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Backgrounds: Both exosome and circular RNA (circRNA) have been reported to participate in the pathogenesis of type 1 diabetes mellitus (T1DM). However, the exact role of exosomal circRNA in T1DM is largely unknown. Here, we identified the exosomal circRNA expression profiles in the plasma of T1DM patients and explored their potential function using bioinformatics analysis. Material and Methods . Exosomes were extracted by the size exclusion chromatography method from plasma of 10 T1DM patients and 10 age- and sex- matched control subjects. Illumina Novaseq6000 platform was used to detect the exosomal circRNA expression profiles. Multiple bioinformatics analysis was applied to investigate the potential biological functions of exosomal circRNAs., Results: A total of 784 differentially expressed exosomal circRNAs have been identified in T1DM patients, of which 528 were upregulated and 256 were downregulated. Gene Ontology analysis enriched terms such as protein ubiquitination involved in ubiquitin-dependent protein catabolic protein (GO:0042787), membrane (GO:0016020), and GTPase activator activity (GO:0005096). The most enriched pathway in Kyoto Encyclopedia of Genes and Genomes was ubiquitin-mediated proteolysis (ko04120). The miRNA-targeting prediction method was used to identify the miRNAs that bind to circRNAs, and circRNA-miRNA-mRNA pathways were constructed, indicating that interactions between circRNA, miRNA, and gene might be involved in the disease progression., Conclusions: The present study identified the exosomal circRNA expression profiles in T1DM for the first time. Our results threw novel insights into the molecular mechanisms of T1DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Haipeng Pang et al.)

In recent ten years, with the fast development of digital and engineering manufacturing technology, additive manufacturing has already been more and more widely used in the field of dentistry, from the first personalized surgical guides to the latest personalized restoration crowns and root implants. In particular, the bioprinting of teeth and tissue is of great potential to realize organ regeneration and finally improve the life quality. In this review paper, we firstly presented the workflow of additive manufacturing technology. Then, we summarized the main applications and recent research progresses of additive manufacturing in dentistry. Lastly, we sketched out some challenges and future directions of additive manufacturing technology in dentistry., Competing Interests: The authors declare that there are no conflicts of interests regarding the publication of this paper., (Copyright © 2022 Gan Huang et al.)

Previous functional magnetic resonance imaging (fMRI) studies have shown that brain responses to nociceptive pain, non-nociceptive somatosensory, visual, and auditory stimuli are extremely similar. Actually, perception of external sensory stimulation requires complex interactions among distributed cortical and subcortical brain regions. However, the interactions among these regions elicited by nociceptive pain remain unclear, which limits our understanding of mechanisms of pain from a brain network perspective. Task fMRI data were collected with a random sequence of intermixed stimuli of four sensory modalities in 80 healthy subjects. Whole-brain psychophysiological interaction analysis was performed to identify task-modulated functional connectivity (FC) patterns for each modality. Task-modulated FC strength and graph-theoretical-based network properties were compared among the four modalities. Lastly, we performed across-sensory-modality prediction analysis based on the whole-brain task-modulated FC patterns to confirm the specific relationship between brain patterns and sensory modalities. For each sensory modality, task-modulated FC patterns were distributed over widespread brain regions beyond those typically activated or deactivated during the stimulation. As compared with the other three sensory modalities, nociceptive stimulation exhibited significantly different patterns (more widespread and stronger FC within the cingulo-opercular network, between cingulo-opercular and sensorimotor networks, between cingulo-opercular and emotional networks, and between default mode and emotional networks) and global property (smaller modularity). Further, a cross-sensory-modality prediction analysis found that task-modulated FC patterns could predict sensory modality at the subject level successfully. Collectively, these results demonstrated that the whole-brain task-modulated FC is preferentially modulated by pain, thus providing new insights into the neural mechanisms of pain processing., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Head and neck cancer is a highly genetic and metabolic heterogeneous collection of malignancies of the lip, oral cavity, salivary glands, pharynx, esophagus, paranasal sinuses, and larynx with five-year survival rates ranging from 12% to 93%. Patients with head and neck cancer typically present with advanced stage III, IVa, or IVb disease and are treated with comprehensive modality including chemotherapy, radiotherapy, and surgery. Despite advancements in treatment modality and technique, noisome recurrence, invasiveness, and resistance as well as posttreatment complications severely influence survival rate and quality of life. Thus, new therapeutic strategies are urgently needed that offer enhanced efficacy with less toxicity. ROS in cancer cells plays a vital role in regulating cell death, DNA repair, stemness maintenance, metabolic reprogramming, and tumor microenvironment, all of which have been implicated in resistance to chemo-/radiotherapy of head and neck cancer. Adjusting ROS generation and elimination to reverse the resistance of cancer cells without impairing normal cells show great hope in improving the therapeutic efficacy of chemo-/radiotherapy of head and neck cancer. In the current review, we discuss the pivotal and targetable redox-regulating system including superoxide dismutases (SODs), tripeptide glutathione (GSH), thioredoxin (Trxs), peroxiredoxins (PRXs), nuclear factor erythroid 2-related factor 2/Kelch-like ECH-associated protein 1 (Nrf2/keap1), and mitochondria electron transporter chain (ETC) complexes and their roles in regulating ROS levels and their clinical significance implicated in chemo-/radiotherapy of head and neck cancer. We also summarize several old drugs (referred to as the non-anti-cancer drugs used in other diseases for a long time) and small molecular compounds as well as natural herbs which effectively modulate cellular ROS of head and neck cancer to synergize the efficacy of conventional chemo-/radiotherapy. Emerging interdisciplinary techniques including photodynamic, nanoparticle system, and Bio-Electro-Magnetic-Energy-Regulation (BEMER) therapy are promising measures to broaden the potency of ROS modulation for the benefit of chemo-/radiotherapy in head and neck cancer., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Gan Huang and Shu-Ting Pan.)

