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Apelin (APLN) is an endogenous ligand of the G protein-coupled receptor APJ (APLNR). APLN/APLNR system was involved in a variety of pathological and physiological functions, such as tumorigenesis and development. However, its prognostic roles in patients with central nervous system (CNS) cancers remain unknown. The present study was designed to explore the expression profile, prognostic significance, and interaction network of APLN/APLNR by integrating data from Oncomine, GEPIA, LOGpc, STRING, GeneMANIA, and immunohistochemical staining. The results demonstrated that APLN and APLNR mRNA expression were significantly increased in CNS cancers, including both low-grade glioma (LGG) and glioblastoma (GBM), when compared with normal CNS tissues. The high APLN, but not APLNR, expression was significantly correlated with overall survival (OS), recurrence free survival (RFS), and progression free survival (PFS) of LGG patients. However, neither APLN nor APLNR expression was significantly related to prognostic value in terms of OS, disease free interval (DFI), disease specific survival (DSS), or progression free interval (PFI) for GBM patients. Additionally, immunohistochemistry staining confirmed the increased APLN expression in tissues of LGG patients with grade II than grade I. These results showed that an elevated APLN level could predict poor OS, RFS, and PFS for LGG patients, and it could be a promising prognostic biomarker for LGG.

Cancer is a public health problem that is extremely harmful to people’s health. Most cancer patients experience severe pain in the advanced stage, which will seriously affect their prognosis. At present, opioids, such as morphine, have been used as the drug of choice for treating moderate to severe cancer-related pain. Mu (μ)-opioid receptor (MOR) is expressed in many different cancer cells. In this article, we present the relationship between MOR and tumor pathophysiology; summarize the molecular mechanism and effect of MOR on tumor proliferation and progression, tumor angiogenesis, tumor immunity, and cancer therapy; and propose the future research direction of MOR for cancer treatment. MOR could be as a promising prognostic biomarker and immune checkpoint in cancer therapy.

Introduction ZnO quantum dots (QDs) have drawn much attention recently as they are Cd-free, low-cost, and have excellent optical properties. With the expanded production and application of ZnO nanoparticles, concerns about their potential toxicity have also been raised. Materials and Methods We used RNA sequencing (RNA-seq) to analyze the global gene expression of liver and lung tissues after ZnO QDs treatment. Differentially expressed genes (DEGs) were screened, with a fold change >1.5 and padj

TXLNA (taxilin alpha), a binding partner of the syntaxin family, was identified as a key factor in the coordination of intracellular vesicle trafficking and highly expressed in various tumor cells. However, the accurate relation between TXLNA and tumorigenesis and progression of pancreatic adenocarcinoma (PAAD) is still unclear. The present study was designed to examine the expression profile of TXLNA and explore its prognostic significance in PAAD patients and the possible molecular regulatory mechanism by analyzing a series of data from databases, including GEPIA, LOGpc, STRING, and GeneMANIA. The results indicate that TXLNA mRNA and protein were remarkably increased in PAAD tissues compared with normal pancreatic tissues. The high TXLNA expression was significantly correlated with superior overall survival (OS), disease-free interval (DFI), disease specific survival (DSS), and progression-free interval (PFI) for PAAD patients. In summary, high TXLNA expression could predict favourable OS, DFI, DSS, and PFI for PAAD patients, and it might be as potential prognostic biomarkers and targets for PAAD.

Inflammasome is a complex composed of several proteins and an important part of the natural immune system. Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is composed of NLRP3, apoptosis associated speck like protein (ASC) and pro-caspase-1. It plays an important role in many diseases. Hydrogen sulfide (H2S) is an important signaling molecule that regulates many physiological and pathological processes. Recent studies indicated that H2S played anti-inflammatory and pro-inflammatory roles in many diseases through influencing NLRP3 inflammasome, but its mechanism was not fully understood. This article reviewed the progress about the effects of H2S on NLRP3 inflammasome and its mechanisms involved in recent years to provide theoretical basis for in-depth study.

The endoplasmic reticulum is an important organelle responsible for protein synthesis, modification, folding, assembly and transport of new peptide chains. When the endoplasmic reticulum protein folding ability is impaired, the unfolded or misfolded proteins accumulate to lead to endoplasmic reticulum stress. Hydrogen sulfide is an important signaling molecule that regulates many physiological and pathological processes. Recent studies indicate that H2S plays an important protective role in many diseases through influencing endoplasmic reticulum stress, but its mechanism is not fully understood. This article reviewed the progress about the effect of H2S on endoplasmic reticulum stress and its mechanisms involved in diseases in recent years to provide theoretical basis for in-depth study.

