Category Archives: RESEARCH ARTICLE

Vulvar‐vaginal‐gingival‐otic syndrome

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Abstract

In order to retrospectively analyse the multi-site involvement pattern of erosive lichen planus patients, we retrospectively reported the clinical and medical data of three patients with erosive lichen planus which involving their vulva, vagina, gingiva, and ear canal. We confirmed the existence of otic lichen planus, and found that it is more common in patients with vulvovaginal-gingival syndrome of erosive lichen planus. Therefore, we propose ‘vulvovaginal-gingival-otic syndrome’ to further describe this rare compound pattern of lichen planus.

Reduced iron and cobalt levels in response to curcumin supplementation are not responsible for the prolonged larval development and do not affect the oxidative stress tolerance and polyamine status of D. melanogaster

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Reduced iron and cobalt levels in response to curcumin supplementation are not responsible for the prolonged larval development and do not affect the oxidative stress tolerance and polyamine status of D. melanogaster

Curcumin supplementation, similar to the iron chelator bathophenanthroline, lowered the iron but also the cobalt content, and to a lesser extent affected the manganese and zinc status of D. melanogaster. However, these alterations in trace metal balance did not affect catalase activity, oxidative stress tolerance, and polyamine status in fruit flies. In contrast, in curcumin-supplemented mice, the spleen exhibits an elevated spermidine production, which is most probably related to a compensatory growth due to curcumin-induced iron deficiency.


Abstract

Recent reports indicated that the phytochemical curcumin possesses iron-chelating activity. Here, by employing the fruit fly Drosophila melanogaster, we conducted feeding studies supplementing curcumin or, as a control, the iron chelator bathophenanthroline (BPA). First, the absorption and further metabolization of dietary curcuminoids were proved by metabolomics analyses. Next, we found that 0.2% dietary curcumin, similar to BPA, lowered the iron but also the cobalt content, and to a lesser extent affected the manganese and zinc status. Supplementation during larval stages was required and sufficient for both compounds to elicit these alterations in adult animals. However, curcumin-induced retarded larval development was not attributable to the changed trace metal status. In addition, a reduction in the iron content of up to 70% by curcumin or BPA supplementation did not reduce heme-dependent catalase activity and tolerance toward H2O2 in D. melanogaster. Moreover, polyamines were not influenced by curcumin treatment and decreased iron levels. This was confirmed for selected organs from 0.2% curcumin-treated mice, except for the spleen. Here, elevated spermidine level and concomitant upregulation of genes involved in polyamine production were associated with a putatively anemia-derived increased spleen mass. Our data underline that the metal-chelating property of curcumin needs to be considered in feeding studies.

Dapagliflozin improves diabetic cognitive impairment via indirectly modulating the mitochondria homeostasis of hippocampus in diabetic mice

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Dapagliflozin improves diabetic cognitive impairment via indirectly modulating the mitochondria homeostasis of hippocampus in diabetic mice

The goal of this study is to determine the underlying mechanism and look into dapagliflozin's impact on diabetic cognitive impairment. Diabetes-induced cognitive dysfunction was attenuated by dapagliflozin and the effect was indirect rather than direct.


Abstract

Cognitive impairment is increasingly recognized as an important comorbidity of diabetes progression; however, the underlying molecular mechanism is unclear. Dapagliflozin, an inhibitor of sodium-glucose co-transporter 2 (SGLT2), has shown promising effects against diabetes in rodent experiments and human clinical assays. This study aimed to determine the underlying mechanism and examine the effect of dapagliflozin on diabetic cognitive impairment. To create an in vivo model of diabetic cognitive impairment, streptozotocin (STZ)-induced diabetic mice were used. Dapagliflozin was administered to mice for 8 weeks. The context fear condition and Morris water maze test was used to evaluate mice's behavioral change. Western blotting was used to evaluate protein expression. Hematoxylin and eosin (HE) and Nissl staining were applied to monitor morphological and structural changes. Congo red staining was performed to identify the formation of senile plaques. Mitochondria morphology was examined using a transmission electron microscope, and blood flow in the mouse cerebral cortex was measured using a laser Doppler imaging assay. Comparison to the diabetes mellitus (DM) group, the dapagliflozin group had lower glucose levels. Behavioral studies have shown that dapagliflozin can restore memory deficits in diabetic mice. The murky cell membrane edges and Nissl bodies more difficult to identify in the DM group were revealed by HE and Nissl staining, which were both improved by dapagliflozin treatment. Dapagliflozin inhibited the progression of Aβ generation and the reduced cerebral blood flow in the DM group was rescued. After dapagliflozin treatment, damaged mitochondria and lack of SGLT2 in the hippocampus and cortex of diabetic mice were repaired. Diabetes-induced cognitive dysfunction was attenuated by dapagliflozin and the effect was indirect rather than direct.

