Serpin family E member 1 enhances myometrium contractility by increasing ATP production during labor.

The uterine contraction during labor, a process with repetitive hypoxia and high energy consumption, is essential for successful delivery. However, the molecular mechanism of myometrial contraction regulation is unknown. Serpin family E member 1 (SERPINE1), one of the most upregulated genes in laboring myometrium in both transcriptome and proteome, was highlighted in our previous study. Here, we confirmed SERPINE1 is upregulated in myometrium during labor. Blockade of SERPINE1 using small interfering RNA (siRNA) or inhibitor (Tiplaxtinin) under hypoxic conditions in myocytes or myometrium in vitro showed a decrease contractility, which was achieved by regulating ATP production. Chromatin immunoprecipitation (ChIP-seq), Co-immunoprecipitation (Co-IP), and glutathione-S-transferase (GST) pull down explored that the promoter of SERPINE1 is directly activated by hypoxia-inducible factor-1α (HIF-1α) and SERPINE1 interacts with ATP Synthase Peripheral Stalk Subunit F6 (ATP5PF). Together they enhance hypoxia driven myometrial contraction by maintaining ATP production in the key oxidative phosphorylation pathway. The results provide new insight for uterine contraction regulation, and potential novel therapeutic targets for labor management.

Recent advances and pathological mechanisms in photodynamic and sonodynamic therapy in the treatment of bone tumors (Review).

Given the recent advances that have been made with photodynamic therapy (PDT) combined with sonodynamic therapy (SDT) (PDT/SDT; also known as SPDT), the application of this combination therapy in the clinic has provided another major breakthrough in the medical field, especially with regard to the treatment of deep tumors. Concerning its application in the treatment of bone tumors, numerous pathological mechanisms have been taken advantage of to overcome the barrier of tissue hypoxia, and SPDT is expected to achieve radical effects, with high penetration depth and low aggressiveness. In the present review, it is comprehensively shown how, according to the histoanatomy of bone tumors, PDT and SDT target cells in a coordinated manner, affecting such processes as necrotizing apoptosis, pyroptosis, autophagy and ferroptosis on the macroscopic level, and crucially, thrombosis at the vascular level, which leads to the triggering of immunogenic cell death in local and distant locations. Additionally, PDT and SDT have been shown to have roles in: i) degrading the extracellular matrix; ii) influencing the receptor activator of nuclear factor­κB (RANK)/RANK ligand signaling pathway; iii) disrupting the equilibrium between glutathione peroxidase 4 and reactive oxygen species (ROS); and iv) destroying the microscopic structure of the bone tumor. Upon PDT/SDT stimulation, several mechanisms act in concert to ensure that the targeted bone tumor is eliminated. Furthermore, widely distributed ROS have been revealed to promote osteoclast formation and osteogenic mineralization through the regulation of macrophages, processes that greatly improve the effects of postoperative repair. Finally, the developmental prospects of bone tumor engineering in the future are discussed in the present review.

Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins.

Osteosarcoma (OS) is the common primary bone cancer that affects mostly children and young adults. To augment the standard-of-care chemotherapy, we examined the possibility of protein-based therapy using mesenchymal stem cells (MSCs)-derived proteomes and OS-elevated proteins. While a conditioned medium (CM), collected from MSCs, did not present tumor-suppressing ability, the activation of PKA converted MSCs into induced tumor-suppressing cells (iTSCs). In a mouse model, the direct and hydrogel-assisted administration of CM inhibited tumor-induced bone destruction, and its effect was additive with cisplatin. CM was enriched with proteins such as calreticulin, which acted as an extracellular tumor suppressor by interacting with CD47. Notably, the level of CALR transcripts was elevated in OS tissues, together with other tumor-suppressing proteins, including histone H4, and PCOLCE. PCOLCE acted as an extracellular tumor-suppressing protein by interacting with amyloid precursor protein, a prognostic OS marker with poor survival. The results supported the possibility of employing a paradoxical strategy of utilizing OS transcriptomes for the treatment of OS.

Bletilla striata polysaccharide - waterborne polyurethane hydrogel as a wound dressing.

