tDRs) were discovered among small non-coding RNA, as the newly discovered regulatory small RNA. It plays a role in pathological and physiological processes, which is frequently dysregulated in gene expression regulation. tsRNAs can be bounded to argonaute proteins and piwi proteins such as miRNAs and piRNAs sequentially. In addition, it can interact with DNA and histone methylation machinery Results: In initial searching, 2744 unique articles were identified by bio electronically search of following databases: PubMed, Embase, Web of Science, Scopus, and google scholar up to 25 February 2020. Finally, after Full-text assessment 48 related article to gene expression profiling tsRNA in cancer were achieved. Conclusions: In this systematic review, we summarized the most recent findings related to the expression of tsRNAs in 17 cancer types. We suggested that tsRNA in cancer field attracted the researchers' focus and effectively facilitated diagnostic and therapy approaches.

Background: Non-coding RNAs are a cluster of RNAs that do not encode functional proteins, and involve infrastructural and regulatory types, which transfer RNAs (tRNAs) belong to former and small RNAs (sRNA) to the latter one. Recently, tRNA-derived small RNAs (tDRs) were discovered among small non-coding RNA, as the newly discovered regulatory small RNA. It plays a role in pathological and physiological processes, which is frequently dysregulated in gene expression regulation. tsRNAs can be bounded to argonaute proteins and piwi proteins such as miRNAs and piRNAs sequentially. In addition, it can interact with DNA and histone methylation machinery Results: In initial searching, 2744 unique articles were identified by bio electronically search of following databases: PubMed, Embase, Web of Science, Scopus, and google scholar up to 25 February 2020. Finally, after Full-text assessment 48 related article to gene expression profiling tsRNA in cancer were achieved. Conclusions: In this systematic review, we summarized the most recent findings related to the expression of tsRNAs in 17 cancer types. We suggested that tsRNA in cancer field attracted the researchers' focus and effectively facilitated diagnostic and therapy approaches. There is little consensus over tRF production mechanism, and dicer-dependent cleavage of mature tRNAs has been suggested [11]. Dysregulation of tsRNAs could interfere in the gene expression in pre/post transcriptional and protein translation. Furthermore, researchers target the tsRNA via gene repression of mRNAs, reported construct silencing, translation inhibition, cell proliferation modulation, exonuclease mRNAs Xrn2-mediated degradation, Ybx1 protein displacement, and sense-induced trans-silencing [12]. Moreover, they have been engaged in cellular and pathophysiological tools, concerning porphyrin biosynthesis, reverse transcription, cell proliferation, differentiation, viability, cell signalling, control of viral replication, and utterly in disease ranging from metabolic disorders and neuro degenerative disease to various types of cancer [13-19]. At first, in 2009, small RNA sequencing data was recognized as tsRNA in prostate cancer [20]. Then, the scientists analyzed more samples, which were abundant in small RNA [21]. They declared that, this biomarker could be potentially applied in many cancer types as a screening and even be targeted for therapy. Moreover, tsRNA is essential in cell cycle proliferation and propagation as well as playing a significant role in tumorigenesis either oncogenic or tumor-suppressor functions [22]. Besides, induction and dysregulation of a set of hypoxia related tsRNAs and also tsRNA suppressive factors in Notch signaling pathway can help in maintenance and metastasis of cancer stem cell [23, 24]. Unfortunately, the exact pathway of tsRNA in cancer has not been clarified yet and we design the schematic of tRNA-derived small RNAs biogenesis in Fig. 1. In this systematic review, we summarized the frequency and function of tsRNAs in different cancer types. Met...