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Biomedicine & Pharmacotherapy =... Jan 2023Iron homeostasis plays a positive role in articular cartilage health. Excessive iron or iron overload can induce oxidative stress damage in chondrocytes and ferroptosis...
BACKGROUND
Iron homeostasis plays a positive role in articular cartilage health. Excessive iron or iron overload can induce oxidative stress damage in chondrocytes and ferroptosis cell death, advancing knee osteoarthritis (KOA). However, up to date, few effective agents treat iron overload-induced KOA (IOKOA). Chinese herbal medicine (CHM) provides abundant resources for drug selection to manage bone metabolic conditions, including osteoporosis. Biochanin A (BCA) is a novel bioactive multifunctional natural compound isolated from Huangqi, which has protective effects on bone loss. Nevertheless, the function and mechanism of BCA in treating IOKOA are still elusive.
PURPOSE
This study seeks to uncover the potential therapeutic targets and mechanisms of BCA in the management of KOA with iron accumulation.
METHODS
Iron dextrin (500 mg/kg) was intraperitoneally injected into mice to establish the iron overloaded mice model. OA was induced through surgery, and the progression was evaluated eight weeks following surgery. OA severity was evaluated with micro-CT and Safranin-O/Fast green staining in vivo. Iron deposition in the knee joint and synovium was assessed using Perl's Prussian blue staining. Ferric ammonium citrate (FAC) was then administered to primary chondrocytes to evaluate iron regulators mediated iron homeostasis. Toluidine blue staining was utilized to identify chondrocytes in vitro. The vitality of the cells was assessed using the CCK-8 test. The apoptosis rate of cells was measured using Annexin V-FITC/PI assay. The intracellular iron level was detected utilizing the calcein-AM test. Reactive oxygen species (ROS), lipid-ROS, and mitochondrial membrane potentiality were reflected via fluorescence density. Utilizing RT-qPCR and western blotting, the expression level was determined.
RESULTS
Micro-CT and histological staining of knee joints showed greater cartilage degradation and higher iron buildup detected in iron-overloaded mice. BCA can reduce iron deposition and the severity of KOA. Toluidine blue staining and the CCK-8 assay indicated that BCA could rescue chondrocytes killed by iron. Cell apoptosis rates were increased due to iron overload but improved by BCA. Further, the intracellular content of iron, ROS, and lipid-ROS was increased with ferric ammonium citrate (FAC) treatment but restored after treatment with different concentrations of BCA. JC-1 staining revealed that BCA could reduce mitochondrial damage induced by iron overload.
CONCLUSION
Iron overload was shown to promote chondrocyte ferroptosis in vivo and in vitro. Moreover, iron overload suppressed the expression of collagen II and induced MMP expression by catalyzing ROS generation with mitochondrial dysfunction. Our results showed that BCA could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for KOA.
Topics: Animals; Mice; Chondrocytes; Iron; Iron Overload; Lipids; Osteoarthritis, Knee; Reactive Oxygen Species; Tolonium Chloride
PubMed: 36379122
DOI: 10.1016/j.biopha.2022.113915 -
Journal of Clinical Medicine Aug 2023This study aimed to evaluate the efficacy of photodynamic therapy (PDT) using tolonium chloride and a 635 nm diode laser as an adjunct to non-surgical periodontitis...
