Pathogenicity of novel hantavirus isolate and antigenicity and immunogenicity of novel strain-based inactivated vaccine.

BACKGROUND: Hantaan virus (HTNV, Orthohantavirus hantanensae species, Hantaviridae family) is the main etiological agent responsible for hemorrhagic fever with renal syndrome (HFRS). The novel HTNV may pose a potential danger to the control and prevention of HFRS in China, which highlights the importance of vaccine development in public health management. In previous studies, our laboratory discovered and successfully isolated a new HTNV strain, HV004 strain, from Apodemus agrarius captured in an epidemic area in Hubei, China. METHODS: An initial biological and pathogenicity characterization of HTNV 76-118 (standard train), HV114 strain (a clinical isolate from Hubei province in 1986), and the novel isolate HV004 strain from the epidemic areas of Hubei province were performed in susceptible cells and in vivo. An experimental HV004 strain inactivated vaccine was prepared, and its corresponding immunogenicity was analyzed in BALB/c mice. RESULTS: HV004 strain had a similar but higher pathogenicity than HTNV 76-118 and HV114 in suckling mice. A subcutaneous vaccination (s.c.) with the inactivated HTNV vaccine adjuvanted with aluminum, followed by a challenge intraperitoneally with 106 FFU/ml HTNV, afforded full protection against an HTNV challenge. All immunized mice in every group elicited serum neutralizing antibodies with increasing dosages, which may protect mice from HTNV infection. A dose-dependent stimulation index of splenocytes was also observed in immunized mice. The percentage of IFN-γ-producing CD3+CD8+ T cells was significantly higher in the spleens of immunized mice than in those of control mice. CONCLUSIONS: These findings suggest that the inactivated HTNV vaccine may stimulate mice to produce high levels of antibodies with neutralization activity and elicit specific anti-HTNV humoral and cellular immune responses in BALB/c mice against the prevalent strain of HTNV in south central China.

Clinical efficacy in one-year treatment with Artemisia annua-SLIT drops in monosensitized and polysensitized individuals.

PURPOSE: Seasonal allergic rhinoconjunctivitis (SARC) caused by Artemisia seriously affects patients' quality of life in northern China. This study aimed to estimate further the efficacy and safety of a one-year course of Artemisia annua-sublingual immunotherapy (SLIT) on SARC patients. MATERIALS AND METHODS: This was an open-label, randomized, controlled, single-centre study involving 150 SARC patients induced by Artemisia, randomized to SLIT group (n = 75, SLIT along with pharmacotherapy) or control group (n = 75, pharmacotherapy only). According to the skin prick test (SPT) results, the SLIT group was divided into monosensitized and polysensitized groups to analyze the influence of sensitization status on the efficacy of Artemisia annua-SLIT. The clinical indicators of this study were total rhinoconjunctivitis symptom score (TRSS), total medication score (TMS), combined scores of medication and rhinoconjunctivitis symptom (CSMRS), and score of visual analog scale (VAS). Safety was evaluated by the occurrence of adverse events (AEs). Daily administration of the drops was recorded in diaries by the patients. RESULTS: After nearly one year of treatment and follow-ups, there was a significant decline in TRSS, TMS, CSMRS, and VAS from the baseline scores in the SLIT group (p < 0.001). However, as pollen counts increased in 2022, indicators above in the control group increased significantly during the peak pollen phase (PPP) in 2022 grass pollen season (GPS) compared to the baseline. Meanwhile, we found no significant difference in TRSS, TMS, CSMRS, and VAS between the monosensitized and polysensitized groups (p > 0.05). Moreover, the result indicated that the clinical improvement in TRSS, TMS, CSMRS, and VAS was still observed in polysensitized patients who were allergic to Artemisia pollen and sensitized to house dust mite (HDM) (n = 15) in PPP of 2022, compared to the baseline value (p < 0.001). CONCLUSION: Artemisia annua-SLIT was proven effective, tolerable and safe in patients with SARC after nearly one year of treatment, whether monosensitization or polysensitization.

