Abstract Background Oral mucositis (OM) is a complication of chemoradiotherapy treatment of head and neck squamous cell carcinoma (HNSCC) patients with no effective therapy. This study was designed ...to assess the efficacy of preventive low-level laser therapy (LLLT) in reducing the incidence of grade 3–4 OM. Material and methods From June 2007 to December 2010, 94 HNSCC patients entered a prospective, randomized, double-blind, placebo-controlled phase III trial. Chemoradiotherapy consisted of conventional radiotherapy plus concurrent cisplatin every 3 weeks. A diode InGaAlP (660 nm–100 mW–1 J–4 J/cm2 ) was used. OM evaluation was performed by WHO and OMAS scales and quality of life by EORTC questionnaires (QLQ). Results A six-fold decrease in the incidence of grades 3–4 OM was detected in the LLLT group compared to the placebo; (6.4% versus 40.5%). LLLT impacted the incidence of grades 3–4 OM to a relative risk ratio of 0.158 (CI 95% 0.050–0.498). After treatment QLQ-C30 showed, differences favoring LLLT in physical, emotional functioning, fatigue, and pain; while the QLQ-H&N35 showed improvements in LLLT arm for pain, swallowing, and trouble with social eating. Conclusion Preventive LLLT in HNSCC patients receiving chemoradiotherapy is an effective tool for reducing the incidence of grade 3–4 OM. Efficacy data were corroborated by improvements seen in quality of life.
Serjania erecta
Raldk is an essential genetic resource due to its anti-inflammatory, gastric protection, and anti-Alzheimer properties. However, the genetic and evolutionary aspects of the species ...remain poorly known. Here, we sequenced and assembled the complete chloroplast genome of
S. erecta
and used it in a comparative analysis within the Sapindaceae family.
S. erecta
has a chloroplast genome (cpDNA) of 159,297 bp, divided into a Large Single Copy region (LSC) of 84,556 bp and a Small Single Copy region (SSC) of 18,057 bp that are surrounded by two Inverted Repeat regions (IRa and IRb) of 28,342 bp. Among the 12 species used in the comparative analysis,
S. erecta
has the fewest long and microsatellite repeats. The genome structure of Sapindaceae species is relatively conserved; the number of genes varies from 128 to 132 genes, and this variation is associated with three main factors: (1) Expansion and retraction events in the size of the IRs, resulting in variations in the number of
rpl22
,
rps19
, and
rps3
genes; (2) Pseudogenization of the
rps2
gene; and (3) Loss or duplication of genes encoding tRNAs, associated with the duplication of
trnH-GUG
in
X. sorbifolium
and the absence of
trnT-CGU
in the Dodonaeoideae subfamily. We identified 10 and 11 mutational hotspots for Sapindaceae and Sapindoideae, respectively, and identified six highly diverse regions (
tRNA-Lys — rps16, ndhC – tRNA-Val, petA – psbJ, ndhF, rpl32 – ccsA
, and
ycf1
) are found in both groups, which show potential for the development of DNA barcode markers for molecular taxonomic identification of
Serjania
. We identified that the
psaI
gene evolves under neutrality in Sapindaceae, while all other chloroplast genes are under strong negative selection. However, local positive selection exists in the
ndhF
,
rpoC2
,
ycf1
, and
ycf2
genes. The genes
ndhF
and
ycf1
also present high nucleotide diversity and local positive selection, demonstrating significant potential as markers. Our findings include providing the first chloroplast genome of a member of the Paullinieae tribe. Furthermore, we identified patterns in variations in the number of genes and selection in genes possibly associated with the family’s evolutionary history.
Mediterranean temporary ponds (MTPs) are seasonal wetland habitats usually flooded during the rainy season but drying out during the warmer months. Due to their biodiversity, uniqueness, and numerous ...threats, they are listed as a priority for conservation under the Habitats Directive. Despite all the efforts made so far, they are still in poor conservation status in the Mediterranean biogeographic region, making it urgent to define efficient conservation and restoration actions. In this work, we used two case studies to evaluate the conservation status improvement of MTPs located on the southwest coast of Portugal, following the implementation of different management techniques. Sampling was based on floristic surveys to assess plant richness and species frequency, namely of characteristic MTPs species. In the first case, we tested three management techniques (direct grazing, vegetation cutting, and biomass cut/removal, followed by topsoil plowing—simulating wild boar trampling and wallowing) in plots installed in three MTPs between 2017 and 2018. Plots subject to wild boar simulation disturbance showed higher species richness, higher frequency of characteristic species, and lower dominance of
Agrostis stolonifera
. In the second case, we upscaled this technique as an ecological restoration action by using it in 10 MTPs between 2018 and 2021. We observed a positive effect on the habitat's structure and conservation status, although the possible influence of recurrent drought periods in the last decade is discussed. This study provides insights into a rare wetland habitat based on lessons learned from hands‐on conservation actions, while also identifying new challenges and knowledge gaps.
