Formation of a D-shaped optical fiber by in-cavity online polishing for high resolution sensing in a chaotic correlation fiber loop ring down system.

Online monitoring of the polishing process of a D-shaped optical fiber sensor is performed in this paper by means of a chaotic correlation fiber loop ring down (CCFLRD) system. The ring down time of the autocorrelation coefficient decreases with the increase in polishing loss caused by different mesh sizes. A comparison of the sensitivity and resolution of the CCFLRD system with different polishing losses in the length of a fiber loop cavity are carried out. Online polishing in the fiber loop cavity with a very short length is proposed and demonstrated using different polishing mesh numbers to increase the sensitivity and resolution of the system. A high sensitivity of 31.871n s -1 R I U -1 and resolution of 10-4 R I U for refractive index sensing in the range of 1.3347-1.3721 correspond to different concentrations of sodium chloride.

Generation of random soliton-like beams in a nonlinear fractional Schrödinger equation.

We investigate the generation of random soliton-like beams based on the Kuznetsov-Ma solitons in a nonlinear fractional Schrödinger equation (NLFSE). For Lévy index α = 1, the Kuznetsov-Ma solitons split into two nondiffracting beams during propagation in linear regime. According to the different input positions of the Kuznetsov-Ma solitons, the diffraction-free beams can be divided into three different types: bright-dark, dark-bright and bright-bright beams. In the nonlinear regime, the Kuznetsov-Ma solitons can be evolved into random soliton-like beams due to the collapse. The number of soliton-like beams is related to the nonlinear coefficient and the Lévy index. The bigger the nonlinear coefficient, the more beams generated. Moreover, the peak intensity of soliton-like beams presents a Gaussian distribution under the large nonlinear effect. In practice, the evolution of KM soliton can be realized by a plane wave with a Gaussian perturbation, which can be confirmed that they have the similar dynamics of propagation. In two dimensions, the plane wave with a Gaussian perturbation can be evolved into a bright-dark axisymmetric ring beam in the linear regime. Under the nonlinear modulation, the energy accumulates to the center and finally breaks apart into random beam filaments.

SESN2 prevents the slow-to-fast myofiber shift in denervated atrophy via AMPK/PGC-1α pathway.

BACKGROUND: Sestrin2 (SESN2), a stress-inducible protein, has been reported to protect against denervated muscle atrophy through unfolded protein response and mitophagy, while its role in myofiber type transition remains unknown. METHODS: A mouse sciatic nerve transection model was created to evaluate denervated muscle atrophy. Myofiber type transition was confirmed by western blot, fluorescence staining, ATP quantification, and metabolic enzyme activity analysis. Adeno-associated virus (AAV) was adopted to achieve SESN2 knockdown and overexpression in gastrocnemius. AMPK/PGC-1α signal was detected by western blot and activated with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). C2C12 myotubes with rotenone treatment were adopted for in vitro experiments. RESULTS: SESN2 was found to be upregulated in denervated skeletal muscles and rotenone-treated C2C12 cells. Knockdown of SESN2 aggravated muscle atrophy and accelerated myofiber type transition from slow-twitch to fast-twitch. Moreover, AMPK/PGC-1α signaling was proven to be activated by SESN2 after denervation, which further induced the expression of hypoxia-inducible factor HIF2α. Exogenous activation of AMPK/PGC-1α signaling could counteract the addition of slow-to-fast myofiber shift caused by SESN2 knockdown and lead to the retainment of muscle mass after denervation. CONCLUSION: Collectively, the present study indicates that SESN2 prevents myofiber type transition from slow-twitch to fast-twitch and preserves muscle mass in denervated atrophy via AMPK/PGC-1α signaling. These findings contribute to a better understanding of the pathogenesis of muscle atrophy and provide novel insights into the role of SESN2 in myofiber type transition.

Research progress on N6-methyladenosine in the human placenta.

