The role of neck adipose tissue in lymph node metastasis of head and neck cancer.

Previous studies indicated that adipose tissue significantly influences cancer invasion and lymphatic metastasis. However, the impact of neck adipose tissue (NAT) on lymph node metastasis associated with head and neck cancer remains ambiguous. Here, we systematically assess the classification and measurement criteria of NAT and evaluate the association of adipose tissue and cancer-associated adipocytes with head and neck cancer. We delve into the potential mechanisms by which NAT facilitate cervical lymph node metastasis in head and neck cancer, particularly through the secretion of adipokines such as leptin, adiponectin, and Interleukin-6. Our aim is to elucidate the role of NAT in the progression and metastasis of head and neck cancer, offering new insights into prevention and treatment.

Effects of Xenobiotic Compounds on Preeclampsia and Potential Mechanisms.

Preeclampsia (PE) refers to a disease with new hypertension and albuminuria or other end-organ damage after 20 weeks of pregnancy. As a major complication of pregnancy, PE can increase the morbidity and mortality of pregnant women and fetuses and cause serious social burden. Recently, it has been found that exposure to xenobiotic compounds, especially endocrine disruptors in the environment, may contribute to the development of PE. However, the underlying mechanism is still unclear. It is generally believed that PE is related to placental dysplasia, spiral artery remodelling failure, oxidative stress, etc. Therefore, in order to better prevent the occurrence of PE and reduce the damage and impact on mother and fetus, this paper reviews the role and potential mechanism of PE induced by exogenous chemicals and provides an outlook on the environmental etiology of PE.

Biodegradation and potential effect of ranitidine during aerobic composting of human feces.

Ranitidine is widely concerned due to it is mainly related to the transformation into highly toxic carcinogenic products and non-readily biodegradable characteristics in aquatic environment. In this study, biodegradation of ranitidine during rural human feces (HF) aerobic composting was investigated. Results show that both levels of ranitidine are quickly removed in the first-3-day composting. The microorganisms play a vital role in the ranitidine degradation, especially for Firmicutes at the thermophilic period. The effect of ranitidine on the aerobic composting was further analyzed under the normal content (10 mg/kg) and high content (100 mg/kg). The 10 mg/kg ranitidine quickens temperature rise and organic matter degradation of the composting, while the 100 mg/kg ranitidine produces inhibiting effects. However, the effects only occur in the early stage of composting, and then tend to disappear with the removal of ranitidine. Fluorescence spectra confirm that humification and aromatization of dissolved organic matters (DOMs) in the substrates are fastened in 10 mg/kg group, while delayed in 100 mg/kg group. Metagenomic analysis reveals that relative abundances of Firmicutes and sequences related to carbohydrates metabolism increase in the groups mixed with the ranitidine at the early period. The findings provide the first new and systematical insights into degradation characteristics and potential effect of ranitidine during the rural HF composting.

Hypoxia promotes the tolerogenic phenotype of plasmacytoid dendritic cells in head and neck squamous cell carcinoma.

OBJECTIVE: We aim to review the roles of plasmacytoid dendritic cells (pDCs) in head and neck squamous cell carcinoma (HNSCC) and explore the effects of hypoxia on the tolerogenic transformation of pDCs. BACKGROUND: pDCs, best known as professional type I interferon-secreting cells, play key roles in immune surveillance and antitumor immunity. Recently, pDCs have been shown to be tolerogenic and correlate with poor prognosis in a variety of cancers, including HNSCC. However, it remains unclear what drives the tolerogenic transformation of pDCs in the HNSCC microenvironment. Hypoxia, a prominent hallmark of the tumor microenvironment (TME) of HNSCC, can interfere with multiple immune cells and establish an immunosuppressive TME. METHODS: In this review, we summarize the antitumor and protumor functions of pDCs, explore the effects of hypoxia on the migration and maturation of pDCs, and discuss related mechanisms in HNSCC. CONCLUSIONS: pDCs mainly display protumor functions in HNSCC. The hypoxic TME in HNSCC can enhance the migration of pDCs and inhibit the differentiation and maturation of pDCs, promoting the tolerogenic phenotype of pDCs.