Objective: The aim of this study was to clarify the association of two single-nucleotide polymorphisms (SNPs) (rs11651270 and rs2670660) in the NLRP1 (NLR family pyrin domain containing 1) gene with type 1 diabetes (T1D) in the Chinese Han population. We hypothesize that mutations in the NLRP1 gene may affect the susceptibility to T1D., Materials and Methods: A case control study was designed, and participants fulfilling the diagnostic criteria of classical T1D as well as nondiabetic controls were enrolled in the study. The polymorphisms rs11651270 and rs2670660 were genotyped by polymerase chain reaction (PCR) and Sanger sequencing. Chi-squared test and logistic regression analysis were performed to compare the distributions of the allele and genotype between cases and controls. Kruskal-Wallis one-way ANOVA was used to compare the characteristics of different genotypes in participants with T1D., Results: A total of 510 participants with classical T1D as well as 531 nondiabetic controls were enrolled in the study. The two groups were matched in sex ( p = 0.418). The age ( p < 0.001) and BMI ( p < 0.001) were significantly lower in cases compared to controls. Significantly higher values were observed for fasting plasma glucose (FPG) ( p < 0.001) and 2 h postprandial plasma glucose (PPG) ( p < 0.001) in individuals with T1D. Regarding the allelic model, the minor allele C of rs11651270 was significantly associated with lower risk of T1D compared with the T allele (OR = 0.714, 95% CI = 0.579-0.882). Both rs11651270 and rs2670660 polymorphisms were associated with T1D in the Chinese Han population under a dominant model (OR = 0.648, 95% CI = 0.503-0.834 and OR = 0.716, 95% CI = 0.549-0.934, respectively) and an overdominant model (OR = 0.663, 95% CI = 0.511-0.860 and OR = 0.711, 95% CI = 0.541-0.935, respectively). Additionally, the polymorphism rs11651270 was also related to T1D in an additive model (OR = 0.719, 95% CI = 0.583-0.887). Most importantly, when we analyzed the clinical characteristics of T1D individuals with different genotypes, we found that the age of onset with the TT genotype at rs11651270 was younger than those with the other two genotypes ( p = 0.001)., Conclusions: SNPs in the NLRP1 gene were associated with T1D, as well as the age of onset in the Chinese Han T1D individuals. Our study indicated that the NLRP1 gene might play a pivotal role in the etiopathogenesis of T1D and could be applied to genetic screening of T1D in the Chinese Han population., Competing Interests: The authors declare that the study was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Background: Glucose fluctuation confers additional risks on diabetes-related vascular diseases, but the underlying mechanisms are unknown. Macrophage activation mediated by TLR4-JNK signaling plays an important role during the progress of diabetes. In the present study, we hypothesize that glucose fluctuation results in macrophage inflammation through TLR4-JNK signaling pathways., Methods: THP-1 cells were treated with normal glucose (5 mM), constant high glucose (25 mM), and intermittent high glucose (rotation per 6 h in 5 mM or 25 mM) for 24 h. The mRNA and protein expression levels of TLR4, p-JNK, and adipocyte fatty acid-binding protein (A-FABP) were determined, and the proinflammatory cytokines TNF- α and IL-1 β were quantified., Results: In constant high glucose, TLR4 expression and JNK phosphorylation levels increased, and this effect was more pronounced in intermittent high glucose. Accordingly, the expression of A-FABP and the release of the proinflammatory cytokines TNF- α and IL-1 β also increased in response to constant high glucose, an effect that also was more evident in intermittent high glucose. The inhibition of p-JNK by SP600125 did not attenuate TLR4 expression, but totally inhibited both A-FABP expression and the production of the proinflammatory cytokines TNF- α and IL-1 β in both constant and intermittent high glucose., Conclusions: Intermittent high glucose potentiates A-FABP activation and inflammatory responses via TLR4/p-JNK signaling in THP-1 cells. These findings suggest a more detrimental impact of glucose fluctuation on macrophage inflammation in diabetes-related vascular diseases than thus far generally assumed.

B lymphocytes are involved in inflammation and are related to insulin resistance in obesity and type 2 diabetes (T2D). This study investigated the phenotype and frequency of B-lymphocyte subsets in subjects recently diagnosed with T2D ( n = 60), impaired glucose regulation (IGR, n = 73), and normal glucose tolerance (NGT, n = 169) by flow cytometry. T2D subjects had an increased percentage of CD19 + CD23 + (B-2) cells and a decreased percentage of CD19 + CD23 - (B-1) cells attributing to CD19 + CD23 - CD5 - (B-1b) cells, but not CD19 + CD23 - CD5 + (B-1a) cells, compared to NGT and IGR subjects. The proportion of CD19 + CD5 + CD1d hi (B10) cells did not differ between the IGR or T2D group and NGT controls. Of note, HbA1c and triglyceride showed a positive correlation with B-2 cells but an inverse correlation with B-1 and B-1b cells, which were independently associated with the presence of T2D by logistic regression models. In summary, this study shows an unbalanced proinflammatory phenotype of B-cell subsets correlated with glycemia and lipidemia in patients with T2D. Our data provide new insight into chronic activation of the immune system and subclinical inflammation in T2D. Further prospective studies are warranted to confirm our observations.