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1.
Food Chem ; 393: 133361, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-35671660

RESUMO

Oil palm (Elaeis guineensis Jacq.) is the most productive oil-producing crop per hectare of land. The oil that accumulates in the mesocarp tissue of the fruit is the highest observed among fruit-producing plants. A comparative analysis between high-, medium-, and low-yielding oil palms, particularly during fruit development, revealed unique characteristics. Metabolomics analysis was able to distinguish accumulation patterns defining of the various developmental stages and oil yield. Interestingly, high- and medium-yielding oil palms exhibited substantially increased sucrose levels compared to low-yielding palms. In addition, parameters such as starch granule morphology, granule size, total starch content, and starch chain length distribution (CLD) differed significantly among the oil yield categories with a clear correlation between oil yield and various starch parameters. These results provide new insights into carbohydrate and starch metabolism for biosynthesis of oil palm fruits, indicating that starch and sucrose can be used as novel, easy-to-analyze, and reliable biomarker for oil yield.


Assuntos
Arecaceae , Amido , Arecaceae/metabolismo , Biomarcadores/metabolismo , Frutas , Óleo de Palmeira/metabolismo , Amido/metabolismo , Sacarose/metabolismo
2.
Crit Rev Eukaryot Gene Expr ; 32(3): 21-30, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35695607

RESUMO

Malignant melanoma is one of the most aggressive types of skin cancer. Thus, efficient diagnosis and treatment methods are crucial for advanced melanoma. Circular RNAs (circRNAs) have been regarded as a 'splicing noise' in the past decades. However, several circRNAs have been recently reported to be differentially expressed in melanoma, and the cell or tissue-specific expression makes these suitable candidate diagnostic or therapeutic biomarkers. In addition, emerging studies have confirmed that circular RNAs play pivotal roles in the proliferation, invasion, metastasis, and migration of malignant melanoma. However, specific pathogenic mechanisms between melanoma and circRNAs remain unclear. In the present study, it was summarized that circRNAs are associated with the pathogenesis of melanoma, including hsa_circ_0083444, hsa_circ_0005320, hsa_circ_0067531, hsa_circ_0084043, hsa_circ_0000082, hsa_circ_0016418, hsa_circ_0085533 and hsa_circ_0025039, hsa_circ_0001946, hsa_circ_0002770, hsa_circ_0079593, hsa_circ_0027247, hsa_circ_0017247, hsa_circ_0020710. These can provide potential diagnosis, treatment, and prognostication biomarkers for advanced melanoma in clinical applications.


Assuntos
Melanoma , Neoplasias Cutâneas , Biomarcadores/metabolismo , Humanos , Melanoma/genética , RNA Circular/genética , Neoplasias Cutâneas/genética
3.
J Med Chem ; 65(12): 8303-8331, 2022 Jun 23.
Artigo em Inglês | MEDLINE | ID: mdl-35696646

RESUMO

The perinucleolar compartment (PNC) is a dynamic subnuclear body found at the periphery of the nucleolus. The PNC is enriched with RNA transcripts and RNA-binding proteins, reflecting different states of genome organization. PNC prevalence positively correlates with cancer progression and metastatic capacity, making it a useful marker for metastatic cancer progression. A high-throughput, high-content assay was developed to identify novel small molecules that selectively reduce PNC prevalence in cancer cells. We identified and further optimized a pyrrolopyrimidine series able to reduce PNC prevalence in PC3M cancer cells at submicromolar concentrations without affecting cell viability. Structure-activity relationship exploration of the structural elements necessary for activity resulted in the discovery of several potent compounds. Analysis of in vitro drug-like properties led to the discovery of the bioavailable analogue, metarrestin, which has shown potent antimetastatic activity with improved survival in rodent models and is currently being evaluated in a first-in-human phase 1 clinical trial.


Assuntos
Núcleo Celular , Neoplasias , Biomarcadores/metabolismo , Nucléolo Celular/metabolismo , Nucléolo Celular/patologia , Núcleo Celular/metabolismo , Humanos , Neoplasias/metabolismo , Pirimidinas , Pirróis
4.
Food Funct ; 13(12): 6648-6664, 2022 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-35642970

