Recent advances in ultrasound-Fenton/Fenton-like technology for degradation of aqueous organic pollutants.

Organic pollutants in water are a serious problem because of their widespread presence, harming the ecosystem and human health. Of the commonly used advanced oxidation processes, a hybrid of ultrasound and the Fenton/Fenton-like technology has received increasing attention in treatment of aqueous organic pollutants. This hybrid is effective in degradation of organic pollutants, but its application has not been summarised. Herein, first, the application and influencing factors of this hybrid technology for organic pollutants degradation are introduced. Second, the mechanism of its action is discussed. Third, the current challenges and future perspectives associated with this technology are proposed. This review provides valuable information regarding this technology, deepens the understanding of its mechanisms of organic pollutants degradation and provides a reference for its use in treatment of aquatic environments.

[Analysis of COL1A1 and COL1A2 gene variants in two fetuses with osteogenesis imperfecta].

OBJECTIVE: To explore the genetic basis of two fetuses with an osteogenesis imperfecta (OI) phenotype. METHODS: Two fetuses diagnosed at the Affiliated Hospital of Weifang Medical College respectively on June 11, 2021 and October 16, 2021 were selected as the study subjects. Clinical data of the fetuses were collected. Amniotic fluid samples of the fetuses and peripheral blood samples of their pedigree members were collected for the extraction of genomic DNA. Whole exome sequencing (WES) and Sanger sequencing were carried out to identify the candidate variants. Minigene splicing reporter analysis was used to validate the variant which may affect the pre-mRNA splicing. RESULTS: For fetus 1, ultrasonography at 17+6 weeks of gestation had revealed shortening of bilateral humerus and femurs by more than two weeks, in addition with multiple fractures and angular deformities of long bones. WES revealed that fetus 1 had harbored a heterozygous c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in exon 49 of the COL1A1 gene (NM_000088.4). Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), it was classified as a pathogenic variant (PVS1+PS2+PM2_Supporting) for disrupting the downstream open reading frame resulting in premature translational termination, being de novo in origin, and lacking records in the population and disease databases.For fetus 2, ultrasonography at 23 weeks of gestation also revealed shortening of bilateral humerus and femurs by one and four weeks, respectively, in addition with bending of bilateral femurs, tibias and fibulas. Fetus 2 had harbored a heterozygous c.1557+3A>G variant in intron 26 of the COL1A2 gene (NM_000089.4). Minigene experiment showed that it has induced skipping of exon 26 from the COL1A2 mRNA transcript, resulting in an in-frame deletion (c.1504_1557del) of the COL1A2 mRNA transcript. The variant was inherited from its father and had been previously reported in a family with OI type 4. It was therefore classified as a pathogenic variant (PS3+PM1+PM2_Supporting+PP3+PP5). CONCLUSION: The c.3949_3950insGGCATGT (p.N1317Rfs*114) variant in the COL1A1 gene and c.1557+3A>G variant in the COL1A2 gene probably underlay the disease in the two fetuses. Above findings not only have enriched the mutational spectrum of OI, but also shed light on the correlation between its genotype and phenotype and provided a basis for genetic counseling and prenatal diagnosis for the affected pedigrees.

Whole-exome sequencing identified a novel pathogenic mutation of the CYP4F22 gene in a Chinese patient with autosomal recessive congenital ichthyosis and in vitro study of the mutant CYP4F22 protein.

Autosomal recessive congenital ichthyosis (ARCI) is a heterogeneous group of rare cornification disorders. Of the 14 genes already known to cause ARCI, CYP4F22 is a relatively new genetic etiology, the mutation spectrum of which has yet to be profiled. Using whole-exome sequencing in family trios, we identified the compound heterozygous mutations, c.844C>T (p.R282W) and c.1189C>T (p.R397C), of the CYP4F22 gene (NM_173483.4) in a Chinese neonatal boy with a congenital ichthyosis phenotype. In combination with multiple in silico analyses and the following in vitro functional studies, we provided evidence to classify these two variations as pathogenic mutations and demonstrated that both variants significantly reduced the CYP4F22 protein amount. Interestingly, the reduction of both mutant CYP4F22 protein could be recovered by trichostatin A (TSA) treatment, suggesting some deacetylation factors involved in regulating the mutant CYP4F22 protein and implying TSA might be a potential candidate compound for congenital ichthyosis caused by CYP4F22 variations.

Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics.

