Research Progress of Bioactive Components in Sanghuangporus spp.

The species in Sanghuangporus are a group of edible mushrooms with a long history of oral use in East Asia as a health-improvement method. They should be classified under the genus Sanghuangporus rather than mistakenly in Phellinus or Inonotus. The major components in this genus consist of polysaccharides, polyphenols, triterpenoids, and flavonoids, all of which exist in the fruiting bodies and mycelia. For extraction, studies have shown methods using hot water, ethanol, DES solvent, and alkaline, followed by purification methods including traditional anion column, Sevag solution, macroporous resin, and magnetic polymers. Proven by modern medical technology, these components possess promising anti-inflammatory, antioxidative, antitumor, and immunoregulation effects; additionally, they have health-improving effects including pulmonary protection, hypoglycemic properties, sleep improvement, gout mitigation, antiaging, neuroprotection, and muscle-strengthening abilities. Several toxicity studies have revealed their safety and recommend a dose of 1 g/kg for mice. As a newly emerged concept, functional food can provide not only life-sustaining nutrients but also some health-improving effects. In conclusion, we substantiate Sanghuang as a functional food by comprehensively presenting information on extraction and purification methods, component medical and structural properties, and nontoxicity, hoping to benefit the development of Sanghuang species as a group of functional food.

CD36: The Bridge between Lipids and Tumors.

It has been found that the development of some cancers can be attributed to obesity, which is associated with the excessive intake of lipids. Cancer cells undergo metabolic reprogramming, shifting from utilizing glucose to fatty acids (FAs) for energy. CD36, a lipid transporter, is highly expressed in certain kinds of cancer cells. High expressions of CD36 in tumor cells triggers FA uptake and lipid accumulation, promoting rapid tumor growth and initiating metastasis. Meanwhile, immune cells in the tumor microenvironment overexpress CD36 and undergo metabolic reprogramming. CD36-mediated FA uptake leads to lipid accumulation and has immunosuppressive effects. This paper reviews the types of FAs associated with cancer, high expressions of CD36 that promote cancer development and progression, effects of CD36 on different immune cells in the tumor microenvironment, and the current status of CD36 as a therapeutic target for the treatment of tumors with high CD36 expression.

A computational study of the influence of nanoparticle shape on clathrin-mediated endocytosis.

Nanoparticles have been widely used in biomedical applications such as gene/drug delivery, molecular imaging and diagnostics. Among the physicochemical properties, shape is a vital design parameter for tuning the cell uptake of nanoparticles. However, the regulatory mechanism remains elusive due to the complexity of the cell membrane and multiple pathways of cell uptake. Therefore, in this computational study, we design and clarify cell membrane wrapping on different shaped nanoparticles (sphere, rod and disk) with a clathrin assembly to model the clathrin-mediated endocytosis, which is an important pathway of nanoparticle cell uptake. Our simulations revealed that the clathrin-mediated endocytosis is shape sensitive for nanoparticles. Spherical nanoparticles are easier to be wrapped by the membrane with the self-assembly of clathrins than the other shaped nanoparticles with the same volume, and the efficiency declines with the increase in the nanoparticle shape anisotropy. Furthermore, simulation results showed clear evidence that rotation is one of the typical characteristics determining the kinetics of clathrin-mediated endocytosis of shaped nanoparticles. Especially for rod nanoparticles with high aspect ratios, nanoparticle rotation occurs in both the invagination and wrapping stages, which is different from the case without clathrins. The size and shape mismatch between the clathrin-mediated vesicle and the nanoparticle determines how the nanoparticle rotates and is wrapped by the membrane. In addition, the wrapping time of nanoparticles depends not only on the shape of the nanoparticle but also on its initial orientation and size, the rate of clathrin self-assembly and the surface tension of the membrane. These results provide insights into the interplay between cell membrane wrapping and clathrin assembly, where the nanoparticle shape matters. Understanding the dynamics mechanism of clathrin-mediated endocytosis of nanoparticles will help to design targeted nanomedicines with an improved efficacy.

ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer's disease process.

