Roles of TRPM channels in glioma.

Gliomas are the most common type of primary brain tumor. Despite advances in treatment, it remains one of the most aggressive and deadly tumor of the central nervous system (CNS). Gliomas are characterized by high malignancy, heterogeneity, invasiveness, and high resistance to radiotherapy and chemotherapy. It is urgent to find potential new molecular targets for glioma. The TRPM channels consist of TRPM1-TPRM8 and play a role in many cellular functions, including proliferation, migration, invasion, angiogenesis, etc. More and more studies have shown that TRPM channels can be used as new therapeutic targets for glioma. In this review, we first introduce the structure, activation patterns, and physiological functions of TRPM channels. Additionally, the pathological mechanism of glioma mediated by TRPM2, 3, 7, and 8 and the related signaling pathways are described. Finally, we discuss the therapeutic potential of targeting TRPM for glioma.

•TRPM channels are widely expressed in the human body and play an important role in gliomas.• Abnormal expression of TRPM2, 3, 7, and 8 channels in gliomas is associated with disease severity and prognosis.•TRPM2, 3, 7, and 8 channels are effective targets in glioma.

Identifying influential nodes based on the disassortativity and community structure of complex network.

The complex networks exhibit significant heterogeneity in node connections, resulting in a few nodes playing critical roles in various scenarios, including decision-making, disease control, and population immunity. Therefore, accurately identifying these influential nodes that play crucial roles in networks is very important. Many methods have been proposed in different fields to solve this issue. This paper focuses on the different types of disassortativity existing in networks and innovatively introduces the concept of disassortativity of the node, namely, the inconsistency between the degree of a node and the degrees of its neighboring nodes, and proposes a measure of disassortativity of the node (DoN) by a step function. Furthermore, the paper analyzes and indicates that in many real-world network applications, such as online social networks, the influence of nodes within the network is often associated with disassortativity of the node and the community boundary structure of the network. Thus, the influential metric of node based on disassortativity and community structure (mDC) is proposed. Extensive experiments are conducted in synthetic and real networks, and the performance of the DoN and mDC is validated through network robustness experiments and immune experiment of disease infection. Experimental and analytical results demonstrate that compared to other state-of-the-art centrality measures, the proposed methods (DoN and mDC) exhibits superior identification performance and efficiency, particularly in non-disassortative networks and networks with clear community structures. Furthermore, we find that the DoN and mDC exhibit high stability to network noise and inaccuracies of the network data.

Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.

BACKGROUND: The mesenchymal (MES) subtype of glioblastoma (GBM) is believed to be influenced by both cancer cell-intrinsic alterations and extrinsic cellular interactions, yet the underlying mechanisms remain unexplored. METHODS: Identification of microglial heterogeneity by bioinformatics analysis. Transwell migration, invasion assays, and tumor models were used to determine gene function and the role of small molecule inhibitors. RNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to explore the underlying regulatory mechanisms. RESULTS: We identified the inflammatory microglial subtype of tumor-associated microglia (TAM) and found that its specific gene ITGB2 was highly expressed in TAM of MES GBM tissues. Mechanistically, the activation of ITGB2 in microglia promoted the interaction between the SH2 domain of STAT3 and the cytoplasmic domain of ITGB2, thereby stimulating the JAK1/STAT3/IL-6 signaling feedback to promote the MES transition of GBM cells. Additionally, microglia communicated with GBM cells through the interaction between the receptor ITGB2 on microglia and the ligand ICAM-1 on GBM cells, while an increased secretion of ICAM-1 was induced by the proinflammatory cytokine LIF. Further studies demonstrated that inhibition of CDK7 substantially reduced the recruitment of SNW1 to the super-enhancer of LIF, resulting in transcriptional inhibition of LIF. We identified notoginsenoside R1 as a novel LIF inhibitor that exhibited synergistic effects in combination with temozolomide. CONCLUSIONS: Our research reveals that the epigenetic-mediated interaction of GBM cells with TAM drives the MES transition of GBM and provides a novel therapeutic avenue for patients with MES GBM.

Super-enhancers complexes zoom in transcription in cancer.

Super-enhancers (SEs) consist of multiple typical enhancers enriched at high density with transcription factors, histone-modifying enzymes and cofactors. Oncogenic SEs promote tumorigenesis and malignancy by altering protein-coding gene expression and noncoding regulatory element function. Therefore, they play central roles in the treatment of cancer. Here, we review the structural characteristics, organization, identification, and functions of SEs and the underlying molecular mechanism by which SEs drive oncogenic transcription in tumor cells. We then summarize abnormal SE complexes, SE-driven coding genes, and noncoding RNAs involved in tumor development. In summary, we believe that SEs show great potential as biomarkers and therapeutic targets.

