Nucleocapsid 203 mutations enhance SARS-CoV-2 immune evasion

Previous work indicated that the nucleocapsid 203 mutation increase the virulence and transmission of the SARS-CoV-2 Alpha variant. However, Delta later outcompeted Alpha and other lineages, promoting a new wave of infections. Delta also possesses a nucleocapsid 203 mutation, R203M. Large-scale epidemiological analyses suggest a synergistic effect of the 203 mutation and the spike L452R mutation, associated with Delta expansion. Viral competition experiments demonstrate the synergistic effect in fitness and infectivity. More importantly, we found that the combination of R203M and L452R brings in a 3.2-fold decrease in neutralizing titers to the neutralizing serum relative to L452R-only virus. R203M/L452R show an increased fitness after the initiation of global vaccination programmes, possibly associated with the enhanced immune evasion. Another rapidly emerging variant Omicron also bears the 203 mutation. Thus, we proposed that nucleocapsid mutations play an essential role for the rise and predominance of variants in concern.

Expression of microRNA-100 and its relation with prognosis of colorectal cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to investigate the expression of microRNA-100 (miR-100) and its relation with prognosis in colorectal cancer (CRC).</p><p><b>METHODS</b>The expression of miR-100 was analyzed by quantitative real-time PCR (qRT-PCR) in 172 CRC tissue samples. The relation of miR-100 expression patterns with clinical pathological significance in CRC was analyzed. The effects of alterations of miR-100 expression and its consequences on CRC cell proliferation, apoptosis and migration were demonstrated in cells cultured in vitro.</p><p><b>RESULTS</b>The relative expression of miR-100 in CRC tissues and peritumoral tissues were -6.185 ± 1.921 and -3.698 ± 1.786, respectively, with a significant difference between the two groups (P<0.01). There was a significant difference between the relative expression of miR-100 in CRC with lymph node metastasis (-5.706 ± 1.809) and without lymph node metastasis (-6.775 ± 1.902, P<0.01). The relative expression of miR-100 in tumors of different TNM stages were -7.267 ± 1.888 in stage I, -6.443 ± 1.859 in stage II, -5.923 ± 1.796 in stage III, and -4.639 ± 1.516 in stage IV, with a significant difference among them (P<0.01). Different differentiation grades showed different expression of miR-100, i.e. -7.389 ± 1.828 in well differentiated tumors, -6.095 ± 1.843 in moderately differentiated tumors, and -5.476 ± 2.088 in poorly differentiated tumors (P<0.01). There was no significant correlation between miR-100 expression and overall survival rates of the CRC patients (P=0.179). Overexpression of miR-100 in the CRC cell line HCT-8 inhibited cell proliferation, but promoted cell apoptosis and migration.</p><p><b>CONCLUSIONS</b>The expression of miR-100 is correlated with lymph node metastasis, TNM stage and differentiation grade, and may be a potential biomarker indicating the development of CRC.</p>

Therapeutic study of leukemia by pegylated liposomal daunorubicin / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the antitumor effect and toxicity of pegylated liposomal daunorubicin (PL-DNR) on leukemia.</p><p><b>METHODS</b>PL-DNR was prepared by dry lipid hydration and remote loading, and its physicochemical indexes were analyzed. The inhibiting effect of PL-DNR on leukemia cells was observed in terms of in vitro cytotoxicity experiment. The therapeutic effect in vivo was assessed by tumor inhibition in leukemia L1210-bearing mice. Apoptosis in cardiomyocytes was detected using the terminal deoxynucleotidyl transferase mediated dUTP nick end labeling method (TUNEL staining).</p><p><b>RESULTS</b>The average diameter of PL-DNR was (110 ± 10)nm and the encapsulation efficiency was 94.21%. The in vitro cytotoxicity experiment showed that the inhibiting ability of PL-DNR in the treatment groups was continuously enhanced as the experiment proceeded. The in vivo pharmacodynamic experiment also indicated obvious tumor-inhibiting effect of PL-DNR. At the end of the experiment, the tumor volume of the PL-DNR group was (433.71 ± 234.77)mm(3), significantly smaller than that of (1 293.77 ± 381.26) mm(3) in the DNR group (P < 0.05). Moreover, the tumor weight of the PL-DNR group was (0.66 ± 0.29)g and that of the DNR group was (1.25 ± 0.43)g (P < 0.05). The myocardial toxicity experiment showed that the median apoptosis index of cardiomyocytes in the PL-DNR group was 13.83%, significantly lower than that of 42.67% in the DNR group (P < 0.05), indicating a lower toxicity of PL-DNR to the myocardium.</p><p><b>CONCLUSION</b>Compared with the free DNR, PL-DNR can improve the therapeutic effect on leukemia and reduce the.</p>

Expression and clinical significance of plasma small RNA in patients with pancreatic cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>The aim of this study was to identify six miRNAs expressed in plasma of patients with pancreatic cancer (PCa) and analyze their value as a diagnostic index of pancreatic cancer.</p><p><b>METHODS</b>Plasma total RNAs were extracted from 30 PCa patients and 26 normal controls, and the abundance of six microRNAs was measured using real-time PCR. The possibility to combine them with CA19-9 as diagnostic biomarkers was analyzed.</p><p><b>RESULTS</b>The expression level of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a in plasma of patients with pancreatic cancer were 1.65×10(6), 5.98×10(4), 2.83×10(3), 3.47×10(6), 2.76×10(6), and 1.03×10(3) (copies/µl), while the normal controls were 4.08×10(5), 2.54×10(4), 8.55×10(2), 1.79×10(6), 9.32×10(5), and 4.67×10(2) (copies/µl), respectively, with a significant difference between the two groups (P < 0.05). The areas under the ROC curve of miR-21, miR-210, miR-155, miR-20a, miR-25 and miR-196a were 0.893, 0.810, 0.820, 0.766, 0.816 and 0.729, respectively. MiR-21 had the highest diagnostic value when it was used as diagnostic marker alone. The combination of miR-155 and miR-25 was more effective to distinguish PCa from normal than to be used alone, and the area under the ROC curve was 0.913 (95%CI 0.838-0.988) .When CA199 associated with miR -210 and miR-25, respectively, the areas under the ROC curves were 0.96 (95%CI was 0-1.0) and 0.942 (95% CI was 0.876-1.0), which were higher than CA199 alone (0.862, 95%CI was 0.748-0.975). There was a high improvement in diagnostic sensitivity and accuracy when miR-210 and miR-25 were combined with CA19-9, respectively.</p><p><b>CONCLUSIONS</b>Plasma miR-21, miR-155, miR-25, miR-210 have diagnostic value for pancreatic cancer, and deserve further study.</p>