OBJECTIVES: N6-methyladenosine (m6A) is one of the most common epigenetic modifications of eukaryotic RNA. Under the jointly reversible regulation of related enzymes, m6A regulates many aspects of RNA, such as translation, stability and degradation. The aim of this study is to investigate the role of m6A in placenta-related diseases. METHODS: Data were compiled from 2018 to 2021 citations in PubMed and Google Scholar using the keywords: placenta AND N6-methyladenosine. Seven studies were included. RESULTS: In this study, we introduced some conventional methods to detect m6A modification at the whole RNA, region (peak) and single base levels. We also summarized the current studies of m6A modification in the placenta and briefly describe m6A in placental-related diseases, including recurrent miscarriage (RM), preeclampsia (PE) and gestational diabetes mellitus (GDM). CONCLUSIONS: Although the relevant reports are still in the preliminary stage and some results are inconsistent, studies on methylation m6A modification have contributed new ideas for the research of reproductive diseases, providing a new basis for the diagnosis, treatment, prognosis and monitoring of related diseases.

Nrf2/HO-1 pathway is involved the anti-inflammatory action of intrauterine infusion of platelet-rich plasma against lipopolysaccharides in endometritis.

OBJECTIVE(S): Endometritis is the inflammatory response of the uterine lining which is linked to infertility. Administration of platelet-rich plasma (PRP) represents a well-recommended strategy for the treatment of endometrium-associated infertility. In this study, we set to characterize the role and molecular mechanism of PRP intrauterine infusion in mice with endometritis. METHODS: A mouse model of endometritis was established using lipopolysaccharide (LPS). Mouse endometrial epithelial cells were obtained in primary culture. PRP-treated cells were assayed for proliferative and apoptotic activities. Moreover, iNOS expression and chemokine and inflammatory factor contents in cells were assessed using RT-qPCR and ELISA. The mice were subjected to PRP intrauterine infusion. The expression of genes related to uterine development was analyzed by qPCR and the ki-67 content and caspase-3 activation in endometrial tissues were examined by immunohistochemistry. Finally, the Nrf2/HO-1 pathway activity in tissues was examined by Western blot. RESULTS: LPS induced inflammatory cell recruitment and tissue damage in the endometrium of mice, along with significantly increased levels of inflammatory and chemokine factors. PRP significantly enhanced endometrial epithelial cell activity, decreased apoptosis, and reduced inflammatory factor secretion. In addition, PRP intrauterine infusion significantly increased the expression of genes related to uterine development, promoted tissue proliferation, decreased apoptosis, and diminished inflammatory response in endometrial tissues of mice. PRP intrauterine infusion significantly elevated Nrf2/HO-1 pathway activity in endometrial epithelial cells and tissues. CONCLUSION: PRP intrauterine infusion significantly inhibited endometrial cell injury and alleviated the inflammatory response through activating the Nrf2/HO-1 pathway.

A novel protoapigenone analog RY10-4 induces apoptosis of breast cancer cells by exacerbating mitochondrial Ca2+ influx through mitochondrial calcium uniporter.

RY10-4, a novel protoapigenone analog with a specific nonaromatic B-ring, displayed enhanced cytotoxicity in various tumor cells, especially for breast cancer cells, but the underlying mechanism remains unclear. In the present study, we confirmed the pro-apoptotic effect of RY10-4 on breast cancer cells. Furthermore, mitochondrial calcium uniporter (MCU) was proved to be up-regulated in RY10-4-treated MDA-MB-231 cells, which resulted in the overload of mitochondrial calcium ([Ca2+]m) and subsequently disrupted mitochondrial functions (characterized by mitochondrial reactive oxygen species (mtROS) accumulation, membrane potential (ΔΨm) depolarization and permeability transition pore (mPTP) opening). And finally, the mitochondrial apoptosis was activated by the release of cytochrome C. Interestingly, knockdown of MCU attenuated the overload of [Ca2+]m and blocked the apoptosis of MDA-MB-231 cells induced by RY10-4, which was consistent with the in vivo results. Taken together, this study proved that RY10-4 could induce apoptosis of breast cancer cells by elevating [Ca2+]m through MCU. Our work contributed previously unknown insights into the mechanisms involving in the clinical efficacy of RY10-4 on breast cancer cells, which also advanced calcium homeostasis as a potential target for chemotherapeutic drugs.

