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AAPS PharmSciTech Jul 2022Diseases caused by upper respiratory tract (URT) and pulmonary infections have been a serious threat to human health for millennia and lack of targeted effective...
Diseases caused by upper respiratory tract (URT) and pulmonary infections have been a serious threat to human health for millennia and lack of targeted effective therapeutic techniques. In this study, two kinds of cyclodextrin particles with typical particle shapes of nanocubes and microbars were synthesized through a facile process. Subsequently, the particles were used as carriers for loading and stabilizing iodine and characterizations were performed to demonstrate the loading mechanism. Next-generation impactor (NGI) experiments showed that iodine-loaded microbars (I@microbars) had a deposition rate of 79.75% in URT, while iodine-loaded nanocubes (I@nanocubes) were delivered to the deep lungs with a fine particle fraction (FPF) of 46.30%. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) indicated that the iodine-loaded nanocubes and microbars had similar bactericidal effect to povidone iodine solution. Cell viability studies and extracellular pro-inflammatory factor (TNF-α, IL-1β, IL-6) evaluations demonstrate noncytotoxic effects of the blank carriers and anti-inflammatory effects of iodine-loaded samples. The irritation of the rat pharynx by I@microbars was evaluated for the behavioral observations, body weight changes, histopathological studies, and TNF-α, IL-1β, and IL-6 levels in pharyngeal tissues. The results showed that I@microbars had no irritation to rat pharyngeal tissues at therapeutic doses. In conclusion, the present study provides novel treatment of URT infections via supramolecular cyclodextrin carriers for URT local therapy with iodine loading by a solvent-free method, which enhances the stability and reduces the inherent irritation without inhibiting their antimicrobial effects. Two kinds of cyclodextrin particles with typical shapes of microbars and nanocubes were synthesized by a facile process. Subsequently, iodine was successfully loaded into the particles by gas-solid interaction. The iodine-loaded microbars showed air dynamics characteristics for inhalation delivery to the upper respiratory tract with little alveolar deposition in the lungs.
Topics: Administration, Inhalation; Animals; Cyclodextrins; Interleukin-6; Iodine; Particle Size; Pneumonia; Rats; Tumor Necrosis Factor-alpha
PubMed: 35804252
DOI: 10.1208/s12249-022-02277-x -
Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2022Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but...
Dendrobium officinale can serve as Chinese medicinal material effective in nourishing yin, clearing heat, and producing fluid, and is used to treat throat diseases, but its active substances and mechanism are not clear. To clarify the active fraction and underlying mechanism of D. officinale against chronic pharyngitis(CP), the present study induced a CP model in rats by pepper water combined with low-concentration ammonia, and crude polysaccharides of D. officinale(DOP), non-polysaccharides of D. officinale(DON), and total extract of D. officinale(DOT)(0.33 g·kg~(-1), calculated according to the crude drug) were administered by gavage for six weeks. The changes in oral secretions and pharyngeal conditions of rats with CP were observed and rated. The hematological indicators were determined by an automatic hematology analyzer. The serum levels of pro-inflammatory factors, such as tumor necrosis factor-alpha(TNF-α), interleukin 1β(IL-1β), and interleukin 6(IL-6), and T-lymphocyte cytokines, including interferon γ(IFN-γ), interleukin 4(IL-4), interleukin 17(IL-17), and transforming growth factor β1(TGF-β1) were detected by the enzyme-linked immunosorbent assay(ELISA). The proportions of CD3~+, CD4~+, and CD8~+cells in peripheral blood T lymphocyte subsets were determined by the flow cytometry. The histomorphological changes of the pharynx were observed by hematoxylin-eosin(HE) staining. The protein expression of nuclear factor-κB P65(NF-κB P65), cyclooxygenase-2(COX-2), F4/80, and monocyte chemoattractant protein-1(MCP-1) in the pharynx were detected by immunohistochemistry and Western blot. The results showed that DOP and DON could significantly relieve pharyngeal lesions, reduce white blood cells(WBC) and lymphocytes(LYMP), decrease the levels of pro-inflammatory factors TNF-α, IL-6, and IL-1β, and inhibit the protein expression of NF-κB P65, COX-2, F4/80, and MCP-1 in the pharynx. DOP was superior in reducing oral secretions and serum IL-17 level and inferior in increasing CD4~+/CD8~+ratio to DON. It is suggested that both polysaccharides and non-polysaccharides of D. officinale have anti-PC effects and the anti-inflammatory mechanism may be related to the regulation of T lymphocyte distribution and inhibition of the inflammatory signaling pathways mediated by NF-κB P65. The anti-inflammatory effect of DOP may be related to the regulation of Th17/Treg balance, while that of DON may be related to the regulation of the Th/Tc ratio.