Ischemia/reperfusion (I/R) injury refers to the functional and structural changes in the process of blood flow recovery after ischemia. In addition to ischemia, the blood flow recovery can also lead to very harmful damage, such as the obvious cell swelling and the irreversible cell necrosis. I/R injury is related with many diseases, including myocardial I/R injury. Myocardial I/R injury refers to the aggravation of ischemic myocardial tissue injury due to sudden disorder of blood circulation. Although there are many studies on myocardial I/R injury, the exact mechanism is not fully understood. Hydrogen sulfide (H2S), like carbon monoxide and nitric oxide, is an important gas signal molecule. It plays an important role in many physiological and pathological processes. Recent studies indicate that H2S can improve myocardial I/R injury, however, its mechanism is not fully understood, especially the involved signal pathways. In this review, we summarize the related researches about the role of the signaling pathways involved in the protective effects of exogenous H2S on myocardial I/R injury, so as to provide theoretical reference for the future in-depth researches.

Mn-doped ZnS quantum dots (QDs) with excellent optical properties have been explored in a wide range of fields. Their potential adverse effects on biological systems and human health should be evaluated before biological application. In the present study, we investigated the effect of Mn-doped ZnS QDs on the intestinal tract and gut microbiota structures at 2 h and 14 days (d) after 14 d repeated oral exposure in mice. Flame atomic absorption spectrophotometry (FAAS), histopathological examination, and transmission electron microscopy (TEM) were used to assess the absorption and toxicity of Mn-doped ZnS QDs on the intestinal tract. The 16S rRNA gene sequencing was used to evaluate the gut microbial communities. Mn-doped ZnS QDs did not accumulate in the duodenum, jejunum, ileum, or colon. The Zn content of feces was not significantly higher than in the control group. No major histological changes were found in these tissues. The intestinal microvilli remained regular, but swelling of mitochondria and endoplasmic reticulum was detected by TEM at 14 d after the last gavage. A total of 2,712 operational taxonomic units (OTUs) were generated. Mn-doped ZnS QDs treatment did not significantly change the α-diversity of Richness, Chao1, Shannon, and Simpson indexes. According to principal component analysis (PCA), Mn-doped ZnS QDs had no effect on the overall structure of the gut microbiota. No significant change occurred at the phylum level, while three genera were downregulated at 2 h and seven changed at 14 d after the last gavage. Our findings revealed that Mn-doped ZnS QDs had a little stimulation of the intestinal tract and gut microbiota, and oral administration may be a safe route for biological application (such as bioimaging and drug delivery).

Ischemia/reperfusion (I/R) injury is characterized by a limited blood supply to organs, followed by the restoration of blood flow and reoxygenation. In addition to ischemia, blood flow recovery can also lead to very harmful injury, especially inflammatory injury. Autophagy refers to the transport of cellular materials to the lysosomes for degradation, leading to the conversion of cellular components and offering energy and macromolecular precursors. It can maintain the balance of synthesis, decomposition and reuse of the intracellular components, and participate in many physiological processes and diseases. Inflammasomes are a kind of protein complex. Under physiological and pathological conditions, as the cellular innate immune signal receptors, inflammasomes sense pathogens to trigger an inflammatory response. TheNLRP3 inflammasome is the most deeply studied inflammasome and is composed of NLRP3, the adaptor apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC) and pro-caspase-1. Its activation triggers the cleavage of pro-interleukin (IL)-1β and pro-IL-18 mediated by caspase-1 and promotes a further inflammatory process. Studies have shown that autophagy and the NLRP3 inflammasome play an important role in the process of I/R injury, but the relevant mechanisms have not been fully explained, especially how the interaction between autophagy and the NLRP3 inflammasome participates in I/R injury, which remains to be further studied. Therefore, we reviewed the recent studies about the interplay between autophagy and the NLRP3 inflammasome in I/R injury and analyzed the mechanisms to provide the theoretical references for further research in the future.

Autophagy is a vital cell mechanism which plays an important role in many physiological processes including clearing long-lived, accumulated and misfolded proteins, removing damaged organelles and regulating growth and aging. Autophagy also participates in a variety of biological functions, such as development, cell differentiation, resistance to pathogens and nutritional hunger. Recently, autophagy has been reported to be involved in diabetes, but the mechanism is not fully understood. Hydrogen sulfide (H2S) is a colorless, water-soluble, flammable gas with the typical odor of rotten eggs, which has been known as a highly toxic gas for many years. However, it has been reported recently that H2S, together with nitric oxide and carbon monoxide, is an important gas signal transduction molecule. H2S has been reported to play a protective role in many diabetes-related diseases, but the mechanism is not fully clear. Recent studies indicate that H2S plays an important role by regulating autophagy in many diseases including cancer, tissue fibrosis diseases and glycometabolic diseases; however, the related mechanism has not been fully studied. In this review, we summarize recent research on the role of H2S in regulating autophagy in diabetic-related diseases to provide references for future related research.

