Objective
The present study aimed to evaluate and clarify how the age at which the intake of a high-fat and high-fructose diet begins can affect animals’ livers.
Methods
Thirty-eight male wistar rats ...aged 6 and 12 weeks were fed a high-fat and high-fructose diet for 13 weeks. Inflammatory cytokines, hepatic glycogen, serum and hepatic triacylglycerol and pAkt protein content in the liver were assessed. Percentage of weight gained, and visceral adiposity were also evaluated.
Results
Young animal presented increased hepatic triacylglycerol and decreased glycogen, while adult animals had no significant alterations regarding its contents. IL6 and IL10 to IL6 ratio were also altered in young animals exposed to HFHF, while adult animals fed with HFHF had only increases in TNF-α. Both groups which received HFHF had increased serum triacylglycerol and visceral adiposity. However, only young animals gained more relative weight and had greater final body weight, gains which were related to alterations found in hepatic triacylglycerol and glycogen.
Conclusion
Age of which consumption begins interferes in how the liver deals with an excess of nutrient and subsequent proinflammatory stimulation, leading to different phenotypes.
•The relationship between PPO activity and browning in pears depends on the phenolic substrate.•PPO activity against a water-soluble pear extract did not correlate with tissue color changes.•PPO ...activity is not a good indicator of tissue browning in fresh-cut pear.•Direct assessment of color changes is a rapid and accurate method to estimate relevant response to antibrowning treatments.•pH of the antibrowning solution significantly affects color changes.
The effect of pH, phenolic substrates, and food additives on polyphenoloxidase (PPO) activity and on tissue browning was studied in fresh-cut ‘Rocha’ pear. Substrates 4-methylcatechol, caffeic acid, (+)-catechin hydrate, catechol, chlorogenic acid, dopamine hydrochloride, and pyrogallol, were prepared in citric acid-phosphate buffer at pHs ranging from 3.0 to 8.0. pH optima for PPO activity depended on the phenolic substrate. Activity was optimal at pH 5.0 for catechol and 4-methylcatechol; pH 6.0 for chlorogenic acid; pH 7.0 for dopamine, caffeic acid, and catechin; and pH 8.0 for pyrogallol. Discrepancies were observed between the pH dependency of PPO activity and browning, as assessed by objective color measurement. Significant correlations were obtained between enzyme activity and metric-hue difference (ΔH*) over the pH range 3.0–8.0 for four of the eight phenolics. Chlorogenic acid, the main PPO substrate in ‘Rocha’ pear, induced high tissue browning but very low PPO activity at pH 3.0–4.0. Chemical inhibition of PPO was tested using catechol as substrate, and buffer solutions containing 250mM Ca2+ in four salts (ascorbate, chloride, lactate and propionate), 57mM ascorbic acid, 61mM N-acetyl-l-cysteine and 3mM 4-hexylresorcinol. PPO inhibition by additives was affected by the pH of the buffer, and was more effective with ascorbic acid, N-acetyl-l-cysteine and calcium ascorbate. It was concluded that inferences on tissue browning based on PPO activity can be misleading. Measurement of tissue color is proposed as a reliable means to assess the antibrowning effectiveness of additives and the pH of additives for cut pear should be corrected to reduce the browning potential.
Commonly used to treat skin injuries in Asia, several Homalium spp. have been found to promote skin regeneration and wound healing. While ethnobotanical surveys report the use of H. bhamoense trunk ...bark as a wound salve, there are no studies covering bioactive properties. As impaired cutaneous healing is characterized by excessive inflammation, a series of inflammatory mediators involved in wound healing were targeted with a methanol extract obtained from
trunk bark. Results showed concentration-dependent inhibition of hyaluronidase and 5-lipoxygenase upon exposure to the extract, with IC
values of 396.9 ± 25.7 and 29.0 ± 2.3 µg mL
, respectively.
trunk bark extract also exerted anti-inflammatory activity by significantly suppressing the overproduction of interleukin 6 (IL-6) in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages at concentrations ranging from 125 to 1000 µg mL
, while leading to a biphasic effect on nitric oxide (NO) and tumor necrosis factor alpha (TNF-α) levels. The phenolic profile was elucidated by HPLC-DAD, being characterized by the occurrence of ellagic acid as the main constituent, in addition to a series of methylated derivatives, which might underlie the observed anti-inflammatory effects. Our findings provide in vitro data on anti-inflammatory ability of
trunk bark, disclosing also potential cutaneous toxicity as assessed in HaCaT keratinocytes.