Feeding preference of insect larvae to waste electrical and electronic equipment plastics.

Waste electrical and electronic equipment (WEEE) plastics not only pollute the environment, but are challenging to treat in an environmentally friendly manner. Biodegradation by insect larvae is potentially an eco-friendly method to treat WEEE plastics, but information about the feeding preference of insect larvae to WEEE plastics is lacking. In this study, a total of nine WEEE and pristine plastics were chosen to feed larvae of the following two insect species, i.e. Galleria mellonella and Tenebrio molitor. G. mellonella larvae significantly favor corresponding pristine plastics compared to two types of WEEE plastics, waste rigid polyurethane (RPU) and waste polystyrene (PS). One possible explanation is the increased chlorine or metals in the WEEE plastics measured using X-ray fluorescence spectrometer analysis. Scanning electron microscopy and Fourier transform infrared spectroscopy show that the destruction of physical structures and changes in surface functional groups were found in the two types of WEEE plastics in the larval frass, implying that the larvae partly biodegraded the plastics. Meanwhile, the powdered waste high impact polystyrene plastics (WHIPS) were ingested, but not the lumpy ones, indicating that the consumption by G. mellonella larvae is improved by the WHIPS physical modification. In addition, G. mellonella larvae presented the following decreasing preference for pristine plastics under individual-plastic-fed mode: RPU > phenol-formaldehyde resin > polyethylene (PE) > polypropylene > PS ≈ polyvinyl chloride; this is possibly due to differences in physical properties and chemical structures of the plastics; feeding preference of the larvae under multiple-plastics-fed mode is relatively consistent to that under individual-plastic-fed mode. Interestingly, the consumption by G. mellonella larvae of PE is higher than that of PS, while T. molitor larvae showed the opposite trend, implying that insect larvae have different plastics preference. The findings provide insights into biodegradation of WEEE plastics by insect larvae.

Radix Tetrastigma Extracts Enhance the Chemosensitivity in Triple-Negative Breast Cancer Via Inhibiting PI3K/Akt/mTOR-Mediated Autophagy.

OBJECTIVE: Drug resistance in tumors is one of the major factors that leads to chemotherapy failure. This study aims to investigate the effect of Radix Tetrastigma extracts (RTEs) on Taxol-induced autophagy and the chemosensitivity against drug resistance in triple-negative breast cancer (TNBC). METHODS: Taxol-resistant MDA-MB-468 (MDA-MB-468/Taxol) cells were induced and treated with RTEs and/or Taxol. Mice were subcutaneously inoculated with MDA-MB- 468/Taxol cells to establish xenograft models. The associated protein levels were measured by western blotting. Flow cytometry, CCK-8 and EdU assay were performed to detect cell apoptosis, viability, and proliferation, respectively. RESULTS: In MDA-MB-468/Taxol cells, RTEs & Taxol treatment increased cell apoptosis, reduced cell viability and proliferation, up-regulated anti-autophagy marker LC3I/LC3II ratio, and enhanced mTOR level. With RTEs & Taxol treatment, mTOR silencing downregulated LC3I/LC3II ratio, increased cell viability and proliferation, and reduced cell apoptosis, while mTOR overexpression showed the opposite results. PI3K inhibitor reduced AKT and mTOR levels, and the effects on cell activities were similar to the results of mTOR silencing. After RTEs & Taxol injection, xenograft tumor was smaller, and AKT, mTOR, LC3I/LC3II ratio and apoptotic marker cleaved caspase-3 were increased. CONCLUSION: RTEs enhanced the chemosensitivity of resistant TNBC cells to Taxol through inhibiting PI3K/Akt/mTOR-mediated autophagy. MICRO: RTEs exerted anti-tumor effects in various cancers, and this study determined its role in TNBC. Taxol-resistant MDA-MB-468 cells were induced and xenograft models were established. We found that RTEs inhibited autophagy of MDA-MB-468/Taxol cells and reduced tumor growth. Inhibition of PI3K/Akt/mTOR pathway promoted autophagy of MDA-MB-468/Taxol cells. We may provide a new potential strategy for TNBC treatment.

