Targeting Degradation of the Transcription Factor C/EBPß Reduces Lung Fibrosis by Restoring Activity of the Ubiquitin-Editing Enzyme A20 in Macrophages.

Although recent progress provides mechanistic insights into the pathogenesis of pulmonary fibrosis (PF), rare anti-PF therapeutics show definitive promise for treating this disease. Repeated lung epithelial injury results in injury-repairing response and inflammation, which drive the development of PF. Here, we report that chronic lung injury inactivated the ubiquitin-editing enzyme A20, causing progressive accumulation of the transcription factor C/EBPß in alveolar macrophages (AMs) from PF patients and mice, which upregulated a number of immunosuppressive and profibrotic factors promoting PF development. In response to chronic lung injury, elevated glycogen synthase kinase-3ß (GSK-3ß) interacted with and phosphorylated A20 to suppress C/EBPß degradation. Ectopic expression of A20 or pharmacological restoration of A20 activity by disturbing the A20-GSK-3ß interaction accelerated C/EBPß degradation and showed potent therapeutic efficacy against experimental PF. Our study indicates that a regulatory mechanism of the GSK-3ß-A20-C/EBPß axis in AMs may be a potential target for treating PF and fibroproliferative lung diseases.

Manifold fitting with CycleGAN.

Manifold fitting, which offers substantial potential for efficient and accurate modeling, poses a critical challenge in nonlinear data analysis. This study presents an approach that employs neural networks to fit the latent manifold. Leveraging the generative adversarial framework, this method learns smooth mappings between low-dimensional latent space and high-dimensional ambient space, echoing the Riemannian exponential and logarithmic maps. The well-trained neural networks provide estimations for the latent manifold, facilitate data projection onto the manifold, and even generate data points that reside directly within the manifold. Through an extensive series of simulation studies and real data experiments, we demonstrate the effectiveness and accuracy of our approach in capturing the inherent structure of the underlying manifold within the ambient space data. Notably, our method exceeds the computational efficiency limitations of previous approaches and offers control over the dimensionality and smoothness of the resulting manifold. This advancement holds significant potential in the fields of statistics and computer science. The seamless integration of powerful neural network architectures with generative adversarial techniques unlocks possibilities for manifold fitting, thereby enhancing data analysis. The implications of our findings span diverse applications, from dimensionality reduction and data visualization to generating authentic data. Collectively, our research paves the way for future advancements in nonlinear data analysis and offers a beacon for subsequent scholarly pursuits.

Single-cell analysis via manifold fitting: A framework for RNA clustering and beyond.

Single-cell RNA sequencing (scRNA-seq) data, susceptible to noise arising from biological variability and technical errors, can distort gene expression analysis and impact cell similarity assessments, particularly in heterogeneous populations. Current methods, including deep learning approaches, often struggle to accurately characterize cell relationships due to this inherent noise. To address these challenges, we introduce scAMF (Single-cell Analysis via Manifold Fitting), a framework designed to enhance clustering accuracy and data visualization in scRNA-seq studies. At the heart of scAMF lies the manifold fitting module, which effectively denoises scRNA-seq data by unfolding their distribution in the ambient space. This unfolding aligns the gene expression vector of each cell more closely with its underlying structure, bringing it spatially closer to other cells of the same cell type. To comprehensively assess the impact of scAMF, we compile a collection of 25 publicly available scRNA-seq datasets spanning various sequencing platforms, species, and organ types, forming an extensive RNA data bank. In our comparative studies, benchmarking scAMF against existing scRNA-seq analysis algorithms in this data bank, we consistently observe that scAMF outperforms in terms of clustering efficiency and data visualization clarity. Further experimental analysis reveals that this enhanced performance stems from scAMF's ability to improve the spatial distribution of the data and capture class-consistent neighborhoods. These findings underscore the promising application potential of manifold fitting as a tool in scRNA-seq analysis, signaling a significant enhancement in the precision and reliability of data interpretation in this critical field of study.

Tumor microenvironment characteristics association with clinical outcome in patients with resected intestinal-type gastric cancer.

