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Genome Biology and Evolution Jun 2024Aposematic organisms rely on their conspicuous appearance to signal that they are defended and unpalatable. Such phenotypes are strongly tied to survival and...
Aposematic organisms rely on their conspicuous appearance to signal that they are defended and unpalatable. Such phenotypes are strongly tied to survival and reproduction. Aposematic colors and patterns are highly variable; however, the genetic, biochemical and physiological mechanisms producing this conspicuous coloration remain largely unidentified. Here, we identify genes potentially affecting color variation in two color morphs of Ranitomeya imitator: the orange-banded Sauce and the redheaded Varadero morphs. We examine gene expression in black and orange skin patches from the Sauce morph and black and red skin patches from the Varadero morph. We identified genes differentially expressed between skin color patches, including those that are involved in melanin synthesis (e.g., mlana, pmel, tyrp1), iridophore development (e.g., paics, ppat, ak1), pteridine synthesis (e.g., gch1, recql4, xdh), and carotenoid metabolism (e.g., dgat2, rbp1, scarb2). In addition, using weighted gene network analysis, we identified the top 50 genes with high connectivity from the most significant network associated with gene expression differences between color morphs. Of these 50 genes, 14 were known to be related to color production (gch1, gmps, gpr143, impdh1, mc1r, pax3-a, pax7, ppat, rab27a, rlbp1, tfec, trpm1, xdh).
PubMed: 38874406
DOI: 10.1093/gbe/evae123 -
Frontiers in Immunology 2024The intricate immune mechanisms governing mucosal healing following intestinal damage induced by cytotoxic drugs remain poorly understood. The goal of this study was to...
The intricate immune mechanisms governing mucosal healing following intestinal damage induced by cytotoxic drugs remain poorly understood. The goal of this study was to investigate the role of lymphotoxin beta receptor (LTβR) signaling in chemotherapy-induced intestinal damage. LTβR deficient mice exhibited heightened body weight loss, exacerbated intestinal pathology, increased proinflammatory cytokine expression, reduced IL-22 expression, and proliferation of intestinal epithelial cells following methotrexate (MTX) treatment. Furthermore, LTβRIL-22 mice succumbed to MTX treatment, suggesting that LTβR- and IL-22- dependent pathways jointly promote mucosal repair. Although both LTβR ligands LIGHT and LTβ were upregulated in the intestine early after MTX treatment, LIGHT mice, but not LTβ mice, displayed exacerbated disease. Further, we revealed the critical role of T cells in mucosal repair as T cell-deficient mice failed to upregulate intestinal LIGHT expression and exhibited increased body weight loss and intestinal pathology. Analysis of mice with conditional inactivation of LTβR revealed that LTβR signaling in intestinal epithelial cells, but not in Lgr5 intestinal stem cells, macrophages or dendritic cells was critical for mucosal repair. Furthermore, inactivation of the non-canonical NF-kB pathway member RelB in intestinal epithelial cells promoted MTX-induced disease. Based on these results, we propose a model wherein LIGHT produced by T cells activates LTβR-RelB signaling in intestinal epithelial cells to facilitate mucosal repair following chemotherapy treatment.
Topics: Animals; Intestinal Mucosa; Lymphotoxin beta Receptor; Signal Transduction; Mice; Mice, Knockout; Transcription Factor RelB; Methotrexate; Epithelial Cells; Mice, Inbred C57BL; Interleukin-22; Interleukins
PubMed: 38873613
DOI: 10.3389/fimmu.2024.1388496 -
Scientific Reports Jun 2024Low-grade chronic inflammation is associated with many age-related conditions. Non-invasive methods to monitor low-grade chronic inflammation may improve the management...
Low-grade chronic inflammation is associated with many age-related conditions. Non-invasive methods to monitor low-grade chronic inflammation may improve the management of older people at risk of poorer outcomes. This longitudinal cohort study has determined baseline inflammation using neopterin volatility in monthly urine samples of 45 independent older adults (aged 65-75 years). Measurement of neopterin, an inflammatory metabolite, enabled stratification of individuals into risk categories based on how often in a 12-month period their neopterin level was raised. Hearing was measured (pure-tone audiometry) at baseline, 1 year and 3 years of the study. Results show that those in the highest risk category (neopterin raised greater than 50% of the time) saw greater deterioration, particularly in high-frequency, hearing. A one-way Welch's ANOVA showed a significant difference between the risk categories for change in high-frequency hearing (W (3, 19.6) = 9.164, p = 0.0005). Despite the study size and duration individuals in the highest risk category were more than twice as likely to have an additional age-related morbidity than those in the lowest risk category. We conclude that volatility of neopterin in urine may enable stratification of those at greatest risk of progression of hearing loss.
