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1.
Photodermatol Photoimmunol Photomed ; 40(1): e12946, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38288767

RESUMO

BACKGROUND: Periodontitis, a chronic infectious disease, is primarily caused by a dysbiotic microbiome, leading to the destruction of tooth-supporting tissues and tooth loss. Photodynamic therapy (PDT), which combines excitation light with photosensitizers (PS) and oxygen to produce antibacterial reactive oxygen species, is emerging as a promising adjuvant treatment for periodontitis. METHODS: This review focuses on studies examining the antibacterial effects of PDT against periodontal pathogens. It also explores the impact of PDT on various aspects of periodontal health, including periodontal immune cells, human gingival fibroblasts, gingival collagen, inflammatory mediators, cytokines in the periodontium, vascular oxidative stress, vascular behavior, and alveolar bone health. Clinical trials assessing the types of PSs and light sources used in PDT, as well as its effects on clinical and immune factors in gingival sulcus fluid and the bacterial composition of dental plaque, are discussed. RESULTS: The findings indicate that PDT is effective in reducing periodontal pathogens and improving markers of periodontal health. It has shown positive impacts on periodontal immune response, tissue integrity, and alveolar bone preservation. Clinical trials have demonstrated improvements in periodontal health and alterations in the microbial composition of dental plaque when PDT is used alongside conventional treatments. CONCLUSIONS: PDT offers a promising adjunctive treatment for periodontitis, with benefits in bacterial reduction, tissue healing, and immune modulation. This article highlights the potential of PDT in periodontal therapy and emphasizes the need for further research to refine its clinical application and efficacy.


Assuntos
Placa Dentária , Periodontite , Fotoquimioterapia , Humanos , Placa Dentária/tratamento farmacológico , Periodontite/tratamento farmacológico , Fármacos Fotossensibilizantes/uso terapêutico , Antibacterianos
2.
Alzheimers Dement ; 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38924662

RESUMO

INTRODUCTION: Identification of individuals with mild cognitive impairment (MCI) who are at risk of developing Alzheimer's disease (AD) is crucial for early intervention and selection of clinical trials. METHODS: We applied natural language processing techniques along with machine learning methods to develop a method for automated prediction of progression to AD within 6 years using speech. The study design was evaluated on the neuropsychological test interviews of n = 166 participants from the Framingham Heart Study, comprising 90 progressive MCI and 76 stable MCI cases. RESULTS: Our best models, which used features generated from speech data, as well as age, sex, and education level, achieved an accuracy of 78.5% and a sensitivity of 81.1% to predict MCI-to-AD progression within 6 years. DISCUSSION: The proposed method offers a fully automated procedure, providing an opportunity to develop an inexpensive, broadly accessible, and easy-to-administer screening tool for MCI-to-AD progression prediction, facilitating development of remote assessment. HIGHLIGHTS: Voice recordings from neuropsychological exams coupled with basic demographics can lead to strong predictive models of progression to dementia from mild cognitive impairment. The study leveraged AI methods for speech recognition and processed the resulting text using language models. The developed AI-powered pipeline can lead to fully automated assessment that could enable remote and cost-effective screening and prognosis for Alzehimer's disease.

3.
J Biol Chem ; 298(8): 102238, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35809644

RESUMO

Inhibitors that bind competitively to the ATP binding pocket in the kinase domain of the oncogenic fusion protein BCR-Abl1 are used successfully in targeted therapy of chronic myeloid leukemia (CML). Such inhibitors provided the first proof of concept that kinase inhibition can succeed in a clinical setting. However, emergence of drug resistance and dose-dependent toxicities limit the effectiveness of these drugs. Therefore, treatment with a combination of drugs without overlapping resistance mechanisms appears to be an appropriate strategy. In the present work, we explore the effectiveness of combination therapies of the recently developed allosteric inhibitor asciminib with the ATP-competitive inhibitors nilotinib and dasatinib in inhibiting the BCR-Abl1 kinase activity in CML cell lines. Through these experiments, we demonstrate that asciminib significantly enhances the inhibition activity of nilotinib, but not of dasatinib. Exploring molecular mechanisms for such allosteric enhancement via systematic computational investigation incorporating molecular dynamics, metadynamics simulations, and density functional theory calculations, we found two distinct contributions. First, binding of asciminib triggers conformational changes in the inactive state of the protein, thereby making the activation process less favorable by ∼4 kcal/mol. Second, the binding of asciminib decreases the binding free energies of nilotinib by ∼3 and ∼7 kcal/mol for the wildtype and T315I-mutated protein, respectively, suggesting the possibility of reducing nilotinib dosage and lowering risk of developing resistance in the treatment of CML.