Polysaccharides are widely used in biomedicine because of their unique biological activity, low costs, and easy-to-obtain. In this paper, Bletilla striata polysaccharide (BSP) was integrated into waterborne polyurethane (WPU) to prepare a series of WPU-BSP (WPUB) hydrogels. The hydrogels showed good compressive strength, water absorption and retention ability, which are favorable for wound healing. Among them, the WPUB4 gel has the best comprehensive performances, including a compressive strength of 1.07 MPa, a swelling rate of 16.3, a reasonable WVRT of 2013 g/m2/day, and a long water retention time. About the in vitro biocompatibility, moreover, the WPUB4 hydrogel has a low hemolysis rate of 2.47%, a hydroxyl radical clearance rate of 35.5%, and little cytotoxicity with cell viability of 101.4%. Most importantly, the WPUB hydrogel dressings showed excellent ability in promoting wound healing. Compared to the conventional gauze, the wound surface area of mice treated with WPUB hydrogel was significantly reduced on day 3 after surgery and the wounds were healed on day 7. The new skin had a thicker epidermis and more capillaries. The WPUB hydrogels integrating BSP are promising to function as wound dressings.

Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors.

This study aimed to evaluate the effects of delayed femoral vein ligation on the clinical outcomes of hip disarticulation. We retrospectively reviewed 20 patients with extremity tumors (10 bone tumors and 10 soft tissue sarcomas [STS]) who underwent hip disarticulation. Patients treated for hip disarticulation with synchronous femoral vein ligation (n = 10, regular surgery group) and hip disarticulation with delayed femoral vein ligation (n = 10, delayed ligation group), respectively, were enrolled in this study. The operative time and blood loss were used to evaluate the clinical outcomes. The delayed ligation group had significantly lower operative times than the regular surgery group (P < 0.05). Total, hidden, and intraoperative blood loss were all significantly lower in the delayed ligation group than in the regular surgery group (P < 0.05). However, there were no significant differences in postoperative blood loss. In conclusion, delayed femoral vein ligation could significantly reduce the operative time, hidden blood loss, and intraoperative blood loss in patients undergoing hip disarticulation.

Nicotine ameliorates inflammatory mediators in RU486 induced preterm labor model through activating cholinergic anti-inflammatory pathway.

BACKGROUND: Preterm birth is a global public health threat. Inflammatory reaction is thought to mediate preterm birth. The role of nicotine, an anti-inflammatory agent that is mediated by cholinergic anti-inflammatory pathways (CAP), remains unclear in the pathogenesis. METHODS: Pregnant rats were randomly divided into four groups (20 rats each): pregnant control group (P), RU486-treated group (PTL), RU486 and nicotine-treated group (PTL + N), RU486, nicotine and α-BGT treated group (PTL + N + A). Rats were administered RU486 (1.0 mg/kg) by subcutaneous injection on gestational day (GD) 18 to establish PTL model. Subcutaneous injection of nicotine (1 mg/kg) was administered daily from GD 16 to 18. α-BGT (1 µg/kg) was administrated subcutaneously in two sessions and each session was 30 min prior to nicotine. TNF-α, IL-1ß, IL-4, IL-6, IL-10 in myometrium and serum were detected by Luminex. Macrophage infiltration and α7nAChR were detected by IHC. RESULTS: We established a RU486-induced preterm labor rat model. Preterm labor was associated with a striking upregulation inflammatory mediators and increased macrophage infiltration. Nicotine significantly prolonged gestation (P < 0.05) and α-BGT treatment reversed the prolonged interval (P < 0.05). The cytokines all markedly elevated at 12 h, but deceased after delivery (P < 0.05). The IL-1ß and TNF-α in serum were significantly increased in PTL group vs P group (P < 0.05), and decreased after nicotine treatment (P < 0.05). The cytokines IL-1ß, IL-4, IL-6, IL-10 and TNF-α in myometrium increased as the same trend as in serum. Nicotine treatment also downregulated the expression of α7nAChR in pregnant tissue. CONCLUSION: We confirmed the increased inflammation in preterm birth. Nicotine was able to down-regulate the inflammatory mediates and prolong the pregnant duration in PTL model, which might be induced by activating α7nAChR through CAP. This study provides a novel evidence supporting the future development of therapeutic target for preterm birth.

Thymic Extranodal Marginal-Zone Lymphoma of Mucosa-Associated Lymphoid Tissue: Pathological Features, 18F-FDG PET/CT Findings and Prognosis in 12 Cases.

