Ubiquitination has emerged as a crucial mechanism that regulates signal transduction in diverse biological pro- cesses, including different aspects of immune functions. Ubiquitination regulates ...pattern-recognition receptor sig- naling that mediates both innate immune responses and dendritic cell maturation required for initiation of adaptive immune responses. Ubiquitination also regulates the development, activation, and differentiation of T cells, thereby maintaining efficient adaptive immune responses to pathogens and immunological tolerance to self-tissues. Like phosphorylation, ubiquitination is a reversible reaction tightly controlled by the opposing actions of ubiquitin ligases and deubiquitinases. Deregulated ubiquitination events are associated with immunological disorders, including auto- immune and inflammatory diseases.
Metal-organic frameworks (MOFs) have emerged as promising materials in the areas of gas storage, magnetism, luminescence, and catalysis owing to their superior property of having highly crystalline ...structures. However, MOF stability toward heat or humidity is considerably less as compared to carbons because they are constructed from the assembly of ligands with metal ions or clusters
via
coordination bonds. Transforming MOFs into carbons is bringing the novel potential for MOFs to achieve industrialization, and carbons with controlled pore sizes and surface doping are one of the most important porous materials. By selecting MOFs as a precursor or template, carbons with heteroatom doping and well-developed pores can be achieved. In this review, we discussed the state-of-art study progress made in the new development of MOF-derived metal-free porous carbons. In particular, the potential use of metal-free carbons from environmental and energy perspectives, such as adsorption, supercapacitors, and catalysts, were analyzed in detail. Moreover, an outlook for the sustainable development of MOF-derived porous carbons in the future was also presented.
Transforming MOFs into metal-free carbons is bringing the novel potential for MOFs to achieve industrialization owing to their with highly crystalline porous structures, showing great potential on the energy storage and environmental applications.
Acetaminophen (APAP) overdose is the leading cause of drug-induced acute liver failure in many developed countries. Mitochondrial oxidative stress is considered to be the predominant cellular event ...in APAP-induced liver injury. Accordingly, N-acetyl cysteine, a known scavenger of reactive oxygen species (ROS), is recommended as an effective clinical antidote against APAP-induced acute liver injury (AILI) when it is given at an early phase; however, the narrow therapeutic window limits its use. Hence, the development of novel therapeutic approaches that can offer broadly protective effects against AILI is clearly needed. To this end, it is necessary to better understand the mechanisms of APAP hepatotoxicity. Up to now, in addition to mitochondrial oxidative stress, many other cellular processes, including phase I/phase II metabolism, endoplasmic reticulum stress, autophagy, sterile inflammation, microcirculatory dysfunction, and liver regeneration, have been identified to be involved in the pathogenesis of AILI, providing new targets for developing more effective therapeutic interventions against APAP-induced liver injury. In this review, we summarize intracellular and extracellular events involved in APAP hepatotoxicity, along with emphatic discussions on the possible therapeutic approaches targeting these different cellular events.
Selenium (Se) is an essential micronutrient for mammals, and its deficiency seriously threatens human health. A series of biofortification strategies have been developed to produce Se-enriched foods ...for combating Se deficiency. Although there have been some inconsistent results, extensive evidence has suggested that Se supplementation is beneficial for preventing and treating several chronic diseases. Understanding the association between Se and chronic diseases is essential for guiding clinical practice, developing effective public health policies, and ultimately counteracting health issues associated with Se deficiency. The current review will discuss the food sources of Se, biofortification strategies, metabolism and biological activities, clinical disorders and dietary reference intakes, as well as the relationship between Se and health outcomes, especially cardiovascular disease, diabetes, chronic inflammation, cancer, and fertility. Additionally, some concepts were proposed, there is a non-linear U-shaped dose-responsive relationship between Se status and health effects: subjects with a low baseline Se status can benefit from Se supplementation, while Se supplementation in populations with an adequate or high status may potentially increase the risk of some diseases. In addition, at supra-nutritional levels, methylated Se compounds exerted more promising cancer chemo-preventive efficacy in preclinical trials.
