ABSTRACT
This study investigated the role of the axis involving chemokine receptor 6 (CCR6) and its ligand chemokine (C-C motif) ligand 20 (CCL20) in acute kidney disease (AKD) using an ischemia-reperfusion injury (IRI) model. The model was established by clamping the unilateral renal artery pedicle of C57BL/6 mice for 30 min, followed by evaluation of CCL20/CCR6 expression at 4 weeks post-IRI. In vitro studies were conducted to examine the effects of hypoxia and H2 O2 -induced oxidative stress on CCL20/CCR6 expression in kidney tissues of patients with AKD and chronic kidney disease (CKD). Tubular epithelial cell apoptosis was more severe in C57BL/6 mice than in CCL20 antibody-treated mice, and CCR6, NGAL mRNA, and IL-8 levels were higher under hypoxic conditions. CCL20 blockade ameliorated apoptotic damage in a dose-dependent manner under hypoxia and reactive oxygen species injury. CCR6 expression in IRI mice indicated that the disease severity was similar to that in patients with the AKD phenotype. Morphometry of CCL20/CCR6 expression revealed a higher likelihood of CCR6+ cell presence in CKD stage 3 patients than in stage 1-2 patients. Kidney tissues of patients with CKD frequently contained CCL20+ cells, which were positively correlated with interstitial inflammation. CCL20/CCR6 levels were increased in fibrotic kidneys at 4 and 8 weeks after 5/6 nephrectomy. These findings suggest that modulating the CCL20/CCR6 pathway is a potential therapeutic strategy for managing the progression of AKD to CKD.
Subject(s)
Acute Kidney Injury , Renal Insufficiency, Chronic , Humans , Animals , Mice , Mice, Inbred C57BL , Ligands , Kidney , Epithelial Cells , Renal Artery , Hypoxia , Receptors, CCR6/genetics , Chemokine CCL20/geneticsABSTRACT
Ag nanoparticles have garnered significant attention for their excellent plasmonic properties and potential use as plasmonic cavities, primarily because of their intrinsically low ohmic losses and optical properties in the visible range. These are particularly crucial in systems involving quantum dots that absorb light at low wavelengths, where the need for a high threshold energy of interband transitions necessitates the incorporation of Ag nanostructures. However, the synthesis of Ag nanoparticles still encounters challenges in achieving structural uniformity and monodispersity, along with chemical stability, consequentially inducing inconsistent and poorly reliable optical responses. Here, we present a two-step approach for synthesizing highly uniform spherical Ag nanoparticles involving depletion-induced flocculation and Cu(II)-mediated oxidative etching. We found that the selective flocculation of multitwinned Ag nanocrystals significantly enhances the uniformity of the resulting Ag nanostructures, leaving behind only single-crystalline and single-twinned nanostructures. Subsequent oxidative etching, in which cupric ions are directly involved in the reaction, was designed based on Pourbaix diagrams to proceed following thermodynamically favorable states and circumvent the generation of reactive chemical species such as H2O2. This leads to perfectly spherical shapes of final Ag nanoparticles with a synthetic yield of 99.5% and additionally reduces the overall reaction time. Furthermore, we explore the potential applications of these monodisperse Ag nanospheres as uniform plasmonic cavities. The fabricated Ag nanosphere films uniformly enhanced the photoluminescence of InP/ZnSe/ZnS quantum dots, showcasing their capabilities in exhibiting consistent plasmonic responses across a large area.
ABSTRACT
Peritoneal fibrosis (PF) is an irreversible complication of peritoneal dialysis (PD) that leads to loss of peritoneal membrane function. We investigated PD effluent and serum levels and the tissue expression of chemokine (C-C motif) ligand 8 (CCL8) in patients with PD. Additionally, we investigated their association with PF in a mouse model. Eighty-two end-stage renal disease (ESRD) patients with PD were examined. CCL8 levels were measured via enzyme-linked immunosorbent assays in PD effluents and serum and analyzed with peritoneal transport parameters. Human peritoneal mesothelial cells (hPMCs) were obtained from the PD effluents of 20 patients. Primary cultured hPMCs were treated with recombinant (r) transforming growth factor (TGF)-ß, and CCL8 expression was assessed via western blotting. As the duration of PD increased, the concentration of CCL8 in PD effluents significantly increased. Correlations between peritoneal transport parameters and dialysate CCL8 levels were observed. Western blotting analysis showed that CCL8 was upregulated via rTGF-ß treatment, accompanied by increases in markers of inflammation, fibrosis, senescence, and apoptosis in hPMCs after induction of fibrosis with rTGF-ß. Anti-CCL8 monoclonal antibody (mAb) treatment suppressed the rTGF-ß-induced increase in all analyzed markers. Immunohistochemical analysis revealed that CCL8 along with fibrosis- and inflammation-related markers were significantly increased in the PF mouse model. Functional blockade of CCL8 using a CCR8 inhibitor (R243) abrogated peritoneal inflammation and fibrosis in vivo. In conclusion, high CCL8 levels in PD effluents may be associated with an increased risk of PD failure, and the CCL8 pathway is associated with PF. CCL8 blockade can ameliorate peritoneal inflammation and fibrosis.
