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AIM: To elucidate whether mitochondrial biogenesis disorder and damage from oxidative stress promote refractory apical periodontitis (RAP) in rat and human. METHODOLOGY: Twenty Enterococcus faecalis-induced RAPs were established in the maxillary first molars of male Wistar rats. Concurrently, 12 periapical lesion specimens from patients presenting with RAP were obtained by apicoectomy. Radiographic examination and histologic analysis were conducted to evaluate periapical bone tissue destruction and morphological changes. The expression of key regulators of mitochondrial biogenesis, PGC-1α and Nrf2, were detected by immunohistochemistry and double immunofluorescence staining, Western blot and real-time PCR were also assayed. Mitochondrial ROS (mtROS) was identified by MitoSOX staining. Mitochondrial function was detected by the quantification of ATP production, mitochondrial DNA (mtDNA) copy number and activities of mitochondrial respiratory chain complexes. Furthermore, mitochondrial oxidative stress was evaluated by the determination of 3-nitrotyrosine (3-NT), 4-hydroxy-2-nonenal (4-HNE) and 8-hydroxy-deoxyguanosine (8-OHdG) expression levels, as well as malondialdehyde (MDA) expression and antioxidant capacity. Student's t-test was performed to determine significance between the groups; p < .05 was considered significant. RESULTS: In the maxilla, significantly more bone resorption, greater number of periapical apoptotic cells and Tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells were observed in the RAP group compared with the control group (p < .01). PGC-1α and Nrf2 were significantly reduced in rat and human RAP lesions compared to the control group (p < .01) at both the mRNA and protein levels. Double immunofluorescence analysis of PGC-1α or Nrf2 with TOMM20 also indicated that mitochondrial biogenesis was impaired in RAP group (p < .01). Additionally, mitochondrial dysfunction was observed in RAP group, as reflected by increased mtROS, decreased ATP production, reduced mtDNA copy number and complexes of the mitochondrial respiratory chain. Finally, the expression levels of mitochondrial oxidative stress markers, 3-NT, 4-HNE and 8-OHdG, were significantly increased in the RAP group (p < .01). Consistent with this, systemic oxidative damage was also present in the progression of RAP, including increased MDA expression and decreased antioxidant activity (p < .01). CONCLUSIONS: Mitochondrial biogenesis disorder and damage from oxidative stress contribute to the development of RAP.
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Fator 2 Relacionado a NF-E2 , Biogênese de Organelas , Estresse Oxidativo , Periodontite Periapical , Ratos Wistar , Periodontite Periapical/metabolismo , Periodontite Periapical/patologia , Animais , Masculino , Humanos , Ratos , Fator 2 Relacionado a NF-E2/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Mitocôndrias/metabolismo , Adulto , DNA Mitocondrial/metabolismo , Modelos Animais de DoençasRESUMO
PURPOSE: To systematically review in-vitro studies that evaluated the influence of erbium laser pretreatment on dentin shear bond strength (SBS) and bond failure modes. MATERIALS AND METHODS: Electronic databases (PubMed, Cochrane Central, Embase, and Web of Science) were searched. Only in-vitro studies involving erbium laser irradiation of the dentin surface and SBS testing of the bonded resin block were included. The three common modes of bond failure (1. adhesive, 2. cohesive, and 3. mixed) were observed and analyzed. The network meta-analysis (NMA) was performed by Stata 15.0 software, the risk of bias was evaluated, and the certainty of the evidence was assessed by the Confidence in Network Meta-analysis (CINeMA). RESULTS: Forty studies with nine pretreatments (1. blank group: BL; 2. phosphoric acid etch-and-rinse: ER; 3. self-etch adhesive: SE; 4. Er:YAG laser: EL; 5. Er,Cr:YSGG laser: ECL; 6. ER+EL; 7. ER+ECL; 8. SE+EL; 9. SE+ECL) were included in this analysis. The NMA of SBS showed that ER+EL [SMD = 0.32, 95% CI (0.11, 0.98)] had the highest SBS next to ER, especially when using one of the 3M ESPE adhesives, followed by EL, ECL, SE and SE+EL. The Ivoclar Vivadent adhesives significantly increased the SBS of the ECL [SMD = 0.37, 95% CI (0.16,0.90)] and was higher than ER+EL [SMD = 0.25,95% CI (0.07,0.85)]. Finally, the surface under the cumulative ranking curve (SUCRA) value indicated that ER+EL (SUCRA = 71.0%) and EL (SUCRA = 62.9%) were the best treatments for enhancing dentin SBS besides ER. ER+EL (SUCRA = 85.3%), ER (SUCRA = 83.7%) and ER (SUCRA = 84.3%) had the highest probability of occurring in adhesive, cohesive and mixed failure modes, respectively. CONCLUSION: Er:YAG and Er,Cr:YSGG lasers improved dentin SBS compared to the blank group, especially when the acid etch-and-rinse pretreatment was combined with Er:YAG laser. Shear bond strength and failure mode do not appear to be directly related.