Since nuclear factor of κ‐light chain of enhancer‐activated B cells (NF‐κB) was discovered in 1986, extraordinary efforts have been made to understand the function and regulating mechanism of NF‐κB ...for 35 years, which lead to significant progress. Meanwhile, the molecular mechanisms regulating NF‐κB activation have also been illuminated, the cascades of signaling events leading to NF‐κB activity and key components of the NF‐κB pathway are also identified. It has been suggested NF‐κB plays an important role in human diseases, especially inflammation‐related diseases. These studies make the NF‐κB an attractive target for disease treatment. This review aims to summarize the knowledge of the family members of NF‐κB, as well as the basic mechanisms of NF‐κB signaling pathway activation. We will also review the effects of dysregulated NF‐κB on inflammation, tumorigenesis, and tumor microenvironment. The progression of the translational study and drug development targeting NF‐κB for inflammatory diseases and cancer treatment and the potential obstacles will be discussed. Further investigations on the precise functions of NF‐κB in the physiological and pathological settings and underlying mechanisms are in the urgent need to develop drugs targeting NF‐κB for inflammatory diseases and cancer treatment, with minimal side effects.
This year (2021) marks the 35th anniversary of the discovery of NF‐κB. With so many years of in‐depth research on NF‐κB, people have realized that the NF‐κB signaling pathway plays an important role in inflammation, immunity, cell survival and proliferation. This review summarizes the relevant knowledge of the NF‐κB signaling pathway, inflammation, and cancer. The progression of the translational study and drug development targeting NF‐κB for inflammatory diseases and cancer treatment and the potential obstacles will also be discussed.
The tripartite motif (TRIM) proteins have been intensively studied as essential modulators in various biological processes, especially in regulating a wide range of signaling pathways involved in ...immune responses. Most TRIM proteins have E3 ubiquitin ligase activity, mediating polyubiquitination of target proteins. Emerging evidence demonstrates that TRIM proteins play important roles in innate immunity by regulating pattern recognition receptors, vital adaptor proteins, kinases, and transcription factors in innate immune signaling pathways. Additionally, the critical roles of TRIM proteins in adaptive immunity, especially in T cell development and activation, are increasingly appreciated. In this review, we aim to summarize the studies on TRIMs in both innate and adaptive immunity, focusing on their E3 ubiquitin ligase functions in pattern recognition receptor signaling pathways and T cell functions, shedding light on the developing new strategies for modulating innate and adaptive immune responses against invading pathogens and avoiding autoimmunity.
Bacteria belonging to the genera Sphingomonas and Sphingobium are known for their ability to catabolize aromatic compounds. In this study, we analyzed the whole genome sequences of 26 strains in the ...genera Sphingomonas and Sphingobium to gain insight into dissemination of bioremediation capabilities, biodegradation potential, central pathways and genome plasticity. Phylogenetic analysis revealed that both Sphingomonas sp. strain BHC-A and Sphingomonas paucimobilis EPA505 should be placed in the genus Sphingobium. The bph and xyl gene cluster was found in 6 polycyclic aromatic hydrocarbons-degrading strains. Transposase and IS coding genes were found in the 6 gene clusters, suggesting the mobility of bph and xyl gene clusters. β-ketoadipate and homogentisate pathways were the main central pathways in Sphingomonas and Sphingobium strains. A large number of oxygenase coding genes were predicted in the 26 genomes, indicating a huge biodegradation potential of the Sphingomonas and Sphingobium strains. Horizontal gene transfer related genes and prophages were predicted in the analyzed strains, suggesting the ongoing evolution and shaping of the genomes. Analysis of the 26 genomes in this work contributes to the understanding of dispersion of bioremediation capabilities, bioremediation potential and genome plasticity in strains belonging to the genera Sphingomonas and Sphingobium.
