Nasal mucosal fibroblasts produce IL-4 to induce Th2 response.

Th2 polarization is essential for the pathogenesis of allergic rhinitis (AR). Th2 polarization's mechanism requires further understanding. IL-4 is the primary cytokine involved in Th2 response. Fibroblasts play a role in immune regulation. This study aims to elucidate the role of nasal mucosal fibroblast-derived IL-4 in the induction of Th2 responses. Nasal mucosal tissues were obtained from surgically removed samples from patients with nasal polyps, whether with or without AR. Fibroblasts were isolated from the tissues by flow cytometry cell sorting, and analyzed by RNA sequencing (RNAseq). The data from RNAseq showed that nasal fibroblasts expressed genes of GATA3, CD80, CD83, CD86, STAT6, IL2, IL4, IL5, IL6, IL13 and costimulatory factor. The data were verified by RT-qPCR. The level of gene activity was positively correlated with those of AR-related cytokines present in nasal secretions. Nasal fibroblasts release IL-4 upon activation. Nasal fibroblasts had the ability to transform naive CD4+ T cells into Th2 cells, which can be eliminated by inhibiting IL-4 receptor or CD28 in CD4+ T cells. To sum up, nasal mucosal fibroblasts produce IL-4, which can induce Th2 cell development. The data implicate that nasal fibroblasts are involved in the pathogenesis of nasal allergy.

Inorganic salt starvation improves the polysaccharide production and CO2 fixation by Porphyridium purpureum.

The microalgae industry shows a promising future in the production of high-value products such as pigments, phycoerythrin, polyunsaturated fatty acids, and polysaccharides. It was found that polysaccharides have high biomedical value (such as antiviral, antibacterial, antitumor, antioxidative) and industrial application prospects (such as antioxidants). This study aimed to improve the polysaccharides accumulation of Porphyridium purpureum CoE1, which was effectuated by inorganic salt starvation strategy whilst supplying rich carbon dioxide. At a culturing temperature of 25 °C, the highest polysaccharide content (2.89 g/L) was achieved in 50% artificial seawater on the 12th day. This accounted for approximately 37.29% of the dry biomass, signifying a 25.3% increase in polysaccharide production compared to the culture in 100% artificial seawater. Subsequently, separation, purification and characterization of polysaccharides produced were conducted. Furthermore, the assessment of CO2 fixation capacity during the cultivation of P. purpureum CoE1 was conducted in a 10 L photobioreactor. This indicated that the strain exhibited an excellent CO2 fixation capacity of 1.66 g CO2/g biomass/d. This study proposed an efficient and feasible approach that not only increasing the yield of polysaccharides by P. purpureum CoE1, but also fixing CO2 with a high rate, which showed great potential in the microalgae industry and Bio-Energy with Carbon Capture and Storage.

Allergen specific immunotherapy regulates macrophage property in the airways.

BACKGROUND: Allergen specific immunotherapy (AIT) has been widely used in allergy clinics. The therapeutic effects of it are to be improved. Macrophages occupy the largest proportion of airway immune cells. The aim of this study is to measure the effects of nasal instillation AIT (nAIT) on airway allergy by regulating macrophage functions. METHODS: An airway allergy mouse model was established with the ovalbumin-alum protocol. nAIT was conducted for mice with airway allergy through nasal instillation. The effects of nAIT were compared with subcutaneous injection AIT (SCIT) and sublingual AIT (SLIT). RESULTS: Mice with airway allergy showed the airway allergic response, including lung inflammation, airway hyper responsiveness, serum specific IgE, increase in the amounts of eosinophil peroxidase, mouse mast cell protease-1, and Th2 cytokines in bronchoalveolar lavage fluid. nAIT had a much better therapeutic effect on the airway allergic response than SCIT and SLIT. Mechanistically, we observed better absorption of allergen in macrophages, better production of IL-10 by macrophages, and better immune suppressive functions in macrophages in mice received nAIT than SCIT and SLIT. CONCLUSIONS: The nAIT has a much better therapeutic effect on suppressing the airway allergic response, in which macrophages play a critical role.

ILC2s: Unraveling the innate immune orchestrators in allergic inflammation.