Topics: Ammonia; Animals; Anti-Inflammatory Agents; Cyclooxygenase 2; Dendrobium; Interleukin-17; Interleukin-6; NF-kappa B; Pharyngitis; Plant Extracts; Polysaccharides; Rats; Tumor Necrosis Factor-alpha; Water
PubMed: 35531700
DOI: 10.19540/j.cnki.cjcmm.20211223.703 -
Clinical Oral Investigations May 2022To determine the relation between the severity of periodontitis and osteonecrosis of the jaw (ONJ) occurrence among different cancer locations and estimate the effect of...
OBJECTIVES
To determine the relation between the severity of periodontitis and osteonecrosis of the jaw (ONJ) occurrence among different cancer locations and estimate the effect of dental care on ONJ prevention in cancer patients.
MATERIALS AND METHODS
This population-based cross-sectional study was conducted through the Longitudinal Health Insurance Database, Taiwan. Patients with malignancies were collected and subdivided into groups according to their different cancer locations, the severity of periodontitis, and dental care. Multivariable logistic regression analysis was performed to assess the associations between ONJ and ONJ-related factors.
RESULTS
A total of 8,234 ONJ patients and 32,912 control patients were investigated. Lip, oral cavity, and pharynx malignancies had the highest ONJ risk among all cancer locations (OR from 3.07 to 9.56, P < 0.01). There is a linear relationship between different severities of periodontitis and ONJ. Patients with radiotherapy and severe periodontitis had the highest ONJ risk (adjusted OR, 9.56; 95% CI, 5.34-17.1). Patients with good dental care had a lower ONJ risk.
CONCLUSIONS
The periodontal condition and cancer location showed a significant impact on the risk of developing ONJ after adjusting for bisphosphonate use. Good dental care could decrease the risk of ONJ in cancer patients. The severity of periodontitis might be a target to predict the potency of ONJ.
CLINICAL RELEVANCE
Dentists must be vigilant about the increased risk of ONJ in cancer patients with periodontitis, especially in the head and neck cancer population. Good dental care is advised for cancer patients with severe periodontitis.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Cross-Sectional Studies; Diphosphonates; Head and Neck Neoplasms; Humans; Osteonecrosis; Periodontitis; Risk Factors
PubMed: 35482084
DOI: 10.1007/s00784-021-04175-1 -
Nutrients Jan 2022Pharyngitis is an inflammation of the pharynx caused by viral, bacterial, or non-infectious factors. In the present study, the anti-inflammatory efficacy of carvacrol...
Pharyngitis is an inflammation of the pharynx caused by viral, bacterial, or non-infectious factors. In the present study, the anti-inflammatory efficacy of carvacrol was assessed using an in vitro model of streptococcal pharyngitis using human tonsil epithelial cells (HTonEpiCs) induced with cell wall antigens. HTonEpiCs were stimulated by a mixture of lipoteichoic acid (LTA) and peptidoglycan (PGN) for 4 h followed by exposure to carvacrol for 20 h. Following exposure, interleukin (IL)-6, IL-8, human beta defensin-2 (HBD-2), epithelial-derived neutrophil-activating protein-78 (ENA-78), granulocyte chemotactic protein-2 (GCP-2), cyclooxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and prostaglandin (PGE) were measured by enzyme-linked immunosorbent assays (ELISA). The levels of pro-inflammatory cytokines, IL-6, IL-8, ENA-78, and GCP-2 were decreased in a carvacrol dose-dependent manner. The production of HBD-2 was significantly suppressed over 24 h carvacrol treatments. PGE and COX-2 levels in the cell suspensions were affected by carvacrol treatment. TNF-α was not detected. The cell viability of all the tested carvacrol concentrations was greater than 80%, with no morphological changes. The results suggest that carvacrol has anti-inflammatory properties, and carvacrol needs to be further assessed for potential clinical or healthcare applications to manage the pain associated with streptococcal pharyngitis.
Topics: Biomarkers; Cell Wall; Cymenes; Epithelial Cells; Humans; Lipopolysaccharides; Palatine Tonsil; Peptidoglycan; Teichoic Acids
PubMed: 35276864
DOI: 10.3390/nu14030503 -
Radiation Oncology (London, England) Jan 2022To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of...
Irradiation-induced nasopharyngeal necrosis (INN) in newly diagnosed nasopharyngeal carcinoma treated by intensity-modulated radiation therapy: clinical characteristics and the influence of treatment strategies.