Efficacy and safety of Artemisia annua sublingual immunotherapy in patients with seasonal allergic rhinoconjunctivitis over two pollen seasons.

OBJECTIVE: This study investigates the efficacy and safety of sublingual immunotherapy (SLIT) with A. annua allergens in patients with seasonal allergic rhinoconjunctivitis over two pollen seasons. METHODS: Seventy patients with moderate-severe seasonal allergic rhinoconjunctivitis were divided evenly into the SLIT and control groups. The SLIT last from 3 months before the summer-autumn pollen season in 2021 till the end of the summer-autumn pollen season in 2022. The daily individual symptom score, total rhinoconjunctivitis symptom score (dTRSS), total medication score (dTMS), combined score of medication and rhinoconjunctivitis symptom (dCSMRS), visual analog scale (VAS) score, and adverse events (AEs) were evaluated. RESULTS: The average pollen concentration in 2022 was twice that previous two-year during the pollen season. Fifty-six patients completed treatments (SLIT group: 29, control group: 27). Compared with baseline, the individual symptoms, dTRSS, dTMS, dCSMRS, and VAS scores of SLIT group declined in 2021. After 16 months of SLIT, all efficacy indexes in 2022 were still lower than baseline and equivalent to those in 2021. In control group, the efficacy indexes in 2022 were higher than that in 2020 and 2021. The efficacy indexes of SLIT group were lower than those of control group in 2021 and 2022. SLIT is effective for both mono- and poly-sensitized patients. AEs incidence in SLIT group was 82.7% without severe AEs. CONCLUSIONS: The A. annua-SLIT can obtain efficacy and safety over two pollen seasons for patients with moderate-severe seasonal allergic rhinoconjunctivitis.

Effects of Mitochondrial ATP-Sensitive Potassium Channel in Rats with Acute Myocardial Infarction and Its Association with the AKT/mTOR Pathway.

BACKGROUND: Myocardial infarction is associated with the autophagy and apoptosis of cardiomyocytes, and the protein kinase B/mammalian target of rapamycin (AKT/mTOR) pathway plays a crucial role in this mechanism. METHODS: Acute myocardial infarction rat models were assessed 0.5, 2, 4, and 6 hours after the induction of the myocardial infarction using hematoxylin and eosin staining, triphenyl tetrazolium chloride staining, myocardial enzyme measurements, and levels of autophagic activity. Additionally, diazoxide, 5-hydroxydecanoate, and LY294002 were intraperitoneally administered to rat models at peak myocardial injury to assess their effects on cardiac injury. The expression levels of autophagy-related and apoptosis-related proteins, as well as p-AKT and p-mTOR, were measured. Electron microscopy was used to assess the ultrastructure and the number of autophagosomes in the cardiac tissue. RESULTS: We demonstrated that the degree of myocardial injury and the level of autophagy were significantly elevated in the experimental cohort compared with the control cohort. In addition, the myocardial infarct size was significantly smaller in diazoxide-treated acute myocardial infarction rats compared with untreated rats. Diazoxide also decreased the levels of myocardial injury markers, autophagy, and apoptosis, while it also induced the levels of AKT and mTOR phosphorylation, decreased the number of autophagosomes, and improved the myocardial ultrastructure of the acute myocardial infarction rats. 5-Hydroxydecanoate treatment resulted in an opposite effect to those observed upon diazoxide treatment. LY294002 was also able to reverse diazoxide treatment effects. CONCLUSION: Peak levels of myocardial tissue injury and autophagy were observed 2 hours post-acute myocardial infarction induction in rats. Diazoxide treatment inhibited myocardial autophagy and apoptosis while protecting cardiac tissue from ischemic injury, which is likely to have proceeded through activation of the AKT/mTOR pathway.

Dexmedetomidine Combined with Low-Dose Norepinephrine Continuous Pumping to Prevent Hypotension after Cesaresan Section: A Randomized Controlled Trial.

