Observation of robust edge mode and in-gap corner mode in Kagome surface-wave photonic crystals.

Recent theory has demonstrated that Kagome photonic crystals (PCs) support first-order and second-order topological phenomena. Here, we extend the topological physics of the Kagome lattice to surface electromagnetic waves and experimentally show a Kagome surface-wave PC. Under the protection of first-order and second-order topologies, both robust edge modes and in-gap corner modes are observed. The robust transport of edge modes is demonstrated by high transmission through the waveguide with a sharp bend. The localized corner mode is found at the corner with one isolated rod when a triangle-shaped sample is constructed. Our work not only shows a platform to mimic the topological physics in classical wave systems, but also offers a potential application in designing high-performance photonic devices.

Sex Hormones Had Mediation in the Connection Between Certain Blood Routine Parameters and Bone Loss.

To investigate the association between blood routine (BRT) parameters and bone loss as well as the possible mechanism of this association with bone loss in the middle- aged and elderly patients. A total of nine hundred and ninety-eight subjects (the total) aged≥40 years in General Hospital of Southern Theater Command of People's Liberation Army from March 2015 to January 2018 were enrolled in a cross-sectional studyPatients were divided into two groups as "at least osteopenia group" (including osteopenia, osteoporosis, and severe osteoporosis) and "normal group" according to the diagnosis standard of OP. The above indicators were analyzed and compared between the two groups. Binary multivariate logistic regression analysis was carried out to explore the association between BRT parameters and risk of bone loss in the subjects Mediation Effect was conducted to test endocrine variables as mediators in the correlation of BRT parameters with the bone loss for the possible mechanisms. There were 669 cases in the at least osteopenia group and 329 in the normal group. RBC, Hb, HCT and MCHC were all positively correlated with BMD of lumbar spine(L1-4), left femoral neck and left femur, along with lymph positively correlated with BMD of left femoral neck and left femur, respectively. Eosinophils(Eo) was positively correlated with BMD of L1-L4 and RDW-SD together with RDW-CV were both negatively correlated with BMD of left femoral neck and left femur. By binary multivariate logistic regression, only Hb was associated with bone loss and the OR value was 0.478 as protective factor for BMD. Estradiol (E2) and testosterone (T) had partial mediating effect on the association of BRT parameters with the risk of bone loss. The mediating effect of E2 on the relationship between WBC and bone loss accounted for 46.35% of the total effect, and that of T on the relationship between RBC, Hb, HCT, MCHC and bone loss accounted for 27%, 18.3%, 31.1% and 26.8%, respectively. Bone loss in the middle-aged and elderly population is accompanied with the change of BRT parameters and the erythrocyte indices tend to be more obvious especially the Hb, which indicates anemia had a potential connection with bone loss. Sex hormone, especially T, is an important mediating variable in the association between blood routine parameters and bone loss.

IL-17A promotes fatty acid uptake through the IL-17A/IL-17RA/p-STAT3/FABP4 axis to fuel ovarian cancer growth in an adipocyte-rich microenvironment.

Pro-inflammatory cytokines are crucial mediators of cancer development, representing potential targets for cancer therapy. The molecular mechanism of a vital pro-inflammatory cytokine, IL-17A, in cancer progression and its potential use in therapy through influencing fatty acid (FA) metabolism, especially FA uptake of cancer cells, remains unknown. In the present study, we used IL-17A and ovarian cancer (OvCa), a representative of both obesity-related and inflammation-related cancers, to explore the interactions among IL-17A, cancer cells and adipocytes (which can provide FAs). We found that in the presence of palmitic acid (PA), IL-17A could directly increase the cellular uptake of PA, leading to the proliferation of OvCa cells via the IL-17A/IL-17RA/p-STAT3/FABP4 axis rather than via CD36. Moreover, in vivo experiments using an orthotopic implantation model in IL-17A-deficient mice demonstrated that endogenous IL-17A could fuel OvCa growth and metastasis with increased expression of FABP4 and p-STAT3. Furthermore, analysis of clinical specimens supported the above findings. Our data not only provide useful insights into the clinical intervention of the growth and metastasis of the tumors (such as OvCa) that are prone to growth and metastasis in an adipocyte-rich microenvironment (ARM) but also provides new insights into the roles of IL-17A in tumor progression and immunomodulatory therapy of OvCa.

Risk Interval of Complete Blood Counts May be Closely Associated with Bone Mineral Density in the Elderly Chinese Population.

