Insula→Amygdala and Insula→Thalamus Pathways Are Involved in Comorbid Chronic Pain and Depression-Like Behavior in Mice.

The comorbidity of chronic pain and depression poses tremendous challenges for the treatment of either one because they exacerbate each other with unknown mechanisms. As the posterior insular cortex (PIC) integrates multiple somatosensory and emotional information and is implicated in either chronic pain or depression, we hypothesize that the PIC and its projections may contribute to the pathophysiology of comorbid chronic pain and depression. We show that PIC neurons were readily activated by mechanical, thermal, aversive, and stressful and appetitive stimulation in naive and neuropathic pain male mice subjected to spared nerve injury (SNI). Optogenetic activation of PIC neurons induced hyperalgesia and conditioned place aversion in naive mice, whereas inhibition of these neurons led to analgesia, conditioned place preference (CPP), and antidepressant effect in both naive and SNI mice. Combining neuronal tracing, optogenetics, and electrophysiological techniques, we found that the monosynaptic glutamatergic projections from the PIC to the basolateral amygdala (BLA) and the ventromedial nucleus (VM) of the thalamus mimicked PIC neurons in pain modulation in naive mice; in SNI mice, both projections were enhanced accompanied by hyperactivity of PIC, BLA, and VM neurons and inhibition of these projections led to analgesia, CPP, and antidepressant-like effect. The present study suggests that potentiation of the PIC→BLA and PIC→VM projections may be important pathophysiological bases for hyperalgesia and depression-like behavior in neuropathic pain and reversing the potentiation may be a promising therapeutic strategy for comorbid chronic pain and depression.

The anterior cingulate cortex controls the hyperactivity in subthalamic neurons in male mice with comorbid chronic pain and depression.

Neurons in the subthalamic nucleus (STN) become hyperactive following nerve injury and promote pain-related responses in mice. Considering that the anterior cingulate cortex (ACC) is involved in pain and emotion processing and projects to the STN, we hypothesize that ACC neurons may contribute to hyperactivity in STN neurons in chronic pain. In the present study, we showed that ACC neurons enhanced activity in response to noxious stimuli and to alterations in emotional states and became hyperactive in chronic pain state established by spared nerve injury of the sciatic nerve (SNI) in mice. In naïve mice, STN neurons were activated by noxious stimuli, but not by alterations in emotional states. Pain responses in STN neurons were attenuated in both naïve and SNI mice when ACC neurons were inhibited. Furthermore, optogenetic activation of the ACC-STN pathway induced bilateral hyperalgesia and depression-like behaviors in naive mice; conversely, inhibition of this pathway is sufficient to attenuate hyperalgesia and depression-like behaviors in SNI mice and naïve mice subjected to stimulation of STN neurons. Finally, mitigation of pain-like and depression-like behaviors in SNI mice by inhibition of the ACC-STN projection was eliminated by activation of STN neurons. Our results demonstrate that hyperactivity in the ACC-STN pathway may be an important pathophysiology in comorbid chronic pain and depression. Thus, the ACC-STN pathway may be an intervention target for the treatment of the comorbid chronic pain and depression.

Targeting DGAT1 inhibits prostate cancer cells growth by inducing autophagy flux blockage via oxidative stress.

Impaired macroautophagy/autophagy flux has been implicated in the treatment of prostate cancer (PCa). However, the mechanism underlying autophagy dysregulation in PCa remains unknown. In the current study, we investigated the role of diacylglycerol acyltransferases 1 (DGAT1) and its potential effects on cellular energy homeostasis and autophagy flux in PCa. The results of immunohistochemical staining suggested that DGAT1 expression was positively corrected with tumor stage and node metastasis, indicating DGAT1 is an important factor involved in the development and progression of PCa. Furthermore, targeting DGAT1 remarkably inhibited cell proliferation in vitro and suppressed PCa growth in xenograft models by triggering severe oxidative stress and subsequently autophagy flux blockage. Mechanically, DGAT1 promoted PCa progression by maintaining cellular energy homeostasis, preserving mitochondrial function, protecting against reactive oxygen species, and subsequently promoting autophagy flux via regulating lipid droplet formation. Moreover, we found that fenofibrate exhibits as an upstream regulator of DGAT1. Fenofibrate performed its anti-PCa effect involved the aforementioned mechanisms, and partially dependent on the regulation of DGAT1. Collectively. These findings indicate that DGAT1 regulates PCa lipid droplets formation and is essential for PCa progression. Targeting DGAT1 might be a promising method to control the development and progression of PCa. Schematic representation of DGAT1 affects autophagy flux by regulating lipid homeostasis and maintaining mitochondrial function in prostate cancer (PCa). PCa is characterized up-regulation of DGAT1, leading to the translocation of free fatty acids into lipid droplets, thereby preventing PCa cell from lipotoxicity. Inhibition of DGAT1 suppresses growth of PCa by inducing oxidative stress and subsequently autophagy flux blockage. Further, the current results revealed that fenofibrate exhibits as an upstream regulator of DGAT1, and fenofibrate plays an anti-PCa role partially dependent on the regulation of DGAT1, suggesting a potential therapeutic approach to ameliorate this refractory tumor.

