Cloprostenol sodium improves reproductive performance of multiparous sows during lactation.

This study aimed to determine the effect of prostaglandin F2α (PGF2α) analog (D-cloprostenol sodium and DL-cloprostenol sodium) administration on the milk yield of multiparous sows (MS) and piglet growth performance. In total, 320 Landrace×Yorkshire parturient MS were randomly divided into three groups on day 115 of pregnancy: without treatment (N = 50), with 75 µg D-cloprostenol sodium (N = 137), and with 200 µg DL-cloprostenol sodium (N = 133). After delivery, the sows treated with D-cloprostenol sodium and DL-cloprostenol sodium were randomly allocated into three subgroups, respectively: (i) no additional treatment after farrowing; (ii) administration of cloprostenol sodium at 3 h and 5 days after farrowing; and (iii) administration of cloprostenol sodium at 3 h, 5 days, and 10 days after farrowing. Cloprostenol sodium effectively induced sows to synchronize parturition approximately 23 h after administration and increased the daytime delivery rates (p < 0.05). Compared with DL-cloprostenol sodium, D-cloprostenol sodium shortened the farrowing duration and birth interval of sows for inducing farrowing (p < 0.05). Moreover, we observed that a single administration of both D-cloprostenol sodium and DL-cloprostenol sodium a day before delivery significantly reduced the rates of stillborn piglets type II in MS (p < 0.05). Compared to no treatment and single treatment with cloprostenol sodium, quartic treatments with cloprostenol sodium significantly increased the daily feed intake of MS, litter weight after weaning, and average daily gain of piglets (p < 0.05). Cloprostenol sodium improved the 21-day milk yield, with D-cloprostenol sodium showing the best effect, which increased lactation ability by 30.30% (176.72 kg vs. 135.63 kg) (p < 0.05). DL-cloprostenol sodium followed closely, increasing lactation ability by approximately 25.00% (169.71 kg vs. 135.63 kg) (p < 0.05). During lactation, sows administered with D-cloprostenol sodium observed increased serum prolactin levels. Compared to untreated sows, the sows administered with D-cloprostenol sodium and multiple DL-cloprostenol sodium visibly shortened the weaning-to-estrus interval (WEI) and weaning-to-service interval (WSI) (p < 0.05). Furthermore, quartic injections of D-cloprostenol sodium resulted in an 18 percentage point increase in the pregnancy rate of breeding sows compared to controls (82.61% vs. 64.58%) (p > 0.05). In summary, cloprostenol sodium could enhance the reproductive performance of MS, particularly in terms of lactation performance. Additionally, the effect of quartic injections of D-cloprostenol sodium was the most pronounced.

Carboxypeptidase E protein regulates porcine sperm Ca2+ influx to affect capacitation and fertilization.

Mammalian spermatozoa acquire their fertilizing ability in the epididymis, which is important for sperm maturation and capacitation. Carboxypeptidase E (CPE) is a prohormone-processing enzyme and sorting receptor that functions intracellularly. Recently, CPE was identified to exist in the seminal plasma. However, little is known about the effects of CPE on reproductive function. This study focused on the effects of CPE on sperm function and fertilization. Herein, CPE was identified to be localized in the boar sperm, testis, epididymis, accessory gonad and seminal plasma, with high expression found in the bulbourethral glands and cauda epididymis. Furthermore, compared with high motility spermatozoa, a decrease in CPE abundance was observed in low motile spermatozoa by Western blot analysis. The use of specific antibody to inhibit the CPE in spermatozoa led to a decrease in sperm motility, followed by an expected decrease in acrosome exocytosis and tyrosine phosphorylation in the capacitation process. These changes were accompanied by a decrease in intracellular Ca2+ ([Ca2+]i) influx, which resulted in a significant decrease in the cleavage rate during in vitro fertilization (IVF). Based on these observations, we suggest that CPE might affect porcine sperm Ca2+ influx to participate in the regulation of sperm function during capacitation.

Plasma thioredoxin reductase: a potential diagnostic biomarker for gastric cancer.