Tlr2/4 Double Knockout Attenuates the Degeneration of Primary Auditory Neurons: Potential Mechanisms From Transcriptomic Perspectives.

The transcriptomic landscape of mice with primary auditory neurons degeneration (PAND) indicates key pathways in its pathogenesis, including complement cascades, immune responses, tumor necrosis factor (TNF) signaling pathway, and cytokine-cytokine receptor interaction. Toll-like receptors (TLRs) are important immune and inflammatory molecules that have been shown to disrupt the disease network of PAND. In a PAND model involving administration of kanamycin combined with furosemide to destroy cochlear hair cells, Tlr 2/4 double knockout (DKO) mice had auditory preservation advantages, which were mainly manifested at 4-16 kHz. DKO mice and wild type (WT) mice had completely damaged cochlear hair cells on the 30th day, but the density of spiral ganglion neurons (SGN) in the Rosenthal canal was significantly higher in the DKO group than in the WT group. The results of immunohistochemistry for p38 and p65 showed that the attenuation of SGN degeneration in DKO mice may not be mediated by canonical Tlr signaling pathways. The SGN transcriptome of DKO and WT mice indicated that there was an inverted gene set enrichment relationship between their different transcriptomes and the SGN degeneration transcriptome, which is consistent with the morphology results. Core module analysis suggested that DKO mice may modulate SGN degeneration by activating two clusters, and the involved molecules include EGF, STAT3, CALB2, LOX, SNAP25, CAV2, SDC4, MYL1, NCS1, PVALB, TPM4, and TMOD4.

Sensorineural hearing loss may lead to dementia-related pathological changes in hippocampal neurons.

Presbycusis contributes to cognitive decline and Alzheimer's disease. However, most research in this area involves clinical observations and statistical modeling, and few studies have examined the relationship between hearing loss and the molecular changes that lead to cognitive dysfunction. The present study investigated whether hearing loss contributes to dementia in the absence of aging and noise using a mouse model of severe bilateral hearing loss induced by kanamycin (1000 mg/kg) and furosemide (400 mg/kg). Immunohistochemistry, silver staining, immunofluorescence analysis, and Western blotting were used to observe pathological changes in different regions of the hippocampus in animals with hearing loss. Changes in the cognitive function of animals with hearing loss were assessed using the Morris water maze test. The results showed that neurons began to degenerate 60 days after hearing loss, and this degeneration was accompanied by structural disorganization and decreased neurogenesis. The level of phosphorylated tau increased over time. Increases in escape latency and distance traveled during the training phase of the Morris water maze test were observed 90 days after hearing loss. Activated microglia and astrocytes with increased levels of inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were detected in the hippocampus. These results suggest that hearing loss alone causes neuronal degeneration, inhibition of neurogenesis, increased tau protein phosphorylation, and increased neuroinflammation in the hippocampus. Early intervention in individuals with hearing loss may reduce the risk of cognitive decline.

PRF1 is a prognostic marker and correlated with immune infiltration in head and neck squamous cell carcinoma.

