A new contribution for an old drug: Prospect of metformin in colorectal oncotherapy.

Metformin is well known as a hypoglycemic drug, which maintains glucose blood balance by attenuating hepatic glycogen synthesis and enhancing muscle glucose decomposition. The accumulation of epidemiologic studies demonstrates that metformin plays a beneficial role in preventing or treating colorectal carcinoma (CRC). Metformin intake alone or along with traditional chemotherapeutic drugs has been proved to attenuate the growth of colon cancer cells.

Physicochemical Properties and Elimination of the Activity of Anti-Nutritional Serine Protease Inhibitors from Mulberry Leaves.

Mulberry leaf is an excellent protein resource that can be used as feed additive for livestock and poultry. Nevertheless, the use of mulberry leaves in animal diets is limited by its protease inhibitors, tannic acid and other anti-nutritional factors. This study systematically analyzed the type and activity of serine protease inhibitors (SPIs) from the leaves of 34 mulberry varieties, aiming to reveal the physicochemical properties and inactivation mechanism of SPIs.

F4/80 Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway.

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80 KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80 KCs during the regenerative process.

MicroRNA-221 promotes papillary thyroid carcinoma cell migration and invasion via targeting RECK and regulating epithelial-mesenchymal transition.

Aim: The aim of this study was to detect the effects and potential mechanisms of microRNA-221 on a series of biological behaviors of papillary thyroid carcinoma (PTC) cells in vitro and in vivo.

Methods: First, we analyzed the relationship between the expression of miR-221 and several clinicopathological features of PTC patients and then detected the expression of the miR-221 in tumor tissues and cell lines. The effects of miR-221 on proliferation and invasion of PTC cells were verified by cell counting kit-8 (CCK-8) assay, wound healing assay and transwell assay.

Diet-induced hepatic steatosis activates Ras to promote hepatocarcinogenesis via CPT1α.

Aberrant activation of the RAS cascade ubiquitously occurs in human hepatocellular carcinomas (HCC), regardless of rare mutations of RAS. However, the association between the Ras cascade and hepatic steatosis during hepatocarcinogenesis remains under-investigated. Here, the variation in the constitutive activity of Ras signaling and HCC incidence was found in a nonalcoholic fatty liver disease (NAFLD)-HCC mouse model, and Ras activity was induced by hepatic steatosis.

Cyclic stretch induced-retinal pigment epithelial cell apoptosis and cytokine changes.

Background: The pathogenesis of age-related macular degeneration (AMD) is complex. It has been shown that vitreomacular traction (VMT) plays a role in the pathogenesis of AMD. We speculate that the continuous stretch induced by VMT might impair the function of retinal pigment epithelium (RPE) cells and it might also be involved in the progression of AMD.

Partial Optic Nerve Transection in Rats: A Model Established with a New Operative Approach to Assess Secondary Degeneration of Retinal Ganglion Cells.

Previous studies have shown that the secondary degeneration of retinal ganglion cells (RGCs) occurs commonly in glaucoma. Partial optic nerve transection is considered a useful and reproducible model. Compared with other optic nerve injury models used commonly for assessing secondary degeneration, e.

Chitosan Promoted the Corneal Epithelial Wound Healing via Activation of ERK Pathway.

Purpose: To investigate the mechanism of chitosan promoting corneal wound healing though evaluating its effect on extracellular signal-regulated kinases (ERK) and p38 pathway activity in a rabbit animal model.

Methods: Cell proliferation and migration assay were performed 24 hours after chitosan treatment. The activity of ERK and p38 pathways was detected by using immunofluorescence and Western blotting in the presence of chitosan and an ERK inhibitor.

Apr3 accelerates the senescence of human retinal pigment epithelial cells.

Senescence of retinal pigment epithelium (RPE) cells is a major contributor to age‑related macular degeneration (AMD). However, the molecular mechanisms underlying RPE dysfunction are not well understood. Apoptosis related protein 3 (Apr3) was originally cloned from HL‑60 cells induced by all‑trans retinoic acid (ATRA).

Lycium barbarum polysaccharides promotes in vivo proliferation of adult rat retinal progenitor cells.

Lycium barbarum is a widely used Chinese herbal medicine prescription for protection of optic nerve. However, it remains unclear regarding the effects of Lycium barbarum polysaccharides, the main component of Lycium barbarum, on in vivo proliferation of adult ciliary body cells. In this study, adult rats were intragastrically administered low- and high-dose Lycium barbarum polysaccharides (1 and 10 mg/kg) for 35 days and those intragastrically administered phosphate buffered saline served as controls.

Dynein, kinesin and morphological changes in optic nerve axons in a rat model with cerebrospinal fluid pressure reduction: the Beijing Intracranial and Intraocular Pressure (iCOP) study.

Purpose: To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) as compared to elevated intraocular pressure (IOP) on axonal morphology and axonal motor proteins in retinal ganglion cells (RGCs).

Methods: The experimental study included 39 rats which underwent cerebrospinal fluid drainage for 6 hr, 30 rats which unilaterally underwent IOP elevation for 6 hr and 30 rats in a control group. Six hours after baseline, the animals were killed and the eyes were histologically and immunohistochemically examined.

Expression and clinical significance of mammalian target of rapamycin/P70 ribosomal protein S6 kinase signaling pathway in human colorectal carcinoma tissue.

The activation of mammalian target of rapamycin (mTOR) has been reported in tumor development, but the role of mTOR in colorectal carcinomas remains unclear. The aim of the present study was to investigate the significance of mTOR and its downstream effector 70 kDa ribosomal protein S6 kinase (P70S6K) in human colorectal carcinomas. The phosphorylated (p-)mTOR and p-P70S6K proteins were examined by immunohistochemistry performed on tissue microarray containing tissue samples obtained from colorectal carcinoma (n=111), adenomatous polyps (n=40) and normal colonic mucosa (n=40), with a comparison between the expression of these proteins and the clinicopathological parameters of patients with carcinomas.