BACKGROUND: Accumulating research suggests that hematopoiesis and bone metabolism are interconnected. Several studies have investigated the partial indexes of peripheral blood counts related to bone mineral density (BMD). The aim of this study was to investigate the associations between all of the parameters, especially the risk interval of complete blood counts (CBC) and BMD in a sample of elderly subjects aged >70 years. METHODS: Three hundred and eighty-six subjects aged > 70 years in our hospital were enrolled in a cross-sectional study and underwent BMD measurement along with a CBC test. Patients were divided into two groups: "at least osteopenia" (T-score < -1) and a normal group (T-score ≥ -1). The clinicopathological characteristics, CBC parameters, and BMD were analyzed between the two groups. We performed a supervised discretization (using a conditional inference tree algorithm) to find the risk interval for the continuous variables, especially for CBC parameters, and bootstrap multivariable logistic regression to estimate the odds of CBC parameters associated with BMD. RESULTS: A total of 248 subjects were included in the study and divided into the normal (n = 43) and "at least osteopenia" groups (n = 205). Subjects in the "at least osteopenia" group had varying degrees of decreases in white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (Hb), mean corpuscular hemoglobin concentration (MCHC), hematocrit (HCT), platelet volume distribution width (PDW) mean platelet volume (MPV), eosinophils, and lymphocytes, and had increases in platelets (PLTs). MCHC, WBC, RBC, PDW, MPV, Hb, and lymphocytes were successfully divided into two (low and high) intervals. Bootstrap logistic regression showed that low levels of body mass index (BMI) [(11.88, 23.53); OR: 4.07; p < 0.0001], lymphocytes [(0.54, 2.3); OR: 3.95; p < 0.0001] and PDW [(8.5, 12.7); OR: 2.44; p < 0.0001] along with being female and older age [(72, 97); OR: 2.16; p < 0.0001] were significantly associated with BMD as risk factors. CONCLUSIONS: The elderly with BMD loss tended to show an abnormal sign in the CBC test. Low levels of lymphocytes and PDW may contribute to the evaluation of osteoporosis risk in the elderly. Bone remodeling and hematopoiesis may have stronger associations and interactions than has been previously recognized.

Direct Observation of Corner States in Second-Order Topological Photonic Crystal Slabs.

Recently, higher-order topological phases that do not obey the usual bulk-edge correspondence principle have been introduced in electronic insulators and brought into classical systems, featuring in-gap corner or hinge states. In this Letter, using near-field scanning measurements, we show the direct observation of corner states in second-order topological photonic crystal slabs consisting of periodic dielectric rods on a perfect electric conductor. Based on the generalized two-dimensional Su-Schrieffer-Heeger model, we show that the emergence of corner states roots in the nonzero edge dipolar polarization instead of the nonzero bulk quadrupole polarization. We demonstrate the topological transition of two-dimensional Zak phases of photonic crystal slabs by tuning intracell distances between two neighboring rods. We also directly observe in-gap one-dimensional edge states and zero-dimensional corner states in the microwave regime. Our work presents that the photonic crystal slab is a powerful platform to directly observe topological states and paves the way to study higher-order photonic topological insulators.

Serum Periostin Level is not a Predictor of Early Stage Bone Loss in Chinese Postmenopausal Women.

BACKGROUND: Postmenopausal osteoporosis (PMOP) is one of the main threats to the health of women, which makes the early detection of bone loss vital. Many studies were carried out dedicated to finding new parameters and improving the discovery rate of early stage bone loss in postmenopausal women. Periostin is a newly discovered secreted protein that has been reported to participate in the processes of many agerelated diseases including osteoporosis. But the potential of serum periostin being a predictive marker of early stage bone loss remains to be determined. METHODS: Two hundred thirty-seven Chinese postmenopausal women from the patients of General Hospital of Southern Theater Command of People's Liberation Army were included as the subjects of this baseline study. Serum periostin level, BMD, the serum levels of a series of bone turnover markers (P1NP, ß-CTx and N-MID Osteo-calcin) and serum PTH level were measured. The follow-up study included 81 subjects with baseline BMD T-score ≥ -1.0 SD. BMD data at one year after baseline was available for all 81 subjects. The changes of BMD in different quartiles of serum periostin level were investigated. RESULTS: Serum periostin level was correlated with age but no matter whether adjusted by age there were no significant correlations between serum periostin levels and BMD, PTH, P1NP, ß-CTx, and N-MID-OT levels at baseline. There were no differences in serum periostin level between women with normal and abnormal BMD T-scores (p = 0.89). BMD data at one year after baseline indicated that the femur neck BMC and T-score became lower in women with higher baseline serum periostin (3/4 and 4/4 in quartiles, p = 0.025, p < 0.001, respectively). CONCLUSIONS: Serum periostin is not a predictor of early stage bone loss in Chinese postmenopausal women. However, a downtrend of femur neck BMC was found in women who had a higher baseline serum periostin level at the one-year follow-up bone mineral densitometry, which suggests that the exact association between periostin, bone turnover, and fracture risk are worth further research and long-term clinical follow-up study.

