Neonatal hypoxic-ischemic encephalopathy is a disorder with heterogeneous manifestation due to asphyxia during perinatal period. It affects approximately 3-12 children per 1000 live births and cause death of 1 million neonates worldwide per year. Besides, motor disabilities, seizures, impaired muscle tone and epilepsy are few of the consequences of hypoxic-ischemic encephalopathy. Despite an extensive research effort regarding various treatment strategies, therapeutic hypothermia with intensive care unit supportive treatment remains the only approved method for neonates who have suffered from moderate to severe hypoxicischemic encephalopathy. However, these protocols are only partially effective given that many infants still suffer from severe brain damage. Thus, further research to systematically test promising neuroprotective treatments in combination with hypothermia is essential. In this review, we discussed the pathophysiology of hypoxic-ischemic encephalopathy and delved into different promising treatment modalities, such as melatonin and erythropoietin. However, preclinical studies and clinical trials are still needed to further elucidate the mechanisms of action of these modalities.
In as early as 1997, the World Health Organization officially recognized obesity as a chronic disease. The current epidemic of obesity and overweightness has aroused great interest in the study of adipose tissue formation. The transcription factor peroxisome proliferator-activated receptor γ (PPARγ) binds to the target gene promoter regulatory sequences, acting as a key factor in regulating the differentiation of preadipocytes in the adipose tissue, and plays an important role in regulating the adipocyte metabolism. A further understanding of the structure and expression characteristics of PPARγ, in addition to its mechanisms of action in adipocyte differentiation, may be applied to control obesity and prevent obesity-related diseases. In this article, recent studies investigating the effect of regulating PPARγ on adipocyte differentiation are reviewed. In particular, the structural characteristics, expression patterns, and molecular mechanisms of PPARγ function in adipocyte differentiation are considered., Hui Wu, Xiaohua Li, Chunyan Shen., and Obsahuje bibliografii
Vascular calcification (VC) is an independent risk factor for cardiovascular events and all-cause mortality with the absence of current treatment. This study aimed to investigate whether eIF2α phosphorylation inhibition could ameliorate VC. VC in rats was induced by administration of vitamin D3 (3×105 IU/kg, intramuscularly) plus nicotine (25 mg/kg, intragastrically). ISRIB (0.25 mg/kg·week), an inhibitor of eIF2α phosphorylation, ameliorated the elevation of calcium deposition and ALP activity in calcified rat aortas, accompanied by amelioration of increased SBP, PP, and PWV. The decreased protein levels of calponin and SM22α, and the increased levels of RUNX2 and BMP2 in calcified aorta were all rescued by ISRIB, while the increased levels of the GRP78, GRP94, and C/EBP homologous proteins in rats with VC were also attenuated. Moreover, ISRIB could prevent the elevation of eIF2α phosphorylation and ATF4, and partially inhibit PERK phosphorylation in the calcified aorta. These results suggested that an eIF2α phosphorylation inhibitor could ameliorate VC pathogenesis by blocking eIF2α/ATF4 signaling, which may provide a new target for VC prevention and treatment.
Acute liver failure (ALF) is known for extremely high mortality
rate, the result of widespread damage of hepatocytes. Orthotopic
liver transplantation is the only effective therapy but its
application is limited by the scarcity of donor organs. Given the
importance in the liver biology of Wnt/β-catenin signaling
pathway, we hypothesized that its stimulation could enhance
hepatocyte regeneration and attenuate the course of
thioacetamide (TAA)-induced ALF in Lewis rats. Chronic
treatment with Wnt agonist was started either immediately after
hepatotoxic insult (“early treatment”) or when signs of ALF had
developed (“late treatment”). Only 23 % of untreated Lewis rats
survived till the end of experiment. They showed marked
increases in plasma alanine aminotransferase (ALT) activity and
bilirubin and ammonia (NH3) levels; plasma albumin decreased
significantly. “Early” and “late” Wnt agonist treatment raised the
final survival rate to 69 % and 63 %, respectively, and
normalized ALT, NH3, bilirubin and albumin levels. In conclusion,
the results show that treatment with Wnt agonist attenuates the
course of TAA-induced ALF in Lewis rats, both with treatment
initiated immediately after hepatotoxic insult and in the phase
when ALF has already developed. Thus, the pharmacological
stimulation of Wnt/β-catenin signaling pathway can present
a new approach to ALF treatment.
