BACKGROUND: Cervical cancer is currently estimated to be the fourth most common cancer among women worldwide and the leading cause of cancer-related deaths in some of the world's poorest countries. C/EBPβ has tumor suppressor effects because it is necessary for oncogene-induced senescence. However, C/EBPβ also has an oncogenic role. The specific role of C/EBPβ in cervical cancer as a tumor suppressor or oncoprotein is unclear.OBJECTIVE: To explore the role of the C/EBPβ protein in cervical tumorigenesis and progression.METHODS: Quantitative RT-PCR was used to analyze C/EBPβ (15 cervical cancer tissue samples and 15 corresponding normal cervical tissue samples), miR-661, and MTA1 mRNA expression in clinical samples (10 cervical cancer tissue samples and 10 corresponding normal cervical tissue samples). Immunohistochemistry was used to analyze C/EBPβ (381 clinical samples), Ki67 (80 clinical samples) and PCNA ( 60 clinical samples) protein expression. MALDI-TOF MassARRAY was used to analyze C/EBPβ gene methylation (13 cervical cancer tissues and 13 corresponding normal cervical tissues). Cell proliferation was analyzed by CCK-8 in cervical cancer cell lines. Western blotting and immunohistochemistry were performed to detect C/EBPβ protein expression levels, and mRNA expression was analyzed by quantitative RT-PCR analysis. Flow cytometry was performed to measure cell cycle distribution and cell apoptosis. Colony formation, Transwell, cell invasion, and wound healing assays were performed to detect cell migration and invasion.RESULTS: C/EBPβ protein expression was significantly reduced in cervical cancer tissues compared with cervicitis tissues (P < 0.01). Ki67 protein and PCNA protein expression levels were significantly higher in cervical cancer tissues compared with cervicitis tissues. The rate of C/EBPβ gene promoter methylation of CpG12, 13, 14 and CpG19 in cervical cancer tissues was significantly increased compared with normal cervical tissue (P < 0.05). In addition, C/EBPβ was overexpressed in cervical cancer cells and this overexpression inhibited cell proliferation, migration, invasion, arrested cells in S phase, and promoted apoptosis.CONCLUSIONS: We have demonstrated that C/EBPβ decreased in cervical cancer tissues and overexpression of the C/EBPβ gene in cervical cancer cells could inhibit proliferation, invasion and migration. <<<

OBJECTIVE: To explore and analyze the expression of eukaryotic translation elongation factor 1 alpha 2 (eEF1A2) gene in cervical cancer tissues, its relationship with patient survival, gene mutations, and changes in copy number in cervical cancer and chronic cervicitis tissues.METHODS: The expression of the eEF1A2 gene in cervical cancer and its relationship with patient survival were analyzed using gene expression profile interactive analysis. Changes in eEF1A2 expression in cervical cancer tissues were analyzed using cBioPortal, a portal for cancer genomics analysis. The eEF1A2 copy number in cervical cancer tissues and chronic cervicitis tissues was determined by real-time fluorescence quantitative polymerase chain reaction. The relationship between the expression of eEF1A2 protein and the clinical stage, pathological grade, and patient survival of cervical cancer was analyzed by the database: The Human Protein Atlas, an integrated repository portal for tumor-immune system interactions.RESULTS: Gene expression profile interactive analysis database analysis showed no significant differences in the expression of eEF1A2 between cervical cancer and normal cervical tissues (P > .05). The eEF1A2 gene expression level was not correlated with the survival of cervical cancer patients (P > .05). Analysis of the cBioPortal database showed that 18 of 297 cervical cancer patients had eEF1A2 gene changes, including missense mutation, splice mutation, amplification, and messenger RNA increase. There was no significant difference in eEF1A2 gene copy number between cervical cancer and chronic cervicitis (P > .05). The Human Protein Atlas and an integrated repository portal for tumor-immune system interactions database analysis of immunohistochemical data showed that eEF1A2 protein expression was no significant difference in clinical stage, pathological grade and patient survival of cervical cancer (P > .05).CONCLUSION: The eEF1A2 gene was mutated in cervical cancer tissues. The eEF1A2 gene copy number was not associated with changes in the expression of the eEF1A2 gene in cervical cancer tissues. <<<