Increased METTL3-mediated m6A methylation inhibits embryo implantation by repressing HOXA10 expression in recurrent implantation failure.

BACKGROUND: Recurrent implantation failure (RIF) is a major limitation of assisted reproductive technology, which is associated with impaired endometrial receptivity. Although N6-methyladenosine (m6A) has been demonstrated to be involved in various biological processes, its potential role in the endometrium of women with RIF has been poorly studied. METHODS: Global m6A levels and major m6A methyltransferases/demethylases mRNA levels in mid-secretory endometrium from normal and RIF women were examined by colorimetric m6A quantification strategy and quantitative real-time PCR, respectively. The effects of METTL3-mediated m6A modification on embryo attachment were evaluated by an vitro model of a confluent monolayer of Ishikawa cells co-cultured with BeWo spheroids, and the expression levels of homeo box A10 (HOXA10, a well-characterized marker of endometrial receptivity) and its downstream targets were evaluated by quantitative real-time PCR and Western blotting in METTL3-overexpressing Ishikawa cells. The molecular mechanism for METTL3 regulating HOXA10 expression was determined by methylated RNA immunoprecipitation assay and transcription inhibition assay. RESULTS: Global m6A methylation and METTL3 expression were significantly increased in the endometrial tissues from women with RIF compared with the controls. Overexpression of METTL3 in Ishikawa cells significantly decreased the ration of BeWo spheroid attachment, and inhibited HOXA10 expression with downstream decreased ß3-integrin and increased empty spiracles homeobox 2 expression. METTL3 catalyzed the m6A methylation of HOXA10 mRNA and contributed to its decay with shortened half-life. Enforced expression of HOXA10 in Ishikawa cells effectively rescued the impairment of METTL3 on the embryo attachment in vitro. CONCLUSION: Increased METTL3-mediated m6A modification represents an adverse impact on embryo implantation by inhibiting HOXA10 expression, contributing to the pathogenesis of RIF.

Up-regulation of CD81 inhibits cytotrophoblast invasion and mediates maternal endothelial cell dysfunction in preeclampsia.

Preeclampsia (PE) is initiated by abnormal placentation in the early stages of pregnancy, followed by systemic activation of endothelial cells of the maternal small arterioles in the late second or third trimester (TM) of pregnancy. During normal pregnancy, placental cytotrophoblasts (CTBs) invade the maternal uterine wall and spiral arteries, whereas this process is interrupted in PE. However, it is not known how the malformed placenta triggers maternal endothelial crisis and the associated manifestations. Here, we have focused on the association of CD81 with PE. CD81, a member of the tetraspanin superfamily, plays significant roles in cell growth, adhesion, and motility. The function of CD81 in human placentation and its association with pregnancy complications are currently unknown. In the present study, we have demonstrated that CD81 was preferentially expressed in normal first TM placentas and progressively down-regulated with gestation advance. In patients with early-onset severe PE (sPE), CD81 expression was significantly up-regulated in syncytiotrophoblasts (STBs), CTBs and the cells in the villous core. In addition, high levels of CD81 were observed in the maternal sera of patients with sPE. Overexpressing CD81 in CTBs significantly decreased CTB invasion, and culturing primary human umbilical vein endothelial cells (HUVECs) in the presence of a high dose of exogenous CD81 resulted in interrupted angiogenesis and endothelial cell activation in vitro. Importantly, the phenotype of human PE was mimicked in the CD81-induced rat model.

HMGB1/autophagy pathway mediates the atrophic effect of TGF-ß1 in denervated skeletal muscle.

