Protective effects of ginsenoside F2 on isoproterenol-induced myocardial infarction by activating the Nrf2/HO-1 and PI3K/Akt signaling pathways.

BACKGROUND: Ginsenoside F2 (GF2) serves as the principal intestinal metabolite resulting from the oral intake of Panax ginseng and Panax quinquefolius, exhibiting antioxidative, hypolipidemic, antitumor, and anti-inflammatory properties. Nevertheless, its effect on myocardial infarction (MI) is still unknown. PURPOSE: The purpose of this study is to investigate the protective effect and the underlying mechanisms of GF2 against isoproterenol (ISO)-induced MI. METHODS: ISO-induced H9c2 cardiomyocytes and MI rat models were utilized as in vitro and in vivo models to evaluate the impact of anti-MI of GF2. The underlying mechanisms were investigated using a variety of methodologies, including electrocardiography, Western blot analysis, histopathological examination, immunofluorescence, immunohistochemistry, and ELISA techniques. RESULTS: In vivo experiments, our results indicated that GF2 significantly ameliorated ISO-induced electrocardiographic (ECG) abnormalities, myocardial fiber necrosis, rupture, fibrosis of myocardial tissues, and suppressed cardiac enzyme activities. Meanwhile, GF2 notably raised the activity of antioxidant enzymes like CAT, GSH, and SOD. Furthermore, it downregulated Keap1 expression level while upregulating NQO1, Nrf2, and HO-1 expression levels. Additionally, GF2 suppressed the expression of the cleaved caspase-3 and pro-apoptotic protein Bax while promoting the expression of anti-apoptotic proteins Bcl-2, p-PI3K, and p-Akt. TUNEL fluorescence results also demonstrated that GF2 effectively inhibited cardiomyocyte apoptosis. Furthermore, consistent with the results of animal experiments, GF2 considerably attenuated ROS generation, changed apoptosis and mitochondrial function, and reduced oxidative stress in ISO-induced H9c2 cardiomyocytes through activating Nrf2/HO-1 and PI3K/Akt signaling pathways. CONCLUSION: Taken together, GF2 ameliorated MI by preventing cardiocyte apoptosis, oxidative stress, and mitochondrial dysfunction via modulating the Nrf2/HO-1 and PI3K/Akt signaling pathways, showing potential as a treatment strategy for treating MI.

Nuclear protein in testis carcinoma of the lung.

Nuclear protein in testis (NUT) carcinoma is a kind of highly aggressive and fatal solid tumor characterized by a rearrangement of the NUT carcinoma family member 1 (NUTM1) gene located on chromosome 15 q l4, where the most common form of fusion is BRD4-NUT. NUT carcinoma occurred in different organs and was most commonly found in the midline organs and the lungs. NUT carcinoma can occur in patients of almost all ages, having a roughly consistent incidence in both sexes. Most of the patients were diagnosed in advanced stages with an extremely poor prognosis due to the lack of effective treatment. After years of research, the mechanism of NUT carcinoma is still not fully clear, and its therapeutic approaches need to be further studied and explored. In order to gain a more comprehensive understanding of NUT carcinoma and explore the effective treatments, this review aimed to summarize the clinical features, pathological characteristics, differential diagnosis, and treatment strategies for this disease.

Pulmonary Combined Large Cell Neuroendocrine Carcinoma.

Pulmonary combined large-cell neuroendocrine carcinoma (CLCNEC) is a rare neuroendocrine tumor pertained to lung large cell neuroendocrine carcinoma (LCNEC) with aggressive behavior and poor prognosis generally. The clinical features of CLCNEC are not specific including cough, expectoration, chest distress, chest pain, etc., which are prone to have different manifestations of the mixed components. Owing to the low incidence, there are few related small-scale retrospective studies and case reports. Currently, the treatment regimen of CLCNEC mainly refers to LCNEC that complete surgical resection is preferred in the early stage and according to previous researches, platinum-based small cell lung cancer (SCLC) standard treatment regimen showed promising results in postoperative and advanced CLCNEC as compared to that of non-small cell lung cancer (NSCLC). Adenocarcinoma-CLCNEC more likely harbor driver gene mutation, and may benefit from targeted therapy. As for immunotherapy, more clinical trial data are needed to support its benefits. This article will fill the gap and will provide new insight into the clinical characteristics, pathological diagnosis and treatment endeavors of CLCNEC.

