A multifunctional biomimetic nanoplatform for image-guideded photothermal-ferroptotic synergistic osteosarcoma therapy.

Much effort has been devoted to improving treatment efficiency for osteosarcoma (OS). However, most current approaches result in poor therapeutic responses, thus indicating the need for the development of other therapeutic options. This study developed a multifunctional nanoparticle, PDA-MOF-E-M, an aggregation of OS targeting, programmed death targeting, and near-infrared (NIR)-aided targeting. At the same time, a multifunctional nanoparticle that utilises Fe-MOFs to create a cellular iron-rich environment and erastin as a ferroptosis inducer while ensuring targeted delivery to OS cells through cell membrane encapsulation is presented. The combination of PDA-MOF-E-M and PTT increased intracellular ROS and LPO levels and induced ferroptosis-related protein expression. A PDA-based PTT combined with erastin showed significant synergistic therapeutic improvement in the anti-tumour efficiency of the nanoparticle in vitro and vivo. The multifunctional nanoparticle efficiently prevents the osteoclasia progression of OS xenograft bone tumors in vivo. Finally, this study provides guidance and a point of reference for clinical approaches to treating OS.

Gestational cadmium exposure disrupts fetal liver development via repressing estrogen biosynthesis in placental trophoblasts.

Cadmium (Cd), commonly found in diet and drinking water, is known to be harmful to the human liver. Nevertheless, the effects and mechanisms of gestational Cd exposure on fetal liver development remain unclear. Here, we reported that gestational Cd (150 mg/L) exposure obviously downregulated the expression of critical proteins including PCNA, Ki67 and VEGF-A in proliferation and angiogenesis in fetal livers, and lowered the estradiol concentration in fetal livers and placentae. Maternal estradiol supplement alleviated aforesaid impairments in fetal livers. Our data showed that the levels of pivotal estrogen synthases, such as CYP17A1 and 17ß-HSD, was markedly decreased in Cd-stimulated placentae but not fetal livers. Ground on ovariectomy (OVX), we found that maternal ovarian-derived estradiol had no major effects on Cd-impaired development in fetal liver. In addition, Cd exposure activated placental PERK signaling, and inhibited PERK activity could up-regulated the expressions of CYP17A1 and 17ß-HSD in placental trophoblasts. Collectively, gestational Cd exposure inhibited placenta-derived estrogen synthesis via activating PERK signaling, and therefore impaired fetal liver development. This study suggests a protective role for placenta-derived estradiol in fetal liver dysplasia shaped by toxicants, and provides a theoretical basis for toxicants to impede fetal liver development by disrupting the placenta-fetal-liver axis.

Environmental cadmium exposure during gestation impairs fetal brain and cognitive function of adult offspring via reducing placenta-derived E2 level.

Early-life exposure to environmental cadmium (Cd) is known to cause developmental disorders, yet the effect and mechanism of gestational exposure to Cd on the offspring's cognitive function remains unclear. Placenta as a well-established target organ for Cd-impaired fetal development, its role in estrogen regulation and offspring cognitive function is unknown. Our in vivo experiments found that gestational Cd exposure impaired cognitive function in adult male offspring, accompanied with lowered 17ß-estradiol (E2) level in the male fetal brain upon Cd exposure. Correspondingly, the expression of synapse-associated proteins including brain-derived neurotrophic factor (BDNF), post-synaptic density protein 95 (PSD95) and synapsin-1 were downregulated, which were reversed when supplemented with E2 hormone during gestation. Further observation showed placental estrogen synthesis inhibition and general control non-derepressible 2 (GCN2) signaling activation upon Cd exposure, whereas placental estrogen synthesis could be restored through inhibiting GCN2 activity. Based on ovariectomy (OVX) of pregnant mice, we confirmed that Cd exposure reduced E2 level in fetal brain via inhibiting placenta-derived estrogen synthesis. The aforementioned Cd-induced fetal brain injury and cognitive impairment in adult offspring were significantly alleviated when pregnant dams were supplemented with anti-stress agent N-Acetyl-l-cysteine. In summary, Cd disrupted placenta-derived estrogen synthesis via activating GCN2 signaling, and thereby caused cognitive impairment in adult offspring mice. Our findings suggest that placenta-derived estrogen may be an effect marker of environmental toxicants-evoked cognitive dysfunction in adult offspring and suggest that environmental toxicants may affect the fetal brain development via placenta-fetal-brain axis.

