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1.
Biomed Chromatogr ; 37(12): e5741, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37688464

ABSTRACT

Matrix effect and sample pretreatment significantly affect the percentage recovery of peptides in biological matrices, affecting the method robustness and accuracy. To counteract this effect, an internal standard (IS) is used; however, in most cases this is not available, which limits the analytical method. It is important to identify short peptides that can be used as ISs in the quantification of peptides in biological matrices. In this study, doping peptides GHRP-4, GHRP-5, GHRP-6, Sermorelin (1-11), Sermorelin (13-20) and Sermorelin (22-29) were synthesized using solid-phase peptide synthesis. Treatment with human blood, trypsin and chymotrypsin was used to determine the stability of the peptides. Products were evaluated using the high-performance liquid chromatography-diode array detector (HPLC-DAD) method. The analytical methodology and sample pretreatment were effective for the analysis of these molecules. A unique profile related to protein binding and enzymatic stability of each peptide was established. GHRP-4, GHRP-6 and Sermorelin (22-29) can be considered as in-house ISs as they were stable to enzyme and blood treatment and can be used for the quantification of peptides in biological samples. Peptides GHRP-6 and Sermorelin (22-29) were used to analyse a dimeric peptide (26 [F] LfcinB (20-30)2 ) in four different matrices to test these peptides as in-house IS.


Subject(s)
Clinical Chemistry Tests , Doping in Sports , Growth Hormone-Releasing Hormone , Growth Substances , Peptides/analysis , Humans , Serum/chemistry , Protein Stability , Blood Chemical Analysis/standards , Clinical Chemistry Tests/standards , Growth Hormone-Releasing Hormone/analysis , Growth Substances/analysis
2.
PLoS Comput Biol ; 17(6): e1009077, 2021 06.
Article in English | MEDLINE | ID: mdl-34161317

ABSTRACT

The vertebrate hindbrain is segmented into rhombomeres (r) initially defined by distinct domains of gene expression. Previous studies have shown that noise-induced gene regulation and cell sorting are critical for the sharpening of rhombomere boundaries, which start out rough in the forming neural plate (NP) and sharpen over time. However, the mechanisms controlling simultaneous formation of multiple rhombomeres and accuracy in their sizes are unclear. We have developed a stochastic multiscale cell-based model that explicitly incorporates dynamic morphogenetic changes (i.e. convergent-extension of the NP), multiple morphogens, and gene regulatory networks to investigate the formation of rhombomeres and their corresponding boundaries in the zebrafish hindbrain. During pattern initiation, the short-range signal, fibroblast growth factor (FGF), works together with the longer-range morphogen, retinoic acid (RA), to specify all of these boundaries and maintain accurately sized segments with sharp boundaries. At later stages of patterning, we show a nonlinear change in the shape of rhombomeres with rapid left-right narrowing of the NP followed by slower dynamics. Rapid initial convergence improves boundary sharpness and segment size by regulating cell sorting and cell fate both independently and coordinately. Overall, multiple morphogens and tissue dynamics synergize to regulate the sizes and boundaries of multiple segments during development.


Subject(s)
Body Patterning/physiology , Models, Biological , Zebrafish/embryology , Animals , Body Patterning/genetics , Computational Biology , Embryonic Development/genetics , Embryonic Development/physiology , Fibroblast Growth Factors/physiology , Gene Expression Regulation, Developmental , Growth Substances/physiology , Rhombencephalon/cytology , Rhombencephalon/embryology , Signal Transduction , Stochastic Processes , Tretinoin/physiology , Zebrafish/genetics
3.
Sci Rep ; 11(1): 10485, 2021 05 18.
Article in English | MEDLINE | ID: mdl-34006921

ABSTRACT

NAFLD is a leading comorbidity in HIV with an exaggerated course compared to the general population. Tesamorelin has been demonstrated to reduce liver fat and prevent fibrosis progression in HIV-associated NAFLD. We further showed that tesamorelin downregulated hepatic gene sets involved in inflammation, tissue repair, and cell division. Nonetheless, effects of tesamorelin on individual plasma proteins pertaining to these pathways are not known. Leveraging our prior randomized-controlled trial and transcriptomic approach, we performed a focused assessment of 9 plasma proteins corresponding to top leading edge genes within differentially modulated gene sets. Tesamorelin led to significant reductions in vascular endothelial growth factor A (VEGFA, log2-fold change - 0.20 ± 0.35 vs. 0.05 ± 0.34, P = 0.02), transforming growth factor beta 1 (TGFB1, - 0.35 ± 0.56 vs. - 0.05 ± 0.43, P = 0.05), and macrophage colony stimulating factor 1 (CSF1, - 0.17 ± 0.21 vs. 0.02 ± 0.20, P = 0.004) versus placebo. Among tesamorelin-treated participants, reductions in plasma VEGFA (r = 0.62, P = 0.006) and CSF1 (r = 0.50, P = 0.04) correlated with a decline in NAFLD activity score. Decreases in TGFB1 (r = 0.61, P = 0.009) and CSF1 (r = 0.64, P = 0.006) were associated with reduced gene-level fibrosis score. Tesamorelin suppressed key angiogenic, fibrogenic, and pro-inflammatory mediators. CSF1, a regulator of monocyte recruitment and activation, may serve as an innovative therapeutic target for NAFLD in HIV. Clinical Trials Registry Number: NCT02196831.