BACKGROUND: Tumor microenvironment (TME) characteristics including tumor stroma ratio (TSR), tumor budding (TB), and tumor-infiltrating lymphocytes (TILs) were examined in resected gastric cancer. These TME features have been shown to indicate metastatic potential in colon cancer, and intestinal-type gastric cancer (IGC) has pathological similarities with that malignancy. METHODS: TSR, TB, and TILs were quantified in routine histological sections from 493 patients with IGC who underwent radical resection at 2 university hospitals in China from 2010 to 2016. TME variables were dichotomized as follows: TSR (50%), TILs (median), TB per international guidelines (4 buds/0.785mm2), and platelet-lymphocyte ratio (PLR) per survival ROC. Association of TME features with patient clinicopathological characteristics, time-to-recurrence (TTR), and cancer-specific-survival (CSS) were examined using univariate and multivariate analysis, including a relative contribution analysis by Cox regression. RESULTS: Patients whose tumors showed high TSR or high TB or low TILs were each significantly associated with increased T and N stage, higher histological grade, and poorer TTR and CSS at 5 years. Only TSR and N stage were independently associated with TTR and CSS after adjustment for covariates. PLR was only independently associated with TTR after adjustment for covariates. Among the variables examined, only TSR was significantly associated with both TTR (HR 1.72, 95% CI, 1.14-2.60, P = .01) and CSS (HR 1.62, 95% CI, 1.05-2.51, P = .03) multivariately. Relative contribution to TTR revealed that the top 3 contributors were N stage (45.1%), TSR (22.5%), and PLR (12.9%), while the top 3 contributors to CSS were N stage (59.9%), TSR (14.7%), and PLR (10.9%). CONCLUSIONS: Among the examined TME features, TSR was the most robust for prognostication and was significantly associated with both TTR and CSS. Furthermore, the relative contribution of TSR to patient TTR and CSS was second only to nodal status.

Predicting Progestin Therapy Response With PTEN, PAX2, and ß-Catenin in Patients With Endometrioid Precancer.

This study investigates the predictive value of biomarkers PTEN, PAX2, and ß-catenin for therapeutic outcomes in patients with atypical endometrial hyperplasia or endometrioid intraepithelial neoplasia undergoing progestin therapy. In a retrospective study of 128 patients, we analyzed a total of 351 endometrial biopsy samples and categorized outcomes into responders (absence of residual disease) and nonresponders (presence of residual disease). We found aberrant biomarker expression in pretreatment cases: 48% for PTEN, 65% for PAX2, and 36% for ß-catenin. Approximately 77.3% of patients responded to progestin treatment, with nonresponders showing significantly higher initial PTEN loss (75.86% vs 39.79%, P < 0.001). Nonresponders also demonstrated significant PTEN loss (53.33% vs 20.55%, P < 0.001), PAX2 loss (57.33% vs 41.22%, P < 0.05), and ß-catenin nuclear staining (53.45% vs 27.91%, P < 0.01) in follow-up samples. In addition, nonresponders exhibited lower recovery of intact PTEN and PAX2, along with higher ß-catenin aberrancy in cases initially showing normal ß-catenin levels. We conclude that persistent aberrant PTEN and PAX2 expression, coupled with emerging aberrant ß-catenin in follow-ups, indicates a greater likelihood of treatment failure. Conversely, the absence of these aberrations suggests successful progestin therapy. Our findings highlight the utility of this 3-marker panel in assessing residual disease status and predicting progestin treatment outcomes, thus offering critical insights for patient management.

Prognostic significance of surgery and radiotherapy in elderly patients with localized prostate cancer: establishing and time-based external validation a nomogram from SEER-based study.

OBJECTIVE: Prostate cancer (PC) is a significant disease affecting men's health worldwide. More than 60% of patients over 65 years old and more than 80% are diagnosed with localized PC. The current choice of treatment modalities for localized PC and whether overtreatment is controversial. Therefore, we wanted to construct a nomogram to predict the risk factors associated with cancer-specific survival (CSS) and overall survival (OS) in elderly patients with localized PC while assessing the survival differences in surgery and radiotherapy for elderly patients with localized PC. METHODS: Data of patients with localized PC over 65 years were obtained from the Surveillance, Epidemiology, and End Results (SEER) database. Univariate and multivariate Cox regression models were used to determine independent risk factors for CSS and OS. Nomograms predicting CSS and OS were built using multivariate Cox regression models. The consistency index (C-index), the area under the subject operating characteristic curve (AUC), and the calibration curve were used to test the accuracy and discrimination of the prediction model. Decision curve analysis (DCA) was used to test the potential clinical value of this model. RESULTS: A total of 90,434 patients over 65 years and diagnosed with localized PC from 2010 to 2018 were included in the study. All patients were randomly assigned to the training set (n = 63,328) and the validation set (n = 27,106). Univariate and multivariate Cox regression model analysis showed that age, race, marriage, T stage, surgical, radiotherapy, prostate-specific antigen (PSA), and Gleason score (GS) were independent risk factors for predicting CSS in elderly patients with localized PC. Age, race, marriage, surgery, radiotherapy, PSA, and GS were independent risk factors for predicting OS in elderly patients with localized PC. The c-index of the training and validation sets for the predicted CSS is 0.802(95%CI:0.788-0.816) and 0.798(95%CI:0.776-0.820, respectively). The c-index of the training and validation sets for predicting OS is 0.712(95%:0.704-0.720) and 0.724(95%:0.714-0.734). It shows that the nomograms have excellent discriminatory ability. The AUC and the calibration curves also show good accuracy and discriminability. CONCLUSION: We have developed new nomograms to predict CSS and OS in elderly patients with localized PC. After internal validation and external temporal validation with reasonable accuracy, reliability and potential clinical value, the model can be used for clinically assisted decision-making.