Objective: The aim of the study is to explore the clinical effect of dexmedetomidine combined with low-dose norepinephrine (NE) continuous pumping in preventing supine hypotension. Methods: A total of 160 puerperaes who underwent elective cesarean section were selected. The puerperaes were equally divided into S group (saline), D group (dexmedetomidine), N group (norepinephrine), and DN group (dexmedetomidine combined with norepinephrine) by a random number table method. Apgar scores and umbilical cord venous blood gas values were recorded at 1 and 5 minutes. Results: There were no statistically significant differences in the age, gestational age, body mass index, bleeding volume, fluid supplement volume, Apgar scores of new borns at the 1st and 5th minute, the blood gas values of umbilical cord arterial and venous in the four groups (P > 0.05). Compared with the S group, the incidence of supine hypotension, the number of NE supplements, the supplementary doses of NE, and the incidence of adverse reactions were significantly reduced in the D, N, and DN groups after spinal anesthesia (P < 0.05). Compared with group D, the incidence of supine hypotension, the number of additional NE, additional dose of NE, and the incidence of adverse reactions in the DN group after spinal anesthesia were significantly reduced (P < 0.05). Compared with the N group, the incidence of supine hypotension, the number of additional NE, the additional dose of NE, and the incidence of adverse reactions in the DN group after spinal anesthesia were significantly reduced (P < 0.05). Conclusion: Dexmedetomidine combined with continuous pumping of low-dose norepinephrine can effectively prevent the occurrence of supine hypotension, reduce the occurrence of other adverse reactions, and have no obvious adverse effects on neonates. Registration. Chinese Clinical Trial Registry (https://www.chictr.org.cn/enIndex.aspx; ChiCTR2000040979).

A case of lung adenocarcinoma with MET∆ex14 mutation regressed after preoperative treatment with savolitinib, and successfully underwent radical resection.

Non-small cell lung carcinoma (NSCLC) is a complex disease, with many different potential gene mutations that drive its formation, occurrence, and development. It is estimated that about 3% of NSCLC patients are accompanied by MET exon 14 skipping (METex14) mutations, and the prognosis of such patients is generally poor, which forms a formidable challenge for us. Savolitinib (Orpathys) is the first highly selective MET inhibitor in China. Here, we presented an NSCLC patient with MET∆ex14 mutation, who was initially uncertain whether existed intrapulmonary metastasis and recently underwent percutaneous coronary intervention for acute myocardial infarction and received savolitinib 600 mg once a day. The tumor was significantly shrunk 6 months later, and no metastatic lesions were found. Eventually, it was determined that the patient was in the early stage of lung cancer. After experts' consultation and evaluation, the patient accepted radical tumor resection and recovered well. Therefore, savolitinib is an important treatment strategy for NSCLC patients with MET∆ex14 mutation, who was not suitable for surgery. Our experience may provide supporting evidence and guidance for implementing an effective therapeutic strategy for similar cases.

Clinical Efficacy and Safety of Artesimia annua-Sublingual Immunotherapy in Seasonal Allergic Rhinitis Patients Based on Different Intervention Time.