S100 proteins are small dimeric calcium-binding proteins which control cell cycle, growth and differentiation via interactions with different target proteins. Intrinsic disorder is a hallmark among ...many signaling proteins and S100 proteins have been proposed to contain disorder-prone regions. Interestingly, some S100 proteins also form amyloids: S100A8/A9 forms fibrils in prostatic inclusions and S100A6 fibrillates in vitro and seeds SOD1 aggregation. Here we report a study designed to investigate whether β-aggregation is a feature extensive to more members of S100 family. In silico analysis of seven human S100 proteins revealed a direct correlation between aggregation and intrinsic disorder propensity scores, suggesting a relationship between these two independent properties. Averaged position-specific analysis and structural mapping showed that disorder-prone segments are contiguous to aggregation-prone regions and that whereas disorder is prominent on the hinge and target protein-interaction regions, segments with high aggregation propensity are found in ordered regions within the dimer interface. Acidic conditions likely destabilize the seven S100 studied by decreasing the shielding of aggregation-prone regions afforded by the quaternary structure. In agreement with the in silico analysis, hydrophobic moieties become accessible as indicated by strong ANS fluorescence. ATR-FTIR spectra support a structural inter-conversion from α-helices to intermolecular β-sheets, and prompt ThT-binding takes place with no noticeable lag phase. Dot blot analysis using amyloid conformational antibodies denotes a high diversity of conformers; subsequent analysis by TEM shows fibrils as dominant species. Altogether, our data suggests that β-aggregation and disorder-propensity are related properties in S100 proteins, and that the onset of aggregation is likely triggered by loss of protective tertiary and quaternary interactions.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A
matching cut
is a partition of the vertex set of a graph into two sets
A
and
B
such that each vertex has at most one neighbor in the other side of the cut. The
Matching Cut
problem asks whether a ...graph has a matching cut, and has been intensively studied in the literature. Motivated by a question posed by Komusiewicz et al. Discrete Applied Mathematics, 2020, we introduce a natural generalization of this problem, which we call
d
-Cut
: for a positive integer
d
, a
d
-
cut
is a bipartition of the vertex set of a graph into two sets
A
and
B
such that each vertex has at most
d
neighbors across the cut. We generalize (and in some cases, improve) a number of results for the
Matching Cut
problem. Namely, we begin with an NP-hardness reduction for
d
-Cut
on
(
2
d
+
2
)
-regular graphs and a polynomial algorithm for graphs of maximum degree at most
d
+
2
. The degree bound in the hardness result is unlikely to be improved, as it would disprove a long-standing conjecture in the context of internal partitions. We then give FPT algorithms for several parameters: the maximum number of edges crossing the cut, treewidth, distance to cluster, and distance to co-cluster. In particular, the treewidth algorithm improves upon the running time of the best known algorithm for
Matching Cut
. Our main technical contribution, building on the techniques of Komusiewicz et al. DAM, 2020, is a polynomial kernel for
d
-Cut
for every positive integer
d
, parameterized by the vertex deletion distance of the input graph to a cluster graph. We also rule out the existence of polynomial kernels when parameterizing simultaneously by the number of edges crossing the cut, the treewidth, and the maximum degree. Finally, we provide an exact exponential algorithm slightly faster than the naive brute force approach running in time
O
∗
2
n
.
Genomic imprinting alterations have been shown to be associated with assisted reproductive technologies (ARTs) in animals. At present, data obtained in humans are inconclusive; however, some ...epidemiological studies have demonstrated an increased incidence of imprinting disorders in children conceived by ARTs. In the present study, we focused on the effect of ARTs IVF and intracytoplasmic sperm injection (ICSI) on the epigenetic reprogramming of the maternally methylated imprinting control region KvDMR1 in clinically normal children. Qualitative and quantitative methylation at KvDMR1 were assessed by the methylation-specific PCR approach and by the methylation-sensitive enzymatic digestion associated with real-time PCR method, respectively. DNA was obtained from peripheral blood of 12/18 and umbilical cord blood and placenta of 6/18 children conceived by IVF or ICSI. The methylation patterns observed in this group were compared with the patterns observed in 30 clinically normal naturally conceived children (negative controls) and in 3 naturally conceived Beckwith–Wiedemann syndrome patients (positive controls). Hypomethylation at KvDMR1 was observed in 3/18 clinically normal children conceived by ARTs (2 conceived by IVF and 1 by ICSI). A discordant methylation pattern was observed in the three corresponding dizygotic twins. Our findings corroborate the hypothesis of vulnerability of maternal imprinting to ARTs. Furthermore, the discordant methylation at KvDMR1 observed between dizygotic twins could be consequent to one of the following possibilities: (i) a differential vulnerability of maternal imprints among different embryos; or (ii) epimutations that occurred during gametogenesis resulting in the production of oocytes without the correct primary imprint at KvDMR1.