Purpose: Primary thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of MALT lymphoma. We aim to investigate the clinicopathologic features, 18F-FDG PET/CT findings and outcomes for patients with primary thymic MALT lymphoma; to explore the correlation between metabolic parameters and immunohistochemical phenotypes. Methods: A retrospective single-center study enrolled 12 patients with primary thymic MALT lymphoma between 2010 and 2021. Nineteen 18F-FDG PET/CT scans were performed, and clinicopathologic and immunohistochemical characteristics, PET/CT imaging features, and outcomes were analyzed. Results: The male-to-female ratio was 1. The median age at diagnosis was 40 (range 31-68). The long diameter of the lesions ranged from 3.5 to 15.7. Histopathological examinations revealed that the normal thymic lobular architecture was effaced by a diffuse lymphoid infiltrate, but residual Hassall corpuscles could still be identified, mostly with CD20+, PAX5+, CD3-, CD23-, CD10-, BCL-6-, cyclin D1-, EBER- and low Ki-67. The gene rearrangement indicated that the IGH gene but not TCR gene was found in 7 patients. Six initial PET/CT scans showed a mean SUVmax of 6.8 (range, 3.1-12.4), a mean MTV = 40.0 (range, 6.7-81.4), and a mean TLG = 144.3 (range, 19.7-286.4). During the follow-up period, there was no death except for the patient with DLBCL who died 59 months after diagnosis of primary thymic MALT. No significant correlation between SUVmax and Ki-67 index was observed (r = 0.355, P > 0.05). Conclusion: Primary thymic MALT lymphoma should be considered in patients with multilocular cystic lesions with different degrees of 18F-FDG uptake in the anterior mediastinum. The results of this study showed no correlation between SUVmax and Ki-67 index.

Application of 18F Prostate-Specific Membrane Antigen Positron Emission Tomography/Computed Tomography in Monitoring Gastric Metastasis and Cancer Thrombi from Renal Cell Carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) with gastric metastasis is rare, particularly accompanied by multiple cancer thrombi. METHODS: We reported a 66-year-old man with a history of a right radical nephrectomy because of RCC. The patient underwent 18F prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) scanning after 6 months of targeted therapy because of gastric metastasis and cancer thrombi. We conducted a systematic review of the literature and identified 73 cases of RCC with gastric metastasis. We analyzed the clinicopathological characteristics, therapies, and outcomes of patients. RESULTS: 18F-PSMA PET/CT showed a large mass in the gastric fundus and cancer thrombi in the right atrium, inferior vena cava, and splenic vein with intense tracer uptake. Other metastases with increased tracer uptake included multiple bones and abdominal lymph nodes. The majority of gastric metastasis of RCC were men (53/73, 72.6%), with a median age at presentation of 67 (from 48 to 87) years. Gastric metastasis of RCC was mainly metachronous, and presented with small polyps or mass appearance and often accompanied by multiple-site metastases and gastrointestinal symptoms. An overall median interval between nephrectomy and diagnosis of gastric metastasis was 6 (from 0.1 to 23) years, and an overall median survival time was 14 (from 0.25 to 72) months. The median interval time of solitary gastric metastasis was longer than gastric metastasis with multiple-site metastases (7 vs.5 years; P=0.034). Patients with gastric and multiple-site metastases had higher mortality than patients with solitary metastasis (17 vs.1; P=0.028). The patients with synchronous gastric metastasis had a shorter survival time than metachronous gastric metastasis (6 vs.17 months; P=0.018). CONCLUSIONS: Postoperative follow-up of multiple imaging modalities to monitor recurrence and metastasis is necessary and important. PSMA PET/CT can improve the detection sensitivity of RCC, especially in metastatic clear cell renal cell carcinoma (ccRCC), and could provide a basis for disease staging, restaging, and therapeutic efficacy evaluation.

Long noncoding RNA LINC00649 functions as a microRNA­432­5p sponge to facilitate tumourigenesis in colorectal cancer by upregulating HDGF.

