Cathodal bilateral transcranial direct-current stimulation regulates selenium to confer neuroprotection after rat cerebral ischaemia-reperfusion injury.

Non-invasive transcranial direct-current stimulation (tDCS) is a safe ischaemic stroke therapy. Cathodal bilateral tDCS (BtDCS) is a modified tDCS approach established by us recently. Because selenium (Se) plays a crucial role in cerebral ischaemic injury, we investigated whether cathodal BtDCS conferred neuroprotection via regulating Se-dependent signalling in rat cerebral ischaemia-reperfusion (I/R) injury. We first showed that the levels of Se and its transport protein selenoprotein P (SEPP1) were reduced in the rat cortical penumbra following I/R, whereas cathodal BtDCS prevented the reduction of Se and SEPP1. Interestingly, direct-current stimulation (DCS) increased SEPP1 level in cultured astrocytes subjected to oxygen-glucose deprivation reoxygenation (OGD/R) but had no effect on SEPP1 level in OGD/R-insulted neurons, indicating that DCS may increase Se in ischaemic neurons by enhancing the synthesis and secretion of SEPP1 in astrocytes. We then revealed that DCS reduced the number of injured mitochondria in OGD/R-insulted neurons cocultured with astrocytes. DCS and BtDCS prevented the reduction of the mitochondrial quality-control signalling, vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4), in OGD/R-insulted neurons cocultured with astrocytes and the ischaemic brain respectively. Under the same experimental conditions, downregulation of SEPP1 blocked DCS- and BtDCS-induced upregulation of VAMP2 and STX4. Finally, we demonstrated that cathodal BtDCS increased Se to reduce infract volume following I/R. Together, the present study uncovered a molecular mechanism by which cathodal BtDCS confers neuroprotection through increasing SEPP1 in astrocytes and subsequent upregulation of SEPP1/VAMP2/STX4 signalling in ischaemic neurons after rat cerebral I/R injury. KEY POINTS: Cathodal bilateral transcranial direct-current stimulation (BtDCS) prevents the reduction of selenium (Se) and selenoprotein P in the ischaemic penumbra. Se plays a crucial role in cerebral ischaemia injury. Direct-current stimulation reduces mitochondria injury and blocks the reduction of vesicle-associated membrane protein 2 (VAMP2) and syntaxin-4 (STX4) in oxygen-glucose deprivation reoxygenation-insulted neurons following coculturing with astrocytes. Cathodal BtDCS regulates Se/VAMP2/STX4 signalling to confer neuroprotection after ischaemia.

Schisandrin B Alleviates LPS Induced Mitochondrial Damage in C28I2 Cells.

Osteoarthritis is a common joint disease characterized by damage to the joint cartilage that occurs throughout the entire joint tissue. This damage primarily manifests as pain in the affected area. In clinical practice, medication is commonly used to relieve pain, but the treatment's effectiveness is poor and recurrent attacks are likely. Schisandrin B is the most abundant biphenylcyclohexene lignan found in the traditional Chinese medicine Schisandra chinensis, and it possesses various pharmacological effects. This study aims to investigate the protective effect of Schisandrin B on mitochondrial damage in osteoarthritis (C28I2 cells) under an inflammatory environment induced by LPS. Cell proliferation and activity, scratch tests, and LDH release tests are utilized to assess cell growth and migration ability. The immunofluorescence assay was used to detect the expression levels of proliferation and apoptosis proteins. The Western Blot assay was used to detect the expression levels of mitochondrial fusion and division proteins. The JC-1 assay was used to detect changes in mitochondrial membrane potential. The mitochondrial fluorescence probe assay was used to detect mitochondrial activity. Through research, it was found that Schisandrin B promotes the proliferation, growth, and migration of C28I2 cells, reduces apoptosis of C28I2 cells, balances mitochondrial fusion and division, stabilizes mitochondrial membrane potential, and promotes mitochondrial activity in an LPS induced inflammatory environment.

CCR2 is a potential therapeutic target in peri-implantitis.

