A new direction in periodontitis treatment: biomaterial-mediated macrophage immunotherapy.

Periodontitis is a chronic inflammation caused by a bacterial infection and is intimately associated with an overactive immune response. Biomaterials are being utilized more frequently in periodontal therapy due to their designability and unique drug delivery system. However, local and systemic immune response reactions driven by the implantation of biomaterials could result in inflammation, tissue damage, and fibrosis, which could end up with the failure of the implantation. Therefore, immunological adjustment of biomaterials through precise design can reduce the host reaction while eliminating the periodontal tissue's long-term chronic inflammation response. It is important to note that macrophages are an active immune system component that can participate in the progression of periodontal disease through intricate polarization mechanisms. And modulating macrophage polarization by designing biomaterials has emerged as a new periodontal therapy technique. In this review, we discuss the role of macrophages in periodontitis and typical strategies for polarizing macrophages with biomaterials. Subsequently, we discuss the challenges and potential opportunities of using biomaterials to manipulate periodontal macrophages to facilitate periodontal regeneration.

TU-LESS procedure for acute abdomen in late pregnancy: a retrospective study.

BACKGROUND: Acute abdominal conditions during pregnancy are significant risks to maternal and fetal health, necessitating timely diagnosis and intervention. The choice of surgical approach is a major concern for obstetricians. OBJECTIVE: To evaluate the safety and efficacy of the TU-LESS procedure for acute abdomen in late pregnancy. METHODS: We retrospectively analyzed 12 patients who underwent TU-LESS for acute abdominal conditions in the third trimester from 2020 to 2023. We reviewed medical records for clinical characteristics, surgical interventions, postoperative complications, and pregnancy outcomes. RESULTS: The study included patients with a median age of 27 (range 20-35) and a BMI of 24.33 kg/m2 (range 21.34-31.96). The median gestational age at surgery was 30 weeks (range, 28 + 3-32 + 4 weeks), with surgeries lasting an average of 60 min (range, 30-163 min). Blood loss was 2-20 mL, and the median hospital stay post-surgery was 6 days (range, 2-16 days). There were no significant complications. The median time to delivery after TU-LESS was 56 days (range, 26-66 days), resulting in 8 full-term deliveries, 2 preterm cesareans, and 2 preterm vaginal deliveries. All newborns were healthy, with no fetal losses or neonatal deaths. CONCLUSION: TU-LESS, performed by experienced obstetricians and gynecologists with proper preoperative preparation, is safe and effective for managing acute abdomen in late pregnancy, without the need to delay surgery due to gestational age.

Mesenchymal stem cells-derived extracellular vesicles protect against oxidative stress-induced xenogeneic biological root injury via adaptive regulation of the PI3K/Akt/NRF2 pathway.

Xenogeneic extracellular matrices (xECM) for cell support have emerged as a potential strategy for addressing the scarcity of donor matrices for allotransplantation. However, the poor survival rate or failure of xECM-based organ transplantation is due to the negative impacts of high-level oxidative stress and inflammation on seed cell viability and stemness. Herein, we constructed xenogeneic bioengineered tooth roots (bio-roots) and used extracellular vesicles from human adipose-derived mesenchymal stem cells (hASC-EVs) to shield bio-roots from oxidative damage. Pretreatment with hASC-EVs reduced cell apoptosis, reactive oxygen species generation, mitochondrial changes, and DNA damage. Furthermore, hASC-EV treatment improved cell proliferation, antioxidant capacity, and odontogenic and osteogenic differentiation, while significantly suppressing oxidative damage by activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway and nuclear factor erythroid 2 (NFE2)-related factor 2 (NRF2) nuclear translocation via p62-associated Kelch-like ECH-associated protein 1 (KEAP1) degradation. Inhibition of PI3K/Akt and Nrf2 knockdown reduced antioxidant capacity, indicating that the PI3K/Akt/NRF2 pathway partly mediates these effects. In subcutaneous grafting experiments using Sprague-Dawley rats, hASC-EV administration significantly enhanced the antioxidant effect of the bio-root, improved the regeneration efficiency of periodontal ligament-like tissue, and maximized xenograft function. Conclusively, therefore, hASC-EVs have the potential to be used as an immune modulator and antioxidant for treating oxidative stress-induced bio-root resorption and degradation, which may be utilized for the generation and restoration of other intricate tissues and organs.