Long intergenic nonprotein coding RNA 649 (LINC00649) is a functional regulator in acute myeloid leukaemia. However, the contribution of LINC00649 in colorectal cancer (CRC) has yet to be confirmed. Accordingly, the present investigation was devoted to exploring the detailed functions of LINC00649 and reveal the mechanisms underlying the LINC00649­induced promotion of CRC progression. LINC00649 expression in CRC was investigated by reverse transcription­quantitative PCR. Knockdown of LINC00649 was achieved using small interfering RNAs or short hairpin RNA, followed by functional experiments. The binding between LINC00649 and microRNA (miR)­432­5p was predicted by a bioinformatics tool, and corroborated by luciferase reporter assay and RNA immunoprecipitation. In the present study, LINC00649 was expressed at a high level in CRC. The aberrant expression of LINC00649 exhibited an inverse association with CRC patient prognosis. Functionally, the downregulation of LINC00649 exerted anticarcinogenic activities in CRC by decreasing cell proliferation, migration, and invasion and inducing cell apoptosis. Furthermore, the growth of CRC cells in vivo was attenuated after LINC00649 deficiency. Mechanistically, LINC00649 functioned as a competitive endogenous RNA by competitively binding to miR­432­5p in CRC cells, inducing an increase in hepatoma­derived growth factor (HDGF). Ultimately, functional rescue experiments highlighted that the exogenous introduction of miR­432­5p inhibitor or HDGF overexpression plasmid partially abated the inhibitory effects of LINC00649 silencing. In conclusion, LINC00649 promoted the aggressiveness of CRC cells by adjusting the miR­432­5p/HDGF axis. Thus, the LINC00649/miR­432­5p/HDGF pathway may be a promising target for CRC therapy.

Application of Intelligent Monitoring of Percutaneous Partial Oxygen Pressure in Evaluating the Evolution of Scar Hyperplasia.

The study aimed to investigate the dynamic changes of percutaneous partial oxygen pressure during the development and evolution of a hypertrophic scar. Twenty cases of hypertrophic scar patients at different stages were selected. A percutaneous oxygen monitor was used to measure oxygen partial pressure in the scar and normal skin tissue at 14, 30, 60, and 90 days after surgery. The changes of oxygen partial pressure, tissue structure, HIF-1α, and VEGF expression in the scar tissue were observed, and the correlation was analyzed. In the scar maturation process, with the prolongation of time, the partial oxygen pressure in the tissue increased gradually. The expression intensity of HIF-1α and VEGF decreased gradually, HIF-1α was positively correlated with VEGF (r = 0.98, P < 0.01), there was a negative correlation between oxygen partial pressure and HIF-1 α expression (r = -0.92, P < 0.01), and it was negatively correlated with VEGF (r = -0.88, P < 0.01). TcPO2 measurement can be used to assess scar maturity; HIF-1 α and VEGF may play an essential role in regulating partial oxygen pressure in the scar tissue.

Glycogen synthase kinase 3ß promotes osteosarcoma invasion and migration via regulating PTEN and phosphorylation of focal adhesion kinase.

AIM: Typical features of human osteosarcoma are highly invasive and migratory capacities. Our study aimed to investigate the roles of glycogen synthase kinase 3ß (GSK3ß) in human osteosarcoma metastasis. METHODS: GSK3ß expressions in clinical osteosarcoma tissues with or without metastasis were examined by immunohistochemical staining. The expressions of GSK3ß, p-GSK3ßSer9, and p-GSK3ßTyr216 in human osteoblast cells (hFOB1.19) and human osteosarcoma cells (MG63, SaOS-2, and U2-OS) were detected by Western blotting. The GSK3ß activity was measured by non-radio isotopic in vitro kinase assay. Migration and invasion abilities of MG-63 cells treated with small-molecular GSK3ß inhibitors were respectively examined by monolayer-based wound-healing assay and transwell assay. The mRNA expressions of GSK3ß, matrix metalloproteinase-2 (MMP-2), MMP-9, phosphatase with tensin homology (PTEN), and focal adhesion kinase (FAK) were detected after siRNA transfection for 72 h. Meanwhile, protein expressions of GSK3ß, FAK, p-FAKY397, PTEN, MMP-2, and MMP-9 were measured by Western blotting. RESULTS: Clinical osteosarcoma tissues with metastasis showed higher GSK3ß expressions. MG63 and U2-OS cells that were easy to occur metastasis showed significantly higher expressions and activities of GSK3ß than SaOS-2 cells. Inhibition of GSK3ß with small-molecular GSK3ß inhibitors in MG63 cells significantly attenuated cell migration and invasion. These effects were associated with reduced expressions of MMP-2 and MMP-9. Moreover, increased PTEN and decreased p-FAKY397 expressions were observed following GSK3ß knockdown by siRNA transfection. CONCLUSION: GSK3ß might promote osteosarcoma invasion and migration via pathways associated with PTEN and phosphorylation of FAK.