AIM: CCR2 (C-C chemokine receptor type 2) plays a crucial role in inflammatory and bone metabolic diseases; however, its role in peri-implantitis remains unclear. This study aimed to explore whether CCR2 contributes to peri-implantitis and the treatment effects of cenicriviroc (CVC) on peri-implant inflammation and bone resorption. MATERIALS AND METHODS: The expression of CCR2 was studied using clinical tissue analysis and an in vivo peri-implantitis model. The role of CCR2 in promoting inflammation and bone resorption in peri-implantitis was evaluated in Ccr2-/- mice and wild-type mice. The effect of CVC on peri-implantitis was evaluated using systemic and local dosage forms. RESULTS: Human peri-implantitis tissues showed increased CCR2 and CCL2 levels, which were positively correlated with bone loss around the implants. Knocking out Ccr2 in an experimental model of peri-implantitis resulted in decreased monocyte and macrophage infiltration, reduced pro-inflammatory cytokine generation and impaired osteoclast activity, leading to reduced inflammation and bone loss around the implants. Treatment with CVC ameliorated bone loss in experimental peri-implantitis. CONCLUSIONS: CCR2 may be a potential target for peri-implantitis treatment by harnessing the immune-inflammatory response to modulate the local inflammation and osteoclast activity.

Ridge preservation in periodontally compromised molar sockets with and without primary wound closure: A comparative controlled clinical trial.

OBJECTIVE: This study aimed to compare hard- and soft-tissue changes after ridge preservation in periodontally compromised molar sockets with and without primary wound closure. MATERIALS AND METHODS: Forty molars with severe periodontitis requiring extraction were included and allocated to two treatment modalities. After tooth extraction, the sockets were filled with deproteinized bovine bone mineral and covered with a bioabsorbable porcine collagen membrane. Primary wound closure was achieved in the control group, whereas the test group underwent minimally invasive open healing. The dimensions of the bone and soft tissue were recorded at baseline and 6 months. RESULTS: Over 6 months, the control and test groups had similar mean ridge heights at the center of sockets of 8.59 ± 2.47 mm and 8.47 ± 2.51 mm, respectively. The total volume of the control group increased from 1070.17 to 1713.52 mm3 for a mean gain of 643.35 mm3 , whereas that of the test group increased from 992.51 to 1514.05 mm3 for a mean gain of 521.54 mm3 . Compared with the test group, the control group showed a statistically significant decrease in keratinized tissue width of 1.08 ± 1.63 mm. CONCLUSIONS: Bone dimensional changes following ridge preservation with and without primary wound closure were comparable. ARP without primary wound closure preserves more keratinized tissue than that with (Chinese Clinical Trial Registry: ChiCTR-ONN-16009433).

Effects of Potassium-Containing Fertilizers on Sugar and Organic Acid Metabolism in Grape Fruits.

To identify suitable potassium fertilizers for grape (Vitis vinifera L.) production and study their mechanism of action, the effects of four potassium-containing fertilizers (complex fertilizer, potassium nitrate, potassium sulfate, and potassium dihydrogen phosphate) on sugar and organic acid metabolism in grape fruits were investigated. Potassium-containing fertilizers increased the activity of sugar and organic acid metabolism-related enzymes at all stages of grape fruit development. During the later stages of fruit development, potassium-containing fertilizers increased the total soluble solid content and the sugar content of the different sugar fractions and decreased the titratable acid content and organic acid content of the different organic acid fractions. At the ripening stage of grape fruit, compared with the control, complex fertilizer, potassium nitrate, potassium sulfate, and potassium dihydrogen phosphate increased the total soluble solid content by 1.5, 1.2, 3.5, and 3.4 percentage points, decreased the titratable acid content by 0.09, 0.06, 0.18, and 0.17 percentage points, respectively, and also increased the total potassium content in grape fruits to a certain degree. Transcriptome analysis of the differentially expressed genes (DEGs) in the berries showed that applying potassium-containing fertilizers enriched the genes in pathways involved in fruit quality, namely, carbon metabolism, carbon fixation in photosynthetic organisms, glycolysis and gluconeogenesis, and fructose and mannose metabolism. Potassium-containing fertilizers affected the expression levels of genes regulating sugar metabolism and potassium ion uptake and transport. Overall, potassium-containing fertilizers can promote sugar accumulation and reduce acid accumulation in grape fruits, and potassium sulfate and potassium dihydrogen phosphate had the best effects among the fertilizers tested.

