Hongcurrin9941

In this study, we report the complete mitogenome sequence of the polychaete, Melinna cristata (Sars, 1851). The circular M. cristata mitochondrial genome is 15,696 bp in length and has an AT content of 66%. As in other polychaetes, the genome has 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, 22 transfer RNA (tRNA) genes, and a non-coding region. Gene composition and their order in the M. cristata mitochondrion are identical to the Terebelliformia mitogenomes. A maximum-likelihood gene tree based on the M. cristata mitogenome combined with previously published Sedentaria and Errantia mitogenomes revealed that M. cristata forms a clade with two Terebelliformia species.The complete chloroplast genome sequence of Thrixspermum amplexicaule was assembled and analyzed in this work. The total chloroplast genome size of T. amplexicaule was 148,124 bp in length, containing a large single-copy (LSC) region of 86,079 bp, a small single-copy (SSC) region of 10,799 bp, and a pair of inverted repeat (IR) regions of 25,623 bp. The GC content of T. IC-87114 amplexicaule was 36.4%. It encoded a total of 120 unique genes, including 75 protein-coding genes, 37 tRNA genes, and eight rRNA genes. The results of phylogenetic analysis strongly supported that all four samples of Thrixspermum are monophyletic and T. amplexicaule was closely related to T. centipeda.The figleaf gourd (Cucurbita ficifolia Bouché), is a member of the Cucurbitaceae. Figleaf gourd genotypes are exclusively used as a rootstock for cucumber owing to their high physiological compatibility with cucumber. link2 In this study, the complete chloroplast (cp) genome of C. ficifolia was assembled. The cp genome of C. ficifolia was 157,631 bp in length, it consists of a pair of inverted repeats (IRa and IRb) regions (25,638 bp) separated by the large single-copy (LSC, 88,211 bp) and small single-copy (SSC, 18,144 bp) regions. The cp genome encodes 111 unique genes, including 80 protein-coding genes, 27 transfer RNA genes, and four ribosomal RNA genes. The overall GC content of C. ficifolia cp genome was 37.2%. The phylogenetic tree of Cucurbitaceae showed that C. ficifolia was clustered into genus Cucurbita and the bootstrap value is 100%.Mahonia duclouxiana is a member of the genus Mahonia of Berberidaceae and is distributed in South Asia. Here, the complete chloroplast genome sequence of M. duclouxiana was reported. The complete chloroplast genome is 165,384 bp in length, which has a large single-copy (LSC) region of 73,477 bp, a small single-copy (SSC) region of 18,563 bp, and two inverted repeat (IR) regions of 36,672 bp. The G/C content in the chloroplast genome is 38.1%. The whole chloroplast genome contains 151 genes, including 38 unique tRNA genes, 105 unique protein-coding genes, and 8 unique rRNA genes. The phylogenetic analysis supported that this species should be included in Maddenia. The complete chloroplast genome sequence of M. link3 duclouxiana will provide extremely important information in tracing the evolutionary history of the genus Mahonia and the development of the medicinal value.Mincle is essential for tumor-associated macrophage (TAM)-driven cancer progression and represents a potential immunotherapeutic target for cancer. Nevertheless, the lack of a specific inhibitor has largely limited its clinical translation. Here, we successfully developed a gene therapeutic strategy for silencing Mincle in a virus-free and tumor-specific manner by combining RNA interference technology with an ultrasound-microbubble-mediated gene transfer system (USMB). We identified a small hairpin RNA (shRNA) sequence shMincle that can silence not only Mincle expression but also the protumoral effector production in mouse bone marrow- and human THP-1-derived macrophages in the cancer setting in vitro. By using our well-established USMB system (USMB-shMincle), the shMincle-expressing plasmids were delivered in a tissue-specific manner into xenografts of human lung carcinoma A549 and melanoma A375 in vivo. Encouragingly, we found that USMB-shMincle effectively inhibited the protumoral phenotypes of TAMs as well as the progression of both A549 and A375 xenografts in a dose-dependent manner in mice without significant side effects. Mechanistically, we identified that USMB-shMincle markedly enhanced the anticancer M1 phenotype of TAMs in the A549 and A375 xenografts by blocking the protumoral Mincle/Syk/nuclear factor κB (NF-κB) signaling axis. Thus, USMB-shMincle may represent a clinically translatable novel and safe gene therapeutic approach for cancer treatment.5-Fluorouracil (5-Fu) is a widely applied anti-cancer agent against colorectal cancer (CRC), yet a number of CRC patients have developed resistance to 5-Fu-based chemotherapy. The epidermal growth factor receptor (EGFR) is recognized as an oncogene that promotes diverse cancer progresses. In addition, long noncoding RNAs (lncRNAs) are essential regulators of cancers. Here we report that EGFR and lncRNA-FGD5-AS1 promoted 5-Fu resistance of CRC. By establishing the 5-Fu-resistant CRC cell line, we detected that EGFR, FGD5-AS1, and glucose metabolism were significantly elevated in 5-Fu-resistant CRC cells. A microRNA-microarray analysis revealed that miR-330-3p functions as a downstream effector of FGD5-AS1. FGD5-AS1 directly sponged miR-330-3p to form a competing endogenous RNA (ceRNA) network, leading to inhibition of miR-330-3p expression. Furthermore, bioinformatics analysis revealed that Hexokinase 2 (HK2) was a potential target of miR-330-3p, which was validated by luciferase assay. Rescue experiments demonstrated that FGD5-AS1 promotes glycolysis through modulating the miR-330-3p-HK2 axis, leading to 5-Fu resistance of CRC cancer cells. Finally, in vitro and in vivo