Axonal Transport in the Rat Optic Nerve Following Short-Term Reduction in Cerebrospinal Fluid Pressure or Elevation in Intraocular Pressure.

Purpose: To examine the influence of short-term reduction in cerebrospinal fluid pressure (CSFP) as compared with short-term elevation in IOP on axonal transport.

Methods: The study included 111 adult Sprague-Dawley rats. For 6 hours, IOP was unilaterally elevated to 40 mm Hg (IOP40-group; n = 27), IOP was unilaterally increased to a value of 25 mm Hg below the mean blood pressure (PP25-group; n = 27), or CSFP was reduced by continuous aspiration of cerebrospinal fluid (Low-CSFP-group; n = 27).

Development of gene and stem cell therapy for ocular neurodegeneration.

Retinal degenerative diseases pose a serious threat to eye health, but there is currently no effective treatment available. Recent years have witnessed rapid development of several cutting-edge technologies, such as gene therapy, stem cell therapy, and tissue engineering. Due to the special features of ocular structure, some of these technologies have been translated into ophthalmological clinic practice with fruitful achievements, setting a good example for other fields.

IKK2 inhibition using TPCA-1-loaded PLGA microparticles attenuates laser-induced choroidal neovascularization and macrophage recruitment.

The inhibition of NF-κB by genetic deletion or pharmacological inhibition of IKK2 significantly reduces laser-induced choroid neovascularization (CNV). To achieve a sustained and controlled intraocular release of a selective and potent IKK2 inhibitor, 2-[(aminocarbonyl)amino]-5-(4-fluorophenyl)-3-thiophenecarboxamide (TPCA-1) (MW: 279.29), we developed a biodegradable poly-lactide-co-glycolide (PLGA) polymer-delivery system to further investigate the anti-neovascularization effects of IKK2 inhibition and in vivo biosafety using laser-induced CNV mouse model.

Mertk deficiency affects macrophage directional migration via disruption of cytoskeletal organization.

Mertk belongs to the Tyro3, Axl and Mertk (TAM) family of receptor tyrosine kinases, and plays a pivotal role in regulation of cytoskeletal rearrangement during phagocytosis. Phagocytosis by either professional or non-professional phagocytes is impaired in the Mertk deficient individual. In the present study, we further investigated the effects of Mertk mutation on peritoneal macrophage morphology, attachment, spreading and movement.

Mertk deficiency alters expression of micrornas in the retinal pigment epithelium cells.

Phagocytic clearance of the spent photoreceptor outer segments (OS) by RPE cells is regulated by circadian rhythm cycle and is essential for photoreceptor integrity and function. Mertk regulates RPE phagocytosis and a deficiency in Mertk causes photoreceptor degeneration and visual loss. This study aimed to investigate Mertk regulation of the microRNAs (miRNA), potentially regulating expression of their target genes, which affect phagocytosis.

Optic neuropathy induced by experimentally reduced cerebrospinal fluid pressure in monkeys.

Purpose: To examine the influence of experimentally reduced cerebrospinal fluid pressure (CSFP) on retinal nerve fiber layer (RNFL) thickness and neuroretinal rim area of the optic nerve head.

Methods: This experimental study included nine monkeys that underwent implantation of a lumbar-peritoneal cerebrospinal fluid (CSF) shunt. In the study group (n = 4 monkeys), the shunt was opened to achieve a CSF of approximately 40 mm H2O, while the shunt remained closed in the control group (n = 5 monkeys).

TAM receptors affect adult brain neurogenesis by negative regulation of microglial cell activation.

TAM tyrosine kinases play multiple functional roles, including regulation of the target genes important in homeostatic regulation of cytokine receptors or TLR-mediated signal transduction pathways. In this study, we show that TAM receptors affect adult hippocampal neurogenesis and loss of TAM receptors impairs hippocampal neurogenesis, largely attributed to exaggerated inflammatory responses by microglia characterized by increased MAPK and NF-κB activation and elevated production of proinflammatory cytokines that are detrimental to neuron stem cell proliferation and neuronal differentiation. Injection of LPS causes even more severe inhibition of BrdU incorporation in the Tyro3(-/-)Axl(-/-)Mertk(-/-) triple-knockout (TKO) brains, consistent with the LPS-elicited enhanced expression of proinflammatory mediators, for example, IL-1β, IL-6, TNF-α, and inducible NO synthase, and this effect is antagonized by coinjection of the anti-inflammatory drug indomethacin in wild-type but not TKO brains.

Preparation and characterization of a hydrogel carrier to deliver gatifloxacin and its application as a therapeutic contact lens for bacterial keratitis therapy.

A soft and biocompatible hydrogel exhibiting a higher loading and the sustained release of gatifloxacin (GFLX) was developed as the potential matrix to fabricate a therapeutic contact lens for curing bacterial keratitis. 2-hydroxyethyl methacrylate (HEMA) and five other kinds of vinyl monomers with different side groups were used as co-monomers. Copolymerization took place in a cornea shaped mould via the gradient temperature-elevating method.

[Screening of key genes and inflammatory signalling pathway involved in the pathogenesis of HLA-B27-associated acute anterior uveitis by gene expression microarray].

Objective: To investigate the genes and signalling pathways located upstream of the inflammatory processes in human leukocyte antigen (HLA)-B27-associated acute anterior uveitis by gene expression microarray.

Methods: Experimental study. HLA-B27-positive and-negative monocytes isolated from human peripheral blood were stimulated with Vibrio cholera lipopolysaccharide (LPS).