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Background: The psychosocial impact of dental aesthetics (PIDA) has a significant effect on well-being and quality of life. This study aimed to explore the latent heterogeneous classes of the PIDA among adolescents and investigate the relationships among identified subtypes and sociodemographic variables, the status of left-behind children, and the clinical manifestations of malocclusion. Methods: A cross-sectional study on the PIDA among 1451 adolescents aged 11 to 12 years in elementary schools in a rural area in Guangxi, China, was conducted. The PIDA on adolescents was also investigated via latent profile analysis; each predictor was tested via ordinal logistic regression. Results: Three latent classes for the PIDA were identified: low-risk (48.2%), medium-risk (39.8%), and high-risk (11.9%) groups. There were significant differences among the three latent classes. The results revealed that being female, The duration of maternal employment outside the hometown, the largest anterior maxillary irregularity, the largest anterior mandibular irregularity, and the antero-posterior molar relationship (ORs of 1.737, 1.138, 1.117, 1.157, and OR = 1.242; P < 0.001, < 0.01, < 0.01, < 0.01 and < 0.05, respectively) had significant effects on the PIDA on adolescents. Conclusions: The occlusal features, being female and the duration of maternal employment outside the hometown are risk factors that influence the PIDA on adolescents. This provides an evidence for improving the PIDA status among rural adolescents. [ABSTRACT FROM AUTHOR]

Killer cell lectin-like receptor G1 (KLRG1) is an immune checkpoint receptor expressed predominantly in NK and T-cell subsets that downregulates the activation and proliferation of immune cells and participates in cell-mediated immune responses. Accumulating evidence has demonstrated the importance of KLRG1 as a noteworthy disease marker and therapeutic target that can influence disease onset, progression, and prognosis. Blocking KLRG1 has been shown to effectively mitigate the effects of downregulation in various mouse tumor models, including solid tumors and hematologic malignancies. However, KLRG1 inhibitors have not yet been approved for human use, and the understanding of KLRG1 expression and its mechanism of action in various diseases remains incomplete. In this review, we explore alterations in the distribution, structure, and signaling pathways of KLRG1 in immune cells and summarize its expression patterns and roles in the development and progression of autoimmune diseases, infectious diseases, and cancers. Additionally, we discuss the potential applications of KLRG1 as a tool for tumor immunotherapy. [ABSTRACT FROM AUTHOR]

The reversible oxidation-reduction homeostasis mechanism functions as a specific signal transduction system, eliciting related physiological responses. Disruptions to redox homeostasis can have negative consequences, including the potential for cancer development and progression, which are closely linked to a series of redox processes, such as adjustment of reactive oxygen species (ROS) levels and species, changes in antioxidant capacity, and differential effects of ROS on downstream cell fate and immune capacity. The tumor microenvironment (TME) exhibits a complex interplay between immunity and regulatory cell death, especially autophagy and apoptosis, which is crucially regulated by ROS. The present study aims to investigate the mechanism by which multi-source ROS affects apoptosis, autophagy, and the anti-tumor immune response in the TME and the mutual crosstalk between these three processes. Given the intricate role of ROS in controlling cell fate and immunity, we will further examine the relationship between traditional cancer therapy and ROS. It is worth noting that we will discuss some potential ROS-related treatment options for further future studies. [ABSTRACT FROM AUTHOR]

Background: Uveitis and posterior scleritis are sight-threatening diseases with undefined pathogenesis and accurate diagnosis remains challenging. Methods: Two plasma-derived extracellular vesicle (EV) subpopulations, small and large EVs, obtained from patients with ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis were subjected to proteomics analysis alongside plasma using SWATH-MS. A comprehensive bioinformatics analysis was performed on the proteomic profiles of sEVs, lEVs, and plasma. Candidate biomarkers were validated in a new cohort using ELISA. Pearson correlation analysis was performed to analyze the relationship between clinical parameters and proteomic data. Connectivity map database was used to predict therapeutic agents. Results: In total, 3,668 proteins were identified and over 3000 proteins were quantified from 278 samples. When comparing diseased group to healthy control, the proteomic profiles of the two EV subgroups were more correlated with disease than plasma. Comprehensive bioinformatics analysis highlighted potential pathogenic mechanisms for these diseases. Potential biomarker panels for four diseases were identified and validated. We found a negative correlation between plasma endothelin-converting enzyme 1 level and mean retinal thickness. Potential therapeutic drugs were proposed, and their targets were identified. Conclusions: This study provides a proteomic landscape of plasma and EVs involved in ankylosing spondylitis-related uveitis, Behcet's disease uveitis, Vogt-Koyanagi-Harada syndrome, and posterior scleritis, offers insights into disease pathogenesis, identifies valuable biomarker candidates, and proposes promising therapeutic agents. [ABSTRACT FROM AUTHOR]

