Multi-omics technologies and molecular biomarkers in brain tumor-related epilepsy.

BACKGROUND: Brain tumors are one of the leading causes of epilepsy, and brain tumor-related epilepsy (BTRE) is recognized as the major cause of intractable epilepsy, resulting in huge treatment cost and burden to patients, their families, and society. Although optimal treatment regimens are available, the majority of patients with BTRE show poor resolution of symptoms. BTRE has a very complex and multifactorial etiology, which includes several influencing factors such as genetic and molecular biomarkers. Advances in multi-omics technologies have enabled to elucidate the pathophysiological mechanisms and related biomarkers of BTRE. Here, we reviewed multi-omics technology-based research studies on BTRE published in the last few decades and discussed the present status, development, opportunities, challenges, and prospects in treating BTRE. METHODS: First, we provided a general review of epilepsy, BTRE, and multi-omics techniques. Next, we described the specific multi-omics (including genomics, transcriptomics, epigenomics, proteomics, and metabolomics) techniques and related molecular biomarkers for BTRE. We then presented the associated pathogenetic mechanisms of BTRE. Finally, we discussed the development and application of novel omics techniques for diagnosing and treating BTRE. RESULTS: Genomics studies have shown that the BRAF gene plays a role in BTRE development. Furthermore, the BRAF V600E variant was found to induce epileptogenesis in the neuronal cell lineage and tumorigenesis in the glial cell lineage. Several genomics studies have linked IDH variants with glioma-related epilepsy, and the overproduction of D2HG is considered to play a role in neuronal excitation that leads to seizure occurrence. The high expression level of Forkhead Box O4 (FOXO4) was associated with a reduced risk of epilepsy occurrence. In transcriptomics studies, VLGR1 was noted as a biomarker of epileptic onset in patients. Several miRNAs such as miR-128 and miRNA-196b participate in BTRE development. miR-128 might be negatively associated with the possibility of tumor-related epilepsy development. The lncRNA UBE2R2-AS1 inhibits the growth and invasion of glioma cells and promotes apoptosis. Quantitative proteomics has been used to determine dynamic changes of protein acetylation in epileptic and non-epileptic gliomas. In another proteomics study, a high expression of AQP-4 was detected in the brain of GBM patients with seizures. By using quantitative RT-PCR and immunohistochemistry assay, a study revealed that patients with astrocytomas and oligoastrocytomas showed high BCL2A1 expression and poor seizure control. By performing immunohistochemistry, several studies have reported the relationship between D2HG overproduction and seizure occurrence. Ki-67 overexpression in WHO grade II gliomas was found to be associated with poor postoperative seizure control. According to metabolomics research, the PI3K/AKT/mTOR pathway is associated with the development of glioma-related epileptogenesis. Another metabolomics study found that SV2A, P-gb, and CAD65/67 have the potential to function as biomarkers for BTRE. CONCLUSIONS: Based on the synthesized information, this review provided new research perspectives and insights into the early diagnosis, etiological factors, and personalized treatment of BTRE.

Removal of phosphate from wastewater by Fe-C micro-electrolysis: application of a novel integrated Fe/C aggregate.

To overcome the drawbacks of typical Fe-C micro-electrolysis in wastewater treatment, we developed a new electrolysis material, integrated Fe/C aggregate (FCA) made from Fe0 and carbon powder, and used it for phosphate removal from wastewater. Results show that the free iron ions could quickly react with PO43- and form an iron phosphate precipitate in phosphate-containing wastewater. The release rate of iron ions was extremely rapid in the first 10 h, indicating that Fe-C microscopic galvanic cells formed on the aggregate surface. Acid conditions are beneficial for accelerating the Fe-C micro-electrolysis reaction and enhancing the iron ion release capacity and phosphate removal capacity. In batch experiments, the maximum phosphate removal capacity of FCA was found to be 10.84 mg P/g. The phosphate removal behaviour of FCA can be well described by the Langmuir isotherm model and the pseudo-second-order kinetic model. SEM and XPS investigations also revealed that phosphates were absorbed by ferrous or ferric hydroxide and generated Fe-P precipitate, which adhered to the surface of FCA throughout the phosphate removal process. Because of its low cost and outstanding performance, the FCA aggregate has a high potential for P removal in wastewater treatment.

