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Investigative Ophthalmology & Visual... Jun 2024To investigate the molecular mechanism of pathological keratinization in the chronic phase of ocular surface (OS) diseases.
PURPOSE
To investigate the molecular mechanism of pathological keratinization in the chronic phase of ocular surface (OS) diseases.
METHODS
In this study, a comprehensive gene expression analysis was performed using oligonucleotide microarrays on OS epithelial cells obtained from three patients with pathological keratinization (Stevens-Johnson syndrome [n = 1 patient], ocular cicatricial pemphigoid [n = 1 patient], and anterior staphyloma [n = 1 patient]). The controls were three patients with conjunctivochalasis. The expression in some transcripts was confirmed using quantitative real-time PCR.
RESULTS
Compared to the controls, 3118 genes were significantly upregulated by a factor of 2 or more than one-half in the pathological keratinized epithelial cells (analysis of variance P < 0.05). Genes involved in keratinization, lipid metabolism, and oxidoreductase were upregulated, while genes involved in cellular response, as well as known transcription factors (TFs), were downregulated. Those genes were further analyzed with respect to TFs and retinoic acid (RA) through gene ontology analysis and known reports. The expression of TFs MYBL2, FOXM1, and SREBF2, was upregulated, and the TF ELF3 was significantly downregulated. The expression of AKR1B15, RDH12, and CRABP2 (i.e., genes related to RA, which is known to suppress keratinization) was increased more than twentyfold, whereas the expression of genes RARB and RARRES3 was decreased by 1/50. CRABP2, RARB, and RARRES3 expression changes were also confirmed by qRT-PCR.
CONCLUSIONS
In pathological keratinized ocular surfaces, common transcript changes, including abnormalities in vitamin A metabolism, are involved in the mechanism of pathological keratinization.
Topics: Humans; Real-Time Polymerase Chain Reaction; Gene Expression Regulation; Female; Male; Aged; Middle Aged; Oligonucleotide Array Sequence Analysis; Gene Expression Profiling; Pemphigoid, Benign Mucous Membrane; Keratins; Corneal Diseases; Epithelial Cells; Conjunctival Diseases
PubMed: 38935029
DOI: 10.1167/iovs.65.6.37 -
Journal of Food and Drug Analysis Jun 2024Investigation of utilization possibilities of natural sources has been an important area for research. Tyrosinase inhibitory activity plays a key role in food and...
Investigation of utilization possibilities of natural sources has been an important area for research. Tyrosinase inhibitory activity plays a key role in food and medicine industry. Strawberry tree (Arbutus unedo), a widely distributed plant among Mediterranean countries, possess fruits and leaves with rich bioactive phytochemicals, especially polyphenolic compounds. In this study, we aimed to investigate the antityrosinase activity of the fruit and leaf extracts of the plant, and to determine the phenolic compounds that contribute to the antityrosinase activity. In this regard, we evaluated the effect of solvent composition on the extraction of phenolic compounds from A. unedo and on its antityrosinase activity using a simplex centroid design approach, and used chromatographic and LC-MS/MS techniques. The leaf extracts prepared using EtOH:water (50:50) provided higher TPC (456.39 mg GAE/g extract) and acetone:EtOH:water (33:33:33) provided higher TFC (56.15 mg QE/g extract) values than of fruit extracts. LC-MS/MS analysis revealed 23 phenolic/flavonoid compounds in leaf extracts (L1-8), and major metabolites were detected as quercitrin, quinic acid, catechin, tannic acid, isoquercitrin, gallic acid, and ellagic acid. Among the leaf extracts, L3 (aceton:water, 50:50) exhibited 72.01% tyrosinase inhibition at 500 μg/mL. After fractionation studies guided by antityrosinase activity, its subfraction L3-Fr2 exhibited 40.06% inhibition at 50 μg/mL concentration (IC: 146 ± 7.75 μg/mL), and catechin (113.19 mg/g), tannic acid (53.14 mg/g), ellagic acid (22.14 mg/g), gallic acid (10.27 mg/g), and epicatechin gallate (8.65 mg/g) were determined as major metabolites. Its subfraction L3-Fr2-sub7 exhibited better antityrosinase activity (IC: 206.23 ± 9.87 μg/mL), and quantitative analysis results revealed the presence of tannic acid (127.40 mg/g), gallic acid (13.96 mg/g), ellagic acid (7.66 mg/g), quercetin-3-O-glucuronide (5.06 mg/g), and quinic acid (3.2 mg/g) as major metabolites, and correlation analysis showed that ellagic acid and quinic acid were positively correlated with antityrosinase activity.
