Associated factors of periodontitis and predicted study among young man in China: a population-based cross-sectional study.

BACKGROUND: Periodontitis represents the foremost oral condition in young men, strongly correlated with socioeconomic elements and oral health behaviors. This research aimed to assess the prevalence of periodontitis and associated associations with socio-demographics and oral health practices for subsequent Hazard Ratio (HR) estimation. METHODS: A total of 46,476 young men were recruited to the study between August 2022 and October 2023. A questionnaire on socio-demographic factors and oral health-related behaviors related to periodontitis was completed. The standard procedure was used for oral examination. Logistic regression and hazard ratios were used to estimate the influencing factors, whereas the nomogram was used to predict the risk of periodontitis in young men. RESULTS: A total of 46,476 young men were surveyed and completed the questionnaire. The overall prevalence of periodontitis among young men was 1.74%. Out of these, 1.7% had mild periodontitis and 0.6% had moderate periodontitis. Age and dental calculus were important factors in the periodontal health of young men. This nomogram, which includes 7 easily obtainable clinical characteristics routinely collected during periodontitis risk assessment, provides clinicians with a user-friendly tool to assess the risk of periodontal disease in young men. CONCLUSIONS: Regular dental prophylaxis is crucial for young men to maintain their gingival health and prevent the onset of periodontitis. Dental calculus plays a prominent role in this matter, as it serves as a significant contributing factor.

Periodontal disease and risk of Alzheimer's disease: A two-sample Mendelian randomization.

BACKGROUND: Evidence from observational studies and clinical trials suggests an association between periodontal disease and Alzheimer's disease (AD). However, the causal relationship between periodontal disease and AD remains to be determined. METHODS: We obtained periodontal disease data from the FinnGen database and two sets of AD data from the IEU consortium and PGC databases. Subsequently, we conducted a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between periodontal disease and AD. RESULTS: The results of the random-effects IVW analysis revealed no evidence of a genetic causal relationship between periodontal disease and AD, regardless of whether the AD data from the IEU consortium or the AD data from the PGC database were utilized. No heterogeneity, multiple effects of levels, or outliers were observed in this study. CONCLUSIONS: Our findings indicate that there is no causal relationship between periodontal disease and AD at the genetic level.

Nano implant surface triggers autophagy through membrane curvature distortion to regulate the osteogenic differentiation.

Anodized titania nanotubes have been considered as an effective coating for bone implants due to their ability to induce osteogenesis, whereas the osteogenic mechanism is not fully understood. Our previous study has revealed the potential role of autophagy in osteogenic regulation of nanotubular surface, whereas how the autophagy is activated remains unknown. In this study, we focused on the cell membrane curvature-sensing protein Bif-1 and its effect on the regulation of autophagy. Both autophagosomes formation and autophagic flux were enhanced on the nanotubular surface, as indicated by LC3-II accumulation and p62 degradation. In the meanwhile, the Bif-1 was significantly upregulated, which contributed to autophagy activation and osteogenic differentiation through Beclin-1/PIK3C3 signaling pathway. In conclusion, these findings have bridged the gap between extracellular physical nanotopography and intracellular autophagy activation, which may provide a deeper insight into the signaling transition from mechanical to biological across the cell membrane.

Swim bladder-derived biomaterials: structures, compositions, properties, modifications, and biomedical applications.

Animal-derived biomaterials have been extensively employed in clinical practice owing to their compositional and structural similarities with those of human tissues and organs, exhibiting good mechanical properties and biocompatibility, and extensive sources. However, there is an associated risk of infection with pathogenic microorganisms after the implantation of tissues from pigs, cattle, and other mammals in humans. Therefore, researchers have begun to explore the development of non-mammalian regenerative biomaterials. Among these is the swim bladder, a fish-derived biomaterial that is rapidly used in various fields of biomedicine because of its high collagen, elastin, and polysaccharide content. However, relevant reviews on the biomedical applications of swim bladders as effective biomaterials are lacking. Therefore, based on our previous research and in-depth understanding of this field, this review describes the structures and compositions, properties, and modifications of the swim bladder, with their direct (including soft tissue repair, dural repair, cardiovascular repair, and edible and pharmaceutical fish maw) and indirect applications (including extracted collagen peptides with smaller molecular weights, and collagen or gelatin with higher molecular weights used for hydrogels, and biological adhesives or glues) in the field of biomedicine in recent years. This review provides insights into the use of swim bladders as source of biomaterial; hence, it can aid biomedicine scholars by providing directions for advancements in this field.

