NUDCD1 knockdown inhibits the proliferation, migration, and invasion of pancreatic cancer via the EMT process.

NudC domain containing 1 (NUDCD1) is an oncoprotein frequently activated or upregulated in various human cancers, but its role in pancreatic cancer (PC) remains unknown. Thus, we aimed to determine the function and mechanism of NUDCD1 in PC. We employed Western blot and quantitative real-time polymerase chain reaction to assess NUDCD1 expression in cells and PC tissues. NUDCD1 was knocked down in Patu8988 and PANC-1 cells. We conducted real-time cell analysis, wound healing assay, transwell assay and colony formation assay to evaluate the metastatic and proliferative abilities of PC cells. Western blot was conducted to assess the expression of markers associated with apoptosis and epithelial-mesenchymal transition (EMT). Also, we established a tumor xenograft model to determine the role of NUDCD1 in vivo. NUDCD1 was overexpressed in PC tissues and cells. NUDCD1 knockdown suppressed the invasion, migration, and proliferative abilities of the cells and induced PC cell apoptosis. The specific mechanism of NUDCD1 was related to the modulation of the EMT process. Data obtained from in vivo experiments revealed that NUDCD1 knockdown inhibited the tumor growth, proliferation, and metastasis by modulating the EMT and inducing the apoptosis of PC cells.

Gastrodin alleviates bone damage by modulating protein expression and tissue redox state.

Fluorosis is a common disease characterized by disruptions in bone metabolism and enamel development. The production of reactive oxygen species is thought to play an important role in fluorosis. Gastrodin (4-hydroxybenzylalcohol4-O-beta-D-glucopyranoside) has been reported to have antioxidative activity, and so here we examined whether gastrodin has protective effects against oxidative stress and bone tissue toxicity in rats with fluorosis. Wistar rats were given different doses of gastrodin 1 month after fluoride administration, and samples of blood, bone and teeth were collected after 2, 3 and 4 months; glutathione peroxidase glu, CAT and SOD levels in the fluorosis group were lower than those in the control group. Gastrodin treatment in rats ameliorated oxidative stress and fluoride accumulation that were induced by fluoride; treatment with 400 mg·kg-1 gastrodin protected trabecular bone structure and reduced femur and alveolar bone injury in rats with fluorosis. Enhanced expression of cysteinyl aspartate-specific proteinase (caspase) 3, caspase-9 and Bax and decreased expression of Bcl-2 induced by fluoride were also reversed by gastrodin. In summary, the present data suggest that gastrodin, and in particular a dose of 400 mg·kg-1 , can improve the antioxidative capacity of rats, reduce concentration of fluoride in tissues, alleviate bone damage and modulate expression of Bcl-2, Bax, caspase-3 and caspase-9.

Supramolecular micellar drug delivery system based on multi-arm block copolymer for highly effective encapsulation and sustained-release chemotherapy.

Poly(phosphoester)-based biomaterials have great potential in drug delivery systems (DDSs) because of their multifunctional adjustability, stealth effect, excellent biodegradability, and biocompatibility. To further increase the drug loading efficiency (DLE) and sustained release ability, a multi-arm block copolymer, poly(amido amine)-b-poly(2-butenyl phospholane)-b-poly(2-methoxy phospholane) conjugated with folic acid (abbreviated as PAMAM-PBEP-PMP-FA), was designed and prepared. Compared to the traditional linear copolymers, this multi-arm phosphoester block copolymer integrates a balanced combination of unique features. As an advanced DDS, the PAMAM-PBEP-PMP-FA based supramolecular micelle provides good architectural stability, low protein adsorption, extremely high DLE, and sustained drug release for chemotherapy and abundant surface chemistry for target engineering. Benefitting from these novel functions, the supramolecular micellar drug delivery system exhibits great performances both in in vitro and in vivo evaluations. Doxorubicin (DOX)-loaded supramolecular micelles PAMAM-PBEP-PMP-FA/DOX are fast taken up by HepG2 cells and inhibit the tumor growth effectively in HepG2-tumor-bearing nude mice without obvious system toxicity. This work not only suggests a targeted sustained release DDS for effective chemotherapy but also enlightens, through a delicate design at the molecular scale, the brilliance of multifunctional PPE-based nanomaterials towards versatile bio-applications.

Retracted: Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor 5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma).

In the article entitled, "Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor 5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma)", which was published in Medical Science Monitor 2017-04-23, Med Sci Monit 2017; 23: 1947-1955, the text has been directly copied from a previously published article entitled, "Immunohistochemical expression of somatostatin receptor subtypes 2 and 5 in thyrotropin-secreting pituitary adenomas: a consecutive case series of pituitary adenomas" by Hong-Juan Fang, Yang-Fang Li, Yu Fu, Li-Yong Zhong, and Ya-Zhuo Zhan in Int J Clin Exp Pathol 2017;10(1): 479-488 (www.ijcep.com /ISSN: 1936-2625/IJCEP0042895). Thus, owing to the duplicity of text, the article is being retracted.

miR-26a suppresses osteosarcoma migration and invasion by directly targeting HMGA1.

