MicroRNAs in tumorigenesis, metastasis, diagnosis and prognosis of gastric cancer.

MicroRNAs (miRNAs), which are small single-stranded RNA molecules composed of 18-23 nucleotides, act as oncogenes or tumor suppressor genes playing important roles in tumor formation, infiltration and metastasis. Subsequently, miRNAs expression contributes to cancer diagnosis and prognosis. Gastric cancer currently has high morbidity and mortality among all malignant tumors, yet it lacks early specific diagnostic markers and effective treatments. In gastric cancer, many studies have detected abnormal expression forms of miRNAs and confirmed their involvement in its tumorigenesis, progression, invasion and metastasis. They may become valuable diagnostic markers and therapeutic targets for gastric cancer. Studying the role of miRNAs in gastric cancer and its relationship with diagnostic and prognostic parameters might help to improve the sensitivity of diagnosis as well as the efficacy of gastric cancer treatment. This review aims to highlight the advancements which might provide new methods for early clinical diagnosis and effective therapeutic options, along with predict response to treatment for gastric cancer.

Effects of short-term sitagliptin treatment on immune parameters in healthy individuals, a randomized placebo-controlled study.

Sitagliptin, a dipeptidyl-peptidase 4 (DPP-4) inhibitor, improves blood glucose control in patients with type 2 diabetes by blocking cleavage of glucagon-like peptide 1 (GLP-1). In type 2 diabetes patients sitagliptin use is associated with an increase in minor infections, and in new-onset type 1 diabetes patients the ability of sitagliptin to dampen autoimmunity is currently being tested. DPP-4, also known as CD26, is expressed on leucocytes and can inactivate many chemokines important for leucocyte migration, as well as act as a co-stimulatory molecule on T cells. Therefore, this study was conducted to test whether sitagliptin is immunomodulatory. In this randomized, placebo-controlled trial, healthy volunteers were given sitagliptin or placebo daily for 28 days, and blood was drawn for immune assays. No significant differences were observed in the percentage of leucocyte subsets within peripheral blood mononuclear cells (PBMCs), plasma chemokine/cytokine levels or cytokines released by stimulation of PBMCs with either lipopolysaccharide (LPS) or anti-CD3. Individuals taking sitagliptin displayed increases in the percentage of cells expressing higher levels of CD26 at early time-points compared to placebo controls, but these differences resolved by day 28 of treatment. Therefore, in healthy volunteers, treatment with sitagliptin daily for 28 days does not overtly alter systemic immune function.

Opioid-associated central sleep apnea: a case series.

INTRODUCTION: Subjects on methadone maintenance for drug addiction have been reported to have central sleep apnea (CSA). However, there are few reports of disordered breathing in patients receiving opioids for chronic pain. MATERIALS AND METHODS: We report on six patients (ages 41-68, two females, body mass index 27-34, morphine equivalent doses 120-420 mg/day, Epworth Scales 7-21) referred to our sleep center receiving sustained release opioids for more than 6 months with excessive daytime sleepiness. CSA was defined as apnea-hypopnea index (AHI) more than 5 per hour with > or =50% central events. Bilevel (BLV) titration was done to determine settings and all patients were followed for at least 6 months on nocturnal BLV. AHI ranged 28.4-106 per hour. Time less than 90% O(2) saturation ranged 1.8 min to 6.4 h. Four of the patients were treated with chronic BLV ventilation with settings ranging 12-16 cm H(2)O (inspiratory positive airway pressure)/4-8 cm H(2)O (expiratory positive airway pressure) with backup rate of 12-16. Among the four patients who used BLV treatment for at least 6 months, Epworth scores improved (by 4, 12, 5, and 9, respectively). CONCLUSION: Treatment of opioid-associated CSA with BLV corrected nocturnal hypoxemia and reduced sleep fragmentation. Randomized controlled trials, with objective measures of daytime function, are recommended in opioid-induced CSA patients.

Sepsis-induced alteration in T-cell Ca(2+) signaling in neonatal rats.

Sepsis-induced suppression in T-cell proliferation follows deranged Ca(2+) signaling in adult rats. In preliminary studies, we observed suppression in T-cell proliferation in septic neonatal rats as well. In this study, we assessed splenic T-cell cytosolic Ca(2+) concentration, [Ca(2+)](i), as its elevation plays an important role in T-cell proliferation. Also, we investigated the role of PGE(2) in sepsis-related changes in T-cell [Ca(2+)](i) in animals pretreated with cyclooxygenase-1 (COX-1) inhibitor (resveratrol) and cyclooxygenase-2 (COX-2) inhibitor (NS-398). Sepsis was induced in 15-day-old rat pups by intraperitoneal implantation of fecal pellets containing Escherichia coli and Bacteroides fragilis. The sham group consisted of pups implanted with sterile fecal pellets. Septic and sham pups were sacrificed 24 h after implantation and their spleens were removed. The spleens from sham and septic pups, along with spleens from unoperated control pups, were processed for single cell suspensions, and T cells were isolated using nylon wool columns. Fura-2 fluorophotometry was employed for the measurement of [Ca(2+)](i) (in nM units) in T cells stimulated with concanavalin A (ConA). Our results show that ConA-mediated T-cell [Ca(2+)](i) response is significantly suppressed in septic neonatal rats. Pretreatment of pups with COX-2, but not COX-1 inhibitor, prevented the decrease in the [Ca(2+)](i) response. These findings suggest that PGE(2) might induce the attenuation in T-cell Ca(2+) signaling during sepsis in neonatal rats.

The effect of chiropractic care on jet lag of Finnish junior elite athletes.