[Roles of cyclins in the progression of spermatogenesis].

Spermatogenesis is a complex and precise process of differentiation of germ cells, which involves three stages: mitosis of spermatogonia, meiosis of spermatocytes and formation of spermatozoa. The process is controlled by many factors, including regulation of cyclins in spermatogenic cells, which plays a pivotal role. Cyclins form heterologous dimer compounds with protein kinase activity by binding to cyclin-dependent kinases, then phosphorylate multiple proteins and promote the orderly conduct of each phase of the cell cycle. In recent years, cyclins A, B, D and E have been found to play important roles in the regulation of spermatogenesis. This article presents an overview on the roles of these four cyclins in regulating the progression of spermatogenesis.

Mechanisms of Yangjing Capsule in Leydig Cell Apoptosis and Testosterone Synthesis via Promoting StAR Expression.

The present study aims to investigate the roles of steroidogenic acute regulatory protein (StAR) in Yangjing Capsule (YC) induced anti-apoptotic effects on Leydig cells and the related mechanism. Leydig tumor cells (MLTC-1) were cultured and treated with YC, and immunofluorescence assay was performed to examine the expression of StAR; furthermore, luciferase reporter assay was conducted to evaluate the impact of YC on StAR promoter; next, MLTC-1 cells were treated with StAR small interfering RNA (siRNA), and flow cytometry was carried out to examine the effect of StAR siRNA on the apoptosis of the cells; furthermore, quantitative (q)RT-PCR and Western blot methods was used to determine the expression of StAR and apoptosis related molecules Bcl-2, Bax and Caspase-3 on both mRNA and protein levels in different groups; finally the secretion of testosterone in different groups was examined by radioimmunoassay. We observed that the YC can increase the expression of StAR in a dose-dependent manner, and YC can activate the promoter of StAR; moreover, transfection of StAR siRNA can block YC induced anti-apoptotic effects and increased production of testosterone. In conclusion, our results suggested that YC might suppress the apoptosis of MLTC-1 cells and enhance the production of testosterone through regulating the expression of StAR.

Serum serotonin concentration associated with bone mineral density in Chinese postmenopausal women.

Recent studies have shown that circulating serotonin plays a potential role in bone metabolism. However, conflicting results have been reported for the relationship between serum serotonin concentrations and bone mineral density (BMD). We investigated whether the serum serotonin concentrations related to BMD in Chinese postmenopausal women. Serum serotonin and bone turnover concentrations of 117 premenopausal women and 262 asymptomatic postmenopausal women were analyzed by enzyme-linked immunosorbent assay. BMD at the lumbar spine and femoral neck was measured by dual energy X-ray absorptiometry. The relationship between serotonin and BMD was investigated. The postmenopausal women had lower mean serum serotonin concentrations compared to the premenopausal women. Serotonin concentrations were negatively associated with age, weight, BMI, fat mass, and ß-CTX concentrations in postmenopausal women. No significant correlations were found between serotonin and these parameters in premenopausal women. In postmenopausal women, age- and BMI-adjusted serotonin concentrations were positively correlated with BMD of the lumbar spine and femoral neck. Multiple regression analyses showed serum serotonin and ß-CTX were the predictors for lumbar spine BMD. Only serum serotonin was the determinant for femoral neck BMD. In conclusion, lower serum serotonin concentrations are linked to low lumbar spine and femoral neck BMD in postmenopausal women.

Serum osteopontin levels in relation to bone mineral density and bone turnover markers in postmenopausal women.