The M2 Macrophages Derived Migrasomes From the Surface of Titania Nanotubes Array as a New Concept for Enhancing Osteogenesis.

As newly discovered substrate anchored extracellular vesicles, migrasomes (Migs) may bring a new opportunity for manipulating target cells bioactivities. In this study, the M2 macrophages derived Migs are obtained by titania nanotubes surface (NTs). Due to the benefits of nanostructuring, the NTs surface is not only able to induce RAW264.7 for M2 polarization but also to generate more Migs formation, which can be internalized by following seeded mesenchymal stem cells (MSCs). Then, the NTs surface induced Migs are collected by density-gradient centrifugation for MSCs treatment. As indicated by immunofluorescence staining, alkaline phosphatase activity, and alizarin red staining, the osteogenic differentiation capacity of MSCs is significantly enhanced by Migs treatment, in line with the dosage. By RNA-sequence analysis, the enhancement of osteogenic differentiation is correlated with PI3K-AKT pathway activation that may originate from the M2 polarization state of donor cells. Finally, the Migs are coated onto Ti surface for therapeutic application. Both the in vitro and in vivo analysis reveal that the Migs coated Ti implant shows significant enhancement of osteogenesis. In conclusion, this study suggests that the nanosurface may be a favorable platform for Migs production, which may bring a new concept for tissue regeneration.

Has collateral blood flow any effect on restenosis rate? Our experience.

Objectives: Restenosis is one of the important factors affecting the effectiveness of percutaneous transluminal angioplasty and stenting in the treatment of intracranial atherosclerotic stenosis. We aimed to clarify whether recruitable collateral flow could cause restenosis in patients treated with percutaneous transluminal angioplasty and stenting. Material and methods: Our study retrospectively analyzed patients with symptomatic severe intracranial atherosclerotic stenosis (≥70%) who underwent percutaneous transluminal angioplasty and stenting. We enrolled 28 patients with restenosis and 71 patients without restenosis. We analyzed baseline data, perioperative events, and follow-up results of patients in the two groups. Binary logistic regression analysis was used to identify restenosis predictors. Results: For preoperative stroke, the restenosis group had a greater likelihood of having a previous stroke (89.3%), which was less prevalent in the non-restenosis group (66.2%) (P = 0.020). The restenosis group had a higher rate of re-stroke (21.4 vs. 4.2%, P = 0.022). After binary logistic regression analysis, collateral circulation and residual stenosis were independent risk factors of restenosis, with overall risk (95% confidence intervals) of 5.034 (1.484-4.066, P < 0.001) and 1.064 (1.006-1.125, P = 0.030), respectively. Restenosis risk increased 1.456-fold for each collateral circulation grade increase. However, for each 1% increase in residual stenosis, restenosis risk increased by 5.9% (P = 0.03). The chance of restenosis is minimal when the residual stenosis rate after percutaneous transluminal angioplasty and stent implantation is 15.85%. Conclusions: Good collateral circulation was significantly associated with restenosis in patients undergoing intracranial angioplasty, the residual stenosis rate tends to be 15.85% to reduce restenosis risk. Compared to patients with restenosis, those without restenosis have a low stroke risk during follow-up.

Serotonin transporter imaging agent as a probe for ß-cells of pancreas.

