There is highly credible evidence that melatonin mitigates cancer at the initiation, progression and metastasis phases. In many cases, the molecular mechanisms underpinning these inhibitory actions have been proposed. What is rather perplexing, however, is the large number of processes by which melatonin reportedly restrains cancer development and growth. These diverse actions suggest that what is being observed are merely epiphenomena of an underlying more fundamental action of melatonin that remains to be disclosed. Some of the arresting actions of melatonin on cancer are clearly membrane receptor-mediated while others are membrane receptor-independent and involve direct intracellular actions of this ubiquitously-distributed molecule. While the emphasis of melatonin/cancer research has been on the role of the indoleamine in restraining breast cancer, this is changing quickly with many cancer types having been shown to be susceptible to inhibition by melatonin. There are several facets of this research which could have immediate applications at the clinical level. Many studies have shown that melatonin’s co-administration improves the sensitivity of cancers to inhibition by conventional drugs. Even more important are the findings that melatonin renders cancers previously totally resistant to treatment sensitive to these same therapies. Melatonin also inhibits molecular processes associated with metastasis by limiting the entrance of cancer cells into the vascular system and preventing them from establishing secondary growths at distant sites. This is of particular importance since cancer metastasis often significantly contributes to death of the patient. Another area that deserves additional consideration is related to the capacity of melatonin in reducing the toxic consequences of anti-cancer drugs while increasing their efficacy. Although this information has been available for more than a decade, it has not been adequately exploited at the clinical level. Even if the only beneficial actions of melatonin in cancer patients are its ability to attenuate acute and long-term drug toxicity, melatonin should be used to improve the physical wellbeing of the patients. The experimental findings, however, suggest that the advantages of using melatonin as a co-treatment with conventional cancer therapies would far exceed improvements in the wellbeing of the patients.
Melatonin has been speculated to be mainly synthesized by mitochondria. This speculation is supported by the recent discovery that aralkylamine N-acetyltransferase/serotonin N-acetyltransferase (AANAT/SNAT) is localized in mitochondria of oocytes and the isolated mitochondria generate melatonin. We have also speculated that melatonin is a mitochondria-targeted antioxidant. It accumulates in mitochondria with high concentration against a concentration gradient. This is probably achieved by an active transportation via mitochondrial melatonin transporter(s). Melatonin protects mitochondria by scavenging reactive oxygen species (ROS), inhibiting the mitochondrial permeability transition pore (MPTP), and activating uncoupling proteins (UCPs). Thus, melatonin maintains the optimal mitochondrial membrane potential and preserves mitochondrial functions. In addition, mitochondrial biogenesis and dynamics is also regulated by melatonin. In most cases, melatonin reduces mitochondrial fission and elevates their fusion. Mitochondrial dynamics exhibit an oscillatory pattern which matches the melatonin circadian secretory rhythm in pinealeocytes and probably in other cells. Recently, melatonin has been found to promote mitophagy and improve homeostasis of mitochondria.
SummaryBackground. Oxidative stress and low antioxidant status are implicated in the pathogenesis of inflammatory and autoimmune diseases. Pemphigus vulgaris (PV) is an extremely severe autoimmune bullous dermatosis characterized by intraepithelial bullae on the skin and mucosa, and its antioxidant status is not fully understood. Aim. To assess correlations between PV and serum antioxidant levels of bilirubin, uric acid (UA) and albumin. Methods. We enrolled 116 patients newly diagnosed with PV who were admitted to the First Affiliated Hospital of Guangxi Medical University (Guangxi, China), and 108 healthy controls (HCs). Clinical characteristics and laboratory parameters of patients were retrospectively analysed. Results. Our survey shows that compared with the HC groups, serum levels of bilirubin [total bilirubin (Tbil), direct bilirubin (Dbil) and indirect bilirubin (Ibil)], UA and albumin were significantly lower in patients with PV, regardless of sex. In all groups, serum Tbil, Dbil, Ibil, UA and albumin levels were lower for women than for men. Severity of pemphigus was slightly negatively associated with Tbil, Dbil and Ibil, but was not associated with UA or albumin. Moreover, when the data were adjusted for the covariances of age and sex separately, Tbil, Dbil, Ibil, UA and albumin were all relevant to PV.Conclusions. Our findings demonstrate that serum levels of bilirubin (Tbil, Dbil and Ibil), UA and albumin are reduced in patients with PV supporting the hypothesis that oxidative stress and antioxidant status are important in the pathogenic mechanism of PV.