Assuntos
Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva , Niacinamida , Pirazóis , Pirimidinas , Trifosfato de Adenosina/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Dasatinibe/farmacologia , Resistencia a Medicamentos Antineoplásicos , Proteínas de Fusão bcr-abl/metabolismo , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Mutação , Niacinamida/análogos & derivados , Niacinamida/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirazóis/farmacologia , Pirimidinas/farmacologia
4.
Cancer Cell Int ; 23(1): 161, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37568211

RESUMO

BACKGROUND: Acute myeloid leukaemia (AML) remains difficult to treat despite the development of novel formulations and targeted therapies. Activating mutations in the FLT3 gene are common among patients and make the tumour susceptible to FLT3 inhibitors, but resistance to such inhibitors develops quickly. METHODS: We examined combination therapies aimed at FLT3+-AML, and studied the development of resistance using a newly developed protocol. Combinations of FLT3, CDK4/6 and PI3K inhibitors were tested for synergism. RESULTS: We show that AML cells express CDK4 and that the CDK4/6 inhibitors palbociclib and abemaciclib inhibit cellular growth. PI3K inhibitors were also effective in inhibiting the growth of AML cell lines that express FLT3-ITD. Whereas resistance to quizartinib develops quickly, the combinations overcome such resistance. CONCLUSIONS: This study suggests that a multi-targeted intervention involving a CDK4/6 inhibitor with a FLT3 inhibitor or a pan-PI3K inhibitor might be a valuable therapeutic strategy for AML to overcome drug resistance. Moreover, many patients cannot tolerate high doses of the drugs that were studied (quizartinib, palbociclib and PI3K inhibitors) for longer periods, and it is therefore of high significance that the drugs act synergistically and lower doses can be used.

5.
Lasers Med Sci ; 38(1): 29, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36585474

RESUMO

Halitosis is a widespread health problem with complex factors, and therapeutic effects sometimes are unsatisfactory. Plenty of clinical trials have tried to prove the effectiveness of photodynamic therapy (PDT), but the results are indeterminate. This study aimed to evaluate the clinical efficacy of PDT on halitosis. We searched PubMed, Cochrane Library, Embase, Web of Science, and Scopus from inception to August 10, 2022, and only studies about the PDT on halitosis were included. The criteria for meta-analysis comprised randomized controlled trials (RCTs) comparing the treatment of PDT with tongue scraper (TS) immediately after the halitosis therapy and during a 7-, 14-, 30-, and 90-day follow-up. Eight eligible studies involving 345 patients were included in this study. It was shown that PDT (MD = - 34.49, 95% CI [- 66.34, - 2.64], P = 0.03) or PDT + TS (MD = - 67.72, 95% CI [- 101.17, - 34.28], P < 0.001) had better efficacy than TS on the H2S concentration reduction immediately after the halitosis therapy. No significant differences were observed in reducing the H2S among TS, PDT alone, and PDT + TS at the follow-up. Besides, no difference between PDT and TS was found in the reduction of CH3SCH3 and CH3SH. Based on the current evidence, PDT and PDT + TS demonstrate efficacy in the treatment of halitosis in the short term, and PDT was shown to be a beneficial and promising therapeutic method.