Purpose Mn-doped ZnS quantum dots (QDs) with special luminescent properties have been widely researched and applied in various fields. Thus, their release toxicity and security cannot be ignored. Methods In the present study, the toxicity and non-targeted metabolomics of Mn-doped ZnS QDs were investigated after single intravenous injection. Serum metabolites were evaluated based on gas chromatography-mass spectrometry together with multivariate statistical analyses [principal component analysis, partial least squares discriminant analysis, and orthogonal PLS-DA]. Results The modified metabolites (variable importance in the projection (VIP) >1 and p

Spexin/NPQ is a novel highly conserved neuropeptide. It has a widespread expression in the periphery and central nervous system. However, the effects of central spexin on acute inflammatory pain are still unknown. This study explored the mechanisms and effects of supraspinal spexin on inflammatory pain. The results from the mouse formalin test show that i.c.v. administration of spexin decreased licking/biting time during the late and early phases. The nonamidated spexin had no effect on pain response. The antinociception of spexin was blocked by galanin receptor 3 antagonist SNAP 37889. The Galr3 and Adcy4 mRNA levels in the brain were increased after injection with spexin. The antinociceptive effects of spexin were completely reversed by opioid receptor antagonist naloxone and κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride. Spexin up-regulated the dynorphin and κ-opioid receptor gene and protein expression. PCR array assay and real-time PCR analysis show that spexin up-regulated the mRNA level of the FBJ osteosarcoma oncogene (Fos). T-5224, the inhibitor of c FBJ osteosarcoma oncogene (c-Fos)/activator protein 1 (AP-1), blocked the increased mRNA level of Pdyn and Oprk1 induced by spexin. I.C.V. spexin (2.43 mg/kg) increased the number of c-Fos-positive neurons in most subsections of periaqueductal gray. In addition, in the acetic acid-induced writhing test, i.c.v. spexin produced an antinociceptive effect. Our results indicate that spexin might be a novel neuropeptide with an antinociceptive effect against acute inflammatory pain.

Ischemia/reperfusion (I/R) injury is characterized by limiting blood supply to organs, then restoring blood flow and reoxygenation. It leads to many diseases, including acute kidney injury, myocardial infarction, circulatory arrest, ischemic stroke, trauma, and sickle cell disease. Autophagy is an important and conserved cellular pathway, in which cells transfer the cytoplasmic contents to lysosomes for degradation. It plays an important role in maintaining the balance of cell synthesis, decomposition and reuse, and participates in a variety of physiological and pathological processes. Hydrogen sulfide (H2S), along with carbon monoxide (CO) and nitric oxide (NO), is an important gas signal molecule and regulates various physiological and pathological processes. In recent years, there are many studies on the improvement of I/R injury by H2S through regulating autophagy, but the related mechanisms are not completely clear. Therefore, we summarize the related research in the above aspects to provide theoretical reference for future in-depth research.

Endoplasmic reticulum (ER) is an important organelle for the protein synthesis, modification, folding, assembly, and the transport of new peptide chains. When the folding ability of ER proteins is impaired, the accumulation of unfolded or misfolded proteins in ER leads to endoplasmic reticulum stress (ERS). The nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome, can induce the maturation and secretion of interleukin-1beta (IL-1β) and IL-18 through activating caspase-1. It is associated with many diseases. Studies have shown that ERS can regulate NLRP3 inflammasome in many diseases including diabetes. However, the mechanism of the effects of ERS on NLRP3 inflammasome in diabetes has not been fully understood. This review summarizes the recent researches about the effects of ERS on NLRP3 inflammasome and the related mechanism in diabetes to provide ideas for the relevant basic research in the future.

Apelin, a peptide hormone, is an endogenous ligand for G protein-coupled receptor and has been shown to be widely expressed in human and animal tissues, such as the central nervous system and adipose tissue. Recent studies indicate that the apelin/APJ system is involved in the regulation of multiple physiological and pathological processes, and it is associated with cardiovascular diseases, metabolic disorders, neurological diseases, ischemia-reperfusion injury, aging, eclampsia, deafness, and tumors. The occurrence and development of these diseases are closely related to the local inflammatory response. Oxidative stress is that the balance between oxidation and antioxidant is broken, and reactive oxygen species are produced in large quantities, causing cell or molecular damage, which leads to vascular damage and a series of inflammatory reactions. Hence, this article reviewed recent advances in the relationship between apelin/APJ and oxidative stress, and inflammation-related diseases, and highlights them as potential therapeutic targets for oxidative stress-related inflammatory diseases.