Subject(s)
Peritoneal Fibrosis , Peritonitis , Animals , Mice , Humans , Peritoneal Fibrosis/prevention & control , Chemokine CCL8 , Peritoneum , Chemokines , Ligands , Inflammation , Disease Models, AnimalABSTRACT
A 13-year-old spayed female Persian cat presented with dyspnea and nasal discharge. Thoracic radiography revealed a dome-shaped soft-tissue opacity in the carina. Computed tomography confirmed a soft tissue-attenuating mass in the carina and the left and right proximal main bronchi that appeared to arise from the tracheal wall. Tracheoscopy revealed an intraluminal broad-based mass with multilobulated borders at the same location. Histopathological evaluation revealed a benign neoplastic process of the glandular epithelial lineage, which was considered an adenoma. Tracheal adenomas should be included in the differential diagnosis of tracheal masses.
Subject(s)
Adenoma , Cat Diseases , Tomography, X-Ray Computed , Tracheal Neoplasms , Animals , Cats , Female , Cat Diseases/diagnostic imaging , Cat Diseases/pathology , Tracheal Neoplasms/veterinary , Tracheal Neoplasms/diagnostic imaging , Adenoma/veterinary , Adenoma/diagnostic imaging , Adenoma/pathology , Tomography, X-Ray Computed/veterinary , Diagnosis, Differential , Trachea/diagnostic imaging , Trachea/pathology , Radiography, Thoracic/veterinaryABSTRACT
Fascial space abscess is a condition in which infections spread into fascial spaces. It is a severe and life-threatening disease unless treated at an early stage. Due to the similarity of clinical symptoms, fascial space abscesses in the orofacial area are often disguised as other diseases, such as temporomandibular disorder (TMD). In this case series, we report three cases of fascial space abscesses disguised as TMD. In all cases, patients complained of severely limited mouth opening and pain in the temporomandibular joint (TMJ) and masseter muscles, which led clinicians to diagnose them with TMD. After two patients showed facial swelling and the third complained of dyspnea, clinicians realized the possibility of an orofacial fascial space abscess. On further evaluation, all patients showed increased C-reactive protein in blood tests, and the location of the fascial space abscess was confirmed by enhanced computed tomography images. Moreover, all patients had suspicious sources of odontogenic infections in panoramic images, periapical abscess on maxillary molars and periodontal disease on maxillary and mandibular molars, which were not appropriately evaluated at the first visit. This case series emphasizes the need for clinicians to realize the possibility of orofacial fascial space abscesses based on: clinical symptoms of severely limited mouth opening (< 15 mm) with pain in the facial area, including TMJ or masseter muscle, and possible sources of infection such as odontogenic infection, other infectious lesions, trauma, or invasive treatments. These clinical insights will enable the early detection of fascial space abscesses.
Subject(s)
Periapical Abscess , Temporomandibular Joint Disorders , Humans , Abscess/diagnostic imaging , Temporomandibular Joint Disorders/diagnostic imaging , Temporomandibular Joint , PainABSTRACT
This study analyzed survey results regarding awareness of living minors' organ donation. The questionnaires focused on changes in how respondents felt about donations by living minors after eliciting the uncertainty of long-term outcomes for living donors and recipients. The respondents were categorized as minors, adults affiliated with non-medical jobs (Non-Meds), and adults affiliated with medical jobs (Meds). The rates of awareness of living organ donation were significantly different; minors at 86.2%, non-Meds at 82.0%, and Meds at 98.7% (p < 0.001). Only 41.4% of Minors and 32.0% of Non-Meds were aware of organ donation by minors, while 70.3% of Meds were (p < 0.001). The response rate of opposition to organ donation by minors was highest for Meds and remained the same before and after (54.4%-57.7%, p = 0.311). However, the opposition rate in Non-Meds significantly increased (32.4%-46.7%) after learning about the uncertainty of long-term outcomes (p = 0.009). The study found that Non-Meds lacked adequate knowledge regarding organ donation by minors and their potential lethal outcomes. Their attitudes toward organ donation by minors could be changed by giving structured information. It is necessary to provide exact information and raise social awareness regarding organ donation by living minors.