Alzheimer's disease (AD) accounts for approximately 60% of dementia cases worldwide. Advanced age is the most significant risk factor for AD and approximately two-thirds of cases relate to women. While the previous meta-analysis suggests that estrogen receptor (ESR) genetic polymorphisms are closely associated with dementia, the implications of this observation on a molecular level are not entirely understood. Our study explores this intricate molecular puzzle through the use of a variety of bioinformatics tools. Initially, we attempted to elucidate mechanisms underlying breast cancer development by identifying the high-throughput dataset of ESR1-knockdown breast cancer tissue samples. Surprisingly, KEGG pathway enrichment showed that the most frequently occurring proteins were related to axonal guidance and inflammation-related gene markers. These observations were supported by an external high throughput dataset of AD inflammatory samples in vivo. Our results suggest that ESR1 is modulated by apolipoprotein E (APOE) through CEBPB/ATF4, mir-155-5p, or mir-1-3p. Moreover, sea hare-hydrolysates (SHH), as one of the axonal guidance molecules, could regulate the STAT3/PRDM1/CEBPB pathway and consequently induce cell death through pyroptosis signaling pathways, trigger the secretion of IL1ß, leading to neuroinflammation and worsening AD pathogenesis. Molecular docking verification demonstrated that the predicted natural products scoulerine and genistein displayed strong binding affinities for BACE1 and ESR1, respectively. This strategy can be used to design novel, personalized therapeutic approaches to treatment and a first-in-class clinical lead for the personalised treatment of AD.

Salinomycin-Loaded High-Density Lipoprotein Exerts Promising Anti-Ovarian Cancer Effects by Inhibiting Epithelial-Mesenchymal Transition.

Background: Effective treatments for ovarian cancer remain elusive, and survival rates have long been considered grim. Ovarian cancer stem cells (OCSCs) and epithelial-mesenchymal transition (EMT) are associated with cancer progression and metastasis, as well as drug resistance and eventual treatment failure. Salinomycin (Sal) has an extensive effect on a variety of cancer stem cells (CSCs); however, its poor water solubility and toxicity to healthy tissues at high doses limit further research into its potential as an anti-cancer drug. We proposed a therapeutic strategy by constructing a tumor-targeting carrier that mimics high-density lipoprotein (HDL) to synthesize salinomycin-loaded high-density lipoprotein (S-HDL). This strategy helps reduce the side effects of salinomycin, thereby improving its clinical benefits. Methods: OCSCs were isolated from ovarian cancer cells (OCCs) and the uptake of HDL nanoparticles was observed using laser confocal microscopes. After the cell viability analysis revealed the inhibitory effect of S-HDL on OCCs and OCSCs, the main biological processes influenced by S-HDL were predicted with a transcriptome sequencing analysis and verified in vitro and in vivo. Results: Cellular uptake analysis showed that the HDL delivery system was able to significantly enhance the uptake of Sal by OCCs, tentatively validating the targeting role of recombinant HDL, so that S-HDL could reduce the toxicity of Sal and increase its anti-ovarian cancer effects. Conversely, S-HDL could exert anti-ovarian cancer effects by inhibiting the proliferation of OCCs and OCSCs, promoting apoptosis, blocking EMT, and suppressing stemness and angiogenesis-related protein expression in vitro and in vivo. Conclusion: S-HDL had stronger anti-ovarian cancer effects than unencapsulated Sal. Thus, it may be a potential agent for ovarian cancer treatment in the future.

Selective membrane wrapping on differently sized nanoparticles regulated by clathrin assembly: A computational model.

Nanoparticles (NPs) enter cells via multiple pathways, all of which are NP size dependent. Previous studies indicated that the clathrin-mediated endocytosis has different selectivity for the NP size, but the regulatory mechanism remains unclear and difficult to study at the molecular scale in vivo. By means of computer simulation, here we design membrane wrapping on differently sized NPs with mimic clathrin assembly at the opposite membrane side. With relatively large NPs readily wrapped by a pure membrane as manifested, clathrin modulates the process and tunes the size selectivity. Although finite curvature can be generated by cage-like clathrin assembly to facilitate membrane wrapping on relatively small NPs, the clathrin assemblage has a certain range of size, which is mismatched with larger NPs. Besides, the local membrane patch is rigidified by clathrin to increase the barrier of membrane wrapping on larger NPs. Competition of these items determines whether membrane wrapping on NPs is promoted or suppressed, and can be tuned by the NP-membrane adhesion strength, clathrin concentration, and inter-NP distance. Our results highlight the significance of complex environment in altering the nature of NP interaction with cell membranes, and are expected to help design NPs for biomedical applications requiring precise control of NP uptake or cell membrane attachment.

