Cancer cachexia is a wasting syndrome resulting from decreased protein synthesis and increased protein degradation. Calpain-dependent cleavage of myofilament is the initial step of myofilament degradation and plays a critical role in muscle atrophy. Ghrelin is a multifunctional hormone known to improve protein synthesis and inhibit protein degradation. However, its mechanism of action is not fully understood. Here we investigated whether acylated ghrelin (AG) and unacylated ghrelin (UnAG) could protect against cancer cachexia in mice bearing CT26 colorectal adenocarcinoma. We found for the first time that both AG and UnAG could inhibit calpain activity in skeletal muscle of cancer cachectic mice. AG and UnAG also improved tumor-free body weight, grip strength, muscle mass, epididymal fat mass, and nutritional state in tumor-bearing (TB) mice. Moreover, AG and UnAG reduced serum tumor necrosis factor-± concentration, increased Akt activity, and downregulated atrogin-1 expression in TB mice. Our results may contribute to the development of an AG/UnAG-based therapy for cancer cachexia.

Despite the wide application of carvacrol (CAR) in different biological and medical areas, there is still insufficient electrophysiological data on the mechanisms of action of CAR, particularly in the pregnant uterine function. The aim of this study was to evaluate the in vitro tocolytic effect of CAR on the contractility of isolated pregnant rat uterus in the presence of a calcium channel antagonist (nifedipine) and a cyclooxygenase inhibitor (indomethacin). The uteri were isolated from pregnant Wistar rats at 16–18 days of pregnancy and suspended in an isolated organ bath chamber containing a Ringer's physiological solution and aerated with 95% O₂ and 5% CO₂. Samples were used in functional tests to evaluate the inhibitory effect of CAR at increasing concentrations on the rhythmic spontaneous, oxytocin-induced phasic, K⁺-induced tonic, and Ca²⁺-induced contractions. The differences in inhibitory concentration-50 and E_max among the compounds were determined using the one-way ANOVA followed by a post hoc Student-Newman-Keuls or Bonferroni test, in all cases P < 0.05 was considered statistically significant. Nifedipine was used as positive controls where required. CAR caused a significant concentration-dependent inhibition of the uterine contractions induced by the pharmaco- and electro-mechanic stimuli. We showed that the inhibitory effects of CAR depends on the type of muscle contraction stimuli, and that it acts stronger in spontaneous rhythmic activity and in contractions of isolated rat uterus induced by Ca²⁺. Nifedipine was more potent than CAR and indomethacin on the uterine contractility (P < 0.05), but none of them was more effective than nifedipine. Therefore, the tocolytic effect induced by CAR was associated with the blockade of the calcium channels in the pregnant rat uterus. This property placed CAR as a potentially safe and effective adjuvant agent in cases of preterm labor, an area of pharmacological treatment that requires urgent improvement.

Lenalidomide with dexamethasone (Len/Dex) is considered to be an effective and well-tolerated regimen to treat multiple myeloma (MM) patients relapsing after bortezomib induction therapy. With the increase in novel agents targeting refractory and relapsed MM, the identification of clinical or laboratory variables that can predict the appropriate candidates of Len/Dex is essential. To address this question, we prospectively assessed 38 adult MM patients who received bortezomib-based induction therapy and were administered Len/Dex for their first relapse. These 38 patients were stratified into the symptomatic relapse group (n = 10) and biological relapse group (n = 28) according to the disease status when Len/Dex was initiated. The overall response rate in the symptomatic group and biological relapse group was 70.0% (7/10) and 60.7% (17/28), respectively (P = 0.964). These two groups harbored a comparable median Len/Dex treatment duration (139 vs. 225 days; P = 0.876) and progression-free survival 2 (PFS2) (501 vs. 1289 days; P = 0.410). Multivariate analyses failed to show that treating biological relapse (hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 0.43–3.88; P = 0.648), PFS with bortezomib-based induction therapies ≥18 months (HR: 1.79; 95% CI: 0.64–5.01; P = 0.266), autologous hematopoietic stem cell transplantation (HR: 2.18; 95% CI: 0.56–8.55; P = 0.262), and high-risk cytogenetics (HR: 0.85; 95% CI: 0.18–3.93; P = 0.835) were attributed to depth of Len/Dex treatment. In conclusion, whether MM patients treated by Len/Dex for biological relapse would have a better outcome than those prescribed for symptomatic relapse remains inconclusive. Treating significant biological relapse and symptomatic relapse remains the current consensus.