INTRODUCTION: Artemisia is a major kind of grass pollen in Northern China that can cause multiple kinds of common allergic diseases, such as allergic rhinitis (AR), conjunctivitis, or asthma. Recently, Artemisia annua Allergens Sublingual Immunotherapy Drops have been proved effective and safe for treating seasonal AR (SAR) with or without allergic conjunctivitis patients and were available in China. We sought to further investigate the different intervention times of A. annua-sublingual immunotherapy (SLIT) for evaluating efficacy and safety in patients with SAR. METHODS: A total of 88 subjects aged 18-52 years with SAR were enrolled and randomized into the SLIT group and control group. Forty-five patients received a course of SLIT with A. annua extracts along with pharmacotherapy as SLIT group and 43 patients only used symptomatic drugs as control group. Furthermore, SLIT group was randomly divided into 12-13 weeks' pre-seasonal treatment group and 8-9 weeks' pre-seasonal treatment group to receive different duration of SLIT before pollen season. Monosensitized and polysensitized groups were also the subgroups of SLIT group according to the sensitization status of patients. The combined symptom and medication score (CSMS), total nasal symptom score (TNSS), total medication score (TMS), visual analog score (VAS) were evaluated during the peak pollen phase in 2020 and 2021, respectively. Safety was assessed according to adverse events (AEs) reported. RESULTS: Compared to control group, CSMS, TNSS, TMS, VAS were significantly improved during the course of SLIT (p < 0.001). Besides, clinical improvement in nasal symptoms and reduction of medication use was also observed in SLIT group, compared to the baseline value (p < 0.001). Meanwhile, we observed that there was no significant difference between monosensitized group (n = 8) and polysensitized group (n = 29), as well as 12-13 weeks' preseasonal treatment group (n = 20) and 8-9 weeks' pre-seasonal treatment group (n = 17) belonging to the SLIT group in clinical efficacy (p > 0.05). No severe systemic AEs were reported. CONCLUSIONS: This study proved that A. annua-SLIT can provide equivalent efficacy and safety for SAR patients under the circumstance of accepting the pre-seasonal treatment of 8-9 or 12-13 weeks, regardless of monosensitization or polysensitization.

FERM domain-containing protein 6 exerts a tumor-inhibiting role in thyroid cancer by antagonizing oncogenic YAP1.

The emerging role of FERM domain-containing protein 6 (FRMD6) in cancer progression has been revealed in several malignancies. However, its relevance on thyroid cancer is not well understood. This work evaluated the possible role and mechanism of FRMD6 in thyroid cancer. We demonstrated that FRMD6 expression was downregulated in thyroid cancer by analyzing the Cancer Genome Atlas data. Remarkable reductions in FRMD6 expression were also confirmed in the clinical specimens and cell lines of thyroid cancer. The upregulation of FRMD6 restrained the proliferation, epithelial-mesenchymal transition, and invasion of thyroid cancer. Moreover, FRMD6 overexpression significantly increased the apoptosis and cell cycle arrest. Further molecular research demonstrated that the overexpression of FRMD6 increased the phosphorylation levels of mammalian STE20-like protein kinase 1, large tumor suppressor 1, and Yes-associated protein 1 (YAP1) and prohibited the activation of YAP1. The re-expression of constitutively active YAP1 strikingly reversed FRMD6-induced tumor-inhibiting effects. Thyroid cancer cells overexpressing FRMD6 had a weakened ability to form xenograft tumors in vivo in nude mice. Overall, the overexpression of FRMD6 produces remarkable tumor-inhibiting effects in thyroid cancer by inhibiting oncogenic YAP1.

Impact of KMN network genes on progression and prognosis of non-small cell lung cancer.

The Knl1-Mis12-Ndc80 (KMN) network genes (including KNL, MIS12 and NDC80 complexes) encode a highly conserved network of protein complexes that act in cell mitosis. In recent years, multiple studies revealed that KMN network genes also play a vital role in tumor appearance and growth. However, the role of the KMN gene network in non-small cell lung cancer (NSCLC) remains unknown. In this study, we analyzed the effects of KMN genes expression and clinical phenotype in patients with lung adenocarcinoma (LUAD). The expression of KMN network genes and related clinical information was extracted from The Cancer Genome Atlas. The samples were classified into cluster I and II by consistent clustering. We analyzed the gene distribution by principal component analysis, and the potential risk characteristics were analyzed using the least absolute shrinkage and selection operator Cox regression algorithm. Univariate and multivariate Cox regression analyses were used to analyze the clinical information. The Database for Annotation, Visualization, and Integrated Discovery, Gene MANIA and gene set enrichment analysis were used to analyze function and correlation among genes of the KMN network. The expression levels of nine out of ten KMN genes were significantly up-regulated in LUAD and were associated with poor overall survival (OS). Higher expression of NDC80 and KNL1 was related to low OS in both univariate and multivariate analyses. According to two independent prognostic KMN network genes (KNL1 and NDC80), a risk signature was established to predict the prognosis of patients with LUAD. Additionally, the genes NDC80 and KNL1 were considerably enriched in pathways associated with signaling pathways, biological processes, and the cell cycle. The results indicate that KMN network genes are intimately related to lung adenocarcinoma. KMN network genes are involved in the malignant process of LUAD. Assessment of NDC80 and KNL1 might be helpful for prognostic stratification and treatment strategy development.