Subject(s)
Blood Proteins/metabolism , Growth Hormone-Releasing Hormone/analogs & derivatives , Growth Substances/pharmacology , HIV Infections/complications , Non-alcoholic Fatty Liver Disease/complications , Proteomics/methods , Transcriptome , Adolescent , Adult , Aged , Double-Blind Method , Female , Growth Hormone-Releasing Hormone/pharmacology , HIV Infections/blood , Humans , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/blood , Non-alcoholic Fatty Liver Disease/genetics , Placebos , Randomized Controlled Trials as Topic , Transforming Growth Factor beta1/metabolism , Vascular Endothelial Growth Factor A/metabolism , Young Adult
4.
Respir Res ; 22(1): 8, 2021 Jan 06.
Article in English | MEDLINE | ID: mdl-33407472

ABSTRACT

BACKGROUND: Pulmonary arterial smooth muscle cell (PASMC) proliferation plays a crucial role in hypoxia-induced pulmonary hypertension (HPH). Previous studies have found that resistin-like molecule ß (RELM-ß) is upregulated de novo in response to hypoxia in cultured human PASMCs (hPASMCs). RELM-ß has been reported to promote hPASMC proliferation and is involved in pulmonary vascular remodeling in patients with PAH. However, the expression pattern, effects, and mechanisms of action of RELM-ß in HPH remain unclear. METHODS: We assessed the expression pattern, mitogenetic effect, and mechanism of action of RELM-ß in a rat HPH model and in hPASMCs. RESULTS: Overexpression of RELM-ß caused hemodynamic changes in a rat model of HPH similar to those induced by chronic hypoxia, including increased mean right ventricular systolic pressure (mRVSP), right ventricular hypertrophy index (RVHI) and thickening of small pulmonary arterioles. Knockdown of RELM-ß partially blocked the increases in mRVSP, RVHI, and vascular remodeling induced by hypoxia. The phosphorylation levels of the PI3K, Akt, mTOR, PKC, and MAPK proteins were significantly up- or downregulated by RELM-ß gene overexpression or silencing, respectively. Recombinant RELM-ß protein increased the intracellular Ca2+ concentration in primary cultured hPASMCs and promoted hPASMC proliferation. The mitogenic effects of RELM-ß on hPASMCs and the phosphorylation of PI3K, Akt, mTOR, PKC, and MAPK were suppressed by a Ca2+ inhibitor. CONCLUSIONS: Our findings suggest that RELM-ß acts as a cytokine-like growth factor in the development of HPH and that the effects of RELM-ß are likely to be mediated by the Ca2+-dependent PI3K/Akt/mTOR and PKC/MAPK pathways.


Subject(s)
Hormones, Ectopic/biosynthesis , Hypertension, Pulmonary/metabolism , MAP Kinase Signaling System/physiology , Phosphatidylinositol 3-Kinases/biosynthesis , Protein Kinase C/biosynthesis , Proto-Oncogene Proteins c-akt/biosynthesis , Animals , Calcium/metabolism , Cells, Cultured , Gene Knockdown Techniques/methods , Growth Substances/biosynthesis , Growth Substances/genetics , Hormones, Ectopic/antagonists & inhibitors , Hormones, Ectopic/genetics , Hypertension, Pulmonary/genetics , Male , Rats , Rats, Sprague-Dawley
5.
J Pediatr Endocrinol Metab ; 33(12): 1609-1612, 2020 Dec 16.
Article in English | MEDLINE | ID: mdl-32924381

ABSTRACT

OBJECTIVE: 3-M syndrome is characterized by severe short stature, syndromic features, and characteristic radiographic findings. Growth hormone (GH) has been used with variable success. Recombinant human insulin like growth factor-1 (rhIGF-1) has never been utilized. CASE PRESENTATION: We describe a child with severe growth retardation, macrocephaly, and skeletal abnormalities with evidence of GH insensitivity subsequently treated with rhIGF-1. He developed morbid obesity and comorbidities including voracious appetite, acanthosis nigricans, tonsillar hypertrophy, and severe obstructive sleep apnea with minimal height improvement. Genetic testing done at 11.5 years revealed a compound heterozygous mutation (c.2112G>A(p.W704X) and c.2559delC) in the CUL7 gene consistent with 3-M syndrome-1. rhIGF-1 therapy was discontinued. CONCLUSIONS: This case highlights the novel use of rhIGF-1 therapy on a child with 3-M syndrome-1 with minimal height benefit but accelerated weight gain and serves as a reminder of the importance of re-evaluating therapy efficacy and side effect profile.