L718Q/V mutation in exon 18 of EGFR mediates resistance to osimertinib: clinical features and treatment.

Osimertinib, a mutant-specific third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is emerging as the preferred first-line of treatment for EGFR-mutant lung cancer. However, osimertinib resistance inevitably develops among patients treated with the drug. The modal resistance mechanisms of osimertinib include the occurrence of epithelial transition factor (c-MET) amplification and C797S mutation, whereas rare mutations are presented as case reports. Recently, the L718Q/V mutation in exon 18 of EGFR has been reported to contribute to one of the possible mechanisms of resistance. The clinical features and subsequent treatment strategies for this mutation require further research. This study retrospectively enrolled NSCLC patients with the L718Q/V mutation from 2017 to 2021 at the Cancer Hospital of the University of the Chinese Academy of Sciences (Zhejiang Cancer Hospital), as well as additional patients with the same mutation from PubMed literature, to summarize the clinical features of the mutation. The association between the detection of L718Q/V and resistance to osimertinib, as well as impacts on the therapeutic process and outcome, was analyzed. We included a total of two patients diagnosed at Zhejiang Cancer Hospital and twelve patients from the literature. Of the fourteen total patients, 64.3% were male and 35.7% were female. The average age of the group was 60.2 years (range 45-72). A history of tobacco use was common among the group. In all of the cases we considered, the L718Q/V mutation was secondary to the L858R mutation. The second-generation TKI afatinib was found to provide a high disease control rate (DCR) (85.7%, 6/7) and relatively low objective response rate (ORR) (42/9%, 3/7). The median progression free survival (mPFS) for this treatment reached 2 months (1-6 months). The patients failed to benefit from chemotherapy combined with immunotherapy or other TKI medications. Due to the limited number of cases considered in this study, future studies should explore drugs that more precisely target the L718Q/V mutation of EGFR exon 18.

Speciation and bioaccessibility of arsenic in rice under different cooking methods and its implication in risk assessment.

Numerous studies have studied the health risk assessment of human exposure to As or bioaccessible As via rice intake; however, the bioaccessibility of different As species in rice is seldom reported. In the present study, 31 rice samples were collected from markets or individual growers to investigate the speciation and bioaccessibility of As. Five different species (AsIII, AsV, DMA, MMA, and AsB) were detected in rice samples from different regions, among which AsIII accounted for the largest proportion (62.95% in average), followed by DMA and AsV. In addition, the cooking method could facilitate the release of As from rice into gastric and intestinal juice, and subsequently increase the bioaccessibility of As. The bioaccessibility of inorganic As in cooked rice ranged from 71.83 to 100%, and that of organic As ranged from 31.69 to 61.04%. Non-carcinogenic and carcinogenic risk assessment of children and adults exposure to As via rice intake considering the bioaccessibility of cooked rice was carried out. The target hazard quotient (THQ) of iAs and total As for children ranged from 0.21 to 1.61 and 0.48 to 2.26, respectively, while those for adults ranged from 0.12 to 0.88 and 0.26 to 1.23, respectively. Incremental lifetime cancer risk (ILCR) for children and adults ranged from 9.57 [Formula: see text] 10-5 to 7.25 [Formula: see text] 10-4 and 5.21 [Formula: see text] 10-5 to 3.95 [Formula: see text] 10-4, respectively. The results of risk assessment indicated that children would face a higher health risk than adults when they took the same type of rice as their staple food.

Age-Related Cancer-Associated Microbiota Potentially Promotes Oral Squamous Cell Cancer Tumorigenesis by Distinct Mechanisms.