A subthalamo-parabrachial glutamatergic pathway is involved in stress-induced self-grooming in mice.

Excessive self-grooming is an important behavioral phenotype of the stress response in rodents. Elucidating the neural circuit that regulates stress-induced self-grooming may suggest potential treatment to prevent maladaptation to stress that is implicated in emotional disorders. Stimulation of the subthalamic nucleus (STN) has been found to induce strong self-grooming. In this study we investigated the role of the STN and a related neural circuit in mouse stress-related self-grooming. Body-restraint and foot-shock stress-induced self-grooming models were established in mice. We showed that both body restraint and foot shock markedly increased the expression of c-Fos in neurons in the STN and lateral parabrachial nucleus (LPB). Consistent with this, the activity of STN neurons and LPB glutamatergic (Glu) neurons, as assessed with fiber photometry recording, was dramatically elevated during self-grooming in the stressed mice. Using whole-cell patch-clamp recordings in parasagittal brain slices, we identified a monosynaptic projection from STN neurons to LPB Glu neurons that regulates stress-induced self-grooming in mice. Enhanced self-grooming induced by optogenetic activation of the STN-LPB Glu pathway was attenuated by treatment with fluoxetine (18 mg·kg-1·d-1, p.o., for 2 weeks) or in the presence of a cage mate. Furthermore, optogenetic inhibition of the STN-LPB pathway attenuated stress-related but not natural self-grooming. Taken together, these results suggest that the STN-LPB pathway regulates the acute stress response and is a potential target for intervention in stress-related emotional disorders.

A rare presentation of central pontine myelinolysis secondary to hyperglycaemia.

BACKGROUND: Central pontine myelinolysis (CPM) is a rare demyelinating disorder caused by the loss of myelin in the center of the basis pontis. CPM typically occurs with rapid correction of severe chronic hyponatremia and subsequent disturbances in serum osmolality. Although hyperglycaemia is recognized as a pathogenetic factor in serum osmolality fluctuations, CPM is rarely seen in the context of diabetes. CASE PRESENTATION: A 66-year-old Chinese male presented with a history of gait imbalance, mild slurred speech and dysphagia for two weeks. MRI showed the mass lesions in the brainstem, and laboratory examinations showed high blood glucose and HbA1c, as well as increased serum osmolality. The patient was diagnosed with CPM secondary to hyperosmolar hyperglyceamia and received insulin treatment as well as supportive therapy. After six weeks of followup, the patient had fully recovered to a normal state. CONCLUSION: CPM is a potentially fatal neurological condition and can occur in uncontrolled diabetes mellitus. Early diagnosis and timely treatment are crucial for improving the prognosis.

Improving the effectiveness of watershed environmental management-dynamic coordination through government pollution control and resident participation.

To improve the effectiveness of envir onmental management of watersheds and improve the environmental management mechanism of cross-administrative watersheds, we develop a neoliberal framework for action using incentives, examine the cooperative strategies of local governments in watershed treatment and people-oriented environmental protection under central government subsidies, and analyze the cost effectiveness of multiple strategies in a dynamic perspective, and we have the following important findings: (1) Compared to vertical ecological compensation, the introduction of horizontal cost-sharing contracts is more effective in enhancing inter-local cooperative environmental governance. (2) When the marginal benefit of the downstream local government is greater than half of the upstream marginal benefit, the upstream local government's pollution control investment and the effect of pollution control are improved, and the Pareto improvement of the environmental governance benefit of the watershed is realized, i.e., the cost-sharing contract driven by the downstream can achieve a win-win situation for both environmental and government governance benefits. (3) When the marginal benefit of downstream environmental advocacy is between 0.5 and 1.5 times the marginal benefit of upstream government, the cost-sharing contract is more effective in improving downstream benefits. Conversely, when the marginal benefit of downstream is greater than 1.5 times, the marginal benefit of upstream, the more effective the cost-sharing contract is in improving the marginal benefit of downstream. The results of the study provide useful insights for the government to develop reasonable pollution management cooperation mechanisms to improve environmental management performance and thus enhance the sustainable development of the watershed.