Βeta-cyclodextrin (β-CD) with a hydrophobic cavity enables the formation of inclusion complexes with organic molecules. The formation of host–guest complexes makes the application of β-CD popular in many fields, but their interaction with organisms is poorly understood. In the present study, the effect of β-CD on gut microbiota (16S rRNA gene sequencing), serum metabolites (gas chromatography–mass spectrometry platform), and their correlation (Pearson correlation analysis) was investigated after 14 days repeated oral exposure in mice. β-CD did not significantly affect the α-diversity indexes, including Richness, Chao1, Shannon and Simpson indexes, but disturbed the structure of the gut bacteria according to the result of principal component analysis (PCA). After taxonomic assignment, 1 in 27 phyla, 2 in 48 classes, 3 in 107 orders, 6 in 192 families, and 8 in 332 genera were significantly different between control and β-CD treated groups. The serum metabolites were significantly changed after β-CD treatment according to the result of unsupervized PCA and supervised partial least squares-discriminant analysis (PLS-DA). A total of 112 differential metabolites (89 downregulated and 23 upregulated) were identified based on the VIP >1 from orthogonal PLS-DA and p t-test. The metabolic pathways, including ABC transporters, pyrimidine metabolism, purine metabolism, glucagon signaling pathway, insulin signaling pathway, and glycolysis/gluconeogenesis, were enriched by KEGG pathway analysis. Our study provides a general observation of gut microbiota, serum metabolites and their correlation after exposure to β-CD in mice, which will be helpful for future research and application of β-CD.

Apelin is an endogenous neuropeptide, which has wide distribution in central nervous system and peripheral tissues. Pyroglutamyl apelin-13 [(pyr)apelin-13] is the major apelin isoform in human plasma. However, the role of peripheral (pyr)apelin-13 in pain regulation is unknown. The aim of this study was to investigate the effect of the peripheral injection of (pyr)apelin-13 on inflammatory pain using the formalin test as well as to evaluate the mechanistic basis for the effect. Results showed intravenous (i.v.) injection of (pyr)apelin-13 (10, 20 mg/kg) to significantly decrease licking/biting time during the second phase of the mouse formalin test. In contrast, i.v. injection of apelin-13 had no influence on such effect. Intramuscular injection of (pyr)apelin-13 reduced licking/biting time during the second phase only at a dose of 20 mg/kg. The antinociception of i.v. (pyr)apelin-13 was antagonized by the apelin receptor (APJ, angiotensin II receptor-like 1) antagonist, apelin-13(F13A). (pyr)apelin-13 (i.v. 20 mg/kg) markedly upregulated Aplnr and Adcy2 gene expression in the prefrontal cortex, whereas Fos gene expression was downregulated. The antinociception of i.v. (pyr)apelin-13 was blocked by the opioid receptor antagonist naloxone and the specific kappa opioid receptor (KOR) antagonist nor-binaltorphimine (nor-BNI). (pyr)Apelin-13 upregulated the dynorphin and KOR gene expression and protein levels in the mouse prefrontal cortex, not in striatum. (pyr)Apelin-13 did not influence the motor behavior. Our results demonstrate that i.v. injection of (pyr)apelin-13 induces antinociception via the KOR in the inflammatory pain mouse model.

Zinc oxide (ZnO) quantum dot (QD) is a promising inexpensive inorganic nanomaterials, of which potential toxic effects on biological systems and human health should be evaluated before biomedical application. In this study, the cytotoxicity of ZnO QDs was assessed using HeLa cervical cancer cell and HEK-293T human embryonic kidney cell lines. Cell viability was significantly decreased by treatment with 50 µg/ml ZnO QDs after only 6 h, and the cytotoxicity of ZnO QDs was higher in HEK-293T than in HeLa cells. ZnO QDs increased the level of reactive oxygen species and decreased the mitochondria membrane potential in a dose-dependent manner. Several gene expression involved in apoptosis was regulated by ZnO QDs, including bcl-2 gene and caspase. In HeLa cells, ZnO QDs significantly increased early and late apoptosis, but only late apoptosis was affected in HEK-293T cells. These findings will be helpful for future research and application of ZnO QDs in biomedicine.

Spexin (SPX, NPQ), a novel endogenous neuropeptide, was firstly identified by bioinformatics. Spexin gene and protein widely distributed in the central nervous system and peripheral tissues, such as the hypothalamus and digestive tract. The role of spexin in appetite regulation in mammalian is still unclear. The present study was designed to investigate the mechanism and effect of peripheral spexin on food intake in mice. During the light period, an intraperitoneal (i.p.) injection of spexin (10 nmol/mouse) significantly inhibited cumulative food intake at 2, 4, and 6 h after treatment in fasted mice. During the dark period, spexin (1 and 10 nmol/mouse, i.p.) significantly suppressed cumulative food intake at 4 and 6 h after treatment in freely feeding mice. The GALR3 antagonist SNAP37889, not GALR2 antagonist, significantly antagonized the inhibitory effect on cumulative food intake (0–6 h) induced by spexin. Spexin significantly reduced the mRNA level of Npy mRNA, not Agrp, Pomc, Cart, Crh, Orexin, or Mch, in the hypothalamus. Spexin (10 nmol/mouse, i.p.) increased the number of c-Fos positive neurons in hypothalamic AHA and SCN, but not in ARC, DMN, LHA, PVN, SON, or VMH. The hypothalamic p-CaMK2 protein expression was upregulated by spexin. This study indicated that acute peripheral injection of spexin inhibited mouse food intake. The anorectic effect may be mediated by GALR3, and inhibiting neuropeptide Y (NPY) via p-CaMK2 and c-Fos in the hypothalamus.

