Albumin-to-alkaline phosphatase ratio as a promising indicator of prognosis in human cancers: is it possible?

BACKGROUND: The impact of albumin-to-alkaline phosphatase ratio (AAPR) on prognosis in cancer patients remains uncertain, despite having multiple relevant studies in publication. METHODS: We systemically compiled literatures from 3 databases (Cochrane Library, PubMed, and Web of Science) updated to May 24th, 2020. Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed and synthesized using STATA 14, values were then pooled and utilized in order to assess the overall impact of AAPR on patient's prognosis. RESULTS: In total, 18 studies involving 25 cohorts with 7019 cases were incorporated. Pooled results originated from both univariate and multivariate analyses (HR = 2.14, 95%CI:1.83-2.51, random-effects model; HR = 1.93, 95%CI:1.75-2.12, fixed-effects model; respectively) suggested that decreased AAPR had adverse effect on overall survival (OS). Similarly, pooled results from both univariate and multivariate analysis of fixed-effects model, evinced that decreased AAPR also had adverse effect on disease-free survival (DFS) (HR = 1.81, 95%CI:1.60-2.04, I2 = 29.5%, P = 0.174; HR = 1.69, 95%CI:1.45-1.97, I2 = 13.0%, P = 0.330; respectively), progression-free survival (PFS) (HR = 1.71, 95%CI:1.31-2.22, I2 = 0.0%, P = 0.754; HR = 1.90, 95%CI:1.16-3.12, I2 = 0.0%, P = 0.339; respectively), and cancer-specific survival (CSS) (HR = 2.22, 95%CI:1.67-2.95, I2 = 5.6%, P = 0.347; HR = 1.88, 95%CI:1.38-2.57, I2 = 26.4%, P = 0.244; respectively). Admittedly, heterogeneity and publication bias existed, but stratification of univariate meta-analytic results, as well as adjusted meta-analytic results via trim and fill method, all showed that AAPR still significantly correlated with poor OS despite of confounding factors. CONCLUSIONS: In summary, decreased AAPR had adverse effect on prognosis in cancer patients. As an inexpensive and convenient ratio derived from liver function test, AAPR might become a promising indicator of prognosis in human cancers.

Inhibition of Peripheral Nerve Scarring by Calcium Antagonists, Also Known as Calcium Channel Blockers.

The aim of this research was to investigate the impact of calcium channel blockers (verapamil) on the formation of scars in the sciatic nerve anastomosis after peripheral nerve injury. One hundred twenty healthy, male Sprague-Dawley rats were selected and prepared with right sciatic nerve injury for this study. Samples were selected at the fourth and 12th weeks, respectively, after treatment and observations were made on the nerve anastomosis healing and diameter. Image analysis and statistical processing were carried out relating to the results of the study. The diameter of the anastomosis of the treatment group at weeks 4 and 12 was noticeably smaller than the control group (P < 0.05). In the treatment group at week 4, there were many vesicles observed in the fibroblasts' cytosol and in the control group, the fibroblasts exhibited high number of rough endoplasmic reticulum. The collagen content of the nerve scarring at week 12 in the treatment group was apparently less than the control group (P < 0.01). The calcium channel blocker (verapamil) reduced the axon resistance through the anastomosis during nerve regeneration. It can effectively inhibit the formation of scarring from nerve injury. It also provided an excellent microenvironment for the regeneration of nerve fibers.

Poly[[[µ-1,1'-(butane-1,4-di-yl)diimidazole-κN:N](µ-cyclo-hexane-1,4-dicarboxyl-ato-κO,O:O,O)nickel(II)] 0.25-hydrate].

In the title coordination polymer, {[Ni(C(8)H(10)O(4))(C(10)H(14)N(4))]·0.25H(2)O}(n), the coordination of the Ni(II) ion is distorted octa-hedral. The 1,1'-(butane-1,4-di-yl)diimidazole ligand and the cyclo-hexane-1,4-dicarboxyl-ate dianion bridge metal centres, forming a two-dimensional (4,4) network. The network is consolidated by O-H⋯O hydrogen bonds between the statistically occupied water molecules and O atoms of the two carboxylate groups.

Cardioprotection and improvement in endothelial-dependent vasodilation during late-phase of whole body hypoxic preconditioning in spontaneously hypertensive rats via VEGF and endothelin-1.

The present study was designed to investigate the effect of late phase of whole body hypoxic preconditioning on endothelial-dependent vasorelaxation and cardioprotection from ischemia-reperfusion injury in spontaneously hypertensive rats (SHR). Hypoxic preconditioning was performed by subjecting rats to four episodes of alternate exposure to low O2 (8%) and normal air O2 of 10 min each. After 24 h, the mesenteric arteries and hearts were isolated to determine the vascular function and cardioprotection from ischemia-reperfusion (I/R) injury on the Langendorff apparatus. There was a significant impairment in acetylcholine-induced relaxation in norepinephrine precontracted arteries (endothelium-dependent function) and increase in I/R-induced myocardial injury in SHR in comparison to Wistar Kyoto rats (WKY). However, hypoxic preconditioning significantly restored endothelium-dependent relaxation in SHR and attenuated I/R injury in both SHR and WKY. Hypoxic preconditioning also led to an increase in the levels of endothelin-1 (not endothelin-2 or -3), vascular endothelial growth factor-A (VEGF-A) and HIF-1α levels. Pretreatment with bevacizumab (anti-VEGF-A) and bosentan (endothelin receptor blocker) significantly attenuated hypoxic preconditioning-induced restoration of endothelium-dependent relaxation and cardioprotection from I/R injury. These interventions also attenuated the levels of VEGF-A and HIF-1α without modulating the endothelin-1 levels. It may be concluded that an increase in the endothelin-1 levels with a subsequent increase in HIF-1α and VEGF expression may possibly contribute in improving endothelium-dependent vasorelaxation and protecting hearts from I/R injury in SHR during late phase of whole body hypoxic preconditioning.