Topics: Tandem Mass Spectrometry; Plant Extracts; Monophenol Monooxygenase; Fruit; Enzyme Inhibitors; Plant Leaves; Chromatography, Liquid; Phenols; Chromatography, High Pressure Liquid; Anacardiaceae; Flavonoids; Liquid Chromatography-Mass Spectrometry
PubMed: 38934692
DOI: 10.38212/2224-6614.3496 -
F1000Research 2023The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of...
BACKGROUND
The risk of recurrence after nephrectomy for primary clear cell renal cell carcinoma (ccRCC) is estimated in daily practice solely based on clinical criteria. The aim of this study was to assess the prognostic relevance of common somatic mutations with respect to tumor aggressiveness and outcomes of ccRCC patients after definitive treatment.
METHODS
Primary tumors from 37 patients with ccRCC who underwent radical nephrectomy were analyzed for presence of somatic mutations using a 15-gene targeted next-generation sequencing (NGS) panel. Associations to histopathologic characteristics and outcomes were investigated in the study cohort (n=37) and validated in The Cancer Genome Atlas (TCGA) ccRCC cohort (n=451).
RESULTS
was the most frequently mutated gene (51%), followed by (27%), (13%), (13%), (5%), (5%), (5%), and (3%). One-third of patients did not have any somatic mutations within the 15-gene panel. The vast majority of tumors harboring no mutations at all or VHL-only mutations (51%) were more frequently of smaller size (pT1-2) and earlier stage (I/II), whereas presence of any other gene mutations in various combinations with or without was enriched in larger (pT3) and higher stage tumors (III) (p=0.02). No recurrences were noted in patients with unmutated tumors or -only mutations as opposed to three relapses in patients with non- somatic mutations (p=0.06). Presence of somatic mutations in , or genes in 451 TCGA ccRCC patients was associated with a significantly shorter disease-free survival (DFS) compared to those with unaltered tumors (q=0.01).
CONCLUSIONS
Preliminary findings from this ongoing study support the prognostic value of non- mutations including , and in primary ccRCC tumors as surrogates of earlier recurrence and potential selection for adjuvant immune checkpoint inhibition.
Topics: Humans; Carcinoma, Renal Cell; Male; Female; Kidney Neoplasms; Middle Aged; Mutation; Aged; Immune Checkpoint Inhibitors; Ubiquitin Thiolesterase; Neoplasm Recurrence, Local; Tumor Suppressor Proteins; Ataxia Telangiectasia Mutated Proteins; Von Hippel-Lindau Tumor Suppressor Protein; Prognosis; Histone-Lysine N-Methyltransferase; Adult; Transcription Factors; Aged, 80 and over; Nuclear Proteins; High-Throughput Nucleotide Sequencing; DNA-Binding Proteins; Histone Demethylases
PubMed: 38933491
DOI: 10.12688/f1000research.136087.2 -
Viruses Jun 2024C-terminal binding protein (CtBP), a transcriptional co-repressor, significantly influences cellular signaling, impacting various biological processes including cell... (Review)
Review
C-terminal binding protein (CtBP), a transcriptional co-repressor, significantly influences cellular signaling, impacting various biological processes including cell proliferation, differentiation, apoptosis, and immune responses. The CtBP family comprises two highly conserved proteins, CtBP1 and CtBP2, which have been shown to play critical roles in both tumorigenesis and the regulation of viral infections. Elevated CtBP expression is noted in various tumor tissues, promoting tumorigenesis, invasiveness, and metastasis through multiple pathways. Additionally, CtBP's role in viral infections varies, exhibiting differing or even opposing effects depending on the virus. This review synthesizes the advances in CtBP's function research in viral infections and virus-associated tumorigenesis, offering new insights into potential antiviral and anticancer strategies.
