IL-6 mediated JAK/STAT3 signaling pathway in cancer patients with cachexia.

OBJECTIVES: We investigated the changes in the IL-6 and STAT3 expression levels in cachectic and non-cachectic patients with gastric, lung and breast cancer and evaluated the association between IL-6 and STAT3 levels and cancer types in terms of cachexia condition. BACKGROUND: Cancer-associated cachexia, observed in nearly 50‒80 % of cancer patients, has drawn attention in advanced patients. IL-6/JAK/STAT pathway plays an essential role in the progression of cancer cachexia through the regulation of the inflammatory response. METHODS: This study consisted of 48 gastric, breast and lung cancer patients (18 cachectic and 30 non-cachectic) and healthy individuals. Total RNA isolation and cDNA synthesis was performed after the collection of blood samples. IL-6 and STAT3 expression levels were analyzed by RT- PCR analysis. RESULTS: Our findings demonstrated that IL-6 mRNA levels considerably increased 19.89±8.25, 5.18±2.81 and 15.33±9.54-fold in gastric, lung and breast cancer patients with cachexia, respectively. Additionally, a 16.67±7.13, 14.21±11.72 and 8.85±3.89-fold increase in the STAT3 expression level was detected in cachectic gastric, lung and breast cancer patients, respectively (p<0.01). CONCLUSION: STAT3 may be considered as a therapeutic target for cachectic patients with gastric, lung and breast cancer. Furthermore, IL-6 mediates STAT3 activation in cachectic gastric and breast cancer patients (Tab. 5, Fig. 2, Ref. 62).

The effect of lipoic acid on antioxidant status and lipid peroxidation in rats exposed to chronic restraint stress.

This study was designed to investigate effect of alpha-lipoic acid (LA) on lipid peroxidation, nitric oxide production and antioxidant systems in rats exposed to chronic restraint stress. Twenty four male Wistar rats, aged three months, were divided into four groups: control (C), the group treated with LA (L), the group exposed to restraint stress (S) and the group exposed to stress and treated with LA (LS). Restraint stress was applied for 21 days (1 h/day) and LA (100 mg/kg/day) was injected intraperitonally to the L and LS groups for the same period. Restraint stress significantly decreased brain copper/zinc superoxide dismutase (Cu,Zn-SOD) and brain and retina glutathione peroxidase (GSH-Px) and catalase (CAT) activities compared with the control group. Thiobarbituric acid reactive substances (TBARS), nitrite and nitrate levels were significantly increased in the tissues of the S group compared with the C group. LA produced a significant decrease in brain and retina TBARS, nitrite and nitrate levels of the L and LS groups compared to their corresponding control groups. LA increased all enzyme activities in the tissues of the LS group compared to the S group. Our study indicated that LA is an ideal antioxidant candidate for the prevention of stress-induced lipid peroxidation.

Effects of extremely low-frequency electric fields at different intensities and exposure durations on mismatch negativity.

The effects of extremely low-frequency electric fields (ELF-EFs, 3-300Hz) on lipid peroxidation levels and antioxidant enzyme activities have been shown in many tissues and plasma after exposure to 50-Hz alternating current (AC) electric fields. However, similar studies investigating brain lipid peroxidation status are limited. Moreover and as far as we know, no study has been conducted to examine mismatch negativity (MMN) response in rats following exposure to a 50-Hz AC electric field. Therefore, the purpose of the study was to investigate different intensities and exposure durations of ELF-EFs on MMN component of event-related potentials (ERPs) as well as apoptosis and oxidative brain damage in rats. Ninety male rats, aged 3months were used in our study. A total of six groups, composed of 15 animals each, was formed as follows: sham-exposed rats for 2weeks (C2), sham-exposed rats for 4weeks (C4), rats exposed to 12-kV/m and 18-kV/m electric fields for 2weeks (E12-2 and E18-2), rats exposed to 12- and 18-kV/m electric fields for 4weeks (E12-4 and E18-4). At the end of the experimental period, MMN responses were recorded in urethane-anesthetized rats by electrodes positioned stereotaxically to the surface of the dura. After MMN recordings, animals were killed by exsanguination and their brain tissues were removed for 4-hydroxy-2-nonenal (4-HNE), protein carbonyl and TUNEL analysis. In the current study, different change patterns in ERP parameters were observed dependent on the intensity and exposure duration of ELF-EFs. There were differences in the amplitudes of ERP between the responses to the standard and the deviant tones in all groups. When peak-to-peak amplitude of the difference curves was evaluated, MMN amplitude was significantly decreased in the E18-4 group compared with the C4 group. Additionally, the amount of 4-HNE was increased in all experimental groups compared with the control group. Consequently, it could be concluded that electric field decreased MMN amplitudes possibly induced by lipid peroxidation.