Emerging polymeric materials for treatment of oral diseases: design strategy towards a unique oral environment.

Oral diseases are prevalent but challenging diseases owing to the highly movable and wet, microbial and inflammatory environment. Polymeric materials are regarded as one of the most promising biomaterials due to their good compatibility, facile preparation, and flexible design to obtain multifunctionality. Therefore, a variety of strategies have been employed to develop materials with improved therapeutic efficacy by overcoming physicobiological barriers in oral diseases. In this review, we summarize the design strategies of polymeric biomaterials for the treatment of oral diseases. First, we present the unique oral environment including highly movable and wet, microbial and inflammatory environment, which hinders the effective treatment of oral diseases. Second, a series of strategies for designing polymeric materials towards such a unique oral environment are highlighted. For example, multifunctional polymeric materials are armed with wet-adhesive, antimicrobial, and anti-inflammatory functions through advanced chemistry and nanotechnology to effectively treat oral diseases. These are achieved by designing wet-adhesive polymers modified with hydroxy, amine, quinone, and aldehyde groups to provide strong wet-adhesion through hydrogen and covalent bonding, and electrostatic and hydrophobic interactions, by developing antimicrobial polymers including cationic polymers, antimicrobial peptides, and antibiotic-conjugated polymers, and by synthesizing anti-inflammatory polymers with phenolic hydroxy and cysteine groups that function as immunomodulators and electron donors to reactive oxygen species to reduce inflammation. Third, various delivery systems with strong wet-adhesion and enhanced mucosa and biofilm penetration capabilities, such as nanoparticles, hydrogels, patches, and microneedles, are constructed for delivery of antibiotics, immunomodulators, and antioxidants to achieve therapeutic efficacy. Finally, we provide insights into challenges and future development of polymeric materials for oral diseases with promise for clinical translation.

Saliva - a new opportunity for fluid biopsy.

Saliva is a complex biological fluid with a variety of biomolecules, such as DNA, RNA, proteins, metabolites and microbiota, which can be used for the screening and diagnosis of many diseases. In addition, saliva has the characteristics of simple collection, non-invasive and convenient storage, which gives it the potential to replace blood as a new main body of fluid biopsy, and it is an excellent biological diagnostic fluid. This review integrates recent studies and summarizes the research contents of salivaomics and the research progress of saliva in early diagnosis of oral and systemic diseases. This review aims to explore the value and prospect of saliva diagnosis in clinical application.

Nanocomposite Hydrogels in Regenerative Medicine: Applications and Challenges.

Regenerative medicine is a highly regarded multidisciplinary field that aims to transform the future of clinical medicine through curative strategies rather than palliative therapies. As an emerging field, the development of regenerative medicine cannot be achieved without multifunctional biomaterials. Among the various bioscaffold materials, hydrogels are one of the materials of interest in bioengineering and medical research because of their similarity to the natural extracellular matrix and good biocompatibility. However, conventional hydrogels have simple internal structures and single cross-linking modes, which require improvement in a single function and structural stability. Introducing multifunctional nanomaterials into 3D hydrogel networks physically or chemically avoids their disadvantages. Nanomaterials (NMs) are materials in the size range of 1-100 nm with distinct physical and chemical properties that differ from that of the macroscopic size and enable hydrogels to exhibit multifunctionality. Although regenerative medicine and hydrogels have been well researched in their respective fields, the connection between nanocomposite hydrogels (NCHs) and regenerative medicine has not been elaborated. Therefore, this review briefly describes the preparation and design requirements of NCHs and discusses their applications and challenges in regenerative medicine, hoping to clarify the relationship between the two.

Severe hypertriglyceridemia and hypercholesterolemia accelerating renal injury: a novel model of type 1 diabetic hamsters induced by short-term high-fat / high-cholesterol diet and low-dose streptozotocin.

