Resveratrol (RSV) has been demonstrated to ameliorate nonalcoholic fatty liver disease (NAFLD) in animal studies. However, RSV was given with the dosage that ranged from 7 to 300 mg/kg body weight (BW). Hence, the study aimed to investigate the efficacy of RSV at a lower dosage on high cholesterol-fructose diet (HCFD)-induced rat model of NAFLD. In the study, male Sprague-Dawley rats were fed with HCFD for 15 weeks. RSV was also given at a daily dose of 1 mg/kg BW for 15 days or 15 weeks by oral delivery. At sacrifice, plasma and liver specimens were acquired for detections of alanine and aspartate aminotransferases, proinflammatory cytokines, and lipid contents. Histological examinations and Western blotting analysis were performed using liver tissues. The results showed that RSV administration reduced plasma levels of aminotransferases and proinflammatory cytokines including interleukin-1 beta (IL-1β), IL-6, and tumor necrosis factor-alpha (TNF-α) in HCFD-induced NAFLD. RSV also mitigated hepatic lipid accumulation and expression of IL-1β, IL-6, and TNF-α. Besides, phosphorylation of signal transducer and activator of transcription 3 (STAT3) was reduced with RSV supplementation in the liver of HCFD-fed rats. We concluded that low-dose RSV supplementation attenuated hepatic inflammation and lipid accumulation in HCFD-induced NAFLD. The ameliorative effect of RSV on NAFLD could be associated with downregulation of phosphorylated STAT3.

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Acupuncture is a key component of Traditional Chinese Medicine in which needles are inserted into specific areas in the body to stimulate certain physiological reactions of the body. Clinical research shows that acupuncture is beneficial in treating a variety of illnesses, such as erectile dysfunction. Therefore, we investigated the effect of electroacupuncture (EA) stimulation of both low- and high frequencies at Guanyuan (CV4) and Zhongji (CV3) acupoints on male copulatory behavior in sexually experienced male rats. The animals were randomly divided into four groups: control, sham EA, EA, and only acupuncture. The administered low and high EA were 2 Hz and 80 Hz, respectively, for which the respective intensities were 1.5 mA (30 min/day for 5 days) and 1.5 mA (30 min once). The only acupuncture-administered group received acupunctures at CV4 and CV3 without electrical stimulation. Following the acupuncture treatments, copulatory behavior test was conducted. Eventually, animals were sacrificed and blood samples were collected for testing the serum hormonal profile including luteinizing hormone (LH), testosterone (T), and serotonin (5-HT). Results showed that low-frequency EA-treated rats exhibited increasing intromissions and ejaculation latency compared to control, sham EA, and acupuncture groups, while high-frequency EA-treated rats displayed lower intromissions and ejaculation frequency when compared with those in controls. Furthermore, serum levels of 5-HT and LH in low-frequency EA-treated rats were higher than all the other groups. These results indicate that compared to high-frequency EA, the low-frequency EA might be efficacious in the treatment of premature ejaculation, thereby improving sexual behavior.

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Dietary factors do not only contribute to remission of diseases but also play important roles in the progression of medical conditions. We investigated the effect of different formulations of maize diets on the healing of experimental acetic acid-induced ulcerative colitis (UC) in male rats. Thirty-five (35) male Wistar rats (150–170 g) were randomly divided into control (CTR), UC, UC + high maize diet (HMD), UC + low maize diet (LMD), and UC + maize-free diet (MFD) groups. CTR, UC, UC + HMD, UC + LMD, and UC + MFD groups were administered different formulations of dietary maize ranging from 0% to 70%. Body weight change (BWC), colon weight, macroscopic ulcer score, catalase, glutathione (GSH), tumor necrosis factor-α (TNF-α), myeloperoxidase, diarrhea score, superoxide dismutase (SOD), Ki-67 expression, and histological studies were done. Results were analyzed using SPSS 23. UC + LMD and UC + MFD groups showed a duration-dependent reduction in negative BWC, respectively. When compared with UC group, UC + LMD and UC + MFD significantly increased (P < 0.05) GSH and SOD respectively but had no effect on TNF-α and diarrhea score. UC + HMD increased diarrhea and macroscopic ulcer scores with Ki-67 expression highest in UC + MFD. The study indicated that consumption of either LMD or maize-free diet by colitic rats relatively enhanced healing of UC.

