Table_5_Expression and prognosis analysis of PAQR5 in kidney cancer.docx

Progestin and adipoQ receptor 5 (PAQR5) affects the development of various malignancies and is specifically expressed in kidney. However, the role of PAQR5 in renal carcinoma remains unclear. We assessed the state of PAQR5 expression in kidney renal clear cell carcinoma (KIRC) by The Cancer Genome Atlas and Gene Expression Omnibus datasets. Moreover, immunohistochemistry was performed to observe the expressions of PAQR5 protein in tumor tissues. The relationships between PAQR5 expression and clinical characteristics were investigated by UALCAN. Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier plotter were used to analyze the effect of PAQR5 expression levels on overall survival and relapse-free survival (RFS). The re lationships between clinical characteristics and survival were also evaluated by univariate and multifactorial Cox regression. Gene Ontology term analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis were performed on PAQR5 to explain the enrichment pathways and functions. Protein and protein interactions were explained by GeneMANIA and STRING. We also explored the relevance of PAQR5 to tumor immune cell infiltration and immunomodulatory molecules by TIMER and GEPIA. Finally, we explored the correlation of PAQR5 with the pathway proteins STATs, HIF-1α, and mTOR using the GSE40435 dataset. PAQR5 expression was low in KIRC and correlated significantly with clinical characteristics including cancer stage, tumor grade, and nodal metastasis status. Low PAQR5 expression was significantly associated with poorer survival. Cox regression analysis indicated that upregulation of PAQR5 was an independent factor for a good prognosis of KIRC. PAQR5 downregulation was associated mainly with STAT3 target upregulation, tumorigenesis, and poor differentiation. PAQR5 expression also correlated positively with B cells, neutrophils, macrophages, and dendritic cells and negatively with the infiltration of FOXP3+ Treg cells and the immune checkpoint molecules PD-1, CTLA4, and LAG3. Moreover, PAQR5 expression in KIRC was negatively correlated with the pathway proteins STAT1/2/3/4/5A, HIF-1α, and mTOR. PAQR5 is an excellent predictor of KIRC prognosis and may be a potential molecular therapeutic target.</p

Table_1_Expression and prognosis analysis of PAQR5 in kidney cancer.docx

Progestin and adipoQ receptor 5 (PAQR5) affects the development of various malignancies and is specifically expressed in kidney. However, the role of PAQR5 in renal carcinoma remains unclear. We assessed the state of PAQR5 expression in kidney renal clear cell carcinoma (KIRC) by The Cancer Genome Atlas and Gene Expression Omnibus datasets. Moreover, immunohistochemistry was performed to observe the expressions of PAQR5 protein in tumor tissues. The relationships between PAQR5 expression and clinical characteristics were investigated by UALCAN. Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan–Meier plotter were used to analyze the effect of PAQR5 expression levels on overall survival and relapse-free survival (RFS). The re lationships between clinical characteristics and survival were also evaluated by univariate and multifactorial Cox regression. Gene Ontology term analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and gene set enrichment analysis were performed on PAQR5 to explain the enrichment pathways and functions. Protein and protein interactions were explained by GeneMANIA and STRING. We also explored the relevance of PAQR5 to tumor immune cell infiltration and immunomodulatory molecules by TIMER and GEPIA. Finally, we explored the correlation of PAQR5 with the pathway proteins STATs, HIF-1α, and mTOR using the GSE40435 dataset. PAQR5 expression was low in KIRC and correlated significantly with clinical characteristics including cancer stage, tumor grade, and nodal metastasis status. Low PAQR5 expression was significantly associated with poorer survival. Cox regression analysis indicated that upregulation of PAQR5 was an independent factor for a good prognosis of KIRC. PAQR5 downregulation was associated mainly with STAT3 target upregulation, tumorigenesis, and poor differentiation. PAQR5 expression also correlated positively with B cells, neutrophils, macrophages, and dendritic cells and negatively with the infiltration of FOXP3+ Treg cells and the immune checkpoint molecules PD-1, CTLA4, and LAG3. Moreover, PAQR5 expression in KIRC was negatively correlated with the pathway proteins STAT1/2/3/4/5A, HIF-1α, and mTOR. PAQR5 is an excellent predictor of KIRC prognosis and may be a potential molecular therapeutic target.</p

Table1_m7G-related lncRNAs are potential biomarkers for predicting prognosis and immune responses in patients with oral squamous cell carcinoma.DOC

Among head and neck cancers, oral squamous cell carcinoma (OSCC) is the most common malignant tumor. N-7-methylguanosine (m7G) and lncRNAs are both related to the development and progression of tumors. Therefore, this study aims to explore and establish the prognostic signal of OSCC based on m7G-related lncRNAs. In this study, RNA sequencing transcriptome data of OSCC patients were downloaded from The Cancer Genome Atlas (TCGA) database. Therefore, m7G-related lncRNAs were identified as differentially expressed in OSCC. Then, univariate Cox regression analysis and LASSO regression analysis were conducted to evaluate the prognostic significance of differentially expressed lncRNAs. Consequently, the abovementioned lncRNAs were assigned five OSCC patient risk scores, with high-risk and low-risk patients assigned to each group. Different signaling pathways were significantly enriched between the two groups as determined by set enrichment analysis (GSEA). Multivariate Cox regression analysis confirmed the factors used to construct the nomogram model. Then, the prognosis of the nomogram model was evaluated. Consequently, high-risk individuals had higher immune infiltration levels. According to the results of a study that evaluated the sensitivity of different risk subgroups to antitumour drugs, the high-risk group had a high sensitivity to doxorubicin. By performing real-time polymerase chain reaction (RT‒PCR), we verified the expression of these five m7G lncRNAs. Therefore, the model based on five m7G-related lncRNAs was able to predict the overall survival rates of OSCC patients and guide their treatment. It can also spur new ideas about how to prevent and treat OSCC.</p

