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BMC Veterinary Research Jun 2024Wound management is a critical procedure in veterinary practice. A wound is an injury that requires the body's cells' alignment to break down due to external assault,...
BACKGROUND
Wound management is a critical procedure in veterinary practice. A wound is an injury that requires the body's cells' alignment to break down due to external assault, such as trauma, burns, accidents, and diseases. Re-epithelization, extracellular matrix deposition, especially collagen, inflammatory cell infiltration, and development of new blood capillaries are the four features that are used to evaluate the healing process. Using a natural extract for wound management is preferred to avoid the side effects of synthetic drugs. The current study aimed to assess the effect of major pregnane glycoside arabincoside B (AR-B) isolated from Caralluma arabica (C. arabica) for the wound healing process.
METHOD
AR-B was loaded on a gel for wound application. Rats were randomly distributed into six groups: normal, positive control (PC), MEBO®, AR-B 0.5%, AR-B 1%, and AR-B 1.5%, to be 6 animals in each group. Wounds were initiated under anesthesia with a 1 cm diameter tissue needle, and treatments were applied daily for 14 days. The collected samples were tested for SOD, NO, and MDA. Gene expression of VEGF and Caspase-3. Histopathological evaluation was performed at two-time intervals (7 and 14 days), and immunohistochemistry was done to evaluate α -SMA, TGF-β, and TNF-α.
RESULT
It was found that AR-B treatment enhanced the wound healing process. AR-B treated groups showed reduced MDA and NO in tissue, and SOD activity was increased. Re-epithelization and extracellular matrix deposition were significantly improved, which was confirmed by the increase in TGF-β and α -SMA as well as increased collagen deposition. TNF-α was reduced, which indicated the subsiding of inflammation. VEGF and Caspase-3 expression were reduced.
CONCLUSION
Our findings confirmed the efficiency of AR-B in enhancing the process of wound healing and its potential use as a topical wound dressing in veterinary practice.
Topics: Animals; Wound Healing; Rats; Male; Apocynaceae; Bandages; Vascular Endothelial Growth Factor A; Glycosides; Pregnanes; Tumor Necrosis Factor-alpha; Superoxide Dismutase; Caspase 3; Rats, Sprague-Dawley
PubMed: 38951783
DOI: 10.1186/s12917-024-04128-2 -
BMC Psychiatry Jul 2024Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increasing evidence suggests that leptin is involved in the pathology of autism spectrum disorder (ASD). In this study, our objective was to investigate the levels of leptin in the blood of children with ASD and to examine the overall profile of adipokine markers in ASD through meta-analysis.
METHODS
Leptin concentrations were measured using an enzyme-linked immunosorbent assay (ELISA) kit, while adipokine profiling, including leptin, was performed via meta-analysis. Original reports that included measurements of peripheral adipokines in ASD patients and healthy controls (HCs) were collected from databases such as Web of Science, PubMed, and Cochrane Library. These studies were collected from September 2022 to September 2023 and followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Standardized mean differences were calculated using a random effects model for the meta-analysis. Additionally, we performed meta-regression and explored heterogeneity among studies.
RESULTS
Our findings revealed a significant increase in leptin levels in children with ASD compared to HCs (p = 0.0319). This result was consistent with the findings obtained from the meta-analysis (p < 0.001). Furthermore, progranulin concentrations were significantly reduced in children with ASD. However, for the other five adipokines analyzed, there were no significant differences observed between the children with ASD and HCs children. Heterogeneity was found among the studies, and the meta-regression analysis indicated that publication year and latitude might influence the results of the meta-analysis.
CONCLUSIONS
These findings provide compelling evidence that leptin levels are increased in children with ASD compared to healthy controls, suggesting a potential mechanism involving adipokines, particularly leptin, in the pathogenesis of ASD. These results contribute to a better understanding of the pathology of ASD and provide new insights for future investigations.