Unraveling molecular mechanisms that regulate tumor development and proliferation is of the utmost importance in the quest to decrease the high mortality rate of adrenocortical carcinomas (ACC). Our ...aim was to evaluate the role of two of the mitogen‐activated protein kinase (MAPK) signaling pathways (extracellular signal‐regulated protein kinases ERKs 1/2 and p38) in the adrenocortical tumorigenesis, as well as the therapeutic potential of MAPK/ERK inhibition. ERKs 1/2 and p38 activation were evaluated in incidentalomas (INC; n = 10), benign Cushing's syndrome (BCS; n = 12), malignant Cushing's syndrome (MCS; n = 6) and normal adrenal glands (NAG; 8). ACC cell line (H295R) was used to evaluate the ability of PD184352 (0.1, 1, and 10 µM), a specific MEK‐MAPK‐ERK pathway inhibitor, to modulate cell proliferation, viability, metabolism, and steroidogenesis. ERKs 1/2 activation was significantly higher in MCS (2.83 ± 0.17) compared with NAG (1.00 ± 0.19 “arbitrary units”), INC (1.20 ± 0.13) and BCS (2.09 ± 0.09). Phospho‐p38 expression was absent in all the MCS analyzed. MAPK/ERK kinase (MEK) inhibition with PD184352 significantly decreased proliferation as well as steroidogenesis and also increased the redox state of the H295R cells. This data suggests that MEK‐MAPK‐ERK signaling has a role in adrenocortical tumorigenesis that could be potentially used as a diagnostic marker for malignancy and targeted treatment in ACC.
MEK‐MAPK‐ERK signaling pathways is important for adrenocortical tumorigenesis. Adrenocortical carcinomas (ACC) with Cushing syndrome have increased phospho‐ERK expression. MEK inhibitors also arise as an alternative targeted treatment of ACC.
Conversion of the cellular prion protein (PrPC) into its altered conformation, PrPSc, is believed to be the major cause of prion diseases. Although PrP is the only identified agent for these ...diseases, there is increasing evidence that other molecules can modulate the conversion. We have found that interaction of PrP with double-stranded DNA leads to a protein with higher β-sheet content and characteristics similar to those of PrPSc. RNA molecules can also interact with PrP and potentially modulate PrPC to PrPSc conversion or even bind differentially to both PrP isoforms. Here, we investigated the interaction of recombinant murine PrP with synthetic RNA sequences and with total RNA extracted from cultured neuroblastoma cells (N2aRNA). We found that PrP interacts with N2aRNA with nanomolar affinity, aggregates upon this interaction, and forms species partially resistant to proteolysis. RNA does not bind to N-terminal deletion mutants of PrP, indicating that the N-terminal region is important for this process. Cell viability assays showed that only the N2aRNA extract induces PrP-RNA aggregates that can alter the homeostasis of cultured cells. Small RNAs bound to PrP give rise to nontoxic small oligomers. Nuclear magnetic resonance measurements of the PrP-RNA complex revealed structural changes in PrP, but most of its native fold is maintained. These results indicate that there is selectivity in the species generated by interaction with different molecules of RNA. The catalytic effect of RNA on the PrPC→PrPSc conversion depends on the RNA sequence, and small RNA molecules may exert a protective effect.
Purpose
Evaluate the relationship of leptin receptor (LEPR) rs1137101, fat mass obesity-associated (FTO) receptors 9939609, melanocortin-4 receptors (MC4R) rs2229616 and rs17782313, and ...proliferator-activated receptor-gamma (PPARG) rs1801282 with clinical and metabolic phenotypes in prepubertal children.
Research question
What is the effect of polymorphisms on clinical and metabolic phenotypes in prepubertal children?
Methods
A cross-sectional descriptive study was performed to evaluate anthropometric features, percentage body fat (%BF), biochemical parameters, and genotype in 773 prepubertal children.
Results
FTO rs9939609 was associated with an increase in body mass index (BMI) and BMI
z
-score (zBMI). MC4R rs17782313 was associated with a decrease in BMI and +0.06 units in zBMI. LEPR, and PPARG-2 polymorphisms were associated with decreases in BMI and an increase and decrease units in zBMI, respectively. The homozygous SNPs demonstrated increases (FTO rs993609 and MC4R rs17782313) and decreases (LEPR rs1137101, PPARG rs1801282) in zBMI than the homozygous form of the major allele. In the overweight/obese group, the MC4R rs17782313 CC genotype showed higher average weight, zBMI, waist circumference, waist-circumference-to-height ratio, and waist-hip ratio, and lower BMI, mid-upper arm circumference, calf circumference, and %BF (
P
< 0.05). FTO rs9939609 AT and AA genotypes were associated with lower triglycerides (
P
< 0.05).