BACKGROUND: Hyperlipidemia is thought to be a major risk factor for the progression of renal diseases in diabetes. Recent studies have shown that lipid profiles are commonly abnormal early on type 2 diabetes mellitus (T2DM) with diabetic nephropathy. However, the early effects of triglyceride and cholesterol abnormalities on renal injury in type 1 diabetes mellitus (T1DM) are not fully understood and require reliable animal models for exploration of the underlying mechanisms. Hamster models are important tools for studying lipid metabolism because of their similarity to humans in terms of lipid utilization and high susceptibility to dietary cholesterol and fat. METHODS: Twenty-four male Golden Syrian hamsters (100-110 g) were rendered diabetes by intraperitoneal injections of streptozotocin (STZ) on consecutive 3 days at dose of 30 mg/kg, Ten days after STZ injections, hamsters with a plasma Glu concentration more than 12 mmol/L were selected as insulin deficient ones and divided into four groups (D-C, D-HF, D-HC, and D-HFHC), and fed with commercially available standard rodent chow, high-fat diet, high-cholesterol diet, high-fat and cholesterol diet respectively, for a period of four weeks. RESULTS: After an induction phase, a stable model of renal injury was established with the aspects of early T1DM kidney disease, These aspects were severe hypertriglyceridemia, hypercholesterolemia, proteinuria with mesangial matrix accumulation, upgraded creatinine clearance, significant cholesterol and triglyceride deposition, and increasing glomerular surface area, thickness of basement membrane and mesangial expansion. The mRNA levels of sterol regulatory element binding protein-1c, transforming growth factors-ß, plasminogen activator inhibitor-1, tumor necrosis factor-α and interleukin-6 in the D-HFHC group were significantly up-regulated compared with control groups. CONCLUSIONS: This study presents a novel, non-transgenic, non-surgical method for induction of renal injury in hamsters, which is an important complement to existing diabetic models for pathophysiological studies in early acute and chronic kidney disease, especially hyperlipidemia. These data suggest that both severe hypertriglyceridemia and hypercholesterolemia can accelerate renal injury in the early development of T1DM.

Construction of plastid reference proteomes for maize and Arabidopsis and evaluation of their orthologous relationships; the concept of orthoproteomics.

Plastids are essential organelles because they contribute to primary and secondary metabolism and plant signaling networks. A high-quality inventory of the plastid proteome is therefore a critical tool in plant research. We present reference plastid proteomes for maize (Zea mays) and Arabidopsis (Arabidopsis thaliana) with, respectively, 1564 and 1559 proteins. This was based on manual curation of published experimental information, including >150 proteomics studies regarding different (sub)cellular fractions, and new quantitative proteomics experiments on plastid subfractions specifically designed to fill gaps in current knowledge. These plastid proteomes represent an estimated 40 (maize) to 50% (Arabidopsis) of all plastid proteins and can serve as a "gold standard" because of their low false-positive rate. To facilitate direct comparison of these plastid proteomes, identify "missing" proteins, and evaluate species-specific differences, we determined their orthologous relationships. The multistep strategy to best define these orthologous relationships is explained. Putative plastid locations for orthologs without known subcellular locations were inferred based on the robustness of orthology and weighing of experimental evidence, increasing both plastid proteome sizes. Examples that highlight differences and similarities between maize and Arabidopsis and underscore the quality of the orthology assignments are discussed.

Nucleoid-enriched proteomes in developing plastids and chloroplasts from maize leaves: a new conceptual framework for nucleoid functions.

Plastids contain multiple copies of the plastid chromosome, folded together with proteins and RNA into nucleoids. The degree to which components of the plastid gene expression and protein biogenesis machineries are nucleoid associated, and the factors involved in plastid DNA organization, repair, and replication, are poorly understood. To provide a conceptual framework for nucleoid function, we characterized the proteomes of highly enriched nucleoid fractions of proplastids and mature chloroplasts isolated from the maize (Zea mays) leaf base and tip, respectively, using mass spectrometry. Quantitative comparisons with proteomes of unfractionated proplastids and chloroplasts facilitated the determination of nucleoid-enriched proteins. This nucleoid-enriched proteome included proteins involved in DNA replication, organization, and repair as well as transcription, mRNA processing, splicing, and editing. Many proteins of unknown function, including pentatricopeptide repeat (PPR), tetratricopeptide repeat (TPR), DnaJ, and mitochondrial transcription factor (mTERF) domain proteins, were identified. Strikingly, 70S ribosome and ribosome assembly factors were strongly overrepresented in nucleoid fractions, but protein chaperones were not. Our analysis strongly suggests that mRNA processing, splicing, and editing, as well as ribosome assembly, take place in association with the nucleoid, suggesting that these processes occur cotranscriptionally. The plastid developmental state did not dramatically change the nucleoid-enriched proteome but did quantitatively shift the predominating function from RNA metabolism in undeveloped plastids to translation and homeostasis in chloroplasts. This study extends the known maize plastid proteome by hundreds of proteins, including more than 40 PPR and mTERF domain proteins, and provides a resource for targeted studies on plastid gene expression. Details of protein identification and annotation are provided in the Plant Proteome Database.