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Colagem Dentária , Dentina , Lasers de Estado Sólido , Resistência ao Cisalhamento , Colagem Dentária/métodos , Lasers de Estado Sólido/uso terapêutico , Humanos , Metanálise em Rede , Adesivos Dentinários/química , Condicionamento Ácido do Dente , Análise do Estresse DentárioRESUMO
BACKGROUND: The associations between hysterectomy and cardiovascular disease (CVD) and mortality remains unlcear and a meta-analysis with cohort studies is lacking. OBJECTIVES: This study aimed to conduct a systematic review and meta-analysis of cohort studies to investigate the relationship between hysterectomy and CVD, coronary heart disease (CHD), stroke, heart failure, and all-cause, cardiovascular and cancer mortality. We further explored the effect of oophorectomy on the association between hysterectomy and these health outcomes. SEARCH STRATEGY: PubMed, EMBASE and Web of Science were searched up to 24 July 2023. SELECTION CRITERIA: Cohort studies. DATA COLLECTION AND ANALYSIS: Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were pooled using a random-effects model. We used I2 to assess the heterogeneity between studies. MAIN RESULTS: Forty-three studies were included in the meta-analysis. Hysterectomy was significantly associated with an increased risk of CVD (pooled HR 1.11, 95% CI 1.09-1.13; n = 6; I2 = 0) and stroke (HR 1.09, 95% CI 1.04-1.14; n = 7; I2 = 52%), but with a decreased risk of cancer mortality (HR 0.93, 95% CI 0.86-1.00; n = 4; I2 = 81%). No significant association was observed between hysterectomy and CHD (n = 10; I2 = 83%), all-cause mortality (n = 8; I2 = 81%) or cardiovascular mortality (n = 7; I2 = 89%). Hysterectomy with and without oophorectomy was significantly associated with CVD and stroke risk, but showed a larger effect size for hysterectomy with oophorectomy. A significantly increased risk of CHD was observed in the subgroup of hysterectomy with oophorectomy, but not for the subgroup of hysterectomy alone. CONCLUSIONS: Hysterectomy may increase the risk of CVD, CHD and stroke, but not all-cause, cardiovascular or cancer mortality. Hysterectomy with oophorectomy may have a higher risk of CVD, CHD and stroke than hysterectomy alone. However, the results on CHD and mortality related to hysterectomy should be interpreted cautiously because of the high level of heterogeneity and unstable subgroup analyses.