Phototherapy together with it triggered immunological response for Anti-HPV treatment of oropharyngeal cancer: Removing tumor and pathogenic virus simultaneously.

Oropharyngeal squamous cell carcinoma (OPSCC) is one of most common cancers that often brings lots of inconvenience to the patient in swallowing and phonation even after the operation. Moreover, OPSCC is typically as nodal metastases and high recurrence rate due to the high-risk human papillomavirus (HPV) infection for 90% of patients. Obviously, completely curing OPSCC requires simultaneous removal of solid tumor and related pathogenic virus, which is very indispensable but never be realized by any kind of clinical therapy up to now. In this work, we selected the ZrC nanoparticles as difunctional photoactive substance for synchronous generation of hyperthermia and reactive oxygen species (ROS) under NIR excitation. The resultant synergistic photothermal and photodynamic treatment outcome contributed to an excellent anti-tumor effect. The phototherapy of this work was found not only to be able to damage cancer cells directly, but also could trigger the host immunity for further tumor removal and desirable HPV inactivation. An immunologic mechanism of this work was reasonable proposed by monitoring level of shock protein (HSP), calreticulin (CRT), T lymphocytes and dendritic cells (DCs) and immune check point of B7H3, B7H4 and PD-L1 post phototherapy. It was found that tumor-associated antigens of CRT ("eat-me" signal), HSPs and cell debris were released as cancer cell damage, and then the adaptive immune system and the congenital immunity were triggered to activate DCs maturity, antigen presentation to T cells, proliferation of CD4+ and CD8+ T cells, recruiting macrophages and NK cells and so forth immune responses. Being the first example of using phototherapy for virus-related cancer study, this work opens the door for photo-immunotherapy.

The Relationship Between Human Papillomavirus, OFD1 and Primary Ciliogenesis in the Progression of Oropharyngeal Cancer: A Retrospective Cohort Study.

PURPOSE: Infection with human papillomavirus (HPV) has been indicated to be a important risk factor for oropharyngeal squamous cell carcinoma (OPSCC). Primary ciliogenesis defects contribute to tumorigenesis, and OFD1 at centriolar satellites is a crucial suppressor of primary ciliogenesis. To identify novel markers associated with HPV-induced carcinogenesis, the interactions between HPV infection and primary ciliogenesis in the tumorigenesis and progression of OPSCC were investigated in this study. PATIENTS AND METHODS: The 1530 OPSCC patients recruited in this research were treated from 2000 to 2017. Immunohistochemistry and RT-PCR were performed on tissue samples to compare the expression of p16, TSLP, TGFß1, IFNγ, OFD1, and their relationship with clinical characteristics of patients. RESULTS: We speculate that the positive expression of p16 is related to early primary OPSCC, and the survival rate of p16 positive patients after radiotherapy and surgery is higher. Expression of TSLP on dendritic cells in HPV-positive OPSCC correlated with the expression of OFD1. HPV-positive OPSCC showed increased expression of OFD1 combined with reduced ciliogenesis. Hence, TSLP induced by HPV infection may reduce the invasive potential of OPSCC cells by promoting OFD1 expression, thereby inhibiting primary ciliogenesis. CONCLUSION: Our study demonstrated that HPV may be related to the progression of OPSCC by regulating OFD1 expression and primary ciliogenesis, making this protein a potential therapeutic target.

Identification of Biomarkers for Osteosarcoma Based on Integration Strategy.

BACKGROUND Osteosarcoma (OS) is the most common primary malignant tumor of bone. The identification of novel biomarkers is necessary for the diagnosis and treatment of osteosarcoma. MATERIAL AND METHODS We obtained 11 paired fresh-frozen OS samples and normal controls from patients between September 2015 and February 2017. We used an integration strategy that analyzes next-generation sequencing data by bioinformatics methods based on the pathogenesis of osteosarcoma. RESULTS One susceptibility lncRNA and 7 susceptibility genes regulated by the lncRNA for osteosarcoma were effectively identified, and real-time PCR and clinical index ALP data were used to test their effectiveness. CONCLUSIONS The results showed that the expression levels of the 7 genes were highly consistent in the training and test sample sets, especially between the expression value of the gene ALPL and the plasma detection value of its encoded protein ALP. In particular, both the expression of gene ALPL and the plasma detection values of protein ALP encoded by gene ALPL showed a high degree of consistency among different data types. The identified lncRNA and genes effectively classified the samples proved so that they could be used as potential biomarkers of osteosarcoma. Our strategy may also be helpful for the identification of biomarkers for other diseases.