This study aimed to evaluate the efficacy of photodynamic therapy (PDT) using tolonium chloride and a 635 nm diode laser as an adjunct to non-surgical periodontitis treatment, specifically scaling and root planing (SRP) alone. A total of 32 patients with a pocket probing depth > 5 mm were included in the study. Among them, 16 patients underwent SRP alone (control group), and the remaining 16 patients received SRP along with PDT (study group). The PDT procedure utilized a 635 nm diode laser (Smart M, Lasotronix, Poland) and tolonium chloride. Clinical periodontal parameters, such as the plaque index (PI), bleeding on probing (BOP), gingival recession (GR), probing pocket depth (PPD), and clinical attachment loss (CAL), were assessed before treatment (T0) and at 3 months after treatment (T3). At T3, both groups demonstrated a significant reduction in the PI, BOP, PD, and CAL compared to T0. The SRP + PDT group displayed a significant reduction in PPD (3.79 mm ± 0.35) compared to the SRP alone group (4.85 mm ± 0.42) at T3. Furthermore, the SRP + PDT group exhibited a significant reduction in CAL (5.01 ± 0.81) compared to the SRP group (5.99 ± 1.08) at T3. Within the study's limitations, it was concluded that PDT, with tolonium chloride and a 635 nm diode laser, significantly contributed to the non-surgical treatment of periodontitis.
PubMed: 37629310
DOI: 10.3390/jcm12165270 -
Medicina Oral, Patologia Oral Y Cirugia... May 2016Gold standard for the diagnosis of oral dysplasia (OD) and oral squamous cell carcinoma (OSCC) and malignant lesions is the histological examination. Several adjunctive... (Review)
Review
BACKGROUND
Gold standard for the diagnosis of oral dysplasia (OD) and oral squamous cell carcinoma (OSCC) and malignant lesions is the histological examination. Several adjunctive diagnostic techniques have been proposed in order to increase the sensitivity (SE) and specificity (SP) of conventional oral examination and to improve the diagnostic first level accuracy. The aim of this study is to perform a systematic review on non-invasive tools for diagnosis of OD and early OSCC.
MATERIAL AND METHODS
Medline, Scopus, Web of Knowledge databases were searched, using as entry terms "oral dysplasia AND diagnosis" / "oral cancer AND diagnosis". Data extracted from each study included number of lesions evaluated, histopathological diagnosis, SE, SP, positive and negative predictive values (PPV and NPV), diagnostic accuracy (DA) and the main conclusions.
RESULTS
After title and abstract scanning of 11.080 records, we selected 35 articles for full text evaluation. Most evaluated tools were autofluorescence (AF), chemiluminescence (CL), toluidine blu (TL) and chemiluminescence associated with toluidine blue (CLTB).
CONCLUSIONS
There is a great inhomogeneity of the reported values and there is no significant evidence of superiority of one tool over the other. Further clinical trials with a higher level of evidence are necessary in order to assess the real usefulness visual diagnostic tools.
Topics: Carcinoma, Squamous Cell; Humans; Hyperplasia; Mouth Neoplasms; Sensitivity and Specificity; Tolonium Chloride
PubMed: 26946204
DOI: 10.4317/medoral.20996 -
Brazilian Journal of Otorhinolaryngology 2022Early detection of potentially malignant oral cavity disorders is critical for a good prognosis, and it is unclear whether the use of chemiluminescence as an adjunctive... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Early detection of potentially malignant oral cavity disorders is critical for a good prognosis, and it is unclear whether the use of chemiluminescence as an adjunctive diagnostic screening method improves diagnostic accuracy.
OBJECTIVE
This systematic review and meta-analysis was performed to assess the accuracy of chemiluminescence for diagnosis of oral cancer and precancerous lesions.
METHODS
Sixteen prospective and retrospective studies from PubMed, Cochrane database, SCOPUS, Web of Science, Embase, and Google Scholar were reviewed. Oral mucosal disorder, as detected by chemiluminescence, was compared with oral mucosal disorder detected by toluidine blue or visual examination. True-positive, true-negative, false-positive, and false-negative rates were extracted for each study. Methodological quality was evaluated using the Quality Assessment of Diagnostic Accuracy Studies tool (ver. 2).
