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Journal of Advanced Research Jan 2022Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer's disease (AD), but the poor dissolution hampers its bioavailability and therapeutic...
INTRODUCTION
Honokiol (HO) exerts neuroprotective effects in several animal models of Alzheimer's disease (AD), but the poor dissolution hampers its bioavailability and therapeutic efficacy.
OBJECTIVES
A novel honokiol nanoscale drug delivery system (Nano-HO) with smaller size and excellent stability was developed in this study to improve the solubility and bioavailability of HO. The anti-AD effects of Nano-HO was determined.
METHODS
Male TgCRND8 mice were daily orally administered Nano-HO or HO at the same dosage (20 mg/kg) for 17 consecutive weeks, followed by assessment of the spatial learning and memory functions using the Morris Water Maze test (MWMT).
RESULTS
Our pharmacokinetic study indicated that the oral bioavailability was greatly improved by Nano-HO. In addition, Nano-HO significantly improved cognitive deficits and inhibited neuroinflammation via suppressing the levels of TNF-α, IL-6 and IL-1β in the brain, preventing the activation of microglia (IBA-1) and astrocyte (GFAP), and reducing β-amyloid (Aβ) deposition in the cortex and hippocampus of TgCRND8 mice. Moreover, Nano-HO was more effective than HO in modulating amyloid precursor protein (APP) processing via suppressing β-secretase, as well as enhancing Aβ-degrading enzymes like neprilysin (NEP). Furthermore, Nano-HO more markedly inhibited tau hyperphosphorylation via decreasing the ratio of p-Tau (Thr 205)/tau and regulating tau-related apoptosis proteins (caspase-3 and Bcl-2). In addition, Nano-HO more markedly attenuated the ratios of p-JNK/JNK and p-35/CDK5, while enhancing the ratio of p-GSK-3β (Ser9)/GSK-3β. Finally, Nano-HO prevented the gut microflora dysbiosis in TgCRND8 mice in a more potent manner than free HO.
CONCLUSION
Nano-HO was more potent than free HO in improving cognitive impairments in TgCRND8 mice via inhibiting Aβ deposition, tau hyperphosphorylation and neuroinflammation through suppressing the activation of JNK/CDK5/GSK-3β signaling pathway. Nano-HO also more potently modulated the gut microbiota community to protect its stability than free HO. These results suggest that Nano-HO has good potential for further development into therapeutic agent for AD treatment.
Topics: Alzheimer Disease; Animals; Biphenyl Compounds; Cognition; Cognitive Dysfunction; Gastrointestinal Microbiome; Glycogen Synthase Kinase 3 beta; Lignans; Male; Mice; Neuroinflammatory Diseases
PubMed: 35024199
DOI: 10.1016/j.jare.2021.03.012 -
Frontiers in Immunology 2021Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the...
Tonsil hyperplasia is the most common cause of pediatric obstructive sleep apnea (OSA). Despite the growing knowledge in tissue immunology of tonsils, the immunopathology driving tonsil hyperplasia and OSA remains unknown. Here we used multi-parametric flow cytometry to analyze the composition and phenotype of tonsillar innate lymphoid cells (ILCs), T cells, and B cells from pediatric patients with OSA, who had previous polysomnography. Unbiased clustering analysis was used to delineate and compare lymphocyte heterogeneity between two patient groups: children with small tonsils and moderate OSA (n = 6) or large tonsils and very severe OSA (n = 13). We detected disturbed ILC and B cell proportions in patients with large tonsils, characterized by an increase in the frequency of naïve CD27CD21 B cells and a relative reduction of ILCs. The enrichment of naïve B cells was not commensurate with elevated Ki67 expression, suggesting defective differentiation and/or migration rather than cellular proliferation to be the causative mechanism. Finally, yet importantly, we provide the flow cytometry data to be used as a resource for additional translational studies aimed at investigating the immunological mechanisms of pediatric tonsil hyperplasia and OSA.