Osimertinib is an effective epidermal growth factor receptor-tyrosine kinase inhibitor choice for lung cancer with epidermal growth factor receptor exon 18-25 kinase domain duplication: report of two cases.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are an effective treatment for common EGFR mutations in non-small-cell lung cancer (NSCLC). Rarer EGFR mutations such as kinase domain duplications (KDDs) have been identified, but the optimal therapy following treatment resistance remains unknown. We report two patients who were diagnosed with NSCLC including KDD. For case 1, afatinib (40 mg once daily) was at first effective but then became ineffective. Consequently, osimertinib therapy (80 mg once daily) was administered. As of 26 May 2021, the osimertinib therapy achieved a stable disease state according to the chest computed tomography scan. As for case 2, the patient received second-line chemotherapy and anlotinib (12 mg once daily) for 6 months and died in May 2020. Here, we describe osimertinib as an effective therapy for EGFR-KDD positive lung adenocarcinoma and thereby provide a new alternative for further treatment following resistance to first- and second-generation EGFR-TKIs.

Application of augmented reality and mixed reality navigation technology in laparoscopic limited right hepatectomy / 中华外科杂志

Objective: To investigate the application effect of augmented reality and mixed reality navigation technology in three-dimensional(3D) laparoscopic narrow right hepatectomy(LRH). Methods: A retrospective analysis was performed on the clinical data of 5 patients with hepatic malignancy admitted to the First Department of Hepatobiliary Surgery,Zhujiang Hospital,Southern Medical University from September 2020 to June 2021,all of whom were males,aged from 42 to 74 years.Preoperative evaluation was performed using the self-developed 3D abdominal medical image visualization system; if all the 5 patients were to receive right hemihepatectomy,the remnant liver volume would be insufficient,so LRH were planned.During the operation,the independently developed 3D laparoscopic augmented reality and mixed reality surgical navigation system was used to perform real-time multi-modal image fusion and interaction between the preoperative 3D model and 3D laparoscopic scene.Meanwhile,intraoperative ultrasound assisted indocyanine green fluorescence was used to determine the surgical path.In this way,the LRH under the guidance of augmented reality and mixed reality navigation was completed.The predicted liver resection volume was evaluated before surgery,actual resected liver volume,surgical indicators and postoperative complications were analyzed. Results: All the 5 patients completed LRH under the guidance of augmented reality and mixed reality navigation technology,with no conversion to laparotomy.The median operative time was 300 minutes(range:270 to 360 minutes),no intraoperative blood transfusion was performed,and the median postoperative hospital stay was 8 days(range:7 to 9 days).There were no perioperative deaths,or postoperative complications such as liver failure,bleeding,or biliary fistula. Conclusion: For patients who need to undergo LRH,the use of augmented and mixed reality navigation technology can safely and effectively guide the implementation of surgery,retain more functional liver volume,improve surgical safety,and reduce postoperative complications.

Analysis at the single-cell level indicates an important role of heterogeneous global DNA methylation status on the progression of lung adenocarcinoma.