To improve the early detection of gastric cancer (GC), there is a growing need for novel and efficient biomarkers. We aimed to evaluate diagnostic value of thioredoxin reductase 1 (TXNRD1), which was found to be over expressed in various malignancies. We found that TXNRD1 has a higher expression level in GC tissues compared with adjacent normal tissues, and high TXNRD1 expression was significantly associated with poor outcomes of GC patients. Next, a total of 1446 cases were collected, with 896 cases in GC, 322 in benign gastric disease and 228 in healthy controls. We noticed plasma thioredoxin reductase (TrxR) level in GC [8.4 (7.1, 9.7) U/ml] was significantly higher than that in benign disease [6.1 (5.4, 7.2) U/ml] or healthy controls [3.7 (1.7, 5.6) U/ml]. Receiver operating characteristic analysis showed that the optimal cutoff value of TrxR activity for GC diagnosis was set at 5.75 U/ml with an area under the curve of 0.945. Moreover, a combined panel of TrxR and routine tumor markers could further elevate the diagnostic efficacy compared to a single biomarker. Finally, by measuring pre- and post-treatment TrxR activity and routine tumor markers, we found the change trend of them was broadly consistent, and plasma TrxR activity was significantly decreased in patients treated with platinum/fluorouracil-based therapy. Our findings recommend plasma TrxR activity combined with tumor markers as effective diagnostic tools for GC patients. As well, plasma TrxR has the potential to monitor therapeutic efficacy.

Circ_0064288 acts as an oncogene of hepatocellular carcinoma cells by inhibiting miR-335-5p expression and promoting ROCK1 expression.

BACKGROUND: Reportedly, circular RNA (circRNA) is a key modulator in the development of human malignancies. This work is aimed to probe the expression pattern, biological effects and mechanism of circ_0064288 on hepatocellular carcinoma (HCC) progression. METHODS: The differentially expressed circRNA was screened by analyzing the expression profiles of circRNAs in HCC tissues and normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the expression of circ_0064288, miR-335-5p and Rho associated coiled-coil containing protein kinase 1 (ROCK1) mRNA in HCC specimens. After circ_0064288 was overexpressed or knocked down in HCC cells, cell growth was detected by the CCK-8 experiment, and cell migration was evaluated using Transwell experiment and scratch healing experiment. The targeting relationship between miR-335-5p and circ_0064288 and ROCK1 mRNA was predicted and verified using bioinformatic analysis and dual-luciferase reporter gene experiments, respectively. Western blot was executed to examine ROCK1 protein expression in HCC cells. RESULTS: Circ_0064288 and ROCK1 expression was up-modulated in HCC, while miR-335-5p was down-modulated. High circ_0064288 expression was associated with shorter survival time of HCC patients. It was also revealed that circ_0064288 overexpression remarkably enhanced HCC cell growth and migration, while knockdown of circ_0064288 induced opposite effects. Additionally, circ_0064288 could competitively bind with miR-335-5p thereby up-modulate ROCK1 expression. MiR-335-5p overexpression partly counteracted the effect of circ_0064288 overexpression on HCC cells. CONCLUSION: Circ_0064288 facilitates HCC cell growth and migration by modulating the miR-335-5p/ROCK1 axis.

Self-supported Co9S8-Ni3S2-CNTs/NF electrode with superwetting multistage micro-nano structure for efficient bifunctional overall water splitting.

Electrochemical water splitting for hydrogen production using cost-effective and high-efficiency electrocatalysts in alkaline electrolytes is of great significance for solving energy crisis and environmental pollution. Herein, we reported a superhydrophilic and underwater superaerophobic multistage layered micro-nano structure ofCo9S8-Ni3S2-CNTs/NF on nickel foam (NF) prepared by a simple one-step hydrothermal procedure. Particularly, the multistage layered micro-nano structure makes the electrode superhydrophilic and superaerophobic, which can facilitate the exposure of active sites, accelerate the tansfer of electrolyte and the release of gas bubbles. Consequently, the rough electrode demonstrated excellent catalytic performance in alkaline condition, which only need a low overpotential 127 mV for oxygen evolution reaction (OER) and 243 mV for hydrogen evolution reaction (HER) at 10 mA cm-2 and can keep a long durability for 10 h at 10 mA cm-2. In addition, the production of hydrogen in an electrolytic water device with Co9S8-Ni3S2-CNTs/NF as bifunctional electrode prowered by the electricity derived from solar and wind energy in laboratory condition was artificially simulated. This work represents a perspective in improving the electrocatalytic performance of water splitting by structure and wettability regulation and opens a new avenue for clean energy generation.

Knockdown of nuclear receptor binding SET domain-containing protein 1 (NSD1) inhibits proliferation and facilitates apoptosis in paclitaxel-resistant breast cancer cells via inactivating the Wnt/ß-catenin signaling pathway.