RESUMO

Poria cocos (P. cocos) has been traditionally used as folk medicine and functional food in China for more than 2000 years. The water-soluble polysaccharide is the main component of P. cocos decoction. The effects and mechanisms of the water-soluble polysaccharide from P. cocos (PCWP) were investigated in chronic sleep deprivation (CSD)-induced anxiety in rats. CSD induced anxiety, gut dysbiosis, and inflammatory responses, and reduced neurotransmitter levels, whereas PCWP intervention ameliorated anxiety-like behaviors, increased the levels of 5-hydroxytryptamine, dopamine, norepinephrine, and γ-aminobutyric acid in the hypothalamus, regulated gastrointestinal peptide levels, reduced inflammatory factors, and inhibited the tumor necrosis factor (TNF)-α/nuclear factor (NF)-κB signaling pathway in rats with CSD. The changes in the intestinal flora composition were determined using 16S rDNA sequencing, and indicated that PCWP significantly improved species richness and diversity in the intestinal flora of rats with anxiety, and adjusted the abundance of the following dysregulated bacteria closer to that of the normal group: Rikenellaceae_RC9_gut_group, Ruminococcus, Prevotellaceae_UCG-001, Prevotellaceae_NK3B31_group, Fusicatenibacter. Metabolomics was used to analyze fecal samples to identify significantly altered metabolites in the PCWP-treated groups. Thirty-eight PCWP-related metabolites and four metabolic pathways such as sphingolipid metabolism, taurine and hypotaurine metabolism, vitamin B6 metabolism, and glycerophospholipid metabolism were explored. The results of serum metabolomics showed that 26 biomarkers were significantly changed after PCWP intervention compared with the model group. The regulatory effects of metabolic pathway enrichment on sphingolipid, phenylalanine, and taurine and hypotaurine metabolism, and validation results showed that PCWP intervention regulated the activity of enzymes involved in the above metabolic pathways. A strong correlation between intestinal bacteria and potential biomarkers was found. Our findings present new evidence supporting the potential effect of PCWP in preventing the progression of anxiety by inhibiting the TNF-α/NF-κB signaling pathway, alleviating metabolic disorders, and ameliorating the gut microflora imbalance.


Assuntos
Doenças Metabólicas , Wolfiporia , Animais , Ansiedade/tratamento farmacológico , Biomarcadores/metabolismo , Disbiose/microbiologia , Enteropatias/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Polissacarídeos/farmacologia , Ratos , Transdução de Sinais , Privação do Sono , Esfingolipídeos , Taurina/farmacologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/farmacologia , Água/farmacologia , Wolfiporia/química
5.
Chemosphere ; 303(Pt 2): 135076, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35649444

RESUMO

The petrochemical industry has promoted the development of economy, while polycyclic aromatic hydrocarbons (PAHs) produced by the industry become the threat for environment and humans. Data on human occupational exposure in petrochemical industry are limited. In the present study, urinary hydroxylated PAH metabolites (OH-PAHs) and a biomarker of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)) were measured in 546 workers of a petrochemical group in Northeast China, to investigate PAH exposure and related potential health risk. The concentrations of ∑9OH-PAH in all workers were 0.25-175 µg/g Cre with a median value of 4.41 µg/g Cre. Metabolites of naphthalene were the predominant compounds. The levels of PAH metabolites were significantly different for workers with different jobs, which were the highest for recycling workers (13.7 µg/g Cre) and the lowest for agency managers (5.12 µg/g Cre). Besides, higher levels of OH-PAHs were usually found in males and older workers. There was a dose-response relationship between levels of 8-OHdG and ∑9OH-PAHs (p < 0.01). No difference was observed in concentrations of 8-OHdG for workers of different gender or ages, work history as well as noise. Furthermore, workers simultaneously exposed to other potential pollutants and higher levels of ∑9OH-PAH had significantly higher levels of 8-OHdG compared with those in the corresponding subgroups. Our results suggested that exposure to PAHs or co-exposure to PAHs and potential toxics in the petrochemical plant may cause DNA damage. We call for more researches on the associations among noise, chemical pollution and oxidative stress to workers in the real working environment.


Assuntos
Exposição Ocupacional , Hidrocarbonetos Policíclicos Aromáticos , 8-Hidroxi-2'-Desoxiguanosina , Biomarcadores/metabolismo , Dano ao DNA , Desoxiguanosina/metabolismo , Exposição Ambiental/análise , Humanos , Masculino , Exposição Ocupacional/análise , Estresse Oxidativo , Hidrocarbonetos Policíclicos Aromáticos/análise , Hidrocarbonetos Policíclicos Aromáticos/toxicidade
6.
Exp Cell Res ; 417(2): 113232, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35659970