LncRNA TPT1-AS1 promotes tumorigenesis and metastasis in epithelial ovarian cancer by inducing TPT1 expression.

Increasing numbers of studies have confirmed that long noncoding RNA (lncRNA) play a critical role in epithelial ovarian cancer (EOC) progression. However, the potential function of the lncRNA tumor protein translationally controlled 1 (TPT1) antisense RNA 1 (TPT1-AS1) in EOC is unclear. In this study, we aimed to uncover the biological roles and regulatory mechanisms of TPT1-AS1 in EOC progression and metastasis. First, TPT1-AS1 expression was significantly higher in EOC metastatic tissue and cell lines than in their respective control counterparts. In addition, ectopic TPT1-AS1 expression was strongly associated with unfavorable EOC clinicopathological features, including FIGO stage, tumor size and tumor differentiation. TPT1-AS1 overexpression remarkably induced cell proliferation, migration and invasion, and significantly attenuated cell adhesion ability in vitro and facilitated nude mouse subcutaneous xenograft growth and intraperitoneal metastasis in vivo, while the downregulation of TPT1-AS1 expression produced the opposite effect in vitro. Mechanistically, TPT1-AS1 was proven to be primarily distributed in EOC cell nuclei and positively modulated TPT1 promoter activity and transcription. Moreover, the oncogenic effects of TPT1-AS1 could be reversed by TPT1 depletion, and the PI3K/AKT signaling pathway downstream of TPT1 was also altered. These results suggested that TPT1-AS1 induced EOC tumor growth and metastasis through TPT1 and downstream PI3K/AKT signaling and that TPT1-AS1 may be a promising therapeutic target for EOC.

ß-hCG promotes epithelial ovarian cancer metastasis through ERK/MMP2 signaling pathway.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, with typically extensive intraperitoneal implantation leading to poor prognosis. Our previous study preliminarily demonstrated ß-hCG can promote tumorigenesis in immortalized nontumorigenic ovarian epithelial cells. In this study, the roles and mechanisms of ß-hCG in regulating EOC proliferation and metastasis were thoroughly explored. First, histologically, ß-hCG was aberrantly overexpressed in human EOC metastatic tissues, and significantly correlated with FIGO stage, tumor size, differentiation, histologic grade and high grade serous ovarian carcinoma (HGSOC) (P < 0.05). However, serologically, ß-hCG expression showed no significant difference between EOC and nonmalignant ovarian patients. Second, ß-hCG was confirmed to have no significant effects on EOC proliferation in vitro and in vivo, while ß-hCG upregulation was proven to promote migration and invasion ability in ES-2 and OVCAR-3 cells in vitro (P < 0.05), and ß-hCG downregulation in SKOV3 cells had the opposite effect. Moreover, more invadopodia protrusions, mitochondria accumulations and cytoskeletal rearrangements were observed in ß-hCG-overexpressing ES-2 cells, while ß-hCG-depleted SKOV3 cells produced the opposite effect. Furthermore, ß-hCG was confirmed to clearly facilitate intraperitoneal metastasis in nude mouse orthotopic ovarian xenograft models. Importantly, these effects of ß-hCG were mediated by activation of the ERK/MMP2 signaling pathway, independently of luteinizing hormone/chorionic gonadotropin receptor (LHCGR) presence, and inhibition the pathway with the p-ERK1/2 inhibitor SCH772984 significantly impaired the tumor-promoting effects induced by ß-hCG. Collectively, these data provide new insight into the roles and mechanisms of ß-hCG in regulating EOC metastasis through ERK/MMP2 signaling pathway and may become a new target for therapeutic intervention.

The crystal-form transition behaviours and morphology changes in a polyamide 6 cyclic dimer.