Subject(s)
Organ Transplantation , Tissue and Organ Procurement , Adult , Humans , Living Donors , Surveys and Questionnaires , Uncertainty , Health Knowledge, Attitudes, Practice , Tissue DonorsABSTRACT
In an effort to activate silent biosynthetic gene clusters, Streptomyces samsunensis DSM42010, a producer of geldanamycin, was cultured at four different pHs (4.5, 5.4, 6.6, and 7.4). An acidic culture condition (pH 5.4) was selected for a chemical investigation since S. samsunensis showed a different metabolic profile compared to when it was cultured under other conditions. Seven new (1-7) and four known (8-11) compounds were isolated from these cultures. The structures of the isolated compounds were determined by spectroscopic techniques and chemical derivatization. Relative and absolute configurations of the new compounds (1-5) were established using JBCA, PGME method, advanced Marfey's method, modified Mosher's method, and comparison of observed and calculated ECD data. Interestingly, compounds 1-3 were truncated versions of geldanamycin, and compound 4 was also deduced to originate from geldanamycin. Compound 5 was composed of 3-methyltyrosine and 6-hydroxy-2,4-hexadienoic acid connected through an amide bond. Compounds 6 and 7 were dihydrogenated forms of geldanamycin with a hydroxy substitution. It is possible that culturing this strain under acidic conditions interfered to some degree with the geldanamycin polyketide synthase, leading to production of truncated versions as well as analogues of geldanamycin. Compounds 1, 8, and 9 showed significant antivirulence activity, inhibiting production of α-toxin by methicillin-resistant Staphylococcus aureus without growth attenuation and global regulatory inhibition; compounds 1, 8, and 9 may become promising α-toxin-specific antivirulence leads with less risk of resistance development.
Subject(s)
Methicillin-Resistant Staphylococcus aureus , Streptomyces , Benzoquinones , Streptomyces/chemistryABSTRACT
BACKGROUND: The risk of gadolinium (Gd)-based contrast agent (GBCA)-induced nephrogenic systemic fibrosis (NSF) in patients with end-stage renal disease (ESRD) and the efficacy of prophylactic hemodialysis (HD) for protection against NSF are not well understood or summarized in the literature. PURPOSE: To determine the risk for NSF related to frequency and time per dialysis session after Gd-magnetic resonance imaging (MRI) by emphasizing the safety of Gd-MRI in patients with ESRD. MATERIAL AND METHODS: This retrospective observational study identified all GBCA injections for MRI examinations performed at two tertiary referral hospitals between 2005 and 2020. All clinical data, including dialysis records and medical history, were investigated for each patient through 2021. The end of follow-up coincided with the last hospital visit. RESULTS: Overall, 1129 patients with ESRD underwent 1461 Gd-MRI scans (41.5% gadoterate, 39.4% gadobutrol, and 7.7% gadoxetate); a total of 958 patients with 1229 (84.1%) examinations underwent HD on the day of the MRI study, within 2.1 ± 2.0 h (range = 0.2-15.7 h) immediately after Gd exposure. In 53.4% of scans, frequent HD had been performed urgently and then twice more on consecutive days to prophylactically avoid NSF. No cases of NSF were identified during the follow-up period (mean = 81.7 ± 50.5 months) regardless of dose of HD. CONCLUSION: No cases of NSF were reported in 1461 Gd-MRI examinations of 1129 inpatients with ESRD on HD. Our findings support the lack of benefit of frequent prophylactic HD being performed urgently within 4 h of the receipt of GBCA.