RESUMO

To date, most studies of exosomes related to hepatocellular carcinoma (HCC) have used commercial cancer cell lines or patient plasma as source material. In this study, we isolated exosomes directly from HCC tissues to investigate the potential of exosomal contents as biomarkers for HCC. Exosomes were identified and verified using transmission electron microscopy, nano-flow cytometry analysis, and western blotting. Tissue-derived exosomal miRNA expression was profiled by high-throughput sequencing, and differential expression of miRNAs was validated by quantitative real-time polymerase chain reaction analysis. The diagnostic performance of differentially expressed exosomal miRNAs for HCC was evaluated by receiver operating characteristic curve analysis. Target genes of these miRNAs were verified using luciferase reporter assays, and their functions were studied through in vitro and rescue assays. In total, 225 differentially expressed exosomal miRNAs were identified in HCC samples compared with adjacent liver tissues, and some were associated with HCC tumorigenesis and progression. Comparison of the expression profiles of tissue-derived and plasma-derived exosomal miRNAs identified hsa-miR-483-5p as the only differentially expressed miRNA detected in both HCC tissue and plasma, and this was in a validation group of HCC patients. Analysis of the diagnostic performance of plasma exosomal hsa-miR-483-5p or plasma hsa-miR-483-5p found that both could differentiate HCC and non-HCC cases. In vitro ectopic miR-483-5p expression promoted HCC cell proliferation. CDK15 was confirmed to bind with miR-483-5p directly, and thus, miR-483-5p may function by downregulating CDK15. Hsa-miR-483-5p represents a potential specific and sensitive biomarker for HCC diagnosis.


Assuntos
Carcinoma Hepatocelular , Exossomos , Neoplasias Hepáticas , MicroRNAs , Biomarcadores/metabolismo , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Exossomos/metabolismo , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo
7.
Phytomedicine ; 103: 154199, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35679793

RESUMO

BACKGROUND: Liver fibrosis can be easily developed into irreversible liver cirrhosis or even liver cancer. Lysosomal acid lipase (LAL), encoded by the lipase A (Lipa) gene, is a critical enzyme involved in liver fibrosis development. Morroniside, an iridoid glycoside isolated from Cornus officinalis Sieb. et Zucc., exerts hepatic protective effects. However, the mechanism of action underling the anti-liver fibrosis effects of morroniside have not been fully elucidated. PURPOSE: To explore whether Lipa served as a biomarker for liver fibrosis and investigate the anti-liver fibrosis effects of morroniside and the underlying action mechanism in liver fibrosis cell models. METHODS: LAL expression was examined in the liver tissues of CCl4 and high-fat diet (HFD)-induced liver fibrosis animal models. α-smooth muscle actin (α-SMA) level, collagen and GATA family expressions were analyzed by Real-time PCR and Western blot. Putative transcription factor binding sites in the DNA sequences of Lipa was identified by PROMO-ALGGEN v8.3 online software and ENCODE ChIP-Seq Significance Tool. MD simulation was performed to explore the protein-ligand interaction. RESULTS: We found that the expression of hepatic LAL is lower in the liver fibrosis animal models than the control models. The reduced LAL expression is associated with HSCs activation, suggesting LAL is novel liver fibrosis biomarker. More importantly, our data showed that morroniside exerts anti-liver fibrosis effects in vitro. Mechanistic studies reveal that it binds to the hydrophobic sites of GATA3 and also reduces GATA3 expression, which increases LAL expression. CONCLUSIONS: This study, for the first time, suggests LAL is a novel biomarker for liver fibrosis. Besides, morroniside exerts its anti-liver fibrosis effects by targeting GATA3 and LAL and hence inhibits HSC activation. These findings provide strong scientific evidence to support the development of morroniside as novel alternative or complementary therapeutics for liver injury prevention and treatment.


Assuntos
Células Estreladas do Fígado , Esterol Esterase , Animais , Biomarcadores/metabolismo , Glicosídeos , Fígado/metabolismo , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/metabolismo , Esterol Esterase/metabolismo
8.
Int J Mol Sci ; 23(11)2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35682793

RESUMO

The clinical aspects of hypertrophic scarring vary according to personal constitution and body part. However, the mechanism of hypertrophic scar (HS) formation remains unclear. MicroRNAs (miRNAs) are known to contribute to HS formation, however, their detailed role remains unknown. In this study, candidate miRNAs were identified and analyzed as biomarkers of hypertrophic scarring for future clinical applications. HSfibroblasts and normal skin fibroblasts from patients were used for profiling and validation of miRNAs. An HS mouse model with xenografted human skin on nude mice was established. The miRNA expression between normal human, normal mouse, and mouse HS skin tissues was compared. Circulating miRNA expression levels in the serum of normal mice and mice with HSs were also analyzed. Ten upregulated and twenty-one downregulated miRNAs were detected. Among these, miR-365a/b-3p and miR-16-5p were identified as candidate miRNAs with statistically significant differences; miR-365a/b-3p was significantly upregulated (p = 0.0244). In mouse studies, miR-365a/b-3p expression levels in skin tissue and serum were higher in mice with HSs than in the control group. These results indicate that miRNAs contribute to hypertrophic scarring and that miR-365a/b-3p may be considered a potential biomarker for HS formation.