Layperson assessment of smile lines and upper lip combined images in smile esthetics.

STATEMENT OF PROBLEM: The esthetic assessment of smile lines by laypersons is a subject of ongoing debate. However, smile lines often appear with different types of upper lip curvature, which further complicates the esthetic assessment process, and studies on this combination are lacking. PURPOSE: The purpose of this clinical study was to investigate a layperson's esthetic perception of smile lines and upper lip combined images. MATERIAL AND METHODS: Twenty-six smile images resulting from combinations of 3 upper lip types, 4 anterior smile line types, and 3 posterior smile line types were generated by an image editing software program. Eighty-three laypersons (39 men and 44 women; 18 to 35 years of age) completed rating images using a visual analog scale. Unattractive smiles were designated to be those with scores <50 and attractive ones with scores ≥50. Data were analyzed using 1-way analysis of variance and Bonferroni post hoc tests (α=.05). RESULTS: High anterior smile line with gingival display >4 mm obtained significantly lower scores of <50 when combined with all upper lip curvatures (upward: 28.29 ±22.79, straight: 38.74 ±23.00, downward: 30.67 ±22.25, P<.01). High anterior smile lines with gingival display ≤4 mm combined with upward and straight upper lip curvature images obtained significantly higher scores, and all were ≥50 (upward: 63.24 ±22.22, straight: 61.40 ±21.58, P<.01). CONCLUSIONS: From a layperson's perspective, high anterior smile lines with gingival display >4 mm combined with any lip type were determined to be unattractive. If gingival display was ≤4 mm combined with both upward and straight lip types, the smile was assessed as attractive.

[Histopathological characteristics of peri-implant soft tissue in reconstructed jaws with vascularized bone flaps].

OBJECTIVE: To analyze the histopathological characteristics of peri-implant soft tissue in reconstructed jaws and the changes after keratinized mucosa augmentation (KMA) with free gingival graft (FGG). METHODS: Twenty patients were enrolled in this study. Five patients of them, who were periodontal and systemic healthy and referred for crown lengthening before restoration with healthy keratinized gingiva collected were enrolled as healthy controls. 15 patients of them were with fibula or iliac bone flaps jaw reconstruction (10 with fibula flap and 5 with iliac flap), who were referred to FGG and implant exposures before restoration. Soft tissue was collected before FGG in reconstructed jaws, and in 5 patients (3 with fibula flap and 2 with iliac flap) 8 weeks after FGG if a second surgery was conducted. Histological analysis with hematoxylin-eosin stain and immunological analysis to interlukin-1 (IL-1), interlukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were performed. RESULTS: Thickness from the bottom of stratum basale to the top of stratum granulosum and thickness of keratinized layer in reconstructed jaws were significantly lower compared with that of natural healthy keratinized gingiva [0.27 (0.20, 0.30) mm vs. 0.36 (0.35, 0.47) mm, P<0.05; 16.49 (14.90, 23.37) µm vs. 26.37 (24.12, 31.53) µm, P<0.05]. In the reconstructed area, thickness from the bottom of stratum basale to the top of stratum granulosum increased after KMA with FGG [0.19 (0.16, 0.25) mm vs. 0.38 (0.25, 0.39) mm, P=0.059] and the thickness of keratinized layer significantly increased after KMA with FGG [16.42 (14.16, 22.35) µm vs. 28.57 (27.16, 29.14) µm, P<0.05], which was similar to that in the control group. Furthermore, the number of positive cells of IL-1, IL-6 and TNF-α significantly increased after KMA [0.67 (0.17, 8.93) vs. 11.00 (9.16, 18.00); 13.00 (8.50, 14.14) vs. 21.89 (15.00, 28.12); 0.22 (0.04, 0.63) vs. 2.83 (1.68, 5.00), respectively, P<0.05] as well as the average optical density value [0.15 (0.14, 0.17) vs. 0.18 (0.17, 0.21); 0.28 (0.26, 0.33) vs. 0.36 (0.33, 0.37); 0.23 (0.22, 0.29) vs. 0.30 (0.28, 0.42), respectively, P<0.05], which was similar to that in the healthy keratinized gingiva. CONCLUSION: The lack of rete pegs and inflammatory factors were common in soft tissue with jaw reconstruction. FGG can improve the quality of the epithelium and may improve the stability of the mucosa around implants.