Subject(s)
Kidney Failure, Chronic , Nephrogenic Fibrosing Dermopathy , Humans , Contrast Media/adverse effects , Nephrogenic Fibrosing Dermopathy/chemically induced , Nephrogenic Fibrosing Dermopathy/prevention & control , Gadolinium/adverse effects , Risk Factors , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/therapy , Renal Dialysis , Magnetic Resonance Imaging/methodsABSTRACT
The production of ß-lactamase by nontyphoidal Salmonella has become a public health issue throughout the world. In this study, we aimed to investigate the antimicrobial resistance profiles and molecular characteristics of ß-lactamase-producing Salmonella enterica serovar Albany isolates. A total of 434 Salmonella Albany were obtained from feces and carcasses of healthy and diseased food-producing animals [cattle (n = 2), pigs (n = 3), chickens (n = 391), and ducks (n = 38)] during 2013-2020. Among the 434 Salmonella Albany isolates, 3.7% showed resistance to cefoxitin, and all the cefoxitin-resistant isolates were obtained from chickens. Moreover, Salmonella Albany isolates demonstrated high resistance to nalidixic acid (99.3%), trimethoprim/sulfamethoxazole (97.9%), ampicillin (86.6%), chloramphenicol (86.6%), and tetracycline (85.7%), as well as higher rates of multidrug resistance were detected in cefoxitin-resistant isolates compared to cefoxitin-susceptible isolates. All cefoxitin-resistant isolates harbored CMY-2-type ß-lactamase and belonged to seven different pulsotypes, with type IV-b (43.75%) and IV-a (25%) making up the majority. In addition, genes encoding cefoxitin resistant of all blaCMY-2-harboring Salmonella Albany isolates were horizontally transmitted to a recipient Escherichia coli J53 by conjugation. Furthermore, 93.75% (15/16) of conjugative plasmids harboring blaCMY-2 genes belong to ST12/CC12-IncI1. Genetic characteristics of transmitted blaCMY-2 genes were associated with ISEcp1, which can play an essential role in the effective mobilization and expression of these genes. Salmonella Albany containing blaCMY-2 in chickens can potentially be transferred to humans. Therefore, it is necessary to restrict antibiotic use and conduct continuous monitoring and analysis of resistant bacteria in the poultry industry.
Subject(s)
Chickens , Salmonella enterica , Humans , Animals , Swine , Cattle , Chickens/microbiology , Cefoxitin/pharmacology , Serogroup , beta-Lactamases/genetics , beta-Lactamases/metabolism , Anti-Bacterial Agents/pharmacology , Salmonella/genetics , Republic of Korea , Escherichia coli , Drug Resistance, Microbial , Drug Resistance, Multiple, Bacterial , PlasmidsABSTRACT
Lacquer sap has been traditionally used in coatings and artwork. Suitable types of lacquer are required to preserve and restore artifacts. Recently, unsuitable cashew nut shell liquid (CNSL) has often been mixed with lacquer sap, so it is necessary to identify the characteristics of lacquer sap by the production area. However, research is still focused on urushiol and laccol. In this study, Myanmarese lacquer sap collected from Gluta usitata, which contains thitsiol as the main component, was analyzed by HPLC to quantify thitsiol using the standards 3-(10-phenyldecyl) benzene-1,2-diol (thitsiol 16) and 3-(8Z,11Z-pentadecadienyl)-benzenediol (urushiol 15:2) as markers, and calibration curves were plotted. The coefficients of determination (R2) for thitsiol 16 and urushiol 15:2 were 0.9985 and 0.9983, respectively. In addition, a blind test was conducted to confirm that accurate quantitative analysis was possible even when Myanmarese lacquer was mixed with lacquer from another production area, which contained urushiol as the main component, and CNSL, which contained cardol, a completely different catechol. Quantitative analysis of thitsiol 16 and urushiol 15:2 in Myanmarese lacquer using HPLC can be used to evaluate the quality of lacquer sap and for more sophisticated activities such as restoration by classifying differences in lacquer sap by the production area.
