Effect of leucine on NF-?B pathway in liver regeneration after partial hepatectomy in rats as determined by miniarray analysis

PubMed: 29455543BACKGROUND: Although some amino acids are recognized to have favorable effects on the liver regeneration after partial hepatectomy (PH), molecular mechanisms underlying these effects are barely known. OBJECTIVE: Our study was aimed to investigate the effects of valine, glutamine, and leucine amino acids on PH-induced NF-?B signal pathway. The research team studied Leucine in a rat model in vivo. The study took place in the medical and surgical experimental research center at the Eskisehir Osmangazi University in Eskisehir, Turkey. The animals were Wistar albino male rats. RESULTS: Group I, the sham group, was administered phosphate buffered saline (PBS) after laparotomy. After 70 % PH procedure, group II, III, IV, and V received single intraperitoneal doses of PBS, valine, glutamine, and leucine amino acids, respectively. At hour 6 after PH, expressions of 88 genes involving in NF-?B signal pathway were examined by RT-PCR mini array method in the liver tissue specimen. Fold values below 0.5 and above 2 were regarded as significant. CONCLUSIONS: Our results suggested that valine, glutamine, and leucine amino acids may alter expressions of the genes of NF-?B signal pathway. In addition, among these amino acids, glutamine and valine proved to be much more effective on NF-?B signal pathway after the P

VEXAS syndrome: a Swiss national retrospective cohort study.

VEXAS syndrome is a recently discovered monogenic auto-inflammatory disease caused by a somatic mutation in the UBA1 gene that manifests with rheumatologic and haematologic features. In this report, we present the first Swiss cohort, detailing its manifestations and treatment outcomes among Swiss patients. Data were retrospectively collected from nine hospitals across Switzerland, representing a broad geographic distribution. Treating physicians completed a standardised case report form for each patient. The principal investigator and the co-investigators collected and analysed all case report forms. We identified 23 patients between July 2022 and 2023, of which 17 are described. All were male. They presented with skin manifestations (88%), general symptoms (82%), venous thromboembolism (59%), ocular manifestation (59%), lung infiltrates (59%) and articular manifestations (47%). Central nervous system and kidney manifestations were very rare, and heart and digestive manifestations were absent. Macrocytic anaemia was present in all patients throughout the disease progression but only in two-thirds of patients (12/17, 71%) at the time of diagnosis. Clinical response was reached in all cases treated with ruxolitinib (4/4, 100%), upadacitinib (1/1, 100%), azacytidine (5/5, 100%) and haematopoietic stem cell transplantation (2/2, 100%). All deaths were attributed to infections (5/5, 100%). This study corroborates the clinical spectrum of VEXAS syndrome described in other cohorts. It suggests that VEXAS syndrome is not limited to patients with macrocytic anaemia. In this study, azacytidine has been used effectively among patients with myelodysplastic syndrome. In addition, Janus kinase (JAK) inhibitors, particularly ruxolitinib, have been successfully used even in those without myelodysplastic syndrome. We report two successful treatments by haematopoietic stem cell transplantation

The effect of general anaesthetics on brain lactate release

The effects of anaesthetic agents on brain energy metabolism may explain their shared neurophysiological actions but remain poorly understood. The brain lactate shuttle hypothesis proposes that lactate, provided by astrocytes, is an important neuronal energy substrate. Here we tested the hypothesis that anaesthetic agents impair the brain lactate shuttle by interfering with astrocytic glycolysis. Lactate biosensors were used to record changes in lactate release by adult rat brainstem and cortical slices in response to thiopental, propofol and etomidate. Changes in cytosolic nicotinamide adenine dinucleotide reduced (NADH) and oxidized (NAD+) ratio as a measure of glycolytic rate were recorded in cultured astrocytes. It was found that in brainstem slices thiopental, propofol and etomidate reduced lactate release by 7.4 ± 3.6% (P < 0.001), 9.7 ± 6.6% (P < 0.001) and 8.0 ± 7.8% (P = 0.04), respectively. In cortical slices, thiopental reduced lactate release by 8.2 ± 5.6% (P = 0.002) and propofol by 6.0 ± 4.5% (P = 0.009). Lactate release in cortical slices measured during the light phase (period of sleep/low activity) was ~25% lower than that measured during the dark phase (period of wakefulness) (326 ± 83 μM vs 430 ± 118 μM, n = 10; P = 0.04). Thiopental and etomidate induced proportionally similar decreases in cytosolic [NADH]:[NAD+] ratio in astrocytes, indicative of a reduction in glycolytic rate. These data suggest that anaesthetic agents inhibit astrocytic glycolysis and reduce the level of extracellular lactate in the brain. Similar reductions in brain lactate release occur during natural state of sleep, suggesting that general anaesthesia may recapitulate some of the effects of sleep on brain energy metabolism