Assuntos
Cicatriz Hipertrófica , MicroRNA Circulante , MicroRNAs , Animais , Biomarcadores/metabolismo , Cicatriz Hipertrófica/genética , Perfilação da Expressão Gênica , Humanos , Camundongos , Camundongos Nus , MicroRNAs/metabolismo
9.
FASEB J ; 36(7): e22371, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35704337

RESUMO

Untargeted metabolomics of blood samples has become widely applied to study metabolic alterations underpinning disease and to identify biomarkers. However, understanding the relevance of a blood metabolite marker can be challenging if it is unknown whether it reflects the concentration in relevant tissues. To explore this field, metabolomic and lipidomic profiles of plasma, four sites of adipose tissues (ATs) from peripheral or central depot, two sites of muscle tissue, and liver tissue from a group of nondiabetic women with obesity who were scheduled to undergo bariatric surgery (n = 21) or other upper GI surgery (n = 5), were measured by liquid chromatography coupled with mass spectrometry. Relationships between plasma and tissue profiles were examined using Pearson correlation analysis subject to Benjamini-Hochberg correction. Plasma metabolites and lipids showed the highest number of significantly positive correlations with their corresponding concentrations in liver tissue, including lipid species of ceramide, mono- and di-hexosylceramide, sphingomyelin, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysophosphatidylethanolamine, dimethyl phosphatidylethanolamine, ether-linked PC, ether-linked PE, free fatty acid, cholesteryl ester, diacylglycerol and triacylglycerol, and polar metabolites linked to several metabolic functions and gut microbial metabolism. Plasma also showed significantly positive correlations with muscle for several phospholipid species and polar metabolites linked to metabolic functions and gut microbial metabolism, and with AT for several triacylglycerol species. In conclusion, plasma metabolomic and lipidomic profiles were reflective more of the liver profile than any of the muscle or AT sites examined in the present study. Our findings highlighted the importance of taking into consideration the metabolomic relationship of various tissues with plasma when postulating plasma metabolites marker to underlying mechanisms occurring in a specific tissue.


Assuntos
Metaboloma , Fosfatidiletanolaminas , Biomarcadores/metabolismo , Éteres/metabolismo , Feminino , Humanos , Fígado/metabolismo , Metabolômica/métodos , Músculos/metabolismo , Obesidade/metabolismo , Fosfatidilcolinas/metabolismo , Fosfatidiletanolaminas/metabolismo , Triglicerídeos/metabolismo
10.
PLoS One ; 17(6): e0269621, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35704634

RESUMO

OBJECTIVES: Malnutrition, defined according to Nutritional risk screening (NRS 2002), is commonly observed in patients of Myasthenia gravis (MG), a neuromuscular disorder manifested by varied degrees of skeletal muscle weakness. Because biochemical composition of saliva changes in correspondence to alterations in nutritional status, we tested our hypothesis that a certain saliva component(s) might serve as a biomarker(s) for nutrition status of MG, particularly for those MG patients with high risk of malnutrition. MATERIALS AND METHODS: 60 MG patients and 60 subjects belonging to the healthy control group (HCG) were enrolled in this case-control study. The salivary α-amylase (sAA) activity, salivary flow rate (SFR), pH, total protein density (TPD), and the concentrations of chloride and calcium ions in MG group with or without malnutrition were measured before and after citric acid stimulation. Thereafter, the relationship between sAA activity and BMI was determined in MG and HCG. RESULTS: Compared with HCG, more patients with malnutrition, increased TPD and chloride and calcium concentrations but decreased pH value and SFR both before and after acid stimulation, as well as reduced sAA activity, pH and TPD responses to acid stimulation. MG with malnutrition showed decreased sAA activity and TPD responding to acid stimulation compared with those without malnutrition. Compared with normal BMI, sAA activity response to acid stimulation was reduced in low BMI. There was a significant strong positive correlation between the ratio of sAA activity and BMI in MG. CONCLUSIONS: Salivary biochemical characteristics are abnormally altered in MG with malnutrition. Altered sAA activity responding to acid stimulation was associated with malnutrition. CLINICAL RELEVANCE: Decreased sAA activity responding to acid stimulation can reflect malnutrition state and may be one potential screening marker for MG patients with high risk of malnutrition.


Assuntos
Desnutrição , Miastenia Gravis , alfa-Amilases Salivares , Biomarcadores/metabolismo , Cálcio/metabolismo , Estudos de Casos e Controles , Cloretos/metabolismo , Ácido Cítrico/metabolismo , Humanos , Desnutrição/metabolismo , Saliva/metabolismo , alfa-Amilases Salivares/análise
11.
Sci Rep ; 12(1): 9104, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35650234

RESUMO

Hair follicle stem cells are key for driving growth and homeostasis of the hair follicle niche, have remarkable regenerative capacity throughout hair cycling, and display fate plasticity during cutaneous wound healing. Due to the need for a transgenic reporter, essentially all observations related to LGR5-expressing hair follicle stem cells have been generated using transgenic mice, which have significant differences in anatomy and physiology from the human. Using a transgenic pig model, a widely accepted model for human skin and human skin repair, we demonstrate that LGR5 is a marker of hair follicle stem cells across species in homeostasis and development. We also report the strong similarities and important differences in expression patterns, gene expression profiles, and developmental processes between species. This information is important for understanding the fundamental differences and similarities across species, and ultimately improving human hair follicle regeneration, cutaneous wound healing, and skin cancer treatment.