Background: Langerhans cell histiocytosis (LCH) is a rare disorder. The treatment options vary depending on how many organs are involved and how extensive the disease is. In this report, a case of LCH with isolated 6th cervical vertebra (C6) collapse was presented. This case was treated with anterior corpectomy and instrumented fusion, followed by local radiotherapy (RT), with a good clinical outcome up to postoperative six months. Case presentation: This was a 47-year-old female patient with a complaint of neck pain and bilateral shoulder pain for two months before consultation. She was initially treated with analgesics, but the pain was persistent. Further radiological evaluations revealed an osteolytic lesion within the C6 vertebral body with a pathological fracture. Magnetic resonance imaging (MRI) with contrast of the cervical spine revealed diffused hypointense signal changes on the T1-weighted images and hyperintense signal changes on the T2-weighted images in the C6 vertebral body, with significant contrast-enhanced infiltration signals. Furthermore, in positron emission tomography-computed tomography (PET-CT), focal hypermetabolism and abnormal uptake signals were seen only in the C6 vertebral body. The patient underwent an anterior cervical corpectomy with instrumented fusion. The histopathological results confirmed the diagnosis of LCH. The patient reported significant pain relief on postoperative day one. Moreover, she was treated by local RT at postoperative one month. Good clinical outcomes were achieved in the form of no pain and recovery in neck mobility up to postoperative six months. No evidence of recurrence was observed at the final follow-up. Conclusions: This case report describes a treatment option for a solitary C6 collapse with LCH managed by anterior corpectomy and instrumented fusion, followed by local RT, with a good clinical outcome at postoperative six months. More studies are needed to elucidate whether such a treatment strategy is superior to surgery or RT alone. [ABSTRACT FROM AUTHOR]

Background: Radiation-induced lung injury (RILI) is considered one of the most common complications of thoracic radiation. Recent studies have focused on stem cell properties to obtain ideal therapeutic effects, and Sox9 has been reported to be involved in stem cell induction and differentiation. However, whether Sox9-expressing cells play a role in radiation repair and regeneration remains unknown. Methods: We successfully obtained Sox9CreER, RosatdTomato and RosaDTA mice and identified Sox9-expressing cells through lineage tracing. Then, we evaluated the effects of the ablation of Sox9-expressing cells in vivo. Furthermore, we investigated the underlying mechanism of Sox9-expressing cells during lung regeneration via an online single-cell RNA-seq dataset. Results: In our study, we demonstrated that Sox9-expressing cells promote the regeneration of lung tissues and that ablation of Sox9-expressing cells leads to severe phenotypes after radiation damage. In addition, analysis of an online scRNA-Seq dataset revealed that the PI3K/AKT pathway is enriched in Sox9-expressing cells during lung epithelium regeneration. Finally, the AKT inhibitor perifosine suppressed the regenerative effects of Sox9-expressing cells and the AKT pathway agonist promotes proliferation and differentiation. Conclusions: Taken together, the findings of our study suggest that Sox9-expressing cells may serve as a therapeutic target in lung tissue after RILI. [ABSTRACT FROM AUTHOR]

Background: G protein-coupled receptors (GPR) are involved in a wide range of physiological processes, some of which, however, can be hijacked by tumor cells. Over-expression of G protein-coupled receptors 137 (GPR137) are associated with the growth of tumor cells, but under-expression of GPR137 has shown to inhibit cell proliferation in several different types of cancers. Currently, the role of GPR137 in leukemia is still unclear. In this study, the effect of under-expression of GPR137 on inhibiting the proliferation of leukemia cells is explored, to identify a novel target for leukemia treatment. Materials and methods: In this study, lentivirus-mediated RNA interference (RNAi) was employed to investigate the role of GPR137 in two leukemia cell lines K562 and HL60. The gene expression of GPR137 was analyzed by RT-PCR and its protein expression was determined by Western blot. Flow cytometry and Annexin V/7-AAD Apoptosis Detection Kit was used respectively in cell cycle and apoptosis analysis. The protein expression of CyclinD1, CDK4, BCL-2 and caspase-3 were also determined. Results: There was high level of constitutive expression of GPR137 in leukemia cancer cell lines K562 and HL60. Lentivirus-mediated RNAi could significantly down-regulate gene and protein expression of GPR137 in both cell lines. Down regulation of GPR137 was associated with the reduction in proliferation rate and colony forming capacity. In addition, down regulation of GPR137 arrested cells in the G0/G1 phase of cell cycle and induced apoptosis in both leukemia cell lines K562 and HL60. Conclusions: The expression of GPR137 is associated with the proliferation of leukemia cell lines. Down regulation of GPR137 could inhibit proliferation and promote apoptosis in leukemia cells, which makes it a promising bio-marker and therapeutic target to treat patients with leukemia. [ABSTRACT FROM AUTHOR]