The Molecular Mechanism of Multiple Organ Dysfunction and Targeted Intervention of COVID-19 Based on Time-Order Transcriptomic Analysis.

Coronavirus disease 2019 (COVID-19) pandemic is caused by the novel coronavirus that has spread rapidly around the world, leading to high mortality because of multiple organ dysfunction; however, its underlying molecular mechanism is unknown. To determine the molecular mechanism of multiple organ dysfunction, a bioinformatics analysis method based on a time-order gene co-expression network (TO-GCN) was performed. First, gene expression profiles were downloaded from the gene expression omnibus database (GSE161200), and a TO-GCN was constructed using the breadth-first search (BFS) algorithm to infer the pattern of changes in the different organs over time. Second, Gene Ontology enrichment analysis was used to analyze the main biological processes related to COVID-19. The initial gene modules for the immune response of different organs were defined as the research object. The STRING database was used to construct a protein-protein interaction network of immune genes in different organs. The PageRank algorithm was used to identify five hub genes in each organ. Finally, the Comparative Toxicogenomics Database played an important role in exploring the potential compounds that target the hub genes. The results showed that there were two types of biological processes: the body's stress response and cell-mediated immune response involving the lung, trachea, and olfactory bulb (olf) after being infected by COVID-19. However, a unique biological process related to the stress response is the regulation of neuronal signals in the brain. The stress response was heterogeneous among different organs. In the lung, the regulation of DNA morphology, angiogenesis, and mitochondrial-related energy metabolism are specific biological processes related to the stress response. In particular, an effect on tracheal stress response was made by the regulation of protein metabolism and rRNA metabolism-related biological processes, as biological processes. In the olf, the distinctive stress responses consist of neural signal transmission and brain behavior. In addition, myeloid leukocyte activation and myeloid leukocyte-mediated immunity in response to COVID-19 can lead to a cytokine storm. Immune genes such as SRC, RHOA, CD40LG, CSF1, TNFRSF1A, FCER1G, ICAM1, LAT, LCN2, PLAU, CXCL10, ICAM1, CD40, IRF7, and B2M were predicted to be the hub genes in the cytokine storm. Furthermore, we inferred that resveratrol, acetaminophen, dexamethasone, estradiol, statins, curcumin, and other compounds are potential target drugs in the treatment of COVID-19.

Genome-Wide Identification and Analysis of the NPR1-Like Gene Family in Bread Wheat and Its Relatives.

NONEXPRESSOR OF PATHOGENESIS-RELATED GENES 1 (NPR1), and its paralogues NPR3 and NPR4, are bona fide salicylic acid (SA) receptors and play critical regulatory roles in plant immunity. However, comprehensive identification and analysis of the NPR1-like gene family had not been conducted so far in bread wheat and its relatives. Here, a total of 17 NPR genes in Triticum aestivum, five NPR genes in Triticum urartu, 12 NPR genes in Triticum dicoccoides, and six NPR genes in Aegilops tauschii were identified using bioinformatics approaches. Protein properties of these putative NPR1-like genes were also described. Phylogenetic analysis showed that the 40 NPR1-like proteins, together with 40 NPR1-related proteins from other plant species, were clustered into three major clades. The TaNPR1-like genes belonging to the same Arabidopsis subfamilies shared similar exon-intron patterns and protein domain compositions, as well as conserved motifs and amino acid residues. The cis-regulatory elements related to SA were identified in the promoter regions of TaNPR1-like genes. The TaNPR1-like genes were intensively mapped on the chromosomes of homoeologous groups 3, 4, and 5, except TaNPR2-D. Chromosomal distribution and collinearity analysis of NPR1-like genes among bread wheat and its relatives revealed that the evolution of this gene family was more conservative following formation of hexaploid wheat. Transcriptome data analysis indicated that TaNPR1-like genes exhibited tissue/organ-specific expression patterns and some members were induced under biotic stress. These findings lay the foundation for further functional characterization of NPR1-like proteins in bread wheat and its relatives.