Assuntos
Folículo Piloso , Células-Tronco , Animais , Animais Geneticamente Modificados , Biomarcadores/metabolismo , Folículo Piloso/metabolismo , Humanos , Morfogênese , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Pele , Células-Tronco/metabolismo , Suínos
12.
Contrast Media Mol Imaging ; 2022: 6551358, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35655729

RESUMO

Nervous inflammation is an important component of the pathogenesis of neurodegenerative diseases including chronic diabetic neuropathic pain. In order to obtain a decrease in the progression of diabetic neuronal damage, it may be necessary to examine therapeutic options that involve antioxidants and anti-inflammatory agents. The aim of this study was to investigate the attenuation of inflammatory factors with endurance training in the spinal cord of rats with neuropathic pain. Thirty-two 8-week-old male Wistar rats (with a weight range of 204 ± 11.3 g) were randomly divided into 4 groups (n = 8), including (1) diabetic neuropathy (50 mg/kg streptozotocin intraperitoneal injection), (2) diabetic neuropathy training (30 minutes of endurance training at 15 meters per minute, 5 days a week for 6 weeks), (3) healthy training, and (4) healthy control. After confirmation of diabetic neuropathy by behavioral tests, training protocol and supplementation were performed. The NLRP3, P38 MAPK, TNF-α, and IL-1ß gene expressions were measured by a real-time technique in the spinal cord tissue. One-way analysis of variance and Tukey's post hoc test were used for statistical analysis. Endurance training reduced the sensitivity of the nervous system to thermal hyperalgesia and mechanical allodynia; also, compared to the diabetic neuropathy group, the gene expressions of NLTP3, P38 MAPK, TNF-α, and IL-1ß were significantly reduced by endurance training (P < 0.05). Endurance training modulates NLRP3, P38 MAPK, and TNF-α, IL-1ß gene expressions and improves the sensitivity of nociceptors to pain factors. Accordingly, it is recommended to use endurance training to reduce neuropathic pain for diabetics.


Assuntos
Diabetes Mellitus , Neuropatias Diabéticas , Treino Aeróbico , Neuralgia , Animais , Biomarcadores/metabolismo , Neuropatias Diabéticas/tratamento farmacológico , Neuropatias Diabéticas/metabolismo , Neuropatias Diabéticas/patologia , Humanos , Hiperalgesia/metabolismo , Hiperalgesia/patologia , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Neuralgia/tratamento farmacológico , Neuralgia/metabolismo , Ratos , Ratos Wistar , Medula Espinal , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/uso terapêutico , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/uso terapêutico
13.
Orphanet J Rare Dis ; 17(1): 225, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35698232

RESUMO

BACKGROUND: Aberrations to endoplasmic/sarcoplasmic reticulum (ER/SR) calcium concentration can result in the departure of endogenous proteins in a phenomenon termed exodosis. Redistribution of the ER/SR proteome can have deleterious effects to cell function and cell viability, often contributing to disease pathogenesis. Many proteins prone to exodosis reside in the ER/SR via an ER retention/retrieval sequence (ERS) and are involved in protein folding, protein modification, and protein trafficking. While the consequences of their extracellular presence have yet to be fully delineated, the proteins that have undergone exodosis may be useful for biomarker development. Skeletal muscle cells rely upon tightly coordinated ER/SR calcium release for muscle contractions, and perturbations to calcium homeostasis can result in myopathies. Ryanodine receptor type-1 (RYR1) is a calcium release channel located in the SR. Mutations to the RYR1 gene can compromise calcium homeostasis leading to a vast range of clinical phenotypes encompassing hypotonia, myalgia, respiratory insufficiency, ophthalmoplegia, fatigue and malignant hyperthermia (MH). There are currently no FDA approved treatments for RYR1-related myopathies (RYR1-RM). RESULTS: Here we examine the exodosis profile of skeletal muscle cells following ER/SR calcium depletion. Proteomic analysis identified 4,465 extracellular proteins following ER/SR calcium depletion with 1,280 proteins significantly different than vehicle. A total of 54 ERS proteins were identified and 33 ERS proteins significantly increased following ER/SR calcium depletion. Specifically, ERS protein, mesencephalic astrocyte-derived neurotrophic factor (MANF), was elevated following calcium depletion, making it a potential biomarker candidate for human samples. Despite no significant elevation of MANF in plasma levels among healthy volunteers and RYR1-RM individuals, MANF plasma levels positively correlated with age in RYR1-RM individuals, presenting a potential biomarker of disease progression. Selenoprotein N (SEPN1) was also detected only in extracellular samples following ER/SR calcium depletion. This protein is integral to calcium handling and SEPN1 variants have a causal role in SEPN1-related myopathies (SEPN1-RM). Extracellular presence of ER/SR membrane proteins may provide new insight into proteomic alterations extending beyond ERS proteins. Pre-treatment of skeletal muscle cells with bromocriptine, an FDA approved drug recently found to have anti-exodosis effects, curbed exodosis of ER/SR resident proteins. CONCLUSION: Changes to the extracellular content caused by intracellular calcium dysregulation presents an opportunity for biomarker development and drug discovery.


