Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.

Among the numerous complications of diabetes mellitus, diabetic wounds seriously affect patients' quality of life and result in considerable psychological distress. Promoting blood vessel regeneration in wounds is a crucial step in wound healing. Lonicerin (LCR), a bioactive compound found in plants of the Lonicera japonica species and other honeysuckle plants, exhibits anti-inflammatory and antioxidant activities, and it recently has been found to alleviate ulcerative colitis by enhancing autophagy. In this study we investigated the efficacy of LCR in treatment of diabetic wounds and the underlying mechanisms. By comparing the single-cell transcriptomic data from healing and non-healing states in diabetic foot ulcers (DFU) of 5 patients, we found that autophagy and SIRT signaling activation played a crucial role in mitigating inflammation and oxidative stress, and promoting cell survival in wound healing processes. In TBHP-treated human umbilical vein endothelial cells (HUVECs), we showed that LCR alleviated cell apoptosis, and enhanced the cell viability, migration and angiogenesis. Furthermore, we demonstrated that LCR treatment dose-dependently promoted autophagy in TBHP-treated HUVECs by upregulating Sirt1 expression, and exerted its anti-apoptotic effect through the Sirt1-autophagy axis. Knockdown of Sirt1 significantly decreased the level of autophagy, and mitigated the anti-apoptotic effect of LCR. In a STZ-induced diabetic rat model, administration of LCR significantly promoted wound healing, which was significantly attenuated by Sirt1 knockdown. This study highlights the potential of LCR as a therapeutic agent for the treatment of diabetic wounds and provides insights into the molecular mechanisms underlying its effects.

Spatial heterogeneity and source apportionment of soil metal(loid)s in an abandoned lead/zinc smelter.

Metal smelting have brought severe metal(loid)s contamination to the soil. Spatial distribution and pollution source analysis for soil metal(loid)s in an abandoned lead/zinc smelter were studied. The results showed that soil was contaminated heavily with metal(loid)s. The mean of lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg) and antimony (Sb) content in topsoil is 9.7, 8.2, 5.0, 2.3, and 1.2 times higher than the risk screening value for soil contamination of development land of China (GB36600-2018), respectively. Cd is mainly enriched in the 0-6 m depth of site soil while As and Pb mainly deposited in the 0-4 m layer. The spatial distribution of soil metal(loid)s is significantly correlated with the pollution source in the different functional areas of smelter. As, Hg, Sb, Pb and copper (Cu) were mainly distributed in pyrometallurgical area, while Cd, thallium (Tl) and zinc (Zn) was mainly existed in both hydrometallurgical area and raw material storage area. Soil metal(loid)s pollution sources in the abandoned smelter are mainly contributed to the anthropogenic sources, accounting for 84.5%. Specifically, Pb, Tl, As, Hg, Sb and Cu mainly from atmospheric deposition (55.9%), Cd and Zn mainly from surface runoff (28.6%), While nickel (Ni) mainly comes from parent material (15.5%). The results clarified the spatial distribution and their sources in different functional areas of the smelter, providing a new thought for the risk prevention and control of metal(loid)s in polluted site soil.

Diagnostic value of calcaneal quantitative ultrasound in the evaluation of osteoporosis in middle-aged and elderly patients.

ABSTRACT: To study the correlation between calcaneal quantitative ultrasound (QUS) and dual-energy X-ray absorptiometry (DXA), and analyze the diagnostic value of calcaneal QUS in the evaluation of middle-aged and elderly osteoporosis.We assessed bone mineral density (BMD) at the femoral neck and intertrochanteric of left hip and lumbar spine (L1-L4) sites with DXA and QUS parameters of the right and left calcanei in a cohort of 82 patients over the age of 50 years. Using DXA parameters as the gold standard for the diagnosis of osteoporosis, the correlation coefficient between BMD and QUS parameters was calculated. Receiver operating characteristic curve was generated and areas under the curves were evaluated. Cut-off values for QUS were defined.In men, there was a moderate correlation between calcaneal QUS and proximal femoral BMD (P < .05), but no significant correlation between calcaneal QUS and lumbar BMD (P > .05). In women, calcaneal QUS were moderately correlated with lumbar spine and proximal femoral BMD (P < .05). Using DXA as the gold standard, the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of calcaneal QUS in the diagnosis of osteoporosis were 90.2%, 89.2%, 100%, 100%, and 50.0%, respectively. According to the receiver operating characteristic curve, when the QUS T-score of calcaneum was -1.8, the area under the curve was 0.888, the sensitivity was 73.21%, and the specificity was 92.31% (P < .05). When the QUS T-score of calcaneum was -2.35, the sensitivity was 37.2% and the specificity was 100%.Calcaneal QUS can be used to predict proximal femoral BMD in middle-aged and elderly people, as well as lumbar BMD in women. As a screening method for osteoporosis, calcaneal QUS has good specificity, so it can be recommended to use it as a pre-screening tool to reduce the number of DXA screening. When the QUS T-score of calcaneum is -1.8, it has the greatest diagnostic efficiency for osteoporosis; when the QUS T-score of calcaneum is ≤-2.35, it can be diagnosed as osteoporosis.