Subject(s)
Cullin Proteins/genetics , Dwarfism/drug therapy , Growth Substances/therapeutic use , Insulin-Like Growth Factor I/therapeutic use , Muscle Hypotonia/drug therapy , Mutation , Recombinant Proteins/therapeutic use , Spine/abnormalities , Child, Preschool , Dwarfism/etiology , Dwarfism/pathology , Humans , Male , Muscle Hypotonia/etiology , Muscle Hypotonia/pathology , Prognosis , Spine/pathology
6.
Biomed Pharmacother ; 131: 110680, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32861071

ABSTRACT

Chitinase 3-like protein 1(CHI3L1) participates in physiological and pathophysiological process, such as cell survival, cell proliferation, tissue remodeling, angiogenesis, etc. Some studies demonstrated that CHI3L1 is liver-enriched and has better application value in staging liver fibrosis than platelet ratio index(APRI) and fibrosis-4 index(FIB-4) and that CHI3L1 can be used in monitoring the prognosis of hepatocellular carcinoma (HCC). In this review, we summarized the pathophysiological role and the diagnostic value of CHI3L1 in liver fibrosis in different background and HCC.


Subject(s)
Chitinase-3-Like Protein 1/metabolism , Growth Substances/metabolism , Liver Cirrhosis/diagnosis , Liver Cirrhosis/metabolism , Biomarkers/metabolism , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/physiopathology , Humans , Liver Cirrhosis/physiopathology , Liver Diseases/diagnosis , Liver Diseases/metabolism , Liver Diseases/physiopathology , Liver Neoplasms/diagnosis , Liver Neoplasms/metabolism , Liver Neoplasms/physiopathology
7.
Nutrients ; 12(8)2020 Jul 24.
Article in English | MEDLINE | ID: mdl-32722351

ABSTRACT

Satellite cells (SC) aid skeletal muscle growth and regeneration. SC-mediated skeletal muscle repair can both be influenced by and exacerbate several diseases linked to a fatty diet, obesity, and aging. The purpose of this study was to evaluate the effects of different lifestyle factors on SC function, including body mass index (BMI), age, and high-fat overfeeding. For this study, SCs were isolated from the vastus lateralis of sedentary young (18-30 years) and sedentary older (60-80 years) men with varying BMIs (18-32 kg/m2), as well as young sedentary men before and after four weeks of overfeeding (OVF) (55% fat/ + 1000 kcal, n = 4). The isolated SCs were then treated in vitro with a control (5 mM glucose, 10% fetal bovine serum (FBS)) or a high substrate growth media (HSM) (10% FBS, 25 mM glucose, and 400 µM 2:1 oleate-palmitate). Cells were assessed on their ability to proliferate, differentiate, and fuel substrate oxidation after differentiation. The effect of HSM was measured as the percentage difference between SCs exposed to HSM compared to control media. In vitro SC function was not affected by donor age. OVF reduced SC proliferation rates (-19% p < 0.05) but did not influence differentiation. Cellular proliferation in response to HSM was correlated to the donor's body mass index (BMI) (r2 = 0.6121, p < 0.01). When exposed to HSM, SCs from normal weight (BMI 18-25 kg/m2) participants exhibited reduced proliferation and fusion rates with increased fatty-acid oxidation (p < 0.05), while SCs from participants with higher BMIs (BMI 25-32 kg/m2) demonstrated enhanced proliferation in HSM. HSM reduced proliferation and fusion (p < 0.05) in SCs isolated from subjects before OVF, whereas HSM exposure accelerated proliferation and fusion in SCs collected following OVF. These results indicated that diet has a greater influence on SC function than age and BMI. Though age and BMI do not influence in vitro SC function when grown in controlled conditions, both factors influenced the response of SCs to substrate challenges, indicating age and BMI may mediate responses to diet.


Subject(s)
Age Factors , Body Mass Index , Diet, High-Fat/adverse effects , Growth Substances/pharmacokinetics , Satellite Cells, Skeletal Muscle/drug effects , Adolescent , Adult , Aged , Aged, 80 and over , Biological Availability , Cell Differentiation/drug effects , Cell Proliferation/drug effects , Humans , Male , Middle Aged , Oxidation-Reduction/drug effects , Young Adult
8.
Elife ; 92020 06 04.
Article in English | MEDLINE | ID: mdl-32496193

ABSTRACT

Blood vessels (BVs) are considered an integral component of neural stem cells (NSCs) niches. NSCs in the dentate gyrus (DG(have enigmatic elaborated apical cellular processes that are associated with BVs. Whether this contact serves as a mechanism for delivering circulating molecules is not known. Here we uncovered a previously unrecognized communication route allowing exclusive direct access of blood-borne substances to hippocampal NSCs. BBB-impermeable fluorescent tracer injected transcardially to mice is selectively uptaken by DG NSCs within a minute, via the vessel-associated apical processes. These processes, measured >30 nm in diameter, establish direct membrane-to-membrane contact with endothelial cells in specialized areas of irregular endothelial basement membrane and enriched with vesicular activity. Doxorubicin, a brain-impermeable chemotherapeutic agent, is also readily and selectively uptaken by NSCs and reduces their proliferation, which might explain its problematic anti-neurogenic or cognitive side-effect. The newly-discovered NSC-BV communication route explains how circulatory neurogenic mediators are 'sensed' by NSCs.