Assuntos
Halitose , Fotoquimioterapia , Humanos , Halitose/tratamento farmacológico , Língua , Resultado do Tratamento
6.
Cancer Cell Int ; 21(1): 198, 2021 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-33832508

RESUMO

BACKGROUND: Acute myeloid leukaemia (AML) is an aggressive blood cancer. In approximately 30% of the cases, driver mutations in the FLT3 gene are identified. FLT3 inhibitors are used in treatment of such patients together with cytotoxic drugs or (in refractory AML) as single agents. Unfortunately, resistance to FLT3 inhibitors limits their efficacy. Resistance is often due to secondary mutations in the gene encoding the molecular target. The gatekeeper mutation F691L confers resistance to specific FLT3 inhibitors such as quizartinib, but pexidartinib is much less resistance to this mutation. Pexidartinib alone is however sensitive to many other resistance mutations. In chronic myeloid leukaemia (CML), it has been suggested that rotation between drugs with a different landscape of resistance mutations might postpone the emergence of resistance. METHODS: We studied the effect of quizartinib and pexidartinib in AML cell lines that express FLT3 (MOLM-14 and MV4-11). Using a rotation protocol, we further examined whether the emergence of resistance could be postponed. Computational modelling was used to analyse the onset of resistance and suggest which mutations are most likely to occur in a quantitative fashion. RESULTS: The cells were sensitive to both inhibitors but quickly developed resistance that could be inherited, suggesting a genetic origin. Rotation protocols were not useful to postpone the emergence of resistance, which implies that such protocols, or changing from pexidartinib to quizartinib (or vice-versa) should not be used in patients. The computational modelling led to similar conclusions and suggested that F691L is the most common mutation to occur with quizartinib, and also when both drugs are used in rotation. CONCLUSIONS: AML patients are not likely to benefit from a quizartinib/pexidartinib rotation protocol. A combination of tyrosine kinase inhibitors (with different molecular targets) might be more useful in the future. Development of specific FLT3 inhibitors that are less sensitive to resistance mutations might also lead to a better outcome.

7.
Biofouling ; 37(6): 656-665, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34304642

RESUMO

Antimicrobial photodynamic therapy (aPDT) has been considered as a potential alternative to antibiotics for the treatment of biofilm infections. There is evidence that an additional H2O2 enhances the antimicrobial efficacy of aPDT. However, the minimum H2O2 concentration to achieve this synergistic effect is unclear. A saliva-derived multi-species biofilm was treated with the photosensitizer chlorin e6 (Ce6, 50 µM), H2O2 (0.3, 3.3, 33.3 mM), or their combination for 5 min, followed by no irradiation or irradiation at 15 J (cm2)-1 (λ = 450 nm or 660 nm), with or without oxygen. Biofilm viability and metabolic activity were evaluated. The combination of 33.3 mM H2O2 and Ce6-aPDT strongly enhanced antimicrobial efficacy compared with either component alone, irrespective of oxygen availability and irradiation wavelength. In particular, the combination resulted in a 6.6-log colony forming unit (CFU) reduction anaerobically under blue irradiation. This combination is a promising treatment for biofilm infections, especially those thriving in an anaerobic microenvironment.


Assuntos
Anti-Infecciosos , Fotoquimioterapia , Porfirinas , Anti-Infecciosos/farmacologia , Biofilmes , Clorofilídeos , Peróxido de Hidrogênio/farmacologia , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/farmacologia
8.
Phytother Res ; 35(11): 5980-5991, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34216058

RESUMO

This study aims to evaluate the clinical efficacy of curcumin versus chlorhexidine as adjuncts to scaling and root planing (SRP) for periodontitis treatment. We searched PubMed, EMbase, Cochrane Library, and ClinicalTrials.gov from inception to February 18, 2021 and identified studies with relevant randomized controlled trials (RCTs) using curcumin or chlorhexidine as an adjunct to SRP. Nine RCTs involving 420 patients/sites were included. A meta-analysis with a random-effects model revealed that curcumin and chlorhexidine, as an adjunct to SRP, reduced probing pocket depth (PPD) at similar levels during a 3-, 4-, 6-, and 12-week follow-up. No significant differences were observed in reducing clinical attachment loss (CAL) between curcumin and chlorhexidine as an adjunct to SRP at 4 weeks and 6 weeks. Furthermore, gingival index (GI) and plaque index (PI) were similar using curcumin versus chlorhexidine as an adjunct to SRP at the 4-week-, 6-week-, and 12-week follow-up. Based on the available evidence in RCTs, compared with chlorhexidine as an adjunct to SRP, curcumin has a similar effect on reducing PPD, CAL, GI, and PI. The quality of evidence is low, limited by the number of studies and their limitations. Further studies are needed to firmly establish the clinical efficacy of curcumin.


