Protective Potential of Saussurea costus (Falc.) Lipsch. Roots against Cyclophosphamide-Induced Pulmonary Injury in Rats and Its In Vitro Antiviral Effect.

Diseases and infections of the respiratory tract are common global causes of morbidity and mortality. Our study attempts to elucidate a novel remedy for respiratory ailments, in addition to identifying and quantifying the metabolites of Saussurea costus root extract (SCRE) using HPLC. Then, in vitro antiviral and in vivo lung protective effects were elucidated. The in vitro antiviral potential of SCRE was analyzed via plaque assay against the low pathogenic human coronavirus (HCoV-229E) and human influenza virus (H1N1). The value of the half maximal inhibitory concentrations (IC50) of SCRE against HCoV-229E and H1N1 influenza virus were 23.21 ± 1.1 and 47.6 ± 2.3 µg/mL, respectively. SCRE showed a histological improvement, namely a decrease in inducible nitric oxide synthase (iNOS) and caspase-3 immunoexpression in in vivo cyclophosphamide (CP)-induced acute lung injury (ALI). Moreover, there was a considerable decline in microRNA-let-7a gene expression and a significant rise in heme oxygenase-1 (HO-1) gene expression, with a marked decrease in the malondialdehyde (MDA) level. Molecular docking studies revealed that the major constituents of SCRE have a good affinity for caspase-3, HO-1, and iNOS proteins. In conclusion, a traditional plant SCRE could be a promising source of novel therapeutic agents for treating and protecting respiratory tract diseases. More future investigations should be carried out to reveal its efficacy clinically.

PTEN rs701848 Polymorphism is Associated with Trastuzumab Resistance in HER2-positive Metastatic Breast Cancer and Predicts Progression-free Survival.

BACKGROUND: Trastuzumab is an effective therapeutic approach for HER2-positive metastatic breast cancer (BC). However, a considerable number of patients develop resistance along the course of the disease. PTEN rs701848 polymorphisms are associated with an increased risk of developing cancer and have a potential role in predicting drug resistance. OBJECTIVE: We studied the significance of PTEN rs701848 variants as significant predictors for trastuzumab resistance in HER2-positive metastatic BC patients. Therefore, considering their value in predicting clinical outcomes. MATERIALS AND METHODS: This case-control study was conducted among female patients with HER2-positive metastatic breast cancer who underwent Trastuzumab therapy during the period from March 2017 to December 2020. PTEN rs701848 genotypes were analyzed in 160 HER2-positive metastatic breast cancer who received Trastuzumab therapy and clinically monitored for therapeutic response. RESULTS: PTEN rs701848 is deemed a significant predictor of Trastuzumab resistance and an independent prognostic factor of progression-free survival (PPFS). In particular, the C allele is associated with increased risk for Trastuzumab resistance and shorter PFS as compared to the homozygous TT genotype. CONCLUSION: PTEN rs701848 is significant predictor of trastuzumab resistance. Therefore, their value in predicting clinical outcomes is recommended.

Competing endogenous RNA network crosstalk reveals novel molecular markers in colorectal cancer.

The competing endogenous RNA networks play a pivotal role in cancer diagnosis and progression. Novel properstrategies for early detection of colorectal cancer (CRC) are strongly needed. We investigated a novel CRC-specific RNA-based integrated competing endogenous network composed of lethal3 malignant brain tumor like1 (L3MBTL1) gene, long non-coding intergenic RNA- (lncRNA RP11-909B2.1) and homo sapiens microRNA-595 (hsa-miRNA-595) using in silico data analysis. RT-qPCR-based validation of the network was achieved in serum of 70 patients with CRC, 40 patients with benign colorectal neoplasm, and 20 healthy controls. Moreover, in cancer tissues of 20 of the 70 CRC cases were involved in the study. The expression of RNA-based biomarker network in both CRC and adjacent non-tumor tissues and their correlation with the serum levels of this network members was investigated. Lastly, the expression levels of the chosen ceRNA was verified in CRC cell line. Our results revealed that the three RNAs-based biomarker network (long non-coding intergenic RNA-[lncRNA RP11-909B2.1], Homo sapiens microRNA-595 [hsa-miRNA-595], and L3MBTL1 mRNA), had high sensitivity and specificity for discriminating CRC from healthy controls and also from benign colorectal neoplasm. The data suggest that among these three RNAs, serum lncRNA RP11-909B2.1 could be a promising independent prognostic factors in CRC. The circulatory RNA based biomarker panel can act as potential biomarker for CRC diagnosis and prognosis.