Subject(s)
Endothelial Cells/cytology , Hippocampus/cytology , Neural Stem Cells/physiology , Animals , Antibiotics, Antineoplastic/metabolism , Basement Membrane/cytology , Basement Membrane/metabolism , Blood-Brain Barrier/cytology , Blood-Brain Barrier/metabolism , Cell Communication , Cell Surface Extensions/metabolism , Cell Surface Extensions/physiology , Cytoplasmic Vesicles/metabolism , Doxorubicin/metabolism , Endothelial Cells/metabolism , Female , Growth Substances/metabolism , Male , Mice , Neural Stem Cells/cytology , Neural Stem Cells/metabolism , Neurogenesis
9.
Arch. Soc. Esp. Oftalmol ; 95(5): 211-216, mayo 2020. tab, ilus
Article in Spanish | IBECS | ID: ibc-198609

ABSTRACT

OBJETIVO: Analizar las características clínicas, el manejo y los resultados de los pacientes con endoftalmitis estéril asociada con el factor de crecimiento endotelial antivascular intravítreo. MÉTODOS: Serie de casos de observación retrospectiva de pacientes con endoftalmitis estéril después de inyecciones intravítreas anti-VEGF. Se han revisado los datos clínicos de pacientes tratados con anti-VEGF intravítreos durante un año. Se analizan los que han presentado un episodio de endoftalmitis estéril y se estudia su causalidad y manejo. RESULTADOS: Siete pacientes tuvieron un inicio de endoftalmitis estéril en los 4días posteriores a la inyección intravítrea (aflibercept n = 5 y ranibizumab n = 2). Estos pacientes tienen alguna condición neovascular activa: degeneración macular relacionada con la edad (n = 4), neovascularización coroidea miope (n = 1) o edema macular: edema macular diabético (n = 1), oclusión de la vena retiniana ramificada (n = 1). Los signos y síntomas compartidos incluyeron pérdida de visión indolora, células en cámara anterior o vítrea y falta de hipopión. En todos los pacientes, la agudeza visual volvió a estar dentro de una línea de agudeza basal. CONCLUSIÓN: Diferenciar casos de endoftalmitis estéril de infecciosa puede ser un desafío. Es crucial diferenciar ambas entidades, ya que un buen diagnóstico determina el pronóstico visual. Debemos ser conscientes de una inflamación mínima después de repetidas inyecciones intravítreas para establecer el tratamiento adecuado


PURPOSE: Analyze clinical features, management and outcomes of patients with sterile endophthalmitis associated with intravitreal antivascular endothelial growth factor. METHODS: Observational retrospective case series of patients with sterile endophthalmitis following anti-VEGF intravitreal injections. Clinical data of patients treated with intravitreal anti-VEGFs during one year have been revised. Those who have presented an episode of sterile endophthalmitis are analyzed and their causality and management are studied. RESULTS: Seven patients have had a sterile endophthalmitis onset within 4days after intravitreal injection (aflibercept n = 5 and ranibizumab n = 2). These patients have some active neovascular condition: age related macular degeneration (n = 4), myopic choroidal neovascularization (n = 1) or macular edema: diabetic macular edema (n = 1), branch retinal vein occlusion (n = 1). Shared signs and symptoms included painless vision loss, anterior chamber and vitreous cell and lack of hypopyon. In all patients, visual acuity returned to within one line of baseline acuity. CONCLUSIÓN: Differentiating cases of sterile from infectious endophthalmitis may be challenging. It is crucial to differentiate both entities as a good diagnosis determines the visual prognosis. We should be aware of minimal inflammation after repeated intravitreal injections in order to establish the adequate treatment


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Aged , Aged, 80 and over , Endophthalmitis/chemically induced , Endophthalmitis/pathology , Intravitreal Injections/adverse effects , Endothelial Growth Factors/adverse effects , Growth Substances/adverse effects , Endothelial Growth Factors/administration & dosage , Growth Substances/administration & dosage , Retrospective Studies , Algorithms , Ranibizumab/administration & dosage , Ranibizumab/adverse effects
10.
Muscle Nerve ; 61(5): 623-631, 2020 05.
Article in English | MEDLINE | ID: mdl-32108355