BACKGROUND: Transforming growth factor beta 1 (TGF-ß1) is a classical modulator of skeletal muscle and regulates several processes, such as myogenesis, regeneration and muscle function in skeletal muscle diseases. Skeletal muscle atrophy, characterized by the loss of muscle strength and mass, is one of the pathological conditions regulated by TGF-ß1, but the underlying mechanism involved in the atrophic effects of TGF-ß1 is not fully understood. METHODS: Mice sciatic nerve transection model was created and gastrocnemius were analysed by western blot, immunofluorescence staining and fibre diameter quantification after 2 weeks. Exogenous TGF-ß1 was administrated and high-mobility group box-1 (HMGB1), autophagy were blocked by siRNA and chloroquine (CQ) respectively to explore the mechanism of the atrophic effect of TGF-ß1 in denervated muscle. Similar methods were performed in C2C12 cells. RESULTS: We found that TGF-ß1 was induced in denervated muscle and it could promote atrophy of skeletal muscle both in vivo and in vitro, up-regulated HMGB1 and increased autophagy activity were also detected in denervated muscle and were further promoted by exogenous TGF-ß1. The atrophic effect of TGF-ß1 could be inhibited when HMGB1/autophagy pathway was blocked. CONCLUSIONS: Thus, our data revealed that TGF-ß1 is a vital regulatory factor in denervated skeletal muscle in which HMGB1/ autophagy pathway mediates the atrophic effect of TGF-ß1. Our findings confirmed a new pathway in denervation-induced skeletal muscle atrophy and it may be a novel therapeutic target for patients with muscle atrophy after peripheral nerve injury.

Dihydrotestosterone Treatment Accelerates Autograft Reversal Sciatic Nerve Regeneration in Rats.

Neuroactive steroids such as progesterone, testosterone, and their derivatives have been widely studied for their neuroprotective roles in the nervous system. Autologous nerve transplantation is considered as the gold standard repair technique when primary suture is impossible; nevertheless, this method is far from ideal. In this study, we aimed to explore the impact of dihydrotestosterone (DHT), a 5α-reduced derivative of testosterone, on the recovery of peripheral nerve injury treated with autologous nerve transplantation. Sprague-Dawley rats were subjected to a 10-mm right side sciatic nerve reversed autologous nerve transplantation and randomly divided into groups that received DHT or DHT + flutamide (an androgen receptor blocker) daily for 8 weeks after operation. Our results demonstrated that DHT could speed up the rate of axonal regeneration and increase the expression of myelin protein zero (P0) in autograft reversal sciatic nerves. Thus, our study provided new insights into improving the prognosis of patients with long gap peripheral nerve defects.

Optical sensors using chaotic correlation fiber loop ring down.

We have proposed a novel optical sensor scheme based on chaotic correlation fiber loop ring down (CCFLRD). In contrast to the well-known FLRD spectroscopy, where pulsed laser is injected to fiber loop and ring down time is measured, the proposed CCFLRD uses a chaotic laser to drive a fiber loop and measures autocorrelation coefficient ring down time of chaotic laser. The fundamental difference enables us to avoid using long fiber loop as required in pulsed FLRD, and thus generates higher sensitivity. A strain sensor has been developed to validate the CCFLRD concept. Theoretical and experiment results demonstrate that the proposed method is able to enhance sensitivity by more than two orders of magnitude comparing to the existing FLRD method. We believe the proposed method could find great potential applications for chemical, medical, and physical sensing.

Differentiation of bone marrow stromal cells into schwann-like cells using dihydrotestosterone combined with a classical induction method.

OBJECTIVE: To investigate the effect of dihydrotestosterone (DHT) combined with Dezawa's method on the differentiation of bone marrow stromal cells (BMSCs) into schwann-like cells. RESULTS: Compared to the Dezawa's method, schwann-like cells obtained from our modified method were longer and thinner and exhibited a typical bipolar or tripolar shape. These cells had a higher mRNA expression of S100 and myelin protein zero (P0), about 1.7- and 2.5-fold respectively, while the glial fibrillary acidic protein (GFAP) mRNA level was decreased about 92 %. No significant difference in peripheral myelin protein 22 (PMP22) mRNA expression was found. Immunofluorescence and Western blot showed the similar results. CONCLUSION: DHT in combination with Dezawa's method to induce a BMSCs to differentiate into schwann-like cells with higher expression of P0, which might be more effective in clinical application than previous method for nerve regeneration.