A Retrospective Clinicopathological Study of Osteosarcoma Patients with Metachronous Metastatic Relapse.

Purpose: Although osteosarcoma patients receive a standardized treatment, metachronous metastatic relapse still impairs the overall survival (OS). This study aimed to explore the clinicopathological features and prognostic factors of osteosarcoma patients with metachronous metastatic relapse. Patients and methods: We retrospectively analyzed 59 patients, between January 1st, 2004 and December 31st, 2013. Employed Chi-square test to recognize the differences in clinicopathological characteristics between early and late metastatic patients, and the differences between shorter and longer survival patients. Used the Kaplan-Meier method to evaluate the survival data, cox step proportional hazard test to analyze the prognostic factors associated with OS. Results: We found that early metastatic patients were prominently correlated with the male, tumor size ≥8 cm, histological grade G2, Enneking stages II, anatomic location of the distal femur, pathological of conventional types, and elevated alkaline phosphatase (ALP) level at diagnosis, (p<0.05). In parallel, the shorter survival patients were primarily linked to tumor size ≥8 cm, histological grade G2, Enneking stages II, early metastasis, multiple pulmonary metastases, lack of curative treatment after metastasis, increased level of ALP at diagnosis and LDH after metastasis, (p<0.05). The univariate analyses of the prognostic factors showed that patients who had these clinicopathological characteristics, such as male, tumor size ≥8 cm, Enneking stage IIB, multiple pulmonary metastases, lack of curative treatment after metastasis, the elevated ALP at diagnosis, elevated ALP and LDH after metastasis, had a worse OS in osteosarcoma patient with metachronous metastatic relapse, (p<0.05). The multivariate analyses showed that tumor size, type of metastasis and ALP level at diagnosis were independent factors for OS in osteosarcoma patient with metachronous metastatic relapse (p<0.05). Conclusion: These results indicated that osteosarcoma patients with metachronous metastatic relapse have special features which might be utilized to effectively predict the likelihood of early metastatic relapse and the prognosis.

Nicotine protects fetus against LPS-induced fetal growth restriction through ameliorating placental inflammation and vascular development in late pregnancy in rats.

Our previous work has shown that nicotine suppressed lipopolysaccharide (LPS)-induced placental inflammation by inhibiting cytokine release as well as infiltration of leukocytes into the placenta through the cholinergic anti-inflammatory pathway. Nicotine also increased fetal survival and restored pup weight. In the present study, we aim to further investigate if fetal growth restriction (FGR) occurs with LPS treatment, and evaluate the protective effects of nicotine on fetuses in late gestation of rats. Pregnant Sprague-Dawley rats were divided into control group, nicotine group, LPS group and LPS + nicotine group. Rats were first pretreated with nicotine or vehicle by subcutaneous injection on gestation day (GD)14 and GD15, followed by LPS or vehicle intraperitoneal injection on GD16, and were killed on GD18. Loss of fetuses, number and weights of live fetuses and weights of placentas were recorded. Placentas were collected to evaluate placental pathology and determine inflammatory cytokines and vascular endothelial growth factor (VEGF) levels. We found that LPS treatment increased levels of placental inflammatory cytokines and placental pathological damage, decreased levels of VEGF, reduced number of live fetuses and induced FGR. Pretreatment with nicotine reversed LPS-induced high levels of placental inflammatory cytokines, low levels of placental VEGF and placental pathological damage, then rescued the number and weights of live fetuses. These data demonstrated that activation of the cholinergic anti-inflammatory pathway by nicotine protected fetus against LPS-induced FGR through ameliorating placental inflammation and vascular development in late pregnancy in rats. It may be an alternative therapeutic strategy for inflammation- induced FGR in late pregnancy.

Thioredoxin-interacting protein induced α-synuclein accumulation via inhibition of autophagic flux: Implications for Parkinson's disease.