ABSTRACT
BACKGROUND: Psychological stress is a crucial parameter in defining the symptoms of burning mouth syndrome (BMS). We hypothesized that the level of psychological stress in patients with BMS would correlate with severity of clinical symptoms, cortisol levels, and cortisol/ adrenocorticotropic hormone (ACTH) ratio. We aimed to comprehensively investigate the influence of clinical and hematologic parameters on the hypothalamic-pituitary-adrenal axis, particularly concerning the presence or absence of self-perceived psychological stress in patients with BMS. In addition, we aimed to identify parameters predicting psychological stress in these patients. METHODS: One hundred and forty-one patients with BMS (117 women, 82.98%; 56.21 ± 13.92 years) were divided into psychological stress (n = 68; 55 females, 56.39 ± 12.89 years) and non-psychological stress groups (n = 73; 62 females, 56.03 ± 14.90 years), and inter- and intra-group statistical analyses were conducted. Significant predictors of psychological stress in patients with BMS were investigated through multiple logistic regression analysis. RESULTS: The prevalence of xerostomia was significantly higher (67.6% vs. 34.2%, p < 0.001), while unstimulated salivary flow rate was lower (0.66 ± 0.59 vs. 0.91 ± 0.53 mL/min, p < 0.01) in the psychological stress group than in the non-psychological stress group. SCL-90R subscale values for somatization, hostility, anxiety, and depression, as well as cortisol and ACTH levels and the cortisol/ACTH ratio, were also higher in the psychological stress group (all p < 0.05). Above-mean values for cortisol (AUC = 0.980, 95%CI: 0.959-1.000) and cortisol/ACTH (AUC = 0.779; 95%CI, 0.701-0.856) were excellent predictors of psychological stress, with cortisol (r = 0.831, p < 0.01) and cortisol/ACTH (r = 0.482, p < 0.01) demonstrating substantial correlations. Above-average values for cortisol (OR = 446.73) and cortisol/ACTH (OR = 6.159) significantly increased incidence of psychological stress in patients with BMS (all p < 0.001). CONCLUSIONS: Among patients with BMS, xerostomia, decreased salivary flow rate, increased cortisol levels, and cortisol/ACTH ratio were associated with psychological stress, highlighting the psycho-neuro-endocrinological features of this condition. Cortisol and cortisol/ACTH ratio were strong predictors of psychological stress in patients with BMS.
Subject(s)
Burning Mouth Syndrome , Xerostomia , Humans , Female , Adrenocorticotropic Hormone , Hydrocortisone , Hypothalamo-Hypophyseal System , Pituitary-Adrenal System , Xerostomia/complicationsABSTRACT
Surface-enhanced Raman scattering (SERS) provides significantly enhanced Raman scattering signals from molecules adsorbed on plasmonic nanostructures, as well as the molecules' vibrational fingerprints. Plasmonic nanoparticle systems are particularly powerful for SERS substrates as they provide a wide range of structural features and plasmonic couplings to boost the enhancement, often up to >108-1010. Nevertheless, nanoparticle-based SERS is not widely utilized as a means for reliable quantitative measurement of molecules largely due to limited controllability, uniformity, and scalability of plasmonic nanoparticles, poor molecular modification chemistry, and a lack of widely used analytical protocols for SERS. Furthermore, multiscale issues with plasmonic nanoparticle systems that range from atomic and molecular scales to assembled nanostructure scale are difficult to simultaneously control, analyze, and address. In this perspective, we introduce and discuss the design principles and key issues in preparing SERS nanoparticle substrates and the recent studies on the uniform and controllable synthesis and newly emerging machine learning-based analysis of plasmonic nanoparticle systems for quantitative SERS. Specifically, the multiscale point of view with plasmonic nanoparticle systems toward quantitative SERS is provided throughout this perspective. Furthermore, issues with correctly estimating and comparing SERS enhancement factors are discussed, and newly emerging statistical and artificial intelligence approaches for analyzing complex SERS systems are introduced and scrutinized to address challenges that cannot be fully resolved through synthetic improvements.
Subject(s)
Metal Nanoparticles , Nanostructures , Spectrum Analysis, Raman/methods , Metal Nanoparticles/chemistry , Artificial IntelligenceABSTRACT
Alzheimer's disease (AD) is a deadly brain degenerative disorder that leads to brain shrinkage and dementia. AD is manifested with hyperphosphorylated tau protein levels and amyloid beta (Aß) peptide buildup in the hippocampus and cortex regions of the brain. The nervous tissue of AD patients also contains fungal proteins and DNA which are linked to bacterial infections, suggesting that polymicrobial infections also occur in the brains of those with AD. Both immunohistochemistry and next-generation sequencing (NGS) techniques were employed to assess fungal and bacterial infections in the brain tissue of AD patients and non-AD controls, with the most prevalent fungus genera detected in AD patients being Alternaria, Botrytis, Candida, and Malassezia. Interestingly, Fusarium was the most common genus detected in the control group. Both AD patients and controls were also detectable for Proteobacteria, followed by Firmicutes, Actinobacteria, and Bacteroides for bacterial infection. At the family level, Burkholderiaceae and Staphylococcaceae exhibited higher levels in the brains of those with AD than the brains of the control group. Accordingly, there is thought to be a viscous cycle of uncontrolled neuroinflammation and neurodegeneration in the brain, caused by agents such as the herpes simplex virus type 1 (HSV1), Chlamydophilapneumonia, and Spirochetes, and the presence of apolipoprotein E4 (APOE4), which is associated with an increased proinflammatory response in the immune system. Systemic proinflammatory cytokines are produced by microorganisms such as Cytomegalovirus, Helicobacter pylori, and those related to periodontal infections. These can then cross the blood-brain barrier (BBB) and lead to the onset of dementia. Here, we reviewed the relationship between the etiology of AD and microorganisms (such as bacterial pathogens, Herpesviridae viruses, and periodontal pathogens) according to the evidence available to understand the pathogenesis of AD. These findings might guide a targeted anti-inflammatory therapeutic approach to AD.