BACKGROUND: This study was designed to investigate the clinical application, efficacy, and safety of immune checkpoint inhibitors (ICIs) in the treatment of lung cancer in the real world.METHODS: A retrospective, observational analysis was conducted on patients treated with ICIs in four tertiary hospitals in the region from January 2015 to March 2021, to evaluate the clinical efficacy of ICIs single-agent or combined chemotherapy and anti-vascular drugs in the first-line or second-line treatment of patients with lung cancer.RESULTS: Three hundred and fifteen patients were enrolled in this study. In patients with stage III-IV adenocarcinoma and Squamous cell carcinoma, the objective response rate (ORR) and disease control rate (DCR) were 35.5% (87/245) and 93.5% (229/245), respectively, the median progression-free survival (PFS) was 10.8 months, and the median overall survival (OS) was not reached. A total of 132 patients received ICIs as the first-line treatment, the median treatment cycle was 8 cycles (2-20 cycles), the short-term efficacy ORR was 38.6%, DCR was 93.9%, and the median PFS was 11.4 months. One hundred thirteen patients received ICIs treatment as second-line treatment, the median treatment cycle was five cycles (2-10 cycles), the short-term efficacy ORR was 31.9%, DCR was 92.9%, and the median PFS was 10.0 months. There were no statistically significant differences in ORR, DCR, or median PFS with ICIs as the first-line treatment compared with the second-line treatment(P > 0.05). The results of subgroup analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), epidermal growth factor receptor (EGFR) mutation status, pathological type and number of treatment lines were not correlated with median PFS(P > 0.05). However, there were statistically significant differences in programmed death-ligand 1(PD-L1) expression, corticosteroid interference, and antibiotic (Abx) treatment among all groups (P < 0.05). In terms of safety, the overall incidence of adverse reactions in 315 patients was 62.5%, and the incidence of immune-related adverse events (irAEs) was 13.7%. Grade 1-2 and 3-4 incidence of adverse events were 34.9 and 27.65%, respectively. There were four patients who experienced fatal irAEs, two cases were liver damage leading to liver failure, one case was immune related pneumonia, and one case was immune related myocarditis.CONCLUSION: In the real world, ICIs has a good effect on patients with lung cancer and significantly improves ORR and PFS. <<<

INTRODUCTION: The impact of pectoralis muscle mass index (PMI) on cardiac events is not well studied in cancer patients, especially in those who have received chemotherapy with high potential cardiac toxicity such as anthracyclines.METHODS: Individuals aged ≥18 years with a diagnosis of breast cancer, sarcoma, or lymphoma who received anthracycline-based chemotherapy at the University of Minnesota MHealth Fairview between 2009 and 2014. Eligible patients had to have two CT scans: a baseline CT scan within 6 months prior to chemotherapy and a follow-up CT scan within 2 years after treatment. The PMI was calculated as the right pectoralis muscle area indexed to height squared. Multivariable linear regression was used to analyze factors associated with PMI at follow-up, overall mortality, and major cardiac events (MACE).RESULTS: A total of 474 patients (breast cancer 192; lymphoma 184; sarcoma 98) participated with a median age of 61 years at the time of baseline CT scan; 161 (34%) were male. Almost all patients received anthracyclines except 12% who received trastuzumab only. The median baseline PMI was 5.8 cm2/m2 (4.9, 7.7) which decreased 10.5% after chemotherapy, to 5.2 cm2/m2 (4.4, 6.4). Baseline PMI was not significantly associated with OS, but we detected lower risks of MACE with larger PMI at baseline. Greater baseline PMI was associated with greater follow-up PMI, but also with greater relative PMI loss. Female gender, older age, and history of smoking were also associated with greater PMI losses.CONCLUSION: Greater pre-treatment pectoralis muscle index in patients treated with anthracyclines have a lower risk of MACE. Early identification of sarcopenia using PMI could trigger proactive engagement for intervention and risk-stratified therapies. <<<

BACKGROUND: Clinical staging of gastric cancer (GC) before treatment is essential. Endoscopic ultrasound (EUS) is a recommended staging tool, but its efficacy remains controversial. Our previous prospective study evaluated the potential value of EUS for T staging and presented discrepancies. In this study, we aimed to evaluate the efficacy of EUS in T staging by comparing it with pathological staging. We analyze the factors that can potentially affect accuracy to identify suitable subgroups for EUS staging.METHODS: Data from a total of 1763 consecutive patients with GC from January 2015 to December 2017 were analyzed. Results from EUS and pathological T staging were compared. The factors that might affect EUS's accuracy were analyzed.RESULTS: The sensitivity, specificity, positive predictive value, and negative predictive value of EUS in patients with early GC were 62.08%, 96.13%, 90.94%, and 80.21%, respectively. The accuracy rates of uT1, uT2-uT4, and uT3-uT4 were 90.94%, 79.02%, and 78.39%, respectively. In multivariate analysis, underestimation was more likely to be observed in patients with tumors located in the middle or upper third of the stomach. Overestimation was more likely to be observed in patients with tumors located in the lower third or those without ulcer. Other factors affecting accuracy included ulcer, differentiation, larger size and undergoing surgery.CONCLUSION: Our findings highlight the role of EUS in determining the T staging of GC. Overestimation and underestimation in T-staging were significantly associated with the tumor location in early GC, and a decision-making algorithm was proposed for clinical practice in early cancers based on these findings. <<<