Aberrant DNA modifications affect the tumorigenesis and progression of lung cancer. However, the global methylation status of tumor cells and the heterogeneous methylation status of cells within the same tumor need further study. We used publicly available single-cell RNAseq data to investigate the impact and diversity of global methylation status on lung adenocarcinoma. Clustering cells into subgroups and cell differentiation pseudotime analysis, based on expression profile, demonstrated that the global methylation status was crucial to lung adenocarcinoma function and progression. Hypermethylated tumor cells had increased activity related to the hypoxia response. Hyper- and hypomethylated cells indicated upregulation in pathways involving focal adhesion and cell junctions. Pseudotime analysis showed that cell clusters with unique methylation activities were located at the ends of the putative trajectories, suggesting that DNA methylation and demethylation activities were essential to tumor cell progression. Expression of SPP1 was associated with the global methylation status of tumor cells and with patient prognosis. Our study identified the importance and diversity of global DNA methylation status by analysis at the single-cell level. Our findings provide new information about the global DNA methylation status of tumor cells and suggest new approaches for precision medical treatments for lung adenocarcinoma.

Long non-coding RNA SNHG16, binding with miR-106b-5p, promoted cell apoptosis and inflammation in allergic rhinitis by up-regulating leukemia inhibitory factor to activate the JAK1/STAT3 signaling pathway.

Allergic rhinitis (AR) is a type I hypersensitive disease. Long non-coding RNA (lncRNA) SNHG16 acts as an oncogene in a variety of tumors and promotes the occurrence of inflammation in many inflammatory diseases. The study aims to investigate the expression of SNHG16 and its potential biological functions in AR. RT-qPCR results showed that the expression of SNHG16 in AR was up-regulated. The AR cell model was constructed by stimulating primary nasal mucosal epithelial cells from AR patients with IL-13. After knocking down the expression of lncRNA SNHG16, cell apoptosis was detected by flow cytometry, and the expression of inflammatory factors was detected by ELISA. The results showed that SNHG16 promoted cell apoptosis and inflammation. Then, bioinformatics analysis was used to screen miRNAs bound with SNHG16. Luciferase reporter gene assay and RNA pull-down experiment were used to verify the relationship. We found that the expression of miR-106b-5p was down-regulated and leukemia inhibitory factor (LIF) expression was up-regulated in the AR cell model. The expression of phospho-Janus kinase 1 and p-signal transducer and activator of transcription 3 (STAT3) were detected by Western blotting. Silencing the expression of LIF could inhibit the activity of JAK1/STAT3 pathway and further inhibit cell apoptosis and the occurrence of inflammation. Then transfected SNHG16 shRNA alone or together with miR-106b-5p antagomir into the AR cell model, we found that silencing the expression of SNHG16 down-regulated the expression of LIF and inhibited the activity of the JAK1/STAT3 pathway, cell apoptosis, and inflammation. However, miR-106b-5p antagomir weakened its inhibitory effects. The role of SNHG16 in AR was further verified by the ovalbumin-induced AR mouse model in vivo. In conclusion, SNHG16 up-regulates LIF expression by binding with miR-106b-5p, thus promoting the activity of JAK1/STAT3 pathway, and promoting the development of AR. These results provide new targets for the treatment of AR and may help reduce the damage caused by AR.

FBP1 enhances the radiosensitivity by suppressing glycolysis via the FBXW7/mTOR axis in nasopharyngeal carcinoma cells.

AIMS: The high glycolysis state of tumor cells is closely related to radioresistance. Fructose-1,6-bisphosphatase (FBP1) can regulate aerobic glycolysis and exerts tumor suppressor effects in many cancers, but its role in nasopharyngeal carcinoma (NPC) remains to be investigated. MATERIALS AND METHODS: RT-qPCR was used to measure FBP1 mRNA level. Glucose consumption, lactic acid production and ATP level was determined to evaluate glycolysis. The sensitivity of NPC cells to radiation was analyzed by MTT assay. Apoptosis was performed using flow cytometry. Gain- and loss-of function assays were carried out to explore the specific role of FBP1 and FBXW7 (F-box and WD repeat domain-containing 7) in NPC cell functions. The interactions between FBXW7 and FBP1 or mTOR were validated with co-immunoprecipitation assay. The in vivo experiments with xenografts were used to evaluate the role of FBP1 in tumor growth. KEY FINDINGS: FBP1 expression was lower in NPC tissues and cells than in normal controls and nasopharyngeal epithelial cells. Human recombinant FBP1 (rh-FBP1) treatment suppressed glycolysis in NPC cells. Besides, silencing FBP1 weakened the radiosensitivity and alleviated radiation-induced apoptosis and DNA damage by promoting glycolysis. Mechanism exploration found that FBP1 promoted FBXW7 protein level through suppressing the autoubiquitination of FBXW7. Then, FBXW7 restrained mTOR level by facilitating mTOR ubiquitination, thereby suppressing glycolysis and promoting radiation-induced apoptosis and DNA damage. Furthermore, overexpressing FBP1 in vivo hindered tumor growth and enhanced the antitumor activity of radiation. SIGNIFICANCE: FBP1 promoted the radiosensitivity in NPC cells by inhibiting glycolysis through the FBXW7/mTOR axis.