Topics: Humans; Neopterin; Aged; Male; Female; Longitudinal Studies; Hearing Loss; Audiometry, Pure-Tone; Biomarkers; Auditory Threshold; Inflammation
PubMed: 38871776
DOI: 10.1038/s41598-024-64648-7 -
Cancer Radiotherapie : Journal de La... Jun 2024
Topics: Humans; Fluorouracil; Leucovorin; Rectal Neoplasms; Organoplatinum Compounds; Neoadjuvant Therapy; Antineoplastic Combined Chemotherapy Protocols
PubMed: 38871603
DOI: 10.1016/j.canrad.2023.12.002 -
Proceedings of the National Academy of... Jun 2024Biofilm formation and surface attachment in multiple Alphaproteobacteria is driven by unipolar polysaccharide (UPP) adhesins. The pathogen produces a UPP adhesin, which...
Biofilm formation and surface attachment in multiple Alphaproteobacteria is driven by unipolar polysaccharide (UPP) adhesins. The pathogen produces a UPP adhesin, which is regulated by the intracellular second messenger cyclic diguanylate monophosphate (c-di-GMP). Prior studies revealed that DcpA, a diguanylate cyclase-phosphodiesterase, is crucial in control of UPP production and surface attachment. DcpA is regulated by PruR, a protein with distant similarity to enzymatic domains known to coordinate the molybdopterin cofactor (MoCo). Pterins are bicyclic nitrogen-rich compounds, several of which are produced via a nonessential branch of the folate biosynthesis pathway, distinct from MoCo. The pterin-binding protein PruR controls DcpA activity, fostering c-di-GMP breakdown and dampening its synthesis. Pterins are excreted, and we report here that PruR associates with these metabolites in the periplasm, promoting interaction with the DcpA periplasmic domain. The pteridine reductase PruA, which reduces specific dihydro-pterin molecules to their tetrahydro forms, imparts control over DcpA activity through PruR. Tetrahydromonapterin preferentially associates with PruR relative to other related pterins, and the PruR-DcpA interaction is decreased in a mutant. PruR and DcpA are encoded in an operon with wide conservation among diverse Proteobacteria including mammalian pathogens. Crystal structures reveal that PruR and several orthologs adopt a conserved fold, with a pterin-specific binding cleft that coordinates the bicyclic pterin ring. These findings define a pterin-responsive regulatory mechanism that controls biofilm formation and related c-di-GMP-dependent phenotypes in and potentially acts more widely in multiple proteobacterial lineages.
Topics: Biofilms; Agrobacterium tumefaciens; Pterins; Cyclic GMP; Bacterial Proteins; Proteobacteria; Molybdenum Cofactors; Periplasm; Periplasmic Proteins; Periplasmic Binding Proteins; Gene Expression Regulation, Bacterial
PubMed: 38870058
DOI: 10.1073/pnas.2319903121 -
ACS Applied Materials & Interfaces Jun 2024Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in...
Atherosclerotic plaques exhibit high cholesterol deposition and oxidative stress resulting from high reactive oxygen species (ROS). These are the major components in plaques and the main pro-inflammatory factor. Therefore, it is crucial to develop an effective therapeutic strategy that can simultaneously address the multiple pro-inflammatory factors removing cholesterol and inhibiting the overaccumulated ROS. In this study, we constructed macrophage membrane-encapsulated biomimetic nanoparticles (MM@DA-pCD@MTX), which not only alleviate cholesterol deposition at the plaque lesion reverse cholesterol transport but also scavenge the overaccumulated ROS. β-Cyclodextrin (β-CD) and the loaded methotrexate (MTX) act synergistically to induce cholesterol efflux for inhibiting the formation of foam cells. Among them, MTX up-regulated the expression of ABCA1, CYP27A1, and SR-B1. β-CD increased the solubility of cholesterol crystals. In addition, the ROS scavenging property of dopamine (DA) was perfectly preserved in MM@DA-pCD@MTX, which could scavenge the overaccumulated ROS to alleviate the oxidative stress at the plaque lesion. Last but not least, MM-functionalized "homing" targeting of atherosclerotic plaques not only enables the targeted drug delivery but also prolongs circulation time and drug half-life. In summary, MM@DA-pCD@MTX emerges as a potent, multifunctional therapeutic platform for AS treatment, offering a high degree of biosafety and efficacy in addressing the complex pathophysiology of atherosclerosis.
Topics: Dopamine; Nanoparticles; Atherosclerosis; Mice; Animals; Biomimetic Materials; Methotrexate; Cholesterol; Macrophages; Reactive Oxygen Species; Humans; Cyclodextrins; RAW 264.7 Cells; Oxidative Stress; Drug Carriers; beta-Cyclodextrins
PubMed: 38867426
DOI: 10.1021/acsami.4c04431 -
Journal of Cellular and Molecular... Jun 2024Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded...