Corrosion Behavior of Nitrogen-Containing Low-Nickel Weld Cladding in KCl-MgCl2 Eutectic Molten Salt at 900 °C.

In this paper, the element nitrogen (N) is used to partially replace the element nickel (Ni) in flux-cored wire. A 44%Ni-24%Cr-0.18N nitrogen-containing low-nickel flux-cored wire with excellent corrosion resistance is prepared. The corrosion behavior of nitrogen-containing low-nickel weld cladding and Inconel 625 weld cladding in 40 KCl + 60 MgCl2 (wt%) molten salt at 900 °C is studied. The results show that the selective dissolution of Cr occurs in both weld claddings. The corrosion resistance of the 44%Ni-24%Cr-0.18N nitrogen-containing low-nickel weld cladding is better than that of the Inconel 625 weld cladding. The reason is that added N can react with H+ in molten salt to generate NH4+, remove corrosive impurities of MgOH+ in molten salt and change the corrosion environment. N preferentially combines with Cr to form Cr2N, reduces the diffusion precipitation of Cr and improves the corrosion resistance.

Implications of p53 in mitochondrial dysfunction and Parkinson's disease.

Purpose: To study the underlying molecular mechanisms of p53 in the mitochondrial dysfunction and the pathogenesis of Parkinson's disease (PD), and provide a potential therapeutic target for PD treatment.Methods: We review the contributions of p53 to mitochondrial changes leading to apoptosis and the subsequent degeneration of dopaminergic neurons in PD.Results: P53 is a multifunctional protein implicated in the regulation of diverse cellular processes via transcription-dependent and transcription-independent mechanisms. Mitochondria are vital subcellular organelles for that maintain cellular function, and mitochondrial defect and impairment are primary causes of dopaminergic neuron degeneration in PD. Increasing evidence has revealed that mitochondrial dysfunction-associated dopaminergic neuron degeneration is tightly regulated by p53 in PD pathogenesis. Neurodegenerative stress triggers p53 activation, which induces mitochondrial changes, including transmembrane permeability, reactive oxygen species production, Ca2+ overload, electron transport chain defects and other dynamic alterations, and these changes contribute to neurodegeneration and are linked closely with PD occurrence and development. P53 inhibition has been shown to attenuate mitochondrial dysfunction and protect dopaminergic neurons from degeneration under conditions of neurodegenerative stress.Conclusions: p53 appears to be a potential target for neuroprotective therapy of PD.

A nigro-subthalamo-parabrachial pathway modulates pain-like behaviors.

The basal ganglia including the subthalamic nucleus (STN) and substantia nigra pars reticulata (SNr) are involved in pain-related responses, but how they regulate pain processing remains unknown. Here, we identify a pathway, consisting of GABAergic neurons in the SNr (SNrGABA) and glutamatergic neurons in the STN (STNGlu) and the lateral parabrachial nucleus (LPBGlu), that modulates acute and persistent pain states in both male and female mice. The activity of STN neurons was enhanced in acute and persistent pain states. This enhancement was accompanied by hypoactivity in SNrGABA neurons and strengthening of the STN-LPB glutamatergic projection. Reversing the dysfunction in the SNrGABA-STNGlu-LPBGlu pathway attenuated activity of LPBGlu neurons and mitigated pain-like behaviors. Therefore, the SNrGABA-STNGlu-LPBGlu pathway regulates pathological pain and is a potential target for pain management.

Does Water Matter? The Impact of Water Vulnerability on Corporate Financial Performance.