OBJECTIVE: To determine the effect of chiropractic care on jet lag in Finnish junior elite athletes. SUBJECTS: Fifteen Finnish junior elite athletes. METHODS: Through use of a table of random numbers, each athlete was assigned by sex to one of 3 groups: chiropractic adjustment, sham adjustment, or control. As needed, the chiropractic adjustment group athletes (n = 5) were adjusted on a daily basis by licensed chiropractors using a toggle/recoil procedure. The sham adjustment group athletes (n = 5) received sham adjustments on a daily basis by licensed chiropractors. The control group athletes (n = 5) were not adjusted or sham-adjusted but participated in all test protocols. Sleep, jet lag, chiropractic, and mood data (the last acquired through use of the Profile of Mood States) were collected on a daily basis for 18 consecutive days. RESULTS: Repeated-measures analyses of variance (3 x 2) of total mood disturbance scores and heart rate variables indicated that there were no significant (.05 level) between-group differences. Sleep data were analyzed through use of a 3 x 2, repeated-measures multivariate analysis of variance. Pillai's trace indicated that there were no between-group differences. Self-assessment of jet lag by participants after traveling to Georgia and after returning to Finland showed no between-group differences. CONCLUSIONS: It was concluded that chiropractic care did not reduce the effects of jet lag.

Hepatocyte growth factor stimulates phosphoinositide hydrolysis and mitogenesis in cultured renal epithelial cells.

Hepatocyte growth factor (HGF), a novel heparin-binding peptide growth factor of MW 97-kDa, is a potent mitogen for parenchymal hepatocytes. HGF is present in normal serum and increases following liver injury or partial hepatectomy. In addition to liver, HGF mRNA has been detected in kidney. In cultured rabbit proximal tubule cells, recombinant human HGF (10(-10) M) increased DNA synthesis, measured as [3H] thymidine incorporation, from 1345 +/- 213 to 2931 +/- 636 cpm/10(6) cells; n = 9; p < 0.005). HGF was found to exert mitogenic effects at lower concentrations than epidermal growth factor (EGF), with half maximal effects seen at 6 x 10(-11) M compared to 7 x 10(-10) M for EGF. HGF was additive with EGF in stimulating [3H] thymidine incorporation. In addition to rabbit proximal tubule cells, HGF increased proliferation in a cultured mouse proximal tubule cell line, MCT, and in rat glomerular epithelial cells. In contrast, HGF did not stimulate proliferation of either rat mesangial cells or a rat aortic smooth muscle cell line, A7r5. The HGF receptor is the product of the c-met proto-oncogene. C-met mRNA was detected in total kidney and in cultured proximal tubule cells but was not detected in cultured mesangial cells. In contrast, HGF mRNA was detected in mesangial cells but not in cultured proximal tubule cells. Preincubation of rabbit proximal tubule cells with the tyrosine kinase inhibitor, genistein (50 microM), prevented HGF-stimulation of [3H] thymidine incorporation. In LiCl pretreated rabbit proximal tubule cells loaded with [3H] myoinositol, HGF increased total inositol phosphate release, measured by anion exchange chromatography (control: 2181 +/- 414 vs HGF: 2609 +/- 478 cpm/10(6) cells; n = 6; p < 0.05). Although genistein did not affect baseline phosphoinositide hydrolysis, it inhibited the HGF stimulation. Thus, HGF is mitogenic for cultured proximal tubule cells as well as glomerular epithelial cells. Inhibition of proliferation and PI turnover by genistein suggests that HGF's actions are mediated in part by tyrosine kinase activity. In mammalian kidney, HGF released from mesangial cells may serve as a paracrine activator of the adjacent epithelial cells.

Pathological sequelae of "neglected" impacted third molars.

An NIH conference on "Removal of Third Molars" debated the need for removal of asymptomatic impacted teeth with no evidence of pathology but stressed the need for long-range studies. The assumption is that "neglected" impacted third molars (ITMs) will sometime cause serious pathology. Examination of panoramic radiographs of 11,598 patients revealed 1,756 patients with 3,702 impacted teeth; average age 47 years, and an average retention period approximately 27 years. Dentigerous cystic changes occurred in about 30 ITMs (0.81%), internal resorption in 16 (0.43%), periodontal ligament damage and bone loss distal to the 2nd molar 166 times (4.48%), and pressure resorption of the 2nd molar 113 times (3.05%). No great surge in pathology occurred with increasing age. Some type of pathological change can be expected eventually in approximately 12.0% of an impacted 3rd molar population and 1.82% of the general population. A reappraisal of routine removal of ITMs might be indicated.

A survey of panoramic radiographs for evaluation of normal and pathologic findings.

Six thousand seven hundred eighty panoramic radiographs were screened to monitor the incidence of normal and pathologic findings. Three different types of panoramic radiograph were used in this study: Panorex, Orthopantomograph, and Panelipse. Visualization of four different anatomic landmarks was used for a statistical comparison of the diagnostic value of the three films: the temporomandibular joint compartments, the external oblique ridge, the mental foramen, and the mandibular canal. The orthopantomograph was judged to be slightly more reliable in producing radiographs for the visualization of the selected anatomic structures. The most common form of pathosis detected was impacted teeth, seen in 22.3 percent followed by retained roots, which appeared in 12.6 percent of the films. Comparing these survey data with three other major studies suggests that confining the previous radiographic examinations to certain selected groups of people may have distorted the incidence of some pathologic conditions in the population. The panoramic radiograph is still considered a supplement to, not a substitute for, the intraoral radiograph.