Compared to normal tissues, unique conditions in the tumor microenvironment, such as a lower pH, can induce accurate release of a drug into specific lesions. This strategy provides an efficient approach to overcome the issues of unexpected drug leakage and poor circulation stability, thereby reducing the side effects and enhancing the effect of cancer treatment. In this study, we designed a class of acid activatable supramolecular nano-prodrugs (DOM@DOX) with a bottlebrush architecture based on the dextran (DEX) polysaccharide, which connects with a hydrophilic polyethylene glycol chain by atom transfer radical polymerization and further conjugates with an anticancer drug doxorubicin (DOX) at the backbone of the copolymer via an acidity-responsive hydrazine bond. Furthermore, the DOM@DOX prodrug has a high drug loading up to 48 wt% for DOX, and the prodrug can maintain a stable nano-sized spherical shape in aqueous solution by a self-assembly strategy. In an acidic environment inside tumor cells, the hydrazine bond of the prodrug breaks, leading to the release of DOX from parental micelles. Owing to the small size of the carrier, the prodrug exhibits good intratumoral permeability, good circulation stability and significant tumor suppression efficiency in tumor-bearing mouse models, which is beneficial for the development of new generation nanomedicine for enhanced chemotherapy.

Apelin, an endogenous neuropeptide, has been identified as the cognate ligand for the G-protein-coupled receptor APJ. Apelin, APJ messenger RNA, and protein are widely expressed in the central nervous system and peripheral tissues of humans and animals. The apelin/APJ system has been implicated in diverse physiological and pathological processes. The present article reviews the progress of the latest research investigating the apelin/APJ system in pain, depression, anxiety, memory, epilepsy, neuroprotection, stroke, and brain injury and protection, and highlights its promising potential as a therapeutic target for treatment of psychosis and neuropathy.

Spexin (SPX), also called neuropeptide Q (NPQ), is a novel endogenous neuropeptide. Spexin gene and protein are widely expressed in central nervous system and peripheral tissues in humans, rodents, goldfish, etc. A few of physiological and pathological roles of spexin are gradually emerged recently. This article summarized the roles of spexin in feeding behavior, gastrointestinal motility, obesity, diabetes, energy metabolism, endocrine, mental diseases, and cardiovascular function. Given the broad roles of spexin, this neuropeptide has attracted much interest from investigators and will be as a promising future target for novel therapeutic research and drug design.

Apelin participates in cardiovascular functions, metabolic disease, and homeostasis disorder. However, the biological function of apelin in liver diseases, especially liver fibrosis is still under investigation. The present study aimed to investigate the expression of apelin in nonalcoholic fatty liver disease (NAFLD) and the mechanism of apelin promoting hepatic fibrosis through ERK signaling in hepatic stellate LX-2 cells. The results showed that the ALT and AST levels in serum were increased in the mice fed HFC. The histological staining revealed that hepatocellular steatosis and ballooning degeneration was severe, and fibrogenesis appeared as increased pericellular collagen deposition along with pericentral (lobular) collagen deposition in the mice fed HFC. Immunochemistry and qRT-PCR results showed that the expression of apelin and profibrotic genes was higher as compared to the control group. The in vitro experiments demonstrated that apelin-13 upregulated the transcription and translation levels of collagen type I (collagen-I) and α-smooth muscle actin (α-SMA) in LX-2 cells. The immunofluorescent staining, qRT-PCR, and Western blot results showed that the overexpression of apelin markedly increased the expression of α-SMA and cyclinD1. The LX-2 cells treated with apelin-13 displayed an increased expression of pERK1/2 in a time-dependent manner, while the pretreatment with PD98059 abolished the apelin-induced expression of α-SMA and cyclinD1. Furthermore, the in vivo and in vitro assays suggested a key role of apelin in promoting liver fibrosis, and the underlying mechanism might be ascribed to the apelin expression of profibrotic genes via ERK signaling pathway. Electronic supplementary material The online version of this article (10.1007/s11010-019-03581-0) contains supplementary material, which is available to authorized users.