Host exposure to a common pollutant can influence diversity–disease relationships

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Host exposure to a common pollutant can influence diversity–disease relationships

This study is the first to explore the influence of a ubiquitous pollutant of freshwater (NaCl) on diversity–disease dynamics via the influence of NaCl on host susceptibility to parasites.


Abstract

Hosts and parasites are embedded in communities where species richness and composition can influence disease outcomes (diversity–disease relationships). The direction and magnitude of diversity–disease relationships are influenced by variation in competence (ability to support and transmit infections) of hosts in a community. However, host susceptibility to parasites, which mediates host competence, is not static and is influenced by environmental factors, including pollutants. Despite the role that pollutants can play in augmenting host susceptibility, how pollutants influence diversity–disease dynamics is not well understood. Using an amphibian–trematode model, we tested how NaCl influences diversity–disease dynamics. We predicted that NaCl exposure can alter relative susceptibility of host species to trematodes, leading to cascading effects on the diversity–disease relationship. To test these predictions, we exposed hosts to benign or NaCl environments and generated communities that differed in number and composition of host species. We exposed these communities to trematodes and measured disease outcomes at the community (total infections across all hosts within a community) and species levels (average number of infections per host species within a community). Host species differed in their relative susceptibility to trematodes when exposed to NaCl. Consequently, at the community level (total infections across all hosts within a community), we only detected diversity–disease relationships (dilution effects) in communities where hosts were exposed to NaCl. At the species level, disease outcomes (average number of infections/species) and whether multi-species communities supported lower number of infections relative to single-species communities depended on community composition. Notably, however, as with overall community infection, diversity–disease relationships only emerged when hosts were exposed to NaCl. Synthesis. Pollutants are ubiquitous in nature and can influence disease dynamics across a number of host–parasite systems. Here, we show that NaCl exposure can alter the relative susceptibility of host species to parasites, influencing the relationship between biodiversity and disease at both community and species levels. Collectively, our study contributes to the limited knowledge surrounding environmental mediators of host susceptibility and their influence on diversity–disease dynamics.

Bioactive peptides in preterm human milk: Impact of maternal characteristics and their association to neonatal outcomes

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Bioactive peptides in preterm human milk: Impact of maternal characteristics and their association to neonatal outcomes

Hormone content of very preterm human milk is partially determined by maternal factors most of them regarding metabolic health and obstetric characteristics. Human milk concentration impacts on growth and development of preterm infants during their stay in the neonatal unit.