Chronic inflammation as a potential mediator between phthalate exposure and depressive symptoms.

BACKGROUND: A few studies have reported phthalate exposure as a risk factor for depressive symptoms, but the results have been inconsistent. Whether chronic inflammation mediates the relationship between phthalates (PAEs) and depressive symptoms remains unclear. In this study, we establish mediating models of inflammatory factors and explore the mediating role of chronic inflammation in the association between PAEs exposure and depressive symptoms. METHODS: The sample included 989 participants from the Study on Health and Environment of the Elderly in Lu'an City, Anhui Province. Geriatric depression scale (GDS-30) was used to screen depressive symptoms of the elderly. The levels of seven kinds of PAEs in urine samples and four inflammatory factors in serum of the elderly were measured. To establish the mediating effect of inflammatory factors to explore the potential effect of PAEs exposure on the increased odds of depressive symptoms. RESULTS: Adjusted for multiple variables, the highest tertiles of Mono (2-ethylhexyl) phthalate (MEHP) (95%CI = 1.051-2.112), Mono benzyl phthalate (MBzP) (95%CI = 1.016-2.082) and Mono butyl phthalate (MBP) (95%CI = 1.102-2.262) were positively correlated with depressive symptoms. The mediating effect of IL-6 and generalized inflammation factor between MEHP exposure and depressive symptoms were 15.96% (95%CI=0.0288-0.1971) and 14.25% (95%CI = 0.0167-0.1899). CONCLUSIONS: High levels of MEHP, MBzP and MBP increased the odds of depressive symptoms in the elderly, and chronic inflammation had a partial mediating effect on the increased odds of depressive symptoms due to MEHP exposure.

A simple, universal and multifunctional template agent for personalized treatment of bone tumors.

Bone tumors occur in bone or its accessory tissues. Benign bone tumors are easy to cure and have good prognosis, while malignant bone tumors develop rapidly and have poor and high mortality. So far, there is no satisfactory treatment method. Here, we designed a universal template vector for bone tumor therapy that simultaneously meets the needs of bone targeting, tumor killing, osteoclast suppression, and tumor imaging. The template is composed of a polydopamine (PDA) core and a multifunctional surface. PDA has excellent biosafety and photothermal performance. In this study, alendronate sodium (ALN) is grafted to enable its general bone targeting function. PDA core can carry a variety of chemotherapy drugs, and the rich ALN group can carry a variety of metal ions with an imaging function. Therefore, more personalized treatment plans can be designed for different bone tumor patients. In addition, the PDA core enables photothermal therapy and enhanced chemotherapy. Through template drug Doxorubicin (DOX) and template imaging ion Fe (Ⅱ), we systematically verified the therapeutic effect, imaging effect, and inhibition of bone dissolution of the agent on Osteosarcoma (OS), a primary malignant bone tumor, in vivo. In conclusion, our work provides a more general template carrier for the clinical treatment of bone tumors, through which personalized treatment of bone tumors can be achieved.

Gestational exposure to environmental cadmium induces placental apoptosis and fetal growth restriction via Parkin-modulated MCL-1 degradation.