Long non-coding RNA AGAP2-AS1 promotes proliferation and metastasis in papillary thyroid cancer by miR-628-5p/KLF12 axis.

Long non-coding RNA (lncRNA) AGAP2-AS1 acts as an oncogene in several types of cancers. However, the role and mechanism of AGAP2-AS1 in papillary thyroid carcinoma (PTC) remain unclear. Thus, in this study, we aimed to explore the role of AGAP2-AS1 in PTC. Our results showed that AGAP2-AS1 was significantly upregulated in PTC tissues. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion of PTC cells. In vivo experiment showed that AGAP2-AS1 knockdown inhibited the tumorigenesis of PTC. MiR-628-5p was found to act as a target miRNA of AGAP2-AS1 in PTC. The expression level of miR-628-5p in PTC tissues was negatively associated with that of AGAP2-AS1. Inhibition of miR-628-5p attenuated the effects of AGAP2-AS1 knockdown on PTC. Moreover, miR-628-5p directly bound to the 3'UTR of KLF12 and inhibited the expression of KLF12. Knockdown of KLF12 enhanced the inhibitory effects of miR-628-5p on PTC cell proliferation and metastasis. In conclusion, these findings indicated that AGAP2-AS1 exerted an oncogenic role in PTC progression and metastasis. The effects of AGAP2-AS1 might be mediated by the regulation of miR-628-5p/KLF12 axis.

Transcriptional profiling and network pharmacology analysis identify the potential biomarkers from Chinese herbal formula Huosu Yangwei Formula treated gastric cancer in vivo / 中国天然药物

Huosu Yangwei (HSYW) Formula is a traditioanl Chinese herbal medicine that has been extensively used to treat chronic atrophic gastritis, precancerous lesions of gastric cancer and advanced gastric cancer. However, the effective compounds of HSYW and its related anti-tumor mechanisms are not completely understood. In the current study, 160 ingredients of HSYW were identified and 64 effective compounds were screened by the ADMET evaluation. Furthermore, 64 effective compounds and 2579 potential targets were mapped based on public databases. Animal experiments demonstrated that HSYW significantly inhibited tumor growth in vivo. Transcriptional profiles revealed that 81 mRNAs were differentially expressed in HSYW-treated N87-bearing Balb/c mice. Network pharmacology and PPI network showed that 12 core genes acted as potential markers to evaluate the curative effects of HSYW. Bioinformatics and qRT-PCR results suggested that HSYW might regulate the mRNA expression of DNAJB4, CALD, AKR1C1, CST1, CASP1, PREX1, SOCS3 and PRDM1 against tumor growth in N87-bearing Balb/c mice.

Hypoxia-inducible factor-1α attenuates myocardial inflammatory injury in rats induced by coronary microembolization.