The burden of breast cancer (BC) has exacerbated over decades. Paclitaxel resistance is responsible for increasing BC treatment burden. Nuclear receptor binding SET domain-containing protein 1 (NSD1) is positively correlated with a poor prognosis in patients with BC. This study investigates the function of NSD1 in paclitaxel-resistant (PR) BC cells. The high levels of NSD1 and Wnt10b in PR BC cell lines (MCF-7/PR) or MCF-7 parental cells were determined by RT-qPCR. Western blotting was conducted to measure the levels of NSD1 protein, apoptosis-associated proteins, Wnt10b protein, H3K36me2 protein, H3K27me3 protein, and signal pathway-associated proteins in MCF-7/PR cells or MCF-7 cells or in vivo subcutaneous xenografted tumor model, and the results demonstrated that NSD1 inhibited cell apoptosis and promoted cell proliferation and tumor growth via activating Wnt/ß-catenin pathway. Cell apoptosis and viability were estimated using cell counting kit-8 assays and flow cytometry. Positive correlation between NSD1 and Wnt10b was identified by chromatin immunoprecipitation assay. The distribution of ß-catenin was determined by immunofluorescence assays. We conclude that NSD1 knockdown inhibits the viability and promotes the apoptosis of paclitaxel-resistant BC cells by inactivating the NSD1/H3K27me3/Wnt10b/ß-catenin signaling pathway.

The drugs screened by OncoVeeTM-Mini-PDX have significantly benefited the patient with HER2-positive advanced gastric cancer.

INTRODUCTION: At present, the prognosis of HER2-positive advanced gastric cancer is extremely poor, and some patients fail to benefit from first-line Herceptin treatment, thus facing difficulties in choosing second-line drugs. CASE REPORT: Here, we report a 61-year-old male patient with HER2-positive advanced gastric cancer who is primarily resistant to Herceptin and has poor therapeutic effect. MANAGEMENT & OUTCOME: Afterwards, the OncoVeeTM-MiniPDX-guided anticancer method was used to screen drugs for second-line treatment, which resulted in liquefaction and necrosis of the patient's lesions and improved liver function indicators, as well as rapid relief of the patient's clinical symptoms. DISCUSSION: In the treatment of the Herceptin-resistant patient with advanced gastric cancer, OncoVeeTM-MiniPDX method screened drugs and brought clinical benefits.

Nuclear receptor binding SET domain protein 1 promotes epithelial-mesenchymal transition in paclitaxel-resistant breast cancer cells via regulating nuclear factor kappa B and F-box and leucine-rich repeat protein 11.

Breast cancer (BC) is regarded as the major cause of cancer-associated deaths in women. Paclitaxel exerts a critical impact on the chemotherapy of BC, but the resistance to paclitaxel becomes a great obstacle in treating the disease. It is reported that noncoding RNA nuclear receptor binding SET domain protein 1 (NSD1) plays a significant role in drug resistance; however, the special role of NSD1 in paclitaxel-resistant BC is unclear. Human BC cell line MCF-7 was used to establish paclitaxel-resistant BC cells (MCF-7/PR). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) displayed that NSD1 and F-box and leucine-rich repeat protein 11 (FBXL11) were highly expressed in BC tissues. Western blotting was utilized for protein level assessment. Cell counting kit-8 (CCK-8), Transwell, wound healing assays, and animal experiments were conducted to examine the influence of NSD1 or FBXL11 on the malignant behaviors of BC in vitro and in vivo, respectively. Transfected MCF-7/PR cells were injected subcutaneously into BALB/c nude mice with or without treatment of paclitaxel. The nuclear factor kappa B (NF-kB) activity was evaluated by the luciferase reporter assay. Results showed that NSD1 knockdown inhibited the epithelial-mesenchymal transition (EMT), migration and invasiveness of BC in vitro, which was rescued by FBXL11 overexpression. Furthermore, NSD1 silencing promoted paclitaxel sensitivity of paclitaxel-resistant BC cells and suppressed tumor growth and paclitaxel resistance in vivo. NSD1 knockdown reduced NF-kB activity, while FBXL11 inhibition markedly increased NF-kB activity. Collectively, NSD1 facilitates the EMT, migration and invasion in paclitaxel-resistant BC cells via regulating NF-kB and FBXL11.