This study aimed to evaluate the clinical significance of pretreatment red cell distribution width (RDW), monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR) in patients with urothelial carcinoma of the bladder (UCB).Hematological parameters of 127 consecutive patients with UCB and 162 healthy controls were retrospectively analyzed. Receiver operating characteristic curve was plotted to determine the optimal cut-off value of RDW, MLR, NLR, and PLR to predict UCB. Whether these parameters could be independent predictors of UCB and had an association with the demographics and clinical characteristics of patients were also assessed.Patients with UCB had higher pretreatment RDW, MLR, NLR, and PLR compared with the healthy controls. With the tumor progression, MLR, NLR, and PLR rose consistently, whereas no significant difference was observed in RDW across tumor stages. NLR and PLR were associated with tumor size and tumor grade, while MLR was correlated with tumor size only. The best threshold of RDW, MLR, NLR, and PLR to predict UCB was 13.50%, 0.26, 2.16, and 128.46, respectively. Multivariate logistic regression model identified NLR ≥ 2.16 (odds ratio [OR] = 2.914; P < .001) and PLR ≥ 128.46 (OR = 2.761; P < .001) as independent predictors of UCB. High NLR and PLR were also associated with tumor markers, such as carcinoembryonic antigen and α-fetoprotein.Pretreatment NLR and PLR could be significant independent predictors of UCB. These simple and readily available inflammatory markers therefore might be used to manage the disease.
Raised triglycerides (TG) and reduced high density lipoprotein cholesterol (HDL‐c) are components of metabolic syndrome. Both high TG and metabolic syndrome have been reported to be risk factors of endometrial cancer. Therefore, triglycerides‐to‐high density lipoprotein cholesterol ratio (TG/HDL‐c ratio) may be a useful biological indicator in managing endometrial cancer. We aimed to explore the association between pretreatment TG/HDL‐c ratio and endometrial cancer in postmenopausal women, and to evaluate its potential role in the disease. Pretreatment serum lipid profile and TG/HDL‐c ratio were retrospectively analyzed for 167 postmenopausal women with endometrial cancer and 464 matched noncancer controls. Compared with controls, pretreatment TG/HDL‐c ratio in endometrial cancer patients significantly elevated regardless of whether patients had diabetes or overweight/obesity (P < 0.05). Further analyses showed that pretreatment TG/HDL‐c ratio increased significantly with advanced tumor stage. Interestingly, TG/HDL‐c ratio of type I endometrial cancer patients was higher than those with type II endometrial cancer. A positive association was found between pretreatment TG/HDL‐c ratio and tumor stage (adjusted r = 0.176, P = 0.027) in endometrial cancer group. Receiver operating characteristic curve analysis yielded the cut‐off value of 1.52 for TG/HDL‐c ratio to discriminate patients with cancer from controls (area under the curve, 0.689; sensitivity, 51.5%; specificity, 84.1%). Multivariate logistic regression model identified TG/HDL‐c ratio ≥ 1.52 (odds ratio = 4.123; P < 0.001) as an independent predictor of endometrial cancer. TG/HDL‐c ratio was positively associated with endometrial cancer clinical features, such as tumor stage and pathogenetic type. Accordingly, pretreatment TG/HDL‐c ratio might be a potential marker for endometrial cancer.
Background Henoch-Schonlein purpura is a systemic small-vessel vasculitis that occurs mainly in children. A review of the literature has suggested a correlation between mean platelet volume and several inflammatory disorders. However, to the best of our knowledge, any potential correlation between mean platelet volume and Henoch-Schonlein purpura has not been reported in the literature. Therefore, our study aimed to evaluate the role of mean platelet volume concentrations in patients with Henoch-Schonlein purpura. Methods This study included 97 children with Henoch-Schonlein purpura and 120 healthy individuals as controls. Results Mean platelet volume concentrations were found to be significantly lower in Henoch-Schonlein purpura patients compared with healthy controls (8.1 ± 0.86 vs. 9.4 ± 0.81, P < 0.001). Similarly, significant negative correlations were observed between mean platelet volume and neutrophil count, platelet count and erythrocyte sedimentation rate in patients with Henoch-Schonlein purpura (r=-0.327, P = 0.001; r=-0.419, P < 0.001; r=-0.255, P = 0.012). Interestingly, mean platelet volume was significantly lower in the acute phase compared with the convalescent phase of Henoch-Schonlein purpura patients (7.8 ± 0.86 vs. 8.3 ± 0.77, P = 0.002). A cut-off value for mean platelet volume was 7.85 with area under the curve of 0.726 to identify acute phase vs. convalescent phase in patients with Henoch-Schonlein purpura. Mean platelet volume was independently associated with Henoch-Schonlein purpura in logistic regression analysis (odds ratio = 0.114, 95% confidence interval = 0.053-0.243, P < 0.001). Conclusions Our results suggest that mean platelet volume is inversely associated with disease in patients with Henoch-Schonlein purpura, and mean platelet volume may be a useful marker to identify active disease in Henoch-Schonlein purpura patients.
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