Periodontitis is a common oral disease caused by bacteria coupled with an excessive host immune response. Stem cell therapy can be a promising treatment strategy for periodontitis, but the relevant mechanism is complicated. This study aimed to explore the therapeutic potential of mitochondria from human embryonic stem cell-derived mesenchymal stem cells (hESC-MSCs) for the treatment of periodontitis. The gingival tissues of periodontitis patients are characterized by abnormal mitochondrial structure. Human gingival fibroblasts (HGFs) were exposed to 5 μg/mL lipopolysaccharide (LPS) for 24 h to establish a cell injury model. When treated with hESC-MSCs or mitochondria derived from hESC-MSCs, HGFs showed reduced expression of inflammatory genes, increased adenosine triphosphate (ATP) level, decreased reactive oxygen species (ROS) production, and enhanced mitochondrial function compared to the control. The average efficiency of isolated mitochondrial transfer by hESC-MSCs was determined to be 8.93%. Besides, a therapy of local mitochondrial injection in mice with LPS-induced periodontitis showed a reduction in inflammatory gene expression, as well as an increase in both the mitochondrial number and the aspect ratio in gingival tissues. In conclusion, our results indicate that mitochondria derived from hESC-MSCs can reduce the inflammatory response and improve mitochondrial function in HGFs, suggesting that the transfer of mitochondria between hESC-MSCs and HGFs serves as a potential mechanism underlying the therapeutic effect of stem cells.
Humans ; Gingiva/cytology* ; Fibroblasts/metabolism* ; Mitochondria/physiology* ; Mesenchymal Stem Cells/cytology* ; Animals ; Periodontitis/therapy* ; Mice ; Reactive Oxygen Species/metabolism* ; Inflammation ; Lipopolysaccharides ; Human Embryonic Stem Cells/cytology* ; Cells, Cultured ; Adenosine Triphosphate/metabolism* ; Male

Volume-regulated anion channels(VRACs)are present in vertebrate cells and a variety of tumor cells.VRACs include leucine-rich-repeat-containing 8A(LRRC8A)and its four homologous family members(LRRC8B-E),of which LRRC8A is an essential subunit.It has been confirmed that the VRAC LRRC8A is involved in the proliferation,migration,invasion,and multi-drug resistance of tumor cells through various signaling pathways.This ion transporter has shown good potential for use in strategies to kill tumor cells and prevent the development of tumors and can be used as a new target for tumor therapy.Therefore,this paper reviews the latest research on the involvement of LRRC8A in tumorigenesis and development.The molecular structure,function,and regulation of LRRC8A in tumor and immune cells,with emphasis on targeting LRRC8A in tumor diagnosis and immunotherapy,are discussed,providing a reference for studies exploring LRRC8A as a new tumor therapy target.

Pancreatic ductal adenocarcinoma(PDAC)is a common type of pancreatic cancer that is insidious,develops rapidly,and is highly malignant.Traditional treatment strategies are ineffective for PDAC because of its rich extracellular matrix(ECM).Cancer-associated fibroblast(CAF)are the most important component of the ECM,and interact with other immune components in the tumor microenvironment(TME)by secreting numerous effector molecules to form an immunosuppressive TME,which may then allow cancer cells to evade immune system surveillance,promote tumor growth,invasion,and metastasis,and induce ECM remodeling and drug resistance.This review summarizes research progress on the application of targeted CAF in PDAC immunotherapy.We focus on exploring research strategies that promote the transition of TME from an immunosuppressive to an immune-activated state through depleting CAF,inhibiting effector molecules secreted by CAF,reprogramming CAF,and limiting CAF-induced ECM remodeling.This review aims to support the production of more effective therapeutic strategies and provide new method for the immunotherapy of PDAC.

