Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Sustained inflammatory responses are closely related to various severe diseases, and inhibiting the excessive activation of inflammasomes and pyroptosis has significant implications for clinical treatment. Natural products have garnered considerable concern for the treatment of inflammation. Huanglian-Wumei decoction (HLWMD) is a classic prescription used for treating inflammatory diseases, but the necessity of their combination and the exact underlying anti-inflammatory mechanism have not yet been elucidated. Inspired by the supramolecular self-assembly strategy and natural drug compatibility theory, we successfully obtained berberine (BBR)-chlorogenic acid (CGA) supramolecular (BCS), which is an herbal pair from HLWMD. Using a series of characterization methods, we confirmed the self-assembly mechanism of BCS. BBR and CGA were self-assembled and stacked into amphiphilic spherical supramolecules in a 2:1 molar ratio, driven by electrostatic interactions, hydrophobic interactions, and π-π stacking; the hydrophilic fragments of CGA were outside, and the hydrophobic fragments of BBR were inside. This stacking pattern significantly improved the anti-inflammatory performance of BCS compared with that of single free molecules. Compared with free molecules, BCS significantly attenuated the release of multiple inflammatory mediators and lipopolysaccharide (LPS)-induced pyroptosis. Its anti-inflammatory mechanism is closely related to the inhibition of intracellular nuclear factor-kappaB (NF-κB) p65 phosphorylation and the noncanonical pyroptosis signalling pathway mediated by caspase-11.

OBJECTIVE: Gastric cancer (GC) is one of the most common malignancies seen in clinic and requires novel treatment options. Morin is a natural flavonoid extracted from the flower stalk of a highly valuable medicinal plant Prunella vulgaris L., which exhibits an anti-cancer effect in multiple types of tumors. However, the therapeutic effect and underlying mechanism of morin in treating GC remains elusive. The study aims to explore the therapeutic effect and underlying molecular mechanisms of morin in GC. METHODS: For in vitro experiments, the proliferation inhibition of morin was measured by cell counting kit-8 assay and colony formation assay in human GC cell line MKN45, human gastric adenocarcinoma cell line AGS, and human gastric epithelial cell line GES-1; for apoptosis analysis, microscopic photography, Western blotting, ubiquitination analysis, quantitative polymerase chain reaction analysis, flow cytometry, and RNA interference technology were employed. For in vivo studies, immunohistochemistry, biomedical analysis, and Western blotting were used to assess the efficacy and safety of morin in a xenograft mouse model of GC. RESULTS: Morin significantly inhibited the proliferation of GC cells MKN45 and AGS in a dose- and time-dependent manner, but did not inhibit human gastric epithelial cells GES-1. Only the caspase inhibitor Z-VAD-FMK was able to significantly reverse the inhibition of proliferation by morin in both GC cells, suggesting that apoptosis was the main type of cell death during the treatment. Morin induced intrinsic apoptosis in a dose-dependent manner in GC cells, which mainly relied on B cell leukemia/lymphoma 2 (BCL-2) associated agonist of cell death (BAD) but not phorbol-12-myristate-13-acetate-induced protein 1. The upregulation of BAD by morin was due to blocking the ubiquitination degradation of BAD, rather than the transcription regulation and the phosphorylation of BAD. Furthermore, the combination of morin and BCL-2 inhibitor navitoclax (also known as ABT-737) produced a synergistic inhibitory effect in GC cells through amplifying apoptotic signals. In addition, morin treatment significantly suppressed the growth of GC in vivo by upregulating BAD and the subsequent activation of its downstream apoptosis pathway. CONCLUSION Morin suppressed GC by inducing apoptosis, which was mainly due to blocking the ubiquitination-based degradation of the pro-apoptotic protein BAD. The combination of morin and the BCL-2 inhibitor ABT-737 synergistically amplified apoptotic signals in GC cells, which may overcome the drug resistance of the BCL-2 inhibitor. These findings indicated that morin was a potent and promising agent for GC treatment. Please cite this article as: Wang Y, Sun XY, Ma FQ, Ren MM, Zhao RH, Qin MM, Zhu XH, Xu Y, Cao ND, Chen YY, Dong TG, Pan YF, Zhao AG. Morin inhibits ubiquitination degradation of BCL-2 associated agonist of cell death and synergizes with BCL-2 inhibitor in gastric cancer cells. J Integr Med. 2025; 23(3): 320-332.