Background: Elevated plasma homocysteine (Hcy) levels have been indicated as a strong and modifiable risk factor of ischemic stroke; the previous studies have shown that exposure to Hcy activates cultured microglia. However, whether neurotoxicity of Hcy involves microglia activation following brain ischemia and the underlying mechanisms remains incompletely understood.Methods: The cerebral damage was evaluated by staining with 2,3,5-triphenyltetrazolium chloride, hematoxylin-eosin, and Fluoro Jade B. The activation state of microglia was assessed via immunoreaction using the microglial markers Iba1 and OX-42. Then, the inflammatory factors such as tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) were examined by Western blot analysis and fluorescence immunohistochemistry.Results: Elevated Hcy level augmented brain damage and neural cell toxicity in the brain cortex and the dentate gyrus region of the hippocampus after cerebral ischemia/reperfusion. Meanwhile, Hcy activated microglia and induced the expression of the inflammatory factors such as TNF-α and IL-6. Moreover, Hcy caused an increase in pSTAT3 expression which occurs in microglial cells. AG490, a JAK2-STAT3 inhibitor, effectively inhibited the phosphorylation of STAT3, microglial cell activation and the secretion of IL-6, TNF-α raised by Hcy treatment.Conclusions: STAT3 signaling pathway located in microglia plays a critical role in mediating Hcy-induced activation of microglia and neuroinflammation in rat MCAO model. This suggests the feasibility of targeting the JAK2/STAT3 pathway as an effective therapeutic strategy to alleviate the progression of Hcy-associated ischemia stroke. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to assess the impact of hypertension with or without diabetes on left ventricular (LV) remodeling in rural Chinese population.Methods: A total of 10,270 participants were classified into control group, hypertension without diabetes (HT) group, and hypertension with diabetes (HT + DM) group. We compared clinical characteristics and echocardiographic parameters, and used multivariable logistic regression analysis to assess the associations of interest.Results: HT + DM group had higher interventricular septal thickness (IVSd), posterior wall thickness (PWTd), left ventricular mass (LVM), LVM index (LVMI), relative wall thickness (RWT), left atrial diameter (LAD), A wave and lower E wave than HT group (all P < 0.05). The prevalence rates of left ventricular hypertrophy (LVH) and abnormal geometry were statistically different among three groups (P < 0.001) and eccentric hypertrophy was the highest proportion of geometry abnormality. Logistic regression analysis suggested that subjects in HT and HT + DM groups had odds ratio (OR) values of 2.81, 4.41, 2.24 and 3.94, 7.20, 2.38 for LVH, concentric hypertrophy and eccentric hypertrophy in the total population, respectively, compared to control group. When compared with HT group, those in HT + DM group had approximately 1.40-, 1.61- and 1.38-, 1.71-fold increased risk for LVH and concentric hypertrophy in the total and female population separately, but no association of HT + DM with LVH and abnormal geometrical patterns was found in men.Conclusions: This study demonstrated that, to varying degrees, hypertension was associated with LV remodeling in rural Chinese population, and this risk association was obviously increased for LVH and concentric hypertrophy when accompanied by diabetes, especially for women. [ABSTRACT FROM AUTHOR]

Background: Studies regarding the association between prehypertension and the structual changes of left heart are scanty. However, which type of the geometrical change of left heart is predominated one in prehypertension and hypertension is controversial. It is therefore important to investigate geometrical and functional changes of left heart in adults with prehypertension and hypertension because of their prognostic significance.Methods: The study was based on a cross-sectional design, a total of 10547 participants were classified into normotension group, prehypertension group and hypertension group. We analyzed clinical characteristics, echocardiographic parameters and distribution of left ventricular (LV) geometrical patterns in different groups.Results: Participants with prehypertension had higher values of most of echocardiographic parameters than those with normotension. The prevalence of left ventricular hypertrophy(LVH) was statistically different among three groups (P <0.001), and the rates of LVH in the three groups were 5.9, 8.6, 28.4 % by indexation to height(2.7) and 4.9, 5.3, 19.3 % by indexation to BSA, respectively. The prevalence rates of eccentric hypertrophy, concentric remodeling and concentric hypertrophy were 7.3 %, 5.3 % and 1.4 % in prehypertension group, and 17.8 %, 8.8 % and 10.6 % in hypertension group. Logistic regression analysis showed that systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean artery pressure (MAP) were all independent risk factors for left cardiac structural changes, and pulse pressure (PP) was independent risk factor for concentric and eccentric hypertrophy. Among four indices, DBP levels with OR values of 1.192, 1.759 and 1.278 were the strongest indicator for concentric remodeling, concentric hypertrophy and eccentric hypertrophy, respectively (P <0.001).Conclusions: There exists LV geometrical change in adults with prehypertension and hypertension in rural Chinese population, and the eccentric hypertrophy was the highest proportion of geometric alterations. SBP, DBP, MAP and PP were all positively associated with left cardiac structural changes, and the association of DBP was the strongest. [ABSTRACT FROM AUTHOR]