PPh₃‑Catalyzed (3 + 3) Annulations of 5‑Acetoxypenta-2,3-dienoate with 1C,3O-Bisnucleophiles: Facile Entry to Stable Monocyclic 2<i>H</i>‑Pyrans

Phosphine-catalyzed (3 + 2) and (3 + 3) annulations between 5-acetoxypenta-2,3-dienoate and 1C,3O-bisnucleophiles are presented. The former cases can be achieved with the assistance of base while the latter is dominant without any additive. A series of deuterium-labeling experiments disclosed that the divergence in annulations is likely determined by the involved proton transfer processes

Inhibition of influenza A virus infection by ginsenosides

<div><p>Influenza viruses cause mild to severe respiratory infections in humans. Due to efficient means of transmission, the viruses infect human population on a large scale. Apart from vaccines, antiviral drugs are used to control infection; neuraminidase inhibitors are thought to be the first choice of treatment, particularly for severe cases. Rapidly evolving and emerging influenza viruses with increased frequency of viral resistance to these drugs stress the need to explore novel antiviral compounds. In this study, we investigated antiviral activity of ginseng extract and ginsenosides, the ginseng-derived triterpene and saponin compounds, against 2009 pandemic H1N1 virus in vitro and in vivo. Our data showed that treatment of mice with ginsenosides protected the animals from lethal 2009 pandemic H1N1 infection and lowered viral titers in animal lungs. Mechanistic studies revealed that ginsenosides interact with viral hemagglutinin protein and prevent the attachment of virus with α 2–3’ sialic acid receptors present on host cell surfaces. The interference in the viral attachment process subsequently minimizes viral entry into the cells and decreases the severity of the viral infection. We also describe that sugar moieties present in ginsenosides are indispensible for their attachment with viral HA protein. On the basis of our observations, we can say that ginsenosides are promising candidates for the development of antiviral drugs for influenza viruses.</p></div

Protective effect of ginsenosides on lethal infection of 2009 pandemic H1N1 influenza virus infection in mice.

<p>Balb/c mice (n = 10/group) were infected with a mixture of A/Nanchang/8002/2009 (H1N1) and ginsenoside compounds such as Rb1, Rb2, Rb3, panaxadiol, Rg1 and panaxatriol or HBSS (mock) which was pre-incubated for 1 hour. Protective effect of ginsenosides was observed on (A) weight loss and (B) mortality of infected animals.</p

Antiviral activity of ginseng extract (GE) against 2009 pandemic H1N1 influenza A virus infection.

<p>(A) A dose dependent reduction in viral titer was observed when MDCK cells were infected with GE-pretreated A/Nanchang/8002/2009 (H1N1) virus. Protective effect of GE was observed on (B) weight loss and (C) survival of mice infected with A/Nanchang/8002/2009 (H1N1) virus. GE oral_ mice treated with 80mg/kg of GE by oral route. GE_ mice were infected with a mixture of 10³ EID₅₀ of virus and GE. Mock_ there was no GE treatment given. *** P < 0.0005, ** P < 0.005.</p

Sugar motifs are indispensible for antiviral activity of ginsenosides.

<p>The chemical structure (A) protopanaxadiol (PPD) and protopanaxatriol (PPT) show positions of sugar motifs present in their related saponins. Comparison of antiviral activity of Rb1 with carbohydrate-free metabolites of ginsenosides such as g-PPD and g-PPT was observed by (C) change in animal body weight and (D) mortality. Loss of antiviral activity was found with loss of sugar motifs.</p

Interaction of Rb1 with viral hemagglutinin.

<p>(A) Serially diluted A/Nanchang/8002/2009 (H1N1) virus was pre-incubated with different concentrations of Rb1 or HBSS for 1 hour and used for hemagglutination inhibition assay. A significant reduction in HA titer of Rb1 treated virus was observed in dose dependent manner. To see the interaction of Rb1 with recombinant HA protein, HA was pre-incubated with different concentrations of Rb1 or H2O and assessed by (B) captured ELISA and (C) immunoblot assay. (D) Recombinant HA of H7N9 influenza virus was pre-incubated with 5μg of Rb1 and assessed by captured ELISA. Rb1 decreases the availability of HA protein for antibodies for anti-HA antibodies in dose dependent manner in panel B and C.</p

Dose dependent antiviral activity of ginsenoside Rb1.

<p>Balb/c mice (n = 10/group) were infected with 10³EID₅₀ of A/Nanchang/8002/2009 (H1N1) pre-incubated with varying concentration of Rb1. Significant changes in (A) animal weight and (B) survival rate was observed in these group compared to mock (untreated) group. (C) MDCK cells were used to titrate viral loads present in lung tissues of Rb1(2mg/ml) treated and untreated animals at 3 and 6 dpi. (D-E) Mice (n = 10/group) were infected with different viral inoculum pre-incubated with 2mg/ml of Rb1. (D) changes in animal weight and (E) survival was observed in these group. (F) lung viral loads were titrated on 3 dpi (n = 3/group). Results were expressed as log10 values of the mean of viral load ± SEM. *** P < 0.0005.</p