Humans ; Flavonoids/therapeutic use* ; Stomach Neoplasms/pathology* ; Animals ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; Cell Line, Tumor ; Apoptosis/drug effects* ; Cell Proliferation/drug effects* ; Ubiquitination/drug effects* ; Mice ; Drug Synergism ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays ; Flavones

AIM:To investigate the molecular mechanism of long noncoding RNA(lncRNA)SNHG1 in regu-lating ferroptosis to alleviate inflammation in CHME-5 human microglia induced by HIV-1 gp120 V3 loop.METHODS:CHME-5 human microglia were cultured in vitro,and were divided into 7 groups:blank group,random peptide group,gp120 V3 loop group(HIV-1 gp120 group),HIV-1 gp120+shCon group,HIV-1 gp120+SNHG1 sh2 group,HIV-1 gp120+SNHG1 sh2+ferrostatin-1(Fer-1;ferroptosis inhibitor)group,and HIV-1 gp120+SNHG1 sh2+EX527(Sirt1 in-hibitor)group.Normal CHME-5 cells were treated with random peptide or gp120 V3 loop for 24 h.After pretreatment of SNHG1 sh2 cells with inhibitors for 2 h,the cells were then treated with gp120 V3 loop for 24 h.The levels of inflammato-ry cytokines in the cell supernatants were detected by ELISA.Western blot was used to detect the protein expression levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),Sirt1 and p53.Microplate reader was used to detect the levels of intracellular ferrous ion(Fe2+)and malondialdehyde(MDA).RESULTS:(1)The results of ELISA showed that the expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β in HIV-1 gp120 group were significantly higher than those in blank group(P<0.05).Compared with HIV-1 gp120 group,the ex-pression levels of inflammatory cytokines in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.05).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of inflammatory factors in HIV-1 gp120+SNHG1 sh2+Fer-1 were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group were significant-ly increased(P<0.01).(2)The results of Western blot showed that compared with blank group,the expression levels of ferroptosis-related proteins SLC7A11 and GPX4 in HIV-1 gp120 group were significantly down-regulated(P<0.01).Com-pared with HIV-1 gp120 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2 group were sig-nificantly up-regulated(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly up-regulated(P<0.05),but the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+EX527 group were significantly down-regulated(P<0.01),and the expression level of p53 was significantly up-regulated(P<0.05).(3)Compared with blank group,the levels of Fe2+and MDA in HIV-1 gp120 group were significantly increased(P<0.05).Compared with HIV-1 gp120 group,the levels of Fe2+and MDA in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,Fe2+and MDA in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group was significantly increased(P<0.05).CONCLUSION:Knockdown of SNHG1 can attenuate the inflammation in microglia induced by HIV-1 gp120 V3 loop,which may be achieved by regulating ferrop-tosis-related signaling molecules through the Sirt1/p53 signaling pathway.

Objective:To investigate the value of systemic inflammatory response syndrome (SIRS), pediatric sequential organ failure assessment (pSOFA) and pediatric critical illness score (PCIS) in predicting mortality of pediatric sepsis in pediatric intensive care units (PICU) from Southwest China.Methods:This was a prospective multicenter observational study. A total of 447 children with sepsis admitted to 12 PICU in Southwest China from April 2022 to March 2023 were enrolled. Based on the prognosis, the patients were divided into survival group and non-survival group. The physiological parameters of SIRS, pSOFA and PCIS were recorded and scored within 24 h after PICU admission. The general clinical data and some laboratory results were recorded. The area under the curve (AUC) of the receiver operating characteristic curve was used to compare the predictive value of SIRS, pSOFA and PCIS in mortality of pediatric sepsis.Results:Amongst 447 children with sepsis, 260 patients were male and 187 patients were female, aged 2.5 (0.8, 7.0) years, 405 patients were in the survival group and 42 patients were in the non-survival group. 