The oral squamous cell cancer (OSCC) incidence in young patients has increased since the end of the last century; however, the underlying mechanism is still unclear. Oral microbiota dysbiosis was proven to be a tumorigenesis factor, and we propose that there is a distinct bacterial composition in young patients that facilitates the progression of OSCC. Twenty elderly (>60 years old) and 20 young (<50 years old) subjects were included in this study. OSCC tissue was collected during surgery, sent for 16S rDNA sequencing and analyzed by the QIIME 2 pipeline. The results showed that Ralstonia, Prevotella, and Ochrobactrum were significantly enriched in younger OSCC tissue microbiota, while Pedobacter was more abundant in elderly OSCC tissues. Fusobacterium had high relative abundance in both cohorts. At the phylum level, Proteobacteria was the dominant taxon in all samples. The functional study showed that there were significant differences in the taxa abundance from metabolic and signaling pathways. The results indicated that the microbiota of younger OSCC tissues differed from that of elderly OSCC tissues by both taxon composition and function, which partially explains the distinct roles of bacteria during tumorigenesis in these two cohorts. These findings provide insights into different mechanisms of the microbiota-cancer relationship with regard to aging.

Progesterone modulates CD4+ CD25+ FoxP3+ regulatory T Cells and TGF-ß1 in the maternal-fetal interface of the late pregnant mouse.

OBJECTIVE: Progesterone supplementation is recommended to prevent spontaneous preterm birth (sPTB) in clinical practice. However, the exact mechanism is still unclear. This study aims to better understand the mechanisms that progesterone can prevent PTB. METHODS: Late pregnant mice were given various doses of progesterone receptor antagonist mifepristone, and pregnancy outcomes were observed. Then, non-pregnant and pregnant mice were given a subcutaneous injection of 40 mg/kg progesterone and 5 mg/kg mifepristone, respectively. CD4+ CD25+ FoxP3+ Treg cells in peripheral blood and decidua basalis were detected by FACS. Expressions of FoxP3 and TGF-ß1 in the decidua basalis were detected. RESULTS: Mifepristone induced preterm birth, and an obvious dose-response was found. Proportions of CD4+ CD25+ FoxP3+ Treg cells in the peripheral blood of non-pregnant mice increased significantly after progesterone injection. CD4+ CD25+ FoxP3+ Treg cells in the peripheral blood of pregnant mice increased significantly compared with those of non-pregnant mice. In pregnant mice, mifepristone significantly decreased the proportions of CD4+ CD25+ FoxP3+ Treg cells in peripheral blood, and reduced proportions of Treg cells at the maternal-fetal interface and expressions of FoxP3 and TGF-ß1 in the maternal-fetal interface. Total 40 mg/kg of progesterone did not increase CD4+ CD25+ FoxP3+ Treg in the peripheral blood of pregnant mice, but increased proportions of Treg cells at the maternal-fetal interface and up-regulated FoxP3 and TGF-ß1 expressions in the maternal-fetal interface. CONCLUSION: Progesterone promotes pregnancy immune homeostasis by up-regulating Treg cells and TGF-ß1 expression in the maternal-fetal interface. It may be one of the mechanisms of progesterone in preventing sPTB.

Methylation statuses of NCOR2, PARK2, and ZSCAN12 signify densities of tumor-infiltrating lymphocytes in gastric carcinoma.

Individual cell types of human tissues have their own CpG site methylation profiles, which might be utilized for the development of methylation markers to denote tumor-infiltrating lymphocytes (TILs). We aimed to develop DNA methylation markers that recapitulate the densities of TILs in gastric carcinoma (GC). Through genome-wide methylation profiling, NCOR2, PARK2, and ZSCAN12 were found to be highly methylated in CD3-positive and CD8-positive cells and rarely methylated in tumor cells. Scores of the three methylation markers were analyzed for their relationship with the overall survival and recurrence-free survival of patients with advanced GC (n = 471). The scores of three methylation markers were closely associated with densities of CD3-positive or CD8-positive cells at the tumor center or invasive front of GCs and found to be a significant prognostic factor in univariate analysis of overall survival and recurrence-free survival. In multivariate analysis, the highest score showed hazard ratios of 0.513 (CI 0.306-0.857) and 0.434 (CI 0.261-0.720) for overall survival and recurrence-free survival, respectively. The findings suggest that methylation markers signifying TILs might be utilized for the recapitulation of TIL density in GCs and serve as biomarkers for predicting prognosis in patients with GC.