Transcranial direct-current stimulation confers neuroprotection by regulating isoleucine-dependent signalling after rat cerebral ischemia-reperfusion injury.

Isoleucine is a branched chain amino acid. The role of isoleucine in cerebral ischemia-reperfusion injury remains unclear. Here, we show that the concentration of isoleucine is decreased in cerebrospinal fluid in a rat model of cerebral ischemia-reperfusion injury, the rat middle cerebral artery occlusion (MCAO). To our surprise, the level of intraneuronal isoleucine is increased in an in vitro model of cerebral ischemia injury, the oxygen-glucose deprivation (OGD). We found that the increased activity of LAT1, an L-type amino acid transporter 1, leads to the elevation of intraneuronal isoleucine after OGD insult. Reducing the level of intraneuronal isoleucine promotes cell survival after cerebral ischemia-reperfusion injury, but supplementing isoleucine aggravates the neuronal damage. To understand how isoleucine promotes ischemia-induced neuronal death, we reveal that isoleucine acts upstream to reduce the expression of CBFB (core binding factor ß, a transcript factor involved in cell development and growth) and that the phosphatase PTEN acts downstream of CBFB to mediate isoleucine-induced neuronal damage after OGD insult. Interestingly, we demonstrate that direct-current stimulation reduces the level of intraneuronal isoleucine in cortical cultures subjected to OGD and that transcranial direct-current stimulation (tDCS) decreases the cerebral infarct volume of MCAO rat through reducing LAT1-depencent increase of intraneuronal isoleucine. Together, these results lead us to conclude that LAT1 over activation-dependent isoleucine-CBFB-PTEN signal transduction pathway may mediate ischemic neuronal injury and that tDCS exerts its neuroprotective effect by suppressing LAT1 over activation-dependent signalling after cerebral ischemia-reperfusion injury.

High beam quality yellow laser at 588†nm by an intracavity frequency-doubled composite Nd:YVO4 Raman laser.

High beam quality 588 nm radiation was realized based on a frequency-doubled crystalline Raman laser. The bonding crystal of YVO4/Nd:YVO4/YVO4 was used as the laser gain medium, which can accelerate the thermal diffusion. The intracavity Raman conversion and the second harmonic generation were realized by a YVO4 crystal and an LBO crystal, respectively. Under an incident pump power of 49.2 W and a pulse repetition frequency of 50 kHz, the 588 nm power of 2.85 W was obtained with a pulse duration of 3 ns, corresponding to a diode-to-yellow laser conversion efficiency of 5.75% and a slope efficiency of 7.6%. Meanwhile, a single pulse's pulse energy and peak power were 57 µJ and 19 kW, respectively. The severe thermal effects of the self-Raman structure were overcome in the V-shaped cavity, which has excellent mode matching, and combined with the self-cleaning effect of `Raman scattering, the beam quality factor M2 was effectively improved, which was measured optimally to be Mx 2 = 1.207, and My 2 = 1.200, with the incident pump power being 49.2 W.

PDGF-C promotes cell proliferation partially via downregulating BOP1.