The regulatory relationship and function of LncRNA FAM225A-miR-206-ADAM12 in gastric cancer.

OBJECTIVE: To investigate the role and functions of FAM225A in gastric cancer. METHODS: The expressions of FAM225A, miR-206, ADAM12 and epithelial-mesenchymal transition (EMT)-related genes were detected by quantitative real-time PCR and Western blot. Functional experiments including cell counting kit-8, colony formation, wound-healing, and Transwell assays were conducted to analyze the biological characteristics of gastric cancer cells in different groups. Bioinformatics, dual-luciferase reporter assay and Pearson correlation coefficients were performed for determining the regulatory relationship of lncRNA-miRNA-mRNA. In vivo nude mouse xenografts and immunohistochemistry were used to verify the results in vitro. RESULTS: In gastric cancer, FAM225A and ADAM12 expressions were up-regulated, while miR-206 expression was down-regulated. Opposite to the regulatory effects of overexpressed FAM225A, blocking FAM225A expression reduced cell viability, migration, invasion and number of cell clones, increased E-Cadherin expression, inhibited N-Cadherin and Vimentin expressions, and ultimately promoted tumor growth. MiR-206 inhibitor partially offset the effects of siFAM225A. Moreover, FAM225A competitively bound to miR-206 to up-regulate ADAM12 expression. Overexpressed ADAM12 partially reversed the effect of miR-206 mimic on the biological characteristics of gastric cancer cells and EMT-related proteins. CONCLUSION: Our research revealed that FAM225A-miR-206-ADAM12 axis may be a potential pathway for regulating gastric cancer.

Progress and challenges of immunotherapy in triple-negative breast cancer.

Triple-negative breast cancer (TNBC), a subtype of breast cancer, is defined as lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) expression. Compared with other subtypes in breast cancer, TNBC is more likely to recur and metastasize, with a lower survival rate. Due to the absence of definitive targets, there was limited novel therapeutic interventions and chemotherapy remained the primary treatment in the past decades. Following the development of immune checkpoint inhibition (ICI) in solid tumors and validation of the immunogenicity in TNBC, immunotherapy has attracted more and more attentions. On basis of accumulating clinical studies, we reviewed the current progress targeting different immune checkpoints in several-lines treatment for TNBC, including programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitors, cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) inhibitor, and other novel immunotherapeutic approaches (e.g., individualized peptide vaccine, cancer-testis antigen (CTA), new antigen vaccine, RNA vaccine and chimeric antigen receptor modified T cells (CAR-T)). In order to improve the survival outcome of TNBC populations, we further discussed potential predictive biomarkers for immunotherapy (e.g., PD-L1 expression, tumor mutational burden (TMB), tumor-infiltrating lymphocytes (TILs), microsatellite instability (MSI)/mismatch repair (MMR) deficiency) and challenges in the future treatment of TNBC.

Biotemplated Fabrication of a Multifunctional Superwettable Shape Memory Film for Wearable Sensing Electronics and Smart Liquid Droplet Manipulation.

Wearable superwettable surfaces with dynamic tunable wettability and self-healability are promising for advanced wearable electronics, whereas have been rarely reported. Herein, a flexible superhydrophobic shape memory film (SSMF) with switchable surface wettability and high strain sensitivity has been conveniently fabricated. The surface topography of the SSMF can be finely adjusted by a reversible stretching (bending)/recovery way, which makes it feasible to control the surface-switchable adhesive superhydrophobicity by simple body movements, demonstrating great advantages in selective droplet manipulation and smart control of droplet movement. Moreover, benefitting from the hierarchical micro/nanostructures and outstanding sensing performance, the flexible SSMFs with good adaptivity and durability can serve as smart wearable sensors attached to human skin to achieve full-range and real-time detection of human motions and intelligent control of Internet of Things. More interestingly, the unique dynamic dewetting property enables the sensors to work in a humid environment or rainy days. Overall, this work successfully integrates dynamic tunable superwettability into design of intelligent wearable electronics with multifunctions. The obtained SSMF-based wearable surface with dynamic dewetting properties reveals great potential in versatile application fields such as liquid-repellent electronics, wearable droplet manipulators, and all-weather intelligent actuators.

HER2-targeted therapies in gastric cancer.