Topics: Child, Preschool; Female; Flow Cytometry; Humans; Hyperplasia; Immunity, Innate; Lymphocytes; Male; Memory B Cells; Palatine Tonsil; Receptors, CXCR5; Sleep Apnea, Obstructive; Tumor Necrosis Factor Receptor Superfamily, Member 7
PubMed: 34745084
DOI: 10.3389/fimmu.2021.674080 -
PloS One 2022A subset of individuals with COVID-19 can suffer from a severe form of the disease requiring breathing support for respiratory failure and even death due to disease...
INTRODUCTION
A subset of individuals with COVID-19 can suffer from a severe form of the disease requiring breathing support for respiratory failure and even death due to disease complications. COVID-19 disease severity can be attributed to numerous factors, where several studies have associated changes in the expression of serum pro-inflammatory cytokines with disease severity. However, very few studies have associated the changes in expression of pro-inflammatory changes in the nasopharyngeal milieu with disease severity. Therefore, in the current study, we performed differential gene expression analysis of various pro-inflammatory cytokines in the nasopharyngeal milieu of mild & severe COVID-19 cases.
MATERIAL AND METHOD
For this retrospective, cross-sectional study, a total of 118 nasopharyngeal swab samples, previously collected from mild and severe (based on the WHO criteria) COVID-19 patients were used. A real-time qPCR was performed to determine the viral loads and also evaluate the mRNA expression of eight cytokines (IL-1, IL-2, IL-4, IL-6, IL-10, IFN-γ, TGF-β1, and TNF-α). Subsequently, an unpaired T-test was applied to compare the statistical difference in mean expression of viral loads and each cytokine between the mild and severe groups, while the Pearson correlation test was applied to establish a correlation between disease severity, viral load, and cytokines expression. Similarly, a multivariable logistic regression analysis was performed to assess the relationship between different variables from the data and disease severity.
RESULTS
Out of 118 samples, 71 were mild, while 47 were severe. The mean viral load between the mild and severe groups was comparable (mild group: 27.07± 5.22; severe group: 26.37 ±7.89). The mRNA expression of cytokines IL-2, IL-6, IFN- γ, and TNF-α was significantly different in the two groups (p<0.05), where the Log2 normalized expression of IL-2, IL-6, IFN- γ, and TNF-α was found to be 2.2-, 16-, 2.3-, and 1.73-fold less in the severe group as compared to the mild group. Furthermore, we also observed a significant positive correlation between all the cytokines in the severe group. The multivariate analysis showed a significant relationship between age, IL-6, and disease severity.
CONCLUSION
This decreased expression of certain cytokines (IL-2, IL-6, TNF-α, and IFN-γ) in the nasopharyngeal milieu may be considered early biomarkers for disease severity in COVID-19 patients.
Topics: Humans; Cytokines; Tumor Necrosis Factor-alpha; Interleukin-6; Interleukin-2; Retrospective Studies; Cross-Sectional Studies; COVID-19; Gene Expression; Nasopharynx; RNA, Messenger
PubMed: 36584119
DOI: 10.1371/journal.pone.0279270 -
Diagnostic Pathology Dec 2013Human papillomavirus-associated oropharyngeal carcinoma (HPV-OPC) is clinicopathologically distinct entity from the HPV-unassociated one (nHPV-OPC). This study aimed to...
BACKGROUND
Human papillomavirus-associated oropharyngeal carcinoma (HPV-OPC) is clinicopathologically distinct entity from the HPV-unassociated one (nHPV-OPC). This study aimed to determine the relationship between histological subtypes of OPC and HPV status for Japanese cases and to identify histological structures of HPV-OPC.
METHODS
66 OPC cases were categorized into conventional squamous cell carcinoma (SCC) and the variants. Conventional SCC was subcategorized into keratinizing (KSCC), non-keratinizing (NKSCC), and hybrid SCC (HSCC). HPV status of all cases was determined using p16-immunohistochemistry and HPV-DNA ISH.