Assuntos
Anti-Infecciosos Locais , Periodontite Crônica , Curcumina , Clorexidina , Curcumina/uso terapêutico , Humanos , Aplainamento Radicular , Resultado do Tratamento
9.
Macromol Rapid Commun ; 40(1): e1800650, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30468540

RESUMO

Sulfur and its functional groups are major players in an area of exciting research taking place in modern polymer and materials science, both in academia and industry. In fact, manifold sulfur-based reactions that are both exceptionally versatile as well as tremendously useful have been implemented, and further utilized for the design and preparation of polymeric materials that lead to a plethora of applications ranging from medicine to optics and nanotechnology to separation science. Hence, within this review, an overview of strategies and developments used over the last 5 years to reinforce the importance of the sulfur functional group in modern polymer and materials science is presented. In particular, many important references in the primary literature of sulfur chemistry are referred to, including thiol-ene, thiol-yne, thiol-Michael addition, disulfide cross-linking, and thiol-disulfide exchange, among others, by explaining and illustrating the important principles. Last but not least, the grand aim to underpin the importance of sulfur in modern polymer and materials science is achieved by presenting selected examples in diverse fields and postulating the respective potential for real-world applications.


Assuntos
Ciência dos Materiais , Polímeros/química , Enxofre/química , Estrutura Molecular
10.
Pestic Biochem Physiol ; 158: 128-134, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31378348

RESUMO

Indoleacetic acid (IAA)-carbendazim was synthesized to assess whether this conjugate could retain the fungicidal activity of carbendazim and gain root-inducing properties upon the addition of an indoleacetic acid group. An indoor virulence test demonstrated that the conjugate retained the fungicidal activity of carbendazim towards Cylindrocladium parasiticum. The conjugate was detected in roots after soaking Ricinus communis L. leaves into a solution of the IAA-carbendazim, which confirmed its phloem mobility. The activities of the cellulase, polygalacturonase and xylanase produced by Cylindrocladium parasiticum treated with different concentrations of the conjugate were determined, and the peak activities appeared at 72 h or 96 h. More importantly, the conjugate showed the ability to promote root growth. These results revealed that indoleacetic acid-carbendazim may be useful in preventing Cylindrocladium parasiticum and other diseases.


Assuntos
Ascomicetos/efeitos dos fármacos , Benzimidazóis/farmacologia , Carbamatos/farmacologia , Fungicidas Industriais/farmacologia , Ácidos Indolacéticos/farmacologia , Celulase/metabolismo , Floema/efeitos dos fármacos , Raízes de Plantas/efeitos dos fármacos , Poligalacturonase/metabolismo , Ricinus/efeitos dos fármacos
11.
J Biol Chem ; 291(8): 4211-25, 2016 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-26668309