Conclusions
We showed that MC4R rs17782313 and FTO rs9939609 were positively associated with zBMI, with weak and very weak effects, respectively, suggesting a very scarce contribution to childhood obesity. LEPR rs1137101 and PPARG-2 rs1801282 had weak and medium negative effects on zBMI, respectively, and may slightly protect against childhood obesity.
Single Anastomosis Duodenal-Ileal Bypass with Sleeve Gastrectomy (SADI-S) is a restrictive/hypoabsorptive procedure recommended for patients with obesity class 3. For safety reasons, SADI-S can be ...splited into a two-step procedure by performing a sleeve gastrectomy (SG) first. This stepwise approach also provides an unprecedented opportunity to disentangle the weight loss mechanisms triggered by each component. The objective was to compare weight trajectories and postprandial endocrine and metabolic responses of patients with obesity class 3 submitted to SADI-S or sleeve gastrectomy (SG) as the first step of SADI-S.
Subjects submitted to SADI-S (n=7) or SG (n=7) at a tertiary referral public academic hospital, underwent anthropometric evaluation and a liquid mixed meal tolerance test (MMTT) pre-operatively and at 3, 6, and 12 months post-operatively.
Anthropometric parameters, as well as metabolic and micronutrient profiles, were not significantly different between groups, neither before nor after surgery. There were no significant differences in fasting or post-prandial glucose, insulin, C-peptide, ghrelin, insulin secretion rate (ISR) and insulin clearance during the MMTT between subjects submitted to SADI-S and SG. There was no lost to follow-up.
The restrictive component seems to be the main driver for weight loss and metabolic adaptations observed during the first 12 months after SADI-S, given that the weight trajectories and metabolic profiles do not differ from SG. This data provides support for a surgeons' choice of a two-step SADI-S without jeopardizing the weight loss outcomes.
Neurotensin (NT) is a gastro-intestinal hormone involved in several pathways that regulate energy and glucose homeostasis. NT was hypothesized to act in synergy with incretin hormones to potentiate ...its anti-diabetic effects. Additionally, circulating NT levels were shown to rise after bariatric surgery-induced weight loss. Knowledge of NT-secreting cells distribution along the small intestine and its variation according to diabetes status could provide insights on NT role in mediating type 2 diabetes (T2D) improvement after bariatric surgery. So, our aims were to characterize NT-expressing cell distribution along the human small intestine and to compare the relative density of NT-expressing cells in the small intestine of individuals with and without T2D undergoing bariatric surgery for obesity treatment. Autopsy-derived small intestine fragments (
n
= 30) were obtained at every 20 cm along the entire intestinal length. Additionally, jejunum biopsies (
n
= 29) were obtained during elective gastric bypass interventions from patients with (
n
= 10) or without T2D (
n
= 18). NT-expressing cells were identified by immunohistochemistry and quantified via computerized morphometric analysis. NT-expressing cell density increased along the human small intestine. NT-expressing cell density was significantly higher from 200 cm distal to the duodenojejunal flexure onward, as well as in subjects with T2D when compared to those without T2D. NT-expressing cell density increases along the human small gut, and a higher density is found in individuals with T2D. This finding suggests a potential role for NT in the mechanisms of disease and T2D improvement observed after bariatric surgery.
Conversion of the cellular prion protein (PrPC) into the scrapie form (PrPSc) is the leading step to the development of transmissible spongiform encephalopathies (TSEs), still incurable ...neurodegenerative disorders. Interaction of PrPC with cellular and synthetic ligands that induce formation of scrapie-like conformations has been deeply investigated in vitro. Different nucleic acid (NA) sequences bind PrP and convert it to β-sheet-rich or unfolded species; among such NAs, a 21-mer double-stranded DNA, D67, was shown to induce formation of PrP aggregates that were cytotoxic. However, in vivo effects of these PrP-DNA complexes were not explored. Herein, aggregates of recombinant full-length PrP (rPrP23-231) induced by interaction with the D67 aptamer were inoculated into the lateral ventricle of Swiss mice and acute effects were investigated. The aggregates had no influence on emotional, locomotor and motor behavior of mice. In contrast, mice developed cognitive impairment and hippocampal synapse loss, which was accompanied by intense activation of glial cells in this brain region. Our results suggest that the i.c.v. injection of rPrP:D67 aggregates is an interesting model to study the neurotoxicity of aggregated PrP in vivo, and that glial cell activation may be an important step for behavioral and cognitive dysfunction in prion diseases.
Highlights • We are the first to investigate the impact of LLLT on the cost of treatment those patients. • We report data suggesting that morbidity was lower in the Laser Group. • The incremental ...cost-effectiveness ratio (ICER) was US$ 4961.37 per grade 3–4 OM case prevented compared to no treatment. • LLLT was more cost-effective than placebo.
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