Brain tissue heterotopic in the adrenal gland in a child: a scarce case report.

Heterotopic brain tissue is rare and has not been reported. Our center made the first report. 4 years and 2 months old Girl presented with a cystic mass in the right adrenal gland 2 weeks after right upper abdominal pain. The operation was successful, and the diagnosis was confirmed by postoperative pathology. 6 months after the procedure, the incision healed well without recurrence. This case report has a detailed diagnosis and treatment process and satisfactory examination results. It can provide a reference for diagnosing and treating clinical HBT and reduce the risk of misdiagnosis and mistreatment.

The preliminary exploration of immune microenvironment in oral leukoplakia concomitant with oral submucosal fibrosis: A comparative immunohistochemical study.

BACKGROUND: Oral leukoplakia concomitant with oral submucous fibrosis is a high-risk oral potentially malignant disorder, but little is known about its immune microenvironment. METHODS: Thirty samples of oral leukoplakia concomitant with oral submucous fibrosis, 30 oral leukoplakia samples, and 30 oral submucous fibrosis samples were collected from two hospitals. Immunohistochemistry was performed to analyze expression of T cell biomarkers [CD3, CD4, CD8, and Forkhead box P3 (Foxp3)], a B cell biomarker (CD20), macrophage biomarkers (CD68 and CD163), an immune inhibitory receptor ligand (PD-L1), and Ki-67. RESULTS: The numbers of CD3+ (p < 0.001), CD4+ (p = 0.018), and CD8+ (p = 0.031) cells in oral leukoplakia concomitant with oral submucous fibrosis were less than those in oral leukoplakia. The number of CD4+ cells (p = 0.035) in oral leukoplakia concomitant with oral leukoplakia was higher than that in oral submucous fibrosis. More CD3+ (p < 0.001), CD4+ (p < 0.001), Foxp3+ (p = 0.019), and CD163+ (p = 0.029) cells were found in oral leukoplakia than in oral submucous fibrosis. CONCLUSION: Various levels of immune infiltration were observed among oral leukoplakia concomitant with oral submucous fibrosis, oral leukoplakia, and oral submucous fibrosis. Characterization of the immune microenvironment may contribute to personalized immunotherapy.

Primary spindle cell sarcoma of the seminal vesicle: A case report and literature review.

We report a case of primary seminal vesicle spindle cell sarcoma of a 57-year-old man who underwent multiple surgical treatment. The first diagnosis of a local hospital was a right seminal vesicle cyst, so only laparoscopic decompression was performed. Postoperatively, the patient gradually developed lower abdominal discomfort, frequent and urgent urination, dysuria and constipation. Digital rectal examination palpated a heterogeneous mass. Magnetic resonance imaging showed a multilocular cystic mass of about 4.5 cm in diameter in the right seminal vesicle, which was diagnosed as a recurrent cyst. The patient underwent a second operation in our hospital, but the tumour could not be completely removed because of severe peripheral adhesions. The postoperative pathological diagnosis was seminal vesicle cystadenoma with spindle cell sarcoma. One month later, a computed tomography scan performed at another hospital showed that the mass had invaded the bladder and sigmoid colon. The pathological diagnosis of re-examination was spindle cell liposarcoma. After neoadjuvant chemotherapy, extended resection of the tumour was performed, and adjuvant chemotherapy was continued after surgery. The total duration of follow-up was 19 months and 3 months after the third surgery. The patient survived with no recurrence or metastasis.