RESUMO

p53 inactivation is a hallmark in non-small-cell lung cancer (NSCLC). It is therefore highly desirable to develop tumor-specific treatment for NSCLC therapy by restoring p53 function. Herein, a novel naphthalimide compound, NA-17, was identified as a promising drug candidate in view of both its anticancer activity and mechanism of action. NA-17 exhibited strong anticancer activity on a broad range of cancer cell lines but showed low toxicity to normal cell lines, such as HL-7702 and WI-38. Moreover, NA-17 showed p53-dependent inhibition selectivity in different NSCLC cell lines due to the activation state of endogenous p53 in the background level. Further studies revealed that NA-17 caused cell cycle arrest at the G1 phase, changed cell size, and induced apoptosis and cell death by increasing the proportion of sub-G1 cells. Molecular mechanism studies suggested that targeted accumulation of phospho-p53 in mitochondria and nuclei induced by NA-17 resulted in activation of Bak and direct binding of phospho-p53 to the target DNA sequences, thereby evoking cell apoptosis and cell cycle arrest and eventually leading to irreversible cancer cell inhibition. This work provided new insights into the molecular interactions and anticancer mechanisms of phospho-p53-dependent naphthalimide compounds.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/metabolismo , Neoplasias Pulmonares/metabolismo , Naftalimidas , Transcrição Gênica/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Proteína bcl-X/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Pontos de Checagem da Fase G1 do Ciclo Celular/genética , Células Hep G2 , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Células MCF-7 , Complexos Multiproteicos/genética , Complexos Multiproteicos/metabolismo , Naftalimidas/química , Naftalimidas/farmacologia , Proteína Killer-Antagonista Homóloga a bcl-2/genética , Proteína bcl-X/genética
12.
Caries Res ; 51(5): 507-514, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28965113

RESUMO

Previous studies have shown that Streptococcus oligofermentans inhibits the growth of cariogenic Streptococcus mutans in biofilms in vitro and is considered a probiotic candidate for caries prevention. This study aimed to examine the effects of various environmental factors on the competition between S. oligofermentans and S. mutans in a dual-species biofilm model. Single or dual S. oligofermentans and S. mutans biofilms were grown in a 96-well active attachment model for 48 h. Several growth conditions were examined in the model, namely: S. oligofermentans was inoculated 24 h before S. mutans or vice versa; the growth medium was supplemented with 0.2% sucrose or 0.4% glucose; biofilms were grown under a constantly neutral pH or pH-cycling condition, which included 8 h of neutral pH and 16 h of pH 5.5. The 48-h biofilms were examined for viable cell counts and lactic acid and hydrogen peroxide production ability. When S. oligofermentans was inoculated first, it clearly inhibited the growth of S. mutans and reduced the biofilm lactic acid production by up to 8-fold through hydrogen peroxide production, independently of sugar supply and pH conditions. When S. mutans was inoculated first, the level of inhibition by S. oligofermentans varied depending on the sugar supply and pH conditions. Thus, the inhibition efficacy of S. oligofermentans against S. mutans in dual-species biofilms is influenced by environmental factors. This study provides practical information on how to maximize the efficacy of S. oligofermentans.


Assuntos
Antibiose/fisiologia , Biofilmes/crescimento & desenvolvimento , Streptococcus mutans/crescimento & desenvolvimento , Streptococcus mutans/fisiologia , Streptococcus/crescimento & desenvolvimento , Técnicas Bacteriológicas , Contagem de Células , Peróxido de Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Ácido Láctico/metabolismo
13.
Comput Biol Med ; 169: 107889, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38199214

RESUMO

Synergetic interactions between drugs can make a drug combination more effective. Alternatively, they may allow to use lower concentrations and thus avoid toxicities or side effects that not only cause discomfort but might also reduce the overall survival. Here, we studied whether synergy exists between agents that are used for treatment of acute myeloid leukaemia (AML). Azacitidine is a demethylation agent that is used in the treatment of AML patients that are unfit for aggressive chemotherapy. An activating mutation in the FLT3 gene is common in AML patients and in the absence of specific treatment makes prognosis worse. FLT3 inhibitors may be used in such cases. We sought to determine whether combination of azacitidine with a FLT3 inhibitor (gilteritinib, quizartinib, LT-850-166, FN-1501 or FF-10101) displayed synergy or antagonism. To this end, we calculated dose-response matrices of these drug combinations from experiments in human AML cells and subsequently analysed the data using a novel consensus scoring algorithm. The results show that combinations that involved non-covalent FLT3 inhibitors, including the two clinically approved drugs gilteritinib and quizartinib were antagonistic. On the other hand combinations with the covalent inhibitor FF-10101 had some range of concentrations where synergy was observed.