The tumor microenvironment is a dynamic cellular milieu that interacts with cancer cells and promotes tumor progression and metastasis. However, the specific mechanisms by which the tumor microenvironment impacts cancer cells' behaviors remain poorly understood. In this study, enriched cancer-associated fibroblasts (CAFs) were observed in tumor tissues isolated from epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKIs) resistant non-small cell lung cancer (NSCLC) patients. CAFs isolated from tumor tissues were capable of producing tryptophan metabolite kynurenine (Kyn), which significantly increased the proliferation and EGFR TKIs resistance of NSCLC cells. In this study, it was further observed that the activation of tryptophan 2,3-dioxygenase (TDO) in CAFs, resulted in the enhanced capability of tryptophan metabolism in them compared to normal fibroblasts. As a result, Kyn produced by CAFs facilitated the up-regulation of Aryl Hydrocarbon Receptor (AhR) signals in NSCLC, thereby resulting in the downstream ATK and ERK signaling pathways activation. Finally, inhibition of AhR signals efficiently prevented tumor growth and development of EGFR TKIs resistance, eventually improved the outcome of EGFR TKIs, and described a promising therapeutic strategy for NSCLC. <<<

Daniel B Rosen, Elisabeth A Murphy, Ron S Gejman, Allyson Capili, Rachel L Friedlander, Sophie Rand, Kristen A Cagino, Shannon M Glynn, Kathy C Matthews, Jeff M Kubiak, Jim Yee, Malavika Prabhu, Laura E Riley, Yawei J Yang <<<

OBJECTIVE: To study how severity and progression of coronavirus disease (COVID-19) affect cytokine profiles in pregnant women.MATERIALS AND METHODS: 69 third-trimester, pregnant women were tested for COVID-19 infection and SARS-CoV-2 specific IgM and IgG antibodies. Patients were stratified according to SARS-CoV-2 Reverse Transcriptase-PCR (RT-PCR) status and serology (IgM and IgG) status. Cytokines G-CSF, HGF, IL-18, IL-1Ra, IL-2Ra, IL-8, and IP-10 were measured via ELISA. Retrospective chart review for COVID-19 symptoms and patient vitals was conducted, and cytokine levels were compared between SARS-CoV-2 positive and negative cohorts, by seronegative and seropositive infection, by time course since onset of infection, and according to NIH defined clinical severity.RESULTS: IL-18, IL-1Ra, and IP-10 increased in the 44 RT-PCR positive pregnant women compared to the 25 RT-PCR negative pregnant controls. Elevated cytokine levels were found in early infections, defined by positive RT-PCR and seronegative status, and higher cytokine levels were also associated with more severe disease. By IgM seroconversion, IL-8 and IP-10 returned to levels seen in uninfected patients, while IL-18 levels remained significantly elevated.CONCLUSION: Cytokine profiles of third-trimester pregnant women vary with the time course of infection and are correlated with clinical severity. <<<

8-Oxoguanine (8oxoG) in DNA is a major oxidized base that poses a severe threat to genome stability. To counteract the mutagenic effect generated by 8oxoG in DNA, cells have evolved 8oxoG DNA glycosylase (OGG) that can excise this oxidized base from DNA. Currently, OGG enzymes have been divided into three families: OGG1, OGG2 and AGOG (archaeal 8oxoG DNA glycosylase). Due to the limited reports, our understanding on AGOG enzymes remains incomplete. Herein, we present evidence that an AGOG from the hyperthermophilic euryarchaeon Ch5 (Tb-AGOG) excises 8oxoG from DNA at high temperature. The enzyme displays maximum efficiency at 75°C-95°C and at pH 9.0. As expected, Tb-AGOG is a bifunctional glycosylase that harbors glycosylase activity and AP (apurinic/apyrimidinic) lyase activity. Importantly, we reveal for the first time that residue D41 in Tb-AGOG is essential for 8oxoG excision and intermediate formation, but not essential for DNA binding or AP cleavage. Furthermore, residue E79 in Tb-AGOG is essential for 8oxoG excision and intermediate formation, and is partially involved in DNA binding and AP cleavage, which has not been described among the reported AGOG members to date. Overall, our work provides new insights into catalytic mechanism of AGOG enzymes. <<<