Micromolar sodium fluoride promotes osteo/odontogenic differentiation in dental pulp stem cells by inhibiting PI3K/AKT pathway.

OBJECTIVE: Sodium fluoride (NaF) plays an important role in preventing dental caries. However, the regulatory effect of NaF on the committed differentiation of DPSCs is not fully understood. In this study, we characterized the impact of micromolar levels of NaF on the osteo/odontogenic differentiation of DPSCs. DESIGN: DPSCs were isolated from healthy human third molars and were cultured in conditioned media with different concentrations of NaF. RNA sequencing (RNA-seq) combined with Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was used to assess the pathways regulated by NaF. Alkaline phosphatase activity, Alizarin red staining, Western blotting, and real-time qRT-PCR were used to determine the osteo/odontogenic differentiation in DPSCs treated with NaF. RESULTS: NaF significantly promoted the osteo/odontogenic differentiation of DPSCs at micromolar levels. Furthermore, RNA-seq and KEGG pathway enrichment analysis indicated that the PI3K/AKT pathway was involved in the pro-osteoclastogenesis effect of NaF. Western blotting analysis exhibited that the phosphorylation of AKT was decreased in NaF-treated DPSCs. Chemical inhibition of the PI3K/AKT pathway abrogated the NaF-promoted DPSCs osteo/odontogenic differentiation. CONCLUSION: Micromolar NaF can promote the osteo/odontogenic differentiation of DPSCs by inhibiting the PI3K/AKT pathway. DATA AVAILABILITY: The data used to support the findings of this study are available from the corresponding author upon request.

Neu5Ac Induces Human Dental Pulp Stem Cell Osteo-/Odontoblastic Differentiation by Enhancing MAPK/ERK Pathway Activation.

Dental pulp stem cells (DPSCs) must undergo odontoblastic differentiation in order to facilitate the process of dentin-pulp complex repair. Herein, we sought to explore the ability of Neu5Ac (one form of sialic acid) to influence DPSC osteo-/odontoblastic differentiation via modulating mitogen-activated protein kinase (MAPK) signaling. Methodology. DPSCs were isolated from human third permanent teeth and were grown in vitro. Fluorescent microscopy was used to detect the existence of sialic acid on the DPSC membrane. Following the treatment of different concentrations of Neu5Ac and removing sialic acid from the cell surface by neuraminidase, the osteo-/odontoblastic differentiation of these cells was evaluated via mineralization, alkaline phosphatase, and in vivo assays. In addition, the expression of genes related to osteo-/odontoblastic differentiation and MAPK signaling at different stages of this differentiation process was analyzed in the presence or absence of Neu5Ac. Results. The existence of sialic acid on the DPSC membrane was confirmed by fluorescent microscopy, and the ability of osteo-/odontoblastic differentiation was decreased after removing sialic acid by neuraminidase. Treatment of DPSCs with Neu5Ac (0.1 mM or 1 mM) significantly enhanced their mineralization ability and alkaline phosphatase activity. The expression levels of DMP1, DSPP, BSP, and RUNX2 were also increased. Treatment of nude mice with ManNAc (the prerequisite form of Neu5Ac) also enhanced DPSC mineralization activity in vivo. Furthermore, Neu5Ac treatment enhanced p-ERK expression in DPSCs, while ERK pathway inhibition disrupted the ability of Neu5Ac to enhance the osteo-/odontoblastic differentiation of these cells. Conclusions. Neu5Ac can promote DPSC osteo-/odontoblastic differentiation through a process associated with the modulation of the ERK signaling pathway activity.

MicroRNA 26a targets Ezh2 to regulate apoptosis in mouse ovarian granulosa cells.