ABSTRACT
BACKGROUND: An investigation into the causality of the effects of physical activity and specific sedentary activities on kidney function in the general population is warranted. METHODS: In this observational cohort study, first, the clinical associations of the prevalence of stages 3-5 chronic kidney disease (CKD) and the estimated glomerular filtration rate (eGFR) with physical activity, determined by self-report or objective wrist-band accelerometer results, and sedentary activities (watching television, using a computer and driving) were investigated in 329 758 UK Biobank participants. To assess causality, a two-sample Mendelian randomization (MR) analysis was performed to investigate the associations of a genetic predisposition to physical activity and a sedentary lifestyle with the risk of kidney function impairment in an independent CKDGen genome-wide association study (N = 567 460). The findings were replicated with the 321 024 UK White British Biobank participants in the allele-score-based one-sample MR. RESULTS: A higher degree of self-reported or accelerometer-determined moderate-to-vigorous physical activity was associated with a higher eGFR, while a longer time spent watching television was significantly associated with a lower eGFR and a higher prevalence of CKD. The two-sample MR demonstrated that the genetic predisposition to a higher degree of physical activity was associated with a lower risk of CKD and a higher eGFR, while the genetically predicted television watching duration was associated with a higher risk of CKD and a lower eGFR. The other sedentary behaviors yielded inconsistent results. The findings were similarly replicated in the one-sample MR. CONCLUSION: Physical activity and television watching causally affect kidney function in the general population.
Subject(s)
Mendelian Randomization Analysis , Renal Insufficiency, Chronic , Exercise , Genetic Predisposition to Disease , Genome-Wide Association Study , Humans , Kidney , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/genetics , Sedentary BehaviorABSTRACT
Recent efforts in designing nanomaterials to deliver potential therapeutics to the targeted site are overwhelming and palpable. Engineering nanomaterials to deliver biological molecules to exert desirable physiological changes, with minimized side effects and optimal dose, has revolutionized the next-generation therapy for several diseases. The rapid progress of nucleic acids as biopharmaceutics is going to alter the traditional pharmaceutics practices in modern medicine. However, enzymatic instability, large size, dense negative charge (hydrophilic for cell uptake), and unintentional adverse biological responses-such as prolongation of the blood coagulation and immune system activation-hamper the potential use of nucleic acids for therapeutic purposes. Moreover, the safe delivery of nucleic acids into the clinical setting is an uphill task, and several efforts are being put forward to deliver them to targeted cells. Advances in Metal-based NanoParticles (MNPs) are drawing attention due to the unique properties offered by them for drug delivery, such as large surface-area-to-volume ratio for surface modification, increased therapeutic index of drugs through site-specific delivery, increased stability, enhanced half-life of the drug in circulation, and efficient biodistribution to the desired targeted site. Here, the potential of nanoparticles delivery systems for the delivery of nucleic acids, specially MNPs, and their ability and advantages over other nano delivery systems are reviewed.