Glucocorticoids (GCS) are known to modulate cardiovascular response during stress conditions. The present study was aimed to test the hypothesis that permissive and/or stimulating effect of GCs is essential for the maintenance of peripheral vascular resistance and for the adequate response of cardiovascular system to stressor exposure. The effects of acute pharmacological adrenalectomy (PhADX) on humoral and cardiovascular parameters were studied in adult Wistar rats under the basal conditions and during the acute restraint stress. Acute PhADX was performed by the administration of metyrapone and aminoglutethimide (100 mg/kg s.c. of each drug) resulting in a suppression of endogenous glucocorticoid synthesis. Blood pressure (BP), heart rate (HR) and core body temperature were measured using radiotelemetry. BP responses to administration of vasoactive agents were determined in pentobarbital-anesthetized animals. PhADX considerably attenuated stress-induced increase of BP, HR and core body temperature. PhADX did not abolish BP and HR lowering effects of ganglionic blocker pentolinium indicating preserved sympathetic function in PhADX rats. BP response to exogenous norepinephrine administration was attenuated in PhADX rats, suggesting reduced sensitivity of cardiovascular system. Suppression of corticosterone synthesis by PhADX increased basal plasma levels of ACTH, aldosterone and plasma renin activity in unstressed animals but there was no further increase of these hormones following stressor exposure. In conclusion, PhADX attenuated stress-induced rise of blood pressure, heart rate and core body temperature indicating an important permissive and/or stimulating role of glucocorticoids in the maintenance of the adequate response of cardiovascular system and thermoregulation to several stimuli including acute exposure to stressor.
The water-hyacinth grasshopper, Cornops aquaticum, occurs in freshwater environments in the New World between latitudes 23°N and 35°S. At the southernmost margin of this distribution the populations are polymorphic for three centric fusions (Robertsonian translocations). The frequencies of these chromosome rearrangements increase southwards and the recombination in structural homozygotes and heterozygotes diminishes both along the middle and lower courses of the Paraná River. In the present paper we report a similar cline along the southward flowing Uruguay River. In addition, we report the morphological effects of two of these centric fusion polymorphisms, namely the fusions between chromosomes 2 and 5 of the standard complement (fusion 2/5) and chromosomes 3 and 4 (fusion 3/4) and extend this study to the Uruguay River. There is a strong inverse correlation of fusion frequency with temperature, which indicates that these polymorphisms may be related to increased tolerance of colder climates in this originally tropical species, or some other correlated variable. This study is a further example of chromosomal clines correlated with latitude and is one of a few examples of chromosome polymorphisms associated with phenotypic effects. Finally, it indicates ways of using this species for controlling pests., Pablo C. Colombo, María I. Remis., and Obsahuje bibliografii
Two light treatments [ambient sunlight (L1) during the entire growth period and 40% shade (L2) from 40 d after sowing until 24 d after flowering] and two phosphate fertilizer treatments [no phosphate fertilizer application (P0) and a conventional phosphate fertilizer application (P1)] were used to determine how phosphate fertilizer regulates soybean [Glycine max (L.) Merr.] photosynthesis under shading. We showed that phosphorus significantly increased chlorophyll content and grain yield under shading. The light-saturated net photosynthetic rate, apparent quantum yield, maximum electron transport rate, and maximum Rubisco carboxylation rate in P1 under L2 significantly increased. Moreover, phosphate fertilizer significantly improved the electron transfer and PSII reaction center performance under shading. Therefore, phosphate fertilizer increases low light-utilization efficiency by improving PSII performance, promoting ribulose-1,5-bisphosphate regeneration, ensuring a source of carboxylate substrates, and coordinating the balance between photochemical reaction and Calvin cycle under shading.
Phosphene is the experience of light without natural visual stimulation. It can be induced by electrical stimulation of the retina, optic nerve or cortex. Induction of phosphenes can be potentially used in assistive devices for the blind. Analysis of phosphene might be beneficial for practical reasons such as adjustment of transcranial alternating current stimulation (tACS) frequency and intensity to eliminate phosphene perception (e.g., tACS studies using verum tACS group and sham group) or, on the contrary, to maximize perception of phosphenes in order to be more able to study their dynamics. In this study, subjective reports of 50 healthy subjects exposed to different intensities of retinal tACS at 4 different frequencies (6, 10, 20 and 40 Hz) were analyzed. The effectiveness of different tACS frequencies in inducing phosphenes was at least 92 %. Subject reported 41 different phosphene types; the most common were light flashes and light circles. Changing the intensity of stimulation often induced a change in phosphene attributes. Up to nine phosphene attributes changed when the tACS intensity was changed. Significant positive correlation was observed between number of a different phosphene types and tACS frequency. Based on these findings, it can be concluded that tACS is effective in eliciting phosphenes whose type and attributes change depending on the frequency and intensity of tACS. The presented results open new questions for future research.
The oxygen-evolving complex (OEC) of Zostera marina is prone to deactivation under visible light, which results in a formation of the long-lived radical P680+. The mechanism to prevent damage caused by P680+ remains unclear. In this study, following light exposure, the upregulation in ascorbate (AsA) content and the presence of PSII cyclic electron flow (PSII-CEF) provide evidence that AsA and PSII-CEF donate electrons to PSII. Furthermore, a factorial design experiment with different combinations of inhibition of AsA and PSII-CEF demonstrates that both inhibition treatments lead to decreases in maximal photochemical yield of PSII, increases in relative variable fluorescence at the K-step, as well as the net loss of PSII reaction center proteins and further degradation of OEC peripheral proteins. These results suggest that AsA and PSII-CEF play photoprotective roles by providing electrons to efficiently prevent damage to PSII from the highly oxidizing radical P680+ in Z. marina.