Assuntos
Amidas , Compostos de Anilina , Azacitidina , Benzotiazóis , Leucemia Mieloide Aguda , Compostos de Fenilureia , Inibidores de Proteínas Quinases , Pirazinas , Pirimidinas , Humanos , Compostos de Anilina/farmacologia , Compostos de Anilina/uso terapêutico , Azacitidina/farmacologia , Azacitidina/uso terapêutico , Tirosina Quinase 3 Semelhante a fms/genética , Tirosina Quinase 3 Semelhante a fms/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Mutação , Inibidores de Proteínas Quinases/farmacologia , Inibidores de Proteínas Quinases/uso terapêutico
14.
Jpn Dent Sci Rev ; 60: 95-108, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38314143

RESUMO

Guided tissue regeneration (GTR) has been widely used in the periodontal treatment of intrabony and furcation defects for nearly four decades. The treatment outcomes have shown effectiveness in reducing pocket depth, improving attachment gain and bone filling in periodontal tissue. Although applying GTR could reconstruct the periodontal tissue, the surgical indications are relatively narrow, and some complications and race ethic problems bring new challenges. Therefore, it is challenging to achieve a consensus concerning the clinical benefits of GTR. With the appearance of stem cell-based regenerative medicine, mesenchymal stem/stromal cells (MSCs) have been considered a promising cell resource for periodontal regeneration. In this review, we highlight preclinical and clinical periodontal regeneration using MSCs derived from distinct origins, including non-odontogenic and odontogenic tissues and induced pluripotent stem cells, and discuss the transplantation procedures, therapeutic mechanisms, and concerns to evaluate the effectiveness of MSCs.

15.
Int J Med Inform ; 189: 105500, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38815316

RESUMO

OBJECTIVE: The rapid expansion of the biomedical literature challenges traditional review methods, especially during outbreaks of emerging infectious diseases when quick action is critical. Our study aims to explore the potential of ChatGPT to automate the biomedical literature review for rapid drug discovery. MATERIALS AND METHODS: We introduce a novel automated pipeline helping to identify drugs for a given virus in response to a potential future global health threat. Our approach can be used to select PubMed articles identifying a drug target for the given virus. We tested our approach on two known pathogens: SARS-CoV-2, where the literature is vast, and Nipah, where the literature is sparse. Specifically, a panel of three experts reviewed a set of PubMed articles and labeled them as either describing a drug target for the given virus or not. The same task was given to the automated pipeline and its performance was based on whether it labeled the articles similarly to the human experts. We applied a number of prompt engineering techniques to improve the performance of ChatGPT. RESULTS: Our best configuration used GPT-4 by OpenAI and achieved an out-of-sample validation performance with accuracy/F1-score/sensitivity/specificity of 92.87%/88.43%/83.38%/97.82% for SARS-CoV-2 and 87.40%/73.90%/74.72%/91.36% for Nipah. CONCLUSION: These results highlight the utility of ChatGPT in drug discovery and development and reveal their potential to enable rapid drug target identification during a pandemic-level health emergency.

16.
J Periodontol ; 95(6): 535-549, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38501762

RESUMO

BACKGROUND: The aim of this study was to assess the efficacy of photodynamic therapy (PDT) as an adjunct to scaling and root planing (SRP) on clinical parameters and microbial composition in subgingival plaque of periodontitis patients. METHODS: Seventeen patients were included in this split-mouth randomized clinical trial. Sites with probing pocket depth (PPD) ≥5 mm in combination with bleeding on probing in different quadrants were randomized into the control group, the group with a single PDT application right after SRP, and the group with three repeated PDT applications 1 week after SRP. The subgingival plaque was collected for 16S rRNA gene sequencing at baseline, Week 2, and Week 8. RESULTS: Seventeen patients with 60 sites completed this 8-week follow-up, and 157 subgingival plaques were successfully analyzed by sequencing. Significant improvements were observed in two primary outcomes: PPD at Week 8 and subgingival microbial composition. Compared to the control group, the repeated-PDT group showed a notable improvement in PPD, substantial alterations in the microbial profile, including a reduction in α-diversity and anaerobic bacteria, and an increase in aerobic bacteria at Week 2. Secondary outcomes, such as clinical attachment level and sulcus bleeding index, also showed improvement at Week 8. Furthermore, both the single- and repeated-PDT groups exhibited a decrease in periodontopathogens and an increase in beneficial bacteria compared with baseline. CONCLUSION: PDT promotes changes in the microbial composition of periodontitis patients' subgingival plaque in a direction favorable to periodontal health, and repeated PDT is a promising adjunctive therapy for periodontal treatment.