Chemotherapy resistance remains a significant challenge in treating ovarian cancer effectively. This study addresses this issue by utilizing a dual drug-loaded nanomicelle system comprising albendazole (ABZ) and paclitaxel (PTX), encapsulated in a novel carrier matrix of D-tocopheryl polyethylene glycol 1000 succinate vitamin E (TPGS), soluplus and folic acid. Our objective was to develop and optimize this nanoparticulate delivery system using solvent evaporation techniques to enhance the therapeutic efficacy against ovarian cancer. The formulation process involved pre-formulation, formulation, optimization, and comprehensive characterization of the micelles. Optimization was conducted through a 32 factorial design, focusing on the effects of polymer ratios on particle size, zeta potential, polydispersity index (PDI) and entrapment efficiency (%EE). The optimal formulation demonstrated improved dilution stability, as indicated by a critical micelle concentration (CMC) of 0.0015 mg/mL for the TPGS-folic acid conjugate (TPGS-FOL). Extensive characterization included differential scanning calorimetry (DSC), nuclear magnetic resonance (NMR), and Fourier-transform infrared spectroscopy (FTIR). The release profile exhibited an initial burst followed by sustained release over 90 h. The cytotoxic potential of the formulated micelles was superior to that of the drugs alone, as assessed by MTT assays on SKOV3 ovarian cell lines. Additionally, in vivo studies confirmed the presence of both drugs in plasma and tumour tissues, suggesting effective targeting and penetration. In conclusion, the developed TPGS-Fol-based nanomicelles for co-delivering ABZ and PTX show promising results in overcoming drug resistance, enhancing solubility, sustaining drug release, and improving therapeutic outcomes in ovarian cancer treatment.
Topics: Female; Paclitaxel; Micelles; Albendazole; Ovarian Neoplasms; Humans; Animals; Cell Line, Tumor; Drug Carriers; Polyethylene Glycols; Vitamin E; Folic Acid; Mice; Drug Liberation; Particle Size; Polyvinyls; Polymers; Xenograft Model Antitumor Assays
PubMed: 38864691
DOI: 10.1111/jcmm.18389 -
Journal of Obstetrics and Gynaecology :... Dec 2024The pre-treatment characteristics of the patient and ectopic pregnancy to determine the patients who are likely to successfully respond to methotrexate (MTX) therapy...
BACKGROUND
The pre-treatment characteristics of the patient and ectopic pregnancy to determine the patients who are likely to successfully respond to methotrexate (MTX) therapy remain controversial. This study investigated the outcomes of ectopic pregnancy after one and two MTX doses and their independent predictors.
METHODS
Retrospective cross-sectional study of women who consented to MTX treatment in 2017-2018 at our institution ( = 317). Of these, patients with Caesarean scar pregnancies were excluded because they require different treatment protocols ( = 25). All patients were treated according to our institution's protocol based on international guidelines and standardised across the three hospitals included in the current study. We retrieved patients' demographics, laboratory, ultrasonography, and clinical characteristics from our hospital database. Serum β-human chorionic gonadotropin (β-hCG) was measured using electrochemiluminescence immunoassay; ectopic pregnancy was diagnosed using ultrasonography (transvaginal probe).
RESULTS
Two ninety-two patients were included in the current analysis. Age, pre-treatment β-hCG levels, sonographic presence of yolk sac, presence of foetal cardiac activity, and pelvic pain were significantly different between patients with successful and unsuccessful outcomes. Younger age (adjusted odds ratio [aOR] 2.33, 95% confidence interval (CI) 1.16-4.66, = .017), no pelvic pain (aOR 2.65, 95%CI 1.03-6.83, = .043), lower initial β-hCG level (aOR 1.32, 95%CI 1.08-1.59, = .005), and absence of foetal cardiac activity (aOR 12.63; 95% CI 1.04-153.6; = .047) were independently associated with success. Treatment failure odds were >2 folds higher for each 10-year age increase ( = .017), 32% higher for each 1000 IU/L increase in initial β-hCG level ( = .005), and >2 folds higher in presence of pelvic pain ( = .043).
CONCLUSIONS
MTX is effective in most patients, averting invasive surgery, which might affect fertility. Pre-treatment β-hCG levels, age, pelvic pain, and foetal cardiac activity was independently associated with outcomes. Research should assess the relationship between the ectopic pregnancy size and treatment outcomes and refine β-hCG titres where treatment would be ineffective.
Topics: Humans; Female; Methotrexate; Pregnancy; Adult; Retrospective Studies; Cross-Sectional Studies; Abortifacient Agents, Nonsteroidal; Chorionic Gonadotropin, beta Subunit, Human; Pregnancy, Tubal; Treatment Outcome
PubMed: 38864434
DOI: 10.1080/01443615.2024.2361456 -
Scientific Reports Jun 2024Iron deficiency is a widespread micronutrient deficiency, impacting over 30% of the global population. Iron Folic Acid supplement is recommended for pregnant women to...