Heavy metal cadmium (Cd), a classical environmental pollutant, causes placental apoptosis and fetal growth restriction (FGR), whereby the mechanism remains unclear. Here, our human case-control study firstly showed that there was a positive association of Parkin mitochondrial translocation, MCL-1 reduction, placental apoptosis, and all-cause FGR. Subsequently, Cd was administered to establish in vitro and in vivo models of placental apoptosis or FGR. Our models demonstrated that Parkin mitochondrial translocation was observed in Cd-administrated placental trophoblasts. Meaningfully, Parkin siRNA (siR) dramatically mitigated Cd-triggered apoptosis in placental trophoblasts. Mdivi-1 (M-1), an inhibitor for Parkin mitochondrial translocation, mitigated Cd-induced apoptosis in placental trophoblasts, which further ameliorated the effect of attenuated placental sizes in Cd-exposed mice. Furthermore, the interaction of MCL-1 with Parkin or Ub in Cd-stimulated cells was stronger than that in controls. MG132, an inhibitor for proteasome, abolished MCL-1 degradation in Cd-stimulated cells. Importantly, Parkin siR and M-1 memorably abolished the ubiquitin-dependent degradation of MCL-1 in placental trophoblasts. Interestingly, mito-TEMPO and melatonin, two mitochondria-targeted antioxidants, obviously rescued Cd-caused mitochondrial membrane potential (MMP) decrease, Parkin mitochondrial translocation, MCL-1 degradation, and apoptosis in placental trophoblasts. In conclusion, cadmium induces placental apoptosis and FGR via mtROS-mediated Parkin-modulated degradation of MCL-1.

Environmental cadmium impairs blood-testis barrier via activating HRI-responsive mitochondrial stress in mice.

Cadmium (Cd) is a well-known testicular toxicant. Blood-testis barrier (BTB), a vital part of testes, which has been reported to be damaged upon Cd exposure. However, the detailed mechanism about Cd-mediated disruption of BTB remains unclear. This study aims to investigate the role of Heme-Regulated Inhibitor (HRI)-responsive mitochondrial stress in Cd-mediated disruption of BTB. Male mice are intraperitoneally injected (i.p.) with melatonin (Mel, a cellular stress antagonist, 5.0 mg/kg) before Cd treatment (i.p., 2.0 mg/kg) for 8 h, and then treated with Cd for 0-48 h. Mouse Sertoli cells are pretreated with Mel (10 µM) for 1 h, and then treated with Cd (10 µM) for 0-24 h. We find that Cd damages the BTB and reduces the Occludin protein, a crucial BTB-related protein via activating p38/matrix metalloproteinase-2 (p38/MMP2) pathway and Integrated Stress Response (ISR). Further experiments reveal that the Heme-Regulated Inhibitor (HRI)-responsive mitochondrial stress is triggered in Cd-treated Sertoli cells. Most importantly, Cd-activated p38 signaling and ISR are regulated by HRI-responsive mitochondrial stress in Sertoli cells. Unexpectedly, we find that melatonin rescues the Cd-mediated disruption of BTB through blocking HRI-responsive mitochondrial stress in testes. Overall, these data indicate that environmental cadmium exposure impairs the BTB through activating HRI-responsive mitochondrial stress in Sertoli cells.

miR-6769b-5p targets CCND-1 to regulate proliferation in cadmium-treated placental trophoblasts: Association with the impairment of fetal growth.