ABSTRACT

INTRODUCTION: Recombinant human insulin-like growth factor-1 (rhIGF-1) is a growth factor and has anabolic effects on muscle. We investigated whether rhIGF-1 therapy: 1) improves or preserves muscle function; and 2) improves growth in boys with Duchenne muscular dystrophy (DMD). METHODS: In this study we compared prepubescent, ambulatory, glucocorticoid-treated boys with DMD (n = 17) vs controls (glucocorticoid therapy only, n = 21) in a 6-month-long, prospective, randomized, controlled trial of subcutaneous rhIGF-1 therapy. The primary outcome was 6-minute walk distance (6MWD). Secondary outcomes included height velocity (HV), change in height standard deviation score (ΔHtSDS), motor function, cardiopulmonary function, body composition, insulin sensitivity, quality of life, and safety. RESULTS: Change in 6MWD was similar between groups (rhIGF-1 vs controls [mean ± SD]: 3.4 ± 32.4 vs -5.1 ± 50.2 meters, P = .53). Treated subjects grew more than controls (HV: 6.5 ± 1.7 vs 3.3 ± 1.3 cm/year, P < .0001; 6-month ΔHtSDS: 0.25, P < .0001). Lean mass and insulin sensitivity increased in treated subjects. DISCUSSION: In boys with DMD, 6 months of rhIGF-1 therapy did not change motor function, but it improved linear growth.


Subject(s)
Body Height , Growth Substances/therapeutic use , Insulin Resistance , Insulin-Like Growth Factor I/therapeutic use , Muscle Strength , Muscular Dystrophy, Duchenne/drug therapy , Recombinant Proteins/therapeutic use , Absorptiometry, Photon , Blood Glucose/metabolism , Blood Glucose Self-Monitoring , Body Composition , Child , Drug Therapy, Combination , Glucocorticoids/therapeutic use , Humans , Magnetic Resonance Imaging , Male , Muscular Dystrophy, Duchenne/metabolism , Muscular Dystrophy, Duchenne/physiopathology , Quality of Life , Treatment Outcome , Walk Test
12.
Endocr J ; 67(2): 167-175, 2020 Feb 28.
Article in English | MEDLINE | ID: mdl-31776295

ABSTRACT

Non-functioning pituitary adenoma (NFPA) is one common cause of adult growth hormone deficiency (AGHD). In Japan, a GH-releasing peptide (GHRP)-2 test is used to evaluate GH secretion. Although the cut-off for peak GH during a GHRP-2 test for severe AGHD is ≤9 ng/mL, severe AGHD may further diminish responses (range, nearly no-response to ≤9 ng/mL). We studied whether the peak GH responses during a GHRP-2 test could be predicted based on clinical characteristics of patients with NFPA. We compared patients with almost no-response during a GHRP-2 test with other patients considered as severe AGHD. Among the 76 patients with NFPA who were admitted to our institution, 36 patients (mean age, 61 years; male/female, n = 23/n = 13) were diagnosed with severe AGHD based on a preoperative GHRP-2 test. Based on the preoperative median peak GH concentration (2.83 ng/mL), patients were divided into two groups (

Subject(s)
Adenoma/surgery , Human Growth Hormone/deficiency , Hypopituitarism/metabolism , Pituitary Function Tests , Pituitary Neoplasms/surgery , Adenoma/complications , Adenoma/diagnostic imaging , Adrenocorticotropic Hormone/deficiency , Adult , Aged , Aged, 80 and over , Female , Growth Substances , Human Growth Hormone/metabolism , Humans , Hypogonadism , Hypopituitarism/etiology , Insulin-Like Growth Factor I/metabolism , Magnetic Resonance Imaging , Male , Middle Aged , Oligopeptides , Pituitary Neoplasms/complications , Pituitary Neoplasms/diagnostic imaging , Postoperative Period , Preoperative Period , Prognosis , Recovery of Function , Retrospective Studies , Severity of Illness Index , Young Adult
13.
J Invest Dermatol ; 140(4): 860-868.e3, 2020 04.
Article in English | MEDLINE | ID: mdl-31622598

ABSTRACT

YKL-40, one of the chitinase-like proteins, is associated with the pathogenesis of a wide variety of human diseases through modulation of inflammation and tissue remodeling by its diverse roles in cell proliferation, differentiation, and survival. Emerging evidence shows that aberrantly expressed YKL-40 promotes the development of malignancies by inducing proliferation of tumor cells, cytokine production, and angiogenesis by acting on various stromal cells, immune cells, and tumor cells. In this study, we investigated the expression and function of YKL-40 in cutaneous T-cell lymphoma (CTCL). We first revealed that serum YKL-40 levels were increased in patients with CTCL and correlated with disease severity markers. We also found that YKL-40 was expressed by epidermal keratinocytes and tumor cells in lesional skin of CTCL by immunohistochemistry. Although YKL-40 did not affect cytokine production from CTCL cell lines, YKL-40 promoted the proliferation of Hut78 cells and HH cells in vitro, which was dependent on extracellular signal-regulated kinase 1/2 pathways. Moreover, exogenous YKL-40 administration enhanced tumor growth of HH cells in vivo. Our study has suggested that YKL-40 produced from epidermal keratinocytes and CTCL cells promoted the proliferation of CTCL cells through extracellular signal-regulated kinase 1/2 pathways in autocrine and paracrine manners, leading to development of CTCL.