To investigated the role of HIF-1α in myocardial inflammatory injury in rats induced by CME and its possible mechanism. Forty SD rats were separated randomly and equally into four groups, i.e. CME+HIF-1α stabilizer dimethyloxalyl glycine (CME+DMOG) group, CME+HIF-1α inhibitor YC-1 (CME+YC-1) group, CME group, and Sham group. HBFP staining, myocardial enzyme assessment, and cardiac ultrasound were used to measure microinfarct, serum c-troponin I (cTnI) level, and Cardiac function. ELISA and western blot were applied for detecting NLRP3 inflammasome pathway and TLR4/MyD88/NF-κB signaling level.Pro-inflammatory factors of IL-18, IL-1ß and TNF-α increased their expression levels after CME, which indicated inflammatory responses in the myocardium. Additionally, in the inflammatory process, NLRP3 inflammasome and TLR4/MyD88/NF-κB signaling were involved. DMOG reverses these effects of CME, whereas YC-1 aggravates these effects. HIF-1α may attenuate myocardial inflammatory injury induced by CME and improve cardiac function, which can perhaps be explained by the fact that TLR4/MyD88/NF-κB signaling pathway activation is inhibited.

Potential therapeutic targets of the nuclear division cycle 80 (NDC80) complexes genes in lung adenocarcinoma.

Background: Lung cancer is the most common cancer worldwide, both in terms of the incidence and mortality. NDC80 complex comprising of NDC80, NUF2, SPC24, and SPC25 is a heterotetrameric protein complex located in the outer layer of the kinetochore and plays a critical role in mitosis. This study focuses on the effects of NDC80 complex genes on clinical features and prognosis in lung adenocarcinoma (LUAD). Materials and methods: Expression of NDC80 complex in LUAD and related clinical information was extracted from the TCGA website. NDC80 complex gene functional analysis and correlation analysis was conducted by using DAVID, BiNGO, Gene MANIA, STRING and GSEA. Survival probability was predicted by nomogram. Statistical analysis was used to predict NDC80 complex gene expression on clinical features and prognosis in patients with LUAD. Results: Expression of NDC80, NUF2, SPC24 and SPC25 was significantly elevated in LUAD tumors compared with normal tissues (P < 0.05). These genes showed diagnostic values for LUAD (P < 0.001 for each; area under the curve (AUC), 0.958, 0.968, 0.951, and 0.932 respectively); combinatorial analysis of these genes was more advantageous than single analysis alone (P < 0.001; AUC > 0.900 for each). Expression of both NDC80 and SPC25 correlated with the prognosis of LUAD (P < 0.001; AUC > 0.600 for each). Higher expression of NDC80, NUF2, SPC24 and SPC25 was associated with low overall survival (OS) in univariate analysis. Higher expression of NDC80 and SPC25 was associated with low OS in multivariate analysis. High expression of NDC80 combined with high expression of SPC25 was predictive of poor OS in LUAD in joint analysis. Conclusion: NDC80 complex gene might be an early indicator of diagnosis and prognosis of LUAD. The combined detection of NDC80, NUF2, SPC24 and SPC25 may become a new research direction in LUAD diagnosis and a new target for tumor targeted gene therapy.

Ceramide-Induced Cell Death Depends on Calcium and Caspase-Like Activity in Rice.

Ceramide sphingolipids are major components of membranes. C2 and C6 ceramides induce programmed cell death (PCD) in animals and plants, and we previously showed that C2 and C6 ceramides induce PCD in rice (Oryza sativa) protoplasts. However, the mechanistic link between sphingolipids and PCD in rice remains unclear. Here, we observed that calcium levels increased rapidly after ceramide treatment. Moreover, the calcium channel inhibitor LaCl3 and the intracellular calcium chelator acetoxymethyl-1, 2-bis (2-aminophenoxy) ethic acid (BAPTA-AM) inhibited this calcium increase and prevented ceramide-induced PCD. Moreover, caspase-3-like protease activity increased significantly in C6 ceramide-treated protoplasts, and a caspase-specific inhibitor prevented C6 ceramide-induced cell death. We also detected the other typical PCD events including ATP loss. DIDS (4, 49-diisothiocyanatostilbene- 2, 29-disulfonic acid), an inhibitor of voltage-dependent anion channels (VDACs), decreased C6 ceramide-induced cell death. Together, this evidence suggests that mitochondria played an important role in C6 ceramide-induced PCD.