We investigated the mechanisms underlying the increase in mononuclear leukocyte (MNL) beta 2-adrenergic receptor (AR) number and responsiveness after acute infusion of catecholamines. Infusion of isoproterenol and epinephrine, but not of norepinephrine, acutely increased MNL beta-AR density, and this was blocked by the beta 2-selective antagonist ICI 118,551 but not by the beta 1-selective antagonist bisoprolol, suggesting a beta 2-AR-mediated effect. Infusion of isoproterenol but not of norepinephrine also induced a lymphocytosis, with an increase in the number of circulating suppressor/cytolytic T (Ts/c)- and natural killer (NK)-cells but a decrease in helper T (Th)-cells, leading to a decreased Th-Ts/c-cell ratio. beta-AR density was higher in Ts/c-cells than in Th-cells. After isoproterenol infusion, beta-AR density was elevated in all lymphocyte subsets but not in monocytes or platelets, suggesting a lymphocyte-specific phenomenon. Infusion of isoproterenol in splenectomized patients did not alter lymphocyte subset composition and only slightly increased beta 2-AR density. In healthy subjects lymphocyte proliferation in response to various mitogens was attenuated after infusion of isoproterenol but not of norepinephrine; this effect was abolished in splenectomized patients. We conclude that the elevated MNL beta-AR density after acute exposure to beta-adrenergic agonists is caused by a release of lymphocyte subsets from the spleen into the circulation and/or by an exchange of lymphocyte subsets between the spleen and the circulation, whereby freshly released splenic lymphocytes appear to carry more beta-AR than those found in the circulation. This appears to impair immune responsiveness in a dual manner, by decreasing the Th-/Ts/c-cell ratio and by rendering lymphocytes more sensitive to the antiproliferative effects of catecholamines via a higher beta-AR density.

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Background: Investigating and evaluating possible alternative therapeutic strategies to control hepatocellular carcinoma (HCC) is a critical need because of its high prevalence and being one of the most lethal cancers. Curcumin and taurine showed potent anti-tumor activities in pre-clinical and clinical studies by targeting multiple pathways. Thus, this study was designed to assess the effect of a combined treatment consisted of curcumin, piperine, and taurine on circulating levels of interleukin-10 (IL-10), and microRNAs miR-141 and miR-21. Methods: Twenty eligible HCC patients administrated an oral dose of 4 g curcumin, 40 mg piperine, and 500 mg taurine daily for three successive treatment cycles, each was a 30-day. The level of IL-10 along with the expression levels of miR-141, and miR-21 were monitored in serum before starting the treatment and after each cycle. Patients were followed-up for a period of 24 months. Results: The combined treatment was able to produce a significant decrease in the levels of serum IL-10, and miR-21 while it resulted in a non-significant up-regulation of serum miR-141 expression level. At the end of the follow-up period, the median overall survival (OS) rate was found to be 17.00 months with a worse OS in patients with high baseline levels of circulating IL-10 and miR-21 compared to those with low levels. In contrast, a low baseline level of circulating miR-141 was associated with poor prognosis. Conclusions: The combined treatment may be able to increase the OS rate by altering the circulating level of IL-10 and miR-21.

Objective To assess telomerase activity (involved in cell immortalization and detectable in most malignant tumours but not in normal somatic tissues) as a marker in cancer diagnosis. Patients and methods Tissue telomerase activity was assayed by two different techniques, the telomeric repeat amplification protocol‐polymerase chain reaction (TRAP‐PCR) and a telomerase PCR‐enzyme linked immunosorbent assay. Malignant and inflammatory bladder lesions and their adjacent normal tissues were assessed for telomerase activity in a group of 18 patients, 14 of whom had urothelial carcinoma and four a nonspecific inflammatory lesion of the bladder. Results Eleven of the 14 tumour samples analysed were telomerase‐positive and two of the three telomerase‐negative tumour samples had a detectable ‘telomerase inhibitor’. In the apparently normal tissues next to bladder tumours, four of the 14 specimens were telomerase‐positive. Interestingly, these lesions were always next to high‐grade muscle‐invasive bladder tumours (pT2G3). Two of the four nonspecific inflammatory lesions (one of cystitis glandularis and one of severe dysplasia), known to be preneoplastic lesions, were also telomerase‐positive. Conclusion These results strongly suggest that the reactivation of telomerase may be an early event in bladder carcinogenesis, preceding morphological changes related to malignant transformation. Telomerase activity may therefore be useful both as an indicator of malignant potential in preneoplastic lesions, e.g. cystitis glandularis and severe dysplasia, and as a prognostic marker of bladder tumour relapse or progression.

Despite their clinical benefits in cancer treatment, the deleterious effects on heart following chemo/radiotherapy are of increasing importance. Zingerone, a natural polyphenol, possesses multiple biological activities, such as antioxidant and anti-inflammatory. Thus, the current study was designed to assess the potential cardioprotective effects of zingerone against cisplatin or γ-radiation. Zingerone was given by intragastric intubation (25 mg/kg) daily for three successive weeks prior to the induction of cardiotoxicity using a single dose of cisplatin (20 mg/kg, i.p.) or a whole body γ-irradiation at a single dose of 6 Gy. Zingerone pre-treatment significantly reduced the abnormalities in heart histology and the increase in the cardiotoxicity indices, serum lactate dehydrogenase, and creatine kinase-MB activities, as well as plasma cardiac troponin T and B-natriuretic peptide, induced by cisplatin or γ-radiation. Further, zingerone, except for superoxide dismutase, notably ameliorated the state of oxidative stress as evidenced by a significant decrease in malondialdehyde level accompanied with a significant increase in the reduced glutathione content and catalase activity. Additionally, zingerone mitigated the increase in the inflammatory markers including serum level of tumor necrosis factor-alpha, cardiac myeloperoxidase activity, and cyclooxygenase-2 protein expression. Moreover, zingerone alleviated the elevation of caspase-3 gene expression and the prominent nuclear DNA fragmentation and attenuated the decrease in mitochondrial complexes' activities. This study sheds the light on a probable protective role of zingerone as an antioxidant, anti-inflammatory, and antiapoptotic agent against cisplatin- or γ-radiation-induced cardiotoxicity and holds a potential in regard to therapeutic intervention for chemo/radiotherapy mediated cardiac damage.

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BackgroundAlkali-burned corneas can seldom heal properly to restore corneal transparency. Treatment of this severe disorder of the ocular surface remains a challenge.Aim of the Workwas to investigate whether systemically transplanted bone marrow mesenchymal stem cells (BM-MSCs) can promote corneal wound healing after alkali burn.Material and MethodsThirty five male New Zealand rabbits were used in this study. The animals were divided into three groups. Group I; the control group was sham operated. Group II; corneal alkali burn was created. Group III; underwent corneal alkali burn then treated with BM-MSCs. All corneas were collected after fourteen and twenty eight days. Evaluation using H&E, PAS & alkaline phosphatase reaction was carried out. Immune histo-chemical staining for CD44 and vimentin was performed as well.Resultsthe corneal epithelium of (Group II) showed marked alterations. Vascularization, cellular infiltration and irregularity of the collagen fibers were also seen in the substantia propria. Increase in the thickness of the Descemet’s membrane was noticed as well. On the other hand, at the time of 28 days, Group III rabbits showed best histological results with nearly healed corneas compared to other groups. Meanwhile, vimentin was more strongly expressed in Group III assessing the differentiating ability of BM-MSCs.ConclusionBM-MSCs could effectively promote corneal alkali burn healing.

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