Subject(s)
Chitinase-3-Like Protein 1/pharmacology , Extracellular Signal-Regulated MAP Kinases/metabolism , Keratinocytes/metabolism , Lymphoma, T-Cell, Cutaneous/drug therapy , Skin Neoplasms/drug therapy , Cell Line, Tumor , Cell Proliferation , Growth Substances/pharmacology , Humans , Immunohistochemistry , Keratinocytes/drug effects , Keratinocytes/pathology , Lymphoma, T-Cell, Cutaneous/metabolism , Lymphoma, T-Cell, Cutaneous/pathology , Skin Neoplasms/metabolism , Skin Neoplasms/pathology
14.
World J Gastroenterol ; 26(48): 7619-7632, 2020 Dec 28.
Article in English | MEDLINE | ID: mdl-33505140

ABSTRACT

BACKGROUND: Stress-related gastric mucosal damage or ulcer remains an unsolved issue for critically ill patients. Stress ulcer prophylaxis has been part of routine intensive care, but uncertainty and controversy still exist. Co-secreted with mucins, intestinal trefoil factor (ITF) is reported to promote restitution and regeneration of intestinal mucosal epithelium, although the mechanism remains unknown. AIM: To elucidate the protective effects of ITF on gastric mucosa and explore the possible mechanisms. METHODS: We used a rat model of gastric mucosal damage induced by water immersion restraint stress and lipopolysaccharide-treated human gastric epithelial cell line to investigate the potential effects of ITF on damaged gastric mucosa both in vivo and in vitro. RESULTS: ITF promoted the proliferation and migration and inhibited necrosis of gastric mucosal epithelia in vitro. It also preserved the integrity of gastric mucosa by upregulating expressions of occludin and zonula occludens-1. In the rat model, pretreatment with ITF ameliorated the gastric mucosal epithelial damage and facilitated mucosal repair. The protective effects of ITF were confirmed to be exerted via activation of Akt signaling, and the specific inhibitor of Akt signaling LY249002 reversed the protective effects. CONCLUSION: ITF might be a promising candidate for prevention and treatment of stress-induced gastric mucosal damage, and further studies should be undertaken to verify its clinical feasibility.


Subject(s)
Neuropeptides , Proto-Oncogene Proteins c-akt , Animals , Gastric Mucosa , Growth Substances , Humans , Intestinal Mucosa , Muscle Proteins , Peptides , Rats , Trefoil Factor-2 , Trefoil Factor-3
15.
ACS Sens ; 4(10): 2771-2777, 2019 10 25.
Article in English | MEDLINE | ID: mdl-31593439

ABSTRACT

Paramagnetic ion-mediated sensors can greatly simplify current magnetic sensors for biochemical assays, but it remains challenging because of the limited sensitivity. Herein, we report a magnetic immunosensor relying on Mn(VII)/Mn(II) interconversion and the corresponding change in the low-field nuclear magnetic resonance (LF-NMR) of the transverse relaxation rate (R2). The fact that the NMR R2 of the water protons detected in Mn(II) aqueous solution is much stronger than Mn(VII) aqueous solution enables the modulation of the LF-NMR signal intensity of R2. By employing immunomagnetic separation and enzyme-catalyzed reaction, this Mn(VII)/Mn(II) interconversion allows the development of a background signal-free magnetic immunosensor with a high signal-to-background ratio that enables detection of ractopamine and Salmonella with high sensitivity (the limits of detection for ractopamine and Salmonella are 8.1 pg/mL and 20 cfu/mL, respectively). This Mn-mediated magnetic immunosensor not only retains the good stability but also greatly improves the sensitivity of conventional paramagnetic ion-mediated magnetic sensors, offering a promising platform for sensitive, stable, and convenient bioanalysis.


Subject(s)
Biosensing Techniques , Growth Substances/analysis , Immunoassay , Manganese/chemistry , Metal Nanoparticles/chemistry , Phenethylamines/analysis , Salmonella/isolation & purification , Veterinary Drugs/analysis , Alkaline Phosphatase/analysis , Alkaline Phosphatase/chemistry , Animals , Antibodies , Food Safety , Growth Substances/chemistry , Growth Substances/urine , Magnetic Phenomena , Phenethylamines/chemistry , Phenethylamines/urine , Serum Albumin, Bovine , Swine , Veterinary Drugs/chemistry
16.
Respir Med ; 158: 49-54, 2019.
Article in English | MEDLINE | ID: mdl-31605921