RESULTS
Two histological subtypes, NKSCC and HSCC, tended to be HPV-OPC and KSCC tended to be nHPV-OPC with statistical significance. Two histological structures, abrupt keratinization, defined in the text, and comedo-necrosis among non-maturing tumor island, were observed for 58.1% and 38.7% of HPV-OPC, and tended to exist for HPV-OPC with statistical significance.
CONCLUSIONS
This study showed the association of NKSCC/HSCC with HPV-OPC in Japanese cases, and two histological structures, abrupt keratinization and comedo-necrosis among non-maturing island, were considered characteristic histological features of HPV-OPC.
VIRTUAL SLIDES
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1816432541113073.
Topics: Adult; Aged; Aged, 80 and over; Asian People; Biomarkers, Tumor; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; DNA, Viral; Female; Humans; In Situ Hybridization; Japan; Male; Middle Aged; Oropharyngeal Neoplasms; Oropharynx; Papillomaviridae; Papillomavirus Infections; Retrospective Studies
PubMed: 24354780
DOI: 10.1186/1746-1596-8-211 -
Indian Journal of Dental Research :... 2016Oral submucous fibrosis (OSMF) is a chronic insidious disease affecting any part of the oral cavity and sometimes the pharynx. It is a collagen-related disorder...
BACKGROUND
Oral submucous fibrosis (OSMF) is a chronic insidious disease affecting any part of the oral cavity and sometimes the pharynx. It is a collagen-related disorder predominantly associated with tobacco/areca nut chewing habit and characterized by progressive hyalinization of the submucosa. Prevalence of OSMF is 2.01%, and malignant transformation rate of 2.3%-7.6% has been reported in the literature. Measures such as forcing the mouth open and cutting the fibrotic bands have resulted in more fibrosis and disability.
AIM
Various surgical treatment modalities have been advocated in the surgical management of OSMF with variable results. This retrospective study evaluates the efficacy of nasolabial flap in the surgical treatment of OSMF.
MATERIALS AND METHODS
Retrospective analysis of 42 patients who underwent surgical management of OSMF with mouth opening <20 mm by nasolabial flap at authors center from 2000 to 2015. Only the cases diagnosed as advanced OSMF based on long-standing positive history of habits (chewing tobacco, betel nut, etc.), clinical and histopathological examination. OSMF due to other causes such as nutritional deficiency, immunological diseases, and systemic illness with medically compromised patients were excluded from the study. Inferiorly based nasolabial flaps were raised in the supramuscular plane and transferred intraorally through a transbuccal tunnel.
RESULTS
The study groups consist of 42 cases of clinical and histopathologically proven cases of OSMF treated by nasolabial flap. Out of 42 cases, 39 (92.85%) were males and 3 (7.15%) were females which showed a male predominance and the ratio was 13:1. The mean (standard deviation [SD]) preoperative mouth opening was 14.60 mm (3.06). After release of fibrotic bands, a mean forced intraoperative mouth opening of 36.27 (2.11) mm was achieved. The mean (SD) postoperative mouth opening was 33.05 mm (2.40) at the end of 2-year follow-up. The mean (SD) increase in mouth opening after surgical management at the end of 2-year follow-up is 18.46 mm (1.89). Sixteen out of 42 patients' histopathological report turned out to be dysplastic. The mean (SD) follow-up was 2.79 years (1.08). There was no incidence of infection in the transferred flap and the recipient site in all cases except one case with malignant transformation. All flaps healed without evidence of infection, dehiscence, or necrosis. Results were assessed by comparing the pre- and post-operative maximum mouth opening.
CONCLUSION
The nasolabial flap is a versatile flap, which can be successfully used in the reconstruction of defects created after the release of fibrotic bands in OSMF. The versatility of the nasolabial flap has been attributed to its reliable vascularity derived from numerous vessels in the vicinity. Major advantage is the ease of elevation, proximity to the defect, suitable size for coverage of defect, minimal swallowing and speech difficulties, and a relatively cosmetic result as scar is in natural crease. All the cases treated for OSMF using bilateral nasolabial flaps showed adequate mouth opening at 2-year follow-up postoperatively, recommending its use.