Patients with ulcerative colitis (UC) have a high prevalence of mental disorders, such as depression and anxiety. Gut microbiota imbalance and disturbed metabolism have been suggested to play an important role in either UC or mental disorders. However, little is known about their detailed multi-omics characteristics in patients with UC and depression/anxiety. In this prospective observational study, 240 Chinese patients were enrolled, including 129 patients with active UC (69 in Phase 1 and 60 in Phase 2; divided into depression/non-depression or anxiety/non-anxiety groups), 49 patients with depression and anxiety (non-UC), and 62 healthy people. The gut microbiota of all subjects was analyzed using 16S rRNA sequencing. The serum metabolome and proteome of patients with UC in Phase 2 were analyzed using liquid chromatography/mass spectrometry. Associations between multi-omics were evaluated by correlation analysis. The prophylactic effect of candidate metabolites on the depressive-like behavior of mice with colitis was investigated. In total, 58% of patients with active UC had depression, while 50% had anxiety. Compared to patients with UC without depression/anxiety, patients with UC and depression/anxiety had lower fecal microbial community richness and diversity, with more Lactobacillales, Sellimonas, Streptococcus, and Enterococcus but less Prevotella_9 and Lachnospira. Most metabolites (e.g., glycochenodeoxycholate) were increased in the serum, while few metabolites, including 2'-deoxy-D-ribose and L-pipecolic acid, were decreased, accompanied by a general reduction in immunoglobulin proteins. These related bacteria, metabolites, and proteins were highly connected. A prophylactic administration of 2'-deoxy-D-ribose and L-pipecolic acid significantly reduced the depressive-like behaviors in mice with colitis and alleviated the inflammatory cytokine levels in their colon, blood and brain. This study has identified a comprehensive multi-omics network related to depression and anxiety in active UC. It is composed of a certain set of gut microbiota, metabolites, and proteins, which are potential targets for clinical intervention for patients with UC and depression/anxiety.

Ipsilateral hypoperfusion caused by intracerebral steal phenomenon after carotid artery stenting: a case report.

BACKGROUND: Abnormal hypoperfusion on the surgical side after carotid artery stenting is rare. Neurological deterioration caused by it is deceptive, which can easily lead to misdiagnosis. The mechanism of hypoperfusion has rarely been demonstrated. We present here a fully studied case with a high probability of intracerebral steal phenomenon. CASE PRESENTATION: A 68-year-old male with severe right internal carotid artery stenosis and left internal carotid artery occlusion underwent right stenosis stent implantation. Restlessness and left limb hemiplegia occurred within 24 h after the procedure, which was similar to hyperperfusion syndrome. However, postoperative computerized tomography perfusion (CTP) revealed abnormal hypoperfusion in the right hemisphere. Transcranial Doppler (TCD) also showed decreased flow velocity in the right middle cerebral artery, and increased flow velocity in the right anterior cerebral artery. We considered that intracerebral steal phenomenon might be the cause, then hypervolemic therapy was accepted and the symptoms completely resolved after 3 days. CONCLUSIONS: Ipsilateral hypoperfusion is rarely seen after carotid artery stenting. Intracerebral steal phenomenon may be the underlying mechanism. CTP or TCD is helpful for the early detection of this adverse event.

SWAP-70 promotes glioblastoma cellular migration and invasion by regulating the expression of CD44s.

BACKGROUND: Switch-associated protein 70 (SWAP-70) is a guanine nucleotide exchange factor that is involved in cytoskeletal rearrangement and regulation of migration and invasion of malignant tumors. However, the mechanism by which SWAP-70 regulates the migration and invasion of glioblastoma (GB) cells has not been fully elucidated. METHODS: This study used an online database to analyze the relationship between SWAP-70 expression and prognosis in GB patients. The in vitro wound healing assay and transwell invasion assay were used to determine the role of SWAP-70 in GB cell migration and invasion as well as the underlying mechanism. RESULTS: We found that patients with high SWAP-70 expression in the GB had a poor prognosis. Downregulation of SWAP-70 inhibited GB cell migration and invasion, whereas SWAP-70 overexpression had an opposite effect. Interestingly, SWAP-70 expression was positively correlated with the expression of the standard form of CD44 (CD44s) in GB tissues. Downregulation of SWAP-70 also reduced CD44s protein expression, whereas SWAP-70 overexpression enhanced CD44s protein expression. However, downregulation of SWAP-70 expression did not affect the mRNA expression of CD44s. Reversal experiments showed that overexpressing CD44s in cell lines with downregulated SWAP-70 partially abolished the inhibitory effects of downregulated SWAP-70 on GB cell migration and invasion. CONCLUSIONS: These results suggest that SWAP-70 may promote GB cell migration and invasion by regulating the expression of CD44s. SWAP-70 may serve as a new biomarker and a potential therapeutic target for GB.