Environmental cadmium (Cd) is positively associated with placental impairment and fetal growth retardation. Nevertheless, its potential mechanisms remain unclear. microRNAs (miRNAs) are known to influence placental development and fetal growth. This work was aimed to determine which miRNAs are involved in Cd-impaired placental and fetal development based on the mRNA and miRNA expression profiles analysis. As a result, gestational Cd exposure deceased fetal and placental weight, and reduced the protein level of PCNA in human and mouse placentae. Furthermore, the results of mRNA microarray showed that Cd-downregulated mRNAs were predictively correlated with several biological processes, including cell proliferation, differentiation and motility. In addition, the results of miRNA microarray and qPCR assay demonstrated that Cd significantly increased the level of miR-6769b-5p, miR-146b-5p and miR-452-5p. Integrated analysis of Cd-upregulated miRNAs predicted target genes and Cd-downregulated mRNAs found that overlapping mRNAs, such as CCND1, CDK13, RINT1 and CDC26 were also significantly associated with cell proliferation. Further experiments showed that miR-6769b-5p inhibitor, but not miR-146b-5p and miR-452-5p, markedly reversed Cd-downregulated the expression of proliferation-related mRNAs, and thereby restored Cd-decreased the proteins level of CCND1 and PCNA in human placental trophoblasts. Dual luciferase reporter assay further revealed that miR-6769b-5p directly targets CCND1. Finally, the case-control study demonstrated that increased miR-6769b-5p level and impaired cell proliferation were observed in small-for-gestational-age human placentae. In conclusion, miR-6769b-5p targets CCND-1 to regulate proliferation in Cd-treated placental trophoblasts, which is associated with the impairment of fetal growth. Our findings imply that placental miR-6769b-5p may be used as an epigenetic marker for environmental pollutants-caused fetal growth restriction and its late-onset chronic diseases.

Gestational cadmium exposure impairs placental angiogenesis via activating GC/GR signaling.

Gestational exposure to environmental Cd caused placental angiogenesis impairment and fetal growth restriction (FGR). However, its mechanism remained unclear. This study was to investigate the effects of Cd exposure during pregnancy on placental angiogenesis and its mechanism. Pregnant mice were exposed to CdCl2 (4.5 mg/kg) on gestational day (GD) 8 with or without melatonin (MT) (5.0 mg/kg), an anti-endoplasmic reticulum stress agent, from GD7 to GD15. Human primary placental trophoblasts and JEG-3 cells were stimulated using CdCl2 (20 µM) after MT (1 mM) preprocessing. We firstly found MT treatment obviously mitigated environmental Cd-induced placental angiogenesis disorder and reduction of the VEGF-A level. Mechanistically, MT reversed environmental Cd-downregulated the protein expression of VEGF-A via inhibiting glucocorticoid receptor (GR) activation. Notably, our data showed MT treatment antagonized Cd-activated GC/GR signaling via blocking PERK signaling and thereby upregulated VEGF-A and 11ß-HSD2 protein expression. Based upon the population case-control study, the levels of VEGF-A and 11ß-HSD2 protein in small-for-gestational-age placentae were significantly reduced when compared to appropriate-for-gestational-age placentae. Overall, environmental Cd exposure during gestation impaired placental angiogenesis via PERK-regulated GC/GR signaling in placental trophoblasts. Our findings will provide a basis for prevention and treatment of placental impairments and fetal growth restriction caused by environment toxicants in future.

Environmental cadmium exposure during pregnancy causes diabetes-like phenotypes in mouse offspring: Association with oxidative stress in the fetal liver.

Cadmium (Cd), a noxious heavy metal, is widespread in the living environment. Gestational exposure to Cd at environmental dose has been shown to cause fetal growth restriction (FGR). However, the long-term effects and the mechanisms underlying environmental Cd exposure on glucose metabolism in offspring remain unclear. Here, we established a murine model to study the impacts of gestational exposure to environmental Cd on glucose metabolism at different life stages of offspring. Results demonstrated that the offspring mice developed hyperglycemia in puberty and impaired glucose tolerance in adulthood following maternal Cd exposure during gestation. Further mechanistic investigation showed that Cd exposure upregulated the expression of key proteins in hepatic gluconeogenesis, including p-CREB, PGC-1α and G6PC, in pubertal and adult offspring. In addition, we demonstrated that Cd exposure during pregnancy markedly elevated the level of oxidative stress-related proteins, including NOX2, NOX4 and HO-1, in the fetal liver. The effects of gestational exposure to N-acetylcysteine (NAC), a free-radical scavenging antioxidant, presented that NAC supplementation alleviated hepatic oxidative stress in fetuses, and thereby reversed hyperglycemia and glucose intolerance in mouse offspring. Collectively, our data suggested that gestational exposure to environmental Cd caused diabetes-like phenotypes via enhancing hepatic gluconeogenesis, which is associated with oxidative stress in fetal livers. This work provides new insights into the protective effects of antioxidants on fetal-originated diabetes triggered by environmental toxicants.