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•Gene clusters analysis for aromatic compounds degradation in Sphingomonas and Sphingobium strains•Catechol as a key intermediate in degradation pathway for aromatic compounds•Horizontal gene transfer related element in abundance suggesting an ongoing evolution and shaping of the genomes
The immune system plays pivotal roles in the occurrence and progression of cancers. As blockade of immune-checkpoint has been proven effective at improving anti-tumor immune response in multiple ...tumor types, the tumor immunotherapy still faces many challenges. Emerging evidence indicates lymphoid organ-like structures, also called tertiary lymphoid organs (TLOs) or ectopic lymphoid organs (ELOs), have been identified in cancers, as the result of lymphoid neoorganogenesis. The prognostic value of TLOs in cancer patients has been evaluated with debates, however, such well-organized lymphoid structures in the site of cancer indicate TLOs are the important modulators of cancer immunological microenvironment. TLOs have attracted remarkable efforts to investigate their neoorganogenesis and function in immune responses, aiming to develop new strategies for cancer immunotherapy. In this review, we summarize the current understandings about the molecular and cellular mechanisms governing the formation and function of TLOs in immune responses against cancer.
Cancer-associated fibroblasts (CAFs) are the predominant components of the tumor microenvironment (TME) and influence cancer hallmarks, but without systematic investigation on their ubiquitous ...characteristics across different cancer types. Here, we perform pan-cancer analysis on 226 samples across 10 solid cancer types to profile the TME at single-cell resolution, illustrating the commonalities/plasticity of heterogenous CAFs. Activation trajectory of the major CAF types is divided into three states, exhibiting distinct interactions with other cell components, and relating to prognosis of immunotherapy. Moreover, minor CAF components represent the alternative origin from other TME components (e.g., endothelia and macrophages). Particularly, the ubiquitous presentation of endothelial-to-mesenchymal transition CAF, which may interact with proximal SPP1
tumor-associated macrophages, is implicated in endothelial-to-mesenchymal transition and survival stratifications. Our study comprehensively profiles the shared characteristics and dynamics of CAFs, and highlight their heterogeneity and plasticity across different cancer types. Browser of integrated pan-cancer single-cell information is available at https://gist-fgl.github.io/sc-caf-atlas/ .
•Ca-alginate entrapped and free MnP were used to treat textile effluent.•The efficiency was evaluated on the basis of decolorization and detoxification.•Various bio-degradation process variables were ...optimized.•Cytotoxicity and mutagenicity reduced significantly of MnP treated effluent.•The use of immobilized MnP is suggested for the remediation of textile effluents.
Present study was aimed to appraise the potential of free and immobilized manganese peroxidase (MnP) for the decolorization and detoxification of textile effluent. MnP was immobilized in Ca-alginate beads at optimized conditions of sodium alginate, calcium chloride and enzyme concentrations. Maximum effluent decolorization of 87.4% was achieved in the presence of H2O2 (1mmoll−1), 1-hydroxybenzotriazole (1mmoll−1), pH (5.0) and temperature (40°C) for 5h of incubation time. The effluent treated at optimized conditions was subjected to toxicity evaluation. The cytotoxicity was evaluated using Allium cepa, brine shrimp and heamolytic bioassays; whereas mutagenicity was tested using Ames test of both treated and untreated effluent. The cytotoxicity of treated sample reduced significantly and A. cepa showed increase in root length, root count and mitotic index up to 38.46%, 43.47% and 41.83%, respectively, whereas red blood cells (RBCs) lysis reduced 69.84% and brine shrimp nauplii death reduced up to 63.64% in immobilized MnP treated effluent. The mutagenicity reduced up to 73.44% and 75.43% for TA98 and TA100 strains, respectively. The Ca-alginate beads encapsulated MnP revealed promising bio-catalytic efficiency and could be used for the decolorization and detoxification of textile effluents.
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