In the mammalian ovary, <1% of the follicles ovulate, with most undergoing degenerative atresia during ovarian follicular development. Follicular atresia is caused by the apoptosis of granulosa cells (GCs), although the precise underpinning mechanism remains unidentified. MiR-26a regulates various cellular events, including cell division, apoptotic signaling, and cell differentiation, migration, and autophagy. Here, we demonstrated that miR-26a regulated apoptosis in GCs in the mouse ovary through Ezh2, a key regulator of GC viability. We also found that transcription of miR-26a changed in response to an LH antagonist and a GnRH agonist. In addition, miR-26a transcription was downregulated following LH-induced transition of GCs to granulosa-lutein cells (GLCs). Dual-luciferase reporter assays confirmed Ezh2 as a miR-26a target. Exogenous expression in GCs of miR-26a mimics resulted in decreased Ezh2 expression, while miR-26a inhibition in GCs induced the opposite phenotype. Ezh2 silencing additionally reduced the anti-apoptotic effect of miR-26a inhibition in GCs. These data highlight the critical role of miR-26a in targeting Ezh2 and regulating apoptosis in mouse ovarian GCs.Abbreviations: GC: Granulosa cell; GLCs: Granulosa-lutein cells; LH: Luteinizing hormone; miRNA: MicroRNA; NC: Negative control; Cyt-c: Cytochrome c; GnRH: Gonadotropin releasing hormone; i.p.: intraperitoneal injection; cKO: conditional knock-out; WB: Western blotting; hCG: Human chorionic gonadotropin; NPC: nasopharyngeal carcinoma.

Pollution characteristics and source identification of soil metal(loid)s at an abandoned arsenic-containing mine, China.

Mining activities can result in serious contamination of soil by heavy metal(loid)s. In this study, the sources and spatial distribution of metal(loid)s, and the risks to public health from these metal(loid)s at an abandoned arsenic mine site were explored. The mean concentrations of arsenic (As), cadmium (Cd), mercury (Hg), manganese (Mn), lead (Pb), antimony (Sb), strontium (Sr), and thallium (Tl) in the soil in the mining area were higher than the mean background values. The main pollutants from the mining activities were As, Hg, and Sb. Five pollutant sources were identified using an approach that combined statistical methods, a positive matrix factorization model, and historical information analysis. As, Hg, Sb, and Tl were associated with the mining resources and related activities (37.29%); Mn (15.57%) and Sr (15.96%) were mainly from crustal origin and pedogenesis, respectively; Pb, Sb, and Tl were mainly from industrial sources (17.57%), and Cd was mainly from the production and application of phosphorous fertilizer (13.60%). Using incremental spatial autocorrelation crystallized that As, Hg, and Sb were mainly contained within 500 m of their source. There were formed existing non-carcinogenic hazards and carcinogenic risks from As, and potential carcinogenic risks from Cd, in the soil for those living locally.

Dynamic hip system blade versus cannulated compression screw for the treatment of femoral neck fractures: A retrospective study.

OBJECTIVE: The aim of this study was to compare clinical outcomes of patients with femoral neck fractures treated with the dynamic hip system blade (DHS-BLADE) or cannulated compression screws. METHODS: Eighty-six patients with femoral neck fractures were treated by closed reduction internal fixation with a DHS-BLADE (n = 42; 18 males and 24 females; mean age: 56.3 years (37-87)) or cannulated compression screws (n = 44; 20 males and 24 females; mean age: 53.8 years (26-83)) between March 2011 and August 2013. The groups were compared with Harris hip score, operation time, surgical blood loss, incision size, hospital stay, and related complications. RESULTS: The average follow-up time was 27 months (range, 24-36 months). There was no significant difference for the operation time, incision size, hospital stay, and Harris hip score between the groups. Also, no statistically significant differences in the rates of nonunion (4.5% vs. 0) and avascular necrosis of the femoral head (9.1% vs. 7.1%) were observed. However, the screw group experienced significantly less surgical blood loss (32.4 ± 24.7 ml) than the blade group (87.2 ± 46.6 ml; P = 0.041). The incidence of femoral neck shortening above 10 mm in the screw group was significantly higher than that in the blade group (15.9% vs. 2.4%, P = 0.031). The blade group had a significantly lower incidence of screw migration than the screw group (4.8% vs. 22.7%, P = 0.016). CONCLUSION: The DHS-BLADE and cannulated compression screws might be equally effective in terms of postoperative fracture union. However, the DHS-BLADE has advantages over cannulated compression screws for preventing femoral neck shortening, screw migration, and cut-out. LEVEL OF EVIDENCE: Level III, Therapeutic study.