Melatonin protects against environmental stress-induced fetal growth restriction via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts.

Gestational exposure to environmental stress induces fetal growth restriction (FGR), and thereby increasing the risk of infant death and chronic noncommunicable diseases in adults. However, the mechanism by which environmental stress induces FGR remains unclear. Based on case-control study, we found that the reduced level of melatonin (MT), a major secretory product from the pineal gland, was observed in placentae of FGR. This work was to investigate the protective effect of MT on environmental stress-caused FGR and its mechanisms. We used cadmium (Cd) as an environmental stressor to stimulate pregnant mice and thereby establishing a FGR model. The data showed that maternal Cd exposure lowered the P4 concentration in maternal sera, placentae and amniotic fluid, and caused FGR. Correspondingly, the expression of CYP11A1, a critical P4 synthase, was markedly downregulated in Cd-treated placentae. Simultaneously, Cd triggered BNIP3-dependent mitophagy in placental trophoblasts, as determined by the degradation of mitochondrial proteins, including HSP60 and COX IV, and the accumulation of puncta representing co-localization of TOM20 with LC3B or BNIP3 with LC3B. Based on our case-control study, we also found that activated BNIP3-dependent mitophagy and P4 synthesis inhibition occurred in SGA placentae. Most importantly, BNIP3 siRNA reversed Cd-induced P4 synthesis suppression in human placental trophoblasts. It is noteworthy that MT alleviated Cd-caused P4 synthesis suppression and FGR via antagonizing BNIP3-dependent mitophagy in placental trophoblasts. Further results confirmed that MT attenuated Cd-triggered BNIP3-dependent mitophagy via blocking GCN2/ATF4 signaling. Amusingly, Cd triggered oxidative stress and then activating GCN2/ATF4 signaling in placental trophoblasts. As expected, MT obviously suppressed Cd-caused reactive oxygen species (ROS) release. In the present study, we propose a neoteric mechanism by which MT protects against environmental stress-impaired P4 synthesis and fetal growth via suppressing ROS-mediated GCN2/ATF4/BNIP3-dependent mitophagy in placental trophoblasts. As above, MT is a potential therapeutic agent antagonizing environmental stress-induced developmental toxicity.

Environmental cadmium exposure induces fetal growth restriction via triggering PERK-regulated mitophagy in placental trophoblasts.

Cadmium (Cd), an environmental toxicant, is positively associated with fetal growth restriction (FGR). However, the mechanism by which gestational exposure to Cd induces FGR remains unclear. This study designed in vitro and in vivo experiments to explore the role of placental mitophagy in Cd-impaired fetal growth. Based on our case-control study, we also investigated the association of placental mitophagy with reduced progesterone (P4) level and all-cause FGR. We firstly found environmental Cd exposure lowered the P4 content in maternal sera, placentae and amnioticfluids of mice. The level of three mitochondrial P4 synthases, including StAR, CYP11A1 and 3ß-HSD, was also reduced in Cd-treated placentae. Furthermore, Cd triggered mitophagy, as determined by the degradation of two mitochondrial proteins HSP60 and COX IV, and the accumulation of co-localizations of TOM20 with LC3B or Parkin in placental trophoblasts. Correspondingly, Cd elevated mitochondrial Parkin level in placental trophoblasts. Mdivi-1, a mitophagy inhibitor, obviously attenuated Cd-induced reduction of placental P4 and FGR in mice. Moreover, mdivi-1 and Parkin siRNA (siR) markedly reversed Cd-caused P4 synthesis inhibition in human placental trophoblasts. Interestedly, the PERK/ATF4 signaling was activated in Cd-stimulated placental trophoblasts. PERK siR inhibited mitochondrial proteins degradation in Cd-stimulated placental trophoblasts. In particularly, mitophagy activation and P4 synthesis suppression occurred in small-for-gestational-age placentae based on our case-control study. Environmental Cd exposure induced FGR via activating PERK-regulated mitophagy and inhibiting P4 synthesis in placentaltrophoblasts. Furthermore, placental mitophagy was related to the reduced progesterone level and all-cause fetal growth restriction based on our case-control study. As above, placental mitophagy maybe the common mechanism of environmental toxicants-impaired fetal growth.