Cognitive impairments are associated with advancing age. Trans-cinnamaldehyde (CIN) and ellagic acid (ELA) have multiplex activities to reduce various age-related cognitive disorders. In this study, we investigated the effects of these compounds separately or in combination on the cognitive outcomes, mitochondrial function, and inflammatory and apoptotic mediators in aged male Wistar rats. Thirty-two old (22 months old) and eight young (5 months old) rats were randomly allocated to five groups of young control, aged control, ELA-aged, CIN-aged, and ELA + CIN-aged. ELA (15 mg/kg, orally) and CIN (50 mg/kg, intraperitoneally) separately or in combination were administered for 1 month in aged animals. Spatial memory and cognitive activity were evaluated by the Barnes maze and novel object recognition tests. Mitochondrial function (its reactive oxygen species [ROS], mitochondrial membrane potential and ATP level), pro-inflammatory cytokines such as interleukin (IL)-1β and IL-6 and pro-apoptotic caspase 3 and Bax, and anti-apoptotic Bcl2 levels and their ratio were assessed in the prefrontal cortex. Behavioral results revealed that CIN separately or in combination with ELA significantly alleviates aging-induced memory impairment. Moreover, co-administration of agents effectively decreased inflammatory cytokines, cleaved-caspase 3, Bax and Bax/Bcl2 levels, mitochondrial ROS production, and mitochondrial membrane depolarization and increased Bcl2 and ATP level as compared with untreated aged control rats. Combination therapy was greater than those of individual treatments in all parameters. Therefore, combination therapy with CIN and ELA improved aging-induced cognitive impairment through anti-inflammatory, anti-apoptotic, and mitochondrial-boosting effects in aged rats.

The aim of this study was to investigate the acute and chronic effects, and their correlation, after combined aerobic and resistance exercises in blood pressure (BP) and its variability (BPV) in hypertensive postmenopausal women. Fourteen hypertensive postmenopausal women monitored BP at rest and during 24 h by ambulatory BP monitoring in a control day without exercise performance a pretraining (baseline), after an acute exercise session (acute), and after a chronic exercise training for 10 weeks (chronic). After exercise training, systolic BP (SBP, Δ = −150 mmHg.24 h), diastolic BP (DBP, Δ = −96 mmHg.24 h), and mean BP (MBP, Δ = −95 mmHg.24 h) area under the curve were smaller than baseline measurements (P < 0.05) with no difference between acute and baseline measurements. The SBP (ΔSD₂₄ = −2, ΔSD_dn = −1.7, and ΔARV₂₄ = −1.9 mmHg), DBP (ΔSD₂₄ = −0.9, ΔSD_dn = −0.8, and ΔARV₂₄ = −0.9 mmHg), and MBP (ΔSD₂₄ = −1.5, ΔSD_dn = −1.3, and ΔARV₂₄ = −1.2 mmHg) variability reduced in acute session in relation to baseline, with no chronic effects. There are moderate correlations between acute and chronic responses in wake SBP, sleep DBP, and SD₂₄. In conclusion, combined exercise reduces ambulatory BP chronically but not acutely. In contrast, BPV decreases after an acute session but not chronically. Awake SBP, sleep DBP, and SD₂₄ indices are promising candidates to predict individual cardiovascular responses to exercise.

Although selenium is known to be essential for reproductive function, studies have indicated the adverse effect with its prolonged use. The present study investigated the duration-related effect of selenium administrations on reproductive hormones and estrous cycle indices in adult female Wistar rats exposed to a model of light pollution using altered photoperiod (AP). Ninety-six cyclic female Wistar rats displaying 4–5 days' estrous cycle length (ECL) and weighing 148–152 g were randomly divided into short and long experimental cohorts consisting of six groups each and spanning for 1 and 8 weeks, respectively. Each consisted of control, high selenium dose (HSE), low selenium dose (LSE), AP, AP + HSE, and AP + LSE. The rats were orally administered high dose (150 μg/kg) and low dose (100 μg/kg) of sodium selenite once per day. The estrous cycle indices were monitored. Plasma levels of follicle-stimulating hormone, luteinizing hormone (LH), estradiol (E), progesterone (P), prolactin, E/P ratio, and histology of ovary and uterine horn were evaluated. The statistical analysis was performed using Statistical Package for the Social Sciences. In AP rats, HSE and LSE caused no significant effect on LH, E, P, and E/P ratio, ECL, estrus interval (EI), and estrous cycle ratio (ECR). The effect of HSE and LSE on LH, E, P, E/P ratio, and ECL showed no duration-dependent increase, but there was a duration-dependent increase in EI and ECR at low dose. The study indicated that administration of HSE of selenium improved reproductive function in photo-pollution-exposed rats irrespective of the duration of treatment.