Objective: To investigate the molecular regulatory mechanism of hypoxia-inducible factor-1α (HIF-1α) in mechanical stress-induced inflammatory cytokine expression in human periodontal ligament cells (hPDLCs), providing a theoretical basis and potential therapeutic target for inflammatory control during orthodontic treatment. Methods: This study was approved by the Institutional Ethics Committee. Primary human periodontal ligament cells (hPDLCs) were isolated and cultured in vitro. Self-renewal capacity was confirmed via colony-forming assays, while osteogenic and adipogenic differentiation potential was evaluated via Alizarin Red S staining, alkaline phosphatase (ALP) activity assays, and Oil Red O staining. An in vitro compressive force stimulation model (1.5 g/cm2, 12 h) was established to compare inflammatory cytokine expression of hPDLCs—interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and HIF-1α—between the Control group (no mechanical stimulation) and the Force group (1.5 g/cm2, 12 h) using quantitative real-time PCR (qRT-PCR), Western blot, and immunofluorescence (IF) staining. Mechanically induced HIF-1α-regulated gene expression changes were analyzed through transcriptomic sequencing. To explore pharmacological inhibition, the small-molecule HIF-1α inhibitor LW-6 was applied at varying concentrations (10 μmol/L, 30 μmol/L, 50 μmol/L) to optimize the treatment dose. Subsequently, qRT-PCR, Western blot, and IF staining were conducted to evaluate inflammatory cytokine of hPDLCs and HIF-1α expression in three groups: Control (no force), Force (1.5 g/cm2, 12 h), and Force+LW6 (1.5 g/cm2, 12 h + 30 μmol/L LW-6). Results: Primary hPDLCs demonstrated self-renewal capacity along with osteogenic and adipogenic differentiation potential. Compared to the Control group, the Force group exhibited significantly increased mRNA and protein expression levels of inflammatory cytokines IL-1β, IL-6, and TNF-α, along with enhanced fluorescence intensity of IL-1β and TNF-α. Transcriptomic analysis revealed that mechanical compressive force activated the HIF-1 signaling pathway, which subsequently mediated inflammatory responses and bone remodeling processes in hPDLCs. Furthermore, the mRNA and protein levels of HIF-1α were considerably elevated in the Force group compared to the Control group. Treatment with LW-6 (10, 30, or 50 μmol/L) effectively suppressed HIF-1α expression, with 30 μmol/L LW-6 identified as the optimal concentration for intervention. In subsequent experiments, the Force group showed significant upregulation in mRNA/protein expression of IL-1β, IL-6, and TNF-α compared to the Control group, as well as intensified HIF-1α, IL-1β, and TNF-α fluorescence signals. Conversely, the Force+LW6 group (mechanical force + 30 μmol/L LW-6) exhibited a notable reduction in inflammatory cytokine expression levels and a weakening of HIF-1α, IL-1β, and TNF-α fluorescence signals compared to the Force group. Conclusion HIF-1α potentiates mechanical stress-induced inflammatory responses in hPDLCs and may serve as a promising therapeutic target for mitigating orthodontic-associated periodontal inflammation.

The connection between tendons and bones is called the tendon bone connection. With the continuous improvement of national sports awareness, excessive exercises and the related intensity are prone to damage the tendon bone connection. Tendon bone healing is a complex repair and healing process involving multiple factors, and good tendon bone healing is a prerequisite for its physiological function. The complexity of tendon bone structure also poses great challenges to the repair of tendon bone injuries. In recent years, researches have found that stem cells, growth factors, macrophages, and other factors are closely related to the healing process of tendon bone injuries, among which macrophages play an important role in the healing process. The authors reviewed relevant research literature in recent years and summarized the role of macrophages in tendon bone healing, in order to provide new ideas and directions for treatment strategies to promote tendon bone healing.
Humans ; Macrophages/metabolism* ; Wound Healing ; Animals ; Tendons/physiology* ; Bone and Bones/injuries* ; Tendon Injuries