OBJECTIVE: Diabetes mellitus (DM) is one of the major diseases in the world. Nuclear medicine imaging may be able to detect functional status of pancreatic ß cells in vivo, which might elucidate the pathological mechanisms of diabetes and develop individualized treatment plans. In this study, we evaluated the ability of [125I]ADAM, a serotonin transporter (SERT) imaging agent, as a probe for detecting pancreatic ß-cell mass (BCM). METHODS: In vitro cell studies were evaluated in INS-1 cells (rat islet ß cell line). Biodistribution studies were performed in male normal Sprague-Dawley rats and alloxan-induced type 1 diabetes mellitus (T1DM) rats. Distribution and expression of SERT protein in pancreas of rats were also measured by immunofluorescence staining and Western blot. RESULTS: In vitro cell studies showed that the concentration of [125I]ADAM associated with the INS-1 cells was increased gradually with incubation time, and the SERT specific inhibitor, escitalopram, exhibited the inhibitory effect on this interaction. Biodistribution studies also showed that the uptake of [125I]ADAM in the pancreas of normal rats was decreased in the presence of escitalopram. However, in the T1DM rat model with a significant ß cells reduction, the uptake of pancreas was increased when compared with the control. Through immunofluorescence staining and Western blot, it was found that both the endocrine and exocrine cells of the normal pancreas expressed SERT protein, and the level of SERT protein in the exocrine cells was higher than islets. In the diabetic state, the expression of SERT in the exocrine cells was further increased. CONCLUSIONS: The SERT imaging agent, [125I]ADAM, at the present form will not be suitable for imaging ß cells, specifically because there were extraordinarily high non-specific signals contributing from the exocrine cells of pancreas. In addition, we noticed that the level of SERT expression was abnormally elevated in the diabetic state, which might provide an unexpected target for studying the pathological mechanisms of diabetes.

Association between obesity and fracture risk in Chinese women above 50 years of age: a prospective cohort study.

BACKGROUND: Fractures present serious health challenges for older adults, including premature mortality and reduced quality of life. Obesity has become significantly prevalent in China. However, the association between obesity and fractures remains unclear. This study aimed to assess the association between obesity and fractures among Chinese women above 50 years of age. METHODS: A prospective cohort study was designed based on the China Health and Nutrition Survey, using data from 1997 to 2015. The average follow-up duration was seven years. Trained investigators measured body mass index (BMI) and waist circumference (WC) at baseline. Obesity was defined according to World Health Organization recommendations. Waist-to-height ratio (W-HtR) was calculated, with 0.5 as the cutoff value. Onset of fractures, self-reported by the participants during the follow-up period, was the primary outcome. Cox hazard regression models were used to assess the association between BMI, WC, W-HtR and subsequent risk of fracture. A sensitivity analysis was conducted by multiple imputation of missing data on the variables at baseline. RESULTS: A total of 2,641 women aged ≥ 50 years were involved in the study. In all the models, no significant association existed between BMI and fracture risk. However, women with WC ≥ 88 cm had significantly higher risk of fracture than those with WC < 80 cm according to both the unadjusted (HR = 1.744, 95% CI: 1.173-2.591) and adjusted models (HR = 1.796, 95% CI: 1.196-2.695). In addition, W-HtR and fracture risk were positively associated according to both the unadjusted (HR = 1.798, 95% CI: 1.230-2.627) and adjusted models (HR = 1.772, 95% CI: 1.209-2.599). Results of the sensitivity analysis were consistent with those of the above analyses. CONCLUSIONS: Abdominal obesity increased the risk of all-cause fractures in Chinese women ≥ 50 years old. Intervention strategies and measures to prevent or address abdominal obesity would be helpful to decrease the fracture incidence.

Effect of electrochemically dealloying Ti6Al4V abutments on human gingival fibroblasts / 口腔疾病防治