This study aims to understand the potential relationship between water vulnerability and corporate financial performance for listed companies in China. Studies have argued that water risk has begun to affect the sustainability of firms, but few studies have included water conditions in the research framework to examine whether and how water conditions have a direct impact on firms. In addition, studies on environment governance have emphasized the impact of government environmental regulation on firms. This study focuses on both regulation and government investments that have been previously neglected. Using a sample of Chinese listed companies from 2016 to 2020, this paper uses pooled cross-sectional regressions with year and industry fixed effects to examine the effects of water vulnerability on corporate financial performance and analyze the mechanism of government water governance (which can be divided into water regulation and water investment) on the relationship between water vulnerability and corporate financial performance. This study finds that water vulnerability could negatively impact corporate financial performance, and water regulation can intensify but water investment couldn't significantly relieve the negative impact. The relationships above differ between SOEs and non-SOEs and water-intensive and non-water-intensive industries.

Salidroside Ameliorates Depression by Suppressing NLRP3-Mediated Pyroptosis via P2X7/NF-κB/NLRP3 Signaling Pathway.

Depression is a common and serious mental disorder. Data on its pathogenesis remain unclear and the options of drug treatments are limited. Here, we explored the role of pyroptosis, a novel pro-inflammatory programmed cell death process, in depression as well as the anti-depression effects and mechanisms of salidroside (Sal), a bioactive extract from Rhodiola rosea L. We established a corticosterone (CORT)-induced or lipopolysaccharide (LPS)-induced mice in vivo, and CORT, or nigericin (NLRP3 agonist)-induced PC12 cells in vitro. Our findings demonstrated that Sal profoundly mediated CORT or LPS-induced depressive behavior and improved synaptic plasticity by upregulating the expression of brain-derived neurotrophic factor (BDNF) gene. The data showed upregulation of proteins associated with NLRP3-mediated pyroptosis, including NLRP3, cleaved Caspase-1, IL-1ß, IL-18, and cleaved GSDMD. The molecular docking simulation predicted that Sal would interact with P2X7 of the P2X7/NF-κB/NLRP3 signaling pathway. In addition, our findings showed that the NLRP3-mediated pyroptosis was regulated by P2X7/NF-κB/NLRP3 signaling pathway. Interestingly, Sal was shown to ameliorate depression via suppression of the P2X7/NF-κB/NLRP3 mediated pyroptosis, and rescued nigericin-induced pyroptosis in the PC12 cells. Besides, knock down of the NLRP3 gene by siRNA markedly increased the inhibitory effects of Sal on pyroptosis and proinflammatory responses. Taken together, our findings demonstrated that pyroptosis plays a crucial role in depression, and Sal ameliorates depression by suppressing the P2X7/NF-κB/NLRP3-mediated pyroptosis. Thus, our study provides new insights into the potential treatment options for depression.

Comparison of biological and mechanical properties of different paranasal sinus mucosa in goat.

OBJECTIVE: The present study was designed to explore endurable pressure intensity of different paranasal sinus mucosa in goats. METHOD: Mucosa commonly involved in maxillary sinus augmentation, including mucosa from maxillary sinus crest, maxillary sinus floor, and frontal sinus, were harvested in a computed tomography-guided manner. The obtained mucosa was then sectioned into square and irregular ones for maximum endurable pressure intensity determination and morphological observation, respectively. RESULTS: Thickness of paranasal sinus mucosa, as determined under morphological staining by an optical microscope with a graduated eyepiece, were calculated. And the results showed that the average thickness of maxillary sinus crest mucosa, floor mucosa, and frontal sinus mucosa in goats were 410.03 ± 65.97 µm, 461.33 ± 91.37 µm and 216.90 ± 46.47 µm, respectively. Significant differences between maxillary sinus crest and frontal sinus, maxillary sinus floor, and frontal sinus were observed (P < 0.05). Maximum endurable pressure intensity was determined by utilizing a self-made clamp device and the results revealed maximum endurable pressure intensity of maxillary sinus crest mucosa, floor mucosa and frontal sinus mucosa in goats were 260.08 ± 80.12Kpa, 306.90 ± 94.37Kpa and 121.72 ± 31.72Kpa, respectively. Also, a statistically significant difference was observed when comparing the endurable pressure intensity between maxillary sinus crest and frontal sinus, maxillary sinus floor, and frontal sinus (P < 0.05). Further correlation analysis also revealed a positive correlation between the thickness of mucosa of the maxillary sinus and frontal sinus and maximum endurable pressure intensity (P < 0.05). CONCLUSION: Mucosal thickness and maximum endurable pressure intensity of maxillary sinus crest and floor were larger than that of frontal sinus mucosa and a positive correlation between the thickness of mucosa and endurable pressure intensity was observed. Our results thus might provide an experimental basis and guidance for mucosa-related problems involved maxillary sinus augmentation.