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OBJECTIVES: To analyze the role of oxidative stress (OS) biomarkers in periimplant diseases using a systematic review and meta-analysis approach. DATE: The review incorporated cross-sectional studies, randomized controlled trials, and case-control trials to evaluate the differences in OS biomarkers of periimplant disease. SOURCES: A comprehensive literature search was conducted in electronic databases such as PubMed, Scopus, Embase, Web of Science, and CNKI, and no restrictions were applied during the search process. STUDY SELECTION: A total of 452 studies were identified, of which 18 were eligible for inclusion. Risk of bias and sensitivity analysis were assessed using Egger's test and funnel plots. RESULTS: We found that the levels of glutathione peroxidase (GSH-Px) in the periimplant sulcus fluid (PISF) of patients with periimplant diseases were significantly reduced (SMD = -1.40; 95 % CI = 1.70, -1.11; p < 0.001), while the levels of total myeloperoxidase (MPO) and malondialdehyde (MDA) were significantly increased (SMD = 0.46; 95 % CI = 0.12, 0.80; p = 0.008; SMD = 0.28; 95 % CI = 0.01, 0.56; p = 0.043). However, there were no significant differences of MPO concentration (SMD = 0.38; 95 % CI = -0.39, 1.15; p = 0.331) and superoxide dismutase (SOD)(SMD = -0.43; 95 % CI = -1.94, 1.07; p = 0.572) in PISF between periimplant disease group and control group. Similarly, salivary MPO did not show significant differences (SMD = 1.62; 95 % CI = -1.01, 4.24; p = 0.227). CONCLUSIONS: Our results supported that the level of local OS biomarkers was closely related to periimplant diseases. GSH-Px, total MPO and MDA may be PISF biomarkers with good capability to monitor the development of periimplant disease. CLINICAL SIGNIFICANCE: This study found significant differences in the levels of local OS biomarkers (GSH-Px, total MPO, and MDA) between patients with periimplant diseases and healthy subjects, which may be ideal candidate biomarkers for predicting and diagnosing periimplant diseases.
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Biomarcadores , Implantes Dentários , Glutationa Peroxidase , Malondialdeído , Estresse Oxidativo , Peri-Implantite , Peroxidase , Humanos , Biomarcadores/análise , Peroxidase/análise , Malondialdeído/análise , Malondialdeído/metabolismo , Peri-Implantite/metabolismo , Glutationa Peroxidase/análise , Glutationa Peroxidase/metabolismo , Líquido do Sulco Gengival/químicaRESUMO
Regarding the impact of microplastics (MPs) on the male reproductive system, previous studies have identified a variety of MPs in both human semen and testicular samples. These studies have put forward the hypothesis that small particles can enter the semen through the epididymis and seminal vesicles. Here, we performed qualitative and quantitative analyses of MPs in human testis, semen, and epididymis samples, as well as in testis, epididymis, seminal vesicle, and prostate samples from mice via pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS). The goal of this approach was to comprehensively characterize the distribution of MPs within the male reproductive system. Additionally, we aimed to evaluate potential sources of MPs identified in semen, as well as to identify possible sources of overall MP exposure. Our results highlighted a general atlas of MPs in the male reproductive system and suggested that MPs in semen may originate from the epididymis, seminal vesicles, and prostate. An exposure questionnaire, coupled with the characteristics of the MPs detected in the male reproductive system, revealed that high urbanization, home-cooked meals, and using scrub cleansers were important sources of MP exposure in men. These findings may provide novel insights into alleviating the exposure of men to MPs.
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Microplásticos , Testículo , Humanos , Masculino , Camundongos , Animais , Plásticos , Genitália Masculina , Glândulas Seminais , SêmenRESUMO
Zinc (Zn)-dysprosium (Dy) binary alloys are promising biodegradable bone fracture fixation implants owing to their attractive biodegradability and mechanical properties. However, their clinical application is a challenge for bone fracture healing, due to the lack of Zn-Dy alloys with tailored proper bio-mechanical and osteointegration properties for bone regeneration. A Zn-5Dy alloy with high strength and ductility and a degradation rate aligned with the bone remodeling cycle is developed. Here, mechanical stability is further confirmed, proving that Zn-5Dy alloy can resist aging in the degradation process, thus meeting the mechanical requirements of fracture fixation. In vitro cellular experiments reveal that the Zn-5Dy alloy enhances osteogenesis and angiogenesis by elevating SIRT4-mediated mitochondrial function. In vivo Micro-CT, SEM-EDS, and immunohistochemistry analyses further indicate good biosafety, suitable biodegradation rate, and great osteointegration of Zn-5Dy alloy during bone healing, which also depends on the upregulation of SIRT4-mediated mitochondrial events. Overall, the study is the first to report a Zn-5Dy alloy that exerts remarkable osteointegration properties and has a strong potential to promote bone healing. Furthermore, the results highlight the importance of mitochondrial modulation and shall guide the future development of mitochondria-targeting materials in enhancing bone fracture healing.