PURPOSE
To define the clinical characteristics of irradiation-induced nasopharyngeal necrosis (INN) after intensity-modulated radiotherapy (IMRT) and identify the influence of treatment strategies on INN in primary nasopharyngeal carcinoma (NPC) patients.
PATIENTS AND METHODS
From 2008 to 2019, NPC patients pathologically diagnosed with INN after primary IMRT were reviewed. Those patients were matched with propensity scores for patients without INN in our center. The impact of treatment strategies on INN occurrence was assessed using univariate and multivariate logistic regression analysis.
RESULTS
The incidence rate of INN was 1.9% among the primary NPC population, and 53 patients with INN were enrolled. Headache and foul odor were the main symptoms, and 71.7% of cases had pseudomembrane during or at the end of radiotherapy. All patients were in early or middle stage INN, and no one presented with skull-based osteoradionecrosis. Then 212 non-INN patients were included based on propensity scores match. Overall survival (p = 0.248) and progression-free survival (p = 0.266) curves were similar between the INN and non-INN groups. Treatment strategies including combining chemotherapy or molecular targeted therapy with radiotherapy were not associated with INN occurrence, while boost dose (OR 7.360; 95% CI 2.301-23.547; p = 0.001) was a predictor factor for it. However, the optimal threshold for an accumulated dose to predict INN's occurrence was failed to determine.
CONCLUSION
In the IMRT era, the severity of INN in primary NPC patients is lessened. This study showed that treatment strategies contributed little to develop INN, while the accumulated dose of radiation may relate to its occurrence.
Topics: Adolescent; Adult; Aged; Female; Humans; Male; Middle Aged; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Nasopharynx; Necrosis; Radiation Injuries; Radiotherapy, Intensity-Modulated; Retrospective Studies; Young Adult
PubMed: 35062991
DOI: 10.1186/s13014-022-01980-0 -
Medicine Jan 2022The nature of pharyngeal swallowing function during the course of recovery of dysphagia due to lateral medullary syndrome (LMS) is unclear. Vacuum swallowing is a...
INTRODUCTION
The nature of pharyngeal swallowing function during the course of recovery of dysphagia due to lateral medullary syndrome (LMS) is unclear. Vacuum swallowing is a compensatory swallowing method that improves the pharyngeal passage of a bolus by creating negative pressure during swallowing in the esophagus in patients with dysphagia due to LMS. We present a case involving a patient with dysphagia due to LMS who involuntarily acquired a swallowing method with prolonged and increased pharyngeal contraction and vacuum swallowing.
PATIENT CONCERNS
We report a unique case involving a 52-year-old patient with dysphagia due to LMS. His dysphagia was severe but improved gradually with swallowing rehabilitation. The patient involuntarily acquired a swallowing method with prolonged and increased pharyngeal contraction and vacuum swallowing.
DIAGNOSIS
The patient presented with dysphagia due to left LMS. A videofluoroscopic examination of swallowing revealed pharyngeal residue.
INTERVENTIONS
Forty-five days after the onset of the dysphagia, the swallowing pressure along the pharynx and esophagus was measured using high-resolution manometry.
OUTCOMES
Vacuum swallowing was observed in six out of 19 swallows (32.5%). The velopharyngeal contractile integral (CI) and mesohypopharyngeal CI values increased during swallowing, reflecting prolonged and increased pharyngeal contraction. We named this swallowing method "prolonged swallowing."
CONCLUSION
The findings in this case indicate that vacuum and prolonged swallowing may be compensatory swallowing methods observed in individuals recovering from dysphagia due to LMS. Further research is needed to clarify the relationship between these swallowing methods and the pathophysiology, prognosis, and treatment of dysphagia in patients with LMS.
Topics: Deglutition Disorders; Humans; Lateral Medullary Syndrome; Manometry; Middle Aged; Pharynx; Pressure; Vacuum
PubMed: 35029918
DOI: 10.1097/MD.0000000000028524 -
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 -
Immunobiology Jan 2022Head and neck squamous cell carcinoma (HNSCC) arises from the malignant mucosal epithelium of the oral cavity, pharynx, and larynx. Natural killer (NK) cells are...
Down-regulation of HLA-B-associated transcript 3 impairs the tumoricidal effect of natural killer cells through promoting the T cell immunoglobulin and mucin domain-containing-3 signaling in a mouse head and neck squamous cell carcinoma model.