Activation and closed-state inactivation mechanisms of the human voltage-gated KV4 channel complexes.

The voltage-gated ion channel activity depends on both activation (transition from the resting state to the open state) and inactivation. Inactivation is a self-restraint mechanism to limit ion conduction and is as crucial to membrane excitability as activation. Inactivation can occur when the channel is open or closed. Although open-state inactivation is well understood, the molecular basis of closed-state inactivation has remained elusive. We report cryo-EM structures of human KV4.2 channel complexes in inactivated, open, and closed states. Closed-state inactivation of KV4 involves an unprecedented symmetry breakdown for pore closure by only two of the four S4-S5 linkers, distinct from known mechanisms of open-state inactivation. We further capture KV4 in a putative resting state, revealing how voltage sensor movements control the pore. Moreover, our structures provide insights regarding channel modulation by KChIP2 and DPP6 auxiliary subunits. Our findings elucidate mechanisms of closed-state inactivation and voltage-dependent activation of the KV4 channel.

Impacts of land use/land cover changes on ecosystem services in ecologically fragile regions.

High-density human activities have rapidly changed the pattern of urban land use/land cover (LULC), affecting the supply of urban ecosystem services (ESs). This poses a challenge to the balance of urban development and ecological protection, which may be more serious in ecologically fragile regions. This study identified key LULC change (LULCC) impacts on ESs in Ordos, an ecologically fragile region in Northwest China. The urbanization process of Ordos will continue in 2030 under the business-as-usual scenario due to its strategic positioning in the National Energy Base of China. The future LULC simulation results showed that developed land in eastern Ordos will continue to expand in 2030, and more forest and grassland will appear in western Ordos as a result of ecological restoration. The results of the InVEST model in calculating four important ESs showed that the ES supply in the densely populated areas (eastern Ordos) has declined, and more attention must be given to natural vegetation protection in the urbanization process. Although carbon storage in the western region has increased due to afforestation, this also reduces the water yield supply, which may exacerbate the water shortage in Ordos. Supported by this framework, more sustainable urban land use management can be undertaken to balance the conflict between ecological protection and urbanization. This will contribute to regional ecological health and sustainable urban development.

Reciprocal associations between shyness, depression, and Internet gaming disorder among Chinese adolescents: A cross-lagged panel study.

While video games are one of the most common online entertainment activities, Internet gaming disorder (IGD) in adolescents is a critical issue that has become a widely raised public concern. This one-year longitudinal study examined the reciprocal associations between shyness, depression, and IGD symptoms in a sample of Chinese adolescents. A fully cross-lagged panel design was used, in which shyness, depression, and IGD symptoms were assessed at two time points with an interval of one year (T1 and T2). A total of 1,047 junior high school students (504 boys; 543 girls; mean age = 12.45 years) participated in the study. Cross-lagged analysis results indicated a significant positive correlation between shyness, depression, and IGD symptoms, as well as a dynamic and bidirectional relationship between them. Specifically, T1 shyness positively predicted T2 depression symptoms (ß = 0.167, p < 0.001), T1 depression symptoms positively predicted T2 shyness (ß = 0.141, p < 0.01), and T1 IGD symptoms positively predicted T2 depression symptoms (ß = 0.073, p < 0.05). In addition to these findings, gender differences were identified in shyness (T1 and T2), IGD symptoms (T1 and T2), and depression symptoms (T2). The results also indicated that shyness and symptoms of depression could significantly positively predict each other over time, and IGD symptoms could significantly predict depression symptoms. However, depression symptoms could not significantly predict IGD symptoms over the one-year study period, and there was no significant two-way prediction between shyness and IGD symptoms. Thus, this study reveals possible reciprocal associations between shyness, depression, and IGD symptoms in Chinese adolescents and provides insights and suggestions for reducing online gaming addiction among adolescents from the perspective of shyness and depression.

The anti-inflammatory activity of specific-sized hyaluronic acid oligosaccharides.