Osteosarcoma (OS) is identified as the most commonly diagnosed malignant cancer of bone, and has approximately three million new cases annually. miR-26a plays an important role in the development of various types of cancer. We investigated whether miR-26a can regulate the migration and invasion of OS by targeting high-mobility group A1 HMGA1. Western blot analysis was used to identify the changes of protein levels. Reverse transcription-quantitative PCR was used to test expression levels of genes and miR-26a. Luciferase reporter assay was used to test the specific target gene of miR-26a. Transwell assay was employed to determine the migration and invasion of OS cell lines. In the present study, miRNA-26a was frequently downregulated in OS tissues and cells. Overexpression of miR-26a inhibited cell migration and invasion in vitro. In addition, miR-26a downregulated HMGA1 by targeting its 3'-UTR and knockdown of HMGA1 significantly suppressed the migration and invasion of two osteosarcoma cell lines in vitro. miR-26a suppressed the migration and invasion of OS cells by targeting HMGA1, suggesting that miR-26a/HMGA1 axis provides a new prospective therapeutic strategy for OS.

Clinical Importance of Somatostatin Receptor 2 (SSTR2) and Somatostatin Receptor 5 (SSTR5) Expression in Thyrotropin-Producing Pituitary Adenoma (TSHoma).

BACKGROUND Thyrotropin-secreting pituitary adenomas (TSHomas) are a rare cause of hyperthyroidism. Somatostatin analogs have proved to be effective for inhibiting pituitary hormones secretion, working via interactions with somatostatin receptors (SSTRs). Moreover, antiproliferative activity of somatostatin analog is now demonstrated in several studies. In the present study, we determined the relative predominance of SSTR2 and SSTR5 subtypes among the different types of adenomas, especially TSHoma, and investigated the relationship between efficacy of short-term octreotide (OCT) treatment and SSTR expression. MATERIAL AND METHODS Serum hormone determinations and histological findings in resected tissue resulted in 5 diagnoses: 16 TSHomas, 8 acromegaly, 3 prolactinomas, 3 corticotropinomas, 4 clinically nonfunctioning adenomas (NFPAs), and 4 normal pituitary specimens. IHC was performed on formalin-fixed and paraffin-embedded tissue in tissue microarrays. RESULTS IHC of SSTR subtypes in the different cohorts showed SSTR2 staining intensity scores higher than SSTR5 in TSHoma, acromegaly and prolactinoma, whereas the expression of SSTR5 was stronger than SSTR2 in corticotropinoma and NFPA. SSTR2 and SSTR5 expressions were significantly higher in TSHoma than in other pituitary adenomas. OCT treatment for a median of 8.4 days (range: 3-18 days) and with a total median dose of 1.9 mg (range: 0.9-4.2 mg) showed a significant decrease of thyroid hormone levels (TSH [µIU/ml] in all patients. Patients with low SSTR5 expression presented a significantly higher TSH suppression rate (P values <0.05). CONCLUSIONS The present data confirm that somatostatin analogs should be considered as a medical alternative to surgical treatment, especially in patients with TSHoma, and short-term response to OCT therapy may be related to the expression of SSTR5.

Controllable Synthesis of Multiarm Star-Shaped Copolymers Composed of Phosphoester Chains and Their Application on Drug Delivery.

Novel biodegradable polymers with specific properties, structures, and tailorable designs or modifications are in great demand. Poly(phosphoester)s with good biocompatibility and degradability, as well as other adjustable properties have been studied widely because of their potential in biomedical applications. To meet more versatile and diverse biomedical applications, a novel multiarm star-shaped phosphorester triblock copolymer poly(amido amine)-block-poly(2-butynyl phospholane)-block-poly(2-methoxy phospholane) (PAMAM-PBYP-PMP) is synthesized via organo-catalyzed sequential ring-opening polymerization. Supramolecular micelles with good architectural stability are self-assembled into uniform spherical morphology in aqueous solution. Doxorubicin (DOX) can be encapsulated into the micelles with efficient loading capacity. A slow and sustained release in the environment of simulated intracellular lysosome (pH 5.0 with phosphodiesterase I) is observed. In addition, the copolymers and DOX-loaded supramolecular micelles exhibit low cell-toxicity and excellent anticancer activity toward HeLa cells. As a consequence, this multiarm star-shaped PAMAM-PBYP-PMP has great potential in drug delivery system for tumor treatment.

Regioselective synthesis and in vitro anticancer activity of 4-aza-podophyllotoxin derivatives catalyzed by L-proline.

A series of 4-aza-podophyllotoxin derivatives have been synthesized regioselectively via the three-component reaction of aldehydes, aromatic amines, and tetronic acid catalyzed by l-proline. This method has the advantages of high yield, high regioselectivity, extensive adaptability, easy operation, and environmental friendliness. These compounds were also investigated in vitro, and some were found to have good anticancer activity.