Background In recent years, nanotechnology has attracted a plethora of attention due of its ability to effectively diagnose and treat various tumors. Virus-like particles (VLPs) have good biocompatibility, are safe and non-toxic, and have an internal hollow space, and as such they are often used as nano drug carriers. In recent years, it has become one of the hot spots in the field of biopharmaceutical engineering. Methods In this study, the tumor-targeting peptide RGD (Arg-Gly-Asp) was genetically inserted into the major immunodominant region (MIR) of the hepatitis B virus core protein (HBc). A series of characterization, including stability and optical properties, were evaluated. A visual diagnosis and analysis of the efficacy against tumor cells were conducted at the cell level and using a live animal model. Results This study demonstrated that the recombinant HBc-based VLPs could participate in self-assembly of monodispersed nanoparticles with well-defined morphology, and the near-infrared dye indocyanine green (ICG) could be packaged into the VLPs without any chemical modification. Moreover, the HBc-based VLPs could specifically target cancer cells via the interaction with overexpressed integrin αvβ3. The treatment with ICG-loaded HBc-based VLPs showed significant inhibition of 4T1 breast cancer cell growth (84.87% tumor growth inhibition). The in vivo imaging experiments demonstrated that the ICG-loaded HBc-based VLPs generated excellent fluorescence in tumor sites in 4T1 breast cancer bearing mice. This provided crucial information on tumor mass location, boundaries, and shape. Moreover, compared to free ICG, the nanosystem showed significantly longer blood circulation time and superior accuracy in targeting the tumor. Conclusions The ICG-loaded HBc-based VLPs prepared in this study were of good stability and biocompatibility. It showed strong tumor targeting specificity and tumor visualization. Thus, it is expected to provide a new experimental basis and theoretical support for the integration of VLPs in the clinical diagnosis and treatment of breast cancer.

Apelin is an endogenous ligand of the apelin receptor (APJ), a seven-transmembrane G protein-coupled receptor. Apelin/APJ system has a wide tissue distribution in the brain as well as in peripheral organs including heart, lung, vessels, and adipose tissue. Apelin/APJ was involved in regulating cardiac and vascular function, heart development, and vascular smooth muscle cell proliferation. In this article, we summarize the role of apelin/APJ system on lung cancer, gastroesophageal and colonic cancer, hepatocellular carcinoma, prostate cancer, endometrial cancer, oral squamous cell carcinoma, brain cancer, and tumor neoangiogenesis. Apelin/APJ may be a potential anticancer therapeutic target.

Hydrogen sulfide (H2S) is the third gaseous signaling molecule that plays important roles in cancer biological processes. Recent studies indicate that H2S has both pro-cancer and anti-cancer effects. Endogenous H2S can exert pro-cancer functions through induction of angiogenesis regulation of mitochondrial bioenergetics, acceleration of cell cycle progression, and anti-apoptosis mechanisms. Thus, the inhibition of the production of H2S in cancer cells may be a new cancer treatment strategy. In contrast to the pro-cancer effect of H2S, relatively high concentrations of exogenous H2S could suppress the growth of cancer cells by inducing uncontrolled intracellular acidification, inducing cell cycle arrest, and promoting apoptosis. Therefore, H2S donors and H2S-releasing hybrids could be designed and developed as novel anti-cancer drugs. In this review, the production and metabolism of H2S in cancer cells are summarized and the role and mechanism of H2S in cancer development and progression are further discussed.

La glandula suprarrenal es un organo endocrino importante en los vertebrados, que produce una amplia variedad de hormonas. Los resultados anatomicos mostraron que la glandula suprarrenal en el Camello bactriano tiene un patron de suministro sanguineo e inervacion tipico. Excepcionalmente, se encontro una conexion infrecuente que consistio principalmente en tejido fibroso, vasos sanguineos y haces nerviosos entre la glandula suprarrenal y el rinon del Camello bactriano, denominandose haz de tejido fibroso-vasos sanguineos-nervio (Haz FSN). Este paquete de haces de nervios es el primero reportado en el Camello bactriano, y aun no se observa en otros animales, en consecuencia sus funciones y mecanismos deben ser estudiados. Creemos que podria existir una funcion directa de esta nueva via para mejorar la comunicacion de la glandula suprarrenal y el rinon. Asi, esta via de comunicacion podria tener un importante significado adaptativo para el Camello bactriano, quien vive en zonas ecologicas aridas y semiaridas.

Apelin, a new bioactive peptide, was identified as an endogenous ligand for APJ (Angiotensin II receptor-like 1). Apelin and its receptor have an abundant distribution in central nervous system and peripheral tissues, including liver. Apelin/APJ has diverse physiological and pathological effects, including regulation of cardiovascular function, angiogenesis, fluid homeostasis and so on. Apelin/APJ system may act as a novel potential therapeutic target for liver disease. In this article, we review the role of apelin/APJ system in liver fibrosis, hepatitis, hepatic cirrhosis, liver injury and metabolic liver disease.

Human opiorphin is a recently identified endogenous pentapeptide, encoded by ProL1 multigenes family that contributes to cardiovascular modulation. The aim of this study was to evaluate the effect of opiorphin through intravenous injection (i.v.) on mean arterial pressure (MAP) regulation. To investigate the bioactivity of opiorphin, a rat cannulation model was developed for MAP measurement and blood sampling. In our present study, opiorphin (200-700 nmol/kg) increased MAP in dose-related and time-dependent manner in conscious rats, which associated highly with the elevation of angiotensin II (AngII) levels in serum. Furthermore, the MAP elevation induced by opiorphin was completely blocked by AngII receptor antagonist valsartan and partially attenuated by angiotensin-converting enzyme inhibitor captopril. Finally, we tested the effect of opiorphin in hypoxia condition, which exhibited that opiorphin reversed hypoxia induced hypotension in conscious rats. Taken together, these results indicated that opiorphin may play an important role in the modulation of blood pressure through AngII dependent pathway, which may help future development of potent clinical therapeutics for emergency treatment.