Topics: Humans; Autism Spectrum Disorder; Leptin; Child; Adipokines; Biomarkers
PubMed: 38951775
DOI: 10.1186/s12888-024-05936-4 -
BMC Pediatrics Jun 2024Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and... (Observational Study)
Observational Study
PURPOSE
Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients.
METHODS
A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05.
RESULTS
In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation.
CONCLUSIONS
MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.
Topics: Humans; Fibroblast Growth Factor-23; Infant, Newborn; Female; Fibroblast Growth Factors; Biomarkers; Prospective Studies; Male; Bone Diseases, Metabolic; Infant, Premature, Diseases; Infant, Premature
PubMed: 38951759
DOI: 10.1186/s12887-024-04897-7 -
Scientific Reports Jul 2024The primary objective of analyzing the data obtained in a mass spectrometry-based proteomic experiment is peptide and protein identification, or correct assignment of...
The primary objective of analyzing the data obtained in a mass spectrometry-based proteomic experiment is peptide and protein identification, or correct assignment of the tandem mass spectrum to one amino acid sequence. Comparison of empirical fragment spectra with the theoretical predicted one or matching with the collected spectra library are commonly accepted strategies of proteins identification and defining of their amino acid sequences. Although these approaches are widely used and are appreciably efficient for the well-characterized model organisms or measured proteins, they cannot detect novel peptide sequences that have not been previously annotated or are rare. This study presents PowerNovo tool for de novo sequencing of proteins using tandem mass spectra acquired in a variety of types of mass analyzers and different fragmentation techniques. PowerNovo involves an ensemble of models for peptide sequencing: model for detecting regularities in tandem mass spectra, precursors, and fragment ions and a natural language processing model, which has a function of peptide sequence quality assessment and helps with reconstruction of noisy sequences. The results of testing showed that the performance of PowerNovo is comparable and even better than widely utilized PointNovo, DeepNovo, Casanovo, and Novor packages. Also, PowerNovo provides complete cycle of processing (pipeline) of mass spectrometry data and, along with predicting the peptide sequence, involves the peptide assembly and protein inference blocks.
Topics: Tandem Mass Spectrometry; Sequence Analysis, Protein; Peptides; Amino Acid Sequence; Software; Proteomics; Algorithms
PubMed: 38951578
DOI: 10.1038/s41598-024-65861-0 -
Scientific Reports Jul 2024Cartilage tissue engineering aims to develop functional substitutes for treating cartilage defects and osteoarthritis. Traditional two-dimensional (2D) cell culture...
Cartilage tissue engineering aims to develop functional substitutes for treating cartilage defects and osteoarthritis. Traditional two-dimensional (2D) cell culture systems lack the complexity of native cartilage, leading to the development of 3D regenerative cartilage models. In this study, we developed a 3D model using Gelatin Methacryloyl (GelMA)-based hydrogels seeded with Y201 cells, a bone marrow mesenchymal stem cell line. The model investigated chondrogenic differentiation potential in response to Wnt3a stimulation within the GelMA scaffold and validated using known chondrogenic agonists. Y201 cells demonstrated suitability for the model, with increased proteoglycan content and upregulated chondrogenic marker expression under chondrogenic conditions. Wnt3a enhanced cell proliferation, indicating activation of the Wnt/β-catenin pathway, which plays a role in cartilage development. GelMA hydrogels provided an optimal scaffold, supporting cell viability and proliferation. The 3D model exhibited consistent responses to chondrogenic agonists, with TGF-β3 enhancing cartilage-specific extracellular matrix (ECM) production and chondrogenic differentiation. The combination of Wnt3a and TGF-β3 showed synergistic effects, promoting chondrogenic differentiation and ECM production. This study presents a 3D regenerative cartilage model with potential for investigating cartilage biology, disease mechanisms, and drug screening. The model provides insights into complex cartilage regeneration mechanisms and offers a platform for developing therapeutic approaches for cartilage repair and osteoarthritis treatment.