The prevalence rate of allergic diseases including asthma, atopic rhinitis (AR) and atopic dermatitis (AD) has been significantly increasing in recent decades due to environmental changes and social developments. With the study of innate lymphoid cells, the crucial role played by type 2 innate lymphoid cells (ILC2s) have been progressively unveiled in allergic diseases. ILC2s, which are a subset of innate lymphocytes initiate allergic responses. They respond swiftly during the onset of allergic reactions and produce type 2 cytokines, working in conjunction with T helper type 2 (Th2) cells to induce and sustain type 2 immune responses. The role of ILC2s represents an intriguing frontier in immunology; however, the intricate immune mechanisms of ILC2s in allergic responses remain relatively poorly understood. To gain a comphrehensive understanding of the research progress of ILC2, we summarize recent advances in ILC2s biology in pathologic allergic inflammation to inspire novel approaches for managing allergic diseases.

Psychological stress to ovalbumin peptide-specific T-cell receptor transgenic mice impairs the suppressive ability of type 1 regulatory T cell.

Numerous diseases of the immune system can be traced back to the malfunctioning of the regulatory T cells. The aetiology is unclear. Psychological stress can cause disruption to the immune regulation. The synergistic effects of psychological stress and immune response on immune regulation have yet to be fully understood. The intention of this study is to analyse the interaction between psychological stress and immune responses and how it affects the functional status of type 1 regulatory T (Tr1) cells. In this study, ovalbumin peptide T-cell receptor transgenic mice were utilised. Mice were subjected to restraint stress to induce psychological stress. An airway allergy murine model was established, in which a mouse strain with RING finger protein 20 (Rnf20)-deficient CD4+ T cells were used. The results showed that concomitant exposure to restraint stress and immune response could exacerbate endoplasmic reticulum stress in Tr1 cells. Corticosterone was responsible for the elevated expression of X-box protein-1 (XBP1) in mouse Tr1 cells after exposure to both restraint stress and immune response. XBP1 mediated the effects of corticosterone on inducing Rnf20 in Tr1 cells. The reduction of the interleukin-10 expression in Tr1 cells was facilitated by Rnf20. Inhibition of Rnf20 alleviated experimental airway allergy by restoring the immune regulatory ability of Tr1 cells. In conclusion, the functions of Tr1 cells are negatively impacted by simultaneous exposure to psychological stress and immune response. Tr1 cells' immune suppressive functions can be restored by inhibiting Rnf20, which has the translational potential for the treatment of diseases of the immune system.

Targeting Nrf2 to treat thyroid cancer.

Oxidative stress (OS) is recognized as a contributing factor in the development and progression of thyroid cancer. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a pivotal transcription factor involved in against OS generated by excessive reactive oxygen species (ROS). It governs the expression of a wide array of genes implicated in detoxification and antioxidant pathways. However, studies have demonstrated that the sustained activation of Nrf2 can contribute to tumor progression and drug resistance in cancers. The expression of Nrf2 was notably elevated in papillary thyroid cancer tissues compared to normal tissues, indicating that Nrf2 may play an oncogenic role in the development of papillary thyroid cancer. Nrf2 and its downstream targets are involved in the progression of thyroid cancer by impacting the prognosis and ferroptosis. Furthermore, the inhibition of Nrf2 can increase the sensitivity of target therapy in thyroid cancer. Therefore, Nrf2 appears to be a potential therapeutic target for the treatment of thyroid cancer. This review summarized current data on Nrf2 expression in thyroid cancer, discussed the function of Nrf2 in thyroid cancer, and analyzed various strategies to inhibit Nrf2.

Sodium-iodide symporter and its related solute carriers in thyroid cancer.

The solute carrier (SLC) family is a large group of membrane transport proteins. Their dysfunction plays an important role in the pathogenesis of thyroid cancer. The most well-known SLC is the sodium-iodide symporter (NIS), also known as sodium/iodide co-transporter or solute carrier family 5 member 5 (SLC5A5) in thyroid cancer. The dysregulation of NIS in thyroid cancer is well documented. The role of NIS in the uptake of iodide is critical in the treatment of thyroid cancer, radioactive iodide (RAI) therapy in particular. In addition to NIS, other SLC members may affect the autophagy, proliferation, and apoptosis of thyroid cancer cells, indicating that an alteration in SLC members may affect different cellular events in the evolution of thyroid cancer. The expression of the SLC members may impact the uptake of chemicals by the thyroid, suggesting that targeting SLC members may be a promising therapeutic strategy in thyroid cancer.

Involvement and repair of epithelial barrier dysfunction in allergic diseases.