Abstract

Human milk adipokines in term babies seem partially determined by maternal factors and affect infant's development. We aimed to describe bioactive peptide concentration in very preterm human milk and associations to maternal characteristics and postnatal growth. Mothers delivering ≤32 weeks of gestation and their infant/s were recruited. At 4 weeks of lactation, an aliquot of 24-h-pooled milk was collected for exclusively breastfeeding dyads. Insulin, leptin, adiponectin, and milk fat globule epidermal growth factor-8 (MFG-E8) were measured by enzyme-linked immunoabsorbent assay in skimmed milk. One hundred mothers (28.8 ± 2.3 weeks at delivery) provided a milk sample. Milk insulin was related to gestational age, pre-pregnancy body mass index (BMI), and galactagogue treatment (final model: adjusted R 2: 0.330, p < 0.0001; adjusted β coefficients: galactagogue treatment: 0.348, p 0.001; pre-pregnancy BMI: 0.274, p 0.009; gestational age: −0.290, p 0.007). Adiponectin was higher in mothers with gestational diabetes (30.7 ± 6.5 vs. 24.8 ± 8 ng/mL, p 0.044). Leptin was associated with pre-pregnancy BMI (Spearman's ρ: 0.648, p < 0.0001) and MFG-E8 to presence of labor and multiple pregnancy (final linear regression model, R 2: 0.073, p 0.028, adjusted β coefficients: presence of labor −0.229, p 0.050; twins: −0.192, p 0.099). Milk adiponectin was associated with a greater decrease in length z-scores from birth to 28 days (Pearson's r: −0.225, p 0.032) and to discharge (Pearson's r: −0.290, p 0.003). Milk MFG-E8 was lower in milk of mothers whose babies experienced late-onset sepsis (13.3 ± 5.8 vs. 16.8 ± 6.3 μg/mL, p 0.023). Adipokines levels in preterm human milk are partially related to maternal metabolic status. Milk peptide concentration associates with early neonatal growth trajectories.

Identification of selection signatures in Capra hircus and Capra aegagrus in Iran

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Abstract

Identification of selection signatures may provide a better understanding of domestication process and candidate genes contributing to this process. In this study, two populations of domestic and wild goats from Iran were analyzed to identify selection signatures. RSB, iHS, and XP-EHH statistics were used in order to identify robust selection signatures in the goat genome. Genotype data of domestic and wild goats from the NextGen project was used. The data was related to 18 Capra aegagrus (wild goat) and 20 Capra hircus (domestic goat) from Iran. The iHS method indicated 675 and 441 selection signatures in C. aegagrus and C. hircus, respectively. RSB and XP-EHH methods showed about 370 and 447 selection signatures in C. aegagrus and C. hircus, respectively. These selection signatures were mainly associated with milk production, fleece trait, mammary epithelial cells, reproduction, and immune system.

Changes of the daily and hourly behavioral time of respiratory disease calves in a group rearing system for 7 days prior to the date of clinical diagnosis

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Abstract

Respiratory disease in calves is one of the most prominent diseases affecting their growth. The early and accurate detection of calf disease on the farm brings proper growth of calves. The objective of this study was to compare the daily and hourly behavioral time of diseased calves with the other calves in same pen (pen-mates) for 7 days prior to the diagnosis day. The calves (from 14 to 20 heads) were reared in a group. Day 0 was defined as the day of diagnosis. The number of diseased calves was 30 in the present experiment. The lying and eating behavior of calves were observed at 10-min intervals. The diseased calves have significantly (P < 0.01) shorter eating times than the pen-mates on the diagnosis day. The longest hourly time of the eating was in the period between 08:00 and 09:00, and shortest lying time was in the period between 09:00 and 10:00. Diseased calves had significantly (P < 0.05) longer daily lying time and shorter daily eating time than the pen-mates almost for the 7 days prior to the diagnosis day. Even though the daily behavioral time was different, the difference of behavioral time in successive hour periods was limited.

Caffeic acid phenethyl ester surmounts acquired resistance of AZD9291 in non‐small cell lung cancer cells

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Caffeic acid phenethyl ester surmounts acquired resistance of AZD9291 in non-small cell lung cancer cells

We developed and characterized a new tyrosine kinase inhibitor resistant non-small cell lung cancer (NSCLC) line, HCC827GR, which (1) was significantly resistant to both gefitinib and AZD9291; (2) had more in vitro tumorigenic potential as evident by a larger colony size from the anchorage-independent growth assay; and (3) exhibited a total of 26 differentially expressed genes (≥two fold-change) as compared to HCC827. These genes were involved in regulating cell growth, transcription, phase 1 metabolism, cell cycle, and apoptosis. Additionally, AZD9291 in combination with CAPE partially reverted the AZD9291 resistance in HCC827GR cells. This was exhibited by (1) synergistically suppressed cell viability; (2) cell cycle arrest and apoptosis induced through suppressing EGFR activation and modulating p53, p21, cyclin D1, and survivin protein expressions; and (3) differentially regulating genes involved in cancer drug resistance pathways.