Platelet-derived growth factor C (PDGF-C) is a member of PDGF/VEGF family, which is well-known for important functions in the vascular system. It is widely reported that PDGF-C is able to modulate cell proliferation. However, it is still not very clear about this cell modulating mechanism at the molecular level. In a screening of factors regulated by PDGF-C protein, we fished out a factor called block of proliferation 1 (BOP1), which is a pivotal regulator of ribosome biogenesis and cell proliferation. In this study, we investigated the regulation of BOP1 by PDGF-C and its role in modulating cell proliferation. We found that BOP1 was downregulated at both mRNA and protein levels in cells treated with PDGF-C-containing conditioned medium. On the other hand, BOP1 was upregulated in PDGF-C deficient mice. Furthermore, we confirmed that overexpression of BOP1 inhibited HEK293A cell proliferation, whereas knockdown of BOP1 promoted cell proliferation. The mitogenic effect of PDGF-C could be attenuated by downregulation of BOP1. Our results demonstrate a clear PDGF-C-BOP1 signaling that modulates cell proliferation.

CCL2 is a key regulator and therapeutic target for periodontitis.

AIM: Our previous study revealed that the C-C motif chemokine receptor 2 (CCR2) is a promising target for periodontitis prevention and treatment. However, CCR2 is a receptor with multiple C-C motif chemokine ligands (CCLs), including CCL2, CCL7, CCL8, CCL13 and CCL16, and which of these ligands plays a key role in periodontitis remains unclear. The aim of the present study was to explore the key functional ligand of CCR2 in periodontitis and to evaluate the potential of the functional ligand as a therapeutic target for periodontitis. MATERIALS AND METHODS: The expression levels and clinical relevance of CCR2, CCL2, CCL7, CCL8, CCL13 and CCL16 were studied using human samples. The role of CCL2 in periodontitis was evaluated by using CCL2 knockout mice and overexpressing CCL2 in the periodontium. The effect of local administration of bindarit in periodontitis was evaluated by preventive and therapeutic medication in a mouse periodontitis model. Microcomputed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, bead-based immunoassays and flow cytometry were used for histomorphology, molecular biology and cytology analysis. RESULTS: Among different ligands of CCR2, only CCL2 was significantly up-regulated in periodontitis gingival tissues and was positively correlated with the severity of periodontitis. Mice lacking CCL2 showed milder inflammation and less bone resorption than wild-type mice, which was accompanied by a reduction in monocyte/macrophage recruitment. Adeno-associated virus-2 vectors overexpressing CCL2 in Ccl2-/- mice gingiva reversed the attenuation of periodontitis in a CCR2-dependent manner. In ligation-induced experimental periodontitis, preventive or therapeutic administration of bindarit, a CCL2 synthesis inhibitor, significantly inhibited the production of CCL2, decreased the osteoclast number and bone loss and reduced the expression levels of proinflammatory cytokines TNF-α, IL-6 and IL-1ß. CONCLUSIONS: CCL2 is a pivotal chemokine that binds to CCR2 during the progression of periodontitis, and targeting CCL2 may be a feasible option for controlling periodontitis.

Mucosal bleeding correlates with submucosal microbial dysbiosis in peri-implant mucositis of patients with periodontitis.

OBJECTIVES: This study aimed to investigate the relationship between microbial communities and the severity of peri-implant mucosal bleeding in peri-implant mucositis. MATERIALS AND METHODS: Submucosal plaque samples were collected from 54 implants divided into the healthy implant (HI) group, peri-implant mucositis (PM) group, and peri-implantitis (PI) group. Sequencing of 16S rRNA was performed using the Illumina MiSeq platform. Alpha diversity (i.e., Shannon and Chao index) and beta diversity were used to measure microbial diversity within and between microbial communities, respectively. Differences in microbial taxa between groups were assessed via linear discriminate analysis effect size. Correlation between the modified sulcus bleeding index (mSBI) and microbial dysbiosis index (MDI) was examined using Spearman correlation analysis and linear models. RESULTS: The submucosal bacterial richness (Chao index) was positively correlated with the mean mSBI in the PM group. As the mean mSBI increased in the PM group, the beta diversity became closer to that of the PI group. In the PM group, the abundances of 47 genera were significantly correlated with the mean mSBI, and the MDI was positively associated with the mean mSBI. Fourteen of the forty-seven genera were discriminative taxa between the HI and PI groups, and the abundances of these biomarkers became closer to those in the PI group in the progression of peri-implant disease. CONCLUSIONS: A higher mSBI value corresponded to a higher risk of microbial dysbiosis in peri-implant mucositis. The biomarkers identified may be useful for monitoring the progression of peri-implant disease.