Topics: Humans; Carcinogenesis; Virus Diseases; Alcohol Oxidoreductases; DNA-Binding Proteins; Animals; Neoplasms
PubMed: 38932279
DOI: 10.3390/v16060988 -
Viruses Jun 2024Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six...
Spontaneous Lethal Outbreak of Influenza A Virus Infection in Vaccinated Sows on Two Farms Suggesting the Occurrence of Vaccine-Associated Enhanced Respiratory Disease with Eosinophilic Lung Pathology.
Influenza A virus (IAV) infections in swine are usually subclinical, but they can reach high morbidity rates. The mortality rate is normally low. In this study, six vaccinated, spontaneously deceased sows revealed IAV infection and enhanced neutrophilic bronchopneumonia with unexpectedly large numbers of infiltrating eosinophils. The purpose of this study was to characterize these lung lesions with special emphasis on the phenotypes of inflammatory cells, the presence of eosinophilic peroxidase (EPO), and neutrophil extracellular traps (NETs). The number of Sirius red-stained eosinophils was significantly higher in the lungs of IAV-infected sows compared to healthy pigs, indicating a migration of eosinophils from blood vessels into the lung tissue stimulated by IAV infection. The detection of intra- and extracellular EPO in the lungs suggests its contribution to pulmonary damage. The presence of CD3 T lymphocytes, CD20 B lymphocytes, and Iba-1 macrophages indicates the involvement of cell-mediated immune responses in disease progression. Furthermore, high numbers of myeloperoxidase-positive cells were detected. However, DNA-histone-1 complexes were reduced in IAV-infected sows, leading to the hypothesis that NETs are not formed in the IAV-infected sows. In conclusion, our findings in the lungs of IAV-infected vaccinated sows suggest the presence of so far unreported field cases of vaccine-associated enhanced respiratory disease.
Topics: Animals; Swine; Lung; Swine Diseases; Orthomyxoviridae Infections; Female; Influenza Vaccines; Influenza A virus; Disease Outbreaks; Eosinophils; Extracellular Traps; Vaccination; Eosinophil Peroxidase
PubMed: 38932247
DOI: 10.3390/v16060955 -
Pharmaceutics May 2024Antibiotic-resistant strains of are being viewed as a serious threat by various public health agencies. Identifying novel targets in this important pathogen is crucial...
Antibiotic-resistant strains of are being viewed as a serious threat by various public health agencies. Identifying novel targets in this important pathogen is crucial to the development of new effective antibacterial formulations. We investigated the antibacterial effect of a colloidal nanosilver formulation, Silversol, against an antibiotic-resistant strain of using appropriate in vitro assays. Moreover, we deciphered the molecular mechanisms underlying this formulation's anti- activity using whole transcriptome analysis. Lower concentrations of the test formulation exerted a bacteriostatic effect against this pathogen, and higher concentrations exerted a bactericidal effect. Silversol at sub-lethal concentration was found to disturb multiple physiological traits of such as growth, antibiotic susceptibility, membrane permeability, efflux, protein synthesis and export, biofilm and exopolysaccharide production, etc. Transcriptome data revealed that the genes coding for transcriptional regulators, efflux machinery, transferases, β-lactam resistance, oxidoreductases, metal homeostasis, virulence factors, and arginine biosynthesis are expressed differently under the influence of the test formulation. Genes ( and ) involved in arginine biosynthesis emerged among the major targets of Silversols antibacterial activity against .
PubMed: 38931848
DOI: 10.3390/pharmaceutics16060726 -
Nutrients Jun 2024This study is aimed to examine the association of plasma homocysteine (Hcy) concentrations with a 10-year risk of all-cause and cardiovascular (CV) mortality and to...