Autophagy in Sertoli cell protects against environmental cadmium-induced germ cell apoptosis in mouse testes.

Cadmium (Cd) was an environmental pollutant, which could result in germ cell apoptosis in testes. Sertoli-germ cell communication was vital for germ cell development and maturity. However, little was known about the effect of Sertoli cell autophagy on Cd-induced germ cell apoptosis. Here, we used male Amh-Cre+/Atg5flox/flox (Atg5-/-) mice, loss of autophagy-related gene 5 (Atg5) in testicular Sertoli cells, to explore the obscure effects. Atg5-/- and Wild-type (WT) mice were given with cadmium chloride (CdCl2, 2.0 mg/kg) for 0-24 h. Our results showed that Cd triggered testicular germ cell apoptosis, as evidenced by the increment of TUNEL-labeled germ cells, cleaved caspase3 and cleaved poly (ADP-ribose) polymerase protein level. Additionally, Cd induced testicular autophagy, as determined by elevating the level of autophagy-related proteins, including Atg5, Atg7, LC3B-II, and the gathering of LC3 puncta. 3-methyladenine, a specific autophagy inhibitor, exacerbated Cd-caused germ cell apoptosis. Inversely, rapamycin, an autophagy inducer, relieved Cd-stimulated germ cell apoptosis. Interestingly, we found that autophagy in Sertoli cells was activated in Cd-treated WT mouse testes as evidenced by the increment of LC3 puncta surrounding SOX9, a specific Sertoli cell marker. More importantly, loss of autophagy in Sertoli cells aggravated Cd-triggered germ cell apoptosis. Taken together, these data indicate that autophagy in Sertoli cells alleviates Cd-triggered germ cell apoptosis in mouse testes.

Cadmium down-regulates 11ß-HSD2 expression and elevates active glucocorticoid level via PERK/p-eIF2α pathway in placental trophoblasts.

Fetal overexposure to active glucocorticoid (GC) is the major cause for fetal growth restriction (FGR). This study investigated the influences of cadmium (Cd) exposure on active GC and its mechanism in placental trophoblasts. Pregnant mice were exposed to CdCl2 (4.5 mg/kg, i.p.). Human JEG-3 cells were treated with CdCl2 (0-20 µM). Prenatal Cd exposure significantly increased active GC level in amniotic fluid and placenta. Similarly, Cd treatment also elevated active GC level in medium. Expectedly, the expression of 11ß-HSD2 protein was markedly downregulated in Cd-exposed placental trophoblasts. We further found that Cd activated the PERK/p-eIF2α signaling pathway in placental trophoblasts. Mechanistically, PERK siRNA pretreatment completely blocked PERK/p-eIF2α signaling, and thereby restoring Cd-downregulated 11ß-HSD2 protein expression in human placental trophoblasts. We further found that N-acetylcysteine, a well-known antioxidant, obviously reversed Cd-downregulated 11ß-HSD2 protein expression by inhibiting p-PERK/p-eIF2α signaling in placental trophoblasts. Overall, our data suggest that Cd activates the PERK/p-eIF2α signaling, down-regulates the protein expression of 11ß-HSD2, and thereby elevating active GC level in placental trophoblast.

Attenuation of the degenerative effects of endothelin-1 on cartilaginous end plate cells by the endothelin receptor antagonist BQ-123 via the Wnt/ß-catenin signaling pathway.