Identification of Key Genes Induced by Different Potassium Levels Provides Insight into the Formation of Fruit Quality in Grapes.

Inadequate potassium (K) availability is a common abiotic stress that limits the growth and quality of fruit trees. Few studies have investigated the physiological and molecular responses of grapes at different potassium levels. In this study, an integrated approach was developed for grapevines grown at four different potassium fertilization levels [0 (K0-CK), 150 (K150), 300 (K300), and 450 (K450) g/plant] in combination with metabolite measurements and transcript analysis. The results showed that different K levels affected the accumulation of sugars and anthocyanins in the fruit. At 78 days after bloom (DAB), the K150, K300, and K450 treatments increased soluble sugar content by 37.39%, 31.10% and 32.59%, respectively, and anthocyanin content by 49.78%, 24.10%, and 13.06%, respectively, compared to K0. Weighted gene co-expression network analysis (WGCNA) of DEGs identified a network of 11 grapevines involved. During fruit development, potassium application promoted the accumulation of anthocyanins and sugars in fruit by regulating the up-regulation of GST, AT, UFGT and SPS, HT, PK gene expressions. These results suggest that potassium deficiency inhibits anthocyanin and sugar metabolism. In addition, it promotes the up-regulation of KUP expression, which is the main cause of K accumulation in fruits. Together, our data revealed the molecular mechanism in response to different K levels during fruit quality formation and provides the scientific foundation for the improvement of fruit quality by adding K fertilizer.

Rapid oxidative removal of Fe2+ and Mn2+ from acidic mining wastewater by a new-type biofilter system: application and mechanism.

Aimed at the problem of excessive concentration of Fe2+ and Mn2+ in acidic mining wastewater during mining and utilization, a new rapid oxidative removal technology of Fe2+ and Mn2+ by a new-type biofilter system was designed and tested. The new-type biofilter system was constructed using a bioreactor filled with special mature bioceramic pellets after continuous biofilm cultivation as the filter layers. The results indicated that the biofilter system could efficiently treat five times its volume of wastewater per hour. The Fe2+ concentration of the influent wastewater was about 500 mg/L, and its Mn2+ concentration was about 20 mg/L. The average Fe2+ and Mn2+ removal rates could reach 99.7% and 90.8%, respectively. In addition, scanning electron microscopy and energy dispersive spectroscopy-energy dispersive spectroscopy and X-ray photoelectron spectroscopy were applied to analyze the migration distribution and valence change of Fe and Mn ions to clarify the removal mechanism of Fe2+ and Mn2+ using the biofilter system. The results showed that iron oxidation products were mainly coated at the surface of the mature bioceramic pellets and could be easily washed out from the filter layer with flowing water, while manganese oxidation products tended to accumulate between the pores of the mature bioceramic pellets. Furthermore, the final filtration products were multivalent complex oxides, indicating that the high-valent oxidation products could adsorb Fe and Mn ions, which were mainly removed by the oxidation effect.

Invited Commentary: Estimation and Bounds Under Data Fusion.

In their recent article, Ogburn et al. (Am J Epidemiol. 2021;190(6):1142-1147) raised a cautionary tale for epidemiologic data fusion: Bias may occur if a variable that is completely missing in the primary data set is imputed according to a regression model estimated from an auxiliary data set. However, in some specific settings, a solution may exist. Focusing on a linear outcome regression model with a missing covariate, we show that the bias can be eliminated if the underlying imputation model for the missing covariate is nonlinear in the common variables measured in both data sets. Otherwise, we describe 2 alternative approaches existing in the data fusion literature that could partially resolve this issue: One fits the outcome model by leveraging an additional validation data set containing joint observations of the outcome and the missing covariate, and the other offers informative bounds for the outcome regression coefficients without using validation data. We justify these 3 methods in a linear outcome model and briefly discuss their extension to general settings.