Structural and metabolic transitions of C4 leaf development and differentiation defined by microscopy and quantitative proteomics in maize.

C(4) grasses, such as maize (Zea mays), have high photosynthetic efficiency through combined biochemical and structural adaptations. C(4) photosynthesis is established along the developmental axis of the leaf blade, leading from an undifferentiated leaf base just above the ligule into highly specialized mesophyll cells (MCs) and bundle sheath cells (BSCs) at the tip. To resolve the kinetics of maize leaf development and C(4) differentiation and to obtain a systems-level understanding of maize leaf formation, the accumulation profiles of proteomes of the leaf and the isolated BSCs with their vascular bundle along the developmental gradient were determined using large-scale mass spectrometry. This was complemented by extensive qualitative and quantitative microscopy analysis of structural features (e.g., Kranz anatomy, plasmodesmata, cell wall, and organelles). More than 4300 proteins were identified and functionally annotated. Developmental protein accumulation profiles and hierarchical cluster analysis then determined the kinetics of organelle biogenesis, formation of cellular structures, metabolism, and coexpression patterns. Two main expression clusters were observed, each divided in subclusters, suggesting that a limited number of developmental regulatory networks organize concerted protein accumulation along the leaf gradient. The coexpression with BSC and MC markers provided strong candidates for further analysis of C(4) specialization, in particular transporters and biogenesis factors. Based on the integrated information, we describe five developmental transitions that provide a conceptual and practical template for further analysis. An online protein expression viewer is provided through the Plant Proteome Database.

Immunotoxicity of metal and metal oxide nanoparticles: from toxic mechanisms to metabolism and outcomes.

The influence of metal and metal oxide nanomaterials on various fields since their discovery has been remarkable. They have unique properties, and therefore, have been employed in specific applications, including biomedicine. However, their potential health risks cannot be ignored. Several studies have shown that exposure to metal and metal oxide nanoparticles can lead to immunotoxicity. Different types of metals and metal oxide nanoparticles may have a negative impact on the immune system through various mechanisms, such as inflammation, oxidative stress, autophagy, and apoptosis. As an essential factor in determining the function and fate of immune cells, immunometabolism may also be an essential target for these nanoparticles to exert immunotoxic effects in vivo. In addition, the biodegradation and metabolic outcomes of metal and metal oxide nanoparticles are also important considerations in assessing their immunotoxic effects. Herein, we focus on the cellular mechanism of the immunotoxic effects and toxic effects of different types of metal and metal oxide nanoparticles, as well as the metabolism and outcomes of these nanoparticles in vivo. Also, we discuss the relationship between the possible regulatory effect of nanoparticles on immunometabolism and their immunotoxic effects. Finally, we present perspectives on the future research and development direction of metal and metal oxide nanomaterials to promote scientific research on the health risks of nanomaterials and reduce their adverse effects on human health.

Advanced Delivery Strategies for Immunotherapy in Type I Diabetes Mellitus.

Type 1 diabetes mellitus (T1DM) has been defined as an autoimmune disease characterised by immune-mediated destruction of the pancreatic ß cells, leading to absolute insulin deficiency and hyperglycaemia. Current research has increasingly focused on immunotherapy based on immunosuppression and regulation to rescue T-cell-mediated ß-cell destruction. Although T1DM immunotherapeutic drugs are constantly under clinical and preclinical development, several key challenges remain, including low response rates and difficulty in maintaining therapeutic effects. Advanced drug delivery strategies can effectively harness immunotherapies and improve their potency while reducing their adverse effects. In this review, we briefly introduce the mechanisms of T1DM immunotherapy and focus on the current research status of the integration of the delivery techniques in T1DM immunotherapy. Furthermore, we critically analyse the challenges and future directions of T1DM immunotherapy.

Family with Sequence Similarity 72 (FAM72) - A prospective biomarker for poor prognosis in patients with oral squamous cell carcinoma.