Subject(s)
Metal Nanoparticles , Nucleic Acids , Tissue Distribution , Drug Delivery Systems , Pharmaceutical PreparationsABSTRACT
OBJECTIVE: We used optical coherence tomography (OCT) to document the time course of retrograde neuronal degeneration following indirect optic nerve injury. METHODS: We retrospectively studied patients diagnosed with unilateral indirect traumatic optic neuropathy (TON). Patients with total or near-total optic atrophy were included. All patients underwent complete ophthalmological examinations, including OCT imaging, within 1 day and at 1, 2, 3, 4, 6, 8, 12, 24, and 48 weeks after trauma. RESULTS: The mean thicknesses of the circumpapillary retinal nerve fiber layer (cpRNFL) and macular retinal ganglion cell-inner plexiform layer (mGCIPL) decreased significantly at 2 weeks after trauma (p = 0.027 and p = 0.043). Changes in mGCIPL thickness preceded changes in cpRNFL thickness. The rates of reduction in mGCIPL and cpRNFL thicknesses were greatest between 2 to 4 weeks and 4 to 6 weeks after trauma. The reduction in mGCIPL thickness then slowed, and stabilized at 12 weeks after trauma. The proportions of cpRNFL and mGCIPL losses at 2, 4, 6, 8, and 12 weeks compared to 24 weeks were 17.1, 33.7, 59.8, 77.9, and 87.9% and 30.0, 73.3, 76.1, 88.3, and 97.9%, respectively. CONCLUSIONS: OCT revealed optic atrophy progression 2 weeks after trauma, which was most rapid from 2 to 6 weeks, and then gradually stabilized. Loss of retinal ganglion cell bodies and dendrites seemed to precede the axonal degeneration. Observations of morphological changes in retinal layers using OCT in TON patients improve our understanding of retrograde neuronal degeneration of the central nervous system.
Subject(s)
Optic Atrophy , Optic Nerve Injuries , Humans , Nerve Fibers , Optic Atrophy/diagnostic imaging , Optic Nerve Injuries/complications , Optic Nerve Injuries/diagnostic imaging , Retinal Ganglion Cells , Retrospective Studies , Tomography, Optical CoherenceABSTRACT
OBJECTIVES: This study aimed to investigate and compare sleep quality between patients with chronic temporomandibular disorder and healthy controls, and to analyze the association of sleep quality with disease characteristics, obstructive sleep apnea risk factors, and excessive daytime sleepiness. METHODS: Chronic temporomandibular disorder patients (n = 503, mean age: 33.10 ± 13.26 years, 333 females) and 180 age- and sex-matched healthy controls (mean age: 32.77 ± 12.95 years, 116 females) were included, who completed well-organized clinical report and answered questions on sleep quality (Pittsburgh Sleep Quality Index), sleep apnea risk factors (STOP-Bang questionnaire), and excessive daytime sleepiness (Epworth sleepiness scale). RESULTS: Mean global Pittsburgh Sleep Quality Index scores were significantly higher in the patients (6.25 ± 2.77) than in healthy controls (3.84 ± 2.29) (p < 0.001). Poor sleep was significantly more prevalent in the patient group (56.9%) than in healthy controls (22.2%) (p < 0.001). Compared with healthy controls, chronic temporomandibular disorder patients had a higher likelihood of obstructive sleep apnea (STOP-Bang total score ≥ 3; 7.2% vs. 16.1%; p < 0.01) and higher excessive daytime sleepiness (Epworth sleepiness scale score ≥ 10; 12.8% vs. 19.7%; p < 0.05). Age (odds ratio = 2.551; p < 0.001), female sex (odds ratio = 1.885; p = 0.007), total Epworth sleepiness scale score (odds ratio = 1.839; p = 0.014), and headache attributed to temporomandibular disorder (odds ratio = 1.519; p = 0.049) were the most powerful predictors of poor sleep (global Pittsburgh Sleep Quality Index score ≥ 5) in chronic temporomandibular disorder patients. CONCLUSION: Chronic temporomandibular disorder patients had markedly impaired sleep quality than healthy controls. Poorer sleep in patients with chronic temporomandibular disorder was associated with a variety of clinical factors, including a higher likelihood of excessive daytime sleepiness, older age, female gender, higher Epworth sleepiness scale scores, and the presence of headache attributed to temporomandibular disorder.