BACKGROUND CONTEXT: Endothelin-1 (ET-1) is an inflammatory mediator associated with cartilage end plate (CEP) degeneration in the intervertebral disc (IVD). SOX9 is downregulated during CEP degeneration, along with its targets, collagen II and aggrecan. Wnt/ß-catenin signaling is associated with CEP degeneration and a downstream target of SOX9; however, the precise mechanism of CEP degeneration and the role of ET-1 are largely unknown. PURPOSE: The purpose of the study was to evaluate the influence of the endothelin-A receptor antagonist, BQ-123, on ET-1-induced effects on cartilaginous end plate cells (CECs) associated with CEP degeneration via the Wnt/ß-catenin signaling pathway. STUDY DESIGN/SETTING: The influence of ET-1 on the expression levels of collagen II, aggrecan, and SOX9 in CECs and the effect of BQ-123 in this context were investigated. METHODS: To establish a model for CEP degeneration, three lumbar discs (L3-L4, L4-L5, and L5-L6 levels) in New Zealand white rabbits were punctured close to the vertebral end plate using a 14G needle. Intervertebral disc degeneration was evaluated by magnetic resonance imaging 4 weeks after vertebral end plate injury. CECs were then isolated from the degenerated CEPs to allow evaluation of the role of ET-1 and BQ-123 and to investigate their effects on the Wnt/ß-catenin signaling pathway. The expression of ET-1 in CECs from degenerated CEPs was analyzed by immunofluorescent staining. Changes in the levels of collagen II, aggrecan, and SOX9 were evaluated in CECs by real-time polymerase chain reaction and by Western blotting. The Wnt/ß-catenin signaling pathway was also investigated by Western blotting. RESULTS: After 4 weeks, IVDs with vertebral end plate injury exhibited clear signs of disc degeneration. Immunofluorescent staining showed that ET-1 was expressed in the cytoplasm of CECs. Endothelin-1 stimulation significantly inhibited the expression of collagen II, aggrecan, and SOX9 in CECs, whereas BQ-123 increased the levels of these three molecules. In addition, ET-1 stimulation increased the expression of ß-catenin, cyclin D1, and Dvl1 in the Wnt/ß-catenin signaling pathway of CECs from degenerated discs and reduced the expression of GSK-3ß, whereas BQ-123 had the opposite effect. CONCLUSIONS: Endothelin-1 can reduce levels of collagen II, aggrecan, and SOX9 in CECs through activation of the Wnt/ß-catenin signaling pathway, whereas BQ-123 attenuates these negative effects, highlighting a new molecular mechanism with potential for exploitation for treatment of CEP degeneration.

Selective Arterial Embolization for the Treatment of Sacral and Pelvic Giant Cell Tumor: A Systematic Review.

Giant cell tumor of the bone (GCTB) is a locally aggressive tumor with a certain distant metastatic rate. For sacral GCT (SGCT) and pelvic GCT (PGCT), surgery has its limitations, especially for unresectable or recurrent tumors. Selective arterial embolization (SAE) is reported to be an option for treatment in several cases, but there are few systematic reviews on the effects of SAE on SGCT and/or PGCT. Medline and Embase databases were searched for eligible English articles. Inclusion and exclusion criteria were conducted before searching. All the clinical factors were measured by SPSS software, with P-values ≤0.05 considered statistically significant. A total of 9 articles were retrieved, including 44 patients receiving SAE ranging from 1 to 10 times. During the mean follow-up period of 85.8 months, the radiographic response rate was 81.8%, with a local control and overall survival rate of 75% and 81.8%, respectively. No bowel, bladder, or sexual dysfunction was observed. Three patients developed distant metastases and finally died. Patients with primary tumors tended to have better prognosis than those with recurrence (P = 0.039). The favorable outcomes of SAE suggest that it may be an alternative treatment for SGCT and PGCT patients for whom surgery is not appropriate.