Titanium Dioxide Nanoparticles Induce Maternal Preeclampsia-like Syndrome and Adverse Birth Outcomes via Disrupting Placental Function in SD Rats.

The escalating utilization of titanium dioxide nanoparticles (TiO2 NPs) in everyday products has sparked concerns regarding their potential hazards to pregnant females and their offspring. To address these concerns and shed light on their undetermined adverse effects and mechanisms, we established a pregnant rat model to investigate the impacts of TiO2 NPs on both maternal and offspring health and to explore the underlying mechanisms of those impacts. Pregnant rats were orally administered TiO2 NPs at a dose of 5 mg/kg body weight per day from GD5 to GD18 during pregnancy. Maternal body weight, organ weight, and birth outcomes were monitored and recorded. Maternal pathological changes were examined by HE staining and TEM observation. Maternal blood pressure was assessed using a non-invasive blood analyzer, and the urinary protein level was determined using spot urine samples. Our findings revealed that TiO2 NPs triggered various pathological alterations in maternal liver, kidney, and spleen, and induced maternal preeclampsia-like syndrome, as well as leading to growth restriction in the offspring. Further examination unveiled that TiO2 NPs hindered trophoblastic cell invasion into the endometrium via the promotion of autophagy. Consistent hypertension and proteinuria resulted from the destroyed the kidney GBM. In total, an exposure to TiO2 NPs during pregnancy might increase the risk of human preeclampsia through increased maternal arterial pressure and urinary albumin levels, as well as causing fetal growth restriction in the offspring.

CHAF1A promotes the proliferation and growth of epithelial ovarian cancer cells by affecting the phosphorylation of JAK2/STAT3 signaling pathway.

The molecular mechanism of chromatin assembly factor 1 unit A (CHAF1A) promoting the proliferation and growth of epithelial ovarian cancer (EOC) cells hasn't been reported at present. In this study, recombinant CHAF1A siRNA/overexpression plasmid (si-RNA1/pcDNA3.1-CHAF1A) was designed and constructed, and stable cell lines with knockdown or overexpression of CHAF1A were constructed. The changes of JAK2/STAT3 pathway were detected by Western blot. JAK2/STAT3 pathway was inhibited by Peficitinib, and then cell proliferation and growth ability were detected. Bioinformatics analysis suggested that CHAF1A was up-regulated in epithelial ovarian cancer. JAK2/STAT3 pathway phosphorylation was inhibited in si-RNA1 group, while it was increased in pcDNA3.1-CHAF1A group. After inhibiting JAK2/STAT3 pathway, the promoting effect of CHAF1A on epithelial ovarian cancer cell proliferation disappeared, meanwhile the inhibitory effect of CHAF1A on apoptosis enhanced. In conclusion, CHAF1A promotes the proliferation and growth of epithelial ovarian cancer cells by affecting the phosphorylation of JAK2/STAT3 signaling pathway.

[AntiEGFRnano inhibites proliferation and migration of estrogen-dependent Ishikawa cells of human endometrial cancer cell line].

Nanobody is a kind of antibody from camel, which misses light chain. Nanobody has the same antigen binding specificity and affinity as mAb. Moreover, because of its small molecular weight, high stability and easy preparation, nanobody has great value of biomedical applications. In this study, we successfully prepared highly pure antiEGFR nanobody in E.coli using genetic engineering techniques. Cell proliferation assay (CCK-8 assay) and migration experiments (cell scratch test and Transwell assay) indicated that the recombinant antiEGFRnano can significantly inhibit the proliferation and migration of endometrial cancer cells. These results provide a new way of thinking and methods for EGFR-targeted therapy of endometrial cancer.

Intrauterine Perfusion of Autologous Platelet-Rich Plasma Before Frozen-Thawed Embryo Transfer Improves the Clinical Pregnancy Rate of Women With Recurrent Implantation Failure.