OBJECTIVE: To study the effect of FAM72 on the prognosis of patients with oral squamous cell carcinoma (OSCC) and to explore the relationship between FAM72 and OSCC. DESIGN: We used a vast array of databases and analytical vehicles to assess the relation between FAM72 and OSCC, including The Cancer Genome Atlas (TCGA), Metascape, and MethSurv. We made a preliminary verification of OSCC lines and tissues by real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: FAM72 was higher in OSCC than in normal tissues. Analysis of univariate COX data indicated that elevated expression of FAM72A, FAM72B, and FAM72C in OSCC was related to poor overall survival. Moreover, FAM72B and FAM72C were independent of overall survival in multiple COX regression. FAM72A-D and its coexpressed genes in Metascape were analyzed by Gene Ontology (GO), they were enriched in cellular cycle, mitotic and DNA metabolism. Gene set enrichment analysis (GSEA) demonstrated an enrichment in pathways related to cell metabolism. Additionally, high FAM72 expression related to a worse prognosis in OSCC patients. FAM72A-D linked to the infiltration of tumor immune cell in OSCC patients. We found that methylation levels are likely linked to prognosis in OSCC patients. We used RT-qPCR to ascertain the differential FAM72B and FAM72C expression levels in cancer and paracancerous tissues of OSCC, human normal oral keratinocytes (HOK), and human tongue squamous cell carcinoma (Cal-33). CONCLUSION: Our findings indicate that FAM72B and FAM72C are potential molecular markers of poor prognosis in OSCC and may act as novel targets for OSCC treatment strategies.

Immunomodulatory functions of microorganisms in tissue regenerative healing.

External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a crucial regulatory role in this process. This review summarises our current understanding of microorganism-immune system interactions, with a focus on how these interactions impact the renewal and repair ability of tissues, including skin, bone, gut, liver, and nerves. This review concludes with a discussion of the mechanisms by which microbes act on various types of immune cells to affect tissue regeneration, offers potential strategies for using microbial therapies to enhance the regenerative repair function of tissues, and suggest novel therapeutic approaches for regenerative medicine. STATEMENT OF SIGNIFICANCE: Microbiological communities have crucial impacts on human health and illness by participating in energy collection and storage and performing various metabolic processes. External pathogenic microorganisms and commensal microorganisms in the body have either harmful or beneficial impacts on the regenerative repair of tissues, and the immune system plays a critical regulatory role in this process. This study reviews the important correlation between microorganisms and the immune system and investigates the mechanism of various microorganism that participate in the regeneration and repair of tissues and organs by modulating immune system.

From nitrate to NO: potential effects of nitrate-reducing bacteria on systemic health and disease.

Current research has described improving multisystem disease and organ function through dietary nitrate (DN) supplementation. They have provided some evidence that these floras with nitrate (NO3-) reductase are mediators of the underlying mechanism. Symbiotic bacteria with nitrate reductase activity (NRA) are found in the human digestive tract, including the mouth, esophagus and gastrointestinal tract (GT). Nitrate in food can be converted to nitrite under the tongue or in the stomach by these symbiotic bacteria. Then, nitrite is transformed to nitric oxide (NO) by non-enzymatic synthesis. NO is currently recognized as a potent bioactive agent with biological activities, such as vasodilation, regulation of cardiomyocyte function, neurotransmission, suppression of platelet agglutination, and prevention of vascular smooth muscle cell proliferation. NO also can be produced through the conventional L-arginine-NO synthase (L-NOS) pathway, whereas endogenous NO production by L-arginine is inhibited under hypoxia-ischemia or disease conditions. In contrast, exogenous NO3-/NO2-/NO activity is enhanced and becomes a practical supplemental pathway for NO in the body, playing an essential role in various physiological activities. Moreover, many diseases (such as metabolic or geriatric diseases) are primarily associated with disorders of endogenous NO synthesis, and NO generation from the exogenous NO3-/NO2-/NO route can partially alleviate the disease progression. The imbalance of NO in the body may be one of the potential mechanisms of disease development. Therefore, the impact of these floras with nitrate reductase on host systemic health through exogenous NO3-/NO2-/NO pathway production of NO or direct regulation of floras ecological balance is essential (e.g., regulation of body homeostasis, amelioration of diseases, etc.). This review summarizes the bacteria with nitrate reductase in humans, emphasizing the relationship between the metabolic processes of this microflora and host systemic health and disease. The potential effects of nitrate reduction bacteria on human health and disease were also highlighted in disease models from different human systems, including digestive, cardiovascular, endocrine, nervous, respiratory, and urinary systems, providing innovative ideas for future disease diagnosis and treatment based on nitrate reduction bacteria.

Current Status, Opportunities, and Challenges of Exosomes in Oral Cancer Diagnosis and Treatment.