Topics: Acute Disease; Adult; Female; Humans; Male; Middle Aged; Nasolabial Fold; Oral Submucous Fibrosis; Retrospective Studies; Surgical Flaps; Treatment Outcome; Trismus
PubMed: 27966506
DOI: 10.4103/0970-9290.195627 -
Journal of Virology Jul 2017Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we...
Despite a great deal of prior research, the early pathogenic events in natural oral poliovirus infection remain poorly defined. To establish a model for study, we infected 39 macaques by feeding them single high doses of the virulent Mahoney strain of wild type 1 poliovirus. Doses ranging from 10 to 10 50% tissue culture infective doses (TCID) consistently infected all the animals, and many monkeys receiving 10 or 10 TCID developed paralysis. There was no apparent difference in the susceptibilities of the three macaque species (rhesus, cynomolgus, and bonnet) used. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia, and virus was isolated from tonsils, gut mucosa, and draining lymph nodes. Viral replication proteins were detected in both epithelial and lymphoid cell populations expressing CD155 in the tonsil and intestine, as well as in spinal cord neurons. Necrosis was observed in these three cell types, and viral replication in the tonsil/gut was associated with histopathologic destruction and inflammation. The sustained response of neutralizing antibody correlated temporally with resolution of viremia and termination of virus shedding in oropharynges and feces. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), extending previous studies of poliovirus pathogenesis in humans. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis and to assess the efficacy of candidate antiviral drugs and new vaccines. Early pathogenic events of poliovirus infection remain largely undefined, and there is a lack of animal models mimicking natural oral human infection leading to paralytic poliomyelitis. All 39 macaques fed with single high doses ranging from 10 to 10 TCID Mahoney type 1 virus were infected, and many of the monkeys developed paralysis. Virus excretion in stool and nasopharynges was consistently observed, with occasional viremia; tonsil, mesentery lymph nodes, and intestinal mucosa served as major target sites of viral replication. For the first time, this model demonstrates that early in the infectious process, poliovirus replication occurs in both epithelial cells (explaining virus shedding in the gastrointestinal tract) and lymphoid/monocytic cells in tonsils and Peyer's patches (explaining viremia), thereby supplementing historical reconstructions of poliovirus pathogenesis. Because the model recapitulates human poliovirus infection and poliomyelitis, it can be used to study polio pathogenesis, candidate antiviral drugs, and the efficacy of new vaccines.
Topics: Animal Structures; Animals; Disease Models, Animal; Epithelial Cells; Feces; Leukocytes; Macaca; Nasopharynx; Poliomyelitis; Poliovirus; Virus Shedding
PubMed: 28356537
DOI: 10.1128/JVI.02310-16 -
Cleveland Clinic Journal of Medicine Aug 2023
Topics: Humans; Infectious Mononucleosis; Splenic Infarction; Palatine Tonsil
PubMed: 37527871
DOI: 10.3949/ccjm.90a.22079 -
Circulation Aug 2020Supplemental Digital Content is available in the text.
Supplemental Digital Content is available in the text.
Topics: Adult; Antiviral Agents; Betacoronavirus; C-Reactive Protein; COVID-19; Cobicistat; Coronavirus Infections; Darunavir; Electrocardiography; Female; Humans; Hypokinesia; Hypotension; International Normalized Ratio; Myocardium; Nasopharynx; Pandemics; Platelet Count; Pneumonia, Viral; SARS-CoV-2; ST Elevation Myocardial Infarction; Thrombosis; Troponin I; Ventricular Dysfunction, Left
PubMed: 32677840
DOI: 10.1161/CIRCULATIONAHA.120.049294 -
BMC Infectious Diseases Mar 2016The occurrence of nasopharyngeal tuberculosis is rare even in areas where tuberculosis is endemic. Here, we report a case of rare primary nasopharyngeal tuberculosis,...