Osteopontin (OPN) is an extracellular matrix protein that is expressed in bone cells such as osteoblast and osteocytes and associated with bone turnover and bone mineral density (BMD) in postmenopausal women. Here, we aimed to investigate the relationship between circulating OPN levels and BMD in postmenopausal women in Southern China. A total of 362 postmenopausal women were consecutively recruited into this study from 2011-2013. Serum levels of OPN, receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL), and bone turnover markers were analyzed. BMD was measured by dual energy X-ray absorptiometry. Osteoporosis and osteopenia were diagnosed according to the World Health Organization criteria. Serum OPN levels were remarkably higher in the osteoporotic group than those in the osteopenic and normal groups (all p < 0.001). The cut-off value of OPN for diagnosing postmenopausal osteoporosis was 10.1 ng/mL, which had a sensitivity of 89.5%, a specificity of 70.8%, and an area under curve of 0.953. Serum OPN was negatively correlated with parathyroid hormone (PTH), lumbar spine BMD, and femoral neck BMD (r = -0.25, p = 0.004; r = -0.66, p < 0.001; r = -0.28, p = 0.001; respectively) and positively associated with type I procollagen amino-terminal propeptide (PINP), carboxy-terminal cross-linking telopeptide of type I collagen (CTX), and RANKL (r = 0.20, p = 0.020; r = 0.17, p = 0.036; r = 0.19, p = 0.028, respectively) in the osteoporotic group. In multiple regression analyses, lumbar spine BMD, PTH and RANKL were the predictors for serum OPN levels. In conclusion, OPN serum levels are negatively related to BMD and positively correlated with bone turnover levels in this group of Chinese postmenopausal women.

Relation of serum 25 hydroxyvitamin D levels to bone mineral density in southern Chinese postmenopausal women: A preliminary study.

BACKGROUND & OBJECTIVES: Vitamin D insufficiency is prevalent in postmenopausal women and has been related to low bone mineral density (BMD). However, controversial results have been reported for the relationship between serum 25-hydroxyvitamin D [25(OH)D] levels and BMD. This study was done to investigate whether serum 25(OH)D levels were associated with BMD in postmenopausal women living in Guangzhou in southern China. METHODS: This cross-sectional study involved 119 asymptomatic postmenopausal women, aged 48-85 yr, who were consecutively selected from Guangzhou city. BMD was measured at the lumbar spine and femoral neck. The correlation between serum 25(OH)D levels and BMD wes investigated. RESULTS: With increasing serum 25(OH)D levels categorized as <20, 20-30, and ≥ 30ng/ml, the PTH levels decreased gradually ( P=0.031). Bivariate correlation analyses showed an inverse relationship between serum 25(OH)D and PTH levels after controlling for age and BMI (r=-0.209, P=0.023). Although subjects with vitamin D<30 ng/ml had significantly lower BMD, age- and BMI-adjusted serum 25(OH)D was weakly correlated with BMD at femoral neck (r=0.185, P0.045), and not at lumbar spine (r=0.172, p =0 0.063). In multiple regression analyses, serum 25(OH)D was a predictor for BMD at femoral neck (R 2= 0.424). However, serum ß-CTX was a determinant for BMD at lumbar spine (R 2= 0.361). INTERPRETATION & CONCLUSIONS: Serum 25(OH)D levels showed a positive correlation with BMD at femoral neck and serum ß-CTX levels were inversely correlated with BMD at lumbar spine in postmenopausal women. Further studies are needed to elucidate the clinical impact of these findings.

Fibrin sealant before wound closure in total knee arthroplasty reduced blood loss: a meta-analysis.

PURPOSE: Fibrin sealant (FS) comprises a mixture of fibrinogen and thrombin that controls bleeding, reduces blood transfusions, improves tissue healing and shortens postoperative recovery time after various surgical procedures. However, no single study has been large enough to definitively determine whether fibrin sealant is safe and effective. We report a meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of fibrin sealant in total knee arthroplasty. METHODS: Articles published before August, 2012 were identified from PubMed, Embase, The Cochrane Library and other internet databases. Relevant journals and the recommendations of expert panels were also searched manually. We included only high-quality RCTs. Two independent reviewers searched and assessed the literature. Relevant data were analysed using RevMan 5.0. RESULTS: Seven RCTs met the inclusion criteria. Use of fibrin sealant significantly reduced haemoglobin decline mean difference (MD = -0.72), 95 % confidence interval [95 % CI (-0.83, -0.62), p < 0.00001], postoperative drainage volume [MD = -354.53, 95 % CI (-482.43, -226.63), p < 0.00001], the proportion of patients requiring blood transfusion risk differences [RD = -0.27, 95 % CI (-0.45, -0.08), p = 0.006] and the incidence of wound haematoma [RD = -0.11, 95 % CI (-0.22, -0.00), p = 0.04]. There were no significant differences in deep vein thrombosis, pulmonary embolism, infection rate or other complications between groups. CONCLUSIONS: Use of fibrin sealant in total knee arthroplasty was effective and safe, reduced haemoglobin decline, postoperative drainage volume, incidence of haematoma and need for blood transfusion, and did not increase the risk of complications. Due to the limited quality of the evidence currently available, more high-quality RCTs are required. LEVEL OF EVIDENCE: II.