Assuntos
Placa Dentária , Raspagem Dentária , Bolsa Periodontal , Fotoquimioterapia , Aplainamento Radicular , Humanos , Fotoquimioterapia/métodos , Raspagem Dentária/métodos , Masculino , Feminino , Aplainamento Radicular/métodos , Pessoa de Meia-Idade , Placa Dentária/microbiologia , Adulto , Resultado do Tratamento , Bolsa Periodontal/microbiologia , Bolsa Periodontal/terapia , Bolsa Periodontal/tratamento farmacológico , Seguimentos , Terapia Combinada , Periodontite/microbiologia , Periodontite/terapia , Periodontite/tratamento farmacológico , Perda da Inserção Periodontal/terapia , Perda da Inserção Periodontal/microbiologia , Perda da Inserção Periodontal/tratamento farmacológico , Índice Periodontal , Fármacos Fotossensibilizantes/uso terapêutico , RNA Ribossômico 16S/análise , Bactérias Anaeróbias/efeitos dos fármacos
17.
Medicine (Baltimore) ; 102(39): e35321, 2023 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-37773856

RESUMO

RATIONALE: Periodontitis is an inflammatory disease with multifactorial etiology. Vitamin D, a fat-soluble vitamin, has protective effects on inflammatory response in various systemic conditions. The clinical features of vitamin D deficiency include growth failure, hypotonia, pathologic fractures, rachitic rosary, tetany and so on. Here we present a case of 12-year-old girl affected by early-onset periodontitis accompanied with vitamin D deficiency. PATIENT CONCERNS: A 12-year-old girl with gingival redness, bleeding associated with tooth brushing, and mandibular anterior teeth movement, with difficulty in mastication for the past 2 months. There is no relevant family history or special systemic disease history. The serological microelement test showed vitamin D levels were significantly lower than normal range. Immunological test showed abnormal CD4+/CD8+(CD3+CD4+/CD3+CD8+) ratio as well. DIAGNOSES: Based on the clinical and serological findings, this patient was ultimately diagnosed with early-onset periodontitis accompanied with vitamin D deficiency. INTERVENTIONS: The main treatments for this patient were 3-fold: periodontal therapy, vitamin D supplement and oral hygiene instructions. OUTCOMES: Following 1-year therapy, periodontal conditions recovered and became stable. And serological vitamin D levels returned to normal range. LESSONS: The case of interest serves as an important reminder to clinicians, that the early-onset periodontitis may be associated with micronutrients abnormalities, and early-diagnosis and treatment could avoid the body heathy disorders.


Assuntos
Periodontite Agressiva , Deficiência de Vitamina D , Feminino , Humanos , Criança , Vitamina D/uso terapêutico , Vitaminas/uso terapêutico , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/tratamento farmacológico , Suplementos Nutricionais
18.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 41(2): 157-164, 2023 Apr 01.
Artigo em Inglês, Zh | MEDLINE | ID: mdl-37056181

RESUMO

OBJECTIVES: This study aims to explore the therapeutic targets of curcumin in periodontitis through network pharmacology and molecular docking technology. METHODS: Targets of curcumin and periodontitis were predicted by different databases, and the protein-protein interaction (PPI) network constructed by String revealed the interaction between curcumin and periodontitis. The key target genes were screened for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Molecular docking was performed to analyze the binding potential of curcumin to periodontitis. RESULTS: A total of 672 periodontitis-related disease targets and 107 curcumin-acting targets were obtained from the databases, and 20 key targets were screened. The GO and KEGG analyses of the 20 targets showed that curcumin might play a therapeutic role through the hypoxia-inducible factor (HIF)-1 and parathyroid hormone (PTH) signaling pathways. Molecular docking analysis showed that curcumin had good binding potential with multiple targets. CONCLUSIONS: The potential key targets and molecular mechanisms of curcumin in treating periodontitis provide a theoretical basis for new drug development and clinical applications.