Apelin was first identified and characterized from bovine stomach extracts as an endogenous ligand for the APJ receptor. Apelin/APJ system is abundantly present in peripheral tissues and central nervous system. Apelin plays a broad role in regulating physiological and pathological functions. Recently, many reports have showed the effects of apelin on feeding behavior, however the results are inconsistent, due to different administration routes, animal species, forms of apelin, etc. Apelin has been involved in stimulating gastric cell proliferation, cholecystokinin (CCK) secretion, histamine release, gastric acid and bicarbonate secretion, and regulation of gastrointestinal motility. In addition, apelin produced regulatory effects on drinking behavior, diuresis, arginine vasopressin (AVP) release and glucocorticoids secretion. This article reviews the role of apelin on feeding behavior, gastrointestinal function and fluid homeostasis.

In the present study, ZnS and ZnO quantum dots (QDs) were synthesized via an all-aqueous process with polyethylene glycol (PEG) chains on their surface, and their toxicity as well as biodistribution were evaluated. No haemolysis occurred at a high concentration of 1600 µg/mL in vitro haemolytic assay, which demonstrated that the QDs-PEG displayed good blood compatibility. Following intravenous administration at 2, 6, and 20 mg/kg of the QDs-PEG in mice, the biodistribution, excretion and biocompatibility were characterized at 1 h, 24 h and 7 days, respectively. Quantitative analysis results indicated that the biodistribution trend of ZnS QDs-PEG was similar to that of ZnO QDs-PEG. The QDs-PEG were mainly trapped in the lung and liver, and almost removed from blood within 1 h. QDs-PEG were primarily excreted in faeces at the 2 and 6 mg/kg doses. Coefficients, haematology, blood biochemistry and histopathology results indicated that the QDs-PEG were safe and biocompatible.

Apelin, as the endogenous ligand of the APJ receptor, is a novel identified neuropeptide whose biological functions are not fully understood. APJ receptor mRNA was found in several brain regions related to descending control system of pain, such as amygdala, hypothalamus and dorsal raphe nucleus (DRN). The present study was designed to determine whether supraspinal apelin-13 may produce antinociceptive effect observed in the acetic acid-induced writhing test, a model of visceral pain. Apelin-13 not only significantly produced preemptive antinociception at the dose of 0.3, 0.5, 1 and 3 μg/mouse when injected intracerebroventricularly (i.c.v.) before acetic acid, but also significantly induced antinociception at a dose of 0.5, 1 and 3 μg/mouse when injected i.c.v. after acetic acid. And i.c.v. apelin-13 did not influence 30-min locomotor activity counts in mice. Intrathecal (i.t.) administration of apelin-13 (1 and 3 μg/mouse) significantly decreased the number of writhes, however, intraperitoneal (i.p.) injection of apelin-13 (10–100 μg/mouse) had no effect on the number of writhes in the writhing test. The specific APJ receptor antagonist apelin-13(F13A), no-specific opioid receptor antagonist naloxone and μ-opioid receptor antagonist β-funaltrexamine hydrochloride (β-FNA) could significantly antagonize the antinociceptive effect of i.c.v. apelin-13, suggesting APJ receptor and μ-opioid receptor are involved in this process. Central low dose of apelin-13 (0.3 μg/mouse, i.c.v.) could significantly potentiate the analgesic potencies of modest and even relatively ineffective doses of morphine administrated at supraspinal level. This enhanced antinociceptive effect was reversed by naloxone, suggesting that the potentiated analgesic response is mediated by opioid-responsive neurons.

Apelin, as the endogenous ligand for the APJ, regulates many biological functions, including blood pressure, neuroendocrine, drinking behavior, food intake and colonic motility. The present study was designed to investigate the effect of central apelin-13 on gastric emptying and gastrointestinal transit in mice. Intracerebroventricular (i.c.v.) injection of apelin-13 (3 and 10 μg/mouse) decreased gastric emptying rate by 10.9% and 17.1%. This effect was significantly antagonized by the APJ receptor antagonist apelin-13(F13A) and the opioid receptor antagonist naloxone, respectively. However, intraperitoneal (i.p.) injection of apelin-13 (10-100 μg/mouse) did not affect gastric emptying. Apelin-13 (0.3, 1 and 3 μg/mouse, i.c.v.) inhibited gastrointestinal transit by 16.8%, 23.4% and 19.2%. Apelin-13(F13A) and naloxone could also reverse this antitransit effect induced by apelin-13. Taken together, these results suggest that i.c.v. injected apelin-13 inhibits gastric emptying and gastrointestinal transit and it seems that APJ receptor and opioid receptor might be involved in these processes.