Hepatoid Adenocarcinoma of the Lung.

Hepatoid adenocarcinoma of the lung (HAL) is an comparatively rare malignant tumor originating from the lung with shorter survival. HAL morphologically and pathologically exhibits hepatocellular carcinoma (HCC)-like characteristics, while its clinical features resemble pulmonary adenocarcinoma. High concentration of alpha-fetoprotein (AFP) is often detected in the serum of HAL patients with no hepatic occupying lesion. Patients with AFP-negative HAL survive a few months longer than those with positive AFP test. HAL is a rare type of carcinoma, so there is a lack of systematic and extensive statistical research. The treatment strategy for HAL is similar to common lung adenocarcinoma. Complete surgical resection and adjuvant chemotherapy are the current major treatments for HAL patients. There are also a few of case reports suggesting that HAL patients may benefit from immunotherapy and targeted therapy. This review focuses on the clinical and pathological features, immunohistochemical staining characteristics, treatment and prognosis of HAL.

Assessment of copy number in protooncogenes are predictive of poor survival in advanced gastric cancer.

The copy number (CN) gain of protooncogenes is a frequent finding in gastric carcinoma (GC), but its prognostic implication remains elusive. The study aimed to characterize the clinicopathological features, including prognosis, of GCs with copy number gains in multiple protooncogenes. Three hundred thirty-three patients with advanced GC were analyzed for their gene ratios in EGFR, GATA6, IGF2, and SETDB1 using droplet dPCR (ddPCR) for an accurate assessment of CN changes in target genes. The number of GC patients with 3 or more genes with CN gain was 16 (4.8%). Compared with the GCs with 2 or less genes with CN gain, the GCs with 3 or more CN gains displayed more frequent venous invasion, a lower density of tumor-infiltrating lymphocytes, and lower methylation levels of L1 or SAT-alpha. Microsatellite instability-high tumors or Epstein-Barr virus-positive tumors were not found in the GCs with 3 or more genes with CN gain. Patients of this groups also showed the worst clinical outcomes for both overall survival and recurrence-free survival, which was persistent in the multivariate survival analyses. Our findings suggest that the ddPCR-based detection of multiple CN gain of protooncogenes might help to identify a subset of patients with poor prognosis.

Physiological and pathological functions of ßB2-crystallins in multiple organs: a systematic review.

Crystallins, the major constituent proteins of mammalian lenses, are significant not only for the maintenance of eye lens stability, transparency, and refraction, but also fulfill various physiopathological functions in extraocular tissues. ßB2-crystallin, for example, is a multifunctional protein expressed in the human retina, brain, testis, ovary, and multiple tumors. Mutations in the ßB2 crystallin gene or denaturation of ßB2-crystallin protein are associated with cataracts, ocular pathologies, and psychiatric disorders. A prominent role for ßB2-crystallins in axonal growth and regeneration, as well as in dendritic outgrowth, has been demonstrated after optic nerve injury. Studies in ßB2-crystallin-null mice revealed morphological and functional abnormalities in testis and ovaries, indicating ßB2-crystallin contributes to male and female fertility in mice. Interestingly, although pathogenic significance remains obscure, several studies identified a clear correlation between ßB2 crystallin expression and the prognosis of patients with breast cancer, colorectal cancer, prostate cancer, renal cell carcinoma, and glioblastoma in the African American population. This review summarizes the physiological and pathological functions of ßB2-crystallin in the eye and other organs and tissues and discusses findings related to the expression and potential role of ßB2-crystallin in tumors.