418 patients (93.5%) met the criteria of SIRS, and 440 patients (98.4%) met the criteria of pSOFA≥2. There was no significant difference in the number of items meeting the SIRS criteria between the survival group and the non-survival group (3(2, 4) vs. 3(3, 4) points, Z=1.30, P=0.192). The pSOFA score of the non-survival group was significantly higher than that of the survival group (9(6, 12) vs. 4(3, 7) points, Z=6.56, P<0.001), and the PCIS score was significantly lower than that of the survival group (72(68, 81) vs. 82(76, 88) points, Z=5.90, P<0.001). The predictive value of pSOFA (AUC=0.82) and PCIS (AUC=0.78) for sepsis mortality was significantly higher than that of SIRS (AUC=0.56) ( Z=6.59, 4.23, both P<0.001). There was no significant difference between pSOFA and PCIS ( Z=1.35, P=0.176). Platelet count, procalcitonin, lactic acid, albumin, creatinine, total bilirubin, activated partial thromboplastin time, prothrombin time and international normalized ratio were all able to predict mortality of sepsis to a certain degree (AUC=0.64, 0.68, 0.80, 0.64, 0.68, 0.60, 0.77, 0.75, 0.76, all P<0.05). Conclusion:Compared with SIRS, both pSOFA and PCIS had better predictive value in the mortality of pediatric sepsis in PICU.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Objective To analyze the value of magnetic resonance proton density-weighted fat-saturated(PDWI-FS)sequence in the diagnosis of bone marrow edema(BME)in osteoarticular injury.Methods A total of 150 patients with bone and joint trauma were enrolled in the study.All patients underwent sagittal PDWI-FS sequence scan and conventional MRI sequence scan.The BME detection,signal intensity,image quality,and the signal-to-noise ratio and contrast-to-noise ratio of the lesions were compared between two methods.Results Both methods revealed that there were 225 sites of BME signs in 134 out of the 150 patients,with a higher prevalence in knee joint trauma patients.The signal intensity of the lesions was mainly grade 3 on PDWI-FS sequence and grade 2 on conventional MRI sequence,accounting for 97.78%(220/225)and 43.11%(97/225),indicating that the two methods graded signal intensity differently(Z=15.919,P<0.05).PDWI-FS sequence and conventional sequence had scores of 4.09±0.45 vs 3.88±0.39,3.65±0.42 vs 3.41±0.36,3.25±0.37 vs 3.14±0.35 and 4.21±0.38 vs 3.97±0.34 on lesion clarity,spatial resolution,anamorphosis and diagnostic confidence,and the former scored higher(t=4.319,5.314,2.645,5.765;P<0.05).The signal-to-noise ratio and contrast-to-noise ratio of the lesions on PDWI-FS sequence were 2.07±0.23 and 5.52±0.64,higher than 2.01±0.22 and 5.17±0.59 on conventional sequence,and the differences were statistically significant(t=2.309,4.925;P<0.05).Conclusion Compared with conventional MRI sequence,magnetic resonance PDWI-FS sequence can effectively enhance image quality and display lesions more clearly,providing more accurate information for the diagnosis of BME in osteoarticular injury.

To explore the protective mechanisms of a novel molybdenum disulfide (MoS₂) nanozyme in alleviating inflammation-related endothelial cell injury by regulating mitochondrial dynamic, flower like-MoS₂ nanosheets were prepared by hydrothermal method, and its antioxidant enzyme-mimic activities were assessed via electron spin resonance (ESR) spectroscopy. It was shown that MoS₂ nanosheets had strong scavenging ability for hydroxyl radical (·OH) and singlet reactive oxygen species (¹O₂) in a dose-dependent manner. Using an in vitro lipopolysaccharide (LPS)-induced vascular endothelial cell injury model, the protective roles of MoS₂ nanozyme on cytotoxicity and apoptosis of endothelial cells were examined by MTT and Annexin V-FITC/PI assay, respectively. Mitochondrial fission/fusion of endothelial cell were observed by Mito-Tracker green probe. Reactive oxygen species (ROS) probe DCFH-DA and superoxide anion probe DHE were used to detect the level of oxidative stress in vitro. Plasmid GFP-LC3 transfection using colocalization analysis was applied to assess the autophagy of endothelial cells. The results showed that MoS₂ nanozyme could significantly reduce the cytotoxicity and apoptosis of endothelial cells stimulated by LPS, and prevent the impairment mitochondrial dynamics of endothelial cells, thus maintaining mitochondrial dynamics. In addition, MoS₂ nanozyme was also shown to alleviate LPS-mediated endothelial mitochondrial autophagy, thus protecting endothelial cells from inflammatory stress. These results established that MoS₂ nanozyme protected endothelial cells injury from inflammatory stress by regulating mitochondrial dynamics and mitochondrial autophagy of endothelial cells, which is expected to expand the use of MoS₂ nanozyme in the prevention and treatment of inflammation-related vascular endothelial diseases.