This study is aimed to examine the association of plasma homocysteine (Hcy) concentrations with a 10-year risk of all-cause and cardiovascular (CV) mortality and to explore the modification effect of methylenetetrahydrofolate reductase () genetic polymorphism. This study included 5200 participants from a community-based Chinese population. Cox proportional hazard regression models were used to analyze the associations of Hcy and genotype with all-cause and CV mortality. The possible modification effect of the genotype on the Hcy-mortality relationship was assessed. The individuals with Hcy concentrations ≥ 10 μmol/L had a significantly higher risk of all-cause mortality compared to those with Hcy < 10 μmol/L (hazard ratio [HR]: 1.72, 95% confidence interval [CI]: 1.11-2.68, = 0.015). The risk of CV mortality increased by 2% per 1 μmol/L Hcy increment (HR: 1.02, 95% CI: 1.00-1.03, = 0.036). Despite the genotype alone not being correlated with the mortality, the relationship between Hcy and all-cause mortality was significant in the genotype compared with / genotype ( for interaction = 0.036). Elevated plasma Hcy concentrations were associated with an increased 10-year risk of all-cause and CV mortality among the Chinese population. genetic polymorphism could modify the association between Hcy and all-cause mortality.
Topics: Humans; Homocysteine; Male; Female; Methylenetetrahydrofolate Reductase (NADPH2); Cardiovascular Diseases; Middle Aged; China; Asian People; Risk Factors; Genotype; Aged; Proportional Hazards Models; Adult; Cause of Death; Polymorphism, Single Nucleotide; Genetic Predisposition to Disease; East Asian People
PubMed: 38931298
DOI: 10.3390/nu16121945 -
Nutrients Jun 2024Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet...
Polycystic ovary syndrome (PCOS) is a common endocrine disorder that affects women of reproductive age. Many women with PCOS have been found to have an unbalanced diet and deficiencies in essential nutrients. This study aimed to assess the levels of folate and vitamin B12 (B12) and their relationship with metabolic factors in women with PCOS. Anthropometric, clinical, and genetic analyses were conducted to evaluate markers related to one-carbon metabolism in women with PCOS and in a control group. The PCOS group had a higher BMI and HOMA-IR (1.7 vs. 3.1; < 0.0001). HDL cholesterol levels were 23% lower and triglyceride levels were 74% higher in women with PCOS. Although there were no significant differences in folate and B12 levels between the PCOS and control groups, over 60% of women with PCOS had low B12 levels (<300 pg/mL) and high homocysteine levels. In addition, the MTHFR A1298C and C677T polymorphisms were not associated with PCOS. Moreover, erythrocyte folate levels were positively correlated with fasting glucose, triglycerides, and free androgen index, and negatively correlated with SHBG and LH levels. These results suggest that B vitamins may be associated with the metabolic phenotype in PCOS. This study emphasizes the potential link between folate, vitamin B12, and metabolic and hormonal outcomes in women with PCOS.
Topics: Humans; Female; Polycystic Ovary Syndrome; Vitamin B 12; Folic Acid; Adult; Chile; Young Adult; Triglycerides; Homocysteine; Body Mass Index; Blood Glucose; Methylenetetrahydrofolate Reductase (NADPH2); Insulin Resistance; Cholesterol, HDL; Case-Control Studies; Biomarkers
PubMed: 38931291
DOI: 10.3390/nu16121937 -
Nutrients Jun 2024Corn peptide (CP) is a short, naturally occurring, and physiologically active peptide generated from corn-protease-catalyzed hydrolysis. CP plays a role in preventing...