ESR1 as a recurrence-related gene in intrahepatic cholangiocarcinoma: a weighted gene coexpression network analysis.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most common malignant hepatic tumor and has a high postoperative recurrence rate and a poor prognosis. The key roles of most tumor recurrence-associated molecules in iCCA remain unclear. This study aimed to explore hub genes related to the postsurgical recurrence of iCCA. METHOD: Differentially expressed genes (DEGs) between iCCA samples and normal liver samples were screened from The Cancer Genome Atlas (TCGA) database and used to construct a weighted gene coexpression network. Module-trait correlations were calculated to identify the key module related to recurrence in iCCA patients. Genes in the key module were subjected to functional enrichment analysis, and candidate hub genes were filtered through coexpression and protein-protein interaction (PPI) network analysis. Validation studies were conducted to detect the "real" hub gene. Furthermore, the biological functions and the underlying mechanism of the real hub gene in iCCA tumorigenesis and progression were determined via in vitro experiments. RESULTS: A total of 1019 DEGs were filtered and used to construct four coexpression modules. The red module, which showed the highest correlations with the recurrence status, family history, and day to death of patients, was identified as the key module. Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses demonstrated that genes in the red module were enriched in genes and pathways related to tumorigenesis and tumor progression. We performed validation studies and identified estrogen receptor 1 (ESR1), which significantly impacted the prognosis of iCCA patients, as the real hub gene related to the recurrence of iCCA. The in vitro experiments demonstrated that ESR1 overexpression significantly suppressed cell proliferation, migration, and invasion, whereas ESR1 knockdown elicited opposite effects. Further investigation into the mechanism demonstrated that ESR1 acts as a tumor suppressor by inhibiting the JAK/STAT3 signaling pathway. CONCLUSIONS: ESR1 was identified as the real hub gene related to the recurrence of iCCA that plays a critical tumor suppressor role in iCCA progression. ESR1 significantly impacts the prognosis of iCCA patients and markedly suppresses cholangiocarcinoma cell proliferation, migration and invasion by inhibiting JAK/STAT3 signaling pathway.

Alteration in stemness causes exclusivity between Epstein-Barr virus-positivity and microsatellite instability status in gastric cancer.

BACKGROUND: Gastric cancer (GC) is a leading cause of cancer morbidity and mortality worldwide. This is due to the heterogeneous features of GC, which consist of a diverse molecular phenotype. Epstein-Barr virus (EBV)-positive GC and microsatellite instability (MSI)-high GC encompass similar epigenetic traits, including high levels of DNA methylation in CpG islands; however, EBV-positive and MSI-high GCs are mutually exclusive. We aimed to elucidate the underlying mechanism of this exclusivity. METHODS: We knocked out MLH1 in EBV-positive GC cell lines SNU-719 and NCC24 via CRISPR-Cas9, and evaluated the modified cellular properties in vitro and in vivo. The MSI status of each cell line was screened with two marker capillary electrophoresis, and further diagnosed with five marker capillary electrophoresis and parallel sequencing using 21 markers. RESULTS: Initial evaluation showed that cell growth, migration, invasion, and MSI status were not affected by MLH1 silencing. However, with prolonged passage, GC cell lines gradually gained MSI and NCC24 cells were transformed to EBV-positive/MSI-high GC cells after 12 months. Furthermore, MLH1 silencing reduced tumor stemness in SNU-719 and NCC24 regardless of the MSI status in vitro and in vivo. CONCLUSIONS: Our findings suggest that EBV-positivity and MSI-high status are mutually exclusive due to the immediate disadvantage in tumor stemness when MLH1 is silenced, whereas the establishment of MSI-high status in EBV-positive GCs required a longer period.

Comparison of effects of high- and low-frequency electromagnetic fields on proliferation and differentiation of neural stem cells.