Research progress on the effect of autophagy-lysosomal pathway on tumor drug resistance.

Autophagy is an intracellular degradation pathway that is highly conserved during the evolution of eukaryotes and is based on lysosome. Under nutritional deficiencies or stress, cells can clear damaged and necrotic organelles and proteins through autophagy to maintain the homeostasis of cells and organisms. Studies have found that abnormal autophagy is closely related to the occurrence and development of neurodegenerative diseases and tumors. In order to further understand the relationship between lysosomes and autophagy, tumorigenesis and drug resistance, the role of autophagy-lysosomal pathway in tumor resistance and related mechanisms and the relationship between drug resistance and hypoxia-induced autophagy are discussed in this paper.

Could concurrent biopsy and microwave ablation be reliable? Concordance between frozen section examination and final pathology in CT-guided biopsy of lung cancer.

PURPOSE: Microwave ablation combined with concurrent biopsy has been used for lung cancer. Frozen section (FS) diagnosis is an important supplement for the final pathology (FP). Thus, a retrospective study was conducted to evaluate the concordance between FS examination and FP in the computed tomography (CT)-guided biopsy of lung cancer. MATERIALS AND METHODS: Patients who underwent percutaneous transthoracic needle lung biopsies and were diagnosed using both intraoperative FS examination and FP were retrospectively enrolled. Concordance between FS findings and FP in the diagnosis of malignant lung cancer and the definitive histology types were recorded. RESULTS: Overall, 163 patients were enrolled. The concordance rate in the diagnosis of malignant tumors was 96.3%. The definitive histology types were concordant between FS examinations and FP in 112 patients (68.7%). Lung cancers undefined with FS but diagnosed as adenocarcinoma with FP were the most common type, observed in 18 patients. The concordance in the histology type was lower for those requiring immunohistochemistry for FP diagnoses (47.3 vs. 79.6%, p < 0.000). Concordance rates differed for the different histology types diagnosed using FP (adenocarcinoma vs. squamous cell carcinoma vs. small-cell lung cancer vs. others, 76.6 vs. 56.2 vs. 69.2 vs. 0.0%, p < 0.000). CONCLUSIONS: FS was inferior to FP in the diagnosis of definitive histology types, but had a high concordance with FP in the diagnosis of malignant lung cancer.

The repertoire of tumor-infiltrating lymphocytes within the microenvironment of oral squamous cell carcinoma reveals immune dysfunction.

BACKGROUND: The role of tumor-infiltrating lymphocytes (TILs) in the immune remodeling of tumor microenvironments (TME) in oral squamous cell carcinoma (OSCC) remains controversial. In this study, we pursued a comprehensive characterization of the repertoire of TILs and then analyzed its clinical significance and potential prognostic value. METHODS: Fresh tumor tissue samples and peripheral blood from 83 OSCC patients were collected to comprehensively characterize the phenotypes and frequencies of TILs by flow cytometry. Archived paraffin-embedded tissues derived from 159 OSCC patients were analyzed by immunohistochemistry to further assess the TIL repertoire. The clinical significance of TILs and their potential prognostic value were further analyzed. RESULTS: A series of unique features of TILs were observed. IL-17 was highly expressed in betel nut chewers, and CD20 was abundantly expressed in patients who did not drink alcohol; high expression of CD138, PD-L1, and Foxp3 was associated with poor prognosis. The Th17/Treg ratio was an independent prognostic factor for patient survival with greater predictive accuracy for overall survival. CONCLUSIONS: Our results suggest an antigen-driven immune response; however, the immune dysfunction within the microenvironment in OSCC and the Th17/Treg balance may play important roles in the modulation of antitumor immunity.

Repertoire of peripheral T cells in patients with oral squamous cell carcinoma.

BACKGROUND: The establishment of adaptive immune responses to neoplasms involves not only the tumour tissue, but also the peripheral blood. We aimed to conduct a preliminary exploration to understand the immune response of T lymphocytes of peripheral blood mononuclear cells (PBMC-Ts) in oral squamous cell carcinoma (OSCC). METHODS: A total of 103 blood samples from OSCC patients and 18 blood samples from healthy donors (HD) were analysed by flow cytometry. RESULTS: Compared to those in HD, a series of unique features of PBMC-Ts were observed in OSCC patients including a significant increase in CD4+ T cells, a shift from naïve to memory/effector phenotype, an increased frequency of exhausted phenotypes (programmed death-1 [PD-1], T cell Ig and mucin protein-3 [Tim-3] and Tregs), an abundance of Th17s and Tc17s and an imbalance in Th17/Tc17 and Th17/Treg ratios. Furthermore, in OSCC patients, we also found that CD4+ T cells were significantly increased in patients with larger tumours than smaller tumours, memory/effector phenotype and exhausted phenotypes were significantly associated with advanced clinical stage and lymph node metastasis, and the Th17/Treg ratio was associated with early clinical stage and no lymph node metastasis. CONCLUSION: PBMC-Ts may be involved in the development and progression of OSCC, which suggested to be a manifestation of an immune response between host and tumour neoantigens.