Topics: Wnt3A Protein; Chondrogenesis; Cell Differentiation; Tissue Engineering; Cell Proliferation; Hydrogels; Mesenchymal Stem Cells; Humans; Cartilage; Gelatin; Tissue Scaffolds; Transforming Growth Factor beta3; Cell Line; Extracellular Matrix; Wnt Signaling Pathway; Chondrocytes; Animals
PubMed: 38951570
DOI: 10.1038/s41598-024-65970-w -
Nature Communications Jul 2024The conversion of a soluble protein into polymeric amyloid structures is a process that is poorly understood. Here, we describe a fully redox-regulated amyloid system in...
The conversion of a soluble protein into polymeric amyloid structures is a process that is poorly understood. Here, we describe a fully redox-regulated amyloid system in which cysteine oxidation of the tumor suppressor protein p16 leads to rapid amyloid formation. We identify a partially-structured disulfide-bonded dimeric intermediate species that subsequently assembles into fibrils. The stable amyloid structures disassemble when the disulfide bond is reduced. p16 is frequently mutated in cancers and is considered highly vulnerable to single-point mutations. We find that multiple cancer-related mutations show increased amyloid formation propensity whereas mutations stabilizing the fold prevent transition into amyloid. The complex transition into amyloids and their structural stability is therefore strictly governed by redox reactions and a single regulatory disulfide bond.
Topics: Oxidation-Reduction; Amyloid; Humans; Cyclin-Dependent Kinase Inhibitor p16; Cysteine; Disulfides; Sulfhydryl Compounds; Mutation; Polymerization
PubMed: 38951545
DOI: 10.1038/s41467-024-49581-7 -
Scientific Reports Jul 2024Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study... (Comparative Study)
Comparative Study
Digital positron emission tomography/computed tomography (PET/CT) has shown enhanced sensitivity and spatial resolution compared with analog PET/CT. The present study compared the diagnostic performance of digital and analog PET/CT with [Ga]Ga-PSMA-11 in prostate cancer patients who experienced biochemical recurrence (BCR) after prostatectomy. Forty prostate cancer patients who experienced BCR, defined as serum prostate-specific antigen (PSA) concentrations exceeding 0.2 ng/mL after prostatectomy, were prospectively recruited. These patients were stratified into three groups based on their serum PSA levels. [Ga]Ga-PSMA-11 was injected into each patient, and images were acquired using both analog and digital PET/CT scanners. Analog and digital PET/CT showed comparable lesion detection rate (71.8% vs. 74.4%), sensitivity (85.0% vs. 90.0%), and positive predictive value (PPV, 100.0% vs. 100.0%). However, digital PET/CT detected more lesions (139 vs. 111) and had higher maximum standardized uptake values (SUVmax, 14.3 vs. 10.3) and higher kappa index (0.657 vs. 0.502) than analog PET/CT, regardless of serum PSA levels. On both analog and digital PET/CT, lesion detection rates and interrater agreement increased with increasing serum PSA levels. Compared with analog PET/CT, digital PET/CT detected more lesions with a higher SUVmax and better interrater agreement in prostate cancer patients who experienced BCR after prostatectomy.
Topics: Humans; Male; Prostatic Neoplasms; Prostatectomy; Positron Emission Tomography Computed Tomography; Aged; Prospective Studies; Gallium Radioisotopes; Middle Aged; Neoplasm Recurrence, Local; Gallium Isotopes; Prostate-Specific Antigen; Edetic Acid; Oligopeptides
PubMed: 38951530
DOI: 10.1038/s41598-024-65399-1 -
Nature Communications Jun 2024Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is...
Obesity is a major cause of metabolic dysfunction-associated steatohepatitis (MASH) and is characterized by inflammation and insulin resistance. Interferon-γ (IFNγ) is a pro-inflammatory cytokine elevated in obesity and modulating macrophage functions. Here, we show that male mice with loss of IFNγ signaling in myeloid cells (Lyz-IFNγR2) are protected from diet-induced insulin resistance despite fatty liver. Obesity-mediated liver inflammation is also attenuated with reduced interleukin (IL)-12, a cytokine primarily released by macrophages, and IL-12 treatment in vivo causes insulin resistance by impairing hepatic insulin signaling. Following MASH diets, Lyz-IFNγR2 mice are rescued from developing liver fibrosis, which is associated with reduced fibroblast growth factor (FGF) 21 levels. These results indicate critical roles for IFNγ signaling in macrophages and their release of IL-12 in modulating obesity-mediated insulin resistance and fatty liver progression to MASH. In this work, we identify the IFNγ-IL12 axis in regulating intercellular crosstalk in the liver and as potential therapeutic targets to treat MASH.