The history of human populations in Africa is complex and includes various demographic events that influenced patterns of genetic variation across the continent. Through genetic studies of modern-day, and most recently, ancient African genetic variation, it became evident that deep African history is captured by the relationships among hunter-gatherers. Furthermore, it was shown that agriculture had a large influence on the distribution of current-day Africans. These later population movements changed the demographic face of the continent and descendants of farming groups today form the majority populations across Africa. Ancient DNA methods are continually evolving, and we see evidence of this in how research has advanced in the last decade. With the increased availability of full genomic data from diverse sets of modern-day and prehistoric Africans we now have more power to infer human demography. Future ancient DNA research promises to reveal more detailed stories of human prehistory in Africa. <<<

Here, we present 12 loci paternal haplotypes (Y-STR profiles) against the backdrop of the Y-SNP marker system of Bantu males from the Maputo Province of Southeast Africa, a region believed to represent the southeastern fringe of the Bantu expansion. Our Maputo Bantu group was analyzed within the context of 27 geographically relevant reference populations in order to ascertain its genetic relationship to other Bantu and non Bantu (Pygmy, Khoisan and Nilotic) sub-equatorial tribes from West and East Africa. This study entails statistical pair wise comparisons and multidimensional scaling based on YSTR Rst distances, network analyses of Bantu (B2a-M150) and Pygmy (B2b-M112) lineages as well as an assessment of Y-SNP distribution patterns. Several notable findings include the following: 1) the Maputo Province Bantu exhibits a relatively close paternal affinity with both east and west Bantu tribes due to high proportion of Bantu Y chromosomal markers, 2) only traces of Khoisan (1.3%) and Pygmy (1.3%) markers persist in the Maputo Province Bantu gene pool, 3) the occurrence of R1a1a-M17/M198, a member of the Eurasian R1a-M420 branch in the population of the Maputo Province, may represent back migration events and/or recent admixture events, 4) the shared presence of E1b1b1-M35 in all Tanzanian tribes examined, including Bantu and non-Bantu groups, in conjunction with its nearly complete absence in the West African populations indicate that, in addition to a shared linguistic, cultural and genetic heritage, geography (e.g., east vs. west) may have impacted the paternal landscape of sub-Saharan Africa, 5) the admixture and assimilation processes of Bantu elements were both highly complex and region-specific. <<<

The N-methyladenosine (mA) is involved in the regulation of cell proliferation and metastasis formation in multiple cancers. However, the biological significance of RNA mA reader IGF2BP1 and the modification of IGF2BP1 itself have not been fully investigated. Here, we analyzed the functions and mechanism of IGF2BP1 in gastric cancer (GC). Results showed that IGF2BP1 upregulated in GC tissue and acted as a predictor of poor prognosis for GC patients. Functionally, IGF2BP1 promoted the migration and aerobic glycolysis of GC cells in vitro. Moreover, IGF2BP1 knockdown repressed the tumor growth in vivo. We also demonstrated that IGF2BP1 directly interacted with c-MYC mRNA via m6A-dependent manner to by stabilize its stability. Overall, these findings demonstrated that mA reader IGF2BP1 facilitated the carcinogenic of GC in mA/c-Myc-dependent manner, which might provide critical therapeutic strategy for GC. <<<

The presence of senescent cells is associated with renal fibrosis. This study aims to investigate the effect of albumin-induced premature senescence on tubulointerstitial fibrosis and its possible mechanism . Different concentrations of bovine serum albumim (BSA) with or without si-p21 are used to stimulate HK-2 cells for 72 h, and SA-β-gal activity, senescence-associated secretory phenotypes (SASPs), LaminB1 are used as markers of senescence. Immunofluorescence staining is performed to characterize the G2/M phase arrest between the control and BSA groups. Alterations in the DNA damage marker γ-H2AX, fibrogenesis, and associated proteins at the G2/M phase, such as p21, p-CDC25C and p-CDK1, are evaluated. Compared with those in the control group, the SA-β-gal activity, SASP, and γ-H2AX levels are increased in the BSA group, while the level of LaminB1 is decreased. Meanwhile, HK-2 cells blocked at the G2/M phase are significantly increased under the stimulation of BSA, and the levels of p21, p-CDC25C and p-CDK1, as well as fibrogenesis are also increased. When p21 expression is inhibited, the levels of p-CDC25C and p-CDK1 are decreased and the G2/M phase arrest is improved, which decreases the production of fibrogenesis. In conclusion, BSA induces renal tubular epithelial cell premature senescence, which regulates the G2/M phase through the CDC25C/CDK1 pathway, leading to tubulointerstitial fibrosis. <<<