Objective: To evaluate whether the intrauterine perfusion of platelet-rich plasma (PRP) before frozen-thawed embryo transfer (FET) improves the pregnancy outcomes of patients with repeated implantation failure (RIF). Methods: This retrospective study included 288 infertile women with RIF after undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment from October 1, 2019, to January 1, 2021, at Qingdao Women and Children's Hospital. Patients were divided into two groups according to whether they received PRP intrauterine perfusion before embryo transfer in FET cycles. 138 women were in the PRP group, 150 women were in the control group. The primary outcome measure was live birth rates and the secondary outcome were clinical pregnancy, positive ß hCG, miscarriage and implantation rates. Results: No significant differences in baseline demographic and clinical characteristics were observed between the two groups. Overall, significantly more women in the PRP group than in the control group achieved a live birth rate (41 women; 29.71% vs. 27 women; 18%) and a clinical pregnancy (50 women; 36.23% vs. 37 women; 24.67%). The PRP group had a higher implantation rate and lower spontaneous miscarriage rate than the control group, but these differences were not statistically significant. No pregnancy outcome difference between two groups in PCOS patients with RIF. Conclusion: Our results showed that intrauterine perfusion of PRP before embryo transfer in FET cycles can significantly increase the live birth and clinical pregnancy rates in patients with RIF.

Upregulation of METTL14 contributes to trophoblast dysfunction by elevating FOXO3a expression in an m6A-dependent manner.

INTRODUCTION: Preeclampsia, a specific complication of pregnancy, is a leading cause of perinatal and maternal mortality worldwide. N6-methyladenosine (m6A) is a prevalent and reversible modification of mammalian mRNAs, and is known to play an important role in various physiological and pathological processes. However, little is known about its possible effects on trophoblasts in preeclampsia. METHODS: Colorimetric RNA m6A methylation quantification assay and dot blotting were used to assess the levels of global RNA m6A modification in placental tissues collected from females with normal pregnancy and preeclampsia, while the mRNA levels of major m6A methyltransferases/demethylases were investigated by quantitative real-time polymerase chain reaction. The effects of methyltransferase-like 14 (METTL14) on trophoblasts were evaluated using cell counting kit-8, transwell invasion assay, autophagic flux assay, and Annexin V/propidium iodide apoptosis assay. The molecular mechanism underlying the regulation of forkhead box O3a (FOXO3a) expression by METTL14 was determined using methylated RNA immunoprecipitation and transcription inhibition assays. RESULTS: Global RNA m6A methylation and METTL14 expression were significantly increased in placental tissues obtained from patients with preeclampsia. In vitro studies showed that overexpression of METTL14 in HTR-8/SVneo cells inhibited trophoblast proliferation and invasion, but induced trophoblast autophagy and apoptosis. We further demonstrated that METTL14 epigenetically elevated FOXO3a expression via an m6A-dependent mechanism. FOXO3a inhibition effectively prevented the impairment of trophoblast proliferation and invasion, and diminished the induction of trophoblast autophagy and apoptosis in METTL14-overexpressing HTR-8/SVneo cells. DISCUSSION: Increased METTL14-mediated m6A modification results in an adverse impact on trophoblast function by elevating FOXO3a expression.

SESN2 protects against denervated muscle atrophy through unfolded protein response and mitophagy.

Denervation of skeletal muscles results in a rapid and programmed loss of muscle size and performance, termed muscle atrophy, which leads to a poor prognosis of clinical nerve repair. Previous researches considered this process a result of multiple factors, such as protein homeostasis disorder, mitochondrial dysfunction, endoplasmic reticulum stress (ERS), and apoptosis, while their intrinsic association remains to be explored. In this study, Sestrin2 (SESN2), a stress-inducible protein, was shown to act as a key protective signal involved in the crosstalk therein. SESN2 expression was induced in the gastrocnemius two weeks post denervation, which was accompanied by ERS, mitochondrial dysfunction, and apoptosis. Knockdown of SESN2 aggravated this situation and resulted in severer atrophy. Similar results were also found in rotenone-treated C2C12 cells. Furthermore, SESN2 was demonstrated to be induced by an ERS-activated transcription factor CCAAT-enhancer-binding protein beta (C/EBPß). Once induced, SESN2 halted protein synthesis by inhibiting the mammalian target of rapamycin complex 1 (mTORC1), thereby attenuating ERS. Moreover, increased SESN2 activated the specific autophagic machinery and facilitated the aggregation of sequestosome 1 (SQSTM1, p62) on the mitochondrial surface, which promoted the clearance of damaged mitochondria through mitophagy. Collectively, the SESN2-mediated unfolded protein response (UPR) and mitophagy play a critical role in protecting against denervated muscle atrophy, which may provide novel insights into the mechanism of skeletal muscle atrophy following denervation.