The characteristics of pure α- and ß-form of the cyclic dimer (1,8-diazacyclotetradecane-2,9-dione) were systematically and integrally investigated during this study. The results showed that the α-form could dissolve and rapidly transform into the ß-form in methanol, and in caprolactam solution at a lower temperature, an interesting transition occurred and formed co-precipitates, which refract colourful light under PLM. However, these dimers can aggregate in water, and they are then transformed into multi-slice layers and compact structures. The detailed transition behaviours between the two forms were further measured by FT-IR, XRD and DSC by varying the temperature from 25°C to 360°C, respectively, which showed that there are two endothermic transitions over the course of the heating programme. At a temperature of approximately 242°C, the ß crystals were initially converted into α crystals, and then they melted when the temperature reached over 345°C. A video recorded under a light microscope also showed that the sublimation of the ß cyclic dimer occurred after the transition. However, the α-form might sublimate at temperatures lower than 150°C when mixed with volatile matter.

Human chorionic gonadotropin ß regulates epithelial-mesenchymal transition and metastasis in human ovarian cancer.

Human chorionic gonadotropin ß (ß-hCG) is a well-known and accurate marker for the diagnosis and monitoring of pregnancy, trophoblastic tumors and ovarian germ cell tumors. Recently, ß-hCG has been found to be closely related to poor prognosis and metastasis in various other malignant tumors, while its role and mechanism in ovarian cancer is still unclear. In the present study, lentiviral­mediated transfection and small interfering RNA (siRNA) were used to alter ß-hCG expression in the ovarian cancer cell lines ES-2 and SKOV3, respectively. Then, migration and invasion activity regulated by ß-hCG were evaluated by wound-healing and Transwell assays in vitro and in a peritoneal xenograft nude mouse model in vivo. EDTA and trypsin were utilized to investigate the attachment ability of these cells. Moreover, the expression of epithelial mesenchymal transition (EMT) markers (ß-catenin, Slug, vimentin, Snail, claudin, E-cadherin and N-cadherin) was assessed by western blotting and immunofluorescence in ES-2 and SKOV3 cells. Furthermore, ß-hCG and EMT markers were evaluated in human ovarian cancer specimens by IHC. The results showed that overexpression of ß-hCG clearly promoted migration and invasion in ES-2 and SKOV3 cells (P<0.05) and facilitated metastasis in peritoneal xenografts, while silencing of ß-hCG led to the opposite effect. Moreover, ß-hCG was closely associated with cell morphology, attachment ability and EMT marker expression in ES-2 and SKOV3 cells and human ovarian cancer specimens. Upregulation of ß-hCG promoted cells from an epithelial-like morphology to a mesenchymal-like phenotype, decreased the adhesion ability (P<0.05), and reduced the expression of epithelial markers (E-cadherin) while inducing the expression of mesenchymal markers (vimentin, N-cadherin, ß-catenin and Slug). Furthermore, the converse effects were confirmed by knockdown of ß-hCG. These findings strongly suggest that ß-hCG may regulate metastasis of ovarian cancer through EMT, and it may become a new target for therapeutic intervention.

[Fresh amniotic membrane transplantation for ocular surface diseases].

OBJECTIVE: To evaluate the therapeutic effects of fresh amniotic membrane transplantation for ocular surface disorders (OSDs). METHODS: Fresh amniotic membrane transplantation was performed in 38 cases (52 eyes) of ocular surface diseases, including pterygium, recurrent pterygium, Mooren's ulcer, Viral keratitis, and symblepharon. Follow-up studies ranging from 3 to 12 months were conducted. RESULTS: No acute graft rejection was observed following the operation in these cases, and no recurrence was found in cases of pterygium and corneal ulcer during the follow-up period. The ocular movement was restored for the eyes with severe symblepharon. CONCLUSION: Fresh amniotic membrane can be used as a graft material for ocular surface reconstruction, in which complete removal of the pathological tissues and reliable fixation of the amniotic membrane graft are crucial steps.