Disordered p53-MALAT1 pathway is associated with recurrent miscarriage.

Recurrent miscarriage (RM) affects about 1% of couples; however, the etiologies of half of the cases remain unknown. P53, a negative cell cycle regulator, has been found to modulate the expression of several long noncoding RNAs (lncRNAs) and overexpressed p53 has been observed in RM patients. To investigate the relationship between p53 and lncRNAs in the pathogenesis of RM, we detected the expression of p53 and six candidate lncRNAs in the villous from 27 RM patients and paired healthy controls. We found the level of NEAT1 and MALAT1 was reduced significantly and only the MALAT1 level negatively correlated with p53 protein level. By luciferase assay, we confirmed that p53 repress MALAT1 expression through directly binding to the promoter region. Functional study by using human trophoblast cell HTR-8/SVneo, we observed that p53 overexpression lead to decreased cells proliferation, migration, invasion and increased apoptosis. Meanwhile, MALAT1 overexpression partially restored these function of p53 overexpression.

Downregulated MALAT1 relates to recurrent pregnancy loss via sponging miRNAs.

Recurrent pregnancy loss (RPL) is three or more times of consecutive spontaneous loss of pregnancy. The underlying cause is complicated and the etiology of over 50% of RPL patients is unclear. Metastasis associated lung adenocarcinoma transcript-1 (MALAT-1), a multiple lncRNA functions as key regulators of diverse cellular processes. In this study, we found a reduced MALAT1 level in the villus samples of 36 RPL patients. Predicted by bioinformatics tool and confirmed by dual luciferase assay, we identified that MALAT1 directly interacts with miRNAs. Subsequent functional study in HTR-8/SVneo and HUVEC cells indicated that MALAT1 modulates the cell proliferation, apoptosis, migration and invasion via directly interact with miR-383, miR-15, miR-205 and miR-375. By modulating the VEGFA expression, MALAT1 controls the capillary formation of HUVEC cells. In conclusion, MALAT1 as a functional lncRNA controls cell proliferation, apoptosis, migration, invasion and modulates blood vessel formation. Down regulated MALAT1 induced disordered cross-talk between embryo and mother is one of the factor contributes to the pathogenesis of RPL.

CRM1/XPO1 is associated with clinical outcome in glioma and represents a therapeutic target by perturbing multiple core pathways.

BACKGROUND: Malignant gliomas are associated with a high mortality rate, and effective treatment options are limited. Thus, the development of novel targeted treatments to battle this deadly disease is imperative. METHODS: In this study, we investigated the in vitro effects of the novel reversible chromosomal region maintenance 1 (CRM1) inhibitor S109 on cell proliferation in human gliomas. S109 was also evaluated in an intracranial glioblastoma xenograft model. RESULTS: We found that high expression of CRM1 in glioma is a predictor of short overall survival and poor patient outcome. Our data demonstrate that S109 significantly inhibits the proliferation of human glioma cells by inducing cell cycle arrest at the G1 phase. Notably, we observed that high-grade glioma cells are more sensitive to S109 treatment compared with low-grade glioma cells. In an intracranial mouse model, S109 significantly prolonged the survival of tumor-bearing animals without causing any obvious toxicity. Mechanistically, S109 treatment simultaneously perturbed the three core pathways (the RTK/AKT/Foxos signaling pathway and the p53 and Rb1 tumor-suppressor pathways) implicated in human glioma cells by promoting the nuclear retention of multiple tumor-suppressor proteins. CONCLUSIONS: Taken together, our study highlights the potential role of CRM1 as an attractive molecular target for the treatment of human glioma and indicates that CRM1 inhibition by S109 might represent a novel treatment approach.

CRM1 inhibitor S109 suppresses cell proliferation and induces cell cycle arrest in renal cancer cells.

Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor eff ects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory eff ect of S109 on CRM1 is reversible. Our data demonstrated that S109 signifi cantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the eff ects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.

Plumbagin inhibits growth of gliomas in vivo via suppression of FOXM1 expression.