To compare the effects of high- (HF-EMF) and low-frequency electromagnetic fields (LF-EMF) on the proliferation and differentiation of neural stem cells (NSCs). NSCs were obtained from SD rat hippocampus and cultured in suspension and adherent differentiation media. NSCs were exposed to LF-EMF (5 m T, 50 Hz, 30 min daily), HF-EMF (maximum magnetic induction 2.5 T, 40 % MO, 50 Hz, 10 min daily) and no electromagnetic field. At 3 d, cell viability and quantity of NSCs in suspension were detected by CCK-8 assay and cell counting plate. Immunofluorescence staining and qRT-PCR were performed to detect the percentage of Tuj-1 and GFAP-positive NSCs and the expression of Tuj-1 and GFAP mRNA. The P3 NSCs were positive with Nestin and induced NSCs expressed Tuj-1, GFAP and oligodendrocyte markers (MBP). CCK-8 assay and cell counting showed that the OD value and quantity of LF-EMF group were significantly higher than those in other two groups (both P < 0.05). Compared with the control group, the OD value and quantity were significantly higher in the HF-EMF group (P < 0.05). Immunofluorescence staining and qRT-PCR revealed that the percentage of Tuj-1 positive cells and the expression of Tuj-1 mRNA of NSCs exposed to LF-EMF were the highest (both P < 0.05). The proportion of GFAP-positive NSCs and the expression of GFAP mRNA did not significantly differ among three groups (all P> 0.05). Both 50 Hz LF-EMF and HF-EMF can promote the proliferation of NSCs in vitro and LF-EMF can accelerate NSCs to differentiate into neurons.

Bone marrow stromal cells-derived exosomes target DAB2IP to induce microglial cell autophagy, a new strategy for neural stem cell transplantation in brain injury.

Bone marrow stromal cells (MSCs) are a useful source of stem cells for the treatment of various brain injury diseases due to their abundant supply and fewer ethical problems compared with transplant treatment. However, the clinical application of MSCs is limited due to allograft rejection and immunosuppression in the process of MSCs transplantation. According to previous studies, microglial cell autophagy occurs following co-culture with MSCs. In the present study, exosomes were obtained from MSCs and subsequently characterized using transmission electron microscopy, atomic force microscopy and dynamic light scattering particle size analysis. The type of microRNAs (miRs) found in the exosomes was then analyzed via gene chip. The results demonstrated that microglial cell autophagy could be induced by exosomes. This mechanism was therefore investigated further via reverse transcription-quantitative PCR, western blotting and luciferase assays. These results demonstrated that exosomes from MSCs could induce microglial cell autophagy through the miR-32-mediated regulation of disabled homolog 2-interacting protein, thus providing a theoretical basis for the clinical application of miRs in MSCs.

[Analysis of prenatal phenotype and pathogenetic variant in a fetus with Papillorenal syndrome].

OBJECTIVE: To diagnose a fetus with Papillorenal syndrome by prenatal ultrasonography and genetic testing, and to correlate its genotype with phenotype. METHODS: Ultrasound finding of the fetus was reviewed. Muscle sample of the abortus was taken, and genetic variant related to the clinical phenotype was screened by whole exome sequencing (WES). Suspected pathogenic variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasound revealed severe dysplasia of the fetal kidneys and oligohydramnios. WES revealed that the fetus has carried a c.736G>T (p.Glu246Ter) nonsense variant of the PAX2 gene, which was unreported previously. The result of Sanger sequencing was consistent with that of WES. Both parents of the fetus were of the wild-type, suggesting a de novo origin of the fetal variant. CONCLUSION: The novel heterozygous c.736G>T (p.Glu246Ter) variant of the PAX2 gene probably underlay the Papillorenal syndrome in the fetus. Above finding has provided a basis for genetic counseling and clinical decision-making.

[Diagnosis of a fetus with atelosteogenesis type 2 through combined prenatal ultrasonography and whole exome sequencing].

OBJECTIVE: To explore the genetic basis for fetus with short limbs detected by prenatal ultrasonography. METHODS: Results of clinical imaging of the fetus was collected. Amniotic fluid sample was collected through amniocentesis for the extraction of fetal DNA. Whole exome sequencing was carried out to detect variants related to the clinical phenotypes. Candidate variant was verified by Sanger sequencing. RESULTS: Prenatal ultrasound showed that the fetus had short limbs but no other abnormality. Whole exome sequencing has identified that the fetus carried two heterozygous pathogenic variants c.484G>T and c.1436dupA of the SLC26A2 gene, for which its mother and father were heterozygous carriers, respectively. CONCLUSION: The fetus was diagnosed with atelosteogenesis type 2 by combined prenatal ultrasonography and whole exome sequencing, which may be attributed to the compound heterozygous variants of the SLC26A2 gene. Above findings provided evidence for the diagnosis of the fetus and genetic counseling.