Next-generation site-specific cysteine-based antibody-drug-conjugates (ADCs) broaden therapeutic index by precise drug-antibody attachments. However, manufacturing such ADCs for clinical validation ...requires complex full reduction and reoxidation processes, impacting product quality. To overcome this technical challenge, we developed a novel antibody manufacturing process through cysteine (Cys) metabolic engineering in Chinese hamster ovary cells implementing a unique cysteine-capping technology. This development enabled a direct conjugation of drugs after chemoselective-reduction with mild reductant tris(3-sulfonatophenyl)phosphine. This innovative platform produces clinical ADC products with superior quality through a simplified manufacturing process. This technology also has the potential to integrate Cys-based site-specific conjugation with other site-specific conjugation methodologies to develop multi-drug ADCs and exploit multi-mechanisms of action for effective cancer treatments.
•Decrease in complex II activity in depressed bipolar patients.•Increase mitochondrial superoxide, carbonyl and TBARS in depressed bipolar patients.•Increase mitochondrial superoxide dismutase in ...depressed bipolar patients.•Mitochondrial oxidative stress plays important roles in the depressive phase of BD.
The present study aims to investigate the oxidative stress parameters in isolated mitochondria, as well as looking at mitochondrial complex activity in patients with Bipolar Disorder (BD) during depressive or euthymic episodes. This study evaluated the levels of mitochondrial complex (I, II, II-III and IV) activity in lymphocytes from BD patients. We evaluated the following oxidative stress parameters: superoxide, thiobarbituric acid reactive species (TBARS) and carbonyl levels in submitochondrial particles of lymphocytes from bipolar patients. 51 bipolar patients were recruited into this study: 34 in the euthymic phase, and 17 in the depressive phase. Our results indicated that the depressive phase could increase the levels of mitochondrial superoxide, carbonyl and TBARS, and superoxide dismutase, and could decrease the levels of mitochondrial complex II activity in the lymphocytes of bipolar patients. It was also observed that there was a negative correlation between the Hamilton Depression Rating Scale (HDRS) and complex II activity in the lymphocytes of depressive bipolar patients. In addition, there was a positive correlation between HDRS and superoxide, superoxide dismutase, TBARS and carbonyl. Additionally, there was a negative correlation between complex II activity and oxidative stress parameters. In conclusion, our results suggest that mitochondrial oxidative stress and mitochondrial complex II dysfunction play important roles in the depressive phase of BD.
BACKGROUND The objectives of this study were: (i) to evaluate the effects of the levonorgestrel-releasing intrauterine system (LNG-IUS) on both proliferation and apoptosis markers and hormone ...receptors of the eutopic and ectopic endometrium of women experiencing pain related to endometriosis and (ii) to compare the results with those obtained with GnRH agonist (GnRHa) injections. METHODS Pre- and post-treatment endometrium and endometriosis specimens were obtained from 22 women experiencing pain related to endometriosis who were treated with LNG-IUS (n = 11) or GnRHa (n = 11) for 6 months. Changes in the expression of proliferating cell nuclear antigen, Fas, progesterone receptor (PRA) and estrogen receptor α (ER-α) were analyzed by immunohistochemistry. RESULTS The cell proliferation index was significantly reduced in the epithelium and stroma of both the eutopic and the ectopic endometrium after treatment with the LNG-IUS and GnRHa. Only LNG-IUS users showed an increased H-score for Fas in the epithelium of the eutopic and ectopic endometrium (P < 0.05). Expression of ER-α and PRA by the glandular epithelium was lower in the eutopic endometrium after both treatments, but this reduction was noted in the ectopic endometrium only after LNG-IUS treatments (P < 0.05). No difference was detected between groups for any of the markers. CONCLUSIONS LNG-IUS reduced both cell proliferation and the expression of PRA and ER-α and increased Fas expression in the eutopic and ectopic endometrium of patients with endometriosis. Some of these actions were not observed with GnRHa.
PDF