Arecoline suppresses epithelial cell viability by upregulating tropomyosin-1 through the transforming growth factor-ß/Smad pathway.

CONTEXT: Oral submucous fibrosis (OSF) is a chronic and progressive disease. Arecoline, present in betel nuts, has been proposed as a vital aetiological factor. However, the underlying mechanism remains unclear. OBJECTIVES: This research elucidates the expression of tropomyosin-1 (TPM1) and its regulation mechanism in HaCaT cells treated with arecoline. MATERIALS AND METHODS: HaCaT cells were assigned into three groups: (1) Control; (2) Treated with arecoline (0.16 mM) for 48 h (3) Treated with arecoline (0.16 mM) and transfected with small interfering RNA (siRNA) for TPM1 (50 nM) for 48 h. CCK8, cell cycle, and apoptosis phenotypic analyses were performed. PCR and western blot analyses were performed to detect the expression level of TPM1 and examine the related signalling pathway. RESULTS: The IC50 of arecoline was approximately 50 µg/mL (0.21 mM). The arecoline dose (0.16 mM) and time (48 h) markedly increased TPM1 expression at the mRNA and protein levels in HaCaT cells. Arecoline suppressed the cell growth, caused cell cycle arrest at the G1 phase, and induced cell apoptosis in HaCaT cells. siRNA-mediated knockdown of TPM1 attenuated the effect of arecoline on cell proliferation, apoptosis, and cell cycle arrest at the G1 phase. Furthermore, blocking of the transforming growth factor (TGF)-ß receptor using SB431542 significantly suppressed TPM1 expression in the cells treated with arecoline. DISCUSSION AND CONCLUSIONS: Arecoline suppresses HaCaT cell viability by upregulating TPM1 through the TGF-ß/Smad signalling pathway. This research provides a scientific basis for further study of arecoline and TPM1 in OSF and can be generalised to broader pharmacological studies. TPM1 may be a promising molecular target for treating OSF.

Diastereoselective synthesis of α-dicarbonyl cyclopropanes via a lanthanide amide-catalysed reaction.

Lanthanide bis(trimethylsilyl)amides, [(Me3Si)2N]3Ln(µ-Cl)Li(THF)3, were used as efficient catalysts for a one-pot reaction of α-ketoesters, dialkyl phosphite, and activated alkenes to produce α-dicarbonyl cyclopropanes in moderate to high yields. The reaction was stereoselective and the two adjacent carbonyls linked to the cyclopropane were in the cis-configuration. The high efficiency of the lanthanide amide in catalysing the reaction is the result of the cooperation between the lanthanide metal centre and the N(SiMe3)2 anion.

Oral submucous fibrosis: A clinicopathological study of 674 cases in China.

BACKGROUND: Oral submucous fibrosis (OSF) has been reported frequently in India and other countries in South Asia. There are few reports on the clinicopathological features of OSF in China, where OSF is an epidemic. This study analyses the clinicopathological features of OSF in Hunan Province, China. METHODS: A total of 674 cases of OSF were collected from July 2013 to August 2018 in Xiangya Stomatological Hospital, Central South University, and gender, age, site, pathological stage, habits, symptoms and associated lesions were recorded. RESULTS: The male to female ratio was 32.7:1. The average age was 35.23 ± 10.08. The buccal mucosa was the most common site. A total of 99.85% of OSF cases chewed areca nut. Pale mucosa, restricted mouth opening, burning and fibrous bands were common clinical manifestations. Oral leukoplakia (OLK) was the most common associated lesion. The extended duration of chewing areca nut increased the risk of associated lesions (P < 0.05). The risk of OSF associated with OLK decreased with increasing OSF stage (P < 0.05). CONCLUSION: The prevalence of OSF in males was higher than that in females, the buccal mucosa was most affected, and chewing areca nut is the most common habit of OSF patients.