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PKC-mediated inflammation is important in ovarian physiology. The roles of Akt and protein phosphatase 2A (PP2A) in PKC-mediated inflammation in ovarian granulosa cells (GCs) remain mostly unclear. PKC activator phorbol 12-myristate 13-acetate induced the Akt phosphorylation in rat primary GCs but reduced the Akt phosphorylation in KGN human GCs. In rat GCs, an inhibitory effect of PI3K inhibitor wortmannin and a stimulatory effect of Akt activator SC79 on PKC-induced cyclooxygenase-2 (COX-2)/PGE₂production were noted; wortmannin and SC79 acted oppositely in human GCs. In rat GCs, PP2A inhibitor okadaic acid further enhanced the PKC-mediated promoter activation and elevation of mRNA and protein levels of the COX-2 gene, whereas PP2A activator sodium selenate attenuated the PKC-mediated COX-2 expression and promoter activation. PKC activation did not affect PP2A phosphorylation, but okadaic acid indeed augmented the PKC-induced NF-κB nuclear translocation. Thus, PP2A appears to act as a negative modulator in PKC-mediated cellular inflammation in rat GCs, at least in part due to its attenuating effect on the PKC-induced NF-κB activation.

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Thioridazine, belonging to first-generation antipsychotic drugs, is a prescription used to treat schizophrenia. However, the effect of thioridazine on intracellular Ca²⁺ concentration ([Ca²⁺]_i) and viability in human liver cancer cells is unclear. This study examined whether thioridazine altered Ca²⁺ signaling and viability in HepG2 human hepatocellular carcinoma cells. Ca²⁺ concentrations in suspended cells were measured using the fluorescent Ca²⁺-sensitive dye fura-2. Cell viability was examined by WST-1 assay. Thioridazine at concentrations of 25–100 μM induced [Ca²⁺]_i rises. Ca²⁺ removal reduced the signal by 20%. Thioridazine (100 μM) induced Mn²⁺ influx suggesting of Ca²⁺ entry. Thioridazine-induced Ca²⁺ entry was inhibited by 20% by protein kinase C (PKC) activator (phorbol 12-myristate 13 acetate) and inhibitor (GF109203X) and by three inhibitors of store-operated Ca²⁺ channels: nifedipine, econazole, and SKF96365. In Ca²⁺-free medium, treatment with the endoplasmic reticulum Ca²⁺ pump inhibitor thapsigargin (TG) abolished thioridazine-evoked [Ca²⁺]_i rises. On the other hand, thioridazine preincubation completely inhibited the [Ca²⁺]_i rises induced by TG. Furthermore, U73122 totally suppressed the [Ca²⁺]_i rises induced by thioridazine via inhibition of phospholipase C (PLC). Regarding cytotoxicity, at 30-80 μM, thioridazine reduced cell viability in a concentration-dependent fashion. This cytotoxicity was not prevented by preincubation with 1,2-bis (2-aminophenoxy) ethane-N, N, N', N'-tetraacetic acid-acetoxymethyl ester (BAPTA/AM) (a Ca²⁺ chelator). To conclude, thioridazine caused concentration-dependent [Ca²⁺]_i rises in HepG2 human hepatoma cells by inducing Ca²⁺ release from the endoplasmic reticulum via PLC-associated pathways and Ca²⁺ influx from extracellular medium through PKC-sensitive store-operated Ca²⁺ entry. In addition, thioridazine induced cytotoxicity in a Ca²⁺-independent manner.

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During overnight sleep, the longest postabsorptive and inactive phase of the day causes protein catabolism and loss. However, the daytime ingestion of dairy proteins has been shown to stimulate muscle protein synthesis and growth. This study compared the effects of pre-sleep supplementation of a protein blend (PB) composed of micellar casein (MCa) and whey protein (1:1) versus isolate MCa on the plasma levels of branched-chain amino acids (BCAAs) and the activation of the mechanistic target of rapamycin (mTOR) signaling, a critical intracellular pathway involved in the regulation of muscle protein synthesis. After 10 h of fasting during the active phase, rats were fed with a single dose of PB or MCa (5.6 g protein/kg of body mass) by gavage, and samples of blood and gastrocnemius muscle were collected at 30, 90, and 450 min. PB and MCa supplementations induced an increase (~3-fold, P < 0.001) of plasma BCAAs at 30 and 90 min. Most importantly, the stimulatory phosphorylation levels of mTOR and its downstream target p70 ribosomal protein S6 kinase (p70S6K) were similarly higher (~2.5-fold, P < 0.001) 30 and 90 min after MCa and PB. Plasma levels of leucine, isoleucine, valine, and overall BCAAs were correlated with the activation of mTOR (P < 0.001) and p70S6K (P < 0.001). MCa and PB supplementations before the inactive phase of rats resulted in an anabolic milieu in the skeletal muscle by inducing a transient increase in plasma BCAAs and a similar activation of the mTOR/p70S6K axis.

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