Assuntos
Retículo Endoplasmático , Doenças Musculares , Canal de Liberação de Cálcio do Receptor de Rianodina , Retículo Sarcoplasmático , Biomarcadores/metabolismo , Cálcio/metabolismo , Retículo Endoplasmático/metabolismo , Humanos , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/metabolismo , Doenças Musculares/genética , Proteínas/metabolismo , Proteômica , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo
14.
Curr Opin Nephrol Hypertens ; 31(4): 332-338, 2022 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-35703216

RESUMO

PURPOSE OF REVIEW: The burden of fractures is very high in patients with chronic kidney disease (CKD). It is increasingly recognized that knowledge of bone turnover is of paramount importance in guiding mineral metabolism and osteoporosis therapy in CKD. Bone histomorphometry is the gold standard to assess bone turnover, but is seldomly performed in clinical practice. Bone turnover markers (BTMs) may be the long awaited noninvasive diagnostic that may help to close the therapeutic gap in patients with advanced CKD presenting with bone fragility. RECENT FINDINGS: Mounting evidence indicates that BTMs may be useful in skeletal and nonskeletal risk stratification, in guiding mineral metabolism and osteoporosis therapy, and in monitoring the therapeutic response. SUMMARY: BTMs provide information that is complementary to other clinical tests. It may be envisioned that in the near future, the assessment of nonkidney cleared BTMs may become part of routine clinical evaluation and monitoring of bone health in CKD patients, integrated with clinical risk factors, imaging data and, eventually, bone histomorphometry. Panels of BTMs will likely be more informative than single markers, and the same might hold true for trends as opposed to single time point data.


Assuntos
Osteoporose , Insuficiência Renal Crônica , Biomarcadores/metabolismo , Densidade Óssea , Remodelação Óssea , Osso e Ossos/metabolismo , Humanos , Minerais , Insuficiência Renal Crônica/diagnóstico
15.
Oxid Med Cell Longev ; 2022: 5859266, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35720182

RESUMO

Pyriproxyfen (PPF) mimics a natural hormone in insects and disrupts their growth. It is a well-known synthetic insecticide and aromatic juvenile hormone analog frequently used in agriculture and vegetable crops to control various insect species. At present, scanty information is available about the possible potential threats of PPF in aquatic organisms. Therefore, in this study, different toxico-pathologic endpoints of PPF like DNA damage, biomarkers of oxidative stress, and status of antioxidant enzymes were determined in Labeo rohita (freshwater fish). In our study, 60 active, free from any external obvious ailments, same size, age, and body mass were randomly allocated to four glass aquaria (T0-T3) separately containing 100 L water. The fish present in groups T1, T2, and T3 were administered PPF dissolved in water 300, 600, and 900 µg/L for 30 days. Different tissues including the blood and visceral organs were obtained from each fish on days 10, 20, and 30 of the experiment. Results on various morphological and nuclear changes in red blood cells of PPF-exposed Labeo rohita fish including pear-shaped erythrocytes, spherocytes, red blood cells with a blebbed nucleus, micronucleus, and nuclear remnants were significantly increased. Our results on genotoxicity (comet assay) recorded significantly (P ≤ 0.05) increased DNA damage in various tissues of insecticide-exposed fish. The results on oxidative stress profile (reactive oxygen species and thiobarbituric acid reactive substances) and antioxidant enzymes (reduced glutathione superoxide dismutase, peroxidase, and catalase) in multiple tissues of Labeo rohita fish concluded significantly (P ≤ 0.05) higher quantity of biomarkers of oxidative stress and lower concentrations of different antioxidant enzymes in treated fish. Hence, the findings of our experimental research determine that PPF could induce adverse toxic impacts on multiple tissues of Labeo rohita fish.