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a highly invasive malignancy with poor survival. Perforin (PRF1) plays essential roles in host immunity. Our research intended to identify the correlations of PRF1 with clinical prognosis and tumor immune infiltration in HNSCC. METHODS: We explored PRF1 expression and its associations with the clinical features of HNSCC via the Tumor Immune Estimation Resource (TIMER), Oncomine and The Cancer Genome Atlas (TCGA) databases. The prognostic value of PRF1 for HNSCC was further explored by Kaplan-Meier plotter and TIMER. Finally, the relation between PRF1 and immune infiltration in HNSCC was estimated via CIBERSORT and TIMER. RESULTS: PRF1 expression was remarkably elevated in HNSCC and associated with clinical stage and HPV infection. High PRF1 expression predicted favorable outcomes in HNSCC, especially in HPV+ HNSCC. Moreover, higher infiltration of CD8+ T cells and CD4+ T cells were found in the PRF1high group of HNSCC. PRF1 expression in HNSCC was strongly correlated with infiltrating CD8+ T cells and dendritic cells (DCs), with higher relevance in HPV+ HNSCC. CONCLUSION: Our findings suggested that PRF1 could be a novel prognostic biomarker in HNSCC and that its expression was related to immune cell infiltration, which was impacted by HPV status.

The Immune System Can Hear Noise.

As a stressor widely existing in daily life, noise can cause great alterations to the immune system and result in many physical and mental disorders, including noise-induced deafness, sleep disorders, cardiovascular diseases, endocrine diseases and other problems. The immune system plays a major role in maintaining homeostasis by recognizing and removing harmful substances in the body. Many studies have shown that noise may play vital roles in the occurrence and development of some immune diseases. In humans, both innate immunity and specific immunity can be influenced by noise, and different exposure durations and intensities of noise may exert various effects on the immune system. Short-term or low-intensity noise can enhance immune function, while long-term or high-intensity noise suppresses it. Noise can lead to the occurrence of noise-induced hearing loss (NIHL) through the production of autoantibodies such as anti-Hsp70 and anti-Hsp60 and exert adverse effects related to other immune-related diseases such as some autoimmune diseases and non-Hodgkin lymphoma. The neuroendocrine system, mainly including the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic-adrenal-medullary (SAM) system, is involved in the mechanisms of immune-related diseases induced by noise and gut microbiota dysfunction. In addition, noise exposure during pregnancy may be harmful to the immune system of the fetus. On the other hand, some studies have shown that music can improve immune function and alleviate the adverse effects caused by noise.

Restoring autophagic flux attenuates cochlear spiral ganglion neuron degeneration by promoting TFEB nuclear translocation via inhibiting MTOR.

Macroautophagy/autophagy dysfunction is associated with many neurodegenerative diseases. TFEB (transcription factor EB), an important molecule that regulates lysosomal and autophagy function, is regarded as a potential target for treating some neurodegenerative diseases. However, the relationship between autophagy dysfunction and spiral ganglion neuron (SGN) degeneration and the role of TFEB in SGN degeneration has not yet been established. Here, we showed that in degenerated SGNs, induced by sensory epithelial cell loss in the cochlea of mice following kanamycin and furosemide administration, the lipofuscin area and oxidative stress level were increased, the nuclear-to-cytoplasmic TFEB ratio was decreased, and the late stage of autophagic flux was impaired. After autophagy dysfunction was partially ameliorated with an MTOR inhibitor, which promoted TFEB translocation into the nucleus from the cytoplasm, we found that the lysosomal deficits were significantly relieved, the oxidative stress level was reduced, and the density of surviving SGNs and auditory nerve fibers was increased. The results in the present study reveal that autophagy dysfunction is an important component of SGN degeneration, and TFEB may be a potential target for attenuating SGN degeneration following sensory epithelial cell loss in the cochlea of mice. Abbreviations: 3-NT: 3-nitrotyrosine; 4-HNE: 4-hydroxynonenal; 8-OHdG: 8-hydroxy-2'-deoxyguanosine; ABR: auditory brainstem response; APP: amyloid beta (A4) precursor protein; CLEAR: coordinated lysosomal expression and regulation; CTSB: cathespin B; CTSD: cathespin D; SAMR1: senescence-accelerated mouse/resistance 1; SAMP8: senescence-accelerated mouse/prone 8; MAPK1/ERK2: mitogen-activated protein kinase 1; MTOR: mechanistic target of rapamycin kinase; SGN: spiral ganglion neuron; SQSTM1/p62: sequestosome 1; TEM: transmission electron microscope; TFEB: transcription factor EB.