Severe acute inflammatory conditions may cause tissue damage, sepsis, and death. As a critical component of the extracellular matrix, hyaluronic acid (HA) has been reported to possess pro- and anti-inflammatory properties via Toll-like receptors (TLRs). In this study, we prepared different sizes and structures of HA oligosaccharides and derivatives and investigated the effects on inflammation in vitro and in vivo. Our results showed that HA tetra-saccharide was the minimum fragment to enhance inflammation, whereas HA disaccharide competitively blocked TLR4-dependent inflammation. The enzymatic HA disaccharide (ΔHA2) inhibited lipopolysaccharide (LPS)-induced inflammation. Based on structure-activity relationship analysis, we observed that anti-inflammatory activity depended on HAs polymerization degree, acetyl group, and configuration. In addition, we demonstrated that ΔHA2 reduced LPS-induced pro-inflammatory cytokines production in vivo. ΔHA2, a native metabolite of HA polysaccharides, may have a potential role against LPS-mediated inflammatory diseases.

Effect of flushing temperature on preparation ability of rotary nickel-titanium files.

PURPOSE: The effect of flushing at different temperatures on the preparation ability of rotary nickel-titanium files was investigated to provide guideline for clinical application. METHODS: Sixty ProTaper Universal F1 rotary nickel-titanium files were randomly divided into three groups treated by flushing at 6°C, 23°C, and 40°C. Root canal preparation was conducted by step-by-step method on standardized nickel-titanium instrument fracture models. During preparation, the thrust force was set as 10 N, and water was continuously flushed. The motor speed was 350 rpm (rounds per minute), and the torque was 3.0 N cm. When the set torque was reached, the motor automatically rotated in the reverse direction and was pulled out. RESULTS: Root canal preparation was performed using ProTaper Universal F1 rotary nickel-titanium files treated by flushing. The numbers of rotations before the device was fracture were 429.33 ± 214.68, 821.92 ± 410.43, and 1304.92 ± 297.81, respectively. When each root canal was completed, the numbers of instrument rotations were 272.15 ± 88.30, 188.85 ± 34.36, and 163.41 ± 16.18, respectively. Rank sum test and analysis of variance were performed by IBM SPSS Statistics v21.0 software, and both of them were p < 0.01, indicating that the number of cycles to failure (NCF) and the number of instrument rotations for each root tube were statistically different at the three temperatures. CONCLUSIONS: The self-made resin-simulated curved root canal can replace the real root canal to complete the root canal preparation experiment. The group of nickel-titanium files treated by flushing at 23°C can prepare more root canals and prolong the life of nickel-titanium files than at 6°C. When flushing was done at 40°C, the number of root canals prepared by nickel-titanium files was the highest, and it was not easy to damage the instrument, but lateral perforation occurred easily during root canal preparation.

VEGF as a potential molecular target in periodontitis: a meta-analysis and microarray data validation.

BACKGROUND: Anti-vascular endothelial growth factor (VEGF) has been used as a therapeutic drug for the treatment of some human diseases. However, no systematic evidence is performed for assessing the role of VEGF in periodontitis. We carried out a comprehensive analysis to explore the role of VEGF in patients with periodontitis. METHODS: Multiple databases were searched for eligible studies. The pooled standardized mean difference (SMD) and odds ratio (OR) with the corresponding 95% confidence interval (CI) were applied to evaluate the effect sizes. Clinical data validation from microarray analysis was used. Pathway and process enrichment analysis were also investigated. RESULTS: Finally, 16 studies were included in this analysis. Overall, there was a significantly higher level of VEGF expression in periodontitis than in healthy control groups (OR = 16.64, 95% CI = 6.01-46.06, P < 0.001; SMD = 2.25, 95% CI = 1.25-3.24, P < 0.001). Subgroup analysis of ethnicity showed that VEGF expression was still correlated with periodontitis in the Asian and European populations. No correlation was observed between VEGF expression and age, gender, and pathological type. A large clinical sample data (427 periodontitis patients and 136 healthy controls) further validated that VEGF expression was higher in periodontitis than in healthy control groups (P = 0.023). VEGF was involved in many functions such as blood vessel development, response to growth factor, cell proliferation, and cell adhesion. CONCLUSIONS: High levels of VEGF were credible implications for the development of periodontitis. Anti-VEGF therapy may be valuable for the treatment of periodontitis in clinical management.