Interferon-γ produced by tumor-infiltrating NK cells and CD4+ T cells downregulates TNFSF15 expression in vascular endothelial cells.

Endothelial cells in an established vasculature secrete tumor necrosis factor superfamily-15 (TNFSF15; VEGI; TL1A) that functions as a negative modulator of neovascularization to maintain blood vessel stability. TNFSF15 gene expression diminishes at angiogenesis and inflammation sites such as in cancers and wounds. We reported previously that vascular endothelial growth factor and monocyte chemotactic protein-1 contribute to TNFSF15 downmodulation in ovarian cancer. Here we show that interferon-γ (IFNγ) suppresses TNFSF15 expression in human umbilical vein endothelial cells. This activity is mediated by IFNγ receptor and the transcription factor STAT1. Immunohistochemical analysis of ovarian cancer clinical specimens indicates that TNFSF15 expression diminishes while tumor vascularity increases in specimens with high-grades of IFNγ expression. Since tumor-infiltrating NK and CD4(+) T cells are the main sources of IFNγ in tumor lesions, we isolated these cells from peripheral blood of healthy individuals, treated the cells with ovarian cancer OVCAR3 cell-conditioned media, and found a onefold and tenfold increase of IFNγ production in NK and CD4(+) T cells, respectively, compared with that in vehicle-treated cells. These findings support the view that tumor-infiltrating NK and CD4(+) T cells under the influence of cancer cells significantly increase the production of IFNγ, which in turn inhibits TNFSF15 expression in vascular endothelial cells, shifting the balance of pro- and anti-angiogenic factors toward escalated angiogenesis potential in the tumor.

A better method to evaluate the reliability of echocardiography for assessment of pulmonary hypertension: comparison of tricuspid regurgitant spectrum quality grading and tricuspid valve regurgitation degree.

Background: Transthoracic echocardiography (TTE) is recommended as the most important noninvasive screening tool for the diagnosis of pulmonary hypertension (PH), sonographers usually measure the volume of regurgitant flow rather than evaluating the spectral quality, so physicians will determine whether the ultrasound measurements of pulmonary arterial systolic pressure (US-PASP) are reliable based on the volume of tricuspid regurgitation (TR). Therefore, for the first time, we grade the quality of TR spectrum (TRS) based on its integrity and clarity, aiming to assess clinical application value of different tricuspid regurgitant spectrum quality grades (TR-SQG), and investigate whether the accuracy of US-PASP is more trustworthy than TR. Methods: We retrospectively analyzed 108 patients with chronic thromboembolic PH (CTEPH) to compare the correlation and agreement between US-PASP and right heart catheterization measurements of PASP (RHC-PASP). TR area (TRA) and TRS were measured in each patient, and TR-SQG was performed. Results: The correlation coefficients between US-PASP and RHC-PASP were r=0.622 (P<0.001), r=0.754 (P<0.001), r=0.595 (P<0.001) in mild, moderate, severe TR, and r=0.301 (P=0.135), r=0.747 (P<0.001), r=0.739 (P<0.001), r=0.828 (P<0.001) in TR-SQG I-IV, respectively. Bland-Altman analysis revealed the mean biases of 5.05, 3.06, 7.62 mmHg in mild, moderate, severe TR, and -16.47, -8.07, 1.82, 6.09 mmHg in TR-SQG I-IV, respectively. In mild TR with the TR-SQG III and IV, the correlation coefficients between US-PASP and RHC-PASP were r=0.779 (P<0.001), intraclass correlation coefficient (ICC) =0.774, paired t-test P=0.160, respectively; and the consistency was significantly higher than that of mild TR without considering TR-SQG. In moderate TR with the TR-SQG III and IV, the r=0.749, ICC =0.746, paired t-test P=0.298 between US-PASP and RHC-PASP. Conclusions: The US-PASP with TR-SQG III or IV is trustworthy, and its accuracy and consistency are better than those predicted by the traditional severity of TR. The establishment of the ultrasound evaluation system of TR-SQG helps clinicians to judge whether the US-PASP is accurate, credible, and reliable.