Gene expression differences between thyroid carcinoma, thyroid adenoma and normal thyroid tissue.

To identify differences in gene expression profiles of infected cells between thyroid carcinoma (C), thyroid adenoma (A) and normal thyroid (N) epithelial cells, differentially expressed genes were identified using three pairwise comparisons with the GEO2R online tool. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were used to classify them at the functional level. The most significant cluster in the N vs. A pairwise comparison had four hub genes: Insulin-like growth factor 2, Von Willebrand factor (VWF), multimerin 1 (MMRN1) and complement factor D (CFD). In N vs. C, the most significant cluster had 19 genes: IGF2, early growth response 2, transcription factor 3, KIT proto­oncogene receptor tyrosine kinase, SMAD family member 9, MLLT3 super elongation complex subunit, runt related transcription factor 1, CFD, actinin α 1, SWI/SNF related matrix associated actin dependent regulator of chromatin subfamily a member 4, JunD proto­oncogene AP­1 transcription factor subunit, serum response factor (SRF), FosB proto­oncogene, AP­1 transcription factor subunit, connective tissue growth factor (CTGF), SRC proto­oncogene, non­receptor tyrosine kinase, MMRN1, SRY­box 9, early growth response 3 and ETS variant 4. In A vs. C, the most significant cluster had 14 genes: BCL2-like 1, galectin 3, MCL1 BCL2 family apoptosis regulator, DNA damage inducible transcript 3, BCL2 apoptosis regulator, CTGF, matrix metallopeptidase 7, early growth response 1, kinase insert domain receptor, TIMP metallopeptidase inhibitor 1, apolipoprotein E, VWF, cyclin D1 and placental growth factor. Histological evidence was presented to confirm the makeup of the hubs prior to logistic regression analysis to differentiate benign and malignant neoplasms. The results of the present study may aid in the search for novel potential biomarkers for the differential diagnosis, prognosis and development of drug targets of thyroid neoplasm.

Cognitive Decline, Dementia, Alzheimer's Disease and Presbycusis: Examination of the Possible Molecular Mechanism.

The incidences of presbycusis and dementia are high among geriatric diseases. Presbycusis is the general term applied to age-related hearing loss and can be caused by many risk factors, such as noise exposure, smoking, medication, hypertension, family history, and other factors. Mutation of mitochondrial DNA in hair cells, spiral ganglion cells, and stria vascularis cells of the cochlea is the basic mechanism of presbycusis. Dementia is a clinical syndrome that includes the decline of cognitive and conscious states and is caused by many neurodegenerative diseases, of which Alzheimer's disease (AD) is the most common. The amyloid cascade hypothesis and tau hypothesis are the two major hypotheses that describe the AD pathogenic mechanism. Recent studies have shown that deposition of Aß and hyperphosphorylation of the tau protein may cause mitochondrial dysfunction. An increasing number of papers have reported that, on one hand, the auditory system function in AD patients is damaged as their cognitive ability declines and that, on the other hand, hearing loss may be a risk factor for dementia and AD. However, the relationship between presbycusis and AD is still unknown. By reviewing the relevant literature, we found that the SIRT1-PGC1α pathway and LKB1 (or CaMKKß)-AMPK pathway may play a role in the preservation of cerebral neuron function by taking part in the regulation of mitochondrial function. Then vascular endothelial growth factor signal pathway is activated to promote vascular angiogenesis and maintenance of the blood-brain barrier integrity. Recently, experiments have also shown that their expression levels are altered in both presbycusis and AD mouse models. Therefore, we propose that exploring the specific molecular link between presbycusis and AD may provide new ideas for their prevention and treatment.