Critical roles for CCR2 and the therapeutic potential of cenicriviroc in periodontitis: A pre-clinical study.

AIM: CCR2 plays important roles in many inflammatory and bone metabolic diseases, but its specific role in periodontitis is unknown. In the present study, we aimed to explore the role of CCR2 in the progression of periodontitis and evaluate the effect of cenicriviroc (CVC) on periodontitis. MATERIALS AND METHODS: The expression of CCR2 was studied in patients with periodontitis and in ligation-induced murine model of periodontitis. The role of CCR2 in promoting inflammation and bone resorption in periodontitis was evaluated in Ccr2-/- mice and wild-type mice. The effect of CVC in the prevention and treatment of periodontitis was evaluated by systemic and local medication. Microcomputed tomography, haematoxylin and eosin staining, tartrate-resistant acid phosphatase staining, quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and flow cytometry were used for histomorphology, molecular biology, and cytology analysis, respectively. RESULTS: In this study, we demonstrated that CCR2 was highly expressed in human and murine periodontitis and that CCR2 deficiency was associated with decreased inflammatory monocyte and macrophage infiltration and inflammatory mediators, osteoclast number and alveolar bone resorption. Prevention and treatment with CVC significantly reduced the severity of periodontitis, regardless of whether it was administered systemically or locally. CONCLUSIONS: CCR2 plays an important role in the development and progression of periodontitis, and CVC is a potential drug for the prevention and treatment of periodontitis.

Evaluation of implant placement following ridge preservation in periodontally compromised molar extraction sockets: Three-year results of a prospective cohort study.

OBJECTIVE: To investigate the 3-year implant-related outcomes following alveolar ridge preservation in periodontally compromised molar sockets. MATERIAL AND METHODS: Thirty implants were placed in 26 patients following either ridge preservation (test, n = 16) or natural healing (control, n = 14) at deficient molar extraction sites after a 6-month healing period. The need for additional augmentation procedures at implant placement was recorded. Patients were assessed for 3 years following a definitive restoration. Patient information being collected included modified plaque index, the modified sulcus bleeding index, the peri-implant probing depth clinically, and alterations of marginal bone level (MBL) radiographically. RESULTS: There was a 100% survival rate of implants in both groups after 3-year follow-up. During implant placement operation, 35.7% in the control group and 6.3% in the test group required additional augmentation procedures. No statistically significant differences were determined for peri-implant parameters and marginal bone levels between the two groups. The overall mean difference of MBL was 0.072 mm (95% CI [-0.279, 0.423]) during the 3 years of follow-up. The success rate was 81.2% in the test and 78.6% in the control group. CONCLUSIONS: Implants placed into periodontally compromised molar-extracted sites after ridge augmentation resulted in comparable outcomes to implant placement at naturally healed sites after 3-year functional loading. (Chinese Clinical Trial Registry ChiCTR-ONN-16009433).

Ridge preservation in maxillary molar extraction sites with severe periodontitis: a prospective observational clinical trial.