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Ligas , Osteogênese , Implantes Absorvíveis , Ligas/química , Ligas/farmacologia , Teste de Materiais , Mitocôndrias/efeitos dos fármacos , Zinco/química , Disprósio/química , Disprósio/farmacologia , Osteogênese/efeitos dos fármacos , Sirtuínas/efeitos dos fármacos , Humanos , Fraturas Ósseas/tratamento farmacológicoRESUMO
Chimeric antigen receptor (CAR) T cell therapies have successfully treated hematological malignancies. Macrophages have also gained attention as an immunotherapy owing to their immunomodulatory capacity and ability to infiltrate solid tumors and phagocytize tumor cells. The first-generation CD3ζ-based CAR-macrophages could phagocytose tumor cells in an antigen-dependent manner. Here we engineered induced pluripotent stem cell-derived macrophages (iMACs) with toll-like receptor 4 intracellular toll/IL-1R (TIR) domain-containing CARs resulting in a markedly enhanced antitumor effect over first-generation CAR-macrophages. Moreover, the design of a tandem CD3ζ-TIR dual signaling CAR endows iMACs with both target engulfment capacity and antigen-dependent M1 polarization and M2 resistance in a nuclear factor kappa B (NF-κB)-dependent manner, as well as the capacity to modulate the tumor microenvironment. We also outline a mechanism of tumor cell elimination by CAR-induced efferocytosis against tumor cell apoptotic bodies. Taken together, we provide a second-generation CAR-iMAC with an ability for orthogonal phagocytosis and polarization and superior antitumor functions in treating solid tumors relative to first-generation CAR-macrophages.
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Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos de Linfócitos T , Linfócitos T , Linhagem Celular Tumoral , Receptores de Antígenos Quiméricos/genética , Imunoterapia Adotiva/métodos , Macrófagos/patologia , Microambiente TumoralRESUMO
BACKGROUND: Apical periodontitis directly affects the stress state of the affected tooth owing to the destruction of the periapical bone. Understanding the mechanical of periapical bone defects/tooth is clinically meaningful. In this study, we evaluate the effect of periapical bone defects on the stress distribution in teeth with periapical periodontitis using finite element analysis. METHODS: Finite element models of normal mandibular second premolars and those with periapical bone defects (spherical defects with diameters of 5, 10, 15, and 20 mm) were created using a digital model design software. The edges of the mandible were fixed and the masticatory cycle was simplified as oblique loading (a 400 N force loaded obliquely at 45° to the long axis of the tooth body) to simulate the tooth stress state in occlusion and analyze the von Mises stress distribution and tooth displacement distribution in each model. RESULTS: Overall analysis of the models: Compared to that in the normal model, the maximum von Mises stresses in all the different periapical bone defect size models were slightly lower. In contrast, the maximum tooth displacement in the periapical bone defect model increased as the size of the periapical bone defect increased (2.11-120.1% of increase). Internal analysis of tooth: As the size of the periapical bone defect increased, the maximum von Mises stress in the coronal cervix of the tooth gradually increased (2.23-37.22% of increase). while the von Mises stress in the root apical region of the tooth showed a decreasing trend (41.48-99.70% of decrease). The maximum tooth displacement in all parts of the tooth showed an increasing trend as the size of the periapical bone defect increased. CONCLUSIONS: The presence of periapical bone defects was found to significantly affect the biomechanical response of the tooth, the effects of which became more pronounced as the size of the bone defect increased.
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Periodontite Periapical , Software , Humanos , Análise de Elementos Finitos , Estresse Mecânico , Dente Pré-Molar , Análise do Estresse DentárioRESUMO
AIM: To evaluate the effects of root canal treatment (RCT) and post-crown restoration on stress distribution in teeth with periapical bone defects using finite element analysis. METHODOLOGY: Finite element models of mandibular second premolars and those with periapical bone defects (spherical defects with diameters of 5, 10, 15, and 20 mm) were created using digital model design software. The corresponding RCT and post-crown restoration models were constructed based on the different sizes of periapical bone defect models. The von Mises stress and tooth displacement distributions were comprehensively analyzed in each model. RESULTS: Overall analysis of the models: RCT significantly increased the maximum von Mises stresses in teeth with periapical bone defects, while post-crown restoration greatly reduced the maximum von Mises stresses. RCT and post-crown restoration slightly reduced tooth displacement in the affected tooth. Internal analysis of tooth: RCT dramatically increased the maximum von Mises stress in all regions of the tooth, with the most pronounced increase in the coronal surface region. The post-crown restoration balances the internal stresses of the tooth and is most effective in periapical bone defect - 20-mm model. RCT and post-crown restoration slightly reduced the tooth displacement in all regions of the affected tooth. CONCLUSIONS: Root canal treatment seemed not to improve the biomechanical state of teeth with periapical bone defects. In contrast, post-crown restoration might effectively balance the stress concentrations caused by periapical bone defects, particularly extensive ones.