RESULTS
Sensitivity, specificity, negative predictive value, and diagnostic odds ratio (DOR) of the use of toluidine blue were 0.832 (95% confidence interval [CI] 0.692-0.917), 0.429 (95% CI 0.217-0.672), 0.747 (95% CI 0.607-0.849), and 4.061 (95% CI 1.528-10.796; I=9.128%), respectively. The area under the summary receiver operating characteristic (SROC) curve was 0.743. Compared with toluidine blue, as used in 12 studies, chemiluminescence had a higher sensitivity (0.831 vs. 0.694); it had a lower specificity (0.415 vs. 0.734), negative predictive value (0.674 vs. 0.729), and DOR (3.891 vs. 7.705). Compared with clinical examination, as used in three studies, chemiluminescence had lower DOR (4.576 vs. 5.499) and area under the curve (0.818 vs. 0.91).
CONCLUSION
Although chemiluminescence itself has good sensitivity for diagnostic work-up of oral cancer and precancer, the diagnostic accuracy of chemiluminescence is comparable to or worse than toluidine blue and clinical examination. Diagnostic accuracy was therefore insufficient for reliable use of chemiluminescence alone.
Topics: Early Detection of Cancer; Humans; Luminescence; Mouth Diseases; Mouth Neoplasms; Prospective Studies; Retrospective Studies; Sensitivity and Specificity; Tolonium Chloride
PubMed: 32847738
DOI: 10.1016/j.bjorl.2020.06.011 -
Journal of Periodontal Research Aug 2015Peri-implantitis has a prevalence of 11-47%, involves destruction of peri-implant bone and may lead to implant loss. A detailed understanding of the pathogenesis of... (Comparative Study)
Comparative Study
BACKGROUND AND OBJECTIVE
Peri-implantitis has a prevalence of 11-47%, involves destruction of peri-implant bone and may lead to implant loss. A detailed understanding of the pathogenesis of peri-implantitis is lacking. The objective of this study was to develop a murine model of experimental peri-implantitis.
MATERIAL AND METHODS
Machined, smooth-surface, screw-shaped titanium implants were placed in the healed alveolar bone of the left maxillary molars of C57BL/6J male mice, 8 wk after tooth extraction. Peri-implantitis was induced by securing silk ligatures around the head of the implant fixtures. Implant survival and peri-implant bone levels were analyzed by micro-computed tomography (micro-CT) scans and histology, 12 wk after ligature placement.
RESULTS
Implant survival was 60% (six of 10) for implants with ligatures and 100% (eight of eight) for controls. Micro-CT revealed significantly greater bone loss around the implants that received ligatures and that survived, compared with controls. The radiographic findings were confirmed via histology and toluidine blue staining.
CONCLUSION
This study describes a murine model of experimental peri-implantitis around screw-shaped titanium implants placed in the edentulous alveolar bone. This model should be a useful tool to dissect pathogenic mechanisms of peri-implantitis and evaluate potential treatment interventions.
Topics: Alloys; Alveolar Process; Animals; Coloring Agents; Dental Alloys; Dental Implants; Dental Prosthesis Design; Disease Models, Animal; Male; Maxilla; Mice; Mice, Inbred C57BL; Mice, Inbred Strains; Peri-Implantitis; Survival Analysis; Time Factors; Titanium; Tolonium Chloride; Tooth Socket; X-Ray Microtomography
PubMed: 25244403
DOI: 10.1111/jre.12234 -
Scientific Reports Jun 2019Periodontitis is initiated by causative bacteria in the gingival sulcus. However, as the lesion is often deep and out of circulation system and biofilm is frequently...