Head and neck squamous cell carcinoma (HNSCC) arises from the malignant mucosal epithelium of the oral cavity, pharynx, and larynx. Natural killer (NK) cells are fundamental immune cells shaping the anti-HNSCC response. Elucidation of the regulatory mechanisms of NK cell activity is crucial for understanding anti-HNSCC immunity. In this study, we characterized the expression and function of HLA-B-associated transcript 3 (Bat3) in NK cells in a mouse HNSCC model. We found that Bat3 expression was down-regulated in HNSCC-infiltrating NK cells. SCC VII, the mouse HNSCC cell line used in this model, induced Bat3 downregulation through direct cell-to-cell contact. By applying lentivirus-mediated silencing of Bat3, we discovered that Bat3 knockdown impaired the tumoricidal effect of NK cells on SCC VII cells and Hepa1-6, a genetically modified liver cancer cell line. Furthermore, Bat3 knockdown resulted in a significant decrease in perforin, granzyme B, interferon-γ, and tumor necrosis factor-α in NK cells upon co-culture with SCC VII cells. Further investigations revealed that Bat3 knockdown promoted the binding of T cell immunoglobulin and mucin domain-containing-3 (Tim-3) to Fyn and thus activated the Tim-3 signaling. Blockade of Tim-3 with a neutralizing Tim-3 antibody counteracted the effect of Bat3 knockdown on NK cell cytotoxicity. Taken together, our data suggest that HNSCC might down-regulate Bat3 expression to augment Tim-3 signaling and ultimately suppress the tumoricidal activity of NK cells. This study unveils a novel mechanism by which HNSCC evades NK cell killing, and sheds light on designing novel anti-HNSCC immunotherapy targeting Bat3 and Tim-3 signaling.
Topics: Animals; Disease Models, Animal; Down-Regulation; HLA-B Antigens; Head and Neck Neoplasms; Hepatitis A Virus Cellular Receptor 2; Immunoglobulins; Killer Cells, Natural; Mice; Molecular Chaperones; Mucins; Nuclear Proteins; Squamous Cell Carcinoma of Head and Neck; T-Lymphocytes
PubMed: 34968777
DOI: 10.1016/j.imbio.2021.152127 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Dec 2021In recent years, with the increase of magnetic toys, the intake of magnetic foreign bodies is an increasing problem in pediatric emergency.The strong suction of the...
In recent years, with the increase of magnetic toys, the intake of magnetic foreign bodies is an increasing problem in pediatric emergency.The strong suction of the magnetic foreign body can lead to necrosis, perforation, and infection of surrounding tissues.The site of magnetic foreign body injury is mainly the esophagus, intestines, stomach, a few in the pharynx, etc.This requires early assessment and appropriate intervention to avoid further harm.Because of its unique physical properties, magnetic foreign bodies in bilateral nasal cavity are rarely reported. Now we have a case of a bilateral magnetic foreign body in the nasal cavity.
Topics: Child; Esophagus; Foreign Bodies; Humans; Magnetic Phenomena; Nasal Cavity; Pharynx
PubMed: 34886632
DOI: 10.13201/j.issn.2096-7993.2021.12.017 -
NeuroRehabilitation 2022Swallowing disorders represent one of the most common complications after cerebral infarction. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Swallowing disorders represent one of the most common complications after cerebral infarction.
OBJECTIVE
To study the effects of different frequencies of repetitive transcranial magnetic stimulation (rTMS) on swallowing disorders after cerebral infarction.
METHODS
Ninety patients with swallowing disorder after cerebral infarction were enrolled and randomly assigned to three groups: the 10 Hz frequency rTMS group (30 patients), the 5 Hz frequency rTMS group (30 patients), and the 1 Hz frequency rTMS group (30 patients); another 90 healthy persons without swallowing disorders were included as the control group. The Kubota's water-swallow test, the video fluoroscopic swallow study (VFSS), and the Electroencephalograph (EEG) were analyzed before and after treatment; the EEG of the control group was detected as the baseline.
RESULTS
The Kubota's water-swallow test scores were significantly decreased while the scores of pharynx period and the aspiration degree of VFSS significantly increased in 10 Hz frequency rTMS group than before treatment (P≤0.05); the amplitudes of C3 of the EEG significantly increased in three frequency groups than before treatment (P≤0.05).
CONCLUSIONS
10 Hz frequency of rTMS is effective for the treatment of swallowing disorder after cerebral infarction, the excitement of C3 area maybe the therapeutic target of rTMS on swallowing disorder after cerebral infarction.
Topics: Cerebral Infarction; Deglutition Disorders; Humans; Pharynx; Transcranial Magnetic Stimulation
PubMed: 34776422
DOI: 10.3233/NRE-210176