Inhibition of ATM promotes PD-L1 expression by activating JNK/c-Jun/TNF-α signaling axis in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous subtype of breast cancer. Anti-PD-1/PD-L1 treatment for advanced TNBC is still limited to PD-L1-positive patients. Ataxia telangiectasia mutated (ATM) is a switch molecule for homologous recombination and repair. In this study, we found a significant negative correlation between ATM and PD-L1 in 4 TNBC clinical specimens by single-cell RNA sequencing (scRNA-seq), which was confirmed by immunochemical staining in 86 TNBC specimens. We then established ATM knockdown TNBC stable cell lines to perform in vitro studies and animal experiments, proving the negative regulation of PD-L1 by ATM via suppression of tumor necrosis factor-alpha (TNF-α), which was confirmed by cytokine array analysis of TNBC cell line and analysis of clinical specimens. We further found that ATM inhibits TNF-α via inactivating JNK/c-Jun by scRNA-seq, Western blot and luciferase reporter assays. Finally, we identified a negative correlation between changes in phospho-ATMS1981 and PD-L1 levels in TNBC post- and pre-neoadjuvant therapy. This study reveals a novel mechanism by which ATM negatively regulates PD-L1 by downregulating JNK/c-Jun/TNF-α in TNBC, shedding light on the wide application of immune checkpoint blockade therapy for treating multi-line-resistant TNBC.

Adipocyte­rich microenvironment promotes chemoresistance via upregulation of peroxisome proliferator­activated receptor gamma/ABCG2 in epithelial ovarian cancer.

The effects of adipocyte­rich microenvironment (ARM) on chemoresistance have garnered increasing interest. Ovarian cancer (OVCA) is a representative adipocyte­rich associated cancer. In the present study, epithelial OVCA (EOC) was used to investigate the influence of ARM on chemoresistance with the aim of identifying novel targets and developing novel strategies to reduce chemoresistance. Bioinformatics analysis was used to explore the effects of ARM­associated mechanisms contributing to chemoresistance and treated EOC cells, primarily OVCAR3 cells, with human adipose tissue extracts (HATES) from the peritumoral adipose tissue of patients were used to mimic ARM in vitro. Specifically, the peroxisome proliferator­activated receptor Î³ (PPARγ) antagonist GW9662 and the ABC transporter G family member 2 (ABCG2) inhibitor KO143, were used to determine the underlying mechanisms. Next, the effect of HATES on the expression of PPARγ and ABCG2 in OVCAR3 cells treated with cisplatin (DDP) and paclitaxel (PTX) was determined. Additionally, the association between PPARγ, ABCG2 and chemoresistance in EOC specimens was assessed. To evaluate the effect of inhibiting PPARγ, using DDP, a nude mouse model injected with OVCAR3­shPPARγ cells and a C57BL/6 model injected with ID8 cells treated with GW9662 were established. Finally, the factors within ARM that contributed to the mechanism were determined. It was found that HATES promoted chemoresistance by increasing ABCG2 expression via PPARγ. Expression of PPARγ/ABCG2 was related to chemoresistance in EOC clinical specimens. GW9662 or knockdown of PPARγ improved the efficacy of chemotherapy in mice. Finally, angiogenin and oleic acid played key roles in HATES in the upregulation of PPARγ. The present study showed that the introduction of ARM­educated PPARγ attenuated chemoresistance in EOC, highlighting a potentially novel therapeutic adjuvant to chemotherapy and shedding light on a means of improving the efficacy of chemotherapy from the perspective of ARM.

Recombinant GnRH-p53 protein sensitizes breast cancer cells to 5-fluorouracil-induced apoptosis in vitro and in vivo.