Corn peptide (CP) is a short, naturally occurring, and physiologically active peptide generated from corn-protease-catalyzed hydrolysis. CP plays a role in preventing obesity-related disorders, but its impact on reducing inflammation is unknown. Hence, this study examined the possible protective effects of corn peptide powder (CPP) against the harmful effects of lipopolysaccharide (LPS), with a particular emphasis on reducing oxidative damage and inflammation in adipocytes. Hence, mature 3T3-L1 adipocytes underwent exposure to 10 ng/mL LPS, with or without CPP (10 and 20 μg/mL). LPS stimulation increased reactive oxygen species and superoxide anion generation. However, this effect was reduced in a dose-dependent manner by pretreatment with CPP. CPP treatment elevated the mRNA expressions of the antioxidant enzymes manganese superoxide dismutase (mnSOD) and glutathione peroxidase 1 (Gpx1) while reducing the mRNA expressions of the cytosolic reactive oxygen species indicators p40 and p67 (NADPH oxidase 2). In addition, CPP inhibited the monocyte chemoattractant protein-1, tumor necrosis factor-alpha, Toll-like receptor 4, and nuclear factor kappa B mRNA expressions induced by LPS. These findings demonstrate that CPP may ameliorate adipocyte dysfunction by suppressing oxidative damage and inflammatory responses through a new mechanism known as Toll-like receptor 4/nuclear factor kappa B-mediated signaling.
Topics: Animals; Mice; 3T3-L1 Cells; Adipocytes; Lipopolysaccharides; Zea mays; Reactive Oxygen Species; Inflammation; Toll-Like Receptor 4; Oxidative Stress; Superoxide Dismutase; Powders; Peptides; Glutathione Peroxidase; NF-kappa B; Antioxidants; Glutathione Peroxidase GPX1; Signal Transduction; Chemokine CCL2; Tumor Necrosis Factor-alpha; Anti-Inflammatory Agents
PubMed: 38931278
DOI: 10.3390/nu16121924 -
Nutrients Jun 2024Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life....
Osteoarthritis (OA) is a chronic degenerative joint disease that causes chronic pain, swelling, stiffness, disability, and significantly reduces the quality of life. Typically, OA is treated using painkillers and non-steroidal anti-inflammatory drugs (NSAIDs). While current pharmacologic treatments are common, their potential side effects have prompted exploration into functional dietary supplements. Recently, eggshell membrane (ESM) has emerged as a potential functional ingredient for joint and connective tissue disorders due to its clinical efficacy in relieving joint pain and stiffness. Despite promising clinical evidence, the effects of ESM on OA progression and its mechanism of action remain poorly understood. This study evaluated the efficacy of Ovomet, a powdered natural ESM, against joint pain and disease progression in a monosodium iodoacetate (MIA)-induced rodent model of OA in mice and rats. The results demonstrate that ESM significantly alleviates joint pain and attenuates articular cartilage destruction in both mice and rats that received oral supplementation for 5 days prior to OA induction and for 28 days thereafter. Interestingly, ESM significantly inhibited mRNA expression levels of pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), as well as inflammatory mediators, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase in the knee joint cartilage at the early stage of OA, within 7 days after OA induction. However, this effect was not observed in the late stage at 28 days after OA induction. ESM further attenuates the induction of protein expression for cartilage-degrading enzymes like matrix metalloproteinase (MMPs) 3 and 13, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), in the late-stage. In addition, MIA-induced reduction of the protein expression levels of cartilage components, cartilage oligomeric matrix protein (COMP), aggrecan (ACAN) and collagen type II α-1 chain (COL2α1), and cartilage extracellular matrix (ECM) synthesis promoting transcriptional factor SRY-Box 9 (SOX-9) were increased via ESM treatment in the cartilage tissue. Our findings suggest that Ovomet, a natural ESM powder, is a promising dietary functional ingredient that can alleviate pain, inflammatory response, and cartilage degradation associated with the progression of OA.
Topics: Animals; Egg Shell; Cartilage, Articular; Osteoarthritis; Male; Mice; Nitric Oxide Synthase Type II; Rats; Inflammation; Dietary Supplements; Cytokines; Disease Models, Animal; Rats, Sprague-Dawley; Arthralgia; Time Factors; Iodoacetic Acid; Anti-Inflammatory Agents
PubMed: 38931240
DOI: 10.3390/nu16121885