The epithelial barrier serves as a critical defense mechanism separating the human body from the external environment, fulfilling both physical and immune functions. This barrier plays a pivotal role in shielding the body from environmental risk factors such as allergens, pathogens, and pollutants. However, since the 19th century, the escalating threats posed by environmental pollution, global warming, heightened usage of industrial chemical products, and alterations in biodiversity have contributed to a noteworthy surge in allergic disease incidences. Notably, allergic diseases frequently exhibit dysfunction in the epithelial barrier. The proposed epithelial barrier hypothesis introduces a novel avenue for the prevention and treatment of allergic diseases. Despite increased attention to the role of barrier dysfunction in allergic disease development, numerous questions persist regarding the mechanisms underlying the disruption of normal barrier function. Consequently, this review aims to provide a comprehensive overview of the epithelial barrier's role in allergic diseases, encompassing influencing factors, assessment techniques, and repair methodologies. By doing so, it seeks to present innovative strategies for the prevention and treatment of allergic diseases.

Catalase (CAT) Gene Family in Oil Palm (Elaeis guineensis Jacq.): Genome-Wide Identification, Analysis, and Expression Profile in Response to Abiotic Stress.

Catalases (CATs) play crucial roles in scavenging H2O2 from reactive oxygen species, controlling the growth and development of plants. So far, genome-wide identification and characterization of CAT genes in oil palm have not been reported. In the present study, five EgCAT genes were obtained through a genome-wide identification approach. Phylogenetic analysis divided them into two subfamilies, with closer genes sharing similar structures. Gene structure and conserved motif analysis demonstrated the conserved nature of intron/exon organization and motifs among the EgCAT genes. Several cis-acting elements related to hormone, stress, and defense responses were identified in the promoter regions of EgCATs. Tissue-specific expression of EgCAT genes in five different tissues of oil palm was also revealed by heatmap analysis using the available transcriptome data. Stress-responsive expression analysis showed that five EgCAT genes were significantly expressed under cold, drought, and salinity stress conditions. Collectively, this study provided valuable information on the oil palm CAT gene family and the validated EgCAT genes can be used as potential candidates for improving abiotic stress tolerance in oil palm and other related crops.

An Emerging Approach of Age-Related Hearing Loss Research: Application of Integrated Multi-Omics Analysis.

As one of the most common otologic diseases in the elderly, age-related hearing loss (ARHL) usually characterized by hearing loss and cognitive disorders, which have a significant impact on the elderly's physical and mental health and quality of life. However, as a typical disease of aging, it is unclear why aging causes widespread hearing impairment in the elderly. As molecular biological experiments have been conducted for research recently, ARHL is gradually established at various levels with the application and development of integrated multi-omics analysis in the studies of ARHL. Here, the recent progress in the application of multi-omics analysis in the molecular mechanisms of ARHL development and therapeutic regimens, including the combined analysis of different omics, such as transcriptome, proteome, and metabolome, to screen for risk sites, risk genes, and differences in lipid metabolism, etc., is outlined and the integrated histological data further promote the profound understanding of the disease process as well as physiological mechanisms of ARHL. The advantages and disadvantages of multi-omics analysis in disease research are also discussed and the authors speculate on the future prospects and applications of this part-to-whole approach, which may provide more comprehensive guidance for ARHL and aging disease prevention and treatment.

The Olink proteomics profile in nasal secretion of patients with allergic rhinitis.

KEY POINTS: Nasal secretions of allergic rhinitis patients were analyzed by Olink proteomics. Fifteen differentially expressed proteins (DEPs) were identified. The DEPs were significantly correlated with the total nasal symptom scores of patients with allergic rhinitis.

Stemness maintenance of stem cells derived from human exfoliated deciduous teeth (SHED) in 3D spheroid formation through the TGF-ß/Smad signaling pathway.

Mesenchymal stem cells (MSCs) have shown great potential as important therapeutic tools for dental pulp tissue engineering, with the maintenance and enhancement of their stemness being crucial for successful therapeutic application in vivo and three-dimensional (3D) spheroid formation considered a reliable technique for enhancing their pluripotency. Human exfoliated deciduous tooth stem cells (SHED) were cultured in a low attachment plate to form aggregates for five days. Then, the resulting spheroids were analyzed for pluripotent marker expression, paracrine secretory function, proliferation, signaling pathways involved, and distribution of key proteins within the spheroids. The results indicated that 3D spheroid formation significantly increased the activation of the transforming growth factor beta (TGF-ß)/Smad signaling pathway and upregulated the secretion and mRNA expression levels of TGF-ß, which in turn enhanced the expression of pluripotency markers in SHED spheroids. The activation of the TGF-ß/Smad signaling pathway through 3D spheroid formation was found to preserve the stemness properties of SHED. Thus, understanding the mechanisms behind pluripotency maintenance of SHED culture through 3D spheroid formation could have implications for the therapeutic application of MSCs in regenerative medicine and tissue engineering.