Fascin-1 Contributes to Neuropathic Pain by Promoting Inflammation in Rat Spinal Cord.

Neuropathic pain is a complicated clinical syndrome caused by heterogeneous etiology. Despite the fact that the underlying mechanisms remain elusive, it is well accepted that neuroinflammation plays a critical role in the development of neuropathic pain. Fascin-1, an actin-bundling protein, has been proved to be involved in the processing of diverse biological events including cellular development, immunity, and tumor invasion etc. Recent studies have shown that Fascin-1 participates in antigen presentation and the regulation of pro-inflammatory agents. However, whether Fascin-1 is involved in neuropathic pain has not been reported. In the present study we examined the potential role of Fascin-1 by using a rodent model of chronic constriction injury (CCI). Our results showed that Fascin-1 increased rapidly in dorsal root ganglions (DRG) and spinal cord (SC) after CCI. The increased Fascin-1 widely expressed in DRG, however, it localized predominantly in microglia, seldom in neuron, and hardly in astrocyte in the SC. Intrathecal injection of Fascin-1 siRNA not only suppressed the activation of microglia and the release of pro-inflammatory mediators, but also attenuated the mechanical allodynia and thermal hyperalgesia induced by CCI.

Synthesis of a new deoxyglucose derivative modified near-infrared fluorescent probe for tumor diagnosis.

Malignant neoplasms exhibit an elevated rate of glycolysis and a high demand for glucose over normal cells. This characteristic can be exploited for in vivo imaging and tumor targeting examined. In this manuscript, we describe the synthesis of near-infrared (NIR) fluorochrome IR-822-labeled 2-amino-2-deoxy-d-glucose (DG) for optical imaging of tumors in mice. NIR fluorescent dye IR-820 was subsequently conjugated with 3-Mercaptopropionic acid and 2-amino-2-deoxy-d-glucose to form IR-822-DG. The cell experiments and acute toxicity studies demonstrated the low toxicity of IR-822-DG to normal cells/tissues. The dynamic behavior and targeting ability of IR-822-DG in normal mice was investigated with a NIR fluorescence imaging system. The in vitro and in vivo tumor targeting capabilities of IR-822-DG were evaluated in tumor cells and tumor bearing mice, respectively. Results demonstrated that IR-822-DG actively and efficiently accumulated at the site of the tumor. The probe also exhibited good photostability and excellent cell membrane permeability. The study indicates the broad applicability of IR-822-DG for tumors diagnosis, especially in the glucose-related pathologies.

Insulin-like Growth Factor Binding Protein6 Associated with Neuronal Apoptosis Following Intracerebral Hemorrhage in Rats.

The insulin-like growth factor (IGF) system is linked to CNS pathological states. The functions of IGFs are modulated by a family of binding proteins termed insulin-like growth factor binding proteins (IGFBPs). Here, we demonstrate that IGFBP-6 may be associated with neuronal apoptosis in the processes of intracerebral hemorrhage (ICH). We obtained a significant upregulation of IGFBP-6 in neurons adjacent to the hematoma following ICH with the results of Western blot, immunohistochemistry, and immunofluorescence. Increasing IGFBP-6 level was found to be accompanied by the upregulation of Bax, Bcl-2, and active caspase-3. Besides, IGFBP-6 co-localized well with active caspase-3 in neurons, indicating its potential role in neuronal apoptosis. Knocking down IGFBP-6 by RNA-interference in PC12 cells reduced active caspase-3 expression. Thus, IGFBP-6 may play a role in promoting the brain secondary damage following ICH.

Olfactory dysfunction in the APP/PS1 transgenic mouse model of Alzheimer's disease: Morphological evaluations from the nose to the brain.

Olfactory dysfunction is among the signs of Alzheimer's disease (AD) and cognitive impairment. It has been demonstrated Aß was associated with olfactory impairment observed in both transgenic mice and in AD patients. In this study, we evaluated amyloid deposition in the olfactory circuit of APP/PS1 transgenic mouse model of AD, which showed olfactory dysfunction in olfactory behavior tests. We found amyloid depositions were widely distributed in the whole olfactory circuit. Moreover, we think these amyloid depositions contribute to neuronal atrophy, dendritic abnormalities, synapse loss and axonal degeneration. Therefore, there was a correlation between olfactory deficits and amyloid deposition. Our findings provide initial insights into the pathological basis of AD-related olfactory dysfunction.