Inhibition of collagen synthesis by IWR-1 in normal and keloid-derived skin fibroblasts.

AIMS: Keloid is a benign tumor that is characterized by the hyperproliferation of dermal fibroblasts and excessive deposition of extracellular matrix (ECM) especially the collagen. Aberrant activation of Wnt/ß-catenin signaling is implicated in the pathogenesis of keloid. In this study, we investigated the effects of IWR-1, a small molecule inhibitor for Wnt/ß-catenin signaling via the inhibition of tankyrase, on production of collagen and matrix metalloproteinase (MMP) in dermal fibroblasts. MAIN METHODS: We cultured human normal skin- and keloid-derived fibroblasts, then treated with IWR-1. The effects of IWR-1 on collagen and MMP production were determined by Western blot, ELISA and zymography. KEY FINDINGS: IWR-1 significantly suppressed the proliferation and migration of both the normal and keloid fibroblasts. IWR-1 also inhibited the production and secretion of type I collagen from the fibroblasts. In addition, IWR-1 significantly increased the expression of MMPs, such as MMP-1, MMP-3 and MMP-13, along with the increase of gelatinase activity. These results suggest that inhibitory effect of IWR-1 on collagen production may be related with the increased MMP activity. SIGNIFICANCE: This study provides the possible action mechanism of IWR-1 on regulation of collagen expression, on which to base further investigation for preventing skin fibrotic diseases such as keloid.

Rosmarinic acid inhibits poly(I:C)-induced inflammatory reaction of epidermal keratinocytes.

AIMS: Keratinocytes are the predominant cells in the epidermis, exerting their primary role of physical barrier through sophisticated differentiation process. In addition, keratinocytes contribute to the activation of innate immunity, providing the surveillant role against external pathogens. It has been known that chronic skin inflammatory disease such as psoriasis can be provoked by viral pathogens including double-stranded RNA. In this study, we demonstrated that rosmarinic acid (RA) has an inhibitory potential on inflammatory reaction induced by double-stranded RNA mimic poly(I:C) in epidermal keratinocytes. MAIN METHODS: We cultured human epidermal keratinocytes and induced inflammatory reaction by poly(I:C) treatment. The effect of RA on inflammatory reaction of keratinocytes was determined by RT-PCR and Western blot. KEY FINDINGS: RA significantly inhibited poly(I:C)-induced expression of inflammatory cytokines including IL-1ß, IL-6, IL-8, CCL20, and TNF-α, and downregulated NF-κB signaling pathway in human keratinocytes. In addition, RA significantly inhibited poly(I:C)-induced inflammasome activation, in terms of secretion of active form of IL-1ß and caspase-1. Furthermore, RA markedly inhibited poly(I:C)-induced NLRP3 and ASC expression. SIGNIFICANCE: These results indicate that RA can inhibit poly(I:C)-induced inflammatory reaction of keratinocytes, and suggest that it may be a potential candidate for the treatment of psoriasis.

Glycyrrhizin improves p75NTR-associated sciatic nerve regeneration in a BALB/c mouse model.

Glycyrrhizin has a role in immune regulation in the central nervous system, but its impact on sciatic nerve injury had not previously been reported. In this study, a BALB/c mouse model of sciatic nerve injury was used to explore the role of glycyrrhizin in sciatic nerve repair and its underlying mechanism. Glycyrrhizin with intragastric gavage of 10 and 20 mg/kg weight per day (mid- and high-dose, respectively) inhibited p75 neurotrophin receptor (p75NTR) expression at the protein and mRNA levels versus the 5 mg/kg (low-dose) group and control (0.9% NaCl solution) at one, two, four and eight weeks following sciatic nerve injury, and simultaneously improved the action potential amplitude and motor nerve conductive velocity. Combined Marsland, Glees and Erikson's silver stain and Luxol fast blue staining results indicated that high- and mid-dose glycyrrhizin promoted improved sciatic nerve myelination compared with the low-dose or control groups eight weeks after injury. Immunofluorescence staining demonstrated that glycyrrhizin had an inhibitory effect to a certain degree on local hypertrophic scar and inflammatory responses in the mouse model. In conclusion, glycyrrhizin can promote sciatic nerve regeneration and functional repair, in which doses of 10 and 20 mg/kg per day are more effective than lower doses, and such regeneration is associated with the downregulation of p75NTR.