Oral cancer is one of the most common cancers in the world, with more than 300,000 cases diagnosed each year, of which oral squamous cell carcinoma accounts for more than 90%, with a 5-year survival rate of only 40-60%, and poor prognosis. Exploring new strategies for the early diagnosis and treatment of oral cancer is key to improving the survival rate. Exosomes are nanoscale lipid bilayer membrane vesicles that are secreted by almost all cell types. During the development of oral cancer, exosomes can transport their contents (DNA, RNA, proteins, etc) to target cells and promote or inhibit the proliferation, invasion, and metastasis of oral cancer cells by influencing the host immune response, drug-resistant metastasis, and tumour angiogenesis. Therefore, exosomes have great potential and advantages as biomarkers for oral cancer diagnosis, and as drug delivery vehicles or targets for oral cancer therapy. In this review, we first describe the biogenesis, biological functions, and isolation methods of exosomes, followed by their relationship with oral cancer. Here, we focused on the potential of exosomes as oral cancer biomarkers, drug carriers, and therapeutic targets. Finally, we provide an insightful discussion of the opportunities and challenges of exosome application in oral cancer diagnosis and treatment, intending to offer new ideas for the clinical management of oral cancer.

More Than Just a Periodontal Pathogen -the Research Progress on Fusobacterium nucleatum.

Fusobacterium nucleatum is a common oral opportunistic bacterium that can cause different infections. In recent years, studies have shown that F. nucleatum is enriched in lesions in periodontal diseases, halitosis, dental pulp infection, oral cancer, and systemic diseases. Hence, it can promote the development and/or progression of these conditions. The current study aimed to assess research progress in the epidemiological evidence, possible pathogenic mechanisms, and treatment methods of F. nucleatum in oral and systemic diseases. Novel viewpoints obtained in recent studies can provide knowledge about the role of F. nucleatum in hosts and a basis for identifying new methods for the diagnosis and treatment of F. nucleatum-related diseases.

Hydrogels for the treatment of oral and maxillofacial diseases: current research, challenges, and future directions.

Oral and maxillofacial diseases such as infection and trauma often involve various organs and tissues, resulting in structural defects, dysfunctions and/or adverse effects on facial appearance. Hydrogels have been applied in the treatment of oral diseases and defect repair due to their three-dimensional network structure. With their biocompatible structure and unique stimulus-responsive property, hydrogels have been applied as an excellent drug-delivery system for treatments that mainly include oral mucosal diseases, wounds, periodontitis and cancer therapy. Hydrogels are also ideal scaffolds in regenerative engineering of dentin-pulp complex, periodontal tissue, bone and cartilage. This review discusses the fundamental structure of hydrogels in brief and then focuses on the characteristics and limitations in current research and applications of hydrogels. Finally, potential future directions are proposed.

The role and therapeutic potential of gut microbiome in severe burn.

Severe burn is a serious acute trauma that can lead to significant complications such as sepsis, multiple organ failure, and high mortality worldwide. The gut microbiome, the largest microbial reservoir in the human body, plays a significant role in this pathogenic process. Intestinal dysbiosis and disruption of the intestinal mucosal barrier are common after severe burn, leading to bacterial translocation to the bloodstream and other organs of the body, which is associated with many subsequent severe complications. The progression of some intestinal diseases can be improved by modulating the composition of gut microbiota and the levels of its metabolites, which also provides a promising direction for post-burn treatment. In this article, we summarised the studies describing changes in the gut microbiome after severe burn, as well as changes in the function of the intestinal mucosal barrier. Additionally, we presented the potential and challenges of microbial therapy, which may provide microbial therapy strategies for severe burn.

Determination of a phosphorylation site in Nipah virus nucleoprotein and its involvement in virus transcription.

Many viruses use their host's cellular machinery to regulate the functions of viral proteins. The phosphorylation of viral proteins is known to play a role in genome transcription and replication in paramyxoviruses. The paramyxovirus nucleoprotein (N), the most abundant protein in infected cells, is a component of the N-RNA complex and supports the transcription and replication of virus mRNA and genomic RNA. Recently, we reported that the phosphorylation of measles virus N is involved in the regulation of viral RNA synthesis. In this study, we report a rapid turnover of phosphorylation in the Nipah virus N (NiV-N). The phosphorylated NiV-N was hardly detectable in steady-state cells, but was detected after inhibition of cellular protein phosphatases. We identified a phosphorylated serine residue at Ser451 of NiV-N by peptide mass fingerprinting by electrospray ionization-quadrupole time-of-flight mass spectrometry. In the NiV minigenome assay, using luciferase as a reporter gene, the substitution of Ser451 for alanine in NiV-N resulted in a reduction in luciferase activity of approximately 45 % compared with the wild-type protein. Furthermore, the substitution of Ser451 for glutamic acid, which mimics a phosphoserine, led to a more significant decrease in luciferase activity - approximately 81 %. Northern blot analysis showed that both virus transcription and replication were reduced by these mutations. These results suggest that a rapid turnover of the phosphorylation of NiV-N plays an important role in virus transcription and replication.