xenograft experiments consistently demonstrated that inhibition of EGFR by the specific inhibitor erlotinib effectively enhanced the anti-tumor toxicity of 5-Fu by targeting the EGFR-FGD5-AS1-miR-330-3p-HK2 pathway. In summary, this study demonstrates new mechanisms of the EGFR-modulated 5-Fu resistance through modulating the noncoding RNA network, contributing to development of new approaches against chemoresistant CRC.A dual microRNA-detargeted oncolytic Mengovirus, vMC24NC, proved highly effective against a murine plasmacytoma in an immunocompetent syngeneic mouse model; however, there remains the concern of escape mutant development and the potential for toxicity in severely immunocompromised cancer patients when it is used as an oncolytic virus. Therefore, we sought to compare the safety and efficacy profiles of an attenuated Mengovirus containing a virulence gene deletion versus vMC24NC in an immunodeficient xenograft mouse model of human glioblastoma. A Mengovirus construct, vMC24ΔL, wherein the gene coding for the leader protein, a virulence factor, was deleted, was used for comparison. The vMC24ΔL induced significant levels of toxicity following treatment of subcutaneous human glioblastoma (U87-MG) xenografts as well as when injected intracranially in athymic nude mice, reducing the overall survival. The in vivo toxicity of vMC24ΔL was associated with viral replication in nervous and cardiac tissue. In contrast, microRNA-detargeted vMC24NC demonstrated excellent efficacy against U87-MG subcutaneous xenografts and improved overall survival significantly compared to that of control mice without toxicity. These results reinforce microRNA-detargeting as an effective strategy for ameliorating unwanted toxicities of oncolytic picornaviruses and substantiate vMC24NC as an ideal candidate for clinical development against certain cancers in both immunocompetent and immunodeficient hosts.Hepatocellular carcinoma (HCC) is a highly vascularized, inflammatory, and abnormally proliferating tumor. Monotherapy is often unable to effectively and comprehensively inhibit the progress of HCC. In present study, we selected ginsenoside Rg3, ganoderma lucidum polysaccharide (GLP), and oridonin as the combined therapy. These three plant monomers play important roles in anti-angiogenesis, immunological activation, and apoptosis promotion, respectively. However, the low solubility and poor bioavailability seriously hinder their clinical application. To resolve these problems, we constructed a new drug, Rg3, GLP, and oridonin self-microemulsifying drug delivery system (RGO-SMEDDS). We found that this drug effectively inhibits the progression of HCC by simultaneously targeting multiple signaling pathways. RGO-SMEDDS restored immune function by suppressing the production of immunosuppressive cytokine and M2-polarized macrophages, reduced angiogenesis by downregulation of vascular endothelial growth factor and its receptor, and retarded proliferation by inhibiting the epidermal growth factor receptor EGFR/AKT/epidermal growth factor receptor/protein kinase B/glycogen synthase kinase-3 (GSK3) signaling pathway. In addition, RGO-SMEDDS showed considerable safety in acute toxicity tests. Results from this study show that RGO-SMEDDS is a promising therapy for the treatment of HCC.Cancer immunotherapy using immune-checkpoint inhibitors (ICIs) such as PD-1/PD-L1 inhibitors has been well established for various types of cancer. Monotherapy with ICIs, however, can achieve a durable response in only a subset of patients. There is a great unmet need for the ICI-resistant-tumors. Since patients who respond to ICIs should have preexisting antitumor T cell response, combining ICIs with cancer vaccines that forcibly induce an antitumor T cell response is a reasonable strategy. However, the preferred administration sequence of the combination of ICIs and cancer vaccines is unknown. In this study, we demonstrated that combining an oral WT1 cancer vaccine using a Bifidobacterium vector and following anti-PD-1 antibody treatment eliminated tumor growth in a syngeneic mouse model of bladder cancer. This vaccine induced T cell responses specific to multiple WT1 epitopes through the gut immune system. Moreover, in a tumor model poorly responsive to an initial anti-PD-1 antibody, this vaccine alone significantly inhibited the tumor growth, whereas combination with continuous anti-PD-1 antibody could not inhibit the tumor growth. These results suggest that this oral cancer vaccine alone or as an adjunct to anti-PD-1 antibody could provide a novel treatment option for patients with advanced urothelial cancer including bladder cancer.Retinoblastoma (RB) is the most common intraocular tumor among children. Leucine-rich pentatricopeptide repeat (PPR)-motif-containing protein (LRPPRC), a suppressor gene of autophagy, has been proven to play a regulatory role in tumor progression. However, little is known about functional roles and mechanisms of LRPPRC in RB progression. First, we performed a detailed analysis for RB and normal control. The expression of LRPPRC in the RB tissues was significantly higher than that in normal tissues. Moreover, LRPPRC suppression could repress tumor cell migration, invasion, glycolysis, and reactive oxygen species (ROS)/hypoxia-inducible factor-1α (HIF1-α) pathway activation by mediating autophagy. Furthermore, overexpression of HIF1-α partially reversed the above changes induced by LRPPRC knockdown. The regulation of LRPPRC on tumor metastasis and glycolysis was also validated by a xenograft tumor assay. In summary, LRPPRC could regulate metastasis and glycolysis of RB by mediating autophagy suppression and further activating the ROS/HIF1-α pathway, and LRPPRC could be a promising prognostic biomarker for RB.