Objective@#To investigate the effects of electrochemically dealloying of Ti6Al4V abutments on human gingival fibroblasts (HGFs) and to provide experimental evidence for surface modification of implant abutments.@*Methods@#The samples were divided into an NC group (negative control, no other treatment on a smooth surface), an NM-1 group (nanomesh-1, electrochemical dealloying treatment in 1 mol/L NaOH 1 h on 2 V voltage), and an NM-2 group (nanomesh-2, electrochemical dealloying treatment in 5 mol/L NaOH 1 h on 2 V voltage). The surface morphologies of the samples and the adhesion of HGFs on the sample surfaces were observed with scanning electron microscopy (SEM). The surface hydrophilicities of the samples were measured with a contact angle measuring instrument. The proliferation of HGFs on the different samples were evaluated with CCK-8, and the expression of adhesion-related genes, including collagen Ⅰ (COL1A1), collagen Ⅲ (COL3A1), fibronectin 1 (FN1), focal adhesion kinase (FAK), vinculin (VCL), integrin α2 (ITGA2), and integrin β1 (ITGB1), on the different samples was measured with qRT-PCR. The expression of vinculin on the surfaces of HGFs was observed via confocal laser scanning microscopy (CLSM) after immunofluorescent staining. Collagen fiber secretion and syntheses of HGFs from different samples were evaluated via Sirius red staining.@*Results@#SEM revealed the formation of ordered and uniform three-dimensional mesh structures on the surfaces of the NM-1 and NM-2 groups, with grid diameters of approximately 30 nm for the NM-1 group and approximately 150 nm for the NM-2 group. Compared with that of the NC group, the water contact angles of the NM-1 group and NM-2 groups were significantly lower (P<0.000 1). Cell proliferation in the NM-1 group was significantly greater than that in the NC group (P<0.01). Moreover, there was no significant difference in the water contact angles or cell proliferation between the NM-1 group and the NM-2 group. SEM revealed that HGFs were adhered well to the surfaces of all samples, while the HGFs in the NM-1 and NM-2 groups showed more extended areas, longer morphologies, and more developed pseudopodia than did those in the NC group after 24 h. qRT-PCR revealed that the expression levels of the adhesion-related genes COL1A1, COL3A1, FN1, FAK and VCL in the NM-1 group were significantly greater than those in the NC and NM-2 groups (P<0.01). The expression of vinculin protein in the NM-1 group was the highest, and the number of focal adhesions was greatest in the NM-1 group (P<0.01). The results of Sirius red staining showed that the NM-1 group had the highest secretion and syntheses of collagen fibers (P<0.000 1).@*Conclusion@#The three-dimensional nanomechanical structure of Ti6Al4V modified by electrochemical dealloying promoted the adhesion, proliferation, collagen fiber secretion and syntheses of HGFs, and electrochemical dealloying of Ti6Al4V with a grid diameter of approximately 30 nm obviously promoted HGF formation.

Predictive factors of poor outcome and mortality among anterior ischaemic stroke patients despite successful recanalisation in China: a secondary analysis of the CAPTURE trial.

OBJECTIVES: This work aimed to analyse the risk factors for poor outcomes and mortality among patients with anterior large vessel occlusion (LVO) ischaemic stroke, despite successful recanalisation. SETTING AND PARTICIPANTS: This study conducted a secondary analysis among patients who underwent successful recanalisation in the CAPTURE trial. The trial took place between March 2018 and September 2020 at 21 sites in China. The CAPTURE trial enrolled patients who had an acute ischaemic stroke aged 18-80 years with LVO in anterior circulation. INTERVENTIONS: Thrombectomy was immediately performed using Neurohawk or the Solitaire FR after randomisation in CAPTURE trial. Rescue treatment was available for patients with severe residual stenosis caused by atherosclerosis. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary goal was to predict poor 90-day survival or mortality within 90 days post-thrombectomy. Univariate analysis, using the χ2 test or Fisher's exact test, was conducted for each selected factor. Subsequently, a multivariable analysis was performed on significant factors (p≤0.10) identified through univariate analysis using the backward selection logistic regression approach. RESULTS: Among the 207 recruited patients, 79 (38.2%) exhibited poor clinical outcomes, and 26 (12.6%) died within 90 days post-thrombectomy. Multivariate analysis revealed that the following factors were significantly associated with poor 90-day survival: age ≥67 years, internal carotid artery (ICA) occlusion (compared with middle cerebral artery (MCA) occlusion), initial National Institutes of Health Stroke Scale (NIHSS) score ≥17 and final modified Thrombolysis in Cerebral Infarction (mTICI) score 2b (compared with mTICI 3). Additionally, the following factors were significantly associated with mortality 90 days post-thrombectomy: initial NIHSS score ≥17, ICA occlusion (compared with MCA occlusion) and recanalisation with more than one pass. CONCLUSIONS: Age, NIHSS score, occlusion site, mTICI score and the number of passes can be independently used to predict poor 90-day survival or mortality within 90 days post-thrombectomy. TRIAL REGISTRATION NUMBER: NCT04995757.

Investigation of nanotopography on SOCE mediated cell migration via live-cell : Imaging on opaque implant surface.