Periodontitis is initiated by causative bacteria in the gingival sulcus. However, as the lesion is often deep and out of circulation system and biofilm is frequently formed on the bacteria cluster, use of antibacterial agents has been limited and the invasive method such as curettage is thought as an only treatment. Here we designed non-invasive photodynamic therapy (PDT), with the ointment which leads a photosensitizer deliverable into gingival sulcus. We assessed whether 650 nm light-emitting-diode (LED) penetrates the 3-mm soft tissue and effectively activates a photosensitizer toluidine-blue-O (TBO) through the thickness to remove Porphyromonas gingivalis and Fusobacterium nucleatum species. The oral ointment formulation was optimized to efficiently deliver the photosensitizer into gingival sulcus and its efficacy of PDT was evaluated in in vitro and in vivo models. Four weeks of TBO-formulation mediated-PDT treatment significantly attenuated periodontitis-induced alveolar bone loss and inflammatory cytokines production in rats. These results confirm that a 650 nm LED indeed penetrates the gingiva and activates our TBO formulation which is sufficiently delivered to, and retained within, the gingival sulcus; thus, it effectively kills the bacteria that reside around the gingival sulcus. Collectively, TBO-mediated PDT using LED irradiation has potential as a safe adjunctive procedure for periodontitis treatment.
Topics: Animals; Anti-Bacterial Agents; Biofilms; Bone Resorption; Drug Liberation; Fusobacterium nucleatum; Inflammation; Male; Microbial Sensitivity Tests; Periodontitis; Photochemotherapy; Photosensitizing Agents; Porphyromonas gingivalis; Rats, Wistar; Tolonium Chloride; Viscosity
PubMed: 31160615
DOI: 10.1038/s41598-019-44498-4 -
Oral Oncology Jan 2008Historically, the screening of patients for signs of oral cancer and precancerous lesions has relied upon the conventional oral examination. A variety of commercial... (Review)
Review
Historically, the screening of patients for signs of oral cancer and precancerous lesions has relied upon the conventional oral examination. A variety of commercial diagnostic aids and adjunctive techniques are available to potentially assist in the screening of healthy patients for evidence of otherwise occult cancerous change or to assess the biologic potential of clinically abnormal mucosal lesions. This manuscript systematically and critically examines the literature associated with current oral cancer screening and case-finding aids or adjuncts such as toluidine blue, brush cytology, tissue reflectance and autofluorescence. The characteristics of an ideal screening test are outlined and the authors pose several questions for clinicians and scientists to consider in the evaluation of current and future studies of oral cancer detection and diagnosis. Although the increased public awareness of oral cancer made possible by the marketing of recently-introduced screening adjuncts is commendable, the tantalizing implication that such technologies may improve detection of oral cancers and precancers beyond conventional oral examination alone has yet to be rigorously confirmed.
Topics: Coloring Agents; Cytological Techniques; Fluorescence; Humans; Mass Screening; Mouth Neoplasms; Precancerous Conditions; Spectrophotometry; Tolonium Chloride
PubMed: 17825602
DOI: 10.1016/j.oraloncology.2007.06.011 -
Brazilian Journal of Otorhinolaryngology 2022Traditional meta-analyses on the diagnostic accuracy of oral lesions have been conducted, but they were inherently limited to direct pairwise comparisons between a... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Traditional meta-analyses on the diagnostic accuracy of oral lesions have been conducted, but they were inherently limited to direct pairwise comparisons between a single method and a single alternative, while multiple diagnostic options and the ranking thereof were methodologically not possible.
OBJECTIVE
To evaluate the diagnostic values of various methods in patients with oral potential malignant disease by performing a network meta-analysis.
METHODS
Two authors independently searched the databases (MEDLINE, SCOPUS, the Cochrane Register of Controlled Trials, and Google scholar) up to June 2020 for studies comparing the diagnostic accuracy of various tools (autofluorescence, chemiluminescence, cytology, narrow band imaging, and toluidine blue) with visual examination or other tools. The outcomes of interest for this analysis were sensitivity, specificity, negative predictive value, positive predictive value and accuracy. Both a standard pairwise meta-analysis and network meta-analysis were conducted.
RESULTS
Treatment networks consisting of six interventions were defined for the network meta-analysis. The results of traditional meta-analysis showed that, among six methods, narrow band imaging showed higher sensitivity, specificity, negative predictive value, positive predictive value, and accuracy compared to visual examination. The results of network meta-analysis showed that autofluorescence, chemiluminescence, and narrow band imaging had higher sensitivity compared with visual examination, and that chemiluminescence and narrow band imaging had higher negative predictive value compared with visual examination. However, autofluorescence and chemiluminescence had lower specificity compared with visual examination. There were no significant differences in positive predictive value and accuracy among the six interventions.