Objective:To observe the development process of the neuronal synapse in cerebral cortex and basal ganglionic eminence(GE)regions of the mice,and to clarify the differences in the development of excitatory and inhibitory synapses in different brain regions in vivo and in vitro.Methods:The female C57BL/6 mice were euthanized by cervical dislocation from the 13.5th day to the 15.5th day during the pregnancy,and the embryos were collected under the sterile conditions.The cortex and GE regions of brain tissue of the embryonic mice were gradually isolated under microscope.The primary neurons from the embryonic mice were cultured in vitro,and the cell samples were collected on the 3rd,7th,14th,and 21th days,respectively,and regarded as culture 3 d,7 d,14 d,and 21 d groups.The expression levels of postsynaptic density 95(PSD95)and Gephyrin mRNA in the primary neurons from the cortex and GE regions of the mice in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Immunofluorescence method was used to detect the expression levels of vesicular glutamate transporter 1(vGLUT1),PSD95,vesicular GABA transporter(vGAT),and Gephyrin proteins in the neurons from the cortex and GE regions of the mice in various groups.Immunofluorescence method was also used to detect the expression levels of vGLUT1 and vGAT proteins in the neurons from the cortical and GE regions in brain tissue of the embryonic mice.Results:Compared with culture 3 d group,the expression levels of PSD95 and Gephyrin mRNA in cortex and GE regions of the mice in culture 14 d and 21 d groups were significantly increased(P<0.01).Compared with cortex area,the expression level of Gephyrin mRNA in the neurons from GE region of the mice in culture 14 d group was significantly decreased(P<0.01).The microscope observation results showed that the excitatory and inhibitory synapses in the neurons from cortex and GE regions of the mice in culture 14 d group showed preliminary development,with positive expression of relevant proteins;among them,the excitatory synaptic proteins showed more distinct positive expression in the cortex neurons,and the presynaptic vGLUT1 and postsynaptic PSD95 molecules exhibited co-localization in the cell bodies and protrusions of the cortical neurons;the inhibitory presynaptic vGAT protein and postsynaptic Gephyrin protein in the neurons from GE region also exhibited co-localization in the cell bodies and protrusions,and there were more distinct expressions of the presynaptic molecule proteins than postsynaptic molecule proteins.Compared with cortex region,the levels of vGLUT1 and PSD95 proteins in the neurons from GE region of the mice in culture 14 d group were significantly decreased(P<0.01),while the levels of vGAT and gephyrin proteins were significantly increased(P<0.01).In culture 21 d group,the positive expressions of synaptic protein in the neurons from cortex and GE regions were increased,and the excitatory and inhibitory synapses further matured and enhanced.In the neurons from cortex and GE regions,rich patterns of corresponding pre-and postsynaptic expression were formed in the cell bodies and protrusions,and synapse structures showed gradual,positive development,with more apparent expression of presynaptic molecules compared wih postsynaptic proteins.Compared with cortex region,the levels of vGLUT1 and PSD95 proteins in the neurons from GE region of the mice in culture 21 d group were significantly decreased(P<0.01),and the levels of vGAT and Gephyrin proteins were significantly increased(P<0.01).Compared with cortex region,the expression level of vGLUT1 protein in the neurons from GE region in brain tissue of the embryonic mice was significantly decreased(P<0.01),while the expression level of vGAT protein was significantly increased(P<0.05).Conclusion:There are distinct differences in synaptic development between the neurons from cortex and GE regions,the excitatory synapses develope earlier in the cortical region and the inhibitory synapses develope earlier in the GE region.The region-specific development of synapses suggests that different types of neural diseases with different cell types might originate from different developmental processes.

Acute myelogenous leukemia (AML) is a heterogeneous disease characterized by malignant proliferation of hematopoietic stem cells, and its morbidity and mortality are increasing, which seriously threatens human health. In recent years, many studies have shown that PI3K-AKT-mTOR signaling pathway is involved in the management of various biological processes in cells, and its abnormal activation is closely related to the occurrence and development of tumors. Therefore, this article reviews the recent research progress of PI3K-AKT-mTOR signaling pathway in the pathogenesis, progression and treatment of AML.