The exploration of cell response to nanotopography has attracted considerable attentions for years. This article focuses on the influence of nanotopography on the intracellular Ca2+ dynamics, the most ubiquitous but ignored second messenger. The classic titanium nanotubes (NT) were fabricated by anodization to formulate nanoporous surfaces. Firstly, the store operative calcium entry (SOCE) in endoplasmic reticulum (ER) and functional Ca2+ release-activated Ca2+ (CRAC) channels were significantly enhanced on NT surfaces that revealed by live-cell Ca2+ imaging and fluorescence resonance energy transfer (FRET) identification of orai1-stim1 connection. To investigate the potential implication of Ca2+ elevation, the dynamic cell migration trajectory was monitored by a self-made holder, which could not only be suitable for the opaque implant surface but also guarantee the focus fields identical during samples shifting. The cell migration on NT surface was more vigorous and rapid, which was correlated with higher focal adhesion proteins expression, Ca2+-dependent calpain activity and stim1 level. In conclusion, this study has confirmed the novel ER Ca2+ hemostasis pathway on nanosurfaces and its crucial role in cell migration regulation, which may help for more biofavorable implant surface design.

Connexin43 reduces LPS-induced inflammation in hDPCs through TLR4-NF-κB pathway via hemichannels.

OBJECTIVES: Connexin43 (Cx43) is involved in the inflammation of many tissue types. Dental caries is infectious disease resulting from mineralized tissue dissolution by a specific bacterial population, causing pulp inflammation. However, Cx43's role in dental pulp remains unclear. Here, we investigated the function of Cx43 during pulp inflammation. MATERIALS AND METHODS: We constructed a dentin injury model in Sprague-Dawley rats to investigate changes in Cx43 expression during pulp inflammation. Cx43 was inhibited in human dental pulp cells (hDPCs) that had been stimulated with lipopolysaccharide (LPS) to investigate the effect of Cx43 on inflammatory response. Promotion of TLR4-NF-κB pathway activity and special Cx43 channel inhibitors were used to clarify the function of Cx43 in hDPCs. RESULTS: Dentin injury led to low-level inflammation in dental pulp. Following dentin injury, Cx43 expression initially decreased before gradually recovering to normal levels. Cx43 inhibition reduced LPS-induced expression of inflammatory cytokines and NF-κB pathway activity. Promotion of NF-κB pathway activity counteracted the effect of Cx43 in hDPCs. Furthermore, inhibition of Cx43 hemichannels reduced LPS-induced inflammatory cytokine expression. CONCLUSIONS: Cx43 is involved in inflammation of dental pulp, while its inhibition reduced LPS-induced inflammation in hDPCs through NF-κB pathway via blockage of hemichannels.

Design, fabrication, and applications of bioinspired slippery surfaces.

Bioinspired slippery surfaces (BSSs) have attracted considerable attention owing to their antifouling, drag reduction, and self-cleaning properties. Accordingly, various technical terms have been proposed for describing BSSs based on specific surface characteristics. However, the terminology can often be confusing, with similar-sounding terms having different meanings. Additionally, some terms fail to fully or accurately describe BSS characteristics, such as the surface wettability of lubricants (hydrophilic or hydrophobic), surface wettability anisotropy (anisotropic or isotropic), and substrate morphology (porous or smooth). Therefore, a timely and thorough review is required to clarify and distinguish the various terms used in BSS literature. This review initially categorizes BSSs into four types: slippery solid surfaces (SSSs), slippery liquid-infused surfaces (SLISs), slippery liquid-like surfaces (SLLSs), and slippery liquid-solid surfaces (SLSSs). Because SLISs have been the primary research focus in this field, we thoroughly review their design and fabrication principles, which can also be applied to the other three types of BSS. Furthermore, we discuss the existing BSS fabrication methods, smart BSS systems, antifouling applications, limitations of BSS, and future research directions. By providing comprehensive and accurate definitions of various BSS types, this review aims to assist researchers in conveying their results more clearly and gaining a better understanding of the literature.

A non-linear relationship between lesion length and risk of recurrent cerebral ischemia after stenting for symptomatic intracranial stenosis with hemodynamic impairment.