PIWI-interacting RNAs: Critical roles and therapeutic targets in cancer.

P-element-induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a novel class of small regulatory RNAs (approximately 24-31 nucleotides in length) that often bind to members of the PIWI protein family. piRNAs regulate transposons in animal germ cells; piRNAs are also specifically expressed in many human tissues and regulate pivotal signaling pathways. Additionally, the abnormal expression of piRNAs and PIWI proteins has been associated with various malignant tumours, and multiple mechanisms of piRNA-mediated target gene dysregulation are involved in tumourigenesis and progression, suggesting that they have the potential to serve as new biomarkers and therapeutic targets for tumours. However, the functions and potential mechanisms of action of piRNAs in cancer have not yet been elucidated. This review summarises the current findings on the biogenesis, function, and mechanisms of piRNAs and PIWI proteins in cancer. We also discuss the clinical significance of piRNAs as diagnostic or prognostic biomarkers and therapeutic tools for cancer. Finally, we present some critical questions regarding piRNA research that need to be addressed to provide insight into the future development of the field.

Structures and paramagnetism of five heterometallic pentanuclear metal strings containing as many as four different metals: NiPtCo2Pd(tpda)4Cl2.

Five heterometallic pentanuclear metal strings were prepared by stepwise synthesis from two to three and four kinds of metals aligned in one chain. In particular, NiPtCo2Pd(tpda)4Cl2 (5) possesses four different metals, and the SQUID measurement shows that Ni2+ is the only magnetically active center. Besides, the shortest Co(ii)-Co(ii) single bond (2.105(9) Å), so far, is reported.

[Surface-enhanced raman spectroscopic analysis of largehead Atractylodes rhizome decoction].

The normal Raman spectra and surface-enhanced Raman spectra (SERS) of largehead atractylodes rhizome decoction were tested and analyzed. The characteristic Raman bands of largehead atractylodes rhizome decoction were tentatively assigned. Six obvious Raman bands (396, 548, 617, 730, 955 and 1327 cm(-1)) were observed in the SERS of largehead atractylodes rhizome decoction. The absorption spectra of largehead atractylodes rhizome decoction and the mixture of silver colloids and largehead atractylodes rhizome decoction were tested. A new resonance absorption peak (999 nm) appeared in the long-wavelength region in UV-Vis absorption spectra of the mixture. The adsorption characteristics and possible enhancing mechanism of the largehead atractylodes rhizome decoction on silver colloid were speculated. The results showed that the surface-enhanced Raman spectroscopy might provide a new kind of precise, direct and fast detecting method for the largehead atractylodes rhizome decoction or other traditional Chinese medicine.

Interpenetrating polymer networks as a route to tunable multi-responsive biomaterials: development of novel concepts.

Novel concepts are proposed for interpenetrating polymer networks (IPNs) that can be used in biomaterials responsive to multiple types of environmental stimuli. The IPNs can be a route to the tunable biomaterials whose chemical structure and/or morphology can be adjusted to the type of task to be performed. The significance of utilizing new types of processes in polymer chemistry such as the Suzuki polycondensation and living/controlled radical polymerizations to the possibility of extending/modifying component networks in the IPNs and fine-tuning their properties is emphasized. Incorporation of nanofillers into IPNs and application of monomers other than traditional alkylacrylamides as a way to enhance versatility of IPNs are also considered.

Biocompatible poly(N-vinyllactam)-based materials with environmentally-responsive permeability.

Biocompatible polymer-based materials whose properties respond to environmental stimuli are of great value in biomedical and biotechnological applications (e.g., controlled release of drugs and sensitive reactants, bioseparations, spontaneous adjusting of flow of liquids including flow control in microfluidic devices). This study describes preparation and properties of biocompatible poly(N-vinyllactam)-based environment responsive composite membranes. The non-charged network N-vinyl lactam polymers form hydrogels that can exhibit swelling and de-swelling behaviour and, thus, regulate porosity of the membrane. The first part of the study has involved investigation of bulk polymerization reactivity of N-vinylcaprolactam (VCL)-based systems. VCL has been combined with up to 20 mol% of N-vinylpyrrolidone (N-vinylbutyrolactam). These synthetic processes have been investigated as thermal polymerizations (with and without a free-radical initiator) and photopolymerizations. Subsequently, the most reactive systems have been used to prepare composite materials by polymerization-modifying borosilicate microfibre membranes. The modified membranes have been characterized by the net mass gain, infrared spectra, and change in permeability in response to changes in ionic strength of the aqueous media. The permeability experiments have been carried out at constant fluxes and the resultant changes in trans-membrane pressure observed. Those membranes that are ionic-strength responsive could potentially be used for bio-separations and other types of biomedical and biotechnological applications.