Human papillomavirus type 16 (HPV16) belongs to the high-risk-group of HPVs and is causing a variety of anogenital cancers and head and neck cancer. The two HPV16 oncoproteins E6 and E7 prevent apoptosis and promote mitosis and are essential for completion of the HPV16 life cycle and for transformation of the infected cell and maintenance of malignancy. E6 and E7 are produced from two mRNAs that are generated in a mutually exclusive manner by alternative splicing. While E6 protein is made from the unspliced mRNA, E7 is made from the spliced version of the same pre-mRNA. Since sufficient quantities of both E6 and E7 are required for malignant transformation, this intricate arrangement of gene expression renders E6 and E7 expression vulnerable to external interference. Since antiviral drugs to HPV16 are not available, a detailed knowledge of the regulation of HPV16 E6 and E7 mRNA splicing may uncover novel targets for therapy. <<<

Joana Ropio, Alain Chebly, Jacky Ferrer, Martina Prochazkova-Carlotti, Yamina Idrissi, Lamia Azzi-Martin, David Cappellen, Anne Pham-Ledard, Paula Soares, Jean-Philippe Merlio, Edith Chevret <<<

BACKGROUND: Telomere shortening is linked to a range of different human diseases, hence reliable measurement methods are needed to uncover such associations. Among the plethora of telomere length measurement methods, qPCR is reported as easy to conduct and a cost-effective approach to study samples with low DNA amounts.METHODS: Cancer cells' telomere length was evaluated by relative and absolute qPCR methods.RESULTS: Robust and reproducible telomere length measurements were optimized taking into account a careful reference gene selection and by knowing the cancer cells ploidy. qPCR data were compared to "gold standard" measurement from terminal restriction fragment (TRF).CONCLUSIONS: Our study provides guidance and recommendations for accurate telomere length measurement by qPCR in cancer cells, taking advantage of our expertise in telomere homeostasis investigation in primary cutaneous T-cell lymphomas. Furthermore, our data emphasize the requirement of samples with both, high DNA quality and high tumor cells representation. <<<

BACKGROUND: Artesunate (ART) has been used extensively as anti-malarial drugs worldwide. Besides, it has also been reported to have anti-cancer activities. This study was aimed to explore the anti-cancer activity of ART in combination with cisplatin (CIS) on A549 cells.METHODS: Cells were cultured with different concentrations of ART and/or CIS for 24, 48, or 72 h to test the anti-proliferative effects by CCK-8 assay. Colony formation assay and EdU staining were also performed. TUNEL staining was used to illustrate the morphologic changes. Cell cycle and apoptosis were determined by flow cytometry assay, and Western blot analysis was conducted to detect the expression of apoptosis- and proliferation-related proteins. Caspase activities were determined by colorimetric assay kit. Moreover, the synergistic effect of ART with CIS in A549 cell xenograft model was also determined.RESULTS: ART significantly inhibited cell proliferation in dose- and time-dependent manners. Collectively, the combination treatment remarkably decreased colony formation rates and increased the rates of TUNEL-positive cells compared with mono-treatment. Mechanistically, the combination treatment influenced the expression of Bcl-2, Bax, p-P53, Caspase-3/7, Caspase-9, CyclinB1, P34, P21, and synergistically regulated the activity of P38/JNK/ERK1/2 MAPK pathway. In mice A549 xenograft tumors, the combination strategy significantly increased the anti-cancer efficacy of ART and CIS alone, consistent with the in vitro observations.CONCLUSIONS: ART exhibited significant anti-tumor effect on A549 cells and this efficiency could be enhanced by combination with CIS. <<<