Background: Stent placement can be an effective treatment for patients with symptomatic intracranial stenosis (sICAS) and hemodynamic impairment (HI). However, the association between lesion length and the risk of recurrent cerebral ischemia (RCI) after stenting remains controversial. Exploring this association can help predict patients at higher risk for RCI and develop individualized follow-up schedules. Method: In this study, we provided a post-hoc analysis of a prospective, multicenter registry study on stenting for sICAS with HI in China. Demographics, vascular risk factors, clinical variables, lesions, and procedure-specific variables were recorded. RCI includes ischemic stroke and transient ischemic attack (TIA), from month 1 after stenting to the end of the follow-up period. Smoothing curve fitting and segmented Cox regression analysis were used to analyze the threshold effect between lesion length and RCI in the overall group and subgroups of the stent type. Results: The non-linear relationship between lesion length and RCI was observed in the overall population and subgroups; however, the non-linear relationship differed by subgroup of stent type. In the balloon-expandable stent (BES) subgroup, the risk of RCI increased 2.17-fold and 3.17-fold for each 1-mm increase in the lesion length when the lesion length was <7.70 mm and >9.00 mm, respectively. In the self-expanding stent (SES) subgroup, the risk of RCI increased 1.83-fold for each 1-mm increase in the lesion length when the length was <9.00 mm. Nevertheless, the risk of RCI did not increase with the length when the lesion length was >9.00mm. Conclusion: A non-linear relationship exists between lesion length and RCI after stenting for sICAS with HI. The lesion length increases the overall risk of RCI for BES and for SES when the length was <9.00 mm, while no significant relationship was found when the length was >9.00 mm for SES.

MicroRNA-193a-5p Rescues Ischemic Cerebral Injury by Restoring N2-Like Neutrophil Subsets.

Circulating neutrophils are activated shortly after stroke and in turn affect the fate of ischemic brain tissue, and microRNAs (miRNA) participate in regulating neuroinflammation. We probed the role of neutrophilic miRNA in ischemic stroke. miR-193a-5p was decreased in circulating neutrophils of acute ischemic stroke (AIS) patients and healthy controls. In another set of AIS patients treated with recombinant tissue plasminogen activator, higher neutrophilic miR-193a-5p levels were associated with favorable outcomes at 3 months and non-symptomatic intracerebral hemorrhage. An experimental stroke model and human neutrophil-like HL-60 cells were further transfected with agomiR-193a-5p/antagomiR-193a-5p or ubiquitin-conjugating enzyme V2 (UBE2V2)-siRNA prior to model induction for in vivo and in vitro studies. Results of 2,3,5-triphenyl tetrazolium chloride staining and neurological function evaluations at post-experimental stroke showed that intravenous agomiR-193a-5p transfusion protected against ischemic cerebral injury in the acute stage and promoted neurological recovery in the subacute stage. This protective role was suggested to correlate with neutrophil N2 transformation based on the N2-like neutrophil proportions in the bone marrow, peripheral blood, and spleen of the experimental stroke model and the measurement of neutrophil phenotype-associated molecule levels. Mechanistically, analyses indicated that UBE2V2 might be a target of miR-193a-5p. Cerebral injury and neuroinflammation aggravated by miR-193a-5p inhibition were reversed by UBE2V2 silencing. In conclusion, miR-193a-5p protects against cerebral ischemic injury by restoring neutrophil N2 phenotype-associated neuroinflammation suppression, likely, in part, via UBE2V2 induction.

In vivo and in vitro binding of [125 I]I-R-(+)-TISCH: A dopamine D1 receptor ligand for studying pancreatic ß-cell mass.

Diabetes mellitus (DM) and insulinoma are mainly affected by the status of pancreatic ß-cell mass (BCM). Development of imaging agents for BCM allows to study pancreatic ß cells and the relationship between ß cells and DM or insulinoma. In this study, we investigated the density of dopamine D1 receptor on the ß cells and measured BCM by statistical image processing. The pancreatic uptakes of [125 I]I-R-(+)-7-chloro-8-hydroxy-1-(3'-iodopheny1)-3-methyl-2,3,4,5-tetrahydro-1H-3-benzazepine ([125 I]I-R-(+)-TISCH), dopamine D1 receptor tracer, in normal and diabetic rats displayed significant differences at 30 min (1.11 ± 0.08% ID/g vs. 0.63 ± 0.09% ID/g, p < 0.0001). In the presence of SCH23390, the pancreatic uptake of [125 I]I-R-(+)-TISCH at 30 min in normal rats was lower (1.01 ± 0.04% ID/g, p < 0.05). Although the blocking was not complete, [125 I]I-R-(+)-TISCH showed specific binding signals to the pancreas. Furthermore, the uptakes of [125 I]I-R-(+)-TISCH in INS-1 cells were reduced in the presence of SCH23390 at different concentrations. [125 I]I-R-(+)-TISCH displayed a respectable uptake in insulinoma. Overall, [125 I]I-R-(+)-TISCH provided specific binding signals to pancreatic ß cells. Although the specific signal may not be sufficient for imaging in vivo, the dopamine D1 receptor can still be considered as a potential target for studying BCM. Further investigation will be required to optimize the ligand.