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Periodontite Periapical , Coroa do Dente , Humanos , Análise de Elementos Finitos , Cavidade Pulpar , Coroas , Periodontite Periapical/terapiaRESUMO
The flat band system is an ideal quantum platform to investigate the kaleidoscope created by the electron-electron correlation effects. The central ingredient of realizing a flat band is to find its compact localized states. In this work, we develop a systematic way to generate compact localized states by designing destructive interference patterns from 1-dimensional chains. A variety of 2-dimensional new flat band systems are constructed with this method. Furthermore, we show that the method can be extended to generate the compact localized states in multi-orbital systems by carefully designing the block hopping scheme, as well as in quasicrystal and disorder systems.
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Defensive behaviors are critical for animal's survival. Both the paraventricular nucleus of the hypothalamus (PVN) and the parabrachial nucleus (PBN) have been shown to be involved in defensive behaviors. However, whether there are direct connections between them to mediate defensive behaviors remains unclear. Here, by retrograde and anterograde tracing, we uncover that cholecystokinin (CCK)-expressing neurons in the lateral PBN (LPBCCK) directly project to the PVN. By in vivo fiber photometry recording, we find that LPBCCK neurons actively respond to various threat stimuli. Selective photoactivation of LPBCCK neurons promotes aversion and defensive behaviors. Conversely, photoinhibition of LPBCCK neurons attenuates rat or looming stimuli-induced flight responses. Optogenetic activation of LPBCCK axon terminals within the PVN or PVN glutamatergic neurons promotes defensive behaviors. Whereas chemogenetic and pharmacological inhibition of local PVN neurons prevent LPBCCK-PVN pathway activation-driven flight responses. These data suggest that LPBCCK neurons recruit downstream PVN neurons to actively engage in flight responses. Our study identifies a previously unrecognized role for the LPBCCK-PVN pathway in controlling defensive behaviors.
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Hipotálamo , Núcleos Parabraquiais , Ratos , Animais , Hipotálamo/metabolismo , Núcleo Hipotalâmico Paraventricular/metabolismo , Colecistocinina/metabolismo , Neurônios/fisiologia , Núcleos Parabraquiais/fisiologiaRESUMO
OBJECTIVE: To explore the feasibility of computed tomography perfusion imaging (CTP) for evaluating hemodynamics in hemorrhagic moyamoya disease (MMD). METHODS: The retrospective analysis included 25 patients with hemorrhagic MMD who underwent brain CTP examination. Two experienced radiologists manually delineated regions of interest (ROIs) in the bilateral frontal lobe, temporal lobe, brain tissue adjacent to the hemorrhagic foci, and brainstem as a control region. The perfusion values for all ROIs were extracted, including cerebral blood flow (CBF), cerebral blood volume (CBV), mean transit time (MTT), and time to peak (TTP). Subsequently, the differences in perfusion values for different brain tissues were compared between the hemorrhagic side and the nonhemorrhagic side. For patients who underwent revascularization surgery, differences in perfusion values from before to after surgery were determined in brain tissues on the ipsilateral side. RESULTS: CBF in the area around the hematoma and the lateral temporal lobe on the hemorrhage hemisphere was lower than that on the contralateral side, whereas TTP and MTT were higher. Among the 14 patients who underwent revascularization, CBF and CBV in the postoperative temporal lobes were higher than the preoperative values, whereas TTP and MTT were lower. CBF and CBV in the frontal lobe were higher after the operation. CONCLUSIONS: Hemorrhagic MMD results in cerebral ischemia, and CTP could be used to localize such ischemic brain tissue and objectively evaluate the changes in cerebral hemodynamics with revascularization.