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Osteoarthritis(OA)is a common joint disease in clinical practice,and cartilage damage is a typical pathological change.The pathogenesis of OA is complex,and various adverse factors can lead to the occurrence of OA.Mitochondria are im-portant organelles within cells and play important roles in cellular physiological and pathological activ-ities.Mitochondrial quality control is an important regulatory mechanism in the body to maintain nor-mal mitochondrial structure and function,mainly including mitochondrial biogenesis,mitochondrial dynamics,mitochondrial autophagy,mitochondrial oxidative stress,and other forms.The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis,and regulating the balance of mi-tochondrial quality control is a potential therapeu-tic point for osteoarthritis.The author reviewed rel-evant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and develop-ment of osteoarthritis,in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.

Purpose To investigate correlation of ADP ribosylation-like factor 6 interacting protein 4(ARL6IP4)expression with the pathological characteristics and clinical prognosis in primary colon cancer.Methods The ARL6IP4 mRNA expression in tumor and adjacent normal tissues of 133 colon cancer patients was analyzed by RT-qPCR,and its relationship with tumor location,pathological TNM stage,and 3-year survival prognosis was assessed.Additionally,ARL6IP4 protein expression was analyzed by immunohistochemistry in 30 cases,of which 16 cases were analyzed by immunofluorescence.Results The colon cancer presented significantly higher mRNA and protein levels of ARL6IP4 than adjacent normal tissues(t=4.221,P=5.200 × 10-5;t=7.421,P=3.537 × 10-8).The relative ex-pression level of ARL6IP4 mRNA in colon cancer was positively correlated with pathological TNM stage,N stage and M stage(P＜0.05),and negatively correlated with 3-year cumulative survival probability(P＜0.01).Additionally,sig-moid colon cancer presented significantly higher ARL6IP4 expression than other colon cancers,and at the cellular lev-el,ARL6IP4 was predominantly expressed in the cell nucleus.Conclusion The ARL6IP4 expression in colon cancer is higher than that in adjacent normal tissues,which is closely related to tumor metastasis and clinical prognosis.

Abstract To explore the influence of the occurrence and development of bystander behavior in cyberbullying among adolescents, the paper reviews the factors influencing bystander behavior from the perspective of social ecosystem theory at the individual level, microsystem (family and school factors), peripheral system (contextual factors), macrosystem (cultural factors) and digital environment (media factors). It is pointed out that the future research needs to further explore the internal interaction of micro system, the influence of time system and technological development on bystanders, and the complex interaction between social ecosystems, and design feasible intervention strategies to transform passive bystanders into active interveners.

Objective In this study,we investigated the correlation between the scores for different Liebowitz Social Anxiety Scale(LSAS)subscale models and the metabolic activity in specific regions of the brain using 18F-fluorodeoxyglucose(FDG)positron emission tomography/computed tomography(PET/CT)(18F-FDG PET),thereby improving the understanding of the neurobiological characteristics of social anxiety.Methods A total of 39 cognitively normal participants(29 men and 10 women,aged 30-63 years)were enrolled.All participants underwent LSAS assessment and brain 18F-FDG PET scanning.Correlations between metabolic activities in various brain regions and scores from the different LSAS subscales were analyzed accordingly.Results LSAS subscale scores were significantly correlated with metabolic activity in specific brain regions.In the Safren model,the score for the observation by others subscale was positively correlated with the left fusiform gyrus(P<0.001,false discovery rate[FDR]-corrected)and the left caudate tail(P<0.001,FDR-corrected),suggesting a close association between mood states related to observation by others and the metabolic activity in these regions.In the Baker model,the score for the eating and drinking subscale was negatively correlated with the right precuneus(P<0.001,FDR-corrected),while the score for the assertiveness subscale was positively correlated with the left caudate nucleus(P<0.001,FDR-corrected).These findings revealed the complex associative patterns between various mood and behavioral dimensions and metabolic activities in specific brain regions.Conclusion Social anxiety symptoms are closely associated with metabolic changes in specific brain regions,including the left insula,left caudate tail,and right precuneus.Moreover,different social situations activate distinct brain regions.Compared with individuals with social anxiety disorder,normal individuals exhibit involvement of fewer brain regions when experiencing social anxiety.These findings provide new experimental evidence for understanding the neural mechanisms underlying social anxiety.