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most serious malignancies. The main features of HCC are vascular invasion and drug resistance. Ferroptosis is a novel cell program that is involved in several diseases, such as cancer. Heat shock protein beta 1 (HSPB1) is a major component of heat shock proteins. A recent study showed that HSPB1 could be a new therapeutic target for colorectal cancer with 5-fluorouracil-acquired resistance. However, the functional role of HSPB1 in HCC remains unclear.AIM: The aim of this study is to clarify HSPB1 expression in HCC and its potential therapeutic and prognostic value.METHODS: We collected data on HSPB1 expression levels in HCC and normal liver tissues from The Cancer Genome Atlas and Gene Expression Omnibus databases. We then validated it using immunohistochemistry (IHC). Receiver operating characteristic and Kaplan-Meier survival curves were used to investigate the role of HSPB1 in the prognosis analysis of HCC. Further, we used the online Search Tool for the Retrieval of Interacting Genes/Proteins website, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes to conduct enrichment analysis and identify the predictive signaling pathways. Meanwhile, we used the TIMER and GSVA package of R (v3.6.3) to analyze the association between HSPB1 and immunocyte infiltration.RESULTS: Compared to normal tissues, there was differential expression of HSPB1 in pan-cancers. HSPB1 expression was higher in HCC tissues than in normal tissues (p<0.05). There was an evident significant difference between HSPB1 mRNA levels and histologic grade, vascular invasion, and alpha-fetoprotein level (all p values<0.05). Univariate analysis indicated that HCC patients with high HSPB1 levels had shorter overall survival rates than those with low HSPB1 levels (p<0.05). MAPK14, HSPA8, MAPKAPK3, MAPKAPK5, and MAPKAPK2 are essential proteins that interact with HSPB1. There was a significant correlation between HSPB1 expression levels and immune cell infiltration, including CD4+ T cells (r=0.203, p<0.05).CONCLUSION: High HSPB1 expression is closely associated with a worse prognosis in HCC patients, and HSPB1 may be a target of immunotherapy in HCC. <<<

BACKGROUND: To investigate the genotype distribution of human papillomavirus (HPV) in infected Uygur and Han women in Xinjiang, China; analyze the HPV16 E6 gene polymorphism site and relationship with the development of cervical cancer.METHODS: The HPV16 E6 sequence was analyzed using the European standard prototype to perform an evolutionary tree. HPV16 E6-T295/T350, G295/G350, and T295/G350 GV230 vectors were stably transfected into cervical cancer C33A cells to analyze the cell proliferation, migration and invasion, apoptosis by CCK8 and clonogenic assays, transwell and cell scratch assays, FACS experiments.RESULTS: The total HPV infection rate was 26.390% (760/2879), whereas the Uygur 22.87% (196/857) and the Han was 27.89% (564/2022) (P < 0.05). Among 110 mutations, 65 cases of E6 genes were mutated at nucleotide 350 (T350G) with the leucine changing to valine (L83V). Moreover, there were 7 cases of E6 gene mutated at nucleotide 295 (T295G) with aspartic changing to glutamic (D64E). When E6 vector(s) of mutations sites were transfected into C33A cells, they were found to promote cellular proliferation, migration, invasion, and inhibit apoptosis. T295/G350-E6 was significantly stronger than G295/G350 and T295/T350, G295/G350 was significantly stronger than T295/T350 (P < 0.05). The T295/G350 had the strongest effect on C33A cells and G295/G350 was significantly stronger than T295/T350 (P < 0.05).CONCLUSIONS: The positive HPV infection rates differed between the Uygur and Han in Xinjiang, China, and the genotype distribution of infection was different. After transfecting C33A cells with different eukaryotic expression vectors, the T295/G350 mutation site promoted the proliferation, migration, and invasion of C33A cells to a greater extent than G295/G350; however, G295/G350 had a stronger effect than T295/T350. <<<

Longlong Si, Huan Xu, Xueying Zhou, Ziwei Zhang, Zhenyu Tian, Yan Wang, Yiming Wu, Bo Zhang, Zhenlan Niu, Chuanling Zhang, Ge Fu, Sulong Xiao, Qing Xia, Lihe Zhang, Demin Zhou <<<

The conversion of life-threatening viruses into live but avirulent vaccines represents a revolution in vaccinology. In a proof-of-principle study, we expanded the genetic code of the genome of influenza A virus via a transgenic cell line containing orthogonal translation machinery. This generated premature termination codon (PTC)-harboring viruses that exerted full infectivity but were replication-incompetent in conventional cells. Genome-wide optimization of the sites for incorporation of multiple PTCs resulted in highly reproductive and genetically stable progeny viruses in transgenic cells. In mouse, ferret, and guinea pig models, vaccination with PTC viruses elicited robust humoral, mucosal, and T cell-mediated immunity against antigenically distinct influenza viruses and even neutralized existing infecting strains. The methods presented here may become a general approach for generating live virus vaccines that can be adapted to almost any virus. <<<