Abstract

Epithelial growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the first-line therapy for EGFR mutated non-small cell lung cancer (NSCLC); however, resistance rapidly develops. The objective of this study was therefore to establish and characterize a gefitinib resistant NSCLC line (HCC827GR) and evaluate the therapeutic effects of natural products in combination with third-generation EGFR-TKI, AZD9291. The IC50 of gefitinib and AZD9291 in HCC827GR were significantly higher than those of HCC827 (p < 0.05). Furthermore, anchorage-independent colony assay indicated that HCC827GR cells were more aggressive than their predecessors. This was reflected by the gene/protein expression changes observed in HCC827GR versus HCC827 profiled by cancer drug resistance real-time polymerase chain reaction (RT-PCR) array and Western blot. Three natural products were screened and caffeic acid phenethyl ester (CAPE) exhibited the most significant combinative cytotoxic effect with AZD9291. Specifically, flow cytometry revealed that AZD9291 + CAPE considerably increased the fraction of cell in pre-G1 of the cell cycle and caspase-Glo3/7 assay showed a dramatic increase in apoptosis when compared to AZD9291 alone. Furthermore, Western blot showed significant downregulation of p-EGFR/p-AKT in HCC827GR cells treated with AZD9291 + CAPE as compared to AZD9291. Moreover, it is evident that AZD9291 + CAPE specifically resulted in a marked reduction in the protein expressions of the cell-proliferation-related genes p21, cyclin D1, and survivin. Finally, refined RT-PCR/Western blot data indicated that AZD9291 + CAPE may at least partially exert its synergistic effects via the PLK2 pathway. Together, these results suggest that CAPE is a clinically relevant compound to aid AZD9291 in treating EGFR-TKI resistant cells through modulating critical genes/proteins involved in cancer resistance/therapy.

Effects of low‐protein diet and feed restriction on mRNA expression of cationic amino acid transporters in porcine skeletal muscles

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Abstract

We investigated the effects of a low-protein diet and feed restriction on the mRNA expression of cationic amino acid transporters (CATs) in the longissimus dorsi (LD), rhomboideus (RH), and biceps femoris (BF) muscles of pigs. Eighteen piglets were divided into three groups: a control (CP21%), low-protein diet (LP, CP16%), and feed-restricted diet (FR, CP21%, 76% feed intake of control pigs) groups. The expression levels of CAT-1 in the LD and BF muscles of LP pigs were higher than that of control pigs, whereas that of FR pigs showed no difference. The CAT-2A expression levels in the RH muscle of FR pigs were higher than that of control pigs. The free lysine concentrations in all muscles of LP and FR pigs were lower than that of control pigs. To examine the factors that affect CATs mRNA expression, we evaluated the effects of lysine, arginine, insulin-like growth factor-I, and dexamethasone on the expression of CATs in C2C12 myotubes. CAT-1 expression levels increased in lysine and/or arginine deprivation. We show that CAT-1 and CAT-2A expression levels in skeletal muscles differ in response to dietary treatments and CAT-1 expression in skeletal muscles appears to increase in response to low free lysine concentrations.

Increased formation of neutrophil extracellular traps induced by autophagy and identification of autophagy‐related biomarkers in systemic lupus erythematosus

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Abstract

Abnormal death of neutrophils and the subsequent ineffective clearance of cell fragments result in production of autoantigens that can lead to systemic lupus erythematosus (SLE). Excessive formation of neutrophil extracellular traps (NETs) can trigger the synthesis of pro-inflammatory cytokines such as type I interferons, leading to tissue damage and immune dysfunction in SLE patients. In this study, we found that a decrease in neutrophil counts in the peripheral blood was correlated with clinical parameters in SLE patients. Patients with low neutrophil counts had high renal activity index and chronicity index scores. NET formation and neutrophil autophagy in SLE patients were increased. The autophagy inhibitor hydroxychloroquine was shown to restrict NET formation. Using comprehensive bioinformatics analysis, we found that the expression of the autophagy-related gene, hypoxia-inducible factor 1A (HIF1A), was enhanced in peripheral neutrophils and in the renal glomeruli in SLE patients. Targeting HIF1A could be a potential therapeutic approach for SLE.