Carvacrol, a Food-Additive, Provides Neuroprotection on Focal Cerebral Ischemia/Reperfusion Injury in Mice

Carvacrol (CAR), a naturally occurring monoterpenic phenol and food additive, has been shown to have antimicrobials, antitumor, and antidepressant-like activities. A previous study demonstrated that CAR has the ability to protect liver against ischemia/reperfusion injury in rats. In this study, we investigated the protective effects of CAR on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that CAR (50 mg/kg) significantly reduced infarct volume and improved neurological deficits after 75 min of ischemia and 24 h of reperfusion. This neuroprotection was in a dose-dependent manner. Post-treatment with CAR still provided protection on infarct volume when it was administered intraperitoneally at 2 h after reperfusion; however, intracerebroventricular post-treatment reduced infarct volume even when the mice were treated with CAR at 6 h after reperfusion. These findings indicated that CAR has an extended therapeutic window, but delivery strategies may affect the protective effects of CAR. Further, we found that CAR significantly decreased the level of cleaved caspase-3, a marker of apoptosis, suggesting the anti-apoptotic activity of CAR. Finally, our data indicated that CAR treatment increased the level of phosphorylated Akt and the neuroprotection of CAR was reversed by a PI3K inhibitor LY-294002, demonstrating the involvement of the PI3K/Akt pathway in the anti-apoptotic mechanisms of CAR. Due to its safety and wide use in the food industry, CAR is a promising agent to be translated into clinical trials

Polymorphisms in ADAMTS4 and ADAMTS5 are not linked to susceptibility to knee osteoarthritis in the Turkish population

WOS: 000384881100094PubMed ID: 27706574Considering the functions of aggrecanase-1 (ADAMTS4) and -2 (ADAMTS5), which are thought to be the two major enzymes responsible for the destruction of aggrecans in arthritic diseases, we investigated whether important polymorphisms in the ADAMTS4 and ADAMTS5 genes affect osteoarthritis (OA) susceptibility. Our study took place in Mugla, Turkey. Ninety-five cases were recruited following OA diagnosis (72 women and 23 men), and 80 individuals without any symptoms or radiographic signs of OA (56 women and 24 men) were chosen as healthy controls. After obtaining DNA from patients and control subjects, ADAMTS4 and ADAMTS5 genotypes were determined using the ABI Prism StepOnePlus Real-Time system. In addition, we categorized patients based on OA grade. There were no significant differences in the genotype distributions of the four polymorphisms between the groups (P > 0.05). Moreover, ADAMTS4 and ADAMTS5 allele frequencies did not differ between OA and control participants (P > 0.05). These findings suggest that the ADAMTS4 (rs4233367 and rs11807350) and ADAMTS5 (rs226794 and rs2830585) variants examined may not contribute to susceptibility to knee OA in the Turkish population. Other gene polymorphisms should be assessed in order to explain variations in OA susceptibility.Mugla Sitki Kocman UniversityMugla Sitki Kocman UniversityWe would like to thank Mugla Sitki Kocman University for its contribution and financial support to our study

Development and Characterization of a Wearable Ring Providing Haptic Feedback

2022 Innovations in Intelligent Systems and Applications Conference, ASYU 2022 -- 7 September 2022 through 9 September 2022 -- -- 183936Comfort and efficiency are the essential features of any wearable device. A variety of devices use vibration to provide haptic feedback to the user. In this study, a novel haptic flexible ring equipped with four actuators is developed to enhance the user experience for tactile interfaces. The proposed device provides subcutaneous clues at the proximal interphalangeal joint of the index finger to mimic the forces and moments applied to this joint. Thresholding experiments are conducted using a total of nine subjects to evaluate the effects of the vibration amplitude, thickness, and orientation of 1D lines on human perception. The results showed that as the line's thickness and amplitude increase, the participants perform better at identifying the shapes. The minimum thickness that the human participants can detect is 2 mm at the lowest possible vibration level with a single motor. Furthermore, the second vibration amplitude and vertical orientation lead to higher recognition rates and lower recognition times. In the future, we aim to perform further characterization experiments and develop virtual reality applications to test the proposed ring. © 2022 IEEE

Investigation of cytogenetic effects of 2, 4, 5 triphenyl imidazole by rat bone marrow micronucleus test

The cytogenetic effects of 2, 4, 5 triphenyl imidazole on the micronucleus formation were investigated in rats. Increasing doses of the substance were injected i.p. into Wistar rats and polychromatic and normochromatic erythrocytes were scored for the formation of micronuclei in bone marrow smears. The number of micronuclei was found about 2-3 times more in 2,4,5 triphenyl imidazole treated rats than the control groups. This increase in the formation of micronucleus indicates the clastogenic effects of the substance on rats and may have similar effects on other mammals and human population