CONCLUSION
This study demonstrated that narrow banding imaging has superiority in terms of sensitivity and negative predictive value compared with the other five tested agents.
Topics: Humans; Sensitivity and Specificity; Early Detection of Cancer; Mouth Neoplasms; Tolonium Chloride; Narrow Band Imaging; Mouth Diseases
PubMed: 33642212
DOI: 10.1016/j.bjorl.2020.12.019 -
PloS One 2022The objective was to analyze the clinical characteristics and pathological characteristics of sural biopsy in nitrous oxide (N2O) -induced peripheral neuropathy.
OBJECTIVE
The objective was to analyze the clinical characteristics and pathological characteristics of sural biopsy in nitrous oxide (N2O) -induced peripheral neuropathy.
METHODS
We recruited 18 patients with N2O abuse-induced neurological disorders and reported their demographic data, clinical manifestations, laboratory examinations, and nerve conduction studies. Seven patients underwent sural nerve biopsy pathologic examination.
RESULTS
All 18 patients had polyneuropathy, the nerve conduction results showed significant reductions in motor and sensory amplitudes, slowing of conduction velocities, and prolongation of latencies in most tested nerves compared to the controls. Toluidine blue staining of semi-thin sections of sural nerve biopsy showed decreased myelinated nerve fiber density, increased thin myelinated nerve fiber density, and axonal regeneration. Electron microscopy showed axonal degeneration and nerve regeneration.
CONCLUSION
The main manifestations of peripheral nerve damage caused by the abuse of N2O are lower limb weakness and distal sensory disorder. The nerve conduction study results demonstrated that mixed axonal and demyelinating neuropathy was the most common type of neuropathy. Sural biopsy showed the main pathological change was chronic axonal degeneration.
Topics: Biopsy; Humans; Nitrous Oxide; Peripheral Nerve Injuries; Polyneuropathies; Sural Nerve; Tolonium Chloride
PubMed: 36112660
DOI: 10.1371/journal.pone.0274765 -
Head & Neck Oncology Jan 2009The World Health Organization has clearly identified prevention and early detection as major objectives in the control of the oral cancer burden worldwide. At the... (Review)
Review
The World Health Organization has clearly identified prevention and early detection as major objectives in the control of the oral cancer burden worldwide. At the present time, screening of oral cancer and its pre-invasive intra-epithelial stages, as well as its early detection, is still largely based on visual examination of the mouth. There is strong available evidence to suggest that visual inspection of the oral mucosa is effective in reducing mortality from oral cancer in individuals exposed to risk factors. Simple visual examination, however, is well known to be limited by subjective interpretation and by the potential, albeit rare, occurrence of dysplasia and early OSCC within areas of normal-looking oral mucosa. As a consequence, adjunctive techniques have been suggested to increase our ability to differentiate between benign abnormalities and dysplastic/malignant changes as well as to identify areas of dysplasia/early OSCC that are not visible to naked eye. These include the use of toluidine blue, brush biopsy, chemiluminescence and tissue autofluorescence. The present paper reviews the evidence supporting the efficacy of the aforementioned techniques in improving the identification of dysplastic/malignant changes of the oral mucosa. We conclude that available studies have shown promising results, but strong evidence to support the use of oral cancer diagnostic aids is still lacking. Further research with clear objectives, well-defined population cohorts, and sound methodology is strongly required.
Topics: Biopsy; Early Detection of Cancer; Fluorescence; Humans; Luminescent Measurements; Mouth Mucosa; Mouth Neoplasms; Tolonium Chloride
PubMed: 19284694
DOI: 10.1186/1758-3284-1-5