Molecular targeted therapy of cancer has always been the focus of clinicians. Among those therapeutic targets, the human epidermal growth factor receptor-2 (HER-2) signaling pathway is one of the most popular targets for translational research in cancer. However, unlike prospect in breast cancer, HER-2 inhibitor trastuzumab is the only molecular targeted drug approved by US Food and Drug Administration (FDA) for the first-line treatment of HER-2 positive advanced gastric cancer. On this basis, a variety of novel HER2- targeted drugs for gastric cancer are under development, and related clinical researches are in full swing, including small molecular kinase inhibitors (e.g., afatinib, neratinib, pyrotinib), antibody-drug conjugates (e.g., DS-8201a, RC48-ADC) and other novel therapies (e.g., ZW25, CAR-T, BVAC-B). In this study, we will summarize the recent advances in anti-HER-2 agents, potential mechanisms of resistance to HER2-targeted therapy in HER2-positive gastric cancer. We will also discuss the future prospects of potential strategies to overcome anti-HER-2 resistance and development of novel anti-HER-2 approaches for the treatment of HER2-positive gastric cancer patients.

Circulating tumor cells: A surrogate to predict the effect of treatment and overall survival in gastric adenocarcinoma.

BACKGROUND: Circulating tumor cells and serum tumor markers have been found significant in predicting outcome for several malignancies. However, their role in gastric cancer is not fully clarified. We conducted a retrospective study to explore the prognostic value of circulating tumor cells and their applicability in assessing the treatment efficacy in gastric cancers. METHODS: From September 2015 to December 2018, 116 patients with newly pathologically diagnosed gastric adenocarcinoma were enrolled. At both baseline and two courses after chemotherapy, the data of circulating tumor cells and serum tumor markers, such as CEA, CA72-4, CA19-9, CA50, and CA242, were collected. The relationships between the change trend of circulating tumor cells and the treatment efficacy were analyzed after chemotherapy, with a paired t-test. Univariate and multivariable analysis were used to find prognostic factors for overall survival (OS). RESULTS: We found there is a significant difference between the circulating tumor cells-positive and circulating tumor cells-negative before and after therapy (mOS 12.6 vs. 31.6 months, P<0.001; mOS 12.4 vs. 24.2 months, P=0.002), respectively. Also, differentiation, pre-therapeutic circulating tumor cells and therapeutic response were independent predictors of overall survival. Following two courses of chemotherapy, the number of circulating tumor cells increased obviously in the progressive disease group (P=0.002), while they decreased in the non-progressive disease group (P=0.02). Thus, the change in the circulating tumor cells count had a close association with the therapeutic response (P=0.004). CONCLUSION: Generally, circulating tumor cells provide a novel tool to evaluate the outcomes of gastric cancer patients. Since the change of circulating tumor cells was highly related to treatment response, it may be an auxiliary to assess the effect of chemotherapy, leading an earlier adjustment of following regimens.

Immunotoxicity assessment of CdSe/ZnS quantum dots in macrophages, lymphocytes and BALB/c mice.

BACKGROUND: The toxicity of CdSe/ZnS quantum dots (QDs) in the environment and biological systems has become a major concern for the nanoparticle community. However, the potential toxicity of QDs on immune cells and its corresponding immune functions remains poorly understood. In this study, we investigated the immunotoxicity of CdSe/ZnS QDs using the in vitro in macrophages and lymphocytes and in vivo in BALB/c mice. RESULTS: Our results indicated that macrophages treated with 1.25 or 2.5 nM QDs exhibited decreased cell viability, increased levels of reactive oxygen species (ROS), elevated apoptotic events, altered phagocytic ability, and decreased release of TNF-α and IL-6 by upon subsequent stimulation with Lipopolysaccharide (LPS). In contrast, lymphocytes exposed to QDs exhibited enhanced cell viability, increased release of TNF-α and IL-6 following exposure with CpG-ODN, and decreased transformation ability treatment in response to LPS. To study the in vivo effects in mice, we showed that QDs injection did not cause significant changes to body weight, hematology, organ histology, and phagocytic function of peritoneal macrophages in QDs-treated mice. In addition, the QDs formulation accumulated in major immune organs for more than 42 days. Lymphocytes from QDs-treated mice showed reduced cell viability, changed subtype proportions, increased TNF-α and IL-6 release, and reduced transformation ability in response to LPS. CONCLUSIONS: Taken together, these results suggested that exposures to CdSe/ZnS QDs could suppress immune-defense against foreign stimuli, which in turn could result in increased susceptibility of hosts to diseases.