Necroptosis is a regulated process of programmed cell death independent of aspartic acid-specific cysteine protease,which can induce inflammation.Studies have shown that necroptosis is closely related to the progression and prognosis of pancreatic disease and plays an important two-way regulatory role in its progression.Related necroptosis inhibitors and inducers are expected to be used in the treatment of pancreatic disease.We herein review the mechanism of necroptosis and its role in the progression of pancreatic disease to provide a new understanding of the pathogenesis and treatment of pancreatic diseases and offer a theoretical basis for the research and development of targeted drugs.

Prostate cancer is a prevalent malignant tumor in the male genitourinary system,characterized by a high propensity for bone metastasis.It is a leading cause of mortality,with approximately 70％of deaths attributed to this form of metastasis.Mouse models provide a crucial tool in the investigation of prostate cancer bone metastasis,and play a pivotal role in elucidating the underlying pathophysiological mechanisms and in the development and assessment of therapeutic agents.In this review,we summarize research progress in the construction method and evaluation strategies used in establishing prostate cancer bone metastasis mouse models.Notably,this review focuses on the exploration of the mechanisms responsible for prostate cancer bone metastasis,using mouse models,with the aim of offering insights and serving as a valuable reference for prostate cancer bone metastasis.

Volume-regulated anion channels(VRACs)are present in vertebrate cells and a variety of tumor cells.VRACs include leucine-rich-repeat-containing 8A(LRRC8A)and its four homologous family members(LRRC8B-E),of which LRRC8A is an essential subunit.It has been confirmed that the VRAC LRRC8A is involved in the proliferation,migration,invasion,and multi-drug resistance of tumor cells through various signaling pathways.This ion transporter has shown good potential for use in strategies to kill tumor cells and prevent the development of tumors and can be used as a new target for tumor therapy.Therefore,this paper reviews the latest research on the involvement of LRRC8A in tumorigenesis and development.The molecular structure,function,and regulation of LRRC8A in tumor and immune cells,with emphasis on targeting LRRC8A in tumor diagnosis and immunotherapy,are discussed,providing a reference for studies exploring LRRC8A as a new tumor therapy target.

Pancreatic ductal adenocarcinoma(PDAC)is a common type of pancreatic cancer that is insidious,develops rapidly,and is highly malignant.Traditional treatment strategies are ineffective for PDAC because of its rich extracellular matrix(ECM).Cancer-associated fibroblast(CAF)are the most important component of the ECM,and interact with other immune components in the tumor microenvironment(TME)by secreting numerous effector molecules to form an immunosuppressive TME,which may then allow cancer cells to evade immune system surveillance,promote tumor growth,invasion,and metastasis,and induce ECM remodeling and drug resistance.This review summarizes research progress on the application of targeted CAF in PDAC immunotherapy.We focus on exploring research strategies that promote the transition of TME from an immunosuppressive to an immune-activated state through depleting CAF,inhibiting effector molecules secreted by CAF,reprogramming CAF,and limiting CAF-induced ECM remodeling.This review aims to support the production of more effective therapeutic strategies and provide new method for the immunotherapy of PDAC.

Objective To evaluate biomechanical strength of locking compression plate (LCP) for fixation of periprosthetic proximal femur fractures (PPFF). Methods Eight matched pairs of Vancouver type B1 adult cadaveric PPFF specimens were fixed with the LCP and the inverted distal femoral less invasive stabilization system (LISS), respectively. Four bicortical locking screws (LCP group) and four unicortical locking screws were used to the length of prosthesis stem, and four double cortical locking screws were used to fix the distal end of the fracture in two groups, the distance from the locking screws to the fracture were also equal. The maximum bending load, maximum bending displacement, bending stiffness, maximum torque, maximum torsional angle and torsional stiffness of two groups in four-point bending test and torsion test were compared and analyzed. Results The maximum bending load, maximum bending displacement and bending stiffness of LCP group were all larger than those of LISS group, but the difference was not statistically significant (P>0.05). The maximum torque, maximum torsional angle and torsional stiffness of LCP group were obviously larger than those of LISS group，and there was a statistical difference between two groups (P<0.05). Conclusions The stiffness of anti-torsion with LCP is significantly better than that with LISS. Consequently, LCP has better biomechanical stability for PPFF.