Isolation and Characterization of Neural Progenitor Cells From Bone Marrow in Cell Replacement Therapy of Brain Injury.

Many studies supported that bone marrow mesenchymal stem cells (BM-MSCs) can differentiate into neural cells, but few researchers detected mature and function of nerve cells, especially in vivo study. Some researchers even suggested that BM-MSCs transplantation would not be able to differentiate into functional neural cells. To figure out the dispute, this study examined bone marrow-derived sphere-like cells, harvested via neural stem cell suspension culture, then identified as bone marrow-derived neural progenitor cells (BM-NPCs) by finding the expression of neural progenitor cells genes and proteins, neural progenitor cells characteristic and nerve cell differentiation induced through both methods. Moreover, BM-NPCs transplantation showed long-term survival and improved the ethological and histological indexes of brain injury rats, demonstrating functional nervous cells differentiated from BM-NPCs. These in vitro and in vivo results confirmed BM-NPCs differentiating into mature and functional nerve cells. This study provided valuable experimental data for BM-NPCs, suggesting a potential alternative treatment of central nervous injury disease.

Inhibiting of self-renewal, migration and invasion of ovarian cancer stem cells by blocking TGF-ß pathway.

OBJECTIVE: To investigate the effect and mechanism of SB525334 on self-renewal, migration and invasion of ovarian cancer stem cells. METHODS: ALDHhigh-expressing cancer stem cells (CSCs) were isolated from human ovarian cancer cell line SKOV-3 by flow cytometry and treated with 2µg/mL SB525334 for 6h. The sphere forming assay was used to detect the ability of self-renewal of CSCs and the colony formation assay was used to detect the tumorigenicity in vitro. Transwell migration and invasion assay were used to detect the migration and invasion ability of CSCs. To further explore the mechanism, real-time quantitative PCR and flow cytometry were used to detect the mRNA and protein expression of TGF-ß, Smad2, Smad3, phosphorylated Smad2, phosphorylated Smad3 and Smad4, respectively. Expressions of epithelial-mesenchymal transition (EMT)-related genes E-cadherin, Snail, Vimentin were also assessed. RESULTS: The self-renewal ability, tumorigenicity in vitro, migration and invasion ability of CSCs were significantly attenuated after SB525334 treatment. The expressions of TGF-ß, phosphorylated Smad2, phosphorylated Smad3, Snail, and Vimentin were decreased, while Smad4 and E-cadherin expressions were increased. CONCLUSION: SB525334 may inhibit the self-renewal, invasion and migration of ovarian CSCs by blocking the TGF-ß/Smad/EMT pathway.

Compositional and Functional Analysis of the Microbiome in Tissue and Saliva of Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (OSCC) is affected by the interaction between oral pathogen and holobionts, or the combination of the host and its microbial communities. Studies have indicated the structure and feature of the microbiome in OSCC tissue and saliva, the relationships between microbiota and OSCC sites, stages remain unclear. In the present study, OSCC tissue (T), saliva (S) and mouthwash (W) samples were collected from the same subjects and carried out the microbiome study by 16S sequencing. The results showed the T group was significantly different from the S and W groups with the character of lower richness and diversity. Proteobacteria were most enriched in the T group at the phylum level, while Firmicutes were predominant in groups S and W. At the genus level, the predominant taxa of group T were Acinetobacter and Fusobacterium, and for group S and W, the predominant taxa were Streptococcus and Prevotella. The genera related to late stage tumors were Acinetobacter and Fusobacterium, suggesting microbiota may be implicated in OSCC developing. Both compositional and functional analyses indicated that microbes in tumor tissue were potential indicator for the initiation and development of OSCC.