Plumbagin is a natural compound that is isolated from the root of the medicinal plant Plumbago zeylanica L. Based on a previous in vitro study performed by our group, which demonstrated the effectiveness of plumbagin against glioma cells, we further ascertained whether plumbagin exhibits the same effectiveness against glioma cell xenografts in nude mice. Our results revealed that tumor volume was reduced by 54.48% in the plumbagin-treated group compared with the controls. Furthermore, there were no obvious signs of toxicity as assessed by the organ sizes and cell morphologies of the mice that were treated with plumbagin. Immunofluorescence assays further revealed that plumbagin significantly inhibited glioma cell proliferation and induced cell apoptosis. Importantly, we also determined that the expressions of FOXM1 and its downstream target effectors, including cyclin D1 and Cdc25B, were down-regulated in the treated group, while the expressions of p21 and p27 were increased; the latter findings corroborate the results of our previous in vitro study. Taken together, these findings indicate that plumbagin may be a natural downregulator of FOXM1 with potential therapeutic effectiveness for the treatment of gliomas.

Novel reversible selective inhibitor of CRM1 for targeted therapy in ovarian cancer.

BACKGROUND: Ovarian cancer represents the most fatal type of gynecological malignancies. Unfortunately, there are still no effective targeted treatment strategies for ovarian cancer. Overexpression of CRM1 has been correlated with poor prognosis of patients with ovarian cancer. AIM: In this study, we investigated the antitumor effects of a novel reversible inhibitor of CRM1 in ovarian cancer cells. METHODS: The effects of S109 on proliferation was detected by CCK-8, EdU, clonogenic assay. The protein expression were determined by Western blot. The subcellular localization of RanBP1 was analyzed by immunofluorescence microscopy assay. RESULTS: We demonstrated that S109 could induce nuclear accumulation of RanBP1, a canonical biomarker for CRM1 inhibition. This effect was clearly reversible in the majority of the cells, whereas the inhibitory effect of LMB could not be reversed. Our data reveal that treatment with S109 results in decrease in proliferation and colonogenic capacity of ovarian cancer cells by arresting cell cycle. Mechanistically, S109 treatment increase the expression of the cyclin-dependent kinase inhibitor p21, while it reduced the expression of cell cycle promoting proteins, Cyclin D1 and Cyclin B. CRM1 level itself was also down-regulated following S109 treatment. Furthermore, the nuclei of cells incubated with S109 accumulated tumor suppressor proteins (Foxo1, p27 and IκB-α). More importantly, Cys528 mutation of CRM1 abolished the ability of S109 to block proliferation of ovarian cancer cells. CONCLUSIONS: Together, our study identifies CRM1 as a valid target in ovarian cancer and provides a basis for the development of S109 in ovarian cancer.

Plumbagin induces growth inhibition of human glioma cells by downregulating the expression and activity of FOXM1.

Plumbagin, a natural quinonoid constituent isolated from the root of medicinal plant Plumbago zeylanica L, has exhibited anti-tumor and anti-proliferative activities in various tumor cell lines as well as in animal tumor models. However, its anticancer effects and the mechanisms underlying its suppression of glioma cell growth have not been elucidated. Oncogenic transcription factor Forkhead Box M1 (FOXM1) has garnered particular interest in recent years as a potential target for the prevention and/or therapeutic intervention in glioma, nevertheless, less information is currently available regarding FOXM1 inhibitor. Here, we reported that plumbagin could effectively inhibit cell proliferation, migration and invasion and induce apoptosis of glioma cells. Cell cycle assay showed that plumbagin induced G2/M arrest. Interestingly, we found that plumbagin decreased the expression of FOXM1 both at mRNA level and protein level. Plumbagin also inhibited the transactivation ability of FOXM1, resulting in down-regulating the expression of FOXM1 downstream target genes, such as cyclin D1, Cdc25B, survivin, and increasing the expression of p21(CIP1) and p27(KIP1). Most importantly, down-regulation of FOXM1 by siFOXM1 transfection enhanced plumbagin-induced change in viability. On the contrary, over-expression of FOXM1 by cDNA transfection reduced plumbagin-induced glioma cell growth inhibition. These results suggest that plumbagin exhibits its anticancer activity partially by inactivation of FOXM1 signaling pathway in glioma cells. Our findings indicate that plumbagin may be considered as a potential natural FOXM1 inhibitor, which could contribute to the development of new anticancer agent for therapy of gliomas.