Topics: Animals; Interferon-gamma; Interleukin-12; Male; Insulin Resistance; Obesity; Mice; Fatty Liver; Mice, Knockout; Macrophages; Signal Transduction; Liver; Mice, Inbred C57BL; Diet, High-Fat; Receptors, Interferon; Interferon gamma Receptor; Liver Cirrhosis
PubMed: 38951527
DOI: 10.1038/s41467-024-49633-y -
Scientific Reports Jun 2024Fetal alcohol spectrum disorders (FASD) are a severe developmental condition resulting from exposure to alcohol during pregnancy. The aim of this study was to examine...
Fetal alcohol spectrum disorders (FASD) are a severe developmental condition resulting from exposure to alcohol during pregnancy. The aim of this study was to examine the concentrations of hormones involved in appetite regulation-ghrelin, leptin, and putative peptide YY-3 (PYY)-in the serum of individuals with FASD. Additionally, we investigated the relationship between these hormone levels and clinical indicators. We conducted an enzyme-linked immunosorbent assay on samples collected from 62 FASD patients and 23 individuals without the condition. Our results revealed a significant decrease in leptin levels among FASD patients compared to the control group (5.124 vs. 6.838 ng/mL, p = 0.002). We revealed no statistically significant differences in the levels of other hormones studied (ghrelin and PYY). Comparisons of hormone levels were also conducted in three subgroups: FAS, neurobehavioral disorders associated with prenatal alcohol exposure and FASD risk, as well as by sex. Assignment to FASD subgroups indicated changes only for leptin. Sex had no effect on the levels of hormones. Moreover, the levels of leptin showed a negative correlation with cortisol levels and a positive correlation with BMI and proopiomelanocortin. Alterations in appetite regulation can contribute to the improper development of children with FASD, which might be another factor that should be taken into consideration in the proper treatment of patients.
Topics: Humans; Leptin; Fetal Alcohol Spectrum Disorders; Female; Ghrelin; Male; Peptide YY; Pregnancy; Child; Adult; Case-Control Studies; Child, Preschool
PubMed: 38951515
DOI: 10.1038/s41598-024-66052-7 -
Nature Communications Jun 2024Failure to appropriately predict and titrate reactivity to threat is a core feature of fear and anxiety-related disorders and is common following early life adversity...
Failure to appropriately predict and titrate reactivity to threat is a core feature of fear and anxiety-related disorders and is common following early life adversity (ELA). A population of neurons in the lateral central amygdala (CeAL) expressing corticotropin releasing factor (CRF) have been proposed to be key in processing threat of different intensities to mediate active fear expression. Here, we use in vivo fiber photometry to show that ELA results in sex-specific changes in the activity of CeAL CRF+ neurons, yielding divergent mechanisms underlying the augmented startle in ELA mice, a translationally relevant behavior indicative of heightened threat reactivity and hypervigilance. Further, chemogenic inhibition of CeAL CRF+ neurons selectively diminishes startle and produces a long-lasting suppression of threat reactivity. These findings identify a mechanism for sex-differences in susceptibility for anxiety following ELA and have broad implications for understanding the neural circuitry that encodes and gates the behavioral expression of fear.
Topics: Animals; Corticotropin-Releasing Hormone; Fear; Neurons; Mice; Female; Male; Anxiety; Central Amygdaloid Nucleus; Reflex, Startle; Mice, Inbred C57BL; Behavior, Animal; Stress, Psychological
PubMed: 38951506
DOI: 10.1038/s41467-024-49828-3