Objective: To explore the relationship between glycemic control and visceral adiposity index (VAI) among type 2 diabetes mellitus (T2DM) patients.Methods: A community-based epidemiological field study for patients with T2DM aged ≥ 40 years was conducted in China.Every participant underwent physical examinations, biochemical tests of fasting glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and so on, and a questionnaire, including anthropometric characteristics, lifestyle, disease history, family history, and medication use.Those participants with HbA1c ≥7.0% were classified as the poorly controlled in our analysis of relationship between glycemic control and VAI.Anthropometric characteristics, lifestyle, and biochemical indexes of the participants were compared among the groups of different VAI levels.Logistic models were applied in multiple analysis adjusting for possible confounders.Results: A total of 1 607 patients with T2DM were recruited in our analysis with a mean age of (59.4±8.1) years and an average T2DM duration of (7.0±6.4) years.Among them, 78.3% were on hypoglycemic therapy.The cutoff points of quartiles of VAI were calculated for the males and females, respectively.According to the ascending order of the quartiles of VAI, the participants were divided into four groups, i.e.Q1, Q2, Q3, and Q4.The poor glycemic control rate for these groups were 60.6%, 65.7%, 70.1%, and 71.0%, respectively (Trend χ2=12.20, P<0.001).After adjustment for age, gender, systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-C, smoking, cardio-cerebral vascular disease (CVD) history, hypoglycemic therapy, T2DM duration, and family history of diabetes, the Logistic regression models showed that the glycemic control rate was significantly associated with VAI levels among the patients with T2DM.Compared with the participants in group Q1, the ORs of poor glycemic control for those in groups Q2, Q3, and Q4 were 1.239 (95%CI 0.918 to 1.672), 1.513 (95%CI 1.117 to 2.050), and 1.535 (95%CI 1.128to 2.088), respectively (trend P=0.003).With each quartile increase in VAI, the OR of poor glycemic control was 1.162 (95%CI 1.054 to 1.282).Conclusion: The glycemic control among the patients with T2DM is significantly associated with VAI.High level of VAI is an indicator of poor glycemic control.

Objective To evaluate the effect of anterior minimally invasive plate osteosynthesis (MIPO) for treatment of middle humeral shaft fracture.Methods From November 2011 to March 2014,10 cases of middle humeral shaft fracture were treated using MIPO via the anterior approach (MIPO group).Another 26 cases treated by open reduction and internal fixation (ORIF) of the middle humeral shaft fracture between October 2010 and March 2014 were included as controls (ORIF group).Fracture fixation using the 4.5 mm locking compression plate (LCP) was performed in both groups.Parameter measurements included operative time,intraoperative fluoroscopy times,grafting rate,intraoperative blood loss,postoperative drainage,hospital stay,bone healing time and complications.Results MIPO and ORIF groups differed significantly with respect to intraoperative blood loss [(93.5 ± 25.6) ml vs (325.3 ± 158.3) ml],intraoperative fluoroscopy times [(13.2 ± 6.1) vs 4.0 (0-6.0)] and hospitalization [(11.9 ± 1.7)days vs (18.0 ±4.7)days] (P ＜0.05).Bone grafting and drainage were not performed in MIPO group,while bone grafting rate was 54％ and postoperative drainage volume was (120.4 ± 69.6) ml in ORIF group (P ＜0.05).MIPO and ORIF groups were comparable with respect to operative time [(79.0 ± 22.0) min vs (97.5 ± 30.8) min],bone healing time [(15.2 ± 2.5) weeks vs (18.2 ± 4.8)weeks] and postoperative complications (10％ vs23％) (P＞0.05).Conclusion Anterior MIPO is an effective procedure for treatment of middle humeral shaft fracture,with advantages of small trauma,less bleeding,low risk of nerve injury and high rate of fracture healing.