MicroRNA-29b Suppresses Inflammation and Protects Blood-Brain Barrier Integrity in Ischemic Stroke.

Objectives: Following cerebral ischemia, microRNA- (miR-) 29b in circulating blood is downregulated. This study investigates the underlying mechanism and implications of miR-29b in leukocyte induction. Methods: miR-29b from stroke patients and rats with middle cerebral artery occlusion (MCAO) were assessed using real-time polymerase chain reaction (PCR). miR-29b agomir was used to increase miR-29b expression in leukocytes via intravenous injection. C1q and tumor necrosis factor (C1QTNF) 6, interleukin- (IL-) 1ß, zonula occludens- (ZO-) 1, occludin, and ischemic outcomes were assessed in MCAO rats. Additionally, hCMEC/D3 cells were subjected to oxygen-glucose deprivation (OGD) and cocultured with HL-60 cells. Results: miR-29b levels in neutrophils were found to be significantly lower in stroke patients compared with healthy controls, which may indicate its high diagnostic sensitivity and specificity for stroke. Moreover, miR-29b levels in leukocytes showed a negative correlation with National Institute of Health Stroke Scale (NIHSS) scores and C1QTNF6 levels. In MCAO rats, miR-29b overexpression reduced brain infarct volume and brain edema, decreasing IL-1ß levels in leukocytes and in the brain 24 hours poststroke. miR-29b attenuated IL-1ß expression via C1QTNF6 inhibition, leading to decreased blood-brain barrier (BBB) disruption and leukocyte infiltration. Moreover, miR-29b overexpression in HL-60 cells downregulated OGD-induced hCMEC/D3 cell apoptosis and increased ZO-1 and occludin levels in vitro. Conclusion: Leukocytic miR-29b attenuates inflammatory response by augmenting BBB integrity through C1QTNF6, suggesting a novel miR-29b-based therapeutic therapy for ischemic stroke.

Factors Influencing the Outcome of Symptomatic Intracranial Artery Stenosis With Hemodynamic Impairment After Short and Long-Term Stent Placement.

Objective: Stent placement is a feasible approach worldwidely for patients with symptomatic intracranial artery stenosis (sICAS) and hemodynamic impairment (HI) who are at high risk of recurrent stroke after medical treatment. Exploration of factors associated with poor outcomes after stent placement could help develop better individualized therapeutic strategies. Methods: This study conducted a post-hoc analysis of a prospective, multicenter registry study of stent use for sICAS with HI in China. Patient and clinical demographics, and stenotic lesion images were analyzed using univariate and multivariate Cox regression to the time until any endpoints or the end of the follow-up period. The short-term endpoint included any transient ischemic attack (TIA), stroke, or death within 1 month after stent placement. The long-term endpoints included the short-term endpoints and any TIA or stroke in the region of the affected artery that occurred more than 1 month after stent placement. Results: Two hundred and ninety two patients were included, with 13 short-term and 39 long-term endpoints. Multivariate Cox regression analysis revealed that lesions at the arterial origin or bifurcation (Hazard Ratio (HR) = 7.52; 95% CI, 1.89-29.82; p = 0.004) were significantly associated with higher short-term risk. Baseline renal insufficiency reduced the risk (HR = 0.08; 95% CI: 0.01-0.68; p = 0.021). Factors significantly associated with higher long-term risk included irregular or ulcerated plaques at the lesion (HR = 2.15; 95% CI: 1.07-4.33; p = 0.031). Subgroup analyses indicated that higher risk occurred in the older age group (age>59 years, HR = 3.73, 95% CI: 1.27-10.97, p = 0.017), and not in the younger group (age≤59 years, HR = 1.12, 95% CI: 0.42-3.03, p = 0.822). Conclusion: Irregular or ulcerated plaques in older patients and lesions at the arterial opening or bifurcation were more likely to result in adverse endpoints for stent placement during long or short -term follow-up. Investigation of these factors might facilitate the development of individualized therapeutic strategies for this population. Clinical Trial Registration: http://www.clinicaltrials.gov, identifier: NCT01968122.

An Unexpected Alteration Colonic Mucus Appearance in the Constipation Model via an Intestinal Microenvironment.

Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.