OBJECTIVES: To assess alveolar bone changes and treatment modality alterations after ridge preservation on maxillary molar extraction sockets with severe periodontitis, compared to natural healing. MATERIAL AND METHODS: Thirty-six maxillary infected-molar teeth either receiving ridge preservation (RG group) or undergoing natural healing (NT group) were investigated. Cone-beam computed tomography (CBCT) scanning was performed immediately after surgery (the baseline) and repeated 6 months later to measure the linear and volumetric changes of the sockets. RESULTS: Based on radiographic measurements, alveolar bone width decreased by 1.58 ± 4.61 mm in the NT group but increased by 3.74 ± 4.17 mm in the RG group (p < 0.05). Significant increases in ridge height at the center of both the NT (7.54 ± 4.54 mm) and RG (9.20 ± 3.26 mm) groups were observed. Mean sinus pneumatization was 0.19 ± 0.45 mm in the RG group and 0.59 ± 0.63 mm in the NT group (p < 0.05). The relative increase in total ridge volume was 8.0% and 35.5% in the NT and RG group, respectively (p < 0.05). Implant placement with additional sinus augmentation procedure was performed in 16.7% of the RG group cases, whereas 50% in the NT group cases. CONCLUSIONS: Ridge preservation in the maxillary molar extraction sockets with severe periodontitis can improve alveolar ridge dimensions and decrease the necessity of advanced regenerative procedures at implant placement compared to natural healing. CLINICAL RELEVANCE: Ridge preservation on maxillary molar extraction sockets with severe periodontitis maintained the vertical bone height more efficiently and resulted in less need for sinus augmentation procedures at 6 months compared to natural healing.

RIPK3-Dependent Necroptosis Activates MCP-1-Mediated Inflammation in Mice after Intracerebral Hemorrhage.

BACKGROUND: Recent studies have reported that receptor-interacting protein kinase 3 (RIPK3)-dependent necroptosis is related to the pathological process of intracerebral hemorrhage (ICH). Some studies support the view that inhibiting necroptosis is a key mechanism preventing inflammation. Inflammation is a crucial factor contributing to neurological injuries and unfavorable outcomes after ICH. The aim of this study was to clarify the association between necroptosis and monocyte chemoattractant protein-1 (MCP-1)-mediated inflammation and identify a new target for the treatment of ICH. METHODS: An ICH model was established in C57BL/6 mice by injecting collagenase IV into the right basal ganglia. The RIPK3 inhibitor GSK872 was administered through intraventricular injection. Then, we assessed brain edema and neurobehavioral function. Western blotting was employed to detect changes in RIPK3, phospho-mixed lineage kinase domain-like protein (p-MLKL), MCP-1, phospho-c-Jun N-terminal kinase (p-JNK) and interleukin 6 (IL-6) levels in the brain tissue. The localization of RIPK3 and MCP-1 was observed using immunofluorescence staining. Co-immunoprecipitation was performed to determine the interaction between RIPK3 and MCP-1. RESULTS: Compared with the sham group, the levels of RIPK3, p-MLKL, MCP-1, p-JNK and IL-6 were increased post-ICH. GSK872 pretreatment significantly reduced RIPK3, p-MLKL, MCP-1, p-JNK and IL-6 expression, accompanied by mitigated cerebral edema and neurobehavioral defects. RIPK3 and MCP-1 colocalized in the perinuclear region after ICH. We detected the formation of the RIPK3-MCP-1 complex in ICH brain tissue. CONCLUSIONS: There exerted an association between RIPK3 and MCP-1. The inhibition of RIPK3 alleviated MCP-1-mediated inflammation following ICH.

Downregulation of NF-κB by Shp-1 Alleviates Cerebral Venous Sinus Thrombosis-Induced Brain Edema Via Suppression of AQP4.

Aquaporin 4 (AQP4), a water channel protein, has been well studied in arterial stroke-induced brain edema. However, the role of AQP4 in cerebral venous sinus thrombosis (CVST) has not been reported. Here, we showed that AQP4 expression was increased in the brain of a rat CVST model, whereas inhibition of AQP4 decreased cerebral edema. Subsequent experiments showed that Shp-1 (Src homology 2-containing phosphatase-1) expression and NF-κB phosphorylation were upregulated after CVST. We found that Shp-1 inhibition resulted in enhancement of NF-κB activation and increased AQP4 expression accompanied by aggravated brain edema. We further showed that NF-κB inhibition led to decreased AQP4 expression and subsequent attenuation of brain edema but had no significant effect on Shp-1 expression. These results provide the first evidence suggesting that downregulation of NF-κB by Shp-1 alleviates CVST-induced brain edema through suppression of AQP4.