Apelin is a novel bioactive peptide as the endogenous ligand for the orphan G-protein-coupled receptor (GPCR), APJ, a receptor distributed in various tissues such as the hypothalamus and the gastrointestinal tract. Recent reports showed that apelin regulated many biological functions, including blood pressure, neuroendocrine, drinking behavior and food intake. However, the role of apelin in regulating gastrointestinal motility remains unknown. The present study aimed to investigate the actions of intracerebroventricularly administered apelin-13 on colonic transit as well as the actions of apelin-13 on the contraction of isolated distal colon in vitro. Intracerebroventricular (i.c.v.) injection of apelin-13 (0.3, 0.5, 1 and 3 μg/mouse) dose-dependently inhibited fecal pellet output and bead expulsion. This effect was significantly antagonized by the APJ receptor antagonist apelin-13(F13A), indicating an APJ receptor-mediated mechanism. Furthermore, naloxone could also reverse the inhibitory effect of apelin-13 on fecal pellet output and bead expulsion, suggesting the involvement of opioid receptors in the suppressive effect of apelin-13 on distal colon transit. However, apelin-13 (10⁻⁸-10⁻⁶ M) did not affect distal colonic contractions in vitro.

Apelin is the endogenous ligand for the APJ, a member of the G protein coupled receptors family. Apelin/APJ system is widely distributed in central nervous system and peripheral tissues, especially in heart, lung and kidney. Apelin plays important physiological and pathological roles in cardiovascular system, immune system, neuroprotection, etc. This article outlines the protective effect of apelin on ischemia/reperfusion (I/R) injury. Apelin could activate multiple protective mechanisms to prevent heart, brain, liver and kidney I/R injury. Apelin/APJ system may be a promising therapeutic target for ischemic and other related diseases.

Apelin, a novel bioactive peptide highly concentrated in the brain, is identified as the endogenous ligand for angiotensin-like 1 receptor (APJ). The present study was designed to investigate the effect of apelin-13 on emotion-related behavior using the forced swimming test (FST) and tail suspension test (TST). Intracerebroventricular (i.c.v.) administration of apelin-13 (0.3, 1 and 3 μg/mouse) dose-dependently increased the immobility time in the FST and TST, compared with control group. However, the APJ receptor antagonist apelin-13(F13A) (0.3–10 μg/mouse, i.c.v.) had no influence on immobility time in the FST. The increase of immobility time induced by apelin-13 was significantly blocked by apelin-13(F13A), non-selective opioid receptor antagonist naloxone and κ-opioid receptor antagonist nor-binaltorphimine dihydrochloride (nor-BNI), respectively, but not the non-selective corticotrophin-releasing factor (CRF) receptor antagonist α-helical CRF 9–41 in the FST. In order to eliminate the possibility of a false-positive result in the FST or TST, spontaneous activity and motor function were checked. The results demonstrate that apelin-13 alone or antagonists co-administered with apelin-13 did influence spontaneous activity counts. And apelin-13 had no effect on the motor behavior in the rotarod test and wire hanging test. These results indicate that centrally administered apelin-13 elicited depression-like behavior in mice, which was mediated via APJ receptor and κ-opioid receptor, but not CRF receptor.

Yanjie Yang,1,2 Shuang-Yu Lv,2 Bianfei Yu,1 Shuang Xu,1 Jianmin Shen,3 Tong Zhao,1 Haixia Zhang1 1Key Laboratory of Nonferrous Metal Chemistry and Resources Utilization of Gansu Province, Lanzhou University, Lanzhou, Gansu, 2School of Medicine, Henan University, Kaifeng, Henan, 3Institute of Biochemistry and Molecular Biology, School of Life Sciences, Lanzhou University, Lanzhou, Gansu, People’s Republic of China Abstract: Doped ZnS quantum dots (QDs) have a longer dopant emission lifetime and potentially lower cytotoxicity compared to other doped QDs. The liver is the key organ for clearance and detoxification of xenobiotics by phagocytosis and metabolism. The present study was designed to synthesize and evaluate the hepatotoxicity of Mn-doped ZnS QDs and their polyethylene glycol-coated counterparts (1mg/kg and 5mg/kg) in mice. The results demonstrated that daily injection of Mn-doped ZnS QDs and polyethylene glycol-coated QDs via tail vein for 7days did not influence body weight, relative liver weight, serum aminotransferases (alanine aminotransferase and aspartate aminotransferase), the levels of antioxidant enzymes (catalase, glutathione peroxidase, and superoxide dismutase), or malondialdehyde in the liver. Analysis of hepatocyte ultrastructure showed that Mn-doped ZnS QDs and polyethylene glycol-coated QDs mainly accumulated in mitochondria at 24hours after repeated intravenous injection. No damage to cell nuclei or mitochondria was observed with either of the QDs. Our results indicate that Mn-doped ZnS QDs did not cause obvious damage to the liver. This study will assist in the development of Mn-doped ZnS QDs-based bioimaging and biomedical applications in the future. Keywords: liver, serum aminotransferases, antioxidant enzymes, ultrastructure