ABSTRACT

BACKGROUND: _The mitogen response in interferon-γ(IFN-γ) release assays(IGRAs) measures IFN-γ after binding to CD2, a surface adhesion marker found on T-cells and NK cells. A lower mitogen response implies either peripheral blood mononuclear cells have fewer adhesion molecules either in absolute numbers or per T-cells, or the pathway from adhesion molecules to IFN-γ production is not functioning well. To date, it remains poorly understood whether the mitogen response is associated with outcomes in tuberculosis patients. METHODS: _From 2012 to 2017, patients with culture-confirmed tuberculosis were tested for QuantiFERON-TB Gold In-Tube(QFT-GIT). The associations between patient outcomes and QFT-GIT as well as IFN-γ responses to the mitogen were investigated. Outcomes of interest included 1-year mortality after tuberculosis diagnosis and 2-month culture conversion. RESULTS: _In total, 466 culture-confirmed tuberculosis patients were enrolled and QFT-GIT was positive in 309(66%). Within 1 year of diagnosis, 20(4%) died and notably, 15(11%) out of 137 patients with a lower mitogen response did so. The multivariate Cox model showed that a lower mitogen response (hazard ratio, 8.789; 95% confidence interval, 3.074-25.129) was independently associated with 1-year mortality. Moreover, among 160 patients with smear-positive culture-confirmed pulmonary tuberculosis, multivariate logistic analysis indicated that a lower mitogen response (odds ratio, 3.966; 95% confidence interval, 1.182-13.303) was significantly associated with 2-month culture persistence. CONCLUSIONS: _This study found that a lower mitogen response was associated with worse 1-year survival in tuberculosis patients and correlated with 2-month culture persistence in patients with sputum smear-positive culture-confirmed tuberculosis. These findings suggest another application of QFT-GIT for prognostication of tuberculosis patients.


Subject(s)
Growth Substances/immunology , Interferon-gamma/metabolism , Tuberculosis/immunology , Tuberculosis/metabolism , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Prognosis , Survival Rate , Tuberculosis/mortality , Young Adult
17.
Poult Sci ; 98(12): 6659-6667, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31544941

ABSTRACT

This study aimed to estimate the productive and economic impacts caused by the withdrawal of antibiotic growth promoters (AGP) from broilers diet. Indexed publications that compared diets with or without AGP (AGP+/AGP-) for broilers (from initial to final phase) were collected and the results of feed intake, weight gain, and feed conversion were compiled in a database. A meta-analysis was performed following sequential analyses: graphical approach (to observe biological data coherence), correlation (to identify related factors), and variance-covariance (to compare groups). The annual number of broiler slaughtered in Brazil, target weight gain and feed conversion for each phase, the variation in feed conversion, feed cost, and AGP costs were used to build a model to estimate the effects of the AGP withdrawal on feeding costs. The database comprised 174 scientific articles containing 183 experiments, totaling 121,643 broilers, most of which were Ross (52% of the studies). The most frequent AGP sources/forms in the database were Avilamycin (41% of the AGP+ treatments), Flavomycin (19%), Virginiamycin (16%), and Bacitracin (14%). Higher feed intake, weight gain, and lower feed conversion were attributed (P < 0.05) to AGP+ diets during Initial phase (1 to 21 D). In Final phase (22 to 42 D) no differences were observed in performance variables. Treatments AGP+ presented higher weight gain and better feed conversion in the Total period (1 to 42 D). The results of feed conversion were improved (P < 0.05) with Avilamycin and Flavomycin; Virginiamycin improved weight gain and feed conversion. In the Total period, the economic impact was $0.03 per animal and a total of $183,560,232 per year. It was concluded that broilers fed AGP+ diets have higher weight gain and better feed conversion than those fed AGP- diets, and withdrawing AGP increases production costs.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Chickens/physiology , Diet/veterinary , Growth Substances/administration & dosage , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Brazil , Chickens/growth & development , Dietary Supplements/analysis , Female , Male , Models, Theoretical
18.
Nutrients ; 11(8)2019 Aug 07.
Article in English | MEDLINE | ID: mdl-31394828

ABSTRACT

Growth in young children is controlled through the release of several hormonal signals, which are affected by diet, infection, and other exposures. Stunting is clearly a growth disorder, yet limited evidence exists documenting the association of different growth biomarkers with child stunting. This study explored the association between different growth biomarkers and stunting in Bangladeshi children. A quasi-experimental study was conducted among 50 stunted (length-for-age Z-score (LAZ) < -2 SD) and 50 control (LAZ ≥ -2 SD) children, aged 12-18 months, residing in a Bangladeshi slum. The enrolled stunted children received an intervention package, which included food supplementation for three months, psychosocial stimulation for six months, and routine clinical care on community nutrition center at the study field site. The controls received routine clinical care only. All children were clinically screened over the study period. Length, weight, fasting blood and fecal biomarkers were measured. All biomarkers levels were similar in both groups except for oxyntomodulin at enrolment. Leptin (adjusted odds ratio, AOR: 4.0, p < 0.01), leptin-adiponectin ratio (AOR 5.07 × 108, p < 0.01), insulin-like growth factor-1 (IGF-1) (AOR 1.02, p < 0.05), and gamma interferon (IFN-γ) (AOR 0.92, p < 0.05) levels were independently associated with stunting at enrolment. Serum leptin, leptin-adiponectin ratio, interleukin-6 (IL-6), IL-10, tumor necrosis factor-alpha (TNF-α), and fecal alpha-1-antitrypsin (AAT) levels increased significantly (p < 0.001), while IFN-γ levels significantly decreased among stunted children after six months of intervention. Leptin, leptin-adiponectin ratio, IGF-1, and IFN-γ are independently associated with stunting in Bangladeshi children. This trial was registered at clinicaltrials.gov as NCT02839148.