Denervation drives skeletal muscle atrophy and induces mitochondrial dysfunction, mitophagy and apoptosis via miR-142a-5p/MFN1 axis.

Rationale: Peripheral nerve injury is common in clinic, which leads to severe atrophy and dysfunction of the denervated muscles, but the underlying mechanism is not fully understood. Recent studies advanced the causative role of mitochondrial dysfunction in muscle atrophy, while the upstream triggers remained unclear. Methods: In the present study, Atrophy of gastrocnemius and tibialis anterior (TA) were evaluated in mice sciatic nerve transection model. Transmission electron microscopy (TEM) was then used to observe the microstructure of atrophic gastrocnemius and mitochondria. Subsequently, small RNA sequencing, luciferase reporter assay and Electrophoretic Mobility Shift (EMSA) were performed to explore the potential signaling pathway involved in skeletal muscle atrophy. The effects of the corresponding pathway on mitochondrial function, mitophagy, apoptosis and muscle atrophy were further determined in C2C12 cells and denervated gastrocnemius. Results: Gastrocnemius and TA atrophied rapidly after denervation. Obvious decrease of mitochondria number and activation of mitophagy was further observed in atrophic gastrocnemius. Further, miR-142a-5p/ mitofusin-1 (MFN1) axis was confirmed to be activated in denervated gastrocnemius, which disrupted the tubular mitochondrial network, and induced mitochondrial dysfunction, mitophagy and apoptosis. Furthermore, the atrophy of gastrocnemius induced by denervation was relieved through targeting miR-142a-5p/MFN1 axis. Conclusions: Collectively, our data revealed that miR-142a-5p was able to function as an important regulator of denervation-induced skeletal muscle atrophy by inducing mitochondrial dysfunction, mitophagy, and apoptosis via targeting MFN1. Our findings provide new insights into the mechanism of skeletal muscle atrophy following denervation and propose a viable target for therapeutic intervention in individuals suffering from muscle atrophy after peripheral nerve injury.

Up-regulation of PTEN via LPS/AP-1/NF-κB pathway inhibits trophoblast invasion contributing to preeclampsia.

Preeclampsia, a pregnancy-specific disorder, is characterized by abnormal vascular remodeling of the spiral arteries due to deficient trophoblast invasion. Lipopolysaccharide (LPS) administration to pregnant rats on day 5 of pregnancy could induce excessive immune response at the maternal-fetal interface contributing to poor early placentation that culminate in the preeclampsia-like syndrome. Furthermore, the expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a critical tumor suppressor, is markedly increased in the placentas of patients with preeclampsia. Our goal was to investigate the association of PTEN with preeclampsia and the pathways involved using human-trophoblast-derived cell line (HTR-8/SVneo) stimulated with LPS. We found that the expression of PTEN was significantly increased in the placentas of patients with severe preeclampsia and preeclamptic rat model induced by LPS. In vitro trophoblasts results showed that significantly differential expression of PTEN with corresponding changes in JunB/FosB (subunits of AP-1) and NF-κB activity after LPS stimulation. We further demonstrated that LPS-induced PTEN expression was dependent on AP-1 and NF-κB in trophoblasts. The trophoblasts with enforced expression of PTEN showed a reduced ability to invasion. Taken together, LPS may undermine remodelling of the human-trophoblast-derived HTR-8/SVneo cells by increasing PTEN, acting in part through the AP-1 and NF-κB pathways.