Tolerogenic dendritic cells and TLR4/IRAK4/NF-κB signaling pathway in allergic rhinitis.

Dendritic cells (DCs), central participants in the allergic immune response, can capture and present allergens leading to allergic inflammation in the immunopathogenesis of allergic rhinitis (AR). In addition to initiating antigen-specific immune responses, DCs induce tolerance and modulate immune homeostasis. As a special type of DCs, tolerogenic DCs (tolDCs) achieve immune tolerance mainly by suppressing effector T cell responses and inducing regulatory T cells (Tregs). TolDCs suppress allergic inflammation by modulating immune tolerance, thereby reducing symptoms of AR. Activation of the TLR4/IRAK4/NF-κB signaling pathway contributes to the release of inflammatory cytokines, and inhibitors of this signaling pathway induce the production of tolDCs to alleviate allergic inflammatory responses. This review focuses on the relationship between tolDCs and TLR4/IRAK4/NF-κB signaling pathway with AR.

The Role of Inflammation-Associated Factors in Head and Neck Squamous Cell Carcinoma.

Head and neck squamous cell carcinoma (HNSCC), which originates in the head or neck tissues, is characterized by high rates of recurrence and metastasis. Inflammation is important in HNSCC prognosis. Inflammatory cells and their secreted factors contribute to the various stages of HNSCC development through multiple mechanisms. In this review, the mechanisms through which inflammatory factors, signaling pathways, and cells contribute to the initiation and progression of HNSCC have been discussed in detail. Furthermore, the diagnostic and therapeutic potential of targeting inflammation in HNSCC has been discussed to gain new insights into improving patient prognosis.

Role of dendritic cell­derived exosomes in allergic rhinitis (Review).

Allergic rhinitis (AR) is a common pathological condition in otorhinolaryngology. Its prevalence has been increasing worldwide and is becoming a major burden to the world population. Dendritic cells (DCs) are typically activated and matured after capturing, phagocytosing, and processing allergens during the immunopathogenesis of AR. In addition, the process of DC activation and maturation is accompanied by the production of exosomes, which are cell­derived extracellular vesicles (EVs) that can carry proteins, lipids, nucleic acids, and other cargoes involved in intercellular communication and material transfer. In particular, DC­derived exosomes (Dex) can participate in allergic immune responses, where the biological substances carried by them can have potentially important implications for both the pathogenesis and treatment of AR. Dex can also be exploited to carry anti­allergy agents to effectively treat AR. This provides a novel method to explore the pathogenesis of and treatment strategies for AR further. Therefore, the present review focuses on the origin, composition, function, and biological characteristics of DCs, exosomes, and Dex, in addition to the possible relationship between Dex and AR.

[Misdiagnosis of adenoid cystic carcinoma of oropharynx: a case report].

Adenoid cystic carcinoma usually occurs in the salivary glands of the head and neck. It is a malignant tumor with a high degree of malignancy, resistance to radiotherapy and chemotherapy and poor prognosis. The clinical course of adenoid cystic carcinoma is slow and easy to be misdiagnosed. The main diagnosis and treatment means are individualized and precise treatment under the multi-disciplinary consultation mode, that is, surgical treatment and radiotherapy and chemotherapy. Adenoid cystic carcinoma is prone to relapse and hematologic metastasis, and the traditional radiotherapy and chemotherapy based therapies have not achieved satisfactory efficacy in the past three decades. How to detect, diagnose and treat early is an urgent task faced by clinicians.

Potential role of Bcl2 in lipid metabolism and synaptic dysfunction of age-related hearing loss.

