Syndecan-2 modulates the YAP pathway in epithelial-to-mesenchymal transition-related migration, invasion, and drug resistance in colorectal cancer.

Epithelial-to-mesenchymal transition (EMT) is associated with an invasive phenotype in colorectal cancer (CRC). Here, we examined the roles of YES-associated protein (YAP) and syndecan-2 (SDC2) in EMT-related progression, invasion, metastasis, and drug resistance in CRC. The expression levels of YAP and SDC2 in CRC patient tumor tissue were quantified by PCR and western blotting. EMT-associated characteristics were assessed using Transwell assays and immunohistochemistry. Co-immunoprecipitation, glutathione S-transferase pull-down, and luciferase reporter assays were used to assess interactions between YAP and SDC2. YAP was found to be highly expressed in tumor tissue from 13/16 CRC patients, while SDC2 was highly expressed in the tumor tissue of 12/16 CRC patients. Overexpression of YAP in colon cancer cells led to increased cell viability, invasion, migration, and oxaliplatin resistance demonstrating that YAP plays a role in EMT. In addition, overexpression of YAP led to decreased expression of the large tumor suppressor kinase 1 (LATS1) and mammalian sterile 20-like kinases (MST1/2). Decreased LATS1 expression was associated with increased levels of cell proliferation. Knockdown of YAP by shRNA interference led to decreased cell invasion, migration, and drug resistance in colon cancer cells and reduced tumorigenesis in a mouse xenograft model. Finally, we established that YAP interacted with SDC2, and demonstrated that SDC2 mediated the YAP pathway through the EMT-related factors BMP4, CTGF and FOXM1.

Ketamine Inhalation Ameliorates Ovalbumin-Induced Murine Asthma by Suppressing the Epithelial-Mesenchymal Transition.

BACKGROUND Asthma accounts for 0.4% of all deaths worldwide, a figure that increases annually. Ketamine induces bronchial smooth muscle relaxation, and increasing evidence suggests that its anti-inflammatory properties might protect against lung injury and ameliorate asthma. However, there is a lack of evidence of the usefulness and mechanism of ketamine in acute asthma exacerbation. This study aimed to analyze the therapeutic effects and mechanism of action of ketamine on acute ovalbumin (OVA)-induced murine asthma. MATERIAL AND METHODS In vivo, BALB/c mice with OVA-induced asthma were treated with or without ketamine (25 or 50 mg/mL). Serum, lung sections, and mononuclear cell suspensions from the lung were collected for histological, morphometric, immunofluorescence, microRNA, quantitative polymerase chain reaction, regulatory T cell identification, cytokine, and Western blotting analyses. In vitro, bronchial epithelial cells were cultured to analyze the effect and mechanism of ketamine on epithelial-mesenchymal transition (EMT) and transforming growth factor-ß (TGF-ß) signaling. RESULTS The inhalation of ketamine 25 or 50 mg/mL markedly suppressed OVA-induced airway hyper-responsiveness and airway inflammation, significantly increased the percentage of CD4+CD25+ T cells, and significantly decreased OVA-induced up-regulation of TGF-ß1 and the EMT. MiR-106a was present at higher amounts in OVA-induced lung samples and was suppressed by ketamine treatment. The in vitro results showed that TGF-ß1-induced EMT was suppressed by ketamine via miR-106a level regulation. CONCLUSIONS Ketamine ameliorates lung fibrosis in OVA-induced asthmatic mice by suppressing EMT and regulating miR-106a level, while ketamine inhalation might be a new therapeutic approach to the treatment of allergic asthma.

Prevalence of antiseptic resistance genes increases in staphylococcal isolates from orthokeratology lens wearers over initial six-month period of use.