BACKGROUND
The occurrence of nasopharyngeal tuberculosis is rare even in areas where tuberculosis is endemic. Here, we report a case of rare primary nasopharyngeal tuberculosis, promptly evaluated by nasolaryngoscopy.
CASE PRESENTATION
A 78-year-old woman presented with postnasal drip and a cough of 1-month duration. Endoscopic examination of the nasopharynx revealed irregular mucosal thickening of the right lateral and posterior wall of the naso (epi)-pharynx, which was covered with yellow discharge presenting as postnasal drip. Computed tomography (CT) demonstrated enhanced soft tissue area in the right lateral and posterior wall of the nasopharynx. Bacteriological examination from a nasopharyngeal swab revealed that staining for acid-fast bacilli was positive and the quenching probe PCR test was positive for Mycobacterium tuberculosis. Histopathological examination from the thickening nasopharyngeal mucosa revealed granulomatous formation with caseous necrosis. Ziehl-Nielsen staining directly could detect acid-fast bacilli. Chest X-ray and CT scan ruled out the pulmonary tuberculosis. Base on these findings, we diagnosed it as primary nasopharyngeal tuberculosis. After six months anti-tuberculous therapy, the patient's symptoms had completely disappeared. Nasolaryngoscopic examination and CT image after 6 months post therapy revealed a normal nasopharynx with complete resolution of the lesion.
CONCLUSION
We recommend endoscopic examination for patients suffering from chronic postnasal drips to avoid inappropriate diagnosis.
Topics: Aged; Diagnosis, Differential; Female; Humans; Mycobacterium tuberculosis; Nasal Mucosa; Nasopharyngeal Diseases; Tomography, X-Ray Computed; Tuberculosis
PubMed: 26980081
DOI: 10.1186/s12879-016-1449-7 -
Annals of Allergy, Asthma & Immunology... Feb 2015Chronic rhinosinusitis (CRS) and asthma frequently coexist in children and adults. However, the precise pathophysiologic mechanism of this interaction is still poorly...
BACKGROUND
Chronic rhinosinusitis (CRS) and asthma frequently coexist in children and adults. However, the precise pathophysiologic mechanism of this interaction is still poorly understood, especially in children, owing to the lack of direct measurements of mucosal inflammation in the upper airways.
OBJECTIVE
To determine the pathophysiologic mechanism by analyzing the expression of a large array of inflammatory cytokines and chemokines in the sinus and adenoid tissues surgically removed from pediatric patients with CRS refractory to medical management.
METHODS
Twenty-eight children 2 to 12 years old diagnosed with CRS with or without asthma and 10 controls were included in this prospective, nonrandomized study. Mucosal expression of 40 inflammatory cytokines was measured with a multiplex assay and was normalized to total tissue protein.
RESULTS
Compared with children with CRS and without asthma, children with CRS and asthma had significantly higher sinus levels of tumor necrosis factor-α and adenoid levels of epidermal growth factor, eotaxin, fibroblast growth factor-2, growth-related oncogene, and platelet-derived growth factor-AA.
CONCLUSION
The inflammatory response in the upper airway mucosa of children with asthma and CRS was similar, but more severe, compared with children with CRS without asthma. This observation is consistent with the hypothesis that asthma in these patients is caused or exacerbated by severe upper airway disease and supports the concept that treating sinus disease is paramount in the management of chronic asthma in children using, for the first time, direct measurements of airway inflammation in children.
Topics: Adenoidectomy; Adenoids; Asthma; Child; Child, Preschool; Cytokines; Female; Humans; Inflammation; Male; Nasal Mucosa; Palatine Tonsil; Paranasal Sinuses; Prospective Studies; Rhinitis; Sinusitis; Surveys and Questionnaires; Tonsillectomy
PubMed: 25624129
DOI: 10.1016/j.anai.2014.10.024