AIMS: Thioredoxin-interacting protein (TXNIP) is associated with activation of oxidative stress through inhibition of thioredoxin (Trx). However, some evidences point out that TXNIP acts as a scaffolding protein in signaling complex independent of cellular redox regulation. The autophagy-lysosomal pathway plays important roles in the clearance of misfolded proteins and dysfunctional organelles. Lysosomal dysfunction has been involved in several neurodegenerative disorders including Parkinson's disease (PD). Although researchers have reported that TXNIP inhibited autophagic flux, the specific mechanism is rarely studied. METHODS: In this study, we investigated the effects of TXNIP on autophagic flux and α-synuclein accumulation by Western blot in HEK293 cells transfected with TXNIP plasmid. Further, we explored the influence of TXNIP on DA neuron survival in substantia nigra by IHC. RESULTS: We found that TXNIP induced LC3-II expression, but failed to degrade p62, a substrate of autophagy. Also, TXNIP aggravated α-synuclein accumulation. We also found that TXNIP inhibited the expression of ATP13A2, a lysosomal membrane protein. Moreover, we found that overexpression of ATP13A2 attenuated the impairment of autophagic flux and α-synuclein accumulation induced by TXNIP. Furthermore, overexpression of TXNIP in substantia nigra resulted in loss of DA neuron. CONCLUSION: Our data suggested that TXNIP blocked autophagic flux and induced α-synuclein accumulation through inhibition of ATP13A2, indicating TXNIP was a disease-causing protein in PD.

Activation of the cholinergic anti-inflammatory pathway by nicotine ameliorates lipopolysaccharide-induced preeclampsia-like symptoms in pregnant rats.

INTRODUCTION: Preeclampsia (PE) exerts a more intense systemic inflammatory response than normal pregnancy. Recently, the role of the cholinergic anti-inflammatory pathway (CAP) in regulating inflammation has been extensively studied. The aim of this study was to investigate the effect of nicotine, a selective cholinergic agonist, on lipopolysaccharide (LPS)-induced preeclampsia-like symptoms in pregnant rats and to determine the molecular mechanism underlying it. METHODS: Rats were administered LPS (1.0 µg/kg) via tail vein injection on gestational day 14 to induce preeclampsia-like symptoms. Nicotine (1.0 mg/kg/d) and α-bungarotoxin (1.0 µg/kg/d) were injected subcutaneously into the rats from gestational day 14-19. Clinical symptoms were recorded. Serum and placentas were collected to determine cytokine levels using Luminex. The mRNA and protein expression levels of α7 nicotinic acetylcholine receptor (α7nAChR) were determined using Real time-PCR and Western blot analysis. Immunohistochemistry was performed to determine the level of activation of nuclear factor-κB (NF-κB) in placentas. RESULTS: Nicotine significantly ameliorated LPS-induced preeclampsia-like symptoms in pregnant rats (P < 0.05). Nicotine treatment decreased the levels of LPS-induced pro-inflammatory cytokines in the serum (P < 0.05) and placenta (P < 0.05). Nicotine significantly increased the expression of α7nAChR (P < 0.01) and attenuated the activation of NF-κB p65 in the placenta in LPS-induced preeclampsia (P < 0.01). Meanwhile, these protective effects of nicotine were abolished by the administration of the cholinergic antagonist α-bungarotoxin in preeclampsia rats. DISCUSSION: Our findings suggest that the activation of α7nAChR by nicotine attenuates preeclampsia-like symptoms, and this protective effect is likely the result of the inhibition of inflammation via the NF-κB p65 pathway.

Surface Surgery of the Nickel-Rich Cathode Material LiNi0.815Co0.15Al0.035O2: Toward a Complete and Ordered Surface Layered Structure and Better Electrochemical Properties.

A complete and ordered layered structure on the surface of LiNi0.815Co0.15Al0.035O2 (NCA) has been achieved via a facile surface-oxidation method with Na2S2O8. The field-emission transmission electron microscopy images clearly show that preoxidation of the hydroxide precursor can eliminate the crystal defects and convert Ni(OH)2 into layered ß-NiOOH, which leads to a highly ordered crystalline NCA, with its (006) planes perpendicular to the surface in the sintering process. X-ray photoelectron spectroscopy and Raman shift results demonstrate that the contents of Ni2+ and Co2+ ions are reduced with preoxidization on the surface of the hydroxide precursor. The level of Li+/Ni2+ disordering in the modified NCA determined by the peak intensity ratio I(003)/I(104) in X-ray diffraction patterns decreases. Thanks to the complete and ordered layered structure on the surface of secondary particles, lithium ions can easily intercalate/extract in the discharging-charging process, leading to greatly improved electrochemical properties.