Iron deficiency is a widespread micronutrient deficiency, impacting over 30% of the global population. Iron Folic Acid supplement is recommended for pregnant women to counter iron deficiency anemia and neural tube anomalies. Although Iron Folic Acid supplementation is integral to Ethiopian antenatal care, one in four women in Ethiopia experiences anemia during pregnancy suggesting poor compliance. This study aimed to investigate compliance level and associated factors of Iron Folic Acid supplementation among pregnant women attending antenatal care in Wuchale Woreda of North Shoa Zone, Ethiopia. An institutional-based cross-sectional study was conducted among 302 pregnant women from March 20 to April 5, 2021, who were selected using a systematic random sampling technique. Data were collected through face-to-face interview, entered epi-data, and exported to Statistical Package for the Social Sciences for analysis. A multivariable logistic regression was used to identify factors associated with compliance level. All the results were presented with 95% confidence intervals. The compliance with Iron Folic Acid supplementation was 47.0%. Residing nearest to the health facility (AOR = 2.46; 95% CI 1.32, 4.57), initiating antenatal care at health center (AOR = 2.23; 95% CI 1.17, 4.51), having a family size of 4 and above (AOR = 4.99; 95% CI 2.43, 10.24), and receiving information from health extension workers (AOR = 5.52; 95% CI 1.30, 23.54) increased compliance with Iron Folic Acid supplementation. Less than half of the pregnant women were compliant with Iron Folic Acid utilization. There is a need to prioritize promoting the importance of Iron Folic Acid supplementation through health education particularly by targeting pregnant women with identified factors.
Topics: Humans; Female; Folic Acid; Pregnancy; Ethiopia; Adult; Dietary Supplements; Cross-Sectional Studies; Iron; Prenatal Care; Anemia, Iron-Deficiency; Young Adult; Adolescent; Pregnant Women; Patient Compliance
PubMed: 38862566
DOI: 10.1038/s41598-024-63111-x -
BMJ Open Jun 2024This systematic review and meta-analysis aimed to comprehensively assess the impact of weekly iron-folic acid supplementation (WIFAS) on the nutrition, health and... (Meta-Analysis)
Meta-Analysis
Weekly iron-folic acid supplementation and its impact on children and adolescents iron status, mental health and school performance: a systematic review and meta-analysis in sub-Saharan Africa.
OBJECTIVE
This systematic review and meta-analysis aimed to comprehensively assess the impact of weekly iron-folic acid supplementation (WIFAS) on the nutrition, health and educational outcomes of children and adolescents in sub-Saharan Africa.
DESIGN
A systematic review and meta-analysis was used.
DATA SOURCES
Five databases, namely, MEDLINE, Scopus, Web of Science, Cochrane Library and Google Scholar, were systematically searched for relevant articles up to 23 August 2023.
ELIGIBILITY CRITERIA
It was focused on randomised controlled trials involving children and adolescents in sub-Saharan Africa, exploring the effects of iron supplementation on various outcomes, such as serum ferritin and haemoglobin levels, anaemia, mental health and school performance.
DATA EXTRACTION AND SYNTHESIS
The Joanna Briggs Institute Critical Appraisal tools were used for quality assessment, with two independent reviewers thoroughly evaluating each paper. Using the Cochrane risk of bias tool, we evaluated the certainty of evidence such as the risk of bias, inconsistency, indirectness, imprecision and publication bias.
RESULTS
A systematic review of 10 articles revealed that WIFAS significantly increased serum ferritin levels in adolescent girls (Hedge's g=0.53, 95% CI 0.28 to 0.78; heterogeneity I=41.21%, p<0.001) and haemoglobin levels in school-aged children (Hedge's g=0.37, 95% CI 0.01 to 0.73; heterogeneity I=91.62%, p<0.001). The analysis further demonstrated a substantial reduction in the risk of anaemia by 20% (risk ratio=0.8, 95% CI 0.69 to 0.93; heterogeneity I=28.12%, p<0.001).
CONCLUSION
WIFAS proved effective in enhancing serum ferritin and haemoglobin concentrations and lowering the risk of anaemia in school-aged children and adolescents compared with a placebo. Similarly, there are not enough studies to examine the effects of WIFAS on school performance. However, information regarding mental health problems, mortality and potential side effects remains insufficient.
PROSPERO REGISTRATION NUMBER
CRD42023397898.
Topics: Humans; Child; Adolescent; Dietary Supplements; Africa South of the Sahara; Mental Health; Iron; Folic Acid; Ferritins; Anemia, Iron-Deficiency; Hemoglobins; Randomized Controlled Trials as Topic; Female; Nutritional Status
PubMed: 38862227
DOI: 10.1136/bmjopen-2024-084033