The purpose of this study was to investigate the prevalence of antiseptic-resistance (QAC) genes in staphylococci colonizing periorbital tissues and accessories of orthokeratology (ortho-k) lens wearers over a 6-month period and determine the effect of their presence on minimum inhibitory (MIC) and bactericidal concentrations (MBC) of disinfectants and log reduction of multipurpose contact lens solutions (MPS). Staphylococci were isolated from periorbital tissues and accessories of patients before commencing ortho-k therapy and at two subsequent visits. Presence of QAC genes in 116 S. aureus and 67 CNS isolates was determined by PCR and association with period of ortho-k use determined. MICs and MBCs of staphylococci gene-positive were compared with gene-negative strains and the effectiveness of four MPS for rigid contact lenses investigated. S. aureus carriage rates in the conjunctiva decreased significantly from 41.2 % (baseline) to 11.8 % (3-months), and 13.3 % (6-months) (p trend 0.03), while CNS increased from 58.8 %(baseline) to 94.1 % (3-months), and 93.3 % (6-months) (p trend 0.02). Prevalence of qacA/B increased considerably over time (S. aureus: 4.4 % to 15.4 %, CNS: 6.7 % to 25 %), but frequency of smr was relatively stable. Only five CNS isolates harboured qacH. MICs and MBCs of gene-positive isolates were significantly increased and three MPS did not achieve a 3-log reduction of many QAC-positive strains. Ortho-k lens wear contributed to changes of staphylococcal carriage rates in the conjunctival sac. Use of MPS containing quaternary ammonium compounds may select for the carriage of organisms harbouring QAC genes, as the low concentration of disinfecting agents is not adequate for killing gene-positive strains.

A very-low-protein diet ameliorates advanced diabetic nephropathy through autophagy induction by suppression of the mTORC1 pathway in Wistar fatty rats, an animal model of type 2 diabetes and obesity.

AIMS/HYPOTHESIS: The efficacy of a low-protein diet (LPD) on diabetic nephropathy is controversial. We aimed to investigate the renoprotective effects of an LPD and the underlying molecular mechanism in a rat model of type 2 diabetes and obesity. METHODS: Diabetic male Wistar fatty (fa/fa) rats (WFRs) were treated with a standard diet (23.84% protein) or an LPD (5.77% protein) for 20 weeks from 24 weeks of age. We investigated the effect of the LPD on renal function, fibrosis, tubular cell damage, inflammation, mitochondrial morphology of proximal tubular cells (PTCs), apoptosis, autophagy and activation of mammalian target of rapamycin complex 1 (mTORC1). RESULTS: Kidney weight, albuminuria, excretion of urinary liver-type fatty acid binding protein, levels of plasma cystatin C and changes in renal histology, including fibrosis, tubular cell damage and inflammation, were aggravated in WFRs compared with non-diabetic Wistar lean rats (WLRs). Fragmented and swelling mitochondria accumulated in PTCs and apoptosis were enhanced in the kidney of WFRs. Immunohistochemical staining of p62 and p-S6 ribosomal protein (p-S6RP) in the tubular lesions of WFRs was increased compared with WLRs. The LPD intervention clearly ameliorated damage as shown by the assessment of renal function and histology, particularly tubulointerstitial damage in diabetic kidneys. Additionally, the 5.77% LPD, but not the 11.46% LPD, significantly suppressed p-S6RP levels and increased microtubule-associated protein light chain 3-II levels in the renal cortex. The LPD intervention partially decreased HbA1c levels in WFRs, and no differences in mean BP were observed among any of the groups. CONCLUSIONS/INTERPRETATION: A very-low-protein diet improved advanced diabetic renal injuries, including tubulointerstitial damage, by restoring autophagy through the suppression of the mTORC1 pathway.

Cancer biology in diabetes.

Diabetes is a serious metabolic disease that causes multiple organ dysfunctions. Recent evidence suggests that diabetes could contribute to the initiation and progression of certain cancers in addition to the classic diabetic complications. Furthermore, some of the drugs used clinically to treat patients with diabetes might affect cancer initiation, progression and mortality. The recent discovery of the possible anticancer effects of metformin, a classic antidiabetic drug, has led physicians and scientists to reconsider the interaction between diabetes and cancer. In the present review, we analyze recent reports in this field, and explore possible mechanistic links between diabetes and cancer biology.

[Discovery of a new species of the pentastomid genus Porocephalus (Humboldt, 1811) from Taiwan, China and its pathogenic features].

OBJECTIVE: To describe the morphological characteristics of Porocephalus taiwana sp. nov., discuss its pathogenic features and the method of etiological diagnosis of the new disease. METHODS: Fecal sedimentation concentration was used to collect nymphs from the patient's watery stool for species identification. Clinical information was collected for determining the pathogenic features of the new infection. RESULTS: A new pathogenic pentastomid Porocephalus taiwana sp. nov. is discovered and a new disease, porocephaliasis taiwana, is nominated. With the findings from this case it is proposed that the traditional visceral pentastomiasis should be divided into two subtypes, Encystic and Excystic. According to the pathological features, this case belongs to the excystic visceral pentastomiasis. CONCLUSION: Porocephalus taiwana sp. nov. is a new pathogenic pentastomid infecting humans. Porocephaliais taiwana belongs to a novel type (excystic) of visceral pentastomiasis.