Age-related hearing loss (ARHL) is a prevalent condition affecting millions of individuals globally. This study investigated the role of the cell survival regulator Bcl2 in ARHL through in vitro and in vivo experiments and metabolomics analysis. The results showed that the lack of Bcl2 in the auditory cortex affects lipid metabolism, resulting in reduced synaptic function and neurodegeneration. Immunohistochemical analysis demonstrated enrichment of Bcl2 in specific areas of the auditory cortex, including the secondary auditory cortex, dorsal and ventral areas, and primary somatosensory cortex. In ARHL rats, a significant decrease in Bcl2 expression was observed in these areas. RNAseq analysis showed that the downregulation of Bcl2 altered lipid metabolism pathways within the auditory pathway, which was further confirmed by metabolomics analysis. These results suggest that Bcl2 plays a crucial role in regulating lipid metabolism, synaptic function, and neurodegeneration in ARHL; thereby, it could be a potential therapeutic target. We also revealed that Bcl2 probably has a close connection with lipid peroxidation and reactive oxygen species (ROS) production occurring in cochlear hair cells and cortical neurons in ARHL. The study also identified changes in hair cells, spiral ganglion cells, and nerve fiber density as consequences of Bcl2 deficiency, which could potentially contribute to the inner ear nerve blockage and subsequent hearing loss. Therefore, targeting Bcl2 may be a promising potential therapeutic intervention for ARHL. These findings provide valuable insights into the molecular mechanisms underlying ARHL and may pave the way for novel treatment approaches for this prevalent age-related disorder.

Surgical treatment of preauricular fistulas: a 12-year single-center clinical observation.

OBJECTIVE: This study aimed to assess the effects of surgical timing and approach on operative duration, postoperative suture removal time, and postoperative recurrence rate in the management of preauricular fistula. A 12-year single-center clinical observation was conducted to analyze the potential effects of different surgical strategies on these critical outcomes. METHODS: The clinical data from 576 (782 ears) patients who underwent surgical resection for preauricular fistulas were examined in this retrospective study. The patients were classified into various groups based on differences in operative duration, surgical techniques and the use of intraoperative magnifying equipment. Furthermore, the specific data on operative duration, postoperative suture removal time, and postoperative recurrence rate were also recorded. RESULTS: The average operative duration for 782 ears and the average time required for postoperative suture removal were determined to be (34.57 ± 4.25) min and (3.62 ± 0.76) days, respectively. Among the cases examined, recurrence occurred in 13 ears, but all of them were cured after a second surgery, resulting in a recurrence rate of 1.67% (13/782). Interestingly, the operative and postoperative suture removal time was prolonged during the infection period (P < 0.05). The postoperative recurrence rate was significantly higher in the absence of magnifying equipment, as compared to those with the use of a microscope with 2.5× magnification (P < 0.05). No statistically significant differences were noted in the recurrence rate when comparing different anesthesia methods and types of surgical incisions, as well as the intraoperative use of methylene blue, and partial removal of cartilage of the pedicle (P > 0.05). CONCLUSION: The use of methylene blue, partial removal of the cartilage of the pedicle, and surgical incision during preauricular fistula resection did not affect the operative duration, postoperative suture removal time, and postoperative recurrence rate. Therefore, surgeons can select their preferred approaches based on their individual practices and patient-specific situations. However, the use of magnifying equipment during surgery is associated with a reduced risk of recurrence.

Co-pyrolysis of textile dyeing sludge/litchi shell and CaO: Immobilization of heavy metals and the analysis of the mechanism.

To relieve the secondary contamination of heavy metals (HMs), the synergistic effect of co-pyrolysis of textile dyeing sludge (DS)/litchi shell (LS) and CaO on the migration of HMs was demonstrated in this study. The proportions of Cu, Zn, Cr, Mn, and Ni in the F4 fraction increased to 75%, 55%, 100%, 50%, and 62% at the suitable CaO dosages. When 10% CaO was added, the RI value of DLC-10% was reduced to 7.89, indicating low environmental risk. The characterizations of the physicochemical properties of biochar provided support for the HMs immobilization mechanism. HMs combined with inorganic minerals or functional groups to form new stable HMs crystalline minerals and complexes to achieve immobilization of HMs. The pH value and pore structure also play an important role in improving the immobilization performance of HMs. In conclusion, the results provided a new direction for the subsequent harmless treatment of HMs-enriched waste.

Targeted therapy for head and neck squamous cell carcinoma microenvironment.

Head and neck squamous cell carcinoma (HNSCC) originates from the squamous epithelium of the oral cavity, oropharynx, larynx, and hypopharynx. HNSCC in the oral cavity and larynx is strongly associated with tobacco smoking and alcohol consumption, while oropharyngeal cancer is increasingly attributed to infection by human papillomavirus (HPV), particularly HPV-16. The tumor microenvironment (TME) is a complex network of cancer cells, immune cells, stromal cells, surrounding blood vessels, and signaling molecules, and plays a critical role in tumor cell survival, invasion, and recurrence. Therefore, it is critical to elucidate the molecular basis of the interaction between tumor cells and the TME in order to develop innovative anti-cancer therapeutic strategies.