Reconstruction of metabolic pathways, protein expression, and homeostasis machineries across maize bundle sheath and mesophyll chloroplasts: large-scale quantitative proteomics using the first maize genome assembly.

Chloroplasts in differentiated bundle sheath (BS) and mesophyll (M) cells of maize (Zea mays) leaves are specialized to accommodate C(4) photosynthesis. This study provides a reconstruction of how metabolic pathways, protein expression, and homeostasis functions are quantitatively distributed across BS and M chloroplasts. This yielded new insights into cellular specialization. The experimental analysis was based on high-accuracy mass spectrometry, protein quantification by spectral counting, and the first maize genome assembly. A bioinformatics workflow was developed to deal with gene models, protein families, and gene duplications related to the polyploidy of maize; this avoided overidentification of proteins and resulted in more accurate protein quantification. A total of 1,105 proteins were assigned as potential chloroplast proteins, annotated for function, and quantified. Nearly complete coverage of primary carbon, starch, and tetrapyrole metabolism, as well as excellent coverage for fatty acid synthesis, isoprenoid, sulfur, nitrogen, and amino acid metabolism, was obtained. This showed, for example, quantitative and qualitative cell type-specific specialization in starch biosynthesis, arginine synthesis, nitrogen assimilation, and initial steps in sulfur assimilation. An extensive overview of BS and M chloroplast protein expression and homeostasis machineries (more than 200 proteins) demonstrated qualitative and quantitative differences between M and BS chloroplasts and BS-enhanced levels of the specialized chaperones ClpB3 and HSP90 that suggest active remodeling of the BS proteome. The reconstructed pathways are presented as detailed flow diagrams including annotation, relative protein abundance, and cell-specific expression pattern. Protein annotation and identification data, and projection of matched peptides on the protein models, are available online through the Plant Proteome Database.

A Robust Metabolic Enzyme-Based Prognostic Signature for Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is still a menace to public wellbeing globally. However, the underlying molecular events influencing the carcinogenesis and prognosis of HNSCC are poorly known. METHODS: Gene expression profiles of The Cancer Genome Atlas (TCGA) HNSCC dataset and GSE37991 were downloaded from the TCGA database and gene expression omnibus, respectively. The common differentially expressed metabolic enzymes (DEMEs) between HNSCC tissues and normal controls were screened out. Then a DEME-based molecular signature and a clinically practical nomogram model were constructed and validated. RESULTS: A total of 23 commonly upregulated and 9 commonly downregulated DEMEs were identified in TCGA HNSCC and GSE37991. Gene ontology analyses of the common DEMEs revealed that alpha-amino acid metabolic process, glycosyl compound metabolic process, and cellular amino acid metabolic process were enriched. Based on the TCGA HNSCC cohort, we have built up a robust DEME-based prognostic signature including HPRT1, PLOD2, ASNS, TXNRD1, CYP27B1, and FUT6 for predicting the clinical outcome of HNSCC. Furthermore, this prognosis signature was successfully validated in another independent cohort GSE65858. Moreover, a potent prognostic signature-based nomogram model was constructed to provide personalized therapeutic guidance for treating HNSCC. In vitro experiment revealed that the knockdown of TXNRD1 suppressed malignant activities of HNSCC cells. CONCLUSION: Our study has successfully developed a robust DEME-based signature for predicting the prognosis of HNSCC. Moreover, the nomogram model might provide useful guidance for the precision treatment of HNSCC.

Research Progress, Challenges, and Breakthroughs of Organoids as Disease Models.

Traditional cell lines and xenograft models have been widely recognized and used in research. As a new research model, organoids have made significant progress and development in the past 10 years. Compared with traditional models, organoids have more advantages and have been applied in cancer research, genetic diseases, infectious diseases, and regenerative medicine. This review presented the advantages and disadvantages of organoids in physiological development, pathological mechanism, drug screening, and organ transplantation. Further, this review summarized the current situation of vascularization, immune microenvironment, and hydrogel, which are the main influencing factors of organoids, and pointed out the future directions of development.