Assuntos
Cyprinidae , Inseticidas , Poluentes Químicos da Água , Animais , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Cyprinidae/genética , Cyprinidae/metabolismo , Dano ao DNA , Água Doce , Brânquias/química , Brânquias/metabolismo , Estresse Oxidativo , Piridinas , Água
16.
Nat Commun ; 13(1): 3548, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729174

RESUMO

Despite the fact that proteins carry out nearly all cellular functions and mark the differences of cells, the existing single-cell tools can only analyze dozens of proteins, a scale far from full characterization of cells and tissue yet. Herein, we present a single-cell cyclic multiplex in situ tagging (CycMIST) technology that affords the comprehensive functional proteome profiling of single cells. We demonstrate the technology by detecting 182 proteins that include surface markers, neuron function proteins, neurodegeneration markers, signaling pathway proteins, and transcription factors. Further studies on cells derived from the 5XFAD mice, an Alzheimer's Disease (AD) model, validate the utility of our technology and reveal the deep heterogeneity of brain cells. Through comparison with control mouse cells, we have identified differentially expressed proteins in AD pathology. Our technology could offer new insights into cell machinery and thus may advance many fields including drug discovery, molecular diagnostics, and clinical studies.


Assuntos
Doença de Alzheimer , Doença de Alzheimer/metabolismo , Animais , Biomarcadores/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças , Camundongos , Camundongos Transgênicos , Neurônios/metabolismo
17.
Stem Cell Res Ther ; 13(1): 265, 2022 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-35729660

RESUMO

BACKGROUND: This study tested whether two doses of human umbilical-derived mesenchymal stem cells (hUC-MSCs) were superior to one dose for protecting the brain against intracranial hemorrhage (ICH) induced by intracranial injection collagenase and the capacity of ironic-magnetic-nanoparticles (Ir-MNa) coated hUC-MSCs tracked by MRI. METHODS AND RESULTS: Adult male SD rats (n = 40) were equally categorized into group 1 (sham-operated-control), group 2 (ICH), group 3 [ICH + Ir-MNa-coated hUC-MSCs/1.2 × 106 cells with an extracorporeal magnet over rat head (eCMag)/administered by left internal carotid artery (LICA) at post-3 h ICH], and group 4 (ICH + Ir-MNa-coated hUC-MSCs/1.2 × 106 cells with an eCMag/administered post-3 h ICH by LICA and 24 h by IV) and euthanized by day 28. The result showed that by day 28 after ICH induction the neurological function was severely impaired in group 2 than in group 1 that was significantly improved in group 3 and further significantly improved in group 4, whereas ICH volume exhibited an opposite pattern of neurological impairment among the groups (all p < 0.0001). Brain MRI demonstrated that by 4 h after ICH, Ir-MNa-coated hUC-MSCs were abundantly identified in ischemic area in group 4. The protein expressions of inflammatory (TNF-α/MMP-9/IL-1ß/iNOS)/oxidative-stress (NOX-1/NOX-2/oxidized protein)/apoptotic (caspase-3/mitochondrial Bax/PARP)/fibrotic (Smad3/TGF-ß)/mitochondrial-damaged (cytosolic-cytochrome-C) biomarkers displayed an identical pattern of neurological impairment among the groups (all p < 0.0001). The cellular expressions of inflammation (CD68+/CD11b+)/brain edema (AQP4+) biomarkers exhibited an identical pattern, whereas the neuronal-myelin (Doublecortin+/NeuN/nestin) biomarkers displayed an opposite pattern of neurological impairment (all p < 0.0001). CONCLUSION: Two doses of hUC-MSCs were superior to just one dose for protecting the brain against ICH-induced damage and Ir-MNa-coated hUC-MSCs offered a well adopted method for tracking hUC-MSCs homing into the brain.


Assuntos
Nanopartículas de Magnetita , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Biomarcadores/metabolismo , Humanos , Hemorragias Intracranianas/metabolismo , Hemorragias Intracranianas/terapia , Ferro/metabolismo , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley , Cordão Umbilical/metabolismo
18.
Fa Yi Xue Za Zhi ; 38(1): 59-66, 2022 Feb 25.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-35725705