Reduction of adhesion formation after knee surgery in a rat model by botulinum toxin A.

Adhesion of the knee is a major concern after knee surgery, the treatment of which is difficult. Botulinum toxin A (BTX-A) injection is demonstrated as efficient in treating knee adhesion after surgery. However, the treatment outcomes and the mechanism of action are not yet determined. The aim of the present study was to examine the effects and molecular mechanism of a BTX-A treatment in preventing adhesion of the knee. Twenty-four Wistar rats were randomly divided into a BTX-A treatment group and a control group. BTX-A or saline was injected into the cavity of the knee in the BTX-A treatment or control group respectively. Gross and histopathological examinations of interleukin 1 (IL-1) and fibroblast growth factor (FGF) levels, as well as fibroblast cell numbers, were assessed in the knee intra-articular adhesions in each group 6 weeks after recovery from the surgery. Macroscopic observations showed a significant reduction in adhesion severity in the BTX-A treatment group compared with the control group. In addition, the levels of IL-1 and FGF were lower and the number of fibroblasts was smaller in the BTX-A treatment group compared with those in the control group. BTX-A prevented intra-articular adhesion of knee in the rats, which might be associated with reduced expressions of IL-1 and FGF.

[Investigation on the spectrum of complex self-organized plasma photonic crystal].

A complex plasma photonic crystal (PPC) was obtained by self-organization of filaments in air dielectric barrier discharge using two planar water electrodes. The PPC structure consists of many square sublattices, and each sublattice is composed of large spots, two kinds of small spots and lines, corresponding to thick plasma columns, two kinds of thin plasma columns, and plasma slices, respectively. By using the optical emission spectrum method, the electron densities and molecular vibration temperatures at different positions of the PPC were studied. The electron densities were compared by comparing the broadenings of Ar I (2P2-->1S5) spectrum line, and the molecular vibration temperatures were calculated by the spectrum line of nitrogen band of second positive system (C3Πu-->B3Πg) . It was found that the electron densities and molecular vibration temperatures at different positions are both different, showing that the plasma states at different positions are different. The descending order of the electron density is: thin plasma columns around the thick plasma columns, thick plasma columns, plasma slices, and thin plasma columns at junction of plasma slices. The descending order of the molecular vibration temperature is: thin plasma columns at junction of plasma slices, plasma slices, thick plasma columns, and thin plasma columns around the thick plasma columns, which is opposite to that of the electron density. So, the electron densities and the molecular vibration temperatures in different positions of the PPC show the opposite changing trend. As the refractive index of plasma is dependent upon the electron density, the thick plasma columns, two kinds of thin plasma columns and plasma slices in this PPC have different refractive indexes. Together with the surrounding area where no discharges occur, in which the refractive index is also different from the discharging areas, the complex PPC can be seen as a self-organized periodic structure with five different refractive indexes. The PPC has the advantages of being obtained easily, having structural diversity, and being analyzed simply, which may lead to wide applications in many scientific and technical areas.

[Investigation of plasma parameters of the square pattern with two kinds of spatiotemporal symmetry in dielectric barrier discharge].

Two kinds of square patterns with different spatiotemporal symmetry were observed in dielectric barrier discharge, and their plasma parameters were measured by using optical emission spectra. It was found that the spatiotemporal symmetry of the square pattern at lower gas pressure is different from the one at higher gas pressure. Six spectral lines in the emission spectrum of the N2 second positive band were chosen to estimate the vibrational temperature, and the ratio of I391.4/I394.1 was used to represent the average electron energy. The excitation temperature was determined by the ratio of I763.2/I772.1. Furthermore, the width and shift of Ar I 696.54 nm were used to estimate the electron density. The results show that the vibrational temperature, excitation temperature and electron energy of the square pattern at lower gas pressure are higher than those at higher gas pressure, while the electron density is lower than that at higher gas pressure.