An ideal approach to treat cancers with dysfunctional p53 tumor suppressor gene is to reinstate p53 functionality by directly using p53 protein as a therapeutic agent. However, this has not been possible because the cells cannot readily internalize the protein. We constructed a fusion protein consisting of gonadotropin-releasing hormone (GnRH-p53) and p53 moieties. The recombinant protein was directly used to treat human breast cancer cells and athymic nude mice bearing breast cancer xenografts, with or without DNA synthesis-arresting agent 5-fluorouracil (5-FU). Treatments of cells from breast cancer cell-lines MDA-MB-231, T47D, or SKBR-3 with GnRH-p53 in combination with 5-FU significantly enhanced p53-activated apoptosis signals, including PUMA expression, BAX translocation to mitochondria, and activated caspase-3. Intratumoral injection of the GnRH-p53 protein inhibited MDA-MB-231 xenograft growth and induced p53-mediated apoptosis in the tumors. Systemic treatment of the tumor-bearing mice via tail vein injection of GnRH-p53 markedly augmented the anticancer efficacy of 5-FU. Substitution of GnRH-p53 with wild type p53 protein had no effect. Recombinant GnRH-p53 is able to function as a surrogate of p53 with regard to its apoptosis-inducing activity. Combination of GnRH-p53 with DNA-damaging drugs may be of important therapeutic value for cancer treatment.

Effects and mechanisms of anti-CD44 monoclonal antibody A3D8 on proliferation and apoptosis of sphere-forming cells with stemness from human ovarian cancer.

OBJECTIVE: CD44(+) human ovarian cancer stem cells (CSCs) and CSC-like cells have been identified and characterized. Compelling evidence has revealed that CD44 is involved in the occurrence and development of cancers. Our previous study showed that sphere-forming cells (SFCs) from the human ovarian cancer cell line SKOV-3 had CSC capacity. Therefore, in the present study, we aimed to investigate the effects and mechanisms of the anti-CD44 monoclonal antibody A3D8 on the proliferation and apoptosis of SFCs to explore novel strategies for the treatment of ovarian cancer. METHODS: We investigated the effects and mechanisms of A3D8 on the proliferation and apoptosis of SFCs using the MTS assay, cell cycle analysis, an annexin V-fluorescein isothiocyanate/propidium iodide kit, Rh123 apoptosis detection kit, real-time reverse transcription polymerase chain reaction and Western blotting. RESULTS: After CD44 ligation by A3D8, SFC cell proliferation was notably attenuated, cell cycle progression was arrested in the S phase, and apoptosis was significantly increased. The effect of A3D8 was enhanced in a dose- and time-dependent manner, and the effect of apoptosis induction by DDP was enhanced by combination treatment with A3D8. Furthermore, the messenger RNA expression levels of p21 and caspase-3 were up-regulated, whereas those of CDK2, cyclinA, and Bcl-2 were down-regulated. The protein expression levels of caspase-3 were up-regulated, whereas those of CDK2, cyclinA, and Bcl-2 were down-regulated. CONCLUSIONS: Our findings indicate that anti-CD44 monoclonal antibodies may be a potential strategy for the treatment of human ovarian cancer after conventional therapy via inhibition of growth and the promotion of apoptosis in SFCs with stemness.

Yangjing capsule improves oligoasthenozoospermia by promoting nitric oxide production through PLCγ1/AKT/eNOS pathway.

Background: Oligoasthenozoospermia is an important factor leading to male infertility. Yangjing capsule (YC), a traditional Chinese preparation, displays beneficial effects on male infertility. However, whether YC could improve oligoasthenozoospermia remains unclear. Methods: In this study, we aimed to explore the effect of YC in the treatment of oligoasthenozoospermia. Male Sprague-Dawley (SD) rats were treated with 800 mg/kg ornidazole once daily for 30 days to induce in vivo oligoasthenozoospermia; primary Sertoli cells were treated with 400 µg/mL ornidazole for 24 h to induce in vitro oligoasthenozoospermia. Results: We found that YC improved the testicle and epididymis weight, sperm concentration, sperm progressive motility, serum testosterone, fertility rate and testis morphology in ornidazole-exposed rats and enhanced cell survival in ornidazole-stimulated primary Sertoli cells. YC also inhibited the ornidazole-caused decrease in nitric oxide (NO) generation and the phosphorylation of phospholipase C γ1 (PLCγ1), AKT, and eNOS in vivo and in vitro in oligoasthenozoospermia. Furthermore, the knockdown of PLCγ1 blunted the beneficial effects of YC in vitro. Conclusion: Collectively, our data suggested that YC protected against oligoasthenozoospermia by promoting NO levels through the PLCγ1/AKT/eNOS pathway.