Subject(s)
Disorders of Excessive Somnolence , Temporomandibular Joint Disorders , Adult , Disorders of Excessive Somnolence/etiology , Female , Humans , Middle Aged , Sleep , Sleep Quality , Surveys and Questionnaires , Temporomandibular Joint Disorders/complications , Temporomandibular Joint Disorders/diagnosis , Temporomandibular Joint Disorders/epidemiology , Young AdultABSTRACT
BACKGROUND: Further investigation of the causal effects of psychologic wellbeing on kidney function is warranted. METHODS: In this Mendelian randomization (MR) study, genetic instruments for positive affect, life satisfaction, depressive symptoms, and neuroticism were introduced from a previous genome-wide association study meta-analysis of European individuals. Summary-level MR was performed using the CKDGen data of European ancestry (n=567,460), and additional allele score-based MR was performed in the individual-level data of White British UK Biobank participants (n=321,024). RESULTS: In summary-level MR with the CKDGen data, depressive symptoms were a significant causative factor for kidney function impairment (CKD OR, 1.45; 95% confidence interval, 1.07 to 1.96; eGFR change [%] beta -2.18; 95% confidence interval, -3.61 to -0.72) and pleiotropy-robust sensitivity analysis results supported the causal estimates. A genetic predisposition for positive affect was significantly associated with better kidney function (CKD OR, 0.69; 95% confidence interval, 0.52 to 0.91), eGFR change [%] beta 1.50; 95% confidence interval, 0.09 to 2.93) and sensitivity MR analysis results supported the finding for CKD outcome, but was nonsignificant for eGFR. Life satisfaction and neuroticism exposures showed nonsignificant causal estimates. In the UK Biobank with covariate-adjusted allele score MR analysis, allele scores for positive affect and life satisfaction were causally associated with reduced risk of CKD and higher eGFR. In contrast, neuroticism allele score was associated with increased risk of CKD and lower eGFR, and depressive symptoms allele score was associated with lower eGFR, but showed nonsignificant association with CKD. CONCLUSIONS: Health care providers in the nephrology field should be aware of the causal linkage between psychologic wellbeing and kidney function.
Subject(s)
Affect/physiology , Depression/physiopathology , Neuroticism/physiology , Personal Satisfaction , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/physiopathology , Alleles , Databases, Genetic , Depression/genetics , Depression/psychology , Female , Genome-Wide Association Study , Glomerular Filtration Rate , Humans , Male , Mendelian Randomization Analysis , Mental Health , Middle Aged , Polymorphism, Single Nucleotide , Renal Insufficiency, Chronic/genetics , United Kingdom , White PeopleABSTRACT
AIMS: The aim of this study was to investigate the causal effects between atrial fibrillation (AF) and kidney function. METHODS AND RESULTS: We performed a bidirectional summary-level Mendelian randomization (MR) analysis implementing the results from a large-scale genome-wide association study for estimated glomerular filtration rate (eGFR) by the CKDGen (N = 765 348) and AF (N = 588 190) to identify genetic instruments. The inverse variance weighted method was the main MR method used. For replication, an allele score-based MR was performed by individual-level data within a UK Biobank cohort of white British ancestry individuals (N = 337 138). A genetic predisposition to AF was significantly associated with decreased eGFR [for log-eGFR, beta -0.003 (standard error, 0.0005), P < 0.001] and increased risk of chronic kidney disease [beta 0.059 (0.0126), P < 0.001]. The significance remained in MR sensitivity analyses and the causal estimates were consistent when we limited the analysis to individuals of European ancestry. Genetically predicted eGFR did not show a significant association with the risk of AF [beta -0.366 (0.275), P = 0.183]. The results were similar in allele score-based MR, as allele score for AF was significantly associated with reduced eGFR [for continuous eGFR, beta -0.079 (0.021), P < 0.001], but allele score for eGFR did not show a significant association with risk of AF [beta -0.005 (0.008), P = 0.530]. CONCLUSIONS: Our study supports that AF is a causal risk factor for kidney function impairment. However, an effect of kidney function on AF was not identified in this study.
Subject(s)
Atrial Fibrillation , Mendelian Randomization Analysis , Atrial Fibrillation/genetics , Genome-Wide Association Study , Humans , Kidney , Polymorphism, Single Nucleotide/geneticsABSTRACT
Hydrogen sulfide (H2S) is known to participate in bacteria-induced inflammatory response in periodontal diseases. Therefore, it is necessary to quantify H2S produced by oral bacteria for diagnosis and treatment of oral diseases including halitosis and periodontal disease. In this study, we introduce a paper-based colorimetric assay for detecting bacterial H2S utilizing silver/Nafion/polyvinylpyrrolidone membrane and a 96-well microplate. This H2S-sensing paper showed a good sensitivity (8.27 blue channel intensity/µM H2S, R2 = 0.9996), which was higher than that of lead acetate paper (6.05 blue channel intensity/µM H2S, R2 = 0.9959). We analyzed the difference in H2S concentration released from four kinds of oral bacteria (Eikenella corrodens, Streptococcus sobrinus, Streptococcus mutans, and Lactobacillus casei). Finally, the H2S level in Eikenella corrodens while varying the concentration of cysteine and treatment time was quantified. This paper-based colorimetric assay can be utilized as a simple and effective tool for in vitro screening of H2S-producing ability of many bacteria as well as salivary H2S analysis.