RESUMO

OBJECTIVES: The metabolomics technique of LC-MS/MS combined with data analysis was used to detect changes and differences in metabolic profiles in the vitreous humor of early rat carcasses found in water, and to explore the feasibility of its use for early postmortem submersion interval (PMSI) estimation and the cause of death determination. METHODS: The experimental model was established in natural lake water with 100 SD rats were randomly divided into a drowning group (n=50) and a postmortem (CO2 suffocation) immediately submersion group (n=50). Vitreous humor was extracted from 10 rats in each group at 0, 6, 12, 18 and 24 h postmortem for metabolomics analyses, of which 8 were used as the training set to build the model, and 2 were used as test set. PCA and PLS multivariate statistical analysis were performed to explore the differences in metabolic profiles among PMSI and causes of death in the training set samples. Then random forest (RF) algorithm was used to screen several biomarkers to establish a model. RESULTS: PCA and PLS analysis showed that the metabolic profiles had time regularity, but no differences were found among different causes of death. Thirteen small molecule biomarkers with good temporal correlation were selected by RF algorithm. A simple PMSI estimation model was constructed based on this indicator set, and the data of the test samples showed the mean absolute error (MAE) of the model was 0.847 h. CONCLUSIONS: The 13 metabolic markers screened in the vitreous humor of rat corpses in water had good correlations with the early PMSI. The simplified PMSI estimation model constructed by RF can be used to estimate the PMSI. Additionally, the metabolic profiles of vitreous humor cannot be used for early identification of cause of death in water carcasses.


Assuntos
Mudanças Depois da Morte , Corpo Vítreo , Animais , Biomarcadores/metabolismo , Cadáver , Cromatografia Líquida , Imersão , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Corpo Vítreo/metabolismo , Água/metabolismo
19.
Sci Rep ; 12(1): 10513, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35732647

RESUMO

Oral squamous cell carcinoma (OSCC) is a common malignant tumor worldwide that is characterized by abnormal lesions or malignant hyperplasia of soft and hard tissues in the oral cavity. Previous research has found that HDAC6 may be a potential therapeutic target for cancer patients and has the ability to regulate immune cells. However, the mechanism of HDAC6 in OSCC pathogenesis is unclear. We collected clinical samples and analyzed the level of HDAC6 in OSCC patients. The results showed that in the high HDAC6 expression group, HDAC6 expression was positively correlated with the grade of OSCC (R = 0.182, P = 0.036) and that this group had a 3.248-fold increase in the mortality risk compared with the low HDAC6 expression group (P = 0.003). Survival analysis also identified a correlation between the expression of HDAC6 and overall survival in OSCC patients, and it was found that the expression of HDAC6 was inversely correlated with survival (P ≤ 0.001). In addition, we found that HDAC6 induced IL-13 expression through AP-1, resulting in M2 polarization of macrophages. Together, these results demonstrate that the level of HDAC6 may be a useful prognostic biomarker and offer a novel immune cell-related therapeutic strategy of targeting IL-13 in OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Biomarcadores/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Desacetilase 6 de Histona/genética , Desacetilase 6 de Histona/metabolismo , Humanos , Interleucina-13/metabolismo , Macrófagos/metabolismo , Neoplasias Bucais/metabolismo , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Fator de Transcrição AP-1/metabolismo
20.
J Immunol Res ; 2022: 5600190, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35733917

RESUMO

Osteoarthritis (OA) is thought to be the most prevalent chronic joint disease. The incidence of OA is rising because of the ageing population and the epidemic of obesity. This research was designed for the identification of novel diagnostic biomarkers for OA and analyzing the possible association between critical genes and infiltrated immune cells. 10 OA samples from patients with spinal OA and 10 normal samples were collected. GSE55235 and GSE55457 datasets including human OA and normal samples were downloaded from the GEO datasets. Differentially expressed genes (DEGs) were identified between 20 OA and 20 controls. SVM-RFE analysis and LASSO regression model were carried out to screen possible markers. The compositional patterns of the 22 types of immune cell fraction in OA were determined by the use of CIBERSORT. The expression level of the biomarkers in OA was examined by the use of RT-PCR. In this study, an overall 44 DEGs were identified: 18 genes were remarkably upregulated and 26 genes were distinctly downregulated. KEGG pathway analyses revealed that pathways were significantly enriched including IL-17 signal path, rheumatoid arthritis, TNF signal path, and lipid and atherosclerosis. Based on the results of machine learning, we identified APOLD1 and EPYC as critical diagnostic genes in OA, which were further confirmed using ROC assays. Immune cell infiltration analysis revealed that APOLD1 was correlated with mastocytes stimulated, NK cells resting, T cells CD4 memory resting, DCs stimulated, T cells gamma delta, macrophages M0, NK cells stimulated, and mastocytes resting. Moreover, we found that EPYC was correlated with mastocytes stimulated, NK cells resting, T cells CD4 memory resting, DCs stimulated, T cells gamma delta, macrophages M0, NK cells stimulated, and mastocytes resting. Overall, our findings might provide some novel clue for the exploration of novel markers for OA diagnosis. The critical genes and their associations with immune infiltration may offer new insight into understanding OA developments.


Assuntos
Biologia Computacional , Osteoartrite , Biomarcadores/metabolismo , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Humanos , Aprendizado de Máquina , Osteoartrite/diagnóstico , Osteoartrite/genética , Osteoartrite/metabolismo
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