Objective·To investigate the effect of Th17 cell-specific Stat3 knockout on anxiety-and depressive-like behaviors.Methods·Mice with specific Stat3 knockout in Th17 cells(Stat3fl/fl;Il17a-CreERT2),named Stat3△Il17a,and wild-type mice(Stat3fl/fl,WT)were generated through the Cre/LoxP system,and Stat3 knockout was induced by intraperitoneal injection of tamoxifen.CD4+T cells were isolated using magnetic-activated cell sorting and induced to differentiate into Th17 cells.Reverse transcription polymerase chain reaction and Western blotting were used to verify Stat3 knockout efficiency.Mice were assigned into 4 groups:WT-C group,Stat3△Il17a-C group,WT-P group,and Stat3△Il17a-P group.The periodontitis model was established in the WT-P group and the Stat3△Il17a-P group by injection of Porphyromonas gingivalis-lipopolysaccharide(P.gingivalis-LPS)into the gingival sulcus.Behavioral tests,including the open field test,elevated zero maze,and forced swimming test,were conducted to evaluate changes in anxiety-and depressive-like behaviors.Micro-computed tomography was used to observe destruction of alveolar bone.Neuronal injury was observed by H-E staining,and the level of brain-derived neurotrophic factor(BDNF)was detected by enzyme-linked immunosorbent assay.Results·mRNA expression and protein levels of Stat3 in Stat3△Il17a mice were inhibited compared to WT mice(P<0.05).Experimental periodontitis model was successfully established in the WT-P group and the Stat3△Il17a-P group.The degree of alveolar bone destruction was reduced in the Stat3△Il17a-P group compared to the WT-P group.In the WT-P group,decreased residence time in the central area and in the open area was observed in the open field test and elevated zero maze respectively,and increased immortal time was recorded in the forced swimming test(P<0.05).Moreover,neuronal injury was detected and significantly decreased expression levels of BDNF in the brain were measured in the WT-P group compared with the WT-C group(P<0.05).The degree of abnormal behaviors and neuronal injury was reduced in the Stat3△Il17a-P group compared to the WT-P group(P<0.05).Moreover,the level of BDNF in the Stat3△Il17a-P was higher than that in the WT-P group(P<0.05).Conclusion·Periodontitis may contribute to anxiety-and depressive-like behaviors and neuronal damage in mice,while Th17-specific conditional knockout of Stat3 could significantly alleviate pathological behaviors and neuronal damage.Stat3-mediated-Th17 cell immune responses may play a crucial role in the correlation between periodontitis and anxiety and depression.

Osteoarthritis(OA)is a common joint disease in clinical practice,and cartilage damage is a typical pathological change.The pathogenesis of OA is complex,and various adverse factors can lead to the occurrence of OA.Mitochondria are im-portant organelles within cells and play important roles in cellular physiological and pathological activ-ities.Mitochondrial quality control is an important regulatory mechanism in the body to maintain nor-mal mitochondrial structure and function,mainly including mitochondrial biogenesis,mitochondrial dynamics,mitochondrial autophagy,mitochondrial oxidative stress,and other forms.The imbalance of mitochondrial quality control in chondrocytes is closely related to the occurrence and development of osteoarthritis,and regulating the balance of mi-tochondrial quality control is a potential therapeu-tic point for osteoarthritis.The author reviewed rel-evant research literature in recent years to provide a review of the relationship between mitochondrial quality control and the occurrence and develop-ment of osteoarthritis,in order to provide new ideas and directions for the research and diagnosis and treatment strategies of osteoarthritis.