Sordarin- An anti-fungal antibiotic with a unique modus operandi.

Fungal infections cause serious problems in many aspects of human life, in particular infections in immunocompromised patients present serious problems. Current anti-fungal antibiotics target various metabolic pathways, predominantly the cell wall or cellular membrane metabolism. Numerous compounds are available to combat fungal infections, but their efficacy is far from satisfactory and some of them display high toxicity. The emerging antibiotic resistance represents a serious issue as well. Hence, there is a considerable need for new anti-fungal compounds with lower toxicity and higher effectiveness. One of the unique anti-fungal antibiotics is sordarin, the only known compound that acts on the fungal translational machinery per se. Sordarin inhibits protein synthesis at the elongation step of the translational cycle, acting on eukaryotic translation elongation factor 2. In this review, we deliver a robust scientific platform promoting the development of anti-fungal compounds, in particular focusing on the molecular action of sordarin.

First total synthesis of hoshinoamide A.

Hoshinoamides A, B and C, linear lipopeptides, were isolated from the marine cyanobacterium Caldora penicillata, with potent antiplasmodial activity against chloroquine-sensitive Plasmodium falciparum. Herein, we describe the first total synthesis of hoshinoamide A by the combination of liquid-phase and solid-phase peptide synthesis. Liquid-phase synthesis is to improve the coupling yield of ʟ-Val3 and N-Me-ᴅ-Phe2. Connecting other amino acids efficiency and convergence is achieved by solid-state synthesis. Our synthetic strategy could synthesize the target peptide in high yield with good purity.

Bioactive selaginellins from Selaginella tamariscina (Beauv.) Spring.

A new selaginellin named selaginellin O (1), along with three other known selaginellins (2-4) were isolated from Selaginella tamariscina (Beauv.) Spring. On the basis of spectroscopic analysis, the structure of selaginellin O was demonstrated to be 4-[(4'-hydroxy-4-formyl-3-((4-hydroxyphenyl)ethynyl)biphenyl-2-yl)(4-hydroxyphenyl)methylene]cyclohexa-2,5-dien-1-one. Compound 1, 2 and 3 exhibited appreciable cytotoxic activity against cultured HeLa cells (human cervical carcinoma cells), as well as significant antioxidant activity.

2-[(Diphenyl-phosphor-yl)(hy-droxy)meth-yl]-5-meth-oxy-phenol.

In the title compound, C(20)H(19)O(4)P, the dihedral angle between the phenyl rings is 73.3 (4)° and the dihedral angles between the benzene ring and the two phenyl rings are 43.0 (3) and 54.3 (1)°. In the crystal, O-H⋯O hydrogen bonds and weak O-H⋯O inter-actions are observed, which form a supra-molecular sheet parallel to (010).

Photochemical studies on aromatic γ,δ-epoxy ketones: efficient synthesis of benzocyclobutanones and indanones.

Irradiation of terminal aromatic γ,δ-epoxy ketones with a 450 W UV lamp led to Norrish type II cyclization/semi-pinacol rearrangement cascade reaction which formed the benzocyclobutanones containing a full-carbon quaternary center, whereas irradiation of substituted aromatic γ,δ-epoxy ketones led to the indanones through a photochemical epoxy rearrangement and 1,5-biradicals cyclization tandem reaction.

Efficient synthesis of polysubstituted isochromanones via a novel photochemical rearrangement.

A novel and convenient approach to the synthesis of polysubstituted isochromanones is described. Irradiation of 2-formyl phenylalkeno-derivatives with UV light in benzene solution afforded the corresponding products in up to 98% yield. The possible reaction mechanism is proposed and further supported by the isotopic experiments.