Background: Our previous studies indicated that oxidative stress up-regulated the expression of β-amyloid precursor protein cleavage enzyme-1 (BACE1) in rat retina. Pharmacological reports have shown Timosaponin-BII, a purified extract originating from Chinese medical herb Rhizoma Anemarrhenae, is characterized as an antioxidant.Our present study aimed to determine whether Timosaponin-BII affected the expression of BACE1, β-amyloid precursor protein cleavage production of Aβ1-40 and β-C-terminal fragment (β-CTF) in rat retina, which were pre-treated with the oxidizing agent (solution of FeCl3).Results: Few distinctions of BACE1 distribution were observed among all groups (normal control group, model group, Timosaponin-BII treated and vehicle control groups). Rat retinas in model group and vehicle control group manifested an apparent up-regulation of BACE1 expression. Meanwhile, the level of malonaldehyde (MDA), Aβ1-40and β-CTF were increased. However, when comparing with the vehicle control group, the retinas in Timosaponin-BII treated group showed significantly less BACE1 (p<0.05) and accumulated less Aβ1-40 or β-CTF(p<0.05). It also showed significantly decreased level of MDA (p<0.05) and prolonged partial thromboplastin time(p<0.05).Conclusion: Our data suggested that Timosaponin-BII remarkably inhibited the up-regulation of BACE1 and reduced the over-production of β-CTF and Aβ in rat retina, which was induced by FeCl3. The mechanism of Timosaponin-BII on BACE1 expression may be related to its antioxidant property. [ABSTRACT FROM AUTHOR]

Background: Anti-angiogenic therapies demonstrate anti-tumor effects by decreasing blood supply to tumors and inhibiting tumor growth. However, anti-angiogenic therapy may leads to changes in tumor microenvironment and increased invasiveness of tumor cells, which in turn promotes distant metastasis and increased drug resistance. Methods: The CO-IP assays, N-STORM and cytoskeleton analysis were used to confirm the mechanism that p-VEGFR2/VE-cadherin/β-catenin/actin complex regulates vascular remodeling and improves the tumor microenvironment. 6-gingerol (6G), the major bioactive component in ginger, stabilized this complex by enhancing the binding of VEGFa to VEGFR2 with non-pathway dependent. Biacore, pull down and molecular docking were employed to confirm the interaction between 6G and VEGFR2 and enhancement of VEGFa binding to VEGFR2. Results: Here, we report that microvascular structural entropy (MSE) may be a prognostic factor in several tumor types and have potential as a biomarker in the clinic. 6G regulates the structural organization of the microvascular bed to decrease MSE via the p-VEGFR2/VE-cadherin/β-catenin/actin complex and inhibit tumor progression. 6G promotes the normalization of tumor vessels, improves the tumor microenvironment and decreases MSE, facilitating the delivery of chemotherapeutic agents into the tumor core and thereby reducing tumor growth and metastasis. Conclusions: This study demonstrated the importance of vascular normalization in tumor therapy and elucidated the mechanism of action of ginger, a medicinal compound that has been used in China since ancient times. [ABSTRACT FROM AUTHOR]

Background: RIP3 (Receptor-interacting protein 3) pathway was mainly described as the molecular mechanism of necroptosis (programmed necrosis). But recently, non-RIP3 pathways were found to mediate necroptosis. We deliberate to investigate the effect of calpain, a molecule to induce necroptosis as reported (Cell Death Differ 19:245-256, 2012), in RGC-5 following elevated hydrostatic pressure.Results: First, we identified the existence of necroptosis of RGC-5 after insult by using necrostatin-1 (Nec-1, necroptosis inhibitor) detected by flow cytometry. Immunofluorescence staining and western blot were used to detect the expression of calpain. Western blot analysis was carried out to describe the truncated AIF (tAIF) expression with or without pretreatment of ALLN (calpain activity inhibitor). Following elevated hydrostatic pressure, necroptotic cells pretreated with or without ALLN was stained by Annexin V/PI, The activity of calpain was also examined to confirm the inhibition effect of ALLN. The results showed that after cell injury there was an upregulation of calpain expression. Upon adding ALLN, the calpain activity was inhibited, and tAIF production was reduced upon injury along with the decreased number of necroptosis cells.Conclusion: Our study found that calpain may induce necroptosis via tAIF-modulation in RGC-5 following elevated hydrostatic pressure. [ABSTRACT FROM AUTHOR]