Subject(s)
Growth Disorders/blood , Growth Substances/blood , Adipokines/blood , Bangladesh , Biomarkers/analysis , Biomarkers/blood , Body Mass Index , Cytokines/blood , Dietary Supplements , Feces/chemistry , Female , Flumazenil/analogs & derivatives , Flumazenil/analysis , Flumazenil/blood , Growth Disorders/therapy , Humans , Infant , Male , Poverty Areas , Psychology
19.
Food Chem ; 300: 125173, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31319335

ABSTRACT

The administration of anabolic agents in farm animals to improve meat production has been prohibited in EU, due to the potential risks to human health. Meat quality was investigated to detect the effects of illegal administration of dexamethasone or prednisolone or 17ß-estradiol on Charolais bulls. Three groups of 6 bulls were treated and 12 bulls were the control. Meat quality parameters were measured on live animals, carcasses and on samples of Longissimus thoracis and multivariate statistical data analysis was applied. In Charolais bulls, these parameters were affected by growth promoter administration and the multivariate canonical discriminant analysis was able to distinguish between treated and untreated animals mainly due to three electronic nose's parameters, 24 h carcass temperature and drip loss. Therefore, meat quality control and the multivariate analysis could be useful as a first screening to address targeted controls on farms suspected of illicit use of growth promoters.


Subject(s)
Food Analysis/methods , Growth Substances/pharmacology , Meat , Muscle, Skeletal/drug effects , Muscle, Skeletal/growth & development , Animals , Cattle , Dexamethasone/pharmacology , Discriminant Analysis , Electronic Nose , Estradiol/pharmacology , Farms , Food Analysis/instrumentation , Food Analysis/statistics & numerical data , Food Quality , Male , Meat/analysis , Prednisolone/pharmacology
20.
Poult Sci ; 98(10): 4391-4400, 2019 Oct 01.
Article in English | MEDLINE | ID: mdl-31002111

ABSTRACT

A study was conducted to investigate the effects of Bacillus amyloliquefaciens CECT 5940 as a direct-fed microbial (DFM) alone or in association with bacitracin methylene disalicylate (BMD) in broilers under enteric pathogen challenge. A total of 1,530-day-old male Cobb500 chicks were randomly assigned to 5 treatments, with 9 replicate pens with 34 birds each. Treatments included positive control (PC, basal diet without additives or challenge); negative control (NC, basal diet without additive and challenged birds); NC + 0.05 g/kg BMD; NC + 1 g/kg DFM (106 CFU B. amyloliquefaciens CECT 5940/g of feed); and NC + 0.05 g/kg BMD + 1 g/kg DFM. The challenge consisted of oral gavage with Eimeria maxima and Clostridium perfringens inoculum. Body weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were evaluated on days 21, 35, and 42. Ileal and cecal content were collected on days 21 and 28 for C. perfringens enumeration by real-time PCR assay and the intestinal health was evaluated by scores. Uniformity (UN), carcass (CY), and breast meat yields (BMY) were evaluated on day 42. After 14 and 21 d post-inoculation, birds in the challenged groups had significant lower FI and BWG compared to the PC group (P < 0.05). However, the groups receiving DFM, BMD, or its combination presented better FCR, CY, BMY, UN, and lower incidence of footpad lesion and litter quality visual scores, compared to the NC group without feed additives (P < 0.05). Mortality was not affected by treatments (P > 0.05). Broilers fed DFM, BMD, or its combination presented lower C. perfringens in ileal content at 21 and 28 d compared to NC group without additives (P < 0.05) and also maintained gut health by keeping the frequency of ballooning, abnormal content, and swollen mucosa comparable to the PC group (P > 0.05). The study indicates that Bacillus amyloliquefaciens CECT 5940 is effective as BMD to provide similar performance and gut health in challenged broilers.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacillus amyloliquefaciens/chemistry , Chickens , Clostridium Infections/veterinary , Coccidiosis/veterinary , Poultry Diseases/drug therapy , Probiotics/pharmacology , Animal Feed/analysis , Animals , Anti-Bacterial Agents/administration & dosage , Clostridium Infections/drug therapy , Clostridium Infections/microbiology , Clostridium perfringens/physiology , Coccidiosis/drug therapy , Coccidiosis/parasitology , Diet/veterinary , Eimeria/physiology , Gastrointestinal Microbiome/drug effects , Growth Substances/administration & dosage , Growth Substances/pharmacology , Male , Meat/analysis , Poultry Diseases/microbiology , Poultry Diseases/parasitology , Probiotics/administration & dosage , Random Allocation
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