Assuntos
Curcumina , Medicamentos de Ervas Chinesas , Periodontite , Humanos , Farmacologia em Rede , Curcumina/farmacologia , Curcumina/uso terapêutico , Simulação de Acoplamento Molecular , Periodontite/tratamento farmacológico , Medicina Tradicional Chinesa
19.
Pathogens ; 12(7)2023 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-37513751

RESUMO

Methylene blue (MB)- or Curcumin (Cur)-based photodynamic therapy (PDT) has been used as an adjunctive treatment for periodontitis. Its actual clinical efficacy is still in question because the lack of oxygen in a deep periodontal pocket might reduce the PDT efficacy. We aim to investigate the effect of oxygen on PDT efficacy and to examine if the addition of hydrogen peroxide (HP) could improve PDT performance anaerobically. To this end, we cultured 48 h saliva-derived multi-species biofilms and treated the biofilms with 25 µM MB or 40 µM Cur, HP (0.001%, 0.01% and 0.1%), light (L-450 nm or L-660 nm), or combinations thereof under ambient air or strictly anaerobic conditions. MB- and Cur-PDTs significantly reduced biofilm viability in air but not under anaerobic conditions. HP at 0.1% significantly enhanced the killing efficacies of both MB- and Cur-PDTs anaerobically. The killing efficacy of Cur-PDT combined with 0.1% HP was higher anaerobically than in air. However, this was not the case for MB-PDT combined with 0.1% HP. In conclusion, this study demonstrated that the biofilm killing efficacies of MB- and Cur-PDTs diminished when there was no oxygen. HP at 0.1% can enhance the efficacy of PDT performed anaerobically, but the level of enhancement is photosensitizer-dependent.

20.
Front Pharmacol ; 13: 808460, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35140616

RESUMO

Objective: Curcumin has been used as an adjunct to non-surgical periodontal treatment. However, the efficacy of curcumin in the periodontal therapy remained controversial. This study aimed to evaluate the anti-inflammatory efficacy of curcumin as an adjunct to non-surgical periodontal treatment (NPT) by systematic review. Methods: Databases including Embase, PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov were searched to identify relevant RCTs on the use of curcumin as an adjunct to NPT for the treatment of periodontal disease from inception to July 21, 2021. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed using Review Manager 5.3 software. Results: A total of 18 RCTs involving 846 patients/sites were included in this meta-analysis. The results of the meta-analysis revealed that as compared to NPT alone, curcumin as an adjunct to NPT resulted in significant reduction in gingival index (GI) at the 1-week (mean differences (MD) = -0.15, 95% confidence intervals (CI) -0.26 to -0.05, p = 0.005), 2-week (MD = -0.51, 95%CI -0.74 to -0.28, p < 0.0001), 3-week (MD = -0.34, 95%CI -0.66 to -0.02, p = 0.03), 4-week (MD = -0.25, 95%CI -0.48 to -0.02, p = 0.04) or 6-week (MD = -0.33, 95%CI -0.58 to -0.08, p = 0.01) follow-ups. Similar significant reductions were also observed for sulcus bleeding index (SBI) at 1, 2, 4, and 12 weeks. However, there were no statistically significant differences in reducing bleeding on probing (BOP) between curcumin as an adjunct and NPT alone at 4, 12, and 24 weeks. Conclusion: Based on the current evidence, curcumin demonstrates anti-inflammatory efficacies in terms of reducing GI and SBI compared with NPT alone. Moreover, curcumin is a natural herbal medicine with few side effects, and it is a good candidate as an adjunct treatment for periodontal disease.

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